Neurogastroenterology & Motility

Cover image for Vol. 28 Issue 5

Early View (Online Version of Record published before inclusion in an issue)

Edited By: Magnus Simren, Gary Mawe and Jim Galligan, Associate Editor(s): Kirsteen Browning and Arjan Bredenoord

Impact Factor: 3.587

ISI Journal Citation Reports © Ranking: 2014: 25/76 (Gastroenterology & Hepatology); 44/192 (Clinical Neurology); 86/252 (Neurosciences)

Online ISSN: 1365-2982

VIEW

  1. 1 - 60
  1. Original Articles

    1. Prospective cohort study of phenotypic variation based on an anal sphincter function in adults with fecal incontinence

      C. Brochard, G. Bouguen, A. Bodère, A. Ropert, A-L. Mallet, J. Morcet, J-F. Bretagne and L. Siproudhis

      Article first published online: 4 MAY 2016 | DOI: 10.1111/nmo.12855

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      Patients with fecal incontinence and normal anal function had severe constipation, paradoxical puborectal contraction, and pushed harder suggesting the involvement of distal constipation. The management of patients with fecal incontinence and normal anal function should focus on the distal constipation.

    2. Brain responses to uncertainty about upcoming rectal discomfort in quiescent Crohn's disease – a fMRI study

      A. Rubio, S. Pellissier, L. Van Oudenhove, G. H. LI, P. Dupont, J. Tack, C. Dantzer, C. Delon-Martin and B. Bonaz

      Article first published online: 2 MAY 2016 | DOI: 10.1111/nmo.12844

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      During uncertainty regarding the occurrence of visceral discomfort, CD patients have significantly stronger activations than controls in brain regions implicated in sensory, cognitive and emotional aspects of pain and threat appraisal, and in autonomic responses. These brain responses to uncertainty correlate positively with gastrointestinal symptom-specific anxiety, trait-anxiety, and intolerance of uncertainty.

    3. Early life adversity in piglets induces long-term upregulation of the enteric cholinergic nervous system and heightened, sex-specific secretomotor neuron responses

      J. E. Medland, C. S. Pohl, L. L. Edwards, S. Frandsen, K. Bagley, Y. Li and A. J. Moeser

      Article first published online: 2 MAY 2016 | DOI: 10.1111/nmo.12828

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      Early life adversity (ELA) is a risk factor in the later life development of GI diseases such as IBS; however, the mechanisms remain poorly understood. This study demonstrated that early life adversity in a porcine model induces lasting and sex-specific hypersensitivity of secretomotor neuron function and upregulation of the cholinergic ENS. These findings may represent a mechanistic link between ELA and lifelong susceptibility to GI diseases such as IBS.

    4. Long-term efficacy and safety of transanal irrigation in multiple sclerosis

      V. Passananti, A. Wilton, G. Preziosi, J. B. Storrie and A. Emmanuel

      Article first published online: 26 APR 2016 | DOI: 10.1111/nmo.12833

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      These long-term data on a large sample of MS patients confirm that TAI is an effective treatment option for NBD in these patients. TAI reduces the use of other health care services. The only predictive factor for successful therapy was impaired anal electrosensitivity.

  2. Hot Topics

    1. Fructose consumption impairs serotonergic signaling in the murine enteric nervous system

      K. Lowette, A.-S. Desmet, R.M. Farré, J. Tack and P. Vanden Berghe

      Article first published online: 21 APR 2016 | DOI: 10.1111/nmo.12827

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      Prolonged high-fructose consumption can temporarily impair neuronal function and serotonergic signaling in the mouse submucous plexus.

  3. Original Articles

    1. Gastric emptying of solids in children: reference values for the 13C-octanoic acid breath test

      B. Hauser, M. Roelants, J. De Schepper, G. Veereman, V. Caveliers, T. Devreker, E. De Greef and Y. Vandenplas

      Article first published online: 20 APR 2016 | DOI: 10.1111/nmo.12845

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      We compared the 13C-octanoic acid breath test using non-dispersive infrared spectrometry with 99mTechnetium scintigraphy to measure gastric emptying of a standardized pancake test meal in children with upper gastrointestinal problems. We also established normal values for gastric emptying of this standardized pancake test meal measured with the 13C-octanoic acid breath test using non-dispersive infrared spectrometry in healthy children.

    2. Endocannabinoid-related lipids are increased during an episode of cyclic vomiting syndrome

      T. Venkatesan, Y. Zadvornova, H. Raff and C. J. Hillard

      Article first published online: 20 APR 2016 | DOI: 10.1111/nmo.12843

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      Our study examining the endocannabinoid system and the hypothalamic–pituitary–adrenal (HPA) axis in cyclic vomiting syndrome (CVS) demonstrates that endocannabinoid-related lipids, N-oleoylethanolamine (OEA), and N-palmitoylethanolamide (PEA) are increased in the sick phase of CVS and correlate with poor sleep quality and nausea. Salivary cortisol and alpha amylase were also significantly increased in the sick phase of CVS, but only in patients with chronic marijuana use. This suggests that chronic marijuana use enhances the stress response in CVS.

