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PubMed2000

Effects of nonsteroidal antiinflammatory drugs on inflammatory bowel disease: a case-control study.

OBJECTIVE: The aim of this study was to determine whether a relationship exists between the use of nonsteroidal antiinflammatory drugs (NSAIDs) and exacerbation or onset of inflammatory bowel disease (IBD). METHODS: Sixty consecutive IBD patients admitted to the hospital were carefully interviewed to ascertain whether they used NSAIDs and the relationship in time and duration to the exacerbation (or onset) of the IBD; 62 patients with irritable bowel syndrome were similarly interviewed and served as controls. RESULTS: In 31% of our IBD population there was a correlation between use of NSAIDs and IBD activity, whereas in only 2% of the irritable bowel syndrome population who used NSAIDs did this relationship exist. CONCLUSIONS: NSAIDs provoke disease activity in both ulcerative colitis and Crohn's disease and should be avoided in patients with a history of IBD whenever possible.

Adolescent↗
PubMed2000

Homocysteine in inflammatory bowel disease: a risk factor for thromboembolic complications?

OBJECTIVE: Patients with inflammatory bowel disease (IBD) are at increased risk for thromboembolic events. Hyperhomocysteinemia, which is an established risk factor for arterial as well as venous thrombosis, may be more prevalent in IBD because of vitamin deficiencies. METHODS: In this retrospective study, we studied the concentrations of total homocysteine (tHcy), cobalamin, folate, and pyridoxine in 231 consecutive patients with IBD, of whom 16 patients had a history of venous thrombosis, and nine a history of arterial thrombosis. Age- and gender-matched healthy volunteers served as controls (n = 102). RESULTS: Homocysteine concentrations in patients were higher (12.3 micromol/L [range 4.6-51.3] vs 11.1 micromol/L [range 3.9-27.6], p = 0.001) and hyperhomocysteinemia tended to be more prevalent in patients than in the controls (11.1% vs 5%, p = 0.07). Folate, cobalamin, creatinine, and pyridoxine concentrations were correlated with tHcy. Folate deficiency was infrequently encountered in IBD patients (4.3%). The tHcy concentration in patients with a history of venous or arterial thrombosis was not higher than in patients without a history of thrombosis (12.7 micromol/L [range 4.6-40.1] and 15.2 micromol/L (range 10.5-26.8) vs 12.3 micromol/L [range 10.5-26.8], not significant). Hyperhomocysteinemia was found in 18.8% of the patients with venous thrombosis, 11.1% of the patients with arterial thrombosis, and 10.5% of the patients without thrombosis (not significant). CONCLUSIONS: Hyperhomocysteinemia is a common phenomenon in IBD and correlates with serum folate, cobalamin, creatinine, and pyridoxine concentrations. No correlation between tHcy and a history of venous or arterial thromboembolic complications is found. Hyperhomocysteinemia does not seem to be a major contributory factor in the development of venous or arterial thrombosis in IBD patients.

Adolescent↗
PubMed2000

The relationship between heritability and smoking habits in Crohn's disease. Italian Cooperative Study Group.

OBJECTIVE: In Crohn's disease (CD), the relationship between genetic predisposition and smoking has not been well defined. The aim of this study was to compare the smoking habits at the time of the diagnosis of CD patients having familial occurrence of inflammatory bowel disease (IBD) with those of some control groups. METHODS: In a multicenter study, 136 CD patients with a relative with IBD, 272 healthy controls matched for sex and age, 500 CD patients without familial occurrence of IBD, and 84 ulcerative colitis patients (UC) with familial occurrence of IBD were personally interviewed about their smoking habits. In addition, data for 35 healthy siblings of patients with familial CD were collected by interviewing the patients' relatives. RESULTS: The prevalence of smokers was found significantly higher in CD patients with a family history for IBD than in healthy controls and in familial UC patients (OR 2.28 CI 1.5-3.48 and OR 5.81 CI 3.15-10.75, respectively). No significant difference was found either in the percentage of smokers or in the number of cigarettes smoked per day between familial and sporadic CD patients. Among all siblings of CD patients, 72% of affected siblings and 34% of healthy siblings were smokers, concordant with their relatives. CONCLUSIONS: In CD patients with familial occurrence of IBD, the percentage of smokers is elevated. It is possible that in a genetically predisposed population, smoking could be an important environmental factor in determining CD or expressing this disease instead of UC.

