Deficiency for mannan-binding lectin is associated with antibodies to Saccharomyces cerevisiae in patients with Crohn's disease and their relatives.
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Biomedical subjects
Publications and source records attributed to F Seibold.
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Infliximab is a monoclonal chimeric antibody, with high affinity and specificity for tumour necrosis factor alpha (TNFalpha) that plays a central role in the pathogenesis of immune mediated inflammatory disorders including Crohn's disease and ulcerative colitis. Globally over 600000 patients have been treated with infliximab to date. This global experience led to a better definition of the overall safety and efficacy profile of this medication. The goal of the present recommendations is to provide practical information to physicians involved in the care of patients with inflammatory bowel disease.
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Cutaneous or metastatic Crohn's disease is a rare complication of Crohn's disease and is frequently refractory to medical treatment. A case of metastatic Crohn's disease affecting first the abdominal wall and subsequently both submammary folds is reported. These extraintestinal manifestations occurred many years after proctocolectomy. The activity of cutaneous disease was associated with a chronic active fistulizing disease. Skin manifestations were resistant to treatment with steroids, antibiotics and azathioprine. Repetitive treatment with infliximab led to significant improvement of both cutaneous and fistulous disease. However, disease relapsed and even progressed after a period of 6 weeks following each infliximab treatment. Only the introduction of methotrexate, together with repetitive administration of infliximab, allowed maintenance of the patient in remission.
The assessment of disease activity in inflammatory bowel disease is done using clinical parameters and various biological disease markers. Classical disease markers including erythrocyte sedimentation rate, acute phase proteins, such as orosomucoid and CRP, leukocyte and platelet counts, play an important role in the monitoring of disease activity. Furthermore, the determination of zinc, iron, ferritin, vitamin B12, and folic acid is important to avoid deficiencies in patients with severe disease or after surgeries. Stool cultures are helpful to detect bacterial or parasitic infections mimicking inflammatory bowel disease. The detection of specific antibodies such as pANCA, PAB and ASCA is helpful for the differential diagnosis Crohn's disease--ulcerative colitis.
The first-line therapy for inflammatory bowel disease flares is typically medical in nature. Glucocorticoids are a mainstay for the treatment of severe inflammatory bowel disease. Aminosalicylates are efficacious in the treatment of active mild- to- moderate disease. Infliximab, a chimeric monoclonal anti-TNF alpha antibody can be used in refractory Crohn's disease. The recurrence rate after surgery or medical therapy is high. Therefore the introduction of a maintenance therapy is important in patients with repetitive flares. In patients with ulcerative colitis aminosalicylates are useful as maintenance therapy. In severe ulcerative colitis or in Crohn's disease immune suppressive strategies such as a therapy with azathioprine, 6-mercaptopurine or methotrexate should be considered. In Crohn's patients with fistula surgical treatment or a therapy with antibiotics, immunosuppressants or infliximab is recommended.
BACKGROUND: A widespread increase in the use of complementary alternative medicine (CAM) by patients with inflammatory bowel disease (IBD) has been recognized. The aim of our study was to evaluate both the extent and the determinants of CAM use by outpatients with IBD. METHODS: Outpatients of the IBD centre at the University Hospital of Berne and patients of two gastroenterology private practices in Olten (Switzerland) completed a mailed self-administrated questionnaire regarding alternative medicine. The questionnaire addressed the following topics: demographic variables; disease-related data; the use of 16 types of complementary medicine; comparison between attitudes towards alternative versus conventional medicine and out-of pocket expenses. RESULTS: Alternative medicine has been used by 47% of the patients. Diagnosis, duration and activity of disease, gender, age, previous surgery were not predictive for the use of CAM. The most commonly used CAM methods were: homeopathy, acupuncture and traditional Chinese medicine. Reasons cited for the use of CAM were: lack of satisfaction with and side effects of conventional therapy and the perceived safety of CAM. Sixty-one percent of patients noted that their IBD had improved with the use of CAM. By contrast, 16% noted a flare during CAM therapies. Forty-seven percent of patients paid more than Euro400 per year for CAM. CONCLUSIONS: Complementary medicine use is common in patients with IBD. Frequently cited reasons for the use of complementary therapies were safety of CAM; dissatisfaction with conventional therapies, including their side effects; and that CAM can be used in addition to conventional therapy.
BACKGROUND: Immune reactivity towards the bacterial intestinal flora plays an important part in the pathogenesis of inflammatory bowel disease. Disease activity can be positively influenced by the administration of living probiotic bacteria. We investigated the effect of soluble bacterial antigens extracted from Escherichia coli (strain Laves) on the disease activity of murine colitis. METHODS: C3H.IL-10-/- and BALB/c mice with dextran sulphate sodium-induced colitis were treated with either a bacterial lysate from E. coli or with a placebo. Mice were monitored and inflammation was assessed by histological scoring, analysis of fecal IL-1beta and measurement of cytokine production by ELISA. T cell proliferation was quantified by 3H-thymidine incorporation. RESULTS: Clinically and histologically, bacterial-lysate-treated mice revealed significantly (P < 0.05) fewer signs of colitis than placebo-treated mice. Fecal IL-1beta and mucosal TNF-alpha and IFN-gamma concentrations were significantly lower (P < 0.05) in verum-treated mice than in the placebo group. Furthermore, lymphocyte proliferation after stimulation with lipopolysaccharide or caecal bacterial antigen was significantly (P < 0.05) reduced in verum-treated mice. CONCLUSION: The use of E. coli lysate is effective in the amelioration of murine colitis. This effect may be due to a decreased Th1 reaction and to an induction of tolerance against bacterial antigens.
