Recent PubMed Articles on Gut Motility

Cajal Cell Counts are Important Predictors of Outcomes in Drug Refractory Gastroparesis Patients With Neurostimulation.

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Cajal Cell Counts are Important Predictors of Outcomes in Drug Refractory Gastroparesis Patients With Neurostimulation.

J Clin Gastroenterol. 2018 Apr 18;:

Authors: Omer E, Kedar A, Nagarajarao HS, Nikitina Y, Vedanarayanan V, Subramony C, Lahr CJ, Abell TL

Abstract
BACKGROUND AND AIMS: Cajal cells serve as the pacemaker cells of the gastrointestinal tract and regulates peristalsis. On the baisis of that fact, it has been hypothesized that a decrease in Cajal cells can lead to gastroparesis and other motility issues. Treatment with medications has a limited efficacy and most resort to gastric electrical stimulation (GES) devices for symptomatic relief. We believe that the number of Cajal cells present is directly proportional to symptomatic relief with GES.
MATERIALS AND METHODS: Twenty-three (white female) subjects were recruited from the gastric motility clinic University of Mississipi for this study with the criteria of drug refractory gastropersis. Symptoms were measured using Likert scale and gastric emptying times were measured pre-GES and post-GES. Serosal electrogram measurements were recorded during surgical placement of permanent electrical stimulator under various modes. Cajal cell count scoring via immunohistochemistry were performed during the implantaion of the GES.
RESULTS: The data were grouped in 2 categories based on the Cajal cells that is ≥2.00 and <2.00. Subjects with higher Cajal cells reported a statiscially improvement in gastroperesis symptoms. Significant differences were also noted in the first hour gastric emptying study. The mean group difference is 17.5 (95% confidence interval, 1.41-33.58; P=0.035). Serosal amplitude differences were noted being significantly higher in the group with ≥2 cajal cells.
CONCLUSIONS: Electrograms obtained after GES demonstrates immediate improvement in gastric electrical activity and gastroparesis symptoms in patients with relatively higher Cajal cell counts when compared with patients with extensive loss of Cajal cells.

PMID: 29672439 [PubMed - as supplied by publisher]

Etiology and functional validation of gastrointestinal motility dysfunction in a zebrafish model of CHARGE syndrome.

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Etiology and functional validation of gastrointestinal motility dysfunction in a zebrafish model of CHARGE syndrome.

FEBS J. 2018 Apr 16;:

Authors: Cloney K, Steele SL, Stoyek MR, Croll RP, Smith FM, Prykhozhij SV, Brown MM, Midgen C, Blake K, Berman JN

Abstract
CHARGE syndrome is linked to autosomal dominant mutations in the CHD7 gene and results in a number of physiological and structural abnormalities, including heart defects, hearing and vision loss and gastrointestinal (GI) problems. Of these challenges, GI problems have a profound impact throughout an individual's life, resulting in increased morbidity and mortality. A homologue of CHD7 has been identified in the zebrafish, the loss of which recapitulates many of the features of the human disease. Using a morpholino chd7 knockdown model complemented by a chd7 null mutant zebrafish line, we examined GI structure, innervation, and motility in larval zebrafish. Loss of chd7 resulted in physically smaller GI tracts with normal epithelial and muscular histology, but decreased and disorganized vagal projections, particularly in the foregut. chd7 morphant larvae had significantly less ability to empty their GI tract of gavaged fluorescent beads, and this condition was only minimally improved by the prokinetic agents, domperidone and erythromycin, in keeping with mixed responses to these agents in patients with CHARGE syndrome. The conserved genetics and transparency of the zebrafish have provided new insights into the consequences of chd7 gene dysfunction on the GI system and cranial nerve patterning. These findings highlight the opportunity of the zebrafish to serve as a preclinical model for studying compounds that may improve GI motility in individuals with CHARGE syndrome. This article is protected by copyright. All rights reserved.

PMID: 29660852 [PubMed - as supplied by publisher]

Bioactive Immune Components of Anti-Diarrheagenic Enterotoxigenic Escherichia coli Hyperimmune Bovine Colostrum Products.

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Bioactive Immune Components of Anti-Diarrheagenic Enterotoxigenic Escherichia coli Hyperimmune Bovine Colostrum Products.

Clin Vaccine Immunol. 2017 Aug;24(8):

Authors: Sears KT, Tennant SM, Reymann MK, Simon R, Konstantopoulos N, Blackwelder WC, Barry EM, Pasetti MF

