| AbstractⅠInvestigation of Symptom Spectrum,Quality of Life and Psychological Status in Patients with RE and NERDBackgroundGastroesophageal reflux disease(GERD) is a common upper gastrointestinal disorder. Patients with GERD always have multiple symptoms and poor quality of life.It has been assumed that non-erosive reflux disease(NERD) and reflux esophagitis(RE) are two distinct entities of GERD instead of a continuous spectrum.However,until now,there hasn't domestic data about the intimate clinical characteristics of NERD and RE.AimsThe aim of this study was to evaluate the demographics,symptom spectrum,quality of life,and psychological status in patients with NERD and RE.Subjects and MethodsWe prospectively recruited consecutive patients with acid reflux,regurgitation, heartburn or chest pain for at least 6 months.Exclusion criteria included those patients with peptic ulcer,systematic disease and second any esophagitis or history of gastrointestinal surgery.All patients were asked to complete symptom questionnaires,including reflux symptoms,extra-esophageal symptoms,overlapping symptoms,GERD-health related quality of life questionnaire(GERD-HRQL),SF-36 questionnaire,and questionnaires of psychological status(Zung depression and anxiety score).The patients divided into NERD and RE according to presenting of gastroendoscopy.Results1.278 patients(male 107,mean age 48.42,female 165,mean age 51.35) were investigated.The proportion of NERD and RE were 60.8%and 37.1%.2.Compared to patients with RE,patients with NERD were significantly younger(48.54±11.74 vs 52.39±14.28,p＜0.05),more likely to be female(68.4%vs 47.8%,p＜0.05),and higher H.pylori infection rate(50.9%vs 24.6%,p＜0.05).3.Reflux symptom score has no difference between NERD and RE,however,heartburn and retrosternal pain in NERD was more serious than RE(p＜0.05),and regurgitation in RE were more obvious than that in NERD(p＜0.05).4.The percentages of extra-esophageal symptoms and overlapping symptoms in patients with NERD and RE were not significantly different.5.Compared with RE patients,quality of life in patients with NERD were lower in several domains of SF-36(p＜0.05),although GERD-HRQL score has no difference between the two groups (p＞0.05).6.Prevalence of abnormal psychological status in patients with NERD was significantly higher than patients with RE(71.1%vs 58.0%,p＜0.05),especially prevalence of depression in NERD was predominant.7.There was significant correlation between impaired quality of life and abnormal psychological status in patients with NERD(R=0.36, p=0.001),but no correlation between severity of reflux symptoms and abnormal psychological status or impaired quality of life(p＞0.05).ConclusionsThe proportion of NERD in GERD was 60.8%in this investigation.There was no significant difference in reflux and related symptom spectrum between NERD and RE. Compared to patients with RE,patients with NERD were younger,more commonly in female,had a higher prevalence of abnormal psychological status and poorer quality of life, which suggested that NERD and RE may be exist different mechanisms.AbstractⅡInvestigation esophageal hypersensitivity,and related factors in patients with NERDBackgroudReflux symptoms in patients with NERD and RE are similarity.But compared to patients witht RE,patients with NERD tend to have normal esophageal acid exposure and abnormal psychological status.It is assumed that esophageal visceral hypersensitivity plays an important role in physiological mechanism of NERD.AimsTo evaluate the feature of visceral hypersensitivity and related factors including abnormal ANS function and psychological factors in patients with NERD.Subjects and Methods20 health subjects(HS)(male 11,average age 40.9),11 patients with RE(male 6, average age 49.3)and 31 patients with NERD(male 9,average age 45.3) were enrolled in this study.Evaluation of reflux symptom,depression and anxiety scores(SAS/SDS),and quality of life in patients with NERD and RE had been finished in StudyⅠ.24h esophageal pH monitoring were performed in patients with NERD.Then acid perfusion test(APT) was carried out in three groups,including three periods of esophageal perfusion,that was perfused saline(NS) for 3 min,0.1N HCl for 10 min and NS for 10 min in order.APT was considered positive while subject reported heartburn or chest pain.The Acid hypersensitivity parameters were T-lag(time to symptom perception after acid perfusion),Ⅰ(Sensory intensity rating,0-20cm),APSS(acid perfusion symptom score=duration of symptom perception×intensity rating/100,cm·s),Td(time of symptom disappearing during NS stage).Meanwhile,autonomic nerve