Adult↗
PubMed2001

VEGF, basic-FGF, and TGF-beta in Crohn's disease and ulcerative colitis: a novel mechanism of chronic intestinal inflammation.

OBJECTIVE: Inflammatory bowel disease (IBD), the precise etiology of which remains unknown, is comprised of two forms of chronic intestinal inflammation; ulcerative colitis (UC) and Crohn's disease (CD). Recent evidence increasingly suggests that IBD is the result of dysfunctional immunoregulation manifested by inappropriate production of mucosal cytokines. An abnormal microcirculatory system has also been implicated in its pathogenesis. To elucidate the mechanism of ischemic change in IBD, we assesse serum concentration levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF), and plasma level of endothelin-1 (ET-1). We also investigated the expression of VEGF, b-FGF, and transforming growth factor-beta1,2,3 (TGF-beta1,2,3) in tissue by immunostaining. METHODS: Blood samples were obtained from 11 patients with UC, 11 patients with CD, and 10 patients as controls. Paraffin-embedded samples were used for an immunohistochemical study. RESULTS: The concentration levels (in picograms per milliliter) were as follows: for ET-1, UC: 127+/-47.0, CD: 167.3+/-35.1, and controls (asthma: 38.5+/-23.8, p < 0.01; diverticulitis: 40.5+/-25.6, p < 0.01), for b-FGF, UC: 9.2+/-1.9, CD: 9.1+/-1.5, and controls (asthma: 5.0+/-0, p < 0.01; diverticulitis: 5.0+/-0, p < 0.01), for VEGF, UC: 659.8+/-181.0, CD: 740.0+/-182.3, and controls (asthma: 193.7+/-58.7, p < 0.01; diverticulitis: 199.6+/-59.7, p < 0.01). The levels of VEGF and b-FGF were significantly higher in active IBD than those in the controls. There was a significant positive correlation among the serum levels of VEGF and b-FGF and the plasma level of ET-1; that is, elevated VEGF, b-FGF, and ET-1 levels correlated well with each other. Immunohistochemical studies showed increased venula in the submucosa and lamina propria. Overexpression of VEGF and b-FGF in endothelial cells was revealed and TGF-beta2 and TGF-beta3 were found in inflammatory cells of active IBD, but no change was observed around the vessels in the controls. CONCLUSIONS: It is suggested that the reciprocal reaction of these cytokines may contribute to angiogenesis in IBD b inducing intestinal ischemia through vasoconstriction.

Adult↗
PubMed2001

The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study.

OBJECTIVE: The aim of this study was to determine the prevalence of the major extraintestinal manifestations of inflammatory bowel disease (IBD) and their relation to disease diagnosis and gender. METHODS: We used the population-based University of Manitoba IBD Database, which includes longitudinal files on all subjects of all health system contacts identified by International Classification of Diseases, 9th Revision, Clinical Modification codes for visit diagnosis. We extracted a cohort from our database, which included subjects with a known diagnosis of IBD for at least 10 yr. We then determined how many contacts each subject had for each of the following extraintestinal IBD-associated immune diseases: primary sclerosing cholangitis, ankylosing spondylitis, iritis/uveitis, pyoderma gangrenosum, and erythema nodosum. We calculated the prevalence of the extraintestinal diseases using an administrative definition of having at least five health system contacts for the diagnosis in question. This administrative definition has previously been validated in Crohn's disease and ulcerative colitis (UC). RESULTS: A total of 6.2% of patients with IBD had one of six major extraintestinal diseases studied in this report. Only 0.3% of patients had multiple extraintestinal diseases. Iritis/uveitis was the most common extraintestinal disease of all assessed (2.2% of women and 1.1% of men). Iritis/uveitis was more common among women, particularly those with UC (3.8%). Primary sclerosing cholangitis was most common among men with UC (3%). Ankylosing spondylitis was more common among men, and the highest rate was seen among men with Crohn's disease (2.7%). Pyoderma gangrenosum was more common in Crohn's (1.2%) with no gender predilection. Erythema nodosum was similarly present in Crohn's and UC but was more common among women (1.9%). CONCLUSIONS: The associations of immune mediated diseases in extraintestinal sites may help us to further our understanding of IBD pathogenesis, and it may help us in developing a paradigm of disease subsets.

