- Neurogastroenterology and Motility
- Pelvic Floor Disorders
- Benign Anorectal Disorders
Clinical Associate Professor, Medicine - Gastroenterology & Hepatology
GI Program Director, Neuro-Gastroenterology Fellowship, Stanford (2021 - Present)
Director, Neurogastroenterology and Motility, Stanford (2021 - Present)
GI Director, Pelvic Health Center, Stanford (2018 - Present)
Boards, Advisory Committees, Professional Organizations
Councillor, Neurogastroenterology & Motility (NGM) section of the AGA Institute Council (2022 - Present)
Committee Member, ROME V Committee, Functional Anorectal Disorders Work Group (2021 - Present)
Committee Member, International Continence Society (ICS), Bowel Disease Consensus Work Group (2020 - Present)
Chair, Pelvic Floor Disorder Consortium, Pelvic Floor Testing Work Group (2020 - 2021)
Committee Member, American College of Gastroenterology, Irritable Bowel Syndrome patient education task force (2018 - 2021)
Board Certification: American Board of Internal Medicine, Gastroenterology (2015)
Board Certification: American Board of Internal Medicine, Internal Medicine (2011)
Fellowship, Mayo Clinic College of Medicine, Rochester, MN, Gastroenterology and Hepatology (2015)
Rsidency, Einstein Collège of Medicine, Jacobi Medical Centerx, Bronx, NY, Internal Medicine Residency (2012)
M.D., Shahid Beheshti University of Medical Sciences, Tehran, Iran, Medicine (2001)
Graduate and Fellowship Programs
Gastroenterology & Hepatology (Fellowship Program)
Irritable Bowel Syndrome Symptoms in Nonalcoholic Fatty Liver Disease Patients Are an Indicator of Depression and Anxiety.
Journal of clinical gastroenterology
GOALS: Determine factors associated with Irritable bowel syndrome (IBS) in nonalcoholic fatty liver disease (NAFLD) patients.BACKGROUND: IBS affects 10% to 15% of the adult population worldwide and is linked to anxiety and depression. The impact of IBS-type symptoms in NAFLD patients is not well described.STUDY: A cross-sectional study of patients in the hepatology clinic at Houston Methodist Hospital was performed based on a respondent postal survey. IBS was defined by the Rome IV questionnaire, anxiety and depression were assessed with the Hospital Anxiety Depression scale. Patients with inflammatory bowel disease, colorectal carcinoma, or small bowel tumors were excluded. Patients were divided based on Rome IV diagnostic criteria for IBS and Hospital Anxiety Depression scale.RESULTS: 130 patients were included in the analysis, 38 satisfied Rome IV criteria for IBS (IBS group) versus 92 who did not (non-IBS group). Depression was more prevalent in the IBS group (18.4% vs 5.4%, P=0.01). Anxiety was also greater in the IBS group (31.6% vs 9.8%, P=0.002). Female sex, depression, and body mass index (BMI)>30 were independent predictors of IBS in NAFLD in 4 multiple logistic regression models. In newly diagnosed IBS patients, gamma-glutamyl transferase levels were lower (67.5 vs 28, P=0.04). Current abdominal pain was higher than 100% versus 81.3% (P=0.045), as was pain associated with the change in stool frequency (96.3% vs 50%; P<0.001).CONCLUSION: Our study highlights the increased rate of IBS symptoms, depression, and anxiety in patients with NAFLD. Clinicians should be alert when IBS symptoms are reported by a NAFLD patient and be aware of the impact of these comorbidities on quality of life and response to therapy.
View details for DOI 10.1097/MCG.0000000000001770
View details for PubMedID 36226999
Environmental Pollutants are Associated with Irritable Bowel Syndrome in a Commercially Insured Cohort of California Residents.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
BACKGROUND AND AIMS: Prior studies have linked environmental pollutants with gastrointestinal (GI) diseases. Here, we quantify the relationships between seven pollutants and the zip code-level incidence of irritable bowel syndrome (IBS), functional dyspepsia (FD), inflammatory bowel diseases (IBD), and eosinophilic esophagitis (EoE) in California.METHODS: Claims in Optum's Clinformatics Data Mart (CDM) were linked with environmental exposures in California, derived from CalEnviroScreen 3.0. We identified adult patients with new diagnoses of each GI disease, and estimated claims-derived, zip-code level disease incidence rates. Two study periods were considered: 2009-2014 (ICD-9 era) and 2016-2019 (ICD-10 era). Multivariable negative binomial regression models were used to test associations between seven pollutants (ozone, particulate matter <2.5 microns [PM2.5], diesel emissions, drinking water contaminants, pesticides, toxic releases from industrial facilities, traffic density) and zip-code level incidence of the GI diseases along with a negative control outcome, adjusting for numerous potential confounders.RESULTS: Zip code-level IBS incidence was associated with PM2.5 (p<0.001 in both eras) and airborne toxic releases from facilities (p<0.001 in both eras). An increase of 1 microgram/m3 in PM2.5 or 1% in toxic releases translates to an increase in the IBS incidence rate of about 0.02 cases per 100 person-years. Traffic density and drinking water contaminant exposures were also associated with increasing IBS incidence, but these associations were not significant in both eras. Similarly, exposure to PM2.5, drinking water contaminants and airborne toxic releases from facilities were associated with FD incidence, though not in both eras. No significant associations were noted between pollutants and IBD or EoE incidence.CONCLUSION: Exposure to PM2.5 and airborne toxic releases from facilities are associated with higher IBS incidence among a cohort of commercially-insured Californians. Environmental pollutant exposure was not associated with the incidence of IBD and EoE in this cohort.
View details for DOI 10.1016/j.cgh.2022.09.025
View details for PubMedID 36202347
MRI biomarker of muscle composition is associated with severity of pelvic organ prolapse.
