| 1. |
- Aguilera-Lizarraga, J., et al.
(författare)
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Expression of immune-related genes in rectum and colon descendens of Irritable Bowel Syndrome patients is unrelated to clinical symptoms
- 2019
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 31:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mucosal immune activation has been postulated to play an important role in the pathogenesis of irritable bowel syndrome (IBS). However, data are conflicting and often based on small patient cohorts. Here, we aimed to evaluate the gene expression of a large set of immune-related genes in mucosal biopsies from IBS patients and healthy volunteers (HV). Methods: A total of 171 IBS patients and 127 HV were included in the study. Rectum biopsies were collected from a cohort of 70 HV and 77 IBS patients (Rome III) and colon descendens biopsies from another cohort of 57 HV and 94 IBS patients (Rome II). Gene expression was assessed using OpenArray technology, and validated questionnaires were used to evaluate clinical characteristics (GI symptoms, somatization, anxiety, and depression). Key Results: A subset of IBS patients (33%) with increased immune activation in the colon descendens was identified using multivariate analysis and displayed increased gene expression of IL1B (3-fold change), prostaglandin synthase PTGS2 (2.1-fold change), and the G-protein-coupled receptor MRGPRX2 (10.7-fold change). Clinical characteristics in this subgroup were however similar to the rest of the patient cohort. Analysis of rectal biopsies failed to identify such subgroup of “immuno-active” IBS patients in the other patient cohort. Conclusion: A subset of IBS patients reveals evidence of immune activation in the colon descendens, but not in the rectum; however, gene expression is unrelated to clinical symptoms. To what extent this subgroup might however respond to anti-inflammatory therapy remains to be investigated. © 2019 John Wiley & Sons Ltd
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| 2. |
- Arroyo Vázquez, Jorge Alberto, 1979, et al.
(författare)
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Exploring pyloric dynamics in stenting using a distensibility technique
- 2018
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 30:12
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Tidskriftsartikel (refereegranskat)abstract
- © 2018 John Wiley & Sons Ltd Background: Perforated duodenal ulcers can be treated with a covered stent. Stent migration is a severe complication, sometimes requiring surgery. Pyloric physiology during stent treatment has not been studied and mechanisms for migration are unknown. The aim of this study was to investigate the pyloric response to distention, mimicking stent treatment, using the EndoFLIP. Methods: A nonsurvival study in five pigs was carried out, followed by a pilot study in one volunteer. Animals were gastroscoped during anaesthesia and the EndoFLIP was placed straddling the pylorus. Baseline distensibility readings were performed at stepwise balloon distentions to 20, 30, 40, and 50mL, measuring pyloric cross-sectional area and pressure. Measurements were repeated after administration of a prokinetic drug and after a liquid meal. In the human study, readings were performed in conscious sedation at baseline and after stimulation with metoclopramide. Key Results: During baseline readings, the pylorus was shown to open more with increasing distention together with higher amplitude motility waves. Reaching maximum distention-volume (50mL), pyloric pressure increased significantly (P=0.016), and motility waves disappeared. After prokinetic stimulation, the pressure decreased and the motility waves increased in frequency and amplitude. After food stimulation, the pressure stayed low and the motility showed increase in amplitude. During both tests, the pylorus showed higher pressure and lack of motility waves at maximum probe distention. Conclusions and Inferences: The pylorus seems to act as a sphincter at low distention but when further dilated starts acting as a pump. Fully distended the pyloric motility disappears and the pressure remains high, suggesting that a stent with high-radial force might show less migration.
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| 3. |
- Bashashati, M, et al.
(författare)
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Colonic immune cells in irritable bowel syndrome: A systematic review and meta-analysis.
- 2018
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Ingår i: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 30:1
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Tidskriftsartikel (refereegranskat)abstract
- Increases in mucosal immune cells have frequently been observed in irritable bowel syndrome (IBS) patients. However, this finding is not completely consistent between studies, possibly due to a combination of methodological variability, population differences and small sample sizes. We performed a meta-analysis of case-control studies that compared immune cell counts in colonic biopsies of IBS patients and controls.PubMed and Embase were searched in February 2017. Results were pooled using standardized mean difference (SMD) and were considered significant when zero was not within the 95% confidence interval (CI). Heterogeneity was assessed based on I2 statistics where I2 ≤50% and I2 >50% indicated fixed and random effect models, respectively.Twenty-two studies on 706 IBS patients and 401 controls were included. Mast cells were increased in the rectosigmoid (SMD: 0.38 [95% CI: 0.06-0.71]; P=.02) and descending colon (SMD: 1.69 [95% CI: 0.65-2.73]; P=.001) of IBS patients. Increased mast cells were observed in both constipation (IBS-C) and diarrhea predominant IBS (IBS-D). CD3+ T cells were increased in the rectosigmoid (SMD: 0.53 [95% CI: 0.21-0.85]; P=.001) and the descending colon of the IBS patients (SMD: 0.79, 95% CI [0.28-1.30]; P=.002). This was possibly in relation to higher CD4+ T cells in IBS (SMD: 0.33 [95% CI: 0.01-0.65]; P=.04) as there were no differences in CD8+ T cells.Mast cells and CD3+ T cells are increased in colonic biopsies of patients with IBS vs non-inflamed controls. These changes are segmental and sometimes IBS-subtype dependent. The diagnostic value of the quantification of colonic mucosal cells in IBS requires further investigation.
