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Aliyu A, Dellschaft N, Hoad C, Williams H, Gaudoin E, Sulaiman S, Crooks C, Gowland P, Aran A, Lange R, Bois De Fer B, Corsetti M, Marciani L, Spiller R. Magnetic Resonance Imaging Reveals Novel Insights into the Dual Mode of Action of Bisacodyl: A Randomized, Placebo-controlled Trial in Constipation. Clin Pharmacol Ther 2025; 117:1284-1291. [PMID: 39679695 PMCID: PMC11993282 DOI: 10.1002/cpt.3532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 12/02/2024] [Indexed: 12/17/2024]
Abstract
Bisacodyl is a widely used laxative that stimulates both motility and secretion. Our aim was to exploit the unique capabilities of MRI to define bisacodyl's mode of action. Two placebo-controlled cross-over trials were performed, one using a single dose of Bisacodyl 5 mg while the second dosed daily for 3 consecutive days. Serial MRI was performed every 75 minutes. Primary endpoint: ascending colon water content as assessed by T1AC AUC300-450 minutes. Secondary endpoints included: small bowel water content, whole gut transit time (WGTT), colonic volumes, stool frequency, and consistency using Bristol Stool Form Score (BSFS). Exploratory endpoints: changes in the serial segmental volumes were quantified from the number of "mass movements" defined as episodes when segmental volume change from the previous scan was > 20% of baseline volume. We also measure the time to defecate after dosing. After 3 days of bisacodyl, ascending colon water content (T1) was 62% greater than after placebo, mean difference T1 AUC300-450 minutes 50.2 (61.0) sec.min, 95% CI (9.2, 91.2), P = 0.02, while after a single dose difference was only 11% (P = 0.58). Both single and repeated doses shortened WGTT (P < 0.049) and time to defecate (P 0.01). Only repeated doses significantly increased small bowel water content (P < 0.03), the number of "mass movements" (P = 0.048), bowel frequency (P = 0.006), and BSFS (P = 0.03). Repeated, compared to single dosing of Bisacodyl, additionally increases small bowel and colon water content and increases the number of "mass movements" thereby increasing its laxative effect. MRI is a non-invasive, patient-acceptable technique for evaluating drugs which alter secretion and/or motility.
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Affiliation(s)
- Abdulsalam Aliyu
- Nottingham NIHR Research CentreUniversity of NottinghamNottinghamUK
- School of MedicineUniversity of NottinghamNottinghamUK
| | - Neele Dellschaft
- Sir Peter Mansfield Imaging CentreUniversity of NottinghamNottinghamUK
| | - Caroline Hoad
- Sir Peter Mansfield Imaging CentreUniversity of NottinghamNottinghamUK
| | - Hannah Williams
- Sir Peter Mansfield Imaging CentreUniversity of NottinghamNottinghamUK
| | - Emily Gaudoin
- Sir Peter Mansfield Imaging CentreUniversity of NottinghamNottinghamUK
| | | | - Colin Crooks
- Nottingham NIHR Research CentreUniversity of NottinghamNottinghamUK
- School of MedicineUniversity of NottinghamNottinghamUK
| | - Penny Gowland
- Sir Peter Mansfield Imaging CentreUniversity of NottinghamNottinghamUK
| | | | | | | | - Maura Corsetti
- Nottingham NIHR Research CentreUniversity of NottinghamNottinghamUK
- School of MedicineUniversity of NottinghamNottinghamUK
| | - Luca Marciani
- Nottingham NIHR Research CentreUniversity of NottinghamNottinghamUK
- School of MedicineUniversity of NottinghamNottinghamUK
| | - Robin Spiller
- Nottingham NIHR Research CentreUniversity of NottinghamNottinghamUK
- School of MedicineUniversity of NottinghamNottinghamUK
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Manabe N, Fujita M, Haruma K. The Effectiveness of Transabdominal Ultrasonography in Managing Chronic Constipation in the Elderly, with a Focus on the Underlying Pathological Conditions. Diagnostics (Basel) 2025; 15:476. [PMID: 40002627 PMCID: PMC11854504 DOI: 10.3390/diagnostics15040476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 02/05/2025] [Accepted: 02/10/2025] [Indexed: 02/27/2025] Open
Abstract
Chronic constipation is more common in the elderly and associated with numerous diseases. For the diagnosis of chronic constipation in the elderly, it is essential to exclude constipation secondary to colorectal cancer or other causes. Chronic constipation in the elderly also often requires lifestyle modifications, as well as drug treatments because of the involvement of pathologies such as reduced colonic transport capacity and rectal hyposensitivity. Therefore, it is extremely important to evaluate the pathophysiology of both the colon and the rectum. Transabdominal ultrasonography (TUS) is a key technique for providing comprehensive medical care and allows simultaneous functional assessment and exclusion of organic diseases related to constipation such as colorectal cancer. Although several studies have reported the clinical utility of TUS for chronic constipation, which includes its simplicity, noninvasiveness, and low cost, the majority were in children. Thus, there are limited studies in adults. Herein, we review the utility of TUS for indirect assessment of colonic transit time using several TUS parameters that can be applied clinically, as well as treatment options for chronic constipation. The constipation index (i.e., mean transverse diameter of the colon), assessed by TUS, is a useful indirect indicator of colonic transit time. If the constipation index is <21.2, increased fiber or treatment with osmotic agents should be used. If the constipation index is ≥21.2, then the ratio of the left to the right lateral colonic diameters should be evaluated. If this value is ≥0.5, a secretagogue or bile acid transporter inhibitor should be administered. It is noteworthy that nursing care is becoming increasingly important in Japan's super-aging society. A significant proportion of nursing care is provided to patients with chronic constipation, a cohort that is predicted to grow in the future. In these patients, fecal masses often remain in the rectum, which may require an enema or stool extraction. Therefore, it is important to assess both the presence of feces in the rectum and the consistency of the feces. Recently, portable ultrasound (US) devices equipped with artificial intelligence have been developed and used clinically for treatment of patients with chronic constipation in nursing care. Rectal findings using portable US devices can aid in selecting appropriate constipation treatments. Thus, portable US will likely become increasingly important as a next-generation examination device in nursing care. TUS (including portable US) is noninvasive, simple, and repeatable and will become a fundamental modality in the management of chronic constipation.
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Affiliation(s)
- Noriaki Manabe
- Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School, Okayama 700-8505, Japan
| | - Minoru Fujita
- Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School, Okayama 700-8505, Japan
| | - Ken Haruma
- Department of General Internal Medicine 2, Kawasaki Medical School, Okayama 700-8505, Japan
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Abstract
PURPOSE OF REVIEW The gastrocolonic response (GCR), is a physiologic increase in motor activity of the colon, which usually occurs within minutes following meal ingestion. Over the years several triggers that provoke GCR were recognized including gastric dilation, caloric intake, and fat component of the meal. The response is mediated by the vagal nerve and neurohumoral mechanisms, and it can be modified by several pharmacological factors. Assessment of GCR is part of high-resolution colonic manometry studies, performed in patients with suspected colonic dysmotility. This review highlights the physiologic basis of GCR as well as its clinical and diagnostic features and implementation in variable pathological conditions and clinical practice. RECENT FINDINGS GCR has a role in patients with constipation, diabetes, dumping syndrome, bowel hyper and hypomotility and irritable bowel syndrome. Novel sensory triggers for GCR were recently recognized. GCR is a physiological response which is evaluated during colonic manometry studies. Abnormal GCR is a marker of an underlying pathology, which can provide a potential target for treatment.
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Affiliation(s)
- Lev Dorfman
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, 45229, Cincinnati, OH, USA.
| | - Khalil El-Chammas
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, 45229, Cincinnati, OH, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Sherief Mansi
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, 45229, Cincinnati, OH, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Ajay Kaul
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, 45229, Cincinnati, OH, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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Ghusn W, Cifuentes L, Campos A, Sacoto D, De La Rosa A, Feris F, Calderon G, Gonzalez-Izundegui D, Stutzman J, Hurtado MD, Camilleri M, Acosta A. Association Between Food Intake and Gastrointestinal Symptoms in Patients With Obesity. GASTRO HEP ADVANCES 2022; 2:121-128. [PMID: 36741967 PMCID: PMC9894313 DOI: 10.1016/j.gastha.2022.07.019] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 07/25/2022] [Indexed: 06/18/2023]
Abstract
BACKGROUND AND AIMS Hunger, satiation, postprandial satiety, and hedonic eating constitute key food intake parameters. We aim to study whether these symptoms are associated with gastrointestinal symptoms (GIS) in patients with obesity. METHODS This is a cross-sectional study of patients with obesity. Patients completed the following validated biomarkers and questionnaires: hunger was measured via visual analog scale (100 mm) following a standard meal, satiation was measured via ad libitum meal (calories to fullness; kcal), postprandial satiety was measured via gastric emptying scintigraphy (T1/2; mins), and hedonic eating was measured via the Hospital Anxiety and Depression Scale questionnaire. Participants completed the abridged Bowel Disease Questionnaire to evaluate their GIS. We calculated the odds ratios (ORs) adjusted for sex, weight, and age between food intake parameters <25th or >75th percentile observed in a prior cohort of 450 participants with obesity and GIS. RESULTS A total of 274 participants (41 ± 10 [SD] years, 75% females, body mass index 39 ± 8 kg/m2) were included in the analysis. Increased hunger was associated with a lower prevalence of lumpy stools (OR = 0.18, P = .02). Satiation was associated with abdominal pain/discomfort (relieved by defecation [OR = 2.4, P = .02] or associated with change in stool consistency [OR = 2.92, P < .01]), loose/watery stools (OR = 2.09, P = .02), and bloating (OR = 2.49, P < .01). Abnormal postprandial satiety was associated with bloating (OR = 2.26, P < .01) and loose/watery stools (OR = 1.84, P = .04). Hedonic eating was associated with abdominal pain/discomfort with stool frequency change (OR = 2.4, P = .02), >3 bowel movements per day (OR = 1.93, P = .048), bloating (OR = 2.49, P = .01), abdominal pain after meals >1 per month (OR = 4.24, P < .01), and nausea >1 per week (OR = 4.51, P < .01). CONCLUSION Alterations in hunger, satiation, postprandial satiety, and hedonic eating are associated with GIS in patients with obesity.
