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PubMed1999

Cytokine-based therapies in inflammatory bowel disease.

Cytokine-based therapy for inflammatory bowel disease (IBD) has significantly advanced in the last year. This review highlights some of the exciting progress that has occurred. The efficacy of anti-tumor necrosis factor (TNF) monoclonal antibody therapy in Crohn's disease has promoted further research and the development of other anti-TNF therapies, such as thalidomide, phosphodiesterase type IV inhibitors, and new-generation anti-TNF monoclonal antibodies. Current research is also focused on more proximal events in the inflammatory cascade to modify T-cell regulation and to decrease the production and activity of proinflammatory proteins, cytokines, and nuclear regulatory factors. Concurrently, the emerging role of interleukin (IL)-11, IL-12, and IL-18 in the perpetuation of chronic inflammation continues to stimulate much interest. All of these new advancements reveal an exciting future for IBD therapy.

Journal Article↗
PubMed2003

Inflammatory bowel disease after liver transplantation: the effect of different immunosuppressive regimens.

BACKGROUND: Seemingly conflicting results have been reported on the prevalence and severity of inflammatory bowel disease after liver transplantation. Regimens with different combinations of drugs can be used for immunosuppression after transplantation. AIM: To study retrospectively the prevalence of inflammatory bowel disease after liver transplantation, and the possible relationship with maintenance immunosuppressive regimens. METHODS: All 78 patients with end-stage primary sclerosing cholangitis (48 patients) or autoimmune cirrhosis (30 patients), transplanted between 1979 and July 2001, and with a follow-up of at least 1 year, were eligible for this study. In addition to patient and transplant characteristics, data on inflammatory bowel disease and immunosuppression before and after transplantation were collected. The Kaplan-Meier method was used for survival analysis. Possible risk factors for inflammatory bowel disease after transplantation were analysed by Cox univariate and multivariate regression. RESULTS: The median follow-up after transplantation was 7.2 years (range, 1.1-22.3 years). Nine of 25 patients with pre-transplant inflammatory bowel disease experienced flare-ups after transplantation. Six of 53 patients without pre-transplant inflammatory bowel disease developed de novo inflammatory bowel disease after transplantation. The cumulative risks (standard errors in parentheses) for inflammatory bowel disease were 6% (3%), 12% (4%) and 20% (5%) at 1, 3 and 5 years after transplantation, respectively. The inflammatory bowel disease-free survival was significantly higher in patients not receiving tacrolimus vs. those receiving tacrolimus, in patients receiving azathioprine vs. those not receiving azathioprine and in patients taking the regimen prednisolone-azathioprine-ciclosporin A vs. those taking tacrolimus-prednisolone. Pre-transplant inflammatory bowel disease and the use of tacrolimus were found to be independent predictors for inflammatory bowel disease after transplantation. CONCLUSIONS: The prevalence of inflammatory bowel disease after liver transplantation is affected by the immunosuppression used. Azathioprine seems to have a protective effect and tacrolimus a promoting effect.

Adolescent↗
PubMed2000

The incidence of fracture among patients with inflammatory bowel disease. A population-based cohort study.

BACKGROUND: The clinical significance of the high prevalence of osteopenia in inflammatory bowel disease is unclear. OBJECTIVE: To determine whether persons with inflammatory bowel disease have increased incidence of fracture. DESIGN: Population-based matched cohort study. SETTING: Manitoba, Canada. PATIENTS: Patients with inflammatory bowel disease in the University of Manitoba IBD Database (n = 6027) were matched to 10 randomly selected persons in the general population without inflammatory bowel disease (n = 60 270) by year, age, sex, and postal area of residence. MEASUREMENTS: The incidence of hospitalization for hip fracture was determined on the basis of hospital discharge abstracts. Outpatient medical billing records and hospital discharge abstracts were used to calculate the incidence of spine, rib, and forearm fractures. Rates were calculated on the basis of person-years of follow-up for 1984 to 1997. RESULTS: Persons with inflammatory bowel disease had significantly increased incidence of fractures at the spine (incidence rate ratio [IRR], 1.74 [95% CI, 1.34 to 2.24]; P < 0.001), hip (IRR, 1.59 [CI, 1.27 to 2.00]; P < 0.001), wrist/forearm (IRR, 1.33 [CI, 1.11 to 1.58]; P = 0.001), and rib (IRR, 1.25 [CI, 1.02 to 1.52]; P = 0.03) and of any of these fractures (IRR, 1.41 [CI, 1.27 to 1.56]; P < 0.001). CONCLUSION: The incidence of fracture among persons with inflammatory bowel disease is 40% greater than that in the general population.