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| 4. |
- Bennet, Sean, et al.
(författare)
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Systemic cytokines are elevated in a subset of patients with irritable bowel syndrome but largely unrelated to symptom characteristics
- 2018
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 30:10
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSerum levels of pro-inflammatory cytokines tend to be increased in irritable bowel syndrome (IBS) patients, or subgroups thereof. Still, the link between cytokine levels and IBS symptoms is unclear. We aim to determine systemic cytokine levels in IBS patients and healthy subjects (HS), confirm the presence of a subset of patients with an increased immune activity and to establish if cytokines are linked to IBS symptoms and pathophysiological factors. MethodsSerum levels of interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF), and IL-10 were measured. All subjects reported IBS symptoms using validated questionnaires and underwent colonic sensorimotor testing. Multivariate supervised orthogonal partial least squares-discriminant analysis (OPLS-DA) and unsupervised principal component analysis (PCA) and hierarchical cluster analysis (HCA) were implemented. Key ResultsIrritable bowel syndrome patients (n=246) had higher serum levels of IL-1, IL-6, IL-8, TNF, and IL-10 compared to HS (n=21); however, serum cytokine profiles could not discriminate patients from HS. Moreover, cytokine levels were not correlated with symptoms among patients. Supervised OPLS-DA identified 104 patients (40% of patients) and unsupervised HCA analysis identified 49 patients (20%) with an increased immune activity indicated by elevated levels of serum cytokines compared to HS and the other patients. However, irrespective of how patients with increased immune activity were identified they were symptomatically similar to patients with no indication of increased immune activity. Conclusions & InferencesSerum cytokines are elevated in IBS patients compared to HS. Immune activation characterizes a subset of patients, but modest associations between cytokine profile and symptoms suggest immune activity does not directly influence symptoms in IBS.
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| 5. |
- Björkman, Ida, et al.
(författare)
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More similarities than differences between men and women with irritable bowel syndrome
- 2015
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 27:6, s. 796-804
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Tidskriftsartikel (refereegranskat)abstract
- Background: Differences regarding symptoms, coping abilities, and quality of life (QOL) between men and women with irritable bowel syndrome (IBS) have been reported but data are sparse and sometimes conflicting. The aim of present study was to investigate gender differences in gastrointestinal, extra-intestinal, and psychological symptoms, and sense of coherence (SOC) and QOL in a large group of patients diagnosed with IBS. Methods: We analyzed questionnaire data from 557 patients (152 men) diagnosed with IBS consecutively included in studies at an outpatient clinic for functional bowel disorders between 2002 and 2010. Following questionnaires were included: IBS severity scoring system (IBS-SSS), Hospital Anxiety and Depression Scale (HAD), IBSQOL Scale, Visceral Sensitivity Index (VSI), SOC Scale, Bristol Stool Form Scale (BSFS), and Patient Health Questionnaire (PHQ-15). Key Results: Women had harder stools (FDR-adjusted p-value: q = 0.033), more severe bloating (q = 0.020), higher symptom severity (q = 0.042), higher total somatic symptom burden (q = 0.035), lower SOC (q = 0.042), and lower QOL. Women rated more general anxiety (q = 0.017) and gastrointestinal-specific anxiety (q = 0.042), but there were no group differences in depression, pain, stool frequency, impact on daily life, dissatisfaction with bowel habit, or extra-colonic symptoms. The differences found were small (effect sizes: r < 0.3). Conclusions & Inferences: In this study, we demonstrated more similarities than differences between men and women with IBS. The largest difference were seen for QOL which might reflect certain structural stressors to which women in general are more exposed than men. © 2015 John Wiley & Sons Ltd.
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| 6. |
- Boeckxstaens, G. E., et al.
(författare)
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Phenotyping of subjects for large scale studies on patients with IBS
- 2016
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 28:8, s. 1134-1147
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Tidskriftsartikel (refereegranskat)abstract
- Background: Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life-time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity, immunity, epithelial permeability and gastrointestinal microflora. Such complexity means there is currently no specific reliable biomarker for IBS, and thus IBS continues to be diagnosed and classified according to symptom based criteria, the Rome Criteria. Carefully phenotyping and characterisation of a ‘large’ pool of IBS patients across Europe and even the world however, might help identify sub-populations with accuracy and consistency. This will not only aid future research but improve tailoring of treatment and health care of IBS patients. Purpose: The aim of this position paper is to discuss the requirements necessary to standardize the process of selecting and phenotyping IBS patients and how to organise the collection and storage of patient information/samples in such a large multi-centre pan European/global study. We include information on general demographics, gastrointestinal symptom assessment, psychological factors, quality of life, physiological evaluation, genetic/epigenetic and microbiota analysis, biopsy/blood sampling, together with discussion on the organisational, ethical and language issues associated with implementing such a study. The proposed approach and documents selected to be used in such a study was the result of a thoughtful and thorough four-year dialogue amongst experts associated with the European COST action BM1106 GENIEUR (www.GENIEUR.eu). © 2016 John Wiley & Sons Ltd
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| 7. |
- Bonfiglio, F., et al.
