Although much new information about normal and abnormal esophageal motor function has accrued during the past decade, many important questions remain unanswered. This grant proposal represents a comprehensive approach to investigating esophageal motor function in normal subjects, patients with symptomatic gastroesophageal reflux, patients with a variety of esophagopharyngeal motor disorders and in laboratory animals. The specific protocols fall into four general, but interrelated categories: 1) instrumentation and technique, 2) reflux esophagitis and gastroesophageal reflux disease, 3) esophageal motor physiology in normal subjects and experimental animals, and 4) studies of miscellaneous esophagopharyngeal motility disorders such as achalasia, scleroderma and muscular dystrophy. An important aspect of the study is to further refine the instrumentation and methodology for optimal recording of esophagopharyngeal pressure events and intraluminal pH. Particular emphasis will be given to perfecting the instrumentation that will allow long-interval recording of upper esophageal sphincter pressure. Such technical achievements are necessary for optimal investigation of pharyngoesophageal motor physiology and pathophysiology. A major thrust in this grant proposal will be to study further the pathophysiology and treatment of reflux esophagitis. Particular emphasis will be given to the investigation of the mechanisms that enable gastroesophageal reflux, efficacy of esophageal acid clearance and mechanisms associated with acid regurgitation into the pharynx. We will evaluate the neural apparatus and sensory stimuli that trigger the reflex transient lower esophageal sphincter relaxations that underlie most episodes of gastroesophageal reflux. Our plans also include follow-up studies on patients who have undergone fundoplication for the treatment of reflux esophagitis. These studies will not only determine the efficacy of this procedure, but will also clarify the mechanisms whereby fundoplication procedures generally retard gastroesophageal reflux. Studies in normal volunteers and experimental animals are designed to evaluate the normal physiological mechanisms that regulate motor function in the esophageal body and both its sphincters. An enhanced knowledge of normal motor physiology will serve as the basis for a better understanding of the pathophysiology of esophagopharyngeal motor disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK025731-08
Application #
3227559
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1979-07-01
Project End
1991-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
8
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Medical College of Wisconsin
Department
Type
Schools of Medicine
DUNS #
073134603
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Lang, Ivan M; Medda, Bidyut K; Shaker, Reza et al. (2018) The effect of body position on esophageal reflexes in cats: a possible mechanism of SIDS? Pediatr Res 83:731-738
Agrawal, D; Kern, M; Edeani, F et al. (2018) Swallow strength training exercise for elderly: A health maintenance need. Neurogastroenterol Motil 30:e13382
Liu, Xiaolin; Li, Shi-Jiang; Shaker, Reza et al. (2017) Reduced Functional Connectivity Between the Hypothalamus and High-order Cortical Regions in Adolescent Patients With Irritable Bowel Syndrome. J Pediatr Gastroenterol Nutr 65:516-519
Mei, Ling; Jiao, Hongmei; Sharma, Tarun et al. (2017) Comparative effect of the sites of anterior cervical pressure on the geometry of the upper esophageal sphincter high-pressure zone. Laryngoscope 127:2466-2474
Kern, Mark K; Balasubramanian, Gokulakrishnan; Sanvanson, Patrick et al. (2017) Pharyngeal peristaltic pressure variability, operational range, and functional reserve. Am J Physiol Gastrointest Liver Physiol 312:G516-G525
Jiao, Hongmei; Mei, Ling; Sharma, Tarun et al. (2016) A human model of restricted upper esophageal sphincter opening and its pharyngeal and UES deglutitive pressure phenomena. Am J Physiol Gastrointest Liver Physiol 311:G84-90
Lang, Ivan M; Haworth, Steven T; Medda, Bidyut K et al. (2016) Mechanisms of airway responses to esophageal acidification in cats. J Appl Physiol (1985) 120:774-83
Lyros, Orestis; Nie, Linghui; Moore, Tami et al. (2016) Dysregulation of WNT5A/ROR2 Signaling Characterizes the Progression of Barrett-Associated Esophageal Adenocarcinoma. Mol Cancer Res 14:647-59
Liu, X; Silverman, A; Kern, M et al. (2016) Excessive coupling of the salience network with intrinsic neurocognitive brain networks during rectal distension in adolescents with irritable bowel syndrome: a preliminary report. Neurogastroenterol Motil 28:43-53
Lang, Ivan M; Medda, Bidyut K; Jadcherla, Sudarshan R et al. (2016) Characterization and mechanisms of the pharyngeal swallow activated by stimulation of the esophagus. Am J Physiol Gastrointest Liver Physiol 311:G827-G837

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