Techniques in coloproctology
BACKGROUND: The pathophysiology of pelvic organ prolapse is largely unknown. We hypothesized that reduced muscle mass on magnetic resonance defecography (MRD) is associated with increased pelvic floor laxity. The aim of this study was to compare the psoas and puborectalis muscle mass composition and cross-sectional area among patients with or without pelvic laxity.METHODS: An observational retrospective study was conducted on women>age 18years old who had undergone MRD for pelvic floor complaints from January 2020 to December 2020 at Stanford Pelvic Health Center. Pelvic floor laxity, pelvic organ descent, and rectal prolapse were characterized by standard measurements on MRD and compared to the psoas (L4 level) and puborectalis muscle index (cross-sectional area adjusted by height) and relative fat fraction, quantified by utilizing a 2-point Dixon technique. Regression analysis was used to quantify the association between muscle characteristics and pelvic organ measurements.RESULTS: The psoas fat fraction was significantly elevated in patients with abnormally increased resting and strain H and M lines (p<0.05) and increased with rising grades of Oxford rectal prolapse (p=0.0001), uterovaginal descent (p=0.001) and bladder descent (p=0.0005). In multivariate regression analysis, adjusted for age and body mass index, the psoas fat fraction (not muscle index) was an independent risk factor for abnormal strain H and M line; odds ratio (95% confidence interval) of 17.8 (2-155.4) and 18.5 (1.3-258.3) respectively, and rising Oxford grade of rectal prolapse 153.9 (4.4-5383) and bladder descent 12.4 (1.5-106). Puborectalis fat fraction was increased by rising grades of Oxford rectal prolapse (p=0.0002).CONCLUSIONS: Severity of pelvic organ prolapse appears to be associated with increasing psoas muscle fat fraction, a biomarker for reduced skeletal muscle mass. Future prospective research is needed to determine if sarcopenia may predict postsurgical outcomes after pelvic organ prolapse repair.
View details for DOI 10.1007/s10151-022-02651-8
View details for PubMedID 35727428
Alterations in brain activation patterns in women with functional defecatory disorder: A novel fMRI rectal balloon expulsion study.
Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
BACKGROUND: Functional defecatory disorders (FDD) are common among women. Despite the extensive research on peripheral mechanisms involved in FDD, the central-neural contribution to its pathophysiology remains poorly understood. We aimed to delineate specific supra-spinal regions involved in defecation and examine whether their activity, as measured by blood-oxygen-level-dependent (BOLD) signals, is different in FDD.METHODS: We performed functional MRI (fMRI) with concurrent rectal manometry in 15 controls and 18 females with ROME III diagnosis of FDD. A block design was used and brain activation maps based on BOLD effect employing the generalized linear model were calculated for each subject. Statistical significance between groups was assessed by a Student t-test with cluster-based multiple comparisons correction (corrected p<0.01).KEY RESULTS: Simulated defecation was associated with activation of regions of primary and supplementary motor (SMA) and somatosensory cortices, homeostatic afferent (thalamus, mid-cingulate cortex, and insula), and emotional arousal networks (hippocampus and prefrontal cortex), occipital and cerebellum along with deactivation of right anterior cingulate cortex (ACC) in controls. Women with FDD had fewer regions engaged in defecation and BOLD activation was much decreased is areas related to executive-cognitive function (insula, parietal, and prefrontal cortices). Patients unlike controls showed activation in right ACC and otherwise had similar brain activation patterns during anal squeeze.CONCLUSIONS & INFERENCES: Our results provide evidence that distinct differences exist in supra-spinal control of defecation in key regions of motivational-affective regulation and executive-cognitive function, in patients with FDD as compared to controls.
View details for DOI 10.1111/nmo.14389
View details for PubMedID 35478218
Intra-subject Variability in High Resolution Anorectal Manometry Using the London Classification: Diagnostic and Therapeutic Implications.
Digestive diseases and sciences
This retrospective pilot study conducted on a community-based cohort of both men and women of various ages and underlying clinical presentations examined the durability and reproducibility of HR-ARM findings influencing their potential impact on clinical decision-making at the point of care (Jameson et al. in Br J Surg 81:1689-1692, 1994). The key finding of our study was that only a minority of patients who underwent repeat anorectal manometry as analyzed by the London Classification had stable manometric findings, raising questions regarding the validity of a single manometric measurement, as currently analyzed, for clinical decision-making.
View details for DOI 10.1007/s10620-021-07373-9
View details for PubMedID 35194706
Consensus Definitions and Interpretation Templates for Magnetic Resonance Imaging of Defecatory Pelvic Floor Disorders: Proceedings of the Consensus Meeting of the Pelvic Floor Disorders Consortium of the American Society of Colon and Rectal Surgeons, the Society of Abdominal Radiology, the International Continence Society, the American Urogynecologic Society, the International Urogynecological Association, and the Society of Gynecologic Surgeons.
AJR. American journal of roentgenology
The Pelvic Floor Disorders Consortium (PFDC) is a multidisciplinary organization of colorectal surgeons, urogynecologists, urologists, gynecologists, gastroenterologists, radiologists, physiotherapists, and other advanced care practitioners. Specialists from these fields are all dedicated to the diagnosis and management of patients with pelvic floor conditions, but they approach, evaluate, and treat such patients with their own unique perspectives given the differences in their respective training. The PFDC was formed to bridge gaps and enable collaboration between these specialties. The goal of the PFDC is to develop and evaluate educational programs, create clinical guidelines and algorithms, and promote high quality of care in this unique patient population. The recommendations included in this article represent the work of the PFDC Working Group on Magnetic Resonance Imaging of Pelvic Floor Disorders (members listed alphabetically in Table 1). The objective was to generate inclusive, rather than prescriptive, guidance for all practitioners, irrespective of discipline, involved in the evaluation and treatment of patients with pelvic floor disorders.
View details for DOI 10.2214/AJR.21.26488
View details for PubMedID 34505543
PELVIC FLOOR DISORDERS IN PATIENTS WITH HYPERMOBILITY SPECTRUM DISORDERS
W B SAUNDERS CO-ELSEVIER INC. 2021: S500
View details for Web of Science ID 000649085001508
COVID-19 PANDEMIC INCREASED HEALTHCARE UTILIZATION AMONG PATIENTS WITH FUNCTIONAL GASTROINTESTINAL DISORDERS
W B SAUNDERS CO-ELSEVIER INC. 2021: S28-S29
View details for Web of Science ID 000649085000065
STOOL DELIVERY TO THE TERMINAL ILEUM MAY AFFECT RISK OF RECURRENCE OF CLOSTRIDIOIDES DIFFICILE INFECTION FOLLOWING INTESTINAL MICROBIOTA TRANSPLANTATION
W B SAUNDERS CO-ELSEVIER INC. 2021: S369-S370
View details for Web of Science ID 000649085001208
Rectal Prolapse: Age-Related Differences in Clinical Presentation and What Bothers Women Most.