Abstract
Diarrhea is a common illness among travelers to resource-limited countries, the most prevalent attributable agent being enterotoxigenic Escherichia coli (ETEC). At this time, there are no vaccines licensed specifically for the prevention of ETEC-induced traveler's diarrhea (TD), and this has propelled investigation of alternative preventive methods. Colostrum, the first milk expressed after birthing, is rich in immunoglobulins and innate immune components for protection of newborns against infectious agents. Hyperimmune bovine colostrum (HBC) produced by immunization of cows during gestation (and containing high levels of specific antibodies) is a practical and effective prophylactic tool against gastrointestinal illnesses. A commercial HBC product, Travelan, is available for prevention of ETEC-induced diarrhea. Despite its demonstrated clinical efficacy, the underlying immune components and antimicrobial activity that contribute to protection remain undefined. We investigated innate and adaptive immune components of several commercial HBC products formulated to reduce the risk of ETEC-induced diarrhea, including Travelan and IMM-124E, a newer product that has broader gastrointestinal health benefits. The immune components measured included total and ETEC-specific IgG, total IgA, cytokines, growth factors, and lactoferrin. HBC products contained high levels of IgG specific for multiple ETEC antigens, including O-polysaccharide 78 and colonization factor antigen I (CFA/I) present in the administered vaccines. Antimicrobial activity was measured in vitro using novel functional assays. HBC greatly reduced ETEC motility in soft agar and exhibited bactericidal activity in the presence of complement. We have identified immune components and antimicrobial activity potentially involved in the prevention of ETEC infection by HBC in vivo.

PMID: 28637804 [PubMed - indexed for MEDLINE]

Esophageal Atresia: Future Directions for Research on the Digestive Tract.

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Esophageal Atresia: Future Directions for Research on the Digestive Tract.

Eur J Pediatr Surg. 2017 Aug;27(4):306-312

Authors: Rayyan M, Rommel N, Tack J, Deprest J, Allegaert K

Abstract
Esophageal atresia (EA) is a congenital malformation defined by the discontinuity of the esophagus occurring in 2.4 in 10,000 births. As survival rates are high, the significant medical morbidity became more relevant. Short-term and long-term morbidities involve the respiratory and gastrointestinal system in the majority of the patients. The impact of this morbidity seems large enough to inspire researchers to develop experimental animal models that may help understanding the pathogenesis and pathophysiology. These models can also be used to explore potential surgical therapies. We reviewed the clinical and experimental literature focusing on esophageal morbidity in EA. Although the consequences of esophageal motility disorders are very relevant in the clinical setting, research remains largely underexplored. Consequently, we suggest integrating motility function assessment in the existing research models.

PMID: 27533315 [PubMed - indexed for MEDLINE]

The Use of Pyridostigmine in a Child With Chronic Intestinal Pseudo-Obstruction.

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The Use of Pyridostigmine in a Child With Chronic Intestinal Pseudo-Obstruction.

Pediatrics. 2018 Apr;141(Suppl 5):S404-S407

Authors: Choudhury A, Rahyead A, Kammermeier J, Mutalib M

Abstract
Chronic intestinal pseudo-obstruction is a rare disorder that affects the motility of the gastrointestinal tract. It results in acute or subacute intestinal obstruction symptoms in the absence of mechanical lesion. It can lead to intestinal failure in children with significant strain on nutrition, growth, and development. There is no universally agreed protocol for management of chronic intestinal pseudo-obstruction in children, and there is wide variation in clinical practice.

PMID: 29610160 [PubMed - in process]

Prospective evaluation of same day versus next day colon manometry results in children with medical refractory constipation.

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Prospective evaluation of same day versus next day colon manometry results in children with medical refractory constipation.

Neurogastroenterol Motil. 2017 Jul;29(7):

Authors: Arbizu RA, Nurko S, Heinz N, Amicangelo M, Rodriguez L

Abstract
BACKGROUND: We evaluated the change in colon manometry (CM) parameters and interpretation comparing results when the study is performed the same day after the motility catheter is placed under anesthesia or the following day.
METHODS: CM catheter was placed with colonoscopy under anesthesia and recorded on day 1 and repeated on day 2. Study parameters including motility index during fasting, post-prandial and post-Bisacodyl challenge phase; gastrocolonic response; number, presence and propagation of high amplitude propagating contractions (HAPCs); and, study interpretation were compared between both the days.
KEY RESULTS: Motility index (fasting, post-Bisacodyl phase, P<.05), HAPC number (10.1 vs 6.6, P=.01) and the proportion of patients having HAPCs (92% vs 70%, P=.002) was significantly higher on day 2 vs day 1. HAPC propagation improved on day 2 vs day 1 (fully propagated, 49% vs 37%; partially propagated, 43% vs 33%; absent 8% vs 30%). Study interpretation changed from day 1 to day 2. On day 1, 37% had a normal study and 63% had an abnormal study. On day 2, all patients with a normal study on day 1 remained normal, and patients with an abnormal study on day 1, 53% remained abnormal and 47% had a normal study.
CONCLUSIONS & INFERENCES: CM parameters are affected the day the catheter is placed with colonoscopy under anesthesia. The number, presence, and propagation of HAPCs were significantly higher/improved on day 2 compared to day 1. Overall, CM interpretation changed from abnormal to normal from day 1 to day 2 in 47% of the patients.

PMID: 28317231 [PubMed - indexed for MEDLINE]

Low dose naltrexone for induction of remission in Crohn's disease.

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Low dose naltrexone for induction of remission in Crohn's disease.

