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PubMed1999

Lipid treatment of inflammatory bowel disease.

The aetiology of inflammatory bowel disease remains unclear. Local mediators such as arachidonic acid metabolites and peptide mediators (cytokines) appear to contribute to the disease process. The successful administration of neutralizing antibodies against TNF-alpha has confirmed a pathophysiological role for this cytokine in Crohn's disease. Established therapy of inflammatory bowel disease with 5-aminosalicylic acid compounds has been shown to reduce local leukotriene B4 formation by inhibiting lipoxygenases. This therapeutic mechanism formed one rationale for examining the effect of n-3 fatty acids, which also inhibit leukotriene B4 formation, on the course of these diseases. In the first study, published in 1989, we found no beneficial effects of n-3 fatty acids in patients with Crohn's disease; however, there was clinical improvement, just falling short of significance, in patients with ulcerative colitis. Since then two uncontrolled and five controlled studies have further investigated the therapeutic effect of n-3 fatty acids in patients with ulcerative colitis. The size of the patient population in the controlled studies ranged from 10 to 96 patients in the largest study. Two of these studies showed a significant improvement in clinical activity and a steroid-sparing effect, respectively. Another study found only a trend towards improvement and one trial, which also included a treatment group receiving evening primrose oil, found no beneficial effect in the 16 patients receiving n-3 fatty acids. A large, 2 year trial of n-3 fatty acids in patients with ulcerative colitis off steroids, which was recently completed at the Universities of Munich and Mainz, showed a delay of the first episode of relapse, but no reduction in the cumulative relapse rate at 2 years. Controversial results have been published for Crohn's disease. A new enteric-coated formulation reportedly increased the proportion of patients in remission where as another trial using a conventional preparation found no significant effect.

Colitis, Ulcerative↗
PubMed2000

Endothelial cell autoantibodies are a marker of disease susceptibility in inflammatory bowel disease but apparently not linked to persistent measles virus infection.

Intestinal vasculitis caused by persistent measles virus infection of intestinal endothelial cells was described in Crohn's disease. Furthermore, endothelial cell autoantibodies have been demonstrated in inflammatory bowel disease (IBD). Autoantibodies against intestinal endothelial cells were visualized by indirect immunofluorescence in patients with IBD, in their healthy first-degree relatives, in patients with infectious enterocolitis, and in healthy, unrelated controls. In intestinal tissue specimens of 22 antibody-positive IBD patients a search for the measles virus genome was performed. Endothelial cell autoantibodies were significantly more frequent in patients with IBD, in both groups of first-degree relatives, and in patients with infectious enterocolitis than in the healthy controls (P = 0.0002 or less). The measles virus genome was found in none of the intestinal biopsies. Endothelial cell autoantibodies are not a genetic but rather an epigenetic (infectious) marker of disease susceptibility. The expression of these autoantibodies is unlikely to be triggered by a persistent measles virus infection.

Adolescent↗
PubMedDate not supplied

[Genetic polymorphism and treatment of chronic bowel inflammatory diseases: the example of azathioprine].

Azathioprine is an immunosuppressive drug used in the treatment of inflammatory bowel disease. It is a prodrug that is hydrolysed to 6-mercaptopurine, which represents the active form. Azathioprine is also used in the treatment of leukaemia in children and in organ transplantation. Azathioprine treatment is associated with adverse effects such as leukopenia and aplasia. These adverse effects are related to a single nucleotide polymorphism, including the inability of cells to synthesize thiopurine methyltransferase (TPMT). TPMT is a detoxification enzyme that limits 6-thioguanine nucleotide production and thereby interferes with normal DNA and RNA synthesis. This review presents the different approaches used for azathioprine therapeutic monitoring in IBD treatment and discusses the discrepancies in recent clinical trials.

Azathioprine↗
PubMed1978

Ankylosing spondylitis and inflammatory bowel disease. II. Prevalence of peripheral arthritis, sacroiliitis, and ankylosing spondylitis in patients suffering from inflammatory bowel disease.

