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  • Aguilera-Lizarraga, J., et al. (author)
  • Expression of immune-related genes in rectum and colon descendens of Irritable Bowel Syndrome patients is unrelated to clinical symptoms
  • 2019
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 31:6
  • Journal article (peer-reviewed)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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  • Ahlfors, F, et al. (author)
  • Familial intestinal degenerative neuropathy associated with chronic intestinal pseudo-obstruction.
  • 2011
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925. ; 23
  • Journal article (peer-reviewed)abstract
    • Background Few families with autosomal dominant forms of chronic idiopathic pseudo-obstruction (CIP) have been identified and reported. Methods We compared two families by clinical, laboratory, histopathologic, and genealogical investigations. Ten patients (pts) (five women) from two families, A and B, both with a family history suggesting autosomal dominant CIP, were investigated. Key Results All pts had chronic diarrhea, nine of ten pts had chronic abdominal pain and seven of ten chronic vomiting. Median age for onset of symptoms was 23 (A) and 34 years (B). None had dysphagia, urogenital, neurologic, or ocular symptoms. Small bowel transit and jejunal culture were abnormal in eight of nine. Manometry showed severe jejunal hypomotility in the fasting and fed state and absence of normal phase III in all nine pts and neuropathy-like duodenal alterations in eight of nine. Progress to overt CIP had occurred in six pts. Histopathologic re-evaluation (three pts) showed that criteria of visceral degenerative neuropathy were fulfilled in both families including intranuclear inclusions in all three pts. Genealogic exploration using the unique Swedish Register for Catechetical Meetings disclosed that the two families with all likelihood shared a male ancestor in the 1890s. Conclusions & Inferences The compiled results with striking similarities between family A and B together with genealogy findings indicate that this is one, large kindred with a familial autosomal dominant form of intestinal degenerative neuropathy often progressing to CIP but without extra-intestinal manifestations. This is the fourth and, so far, the largest family reported with these characteristics.
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  • Ahluwalia, Bani, et al. (author)
  • Randomized clinical trial: Effects of Aloe barbadensis Mill. extract on symptoms, fecal microbiota and fecal metabolite profiles in patients with irritable bowel syndrome
  • 2020
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 32:8
  • Journal article (peer-reviewed)abstract
    • Background Aloe barbadensis Mill.(Aloe) with potential prebiotic effects has been suggested to reduce symptoms in patients with irritable bowel syndrome (IBS). We therefore aimed to determine the effects of an Aloe extract on symptoms of IBS, and evaluate whether effects may be mediated by fecal microbiota and metabolites in a randomized, double-blind, controlled trial. Methods Patient with IBS diagnosed according to the ROME III criteria (all subtypes), received Aloe or control treatment (inulin) for 4 weeks. IBS Symptom Severity Score (IBS-SSS) was assessed, and fecal samples collected before and at end of treatment. Fecal microbiota composition and metabolomic profile were determined. Key results In total, 160 IBS patients completed the study. The overall severity of IBS symptoms was reduced in both Aloe and control treatment groups (P < .001, both groups, comparing baseline vs end of treatment), without difference between groups (P = .62). The frequency of responders (IBS-SSS reduction >= 50) did not differ between Aloe treatment (n = 33, 39%) and control (n = 34, 45%) (P = .49). However, fecal microbiota and metabolite profiles differed between Aloe, but not control treatment responders and non-responders both before and after treatment. Conclusion In a mixed group of IBS patients, Aloe was not superior to control treatment, although it showed potential to reduce IBS symptom severity in subsets of IBS patients which could be predicted by fecal microbiota and metabolite profiles. ClinicalTrials.gov no: NCT01400048.
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  • Albusoda, A., et al. (author)
  • A fresh look at IBS-opportunities for systems medicine approaches
  • 2017
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925. ; 29:3
  • Journal article (peer-reviewed)abstract
    • NeuroGUT is a EU-funded initial training network (ITN) of 14 research projects in neurogastroenterology that have employed an equal number of early-stage researchers. Neurogut trainees haveamong other activitiesattended an international conference on irritable bowel syndrome (IBS) in Bologna in 2016 and were asked to critically review and evaluate the current knowledge on IBS for their respective research activities, and to state what they were missing. Most appreciated were the topics brain imaging of gut activity, the role of the gut microbiota, the pharmacology of gut functions, the IBS-IBD interrelation, the new Rome IV criteria, the role of gas, and the placebo response in functional disorders. Missed were more detailed coverage of high-resolution manometry, functional brain imaging, advanced systems medicine approaches and bioinformatics technology, better sub-classification of IBS patients, and the development of disease biomarkers, extended at the molecular (genetic/epigenetic, proteonomic) level. They summarize that despite excellent specialized research, there is a gap open that should be filled with systems medicine. For this, it would be necessary that medical research learns even more from the data sciences and other basic disciplines, for example, information technology and system biology, and also welcomes a change in paradigm that enhances open sharing of data, information, and resources.