Diseases of the colon and rectum
BACKGROUND: Rectal prolapse has a diverse symptom profile that affects patients of all ages.OBJECTIVE: We sought to identify bothersome symptoms and clinical presentation that motivated rectal prolapse patients to seek care, characterize differences in symptom severity with age, and determine factors associated with bothersome symptoms.DESIGN: Retrospective analysis of a prospectively maintained registry.SETTINGS: Tertiary referral academic center.PATIENTS: 129 consecutive women with full thickness rectal prolapse.MAIN OUTCOME MEASURES: Primary bothersome symptoms, 5-item Cleveland Clinic/Wexner Fecal Incontinence questionnaire, 5-item Obstructed Defecation Syndrome questionnaire. Patients were categorized by age<65 vs. age≥65 years.RESULTS: Cleveland Clinic/Wexner Fecal Incontinence score>9 was more common in older patients (87% vs 60%, p=.002). Obstructed Defecation Syndrome score>8 was more common in younger patients (57% vs 28%, p<.001). Older patients were more likely than younger patients to report bothersome symptoms of pain (38% vs 19%, p=.021) and bleeding (12% vs 2%, p=.046). Mucus discharge was reported by most patients (older, 72% vs younger, 66%, p=.54) but was bothersome for only 18%, regardless of age. Older patients had more severe prolapse expression than younger patients (at rest, 33% vs 11%; during activity, 26% vs 19%; only with defecation, 40% vs 64%, p=.006). Older patients were more likely to seek care within 6 months of prolapse onset (29% vs 11%, p=.056). Upon multivariable regression, increasing age, narcotic use and non-protracting prolapse at rest were associated with reporting pain as a primary complaint.LIMITATIONS: Single center; small sample size.CONCLUSIONS: Rectal prolapse-related bothersome symptoms and healthcare utilization differ by age. Although rectal pain is often not commonly associated with prolapse, it bothers many women and motivates older women to undergo evaluation. Patient-reported functional questionnaires may not reflect patients' primary concerns regarding specific symptoms and could benefit from supplementation with questionnaires to elicit individualized symptom priorities. See Video Abstract at http://links.lww.com/DCR/B492 .
View details for DOI 10.1097/DCR.0000000000001843
View details for PubMedID 33496475
Regional Gastrointestinal Transit and Contractility Patterns Vary in Postural Orthostatic Tachycardia Syndrome (POTS).
Digestive diseases and sciences
BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is an autonomic disorder that affects multiple organs, including the gastrointestinal system. These patients often have multiple GI complaints with a severe impact on their quality of life. GI dysmotility patterns in POTS remains poorly understood and difficult to manage.AIMS: The aim of this study was to investigate the diagnostic yield of wireless motility capsule in patients with gastrointestinal symptoms and POTS, with use of a symptomatic control group without POTS as a reference.METHODS: We retrospectively reviewed the charts of patients who had both autonomic testing and wireless motility capsule between 2016 and 2020. The two groups were divided into those with POTS and those without POTS (controls) as diagnosed through autonomic testing. We compared the regional transit times and motility patterns between the two groups using the data collected from wireless motility capsule.RESULTS: A total of 25% of POTS patients had delayed small bowel transit compared to 0% of non-POTS patients (p=0.047). POTS patients exhibited hypo-contractility patterns within the small bowel, including decreased contractions/min (2.95 vs. 4.22, p=0.011) and decreased motility index (101.36 vs. 182.11, p=0.021). In multivariable linear regression analysis, migraine predicted faster small bowel transit (p=0.007) and presence of POTS predicted slower small bowel transit (p=0.044).CONCLUSIONS: Motility abnormalities among POTS patients seem to affect mostly the small bowel and exhibit a general hypo-contractility pattern. Wireless motility capsule can be a helpful tool in patients with POTS and GI symptoms as it can potentially help guide treatment.
View details for DOI 10.1007/s10620-020-06808-z
View details for PubMedID 33428036
Gastrointestinal symptoms and healthcare utilization have increased among patients with functional gastrointestinal and motility disorders during the COVID-19 pandemic.
Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
The coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented disruptions in healthcare. Functional gastrointestinal and motility disorders (FGIMD) are associated with significant healthcare utilization. The clinical implications of these healthcare disruptions due to the COVID-19 pandemic on clinical outcomes in patients with FGIMD are unclear.We performed a retrospective study of patients with three common FGIMD (irritable bowel syndrome [IBS], gastroparesis, functional dyspepsia [FD]) tested for SARS-CoV-2 to describe alterations in gastrointestinal symptoms, medication use, and healthcare utilization during and before the pandemic and factors associated with COVID-19.The prevalence of COVID-19 during the pandemic (03/2020-09/2020) was 3.20% (83/2592) among patients with FGIMD, 3.62% in IBS (57/1574), 3.07% in gastroparesis (23/749), and 2.44% in FD (29/1187) at our institution. Patients with FGIMD had increased abdominal pain, nausea/vomiting, diarrhea, constipation, and weight loss (p < 0.001) along with increased proton pump inhibitor, H2 blocker, and opioid use (p < 0.0001). Both inpatient hospitalizations and outpatient visits (p < 0.0001) and number of diagnostic tests including cross-sectional imaging (p = 0.002), and upper and lower endoscopies (p < 0.0001) were significantly higher during the pandemic as compared to 6 months prior. Diarrhea-predominant IBS was positively (OR 2.37, 95% CI 1.34-4.19, p = 0.003) associated with COVID-19, whereas functional dyspepsia was negatively (OR 0.46, 95% CI 0.27-0.79, p = 0.004) associated.Patients with common functional gastrointestinal and motility disorders have reported more gastrointestinal symptoms during the COVID-19 pandemic with concurrent increased medication use and healthcare utilization.
View details for DOI 10.1111/nmo.14243
View details for PubMedID 34378840
- Consensus Definitions and Interpretation Templates for Magnetic Resonance Imaging of Defecatory Pelvic Floor Disorders: Proceedings of the Consensus Meeting of the Pelvic Floor Disorders Consortium of the American Society of Colon and Rectal Surgeons, the Society of Abdominal Radiology, the International Continence Society, the American Urogynecologic Society, the International Urogynecological Association, and the Society of Gynecologic Surgeons. Diseases of the colon and rectum 2021; 64 (10): 1184-1197
- Consensus definitions and interpretation templates for magnetic resonance imaging of Defecatory pelvic floor disorders : Proceedings of the consensus meeting of the pelvic floor disorders consortium of the American Society of Colon and Rectal Surgeons, the Society of Abdominal Radiology, the international continence society, the American Urogynecologic Society, the international Urogynecological association, and the Society of Gynecologic Surgeons. International urogynecology journal 2021
Postoperative complications and recurrence rates after rectal prolapse surgery versus combined rectal prolapse and pelvic organ prolapse surgery.
