BACKGROUND/AIMS: Functional dyspepsia (FD) remains a great clinical challenge since the FD subtypes, defined by Rome III classification, still have heterogeneous pathogenesis. Previous studies have shown notable differences in visceral sensation processing in the CNS in FD compared to healthy subjects (HS). However, the role of CNS in the pathogenesis of each FD subtype has not been recognized. METHODS: Twenty-eight FD patients, including 10 epigastric pain syndrome (EPS), 9 postprandial distress syndrome (PDS), and 9 mixed-type, and 10 HS, were enrolled. All subjects underwent a proximal gastric perfusion water load test and the regional brain activities during resting state and water load test were investigated by functional magnetic resonance imaging. RESULTS: For regional brain activities during the resting state and water load test, each FD subtype was significantly different from HS (P < 0.05). Focusing on EPS and PDS, the regional brain activities of EPS were stronger than PDS in the left paracentral lobule, right inferior frontal gyrus pars opercularis, postcentral gyrus, precuneus, insula, parahippocampal gyrus, caudate nucleus, and bilateral cingulate cortices at the resting state (P < 0.05), and stronger than PDS in the left inferior temporal and fusiform gyri during the water load test (P < 0.05). CONCLUSIONS: Compared to HS, FD subtypes had different regional brain activities at rest and during water load test, whereby the differences displayed distinct manifestations for each subtype. Compared to PDS, EPS presented more significant differences from HS at rest, suggesting that the abnormality of central visceral pain processing could be one of the main pathogenesis mechanisms for EPS.
Brain ; Broca Area ; Caudate Nucleus ; Classification ; Dyspepsia ; Functional Neuroimaging ; Healthy Volunteers ; Humans ; Magnetic Resonance Imaging ; Parahippocampal Gyrus ; Parietal Lobe ; Perfusion ; Prefrontal Cortex ; Sensation ; Somatosensory Cortex ; Visceral Pain ; Water

Objective To investigate the clinical symptoms and mental state of patients with irritable bowel syndrome with diarrhea (IBS-D ) , and to analyze the characteristics of psychological disorders in patients with IBS-D and their impacts on intestinal symptoms .Methods From July 2009 to June 2012 ,patients met Rome Ⅲ criteria of IBS-D were consecutively enrolled at Peking Union Medical College Hospital .The symptoms of IBS were investigated by IBS symptoms questionnaire and mental state were evaluated by Hamilton anxiety scale (HAMA ) and Hamilton depression scale (HAMD ) . The differences in intestinal symptoms between patients with comorbid psychological disorders and without psychological disorders were compared .And the correlation between the scores of HAMA ,HAMD and intestinal symptoms were analyzed . Two independent sample t-tests ,chi square test and Fisher exact probability were performed for statistical analysis .Spearman rank correlation was used for correlation analysis .Results A total of 231 patients with IBS-D were enrolled .There were 133 males and 98 females with an age of (42 .8 ± 11 .1) years old and a disease course of (4 .5 years (8 .0 years)) .The HAMA and HAMD scores were 17 .00 ± 7 .12 and 14 .05 ± 6 .00 ,respectively ,and 72 .29％ (167/231) patients had comorbid psychological disorders ,32 .90％ (76/231 ) patients had moderate to severe anxiety and/or depression ,mainly had anxiety .The proportion of patients with ordinary abdominal pain or discomfort and the proportion of moderate to severe abdominal pain or discomfort in patients with psychological disorders were higher than those of patients without psychological disorders (53 .29％ , 89/167 vs . 34 .37％ , 22/64;49 .44％ ,44/89 vs .18 .18％ ,4/22) ,and the differences were statistically significant (χ2=6 .634 and 7 .002 , P=0 .010 and 0 .009) .In patients with comorbid psychological disorders ,more patients had frequent onset of abdominal pain or discomfort ,less achieved completely improvement after defecation , and often accompanied with defecation related symptoms .The HAMD score was positively correlated with the onset frequency of IBS (r=0 .172 ,P=0 .009) ,and the HAMA score was positively correlated with the degree of abdominal pain or discomfort before defecation (r=0 .134 , P= 0 .042) .The HAMA and HAMD scores were negatively correlated with the improvement degree of abdominal pain or discomfort after defecation (r= -0 .215 , P=0 .001 ;r= -0 .251 , P<0 .01) ,and were positively correlated with waiting time for symptoms improvement (r=0 .175 , P=0 .008;r=0 .219 , P= 0 .001) .Conclusion Most IBS-D patients have comorbid psychological disorders , anxiety and/or depression greatly impact the intestinal symptoms of patients with IBS .

