| 1. |
- Halfvarson, Jonas, 1970-, et al.
(författare)
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Inflammatory bowel disease in a Swedish twin cohort : a long-term follow-up of concordance and clinical characteristics
- 2003
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Ingår i: Gastroenterology. - 0016-5085 .- 1528-0012. ; 124:7, s. 1767-1773
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims:In 1988, we reported the first twin study in inflammatory bowel disease. The aim of the current study was to follow up these twins regarding new cases of inflammatory bowel disease and Crohn’s disease characteristics using the Vienna classification.Methods:The official Swedish population register and the cause of death register were used to search for the twins. All living patients were interviewed.Results:Three monozygotic twins earlier classified as healthy had been diagnosed with inflammatory bowel disease (ulcerative colitis, n = 2; Crohn’s disease, n = 1). Retrospectively, all 3 were symptomatic at the original survey. This changed the pair concordance in monozygotic twins from 6.3% to 18.8% in ulcerative colitis and from 44.4% to 50.0% in Crohn’s disease. A high degree of concordance regarding age at diagnosis, disease location at diagnosis and during the course, and disease behavior was found in concordant monozygotic twin pairs with Crohn’s disease. Seven of 9 pairs were identical in 3 or more of these disease characteristics compared with an expected number of 1.5 (P = 0.000076).Conclusions:This study confirms that the genetic influence is stronger in Crohn’s disease than in ulcerative colitis. A remarkable phenotype similarity within concordant pairs with Crohn’s disease was found using the Vienna classification.
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| 2. |
- Lind, Tore, et al.
(författare)
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The MACH2 study : Role of omeprazole in eradication of Helicobacter pylori with 1-week triple therapies
- 1999
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Ingår i: Gastroenterology. - 0016-5085 .- 1528-0012. ; 116:2, s. 248-253
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: The role of omeprazole in triple therapy and the impact of Helicobacter pylori resistance on treatment outcome are not established. This study investigated the role of omeprazole and influence of primary H. pylori resistance on eradication and development of secondary resistance.Methods: Patients (n = 539) with a history of duodenal ulcer and a positive H. pylori screening test result were randomized into 4 groups. OAC group received 20 mg omeprazole, 1000 mg amoxicillin, and 500 mg clarithromycin; OMC group received 20 mg omeprazole, 400 mg metronidazole, and 250 mg clarithromycin; and AC (amoxicillin, 1000 mg, and clarithromycin, 500 mg) and MC (metronidazole, 400 mg, and clarithromycin, 250 mg) groups received no omeprazole. All doses were administered twice daily for 1 week. H. pylori status was assessed before and after therapy by 13C-urea breath test. Susceptibility testing was performed at entry and in patients with persistent infection after therapy.Results: Eradication (intention to treat [n = 514]/per protocol [n = 449]) was 94%/95% for OAC, 26%/25% for AC (P < 0.001), 87%/91% for OMC, and 69%/72% for MC (P < 0.001). Primary resistance was 27% for metronidazole, 3% for clarithromycin, and 0% for amoxicillin. Eradication in primary metronidazole-susceptible/-resistant strains was 95%/76% for OMC and 86%/43% for MC. Secondary metronidazole and clarithromycin resistance each developed in 12 patients: 8 treated with omeprazole and 16 without omeprazole.Conclusions: Addition of omeprazole achieves high eradication rates, reduces the impact of primary resistance, and may decrease the risk of secondary resistance compared with regimens containing only two antibiotics.
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| 4. |
- Söderholm, Johan D, 1958-, et al.
(författare)
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Epithelial permeability to proteins in the noninflamed ileum of Crohn's disease?
- 1999
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Ingår i: Gastroenterology. - 0016-5085 .- 1528-0012. ; 117:1, s. 65-72
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Crohn's disease (CD) is associated with a disturbed intestinal barrier. Permeability studies have focused on inert molecules, but little is known about transepithelial transport of macromolecules with antigenic potential in humans. The aim of this study was to quantify permeation and to characterize passage routes for macromolecules in ileal mucosa in CD.Methods: Noninflamed and inflamed ileal mucosa specimens from patients with CD (n = 12) and ileal specimens from patients with colon cancer (n = 7) were studied regarding transmucosal permeation of ovalbumin, dextran (mol wt, 40,000), and 51Cr-EDTA for 90 minutes in vitro in Ussing chambers. Transepithelial passage routes for fluorescent ovalbumin and dextran 40,000 were investigated by confocal microscopy.Results: Noninflamed ileum from CD patients showed increased permeation of ovalbumin compared with ileum from colon cancer patients (P < 0.05). Dextran permeation was equal in the three groups, whereas 51Cr-EDTA permeability was increased in inflamed ileum. Ovalbumin passed both transcellularly and paracellularly, but dextran followed a strictly paracellular route. Both markers were subsequently endocytosed by cells of the lamina propria.Conclusions: Noninflamed ileal mucosa from patients with CD shows increased epithelial permeability to ovalbumin, probably by augmented transcytosis. This increase in antigen load to the lamina propria could be an initiating pathogenic event in CD.
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| 5. |
- Bonfiglio, F., et al.