    3. A prospective study on symptom generation according to spicy food intake and TRPV1 genotypes in functional dyspepsia patients

      S.-Y. Lee, T. Masaoka, H. S. Han, J. Matsuzaki, M. J. Hong, S. Fukuhara, H. S. Choi and H. Suzuki

      Article first published online: 19 APR 2016 | DOI: 10.1111/nmo.12841

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      This prospective study was approved by institutional review board (IRB) of Konkuk University Medical Center (No. KUH1010381) and Institutional Ethics Committee of Keio University School of Medicine (No. 20120246). After the IRB approvals, the study was registered at the Clinical Trial registration sites in Korea (https://cris.nih.go.kr) and in Japan (http://umin.co.jp) as KCT0000527 and UMIN000009673, respectively.

  4. Hot Topics

    1. Correlated gene expression encoding serotonin (5-HT) receptor 4 and 5-HT transporter in proximal colonic segments of mice across different colonization states and sexes

      C. S. Reigstad, D. R. Linden, J. H. Szurszewski, J. L. Sonnenburg, G. Farrugia and P. C. Kashyap

      Article first published online: 12 APR 2016 | DOI: 10.1111/nmo.12840

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      A strong, positive correlation was identified between colonic expression of serotonin transporter Slc6a4 and serotonin receptor Htr4 across different colonization states and sexes. These data suggest that expression of Slc6a4 and Htr4 involves coregulation of genes located on different chromosomes which modulate serotonergic activity in the gut.

  5. Original Articles

    1. Impact of electrical stimulation of the stomach on gastric distension-induced emesis in the musk shrew

      C. C. Horn, L. Zirpel, M. G. Sciullo and D. M. Rosenberg

      Article first published online: 12 APR 2016 | DOI: 10.1111/nmo.12821

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      Musk shrew in vivo anesthetized preparation. (A) Preparation. (B) Gastric stimulation electrodes were placed at three sites. (C) A representative example of detection of seven emetic episodes using the Kleinberg algorithm for burst detection.

    2. Exploring the effects of synchronous pharyngeal electrical stimulation with swallowing carbonated water on cortical excitability in the human pharyngeal motor system

      J. Magara, E. Michou, A. Raginis-Zborowska, M. Inoue and S. Hamdy

      Article first published online: 8 APR 2016 | DOI: 10.1111/nmo.12839

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      This study was undertaken to investigate the effect of synchronously combining PES with swallowing CW using TMS. PES was most effective at inducing excitation in the pharyngeal motor cortex. Combination of PES and CW were less effective in producing cortical excitability but induced transient excitation in the brainstem.

    3. Prevalence, characteristics, and treatment outcomes of reflux hypersensitivity detected on pH-impedance monitoring

      A. Patel, G. S. Sayuk and C. P. Gyawali

      Article first published online: 8 APR 2016 | DOI: 10.1111/nmo.12838

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      Reflux hypersensitivity with physiologic acid burden is seen in a third of symptomatic patients referred for pH-impedance monitoring. Use of pH-impedance monitoring shifts proportions of diagnoses toward reflux hypersensitivity rather than functional non-reflux-triggered symptoms. Reflux hypersensitivity to impedance-detected reflux events improves better than acid sensitivity following antireflux therapy. Antireflux surgery can be an option for select reflux hypersensitivity patients with structural disruption at the esophagogastric junction.

  6. Technical Notes

    1. Determinants and clinical impact of pressure drift in manoscan anorectal high resolution manometry system

      G. Parthasarathy, J. McMaster, K. Feuerhak, A. R. Zinsmeister and A. E. Bharucha

      Article first published online: 8 APR 2016 | DOI: 10.1111/nmo.12830

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      During anorectal HRM, Pressure Drift (PD) declines with catheter use, and is greater for newer catheters, when sensors are exposed to higher pressures, and for studies of longer duration. While PD is partially corrected with the thermal compensation algorithm, the impact on interpretation is modest.

  7. Original Articles

    1. Adverse childhood experiences are associated with irritable bowel syndrome and gastrointestinal symptom severity

      S. H. Park, E. J. Videlock, W. Shih, A. P. Presson, E. A. Mayer and L. Chang

      Article first published online: 8 APR 2016 | DOI: 10.1111/nmo.12826

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      This is the first study to measure the prevalence of early adverse life events (EALs) using the Adverse Childhood Experiences (ACE) questionnaire in irritable bowel syndrome (IBS). The main results of the study were: (i) A history of EALs (i.e., ACE score ≥1) was associated with significantly higher odds (twofold) of having IBS, (ii) IBS status was predicted by a history of emotional abuse and a mentally ill or incarcerated household member, and (iii) ACE score significantly correlates with both overall IBS symptom and abdominal pain severity. This study demonstrates that the ACE questionnaire is a useful instrument to measure EALs in IBS based on its use in large studies, its ability to measure prevalence across different EAL domains, and its correlation with symptom severity.

  8. Hot Topics

    1. Competency based medical education in gastrointestinal motility

      R. Yadlapati, R. N. Keswani and J. E. Pandolfino

      Article first published online: 7 APR 2016 | DOI: 10.1111/nmo.12835

  9. Original Articles

    1. A commonly used ecto-ATPase inhibitor, ARL-67156, blocks degradation of ADP more than the degradation of ATP in murine colon

      L. Durnin, N. Moreland, A. Lees and V. N. Mutafova-Yambolieva

      Article first published online: 5 APR 2016 | DOI: 10.1111/nmo.12836

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      ARL-67156, at a concentration commonly used in physiological/pharmacological studies, does not inhibit the degradation of ATP, but rather causes accumulation of ADP. POM-1 appears to be a better inhibitor of ATPases in the murine colon.