BACKGROUND/AIMS: Physical and/or emotional stresses are important factors in the exacerbation of symptoms in irritable bowel syndrome (IBS). Several lines of evidence support that a major impact of stress on the gastrointestinal tract occurs via the enteric nervous system. We aimed to evaluate histological changes in the submucosal plexus (SMP) and myenteric plexus (MP) of the distal ileum in concert with the intestinal motor function in a rat model of IBS with diarrhea. METHODS: The rat model was induced by heterotypic chronic and acute stress (CAS). The intestinal transit was measured by administering powdered carbon by gastric gavage. Double immunohistochemical fluorescence staining with whole-mount preparations of SMP and MP of enteric nervous system was used to assess changes in expression of choline acetyltransferase, vasoactive intestinal peptide, or nitric oxide synthase in relation to the pan neuronal marker, anti-Hu. RESULTS: The intestinal transit ratio increased significantly from control values of 50.8% to 60.6% in the CAS group. The numbers of enteric ganglia and neurons in the SMP were increased in the CAS group. The proportions of choline acetyltransferase- and vasoactive intestinal peptide-immunoreactive neurons in the SMP were increased (82.1 ± 4.3% vs. 76.0 ± 5.0%, P = 0.021; 40.5 ± 5.9% vs 28.9 ± 3.7%, P = 0.001), while nitric oxide synthase-immunoreactive neurons in the MP were decreased compared with controls (23.3 ± 4.5% vs 32.4 ± 4.5%, P = 0.002). CONCLUSIONS: These morphological changes in enteric neurons to CAS might contribute to the dysfunction in motility and secretion in IBS with diarrhea.
Animals ; Carbon ; Choline ; Choline O-Acetyltransferase ; Diarrhea* ; Enteric Nervous System ; Fluorescence ; Ganglia ; Gastrointestinal Motility ; Gastrointestinal Tract ; Ileum ; Intestine, Small* ; Irritable Bowel Syndrome* ; Models, Animal* ; Myenteric Plexus ; Neurons* ; Nitric Oxide ; Nitric Oxide Synthase ; Rats* ; Stress, Psychological ; Submucous Plexus ; Vasoactive Intestinal Peptide

BACKGROUND/AIMS: This integrated analysis aimed to identify the factors associated with the most frequently reported treatment-emergent adverse events (TEAEs) in Asian and non-Asian patients with chronic constipation (CC) who receive prucalopride or placebo over 12 weeks. METHODS: Pooled data from four randomized, double-blind, placebo-controlled, multicenter, phase III studies (NCT00488137, NCT00483886, NCT00485940, and NCT01116206) on patients treated with prucalopride 2 mg or placebo were analyzed. The associations between predictors and TEAEs were evaluated based on a logistic regression model. RESULTS: Overall, 1,821 patients (Asian, 26.1%; non-Asian, 73.9%) were analyzed. Prucalopride treatment was significantly associated with diarrhea, headache, and nausea (p<0.001), but not with abdominal pain, compared with placebo. Differences in the prevalence of TEAEs between prucalopride and placebo decreased greatly after the first day of treatment. Compared with non-Asians, Asians were more likely to experience diarrhea and less likely to develop abdominal pain, headache, and nausea. Prior laxative use, CC duration, and body weight were not predictive of any of these TEAEs. CONCLUSIONS: Prucalopride treatment was positively associated with diarrhea, headache, and nausea. Asian patients tended to have a higher frequency of diarrhea but lower frequencies of headache, abdominal pain, and nausea compared with non-Asians.
Abdominal Pain/*chemically induced ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group/statistics & numerical data ; Benzofurans/*adverse effects ; Clinical Trials, Phase III as Topic ; Constipation/*drug therapy/ethnology ; Diarrhea/*chemically induced ; Double-Blind Method ; Female ; Headache/*chemically induced ; Humans ; Male ; Middle Aged ; Multicenter Studies as Topic ; Nausea/chemically induced ; Randomized Controlled Trials as Topic ; Regression Analysis

