| 1. |
- Karling, Pontus, et al.
(författare)
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Function and dysfunction of the colon and anorectum in adults: working team report of the Swedish Motility Group (SMoG).
- 2009
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Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 44:6, s. 646-60
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Forskningsöversikt (refereegranskat)abstract
- Symptoms of fecal incontinence and constipation are common in the general population. These can, however, be unreliably reported and are poorly discriminatory for underlying pathophysiology. Furthermore, both symptoms may coexist. In the elderly, fecal impaction always must be excluded. For patients with constipation, colon transit studies, anorectal manometry and defecography may help to identify patients with slow-transit constipation and/or pelvic floor dysfunction. The best documented medical treatments for constipation are the macrogols, lactulose and isphagula. Evolving drugs include lubiprostone, which enhances colonic secretion by activating chloride channels. Surgery is restricted for a highly selected group of patients with severe slow-transit constipation and for those with large rectoceles that demonstrably cause rectal evacuatory impairment. For patients with fecal incontinence that does not resolve on antidiarrheal treatment, functional and structural evaluation with anorectal manometry and endoanal ultrasound or magnetic resonance (MR) of the anal canal may help to guide management. Sacral nerve stimulation is a rapidly evolving alternative when other treatments such as biofeedback and direct sphincter repair have failed. Advances in understanding the pathophysiology as a guide to treatment of patients with constipation and fecal incontinence is a continuing important goal for translational research. The content of this article is a summary of presentations given by the authors at the Fourth Meeting of the Swedish Motility Group, held in Gothenburg in April 2007.
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| 4. |
- Münch, Andreas, et al.
(författare)
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Low-dose budesonide for maintenance of clinical remission in collagenous colitis : a randomised, placebo-controlled, 12-month trial
- 2016
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Ingår i: Gut. - : BMJ Publishing Group. - 0017-5749 .- 1468-3288. ; 65:1, s. 47-56
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis.Design: A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase.Results: Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), p<0.001). Health-related quality of life was maintained during the 12-month double-blind phase in budesonide-treated patients. During treatment-free follow-up, 82.1% (23/28 patients) formerly receiving budesonide relapsed after study drug discontinuation. Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all non-serious.Conclusions: Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation.
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| 5. |
- Jansson-Rehnberg, Ann-Sofie, et al.
(författare)
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Diarrhoea of unknown cause: medical treatment in a stepwise manner Management of Idiopathic Diarrhoea Based on Experience of Step-Up Medical Treatment
- 2024
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Ingår i: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY. - : TAYLOR & FRANCIS LTD. - 0036-5521 .- 1502-7708. ; 59:5, s. 543-546
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Forskningsöversikt (refereegranskat)abstract
- The basic principle for the treatment of idiopathic diarrhoea (functional diarrhoea K59.1) is to delay transit through the gut in order to promote the absorption of electrolytes and water. Under mild conditions, bulking agents may suffice. With increasing severity, antidiarrhoeal pharmaceuticals may be added in a stepwise manner. In diarrhoea of unknown aetiology, peripherally-acting opioid receptor agonists, such as loperamide, are first-line treatment and forms the pharmaceutical basis of antidiarrheal treatment. As second-line treatment opium drops have an approved indication for severe diarrhoea when other treatment options fail. Beyond this, various treatment options are built on experience with more advanced treatments using clonidine, octreotide, as well as GLP-1 and GLP-2 analogs which require specialist knowledge the field.
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| 6. |
- Beyder, Arthur, et al.