To establish the prevalence of peripheral arthritis, radiographic sacroiliitis, and ankylosing spondylitis in patients with inflammatory bowel disease, 58 consecutive patients suffering from ulcerative colitis (UC) and 51 with Crohn's disease (CD) underwent a detailed rheumatological examination. In addition, all patients were screened for the presence of the antigen HLA B27. Peripheral arthritis was found in 14 (8 UC, 6 CD) patients (12.8%); radiographic sacroiliitis was diagnosed in 11 (5 UC, 6 CD) (10.1%), of whom 10 were asymptomatic; and ankylosing spondylitis was diagnosed in 2 UC and 2 CD patients (3.7%). 18.9% of the UC and 3.9% of the CD patients were HLA B27 positive. One of the 11 patients with radiographic sacroiliitis and 2 of the 4 with ankylosing spondylitis had the HLA B27 antigen. Peripheral arthritis, radiographic sacroiliitis, and ankylosing spondylitis are apparently frequent manifestations in patients suffering from inflammatory bowel disease. Asymptomatic radiographic sacroiliitis in these patients appears to differ from idiopathic ankylosing spondylitis, both clinically and genetically. Evaluation of subjective rheumatological complaints, necessary for a confident diagnosis of ankylosing spondylitis, according to the New York criteria is difficult during a flare-up of the inflammatory bowel process, as was shown in 4 CD cases with marked limitation of lumbovertebral function and chest expansion, but no radiological abnormalities of the SI joints.

Adult↗
PubMed1997

Validation of the Dutch translation of the Inflammatory Bowel Disease Questionnaire (IBDQ): a health-related quality of life questionnaire in inflammatory bowel disease.

Health-related quality of life assessment can benefit several groups involved with health care. The aim of our study was to assess construct validity, reliability, discriminant ability and sensitivity to change of the Dutch translation of the Inflammatory Bowel Disease Questionnaire (IBDQ), a disease-specific quality-of-life questionnaire. A group of 120 IBD patients completed the IBDQ and two Visual Analogue Scales concerning general well-being and bowel function twice. Fifty-two patients also completed the Short-Form 36 twice. Disease activity was assessed once. Correlations between the IBDQ scores and the global assessments were reasonably high and the IBDQ was shown to be discriminative. High intraclass correlation coefficients between both measurements of the IBDQ were observed in patients who reported no change in bowel complaints. In contrast, significant differences were found between both moments in patients who reported change. The Dutch IBDQ proved to be valid, discriminative and reliable.

Adolescent↗
PubMed1996

Similarities and dissimilarities between asthma and inflammatory bowel diseases.

Because both asthma and inflammatory bowel disease are chronic relapsing inflammatory conditions, comparisons are inevitable. Both disorders reflect the convergence of environmental trigger factors in genetically predisposed individuals. The genetic preposition may be on a polygenic basis or on the basis of genetic heterogeneity. Environmental factors that may trigger the expression or relapse in asthma and inflammatory bowel disease include: cigarette smoking (in Crohn's but not in ulcerative colitis), the use of non-steroidal anti-inflammatory drugs in asthma and Crohn's disease), infection and possibly stress. TH lymphocytes are currently believed to be important in asthma and in Crohn's disease but not in ulcerative colitis. IgE-activated eosinophils and mast cells are central to the maintenance of asthma but do not play such a crucial role in inflammatory bowel disease. TH2 cytokines including IL-4 and IL-5 are believed to be important in the inflammatory response of asthma, and TH cytokines are believed to be in Crohn's disease but a TH1 or TH2 subclassification is not currently evident. The hallmark of asthma is increased reactivity of the airways, in terms of bronchoconstriction. Altered physiology also accompanies inflammatory bowel disease but hyperactivity is not an invariable feature. Finally, it is becoming increasingly evident that neural influences modulate inflammatory processes and this is likely to be relevant to both asthma and inflammatory bowel disease.