Dysphagia is a rare manifestation in a patient with Crohn's disease. We report on the case of a patient with long-standing Crohn's disease who developed progressive dysphagia over 3 years. Endoscopy showed minimal distal oesophagitis with non-specific histological findings. Further investigation with cinematography, barium swallow and manometry established an achalasia-like motility disorder. Biopsies obtained from the oesophagus were non-specific. Balloon dilatation was performed. Initial success was followed by recurrent dysphagia. At repeat endoscopy, an oesophageal fistula was detected. An attempt at conservative medical management failed and oesophagectomy was successfully performed. Pathology results of the resected specimen confirmed the suspected diagnosis of oesophageal Crohn's disease. Even if achalasia is suspected in a Crohn's patient, it should be taken into consideration that the motility disorder could be the result of a transmural inflammation with or without fibrosis caused by Crohn's disease.
The introduction of novel anti-tumor necrosis factor (TNF) agents has not only led to impressive new therapeutic opportunities but also resulted in uncertainty regarding their optimal use and possible side effects. Guidelines are presented here for the use of anti-TNF agents in gastrointestinal disorders. Experts were chosen from different European countries by an algorithm to avoid bias. An expert consensus on guidelines was established using a two-stage procedure of systematic Medline and abstract search for evidence and a qualifying meeting to derive recommendations. Detailed guidelines were developed for the use and the future clinical development of anti-TNF agents in inflammatory bowel disease. Grading of available evidence and grading of recommendations were performed according to AHCPR guidelines. At present infliximab is the only registered agent for Crohn's disease. Infliximab should be always used at a dose of 5 mg/kg. The guidelines define the indications both in refractory and in fistulating disease for the readministration and before surgery. Guidelines for safety and for concomitant treatments are given. Prospects, potential clinical use, and future directions for the clinical development of other anti-TNF agents are detailed. Clinical use of anti-TNF agents will be influenced by a large number of clinical trials being concluded in 2001 and 2002. It is likely that anti-TNF therapies will become an important long-term therapy for a proportion of patients with Crohn's disease. Biological agents will be followed by smaller and more stable, orally available compounds. These guidelines will be succeeded by a formal public consensus in 2002/2003.
BACKGROUND: Antibodies to Saccharomyces cerevisiae (ASCA) have been described as specific markers for Crohn disease (CD). The reason for this disease specific generation of antibodies is not clear. Therefore, a family study was performed to evaluate whether the antibody production was due to genetic or environmental factors. METHODS: Seventy-one patients with CD, 25 patients with ulcerative colitis (UC), their 282 first-degree relatives, and 32 spouses were included. As controls, 43 sera from healthy persons and 69 sera from patients with various autoimmune disorders were tested for ASCA by indirect immunofluorescence and ELISA. RESULTS: ASCA were detected in 68% of the patients with CD and in none of the controls, UC patients included. Forty-eight (25%) first-degree relatives of patients with CD were ASCA-positive. ASCA status of relatives was not related to the fact whether these persons lived in the same household with the patients or not. However, one of the spouses of CD patients (4%) was found to be ASCA-positive and the antibody was also found in 5 (6%) of the relatives of UC patients. CONCLUSIONS: ASCA are specific markers for CD. Since these antibodies are found in 25% of first-degree relatives, the generation of ASCA may be mainly related to genetic influences although environmental factors may also play a certain role.
BACKGROUND: The sensitivity of assays for antineutrophil cytoplasmic antibody (ANCA), anti-Saccharomyces cerevisiae antibody (ASCA), and antipancreatic antibody (PAB) in different laboratories is unknown. Likewise, the sensitivity and diagnostic usefulness of these assays in patients with inflammatory bowel disease (IBD) in the community is unknown. METHODS: An incidence cohort of 290 patients with IBD were offered participation in the study. Blood was obtained from 162 patients (56%) (83 with ulcerative colitis, 79 with Crohn's disease) who agreed to participate. ANCA was determined in five laboratories. ASCA in two laboratories, and PAB in one laboratory. RESULTS: In ulcerative colitis, the sensitivity of ANCA determined in five laboratories varied widely, ranging from 0-63%. In Crohn's disease, the sensitivity of ASCA determined in two laboratories did not vary significantly, ranging from 39-44%; and the sensitivity of PAB determined in one laboratory was 15%. The optimal diagnostic usefulness was obtained from one laboratory where the positive predictive values of a positive ANCA assay combined with a negative ASCA assay for ulcerative colitis, and a negative ANCA combined with a positive ASCA for Crohn's disease, were 75% and 86%, respectively. CONCLUSIONS: In patients with IBD, the sensitivity of ANCA varied widely in different laboratories, whereas the prevalence of ASCA was similar. The positive predictive values of the ANCA assay combined with the ASCA assay for ulcerative colitis and Crohn's disease are high enough to be clinically useful.
