By using combination of the expression of COX-2 and NOS and immunologic reaction in the esophagus with manometry of LES and cruel diaphragm and 24 hr esophageal pH monitoring to investigate the mechanisms and to make a new and more clinically applicable clarification of these reflux diseases will be valuable in the clinical management and prevention. We will perform the following works and complete the objectives: 1) comparing the difference of immuno-inflammatory reactions among NERD, reflux esophagitis and Barrett's esophagus; 2) the different expression of PGs \& COX-2 in functional heartburn, hiatus hernia, NERD, reflux disease and Barrett's esophagus; determining the subtype of EP receptor (EP1\~4); 3) determining and comparing the expression of NOS in the esophagus; 4) investigating the role of ROS in the esophagus; 5) in correlating cytokine, COX-2 and NOS with LESP, TLESR, diaphragm EMG and 24-hour esophageal pH ; 6) the difference of expression of cytokine, atrophic gastritis and Hp in gastric mucosa, in correlating with intragastric acid status, among functional heartburn, hiatus hernia, NERD, erosive esophagitis and Barrett's esophagus; to determine whether should eradicate Hp in reflux esophageal disease; 7) the effects of lipid peroxidation related immunologic reaction, with relation to COX-2 and NOS, in the inflammatory activity and esophageal carcinogenesis of esophagus; 8) the effects of cytokines, COX-2 and NOS on the apoptosis in these reflux esophageal diseases; 9) integrating immuno-inflamatory reaction, COX-2, NOS with manometry of LES and diaphragm, and 24-hour pH monitoring and intragastric pH to newly clarify GERD into evidence based categories.
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