Adult↗
PubMed1998

The sugar permeability test reflects disease activity in children and adolescents with inflammatory bowel disease.

OBJECTIVES: To investigate the relationship of intestinal permeability in children and adolescents with inflammatory bowel disease (IBD) to disease activity, disease extent, and response to therapy. STUDY DESIGN: Patients with new and established diagnoses of IBD (12 Crohn's disease [CD] and 18 ulcerative colitis [UC]) were studied. Intestinal permeability was evaluated by measuring with high-performance liquid chromatography 5-hour urinary excretion ratio of lactulose/L-rhamnose (L/Rh). RESULTS: In 8 of 9 patients with active CD, the L/Rh ratio was higher than the reference range (0.006 to 0.074, n = 36). In inactive CD (n = 3) the L/Rh ratio was within the reference range. In 6 of 7 patients with active extensive UC, the L/Rh ratio was elevated. In inactive extensive UC (n = 6) the normal permeability ratio was shown. In both active CD and active extensive UC, the frequency of elevated intestinal permeability was significantly greater than values in both inactive forms. The permeability ratio was normal in 4 of 5 patients with active left-sided colitis. In 5 of 7 patients (3 CD, 4 UC), repeat permeability values entered the reference range after acute phase therapy. Two patients with persistently elevated intestinal permeability (1 CD, 1 UC) had a disease flare-up within 6 months. CONCLUSIONS: Intestinal permeability is a marker of disease activity in CD and extensive UC. Serial permeability test may be useful in monitoring disease activity.

Adolescent↗
PubMed1999

[Pregnancy outcome in inflammatory bowel diseases].

OBJECTIVE: To assess pregnancy outcome in relation to disease activity and maintenance therapy in patients with inflammatory bowel disease. METHODS: A postal questionnaire was sent to every woman of child-bearing age followed for inflammatory bowel disease in three referral centers (Rothschild, Saint-Lazare, Saint-Louis). Response rate was 65%. RESULTS: One hundred and forty-four pregnancies (153 fetuses) in 138 women (122 had Crohn's disease) were reported. Outcome of pregnancy was normal (baby > 2500 g, without malformation) in 115 cases (77%). There were 17 cases of preterm birth (11.5%), 3 cases of hypotrophy, and 14 pregnancy losses (9 miscarriages (6%), 4 therapeutic abortions for major malformation (2.8%)). Percentages of normal pregnancy outcome were not different between patients who continued maintenance therapy and those who stopped: respective percentages were 75 vs 73% in patients receiving mesalamine or olsalazine (n = 30), and 60 vs 75% in patients receiving azathioprine (n = 22). CONCLUSION: In a selected series of women with inflammatory bowel disease, pregnancy outcome is approaching that observed in a normal population, except for an elevated rate of preterm births. There is no need to stop maintenance therapy with 5-aminosalicylates or azathioprine during pregnancy.

Aminosalicylic Acids↗
PubMed2004

Review article: patients' fears and unmet needs in inflammatory bowel disease.

The management of chronic illness is becoming increasingly patient-centred. Although patients with inflammatory bowel disease have a normal life expectancy, most individuals experience an impact of inflammatory bowel disease on their daily lives as well as on their attitudes, fears and beliefs. Although currently available therapies for ulcerative colitis and Crohn's disease are becoming increasingly effective, there are still many unmet needs to address in this patient population. Physicians and patients' spouses or significant others underestimate the type and severity of problems reported by inflammatory bowel disease patients. Physical problems are frequently measured using disease activity indices. Emotional and social problems are reported using quality of life questionnaires and other specific measurement tools pertinent to the question of interest. Studies have indicated a poorer physical and emotional function in inflammatory bowel disease patients than in the general population. Effective therapies, both medical and surgical, produce significant improvements in the general and disease-specific quality of life. The quality of life is worse when the disease is more severe. Concomitant anxiety or depression appears to impair the quality of life even further. Common fears include the possibility of unanticipated flares, the need for surgery, poor energy levels and the side-effects of medication. Recent studies have suggested that more prominent patient participation in management has the potential for greater patient satisfaction, better outcomes and more efficient health resource utilization. Thus, future studies should focus not only on ensuring the wider availability of effective therapies, but on increasing access to health care that is tailored to individuals--more structure for some and more independence and self-management for others, with health provider supervision.

