Published papers

Background: Barrett's esophagus has been divided into three categories based on the extent of the metaplasia: long-segment (LSBE), short-segment (SSBE), and ultrashort-segment Barrett's esophagus (USBE). While both LSBE and SSBE are thought to be induced by gastroesophageal reflux, the etiology of USBE is still unclear. Methods: We conducted a case-control study to identify the differences in the pathogenesis between SSBE and USBE in a hospital-based population. The endoscopic findings and clinical factors of 199 patients with short-segment endoscopically suspected esophageal metaplasia (SS-ESEM) and 317 patients with ultrashort-segment ESEM (US-ESEM) were compared with those of 199 and 317 age- and gender-matched patients without ESEM. Results: The severity of gastric mucosal atrophy was marginally associated with the presence of US-ESEM [odds ratio (OR) 1.20, 95% confidence interval (CI) 0.98-1.46, p = 0.08], but not with that of SS-ESEM. On the other hand, the presence of gallstones and that of severe reflux esophagitis were associated with the presence of SS-ESEM (OR 2.19, 95% CI 1.21-3.98; OR 1.72, 95% CI 1.08-2.75), but not with that of US-ESEM. Presence of gastric corpus atrophy without gallstones was associated with the presence of US-ESEM, but not with that of SS-ESEM. Conclusions: Presence of gastric corpus atrophy was associated with an increased likelihood of the presence of US-ESEM, whereas the presence of gallstones was associated with an increased likelihood of the presence of SS-ESEM, suggesting difference in etiology between US- and SS-ESEM. © 2010 Springer.

Background: In older adults, kyphosis (slouching posture) can lead to underestimation of height, which may in turn lead to overestimation of body mass index (BMI). We investigated the extent to which inaccurate BMI assessments led to misclassification of elderly people as normal weight (when they were actually underweight) or overweight (actually normal weight). Methods: Anthropometric measurements were taken in 2005 and 2006 for 842 residents aged 65 years or older (women: 491; men: 351). We calculated BMI from measured height and weight (observed BMI) and then predicted BMI from height as determined by demi-span, which is unaffected by kyphosis (predicted BMI). Kyphosis was assessed by the number of blocks placed under the occiput required for the supine participant to achieve a neutral head position. Participants were classified as underweight (BMI < 18.5), normal weight, or overweight (BMI ≥ 25.0) according to both observed and predicted BMI; classification accordance was investigated by cross-tabulation. Results. Kyphosis was present in 17.2% of the participants overall and in 23.6% of those aged 75 years or older. Predicted BMI measurements showed that 11 % of participants with kyphosis requiring ≥ 3 blocks were misclassified as normal weight and that 10% were erroneously classified as overweight. In those aged 75 years or older, the corresponding figures were 15% and 12%. Conclusions. Our results suggest that inaccurate BMIs due to kyphosis lead to substantial numbers of older adults being misclassified as normal weight or overweight, which can cause significant distortions in data on the impact of underweight and overweight on health outcomes. © The Author 2011. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.

The effects of exposure to environmental chemicals, such as heavy metals and fine particulates, on cardiovascular diseases have been reported. To set a permissible exposure standard, an exposure-response relationship should be elucidated. Thus, epidemiologic evidence in relation to long-term, low-level exposure to environmental chemicals (i.e., lead, cadmium, mercury, arsenic, PM(2.5), carbon disulfide) was reviewed. As a result, there exists a clear exposure-response relationship between exposure to lead or PM(2.5) and cardiovascular diseases, but those cohort studies were carried out in the US only. From epidemiologic viewpoint, "consistency" of the observed relationship must be clarified, especially findings of a study in the Japanese population. It is well known that the distribution pattern of cardiovascular risk factors are quite different between two countries, which could modify the true relationship. This will require studies of large samples from the general Japanese population with control for potential confouders. Moreover, to detect a small effect of exposure within low-level range, random misclassification of exposure as well as that of effect must be minimized. Thus, for studies of heavy metals, sensitive biomarkers identified in toxicological studies would be applied. For PM(2.5), a wide range of population samples should be covered by a national sampling network in the near future. Finally, the integration of epidemiologic and toxicological evidence would be more important for risk assessment of environmental chemicals at low exposure levels, because an exposure-response relationship from only epidemiologic observation may be unstable with a wide confidence interval around the threshold.