Adult↗
PubMed2002

Quality of life in inflammatory bowel disease in remission: the impact of IBS-like symptoms and associated psychological factors.

OBJECTIVES: Quality of life is reduced in inflammatory bowel disease (IBD). Whether or not this is true in IBD patients in long-standing remission is unclear. Symptoms compatible with irritable bowel syndrome (IBS) are common in IBD patients in remission. The importance of psychological factors in this process is a matter of controversy. METHODS: Forty-three patients with ulcerative colitis (UC) and 40 with Crohn's disease (CD), who had been in remission for at least 1 yr according to laboratory parameters and clinical and endoscopical appearance, were included. These patients completed four different self-administered questionnaires, evaluating GI symptoms, anxiety, depression, and psychological general well-being. The two patient groups were compared with the general population, and within-group comparisons in psychometric scores were made between patients with and without IBS-like symptoms. RESULTS: The psychological well-being in IBD patients in long-standing remission was similar to that of the general population, despite the presence of more severe GI symptoms. CD patients reported more psychosocial dysfunction, reduced well-being, and GI symptoms than UC patients. Thirty-three percent of UC patients and 57% of CD patients had IBS-like symptoms. The group with IBS-like symptoms (both UC and CD) had higher levels of anxiety and depression and more reduced well-being than those without. Anxiety and reduced vitality were found to be independent predictors for IBS-like symptoms in these patients. CONCLUSION: The prevalence of IBS-like symptoms in IBD patients in long-standing remission is two to three times higher than that in the normal population. Psychological factors seem to be of importance in this process. However, as a group IBD patients in remission demonstrate psychological well-being comparable to that of the general population.

Adaptation, Psychological↗
PubMed2002

Safety of selective cyclooxygenase-2 inhibitors in inflammatory bowel disease.

OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) are relatively contraindicated in patients with inflammatory bowel disease (IBD) for fear of disease aggravation. Cyclooxygenase-2 inhibitors have fewer GI side effects than traditional NSAIDs in unselected patients. We report the safety of these agents in patients with IBD. METHODS: Patients with Crohn's disease, ulcerative colitis, or pouchitis who used celecoxib or rofecoxib were identified from computerized prescription records. A retrospective chart review was conducted. Concomitant medications, past NSAID use, indication for cyclooxygenase-2 inhibitor, dose, and duration were obtained. IBD disease activity before cyclooxygenase-2 inhibitor use was graded using a modified disease activity index. Change in disease activity was graded as improved, no change, or worsened. Patients were contacted to provide data not found in the charts. The proportion of patients receiving cyclooxygenase-2 inhibitors who experienced exacerbation of IBD was determined. RESULTS: Eleven patients were treated with celecoxib (median dose = 200 mg/day), and 16 patients were treated with rofecoxib (median dose = 25 mg/day). Median duration of therapy was 9 months (range = 1 wk-22 months). The drug was beneficial in 14 patients, of partial benefit in eight, and of no benefit in five. Two patients (7.4%) (95% CI = 2-23%) had aggravations of IBD. Three patients (11%) had other adverse events (renal insufficiency, rash, and asymptomatic colonic ulceration). All adverse events were reversible. CONCLUSIONS: Our preliminary results suggest that cyclooxygenase-2 inhibitors may be safe and beneficial in most patients with IBD. A placebo-controlled trial to confirm these preliminary observations is needed.

