Published papers

Background. Observational studies have demonstrated similarities between the underpinning of frailty and biological features of centenarians, suggesting that adaptability to age-related multiple physiological decline may be a core component of successful aging. The aim of this study is to determine whether hormonal pathways potentially involved in energy homeostasis contribute to survival beyond 100 years of age. Methods. We assessed a total of 252 centenarians (mean [standard deviation (SD)] age, 101.5 (1.8) years, range 100-108 years) using a complete set of biomarkers of adipose endocrine function and the insulin-like growth factor-1 (IGF-1) axis. Conventional risk factors at baseline were also assessed. The participants were followed up for all-cause mortality every 12 months by telephone contact. Results. During 2253 days of follow-up, 208 centenarians (82.5%) died. The lowest tertile of leptin and the highest tertile of tumor necrosis factor-α were associated with higher mortality risk among centenarians after adjusting for age (per 6-month increase), sex, education, smoking, activities of daily living (ADL), cognitive function, and comorbidities (hazard ratio [HR] 1.6; 95% confidence interval [CI], 1.14-2.35; and HR 1.45; 95% CI, 1.00-2.08, respectively). The lowest tertiles of both IGF-1 and IGF binding protein 3 (IGFBP3) were also associated with increased mortality. The adipose risk score, indicating cumulative effects of adipokine dysregulation, was strongly associated with increased mortality risk; ADL; cognitive function; and levels of albumin, cholinesterase, high-density lipoprotein-cholesterol, C-reactive protein, interleukin 6, and IGF-1 at baseline. Conclusions. The results suggested that preservation of adipose endocrine function and the IGF-1 axis may be potentially important for maintaining health and function and promoting survival at an extremely old age. Copyright 2008 by The Gerontological Society of America.

Objective: To determine the prevalence of dry eye disease (DED) and risk factors among young and middle-aged Japanese office workers using visual display terminals (VDTs). Design: Cross-sectional prevalence survey. Participants: Four thousand three hundred ninety-three Japanese young and middle-aged office workers using VDTs. Intervention: Office workers completed questionnaires sent by e-mail designed to detect dry eye diagnosis and risk factors. Main Outcome Measures: Clinically diagnosed DED was defined as the presence of a previous clinical diagnosis of DED by dry eye specialists or severe symptoms of DED (both dryness and irritation constantly or often). Current symptoms of DED and possible risk factors such as age, duration of VDT use, type of VDT work, environmental factors, presence of systemic diseases, systemic medicine use, smoking history, and contact lens (CL) use were the main outcome measures. We used logistic regression to examine associations between DED and other demographic factors. Results: Of the 4393 office workers, 3549 (80.1%) completed the questionnaire. Clinically diagnosed DED was present in 266 (10.1%) of 2640 male subjects and in 195 (21.5%) of 909 female subjects. Severe symptoms of DED were observed in 711 male and in 436 female participants. More than 4 hours of VDT use was associated with an increased risk of DED (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.40-2.02). In addition, CL use (OR, 3.91; 95% CI, 3.37-4.53) increased the risk of severe dry eye symptoms. Conclusions: Dry eye disease leading to a clinical diagnosis or severe symptoms is prevalent among young and middle-aged Japanese office workers. The condition is more prevalent among females, CL wearers, and prolonged VDT users. Relevant measures directed against the modifiable risks could provide a positive impact on public health and quality of life of office workers. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. © 2008 American Academy of Ophthalmology.

Objectives: To evaluate the association of hearing impairment, vision impairment and their combination (dual sensory impairment) with negative well-being such as depression, subjective poor health and the reduced functional ability in community-dwelling older adults, and to determine whether any association varies by gender. Methods: Between 2005 and 2006, we objectively examined vision and hearing impairment (using best-corrected visual acuity and pure-tone audiometric test) in 843 people aged 65 years and older (351 males, 492 females) in a rural Japanese town. Through a home visit interview survey using a structured questionnaire, we also collected information on depression (the five-item Geriatric Depression Scale), subjective poor health, and reduced functional activity (the Tokyo Metropolitan Institute of Gerontology's Index of Competence). Results: We observed gender differences in the association between sensory impairment and depression. Multiple logistic regression analysis revealed that hearing impairment in males (adjusted odds ratio: 2.22, 95% confidence interval; 1.07-4.61) and vision impairment in females (1.91, 1.14-3.21) were related to depression. Vision impairment and dual sensory impairment were also associated with subjective poor health and reduced functional activity in both sexes. Conclusions: Sensory impairment is significantly associated with negative well-being in older persons, and its association with depression may differ between males and females. © 2008 Elsevier Inc. All rights reserved.