Cochrane Database Syst Rev. 2018 Apr 01;4:CD010410

Authors: Parker CE, Nguyen TM, Segal D, MacDonald JK, Chande N

Abstract
BACKGROUND: Crohn's disease is a transmural, relapsing inflammatory condition afflicting the digestive tract. Opioid signalling, long known to affect secretion and motility in the gut, has been implicated in the inflammatory cascade of Crohn's disease. Low dose naltrexone, an opioid antagonist, has garnered interest as a potential therapy.
OBJECTIVES: The primary objective was to evaluate the efficacy and safety of low dose naltrexone for induction of remission in Crohn's disease.
SEARCH METHODS: A systematic search of MEDLINE, Embase, PubMed, CENTRAL, and the Cochrane IBD Group Specialized Register was performed from inception to 15 January 2018 to identify relevant studies. Abstracts from major gastroenterology conferences including Digestive Disease Week and United European Gastroenterology Week and reference lists from retrieved articles were also screened.
SELECTION CRITERIA: Randomized controlled trials of low dose naltrexone (LDN) for treatment of active Crohn's disease were included.
DATA COLLECTION AND ANALYSIS: Data were analyzed on an intention-to-treat basis using Review Manager (RevMan 5.3.5). The primary outcome was induction of clinical remission defined by a Crohn's disease activity index (CDAI) of < 150 or a pediatric Crohn's disease activity index (PCDAI) of < 10. Secondary outcomes included clinical response (70- or 100-point decrease in CDAI from baseline), endoscopic remission or response, quality of life, and adverse events as defined by the included studies. Risk ratios (RR) and 95% confidence intervals (CI) were calculated for dichotomous outcomes. The methodological quality of included studies was evaluated using the Cochrane risk of bias tool. The overall quality of the evidence supporting the primary outcome and selected secondary outcomes was assessed using the GRADE criteria.
MAIN RESULTS: Two studies were identified (46 participants). One study assessed the efficacy and safety of 12 weeks of LDN (4.5 mg/day) treatment compared to placebo in adult patients (N = 34). The other study assessed eight weeks of LDN (0.1 mg/kg, maximum 4.5 mg/day) treatment compared to placebo in pediatric patients (N = 12). The primary purpose of the pediatric study was to assess safety and tolerability. Both studies were rated as having a low risk of bias. The study in adult patients reported that 30% (5/18) of LDN treated patients achieved clinical remission at 12 weeks compared to 18% (3/16) of placebo patients, a difference that was not statistically significant (RR 1.48, 95% CI 0.42 to 5.24). The study in children reported that 25% of LDN treated patients achieved clinical remission (PCDAI < 10) compared to none of the patients in the placebo group, although it was unclear if this result was for the randomized placebo-controlled trial or for the open label extension study. In the adult study 70-point clinical response rates were significantly higher in those treated with LDN than placebo. Eighty-three per cent (15/18) of LDN patients had a 70-point clinical response at week 12 compared to 38% (6/16) of placebo patients (RR 2.22, 95% CI 1.14 to 4.32). The effect of LDN on the proportion of adult patients who achieved a 100-point clinical response was uncertain. Sixty-one per cent (11/18) of LDN patients achieved a 100-point clinical response compared to 31% (5/16) of placebo patients (RR 1.96, 95% CI 0.87 to 4.42). The proportion of patients who achieved endoscopic response (CDEIS decline > 5 from baseline) was significantly higher in the LDN group compared to placebo. Seventy-two per cent (13/18) of LDN patients achieved an endoscopic response compared to 25% (4/16) of placebo patients (RR 2.89; 95% CI 1.18 to 7.08). However, there was no statistically significant difference in the proportion of patients who achieved endoscopic remission. Endoscopic remission (CDEIS < 3) was achieved in 22% (4/18) of the LDN group compared to 0% (0/16) of the placebo group (RR 8.05; 95% CI 0.47 to 138.87). Pooled data from both studies show no statistically significant differences in withdrawals due to adverse events or specific adverse events including sleep disturbance, unusual dreams, headache, decreased appetite, nausea and fatigue. No serious adverse events were reported in either study. GRADE analyses rated the overall quality of the evidence for the primary and secondary outcomes (i.e. clinical remission, clinical response, endoscopic response, and adverse events) as low due to serious imprecision (sparse data).
AUTHORS' CONCLUSIONS: Currently, there is insufficient evidence to allow any firm conclusions regarding the efficacy and safety of LDN used to treat patients with active Crohn's disease. Data from one small study suggests that LDN may provide a benefit in terms of clinical and endoscopic response in adult patients with active Crohn's disease. Data from two small studies suggest that LDN does not increase the rate of specific adverse events relative to placebo. However, these results need to be interpreted with caution as they are based on very small numbers of patients and the overall quality of the evidence was rated as low due to serious imprecision. Further randomized controlled trials are required to assess the efficacy and safety of LDN therapy in active Crohn's disease in both adults and children.

PMID: 29607497 [PubMed - as supplied by publisher]

Curriculum for neurogastroenterology and motility training: A report from the joint ANMS-ESNM task force.