Adult↗
PubMed2002

Suspected inflammatory bowel disease--the clinical and economic impact of competing diagnostic strategies.

OBJECTIVES: The suspicion of IBD in patients presenting with nonspecific abdominal pain and diarrhea results in the extensive use of invasive diagnostic testing in patients likely to have a functional GI disorder. Noninvasive serodiagnostic tests, however, accurately identify IBD and may serve as effective screening tools. The objective of this study was to examine the cost-effectiveness of initial serodiagnostic screening followed by standard invasive testing, compared to standard invasive testing alone, in patients presenting with uninvestigated symptoms suggestive of IBD. METHODS: Decision analysis was performed to compare the costs and outcomes of competing diagnostic strategies. Probability estimates were derived from the medical literature and expert opinion. Costs estimates were obtained from the Medicare Fee schedule and the cost-analysis was done from a third party payer perspective. The target population was patients with uninvestigated symptoms suggestive of IBD. The outcome measure was cost per correct diagnosis in competing strategies and was assessed at 1 yr. RESULTS: In the base case analysis, the serodiagnostic strategies were dominant; they were less costly and more accurate than the standard invasive strategies. Sequential serodiagnostic strategies resulted in the largest cost savings ($550 per average patient) with an average cost per correct diagnosis of $1640 compared to $2188 for standard invasive testing. Cost savings were attributable to a 39% reduction in the use of invasive tests. The results were robust to varying model estimates over prespecified ranges in the sensitivity analyses. When costs of invasive testing are reduced by 80% or the prevalence of IBD is at least 83%, serodiagnostic strategies are no longer the most cost-effective. CONCLUSIONS: Initial serodiagnostic screening strategies may represent a cost-effective alternative to standard invasive diagnostic strategies. The economic benefits seem to be achieved by avoiding invasive evaluations in patients without IBD. Confirmation of these findings in a prospective comparative trial seems to be warranted.

Cost-Benefit Analysis↗
PubMed2003

Low vitamin B(6) plasma levels, a risk factor for thrombosis, in inflammatory bowel disease: role of inflammation and correlation with acute phase reactants.

OBJECTIVES: Individuals with inflammatory bowel disease (IBD) are at increased risk for thrombosis and vitamin deficiencies. Low plasma levels of vitamin B(6) are an independent risk factor for thrombosis and may cause hyperhomocysteinemia, another recognized risk factor for thrombosis. The aim of this study was to evaluate vitamin B(6) plasma levels in IBD patients. METHODS: We studied 61 IBD patients: 32 with Crohn's disease and 29 with ulcerative colitis. For each patient, three sex- and age-matched healthy control subjects were studied. RESULTS: Median vitamin B(6) levels were significantly lower in IBD patients (22.0 pmol/L, range 3.6-231.0) than in controls (31.1 pmol/L, 3.7-363.4; p < 0.01). In all, 13.1% IBD patients and 5.5% controls had plasma vitamin B(6) levels lower than the 5th percentile of distribution in normal controls (p < 0.05). Low vitamin B(6) levels were significantly more frequent in patients with active disease than in patients with quiescent disease (seven of 26, 26.9%, vs one of 35, 2.9%; p < 0.001). Moreover, patients with active disease had significantly lower median vitamin B(6) levels (13.4 pmol/L, range 3.6-124.0) than patients in a quiescent phase (27.0 pmol/L, 7.8-231.0; p < 0.001). Low vitamin B(6) levels were significantly correlated with serum concentrations of C-reactive protein (r = -0.36, 95% CI = -0.59 to -0.09, p < 0.01) and alpha(1)-acid-glycoprotein (r = -0.37, 95% CI = -0.59 to -0.10, p < 0.01). Hyperhomocysteinemia was more frequent in patients with low vitamin B(6) levels (three of eight, 37.5%) than in patients with normal levels (nine of 53, 17.0%; p = 0.18). There was no statistically significant correlation between vitamin B(6) and homocysteine plasma levels (r = -0.13, 95% CI = -0.37 to +0.14, p = 0.33). CONCLUSIONS: Low vitamin B(6) plasma levels, an independent risk factor for thrombosis, are frequent in patients with IBD, especially those with active disease.