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Affiliation(s)
- Wissam Ghusn
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Lizeth Cifuentes
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Alejandro Campos
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Daniel Sacoto
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Alan De La Rosa
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Fauzi Feris
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Gerardo Calderon
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Daniel Gonzalez-Izundegui
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Jessica Stutzman
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Maria Daniela Hurtado
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiology Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota
| | - Andres Acosta
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
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Paskaranandavadivel N, Lin AY, Cheng LK, Bissett I, Lowe A, Arkwright J, Mollaee S, Dinning PG, O'Grady G. ManoMap: an automated system for characterization of colonic propagating contractions recorded by high-resolution manometry. Med Biol Eng Comput 2021; 59:417-429. [PMID: 33496911 DOI: 10.1007/s11517-021-02316-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Accepted: 01/15/2021] [Indexed: 11/30/2022]
Abstract
RATIONALE Colonic high-resolution manometry (cHRM) is an emerging clinical tool for defining colonic function in health and disease. Current analysis methods are conducted manually, thus being inefficient and open to interpretation bias. OBJECTIVE The main objective of the study was to build an automated system to identify propagating contractions and compare the performance to manual marking analysis. METHODS cHRM recordings were performed on 5 healthy subjects, 3 subjects with diarrhea-predominant irritable bowel syndrome, and 3 subjects with slow transit constipation. Two experts manually identified propagating contractions, from five randomly selected 10-min segments from each of the 11 subjects (72 channels per dataset, total duration 550 min). An automated signal processing and detection platform was developed to compare its effectiveness to manually identified propagating contractions. In the algorithm, individual pressure events over a threshold were identified and were then grouped into a propagating contraction. The detection platform allowed user-selectable thresholds, and a range of pressure thresholds was evaluated (2 to 20 mmHg). KEY RESULTS The automated system was found to be reliable and accurate for analyzing cHRM with a threshold of 15 mmHg, resulting in a positive predictive value of 75%. For 5-h cHRM recordings, the automated method takes 22 ± 2 s for analysis, while manual identification would take many hours. CONCLUSIONS An automated framework was developed to filter, detect, quantify, and visualize propagating contractions in cHRM recordings in an efficient manner that is reliable and consistent.
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Affiliation(s)
- Niranchan Paskaranandavadivel
- Auckland Bioengineering Institute, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
- Department of Surgery, University of Auckland, Auckland, New Zealand.
| | - Anthony Y Lin
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Leo K Cheng
- Auckland Bioengineering Institute, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand
- Vanderbilt University, Nashville, TN, USA
| | - Ian Bissett
- Department of Surgery, University of Auckland, Auckland, New Zealand
- Auckland City Hospital, Auckland, New Zealand
| | - Andrew Lowe
- Institute of Biomedical Engineering, Auckland University of Technology, Auckland, New Zealand
| | - John Arkwright
- College of Science and Engineering, Flinders University, Adelaide, Australia
| | - Saeed Mollaee
- Auckland Bioengineering Institute, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand
| | - Phil G Dinning
- Departments of Gastroenterology & Surgery Flinders Medical Centre, Flinders University, Adelaide, Australia
| | - Gregory O'Grady
- Auckland Bioengineering Institute, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand
- Department of Surgery, University of Auckland, Auckland, New Zealand
- Auckland City Hospital, Auckland, New Zealand
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6
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Marek T, Mahan MA, Amrami KK, Blackburn PR, Caffes PL, Carter JM, Camilleri M, Spinner RJ. Expanding the phenotypic spectrum of lipomatosis of the sciatic nerve: Early-onset colonic diverticular disease. Neurogastroenterol Motil 2020; 32:e13917. [PMID: 32567170 DOI: 10.1111/nmo.13917] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 05/12/2020] [Accepted: 05/19/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND Lipomatosis of nerve (LN) is a complex peripheral nerve disorder characterized by fibrofatty nerve enlargement. MRI of this pathology is pathognomonic and obviates a diagnostic biopsy. Mutation in PIK3CA has been associated with LN cases with nerve-territory overgrowth which may occur in some cases. We evaluate an association of LN of the sciatic nerve and early-onset colonic diverticular disease and discuss the potential pathogenesis. METHODS Our institutional database was searched for LN cases. Available information of identified cases was reviewed, and cases with a confirmed diagnosis of LN affecting the lumbosacral plexus and/or sciatic nerve; available MRI of the affected nerve(s); and diverticular disease occurring in the area supplied by the nerve(s) affected by LN were further analyzed. PIK3CA mutation testing was performed on available tissue samples. RESULTS We identified 10 LN cases of lumbosacral plexus and/or sciatic nerve. Of these, three fulfilled our inclusion criteria. All three patients had concomitant colonic diverticular disease, diagnosed at a relatively young age. MRI studies of these cases showed LN involvement of the sacral nerves innervating the sigmoid colon. All three also had abnormal diagnostic workup including various GI tests and evidence of associated nerve-territory overgrowth. Colonic tissue samples for PIK3CA mutation were negative. CONCLUSION While the pathogenesis of the colonic diverticular disease is increasingly recognized as being multifactorial, our observations are consistent with the potential role of autonomic nervous system dysfunction affecting either the pelvic floor musculature, or the colon itself (or both) in a subset of patients with early-onset diverticular disease.
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Affiliation(s)
- Tomas Marek
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA.,First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Mark A Mahan
- Department of Neurologic Surgery, University of Utah, Salt Lake City, UT, USA
| | | | - Patrick R Blackburn
- Departments of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Patricia L Caffes
- Departments of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Jodi M Carter
- Departments of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | | | - Robert J Spinner
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA
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7
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Computational analysis of mechanical stress in colonic diverticulosis. Sci Rep 2020; 10:6014. [PMID: 32265489 PMCID: PMC7138845 DOI: 10.1038/s41598-020-63049-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Accepted: 03/18/2020] [Indexed: 12/15/2022] Open
Abstract
Diverticulosis results from the development of pouch-like structures, called diverticula, over the colon. The etiology of the disease is poorly understood resulting in a lack of effective treatment approaches. It is well known that mechanical stress plays a major role in tissue remodeling, yet its role in diverticulosis has not been studied. Here, we used computational mechanics to investigate changes in stress distribution engendered over the colon tissue by the presence of a pouch-like structure. The objectives of the study were twofold: (1) observe how stress distribution changes around a single pouch and (2) evaluate how stress elevation correlates with the size of the pouch. Results showed that high stresses are concentrated around the neck of a pouch, and their values and propagation increase with the size of the pouch neck rather than the pouch surface area. These findings suggest that stress distribution may change in diverticulosis and a vicious cycle may occur where pouch size increases due to stress elevation, which in turn elevates stress further and so on. Significant luminal pressure reduction would be necessary to maintain stress at normal level according to our results and therapeutic approaches aimed directly at reducing stress should rather be sought after.
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8
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Corsetti M, Costa M, Bassotti G, Bharucha AE, Borrelli O, Dinning P, Di Lorenzo C, Huizinga JD, Jimenez M, Rao S, Spiller R, Spencer NJ, Lentle R, Pannemans J, Thys A, Benninga M, Tack J. First translational consensus on terminology and definitions of colonic motility in animals and humans studied by manometric and other techniques. Nat Rev Gastroenterol Hepatol 2019; 16:559-579. [PMID: 31296967 PMCID: PMC7136172 DOI: 10.1038/s41575-019-0167-1] [Citation(s) in RCA: 104] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/30/2019] [Indexed: 12/19/2022]
Abstract
Alterations in colonic motility are implicated in the pathophysiology of bowel disorders, but high-resolution manometry of human colonic motor function has revealed that our knowledge of normal motor patterns is limited. Furthermore, various terminologies and definitions have been used to describe colonic motor patterns in children, adults and animals. An example is the distinction between the high-amplitude propagating contractions in humans and giant contractions in animals. Harmonized terminology and definitions are required that are applicable to the study of colonic motility performed by basic scientists and clinicians, as well as adult and paediatric gastroenterologists. As clinical studies increasingly require adequate animal models to develop and test new therapies, there is a need for rational use of terminology to describe those motor patterns that are equivalent between animals and humans. This Consensus Statement provides the first harmonized interpretation of commonly used terminology to describe colonic motor function and delineates possible similarities between motor patterns observed in animal models and humans in vitro (ex vivo) and in vivo. The consolidated terminology can be an impetus for new research that will considerably improve our understanding of colonic motor function and will facilitate the development and testing of new therapies for colonic motility disorders.
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Affiliation(s)
- Maura Corsetti
- NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Marcello Costa
- Human Physiology and Centre of Neuroscience, College of Medicine, Flinders University, Bedford Park, South Australia, Australia
| | - Gabrio Bassotti
- Department of Medicine, University of Perugia Medical School, Perugia, Italy
| | - Adil E Bharucha
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Osvaldo Borrelli
- Department of Paediatric Gastroenterology, Great Ormond Street Hospital for Sick Children, London, UK
| | - Phil Dinning
- Human Physiology and Centre of Neuroscience, College of Medicine, Flinders University, Bedford Park, South Australia, Australia
- Department of Gastroenterology and Surgery, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - Carlo Di Lorenzo
- Department of Pediatric Gastroenterology, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA
| | - Jan D Huizinga
- Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Marcel Jimenez
- Department of Cell Physiology, Physiology and Immunology and Neuroscience Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Satish Rao
- Division of Gastroenterology/Hepatology, Augusta University, Augusta, GA, USA
| | - Robin Spiller
- NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Nick J Spencer
- Discipline of Human Physiology, School of Medicine, Flinders University, Bedford Park, South Australia, Australia
| | - Roger Lentle
- Digestive Biomechanics Group, College of Health, Massey University, Palmerston North, New Zealand
| | - Jasper Pannemans
- Department of Paediatric Gastroenterology and Nutrition, Emma Children's Hospital/Academic Medical Centre, Amsterdam, Netherlands
| | - Alexander Thys
- Department of Paediatric Gastroenterology and Nutrition, Emma Children's Hospital/Academic Medical Centre, Amsterdam, Netherlands
| | - Marc Benninga
- Translational Research Center for Gastrointestinal disorders (TARGID), Department of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium
| | - Jan Tack
- Department of Paediatric Gastroenterology and Nutrition, Emma Children's Hospital/Academic Medical Centre, Amsterdam, Netherlands.
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9
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Camilleri M, Sandler RS, Peery AF. Etiopathogenetic Mechanisms in Diverticular Disease of the Colon. Cell Mol Gastroenterol Hepatol 2019; 9:15-32. [PMID: 31351939 PMCID: PMC6881605 DOI: 10.1016/j.jcmgh.2019.07.007] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 07/17/2019] [Accepted: 07/18/2019] [Indexed: 02/08/2023]
Abstract
This article reviews epidemiological evidence of heritability and putative mechanisms in diverticular disease, with greatest attention to 3 recent studies of genetic associations with diverticular disease based on genome-wide or whole-genome sequencing studies in large patient cohorts. We provide an analysis of the biological plausibility of the significant associations with gene variants reported and highlight the relevance of ANO1, CPI-17 (aka PPP1R14A), COLQ6, COL6A1, CALCB or CALCA, COL6A1, ARHGAP15, and S100A10 to colonic neuromuscular function and tissue properties that may result in altered compliance and predispose to the development of diverticular disease. Such studies also identify candidate genes for future studies.