Anxiety↗
PubMed1998

Nitric oxide and inflammatory bowel disease: evidence for local intestinal production in children with active colonic disease.

BACKGROUND: Active colitis in patients with inflammatory bowel disease is associated with mucosal vasodilation, increased intestinal permeability and abnormal colonic motility. Nitric oxide is a messenger molecule with many functions, including regulation of local blood flow, vasomotor tone, and inflammation. Increased nitric oxide production and inducible nitric oxide synthase activity have been demonstrated in experimental models of colitis. This study was designed to determine the relationship between nitric oxide production and colonic inflammation in children with active colitis and in control subjects and whether expression of inducible nitric oxide synthase protein is demonstrable in the intestinal epithelium of these patients. METHODS: Nitrate + nitrite were measured in urine, stool, and plasma using the Griess assay. Expression of inducible nitric oxide synthase protein in intestinal tissue was determined by immunohistochemical localization. RESULTS: Urinary nitrate + nitrite levels were not significantly different in patients and control subjects. In contrast, stool and plasma nitrate + nitrite concentrations were significantly higher in children with inflammatory bowel disease compared with levels in control children (stool: 162.4 +/- 31.0 mumol/l versus 77.2 +/- 22.1 mumol/l; plasma: 65.2 +/- 9.9 mumol/l versus 38.1 +/- 6.6 mumol/L; p < 0.05). Stool nitrate + nitrite levels significantly correlated with plasma values. Immunohistochemical staining of colonic tissue from children with inflammatory bowel disease demonstrated inducible nitric oxide synthase protein located exclusively in epithelial cells. CONCLUSION: Increased nitric oxide production and enhanced intestinal epithelial cell expression of inducible nitric oxide synthase protein are associated with active colonic inflammation.

Adolescent↗
PubMedDate not supplied

Systemic levels of free 5-aminosalicylic acid depend on the nature of the 5-aminosalicyclic acid derivative and not on disease activity or extent in patients with inflammatory bowel disease.

INTRODUCTION: Several new derivatives of sulphasalazine that make use of its active moiety, 5-aminosalicylic acid (5-ASA), have been introduced for the treatment of inflammatory bowel disease (IBD). In rats short term intravenous administration of 5-ASA has been associated with nephrotoxicity. A number of cases of nephrotoxicity have been reported recently in IBD patients taking oral maintenance treatment with 5-ASA compounds. OBJECTIVE: To study the urinary and serum levels of acetylated 5-ASA (Ac-5-ASA) and the unacetylated 5-ASA (5-ASA) in patients with IBD maintained on sulphasalazine, olsalazine and mesalazine (pH dependent release form). We also sought correlation between levels of 5-ASA, clinical disease activity and extent of disease. METHODS: We studied 79 patients (male, n = 30; female, n = 49) with established IBD [ulcerative colitis (UC), n = 48; Crohn's disease (CD), n = 31], 72 maintained on 5-ASA compounds (sulphasalazine = 27; olsalazine = 28; mesalazine = 17) and 7 patients were receiving no medication. Urinary and serum analysis of 5-ASA was performed by high performance liquid chromatography (HPLC). Clinical disease activity was quantified using simple index of Harvey and Bradshaw. RESULTS: Patients receiving mesalazine had significantly higher levels of serum free 5-ASA compared to those who were receiving olsalazine and sulphasalazine (mesalazine mean +/- SEM; range; 2.84 +/- 1.21 (0.00-16.00) vs olsalazine 0.45 +/- 0.18 (0.00-16.20); mumol/L; p < 0.04; sulphasalazine 0.37 +/- 0.25 (0.00-3.74); p < 0.03). Similarly levels of urinary free 5-ASA were significantly higher in patients maintained on mesalazine compared to those on olsalazine or sulphasalazine (mesalazine 219 +/- 80.43 (0.00-1050) vs olsalazine 33.3 +/- 17.23 (0.00-317) mumol/L; p < 0.01; and sulphasalazine 15 +/- 8.86 (0.00-192); p < 0.05). However, no significant difference was observed in the levels of urinary free 5-ASA between olsalazine and sulphasalazine. No significant difference was observed in the levels of free-5-ASA in UC patients with left sided disease and those with extensive disease. Furthermore, no significant difference was observed in the levels of serum and urinary 5-ASA in CD patients with ileo-colic disease and colonic disease. Urinary and serum free-5-ASA did not correlate with the clinical disease activity. CONCLUSION: Systemic absorption of 5-ASA from sulphasalazine and olsalazine is relatively low. However, pH-dependent mesalazine formulations may release their contents rapidly in the small intestine and proximal colon resulting in higher plasma and urinary concentrations of free 5-ASA. The effects of free 5-ASA on renal function in the human require further evaluation.