Acute-Phase Proteins↗
PubMed2003

High prevalence of fatigue in quiescent inflammatory bowel disease is not related to adrenocortical insufficiency.

OBJECTIVES: Inflammatory bowel disease (IBD) patients, with active as well as quiescent disease, frequently complain of fatigue. This often has consequences for patients' work and daily lives. The primary aim of this study was to assess the prevalence and severity of fatigue in IBD patients in remission. Furthermore, we studied the correlation between fatigue and disease activity, quality of life, and biochemical and hematological test results, and the role of (secondary) hypocortisolism. METHODS: Eighty subjects with proven IBD were included. Disease activity was assessed using the Clinical Activity Index for Ulcerative Colitis and the Crohn's Disease Activity Index. Quality of life was measured by the Inflammatory Bowel Disease Questionnaire, and fatigue was assessed using the Multidimensional Fatigue Inventory (MFI). Routine biochemical and hematological tests were performed, and basal cortisol was determined. To evaluate adrenocortical reserve in subjects with a cortisol level of <0.4 micromol/L, a low dose adrenocorticotrophin hormone test was performed. Healthy age- and sex-matched subjects (n = 67) served as controls. RESULTS: More than 40% of the IBD patients in remission suffered from fatigue. Mean MFI scores of the IBD patients were comparable to mean MFI scores reported in cancer patients. The Inflammatory Bowel Disease Questionnaire showed a negative correlation with the MFI (r = -0.735; p < 0.001). No correlation was found between fatigue and basal cortisol levels or other laboratory parameters. CONCLUSION: Fatigue is an important feature in IBD in remission, adversely affecting the quality of life. It does not, however, affect all patients, nor does it seem to be the result of hypocortisolism.

Adrenal Insufficiency↗
PubMed2003

Lack of relationship of calcium and vitamin D intake to bone mineral density in premenopausal women with inflammatory bowel disease.

OBJECTIVES: Low bone mineral density has been widely reported in patients with inflammatory bowel disease (IBD). The exact etiology of this condition is not completely understood but is suggested to be multifactorial, possibly including low calcium and vitamin D intake. The objective of this study was to assess calcium and vitamin D intake and its relationship to bone mineral density (BMD) in premenopausal women with IBD. METHODS: A total of 70 premenopausal women with IBD (mean age 33.3 yr, range 18-44 yr) drawn from the population-based University of Manitoba IBD Research Registry participated in the study. Calcium and vitamin D intake was determined using a semiquantitative food frequency questionnaire and compared to the Dietary Reference Intake values for adequacy. BMD of total body, lumbar spine, femoral neck, and hip was measured using dual-energy x-ray absorptiometry. RESULTS: Of the 70 subjects, 66 successfully completed the study. Inadequate calcium intake (<1000 mg/day) was found in 69.7% of the subjects. This low intake group had a mean calcium intake of 508 mg/day. Inadequate vitamin D intake (<200 IU/day) was found in 53% of the subjects with a mean vitamin D intake of 76 IU/day in this group. Calcium and vitamin D intake correlated with each other with R2=0.57, p<0.00001. Daily calcium intake was not significantly different for subjects with T scores greater than -1 (901 mg) and for subjects with T scores less than -1 (875 mg, p=0.44). Daily vitamin D intake was not significantly different for subjects with T scores greater than -1 (297 IU) compared with subjects with T scores less than -1 was (267 IU, p=0.33). Comparing subjects with T scores greater than -1 to those with T score less than -1, there was no difference in the percentage of subjects ingesting >1 g/day calcium (14/43 vs 8/23, p=0.86) or in those with vitamin D intake >200 IU/day (21/43 vs 9/23, p=0.45). CONCLUSIONS: The results show that, on average, premenopausal women with IBD have less than the recommended intake for calcium and vitamin D. However, this does not seem to influence BMD. Calcium and vitamin D intake is not a predictor of bone status in premenopausal women with IBD.