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  • Algera, Joost, 1993, et al. (author)
  • Associations between postprandial symptoms, hydrogen and methane production, and transit time in irritable bowel syndrome
  • 2023
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 35:2
  • Journal article (peer-reviewed)abstract
    • Background Abnormal oroanal transit time (OATT) and visceral hypersensitivity are key pathophysiological factors in irritable bowel syndrome (IBS). The lactulose nutrient challenge test (LNCT) has been developed to assess the postprandial symptoms and gut microbial fermentation. We aimed to investigate associations between OATT, rectal sensitivity, and LNCT in IBS patients. Methods We included 263 IBS patients from two study cohorts, where the link between pathophysiology and symptoms was investigated. During the LNCT, severity of postprandial symptoms was graded, and breath hydrogen/methane concentrations were measured after ingestion of a combined lactulose nutrient drink every 15 min for 4 h. The patients underwent rectal sensitivity (rectal barostat) and OATT (radiopaque markers) investigations. Comorbid conditions (functional dyspepsia, anxiety, depression, and somatization) were assessed with questionnaires. Key Results After controlling for comorbid conditions, rectal sensitivity was associated with abdominal pain (p < 0.05), and more rapid OATT was associated with higher severity of abdominal discomfort, rumbling, nausea, and urgency (p < 0.05 for all) both pre- and post-prandially. Postprandial nausea, urgency, and abdominal pain changed differently over time depending on OATT (p < 0.05 for all). OATT, but not rectal sensitivity, was associated with hydrogen and methane concentrations (p = 0.002 for both). Trajectories over time of postprandial symptoms and exhaled hydrogen/methane concentrations were correlated with different correlations depending on OATT. Conclusion and Inferences This study highlights the importance of oroanal transit and hydrogen and methane production in the pathophysiology of IBS and increases our understanding of pathophysiological factors involved in postprandial symptom generation. Treatments targeting oroanal transit and hydrogen and methane production may improve specific postprandial symptoms.
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  • Andersson, S., et al. (author)
  • Gastric electrical stimulation for intractable vomiting in patients with chronic intestinal pseudoobstruction
  • 2006
  • In: Neurogastroenterology and motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 18:9, s. 823-30
  • Journal article (peer-reviewed)abstract
    • Gastric electrical stimulation (GES) is effective for medically refractory nausea and vomiting in patients with idiopathic or diabetic gastroparesis (DGP). We studied whether GES has similar effects in chronic intestinal pseudoobstruction (CIP). Patients referred for chronic small bowel (SB) motor dysfunction requiring parenteral nutrition and having a weekly vomiting frequency (WVF) >/=7 refractory to prokinetics and antiemetics were included. Patients were implanted for high-frequency GES 12 stimuli min(-1), laparoscopy being the first-line implantation procedure. Results were compared with those obtained in 11 DGP patients. Three patients with familial CIP and one patient with postsurgical CIP fulfilled the criteria. Gastric emptying was delayed in two and was normal in two patients. SB transit time was markedly delayed. Laparoscopy was used in three patients, one patient required laparotomy. During GES, WVF decreased from 24 (mean) before GES to 6.9 at 12 months and 7.5 at last visit. Vomiting reduction was 50-90% at last visit. For the DGP patients, WVF decreased from 23 before GES to 3.5 at 12 months and 3.5 (P < 0.01) at last visit. In patients with CIP and medically refractory vomiting, GES seems to have an anti-vomiting effect comparable to that seen in patients with severe DGP. GES should be considered as a therapeutic option for these patients.
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  • Arroyo Vázquez, Jorge Alberto, 1979, et al. (author)
  • Exploring pyloric dynamics in stenting using a distensibility technique
  • 2018
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 30:12
  • Journal article (peer-reviewed)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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  • Bashashati, M, et al. (author)
  • Colonic immune cells in irritable bowel syndrome: A systematic review and meta-analysis.
  • 2018
  • In: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 30:1
  • Journal article (peer-reviewed)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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  • Bashashati, M, et al. (author)
  • Cytokine imbalance in irritable bowel syndrome: a systematic review and meta-analysis.
  • 2014
  • In: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 26:7, s. 1036-1048
  • Journal article (peer-reviewed)abstract
    • Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder of unknown etiology; although infection and inflammation have recently been considered as important etiologic agents. A recent meta-analysis showed correlations between cytokine [interleukin-10 (IL-10) and tumor necrosis factor (TNF)] gene polymorphisms and IBS; however, it is still unknown whether patients with IBS have different cytokine profiles compared to healthy population.
