NOVEL EVALUATION AND TREATMENT OF GASTRIC DYSMOTILITY

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Gastric dysmotility may be due to delayed gastric emptying, antral hypomotility, and/or gastric dysrhythmias. Gastric motor dysfunction is an important component of several clinical disorders including gastroparesis, functional dyspepsia, and intestinal pseudoobstruction. Our overall hypothesis is that gastric motility can be measured conveniently with noninvasive tests which can have widespread availability and provide clinically relevant information. The studies described in this research protocol will address our long-term research objectives of evaluating and treating disorders of gastric motility using simpler, less expensive, and less invasive techniques. Each of these patient-oriented research protocols involves the close interaction between the principal investigator and beginning clinical investigators in order to encourage and develop their clinical research potential. The first specific aim is to demonstrate the clinical validity of two novel noninvasive techniques to assess gastric motility. We will develop the 13C-octanoate breath test for gastric emptying into a practical, clinically useful test for the measurement of gastric emptying using an easily prepared standardized meal. We will also assess the clinical utility of a newly modified electrogastrographic instrument that records high frequency gastric myoelectric activity (up to 120 cycles per minute), in addition to the usual 3 cpm activity. The second specific aim is to use these two noninvasive tests (breath testing and electrogastrography) to assess gender-related aspects of gastric motility. We will demonstrate the effects of gender and the menstrual cycle on gastric motility and determine if the changes in gastric motility during the menstrual cycle correlate with estrogen . and progesterone levels. We will determine whether gastric motility is altered during pregnancy, and to investigate if nausea and vomiting that occurs in the first trimester of pregnancy are related to gastric dysmotility and/or alterations of estrogen, progesterone, and/or chorionic gonadotropin blood levels. The third specific aim is to explore novel treatment strategies for abnormal gastric emptying. We will determine whether accelerating or delaying gastric emptying affects postprandial glucose tolerance in diabetic patients. We will determine whether botulinum toxin injection into the pyloric sphincter improves gastric emptying and symptoms in gastroparesis. The fourth specific aim is to enable the principal investigator to continue and even expand his mentoring activities for beginning clinical investigators in patient- oriented research to include mentoring of specialized motility fellows, gastroenterology fellows, medical residents, medical students, and college students.