BACKGROUND/AIMS: This integrated analysis aimed to identify the factors associated with the most frequently reported treatment-emergent adverse events (TEAEs) in Asian and non-Asian patients with chronic constipation (CC) who receive prucalopride or placebo over 12 weeks. METHODS: Pooled data from four randomized, double-blind, placebo-controlled, multicenter, phase III studies (NCT00488137, NCT00483886, NCT00485940, and NCT01116206) on patients treated with prucalopride 2 mg or placebo were analyzed. The associations between predictors and TEAEs were evaluated based on a logistic regression model. RESULTS: Overall, 1,821 patients (Asian, 26.1%; non-Asian, 73.9%) were analyzed. Prucalopride treatment was significantly associated with diarrhea, headache, and nausea (p<0.001), but not with abdominal pain, compared with placebo. Differences in the prevalence of TEAEs between prucalopride and placebo decreased greatly after the first day of treatment. Compared with non-Asians, Asians were more likely to experience diarrhea and less likely to develop abdominal pain, headache, and nausea. Prior laxative use, CC duration, and body weight were not predictive of any of these TEAEs. CONCLUSIONS: Prucalopride treatment was positively associated with diarrhea, headache, and nausea. Asian patients tended to have a higher frequency of diarrhea but lower frequencies of headache, abdominal pain, and nausea compared with non-Asians.
Abdominal Pain/*chemically induced ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group/statistics & numerical data ; Benzofurans/*adverse effects ; Clinical Trials, Phase III as Topic ; Constipation/*drug therapy/ethnology ; Diarrhea/*chemically induced ; Double-Blind Method ; Female ; Headache/*chemically induced ; Humans ; Male ; Middle Aged ; Multicenter Studies as Topic ; Nausea/chemically induced ; Randomized Controlled Trials as Topic ; Regression Analysis

Objective To investigate the effects of anxiety and depression on the quality of life (QOL) in patients with irritable bowel syndrome with diarrhea (IBS‐D) and the difference in gender .Methods IBS‐D patients met the Rome Ⅲ diagnostic and subtyping criteria were consecutively enrolled .The intestinal symptoms , psychological status , and QOL of patients were evaluated using IBS‐specific symptom questionnaires , the Hamilton anxiety scale (HAMA) ,the Hamilton depression scale (HAMD) ,and the Chinese Version of IBS‐QOL instrument .The data were analyzed by chi‐square test variance analysis ,t test or Spearman rank correlation analysis .Results A total of 155 IBS‐D patients were enrolled .Among them ,115 were complicated with anxiety and/or depression .The number of male and female with comorbid psychological disorders was 69 cases(71 .13% ) and 46 cases(79 .31% ) ,respectively ,and the difference was not statistically significant (χ2 = 1 .267 ,P= 0 .26) . Compared with 40 patients without anxiety or depression ,there was no statistically significant difference (F=1 .143 ,P> 0 .05) in the scores of intestinal symptoms in 59 patients with comorbid anxiety alone and 56 patients with anxiety and/or depression (20 .85 ± 5 .84 vs .21 .71 ± 7 .47 vs .22 .87 ± 6 .09) .The total IBS‐QOL score of the 155 patients was 71 .61 ± 19 .22 .There was negative correlation between IBS‐QOL score and HAMA , HAMD scores(r= -0 .262 and -0 .268 ,both P= 0 .001) .The total IBS‐QOL score of patients with comorbid anxiety and depression or depression were lower than that of patients without anxiety or depression (66 .05 ± 22 .88 vs 77 .22 ± 15 .35 , F = 4 .412 , P = 0 .005) .Except health worrying and sexual ,the scores in six dimensions(including dysphoria ,interference with activity ,body image ,food avoidance and social reaction) were all significantly decreased (F= 3 .309 ,3 .279 ,4 .177 ,3 .765 ,6 .041 and 3 .830 , P= 0 .013 ,0 .012 ,0 .013 , 0 .007 ,0 .001 and 0 .010) .In male patients ,the total score of IBS‐QOL and the scores of dysphoria ,body image and social reaction of patients with anxiety and depression or depression were lower than those of patients without anxiety and depression (t = 2 .143 ,2 .110 ,2 .279 ,3 .061 ; P = 0 .036 ,0 .039 ,0 .027 ,0 .003) .In female patients ,the score of food avoidance domain significantly decreased (t= 2 .812 ,P= 0 .008) .The scores of IBS‐QOL and six dimensions (including dysphoria ,interference with activity ,body image ,food avoidance and social reaction) of patients with history of severe mental disorders and being abused were even lower than those patients without such histories (t= 3 .241 ,3 .433 ,2 .499 ,2 .296 ,2 .514 ,3 .413 and 2 .601 ;P= 0 .001 ,0 .001 ,0 .014 , 0 .023 ,0 .013 ,0 .001 and 0 .010) .Conclusions The QOL of patients with IBS‐D was significantly affected by psychological factors with gender differences .The approaches to improve the psychological status of IBS patients were helpful to enhance the efficacy of comprehensive therapy .