    2. Interplay between bile acid metabolism and microbiota in irritable bowel syndrome

      M. Dior, H. Delagrèverie, H. Duboc, P. Jouet, B. Coffin, L. Brot, L. Humbert, G. Trugnan, P. Seksik, H. Sokol, D. Rainteau and J.-M. Sabate

      Article first published online: 5 APR 2016 | DOI: 10.1111/nmo.12829

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      We demonstrated that in comparison to healthy subjects, IBS patients have different serum and fecal bile acid profiles that could be secondary to dysbiosis and altered metabolic functions. We also observed variation in bile acid profiles between IBS-C and IBS-D patients, which may explain differences in stool patterns. Bile acid profiles were also correlated with abdominal pain.

    3. Practical and reproducible estimation of myenteric interstitial cells of Cajal in the bowel for diagnostic purposes

      M. den Braber-Ymker, S. Heijker, M. Lammens and I. D. Nagtegaal

      Article first published online: 2 APR 2016 | DOI: 10.1111/nmo.12831

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      We presented a novel semiquantitative estimation method for assessment of the myenteric network of interstitial cells of Cajal in the bowel, which can easily be implemented in diagnostics. The method showed acceptable agreement and reliability. Hence, it might be used in routine diagnostics of intestinal neuromuscular disorders.

    4. Sensory innervation of the guinea pig colon and rectum compared using retrograde tracing and immunohistochemistry

      B. N. Chen, C. Olsson, D. F. Sharrad and S. J. H. Brookes

      Article first published online: 2 APR 2016 | DOI: 10.1111/nmo.12825

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      The extrinsic sensory innervation of the guinea pig rectum and colon were compared by retrograde tracing and immunohistochemistry. Both regions receive innervation from thoracolumbar spinal afferents; only the rectum was innervated by lumbosacral afferents and vagal afferents were very sparse to both regions. Fewer than half of all traced afferents contained either CGRP or TRPV1.

    5. You have full text access to this OnlineOpen article
      Tracking gastrointestinal transit of solids in aged rats as pharmacological models of chronic dysmotility

      J. E. Dalziel, W. Young, P. Bercik, N. J. Spencer, L. J. Ryan, K. E. Dunstan, C. M. Lloyd-West, P. K. Gopal, N. W. Haggarty and N. C. Roy

      Article first published online: 29 MAR 2016 | DOI: 10.1111/nmo.12824

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      This study reports the development of a non-invasive high resolution X-ray imaging technique to track transit of solid material in vivo. Modulatory drugs altered GI transit of contents in a region-specific manner providing rat models of constipation (loperamide) and accelerated transit (prucalopride).

    6. Gut microbes in correlation with mood: case study in a closed experimental human life support system

      L. Li, Q. Su, B. Xie, L. Duan, W. Zhao, D. Hu, R. Wu and H. Liu

      Article first published online: 29 MAR 2016 | DOI: 10.1111/nmo.12822

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      A case study on the correlation between gut microbial alternation and mood swing of healthy adults was conducted in a closed human life support system during a 105-day experiment. Microbial community structures in the three healthy adults were strongly correlated with mood states.

    7. Diagnostic yield of 24-hour esophageal manometry in non-cardiac chest pain

      M. Barret, T. V. K. Herregods, J. M. Oors, A. J. P. M. Smout and A. J. Bredenoord

      Article first published online: 27 MAR 2016 | DOI: 10.1111/nmo.12818

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      Comparing the diagnostic yield of high-resolution manometry and 24-h ambulatory pressure monitoring in patients with non-cardiac chest pain, we found that when the Chicago classification v3.0 was applied, HRM did not identify any of the four (6.8%) patients with esophageal spasm on 24-h measurement. However, taking into account other more subtle abnormalities, such as simultaneous (rapid) or repetitive contractions, HRM had a sensitivity of 75% and a specificity of 98.2% for the diagnosis of esophageal spasm.

    8. Relationships of abdominal pain, reports to visceral and temperature pain sensitivity, conditioned pain modulation, and heart rate variability in irritable bowel syndrome

      M. E. Jarrett, C. J. Han, K. C. Cain, R. L. Burr, R. J. Shulman, P. G. Barney, B. D. Naliboff, J. Zia and M. M. Heitkemper

      Article first published online: 19 MAR 2016 | DOI: 10.1111/nmo.12812

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      Women with IBS experienced significantly more symptom distress response to visceral stimulation. There were no differences in HRV indicators between IBS and HCs.

    9. Central administrations of hemopressin and related peptides inhibit gastrointestinal motility in mice

      X.-H. Li, M.-L. Lin, Z.-L. Wang, P. Wang, H.-H. Tang, Y.-Y. Lin, N. Li, Q. Fang and R. Wang

      Article first published online: 14 MAR 2016 | DOI: 10.1111/nmo.12789

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      Our studies, for the first time, revealed that central administration of hemopressin and related peptides, the novel endogenous peptidic ligands of cannabinoid receptors, significantly inhibited gastrointestinal motility in mice through the activation of CB1, but not CB2 cannabinoid receptors.