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  • Beeckmans, Dorien, et al. (author)
  • Relationship between bile salts, bacterial translocation, and duodenal mucosal integrity in functional dyspepsia
  • 2020
  • In: Neurogastroenterology and Motility. - : WILEY. - 1350-1925 .- 1365-2982. ; 32:5
  • Journal article (peer-reviewed)abstract
    • Background Functional dyspepsia (FD) is a complex disorder, in which multiple mechanisms underlie symptom generation, including impaired duodenal barrier function. Moreover, an altered duodenal bile salt pool was recently discovered in patients with FD. We aimed to evaluate the relationship between bile salts, bacterial translocation, and duodenal mucosal permeability in FD. Methods Duodenal biopsies from patients with FD and healthy volunteers (HV) were mounted in Ussing chambers to measure mucosal resistance and bacterial passage in the absence and presence of fluorescein-conjugated Escherichia coli and glyco-ursodeoxycholic acid (GUDCA) exposure. In parallel, duodenal fluid aspirates were collected from patients and bile salts were analyzed. Key results The transepithelial electrical resistance of duodenal biopsies from patients was lower compared with HV (21.4 +/- 1.3 omega.cm(2) vs. 24.4 +/- 1.2 omega.cm(2); P = .02; N = 21). The ratio of glyco-cholic and glyco-chenodeoxycholic acid (GCDCA) to tauro- and GUDCA correlated positively with transepithelial electrical resistance in patients. Glyco-ursodeoxycholic acid slightly altered the mucosal resistance, resulting in similar values between patient and healthy biopsies (22.1 +/- 1.0 omega.cm(2) vs. 23.0 +/- 1.0 omega.cm(2); P = .5). Bacterial passage after 120 minutes was lower for patient than for healthy biopsies (0.0 [0.0-681.8] vs. 1684.0 [0.0-4773.0] E coli units; P = .02). Glyco-ursodeoxycholic acid increased bacterial passage in patient biopsies (102.1 [0.0-733.0] vs. 638.9 [280.6-2124.0] E coli units; P = .009). No correlation was found between mucosal resistance and bacterial passage. Conclusions amp; inferences Patients with FD displayed decreased duodenal mucosal resistance associated with bile salts, however, not associated with bacterial passage in vitro. In addition, the hydrophilic bile salt glyco-ursodeoxycholic acid abolished differences in mucosal resistance and bacterial passage between patient and control group.
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  • Bennet, Sean, et al. (author)
  • Altered intestinal antibacterial gene expression response profile in irritable bowel syndrome is linked to bacterial composition and immune activation
  • 2018
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925. ; 30:12
  • Journal article (peer-reviewed)abstract
    • Background Immune activity and gut microbiota may impact the pathophysiology of irritable bowel syndrome (IBS). We aimed to determine whether antibacterial gene expression of immune activity-defined IBS patients differed compared to healthy subjects (HS) and ulcerative colitis (UC) patients and whether antibacterial profiles reflected gut microbiota composition and IBS symptoms. Methods Key Results Expression of 84 antibacterial genes in biopsies from HS, IBS patients (clustered according to immune activity (systemic and intestinal cytokines): immunonormal or immunoactive), and UC patients was assessed by Human Antibacterial Response RT2 Profiler PCR Array. In IBS patients, 16S rRNA gene sequencing of fecal and mucosal bacteria was performed and symptom pattern and severity were assessed. Intestinal antibacterial gene expression profiles differed between IBS patients (n = 31) and HS (n = 16), but did not differ between IBS subgroups based on bowel habit predominance or symptom severity. Based on previously identified IBS clusters, IBS patients with normal (n = 15) and enhanced immune activity (n = 16) had clearly separate antibacterial gene expression profiles from active UC patients (n = 12) and differed compared to each other and to HS. The differences in antibacterial gene expression profiles between immunonormal and immunoactive IBS patients were also reflected in distinct fecal and mucosal microbiota composition profiles, but not in symptom pattern or severity. Conclusions & Inferences This study demonstrates an altered antibacterial gene expression profile in IBS patients compared to HS and UC patients. While not linked to symptoms, immune activity-defined IBS clusters showed different intestinal antibacterial gene expression and distinct fecal and mucosal bacterial profiles.