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Affiliation(s)
- Michael Camilleri
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Robert S Sandler
- Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Anne F Peery
- Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
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10
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Zhao M, Liao D, Zhao J. Diabetes-induced mechanophysiological changes in the small intestine and colon. World J Diabetes 2017; 8:249-269. [PMID: 28694926 PMCID: PMC5483424 DOI: 10.4239/wjd.v8.i6.249] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 04/05/2017] [Accepted: 05/05/2017] [Indexed: 02/05/2023] Open
Abstract
The disorders of gastrointestinal (GI) tract including intestine and colon are common in the patients with diabetes mellitus (DM). DM induced intestinal and colonic structural and biomechanical remodeling in animals and humans. The remodeling is closely related to motor-sensory abnormalities of the intestine and colon which are associated with the symptoms frequently encountered in patients with DM such as diarrhea and constipation. In this review, firstly we review DM-induced histomorphological and biomechanical remodeling of intestine and colon. Secondly we review motor-sensory dysfunction and how they relate to intestinal and colonic abnormalities. Finally the clinical consequences of DM-induced changes in the intestine and colon including diarrhea, constipation, gut microbiota change and colon cancer are discussed. The final goal is to increase the understanding of DM-induced changes in the gut and the subsequent clinical consequences in order to provide the clinicians with a better understanding of the GI disorders in diabetic patients and facilitates treatments tailored to these patients.
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11
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Intraluminal pressure patterns in the human colon assessed by high-resolution manometry. Sci Rep 2017; 7:41436. [PMID: 28216670 PMCID: PMC5316981 DOI: 10.1038/srep41436] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Accepted: 12/13/2016] [Indexed: 02/08/2023] Open
Abstract
Assessment of colonic motor dysfunction is rarely done because of inadequate methodology and lack of knowledge about normal motor patterns. Here we report on elucidation of intraluminal pressure patterns using High Resolution Colonic Manometry during a baseline period and in response to a meal, in 15 patients with constipation, chronically dependent on laxatives, 5 healthy volunteers and 9 patients with minor, transient, IBS-like symptoms but no sign of constipation. Simultaneous pressure waves (SPWs) were the most prominent propulsive motor pattern, associated with gas expulsion and anal sphincter relaxation, inferred to be associated with fast propagating contractions. Isolated pressure transients occurred in most sensors, ranging in amplitude from 5–230 mmHg. Rhythmic haustral boundary pressure transients occurred at sensors about 4–5 cm apart. Synchronized haustral pressure waves, covering 3–5 cm of the colon occurred to create a characteristic intrahaustral cyclic motor pattern at 3–6 cycles/min, propagating in mixed direction. This activity abruptly alternated with erratic patterns resembling the segmentation motor pattern of the small intestine. High amplitude propagating pressure waves (HAPWs) were too rare to contribute to function assessment in most subjects. Most patients, dependent on laxatives for defecation, were able to generate normal motor patterns in response to a meal.
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Boeckxstaens G, Camilleri M, Sifrim D, Houghton LA, Elsenbruch S, Lindberg G, Azpiroz F, Parkman HP. Fundamentals of Neurogastroenterology: Physiology/Motility - Sensation. Gastroenterology 2016; 150:S0016-5085(16)00221-3. [PMID: 27144619 DOI: 10.1053/j.gastro.2016.02.030] [Citation(s) in RCA: 78] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Accepted: 02/09/2016] [Indexed: 12/14/2022]
Abstract
The fundamental gastrointestinal functions include motility, sensation, absorption, secretion, digestion and intestinal barrier function. Digestion of food and absorption of nutrients normally occurs without conscious perception. Symptoms of functional gastrointestinal disorders are often triggered by meal intake suggesting abnormalities in the physiological processes are involved in the generation of symptoms. In this manuscript, normal physiology and pathophysiology of gastrointestinal function, and the processes underlying symptom generation are critically reviewed. The functions of each anatomical region of the digestive tract are summarized. The pathophysiology of perception, motility, mucosal barrier, and secretion in functional gastrointestinal disorders as well as effects of food, meal intake and microbiota on gastrointestinal motility and sensation are discussed. Genetic mechanisms associated with visceral pain and motor functions in health and functional gastrointestinal disorders are reviewed. Understanding the basis for digestive tract functions is essential to understand dysfunctions in the functional gastrointestinal disorders.
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Affiliation(s)
- Guy Boeckxstaens
- Department of Gastroenterology, Translational Research Center for Gastrointestinal Disorders (TARGID), University Hospital Leuven, KU Leuven, Leuven, Belgium
| | | | - Daniel Sifrim
- Wingate Institute of Neurogastroenterology, Bart's and the London School of Medicine, Queen Mary, University of London, London, UK
| | - Lesley A Houghton
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Sigrid Elsenbruch
- Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Greger Lindberg
- Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Fernando Azpiroz
- Digestive Diseases Department, University Hospital Vall D'Hebron, Autonomous University of Barcelona, Barcelona, Spain
| | - Henry P Parkman
- Department of Medicine, Temple University School of Medicine, Philadelphia, PA, USA.
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Mañé N, Viais R, Martínez-Cutillas M, Gallego D, Correia-de-Sá P, Jiménez M. Inverse gradient of nitrergic and purinergic inhibitory cotransmission in the mouse colon. Acta Physiol (Oxf) 2016; 216:120-31. [PMID: 26347033 DOI: 10.1111/apha.12599] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2015] [Revised: 07/09/2015] [Accepted: 09/02/2015] [Indexed: 02/06/2023]
Abstract
AIM Gastrointestinal smooth muscle relaxation is accomplished by the neural corelease of ATP or a related purine and nitric oxide. Contractions are triggered by acetylcholine and tachykinins. The aim of this work was to study whether regional differences in neurotransmission could partially explain the varied physiological roles of each colonic area. METHODS We used electrophysiological and myography techniques to evaluate purinergic (L-NNA 1 mm incubated tissue), nitrergic (MRS2500 0.3 μm incubated tissue) and cholinergic neurotransmission (L-NNA 1 mm and MRS2500 0.3 μm incubated tissue) in the proximal, mid and distal colon of CD1 mice (n = 42). RESULTS Purinergic electrophysiological responses elicited by single pulses (28 V) were greater in the distal (IJPfMAX = -35.3 ± 2.2 mV), followed by the mid (IJPfMAX = -30.6 ± 1.0 mV) and proximal (IJPfMAX = -11.7 ± 1.1 mV) colon. In contrast, nitrergic responses decreased from the proximal colon (IJPsMAX = -11.4 ± 1.1 mV) to the mid (IJPsMAX = -9.1 ± 0.4 mV), followed by the distal colon (IJPsMAX = -1.8 ± 0.3 mV). A similar rank of order was observed in neural mediated inhibitory mechanical responses including electrical field stimulation-mediated responses and neural tone. ADPβs concentration-response curve was shifted to the left in the distal colon. In contrast, NaNP responses did not differ between regions. Cholinergic neurotransmission elicited contractions of a similar amplitude throughout the colon. CONCLUSION An inverse gradient of purinergic and nitrergic neurotransmission exists through the mouse colon. The proximal and mid colon have a predominant nitrergic neurotransmission probably due to the fact that their storage function requires sustained relaxations. The distal colon, in contrast, has mainly purinergic neurotransmission responsible for the phasic relaxations needed to propel dehydrated faeces.
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Affiliation(s)
- N. Mañé
- Department of Cell Biology, Physiology and Immunology and Neuroscience Institute; Universitat Autònoma de Barcelona; Barcelona Spain
| | - R. Viais
- Center for Drug Discovery and Innovative Medicines (MedInUP); Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto (ICBAS-UP); Porto Portugal
| | - M. Martínez-Cutillas
- Department of Cell Biology, Physiology and Immunology and Neuroscience Institute; Universitat Autònoma de Barcelona; Barcelona Spain
| | - D. Gallego
- Department of Cell Biology, Physiology and Immunology and Neuroscience Institute; Universitat Autònoma de Barcelona; Barcelona Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd); Instituto de Salud Carlos III; Barcelona Spain
| | - P. Correia-de-Sá
- Center for Drug Discovery and Innovative Medicines (MedInUP); Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto (ICBAS-UP); Porto Portugal
| | - M. Jiménez
- Department of Cell Biology, Physiology and Immunology and Neuroscience Institute; Universitat Autònoma de Barcelona; Barcelona Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd); Instituto de Salud Carlos III; Barcelona Spain
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Mañé N, Martínez-Cutillas M, Gallego D, Jimenez M. Enteric motor pattern generators involve both myogenic and neurogenic mechanisms in the human colon. Front Physiol 2015; 6:205. [PMID: 26257657 PMCID: PMC4508510 DOI: 10.3389/fphys.2015.00205] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2015] [Accepted: 07/06/2015] [Indexed: 01/10/2023] Open
Affiliation(s)
- Noemí Mañé
- Cell Biology, Physiology and Immunology, Universidad Autonoma de Barcelona Barcelona, Spain
| | | | - Diana Gallego
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas Barcelona, Spain
| | - Marcel Jimenez
- Cell Biology, Physiology and Immunology, Universidad Autonoma de Barcelona Barcelona, Spain ; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas Barcelona, Spain
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Iturrino J, Camilleri M, Busciglio I, Burton D, Zinsmeister AR. Pilot trial: pregabalin on colonic sensorimotor functions in irritable bowel syndrome. Dig Liver Dis 2014; 46:113-8. [PMID: 24095618 PMCID: PMC3946640 DOI: 10.1016/j.dld.2013.09.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2013] [Revised: 08/08/2013] [Accepted: 09/01/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND In prior studies, pregabalin reduced rectal or colonic pain in patients with irritable bowel syndrome and healthy adults, suggesting reduction of afferent function. AIM To assess effects of pregabalin on colonic compliance, sensory and motor functions in patients with constipation-predominant irritable bowel syndrome. METHODS In a pilot, double-blind, placebo-controlled, parallel-group study, we tested oral pregabalin, 200mg, in 18 patients with constipation-predominant irritable bowel syndrome. With a barostatically controlled polyethylene balloon in the left colon, we assessed sensation thresholds and colonic compliance using ascending method of limits, sensation ratings over 4 levels of distension, fasting and postprandial colonic tone and phasic motility. Analysis of covariance (adjusted for the corresponding pre-drug response) was used to compare placebo and pregabalin. After 45% participants completed studies, we conducted an interim analysis to assess the conditional power to detect pre-specified treatment effects given the observed variation and treatment group differences based on the planned sample size for the trial. RESULTS Pregabalin did not significantly affect colonic compliance, sensation thresholds, sensation ratings, fasting or postprandial tone or motility index. The study was stopped for futility to detect an effect on visceral pain with the planned design and sample size. CONCLUSION Pregabalin, 200mg, might not reduce distension-related colonic pain in constipation-predominant irritable bowel syndrome patients.