International urogynecology journal
Our primary objectives were to compare < 30-day postoperative complications and RP recurrence rates after RP-only surgery and combined surgery. Our secondary objectives were to determine preoperative predictors of < 30-day complications and RP recurrence.A prospective IRB-approved cohort study was performed at a single tertiary care center from 2017 to 2020. Female patients with symptomatic RP underwent either RP-only surgery or combined surgery based on the discretion of the colorectal and FPMRS surgeons. Primary outcome measures were < 30-day complications separated into Clavien-Dindo (CD) classes and rectal prolapse on physical examination.Seventy women had RP-only surgery and 45 had combined surgery with a mean follow-up time of 208 days. Sixty-eight percent underwent abdominal RP repair, and 32% underwent perineal RP repair. Twenty percent had one or more complications, 14% in the RP-only group and 29% in the combined surgery group (p = 0.06). On multivariate analysis, combined surgery patients had a 30% increased risk of complications compared to RP-only surgery patients (RR = 1.3). Most of these complications were minor (14/17, 82.4%) and categorized as CD I or II, including urinary retention and UTI. Twelve percent of this cohort had RP recurrence, 11% in the RP-only group and 13% in the combined surgery group (p = 0.76). Preoperative risk factors for RP recurrence included a primary complaint of rectal bleeding (RR 5.5) and reporting stools consistent with Bristol Stool Scale of 1 (RR 2.1).Patients undergoing combined RP + POP surgery had a higher risk of complications and equivalent RP recurrence rates compared to patients undergoing RP-only surgery.
View details for DOI 10.1007/s00192-021-04778-y
View details for PubMedID 33864476
- Coronavirus Testing Before Motility Laboratory Procedures: An Update. The American journal of gastroenterology 2020
High Prevalence of Methane Predominant Small Bowel Bacterial Overgrowth and Constipation in Patients With Hypermobile Ehlers-Danlos Syndrome
LIPPINCOTT WILLIAMS & WILKINS. 2020: S238
View details for Web of Science ID 000607196701128
American Neurogastroenterology and Motility Society Task Force Recommendations for Resumption of Motility Laboratory Operations During the COVID-19 Pandemic.
The American journal of gastroenterology
The American Neurogastroenterology and Motility Society Task Force recommends that gastrointestinal motility procedures should be performed in motility laboratories adhering to the strict recommendations and personal protective equipment (PPE) measures to protect patients, ancillary staff, and motility allied health professionals. When available and within constraints of institutional guidelines, it is preferable for patients scheduled for motility procedures to complete a coronavirus disease 2019 (COVID-19) test within 48 hours before their procedure, similar to the recommendations before endoscopy made by gastroenterology societies. COVID-19 test results must be documented before performing procedures. If procedures are to be performed without a COVID-19 test, full PPE use is recommended, along with all social distancing and infection control measures. Because patients with suspected motility disorders may require multiple procedures, sequential scheduling of procedures should be considered to minimize need for repeat COVID-19 testing. The strategies for and timing of procedure(s) should be adapted, taking into consideration local institutional standards, with the provision for screening without testing in low prevalence areas. If tested positive for COVID-19, subsequent negative testing may be required before scheduling a motility procedure (timing is variable). Specific recommendations for each motility procedure including triaging, indications, PPE use, and alternatives to motility procedures are detailed in the document. These recommendations may evolve as understanding of virus transmission and prevalence of COVID-19 infection in the community changes over the upcoming months.
View details for DOI 10.14309/ajg.0000000000000823
View details for PubMedID 32868631
Abnormal Balloon Expulsion Test in Patients with Fecal Incontinence.
Journal of gastrointestinal and liver diseases : JGLD
BACKGROUND AND AIMS: Functional defecatory dysfunction is attributed to the pathophysiology of fecal incontinence (FI) in some patients. We hypothesized that patients with FI and abnormal balloon expulsion test (BET) have distinct manometric characteristics as compared to the patients with FI and normal BET. We aimed to compare the anorectal pressure profile in patients with FI, with or without abnormal BET and to identify risk factors associated with abnormal BET in FI.METHODS: We performed a retrospective review of 77 consecutive patients with ROME IV FI. Wilcoxon rank sum test, t-test, and Fisher exact tests were performed for comparison. Multivariable logistic regression was performed to identify factors associated with abnormal BET.RESULTS: Thirty-two percent of patients had abnormal BET. Demographics and surgical history and clinical symptoms, except for sensation of incomplete evacuation (p=0.02) and abdominal pain (p=0.03), were comparable in both groups. Anorectal pressure profile except for the median rectal propulsive pressures were similar between groups. Rectal propulsive pressures at simulated defecation were significantly lower in patients with abnormal BET (p=0.02). Mean sensory threshold for first sensation was also significantly higher in patients who had abnormal BET (p=0.03). Rectal propulsive pressures (OR: 1.03, 95% CI: 1.00-1.06, p=0.032) and rectal sensory threshold for first sensation (OR:0.94, 95% CI: 0.90-0.99, p=0.02) were able to predict abnormal BET independently.CONCLUSIONS: In patients with FI and similar clinical and anal pressure profile, rectal sensory threshold and rectal propulsive pressures at simulated defecation can determine normal BET.
View details for DOI 10.15403/jgld-2273
View details for PubMedID 32830814
DYNAMIC ECHODEFECOGRAPHY FOR ASSESMENT OF FUNCTIONAL DEFECATORY DISORDERS
W B SAUNDERS CO-ELSEVIER INC. 2020: S388-S389
View details for Web of Science ID 000540349501217
IRRITABLE BOWEL SYNDROME SYMPTOMS IN NON-ALCOHOLIC FATTY LIVER DISEASE PATIENTS ARE AN INDICATOR OF DEPRESSION AND ANXIETY
W B SAUNDERS CO-ELSEVIER INC. 2020: S1429
View details for Web of Science ID 000540349504576
Marijuana, Ondansetron, and Promethazine Are Perceived as Most Effective Treatments for Gastrointestinal Nausea.
Digestive diseases and sciences
BACKGROUND: Many anti-nausea treatments are available for chronic gastrointestinal syndromes, but data on efficacy and comparative effectiveness are sparse.AIMS: To conduct a sectional survey study of patients with chronic nausea to assess comparative effectiveness of commonly used anti-nausea treatments.METHODS: Outpatients at a single center presenting for gastroenterology evaluation were asked to rate anti-nausea efficacy on a scale of 0 (no efficacy) to 5 (very effective) of 29 commonly used anti-nausea treatments and provide other information about their symptoms. Additional information was collected from the patients' chart. The primary outcome was to determine which treatments were better or worse than average using a t test. The secondary outcome was to assess differential response by individual patient characteristics using multiple linear regression.RESULTS: One hundred and fifty-three patients completed the survey. The mean efficacy score of all anti-nausea treatments evaluated was 1.73. After adjustment, three treatments had scores statically higher than the mean, including marijuana (2.75, p<0.0001), ondansetron (2.64, p<0.0001), and promethazine (2.46, p<0.0001). Several treatments, including many neuromodulators, complementary and alternative treatments, erythromycin, and diphenhydramine had scores statistically below average. Patients with more severe nausea responded better to marijuana (p=0.036) and diphenhydramine (p<0.001) and less so to metoclopramide (p=0.020). There was otherwise no significant differential response by age, gender, nausea localization, underlying gastrointestinal cause of nausea, and GCSI.CONCLUSIONS: When treating nausea in patients with chronic gastrointestinal syndromes, clinicians may consider trying higher performing treatments first, and forgoing lower performing treatments. Further prospective research is needed, particularly with respect to highly effective treatments.
