Tetsuji Yokoyama

Dietary risk factors for inflammatory bowel disease A Multicenter Case‐Control Study in Japan

&NA; To evaluate the role of dietary factors in the etiology of inflammatory bowel disease (IBD), we conducted a multicenter hospital‐based case‐control study in a Japanese population. Cases were IBD patients aged 15 to 34 years [ulcerative colitis (UC) 111 patients; Crohns disease (CD) 128 patients] within 3 years after diagnosis in 13 hospitals. One control subject was recruited for each case who was matched for sex, age, and hospital. A semiquantitative food frequency questionnaire was used to estimate preillness intakes of food groups and nutrients. All the available control subjects (n = 219) were pooled, and unconditional logistic models were applied to calculate odds ratios (ORs). In the food groups, a higher consumption of sweets was positively associated with UC risk [OR for the highest versus lowest quartile, 2.86; 95% confidence interval (CI), 1.24 to 6.57], whereas the consumption of sugars and sweeteners (OR, 2.12; 95% CI, 1.08 to 4.17), sweets (OR, 2.83; 95% CI, 1.38 to 5.83), fats and oils (OR, 2.64; 95% CI, 1.29 to 5.39), and fish and shellfish (OR, 2.41; 95% CI, 1.18‐4.89) were positively associated with CD risk. In respect to nutrients, the intake of vitamin C (OR, 0.45; 95% CI, 0.21 to 0.99) was negatively related to UC risk, while the intake of total fat (OR, 2.86; 95% CI, 1.39 to 5.90), monounsaturated fatty acids (OR, 2.49; 95% CI, 1.23 to 5.03) and polyunsaturated fatty acids (OR, 2.31; 95% CI, 1.12 to 4.79), vitamin E (OR, 3.23; 95% CI, 1.45 to 7.17), and n‐3 (OR, 3.24; 95% CI, 1.52 to 6.88) and n‐6 fatty acids (OR, 2.57; 95% CI, 1.24 to 5.32) was positively associated with CD risk. Although this study suffers from the shortcoming of recall bias, which is inherent in most retrospective studies (prospective studies are warranted to confirm the associations between diet and IBD risk), the present findings suggest the importance of dietary factors for IBD prevention.

Improvement in Atrophic Gastritis and Intestinal Metaplasia in Patients in Whom Helicobacter pylori Was Eradicated