Colorectal cancer is one of the complications of ulcerative colitis (UC) and the risk of cancer increases as the duration of the disease becomes longer. Surveillance colonoscopy has been considered to be important for the early detection and early treatment of colorectal cancer, especially in longstanding UC. Because it is not always easy to detect neoplastic lesions in UC endoscopically, guidelines recommend the use of step biopsy in surveillance, in which either 4 biopsy specimens for every 10 cm or a total of 33 or more biopsy specimens are obtained. However, it has been pointed out that a step biopsy obtaining several tens of biopsy specimens may not be an ideal method in terms of invasiveness to the patient or medical cost. Instead of step biopsy, recent studies report the usefulness of target biopsy, in which biopsy tissues are obtained only from regions suspected of neoplasia. Therefore, the Research Group for Intractable Inflammatory Bowel Disease of the Ministry of Health, Labour and Welfare of Japan has initiated a randomized controlled study to compare the efficacy of step biopsy and target biopsy. The present article gives an introduction to this ongoing randomized controlled trial in Japan. © 2010 Springer.

Aim: Gamma-glutamyltransferase (GGT) is known to correlate well with alcohol consumption; however, the relation between GGT and diabetes and that between alcohol consumption and diabetes mellitus (DM) is inconsistent. Thus, several questions, such as whether light to moderate drinkers can be considered as low risk for diabetes incidence irrespective of their GGT level, is unresolved. In this study, we investigated the relation of GGT or alcohol drinking with DM incidence considering the body mass index (BMI) in healthy Japanese workers. Methods: We followed 3095 men who did not have DM at baseline for 4 years. Incident diabetes was defined as a fasting (non-fasting) plasma glucose level of ≥7.0 (11.1) mmol/L, or treatment of diabetes. Multiple adjusted hazard ratios (HR) were calculated using Cox proportional models. Results: Participants with higher GGT (GGT ≥27 IU/L) showed an increased risk of diabetes incidence even when their BMI level was low. Although a U-shaped relation between alcohol drinking and incident diabetes was observed, the risk to light to moderate drinkers (alcohol <23 g/day) was not low if they were either overweight (BMI ≥25 kg/m2) or had higher GGT (HR= 2.60, p= 0.08) or both overweight and higher GGT (HR= 3.16, p= 0.07) compared with never drinkers without higher GGT and overweight. Conclusions: Higher GGT was associated with a higher incidence of DM irrespective of drinking status or obesity. Although a U-shaped relation between alcohol drinking and incident diabetes was observed, the risk to light to moderate drinkers was not low if they were either overweight or had higher GGT.

Background: The prevalence of tinnitus is reported to be high in older Western populations, and several risk factors have been suggested. However, community-based evidence on prevalence is limited and, to our knowledge, there is no such information from older non-Western populations. The purpose of this study was to determine the prevalence and factors associated with tinnitus in community-dwelling Japanese elders. Methods: In this community-based cross-sectional study, 1320 residents of Kurabuchi Town aged 65 years or older (584 men and 736 women; participation proportion = 98.7%) were interviewed at home in 2006, and information on tinnitus and factors associated with tinnitus was collected. We estimated the prevalence of tinnitus by age group and sex and used a logistic regression model to investigate associated factors. Results: The prevalence of tinnitus was 18.6% (men: 18.0%; women: 19.0%); there were no statistically significant differences by age group or sex. Hearing difficulty, depressive mood, prescribed medication, past/current history of coronary heart disease, and knee joint pain requiring medical consultation were associated with tinnitus. Conclusions: These findings suggest that tinnitus is common in Japanese aged over 65 years. Because the factors associated with tinnitus in this cross-sectional study are potentially modifiable, they should be thoroughly investigated in a longitudinal study. © 2010 by the Japan Epidemiological Association.