(författare)
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Loss-of-Function of the Voltage-Gated Sodium Channel Na(V)1.5 (Channelopathies) in Patients With Irritable Bowel Syndrome
- 2014
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 146:7, s. 1659-1668
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: SCN5A encodes the a-subunit of the voltage-gated sodium channel Na(V)1.5. Many patients with cardiac arrhythmias caused by mutations in SCN5A also have symptoms of irritable bowel syndrome (IBS). We investigated whether patients with IBS have SCN5A variants that affect the function of Na(V)1.5. METHODS: We performed genotype analysis of SCN5A in 584 persons with IBS and 1380 without IBS (controls). Mutant forms of SCN5A were expressed in human embryonic kidney-293 cells, and functions were assessed by voltage clamp analysis. A genome-wide association study was analyzed for an association signal for the SCN5A gene, and replicated in 1745 patients in 4 independent cohorts of IBS patients and controls. RESULTS: Missense mutations were found in SCN5A in 13 of 584 patients (2.2%, probands). Diarrhea-predominant IBS was the most prevalent form of IBS in the overall study population (25%). However, a greater percentage of individuals with SCN5A mutations had constipation-predominant IBS (31%) than diarrhea-predominant IBS (10%; P < .05). Electrophysiologic analysis showed that 10 of 13 detected mutations disrupted Na(V)1.5 function (9 loss-of-function and 1 gain-of-function function). The p. A997T-Na(V)1.5 had the greatest effect in reducing Na(V)1.5 function. Incubation of cells that expressed this variant with mexiletine restored their sodium current and administration of mexiletine to 1 carrier of this mutation (who had constipation-predominant IBS) normalized their bowel habits. In the genome-wide association study and 4 replicated studies, the SCN5A locus was strongly associated with IBS. CONCLUSIONS: About 2% of patients with IBS carry mutations in SCN5A. Most of these are loss-of-function mutations that disrupt Na(V)1.5 channel function. These findings provide a new pathogenic mechanism for IBS and possible treatment options.
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| 7. |
- Wouters, Mira M., et al.
(författare)
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Genetic variants in CDC42 and NXPH1 as susceptibility factors for constipation and diarrhoea predominant irritable bowel syndrome
- 2014
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 63:7, s. 1103-1111
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The complex genetic aetiology underlying irritable bowel syndrome (IBS) needs to be assessed in large-scale genetic studies. Two independent IBS cohorts were genotyped to assess whether genetic variability in immune, neuronal and barrier integrity genes is associated with IBS.Design: 384 single nucleotide polymorphisms (SNPs) covering 270 genes were genotyped in an exploratory cohort (935 IBS patients, 639 controls). 33 SNPs with P-uncorrected<0.05 were validated in an independent set of 497 patients and 887 controls. Genotype distributions of single SNPs were assessed using an additive genetic model in IBS and clinical subtypes, IBS-C and IBS-D, both in individual and combined cohorts. Trait anxiety (N=614 patients, 533 controls), lifetime depression (N=654 patients, 533 controls) and mRNA expression in rectal biopsies (N=22 patients, 29 controls) were correlated with SNP genotypes.Results: Two SNPs associated independently in the exploratory and validation cohort: rs17837965-CDC42 with IBS-C (ORexploratory=1.59 (1.05 to 1.76); ORvalidation=1.76 (1.03 to 3.01)) and rs2349775-NXPH1 with IBS-D (ORexploratory=1.28 (1.06 to 1.56); ORvalidation=1.42 (1.08 to 1.88)). When combining both cohorts, the association of rs2349775 withstood post hoc correction for multiple testing in the IBS-D subgroup. Additionally, three SNPs in immune-related genes (rs1464510-LPP, rs1881457-IL13, rs2104286-IL2RA), one SNP in a neuronal gene (rs2349775-NXPH1) and two SNPs in epithelial genes (rs245051-SLC26A2, rs17837965-CDC42) were weakly associated with total-IBS (P-uncorrected<0.05). At the functional level, rs1881457 increased IL13 mRNA levels, whereas anxiety and depression scores did not correlate with rs2349775-NXPH1.Conclusions: Rs2349775 (NXPH1) and rs17837965 (CDC42) were associated with IBS-D and IBS-C, respectively, in two independent cohorts. Further studies are warranted to validate our findings and to determine the mechanisms underlying IBS pathophysiology.
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| 8. |
- Diaz, Hetzel, et al.