Few long-term studies of chronic gastritis associated with Helicobacter pylori have been published. Kuipers (1) and Valle (2) and their colleagues showed that in about one third of infected patients, nonatrophic gastritis progressed to glandular atrophy and intestinal metaplasia before final follow-up (mean duration of follow-up, 11.5 years and 32 years, respectively). Two studies of 10 patients (3) and 35 patients (4) infected with H. pylori found long-term improvement in intestinal metaplasia after H. pylori eradication. However, in one study of more than 100 patients with H. pylori infection, glandular atrophy and intestinal metaplasia did not improve during long-term follow-up (5). We evaluated histologic changes 12 to 15 months after attempted eradication of H. pylori to explore whether glandular atrophy and intestinal metaplasia improve after eradication. Methods Patients We enrolled all consecutive patients with dyspepsia and H. pylori infection who were seen at our gastroenterology clinic in Tokyo, Japan, for diagnostic upper gastrointestinal endoscopy. The proportions of patients who were self-referred, were referred from within our hospital, and were referred from other hospitals were roughly equal. Patients with possible allergy to penicillin, amoxicillin, or proton-pump inhibitors and those with previous gastrectomy were excluded. Written informed consent was obtained from participants in accordance with the Declaration of Helsinki and its later revision. The protocol was approved by the institutional review board of Tokyo Medical and Dental University, Tokyo, Japan. Study Design At entry, patients underwent upper gastrointestinal endoscopy; gastric mucosa was histologically evaluated by performing biopsy. Helicobacter pylori status was assessed by using bacteriologic culture, histologic results, the rapid urease test, and the urea breath test. Eligible patients were treated for 1 week with a proton-pump inhibitor (omeprazole or lansoprazole), amoxicillin, and clarithromycin with or without a mucoprotective agent (ecabet sodium, rebamipide, or sofalcone). At 1 to 3 months (short-term follow-up) and at 12 to 15 months (long-term follow-up) after eradication therapy, patients again underwent upper gastrointestinal endoscopy and gastric biopsy specimens were examined histopathologically. H. pylori Assessment At each endoscopy, three biopsy specimens each were taken from the greater curvature of the antrum and the greater curvature of the corpus of the stomach. One sample from each site was cultured, one was used for the rapid urease test, and one was used for histologic examination. Cultures on modified Skirrow agar with 10% horse blood were incubated for 5 to 7 days at 37 C in a microaerobic atmosphere. We identified H. pylori by observing colony structure and performing biochemical tests for urease, catalase, and oxidase activities. Biopsy specimens for histologic examination were stained with Giemsa stain or hematoxylineosin. After an overnight fast, a [13C]urea breath test was done with 100 mg of [13C]urea per 100 mL of distilled H2O. The results were considered negative if the ratio of 13CO2 to 12CO2 in 15 minutes increased by less than 5 parts per million. The presence of H. pylori was investigated at each endoscopic examination. The bacterium was considered to be present if results of at least two of four tests (bacteriologic culture, histologic results, rapid urease test, and urea breath test) were positive. Helicobacter pylori was considered eradicated if results were negative for all four tests at both short-term and long-term follow-up. No patient had only one positive test result. Gastritis Scores The endoscopists were blinded to the results of treatment. For each patient, two pathologists who were blinded to the results of treatment made independent histologic diagnoses by examining one biopsy specimen each from the antrum and corpus. The pathologists disagreed on the diagnosis in 99 of the 978 specimens examined (49 specimens from the antrum and 50 specimens from the corpus; the final diagnoses were chronic inflammation in 24 specimens, neutrophil activity in 39, glandular atrophy in 27, and metaplasia in 9). Consensus was reached by re-examination and discussion. Severity of chronic inflammation, neutrophil activity, glandular atrophy, and intestinal metaplasia was graded from 0 (normal) to 3 (markedly abnormal) according to the visual analogue scales of the updated Sydney System (6). Specimens stained with Giemsa were evaluated for H. pylori by another investigator. Statistical Analysis We divided patients into two groups on the basis of the success or failure of H. pylori eradication. We examined background factors and histologic findings at baseline to identify pretreatment differences between the two groups. We used the unpaired t-test for age, the chi-square test for sex ratios in the two groups, both the chi-square test and the Fisher exact test for comorbid conditions, and the Wilcoxon rank-sum test for histologic findings. For the antrum and corpus, we performed the Wilcoxon signed-rank test to compare histologic findings at baseline with those at follow-up (1 to 3 months and 12 to 15 months after treatment). To evaluate differences in changes in the histologic findings during follow-up, we performed mixed-effects ordinal logistic regression by using the computer program MIXOR (7). This method prevents problems caused by regression to the mean. We used SAS software, version 6.12 (SAS Institute, Inc., Cary, North Carolina), to perform all other analyses. A P value less than 0.05 was considered statistically significant. Results We studied 207 consecutive patients with H. pylori infection and dyspepsia. Patients underwent endoscopy before treatment and at least once after treatment, at 1 to 3 months. In addition, 163 patients agreed to undergo another endoscopy at 12 to 15 months after treatment (mean, 14 months). Thirty-three patients declined to undergo a second follow-up examination, and 11 patients were untraceable because they had moved out of the area. Helicobacter pylori was eradicated without serious side effects in 115 of the 163 patients who had long-term follow-up. The 115 patients in whom H. pylori was eradicated were similar to the 48 who remained infected in terms of mean (SD) age (54 12 years vs. 59 10 years), sex distribution (84 men and 31 women vs. 30 men and 18 women), and diagnosis (47 and 18 patients with chronic gastritis, 30 and 15 with duodenal ulcers, 25 and 15 with gastric ulcer, and 13 and 0 with gastroduodenal ulcers). The Table shows histologic findings for the gastric mucosa before treatment and again at the two follow-up points. The two groups did not differ significantly in histologic findings before treatment. In patients with successful eradication, scores for chronic inflammation and neutrophil activity at both sites were lower at both follow-up points than before treatment, and scores for glandular atrophy in the corpus and intestinal metaplasia in the antrum were lower at 12 to 15 months than before treatment. Glandular atrophy in the corpus improved in 34 (89%) of the 38 patients with atrophy before treatment, and intestinal metaplasia in the antrum improved in 28 (61%) of the 46 patients with metaplasia before treatment. Table. Histologic Results before Treatment To Eradicate Helicobacter pylori and at Short- and Long-Term Follow-up In patients with unsuccessful eradication of H. pylori, no significant histologic changes were observed at follow-up, except for progression of chronic inflammation. Mixed-effects ordinal logistic regression showed statistically significant differences between groups in changes at follow-up for chronic inflammation and neutrophil activity at both sites and for intestinal metaplasia in the antrum (Table, Figure). Individual histologic changes were as follows (some percentages do not total 100 because of rounding). Among patients with successful eradication of H. pylori, glandular atrophy in the antrum decreased in 29% and 27% at short- and long-term follow-up, respectively, was unchanged in 40% and 30%, and increased in 31% and 43%; in the corpus, glandular atrophy decreased in 24% and 30%, was unchanged in 70% and 64%, and increased in 6% and 6%. Intestinal metaplasia in the antrum decreased in 16% and 25% of patients of these patients, was unchanged in 78% and 71%, and increased in 5% and 4%; intestinal metaplasia in the corpus decreased in 3% and 4%, was unchanged in 88% and 91%, and increased in 10% and 5%. Among patients without eradication of H. pylori, glandular atrophy in the antrum decreased in 23% and 38%, at short- and long-term follow-up, respectively, was unchanged in 44% and 29%, and increased in 33% and 33%; glandular atrophy in the corpus decreased in 25% and 19%, was unchanged in 46% and 65%, and increased in 29% and 17%. Intestinal metaplasia in the antrum decreased in 0% and 0%, was unchanged in 98% and 96%, and increased in 2% and 4%; intestinal metaplasia in the corpus decreased in 12% and 8%, was unchanged in 81% and 83%, and increased in 6% and 8%. Figure. Predicted curves obtained by mixed-effects ordinal logistic regression models for histologic changes in the gastric mucosa in patients in whom Helicobacter pylori infection was or was not successfully eradicated . H. pylori H. pylori P Discussion Tucci and colleagues (8) reported that atrophic gastritis of the corpus of the stomach had regressed by 12 months after discontinuation of treatment in 10 of 20 patients with fundic atrophic gastritis in whom H. pylori was successfully eradicated. In contrast, Witteman and colleagues (10) found no changes at 57 weeks in glandular atrophy of the antrum and corpus of patients in whom the bacterium was eradicated. In a prospective study with a mean follow-up of 1 year (range, 6 to 18 months), van der Hulst and colleagues (5) found that the degree of atrophy did not change; however, their grading of a