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Affiliation(s)
- Johanna Iturrino
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), College of Medicine, Mayo Clinic, Rochester, MN
,Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, Rochester, MN
| | - Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), College of Medicine, Mayo Clinic, Rochester, MN
,Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, Rochester, MN
| | - Irene Busciglio
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), College of Medicine, Mayo Clinic, Rochester, MN
| | - Duane Burton
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), College of Medicine, Mayo Clinic, Rochester, MN
| | - Alan R. Zinsmeister
- Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, College of Medicine, Mayo Clinic, Rochester, MN
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Jeyarajah S, Akbar N, Moorhead J, Haji A, Banerjee S, Papagrigoriadis S. A clinicopathological study of serotonin of sigmoid colon mucosa in association with chronic symptoms in uncomplicated diverticulosis. Int J Colorectal Dis 2012; 27:1597-605. [PMID: 22744736 DOI: 10.1007/s00384-012-1515-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/29/2012] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Neurotransmitter imbalance is hypothesised as a pathogenetic mechanism in several bowel conditions. We previously reported increased 5-HT in the sigmoid mucosa of colon resected for complicated diverticular disease (DD). We aimed to identify if abnormal 5-HT expression is associated with symptoms of uncomplicated DD. METHODS This was a prospective, comparative study and follow-up survey of symptoms. We examined the differences in 5-HT between DD patients and controls, as well as the presence of bowel symptoms at time of endoscopy and also 2 years later. Sigmoid biopsies were collected at colonoscopy. Immunohistochemical staining for 5-HT cells was performed. RESULTS Eighty-seven patients were recruited, 37 (42.5 %) DD and 50 (57.5 %) controls. No patients underwent surgery. There was no significant difference in total mean number of 5-HT-positive cells in DD compared to controls or between patients and controls with abdominal symptoms. Forty-one patients (47.1 %) responded to questionnaires at median 57.8 months from biopsy. Eighteen (43.9 %) were DD and 23(56.1 %) controls. 5-HT counts showed no significant association to symptom persistence. DISCUSSION Although 5-HT expression has previously been found to be increased in complicated DD in whole bowel-resected specimens, the same is not confirmed on colonic mucosal biopsies. This raises the suggestion that 5-HT may be involved in the development of acute complications but may not be involved in the pathogenesis of chronic symptoms.
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Affiliation(s)
- S Jeyarajah
- Department of Colorectal Surgery, Kings College Hospital, London, UK.
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Iturrino J, Camilleri M, Busciglio I, Burton D, Zinsmeister AR. Sensations of gas and pain and their relationship with compliance during distension in human colon. Neurogastroenterol Motil 2012; 24:646-51, e275. [PMID: 22393902 PMCID: PMC3374900 DOI: 10.1111/j.1365-2982.2012.01901.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Colonic mechanosensory afferents 'in parallel' to circular muscle activate prevertebral ganglion reflexes; 'in series', afferents convey visceral sensation to the central nervous system; and pain receptors are activated with muscle distension. Our aim was to analyze the relationships of gas and pain sensations during graded distensions, and the association of sensations with colonic compliance in conscious humans. METHODS The data were acquired in a prior study performed on 60 healthy volunteers (aged 18-75 years) under baseline conditions. Colonic compliance was measured in response to 4 mmHg stepwise balloon distensions to estimate pressure at half-maximum volume (Pr(50%)). Sensation ratings for gas and pain were averaged over distensions at 16, 24, 30 and 36 mmHg above baseline operating pressure. Associations between mean gas and pain ratings, and colonic compliance were assessed with Pearson correlations. KEY RESULTS Gas and pain sensations were significantly correlated at all levels of distension (all P < 0.001). Significant inverse correlations between Pr(50%) and sensations of gas and pain were observed, suggesting that lower compliance was associated with lower sensations. Up to 25% of the variance in sensation may be attributed to colonic compliance. CONCLUSIONS & INFERENCES These data are consistent with the hypothesis that, if circumferential colonic receptors are stimulated by distension to mediate gas and pain in humans, they are, at least partly, arranged 'in parallel' to the muscle layer.
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Affiliation(s)
- Johanna Iturrino
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), College of Medicine, Mayo Clinic, Rochester, MN
- Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, Rochester, MN
| | - Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), College of Medicine, Mayo Clinic, Rochester, MN
- Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, Rochester, MN
- Department of Physiology and Biomedical Engineering, College of Medicine, Mayo Clinic, Rochester, MN
| | - Irene Busciglio
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), College of Medicine, Mayo Clinic, Rochester, MN
| | - Duane Burton
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), College of Medicine, Mayo Clinic, Rochester, MN
| | - Alan R. Zinsmeister
- Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, College of Medicine, Mayo Clinic, Rochester, MN
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Abstract
Human defecation involves integrated and coordinated sensorimotor functions, orchestrated by central, spinal, peripheral (somatic and visceral), and enteric neural activities, acting on a morphologically intact gastrointestinal tract (including the final common path, the pelvic floor, and anal sphincters). The multiple factors that ultimately result in defecation are best appreciated by describing four temporally and physiologically fairly distinct phases. This article details our current understanding of normal defecation, including recent advances, but importantly identifies those areas where knowledge or consensus is still lacking. Appreciation of normal physiology is central to directed treatment of constipation and also of fecal incontinence, which are prevalent in the general population and cause significant morbidity.
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Affiliation(s)
- Somnath Palit
- Academic Surgical Unit (GI Physiology Unit), Barts and the London School of Medicine and Dentistry, Blizard Institute, Queen Mary University, London, UK.
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Iturrino J, Camilleri M, Busciglio I, Burton D, Zinsmeister AR. Effect of the α2δ ligand, pregabalin, on colonic sensory and motor functions in healthy adults. Am J Physiol Gastrointest Liver Physiol 2011; 301:G377-84. [PMID: 21596994 PMCID: PMC3154609 DOI: 10.1152/ajpgi.00085.2011] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Pregabalin, an α2δ ligand, is used clinically to treat somatic pain. A prior study suggested that pregabalin reduces distension-induced pain while increasing rectal compliance. We aimed to quantify effects of pregabalin on colonic sensory and motor functions and assess relationships between sensory effects and colonic compliance. We conducted a randomized, double-blind, placebo-controlled, parallel-group study of a single oral administration of 75 or 200 mg of pregabalin in 62 healthy adults (aged 18-75 yr). Subjects underwent left colon intubation. We assessed "stress-arousal symptoms", compliance, sensation thresholds, sensation ratings averaged over four levels of distension, fasting and postprandial colonic tone, and phasic motility index (MI). Analysis of covariance (adjusted for age, sex, body mass index, and corresponding predrug response) and proportional hazard models were used. There were no clinically important differences among treatment groups for demographics, predrug compliance, tone, MI, and sensation. Treatment was associated with reduced energy and increased drowsiness but no change in tension or relaxation. Sensation ratings averaged over the four distension levels were lower for gas sensation [overall effect P = 0.14, P = 0.05 (pregabalin 200 mg vs. placebo)] and for pain sensation [overall effect P = 0.12, P = 0.04 (pregabalin 200 mg vs. placebo)]. The magnitude of the effect of 200 mg of pregabalin relative to placebo is on average a 25% reduction of both gas and pain sensation ratings. Pregabalin did not significantly affect colonic compliance, sensation thresholds, colonic fasting tone, and MI. Thus 200 mg of pregabalin reduces gas and pain sensation and should be tested in patients with colonic pain.
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Affiliation(s)
- Johanna Iturrino
- 1Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), ,2Division of Gastroenterology and Hepatology,
| | - Michael Camilleri
- 1Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), ,2Division of Gastroenterology and Hepatology,
| | - Irene Busciglio
- 1Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER),
| | - Duane Burton
- 1Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER),
| | - Alan R. Zinsmeister
- 3Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, College of Medicine, Mayo Clinic, Rochester, Minnesota
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Jouët P, Sabaté JM, Coffin B, Lémann M, Jian R, Flourié B. Fermentation of starch stimulates propagated contractions in the human colon. Neurogastroenterol Motil 2011; 23:450-6, e176. [PMID: 21199172 DOI: 10.1111/j.1365-2982.2010.01652.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND In healthy humans, up to 30 g of daily ingested starch escape small intestinal digestion, and are fermented in the colon. This physiological starch malabsorption could modify colonic motility through metabolites such as short-chain fatty acids produced by fermentation. METHODS Ten healthy volunteers swallowed a probe, consisting of an infusion catheter, six perfused catheters and a balloon connected to a barostat. On two consecutive days colonic motility was recorded in fasting subjects in the basal state (1 h), and then during (3 h), and after (2 h) the intracolonic infusion of 750 mL of isoosmotic and isovolumetric solutions containing sodium chloride with or without 15 g wheat starch. We determined (i) the volume of hydrogen and methane exhaled in breath, (ii) a global motility index and the number of high amplitude propagated contractions (HAPCs), and (iii) the mean balloon volume, reflecting the tonic motor activity. KEY RESULTS [median (IQR)] Compared to the basal period, colonic infusion of starch or saline did not modify the colonic motility index and tone. However, the number of HAPCs was significantly higher during and after infusion of starch than of saline [4.5 (2.75-6.5) vs 0.96 (0-2.66)/5 h, starch vs saline respectively; P = 0.011]. CONCLUSIONS & INFERENCES In healthy humans, colonic fermentation of a physiological malabsorbed amount of starch has no effect on the tonic and phasic colonic motor activities, but produces a significant increase in the number of HAPCs. This may participate in the physiological propulsion of colonic contents.