BACKGROUND/AIMS: To compare the efficacy and safety of prucalopride, a novel selective high-affinity 5-hydroxytryptamine type 4 receptor agonist, versus placebo, in Asian and non-Asian women with chronic constipation (CC). METHODS: Data of patients with CC, receiving once-daily prucalopride 2-mg or placebo for 12-weeks, were pooled from 4 double-blind, randomized, phase-III trials (NCT00488137, NCT00483886, NCT00485940 and NCT01116206). The efficacy endpoints were: average of > or = 3 spontaneous complete bowel movements (SCBMs)/week; average increases of > or = 1 SCBMs/week; and change from baseline in each CC-associated symptom scores (bloating, abdominal pain, hard stool and straining). RESULTS: Overall, 1,596 women (Asian [26.6%], non-Asian [73.4%]) were included in this analysis. Significantly more patients in the prucalopride group versus placebo experienced an average of > or = 3 SCBMs/week in Asian (34% vs. 11%, P < 0.001) and non-Asian (24.6% vs. 10.6%, P < 0.001) subgroups. The number of patients reporting an increase of > or = 1 SCBMs/week from baseline was significantly higher in the prucalopride group versus placebo among both Asian (57.4% vs. 28.3%, P < 0.001) and non-Asian (45.3% vs. 24.0%, P < 0.001) subgroups. The difference between the subgroups was not statistically significant. Prucalopride significantly reduced the symptom scores for bloating, hard stool, and straining in both subgroups. CONCLUSIONS: Prucalopride 2-mg once-daily treatment over 12-weeks was more efficacious than placebo in promoting SCBMs and improvement of CC-associated symptoms in Asian and non-Asian women, and was found to be safe and well-tolerated. There were numeric differences between Asian and non-Asian patients on efficacy and treatment emergent adverse events, which may be partially due to the overlap with functional gastrointestinal disorders in non-Asian patients.
Abdominal Pain ; Asian Continental Ancestry Group* ; Constipation* ; Female ; Gastrointestinal Diseases ; Humans ; Serotonin ; Serotonin 5-HT4 Receptor Agonists

Amitriptyline ; therapeutic use ; Child ; Constipation ; drug therapy ; Dyspepsia ; drug therapy ; Gastrointestinal Agents ; therapeutic use ; Gastrointestinal Diseases ; drug therapy ; therapy ; Humans ; Hypnosis ; methods ; Irritable Bowel Syndrome ; therapy ; Polyethylene Glycols ; therapeutic use ; Randomized Controlled Trials as Topic ; Research Design