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  • Bennet, Sean, et al. (author)
  • Systemic cytokines are elevated in a subset of patients with irritable bowel syndrome but largely unrelated to symptom characteristics
  • 2018
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 30:10
  • Journal article (peer-reviewed)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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  • Björkman, Ida, et al. (author)
  • More similarities than differences between men and women with irritable bowel syndrome
  • 2015
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 27:6, s. 796-804
  • Journal article (peer-reviewed)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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  • Boden, K., et al. (author)
  • Swallowing and respiratory pattern in young healthy individuals recorded with high temporal resolution
  • 2009
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 21:11, s. 1163-1163
  • Journal article (peer-reviewed)abstract
    • P>The coordination of swallowing and respiration is essential for a safe swallow. Swallowing consists of several subsecond events. To study this, it is important to use modalities with high temporal resolution. In this study, we have examined young healthy individuals with simultaneous videofluoroscopy, videomanometry and respiratory recording, all with high temporal resolution. The onset of 13 predetermined swallowing and respiratory events and the surrounding respiratory phase pattern were studied in different body positions and during different respiratory drives. An increased respiratory drive was induced by breathing 5% CO2. The results demonstrated a highly repeatable and fixed temporal coordination of the swallowing pattern despite body position and respiratory drive. Previous studies have demonstrated a period of centrally controlled apnoea during swallowing. This apnoea period has a variable length, varying from 1 to 5 s. During increased respiratory drive, we could demonstrate a significantly shorter period of apnoea during swallowing, mainly due to an earlier resumption of respiration. The high temporal recordings in this study have revealed that swallowing during expiration is present basically in all healthy individuals. This swallowing respiratory pattern seems to be appropriate for a safe swallow. This knowledge will be used as a reference for future studies on how swallowing and respiratory coordination might be altered due to ageing and diseases.
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  • Boeckxstaens, G. E., et al. (author)
  • Phenotyping of subjects for large scale studies on patients with IBS
  • 2016
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 28:8, s. 1134-1147
  • Journal article (peer-reviewed)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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  • Bonfiglio, F., et al. (author)
  • A GWAS meta-analysis from 5 population-based cohorts implicates ion channel genes in the pathogenesis of irritable bowel syndrome
  • 2018
  • In: Neurogastroenterology and Motility. - : WILEY. - 1350-1925 .- 1365-2982. ; 30:9
  • Journal article (peer-reviewed)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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  • Bonfiglio, F., et al. (author)
  • A meta-analysis of reflux genome-wide association studies in 6750 Northern Europeans from the general population
  • 2017
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 29:2
  • Journal article (peer-reviewed)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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  • Borg, Julia, et al. (author)
  • Oxytocin reduces satiety scores without affecting the volume of nutrient intake or gastric emptying rate in healthy subjects.
  • 2011
  • In: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 23:1
  • Journal article (peer-reviewed)abstract
    • Background Oxytocin is expressed throughout the gastrointestinal tract and is released in response to a fatty meal. Administration of an oxytocin receptor antagonist prolongs the gastric emptying rate. The aim of this study was to examine the effect of oxytocin on gastric accommodation, gastric emptying time, and satiety after food intake. Methods Ten healthy subjects participated in a slow satiety drinking test with a liquid meal. Every 5min the subjects scored their sensation of satiety using a visual analogue scale (VAS) until maximum satiety was reached and the amount of liquid intake was determined. Twelve subjects participated in a gastric emptying test. They were given a standardized meal containing 20 radio-opaque markers, after which fluoroscopy was performed and VAS was scored every hour. Both tests were performed four times during infusions of saline and three different oxytocin concentrations. Blood was collected for oxytocin concentration measurements. Key Results There were no differences in the volume of nutrient intake at maximum satiety between the three doses of oxytocin and saline. However, lower satiety scores at maximum satiety were seen after oxytocin infusion (P=0.031), with 40mUmin(-1) being the most effective dosage (P=0.013), and this was also true 30min after finishing the meal (P=0.032). There was no difference in gastric emptying time between saline and oxytocin. The oxytocin concentration in plasma was increased proportional to the oxytocin infusions. Conclusions & Inferences Infusion of oxytocin reduces satiety without affecting the volume of nutrient intake or gastric emptying in healthy subjects.
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  • Bosman, M., et al. (author)
  • Placebo response in pharmacological trials in patients with functional dyspepsia-A systematic review and meta-analysis
  • 2023
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 35:2
  • Research review (peer-reviewed)abstract
    • Background Pharmacological trials in functional dyspepsia (FD) are associated with high placebo response rates. We aimed to identify the magnitude and contributing factors to the placebo response. Methods We conducted a systematic review and meta-analysis including randomized controlled trials (RCTs) with a dichotomous outcome in adult patients with FD that compared an active pharmacotherapeutic treatment with placebo. Our main outcome was identification of the magnitude of the pooled placebo response rate for the following endpoints: symptom responder, symptom-free responder, adequate relief responder, and combined endpoint responder (i.e., the primary endpoint of each specific trial regarding treatment response). Several putative moderators (i.e., patient, disease, and trial characteristics) were examined. Key Results We included 26 RCTs in our analysis. The pooled placebo response rate was 39.6% (95% CI 30.1-50.0) using the symptom responder definition, 20.5% (12.8-31.0) using the symptom-free responder definition, 38.5% (33.8-43.6) using the adequate relief responder definition, and 35.5% (31.6-39.7) using the combined endpoint responder definition. A lower overall baseline symptom score was significantly associated with a higher placebo response rate. No other moderators were found to significantly impact the placebo response rate. Due to the lack of data, no analyses could be performed according to individual FD subtypes or symptoms. Conclusions and Inferences The pooled placebo response rate in pharmacological trials in FD is about 39%, depending on which responder definitions is used. Future trials should consider applying an entry criterion based on minimal level of symptom severity to decrease the placebo response. We also suggest separate reporting of core FD symptoms pending more concrete harmonization efforts in FD trials.