Objectives: Following a volcanic eruption in 2000, high concentrations of ambient sulfur dioxide (SO2) are still observed on Miyakejima, Japan despite the reversal 2 years ago of the ban on residents living on the island. This study examines the association between current levels of volcanic SO 2 and the incidence of acute subjective symptoms in volunteers on Miyakejima. Methods: The authors conducted a follow-up study on 611 healthy volunteers, on a person-hour basis (28 413 person-hours), who visited the island to provide support to residents from February to July 2005. Adverse health symptoms were measured by self-administered diary and exposure was approximated using monitoring data across 14 sites. Associations between incidence rates and increasing SO2 levels (reference (the lowest), very low, low, middle and high) were examined using Poisson regression. Results: Hourly incidence of cough, scratchy throat, sore throat and breathlessness showed clear exposureresponse relationships with SO2 concentrations. There were statistically significant risks of those symptoms at relatively low SO 2 levels. Thus, rate ratios in the 0.6-2.0 ppm exposure band (vs <0.01 ppm) were: for cough, 3.4 (95% Cl 1.8 to 6.6) in men and 9.8 (3.9 to 24.9) in women; for sore throat, 3.2 (1.7 to 6.2) in men and 5.8 (2.0 to 16.5) in women; and for breathlessness, 10.5 (4.2 to 26.6) in men and 18.5 (4.6 to 74.3) in women. Little evidence of SO2 effects on sputum and nasal discharge/congestion was observed in this study. Eye and skin irritations showed inconsistent results between hourly maximal and hourly mean SO2 concentrations. Conclusion: The authors observed strong evidence of an exposure-response relationship between volcanic SO2 and subjective acute respiratory symptoms among a healthy population on Miyakejima. The results are consistent with reports that females and non-smokers are more sensitive to irritant gas than males and smokers, respectively.

Background: A new bronchoscopic microsampling (BMS) probe has recently been developed, which allows the minimally invasivecollection of epithelial lining fluid (ELF) simultaneously from multiple sites. While the number of immunocompetent patients with pulmonary Mycobacterium avium complex(MAC) disease is growing, the precise pathogenesis of the disease remains to be clarified. Objectives: This study aimed to measure biochemical markers in the ELF of patients with pulmonary MAC disease using BMS. Methods: We studied 8 healthy volunteers (controls) and 8 patients with pulmonary MAC disease. In the patients, ELF was collected from visibly abnormal (involved) and normal (uninvolved) sites using high-resolution computed tomography (HRCT). Results: The concentration of IFN-γ (means ± SEM) was significantly higher in patient ELF sampled from involved (26.62 ± 9.66 pg/ml) than from uninvolved sites (5.33 ± 1.44 pg/ml; p < 0.05) or from normal controls (<1.56 pg/ml; p < 0.05). In most patients, there was no difference in IFN-γ concentrations between the involved and uninvolved sites. The concentration of KL-6 in ELF was significantly higher in the involved (793 ± 108 U/ml) than in the uninvolved sites (192 ± 43 U/ml;p < 0.05) or in normal controls (186 ± 38 U/ml;p < 0.05). Conclusions: The specific inflammatory reaction caused by MAC infection might not be limited to sites that were visibly abnormal on HRCT. Although further improvement has to be considered, BMS may help to increase the understanding of the pathogenesis of various respiratory disorders. Copyright © 2008 S. Karger AG.

In the present study, we determined iodine concentration in commonly consumed foods in Japan. One hundred thirty-nine foods and beverages were purchased from local markets and convenience stores. These samples were examined for iodine concentration by using gas chromatography after ashing or extraction. The iodine concentrations in various food groups were as follows, The concentrations in cereals, sugar, sweeteners, vegetables, fruit, milk, and meat were too low to be detected (<0.05 mg/100 g). The iodine concentrations of algae and dashi (Japanese broth or stock) from algae were <0.05-225 mg/100 g; Japanese seasoning, <0.05-10.5 mg/100 g; and iodine-rich eggs, 1.09-2.00 mg/100 g. Food and beverages with high iodine concentrations need to be taken into account in the nutritional survey for health hazards and benefits in the evaluation of daily nutritional intake.

Marital status is related to cardiovascular disease (CVD) risk factors in Western countries. However, few studies have addressed the relationship between marital status and CVD risk factors in other populations. We investigated lifestyle and CVD risk factors relative to marital status among middle-aged Japanese men. We analyzed baseline data of 40-59-yr-old male workers who participated in the high-risk and population strategy for occupational health promotion (HIPOP-OHP) study. We compared lifestyle and CVD risk factors between men who were married (Group M; n=1,419, mean age 47.9 ±5.1 yr) and those who had never married (Group N; n=163, mean age 46.7 ±4.3 yr). Men in Group N were more likely to skip breakfast, work more shifts and exercise less. Current smoking rates, as well as average values of diastolic blood pressure (DBP), serum total cholesterol and fasting plasma glucose were also higher in Group N than in Group M. The proportion of participants with three or more CVD risk factors, namely smoking, hypertension, hypercholesterolemia and hyperglycemia was higher in Group N, than in Group M (12.9% vs. 5.0%, p<0.01). The difference between Groups M and N was more evident in the subgroup of living with others, than in the subgroup of living alone. Since men who have never married might be at higher risk for CVD, effort should be made to educate this population about decreasing lifestyle-related risk factors.