Objective To evaluate proximal gastric function in patients with functional dyspepsia (FD) met Rome Ⅲ criteria and its subtypes.Methods Thirty FD patients were enrolled,including 15 patients with postprandial distress syndrome (PDS) and 15 patients with epigastric pain syndrome (EPS).A total of 30 healthy volunteers were recruited as control.All the subjects received barostat examination.Minimal distending pressure (MDP),pressure and volume of thresholds for first sensation and maximal tolerance for gastric sensitivity were recorded.When the pressure level was MDP+2 mmHg (1 mmHg=0.133 kPa),average volume at 30 minutes before meal,averaged volume at 60 minutes after meal and maximum accommodation volume after meal were recorded,and receptive diastolic volume was calculated.The gastric hypersensitivity and impaired accommodation were observed.Student's t test or x2 test was performed for statistical analysis.Results MDP,pressure of first-sensation,maximum sensation pressure,volume of first sensation and maximal sensation volume of FD group were (6.17 ±1.95) mmHg,(8.44±2.01) mmHg,(14.62±3.72) mmHg,(123.59±53.26) mL and (451.26±140.44) mL,respectively; which were lower than those of healthy control group ((9.27±1.99) mmHg,(12.04±2.66) mmHg,(19.74±4.18) mmHg,(168.41±73.06) mL and (556.89±124.07) mL),and the differences were statistically significant (t=-6.080,-5.900,-5.011,-2.723 and-2.995,all P＜0.01).The averaged volume at 30 minutes before meal and 60 minutes after meal was (212.19±120.82) mL and (333.97±121.86) mL while those of healthy control group was (191.69±66.19) mL and (385.58±83.05) mL,and there were no significant differences between the two groups (both P＞0.05).The maximum postprandial accommodation volume and receptive diastolic volume of FD group were (405.10±111.29) mL and (190.16±97.22) mL,which were lower than those of healthy control group ((461.10±87.60) mL and (262.83±78.39) mL),and the differences were statistically significant (t=-2.599 and-3.187,both P＜0.05).The maximum postprandial accommodation volume of FD patients was at 15 to 20 minutes after meal and in healthy control it was at five to ten minutes after meal.Among the 30 FD patients,12 patients (40 ％) had gastric hypersensitivity,including eight PDS patients and four EPS patients,and there was no significant difference in the ratio between two groups (P＞0.05) ;nine patients (30 ％) had impaired accommodation,including five PDS patients and four EPS patients,and there was no significant difference in the ratio between two groups (P＞ 0.05).Conclusions Gastric hypersensitivity and impaired accommodation often appear in FD patients,and there is no significant difference between PDS and EPS subtypes.FD patients with different pathophysiologic mechanisms cannot be efficiently distinguished according to Rome Ⅲ criteria.

Objective To acquire normative values of anorectal manometry and sensation in population of our country with different gender and age.Methods Healthy individuals from four medical centers were collected and divided into three group according to their age,group Ⅰ 18 - 39 years old, group Ⅱ 40-59 years old and group Ⅲ ≥60 years old.The parameters of anal of subjects at resting status was examined by pneumohydraulic capillary perfusion system and high resolution PC Polygraf HR desktop gastrointestinal dynamic monitoring system.Subjects were asked to simulate defecation and then the defecation related indexes were recorded.In the end rectoanal inhibitory reflexes (RAIR)and rectal sensation were assessed by aired balloon.One-way analysis of variance and independent sample test were performed to compare indexes among three groups with different age and between different genders. Results A total of 166 healthy subjects were enrolled,79 in group Ⅰ with 40 male,68 in group Ⅱ with 29 male and 19 in group Ⅲ with 11 male.There was no significant difference in anal sphincter length (ASL),valid anal sphincter length (VASL),resting anal sphincter pressure (RASP),squeeze anal sphincter pressure (SASP)and duration of valid squeeze anal sphincter pressure (VSASP)among three groups with different age (all P > 0.05 ).Compared between male and female,only SASP of male ((180.13±8.10)mmHg,1 mmHg=0.133 kPa)was significantly higher than that of female ((143.93± 6.59)mmHg,t = -3.489,P <0.001 ),no difference in other parameters was found (all P >0.05 ). There was no significant difference in rectal pressure (RP),rectoanal pressure gradient (RAPG),anal sphincter relaxation rate (ASRR),and rectoanal coordination (RAC)among three groups (all P >0.05). During simulated defecation,RP and RAPG of men ((61 .23±3.46)mmHg and (40.04±4.08)mmHg) were significantly higher than those of women ((44.47 ± 2.32)mmHg and (24.00 ± 2.59 )mmHg, t=-4.075 ,-3.367,both P <0.01 ).There was no significant difference in other parameters between men and women (all P >0.05).All participants had RAIR,and there was no significant difference neither among three groups nor between men and women (both P >0.05).There was no significant difference in first rectal sensation (FRS)and constant rectal sensation (CRS)among three groups with different age (all P >0.05).However,the maximum rectal tolerable sensation (MRTS)of group Ⅱ and group Ⅲ was significantly higher than that of group Ⅰ ((194.41 ±6.32)mL and (200.00±12.75)mL vs (167.80 ± 5 .00)mL,F = 6.698,P = 0.002).There was no significant difference in rectal sensation between different gender (all P >0.05 ).Conclusions In our country,SASP,RP and RAPG during simulated defecation of male are higher than those of female.The value of MRTS increases along with the age.