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29.
  • Broeders, B., et al. (author)
  • Epidemiology of disorders of gut-brain interaction in Belgium and differences between two language groups: Results from the Rome foundation global epidemiology study
  • 2023
  • In: Neurogastroenterology and Motility. - 1350-1925. ; 35:6
  • Journal article (peer-reviewed)abstract
    • BackgroundThe Rome Foundation carried out a worldwide epidemiology study on DGBI according to the Rome IV criteria in 33 countries, including Belgium. DGBI prevalence varied between continents and countries, but prevalence differences within language groups in a single country have not yet been described. MethodsWe analyzed the prevalence rates of 18 DGBI and their psychosocial impact in Belgium in the French and Dutch language groups. Key ResultsDGBI prevalence was similar in the French-speaking and Dutch-speaking population. Having one or more DGBI was negatively associated with psychosocial well-being. The scores for depression were lower in the Dutch-speaking participants with one or more DGBI compared to the French-speaking participants. Interestingly, we also found significantly lower scores in the general Dutch-speaking versus the French-speaking population for depression and non-gastrointesinal somatic symptoms, and higher global physical health and mental health quality-of-life component scores. In the Dutch-speaking group, medication use for gastric acid was lower, but use of prescribed analgesics was more common. Nevertheless, the use of non-prescribed pain medication was higher in the French-speaking group. Anxiety and sleep medication use was also higher in the latter group. Conclusions & InterferencesThe results of this first in-depth analysis of Rome IV DGBI in Belgium show a higher prevalence for some DGBI in the French-speaking cohort, and a larger associated disease burden. These differences between language/culture groups in the same country support the psychosocial pathophysiological model of DGBI.
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30.
  • Bucinskaite, V, et al. (author)
  • Receptor-mediated activation of gastric vagal afferents by glucagon-like peptide-1 in the rat
  • 2009
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 21:9, s. 978-e78
  • Journal article (peer-reviewed)abstract
    • The vagus nerve plays a role in mediating effects of the two glucagon-like peptides GLP-1 and GLP-2 on gastrointestinal growth, functions and eating behaviour. To obtain electrophysiological and molecular evidence for the contribution of afferent pathways in chemoreception from the gastrointestinal tract, afferent mass activity in the ventral gastric branch of the vagus nerve and gene expression of GLP-1 receptors and GLP-2 receptors in the nodose ganglion were examined in Sprague–Dawley rats. Intravenous administration of GLP-1 (30–1000 pmol kg−1), reaching high physiological plasma concentrations, increased vagal afferent mass activity peaking (13–52% above basal level, P < 0.05) 3–5 min after injection. Repeated administration of GLP-1 (1000 pmol kg−1; five times, 15 min intervals) elicited similar responses. Pretreatment with GLP-1 receptor antagonist exendin(9-39)amide (500 pmol kg−1) abolished the GLP-1 response to doses 30–300 pmol kg−1 but had no effect on the vagal response to gastric distension. For comparison, GLP-2 (1000 pmol kg−1) had no effect on vagal afferent activity. Vagal chemoreception of GLP-1 is supported by expression of the GLP-1 receptor gene in the nodose ganglion. However, the GLP-2 receptor was also expressed. To conclude, our results show that peripherally administered GLP-1, differently from GLP-2, activates vagal afferents, with no evidence of desensitisation. The GLP-1 effect was blocked by exendin(9-39)amide, suggesting that GLP-1 receptors on vagal afferent nerves mediate sensory input from the gastrointestinal tract or pancreas; either directly or indirectly via the release of another mediator. GLP-2 receptors appear not be functionally expressed on vagal afferents.
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31.