  10. Hot Topics

    1. Drug–resin drug interactions in patients with delayed gastric emptying: What is optimal time window for drug administration?

      M. Camilleri

      Article first published online: 14 MAR 2016 | DOI: 10.1111/nmo.12823

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      This article reviews the functions of the stomach and the kinetics of emptying of different food forms or formulations to make recommendations on timing of medication administration in order to avoid intragastric drug interactions. Based on the profiles and kinetics of emptying of liquid nutrients and homogenized solids, a window of 3 h between administration of a resin drug and another ‘target’ medication would be expected to allow a median of 80% of medications with particle size <1 mm to empty from the stomach and, hence, avoid potential interaction such as binding of the ‘target’ medication within the stomach.

  11. Original Articles

    1. Changes of excitatory and inhibitory neurotransmitters in the colon of rats underwent to the wrap partial restraint stress

      C. Traini, S. Evangelista, V. Girod, M.S. Faussone-Pellegrini and M.G. Vannucchi

      Article first published online: 12 MAR 2016 | DOI: 10.1111/nmo.12816

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      This study aims to investigate possible morphological changes in the colonic wall of wrap restraint stress (WRS) rats and correlates the results with functional data to improve our understanding of irritable bowel syndrome (IBS) pathogenesis. WRS was maintained for 2 h. At the end, fecal pellets were quantitated and abdominal contractions were recorded in the colon-rectum. Colonic specimens were examined by histology, immunohistochemistry, and western blot. The functional data showed a significant increase in fecal pellet production and the presence of a visceral hypersensitivity. The morphological findings showed the presence of a mucosal inflammation and important changes in nerve structures. The present results support the consistency of the WRS as a potential model for understanding IBS pathogenesis. The changes in nerve structures might represent the main substrates for dysmotility and visceral hypersensitivity. This is the first report of an increase in CRF1r expressing neurons. This datum fits well with the role of the receptor in mediating the stress responses and supports our hypothesis that changes in neurotransmission are mainly involved in the genesis of colonic dysmotility.

    2. Role of 5-HT1A receptor in insular cortex mediating stress – induced visceral sensory dysfunction

      H. Sun, S. Xu, L. Yi, Y. Chen, P. Wu, Z. Cao, L. Zhou, Y. Jiang and D. Zhang

      Article first published online: 11 MAR 2016 | DOI: 10.1111/nmo.12815

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      This study aimed to explore the role of 5-HT1A receptors (HTR1As) in mediating stress-induced visceral hypersensitivity and its mechanism in the insular cortex. The results indicated that HTR1A in the insular cortex plays an important role in mediating chronic stress-induced visceral hypersensitivity in rats. N-methyl-d-aspartic acid receptor subtype 2B may be one of the important downstream signaling molecules of HTR1A mediating the visceral hypersensitivity.

    3. Potential association of VAMP5 polymorphisms with total colonic aganglionosis in Hirschsprung disease

      J.-G. Shin, D.-Y. Kim, J.-M. Seo, J.-T. Oh, K.-W. Park, H.-Y. Kim, B. L. Park, J.-H. Kim and H. D. Shin

      Article first published online: 11 MAR 2016 | DOI: 10.1111/nmo.12807

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      We examine the association between VAMP5 SNPs and the risk of Hirschsprung disease in a Korean population. Five genetic variants (rs1561198, rs55971080, rs10206961, rs1254900, and rs14242) were associated with risk of TCA (minimum p = 9.69 × 10−5, pcorr = 0.002 at rs10206961). Results indicating increased association signals in the TCA subgroup compared to other subgroups suggest that VAMP5 may have an effect on the extent of the aganglionic segment in ENS development.

    4. You have full text access to this OnlineOpen article
      Anticipation of thermal pain in diverticular disease

      J. K. Smith, L. Marciani, D. J. Humes, S. T. Francis, P. Gowland and R. C. Spiller

      Article first published online: 11 MAR 2016 | DOI: 10.1111/nmo.12790

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      Symptomatic diverticular disease patients can be separated into low (LSDD) and high (HSDD) somatization groups based on Patient Health Questionnaire-12 (PHQ-12 SS) During anticipation of pain greater deactivations occur (shown in blue) in somatosensory, emotional, and descending noxious inhibitory control pain regions in the asymptomatic (ADD) compared to the symptomatic diverticular disease (SDD) and irritable bowel syndrome (IBS) groups There are fewer anticipatory differences between the ADD and LSDD and the IBS and HSDD groups, suggesting the that LSDD and HSDD grouping identifies DD patients with predominantly peripheral vs central factors, respectively.

    5. Stimulus-induced pacemaker activity in interstitial cells of Cajal associated with the deep muscular plexus of the small intestine

      Y. F. Zhu, X.-Y. Wang, S. P. Parsons and J. D. Huizinga

      Article first published online: 10 MAR 2016 | DOI: 10.1111/nmo.12808

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      The ICC-DMP (ICC associated with the deep muscular plexus of the small intestine) are spontaneously quiescent. Upon stimulation by exogenous substance P, ICC-DMP first exhibit high frequency calcium transients; this activity is not synchronized within the ICC-DMP network and does not lead to electrical activity. Upon further sustained stimulation by substance P, the high-frequency calcium transients become superimposed on strong rhythmic low frequency calcium transients, which are synchronized within the ICC-DMP network; this is associated with rhythmic transient depolarizations. The ICC-DMP exhibit stimulus-induced rhythmicity; we propose ICC-DMP to be stimulus-dependent pacemaker cells.

