NOVEL EVALUATION AND TREATMENT OF GASTRIC DYSMOTILITY

胃动力障碍可能是由于胃排空延迟、胃窦动力低下和/或胃节律障碍。胃运动功能障碍是胃轻瘫、功能性消化不良和肠假性梗阻等多种临床疾病的重要组成部分。我们的总体假设是，胃运动可以通过无创测试方便地测量，这种测试可以广泛使用并提供临床相关信息。本研究方案中描述的研究将解决我们的长期研究目标，即使用更简单、更便宜、侵入性更小的技术来评估和治疗胃运动障碍。每一项以患者为导向的研究方案都涉及到主要研究者和初级临床研究者之间的密切互动，以鼓励和发展他们的临床研究潜力。第一个具体目的是证明两种新的无创技术评估胃运动的临床有效性。我们将开发用于胃排空的13c -辛酸盐呼气试验，使其成为一种实用的、临床上有用的试验，用于使用易于准备的标准化膳食测量胃排空。我们还将评估一种新改良的胃电图仪器的临床应用，该仪器除了通常的3 cpm活动外，还可以记录高频胃肌电活动（高达120周期/分钟）。第二个具体目标是使用这两种无创测试（呼吸测试和胃电图）来评估与性别相关的胃运动方面。我们将展示性别和月经周期对胃动力的影响，并确定月经周期中胃动力的变化是否与雌激素相关。还有黄体酮水平。我们将确定妊娠期间胃运动是否改变，并调查妊娠前三个月发生的恶心和呕吐是否与胃运动障碍和/或雌激素、黄体酮和/或绒毛膜促性腺激素血水平的改变有关。第三个具体目的是探索胃排空异常的新治疗策略。我们将确定加速或延迟胃排空是否会影响糖尿病患者餐后葡萄糖耐量。我们将确定幽门括约肌注射肉毒杆菌毒素是否能改善胃轻瘫患者的胃排空和症状。第四个具体目标是使首席研究员能够继续甚至扩大他对以患者为导向的研究的初级临床研究者的指导活动，包括对专门的运动研究员、胃肠病学研究员、住院医生、医学生和大学生的指导。

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.