  • Bureychak, Tetyana, et al. (author)
  • Symptoms and health experience in irritable bowel syndrome with focus on men
  • 2022
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 34:11
  • Journal article (peer-reviewed)abstract
    • Background Irritable bowel syndrome (IBS) is a disorder with a predominance in women; IBS in men is less studied. The present study evaluated symptoms as well as health and social experiences of men with IBS. Methods This cross-sectional study included 293 patients with IBS (64 men) and 363 non-IBS controls (62 men). Gastrointestinal symptom diaries were filled in prospectively, and data on comorbidities and healthcare-seeking behavior were assessed by questionnaires. Men with IBS were compared with men without IBS and women with IBS. Key results Compared with women with IBS, men with IBS had fewer contacts with the healthcare system, fewer psychiatric comorbidities, fewer sleeping problems, and less chronic pain. Urgency to defecate and nausea were less common, and stool frequency was higher in men with IBS. There was no difference between men with and without IBS in terms of educational level, satisfaction with household economy, or living with a partner. In contrast, women with IBS more often lived alone, were more often dissatisfied with household economy, and had a lower educational level than women without IBS. Men with IBS had the same proportion of full-time employment as men without IBS but in contrast, the proportion of women with IBS in full-time employment was only 34%, compared to 50% of the women without IBS. Conclusion and inferences The present study improves the understanding of mens experiences of IBS and suggests that sex and gender may be integrated into the biopsychosocial model of IBS.
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32.
  • Böhn, Lena, et al. (author)
  • A randomized double-blind placebo-controlled crossover pilot study: Acute effects of the enzyme alpha-galactosidase on gastrointestinal symptoms in irritable bowel syndrome patients
  • 2021
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 33:7
  • Journal article (peer-reviewed)abstract
    • Background Postprandial symptoms presumably related to intestinal gas production are common in patients with irritable bowel syndrome (IBS). The aim of the study was to assess if oral alpha-galactosidase is superior to placebo in reducing gastrointestinal (GI) symptoms and intestinal gas production after ingestion of carbohydrate-rich meals in adult patients with IBS. Methods We studied the effect of 1200 GaIU/meal alpha-galactosidase (Nogasin(R)) or placebo capsules on GI symptoms in patients with IBS after three standardized, meals high in oligosaccharides, in a randomized, double-blind, crossover study. The intensity of eight GI symptoms was rated, and breath hydrogen and methane were measured every 30 min during 7.5 h. The severity of GI symptoms the following morning was assessed and compared with baseline.S Key Results Twenty adult patients with IBS (19 females), mean age 49 years (range 22-75 years), were included. All test meals were well tolerated but induced a gradual increase in GI symptom severity. Neither GI symptom ratings over time, nor hydrogen and methane concentrations differed between the days with alpha-galactosidase or placebo. The severity of abdominal pain and bloating was lower the following morning, but with no differences between alpha-galactosidase and placebo. Conclusions & Inferences The use of alpha-galactosidase together with meals high in oligosaccharides was in this pilot study not superior to placebo in reducing postprandial GI symptoms or the concentration of hydrogen and methane in expired air in IBS.
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33.
  • Böhn, Lena, et al. (author)
  • Nutrient intake in patients with irritable bowel syndrome compared with the general population. : Nutrient intake in IBS
  • 2013
  • In: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 25:1
  • Journal article (peer-reviewed)abstract
    • Background Food and diet are central issues that concern patients with irritable bowel syndrome (IBS). Few studies have thoroughly analyzed dietary intake in IBS. Our aims were to determine the nutrient intake in IBS patients in comparison to the general population, assess nutritional differences between IBS subgroups based on the predominant bowel habit or symptom severity, as well as to evaluate if their nutrient intake meet nutrition recommendations. Methods We included 187 IBS patients (mean 40.2years; 139 women). They completed a 4-days food registration record, which was compared with an age-, and gender-matched control group (n=374; 278 women) from a nation-wide dietary survey and with Nordic Nutrient Recommendations. Key Results Daily nutrient intake in IBS patients was similar to the general population and met national nutrients recommendations. Irritable bowel syndrome patients had similar energy distribution from macronutrients compared to the control group, but the protein percentage tended to be higher. Irritable bowel syndrome patients also had significantly higher daily intake of vitamin E, folate, iron, vitamin C, and dietary fibers, as well as lower intake of vitamin A, riboflavin, calcium, and potassium. There was no association between nutrient intake and IBS subtypes or symptom severity. Conclusions & Inferences Although many IBS patients state that they avoid food items, this does not seem to influence their intake of nutrients to any large extent. The observed minor differences in nutrient intake indicate a tendency toward higher intake of fruit and vegetables and a lower intake of meat and dairy products in IBS patients.
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34.