(författare)
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Female-Specific Association Between Variants on Chromosome 9 and Self-Reported Diagnosis of Irritable Bowel Syndrome
- 2018
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 155:1, s. 168-179
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Genetic factors are believed to affect risk for irritable bowel syndrome (IBS), but there have been no sufficiently powered and adequately sized studies. To identify DNA variants associated with IBS risk, we performed a genome-wide association study (GWAS) of the large UK Biobank population-based cohort, which includes genotype and health data from 500,000 participants. METHODS: We studied 7,287,191 high-quality single nucleotide polymorphisms in individuals who self-reported a doctor's diagnosis of IBS (cases; n = 9576) compared to the remainder of the cohort (controls; n = 336,499) (mean age of study subjects, 40-69 years). Genome-wide significant findings were further investigated in 2045 patients with IBS from tertiary centers and 7955 population controls from Europe and the United States, and a small general population sample from Sweden (n = 249). Functional annotation of GWAS results was carried out by integrating data from multiple biorepositories to obtain biological insights from the observed associations. RESULTS: We identified a genome-wide significant association on chromosome 9q31.2 (single nucleotide polymorphism rs10512344; P = 3.57 x 10(-8)) in a region previously linked to age at menarche, and 13 additional loci of suggestive significance (P < 5.0 x 10(-6)). Sex-stratified analyses revealed that the variants at 9q31.2 affect risk of IBS in women only (P = 4.29 x 10(-10) in UK Biobank) and also associate with constipation-predominant IBS in women (P = .015 in the tertiary cohort) and harder stools in women (P = .0012 in the population-based sample). Functional annotation of the 9q31.2 locus identified 8 candidate genes, including the elongator complex protein 1 gene (ELP1 or IKB-KAP), which is mutated in patients with familial dysautonomia. CONCLUSIONS: In a sufficiently powered GWAS of IBS, we associated variants at the locus 9q31.2 with risk of IBS in women. This observation may provide additional rationale for investigating the role of sex hormones and autonomic dysfunction in IBS.
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| 7. |
- Andersson, Roland, et al.
(författare)
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Appendectomy is followed by increased risk of Crohn's disease
- 2003
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 124:1, s. 40-46
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Appendectomy is associated with a low risk of subsequent ulcerative colitis. This study analyzes the risk of Crohn's disease after appendectomy. Methods: We followed-up 212,218 patients with appendectomy before age 50 years and a cohort of matched controls, identified from the Swedish Inpatient Register and the nationwide Census, for any subsequent diagnosis of Crohn's disease. Results: An increased risk of Crohn's disease was found for more than 20 years after appendectomy, with incidence rate ratio 2.11 (95% confidence interval [CI], 1.21-3.79) after perforated appendicitis, 1.85 (95% CI, 1.10-3.18) after nonspecific abdominal pain, 2.15 (95% CI, 1.25-3.80) after mesenteric lymphadenitis, 2.52 (95% CI, 1.43-4.63) after other diagnoses. After nonperforated appendicitis, there was an increased risk among women but not among men (incidence rate ratio 1.37, 95% CI, 1.03-1.85, respectively, 0.89, 95% CI, 0.64-1.24). Patients operated on before age 10 years had a low risk (incidence rate ratio 0.48, 95% CI, 0.23-0.97). Crohn's disease patients with a history of perforated appendicitis had a worse prognosis. Conclusions: Appendectomy is associated with an increased risk of Crohn's disease that is dependent on the patient's sex, age, and the diagnosis at operation. The pattern of associations suggests a biologic cause.
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| 9. |
- Bednarska, Olga, et al.
(författare)
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Vasoactive Intestinal Polypeptide and Mast Cells Regulate Increased Passage of Colonic Bacteria in Patients With Irritable Bowel Syndrome
- 2017
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Ingår i: Gastroenterology. - : W B SAUNDERS CO-ELSEVIER INC. - 0016-5085 .- 1528-0012. ; 153:4, s. 948-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND amp; AIMS: Irritable bowel syndrome (IBS) is associated with intestinal dysbiosis and symptoms of IBS develop following gastroenteritis. We aimed to study the passage of live bacteria through the colonic epithelium, and determine the role of mast cells (MCs) and vasoactive intestinal polypeptide (VIP) in barrier regulation in IBS and healthy individuals. METHODS: Colon biopsies from 32 women with IBS and 15 age-matched healthy women (controls) were mounted in Ussing chambers; we measured numbers of fluorescently labeled Escherichia coli HS and Salmonella typhimurium that passed through from the mucosal side to the serosal side of the tissue. Some biopsies were exposed to agents that block the VIP receptors (VPAC1 and VPAC2) or MCs. Levels of VIP and tryptase were measured in plasma and biopsy lysates. Number of MCs and MCs that express VIP or VIP receptors were quantified by immunofluorescence. Biopsies from an additional 5 patients with IBS and 4 controls were mounted in chambers and Salmonella were added; we studied passage routes through the epithelium by transmission electron microscopy and expression of tight junctions by confocal microscopy. RESULTS: In colon biopsies from patients with IBS, larger numbers of E coli HS and S typhimurium passed through the epithelium than in biopsies from controls (P amp;lt;.0005). In transmission electron microscopy analyses, bacteria were found to cross the epithelium via only the transcellular route. Bacterial passage was reduced in biopsies from patients with IBS and controls after addition of antibodies against VPACs or ketotifen, which inhibits MCs. Plasma samples from patients with IBS had higher levels of VIP than plasma samples from controls. Biopsies from patients with IBS had higher levels of tryptase, larger numbers of MCs, and a higher percentage of MCs that express VPAC1 than biopsies from controls. In biopsies from patients with IBS, addition of Salmonella significantly reduced levels of occludin; subsequent addition of ketotifen significantly reversed this effect. CONCLUSIONS: We found that colonic epithelium tissues from patients with IBS have increased translocation of commensal and pathogenic live bacteria compared with controls. The mechanisms of increased translocation include MCs and VIP.
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