View details for DOI 10.1007/s10620-020-06195-5
View details for PubMedID 32185665
Pelvic Floor Disorders and Functional Anorectal Pain
DIAGNOSIS AND MANAGEMENT GUIDE FOR ANORECTAL DISEASE: A CLINICAL REFERENCE
View details for Web of Science ID 000497589100006
Rectal Distension Increased the Rectoanal Gradient in Patients with Normal Rectal Sensory Function.
Digestive diseases and sciences
Frequent observation of abnormal manometric patterns consistent with dyssynergia in healthy volunteers has warranted the need for reassessment of the current methods to enhance the diagnostic value of anorectal manometry in functional defecatory disorders. Whether rectal distention at simulated evacuation will affect anorectal pressure profile and increase rectoanal gradient is not known.One hundred and eight consecutive patients with chronic constipation, 93 females, median age 53 years (interquartile range: 40-65), were studied. Simulated evacuation was performed firstly with empty balloon and subsequently after balloon distention to 50 and 100 ml. Anorectal pressures were compared. We also performed subgroup analysis in relation to outcome of balloon expulsion test (BET). In addition, we studied the effect of rectal distension on the rectoanal pressure gradient with respect to rectal sensory function.Rectal balloon distension at simulated evacuation improved rectoanal gradient and decreased the rate of dyssynergia during high-resolution anorectal manometry. In subgroup analysis, the increase in rectoanal gradient and correction of dyssynergia with rectal distension was limited to the patients who had normal BET and normal rectal sensory function. Rate of anal relaxation, residual anal pressures, and rectoanal gradient were significantly different between patients with and without normal BET at 50 ml of rectal distension. Rectoanal gradient recorded only after rectal distension, along with BMI and maximum tolerable volumes, could predict BET results independently in patients with chronic constipation.Rectal distension during simulated evacuation will affect the anorectal pressure profile. Increase in rectoanal gradient and correction of dyssynergia was only significant in patients with normal rectal sensory function and normal BET.
View details for DOI 10.1007/s10620-020-06519-5
View details for PubMedID 32761289
- Motility Abnormalities Identified by Wireless Motility Capsule in Postural Orthostatic Tachycardia Syndrome LIPPINCOTT WILLIAMS & WILKINS. 2019: S279
WHICH ANTI-NAUSEA THERAPIES DO PATIENTS BELIEVE WORK BEST? A PATIENT-REPORTED EFFICACY STUDY
W B SAUNDERS CO-ELSEVIER INC. 2019: S782
View details for Web of Science ID 000467106003108
- High Prevalence of Slow Transit Constipation in Patients With Gastroparesis JOURNAL OF NEUROGASTROENTEROLOGY AND MOTILITY 2019; 25 (2): 267–75
High Prevalence of Slow Transit Constipation in Patients With Gastroparesis.
Journal of neurogastroenterology and motility
Background/Aims: Current evidence suggests the presence of motility or functional abnormalities in one area of the gastrointestinal tract increases the likelihood of abnormalities in others. However, the relationship of gastroparesis to chronic constipation (slow transit constipation and dyssynergic defecation) has been incompletely evaluated.Methods: We retrospectively reviewed the records of all patients with chronic dyspeptic symptoms and constipation who underwent both a solid gastric emptying scintigraphy and a highresolution anorectal manometry at our institution since January 2012. When available, Xray defecography and radiopaque marker colonic transit studies were also reviewed. Based on the gastric emptying results, patients were classified as gastroparesis or dyspepsia with normal gastric emptying (control group). Differences in anorectal and colonic findings were then compared between groups.Results: Two hundred and six patients met the inclusion criteria. Patients with gastroparesis had higher prevalence of slow transit constipation by radiopaque marker study compared to those with normal emptying (64.7% vs 28.1%, P = 0.013). Additionally, patients with gastroparesis had higher rates of rectocele (88.9% vs 60.0%, P = 0.008) and intussusception (44.4% vs 12.0%, P = 0.001) compared to patients with normal emptying. There was no difference in the rate of dyssynergic defecation between those with gastroparesis vs normal emptying (41.1% vs 42.1%, P = 0.880), and no differences in anorectal manometry findings.Conclusions: Patients with gastroparesis had a higher rate of slow transit constipation, but equal rates of dyssynergic defecation compared to patients with normal gastric emptying. These findings argue for investigation of possible delayed colonic transit in patients with gastroparesis and vice versa.
View details for PubMedID 30870880
- Editorial: Botox for levator ani TECHNIQUES IN COLOPROCTOLOGY 2019; 23 (3): 199–200
Neural control properties of the external anal sphincter in young and elderly women.
Neurourology and urodynamics
The prevalence of fecal incontinence (FI) increases with age and affects more than 15% of the elderly population. Sarcopenia, skeletal muscle structural, and functional decline with aging, is known to be caused by neuromuscular dysfunction. However, age-related alterations of the neuromuscular function of the external anal sphincter (EAS) have not been studied. This study aims to quantitatively characterize the effect of aging on the EAS by assessing the firing patterns and size of motor unit action potential (MUAP) using high-density surface electromyography (HD-sEMG) recording and analysis techniques.Thirteen young (31.0 ± 3.6 years) and 14 elderly (64.3 ± 6.2 years) healthy women were recruited for this study. EMG activity of the EAS during maximal voluntary contraction was recorded by a 64-Channel, HD-sEMG intra-rectal probe. HD-sEMG signals were decomposed into MUAP spike trains to extract the firing rate and amplitudes thereof.HD-sEMG decomposition was successfully performed. For the young and elderly groups, mean motor unit (MU) firing rates of 11.4 ± 2.1 pulses per second (PPS) and 9.6 ± 2.3 PPS, and mean MUAP amplitudes of 45.2 ± 14.3 µV and 61.9 ± 21.2 µV were respectively obtained. Both the MU firing rate and MUAP amplitude were significantly different between two groups (P < .05). Moreover, the MUAP firing rate and amplitude correlated with age with a linear regression model (P < .05).This study represents the first effort to examine the effect of aging on the neuromuscular function of EAS. Results suggest an age-related impairment of lower motor neuron descending excitation to the EAS with a compensatory increase in mean MU size.