Animals↗
PubMed1989

Restriction fragment length polymorphism analysis of T-cell receptor genes in inflammatory bowel disease.

The etiology of inflammatory bowel disease is still unknown, but autoimmune phenomena are thought to play an important role. However, only a weak association between HLA or immunoglobulin allotypes and inflammatory bowel diseases has been noted. Recently, DNA markers (restriction fragment length polymorphism (RFLP) pattern) of T-cell receptor gene allotypes have been reported and shown to be linked to susceptibility to autoimmune disease. We investigated the T-cell receptor RFLP pattern in inflammatory bowel diseases. No linkage to the constant region alpha- and beta-chain markers was observed, and no differences in the frequencies of 'genoallotypes' was found between patients and normal blood donors.

Colitis, Ulcerative↗
PubMed2002

Small therapeutic molecules for the treatment of inflammatory bowel disease.

New therapies for inflammatory bowel disease are needed, because standard therapies fail to induce remission in about 30% of patients, and because of the relative inefficacy of current maintenance therapies. This review summarises the current status of the development of small therapeutic molecules for inflammatory bowel disease.

ADAM Proteins↗
PubMed1996

Induction of NGAL synthesis in epithelial cells of human colorectal neoplasia and inflammatory bowel diseases.

In inflammatory and neoplastic disorders of the colon a defect barrier function of the mucosa may result in absorption of bacterial products from the intestinal lumen. These products may further recruit inflammatory cells and thus augment the inflammatory response. A novel lipocalin in neutrophils, neutrophil gelatinase associated lipocalin (NGAL), with the ability to bind bacterial formylpeptides, has been described and therefore it is of interest to investigate the expression of this protein in diseases of the colon. Expression of NGAL was investigated by immunohistochemistry and by mRNA in situ hybridisation in normal colon and in neoplastic and inflammatory colorectal diseases. A very high expression of NGAL was seen in colonic epithelium in areas of inflammation, both in non-malignant epithelium (diverticulitis, inflammatory bowel disease, and appendicitis) as well as in premalignant and malignant neoplastic lesions of the colon. In adenocarcinoma, the NGAL expression was especially abundant in the transitional mucosa and in the superficial ulcerated area. On the other hand, no NGAL expression could be detected in lymph node metastases from these adenocarcinomas. A weak expression of NGAL in some epithelial cells was only occasionally seen in normal colon. In conclusion, NGAL synthesis is induced in epithelial cells in inflammatory and neoplastic, colorectal diseases. NGAL may serve an important anti-inflammatory function as a scavenger of bacterial products.

Acute-Phase Proteins↗
PubMed2004

Review article: gut flora and inflammatory bowel disease.

The pathogenesis of inflammatory bowel disease involves interactions between the host susceptibility, mucosal immunity and intestinal microflora. There is therefore great interest in the changes in the endogenous flora in inflammatory bowel disease patients and in the establishment of potential genetic variations in host responses to endogenous bacteria. In this review, we summarize the modifications in the various regional ecosystems in the gastrointestinal tract during inflammatory bowel disease (luminal bacteria in faeces or inside the gastrointestinal tract, bacteria in mucus and bacteria directly attached to the mucosa). Results were obtained following a 'candidate microorganism strategy' and, as is occurring increasingly frequently, following a 'full description strategy', which has progressed largely due to the development of culture-independent techniques. The possibility of modifying the ecosystem using prebiotics or probiotics offers hope for new treatment developments, particularly in the prevention of relapse.

Bacteria↗
PubMed1992

Quality of life in inflammatory bowel disease.