symptom(ANS) function was assessed of four stages,including baseline stage,second stage which after inserting catheter and before perfusion,acid perfusion stage and NS perfusion stage.The parameters of ANS function included the power in the low-frequency(LF) band reflecting sympathetic tone,power in the high-frequency(HF) band reflecting vagal tone,and the LF/HF ratio(P1/P2) as an indicator of sympathovagal balance.Results1.There was no statistical difference in demographics between the three groups.2. Patients with NERD had similar reflux symptom and quality of life,but has higher abnormal psychological scores than patients with RE(p＜0.05).3.Positive rates of APT in groups of HS,NERD and RE were respectively 5%,81.8%and 61.3%.There were no differences in T-Lag,I and APSS(p＞0.05) between patients with NERD and RE,but Td was obviously prolonged in patients of NERD than that of RE(p＜0.05).4.Acid stimulation didn't cause ANS function alteration in HS,but significantly increased the ratio of P1/P2 in the two patient groups(p＜0.05).The HF band power in patients of RE was significantly cut down to acid stimulation(p＜0.05).In patients of NERD,the LF band power was significantly step up to acid stimulation(p＜0.05),while the HF of baseline was lower than that of HS(p＜0.05).5.In patients with NERD who has normal acid exposure in pH monitoring,there existed positive correlation between the SDS and APSS(R=0.57,p＜0.05) and negative correlation between SDS and I in APT(R=-0.72,p=0.01).ConclusionsThere may be exist different mechanism of esophageal hypersensitivity between patients with NERD and RE.Patients with NERD and RE both existed abnormal ANS function.Abnormal vagal nerve function was presented in patients with RE,while both sympathetic and vagal function were impaired in patients with NERD.Psychosocial factors, esophageal hypersensitivity,and abnormal ANS function might play important roles in the pathophysiological mechanisms of NRED.AbstractⅢIdentification of Oesophageal hypersensitivity and central mechanisms between patients with NERD and FHBackgroudThere were similar symptoms and pathophysiological mechanisms between Non-erosive disease(NERD) and Functional heartburn(FH).But there were few studies investigating the mechanisms of oesophageal hypersensitivity,especially the potential central level mechanism.With the advance of functional magnetic resonance imaging (fMRI) of the brain,it is now possible to objectively investigate the central mechanism of visceral hypersensitivity.Studies using fMRI technique revealed the different patterns of cerebral activation in response to esophageal stimulus between the health and patients with NERD.AimsTo investigate oesophageal hypersensitivity in patients with NERD and FH,and elucidate the potential difference in central mechanisms of visceral hypersensitivity between patients with NERD and FH.Subjects and MethodsAfter acid perfusion test in which the healthy subjects presented negative and patients presented positive,there were 8 HS(4M/4F,mean age 43.8),5 patients with NERD(1M/4F, average age 51.6) and 6 patients with FH(2M/4F,average age 42.8)participated in the study. All subjects had no history of psychological disorders.The two patient groups were compared for symptom,depression and anxiety scores(SAS/SDS),quality of life, additionally,underwent APT and ANS function test.fMRI scan was performed in the three groups.There were two stages in a paradigm-driven fMRI experimental protocol.The first stage was actual acid perfusion,including two rounds,each round contained alternating 5-min intervals of 0.1 N HCl and saline perfusion following an initial 3-min interval of saline perfusion(both in rate of 1 ml/min).In the second stage(anticipated stage),the subjects were told being acid perfusion,but perfusion liquid is saline,fMRI scans were performed on a 3.0-T system(GE Signa VHi EXCITEⅡ) using quadrature head coil. Gradient-echo planar imaging sequences were used(TR=6000ms;TE=40ms;FOV=240×240 mm;flip angle=90°;matrix size=64×64).Data analysis was carried out using AFNI software package.Results1.There was no statistical difference in demographics between the three groups.2. Patients with FH had longer course of disease,poorer quality of life and higher SAS/SDS scores,when compared with patients with NERD(p＜0.05).3.There was no significantly difference between the two patient groups while all these patients had acid hypersensitivity and abnormal ANS function.4.Acid perfusion activated multiple cortical regions including the anterior and posterior cingulate cortices,the insula,operculum,prefrontal cortex and primary somatosensory cortices in all