(författare)
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A GWAS meta-analysis from 5 population-based cohorts implicates ion channel genes in the pathogenesis of irritable bowel syndrome
- 2018
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Ingår i: Neurogastroenterology and Motility. - : WILEY. - 1350-1925 .- 1365-2982. ; 30:9
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIrritable bowel syndrome (IBS) shows genetic predisposition, however, large-scale, powered gene mapping studies are lacking. We sought to exploit existing genetic (genotype) and epidemiological (questionnaire) data from a series of population-based cohorts for IBS genome-wide association studies (GWAS) and their meta-analysis. MethodsBased on questionnaire data compatible with Rome III Criteria, we identified a total of 1335 IBS cases and 9768 asymptomatic individuals from 5 independent European genotyped cohorts. Individual GWAS were carried out with sex-adjusted logistic regression under an additive model, followed by meta-analysis using the inverse variance method. Functional annotation of significant results was obtained via a computational pipeline exploiting ontology and interaction networks, and tissue-specific and gene set enrichment analyses. Key ResultsSuggestive GWAS signals (P5.0x10(-6)) were detected for 7 genomic regions, harboring 64 gene candidates to affect IBS risk via functional or expression changes. Functional annotation of this gene set convincingly (best FDR-corrected P=3.1x10(-10)) highlighted regulation of ion channel activity as the most plausible pathway affecting IBS risk. Conclusion & InferencesOur results confirm the feasibility of population-based studies for gene-discovery efforts in IBS, identify risk genes and loci to be prioritized in independent follow-ups, and pinpoint ion channels as important players and potential therapeutic targets warranting further investigation.
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| 8. |
- Bonfiglio, F., et al.
(författare)
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A meta-analysis of reflux genome-wide association studies in 6750 Northern Europeans from the general population
- 2017
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 29:2
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundGastroesophageal reflux disease (GERD), the regurgitation of gastric acids often accompanied by heartburn, affects up to 20% of the general population. Genetic predisposition is suspected from twin and family studies but gene-hunting efforts have so far been scarce and no conclusive genome-wide study has been reported. We exploited data available from general population samples, and studied self-reported reflux symptoms in relation to genome-wide single nucleotide polymorphism (SNP) genotypes. MethodsWe performed a GWAS meta-analysis of three independent population-based cohorts from Sweden, Finland, and UK. GERD cases (n=2247) and asymptomatic controls (n=4503) were identified using questionnaire-derived symptom data. Upon stringent quality controls, genotype data for more than 2.5M markers were used for association testing. Bioinformatic characterization of genomic regions associated with GERD included gene-set enrichment analysis (GSEA), in silico prediction of genetic risk effects on gene expression, and computational analysis of drug-induced gene expression signatures using Connectivity Map (cMap). Key resultsWe identified 30 GERD suggestive risk loci (P5x10(-5)), with concordant risk effects in all cohorts, and predicted functional effects on gene expression in relevant tissues. GSEA revealed involvement of GERD risk genes in biological processes associated with the regulation of ion channel and cell adhesion. From cMap analysis, omeprazole had significant effects on GERD risk gene expression, while antituberculosis and anti-inflammatory drugs scored highest among the repurposed compounds. ConclusionsWe report a large-scale genetic study of GERD, and highlight genes and pathways that contribute to further our understanding of its pathogenesis and therapeutic opportunities.
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| 9. |
- Casado Bedmar, Maria Teresa, et al.
(författare)
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Upregulation of intestinal mucosal mast cells expressing VPAC1 in close proximity to vasoactive intestinal polypeptide in inflammatory bowel disease and murine colitis
- 2019
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Ingår i: Neurogastroenterology and Motility. - : Wiley-Blackwell Publishing Inc.. - 1350-1925 .- 1365-2982. ; 31:3
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMast cells (MCs) and vasoactive intestinal polypeptide (VIP) have been proposed as regulators of the intestinal barrier and inflammation. Our aim was to map the distribution in inflammatory bowel disease (IBD) and murine colitis.MethodsMCs, VIP, and VIP‐receptors (VPACs) were quantified by immunofluorescence and enzyme‐immunoassay (EIA) in ileal tissues (villus epithelium (VE) and adjacent VE, ie, VE next to the follicle‐associated epithelium, (FAE)) from Crohn's disease (CD; n = 16) and non‐IBD patients, and in colonic specimens of ulcerative colitis (UC; n = 12) and healthy controls (HCs). In addition, VIP levels were measured in plasma from HCs, non‐IBD, and IBD in remission (CD n = 30; UC n = 30). Colon, ileum, and plasma from mice with dextran sulfate sodium (DSS)‐induced colitis and control mice were analyzed likewise.Key ResultsFAE‐adjacent VE in ileum of CD possessed more MCs (P < 0.05) and MCs expressing VPAC1 (P < 0.05), but not VPAC2, compared to controls. Both adjacent and regular VE of CD had more MCs co‐localizing/in close proximity to VIP (P < 0.05). In UC colon, more MCs (P < 0.0005), MCs close to VIP (P < 0.0005), and MCs expressing VPAC1 (P < 0.05) were found compared to controls. VIP levels were elevated in plasma from CD and UC compared to controls (P < 0.0005). Colon of DSS mice showed more MCs and MCs close to VIP (P < 0.05) compared to control mice. In vitro experiments revealed MCs expressing VPACs and internalized VIP after 120 minutes of VIP‐stimulation.Conclusions and InferencesCommunication between MCs and VIP is upregulated during IBD and mice colitis. In CD patients, the epithelium next to FAE seems to be more involved than the surrounding VE, suggesting increased MC‐VIP‐interactions in this intestinal region.