View details for DOI 10.1002/nau.24108
View details for PubMedID 31321803
BRAIN FUNCTIONAL MRI REVEALS ALTERATIONS IN BRAIN ACTIVITY DURING SIMULATED EVACUATION IN PATIENTS WITH FUNCTIONAL DEFECATORY DISORDERS
W B SAUNDERS CO-ELSEVIER INC. 2018: S185
View details for Web of Science ID 000450011100537
BRAIN FUNCTIONAL MRI REVEALS ALTERATIONS IN BRAIN ACTIVITY DURING PELVIC FLOOR CONTRACTION IN PATIENTS WITH FUNCTIONAL DEFECATORY DISORDERS
W B SAUNDERS CO-ELSEVIER INC. 2018: S543-S544
View details for Web of Science ID 000450011102147
- The assessment and management of defecatory dysfunction: a critical appraisal CURRENT OPINION IN GASTROENTEROLOGY 2018; 34 (1): 31-37
- A Case of Gastrointestinal Bleeding as Initial Presentation of Metastatic Cutaneous Melanoma NATURE PUBLISHING GROUP. 2017: S1019
- Anorectal Pressure Profile in IBD Patients as Compared to Non-IBD Patients With Fecal Incontinence NATURE PUBLISHING GROUP. 2017: S238
- EFFECT OF RECTAL DISTENTION ON ANAL PRESSURES DURING SIMULATED DEFECATION IN PATIENTS WITH DEFECATORY DISORDERS W B SAUNDERS CO-ELSEVIER INC. 2017: S317-S318
- SUPRASPINAL CONTROL OF DEFECATION USING CONCURRENT FUNCTIONAL MAGNETIC RESONANCE IMAGING AND RECTAL PRESSURE MONITORING W B SAUNDERS CO-ELSEVIER INC. 2017: S929
- PHENOTYPE IDENTIFICATION OF PATIENTS WITH DEFECATORY DISORDERS WHO WILL BENEFIT FROM SQUATTING STOOL W B SAUNDERS CO-ELSEVIER INC. 2017: S318
- RELATIONSHIPS BETWEEN ANAL PRESSURE PROFILES DERIVED FROM HIGH-DEFINITION ANORECTAL MANOMETRY AND RESULTS OF BALLOON EXPULSION TEST IN PATIENTS WITH CHRONIC CONSTIPATION W B SAUNDERS CO-ELSEVIER INC. 2017: S17
The assessment and management of defecatory dysfunction: a critical appraisal.
Current opinion in gastroenterology
To summarize the advances in diagnostic modalities and management options for defecatory dysfunction and highlight the areas in need of further research.The diagnostic utility of high-resolution anorectal manometry (ARM), which has emerged as a promising tool for the diagnosis of defecatory dysfunction, appears to be questionable in differentiating disease from normal physiology. There also seems to be discrepancy between results of various tests of anorectal function in the diagnosis of defecatory dysfunction. New revisions in diagnostic criteria for defecatory dysfunction by Rome IV consortium, may enhance its diagnostic yield. Biofeedback remains to be the most effective evidence-based treatment option for patients with defecatory dysfunction. Anorectal pressure profile cannot predict or mediate the success of biofeedback. Biofeedback may improve the symptoms through central effects.Despite the advances in the ARM and defecography techniques, no one test has been able to be considered as the 'gold standard' for diagnosis of defecatory dysfunction. The mechanism of action of biofeedback in defecatory dysfunction remains poorly understood.
View details for PubMedID 29064840
Irritable bowel syndrome (IBS) patients have SCN5A channelopathies that lead to decreased NaV1.5 current and mechanosensitivity.
American journal of physiology. Gastrointestinal and liver physiology
The SCN5A-encoded voltage-gated mechanosensitive sodium (Na+) channel NaV1.5 is expressed in human GI smooth muscle cells and interstitial cells of Cajal. NaV1.5 contributes to smooth muscle electrical slow waves and mechanical sensitivity. In predominately Caucasian IBS patient cohorts, 2-3% have SCN5A missense mutations which alter NaV1.5 function and may contribute to IBS pathophysiology. In this study examined a racially and ethnically diverse cohort of IBS patients for SCN5A missense mutations, and compared them to IBS negative controls, and determined the resulting NaV1.5 voltage-dependent and mechanosensitive properties. All SCN5A exons were sequenced from somatic DNA of 252 Rome III IBS patients with diverse ethnic and racial backgrounds. Missense mutations were introduced into wild-type SCN5A by site-directed mutagenesis and co-transfected with GFP into HEK-293 cells. NaV1.5 voltage-dependent and mechanosensitive functions were studied by whole cell electrophysiology with and without shear force. Five of 252 IBS patients (2.0%) had six rare SCN5A mutations, which were absent in 377 IBS-negative controls. All (6/6, 100%) IBS-associated NaV1.5 mutations had voltage-dependent gating abnormalities: current density reduction (R225W, R433C, R986Q, F1293S) and altered voltage dependence (R225W, R433C, R986Q, G1037V, F1293S) and at least one kinetic parameter was altered in all mutations. Four IBS-associated SCN5A mutations (4/6, 67%) resulted in altered NaV1.5 mechanosensitivity (R225W, R433C, R986Q, F1293S). In this racially and ethnically diverse cohort of IBS patients we show that 2% of IBS patients harbor SCN5A mutations that are absent in IBS-negative controls and result in NaV1.5 channels with abnormal voltage-dependent and mechanosensitive function.
View details for DOI 10.1152/ajpgi.00016.2017
View details for PubMedID 29167113
A rare cause of an upper gastrointestinal bleed.