Background: Metabolic syndrome (MS) is associated with an increased risk of cardiovascular disease. However, its prevalence in inflammatory bowel disease (IBD) patients remains largely unknown. This study was planned to determine the prevalence of MS in Japanese IBD patients. Methods: The prevalence of MS among outpatients with IBD aged 18 or older was studied using the modified National Cholesterol Education Program Adult Treatment Panel III definition. Results: A total of 107 quiescent IBD patients, including 76 ulcerative colitis (UC) patients and 31 Crohn's disease (CD) patients, were studied. Sufficient data were collected from a total of 102 patients. Prevalence of MS was significantly higher in UC (23.0%) patients compared to CD patients (7.1%). MS prevalence was substantially higher among male IBD patients (21.1%) compared to female IBD patients (12.9%), particularly in patients over 30 years of age. No difference was observed in the prevalence of MS between our IBD cohort and the general population in both males and females aged 40 years and older (P = 0.707 in males, P = 0.328 in females). IBD patients with MS were also older than those without (50.2 ± 15.0 vs. 38.0 ± 11.9 years, P = 0.013). In a logistic regression analysis, age was the statistically significant predictor of MS among IBD patients. The odds ratio (95% confidence interval) was 1.064 (1.017-1.114). Conclusions: Prevalence of metabolic syndrome in our IBD patients was comparable to that of the general population. Because age was the independent risk factor for developing MS, evaluation for MS is needed for elderly IBD patients. © 2010 Springer.

Objective: We analyzed the database of the Japanese nationwide inflammatory bowel disease (IBD) registry, which was started in 1975, to characterize basic epidemiological and clinical features of childhood IBD, comparing them to those in adults. Study design: We analyzed the age of disease onset, disease severity and anatomical distribution in patients that were newly registered between 2003 and 2006 (n = 2,940 for CD and 14,857 for UC). We also analyzed the current age, gender and family history of IBD of all patients filed in 2005, which included patients who were newly registered in 2005 and those who had been registered before 2005 and for whom an annual report had been received in 2005 (total number of subjects: 10,934 for CD and 37,846 for UC). Results: At the time of registration, 10.6% of CD and 5.9% of UC patients were ≤16 years old. In CD, the male to female ratio was 2.6 in adult- and 1.7 in childhood-onset patients (P < 0.001). In UC, the male to female ratio was close to 1 in both age groups. In comparison with adults, pediatric patients more commonly had a positive family history for CD and UC (P < 0.001), tended to have more severe disease at the time of registry (P < 0.001 for CD, P < 0.05 for UC) and more often had extensive colitis in UC (P < 0.001). Conclusion: The nationwide registry in Japan showed IBD in children has clinical features that are distinct from those in adults. © 2010 Springer.

Background and aims: Patients with inflammatory bowel disease (IBD) who want to have children are anxious to receive medical treatment. The consensus regarding pregnancy has not been surveyed for male IBD patients. The present study was investigated opinions among male IBD patients about pregnancy, conception and neonatal outcomes for partners. Methods: Subjects comprised 364 of 386 patients enrolled (94.3%). Subjects received a questionnaire regarding their opinions and thoughts about pregnancy. The course of partner's conceptions and presence of neonatal malformations was also surveyed. Results: The rate of live births for partners of male IBD patients was 91.6% (219/239). Most patients with CD (29/33; 88%) had their children after surgery had been performed. The rate of expressing hopes to have a child tended to be higher for patients with UC (93/128; 73%) than for patients with CD (61/97; 63%; p = 0.21). Furthermore, the rate of hesitation was significantly higher in CD patients (34/107; 32%) than in UC patients (38/188; 20%; p = 0.03).Patients considered that safety of medication (51%) and maintenance of remission (41%) was more important than receiving no treatment for IBD (19%) when planning to conceive. Mesalamine and infliximab were more favorable at conception than sulfasalazine and immunomodulators. Conclusions: This is the first report to survey the thinking of male IBD patients regarding pregnancy. Most male IBD patients considered "maintaining remission" as important at conception. Our study provides important information for IBD patients and for the treating physician when planning to conceive. © 2009 European Crohn's and Colitis Organisation.