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Affiliation(s)
- P Jouët
- AP-HP, Hôpital Louis Mourier, Department of Hepato-Gastroenterology, Colombes Cedex, France
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Jeyarajah S, Papagrigoriadis S. Review article: the pathogenesis of diverticular disease--current perspectives on motility and neurotransmitters. Aliment Pharmacol Ther 2011; 33:789-800. [PMID: 21306406 DOI: 10.1111/j.1365-2036.2011.04586.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Low-fibre diet, structural abnormalities and ageing are traditional aetiological factors implicated in the development of diverticular disease. More recently, motility disorders are implicated in its causation leading to speculation that neurotransmitters play a role in mediating these disturbances. AIMS To draw together studies on the role of neurotransmitters in the development of diverticular disease and its symptoms. METHODS Medline, GoogleScholar and Pubmed were searched for evidence on this subject using the terms neurotransmitters, motility, diverticular disease and pathogenesis. Articles relevant to the subject were cited and linked references were also reviewed. RESULTS Serotonin, which has been found to be an excitatory colonic neurotransmitter, has been found in early studies to be increased in colonic enterochromaffin cells. Acetylcholine, which is thought to be an excitatory neurotransmitter and cholinergic activity, has also seen to be increased in diverticular disease. These findings may suggest that an increase in excitatory neurotransmitters may result in the hypersegmentation thought to cause pulsion diverticula. Similarly, a decrease in nitric oxide which is inhibitory is found. CONCLUSIONS There is some evidence that neurotransmitters may play a role in the motility disturbances seen in diverticular disease; however, a clear role is yet to be ascertained.
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Affiliation(s)
- S Jeyarajah
- Department of Colorectal Surgery, Kings College Hospital, Denmark Hill, London, UK.
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Abstract
GOAL To examine whether endoscopic mucosal clipping prevents probe migration. BACKGROUND Ambulatory colonic manometry can provide useful pathophysiologic information regarding colonic motor function. However, probe displacement during prolonged recording can be problematic. METHODS Thirty healthy volunteers underwent 24-hour ambulatory colonic manometry with colonoscopic-assisted probe placement, and fluoroscopic confirmation of the location of most proximal sensor at hepatic flexure. Participants were randomized to 2 groups; in 14 participants (m/f=8/6), the probe was anchored to the colonic mucosa using mucosal clips and in 16 participants, (m/f=9/7), the probe was left unattached in the colon. Magnitude of transducer displacement was assessed by fluoroscopic localization. The difference between the number of transducers in each segment at the beginning (x) and at the end (y) of each study was summed up and divided by 2, to calculate the "displacement score" and this was taken as the main outcome measure. RESULTS In participants without clipping, the mean (s.d.) displacement score was 1.6 (0.9), implying displacement of transducers by 1.6 colonic segments relative to their initial location. In contrast, there was no displacement of transducers in those who received clipping. Clipping caused no adverse events. CONCLUSIONS Endoscopic mucosal clipping is safe and effective for prevention of probe displacement, and ensures more accurate temporospatial resolution of data for prolonged colonic manometry recording.
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Abstract
Constipation is one of the most common digestive problems in North America with significant psychosocioeconomic implications. It is caused by either a primary disorder of colonic and anorectal function or by many secondary conditions such as constipating drugs, metabolic disorders and other colorectal problems. Given the heterogeneity of problems that cause constipation, defining the underlying pathophysiology is increasingly being recognized as a key step toward optimal management. Colonic manometry with sensation and tone assessment (barostat) and anorectal manometry with rectal sensation and compliance assessment and balloon expulsion test can provide a comprehensive evaluation of colonic and anorectal sensorimotor function and facilitate a diagnosis of slow transit constipation, dyssynergic defecation or irritable bowel syndrome, or an overlap of these disorders. This review provides a critical appraisal of the role of manometric techniques toward augmenting our understanding of colonic and anorectal physiology, both in health and constipation and discussing their clinical utility in the diagnosis and management of chronic constipation.
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Bharucha AE, Seide BM, Zinsmeister AR. The effects of clonidine on symptoms and anorectal sensorimotor function in women with faecal incontinence. Aliment Pharmacol Ther 2010; 32:681-8. [PMID: 20629973 PMCID: PMC2932810 DOI: 10.1111/j.1365-2036.2010.04391.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Women with faecal incontinence and rectal urgency have increased rectal stiffness and sensation. AIM To evaluate the effects of clonidine, an alpha(2) -adrenergic agonist, in faecal incontinence. METHODS In this open-label uncontrolled study, bowel symptoms and anorectal functions (anal pressures, rectal compliance, and sensation) were assessed before and during treatment with transdermal clonidine (0.2 mg daily, 4 weeks) in 12 women with urge-predominant faecal incontinence. RESULTS Clonidine reduced the frequency (17.8 +/- 3.1 before vs. 8.8 +/- 3.9 after, P = 0.03) and number of days with faecal incontinence (11.8 +/- 1.6 before vs. 6.1 +/- 1.8 after, P = 0.02), faecal incontinence symptom severity score (max = 13, 8.3 +/- 0.7 vs. 5.6 +/- 0.9, P < 0.01), and allowed patients to defer defecation for a longer duration (P = 0.03). Although overall effects on anorectal functions were not significant, the treatment-associated reduction in faecal incontinence episodes was associated with increased rectal compliance (r = -0.58, P < 0.05) and reduced rectal sensation. (r = -0.73, P = 0.007 vs. desire to defecate pressure threshold). CONCLUSIONS Clonidine improves symptoms in women with faecal incontinence; this improvement is associated with increased rectal compliance and reduced rectal sensitivity. A controlled study is necessary to confirm these observations.
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Abstract
After many decades debating whether the clinical manifestations of patients with functional digestive symptoms originate "in their minds" or "in their guts," arguments remain strong on both sides of the controversy. However, advances in understanding of gut physiology and pathophysiology, and persuasive evidence on the bidirectionality of the regulatory traffic between the enteric and central nervous systems, are helping to characterize clinical situations in which we can legitimately speak of gut dysfunction, as opposed to others where symptoms are not associated with apparent or detectable gut disturbances and may truly represent somatization of an affective disorder. In this review, we describe available clinically applicable technology, albeit in specialized clinical research units, that may be used to discern whether or not challenging patients have gut sensory or motor disturbances. The practical yield of applying such methods to diagnostic investigation may be substantial, because it establishes a plausible mechanism of disease that may be used in patient management and patient persuasion, to remove uncertainties and to prevent futile repetition of conventional diagnostic tests. By evolving from symptom analysis to mechanism-based diagnosis, our gastroenterology community may progress toward the goal of delivering the full diagnostic spectrum from altered morphology to disturbed function.
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Affiliation(s)
- Carolina Malagelada
- Digestive System Research Unit, University Hospital Vall d'Hebron, 08035, Barcelona, Spain
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Abstract
BACKGROUND Although colonic manometry provides useful information regarding colonic physiology, considerable variability has been reported both for regional motility and manometric patterns. Whether colonic manometry is reproducible is not known. METHODS Seven healthy volunteers (three men, four women, mean age = 34 years) underwent two studies of 24-h ambulatory colonic manometry, each 2 weeks apart. Manometry was performed by placing a six-sensor solid-state probe, up to the hepatic flexure and anchored to colonic mucosa. Colonic motility was assessed by the number and area-under-curve (AUC) of pressure waves and motility patterns such as high-amplitude propagating contractions (HAPC). Waking and meal-induced gastrocolonic responses were also assessed. Paired t-test was used to examine the reproducibility and intra and interindividual variability. KEY RESULTS The number of pressure waves and propagating pressure waves and HAPC, and AUC were similar between the two studies. Diurnal variation, waking and meal-induced gastrocolonic responses were also reproducible. There was some variability in the incidence of individual colonic motor patterns. CONCLUSIONS & INFERENCES Colonic manometry findings were generally reproducible, particularly for the assessment of key physiologic changes, such as meal-induced gastrocolonic, HAPC, and waking responses.
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Affiliation(s)
- S S C Rao
- Division of Neurogastroenterology, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa city, IA 52242, USA.
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Ravi K, Bharucha AE, Camilleri M, Rhoten D, Bakken T, Zinsmeister AR. Phenotypic variation of colonic motor functions in chronic constipation. Gastroenterology 2010; 138:89-97. [PMID: 19660461 PMCID: PMC2813378 DOI: 10.1053/j.gastro.2009.07.057] [Citation(s) in RCA: 63] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2009] [Revised: 07/15/2009] [Accepted: 07/23/2009] [Indexed: 12/31/2022]
Abstract
BACKGROUND & AIMS Colonic motor disturbances in chronic constipation (CC) are heterogeneous and incompletely understood; the relationship between colonic transit and motor activity is unclear. We sought to characterize the phenotypic variability in chronic constipation. METHODS Fasting and postprandial colonic tone and phasic activity and pressure-volume relationships were assessed by a barostat manometric assembly in 35 healthy women and 111 women with CC who had normal colon transit (NTC; n = 25), slow transit (STC; n = 19), and defecatory disorders with normal (DD-normal; n = 34) or slow transit (DD-slow; n = 33). Logistic regression models assessed whether motor parameters could discriminate among these groups. Among CC, phenotypes were characterized by principal components analysis of these measurements. RESULTS Compared with 10th percentile values in healthy subjects, fasting and/or postprandial colonic tone and/or compliance were reduced in 40% with NTC, 47% with STC, 53% with DD-normal, and 42% with DD-slow transit. Compared with healthy subjects, compliance was reduced (P CONCLUSIONS Fasting and/or postprandial colonic tone are reduced, reflecting motor dysfunctions, even in NTC. Colonic motor assessments allow chronic constipation to be characterized into phenotypes. Further studies are needed to evaluate the relationship among these phenotypes, enteric neuropathology, and response to treatment in CC.
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Affiliation(s)
- Karthik Ravi
- Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
| | - Adil E. Bharucha
- Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
| | - Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
| | - Deborah Rhoten
- Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
| | - Timothy Bakken
- Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
| | - Alan R. Zinsmeister
- Division of Biomedical Statistics and Informatics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
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Camilleri M, Bharucha AE, di Lorenzo C, Hasler WL, Prather CM, Rao SS, Wald A. American Neurogastroenterology and Motility Society consensus statement on intraluminal measurement of gastrointestinal and colonic motility in clinical practice. Neurogastroenterol Motil 2008; 20:1269-82. [PMID: 19019032 DOI: 10.1111/j.1365-2982.2008.01230.x] [Citation(s) in RCA: 167] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Tests of gastric, small intestinal and colonic motor function provide relevant physiological information and are useful for diagnosing and guiding the management of dysmotilities. Intraluminal pressure measurements may include concurrent measurements of transit or intraluminal pH. A consensus statement was developed and based on reports in the literature, experience of the authors, and discussions conducted under the auspices of the American Neurogastroenterology and Motility Society in 2008. The article reviews the indications, methods, performance characteristics, and clinical utility of intraluminal measurements of pressure activity and tone in the stomach, small bowel and colon in humans. Gastric and small bowel motor function can be measured by intraluminal manometry, which may identify patterns suggestive of myopathy, neuropathy, or obstruction. Manometry may be most helpful when it is normal. Combined wireless pressure and pH capsules provide information on the amplitude of contractions as they traverse the stomach and small intestine. In the colon, manometry assesses colonic phasic pressure activity while a barostat assesses tone, compliance, and phasic pressure activity. The utility of colonic pressure measurements by a single sensor in wireless pressure/pH capsules is not established. In children with intractable constipation, colonic phasic pressure measurements can identify patterns suggestive of neuropathy and predict success of antegrade enemas via cecostomy. In adults, these assessments may be used to document severe motor dysfunction (colonic inertia) prior to colectomy. Thus, intraluminal pressure measurements may contribute to the management of patients with disorders of gastrointestinal and colonic motility.
