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.
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