Adolescent↗
PubMed1999

Stress and mind-body impact on the course of inflammatory bowel diseases.

At present, the medical management of inflammatory bowel diseases (IBD) including Crohn's disease and ulcerative colitis, are focused on topical, locally active antiinflammatories and systemic immunosuppressives, which are thought to exert their targeted effects in the gastrointestinal mucosa. There is a paucity of controlled trials assessing the impact of mind, central nervous system (CNS), and neuromodulation on the overly active immune response in the intestinal mucosa. Patients and their physicians have long been aware of a strong association between attitude, stress, and flares of their IBD. Although reports to date remain mostly anecdotal, the degree to which mind-body influences and stress impact levels of local inflammation deserves closer attention with the aim of identifying contributing mechanisms, which may highlight new therapeutic interventions, as well as assist in identifying particular subsets of patients that may respond to novel forms of adjunctive treatments for IBD, including hypnosis, meditation, neuropeptide receptor modulation, and cortisol-releasing factor (CRF) modulation.

Adult↗
PubMed2005

Review article: monitoring of immunomodulators in inflammatory bowel disease.

The armamentarium of medications for the treatment of inflammatory bowel disease is growing and becoming more complicated to use. Immunomodulators are a class of medications that have found a niche for the treatment of Crohn's disease and ulcerative colitis. Because of the mounting supporting evidence for efficacy, the most commonly-used immunomodulators are azathioprine, mercaptopurine, methotrexate and ciclosporin. These medications are being used more often due to their steroid-sparing and potentially surgery-sparing effects. Immunomodulators are also known for a significant side-effect profile and require careful monitoring. This review provides the latest information for clinicians on efficacy, side-effects, dosing and monitoring of these medications for treatment of inflammatory bowel disease.

Azathioprine↗
PubMed2004

Comparison of serological markers of inflammatory bowel disease with clinical diagnosis in children.

BACKGROUND: Our purpose was to study the concordance of serological tests for inflammatory bowel disease with clinical diagnosis established by traditional testing in children. METHODS: All children seen in our division who had IBD Diagnostic System (ie, pANCA, ASCA IgA, and ASCA IgG) performed over a 21-month period (June 1998 to February 2000) were identified. Their medical records were reviewed for basic demographics, test results (endoscopy, histology, and radiology), IBD Diagnostic System results, and patient symptoms/medications. Results of the IBD Diagnostic System were compared with several patient characteristics including age, sex, absence/presence of symptoms, medication use, disease activity and duration. RESULTS: One hundred seven patients were divided into 6 groups based on clinical diagnosis and IBD Diagnostic System results. The sensitivity, specificity and +/- predictive values of the IBD Diagnostic System for ulcerative colitis were 69.2, 95.1, 90.0, and 87.1%, respectively, and for Crohn's disease were 54.1, 96.8, 90.9, and 80.8%, respectively. Overall, the results of the IBD Diagnostic System were concordant with the clinical diagnosis in 76 of the 107 (71%) patients. CONCLUSIONS: In our experience, the specificity of IBD Diagnostic System is better than the sensitivity; the sensitivity is better for ulcerative colitis than Crohn's disease (69.2% vs 54.1%). The low sensitivity, especially for Crohn's disease, precludes the possibility that the IBD Diagnostic System can replace traditional studies when evaluating for inflammatory bowel disease. Though we do not exclude inflammatory bowel disease solely by IBD Diagnostic System results, it is reassuring to note that all patients without clinical evidence of inflammatory bowel disease also had negative IBD Diagnostic System results.