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Curriculum for neurogastroenterology and motility training: A report from the joint ANMS-ESNM task force.

Neurogastroenterol Motil. 2018 Mar 25;:e13341

Authors: Gyawali CP, Savarino E, Lazarescu A, Bor S, Patel A, Dickman R, Pressman A, Drewes AM, Rosen J, Drug V, Saps M, Novais L, Vazquez-Roque M, Pohl D, van Tilburg MAL, Smout A, Yoon S, Pandolfino J, Farrugia G, Barbara G, Roman S

Abstract
Although neurogastroenterology and motility (NGM) disorders are some of the most frequent disorders encountered by practicing gastroenterologists, a structured competency-based training curriculum developed by NGM experts is lacking. The American Neurogastroenterology and Motility Society (ANMS) and the European Society of Neurogastroenterology and Motility (ESNM) jointly evaluated the components of NGM training in North America and Europe. Eleven training domains were identified within NGM, consisting of functional gastrointestinal disorders, visceral hypersensitivity and pain pathways, motor disorders within anatomic areas (esophagus, stomach, small bowel and colon, anorectum), mucosal disorders (gastro-esophageal reflux disease, other mucosal disorders), consequences of systemic disease, consequences of therapy (surgery, endoscopic intervention, medications, other therapy), and transition of pediatric patients into adult practice. A 3-tiered training curriculum covering these domains is proposed here and endorsed by all NGM societies. Tier 1 NGM knowledge and training is expected of all gastroenterology trainees and practicing gastroenterologists. Tier 2 knowledge and training is appropriate for trainees who anticipate NGM disorder management and NGM function test interpretation being an important part of their careers, which may require competency assessment and credentialing of test interpretation skills. Tier 3 knowledge and training is undertaken by trainees interested in a dedicated NGM career and may be restricted to specific domains within the broad NGM field. The joint ANMS and ESNM task force anticipates that the NGM curriculum will streamline NGM training in North America and Europe and will lead to better identification of centers of excellence where Tier 2 and Tier 3 training can be accomplished.

PMID: 29577508 [PubMed - as supplied by publisher]

Pregnancy is possible on long-term home parenteral nutrition in patients with chronic intestinal failure: Results of a long term retrospective observational study.

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Pregnancy is possible on long-term home parenteral nutrition in patients with chronic intestinal failure: Results of a long term retrospective observational study.

Clin Nutr. 2017 08;36(4):1165-1169

Authors: Billiauws L, Armengol Debeir L, Poullenot F, Chambrier C, Cury N, Ceccaldi PF, Latour Beaudet E, Corcos O, Marinier E, Goulet O, Lerebours E, Joly F

Abstract
BACKGROUND & AIMS: Home parenteral nutrition (HPN) improves survival and quality of life in patients with chronic intestinal failure (IF). Few cases of pregnancy on HPN have been published. The aim of this study was to report pregnancy cases on long-term HPN in benign IF.
METHODS: This retrospective study included all pregnant patients on HPN from 4 HPN referral centers. Data on demographics, ongoing pathology, HPN type, maternal and newborn complications were collected.
RESULTS: From 1984 to 2014, 21 pregnancies occurred in 15 patients (short bowel syndrome (n = 11), motility disorders (n = 3), mucosal disease (n = 1)) of whom 14 occurred after 2010. Median follow-up was 12 years. Median HPN duration before pregnancy was 8 years. HPN was adapted monthly during pregnancy, with close monitoring and supplementations. Energy intake was regularly increased and median maternal weight gain was 10 kg. Median age at the first pregnancy was 27 years. In 55% of cases, the newborn was preterm. Maternal complications occurred in 67% of cases (mainly due to underlying disease or HPN complications). There were 3 post-partum hemorrhages and 6 hypotrophic newborns. Eighteen infants were healthy and 2 chronic intestinal pseudo-obstruction (CIPO) were suspected.
CONCLUSION: Our series, the largest reported to date, shows that pregnancy is possible in HPN patients but the complication rate is high. A specific support is necessary, particularly in CIPO patients. As pregnancies have increased over the last 15 years, physicians practicing in HPN referral centers should be aware of the need for implementing a specific multidisciplinary monitoring in HPN patients considering pregnancy.

PMID: 27624996 [PubMed - indexed for MEDLINE]

Paediatric Intestinal Pseudo-Obstruction: Evidence and Consensus-Based Recommendations from an ESPGHAN-Led Expert Group.

Paediatric Intestinal Pseudo-Obstruction: Evidence and Consensus-Based Recommendations from an ESPGHAN-Led Expert Group.

