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Vaali K.,University of Bergen | Lappalainen J.,Wihuri Research Institute | Lin A.H.,University of Bergen | Mayranpaa M.I.,Wihuri Research Institute | And 4 more authors.
Neurogastroenterology and Motility | Year: 2012

Background When sensitized epicutaneously and challenged orally with ovalbumin, Balb/c mice develop allergen-induced diarrhea. As mast cells play important roles in diarrhea, we studied whether allergic diarrhea could be alleviated with imatinib mesylate. Methods Balb/c mice were sensitized and challenged with ovalbumin and treated orally with imatinib. Cytokine mRNA expressions were determined with quantitative RT-PCR and numbers of small intestinal mast cells determined by staining for chloroacetate esterase and mucosal mast cell protease-1. Immunofluorescence staining was used to assess the intestinal CCL1 expression. Key Results Ovalbumin-sensitized and challenged Balb/c mice developed diarrhea, which was associated with increased number of mast cells and expression of interleukin (IL)-4 and -13, and chemokines CCL1 and CCL17 in the small intestine. Treatment with imatinib reduced the incidence of diarrhea, inhibited the development of mastocytosis and jejunal mRNA expression of IL-13, CCL1, CCL17 and CCL22. Mast cell-deficient W/W-V mice, and surprisingly, also their mast cell-competent control (+/+) littermates failed to develop diarrhea as a response to ovalbumin. This strain-dependent difference was associated with the inability of +/+ and W/W-V mice to increase the number of intestinal mast cells and expression of IL-4, IL-13, CCL1 and CCL17 after ovalbumin challenge. Conclusions & Inferences Development of allergic diarrhea is associated with the ability of mice to develop intestinal mastocytosis. Imatinib inhibited the development of intestinal mastocytosis, reduced the incidence of diarrhea, and reduced the expression of IL-13, CCL1, and CCL17. Targeting intestinal mast cells could be a feasible approach to treat allergic diarrhea. © 2012 Blackwell Publishing Ltd. Source

Kristensen V.,Unger Vetlesens Institute | Kristensen V.,University of Oslo | Lauritzen T.,Vestre Viken Hospital Trust | Jelsness-Jorgensen L.-P.,Ostfold Hospital Trust | And 5 more authors.
Clinical Chemistry and Laboratory Medicine | Year: 2016

Faecal (f-) calprotectin is a widely used marker for intestinal inflammation. However, extraction procedure is time consuming and cumbersome. The main aim of this study was to evaluate patient-performed extraction of f-calprotectin compared to extraction performed in the laboratory. Methods: A total of 81 adult patients with an established diagnosis of inflammatory bowel disease provided two samples from the same bowel movement, one conventional faeces sample and one sample with a patient administered extraction device. A laboratory technician extracted the conventional faeces sample with the same extraction device. Results: F-calprotectin results from the laboratory-performed extraction and the patient-performed extraction correlated significantly, with a Spearman rank correlation coefficient of 0.92. Method comparison showed a slope of 1.20 (95% confidence interval 1.08-1.36) with intercept of-0.30 (95% confidence interval-9.00 to 4.62). This demonstrates a small proportional difference between the results from the home extracted samples and the results from the laboratory extracted samples, where the home extracted samples are slightly higher. However, six of the 81 patients had made obvious mistakes in the extraction process and their samples were excluded from the study. Conclusions: Patient administered extraction of f-calprotectin can be a realistic alternative for selected patients. However, instructions must be very precise to avoid mistakes. © 2016 by De Gruyter. Source

Vara E.J.,University of Bergen | Valeur J.,Unger Vetlesens Institute | Hausken T.,University of Bergen | Hausken T.,National Center for Functional Gastrointestinal Disorders | And 2 more authors.
Scandinavian Journal of Gastroenterology | Year: 2016