A 15.5-year follow-up study of stroke in a Japanese provincial city : The Shibata Study

BACKGROUND AND PURPOSE Change toward Western lifestyles, particularly during the high economic growth period (approximately 1960 to 1975), dynamically altered stroke frequency and the distribution of risk factors in the Japanese. We reexamined their association after this environmental change by a cohort study. METHODS The cohort (2302 subjects) comprised residents aged 40 years or older of the Akadani-Ijimino district in Shibata City, Niigata Prefecture, Japan, who were followed up from 1977 for 15.5 years. RESULTS Crude incidence rates per 1000 person-years for all strokes were 5.22 for men and 4.36 for women (3.02 and 2.18 for cerebral infarction, 0.65 and 1.06 for intracerebral hemorrhage, and 0.41 and 0.34 for subarachnoid hemorrhage, respectively). Multivariate analyses performed with the Cox proportional hazard model revealed these risk factors to be independently significant: for cerebral infarction in men, age, blood pressure, atrial fibrillation, albuminuria, funduscopic abnormality, and current smoking: for cerebral infarction in women, age, atrial fibrillation, and history of ischemic heart disease; for intracerebral hemorrhage in men, age and funduscopic abnormality; for intracerebral hemorrhage in women, age, blood pressure, and light physical activity; for all strokes in men, age, blood pressure, atrial fibrillation, albuminuria, funduscopic abnormality, current smoking, and heavy physical activity; and for all strokes in women, age, atrial fibrillation, and light physical activity. CONCLUSIONS Most traditional risk factors, including blood pressure and its related organ diseases, were confirmed, but serum total cholesterol had almost no effect. Physical activity had both negative and positive effects on stroke risk. In these findings, however, some differences related to sex were also observed.