    6. Synchronized functional anal sphincter assessment: maximizing the potential of anal vector manometry and 3-D anal endosonography

      A. M. P. Schizas, A. N. Ahmad, A. V. Emmanuel and A. B. Williams

      Article first published online: 10 MAR 2016 | DOI: 10.1111/nmo.12810

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      Understanding the association between structure and function is vital before considering surgery involving anal sphincter division. By correlating three-dimensional anal endosonography (AES) and three-dimensional anal canal vector volume manometry (VVM), this study details a method to produce measurements of both sphincteric length and pressure leading to identification of the functionally important areas of the anal canal. A majority of resting and squeezing pressure and the least asymmetry, in both sexes, is in the portion of the anal canal covered by external anal sphincter; while in females, the external anal sphincter is shorter and a proportionately longer puborectalis accounts for a greater percentage of pressure.

    7. Malnutrition increases NO production and induces changes in inflammatory and oxidative status in the distal colon of lactating rats

      E. F. dos Santos-Júnior, C. Gonçalves-Pimentel, L. C. C. de ARAÚJO, T. G. da Silva, M. R. de Melo-Júnior, V. Moura-Neto and B. L. D. S. Andrade-da-Costa

      Article first published online: 8 MAR 2016 | DOI: 10.1111/nmo.12820

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      Epidemiological studies have indicated the lack of breast feeding as a risk factor associated with later development of inflammatory bowel disease. Nevertheless, the repercussion of little feeding during suckling on large intestine inflammatory response and anti-oxidant resources has not yet been completely understood. In this study, our results reveal that reduced feeding during suckling changes the inflammatory response and oxidative status in the colon of weanling rats and increase nitric oxide levels in the muscle layers.

    8. Anatomic abnormalities are common potential explanations of manometric esophagogastric junction outflow obstruction

      K. DeLay, G. L. Austin and P. Menard-Katcher

      Article first published online: 6 MAR 2016 | DOI: 10.1111/nmo.12814

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      Esophagogastric junction outflow obstruction (EGJOO) is a high-resolution manometry (HRM) diagnosis associated with a myriad of conditions and of uncertain clinical implication. We compared clinical and manometric features of EGJOO classified as either idiopathic or related to anatomic conditions. We found that EGJOO is frequently encountered and commonly associated with anatomic abnormalities. Cases of idiopathic EGJOO are more likely to have hypercontractility on HRM.

    9. Validating endpoints for therapeutic trials in fecal incontinence

      J. Noelting, A. R. Zinsmeister and A. E. Bharucha

      Article first published online: 6 MAR 2016 | DOI: 10.1111/nmo.12809

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      This study suggests that a 50% reduction in the frequency of fecal incontinence (FI) is clinically meaningful. Daily and weekly instruments are correlated for assessing symptoms of FI.

    10. Baseline features and differences in 48 week clinical outcomes in patients with gastroparesis and type 1 vs type 2 diabetes

      K. L. Koch, W. L. Hasler, K. P. Yates, H. P. Parkman, P. J. Pasricha, J. Calles-Escandon, W. J. Snape, T. L. Abell, R. W. McCallum, L. A. Nguyen, I. Sarosiek, G. Farrugia, J. Tonascia, L. Lee, L. Miriel, F. Hamilton and For the NIDDK Gastroparesis Clinical Research Consortium (GpCRC)

      Article first published online: 6 MAR 2016 | DOI: 10.1111/nmo.12800

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      This study defined similarities and differences in gastroparesis severity, healthcare utilization, psychological function, and quality of life in patients with type 1 (T1DM) and type 2 (T2DM) diabetes mellitus and gastroparesis. At baseline enrollment, T1DM patients had higher hemoglobin A1c levels and more severe emptying delays, but the severity of GI symptoms was similar to those of patients with T2DM and gastroparesis. After 48 weeks of follow-up, gastroparesis symptom scores significantly decreased in T2DM patients but not in T1DM patients despite increased use of prokinetic, acid suppressant, anxiolytic, and gastric electrical stimulation therapy in the T1DM group.

    11. Expression of inducible nitric oxide synthase in mast cells contributes to the regulation of inflammatory cytokines in irritable bowel syndrome with diarrhea

      S. An, G. Zong, Z. Wang, J. Shi, H. Du and J. Hu

      Article first published online: 4 MAR 2016 | DOI: 10.1111/nmo.12811

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      It was found that MCs were increased in number and expressed iNOS in colonic mucosa of IBS-D patients. Supernatant from IBS-D increased iNOS expression in BMMCs. Antibody array showed that agrin, β-NGF, fractalkine, GM-CSF, IL-1β, IL-1R6, IL-13, leptin, TNF-α were suppressed, and CINC-1, CINC-2α, CINC-3, MCP-1, MMP-8 were strongly produced in L-NAME-treated BMMCs, comparable to levels in control groups.