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Affiliation(s)
- M Camilleri
- CENTER Program, Mayo Clinic, Rochester, MN 55905, USA.
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Analysis of rectal dynamic and static compliances in patients with irritable bowel syndrome. Int J Colorectal Dis 2008; 23:659-64. [PMID: 18357460 DOI: 10.1007/s00384-008-0469-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/28/2008] [Indexed: 02/04/2023]
Abstract
AIMS Our aim was to investigate whether the dynamic and static compliances differ between patients with irritable bowel syndrome (IBS) and normal subjects. MATERIALS AND METHODS Fifty-five IBS patients (age range 20-65 years, mean age 39.0 years, 28 women and 27 men; 36 diarrhea-predominant IBS (IBS-D) patients and 19 constipation-predominant IBS (IBS-C) patients) with symptoms that fulfilled the Rome-II criteria and 21 healthy controls (age range 25-58 years, mean age 37.8 years; 11 women and ten men) were recruited. The anorectal functions, including dynamic compliance, were evaluated via barostat tests. A power exponential model was used for the evaluation of static compliance. RESULTS There was no significant difference in dynamic compliance between the normal subjects and the IBS patients (10.3+/-3.1 and 8.9+/-2.9 mmHg, respectively, P>0.05). However, even though no significant difference was detected in the overall shape of the curve (beta; P>0.05), there were significant differences in the kappa and P (half) between the normal subjects and the IBS patients (P<0.05), respectively. When we compared the dynamic and static compliances between the IBS-C and IBS-D patients, there were no significant differences found (P>0.05). CONCLUSIONS An exponential model provided good fit to the actual data, and there were significant differences in static compliance between the normal subjects and the IBS patients. This result can reveal the altered biomechanical properties of the gut wall in IBS patients.
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Bouchoucha M, Devroede G, Faye A, Le Toumelin P, Arhan P, Arsac M. Colonic response to food in constipation. Int J Colorectal Dis 2006; 21:826-33. [PMID: 15968522 DOI: 10.1007/s00384-005-0787-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/26/2005] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Colonic response to food is possibly abnormal in constipation. METHODS The colonic response to food was evaluated in 323 patients and 60 healthy subjects by following the movements of radiopaque markers after ingestion of a standard 1,000-cal test meal. Constipated patients were divided into four groups: one with a normal, and three with a delayed colorectal transit time. When the delay was found mainly in the ascending colon, the group was labeled as suffering from "colonic inertia". In "hindgut dysfunction", the delay was predominantly found in the descending colon, whereas the term "outlet obstruction" was reserved for constipated patients whose major site of delay was the rectosigmoid area. Colonic response to food was quantified by evaluating the variation of markers in a given abdominal region and the evolution of the geometric center on the entire plain film of the abdomen. RESULTS Emptying of the caecum-ascending colon and filling of the rectosigmoid area characterize the colonic response to food in healthy subjects. Constipated patients also filled the rectosigmoid, but different patterns were found in the colon. In constipated patients with transit in the normal range, there was a frequent (41%) absence of colonic response to food as compared to controls (13%) and constipated patients with delayed transit (p<0.0001). The response to food of patients with colonic inertia was similar to that of healthy subjects in terms of distal progression, but less marked. The hindgut dysfunction group emptied the entire left colon but failed to empty the caecum and ascending colon. In the outlet obstruction group, there was no distal progress of the geometric center after meal. CONCLUSIONS Abnormal colonic response to food is frequently found in constipated patients, with different patterns according to the type of constipation.
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Affiliation(s)
- Michel Bouchoucha
- Laboratoire de Physiologie Digestive, Hôpital Broussais, Université Paris V, 96 rue Didot, 75014 Paris, France.
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Sarna SK. Molecular, functional, and pharmacological targets for the development of gut promotility drugs. Am J Physiol Gastrointest Liver Physiol 2006; 291:G545-55. [PMID: 16565417 DOI: 10.1152/ajpgi.00122.2006] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The science of gastrointestinal motility has made phenomenal advances during the last fifty years. Yet, there is a paucity of effective promotility drugs to treat functional bowel disorders that affect 10-29% of the U.S. population. A part of the reason for the lack of effective drugs is our limited understanding of the etiology of these diseases. In the absence of this information, mostly an ad hoc approach has been used to develop the currently available drugs, which are modestly effective or effective in only a subset of the patients with functional bowel disorders. This review discusses a grounds-up approach for development of the next generation of promotility drugs. The approach is based on our current understanding of 1) the different types of contractions that produce overall motility function of mixing and orderly net distal propulsion in major gut organs, 2) the regulatory mechanisms of these contractions, 3) which receptors and intracellular signaling molecules could be targeted to stimulate specific types of contractions to accelerate or retard transit, and 4) the strengths and limitations of animal models and experimental approaches that could screen potential promotility drugs for their efficacy in human gut propulsion in functional bowel disorders.
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Affiliation(s)
- Sushil K Sarna
- Division of Gastroenterology, Dept. of Internal Medicine, University of Texas Medical Branch at Galveston, 9.138 Medical Research Bldg., Galveston, TX 77555-1064, USA.
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Gonlachanvit S, Coleski R, Owyang C, Hasler WL. Nutrient modulation of intestinal gas dynamics in healthy humans: dependence on caloric content and meal consistency. Am J Physiol Gastrointest Liver Physiol 2006; 291:G389-95. [PMID: 16899712 DOI: 10.1152/ajpgi.00526.2005] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The actions of nutrients on gut transit of liquids and solids have been extensively studied, but the effects of meal ingestion on intestinal gas flow are unexplored. We hypothesized that meals of varying caloric content and consistency modulate gas transit to different degrees. Nine healthy volunteers underwent jejunal perfusion of physiological gas mixtures at 12 ml.min(-1).3 h, with ingestion of nothing (control), water (240 ml), 240-kcal liquid meals, and 240-kcal solid meals at the end of the second hour in separate studies. Gas was quantified from an intrarectal catheter. After an initial lag phase, gas evacuation approached steady state by the end of the fasting period. Solid and liquid caloric meals increased total gas volumes evacuated from 5-40 min after ingestion vs. control studies (P < 0.05). These increases resulted from increased numbers of bolus gas evacuations (P < 0.05), whereas bolus volumes, pressures, and flow rates were similar for all test conditions. Solid and liquid caloric meals elicited similar effects on bolus gas dynamic parameters, whereas water did not affect these measures vs. control (NS, not significant). Both caloric meals and the noncaloric liquid meal increased continuous gas flow, which represented <2% of total gas expulsion. In conclusion, caloric meals promote bolus gas transit in healthy humans, whereas noncaloric liquids have no effect. Solids stimulate early postprandial gas dynamics to the same extent as liquid meals of similar caloric content. Thus modulatory effects of meals on intestinal gas transit depend on their caloric content but not their consistency.
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Affiliation(s)
- Sutep Gonlachanvit
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
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Abstract
Left-sided diverticular disease affects upwards of 50% of the population over the age of 60 years in western countries and is becoming more common as the population ages. Studies from the 1960s to 1980s related its occurrence to the use of low fiber diets, and to the prolonged colonic transit time and increased intraluminal pressure associated with low-volume stools. Pulsion diverticula (pseudodiverticula) emerge through the muscularis propria of the left colon at points of penetration of the vasa recta that supply the submucosa and mucosa. Cardinal features of the sigmoid colon in diverticular disease are abnormalities of the muscularis propria, including thickening and elastosis of the teniae, shortening of the bowel, and thickening and folding of the circular muscle with the development of transverse semilunar ridges between the mesenteric and antimesenteric teniae. Complications of diverticular disease such as hemorrhage, diverticulitis, peridiverticular abscess, fistula, and perforation are well recognized.
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Affiliation(s)
- A Brian West
- AmeriPath New York, Gastrointestinal Diagnostics, Shelton, CT 06484, USA.
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Abstract
Diverticular disease affects upwards of 50% of the population over the age of 60 years in Western countries and is becoming more common as the population ages. Studies from the 1970s and 1980s related its occurrence to the use of low-fiber diets and to the prolonged colonic transit time and increased intraluminal pressure associated with low-volume stools. Pulsion diverticula (pseudodiverticula) emerge through the thickened circular layer of the muscularis propria of the left colon at points of penetration of the vasa recta that supply the submucosa and mucosa. Complications of diverticular disease such as hemorrhage, diverticulitis, peridiverticular abscess, fistula, and perforation are well recognized. More recently, attention has been drawn to the polypoid prolapsing mucosal folds that may develop as the affected segment of bowel (usually the sigmoid) becomes shorter and to changes in the mucosa surrounding the diverticula and in the bowel wall that may result in confusion with ulcerative colitis or Crohn disease (sigmoid colitis-associated diverticulosis [SCAD]). Distinguishing SCAD from these entities is extremely important, and pathologists should be aware of the possibility of overdiagnosing chronic inflammatory bowel disease in biopsies or resection specimens of sigmoid colon with diverticular disease.
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Affiliation(s)
- Huihui Ye
- Department of Pathology, New York University, New York, New York 10016, USA
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Abstract
BACKGROUND The colonic neuromuscular dysfunction in patients with constipation and the role of colonic manometry is incompletely understood. AIM To study prolonged colonic motility and assess its clinical significance. METHODS Twenty-four-hour ambulatory colonic manometry was performed in 21 patients with slow-transit constipation and 20 healthy controls by placing a 6-sensor solid-state probe up to the hepatic flexure. Quantitative and qualitative manometric analysis was performed in 8-h epochs. Patients were followed up for 1 yr. RESULTS Constipated patients showed fewer pressure waves and lower area under the curve (p < 0.05) than controls during daytime, but not at night. Colonic motility induced by waking or meal was decreased (p < 0.05) in patients. High-amplitude propagating contractions (HAPCs) occurred in 43% of patients compared to 100% of controls and with lower incidence (1.7 vs 10.1, p < 0.001) and propagation velocity (p < 0.04). Manometric features suggestive of colonic neuropathy were seen in 10, myopathy in 5, and normal profiles in 4 patients. Seven patients with colonic neuropathy underwent colectomy with improvement. The rest were managed conservatively with 50% improvement at 1 yr. CONCLUSIONS Patients with slow-transit constipation exhibited either normal or decreased pressure activity with manometric features suggestive of colonic neuropathy or myopathy as evidenced by absent HAPC or attenuated colonic responses to meals and waking. In refractory patients, colonic manometry may be useful in characterizing the underlying pathophysiology and in guiding therapy.
