| 1. |
- 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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| 2. |
- Westfelt, Petter, et al.
(författare)
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Training nonanesthetist administration of propofol for gastrointestinal endoscopy in scenario-based full-scale hybrid simulation - a pilot study
- 2013
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa Healthcare. - 0036-5521 .- 1502-7708. ; 48:11, s. 1354-1358
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The use of nonanesthetist-administered propofol (NAAP) in GI endoscopy has long been controversial. In the setting of NAAP, acute situations can develop during endoscopy and thus training before starting with NAAPs is considered crucial. The aim was to evaluate a pilot study on crew resource management (CRM)-based training of teams of endoscopists and endoscopy nurses in NAAP in a full-scale hybrid simulation consisting of a full-scale human patient simulator and an endoscopy simulator. Our hypothesis was that the training would increase the self-efficacy of the participants. Material and methods. Four scenarios were created, each with typical side effects of propofol administration. All scenarios included the need for prompt decision-making and treatment. Colonoscopy, gastroscopy or endoscopic retrograde cholangiopancreatography (ERCP) cases were assigned to the course participants in coherence with their main clinical expertise in order to facilitate situated and contextualized training. Twenty-one participants (ten doctors and eleven nurses) completed a questionnaire on self-efficacy before and after the course. A questionnaire regarding the quality and yield of the course was also completed. Results. For all participants, the self-efficacy score was 26.0 (24.0-28.0; interquartile range) before training and 30.0 (27.0-30.5) after training (p = 0.0003). The ten doctors had a self-efficacy score before training of 26.5 (25.0-29.5) and 30.0 (29.0-33.0) after (p = 0.0078). The eleven nurses scored 24.0 (22.0-26.0) before and 28.0 (27.0-30.0) after training (p = 0.0098). Conclusions. Systematic target focused scenario-based training with hybrid simulation of NAAP in endoscopy resulted in increased self-efficacy in both nurses and physicians.
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| 3. |
- Witte, Anne-Barbara, et al.
(författare)
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Involvement of endogenous glucagon-like peptide-1 in regulation of gastric motility and pancreatic endocrine secretion
- 2011
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 46:4, s. 428-435
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To study the role of endogenous glucagon-like peptide-1 (GLP-1) on gastric emptying rates of a solid meal as well as postprandial hormone secretion and glucose disposal. Material and methods. In nine healthy subjects, gastric emptying of a 310-kcal radio-labelled solid meal and plasma concentrations of insulin, glucagon and glucose were measured during infusion of saline or the GLP-1 receptor antagonist exendin(9-39)amide (Ex(9-39)) at 300 pmol·kg−1·min−1. Results. Ex(9-39) infusion had no effect on the total gastric emptying curve, but changed the intra-gastric distribution of the meal. During infusion of Ex(9-39), more content stayed in the upper stomach (79.1 ± 2.5% of total during Ex(9-39) compared to 66.6 ± 5.7% during saline at 5 min). During Ex(9-39) infusion, higher concentrations of plasma glucagon were measured both before (after 40 min of Ex(9-39) infusion the glucagon level was 15.1 ± 0.7 pmol·L−1 compared to 5.4 ± 1.4 during saline) and after the meal, and postprandial GLP-1 levels increased. Basal insulin and glucose levels were not affected by Ex(9-39), but the postprandial rise of insulin and glucose enhanced during Ex(9-39). Conclusions. Endogenous GLP-1 is involved in the regulation of gastric motility in relation to meal intake and also in the regulation of postprandial insulin and glucose levels. Furthermore, endogenous GLP-1 seems to tonically restrain glucagon secretion.
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