Aim: To examine the relation between lifestyle and the number of metabolic syndrome (MetS) diagnostic components in a general population, and to find a means of preventing the development of MetS components. Methods: We examined baseline data from 3,365 participants (2,714 men and 651 women) aged 19 to 69 years who underwent a physical examination, lifestyle survey, and blood chemical examination. The physical activity of each participant was classified according to the International Physical Activity Questionnaire (IPAQ). We defined four components for MetS in this study as follows: 1) high BP: systolic BP ≥ 130 mmHg or diastolic BP ≥85 mmHg, or the use of antihypertensive drugs; 2) dyslipidemia: high-density lipoprotein-cholesterol concentration <40 mg/dL, triglycerides concentration ≥150 mg/dL, or on medication for dyslipidemia; 3) Impaired glucose tolerance: fasting blood sugar level ≥110 mg/d, or if less than 8 hours after meals ≥140 mg/dL), or on medication for diabetes mellitus; 4) obesity: body mass index ≥25 kg/m2. Results: Those who had 0 to 4 MetS diagnostic components accounted for 1,726, 949, 484, 190, and 16 participants, respectively, in the Poisson distribution. Poisson regression analysis revealed that independent factors contributing to the number of MetS diagnostic components were being male (regression coefficient b = 0.600, p<0.01), age (b = 0.027, p<0.01), IPAQ class (b = -0.272, p = 0.03), and alcohol consumption (b = 0.020, p = 0.01). The contribution of current smoking was not statistically significant (b = -0.067, p = 0.76). Conclusion: Moderate physical activity was inversely associated with the number of MetS diagnostic components, whereas smoking was not associated.

Purpose: Bile and acid exposures are thought to be major risk factors for Barrett's esophagus in Western countries. The association of gallstones with Barrett's esophagus has not been fully evaluated. The present study was designed as a case-control study for determining the possible factors associated with endoscopically suspected esophageal metaplasia (ESEM), defined as an endoscopic finding suggestive of Barrett's esophagus, in Japanese patients. Methods: A total of 528 patients with ESEM were allocated to the case group, while 528 age- and gender-matched patients without ESEM were allocated to the control group. Findings on esophagogastroduodenoscopy and clinical background factors were compared using a multivariate logistic regression model. Results: The presence of gallstones and hiatus hernia and the severity of gastric mucosal atrophy were independently associated with the presence of ESEM [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.03-2.69; OR 2.75, 95% CI 1.75-4.33; OR 1.25, 95% CI 1.01-5.6, respectively]. Compared with subjects with neither gastric corpus atrophy nor gallstones, although subjects with gallstones alone were not associated with the presence of ESEM (OR 1.59, 95% CI 0.87-2.92), having both gastric corpus atrophy and gallstones was strongly associated with the presence of ESEM (OR 2.94, 95% CI 1.40-6.17). Conclusions: The presence of gallstones was independently associated with the presence of ESEM in the Japanese outpatient population, suggesting a causal association of distal esophageal bile exposure with the development of ESEM. Further studies are needed to confirm our findings in cases with histologically confirmed Barrett's esophagus. © 2009 Springer.