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| 10. |
- Chen, Bao Nan, et al.
(författare)
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Sensory innervation of the guinea pig colon and rectum compared using retrograde tracing and immunohistochemistry.
- 2016
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Ingår i: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 28:9, s. 1306-1316
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Tidskriftsartikel (refereegranskat)abstract
- Neurons in lumbar and sacral dorsal root ganglia (DRG) comprise extrinsic sensory pathways to the distal colon and rectum, but their relative contributions are unclear. In this study, sensory innervation of the rectum and distal colon in the guinea pig was directly compared using retrograde labeling combined with immunohistochemistry.
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| 11. |
- Cock, C., et al.
(författare)
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Effects of remifentanil on esophageal and esophagogastric junction (EGJ) bolus transit in healthy volunteers using novel pressure-flow analysis
- 2018
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Ingår i: Neurogastroenterology and Motility. - : John Wiley & Sons. - 1350-1925 .- 1365-2982. ; 30:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Remifentanil is associated with subjective dysphagia and an objective increase in aspiration risk. Studies of opioid effects have shown decreased lower esophageal sphincter relaxation. We assessed bolus transit through the esophagus and esophagogastric junction (EGJ) during remifentanil administration using objective pressure-flow analysis.METHODS: Data from 11 healthy young participants (23±3 years, 7 M) were assessed for bolus flow through the esophagus and EGJ using high-resolution impedance manometry (Manoscan™, Sierra Scientific Instruments, Inc., LES Angeles, CA, USA) with 36 pressure and 18 impedance segments. Data were analyzed for esophageal pressure topography and pressure-flow analysis using custom Matlab analyses (Mathworks, Natick, USA). Paired t tests were performed with a P-value of < .05 regarded as significant.KEY RESULTS: Duration of bolus flow through (remifentanil/R 3.0±0.3 vs baseline/B 5.0 ± 0.4 seconds; P < .001) and presence at the EGJ (R 5.1 ± 0.5 vs B 7.1 ± 0.5 seconds; P = .001) both decreased during remifentanil administration. Distal latency (R 5.2 ± 0.4 vs B 7.5 ± 0.2 seconds; P < .001) and distal esophageal distension-contraction latency (R 3.5 ± 0.1 vs B 4.7 ± 0.2 seconds; P < .001) were both reduced. Intrabolus pressures were increased in both the proximal (R 5.3 ± 0.9 vs B 2.6 ± 1.3 mm Hg; P = .01) and distal esophagus (R 8.6 ± 1.7 vs B 3.1 ± 0.8 mm Hg; P = .001). There was no evidence of increased esophageal bolus residue.CONCLUSIONS AND INFERENCES: Remifentanil-induced effects were different for proximal and distal esophagus, with a reduced time for trans-sphincteric bolus flow at the EGJ, suggestive of central and peripheral μ-opioid agonism. There were no functional consequences in healthy subjects.
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| 12. |
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| 13. |
- Diaz Tartera, Hetzel O., et al.
(författare)
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Validation of SmartPill® wireless motility capsule for gastrointestinaltransit time : Intra-subject variability, software accuracy and comparison with video capsule endoscopy
- 2017
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 29:10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is interest in ultimately combining endoscopy and motility assessments. Gastric emptying (GET), small bowel (SBTT), colon (CTT) and whole gut transit (WGTT) times are conveniently obtained by SmartPill® wireless motility capsule (WMC) that records luminal pH, temperature and pressure. Reproducibility within same subjects and accuracy of software derived times (MotiliGI® ) were investigated for diagnostic application. GET and SBTT were separately measured using video capsule endoscopy (VCE). The aim of this investigation was to assess same subject reproducibility of WMC, accuracy of software derived transit times and relate to Pillcam® SB (small bowel) VCE motility data.METHODS: Seventy three healthy adults ingested a 260 kcal mixed meal followed by WMC tests. Food intake was permitted after 6 hours. Regional transit data was obtained for GET, SBTT and CTT, the sum yielding WGTT. Nineteen subjects repeated WMC tests 2 or 4 weeks later; a separate 70 underwent VCE while fasted.KEY RESULTS: Visually derived data from WMC yielded GET 3.46±0.27, SBTT 5.15±0.21, CTT 20.76±1.19 and WGTT 29.53±1.28 hours (mean±SEM). Pearson's correlation coefficients (r) against software derived results were: GET 0.78 (P<.0001), SBTT 0.28 (P<.05), CTT 0.96 (P<.0001), WGTT 0.99 (P<.0001). VCE yielded lower GET (0.71±0.08 hours) and SBTT (4.15±0.13 hours).CONCLUSIONS AND INFERENCES: GET, SBTT, CTT and WGTT obtained by WMC are commensurate with literature values, including by other methods. Visually and software derived transit times have strongest correlations for CTT and WGTT. WMC yields longer GET and SBTT than VCE, perhaps due to meal related effects on motility.