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Affiliation(s)
- Satish S C Rao
- Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
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Ng C, Danta M, Prott G, Badcock CA, Kellow J, Malcolm A. Modulatory influences on antegrade and retrograde tonic reflexes in the colon and rectum. Am J Physiol Gastrointest Liver Physiol 2004; 287:G962-6. [PMID: 15231487 DOI: 10.1152/ajpgi.00460.2003] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Tonic reflexes in the colon and rectum are likely to be important in health and in disorders of gastrointestinal function. The aim of this study was to evaluate the fasting and postprandial "colorectal" and "rectocolic" reflexes in response to 2-min isobaric distensions of the colon and rectum, accounting for enteric sensation, compliance, and distending balloon volume. In 14 healthy fasting subjects, a dual barostat assembly was positioned (descending colon and rectum). A 2-min phasic distension was performed in the colon and rectum in random order while the opposing balloon volume was recorded. Sensation (phasic distension) and compliance (ramp distension) were also determined. The experiment was repeated postprandially. Colonic distension resulted in significant rectal tonic contraction in the fasting (rectal volume change: -35.4 +/- 8.4 ml, P < 0.01) and postprandial (-22.2 +/- 8.4 ml, P < 0.01) states. After adjustment for colonic sensitivity, for compliance, and for distending balloon volume, the rectal volume change remained significant; the extent of the tonic response, however, correlated significantly with increasing pain score (P < 0.01). In contrast, rectal distension did not produce a significant tonic response in the colon (fasting: -6.5 +/- 7.3 ml; postprandial: 2.7 +/- 7.3 ml), either unadjusted or adjusted for rectal sensitivity, compliance, and distending balloon volume. In conclusion, the colorectal reflex, but not the rectocolic reflex, can be readily demonstrated both before and after a meal in response to a 2-min isobaric distension in the colon and rectum, respectively. Although the presence of the colorectal reflex does not depend on colonic sensitivity or the volume of the distending colonic balloon, these factors modulate the reflex, especially in the fasting state.
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Affiliation(s)
- Clinton Ng
- Gastrointestinal Investigation Unit, Royal North Shore Hospital, University of Sydney, St. Leonards, New South Wales 2065, Australia
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Harder H, Serra J, Azpiroz F, Malagelada JR. Reflex control of intestinal gas dynamics and tolerance in humans. Am J Physiol Gastrointest Liver Physiol 2004; 286:G89-94. [PMID: 12946941 DOI: 10.1152/ajpgi.00174.2003] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Intestinal transit of gas is normally adapted to the luminal gas load, but in some patients impaired transit may lead to gas retention and symptoms. We hypothesized that intestinal gas transit is regulated by reflex mechanisms released by segmental distension at various gut levels. In 24 healthy subjects, we measured gas evacuation and perception of jejunal gas infusion (12 ml/min) during simultaneous infusion of duodenal lipids mimicking the postprandial caloric load (Intralipid, 1 kcal/min). We evaluated the effects of proximal (duodenal) distension (n = 8), distal (rectal) distension (n = 8), and sham distension, as control (n = 8). Duodenal lipid infusion produced gas retention (366 +/- 106 ml) with low abdominal perception (1.5 +/- 0.8 score). Distension of either the duodenum or rectum during lipid infusion expedited gas transit and prevented retention (-120 +/- 164 and -124 +/- 162 ml retention, respectively; P < 0.05 vs. control). However, the tolerance to the intestinal gas load differed markedly, depending on the site of distension; perception remained low during rectal distension (2.6 +/- 0.7 score; not significant vs. control) but increased during duodenal distension (4.4 +/- 0.7 score; P < 0.05 vs. control). We conclude that focal gut distension, either at proximal or distal sites, accelerates gas transit, but the symptomatic response depends on the site of stimulation.
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Affiliation(s)
- Hermann Harder
- Digestive System Research Unit, Hospital General Vall d'Hebron, Autonomous University of Barcelona, 08035 Barcelona, Spain
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Abstract
Colonic motility disorders are common conditions. However, our understanding of normal, and, consequently, pathological motor function of the colon remains limited, mainly due to the relative inaccessibility of this organ for study. Investigation of colonic motility may encompass one or more of the four separate components (myoelectric activity, phasic and tonic contractile activity and movement of intraluminal content) using electrophysiological, manometric or transit studies. Although transit studies provide the best 'functional' appreciation of colonic motor activity, and are the only techniques used in contemporary clinical practice, manometric methods are becoming increasingly popular, as they allow a direct study of colonic contractile activity over prolonged periods. To date, the majority of studies have been limited to the pelvic colon by a retrograde (per rectal) approach; however, recent technological advances have facilitated 'pan-colonic' investigation. This review concentrates on manometry of the human colon proximal to the sigmoid, and includes evaluation of both phasic and tonic motor activity, by utilization of perfused-tube and solid-state manometric catheters, and also the electronic barostat. Methodological techniques, experimental protocols and the analysis and interpretation of recorded data are critically explored, and a contemporary classification of colonic contractile activities is presented.
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Affiliation(s)
- S M Scott
- Academic Department of Surgery, GI Physiology Unit, Barts and the London, Queen Mary School of Medicine & Dentistry, The Royal London Hospital, Whitechapel, London, UK.
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Bassotti G, Chistolini F, Morelli A. Pathophysiological aspects of diverticular disease of colon and role of large bowel motility. World J Gastroenterol 2003; 9:2140-2142. [PMID: 14562365 PMCID: PMC4656450 DOI: 10.3748/wjg.v9.i10.2140] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2003] [Revised: 07/07/2003] [Accepted: 07/14/2003] [Indexed: 02/06/2023] Open
Abstract
Colonic diverticular disease (diverticulosis) is one of the most common gastrointestinal disorders in Western countries. This disorder is strictly related to aging and fibre intake, and still bears a discrete amount of morbidity. Numerous etiological co-factors have to date been implicated in the pathogenesis of the disease, yet the supporting evidence is still far from absolute. The present review considers the pathophysiology of colonic diverticular disease, with a special emphasis on factors related to abnormal colonic motility.
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Affiliation(s)
- Gabrio Bassotti
- Clinica di Gastroenterologia ed Epatologia, Dipartimento di Medicina Clinica e Sperimentale, Università di Perugia, Italy.
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Sloots CEJ, Felt-Bersma RJF, Meuwissen SGM, Kuipers EJ. Influence of gender, parity, and caloric load on gastrorectal response in healthy subjects: a barostat study. Dig Dis Sci 2003; 48:516-21. [PMID: 12757163 DOI: 10.1023/a:1022584632011] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
The gastrocolonic response consists of a prompt increase in colonic tone after a meal. With a barostat and a high compliant air-filled bag, it is possible to measure rectal tone by recording changes in volume at a constant intrabag pressure. The aim of this study was to evaluate the gastrorectal response in males and females as well as the effect of different caloric loads on the gastrorectal response. In 33 volunteers a barostat procedure during basal conditions and after a 600-kcal meal was performed. In 26 volunteers the procedure was repeated with a 1000-kcal meal. A meal response was defined as a decrease in volume of more than 10%. Phasic volume events (PVE) were defined as a 10% decrease in volume of 15-60 sec duration. After a 600-kcal meal, the decrease in volume after 1 hr was 28 +/- 7% (mean +/- SEM, P < 0.001). A meal response was found in 64% of the subjects. Parous females had a diminished meal response compared with nulliparous females (2 +/- 5% and 48 +/- 11%, P < 0.001). After the 600-kcal meal, PVEs increased from 3 to 10/hr (P = 0.001). In the 26 subjects, volume decrease was 40 +/- 9% after the 1000-kcal meal and 20 +/- 7% after the 600-kcal meal (P = 0.28). In the high-calorie meal, 18 subjects (69%) had a response versus 14 (54%) in the low-calorie meal (NS). Enhancing the caloric load of the meal did not increase the amounts of PVEs. In conclusion, a gastrorectal response occurs in 64% of the healthy subjects after a 600-kcal meal. The gastrorectal response can be measured to a similar extent in men and nulliparous women; however, the response is significantly impaired in parous women. This is possibly due to neurogenic damage during childbirth. Increasing the caloric load did not increase the gastrorectal response. Therefore, to study gastrorectal meal response with the barostat, a meal of 600-kcal is sufficient and a correction for parity should be made when results are compared.
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Affiliation(s)
- Cornelius E J Sloots
- Department of Gastroenterology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands
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Simrén M, Simms L, D'Souza D, Abrahamsson H, Björnsson ES. Lipid-induced colonic hypersensitivity in irritable bowel syndrome: the role of 5-HT3 receptors. Aliment Pharmacol Ther 2003; 17:279-87. [PMID: 12534414 DOI: 10.1046/j.1365-2036.2003.01399.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Irritable bowel syndrome patients demonstrate colonic hypersensitivity after duodenal lipid infusion. AIM To investigate the role of 5-hydroxytryptamine-3 (5-HT3) receptors in this sensory component of the gastrocolonic response in irritable bowel syndrome. METHODS Fifteen female patients with diarrhoea-predominant irritable bowel syndrome completed a trial with the 5-HT3 receptor antagonist alosetron (1 mg b.d.) or placebo (b.d.) over 15 days, followed by the alternative treatment. Each treatment period was followed by a colonic distension trial before and after duodenal lipids. Changes in colonic thresholds, tone and compliance and viscerosomatic referral pattern after lipids were compared between treatments. RESULTS With placebo, the colonic thresholds after lipids were significantly reduced for all studied sensations, whereas, with alosetron, the thresholds were significantly reduced only for first sensation and discomfort, but not for gas and pain. The reductions in thresholds did not differ significantly between treatments, but the pain threshold after alosetron tended to be less reduced compared with placebo (P = 0.10). The effects of lipids on tone, compliance and viscerosomatic referral pattern were unaffected by alosetron relative to placebo. CONCLUSIONS 5-HT3 receptor antagonism reduces the lipid-induced colonic hypersensitivity in irritable bowel syndrome. However, 5-HT3 receptors do not seem to be the principal mediator, but may be a cofactor for the exaggerated sensory component of the gastrocolonic response in irritable bowel syndrome.
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Affiliation(s)
- M Simrén
- Department of Internal Medicine, Sahlgrenska University Hospital, Göteburg, Sweden.