View details for PubMedID 29102618
- Difficult to Find, Easy to Treat! NATURE PUBLISHING GROUP. 2016: S1130
Long-term Follow-up Study of Fecal Microbiota Transplantation for Severe and/or Complicated Clostridium difficile Infection A Multicenter Experience
JOURNAL OF CLINICAL GASTROENTEROLOGY
2016; 50 (5): 398-402
Our aim was to investigate fecal microbiota transplantation (FMT) efficacy in patients with severe and/or complicated Clostridium difficile infection (CDI).FMT is successful for recurrent CDI, although its benefit in severe or complicated CDI has not specifically been evaluated.A multicenter long-term follow-up study was performed in patients who received FMT for severe and/or complicated CDI (diagnosed using standard criteria). Pre-FMT and post-FMT questionnaires were completed. Study outcomes included cure rates and time to resolution of symptoms.A total of 17 patients (82% inpatients, 18% outpatients) were included (76.4% women; mean age, 66.4 y; mean follow-up, 11.4 mo). Patients had severe and complicated (76.4%) or either severe or complicated (23.6%) CDI. Sixteen patients (94.1%) had diarrhea, which resolved in 12 (75%; mean time to resolution, 5.7 d) and improved in 4 (25%) after FMT. Eleven patients (64.7%) had abdominal pain, which resolved in 8 (72.7%; mean time to resolution, 9.6 d) and improved in 3 (27.3%) after FMT. Two of 17 patients experienced early CDI recurrence (≤90 d) after FMT (primary cure rate, 88.2%); and in 1 patient, a second FMT resulted in cure (secondary cure rate, 94.1%). Late CDI recurrence (≥90 d) was seen in 1 of 17 patients (5.9%) in association with antibiotics and was successfully treated with a repeat FMT. No adverse effects directly related to FMT occurred.FMT was successful and safe in this cohort of patients with severe or complicated CDI. Primary and secondary cure rates were 88.2% and 94.1%, respectively.
View details for Web of Science ID 000375032900010
View details for PubMedID 26125460
- Computational Modeling and Simulation of Fecal Incontinence - The Effect of Stool Consistency on Leakage W B SAUNDERS CO-ELSEVIER INC. 2016: S944
- Balloon Expulsion and Relationship to Anal Sphincter Function in Fecal Incontinence W B SAUNDERS CO-ELSEVIER INC. 2016: S943-S944
Advancing treatment options for chronic idiopathic constipation
EXPERT OPINION ON PHARMACOTHERAPY
2016; 17 (4): 501-511
Chronic constipation is a global problem affecting all ages and associated with considerable morbidity and significant financial burden for society. Though formerly defined on the basis of a single symptom, infrequent defecation; constipation is now viewed as a syndrome encompassing several complaints such as difficulty with defecation, a sense of incomplete evacuation, hard stools, abdominal discomfort and bloating.The expanded concept of constipation has inevitably led to a significant change in outcomes in clinical trials, as well as in patient expectations from new therapeutic interventions. The past decades have also witnessed a proliferation in therapeutic targets for new agents. Foremost among these have been novel prokinetics, a new category, prosecretory agents and innovative approaches such as inhibitors of bile salt transport. In contrast, relatively few effective therapies exist for the management of those anorectal and pelvic floor problems that result in difficult defecation.Though constipation is a common and often troublesome disorder, many of those affected can resolve their symptoms with relatively simple measures. For those with more resistant symptoms a number of novel, effective and safe options now exist. Those with defecatory difficulty (anismus, pelvic floor dysfunction) continue to represent a significant management challenge.
View details for DOI 10.1517/14656566.2016.1127356
View details for Web of Science ID 000370759000001
View details for PubMedID 26630260
Neurogenic Bowel Dysfunction in Patients with Neurogenic Bladder.
Current bladder dysfunction reports
2016; 11 (4): 334–40
Patients with primary neurologic conditions often experience urinary and bowel dysfunction due to loss of sensory and/or motor control. Neurogenic bowel dysfunction is frequently characterized by both constipation and fecal incontinence. In general, the management of neurogenic bowel dysfunction has been less well studied than bladder dysfunction despite their close association.. It is widely accepted that establishment of a multifaceted bowel regimen is the cornerstone of conservative management. Continuing assessment is necessary to determine need for more invasive interventions. In the clinical setting, the Urologist may be the principle provider addressing bowel concerns in addition to bladder dysfunction, and furthermore, treatment of one often impacts the other. Future directions should include development of follow up and management guidelines that address the comprehensive care of this patient population.
View details for PubMedID 28717406
Ranolazine inhibits voltage-gated mechanosensitive sodium channels in human colon circular smooth muscle cells
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
2015; 309 (6): G506-G512
Human jejunum smooth muscle cells (SMCs) and interstitial cells of Cajal (ICCs) express the SCN5A-encoded voltage-gated, mechanosensitive sodium channel NaV1.5. NaV1.5 contributes to small bowel excitability, and NaV1.5 inhibitor ranolazine produces constipation by an unknown mechanism. We aimed to determine the presence and molecular identity of Na(+) current in the human colon smooth muscle and to examine the effects of ranolazine on Na(+) current, mechanosensitivity, and smooth muscle contractility. Inward currents were recorded by whole cell voltage clamp from freshly dissociated human colon SMCs at rest and with shear stress. SCN5A mRNA and NaV1.5 protein were examined by RT-PCR and Western blots, respectively. Ascending human colon strip contractility was examined in a muscle bath preparation. SCN5A mRNA and NaV1.5 protein were identified in human colon circular muscle. Freshly dissociated human colon SMCs had Na(+) currents (-1.36 ± 0.36 pA/pF), shear stress increased Na(+) peaks by 17.8 ± 1.8% and accelerated the time to peak activation by 0.7 ± 0.3 ms. Ranolazine (50 μM) blocked peak Na(+) current by 43.2 ± 9.3% and inhibited shear sensitivity by 25.2 ± 3.2%. In human ascending colon strips, ranolazine decreased resting tension (31%), reduced the frequency of spontaneous events (68%), and decreased the response to smooth muscle electrical field stimulation (61%). In conclusion, SCN5A-encoded NaV1.5 is found in human colonic circular smooth muscle. Ranolazine blocks both peak amplitude and mechanosensitivity of Na(+) current in human colon SMCs and decreases contractility of human colon muscle strips. Our data provide a likely mechanistic explanation for constipation induced by ranolazine.
View details for DOI 10.1152/ajpgi.00051.2015
View details for Web of Science ID 000361817700011
View details for PubMedID 26185330
View details for PubMedCentralID PMC4572410
- A Hidden Cause of Dysphagia. Primary Esophageal Lymphoma. Gastroenterology 2015; 149 (3): 549-550
IBS Patients Have SCN5A Mutations That Result in Decreased Na(V)1.5 Current and Mechanosensitivity
W B SAUNDERS CO-ELSEVIER INC. 2015: S130-S131
View details for Web of Science ID 000359414700453
Macrophages in diabetic gastroparesis - the missing link?