Objective We have previously found that high levels of total IgE, but not atopic sensitization, was a significant predictor for functional gastrointestinal (GI) symptoms. In this study, we aimed to assess the prevalence of extra-intestinal symptoms in IBS patients, and explore their relation to total IgE levels and atopic sensitization. Materials and methods Seventy-one patients with functional GI complaints were included. Severity of GI symptoms, fatigue and musculoskeletal pain was evaluated using the following questionnaires: IBS-Severity Scoring System (IBS-SSS), Fatigue Impact Scale (FIS), FibroFatigue Scale (FFS), and Visual Analog Scales (VAS) for musculoskeletal pain. Levels of total IgE and specific IgE-antibodies were analyzed. Results Fatigue and musculoskeletal pain were demonstrated in 78.9 and 43.7% of the patients, respectively. IBS-SSS scores were significantly correlated with fatigue scores and musculoskeletal pain. Patients with fatigue and musculoskeletal pain had significantly higher IBS-SSS scores than patients without fatigue and musculoskeletal pain. Total IgE levels were significantly higher in IBS patients compared to a healthy control group from a previous study. However, neither total IgE nor atopic sensitization was significantly associated with extra-intestinal symptoms. Conclusions IBS, fatigue, and musculoskeletal pain were significantly associated. Total IgE levels were higher in IBS patients than healthy controls, but not related to intestinal or extra-intestinal symptom severity. Atopy was not associated with any of the co-morbidities. Thus, the clinical significance of high IgE levels in IBS remains unclear and further studies are warranted to explore a common underlying mechanism for the co-morbid triad of IBS, fatigue, and musculoskeletal pain. © 2016 Informa UK Limited, trading as Taylor & Francis Group. Source

Levine A.,Tel Aviv University | Turner D.,Pediatric Gastroenterology Unit | Turner D.,Hebrew University of Jerusalem | Gik T.P.,Tel Aviv University | And 14 more authors.
Inflammatory Bowel Diseases | Year: 2014

Background: Robust evaluation of induction therapies using both clinical and inflammatory outcomes in pediatric Crohn's disease (CD) are sparse. We attempted to evaluate clinical, inflammatory, and composite outcomes of induction of remission therapies (normal C reactive protein [CRP] remission) in a large pediatric prospective multicenter study. Methods: Patients enrolled at diagnosis into the growth relapse and outcomes with therapy in Crohn's disease study were evaluated for disease activity, CRP, and fecal calprotectin at 8, 12 and 52 weeks after starting treatment. The primary endpoint was week-12 steroid-free remission defined by pediatric Crohn's disease activity index and CRP <0.5 mg/dL. The protocol required tapering off corticosteroids by week 11. Results: We analyzed 222 patients (mean age, 12.9±3.2 yr) main evaluated treatment options included: 5-ASA (n = 29), exclusive enteral nutrition (n = 43), and corticosteroids (n = 114). Clinical remission at week 12 was achieved in 155 (73%) patients; both exclusive enteral nutrition and steroids were associated with normal CRP remission at week 12, although in a post hoc subgroup analysis exclusive enteral nutrition was superior in mild-tomoderate disease for this outcome. Among those in steroid-free remission in week 12, normal CRP predicted 1-year sustained remission (86% for normal CRP versus 61% for elevated CRP; P = 0.02). Baseline severity and early immunomodulation were similar in both groups. Conclusions: Normal CRP steroid-free remission at week 12 was impacted by type of induction therapy, but not by early immunomodulation. It was associated with more corticosteroids-free remission at week 52 and a trend for less relapses. Copyright © 2013 Crohn's & Colitis Foundation of America, Inc. Source

Kristensen V.,Unger Vetlesens Institute | Kristensen V.,University of Oslo | Lauritzen T.,Vestre Viken Hospital Trust | Jelsness-Jorgensen L.-P.,Ostfold Hospital Trust | And 2 more authors.
Scandinavian Journal of Clinical and Laboratory Investigation | Year: 2015

Objective: Faecal (f-) calprotectin is a widely used surrogate marker of intestinal inflammation. F-calprotectin analysis is labour demanding partly due to a time consuming extraction step. The aim of this project was to validate a new extraction method for f-calprotectin. Material and methods: A prospective multicentre study included 135 patients with an established diagnosis of inflammatory bowel disease. The patients submitted a faeces sample, which was extracted with both the conventional method at the participating laboratory and the new extraction device. The extracts were analyzed by an automated ELISA instrument. Results: Method comparison of the traditional method and the new device showed a slope of 1.01 (0.93-1.07) with intercept of - 2.2 (- 4.9-0.6). The Spearman rank correlation coefficient was 0.96. Conclusions: The new extraction device is a reliable and time saving alternative to the conventional extraction method. © 2015 Informa Healthcare. Source

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