Serum Vitamin C Concentration Was Inversely Associated With Subsequent 20-Year Incidence of Stroke in a Japanese Rural Community The Shibata Study

Background and Purpose Epidemiological evidence suggests that vitamin C may decrease the risk of stroke. The purpose of the present study was to examine the association of serum vitamin C concentration with the subsequent incidence of stroke. Methods In a Japanese rural community, a cohort of 880 men and 1241 women aged 40 years and older who were initially free of stroke was examined in 1977 and followed until 1997. The baseline examination included a measurement of serum vitamin C concentration. The incidence of stroke was determined by annual follow-up examinations and registry. Results During the 20-year observation period, 196 incident cases of all stroke, including 109 cerebral infarctions and 54 hemorrhagic strokes, were documented. Strong inverse associations were observed between serum vitamin C concentration and all stroke (sex- and age-adjusted hazard ratios were 0.93, 0.72, and 0.59, respectively, for the second, third, and fourth quartiles compared with the first quartile;P for trend=0.002), cerebral infarction (0.71, 0.59, and 0.51;P for trend=0.015), and hemorrhagic stroke (0.89, 0.75, and 0.45;P for trend=0.013). Additional adjustments for blood pressure, serum total cholesterol, body mass index, physical activity, smoking, alcohol drinking, antihypertensive medication, atrial fibrillation, and history of ischemic heart disease did not attenuate these associations markedly. Conclusions Serum vitamin C concentration was inversely related to the subsequent incidence of stroke. This relationship was significant for both cerebral infarction and hemorrhagic stroke. Additional mechanistic hypotheses may be required to explain our findings.

Treatment of functional dyspepsia with antianxiety or antidepressive agents : systematic review

BackgroundThe pathophysiology of functional dyspepsia (FD) has not been elucidated precisely; accordingly, effective management of FD has not yet been found. Until now, treatment with antianxiety or antidepressive agents has been empirically applied; however, the efficacy of these treatments has not been established. We carried out this study to estimate the efficacy of these treatment approaches by systematically reviewing the literature concerning trials with agents that are efficacious against anxiety, neurosis, or depression.MethodsArticles were searched from the MEDLINE database up to October 2003, using the terms, “antianxiety agents”, “antidepressants”, and “dyspepsia”, and from reference lists of published articles. Finally, studies in which the effectiveness of drugs was clearly stated were selected from the retrieved articles.ResultsThirteen articles, on 1717 patients, were selected from among 90 articles retrieved through our literature search. In 11 of the 13 studies, dyspeptic symptoms were improved significantly by treatment. Statistical analysis of 4 trials showed a significant benefit of treatment with antianxiety or antidepressive agents (pooled relative risk, 0.55; 95% confidence interval [CI], 0.36–0.85), although funnel plots were asymmetric.ConclusionsAntianxiety or antidepressive agents may be effective in the treatment of FD patients, though further clinical trials are necessary.

Age-Dependent Association of Apolipoprotein E Genotypes With Stroke Subtypes in a Japanese Rural Population

BACKGROUND AND PURPOSE The association between apolipoprotein E (apoE) polymorphisms and stroke has been controversial. These controversies may be due to inaccurate classification of stroke and differences in age ranges. We investigated the association between apoE genotypes and stroke subtypes (confirmed by CT or MRI findings) by case-control study in a Japanese rural population. METHODS First-ever-stroke patients (n=322; cerebral infarction, n=201, intracerebral hemorrhage, n=84, and subarachnoid hemorrhage, n=37) aged 40 to 89 years were recruited from Hokuetsu Hospital, Japan. Healthy controls (n=1126) were selected from the general population in the same area. ApoE genotypes were determined by restriction fragment-length polymorphism analysis. RESULTS Compared with apoE epsilon3/epsilon3 subjects, epsilon2 carriers had a 2-fold risk of cerebral infarction (OR 1.9, 95% CI 1.1 to 3.2). Among cerebral infarction patients, epsilon2 carriers had increased risks of cortical infarction (OR 2.4, 95% CI 1.3 to 4.6) (an anatomic subtype) and atherothrombosis (OR 3.9, 95% CI 1.7 to 9.0) and cardioembolism (OR 4.9, 95% CI 1.6 to 14.4) but not lacunar infarction (clinical subtypes). ApoE epsilon4 carriers had a 2. 5-fold risk of subarachnoid hemorrhage (OR 2.5, 95% CI 1.1 to 5.4). ApoE epsilon2/epsilon2 subjects had an increased risk of intracerebral hemorrhage (OR 4.4, 95% CI 1.0 to 19.7). ApoE epsilon3/epsilon4 subjects showed approximately 2-fold increased risk of atherothrombosis (OR 2.1, 95% CI 1.0 to 4.1) and intracerebral hemorrhage (OR 1.8, 95% CI 1.0 to 3.3). The association between epsilon2 and stroke was accentuated in subjects aged 70 years or older but not in those aged 40 to 69 years. CONCLUSIONS Our study suggests that apoE epsilon2 is a risk factor for atherothrombosis, cardioembolism, and intracerebral hemorrhage, whereas epsilon4 is a risk factor for atherothrombosis, intracerebral hemorrhage, and subarachnoid hemorrhage. The occurrence of stroke may be affected by interaction between age and apoE gene polymorphisms.