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| 14. |
- Dlugosz, A., et al.
(författare)
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Increased serum levels of lipopolysaccharide and antiflagellin antibodies in patients with diarrhea-predominant irritable bowel syndrome
- 2015
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Ingår i: Neurogastroenterology and Motility. - : Wiley-Blackwell. - 1350-1925 .- 1365-2982. ; 27:12, s. 1747-1754
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Tidskriftsartikel (refereegranskat)abstract
- Background: Innate immune responses to conserved microbial products such as lipopolysaccharide (LPS) and flagellin are likely important in microbial-host interactions and intestinal homeostasis. We hypothesized that bacterial translocation and activation of mucosal immunity against common microbial antigens might be involved in the development of irritable bowel syndrome (IBS). We therefore compared serum levels of LPS, soluble CD14 (sCD14), and flagellin antibodies between patients with different subtypes of IBS and healthy controls.Methods: We analyzed serum obtained from 88 patients (74 females) aged 19(43)-73 years and 106 healthy volunteers (77 females) aged 19(38)-62 years. Diarrhea-predominant IBS (D-IBS) was present in 32 patients (36%), 23 patients (26%) had constipation-predominant IBS (C-IBS), and 33 patients (38%) had A-IBS. We used ELISA for sCD14 and antiflagellin immunoglobulin G and limulus amebocyte assay for LPS. Abdominal symptoms and psychiatric comorbidities were assessed using validated questionnaires.Key Results: We found a significantly higher serum level of LPS in patients with D-IBS compared to controls (p = 0.0155). The level of antibodies to flagellin was higher in patients with IBS than in controls (mainly driven by higher levels in D-IBS, p = 0.0018). The levels of sCD14 were lower in D-IBS patients compared to controls (p = 0.0498). We found a weak, but significant correlation between the levels of antiflagellin antibodies and anxiety among IBS patients ( = 0.38; p = 0.0045).Conclusions & Inferences: Our results support the concept that immune reactivity to luminal antigens may have a role in the development of D-IBS. The serum level of antiflagellin antibodies was found to correlate with patients' self-reported anxiety score.
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| 15. |
- Frändemark, Åsa, 1988, et al.
(författare)
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Fatigue: A distressing symptom for patients with irritable bowel syndrome
- 2017
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 29:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fatigue is a frequent symptom in patients with irritable bowel syndrome (IBS), and is associated with poor quality of life. However, few studies have evaluated its impact on daily life or the perceived distress it can cause. Using a multi-methods approach, this study describes the impact and manifestations of fatigue in patients with IBS and investigates the relationship between fatigue severity and illness-related and health-promoting factors. Methods: A total of 160 patients with IBS completed self-reported questionnaires assessing fatigue, gastrointestinal symptoms, psychological distress, and sense of coherence. Fatigue was assessed with the Fatigue Impact Scale, which also includes structured and open-ended questions which were analyzed with a deductive qualitative analysis. Patients were classified as having severe, moderate, or mild fatigue based on frequency, distress and impact on daily life. Key Results: The open-ended questions revealed a multidimensional impact on life. Fatigue mainly interfered with the ability to perform physical activities, work, and domestic work, and the ability to interact socially. Decreased stamina was evident, along with strategies to limit the bodily consequences of tiredness. Severe fatigue was accompanied by more severe IBS symptoms, anxiety and depression and lower sense of coherence. Conclusions & Inferences: Fatigue is a distressing symptom which occurs in a sizeable proportion of patients with IBS. It affects life in a multidimensional way, with poor bodily stamina being the most prominent feature. Fatigue, along with sense of coherence, depression and anxiety, needs to be assessed, confirmed and targeted for interventions.
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| 16. |
- Graf, Wilhelm, et al.
(författare)
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Results after sacral nerve stimulation for chronic constipation
- 2015
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 27:5, s. 734-739
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sacral nerve stimulation is an established treatment for fecal incontinence and initial reports describe successful results also in subjects with chronic constipation.METHODS: Consecutive patients with slow transit or outlet obstruction type constipation were offered external stimulation through a test electrode inserted in a sacral foramen during a 3-week period. The symptomatic evaluation was based on the number of bowel movements and a validated obstructed defecation score (ODS). A permanent implant was performed provided an overall 50% decrease in symptoms was observed.KEY RESULTS: In total, 44 patients with chronic constipation were treated with a 3-week test stimulation. Fifteen experienced a 50% reduction of symptoms and received a permanent implant. Four of the 15 with permanent implants were explanted during the course of the study. Five subjects (11% of original group) reported sustained symptom relief at final follow-up after a mean of 24 months (range 4-81). Mean ODS score did not change during the treatment. Patients with predominantly slow transit constipation or outlet obstruction did not differ concerning success rate.CONCLUSIONS & INFERENCES: Sacral nerve stimulation has limited efficacy in unselected patients with chronic constipation and cannot be recommended for treatment on routine basis.