BACKGROUND: Mt. Oyama on Miyakejima Island erupted in June 2000 and all Miyake village citizens were forced to evacuate the island in the September, due to continuous eruptions and emission of unsafe amounts of volcanic gas, mainly sulfur dioxide (SO2). Beginning in February 2005, residents returned to live on the island despite the fact that volcanic gas was still being emitted. OBJECTIVE: To examine changes in the respiratory systems of included children from February 2006 to November 2006. METHODS: The study population was 141 children who participated in health checkups in November 2006, including 33 SO2 hypersusceptible children who had a current or past history of asthma, obstructive lung function, current symptoms of whistling and wheezing, and/or deterioration of respiratory symptoms. Respiratory effects were evaluated by a questionnaire for respiratory symptoms and by spirometry. SO2 was monitored at 7 sampling points within inhabited areas, and the mean SO2 concentration from February 2005 to November 2006 was 0.031 ppm. The area was categorized into four areas by average SO2 concentration, namely, areas L, H-1, H-2, and H-3, where the average SO2 levels were 0.019, 0.026, 0.032, and 0.045 ppm, respectively. RESULTS: Compared to children in area L, the frequencies of "phlegm" and "irritation of the nose" were significantly greater in the children in areas H-2 and H-3. %FVC and %FEV1 in hypersusceptible children were significantly reduced in November 2006 as compared to February 2006 (P = 0.047, 0.027), though no reduction observed in normosusceptible children. CONCLUSION: Respiratory functions in hypersusceptible Miyakejima children may be affected by SO2 exposure, and further follow-up observation is necessary.

Background. Several epidemiological studies have shown that self-reported vision and hearing impairments are associated with adverse health outcomes (AHOs) in older populations; however, few studies have used objective sensory measurements or investigated the role of gender in this association. Therefore, we examined the association of vision and hearing impairments (as measured by objective methods) with AHOs (dependence in activities of daily living or death), and whether this association differed by gender. Methods. From 2005 to 2006, a total of 801 residents (337 men and 464 women) aged 65 years or older of Kurabuchi Town, Gunma, Japan, participated in a baseline examination that included vision and hearing assessments; they were followed up through September 2008. Vision impairment was defined as a corrected visual acuity of worse than 0.5 (logMAR = 0.3) in the better eye, and hearing impairment was defined as a failure to hear a 30 dB hearing level signal at 1 kHz in the better ear. Information on outcomes was obtained from the town hall and through face-to-face home visit interviews. We calculated the risk ratios (RRs) of AHOs for vision and hearing impairments according to gender. Results. During a mean follow-up period of 3 years, 34 men (10.1%) and 52 women (11.3%) had AHOs. In both genders, vision impairment was related to an elevated risk of AHOs (multi-adjusted RR for men and women together = 1.60, 95% CI = 1.05-2.44), with no statistically significant interaction between the genders. In contrast, a significant association between hearing impairment and AHOs (multi-adjusted RR = 3.10, 95% CI = 1.43-6.72) was found only in the men. Conclusion. In this older Japanese population, sensory impairments were clearly associated with AHOs, and the association appeared to vary according to gender. Gender-specific associations between sensory impairments and AHOs warrant further investigation. © 2009 Michikawa et al; licensee BioMed Central Ltd.

Purpose: The prevalence of inflammatory bowel diseases is much lower in Asian countries, including Japan, than in Western countries, but it is rapidly increasing. However, no recent reports describe the current prevalence of these diseases in Japan, so we performed a descriptive epidemiological study to remedy this situation and to elucidate various characteristics of inflammatory bowel diseases in this country. Methods: Japan has a nationwide registration system of patients with intractable diseases, including ulcerative colitis and Crohn's disease. To calculate the age-standardized prevalence, we used this registration system to collect patient data, and we obtained detailed population data from the Japanese government's population estimates made in 2003 and 2004 and from the 2005 population census. In addition, information about the characteristics of ulcerative colitis and Crohn's disease patients was collected through the registration system. Results: The age-standardized prevalence of ulcerative colitis in Japan in 2005 was 63.6 per 100,000 persons, and that of Crohn's disease was 21.2. Patient numbers have been steadily increasing with time. The age distribution was found to differ between the two diseases, with Crohn's disease affecting mainly younger people. In both diseases, more than 50% of the patients were male, and over 80% of the patients were classified as mild to moderate in terms of severity. Conclusions: The prevalence of inflammatory bowel diseases in Japan is still much lower than in Western countries. Surveillance should be continued, and research to clarify their etiologies in association with the increasing number of patients in Japan is needed. © Springer 2009.