Newly Developed Antibiotic Combination Therapy for Ulcerative Colitis: A Double-Blind Placebo-Controlled Multicenter Trial

OBJECTIVES:Fusobacterium varium may contribute to ulcerative colitis (UC). We conducted a double-blind placebo-controlled multicenter trial to determine whether antibiotic combination therapy induces and/or maintains remission of active UC.METHODS:Patients with chronic mild-to-severe relapsing UC were randomly assigned to oral amoxicillin 1500 mg/day, tetracycline 1500 mg/day, and metronidazole 750 mg/day, vs. placebo, for 2 weeks, and then followed up. The primary study end point was clinical response (Mayo score at 3 months after treatment completion) and secondary end points were clinical and endoscopic score improvements at 12 months. Anti-F. varium antibodies were measured by enzyme-linked immunosorbent assay.RESULTS:Treatment and placebo groups each had 105 subjects. At the primary end point, response rates were significantly greater with antibiotics than with placebo (44.8 vs. 22.8%, P=0.0011). Endoscopic scores significantly improved at 3 months (P=0.002 vs. placebo). Remission rates were 19.0% (antibiotics) vs. 15.8% (placebo) at 3 months (P=0.59). At the secondary end point, response rates were significantly greater with antibiotics than with placebo (49.5 vs. 21.8%, respectively, P<0.0001). Endoscopic scores were significantly improved at 12 months after antibiotic treatment (P=0.002 vs. placebo). Remission rates had improved to 26.7% with antibiotics vs. 14.9% for placebo, at 12 months (P=0.041). F. varium antibody titers decreased in responders but not in nonresponders, and more in the antibiotic than in the placebo group. More pretreatment steroid-dependent UC patients discontinued corticosteroids after treatment completion (6 months: 28.6 vs. 11.8%, respectively, P=0.046; 9 months: 34.7 vs. 13.7%, respectively, P=0.019; and 12 months: 34.7 vs. 13.7%, respectively, P=0.019). These effects were greater in the subanalysis of the active group (Mayo scores of 6–12) than in that of total cases (0–12). No serious drug-related toxicities occurred.CONCLUSIONS:The 2-week triple antibiotic therapy produced improvement, remission, and steroid withdrawal in active UC more effectively than a placebo.

Risk of postpartum depression in relation to dietary fish and fat intake in Japan: The Osaka Maternal and Child Health Study

BACKGROUND An ecological analysis found that the docosahexaenoic acid content in mothers milk and seafood intake were inversely correlated with postpartum depression. This prospective study investigated the relationship of consumption of selected high-fat foods and specific types of fatty acids with the risk of postpartum depression. METHOD The subjects were 865 Japanese women. Dietary data were obtained from a self-administered diet history questionnaire during pregnancy. The Edinburgh Postnatal Depression Scale (EPDS) was used for the evaluation of postpartum depression. Adjustment was made for age, gestation, parity, cigarette smoking, family structure, family income, education, changes in diet in the previous month, season when data at baseline were collected, body mass index, time of delivery before the second survey, medical problems in pregnancy, babys sex and babys birthweight. RESULTS The percentage of women with high depression scores was 14.0%. No evident dose-response associations were observed between intake of fish, meat, eggs, dairy products, total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, n-6 polyunsaturated fatty acids, linoleic acid, alpha-linolenic acid, arachidonic acid, eicosapentaenoic acid or docosahexaenoic acid and the ratio of n-3 to n-6 polyunsaturated fatty acids and the risk of postpartum depression. However, there was an inverted J-shaped relationship between intake of n-3 polyunsaturated fatty acids and docosahexaenoic acid and the risk of postpartum depression. CONCLUSIONS This study failed to substantiate a clear inverse relationship between fish and n-3 polyunsaturated fatty acid intake and postpartum depression. Further investigations are needed to determine whether fish and n-3 polyunsaturated fatty acid consumption is preventive against postpartum depression.