Adolescent↗
PubMed2001

Intestinal fibrosis in human and experimental inflammatory bowel disease.

Fibrosis is a serious complication of Crohn disease for which there is no effective therapy. It is unclear why fibrosis, particularly fibrosis of the mucosal layer, develops in Crohn disease and not in ulcerative colitis. Smooth muscle cells, subepithelial myofibroblasts, and fibroblasts have traditionally been considered mediators of fibrosis, but new information points to a role of interstitial cells of Cajal and mast cells. Recent evidence about the role of each of these cell types in fibrosis in Crohn disease or other inflammatory bowel diseases is described. Hypothetical models to describe how altered function of these cells could underlie fibrosis of the mucosa or submucosal layers are presented. Fibrosis is not well characterized in any animal model of inflammatory bowel disease. The merits of several animal models for defining the mechanisms of inflammation-induced intestinal fibrosis are reviewed.

Journal Article↗
PubMedDate not supplied

The Crohn's Disease Activity Index, its derivatives and the Inflammatory Bowel Disease Questionnaire: a review of instruments to assess Crohn's disease.

The Crohn's Disease Activity Index (CDAI) has been used to measure Crohn's activity for over a quarter of a century. The development of the CDAI is reviewed and its reliability and validity are examined. Instruments used to assess Crohn's disease that were developed subsequent to the CDAI, including the Harvey-Bradshaw Index, the Cape Town Index and a three-variable version of the CDAI (modified for survey research), are similarly reviewed. The most recent instrument to assess Crohn's disease, the Inflammatory Bowel Disease Questionnaire, which assesses patients in the domains of bowel, systemic, emotional and social function, is also discussed.

Colitis, Ulcerative↗
PubMed2003

Inflammatory bowel disease in pregnancy.

Women and men with inflammatory bowel disease (IBD) frequently express concerns about fertility and pregnancy. The evidence suggests that women with IBD can expect to have a normal pregnancy outcome provided they have inactive disease. They have an increased risk of having a small or premature baby but the majority will have a normal outcome of pregnancy. The commonly used drugs appear to be safe and well tolerated in pregnancy. There remains a need for further studies in this area to help in the difficult decisions about the management of IBD around the time of conception and during pregnancy.

Aminosalicylic Acids↗
PubMed1997

Fertility and pregnancy in inflammatory bowel disease.

OBJECTIVE: A retrospective study of women with inflammatory bowel disease, aged 16-45 years during the 20-year period 1967-1986, was carried out in North East Scotland. METHOD: Five-hundred and three women were identified: 15 patients had died from unrelated causes and 22 had emigrated, but 409 of the remaining 466 patients (88%) replied to the study questionnaire. RESULTS: Women with ulcerative colitis and Crohn's disease had normal fertility when compared with the general population of north east Scotland. However, unresolved infertility problems were more frequent in women who had undergone surgery for inflammatory bowel disease compared with those who had not (12% vs. 5% for Crohn's disease; 25% vs. 7% for ulcerative colitis). Disease relapse rates did not increase in pregnancy. CONCLUSIONS: Overall, at conception women with active disease were as likely to have a normal full-term pregnancy as those in remission. However, spontaneous abortion occurred in five (36%) pregnancies of women who had undergone previous surgery for Crohn's disease and had evidence of recurrent disease. Three of these pregnancies were associated with active disease.

Abortion, Spontaneous↗
PubMed2001

Quality of health care in inflammatory bowel disease: development of a reliable questionnaire (QUOTE-IBD) and first results.