Absorptiometry, Photon↗
PubMed2004

HLA disparity determines disease activity through pregnancy in women with inflammatory bowel disease.

OBJECTIVES: Inflammatory bowel disease (IBD) activity during pregnancy is variable and factors influencing the course unknown. We studied the relationship between maternal-fetal HLA disparity and IBD course. METHODS: Women with IBD and childbirth were recruited and medical records were reviewed for five time periods. Twenty milliliters of blood was obtained from mother and child for genotyping. Each mother/child pair was assigned an HLA disparity status (+/-) for HLA A, B, C, DRB1, and DQ loci. Odds ratios were calculated comparing HLA disparity in women whose IBD improved versus those whose disease worsened or remained active. RESULTS: Fifty pregnancies in 38 women were studied. Forty-two of 50 pregnancies (84%) were disparate at the DRB1 locus; 34 (68%) were mismatched at the DQ locus. There was no difference in average disease score or overall activity score based on DRB1 or DQ disparity (p > 0.05 for all comparisons). There were 31 pregnancies disparate at both DRB1 and DQ loci; a significant difference was found in average disease scores and overall activity scores between women mismatched at both loci versus only one or neither locus (OR 8.4 [1.5-14, p = 0.01). Logistic regression identified prepartum disease activity and disparity at both DRB1 and DQ as significant predictors of overall disease activity during pregnancy. CONCLUSION: Improvement of IBD symptoms during pregnancy is associated with disparity in HLA class II antigens between mother and fetus. This suggests that the maternal immune response to paternal HLA antigens plays a role in pregnancy-induced remission. What is accepted and what this research adds are as follows: . The course of IBD during pregnancy is variable. . The factors involved with disease course are unknown. . The data presented here provides a scientific mechanism for disease course during pregnancy. . This is a novel work and it corroborates what has been seen in other autoimmune conditions.

Colitis, Ulcerative↗
PubMed2005

Long-term psychosocial outcomes reported by children and adolescents with inflammatory bowel disease.

OBJECTIVES: The purpose of this study was to compare the self-reported psychosocial functioning of children with inflammatory bowel disease (IBD) to that of healthy children in the areas of behavioral/emotional functioning, social competence, self-esteem, stress coping strategies, and social support. METHODS: Participants were 50 children with IBD diagnosed at least 1 yr before enrollment, and 42 healthy comparison children aged 11-17 yr. They completed a series of well-validated questionnaires assessing psychosocial functioning. The treating gastroenterologists of participating children with IBD completed the Pediatric Crohn's Disease Activity Index during a clinic visit within a week of completion of the questionnaires. RESULTS: Mean scores fell in the normal range on all normed measures, and there were no significant differences between group means on any of the measures. A subset of 20% of children with IBD reported clinically significant behavioral/emotional symptoms, even a year after diagnosis, which was similar to results found in the healthy comparison group. Most children with IBD were in remission or had mild disease activity at the time of the study. Neither past nor current disease factors differentiated those with significant emotional problems. CONCLUSIONS: These results suggest that most children with currently mild IBD who have been diagnosed for at least a year report normal psychosocial functioning that is similar to that of healthy children. A subset of these children report significant behavioral/emotional difficulty, and future research should seek to identify which children are most at risk for these problems and how best to intervene.

Adolescent↗
PubMed2006

DLG5 variants in inflammatory bowel disease.