NEUROGASTROENTEROLOGY AND MOTILITY
2015; 27 (1): 7-18
Diabetic gastroparesis results in significant morbidity for patients and major economic burden for society. Treatment options for diabetic gastroparesis are currently directed at symptom control rather than the underlying disease and are limited. The pathophysiology of diabetic gastroparesis includes damage to intrinsic and extrinsic neurons, smooth muscle, and interstitial cells of Cajal (ICC). Oxidative damage in diabetes appears to be one of the primary insults involved in the pathogenesis of several complications of diabetes, including gastroparesis. Recent studies have highlighted the potential role of macrophages as key cellular elements in the pathogenesis of diabetic gastroparesis. Macrophages are important for both homeostasis and defense against a variety of pathogens. Heme oxygenase 1 (HO1), an enzyme expressed in a subset of macrophages has emerged as a major protective mechanism against oxidative stress. Activation of macrophages with high levels of HO1 expression protects against development of delayed gastric emptying in animal models of diabetes, while activation of macrophages that do not express HO1 are linked to neuromuscular cell injury. Targeting macrophages and HO1 may therefore be a therapeutic option in diabetic gastroparesis.This report briefly reviews the pathophysiology of diabetic gastroparesis with a focus on oxidative damage and how activation and polarization of different subtypes of macrophages in the muscularis propria determines development of delay in gastric emptying or protects against its development.
View details for DOI 10.1111/nmo.12418
View details for Web of Science ID 000347167100002
View details for PubMedID 25168158
View details for PubMedCentralID PMC4409126
- Ranolazine Blocks Na(V)1.5 Peak Current and Shear Sensitivity in Human Colonic Circular Smooth Muscle NATURE PUBLISHING GROUP. 2014: S194
- Abdominal Pain and Bloating in an Auto Mechanic GASTROENTEROLOGY 2014; 146 (7): 1610-1611
Y1767 Is Important for Block of Na(V)1.5 Shear Sensitivity by Ranolazine
W B SAUNDERS CO-ELSEVIER INC. 2014: S528
View details for Web of Science ID 000371236402465
- Complications of Dropped Gallstones NATURE PUBLISHING GROUP. 2013: S261-S262
- Long-Term Follow-up Study of Fecal Microbiota Transplantation (FMT) for Severe or Complicated Clostridium difficile Infection (CDI) W B SAUNDERS CO-ELSEVIER INC. 2013: S185
- Clostridium difficile Associated Disease in Parturient Women NATURE PUBLISHING GROUP. 2012: S229
- Cytomegalovirus Infection Complicating Management of Inflammatory Bowel Disease in the Immunocompetent Patient NATURE PUBLISHING GROUP. 2010: S353
Distinct modulation of K-v1.2 channel gating by wild type, but not open form, of syntaxin-1A
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
2007; 292 (5): G1233-G1242
SNARE proteins, syntaxin-1A (Syn-1A) and SNAP-25, inhibit delayed rectifier K(+) channels, K(v)1.1 and K(v)2.1, in secretory cells. We showed previously that the mutant open conformation of Syn-1A (Syn-1A L165A/E166A) inhibits K(v)2.1 channels more optimally than wild-type Syn-1A. In this report we examined whether Syn-1A in its wild-type and open conformations would exhibit similar differential actions on the gating of K(v)1.2, a major delayed rectifier K(+) channel in nonsecretory smooth muscle cells and some neuronal tissues. In coexpression and acute dialysis studies, wild-type Syn-1A inhibited K(v)1.2 current magnitude. Of interest, wild-type Syn-1A caused a right shift in the activation curves of K(v)1.2 without affecting its steady-state availability, an inhibition profile opposite to its effects on K(v)2.1 (steady-state availability reduction without changes in voltage dependence of activation). Also, although both wild-type and open-form Syn-1A bound equally well to K(v)1.2 in an expression system, open-form Syn-1A failed to reduce K(v)1.2 current magnitude or affect its gating. This is in contrast to the reported more potent effect of open-form Syn-1A on K(v)2.1 channels in secretory cells. This finding together with the absence of Munc18 and/or 13-1 in smooth muscles suggested that a change to an open conformation Syn-1A, normally facilitated by Munc18/13-1, is not required in nonsecretory smooth muscle cells. Taken together with previous reports, our results demonstrate the multiplicity of gating inhibition of different K(v) channels by Syn-1A and is compatible with versatility of Syn-1A modulation of repolarization in various secretory and nonsecretory (smooth muscle) cell types.
View details for DOI 10.1152/ajpgi.00473.2006
View details for Web of Science ID 000247935800007
View details for PubMedID 17234891
Calcium source diversity in feline lower esophageal sphincter circular and sling muscle
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
2004; 286 (2): G271-G277
Within muscular equivalents of cat lower esophageal sphincter (LES), the circular muscle develops greater spontaneous tone, whereas the sling muscle is more responsive to cholinergic stimulation. Smooth muscle contraction involves a combination of calcium release from stores and of calcium entry via several pathways. We hypothesized that there are differences in the sources of Ca(2+) used for contraction in sling and circular muscles and that these differences could contribute to functional asymmetry observed within LES. Contraction of muscle strips from circular and sling regions of LES was assessed in the presence of TTX. In Ca(2+)-free Krebs, tone was inhibited to a greater degree in circular than sling muscle. L-type Ca(2+) channel blockade with nifedipine or verapamil inhibited tone in LES circular but not sling muscle. Sarcoplasmic reticulum (SR) Ca(2+)-ATPase inhibitor cyclopiazonic acid (CPA) caused greater increase in tone in sling than in circular muscle. The phospholipase C inhibitor U-73122 and the SR inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] receptor blocker 2-aminoethoxydiphenyl borate (2-APB) inhibited tone in circular and sling muscles, demonstrating that continuous release of Ca(2+) from Ins(1,4,5)P(3)-sensitive stores is important in tone generation in both muscles. In Ca(2+)-free Krebs, ACh-induced contractions (AChC) were inhibited to a greater degree in sling than circular muscles. However, nifedipine and verapamil greatly inhibited AChC in the circular but not sling muscle. Depletion of SR Ca(2+) stores with CPA or inhibition of Ins(1,4,5)P(3)-mediated store release with either U-73122 or 2-APB inhibited AChC in both muscles. We demonstrate that LES circular and sling muscles 1) use intracellular and extracellular Ca(2+) sources to different degrees in the generation of spontaneous tone and AChC and 2) use different Ca(2+) entry pathways. These differences hold the potential for selective modulation of LES tone in health and disease.
View details for DOI 10.1152/ajpgi.00291.2003
View details for Web of Science ID 000188002500011
View details for PubMedID 14563670
- Spontaneous tone and cholinergic contractions: Differences in calcium handling in cat lower esophageal sphincter sling and clasp muscles W B SAUNDERS CO. 2003: A161-A162