Salt intake is an important risk factor for hypertension. Because it has been reported that increased salt intake dulls the taste of salt, measuring the sense of taste might be a good way of identifying individuals who consume excessive salt. Using a recently developed simple salt taste test, we investigated the relationship between the taste of salt and blood pressure. The subjects in this cross-sectional study were 823 Japanese adults (479 women and 344 men) 40 years old or older. Following a taste test with salt-impregnated taste strips, the subjects were divided into two groups: normal (recognition threshold of salt at <1.0% concentration) and taste impaired (≥1.0%). We determined hypertension from the measured blood pressure. In women, the multi-adjusted odds ratio (95% CI) of hypertension in the impaired group was 2.47 (1.53-3.99) compared with the normal group, whereas no significant difference was observed between the two male groups. When we excluded subjects with moderate and severe hypertension, similar findings were observed. A sub-analysis of couples living alone showed a higher prevalence of hypertension among men whose wives were in the impairment group (58.8%) than in the normal group (36.7%, P=0.10). In conclusion, the taste of salt is associated with blood pressure in Japanese women, but not in men. Because most family meals in Japan are prepared by women, educating women about salt reduction may contribute to the prevention of hypertension, not only among women but also among their husbands and family members.

Objective: Risperidone is converted to 9-hydroxyrisperidone by CYP2D6. Two parameters were used to examine the influences of CYP2D6 polymorphism and of co-medication on risperidone metabolism: the risperidone:9-hydroxyrisperidone concentration ratio (R:9-OHR ratio) and the sum of the risperidone and 9-hydroxyrisperidone concentrations divided by the dose (C:D ratio). We evaluated the effect of the CYP2D6*10 allele, which is a prevalent mutant allele among East Asians. Methods: Genotyping using the P450 microarray system was performed for 89 Japanese patients with schizophrenia receiving risperidone. The patients with CYP2D6*1/*1, *1 /*2, or *2/*2 were classified as Group 1, those with one CYP2D6a10 allele (CYP2D6*1/2,10 or *2/*10) were classified as Group 2, and those with two CYP2D6,10 alleles were classified as Group 3. The R:9-OHR and C:D ratios were analyzed using two-way ANOVAs with the CYP2D6 genotype and co-medication with CYP2D6-dependent drugs as independent variables. Results: Both the "genotype" and the "co-medication" factors had significant impacts on the R:9-OHR ratio (p=0.011, p<0.001). The "genotype" factor also had a significant impact on the C:D ratio (p=0.032). However, the "co-medication" factor did not have a significant impact on the C:D ratio (p=0.129). Conclusions: The CYP2D6*10 polymorphism and the presence of co-medication exerted significant influences on the pharmacokinetics of risperidone. Copyright © 2009 John Wiley & Sons, Ltd.

Objectives: We evaluated the association of nutrient intake with Fe deficiency with regard to lifestyle factors and health condition in young Japanese women. Uniquely among developed countries, dietary habits render Japanese populations vulnerable to Fe deficiency, owing to their relatively low intake of Fe and high intake of Fe absorption inhibitors, such as green tea and soyabeans. Design: A cross-sectional study. Setting and subjects: The subjects were 1019 female Japanese dietetic students aged 18-25 years. Dietary habits during the preceding month were assessed using a previously validated, self-administered, diet history questionnaire. Blood analysis was performed to assess body Fe status. Subjects were categorized with Fe deficiency when their serum ferritin levels were <12 ng/ml. Twenty-nine dietary variables, i.e. intakes of energy, sixteen nutrients including Fe and twelve food groups, were analysed using multivariate logistic regression models adjusted for possible confounders. Results: Of the subjects, 24.5 % were categorized with Fe deficiency. However, no dietary factors assessed were significantly associated with Fe deficiency. The risk of Fe deficiency was significantly lower in women with infrequent or no menstrual cycles than in those with regular cycles (OR = 0.58; 95 % CI 0.34, 1.00) and significantly higher in women with heavy menstrual flow than in women with average flow, albeit that these were self-reported (OR = 1.83; 95 % CI 1.35, 2.48). Conclusions: These results suggest that dietary habits, including Fe intake, do not significantly correlate with Fe deficiency among young Japanese women. © The Authors 2008.