Clinical Investigation Of Pathophysiologic Mechanisms And Treatment In Patients With Functional Dyspepsia

AbstractⅠA Novel Method to Improve the Liquid Nutrient Load Testby Simultaneous Determination of the Intra-gastric PressureBackgroundIn the liquid nutrient load test (LNLT), the reduced maximal intake volume (MIV) mayresult from either impaired gastric accommodation or gastric visceral hypersensitivity. Thatdifferentiating impaired accommodation from hypersensitivity is very important to diagnosisand treatment of functional dyspepsia (FD). Up to now, the tension of gastric wall and relatedmechanoreceptors are regarded as the primary factor to determine gastric sensitivity. Becausethe tension of gastric wall is very difficult and complex to be detected, it is the best fungibleway to express gastric sensitivity by intra-gastric pressure (IGP). If we determine IGP bymanometric catheters during LNLT, gastric sensitivity can be more exactly presented by IGP.So we can separate impaired accommodation from hypersensitivity by using IGP and MIV.Subjects with lower IGP at the time of MIV will be considered as those havinghypersensitivity. When IGP of patients are same as those of healthy subjects (HS), thereduced MIV can be deduced to result from impaired accommodation. Gastric compliance infed state can be calculated by the reciprocal of slope of gastric volume-IGP curve.AimsThe aims of this study were to transform the hypothesis of theory above to a clinicalfeasible test procedure and appraise its feasibility, safety, tolerability, reproducibility andreliability, and to evaluate the gastric sensitivity of FD patients and explore potentialinfluencing factors, and to investigate whether difference exits in the gastric compliance infed state between HS and FD patients.Subjects and MethodsA total of 40 HS (20M, 20F, mean 42.4yrs) and 80 FD patients (28M, 52F, mean45.3yrs, RomeⅡcriteria) participated in the study. The determination of IGP was by meansof water-perfusion manometric system and catheter with the side-hole positioned in proximalstomach. After transnasal intubation, subjects lay in hemi-supine position on a test bed. Aftera 15min equilibration period, subjects drank liquid nutrient (1.5Kcal/ml, Carbohydrate 48%, Fat 39%, Protein 13%, 50ml/min) until MIV with synchronous IGP monitoring. So bothMIV and IGP at the time of MIV could be obtained. The study was repeated in 24HS onseparate days. In addition, gastric compliance in fed state could be calculated by thereciprocal of slope of gastric volume-IGP curve.Results(1) In HS, no statistical difference was found in IGP divided by sex, age and body massindex (P＞0.05). The coefficient of variation of IGP was 15.3%, which was less than that ofMIV. Twice repeated studies showed quite similar results and the linear interclass correlationcoefficient of IGP was 0.806 (P＜0.05). (2) In FD patients, the proportion of gastrichypersensitivity accounted for 35.0%; the proportion of impaired accommodation accountedfor 25.0%. FD patients with dyspeptic symptoms related to food intake had lower IGP thanthose without dyspeptic symptoms related to food intake (P＜0.05). FD patients withabnormal mental status had lower IGP than those with normal mental status (P＜0.05). Nostatistical difference was found in IGP of FD patients divided by sex, age and dyspepticsymptom subtypes (P＞0.05). (3) No statistical difference was found in gastric compliance infed state between HS and either FD patients or FD patients with hypersensitivity (P＞0.05). (4)The test had a good feasibility, safety and tolerability.ConclusionsLNLT combined with determination of IGP had a good feasibility, safety andtolerability. The index of IGP had a good reproducibility and reliability. The proportion ofgastric hypersensitivity in FD patients accounted for 35.0%; the proportion of impairedaccommodation accounted for 25.0%. Both dyspeptic symptoms related to food intake andabnormal mental status were the influencing factors of gastric hypersensitivity of FDpatients. No abnormal change occurred in gastric compliance in fed state of FD patients.AbstractⅡClinical Investigation of Pathophysiologic Mechanisms ofOverlapping Symptoms in Patients with Functional DyspepsiaBackgroundOverlapping of gastrointestinal symptoms is very common in FD patients. It remainsunknown what causes overlapping symptoms (OS) of FD patients and whether the differenceexits in the diagnosis and treatment of dyspeptic symptoms between FD patients with andwithout OS. Investigation in this field will facilitate us to understand the potentialmechanisms of OS and diagnose and treat different types of FD patients