Quality of life with inflammatory bowel disease has not been well examined. Recently, a questionnaire to determine subjective health status for patients with inflammatory bowel disease has been developed and verified. To examine the quality of life in a group of "well" outpatients with inflammatory bowel disease, we developed a self-administered form of this questionnaire containing 36 questions identifiable to five dimensions: systemic symptoms, bowel symptoms, functional impairment, social impairment, and emotional function. We identified outpatients with inflammatory bowel disease through the local chapter of the Ileitis and Colitis Foundation and distributed 396 questionnaires, by mail, with 182 being returned completed (46% response rate). Forty-eight age- and sex-matched controls filled out and returned an identical questionnaire. Response options for each question were framed on a seven-point scale in which 7 represented best function and 1 represented worst function. Male-to-female ratio and mean age were similar to those of controls for the inflammatory bowel disease group. In each dimension, as well as globally, the quality of life of patients with inflammatory bowel disease was significantly worse than that for their age- and sex-matched controls. In conclusion, this survey demonstrates that inflammatory bowel disease adversely affects quality of life in a highly motivated group of "well" outpatients when compared to an age- and sex-matched population.

Activities of Daily Living↗
PubMedDate not supplied

Chronic inflammatory bowel disease and the 'over-clean' environment: rarity in the Irish 'traveller' community.

The causes of ulcerative colitis and Crohn's disease are unknown. Current research is focused on genetic factors but environmental factors may also be important. Exposure to infections in early life is believed to reduce the incidence of bronchial asthma. We hypothesised that exposure to enteric bacteria and infections in early life may also reduce the incidence of idiopathic inflammatory bowel disease. Chronic inflammatory bowel disease may be a by-product of our over-clean environment. Social groups with poorer living standards might be expected to have a lower prevalence of this condition. The "traveller" or itinerant community in Ireland is one such group. We therefore attempted to estimate the prevalence of inflammatory bowel disease in the traveller population. Twenty five of 30 gastroenterologists or surgeons in Ireland responded to requests for information. None could recall ever seeing a "traveller" with idiopathic inflammatory bowel disease. While genetic factors cannot be excluded, a low prevalence of idiopathic inflammatory bowel disease would support the environmental hypothesis.

Chronic Disease↗
PubMedDate not supplied

Pulmonary function tests, high-resolution computed tomography findings and inflammatory bowel disease.

AIM: The association between inflammatory bowel disease and pulmonary involvement has not been clearly established. The aim of this prospective study was to define the features of pulmonary function tests and high resolution computed tomography in inflammatory bowel disease patients and the relation between these and disease activity. METHOD: Fifty-two patients with inflammatory bowel disease (20 with Crohn's disease and 32 with ulcerative colitis) were enrolled. The standard pulmonary function tests and thorax high resolution computed tomography findings were investigated with respect to inflammatory bowel disease activity. Crohn's disease activity index and the Rachmilewitz endoscopic activity index for ulcerative colitis were used to assess disease activity. Medications used and smoking status were also documented. RESULTS: Among the patients with ulcerative colitis, 6.25% had an obstructive and/or restrictive ventilatory defect compared with 25% of the patients with Crohn's disease. Fifty percent of the patients with ulcerative colitis and 60% of the patients with Crohn's disease showed abnormal findings in high resolution computed tomography. Pulmonary function tests and high resolution computed tomography abnormalities did not differ significantly between Crohn's disease and ulcerative colitis. No significant difference related to inflammatory bowel disease activity was found (P > 0.05). CONCLUSION: Findings of high resolution computed tomography and the pulmonary function tests did not differ between ulcerative colitis and Crohn's disease. Bowel disease activity did not seem to affect these measurements.

Adult↗
PubMed2002

Probiotics--role in inflammatory bowel disease.

The aetiology of inflammatory bowel disease is still unclean. Whilst a specific pathogen agent associated with these diseases has not been found, the rationale for probiotic therapy in inflammatory bowel disease is based on convincing evidence involving intestinal bacteria in their pathogenesis. Encouraging results have been obtained with probiotic therapy in several animal models of experimental colitis. The administration of highly concentrated probiotic preparations represents a valid approach both for the prevention of pouchitis onset and relapses. The encouraging results obtained in ulcerative colitis and Crohn's disease need to be further assessed in large double-blind trials.