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Serra J, Azpiroz F, Malagelada JR. Gastric distension and duodenal lipid infusion modulate intestinal gas transit and tolerance in humans. Am J Gastroenterol 2002; 97:2225-30. [PMID: 12358237 DOI: 10.1111/j.1572-0241.2002.05976.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Patients with unexplained abdominal complaints often attribute their symptoms to intestinal gas and indicate that symptoms are exacerbated by ingestion of a meal. However, the mechanisms responsible are unknown. Our aim was to analyze the specific influence of two meal-related factors, gastric distension, and intestinal nutrients, on intestinal gas dynamics and tolerance. METHODS In 35 healthy subjects, gas evacuation and perception of jejunal gas infusion (12 ml/min) were measured for 3 h, during simultaneous duodenal infusion of saline, as control, lipids at 1 Kcal/min, or gastric distension. RESULTS Infusion of lipids into the duodenum induced gas retention (584 +/- 154 ml, p < 0.05 vs 161 +/- 86 ml after saline infusion) without perception (2.2 +/- 0.5 score), whereas gastric distension induced perception (score 5.6 +/- 0.4, p < 0.05 vs score 1.9 +/- 0.4 after saline) without gas retention (7 +/- 205 ml). CONCLUSIONS Different meal-related factors exert specific effects on intestinal gas dynamics and tolerance, and these mechanisms may interact to produce postprandial gas symptoms.
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Affiliation(s)
- Jordi Serra
- Digestive System Research Unit, Hospital General Vall d'Hebron, Autonomous University of Barcelona, Spain
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Abstract
There is substantial evidence that colonic diverticulosis is related to civilization, industrialization and a "Western" lifestyle and diet, being described as "a disease of Western civilization". Its increased incidence during the 20th century and the morbidity and mortality associated with complications, demand that this condition should receive greater attention in terms of aetiology, prevention and management. It is generally believed that low dietary fibre and ageing are the two main pathogenic factors involved in this disease. Physiological studies have also demonstrated that there is a higher intraluminal pressure in the large bowel with diverticula. This chapter provides the evidence currently available for the pathophysiology of colonic diverticulosis and discusses its aetiological factors, including low dietary fibre, ageing and intraluminal pressure as well as extracelluar matrix such as collagen and elastin. The difference between the left-sided diverticulosis commonly seen in Caucasians and the right-sided predominantly observed in Asians is also presented.
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Affiliation(s)
- Toshiki Mimura
- Department of Gastrointestinal Surgery, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
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Bharucha AE, Hubmayr RD, Ferber IJ, Zinsmeister AR. Viscoelastic properties of the human colon. Am J Physiol Gastrointest Liver Physiol 2001; 281:G459-66. [PMID: 11447026 DOI: 10.1152/ajpgi.2001.281.2.g459] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Our objectives were to characterize colonic viscoelastic properties of the human descending colon by assessing pressure-volume (P-V) relationships during barostatic balloon distension. In 16 healthy subjects, a balloon was inflated to 44 mmHg and then deflated to 0 mmHg in 4-mmHg steps at 10, 30, and 60 ml/min, allowing volume fluctuations to stabilize at each pressure increment. Thereafter, these "quasi-static" P-V curves were compared with "dynamic" distensions to 300 ml, at 1 and 10 ml/s, before and after intravenous atropine in another five subjects. During quasi-static curves, balloon volume stabilized at each pressure increment. Quasi-static P-V curves were reproducible within individuals and approximated to a power exponential function and revealed hysteresis, indicative of viscoelasticity. Body mass index influenced quasi-static P-V curves during inflation but not during deflation. The colon was less compliant during dynamic distensions at 10 ml/s than during quasi-static distensions. Atropine increased quasi-static compliance and attenuated differences between quasi-static and rapid distensions. We conclude that colonic viscoelastic properties can be assessed by quasi-static P-V curves. Rapid colonic distension activated neural reflexes, thereby reducing colonic compliance compared with quasi-static distensions.
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Affiliation(s)
- A E Bharucha
- Gastroenterology Research Unit and Enteric Neurosciences Program, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
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46
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Abstract
Although aging per se affects function throughout the gut, particularly after age 70, the observed changes are relatively modest and often asymptomatic, perhaps because of the vast reserve of neuromuscular functional elements in the gut. The proximal esophagus, anus, and pelvic floor are possible exceptions to this generalization, and the combination of aging and factors such as minor strokes or obstetric damage often results in dysphagia, constipation, or fecal incontinence. Managing elderly patients with functional abdominal pain demands clinical acumen, tact, understanding, and patience. Further studies are required to elucidate the consequences of aging on gastrointestinal sensorimotor function at several levels of the digestive tract. With the expected explosion in the proportion of the population older than age 75, this field should become a high priority for clinical and research efforts. Also required will be a major campaign to educate patients and practitioners and multidisciplinary collaborations among primary care practitioners, gastroenterologists, psychologists, and physiatrists to provide optimal pain management in the elderly.
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Affiliation(s)
- A E Bharucha
- Enteric Neuroscience Group, Gastroenterology Research Unit, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA
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Coulie B, Camilleri M, Bharucha AE, Sandborn WJ, Burton D. Colonic motility in chronic ulcerative proctosigmoiditis and the effects of nicotine on colonic motility in patients and healthy subjects. Aliment Pharmacol Ther 2001; 15:653-63. [PMID: 11328259 DOI: 10.1046/j.1365-2036.2001.00959.x] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND Nicotine decreases diarrhoea and pain in ulcerative colitis without reducing inflammation. AIMS (i) To evaluate the effect of ulcerative proctosigmoiditis on motor functions of an uninflamed segment of descending colon; and (ii) to assess nicotine's effects on colonic motor functions in patients and healthy subjects. METHODS In healthy subjects (n=30) and patients with ulcerative colitis (13; 11 active, two quiescent colitis), we studied the effects of intravenous nicotine on colonic transit of solid residue by scintigraphy (healthy subjects) and on colonic motility in healthy subjects and 11 patients. RESULTS In ulcerative colitis, fasting colonic motility was increased, whereas motor response to a meal was significantly reduced; compliance was unchanged. In healthy subjects, high-dose nicotine induced transient high amplitude propagated contractions and relaxation of the descending colon followed by decreased phasic contractions. This dose also accelerated colonic transit. Low-dose nicotine (mimicking a transdermal nicotine patch) reduced colonic compliance in healthy subjects, but did not affect motor function in ulcerative colitis. CONCLUSIONS Ulcerative proctosigmoiditis increases fasting colonic motility and reduces tone response to a meal in the descending colon without affecting colonic compliance, suggesting changes in physiological responses but not intrinsic wall properties. Nicotine has dose-dependent effects on colonic motor activity in healthy subjects.
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Affiliation(s)
- B Coulie
- Gastroenterology Research Unit, Mayo Clinic, Rochester, MN 55905, USA
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Rao SS, Sadeghi P, Beaty J, Kavlock R, Ackerson K. Ambulatory 24-h colonic manometry in healthy humans. Am J Physiol Gastrointest Liver Physiol 2001; 280:G629-39. [PMID: 11254489 DOI: 10.1152/ajpgi.2001.280.4.g629] [Citation(s) in RCA: 173] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Our aim was to investigate motor activity of the healthy, relatively unprepared colon in the ambulatory state. Twenty-five age- and gender-matched adults had a six-sensor solid-state probe inserted into the proximal transverse colon without sedation. Subjects ambulated freely and ate standard meals. In 528 h of recording, we found a lower (P < 0.05) area under the curve during the night. Waking induced a threefold increase in motility, whereas meals induced a twofold increase. Women showed less activity (P < 0.05) in the transverse/descending colon than men. The transverse/descending colon showed more (P < 0.05) activity than the rectosigmoid colon. Seven patterns were recognized; predominantly, they were simultaneous, propagated, or periodic bursts of 3-cycles/min (cpm) waves. A specialized propagating pressure wave with a high amplitude (>105 mmHg) and a prolonged duration (>14 s) occurred in all subjects (mean 10/day), mostly after waking, after meals, or with defecation. A 3-cpm motor activity was seen in the rectosigmoid region predominantly at night. The colon exhibits a wide spectrum of pressure activity around the clock, with gender and regional differences and circadian rhythm. This comprehensive study provides qualitative and quantitative normative data for colonic manometry.
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Affiliation(s)
- S S Rao
- Department of Internal Medicine and Clinical Research Center, University of Iowa, Iowa City, Iowa 52242, USA.
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Simrén M, Abrahamsson H, Björnsson ES. An exaggerated sensory component of the gastrocolonic response in patients with irritable bowel syndrome. Gut 2001; 48:20-7. [PMID: 11115818 PMCID: PMC1728182 DOI: 10.1136/gut.48.1.20] [Citation(s) in RCA: 168] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND/AIMS Visceral hypersensitivity is a feature of the irritable bowel syndrome (IBS). Postprandial symptoms are common in these patients. The effects of nutrients on colonic perception in IBS are incompletely understood. SUBJECTS We studied 13 healthy subjects and 16 patients with IBS-eight had diarrhoea predominant (IBS-D) and eight constipation predominant (IBS-C) IBS. METHODS Colonic perception thresholds to balloon distension and viscerosomatic referral pattern were assessed before and after duodenal infusion of lipid or saline, respectively. At the end of the infusions, plasma levels of gastrointestinal peptides were determined. RESULTS Lipids lowered the thresholds for first sensation, gas, discomfort, and pain in the IBS group but only for gas in the control group. The percent reduction in thresholds for gas and pain after lipids was greater in the IBS and IBS-D groups but not in the IBS-C group compared with controls. IBS patients had an increased area of referred discomfort and pain after lipids compared with before infusion whereas the referral area remained unchanged in controls. No group differences in colonic tone or compliance were observed. In both groups higher levels of cholecystokinin, pancreatic polypeptide, peptide YY, vasoactive intestinal polypeptide, and neuropeptide Y were seen after lipids. Motilin levels were higher in patients and differences in the subgroups were observed. Levels of corticotrophin releasing factor were lower in the constipated group than in the diarrhoea group. CONCLUSIONS Postprandial symptoms in IBS patients may be explained in part by a nutrient dependent exaggerated sensory component of the gastrocolonic response.
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Affiliation(s)
- M Simrén
- Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
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Camilleri M. Neurogastroenterology: evolving concepts and techniques to study motility and hypersensitivity. Dig Liver Dis 2000; 32 Suppl 3:S227-32. [PMID: 11245304 DOI: 10.1016/s1590-8658(00)80287-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- M Camilleri
- Mayo Clinic and Mayo Foundation, Rochester, MN, USA.
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