OBJECTIVES: Genetic variants within DLG5 were recently reported to be associated with inflammatory bowel disease (IBD). The aim of our study was to test for allelic and haplotype associations of six DLG5 variants in 668 IBD patients from two European populations. Furthermore, we evaluated whether DLG5 variants alter gastrointestinal permeability in Crohn's disease (CD). METHODS: Six DLG5 variants (p.R30Q, p.P1371Q, p.G1066G, rs2289308, DLG_e26, p.D1507D) were genotyped in two study populations: (1) German IBD patients (CD n = 250; ulcerative colitis (UC) n = 150) and German healthy controls (n = 422); (2) Hungarian IBD patients (CD n = 144; UC n = 124) and Hungarian healthy controls (n = 205). Subtyping analysis was performed in respect of CARD15 mutations and clinical characteristics. We also tested for differences within DLG5 genotypes in German CD patients with respect to gastroduodenal and intestinal permeability measured by triple-sugar-test. RESULTS: Allele as well as genotype frequencies of DLG5 variants did not differ between IBD patients and controls in either study population. Indeed, the p.R30Q polymorphism was found more frequently in controls than in patients. The distribution of DLG5 genotypes in German and Hungarian CD patients with CARD15 mutations was not different from patients without mutated CARD15. We did also not observe any association between DLG5 variants and clinical parameters. Importantly, DLG5 variants were not associated with gastroduodenal or intestinal permeability. CONCLUSIONS: We could not replicate that DLG5 is a relevant disease susceptibility gene for IBD in German or Hungarian subjects. In addition, we have no evidence that DLG5 variants are involved in altered gastrointestinal permeability in CD.

Adult↗
PubMed2006

Increasing incidences of inflammatory bowel disease and decreasing surgery rates in Copenhagen City and County, 2003-2005: a population-based study from the Danish Crohn colitis database.

OBJECTIVES: A continuous increase in the incidence of inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), and indeterminate colitis (IC) has been suggested. Since Denmark provides excellent conditions for epidemiological research, we aimed to describe contemporary IBD incidence rates and patient characteristics in Copenhagen County and City. METHODS: All patients diagnosed with IBD during 2003-2005 were followed prospectively. Demographic and clinical characteristics, such as disease extent, extraintestinal manifestations, smoking habits, medical treatment, surgical interventions, cancer, and death, were registered. RESULTS: Five-hundred sixty-two patients were diagnosed with IBD, resulting in mean annual incidences of 8.6/10(5) for CD, 13.4/10(5) for UC, and 1.1/10(5) for IC. Time from onset to diagnosis was 8.3 months in CD and 4.5 months in UC patients. A family history of IBD, smoking, and extraintestinal manifestations was significantly more common in CD than in UC patients. Only 0.6% of UC patients had primary sclerosing cholangitis. In CD, old age at diagnosis was related to pure colonic disease, whereas children significantly more often had proximal and extensive involvement. Twelve percent of CD patients and 6% of UC patients underwent surgery during the year of diagnosis, significantly less than earlier reported. CONCLUSIONS: The incidence of IBD in Copenhagen increased noticeably during the last decades. Time from onset of symptoms until diagnosis decreased markedly, extent of CD was related to age at diagnosis, and the risk of surgery was low in UC.

Adolescent↗
PubMed2006

Inflammation and coagulation in inflammatory bowel disease: The clot thickens.

Inflammation and coagulation play crucial roles in the pathogenesis of multiple chronic inflammatory disorders. Growing evidence highlights a tight mutual network in which inflammation, coagulation, and fibrinolysis play closely related roles. Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel disease (IBD), are chronic inflammatory conditions, characterized by a hypercoagulable state and prothrombotic conditions, and accompanied by abnormalities in coagulation. From a pathophysiological point of view, cells and molecules classically implicated in the physiological process of coagulation have now been shown to behave abnormally in IBD and possibly to also play an active role in disease pathogenesis and/or disease progression. This paper reviews studies performed on the coagulation profile and risk factors for thrombosis in IBD. In particular, an overview is provided of the epidemiology, clinical features, and etiology of thromboembolic complications in IBD. Furthermore, we review hemostatic abnormalities in IBD, as well as the cell types involved in such processes. Finally, we highlight the coagulation system as a dynamic participant in the multifaceted process of chronic intestinal inflammation. Overall, an overview is provided that the coagulation system represents an important, though previously underestimated, component of IBD pathogenesis, and may be a possible target for therapeutic intervention.