Animals↗
PubMed1986

Intestinal permeability to 99mTc-diethylenetriaminopentaacetic acid in inflammatory bowel disease.

Intestinal permeability in inflammatory bowel disease and its relation to periods of disease activity has been investigated by measuring the urinary excretion of DTPA labeled with 99mTc. Urine excretion in 10 control subjects was 2.7 +/- 1% of the test dose. Twelve patients with ulcerative colitis excreted 5.08 +/- 1.6% in remission, 10.61 +/- 2% during periods of mild activity, 19.41 +/- 0.9% during moderate activity, and 15.41 +/- 6.3% with severe activity. Sixteen patients with Crohn's disease excreted 5.7 +/- 1.9% in remission, 8.47 +/- 2.8% during mild activity of the disease, and 14.29 +/- 5.8% during moderate activity. No differences were observed between ulcerative colitis and Crohn's disease, or between ileal and colonic forms of Crohn's disease. Excretion in remission was significantly greater than in control subjects and there was a correlation between excretion and disease activity. In serial determinations done in seven patients we found that urine excretion of the test substance correlated with disease activity. We also studied DTPA excretion in 10 cases with gastric or duodenal ulcer (2.28 +/- 1.4%), six cases of acute gastroenteritis (4.87 +/- 3.1%) and nine cases with other intestinal diseases (3.6 +/- 1.1%). In all these cases, DTPA excretion was lower than in inflammatory bowel disease. Our results show that the urinary excretion of DTPA is a simple test that measures accurately the degree of activity of inflammatory bowel disease. The test is useful in Crohn's disease as well as in ulcerative colitis, and detects intestinal permeability abnormalities even in clinical remission. Significantly lower excretions are found in other intestinal diseases. The test may be recommended as a screening test for use in clinical practice.

Adolescent↗
PubMed2005

Technology insight: calprotectin, lactoferrin and nitric oxide as novel markers of inflammatory bowel disease.

Distinguishing patients with inflammatory bowel disease from those with irritable bowel syndrome can be difficult. A simple and reliable test that detects intestinal inflammation would therefore be very useful in the clinic. If such a test parameter correlated with the intensity of the inflammatory reaction it could also be used to monitor disease activity. Calprotectin, lactoferrin and nitric oxide are produced and released locally in much greater quantities in the inflamed gut than in the noninflamed gut. These compounds can be readily measured in fecal samples (calprotectin and lactoferrin) or directly in the intestinal lumen (nitric oxide gas). Here, we discuss what is known about these markers, how they could be used in clinical practice and how they can complement existing techniques used for the diagnosis and monitoring of inflammatory bowel disease.

Biomarkers↗
PubMed1998

Use of cytotoxic agents and cyclosporine in the treatment of autoimmune disease. Part 2: Inflammatory bowel disease, systemic vasculitis, and therapeutic toxicity.

When cytotoxic agents were introduced, their ability to disrupt nucleic acid and protein synthesis led to their effective use for the treatment of neoplastic disease. During the course of this use, however, it became apparent that these agents also suppress the immune system. This usually unwelcome effect was subsequently studied and beneficially directed toward the treatment of non-neoplastic diseases in which autoimmune mechanisms were considered important to pathogenesis. As a result of these investigations, cytotoxic agents and, more recently, cyclosporine have emerged to become an important part of the therapeutic regimen for many autoimmune diseases. Nonetheless, these medications may still cause treatment-induced illness or even death. It is therefore particularly important to weigh the benefits and risks of cytotoxic therapy when treating a non-neoplastic disease. This two-part Clinical Staff Conference reviews data on the efficacy and toxicity of cytotoxic drugs and cyclosporine in selected autoimmune diseases. In part 2, we focus on the role of these agents in treating inflammatory bowel disease and systemic vasculitis and review the toxic effects of these agents.

Cyclosporine↗