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| 17. |
- Grasa, L., et al.
(författare)
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TLR2 and TLR4 interact with sulfide system in the modulation of mouse colonic motility
- 2019
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 31:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: H2S is a neuromodulator that may inhibit intestinal motility. H2S production in colon is yielded by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) enzymes and sulfate-reducing bacteria (SRB). Toll-like receptors (TLRs) recognize intestinal microbiota. The aim of this work was to evaluate the influence of TLR2 and TLR4 on the endogenous and SRB-mediated synthesis of H2S and its consequences on the colonic motility of mouse. Methods: Muscle contractility studies were performed in colon from WT, Tlr2-/-, and Tlr4-/- mice. The mRNA levels of TLR2, TLR4, CBS, CSE, and SRB were measured by real-time PCR. Free sulfide levels in colon and feces were determined by colorimetric assays. Results: NaHS and GYY4137, donors of H2S, reduced the contractility of colon. Aminooxyacetic acid (AOAA), inhibitor of CBS, and D-L propargylglycine (PAG), inhibitor of CSE, increased the contractility of colon. In vivo treatment with NaHS or GYY4137 inhibited the spontaneous contractions and upregulated TLR2 expression. The in vivo activation of TLR4 with lipopolysaccharide increased the contractile response to PAG, mRNA levels of CSE, and the free sulfide levels of H2S in colon. In Tlr2-/- and Tlr4-/-mice, the contractions induced by AOAA and PAG and mRNA levels of CBS and CSE were lower with respect to WT mice. Deficiency of TLR2 or TLR4 provokes alterations in free sulfide levels and SRB of colon. Conclusions and Inferences: Our study demonstrates interaction between TLR2 and TLR4 and the sulfide system in the regulation of colonic motility and contributes to the pathophysiology knowledge of intestinal motility disorders. © 2019 John Wiley & Sons Ltd
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| 18. |
- Grinsvall, Cecilia, et al.
(författare)
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Psychological factors selectively upregulate rectal pain perception in hypersensitive patients with irritable bowel syndrome.
- 2015
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Ingår i: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 27:12, s. 1772-82
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Tidskriftsartikel (refereegranskat)abstract
- Visceral hypersensitivity and psychological symptoms are frequent features in irritable bowel syndrome (IBS). Exploring mechanistic pathways leading to visceral hypersensitivity is of importance to direct future studies and treatment options. In this study, we evaluated the contribution of psychological factors to the perception of painful and non-painful rectal sensations in hyper- vs normosensitive IBS patients.
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| 19. |
- Gunterberg, Veronica, et al.
(författare)
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Autonomic nervous system function predicts the inflammatory response over three years in newly diagnosed ulcerative colitis patients
- 2016
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 28:11, s. 1655-1662
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe autonomic nervous system (ANS) modulates intestinal inflammation in animal models. Human evidence confirming such modulating influence is limited. We aimed to investigate whether ANS function is associated with inflammatory parameters at disease onset, and whether it predicts the evolution of inflammation in patients with ulcerative colitis (UC). MethodsWe prospectively monitored 51 patients from onset of UC for 3 years. Upon remission of the onset flare, ANS activity was assessed by heart rate variability analysis and compared with healthy controls. Inflammatory parameters in blood, stool, and colonic biopsies obtained at onset and during follow-up visits were analyzed. Generalized linear models were used to test cross-sectional associations between ANS activity and inflammatory parameters at onset; linear mixed models were used to test whether ANS function at onset predicted the evolution of inflammation over the following 3 years. Key ResultsSympathovagal balance was different in UC patients compared to healthy controls, and cross-sectional associated with higher levels of systemic (erythrocyte sedimentation rate [ESR], CRP, TNF-, IFN-) and mucosal inflammation (interleukin-8, IFN-) at onset. Conversely, a negative cross-sectional association with parasympathetic activity was found for ESR & TNF-. Longitudinally, parasympathetic activity at onset predicted systemic (ESR, WBC), but not mucosal inflammation during follow-up. Conclusions & InferencesThis study further strengthens the association between the ANS system and intestinal inflammation previously found in animal models and recently in patients with inflammatory bowel disease. These results may have important implications for the pathogenesis and treatment of UC.
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| 20. |
- Josefsson, Axel, 1984, et al.