    12. Depleted interstitial cells of Cajal and fibrosis in the pylorus: Novel features of gastroparesis

      S. Moraveji, M. Bashashati, S. Elhanafi, J. Sunny, I. Sarosiek, B. Davis, A. Torabi and R. W. McCallum

      Article first published online: 4 MAR 2016 | DOI: 10.1111/nmo.12806

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      Pyloric ICC depletion and collagen fibrosis in the smooth muscle are common findings in gastroparesis. These features can partially explain pyloric dysfunction in these patients.

  12. Review Articles

    1. Functional neuroimaging studies in functional dyspepsia patients: a systematic review

      I.-S. Lee, H. Wang, Y. Chae, H. Preissl and P. Enck

      Article first published online: 4 MAR 2016 | DOI: 10.1111/nmo.12793

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      This systematic review aims to provide an integrative understanding of the abnormal functional brain activity, visceral sensation, dyspeptic symptoms, and psychological changes of FD. The results show that FD is associated with functional abnormalities in sensory and pain modulation, emotion, saliency, and homeostatic processing regions.

  13. Original Articles

    1. Simultaneous urodynamic and anorectal manometry studies in children: insights into the relationship between the lower gastrointestinal and lower urinary tracts

      L. Ambartsumyan, A. Siddiqui, S. Bauer and S. Nurko

      Article first published online: 1 MAR 2016 | DOI: 10.1111/nmo.12794

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      We demonstrate that distention (RD) affects bladder function and describe a physiological correlate of voiding dysfunction which may explain why patients with fecal retention may be predisposed to lower urinary tract problems.

    2. The association between systemic sclerosis disease manifestations and esophageal high-resolution manometry parameters

      J. N. Kimmel, D. A. Carlson, M. Hinchcliff, M. A. Carns, K. A. Aren, J. Lee and J. E. Pandolfino

      Article first published online: 27 FEB 2016 | DOI: 10.1111/nmo.12813

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      Patients with systemic sclerosis (SSc) and previous completed high-resolution manometry were retrospectively evaluated to assign an esophageal motility diagnosis by the Chicago Classification and explore associations with SSc-related clinical characteristics. We identified an association of increased skin severity (measured by the Modified Rodnan Skin Score) and more severe reductions in pulmonary function tests in patients with absent contractility compared with patients with ineffective esophageal motility and normal esophageal motility.

    3. Improvement of meal-related symptoms and epigastric pain in patients with functional dyspepsia treated with acotiamide was associated with acylated ghrelin levels in Japan

      H. Yamawaki, S. Futagami, T. Kawagoe, Y. Maruki, S. Hashimoto, H. Nagoya, H. Sato, Y. Kodaka, K. Gudis, T. Akamizu, C. Sakamoto and K. Iwakiri

      Article first published online: 27 FEB 2016 | DOI: 10.1111/nmo.12805

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      We aimed to clarify whether acotiamide and rabeprazole combination therapy significantly improves clinical symptoms and satisfaction with treatment via its effect on gastric emptying and appetite-related hormones such as ghrelin, compared to acotiamide or rabeprazole monotherapy. Acotiamide and rabeprazole combination therapy significantly improved PDS-like symptoms and epigastric pain and STAI-state scores compared to rabeprazole monotherapy. Acotiamide monotherapy, and acotiamide and rabeprazole combination therapy significantly increased acylated ghrelin/total ghrelin ratios and significantly improved impaired gastric emptying compared to rabeprazole monotherapy.

    4. In vivo neutralization of IL-6 receptors ameliorates gastrointestinal dysfunction in dystrophin-deficient mdx mice

      J. Manning, M. M. Buckley, K. D. O'Halloran and D. O'Malley

      Article first published online: 27 FEB 2016 | DOI: 10.1111/nmo.12803

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      The studies undertaken sought to establish the effects of loss of neuronal and smooth-muscle dystrophin on colonic morphology and function and aimed to determine the therapeutic potential of xIL-6R and uro2 treatment. Neutralizing IL-6 receptor signaling normalizes colonic dysfunction in dystrophin-deficient mdx mice.

  14. Hot Topics

    1. Chronic vagus nerve stimulation in Crohn's disease: a 6-month follow-up pilot study

      B. Bonaz, V. Sinniger, D. Hoffmann, D. Clarençon, N. Mathieu, C. Dantzer, L. Vercueil, C. Picq, C. Trocmé, P. Faure, J-L. Cracowski and S. Pellissier

      Article first published online: 27 FEB 2016 | DOI: 10.1111/nmo.12792

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      Vagus nerve stimulation is feasible and appears as an interesting tool in the treatment of active Crohn's disease (CD) but further investigation in a larger longitudinal cohort of CD patients is warranted. Our aim was to perform a pilot study of chronic vagus nerve stimulation (VNS) in patients with active CD. Seven patients under VNS were followed up for 6 months with a primary endpoint to induce clinical, biological, and endoscopic remission and to restore vagal tone. Vagus nerve stimulation was well-tolerated in all patients. Five patients evolved toward clinical, biological, and endoscopic remission with a restored vagal tone.