Salivary Acetaldehyde Concentration According to Alcoholic Beverage Consumed and Aldehyde Dehydrogenase-2 Genotype

BACKGROUND Acetaldehyde is suspected of playing a critical role in cancer development in the upper aerodigestive tract (UADT). The high salivary acetaldehyde levels after alcohol drinking are partly due to acetaldehyde production by oral bacteria. Some alcoholic beverages, especially Calvados and shochu, contain very high levels of acetaldehyde. Inactive heterozygous aldehyde dehydrogenase-2 (ALDH2) increases the risk of UADT cancer in drinkers. METHODS In a randomized cross-over design study, 19 healthy Japanese volunteers ingested 0.6 g ethanol/kg body weight in the form of 13% ethanol Calvados, 13% ethanol shochu, 13% ethanol red wine, and 5% ethanol beer under the fasting conditions at 3-week intervals. We monitored blood and salivary acetaldehyde concentrations immediately after drinking, and 30, 60, 90, 120, and 180 minutes after completion of drinking. RESULTS The acetaldehyde concentration of each beverage was: Calvados 0.60 mM (1.86 mM in 40% undiluted solution), shochu 0.60 mM (1.16 mM in 25% undiluted solution), red wine 0.25 mM, and beer 0.14 mM. The salivary acetaldehyde concentration immediately after drinking wine was significantly lower than the other beverages, and it was significantly lower immediately after drinking beer than Calvados. The acetaldehyde concentrations 30 to 180 minutes after drinking were unrelated to the beverage type. Throughout the observation period the salivary acetaldehyde concentrations were much higher than the blood acetaldehyde concentrations in all 12 active ALDH2 homozygotes (24 to 53 microM in saliva vs. 2 to 5 microM in blood) and in all 7 inactive ALDH2 heterozygotes (37 to 76 microM in saliva vs. 12 to 25 microM in blood), and they were 13 to 25 microM higher in the ALDH2 heterozygotes than in the ALDH2 homozygotes after adjusting for age, body weight, sex, smoking and drinking habits, and time since the last toothbrushing. The values after subtracting the blood acetaldehyde concentration from the salivary acetaldehyde concentration were also higher in the ALDH2 heterozygotes than in the ALDH2 homozygotes. CONCLUSIONS There are differences in exposure of the UADT to high salivary acetaldehyde concentrations according to the type of alcoholic beverage and ALDH2 genotype, and the differences partly explain the differences in the cancer susceptibility of the UADT according to alcoholic beverage and ALDH2 genotype.

Efficacy of the 5-HT1A Agonist Tandospirone Citrate in Improving Symptoms of Patients With Functional Dyspepsia: A Randomized Controlled Trial

OBJECTIVES:Functional dyspepsia (FD) is a common condition in the general population; however, its treatment remains a challenge. The aim of this study was to examine the efficacy of tandospirone citrate, a new partial agonist of the 5-hydroxytryptamine 1A (5-HT1A) receptor, in improving the symptoms of patients with FD.METHODS:In this double-blind, placebo-controlled, multicenter study, FD patients were randomized to treatment with 10 mg t.i.d. tandospirone citrate or to placebo for 4 weeks. The primary end point was change in abdominal symptom scores. The difference in the proportion of responders (a total abdominal symptom score of 0 or 1) was also assessed. The quality-of-life questionnaire, the SF-8, and a psychological test questionnaire, the State-Trait Anxiety Inventory (STAI), were completed at baseline and at weekly intervals.RESULTS:Data were available for 144 patients: 73 for tandospirone and 71 for placebo. Improvements in total abdominal scores were significantly larger with tandospirone than placebo at weeks 1, 2, and 4. Significantly greater improvements in the tandospirone group were observed in upper abdominal pain (P=0.02) and discomfort (P=0.002) at week 4. The proportion of responders was significantly greater in the active treatment arm at weeks 3 (P=0.017) and 4 (P=0.0016). Significant improvements in STAI (P<0.0001) were reported in both arms, as well as in the majority of questions in the SF-8 (P=0.04). No serious adverse events were reported, with similar rates in both study arms.CONCLUSIONS:Despite a considerable placebo effect, the benefits of tandospirone were shown in terms of improvement in abdominal symptom scores.