(författare)
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Visceral sensitivity remains stable over time in patients with irritable bowel syndrome, but with individual fluctuations
- 2019
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 31:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Visceral hypersensitivity in irritable bowel syndrome (IBS), measured with rectal balloon distensions, using a barostat, has been suggested to be a phenomenon that is reduced due to habituation at repeated investigations. We investigated the stability of rectal sensitivity in patients with IBS who had undergone a previous rectal barostat study and assessed variations in symptom pattern and severity in relation to rectal sensory function. Method: Irritable bowel syndrome patients, who had previously been undergone a rectal barostat study, were included. All patients underwent a second study 8-12years later. Symptoms were characterized by use of questionnaires. Key Results: We included 26 subjects (17 females, median age at the index investigation 44.5 (21-61) years). Pressure and volume sensory thresholds were unchanged at the follow-up compared with the index investigation (P>0.05 for all). At the index investigation, 8/26 patients had rectal hypersensitivity of which four were reclassified as normosensitive, and sixfrom normo- to hypersensitive, meaning that 10/26 patients were hypersensitive at the follow-up investigation. IBS-QOL had improved significantly in six of nine domainsat follow-up (P<0.05 for all). There were no differences in anxiety, depression, IBS symptom severity, or somatization (P>0.05) at follow-up. None of these were associated with change in rectal sensitivity at follow-up. Conclusions and Inferences: Rectal hypersensitivity and IBS symptoms remained stable at the group level over 8-12years in IBS patients, even though individual fluctuations were noted. Our findings contradict previous findings indicating that visceral hypersensitivity is an unstable trait. © 2019 John Wiley & Sons Ltd
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| 21. |
- Lowén, Mats B. O., et al.
(författare)
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Deficient habituation to repeated rectal distensions in irritable bowel syndrome patients with visceral hypersensitivity
- 2015
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 27:5, s. 646-655
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Tidskriftsartikel (refereegranskat)abstract
- Background Irritable bowel syndrome (IBS) patients show evidence of altered central processing of visceral signals. One of the proposed alterations in sensory processing is an altered engagement of endogenous pain modulation mechanisms. The aim was to test the hypothesis that IBS patients with (IBS-S) and without visceral hypersensitivity (IBS-N) differ in their ability to engage endogenous pain modulation mechanism during habituation to repeated visceral stimuli.Methods Brain blood oxygen level dependent (BOLD) response was measured during repeated rectal distension and its anticipation in 33 IBS patients with and without visceral hypersensitivity and 18 healthy controls (HCs). BOLD response to early and late phase of the distension series was compared within and between groups.Key Results While BOLD response was similar during the early phase of the experiment, IBS-S showed greater BOLD response than IBS-N and HCs during the late phase of the distension series. IBS-S showed increasing BOLD response both to the anticipation and delivery of low intensity rectal distensions in brain regions including insula, anterior and mid cingulate cortex. IBS-N showed decreasing BOLD response to repeated rectal distensions in brain regions including insula, prefrontal cortex and amygdala.Conclusions & Inferences These findings are consistent with compromised ability of IBS-S to respond to repeated delivery of rectal stimuli, both in terms of sensitization of sensory pathways and habituation of emotional arousal. The fact that both IBS subgroups met Rome criteria, and did not differ in terms of reported symptom severity demonstrates that similar symptom patterns can result from different underlying neurobiological mechanisms.
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| 22. |
- Midenfjord, Irina, et al.
(författare)
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Anxiety and depression in irritable bowel syndrome: Exploring the interaction with other symptoms and pathophysiology using multivariate analyses
- 2019
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 31:8
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Tidskriftsartikel (refereegranskat)abstract
- Background Anxiety or depression, in other words, psychological distress, are common comorbidities in patients with irritable bowel syndrome (IBS), but their interaction with pathophysiological factors and other symptoms are unclear. Methods Patients with IBS (Rome III criteria), thoroughly characterized regarding pathophysiology (colonic transit time, visceral sensitivity, and autonomic nervous system [ANS] function), symptom profile (IBS severity, somatic symptoms, gastrointestinal [GI]-specific anxiety and fatigue), and quality of life, were explored for differences regarding pathophysiology and symptoms between patients with and without reported psychological distress in univariate and multivariate analyses (Principal Component Analysis [PCA] with Hotelling's T-2 and Orthogonal Partial Least Squares-Discriminant Analysis [OPLS-DA]). Key Results When using Hospital Anxiety and Depression Scale score >= 8 as cut-off score, including both borderline and clinically significant cases, 345 (44.9%) out of 769 IBS patients reported anxiety, and 198 (25.7%) depression. In univariate analyses, patients reporting psychological distress demonstrated more severe GI and non-GI symptoms, fatigue, GI-specific anxiety and lower quality of life, and differences for some pathophysiological measures. IBS patients with and without reported psychological distress showed significant differences between the multivariate means in symptom reporting (PCA; both P < 0.001), and in pathophysiological measures in patients with and without anxiety (P = 0.018). Visceral hypersensitivity, altered ANS function, more severe GI-specific anxiety, fatigue, and higher somatic non-GI symptoms were the factors that most strongly separated patients with and without psychological distress (OPLS-DA). Conclusions and Inferences Reported anxiety and depression are common in IBS patients, and our study demonstrates that they are interwoven in the complex pathophysiological and clinical picture of IBS.
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| 23. |
- Nybacka, Sanna, et al.