  • Cajander, Per, 1976-, et al. (author)
  • Effects of dexmedetomidine on pharyngeal swallowing and esophageal motility : A double-blind randomized cross-over study in healthy volunteers
  • 2023
  • In: Neurogastroenterology and Motility. - : Wiley-Blackwell Publishing Inc.. - 1350-1925 .- 1365-2982. ; 35:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Sedative agents increase the risk of pulmonary aspiration, where an intact swallowing function is an important defense mechanism. Dexmedetomidine is an α2 -adrenoceptor agonist widely used during procedural sedation due to beneficial properties with minimal respiratory effects. The effects of dexmedetomidine on pharyngeal swallowing and esophageal motility are not known in detail.METHODS: To determine the effects of dexmedetomidine on pharyngeal swallowing and esophageal motility, nineteen volunteers were included in this double-blinded, randomized placebo-controlled cross-over study. Study participants received target-controlled dexmedetomidine and placebo infusions. Recordings of pressure and impedance data were acquired using a manometry and impedance solid-state catheter. Data were analyzed from three bolus swallows series: baseline, during dexmedetomidine/placebo infusion at target plasma concentrations 0.6 ng ml-1 and 1.2 ng ml-1 . Subjective swallowing difficulties were also recorded.KEY RESULTS: On pharyngeal swallowing, dexmedetomidine affected the upper esophageal sphincter with decreased pre- and post-swallow contractile pressures and an increase in residual pressure during swallow-related relaxation. On esophageal function, dexmedetomidine decreased contractile vigor of the proximal esophagus and increased velocity of the peristaltic contraction wave. Residual pressures during swallow-related esophagogastric junction (EGJ) relaxation decreased, as did basal EGJ resting pressure. The effects on the functional variables were not clearly dose-dependent, but mild subjective swallowing difficulties were more common at the higher dose level.CONCLUSIONS AND INFERENCES: Dexmedetomidine induces effects on pharyngeal swallowing and esophageal motility, which should be considered in clinical patient management and also when a sedative agent for procedural sedation or for manometric examination is to be chosen.
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35.
  • Cajander, Per, 1976-, et al. (author)
  • Response to Letter to the Editor
  • 2023
  • In: Neurogastroenterology and Motility. - : Wiley-Blackwell. - 1350-1925 .- 1365-2982. ; 35:8
  • Journal article (peer-reviewed)abstract
    • It is crucial to consider the possible influence of anesthetic agents on esophageal function testing. Dexmedetomidine has been shown to affect primary peristalsis during esophageal manometry. In the two case reports presented by Toaz et al., secondary peristalsis during FLIP panometry was also affected. This may be attributed to an alternate pharmacodynamic effect, with a transient direct α2-mediated effect on esophageal smooth muscle, associated with a high plasma concentration following bolus injection, prior to the onset of sympathetic inhibition.
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37.
  • Casado Bedmar, Maria Teresa, et al. (author)
  • Upregulation of intestinal mucosal mast cells expressing VPAC1 in close proximity to vasoactive intestinal polypeptide in inflammatory bowel disease and murine colitis
  • 2019
  • In: Neurogastroenterology and Motility. - : Wiley-Blackwell Publishing Inc.. - 1350-1925 .- 1365-2982. ; 31:3
  • Journal article (peer-reviewed)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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38.
  • Cedborg, A. I. Hardemark, et al. (author)
  • Breathing and swallowing in normal man - effects of changes in body position, bolus types, and respiratory drive
  • 2010
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 22:11, s. 1201-1201
  • Journal article (peer-reviewed)abstract
    • Background Coordination of breathing and swallowing is essential for airway protection and dyscoordination may cause morbidity and mortality. Methods Using a recently developed technique for high accuracy respiratory measurements of airflow during swallowing, we investigated the effects of body position (upright vs left lateral), bolus type (spontaneously swallowed saliva vs water), and respiratory drive (normo- vs hypercapnia) on coordination of breathing and swallowing in 32 healthy volunteers. Key Results Swallows were in all cases (100%) proceded by expiration and 98% were also followed by expiration, regardless of body position, bolus type, or respiratory drive. While the endpoint of postswallow apnea correlated well to the endpoint of pharyngeal swallowing, duration of preswallow apnea was highly variable. In a small fraction of swallows followed by inspiration (3%), the expiratory phase before swallowing and duration of postswallow apnea was significantly longer. Body position and respiratory drive affected the increase in upper esophageal sphincter tone during inspiration. Increased respiratory drive also reduced swallowing frequency and shortened duration of preswallow apnea. Water swallows had longer duration of preswallow apnea. Conclusions & Inferences Swallowing occurs during the expiratory phase of respiration, and the fraction of swallows preceded and followed by expiration approach 100% in healthy humans. This integration between breathing and swallowing remains unchanged regardless of body position, bolus characteristics, or respiratory drive. Our results provide a platform for future studies aiming at understanding how this integration is changed by aging, diseases, and drugs.
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39.
  • Chen, Bao Nan, et al. (author)
  • Sensory innervation of the guinea pig colon and rectum compared using retrograde tracing and immunohistochemistry.
  • 2016
  • In: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 28:9, s. 1306-1316
  • Journal article (peer-reviewed)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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40.