J Pediatr Gastroenterol Nutr. 2018 Mar 22;:

Authors: Thapar N, Saliakellis E, Benninga MA, Borrelli O, Curry J, Faure C, De Giorgio R, Gupte G, Knowles CH, Staiano A, Vandenplas Y, Di Lorenzo C

Abstract
OBJECTIVES: Chronic intestinal pseudo-obstructive (CIPO) conditions are considered the most severe disorders of gut motility. They continue to present significant challenges in clinical care despite considerable recent progress in our understanding of pathophysiology, resulting in unacceptable levels of morbidity and mortality. Major contributors to the disappointing lack of progress in paediatric CIPO include a dearth of clarity and uniformity across all aspects of clinical care from definition and diagnosis to management. In order to assist medical care providers in identifying, evaluating and managing children with CIPO, experts in this condition within the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition as well as selected external experts, were charged with the task of developing a uniform document of evidence- and consensus-based recommendations.
METHODS: Ten clinically relevant questions addressing terminology, diagnostic, therapeutic, and prognostic topics were formulated. A systematic literature search was performed from inception to June 2017 using a number of established electronic databases as well as repositories. The approach of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was applied to evaluate outcome measures for the research questions. Levels of evidence and quality of evidence were assessed using the classification system of the Oxford Centre for Evidence-Based Medicine (diagnosis) and the GRADE system (treatment). Each of the recommendations were discussed, finalized and voted upon using the nominal voting technique to obtain consensus.
RESULTS: This evidence- and consensus- based position paper provides recommendations specifically for chronic intestinal pseudo-obstruction in infants and children. It proposes these be termed paediatric intestinal pseudo-obstructive (PIPO) disorders to distinguish them from adult onset CIPO. The manuscript provides guidance on the diagnosis, evaluation, and treatment of children with PIPO in an effort to standardise the quality of clinical care and improve short and long-term outcomes. Key recommendations include the development of specific diagnostic criteria for PIPO, red flags to alert clinicians to the diagnosis and guidance on the use of available investigative modalities. The group advocates early collaboration with expert centres where structured diagnosis and management is guided by a multi-disciplinary team, and include targeted nutritional, medical and surgical interventions as well as transition to adult services.
CONCLUSIONS: This document is intended to be used in daily practice from the time of first presentation and definitive diagnosis PIPO through to the complex management and treatment interventions such as intestinal transplantation. Significant challenges remain to be addressed through collaborative clinical and research interactions.

PMID: 29570554 [PubMed - as supplied by publisher]

Deletion of choline acetyltransferase in enteric neurons results in postnatal intestinal dysmotility and dysbiosis.

Deletion of choline acetyltransferase in enteric neurons results in postnatal intestinal dysmotility and dysbiosis.

FASEB J. 2018 Mar 23;:fj201701474RR

Authors: Johnson CD, Barlow-Anacker AJ, Pierre JF, Touw K, Erickson CS, Furness JB, Epstein ML, Gosain A

Abstract
Acetylcholine (ACh)-synthesizing neurons are major components of the enteric nervous system (ENS). They release ACh and peptidergic neurotransmitters onto enteric neurons and muscle. However, pharmacological interrogation has proven inadequate to demonstrate an essential role for ACh. Our objective was to determine whether elimination of ACh synthesis during embryogenesis alters prenatal viability, intestinal function, the neurotransmitter complement, and the microbiome. Conditional deletion of choline acetyltransferase ( ChAT), the ACh synthetic enzyme, in neural crest-derived neurons ( ChAT-Null) was performed. Survival, ChAT activity, gut motility, and the microbiome were studied. ChAT was conditionally deleted in ENS neural crest-derived cells. Despite ChAT absence, mice were born live and survived the first 2 wk. They failed to gain significant weight in the third postnatal week, dying between postnatal d 18 and 30. Small intestinal transit of carmine red was 50% slower in ChAT-Nulls vs. WT and ChAT- Het. The colons of many neonatal ChAT-Null mice contained compacted feces, suggesting dysmotility. Microbiome analysis revealed dysbiosis in ChAT-Null mice. Developmental deletion of ChAT activity in enteric neurons results in proximal gastrointestinal tract dysmotility, critically diminished colonic transit, failure to thrive, intestinal dysbiosis, and death. ACh is necessary for sustained gut motility and survival of neonatal mice after weaning.-Johnson, C. D., Barlow-Anacker, A. J., Pierre, J. F., Touw, K., Erickson, C. S., Furness, J. B., Epstein, M. L., Gosain, A. Deletion of choline acetyltransferase in enteric neurons results in postnatal intestinal dysmotility and dysbiosis.

PMID: 29570391 [PubMed - as supplied by publisher]

Artifact Rejection Methodology Enables Continuous, Noninvasive Measurement of Gastric Myoelectric Activity in Ambulatory Subjects.

Artifact Rejection Methodology Enables Continuous, Noninvasive Measurement of Gastric Myoelectric Activity in Ambulatory Subjects.