(författare)
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Motilitetskapsel förenklar gastrointestinal undersökning
- 2016
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Ingår i: Läkartidningen. - : Läkartidningen Förlag. - 0023-7205 .- 1652-7518. ; 113
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Forskningsöversikt (refereegranskat)abstract
- The wireless motility-recording capsule, "SmartPill", is an ingested one-time use electronic capsule that measures gastrointestinal luminal pressure, pH and temperature along the whole gastrointestinal tract. The pH profile and the pressure patterns define the time at which the capsule moves from the stomach to the duodenum and from the ileum to the caecum, whereas changes in temperature define the times of ingestion and expulsion. The recordings from the wireless motility capsule are sent from a radio transmitter in the capsule to a receiver carried around the waist. Wireless motility recordings have several advantages over imaging and manometry that have been used previously. Primarily the simplicity by which motility recordings are done, as well as the tolerability for the patient and limited need of assistance are valuable aspects. The wireless motility capsule provides standardized measures of transit with relevant normal values for the clinical work-up of patients with motility disturbances.
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| 9. |
- Dlugosz, Aldona, et al.
(författare)
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Chlamydia trachomatis antigens in enteroendocrine cells and macrophages of the small bowel in patients with severe irritable bowel syndrome
- 2010
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Ingår i: BMC Gastroenterology. - 1471-230X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inflammation and immune activation have repeatedly been suggested as pathogentic factors in irritable bowel syndrome (IBS). The driving force for immune activation in IBS remains unknown. The aim of our study was to find out if the obligate intracellular pathogen Chlamydia could be involved in the pathogenesis of IBS. Methods: We studied 65 patients (61 females) with IBS and 42 (29 females) healthy controls in which IBS had been excluded. Full thickness biopsies from the jejunum and mucosa biopsies from the duodenum and the jejunum were stained with a monoclonal antibody to Chlamydia lipopolysaccharide (LPS) and species-specific monoclonal antibodies to C. trachomatis and C. pneumoniae. We used polyclonal antibodies to chromogranin A, CD68, CD11c, and CD117 to identify enteroendocrine cells, macrophages, dendritic, and mast cells, respectively. Results: Chlamydia LPS was present in 89% of patients with IBS, but in only 14% of healthy controls (p < 0.001) and 79% of LPS-positive biopsies were also positive for C. trachomatis major outer membrane protein (MOMP). Staining for C. pneumoniae was negative in both patients and controls. Chlamydia LPS was detected in enteroendocrine cells of the mucosa in 90% of positive biopsies and in subepithelial macrophages in 69% of biopsies. Biopsies taken at different time points in 19 patients revealed persistence of Chlamydia LPS up to 11 years. The odds ratio for the association of Chlamydia LPS with presence of IBS (43.1; 95% CI: 13.2-140.7) is much higher than any previously described pathogenetic marker in IBS. Conclusions: We found C. trachomatis antigens in enteroendocrine cells and macrophages in the small bowel mucosa of patients with IBS. Further studies are required to clarify if the presence of such antigens has a role in the pathogenesis of IBS.
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| 10. |
- Dlugosz, Aldona, et al.
(författare)
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No difference in small bowel microbiota between patients with irritable bowel syndrome and healthy controls
- 2015
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have indicated that colonic microbiota may exhibit important differences between patients with irritable bowel syndrome (IBS) and healthy controls. Less is known about the microbiota of the small bowel. We used massive parallel sequencing to explore the composition of small bowel mucosa-associated microbiota in patients with IBS and healthy controls. We analysed capsule biopsies from the jejunum of 35 patients (26 females) with IBS aged 18-(36)-57 years and 16 healthy volunteers (11 females) aged 20-(32)-48 years. Sequences were analysed based on taxonomic classification. The phyla with the highest total abundance across all samples were: Firmicutes (43%), Proteobacteria (23%), Bacteroidetes (15%), Actinobacteria (9.3%) and Fusobacteria (7.0%). The most abundant genera were: Streptococcus (19%), Veillonella (13%), Prevotella (12%), Rothia (6.4%), Haemophilus (5.7%), Actinobacillus (5.5%), Escherichia (4.6%) and Fusobacterium (4.3%). We found no difference among major phyla or genera between patients with IBS and controls. We identified a cluster of samples in the small bowel microbiota dominated by Prevotella, which may represent a common enterotype of the upper small intestine. The remaining samples formed a gradient, dominated by Streptococcus at one end and Escherichia at the other.
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