In recent years it has been possible to establish animal models with colitis by immunological and genetic manipulation. Such animal models share characteristic features with human inflammatory bowel disease. The fact that different immune defects induce inflammation in the intestines supports the theory of heterogeneity in the pathogenesis of human inflammatory bowel disease. Discrepant results concerning the disease association with genetic markers have been obtained in different populations, which may confirm the concept of heterogeneity. So far it has not been possible to identify one single factor which is aetiologically responsible for the development of inflammatory bowel disease. The intestinal inflammation is normally T cell-dependent and caused by a dysbalance of pro- and anti-inflammatory immune responses. Interestingly, animals kept under germfree conditions do not develop disease. Thus, the intestinal bacterial flora plays a crucial role. The loss of immune tolerance towards these bacterial antigens is an important current concept in the pathogenesis of inflammatory bowel disease.
The medical treatment of inflammatory bowel disease is dependent on disease activity and bowel involvement. Severe Crohn's disease and ulcerative colitis are primarily treated with corticosteroids. Alternatively, if inflammation is localised in the right colon and ileum, budesonide may be used in view of its low systemic side effects. In distal colitis and perianal disease, topical therapy with steroids is very effective. In moderate disease preparations containing 5-aminosalicylate (5-ASA) may be used. The latter are highly effective applied locally in distal disease. Steroids should be tapered down and whenever possible not used to maintain remission. In patients with ulcerative colitis, 5-ASA is effective in maintaining remission, whereas this medication plays only a limited role in Crohn's disease. Refractory disease or patients with multiple flare-ups should be treated with azathioprine. Infliximab, an anti-TNF-alpha antibody, is a potent therapy for fistulising Crohn's disease or steroid-refractory disease. Other approved and experimental treatments are discussed.
The indication for preoperative ERCP is about to be changed after the introduction of MRCP. There are however advantages of ERCP especially if the option of a therapeutic procedure, e.g., extraction of stones or placing of stents is considered. Besides ERCP prior laparoscopic cholecystectomy which is discussed elsewhere in this journal, indications for preoperative ERCP consist in patients after concussion trauma and hyperamylasemia as long as CT or MRI are not able to show pancreatic duct rupture. In this context the possibility of a stent placement is a major advantage of ERCP, since surgery may be avoided by this procedure. Preoperative ERCP may be performed in patients with chronic pancreatitis and refractory pain with the option of endoscopic therapy in cases with limited findings (less than 3 stones located in the pancreatic head). Furthermore, ERCP plays an important role in the preoperative differentiation between cystic neoplasms and pancreatic pseudocysts. Pseudocysts may be cured by endoscopical placement of transpapillary, transgastric or transduodenal stents. But so far no prospective studies have compared surgical with endoscopical drainage of pseudocysts. Finally, ERCP in the primary diagnosis of pancreatic carcinoma plays only a limited role and should be performed only if non-invasive methods are not able to clarify the situation.
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In recent years, open cholecystectomy has increasingly been replaced by laparoscopic cholecystectomy, and the latter is now regarded as the standard procedure. As a result of this development, the modalities of conservative treatment of gallstones have lost importance overall, although they may still be of use in the individual case. The following modalities are described, and the indications for their use discussed: litholysis with the aid of bile acids, contact litholysis with ether, ESWL.
BACKGROUND & AIMS: The expression of the lymphocyte homing receptor and activation marker L-selectin is different in colon and small intestinal intraepithelial lymphocytes (IELs). In this study, the mechanism of this difference in L-selectin expression was investigated. METHODS: L-selectin expression on lymphocytes was measured by flow cytometry. L-selectin messenger RNA (mRNA) was detected by reverse-transcription polymerase chain reaction. L-Selectin expression on peripheral lymphocytes was analyzed after incubation with cytokines, food and bacterial antigens, and homogenates of small and large bowel. RESULTS: L-selectin was expressed by none of the small intestinal IELs but by 30% of those in the colon and by 60% of splenocytes. mRNA for L-selectin was detectable in isolated lymphocytes of all three sites. L-Selectin was down-regulated in colon IELs during colitis and up-regulated in small intestinal IELs after in vitro culture for 48 hours. Incubation of splenocytes with small intestinal homogenates led to a rapid down-regulation of L-selectin (1% vs. 60% untreated). Preincubation with a metalloproteinase inhibitor prevented L-selectin loss. CONCLUSIONS: The mechanism of the differential expression of L-selectin in mouse small intestine and colon appears to be an increased functional activity of a metalloproteinase (sheddase) in the small intestine compared with the colon.