OBJECTIVES: As inflammatory bowel disease is a chronic disorder, usually with an early onset in life, quality of care plays an important role for patients. The aim of this study was to develop a questionnaire to measure quality of care through the eyes of patients with inflammatory bowel disease. METHODS: Ten generic questions were already available because the questionnaire is based on an existing instrument. Patients with inflammatory bowel disease in seven countries were involved in the development of additional disease-specific items. Validation and first field testing of the total questionnaire (QUOTE-IBD) was performed in The Netherlands. RESULTS: A total of 380 patients cooperated in the development of 13 disease-specific items, with high internal reliability (Cronbach's alpha = 0.83). Another 162 patients were involved in validating and testing of the QUOTE-IBD, which consists of 23 items in total. Pearson's correlation coefficient between QUOTE-IBD and visual analog scale scores of health care items was 0.55. Intraclass correlation coefficient of two assessments was 0.64. First testing showed that patients gave relatively poor marks to some part of health care services, such as providing information about extraintestinal complaints and the psychological as well as physical approach to complaints. CONCLUSIONS: A short, valid, reliable questionnaire was developed to measure the opinions of patients with inflammatory bowel disease on quality of health care. The QUOTE-IBD can be used for identification of areas for improvement, with the aim of optimizing health care in inflammatory bowel disease.

Europe↗
PubMed2006

Lack of association between IBD5 and Crohn's disease in Japanese patients demonstrates population-specific differences in inflammatory bowel disease.

OBJECTIVE: Population-specific differences in the genetic susceptibility to inflammatory bowel disease (IBD) are indicated by the fact that Crohn's disease (CD) in Japanese patients does not have any of the common CARD15 variants that are associated with CD in Caucasians. Recently, the disease-causing mutation in the IBD5 haplotype was identified. The TC haplotype, composed of L503F in SLC22A4 and -207G/C in SLC22A5 promoters, was reported to alter the function of the organic cation transporter and to be associated with CD in Caucasians. To determine whether the TC haplotype is also associated with IBD in a Japanese population, we genotyped L503F and -207G/C variants in Japanese subjects. Furthermore, we also performed a case-control association study with all representative single nucleotide polymorphisms (SNPs) in IBD5 using previous information of linkage disequilibrium extension reported in Japanese patients to determine whether there were variants in IBD5 specifically associated with IBD in Japanese patients. MATERIAL AND METHODS: A total of 758 Japanese individuals, 241 patients with CD, 247 patients with ulcerative colitis (UC) and 270 healthy controls, were analyzed in this study. Genotyping for SNPs was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: We found L503F and -207G/C to be very rare (<1% frequency) in CD, UC and HC in the Japanese population. Furthermore, we also found that none of the representative SNPs in IBD5 was associated with CD or UC in the Japanese subjects. CONCLUSIONS: In contrast to Caucasians, IBD5 is not a major component of the susceptibility to IBD in the Japanese population.

Adult↗
PubMed2004

Quantification of disease activity in patients undergoing leucocyte scintigraphy for suspected inflammatory bowel disease.

PURPOSE: Whole-body gamma camera counting is an alternative to faecal 111In collection for quantifying disease activity in inflammatory bowel disease (IBD) but requires administration of imaging activities of 111In. The aim of this study was to explore a dedicated whole-body counter which requires 20-fold less activity than gamma camera counting. METHODS: Thirty patients with known or suspected IBD received 99mTc-granulocytes (approximately 200 MBq) and 111In-granulocytes (approximately 0.5 MBq). The 99mTc-cells were injected 45 min after the 111In-cells and immediately after a baseline 111In whole-body count. The decay-corrected count at 120 h was expressed as a fraction of baseline to give whole-body 111In retention (WBR). One patient was excluded as the injected cells were non-viable. RESULTS: Median 45-min intravascular 111In recovery was 35% in patients compared with 43% in six normal volunteers (p<0.05). WBR in normals ranged from 91% to 93% and in 11 patients with negative 99mTc imaging from 87% to 96%. Only one of 11 patients with negative imaging had WBR <90% while 11/12 patients with WBR <90% had abnormal imaging. Ten of 13 patients with Crohn's disease (CD) had abnormal imaging. The lowest WBR in these ten was 77% and six had values of >90%. There was a significant association between WBR and 99mTc image grade (Rs=0.73, p<0.002) in 16 patients without CD, but not in 13 patients with CD (Rs=0.54, p>0.05). CONCLUSION: Dedicated whole-body counting is able to quantify disease activity in IBD but may give normal values in active CD.

Adult↗