Sci Rep. 2018 Mar 22;8(1):5019

Authors: Gharibans AA, Smarr BL, Kunkel DC, Kriegsfeld LJ, Mousa HM, Coleman TP

Abstract
The increasing prevalence of functional and motility gastrointestinal (GI) disorders is at odds with bottlenecks in their diagnosis, treatment, and follow-up. Lack of noninvasive approaches means that only specialized centers can perform objective assessment procedures. Abnormal GI muscular activity, which is coordinated by electrical slow-waves, may play a key role in symptoms. As such, the electrogastrogram (EGG), a noninvasive means to continuously monitor gastric electrical activity, can be used to inform diagnoses over broader populations. However, it is seldom used due to technical issues: inconsistent results from single-channel measurements and signal artifacts that make interpretation difficult and limit prolonged monitoring. Here, we overcome these limitations with a wearable multi-channel system and artifact removal signal processing methods. Our approach yields an increase of 0.56 in the mean correlation coefficient between EGG and the clinical "gold standard", gastric manometry, across 11 subjects (p < 0.001). We also demonstrate this system's usage for ambulatory monitoring, which reveals myoelectric dynamics in response to meals akin to gastric emptying patterns and circadian-related oscillations. Our approach is noninvasive, easy to administer, and has promise to widen the scope of populations with GI disorders for which clinicians can screen patients, diagnose disorders, and refine treatments objectively.

PMID: 29568042 [PubMed - in process]

Upregulation of MiR-369-3p suppresses cell migration and proliferation by targeting SOX4 in Hirschsprung's disease.

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Upregulation of MiR-369-3p suppresses cell migration and proliferation by targeting SOX4 in Hirschsprung's disease.

J Pediatr Surg. 2017 Aug;52(8):1363-1370

Authors: Pan W, Yu H, Zheng B, Gao Y, Li P, Huang Q, Xie C, Ge X

Abstract
BACKGROUND: Hirschsprung disease (HSCR) is a congenital digestive disease in the new born. miR-369-3p has been reported to be involved in many human diseases. However, the relationship between miR-369-3p and HSCR remains largely unknown.
METHODS: In this study, qRT-PCR was used to detect the relative expression of miR-369-3p in 60 HSCR bowel tissue samples and 47 matched controls. Bioinformatic analysis and dual-luciferase reporter assay were performed to evaluate the target for miR-369-3p. Cell Counting Kit-8 (CCK-8) assay, Transwell assay, wound healing assay and flow cytometry were employed to investigate the biological function of miR-369-3p in human SH-SY5Y and 293T cell lines.
RESULTS: We found that ganglion cell numbers were remarkably reduced while miR-369-3p was significantly upregulated in HSCR tissues compared to that in adjacent normal tissues (P<0.01). Dual-luciferase reporter assay showed that the 3'-UTR of SOX4 was a direct target to miR-369-3p. Moreover, an increased level of miR-369-3p was inversely correlated with decreased levels of SOX4 mRNA and protein (P<0.05, respectively). Dysregulation of miR-369-3p and SOX4 significantly suppressed cell proliferation and migration in SH-SY5Y and 293T cell lines in vitro (P<0.05, respectively).
CONCLUSION: Our study demonstrates that aberrant expression of miR-369-3p might play a crucial role in the development HSCR by regulating SOX4 expression, which may infer that it is an effective diagnostic target in the pathogenesis of HSCR, but investigation is still needed to explore the underlying mechanism.

PMID: 28412032 [PubMed - indexed for MEDLINE]

The digestive tract as the origin of systemic inflammation.

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The digestive tract as the origin of systemic inflammation.

Crit Care. 2016 Oct 18;20(1):279

Authors: de Jong PR, González-Navajas JM, Jansen NJ

Abstract
Failure of gut homeostasis is an important factor in the pathogenesis and progression of systemic inflammation, which can culminate in multiple organ failure and fatality. Pathogenic events in critically ill patients include mesenteric hypoperfusion, dysregulation of gut motility, and failure of the gut barrier with resultant translocation of luminal substrates. This is followed by the exacerbation of local and systemic immune responses. All these events can contribute to pathogenic crosstalk between the gut, circulating cells, and other organs like the liver, pancreas, and lungs. Here we review recent insights into the identity of the cellular and biochemical players from the gut that have key roles in the pathogenic turn of events in these organ systems that derange the systemic inflammatory homeostasis. In particular, we discuss the dangers from within the gastrointestinal tract, including metabolic products from the liver (bile acids), digestive enzymes produced by the pancreas, and inflammatory components of the mesenteric lymph.

PMID: 27751165 [PubMed - indexed for MEDLINE]

CHARGE syndrome gastrointestinal involvement: from mouth to anus.

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CHARGE syndrome gastrointestinal involvement: from mouth to anus.

Clin Genet. 2017 Jul;92(1):10-17

Authors: Hudson A, Macdonald M, Friedman JN, Blake K

Abstract
CHARGE syndrome is an autosomal dominant disorder that occurs as a result of a heterozygous loss-of-function mutation in the chromodomain helicase DNA-binding (CHD7) gene, which is important for neural crest cell formation. Gastrointestinal (GI) symptoms and feeding difficulties are highly prevalent but are often a neglected area of diagnosis, treatment, and research. Cranial nerve dysfunction, craniofacial abnormalities, and other physical manifestations of this syndrome lead to gut dysmotility, sensory impairment, and oral-motor function abnormalities. Over 90% of children need tube feeding early in their life and many experience weak sucking/chewing, gastroesophageal reflux disease (GERD), and aspiration. The mainstay of treatment thus far has consisted of feeding therapy, GERD medications, Nissen fundoplication, gastrostomy/jejunostomy, and food texture limitation. Owing to the multitude of severe medical issues associated with this genetic disorder, GI involvement is often overlooked. Here, we report on five patients with CHARGE syndrome who manifested a range of severe GI and feeding difficulties.