Blood Coagulation↗
PubMed2007

Regulation of oxidant-induced intestinal permeability by metalloprotease-dependent epidermal growth factor receptor signaling.

Inflammatory bowel disease (IBD) affects more than 1 million Americans with more than 30,000 new cases diagnosed each year. IBD increases patient morbidity and susceptibility to colorectal cancer, yet its etiology remains unknown. Current models identify two key determinants of IBD pathogenesis: hyperpermeability of the gut epithelial barrier to bacterial products and an abnormal immune response to these products. Two factors seem critical for hyperpermeability: oxidant-induced stress and proinflammatory cytokines (e.g., tumor necrosis factor-alpha). The aim of this study was to investigate the role of oxidant stress-mediated transactivation of the epidermal growth factor receptor (EGFR) in intestinal hyperpermeability. This study used the Caco-2 human colonic epithelial cell in vitro model of intestinal epithelium. Cells were grown on inserts for permeability and signaling studies and glass coverslips for microscopy studies. show that oxidant-induced intestinal hyperpermeability can be blocked by specific inhibitors of the EGFR, tumor necrosis factor convertase (TACE) metalloprotease, transforming growth factor (TGF)-alpha, and mitogen-activated protein kinases, especially extracellular signal-regulated kinase 1/2. We also show that oxidant initiates these signaling events, in part by causing translocation of TACE to cell-cell contact zones. In this study, our data identify a novel mechanism for oxidant-induced intestinal hyperpermeability relevant to IBD. We propose a new intestinal permeability model in which oxidant transactivates EGFR signaling by activation of TACE and cleavage of precursor TGF-alpha. These data could have a significant effect on our view of IBD pathogenesis and provide new therapeutic targets for IBD treatment.

ADAM Proteins↗
PubMed2006

Analysis of serum antibodies in patients suspected of having inflammatory bowel disease.

Inflammatory bowel disease (IBD) is the general term used for a heterogeneous group of intestinal disorders, including Crohn's disease (CD) and ulcerative colitis (UC). Serological markers such as anti-Saccharomyces cerevisiae antibodies (ASCA) and atypical perinuclear antineutrophilic cytoplasmic antibody (atypical pANCA) have proven useful in the diagnosis and differentiation of CD and UC. Immunoglobulin A (IgA) antibody directed against the outer membrane protein C (OmpC) of Escherichia coli is said by one group to have clinical utility in diagnosing IBD, specifically in ASCA-negative CD patients. Our objective in this study was to compare the results obtained from two separate laboratories offering similar IBD tests using sera from suspected IBD patients. One hundred ninety-seven sera received for IBD testing were included in the study. The agreement between the two laboratories was 93.4% for ASCA IgA, 90.9% for ASCA IgG, and 87.8% for atypical pANCA IgG. There were 25 sera with ASCA-negative/OmpC-positive results reported by one laboratory. Thirteen of these 25 (52.0%) ASCA-negative/OmpC-positive sera were also atypical pANCA positive (9 as determined by both laboratories, 3 by one, and 1 by the other). Atypical pANCA antibody is found primarily in IBD patients with UC and colon-limited CD (Crohn's colitis). We conclude that the ASCA and atypical pANCA assays showed good agreement between the two laboratories, but the data for ASCA-negative/OmpC-positive sera suggest that many (52.0%) of these patients were more likely to have had UC or Crohn's colitis based on the presence of an atypical pANCA.

Adult↗