  15. Technical Notes

    1. 13C mannitol as a novel biomarker for measurement of intestinal permeability

      M. Grover, M. Camilleri, J. Hines, D. Burton, M. Ryks, A. Wadhwa, W. Sundt, R. Dyer and R. J. Singh

      Article first published online: 23 FEB 2016 | DOI: 10.1111/nmo.12802

  16. Original Articles

    1. Prevalence of celiac disease and related antibodies in patients diagnosed with irritable bowel syndrome according to the Rome III criteria. A case–control study

      L. A. Sánchez-Vargas, P. Thomas-Dupont, M. Torres-Aguilera, A. A. Azamar-Jacome, K. L. Ramírez-Ceervanes, M. R. Aedo-Garcés, A. Meixueiro-Daza, F. Roesch-Dietlen, P. Grube-Pagola, H. Vivanco-Cid and J. M. Remes-Troche

      Article first published online: 23 FEB 2016 | DOI: 10.1111/nmo.12799

  17. Review Articles

    1. What a gastrointestinal biopsy can tell us about Parkinson's disease?

      A.-G. Corbillé, T. Clairembault, E. Coron, L. Leclair-Visonneau, C. Preterre, M. Neunlist and P. Derkinderen

      Article first published online: 23 FEB 2016 | DOI: 10.1111/nmo.12797

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      A substantial amount of research has been done to detect neuronal pathology in gastrointestinal biopsies in order to develop a premortem histopathological marker of Parkisnon's disease. Aside from neurons, the enteric glial cells and epithelial cells, which are present in a gastrointestinal biopsy, are also dysregulated in Parkinson's disease. We suggest that agastrointestinal biopsy could represent a unique window to assess the neuropathology in living patients with Parkinson's disease.

  18. Original Articles

    1. Surgical intestinal manipulation increases gene expression of TrkA, CGRP, and PAR-2 IN dorsal root ganglia in the rat

      S. Berdún, J. Rychter and P. Vergara

      Article first published online: 22 FEB 2016 | DOI: 10.1111/nmo.12777

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      Intestinal manipulation increased gene expression of mediators related to visceral sensitivity: CGRP, NGF/TrkA, and PAR-2. These mediators should be further explored to prevent postoperative ileus.

    2. You have full text access to this OnlineOpen article
      Electrophysiological and morphological changes in colonic myenteric neurons from chemotherapy-treated patients: a pilot study

      S. E. Carbone, V. Jovanovska, S. J. H. Brookes and K. Nurgali

      Article first published online: 22 FEB 2016 | DOI: 10.1111/nmo.12795

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      This is the first electrophysiological study of human enteric neurons in fresh colon specimens from colorectal cancer patients treated and untreated with chemotherapeutic agents. Neuronal hyperexcitability and morphological changes in myenteric neurons may contribute to the causation of gastrointestinal symptoms experienced by chemotherapy-treated patients.

    3. Probiotic Lactobacillus casei strain Shirota relieves stress-associated symptoms by modulating the gut–brain interaction in human and animal models

      M. Takada, K. Nishida, A. Kataoka-Kato, Y. Gondo, H. Ishikawa, K. Suda, M. Kawai, R. Hoshi, O. Watanabe, T. Igarashi, Y. Kuwano, K. Miyazaki and K. Rokutan

      Article first published online: 20 FEB 2016 | DOI: 10.1111/nmo.12804

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      We examined the effects of the probiotic Lactobacillus casei strain Shirota (LcS) on stress markers and stress-related symptoms in healthy medical students preparing for a major examination, and found that salivary cortisol levels and physical complaints which increased toward the exam day were significantly suppressed by LcS treatment. Results of animal studies suggested that the ingestion of LcS suppresses stress-induced increases in glucocorticoids, possibly through vagal afferent signaling from the upper intestines to the brain and reduced stress reactivity in the hypothalamus.

    4. Smooth muscle and neural dysfunction contribute to different phases of murine postoperative ileus

      G. Farro, P. J. Gomez-Pinilla, M. Di Giovangiulio, N. Stakenborg, M. Auteri, T. Thijs, I. Depoortere, G. Matteoli and G. E. Boeckxstaens

      Article first published online: 18 FEB 2016 | DOI: 10.1111/nmo.12796

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      We aimed to identify alterations in the enteric nervous system that may contribute to the pathogenesis of postoperative ileus. Surgical manipulation of the intestine induced two phases of muscle dysfunction over 24 h and a late prolonged phase of impaired neurotransmission. Our data show that intestinal surgery affect both muscle cells and neurons and different inflammatory mechanisms underlie the different phases.

    5. Mucosal serotonin overflow is associated with colonic stretch rather than phasic contractions

      B. A. Patel

      Article first published online: 17 FEB 2016 | DOI: 10.1111/nmo.12791

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      We observed that 5-HT overflow was associated with longitudinal and circular muscle stretch rather than phasic contractions in the murine distal colon. The change in 5-HT overflow during longitudinal or circular stretch is due to the activation of TRPA1 ion channels. Our study provides new additional insight into the association of mucosal 5-HT with motility patterns.

    6. You have full text access to this OnlineOpen article
      Colonic response to laxative ingestion as assessed by MRI differs in constipated irritable bowel syndrome compared to functional constipation

      C. Lam, G. Chaddock, L. Marciani, C. Costigan, J. Paul, E. Cox, C. Hoad, A. Menys, S. Pritchard, K. Garsed, S. Taylor, D. Atkinson, P. Gowland and R. Spiller

      Article first published online: 12 FEB 2016 | DOI: 10.1111/nmo.12784

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      The underlying disorder of function differs in FC and IBS-C implying that response to treatments altering motility will differ. Using a stimulus such as Moviprep®, FC can be differentiated from IBS-C by assessing the motility of AC and time to first bowel movement, MRI can be used as a tool to clarify the underlying functional abnormality in patients with difficult and resistant constipation, Even without MRI, using 1 L of Moviprep® as a stimulant and measuring the time to first bowel movement can assist in differentiating between FC and IBS-C.