PMID: 28155231 [PubMed - indexed for MEDLINE]

Duhamel operation for children with distal colonic dysmotility.

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Duhamel operation for children with distal colonic dysmotility.

Pediatr Surg Int. 2017 Aug;33(8):861-868

Authors: Tan YW, Borrelli O, Lindley K, Thapar N, Curry J

Abstract
PURPOSE: To report outcomes of children with constipation refractory to medical management and manometrically proven distal colonic dysmotility, managed with rectosigmoidectomy followed by Duhamel operation (Duhamel).
METHODS: Children who underwent a Duhamel from 2009 onwards for intractable constipation and left colonic dysmotility were retrospectively reviewed. The primary end point was resolution of constipation, and secondary end point was postoperative complications. Continuous data were median (range).
RESULTS: 11 patients (4 males) had Duhamel at 11 years (5-16) with constipation started from 2 years (1-8). Hirschsprung's disease was excluded. All Duhamels were performed with a covering ileostomy: 9 following a Hartmann procedure, one following a previously failed reversal of Hartmann, and one Duhamel performed with a pre-existing ileostomy. All ileostomies were subsequently closed. Median resection length was 22 cm (11-31). Length of stay was 8 days (5-23). Follow-up was 5 years (0.5-7). Age at final review was 15 years (10-18). Resolution of constipation occurred in nine patients (4 required antegrade continence enemas (ACE), 5 with laxative); two had persistent constipation and faecal incontinence despite ACE, ultimately requiring an ileostomy. Two postoperative small bowel obstructions required laparotomy.
CONCLUSION: Duhamel performed in children with manometrically proven distal colonic dysmotility yielded 82% resolution of refractory constipation; half of them subsequently needed ACE.

PMID: 28616722 [PubMed - indexed for MEDLINE]

Varied facets of rectal atresia and rectal stenosis.

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Varied facets of rectal atresia and rectal stenosis.

Pediatr Surg Int. 2017 Aug;33(8):829-836

Authors: Sharma S, Gupta DK

Abstract
Rectal atresia (RA) and rectal stenosis (RS) are rare anomalies with varied treatment options. A thorough literature review was done on reported cases/series of RA and RS. Based on evidence from cases managed over last 15 years, new insights into embryology were hypothesized. A comprehensive review was compiled with updated knowledge on diagnosis and management. RA is classified into five types I: II: III: IV: V as RS: RA with septal defect: RA with a fibrous cord between two atretic ends: RA with a gap: Multiple RA and/or RS. Current definitive surgical repair of these anomalies preserves the anal canal, dentate line, and sphincter complex. Most neonates with RA undergo sigmoid colostomy except few with RS who can rarely decompress adequately. Membranous RS and septal RA may seldom respond to dilatation or be amenable to transanal repair. Posterior sagittal anorectoplasty with an end-to-end/side repair is recommended for RA and most intramural RS. RS may be associated with a presacral mass and colonic/rectal motility disorders. The expected postoperative outcome is good if the normally developed anal sphincter complex is retained undamaged. Early recognition of the type of anomaly is necessary for appropriate management.

PMID: 28601898 [PubMed - indexed for MEDLINE]

Patient Health Communication Mediating Effects Between Gastrointestinal Symptoms and Gastrointestinal Worry in Pediatric Inflammatory Bowel Disease.

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Patient Health Communication Mediating Effects Between Gastrointestinal Symptoms and Gastrointestinal Worry in Pediatric Inflammatory Bowel Disease.

Inflamm Bowel Dis. 2017 May;23(5):704-711

Authors: Varni JW, Shulman RJ, Self MM, Saeed SA, Patel AS, Nurko S, Neigut DA, Saps M, Zacur GM, Dark CV, Bendo CB, Pohl JF

Abstract
BACKGROUND: To investigate the effects of patient health communication regarding their inflammatory bowel disease (IBD) to their health care providers and significant others in their daily life as a mediator in the relationship between gastrointestinal symptoms and gastrointestinal worry in pediatric patients.
METHODS: The Pediatric Quality of Life Inventory Gastrointestinal Symptoms, Gastrointestinal Worry, and Communication Scales, and Pediatric Quality of Life Inventory 4.0 Generic Core Scales were completed in a 9-site study by 252 pediatric patients with IBD. Gastrointestinal Symptoms Scales measuring stomach pain, constipation, or diarrhea and patient communication were tested for bivariate and multivariate linear associations with Gastrointestinal Worry Scales specific to patient worry about stomach pain or bowel movements. Mediational analyses were conducted to test the hypothesized mediating effects of patient health communication as an intervening variable in the relationship between gastrointestinal symptoms and gastrointestinal worry.
RESULTS: The predictive effects of gastrointestinal symptoms on gastrointestinal worry were mediated in part by patient health communication with health care providers/significant others in their daily life. In predictive models using multiple regression analyses, the full conceptual model of demographic variables, gastrointestinal symptoms (stomach pain, constipation, or diarrhea), and patient communication significantly accounted for 46, 43, and 54 percent of the variance in gastrointestinal worry (all Ps < 0.001), respectively, reflecting large effect sizes.
CONCLUSIONS: Patient health communication explains in part the effects of gastrointestinal symptoms on gastrointestinal worry in pediatric patients with IBD. Supporting patient disease-specific communication to their health care providers and significant others may improve health-related quality of life for pediatric patients with IBD.