  • Clevers, Egbert, et al. (author)
  • Food-symptom diaries can generate personalized lifestyle advice for managing gastrointestinal symptoms: A pilot study
  • 2020
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 32:8
  • Journal article (peer-reviewed)abstract
    • Background Gastrointestinal (GI) symptoms have a heterogeneous pathophysiology. Yet, clinical management uses group-level strategies. There is a need for studies exploring personalized management options in patients with GI symptoms. From diaries of GI symptoms, food intake, and psychological distress, we extracted and validated personalized lifestyle advice. Secondly, we investigated group-level GI symptom triggers using meta-analysis. Methods We collected 209 diaries of GI symptoms, food intake, and psychological distress, coming from 3 cohorts of patients with GI symptoms (n = 20, 26, and 163, median lengths 24, 17, and 38 days). Diaries were split into training and test data, analyzed, and the triggers emerging from the training data were tested in the test data. In addition, we did a random effects meta-analysis on the full data to establish the most common GI symptom triggers. Key Results Analysis of the training data allowed us to predict symptom triggers in the test data (r = 0.27, P < .001), especially in the subset of patients with a strong global association between lifestyle factors and symptoms (r = 0.45, P < .001). Low exposure to these triggers in the test data was associated with symptom reduction (P = .043). Meta-analysis showed that caloric intake in the late evening or night predicted an increase in GI symptoms, especially bloating. Several food-symptom associations were found, whereas psychological distress did not clearly lead to more severe GI symptoms. Conclusions & Inferences Diaries of GI symptoms, food intake, and psychological distress can lead to meaningful personalized lifestyle advice in subsets of patients.
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41.
  • Cock, C., et al. (author)
  • Effects of remifentanil on esophageal and esophagogastric junction (EGJ) bolus transit in healthy volunteers using novel pressure-flow analysis
  • 2018
  • In: Neurogastroenterology and Motility. - : John Wiley & Sons. - 1350-1925 .- 1365-2982. ; 30:2
  • Journal article (peer-reviewed)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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42.
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43.
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44.
  • Corsetti, M., et al. (author)
  • Chronic constipation in adults: Contemporary perspectives and clinical challenges. 2: Conservative, behavioural, medical and surgical treatment
  • 2021
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982.
  • Journal article (peer-reviewed)abstract
    • Background: Chronic constipation is a prevalent disorder that affects quality of life of patients and consumes resources in healthcare systems worldwide. In clinical practice, it is still considered a challenge as clinicians frequently are unsure as to which treatments to use and when. Over a decade ago, a Neurogastroenterology and Motility journal supplement devoted to the investigation and management of constipation was published (Neurogastroenterol Motil 2009;21(Suppl 2):1). In October 2018, the 3rd London Masterclass, entitled "Contemporary management of constipation" was held. The faculty members of this symposium were invited to write two reviews to present a collective synthesis of talks presented and discussions held during this meeting. The first review addresses epidemiology, diagnosis, clinical associations, pathophysiology, and investigation. Purpose: The present is the second of these reviews, providing contemporary perspectives and clinical challenges regarding behavioral, conservative, medical, and surgical treatments for patients presenting with constipation. It includes a management algorithm to guide clinical practice.
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48.
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49.
  • Delbro, Dick (author)
  • Do neuro-humoral signaling molecules participate in colorectal carcinogenesis/cancer progression?
  • 2012
  • In: Neurogastroenterology and Motility. - : Wiley-Blackwell. - 1350-1925 .- 1365-2982. ; 24:2, s. 96-99
  • Journal article (peer-reviewed)abstract
    • Signaling molecules in the gastrointestinal (GI) tract, as released from intrinsic, or extrinsic neurons, or from local endocrine cells may serve as positive or negative growth factors, and it has been suggested that such could participate also in colorectal carcinogenesis/cancer progression. Sporadic colorectal cancer arises from an initially benign adenoma, which, in turn, develops from the stem cell compartment, located in the bottom of the crypts of the colorectal mucosa. It was recently demonstrated in rat that intrinsic denervation of the colon appeared to be protective against chemically induced carcinogenesis. Of the various GI signaling molecules, noradrenaline (NA) and substance P (SP) may be of particular importance as growth factors involved in colorectal cancer. In the current issue of Neurogastroenterology and Motility, Graf et al. demonstrate that in benign, human colon polyps, there was a loss of innervation compared with adjacent mucosa, affecting efferent, noradrenergic, as well as sensory, SP-ergic fibers, while there was an increase in SP-immunoreactive non-neuronal cells in the polyps. The results obtained could suggest that loss of mucosal innervation, due to e.g. luminal, pro-inflammatory stimuli, could result in unbalanced pro-tumorigenic stimulation of the stem cell region by non-neuronal SP. The current findings may be important for the further understanding of the development of sporadic colorectal cancer.
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