    7. Electrical pharyngeal stimulation increases substance P level in saliva

      S. Suntrup-Krueger, S. Bittner, S. Recker, S. G. Meuth, T. Warnecke, I. Suttrup, T. Marian and R. Dziewas

      Article first published online: 12 FEB 2016 | DOI: 10.1111/nmo.12783

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      Substance P (SP) constitutes an interesting therapeutic target for dysphagia as it is a neuropeptide in pharyngeal sensory afferents known to enhance the swallow response. In our randomized controlled study on healthy volunteers, saliva SP concentration increased after 10 min of electrical pharyngeal stimulation (EPS). We conclude that EPS is able to induce pharyngeal SP release.

    8. Colonic content in health and its relation to functional gut symptoms

      R. A. Bendezú, E. Barba, E. Burri, D. Cisternas, A. Accarino, S. Quiroga, E. Monclus, I. Navazo, J.-R. Malagelada and F. Azpiroz

      Article first published online: 12 FEB 2016 | DOI: 10.1111/nmo.12782

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      The distribution of non-gaseous colonic content was measured using an original program for analysis of abdominal CT images. In healthy subjects intraluminal content was uniformly distributed along the colon and a discrete distal mass movement was observed in the early postprandial period. In patients with functional gut disorders, either during basal conditions or during episodes of abdominal distension, non-gaseous colonic content was within the normal range.

    9. The effect of levosulpiride on in vitro motor patterns in the human gastric fundus, antrum, and jejunum

      D. Gallego, O. Ortega, C. Arenas, I. López, E. Mans and P. Clavé

      Article first published online: 3 FEB 2016 | DOI: 10.1111/nmo.12788

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      We characterized the effects of levosulpiride, a 5HT4 agonist/D2 antagonist, on the main in vitro motility patterns in the human stomach and jejunum using organ bath. Prokinetic effects of the drug are mainly due to the facilitation of the release of acetylcholine by enteric motor neurons in the gastric antrum and the jejunum.

    10. Evaluating the safety and the effects on colonic compliance of neostigmine during motility testing in patients with chronic constipation

      M. A. Mouchli, M. Camilleri, T. Lee, G. Parthasarathy, P. Vijayvargiya, M. Halland, A. Acosta and A. E. Bharucha

      Article first published online: 3 FEB 2016 | DOI: 10.1111/nmo.12786

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      We retrospectively reviewed medical records of a selected group of 144 outpatients with chronic constipation who were refractory to treatment. Neostigmine significantly decreases colonic compliance in patients with refractory chronic constipation. Symptomatic bradycardia in response to neostigmine should be promptly reversed with atropine.

    11. Diabetic gastroparesis alters the biomagnetic signature of the gastric slow wave

      L. A. Bradshaw, L. K. Cheng, E. Chung, C. B. Obioha, J. C. Erickson, B. L. Gorman, S. Somarajan and W. O. Richards

      Article first published online: 3 FEB 2016 | DOI: 10.1111/nmo.12780

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      The non-invasive magnetogastrogram shows a reduction in gastric slow wave propagation velocity and altered propagation patterns in patients with diabetic gastroparesis when compared with healthy control subjects. Temporal slow wave parameters typically measured in the electrogastrogram are not altered by gastroparesis.

    12. Na+/Ca2+ exchanger-heterozygote knockout mice display increased relaxation in gastric fundus and accelerated gastric transit in vivo

      Y. T. Azuma, S. Hayashi, K. Nishiyama, S. Kita, K. Mukai, H. Nakajima, T. Iwamoto and T. Takeuchi

      Article first published online: 19 JAN 2016 | DOI: 10.1111/nmo.12779

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      When an inhibitor of nitric oxide synthase was added following the EFS, neither NCX1 HET nor NCX2 HET exhibited transient relaxation, similar to WT. Furthermore, when a PACAP antagonist was added following the EFS, sustained relaxation in NCX1 HET and NCX2 HET was not observed, similar to WT.

    13. Gastric ghrelin, GOAT, leptin, and leptinR expression as well as peripheral serotonin are dysregulated in humans with obesity

      Y. Ritze, A. Schollenberger, M. Hamze Sinno, N. Bühler, M. Böhle, G. Bárdos, H. Sauer, I. Mack, P. Enck, S. Zipfel, T. Meile, A. Königsrainer, M. Kramer and S. C. Bischoff

      Article first published online: 19 JAN 2016 | DOI: 10.1111/nmo.12773

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      Gastrointestinal hormone release and the regulation of appetite and body weight are thought to be dysbalanced in obesity. We asked whether ghrelin, GOAT, leptin, and leptinR expression demonstrates an increased expression in the stomach tissue and blood and also correlates with elevated inflammatory markers in obese compared with non-obese humans. Our data indicate that obesity causes a dysregulation of gastrointestinal hormones at the tissue level and serum, including a negative correlation with an increased marker of subclinical inflammation.

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