properly.Aims To investigate the differences between FD patients with and without OS at the aspectsof demographics, dyspeptic symptomology, SF-36 quality of life (QOL) and dyspepticpathophysiologies including gastric muscular electrical activity, solid gastric emptying (GE),gastric sensitivity, gastric accommodation and autonomic nerve system function (ANS).Subjects and Methods120 FD patients (33M, 87F, mean 44.7yrs) surveyed with RomeⅡModularQuestionnaire were divided into two groups: the patients without OS (only dyspepticsymptoms) and with OS (esophageal, intestinal or anorectal symptoms). The data includingdemographics, dyspeptic symptomology, QOL and psychological status (Zung depressionand anxiety scale) were recorded. The tests including multi-channels electrogastrography(MEGG), GE (radiopaque makers and scintigraphic evaluation), LNLT combined with IGPdetermination and ANS were performed. All the indexes were compared between FDpatients with and without OS.Results(1) The proportion of the patients with OS accounted for 62.5%. (2) No statisticaldifference was found between the two groups at the aspects of symptom subtypes distribution,severity scores and other aspects (P＞0.05). (3) No statistical difference existed in all indexesrelated to the tests of MEGG, GE, LNLT combined with IGP determination and ANS(P＞0.05). (4) However, the psychological status of the patients with OS was worse than thatof the patients without OS (P＜0.05). (5) The QOL of the patients with OS was worse thanthat of patients without OS including mental and physical dimensions (P＜0.05).ConclusionsOS exited in most of FD patients. The same features were found in dyspepticsymptomology and pathophysiologies between FD patients with and without OS, whichsuggests the strategy of diagnosis and treatment to dyspeptic symptoms between the twogroups of FD patients should be same. The worse psychological status and mental dimensionof QOL in patients with OS suggest that psychological factors may be involved in themechanisms underlying OS.AbstractⅢClinical Investigation of the efficacy of Tegaserod inPatients with Functional DyspepsiaBackgroundPrevious studies have shown that tegaserod has a prokinetic effect on GE, increasemotility activity of gastric antrum, increase gastric compliance and accommodation, which suggest that tegaserod may have a potential to become a new effective drug to FD patients. Itremains unknown whether tegaserod can improve dyspeptic symptoms, QOL, OS anddyspeptic pathophysiologic mechanisms of FD patients.AimsTo evaluate the efficacy of tegaserod to dyspeptic symptoms, QOL related to dyspepticsymptoms, OS and pathophysiologic mechanisms (gastric muscular electrical activity, GE,gastric sensitivity, gastric accommodation and ANS) of FD patients through a randomized,double-blinded and placebo-controlled clinical trial.Subjects and Methods40 FD patients (12M, 28F, mean 43.8yrs) participated in the study and were divided intotegaserod treatment and placebo control group in random style. The dose of tegaserodtreatment is 6mg bid ac30min po 14d. The efficacy of tegaserod to dyspeptic symptoms,QOL related to dyspeptic symptoms, OS and pathophysiologic mechanisms (gastric muscularelectrical activity, GE, gastric sensitivity, gastric accommodation and ANS) of FD patientsbetween the two groups were compared.Results(1) Before treatment, no statistical difference existed between the two groups in allindexes of dyspeptic symptoms, QOL related to dyspeptic symptoms, OS andpathophysiologic mechanisms (gastric muscular electrical activity, GE, gastric sensitivity,gastric accommodation and ANS) (P＞0.05). (2) After treatment, no statistical differenceexisted between the two groups in all indexes of dyspeptic symptoms, QOL related todyspeptic symptoms, OS, pathophysiologic mechanisms (muscular electrical activity, gastricsensitivity, gastric accommodation and ANS) and compliance (P＞0.05). (3) In GE function,compared with control group, FD patients in tegaserod group had shorter time of halfemptying and higher emptying velocity (P＜0.05), but similar in lag phase and residualpercentage of two hour (P＞0.05). (4) 25.0% FD patients in tegaserod group had an adverseeffect of transient and mild diarrhea. No patient discontinued drug treatment because ofdiarrhea.ConclusionsTegaserod (6mg bid ac30min po 14d) has a prokinetic effect on solid GE of FD patientswith a good safety. Tegaserod has no efficacy and impaction on dyspeptic symptoms, QOLrelated to dyspeptic symptoms, OS and pathophysiologic mechanisms (gastric muscularelectrical activity, gastric sensitivity, gastric accommodation and ANS) of FD patients.