PMID: 28394807 [PubMed - indexed for MEDLINE]

Postnatal human enteric neuronal progenitors can migrate, differentiate, and proliferate in embryonic and postnatal aganglionic gut environments.

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Postnatal human enteric neuronal progenitors can migrate, differentiate, and proliferate in embryonic and postnatal aganglionic gut environments.

Pediatr Res. 2017 May;81(5):838-846

Authors: Cheng LS, Hotta R, Graham HK, Belkind-Gerson J, Nagy N, Goldstein AM

Abstract
BACKGROUND: Enteric neural stem/progenitor cells (ENSCs) offer an innovative approach to treating Hirschsprung disease (HSCR) and other enteric neuropathies. However, postnatal-derived human ENSCs have not been thoroughly characterized and their behavior in the embryonic and postnatal intestinal environment is unknown.
METHODS: ENSCs were isolated from the intestines of 25 patients undergoing bowel resection, including 7 children with HSCR. Neuronal differentiation and proliferation of ENSCs from submucosal and myenteric plexuses from patients with and without HSCR were characterized. ENSC migration and differentiation were studied following transplantation into embryonic chick neural crest, embryonic chick hindgut, and postnatal mouse aganglionic colon.
RESULTS: The proliferative and neurogenic potential of ENSCs from HSCR intestine is equivalent to that of non-HSCR controls. Similarly, no difference was observed between myenteric- and submucosal-derived ENSCs. Postnatal ENSCs transplanted to embryonic neural crest pathways and to aneural hindgut migrate normally and differentiate into appropriate neural crest-derived cell types. ENSCs in postnatal mouse aganglionic colon differentiate into neurons and glia both ex vivo and in vivo.
CONCLUSIONS: ENSCs isolated from the postnatal intestine of patients with and without HSCR can behave like embryonic neural crest-derived cells. These results support the feasibility of cell-based therapy for future treatment of neurointestinal disease.

PMID: 28060794 [PubMed - indexed for MEDLINE]

Diabetes-induced colonic slow transit mediated by the up-regulation of PDGFRα+ cells/SK3 in streptozotocin-induced diabetic mice.

Diabetes-induced colonic slow transit mediated by the up-regulation of PDGFRα+ cells/SK3 in streptozotocin-induced diabetic mice.

Neurogastroenterol Motil. 2018 Mar 09;:

Authors: Song NN, Lu HL, Lu C, Tong L, Huang SQ, Huang X, Chen J, Kim YC, Xu WX

Abstract
BACKGROUND: A major complication related to gastrointestinal (GI) symptoms in diabetic patients is chronic constipation. Constipation has serious negative impacts on quality of life; however, without a comprehensive understanding of the disease, currently available treatments cannot provide a cure. Platelet-derived growth factor receptor alpha-positive cells (PDGFRα+ cells), which form the SIP syncytium with interstitial cells of Cajal and smooth muscle cells, play important roles in GI motility. In the present study, the contributions of PDGFRα+ cells to diabetes-induced colonic slow transit were investigated in streptozotocin (STZ)-induced diabetic mice.
METHODS: Western blotting, quantitative PCR, contractile experiments, and intracellular recording were used in the present study.
KEY RESULTS: The results demonstrated that the colon length was increased in STZ-treated mice. The colonic transit of artificial fecal pellets in vitro was significantly delayed in STZ-treated mice. The mRNA and protein expression of PDGFRα, small-conductance Ca2+ -activated K channels (SK3), and P2Y1 receptors were increased in the colons of STZ-treated mice. In contractile experiments, the colonic smooth muscles were more sensitive to the SK3 agonist and antagonist (CyPPA and apamin) and the P2Y1 agonist and antagonist (MRS2365 and MRS2500) in STZ-treated mice. Intracellular recordings showed the responses of membrane potentials in colonic smooth muscle cells to CyPPA, apamin, MRS2365, and MRS2500 were more sensitive in STZ-treated mice. The electric field stimulation-induced P2Y1/SK3-dependent fast inhibitory junctional potentials (fIJPs) of colonic smooth muscles were more significantly hyperpolarized in STZ-treated mice.
CONCLUSIONS AND INFERENCES: These results suggest that the purinergic neurotransmitters/P2Y1/SK3 signaling pathway is up-regulated in the diabetic colons, thereby mediating diabetes-induced colonic slow transit.

PMID: 29521017 [PubMed - as supplied by publisher]

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