(författare)
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Neither self-reported atopy nor IgE-mediated allergy are linked to gastrointestinal symptoms in patients with irritable bowel syndrome
- 2018
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 30:10
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAmong patients with irritable bowel syndrome (IBS), atopic disease has been proposed as a common comorbidity increasing the IBS symptom burden. We therefore assessed the prevalence of self-reported atopy among patients with IBS as compared to non-IBS controls, and whether atopy and higher serum IgE levels were associated with increased IBS symptom severity. MethodsLevels of total and specific IgE in serum were measured and questionnaires assessing the presence of atopic disease (ie, eczema, asthma, rhinoconjunctivitis, and pollen allergy), gastrointestinal symptom burden, food intolerance, somatic, and psychological symptoms were completed. Key resultsIn total, 223 patients with IBS and 47 controls participated. Presence of atopic disease was reported in 55% of patients with IBS compared to 40% of controls (P=.07). IBS patients with atopic manifestations (N=123) had higher total serum IgE levels (median 31 vs 16 kU(A)/L, P<.001) and higher prevalence of self-reported food intolerance (28% vs 9%, P=.002) than non-atopic IBS patients (N=100), respectively, but no major difference in gastrointestinal or psychological symptom burden was noted. However, severe somatic symptoms were more common among atopic than non-atopic patients with IBS (38% vs 27%, P=.028). We found no associations between self-reported atopy and IBS symptom severity using linear regression models. Conclusions & InferencesAtopic disease is common in patients with IBS, but that is also true for subjects without IBS. The presence of atopic disease in IBS is associated with self-reported food intolerance and somatic symptom severity, but unrelated to IBS symptom severity.
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| 24. |
- Olen, O., et al.
(författare)
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Pre- and perinatal stress and irritable bowel syndrome in young adults - A nationwide register-based cohort study
- 2018
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 30:11
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Tidskriftsartikel (refereegranskat)abstract
- Background The etiology of irritable bowel syndrome (IBS) is poorly understood. Animal and human data suggest that early life stress may induce long-term changes in the nociceptive circuitry, but conclusive studies are lacking. MethodsKey ResultsWe identified all Swedish children born between 1973 and 1992 in the Swedish Medical Birth Register. We had access to all diagnostic codes for specialized (nonprimary care) outpatient visits 2001-2009 (the National Patient Register) and identified individuals who were diagnosed with IBS (ICD-10 code: K58) after 18years of age. We compared incidence of IBS in individuals with and without pre- and perinatal stress using multivariable logistic regression. 2056430 children were included in the study. After turning 18years, 14382 of them were diagnosed with IBS in specialized outpatient care. Neither high, nor low birth weight was a risk factor for IBS in young adults. Preterm birth was associated with lower occurrence of IBS (adjusted OR 0.82 [0.75-0.90]) and vaginal instrumental delivery and Cesarean delivery were associated with slightly increased odds of IBS (adjusted OR 1.14 [1.06-1.24] and 1.09 [1.03-1.16] respectively). Neonatal distress and respiratory distress were not associated with future IBS. Female gender was by far the strongest risk factor for IBS in young adults (adjusted OR 3.48 [3.34-3.63]). Conclusions & InferencesIn this large population-based study, we found that mode of delivery was associated with an increased risk for IBS in young adulthood, while other proxies for pre- and perinatal stress were not. Female gender remains the most important risk factor for IBS.
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| 25. |
- Piessevaux, H., et al.
(författare)
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A randomized, double-blind, placebo-controlled trial to evaluate the efficacy, safety, and tolerability of long-term treatment with prucalopride
- 2015
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 27:6, s. 805-815
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Tidskriftsartikel (refereegranskat)abstract
- Background: Randomized trials have confirmed the efficacy of prucalopride for the treatment of chronic constipation up to 12 weeks. This study aimed to assess the efficacy of prucalopride over a 24-week period (ClinicalTrials.gov: NCT01424228). Methods: Adults with chronic constipation and ≤2 spontaneous complete bowel movements (SCBMs)/week were randomized to receive prucalopride 2 mg or placebo daily for 24 weeks. The primary endpoint was the proportion of patients achieving a mean of ≥3 SCBMs/week over the treatment period, assessed using daily e-diaries. Secondary outcomes and safety parameters were assessed throughout the study. Key Results: Overall, 361 patients were randomized and received prucalopride or placebo. Baseline characteristics were similar in the prucalopride (N = 181) and placebo (N = 180) groups. Mean age was 48.9 years (standard deviation, 16.0) and most patients were women. The proportion of participants achieving the primary endpoint was not statistically different between the prucalopride and placebo groups (25.1% vs 20.7%; p = 0.367). There was also no statistically significant difference between groups over the first 12-week period (prucalopride, 25.1%; placebo, 20.1%; p = 0.341). There were no statistically significant differences between groups for most secondary endpoints. No new safety concerns were identified. Conclusions & Inferences: This trial did not show statistically significant improvements in primary or secondary outcomes with prucalopride compared with placebo over 24 or 12 weeks. This is in contrast to the results of four previous 12-week trials, which demonstrated prucalopride to be significantly more effective than placebo. An extensive evaluation did not provide an explanation for the null efficacy results of this study. © 2015 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.
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