three groups,while thalamus only activated in the two patients group.5.Cerebral activity associated with acid exposure in the two patient groups occurred more rapidly and with greater intensity than the activity in HS.6.Patients with FH demonstrated a larger area of activation than NERD(p＜0.05).There existed different cortical activity between patients with FH and NERD:time from initial activation to the time of maximum signal change in FH was shorter than that of NERD(p＜0.05), while the average maximum percent signal increase in FH was significantly lower than in NERD(p＜0.05).7.During anticipated stage,2 patients with FH presented that activities within ACC were strongly correlated with the activity curve during the actual acid perfusion stage(R≥0.4,p＜0.001),while all of HS and patients with NERD didn't demonstrate significant correlation.ConclusionsComparison with patients with NERD,patients with FH had longer course of disease, poorer quality of life and abnormal psychological status.In response to esophageal acid stimulus,patients with NERD and FH demonstrated extensive cortical regions activated, much more rapid activity and greater intensity in the activated cortex than HS.Compared to patients with NERD,activity in FH occurred more rapidly and lower intensity,which suggested patients with FH had different central mechanism of hypersensitivity with that of NERD. AbstractⅣClinical Efficacy of Citalopram in Patients with Functional Heartburn and Investigation Central MechanismBackgroudFunctional heartburn(FH),being one of functional gastrointestinal disorders(FGIDs), always failed to response to PPI therapy.The prevailing view is to consider visceral hypersensitivity and abnormal brain-gut axis as the major factors involved in pathogenesis. Clinically,antidepressants-selective serotonin reuptake inhibitors(SSRIs) appear to be useful for some patients with FGIDs for improving the symptom and quality of life.Recent study have shown that acute administration of SSRIs,citalopram,significantly decreased chemical and mechanical sensitivity in healthy volunteers with hypersensitivity to oesophageal stimulation,which suggests that citalopram may offer therapeutic potential in the treatment of patients with oesophageal hypersensitivity,such as patients with functional heartbum(FH).AimsTo evaluate the clinical efficacy of citalopram to patients with FH,and identify the therapeutic effect of citalopram through CNS mechanism,in order to search effective therapy to FH.Subjects and MethodsAccording with criteria of ROMEⅢ,6 FH patients(1M,5F,mean 42.8yrs),who failed to response to PPI therapy and presented positive in acid perfusion test(APT) participated in the study.The dose of citalopram treatment is 10mg qn 9pm po(1-3d),then 20mg qn 9pm po(4-42d).The efficacy of citalopram to symptom,quality of life,depression and anxiety score and esophageal acid sensitivity were evaluated.Additionally,cerebral activation during esophageal acid perfusion was assessed after treatment by fMRI(the protocol of fMRI is same as the studyⅢ).ResultsAfter six weeks of treatment,citalopram significantly improved heartburn symptom and quality of life(p＜0.05).After treatment,the depression and anxiety score was in normal range,comparing with that either score was abnormal before treatment.Citalopram significantly lowered esophageal acid hypersensitivity of patients with FH.After treatment, activated cortical regions during acid perfusion had no significantly different with before treatment,but activity in regions such as anterior cingulate cortices(ACC),thalamus,the insula and operculum after treatment were significantly different with pre-treatment(p＜0.05).After treatment,the average maximal percent of signal increase in fMRI was significantly lower than pre-treatment(0.64%vs 0.98%,p＜0.05),while the time from initial fMRI signal activation to the time of maximal signal change was longer than pre-treatment(3.58 min vs 3.08 min,p＜0.05).Before treatment,there were 2 patients presented that ACC activity during the anticipated stage was strongly correlated with that of actual acid stage.Citalopram diminished ACC activation during anticipation of acid perfusion in 1 patient.ConclusionsCitalopram,SSRIs,significantly improved FH symptoms,quality of life and also exerted beneficial effect on abnormal psychological status.Citalopram significantly lowered esophageal hypersensitivity in patients with FH and was likely to work through a central neuromodulation,fMRI may be a useful technique for future investigation of central level's mechanism of SSRIs in FGIDs.
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