OBJECTIVE: Studies in Western countries have revealed that urinary incontinence, non-intentional loss of urine, is a common condition in aged populations, and even younger individuals may suffer from urinary incontinence. However, in Japan, the evidence for community residents on this topic is limited. The aim of this study was to estimate the prevalence of urinary incontinence among middle aged using a structured questionnaire and older people and to provide useful information including frequency, voided volume, relation to parity as a risk factor and persons to consult for this condition. METHODS: The study subjects consisted of 985 residents, 350 males (mean age 62.5 +/- 11.2 years)and 635 females (64.3 +/- 11.4), who participated in annual health check-ups and answered a self-reported questionnaire on urinary incontinence. The questionnaire included questions on frequency, voided volume, condition-specific QOL score, self-diagnostic item (above four from Scored International Consultation on Incontinence Questionnaire-Short Form Japanese version), person to consult for this condition and parity (only for females). RESULTS: The proportion of those with urinary incontinence was 11.4% in males and 34.5% in females, and the proportion increased with age (P for trend <0.01). In females, the proportion was high, even in their forties (30.4%). In this study, parity was associated with urinary incontinence: compared to females with no childbirth experience, those giving birth to 4 or more children showed an odds ratio of 4.26 (95% CI: 1.13-16.10). In females, an increase in frequency of urinary incontinence negatively affected the QOL. When asked who they would consult, the majority of males answered either a medical institution (54.2%) or family (34.0%). In females, 39.6% reported a medical institution, 22.6% reported family, 16.5% reported no one, 10.6% reported health nurses other than in medical institutions and 9.5% reported friends. CONCLUSIONS: The study results showed that urinary incontinence is a common condition in this population. Particularly, a large proportion of females suffer from this condition, even in their forties. The study also revealed that urinary incontinence might negatively affect the QOL and that there are some individuals who do not consult (or intend to consult) anyone about their problem. This information might be useful for planning health policy on the topic in the future.

OBJECTIVE: To examine the performance of an interferon-gamma (IFN-γ) release assay (QuantiFERON-TB 2G assay [QFT-G]) to detect Mycobacterium tuberculosis infection in a Japanese general hospital, for the diagnosis of active pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB). DESIGN: We prospectively examined the performance of QFT-G in 194 patients suspected of active TB. Diagnosis was confirmed by 1) positive M. tuberculosis cultures, or 2) clinical manifestations or laboratory or pathological findings consistent with active TB and response to specific therapy. RESULTS: Three patients with indeterminate QFT-G results were excluded. Among the remaining 191 patients, 77 had active TB. When the cut-off concentration of IFN-γ was set at 0.35 IU/ml, as recommended by the manufacturer, the assay was positive in 69 patients and negative in 122. The sensitivity of the assay was 76.6% in all patients, 74.5% in the 47 patients with PTB and 80.0% in the 30 patients with EPTB. The overall specificity of the assay was 91.2%. CONCLUSION: Although the specificity of the QFT-G to detect active TB was high and its sensitivity low, it was as accurate for the detection of active EPTB as for PTB when the 0.35 IU/ml INF-γ cut-off concentration was used. © 2008 The Union.

Objectives: This study evaluated the association between job strain and subclinical indicators of arteriosclerosis simultaneously in the cerebral artery, the aorta, and the carotid artery. Methods: The participants in this cross-sectional study consisted of 352 male factory workers between the ages of 24.9 to 55.8 (mean 41.7) years who had not been exposed to any hazardous chemicals in Japan. Job strain was measured using a Japanese version of the Job Content Questionnaire developed by Karasek. The following subclinical indicators of arteriosclerosis were examined by noninvasive procedures: hyperintense spots in T2-weighted images in brain magnetic resonance imaging (MRI), pulse wave velocity of the aorta, and the stiffness parameter of the carotid artery using ultrasound and systolic and diastolic blood pressure. Results: After control for potential confounders, high job strain was associated with an increased prevalence of hyperintense spots (adjusted odds ratio 2.53, 95% confidence interval 1.14-5.63), and elevated pulse-wave velocity (adjusted increase in percent 3.5, 95% confidence interval 0.0-6.9). The stiffness parameter tended to be elevated in the high job-strain group although this trend was not statistically significant. Job strain showed no relation to blood pressure. Conclusions: In this study, job strain was associated with subclinical indicators of arteriosclerosis in different arteries although the association was not statistically significant for the carotid artery. New information is offered by brain MRI for arteriosclerosis in the cerebral artery. An increase in hyperintense spots may explain the link between job strain and cerebrovascular disease.

In a case-control study in Japan of brain tumours in relation to mobile phone use, we used a novel approach for estimating the specific absorption rate (SAR) inside the tumour, taking account of spatial relationships between tumour localisation and intracranial radiofrequency distribution. Personal interviews were carried out with 88 patients with glioma, 132 with meningioma, and 102 with pituitary adenoma (322 cases in total), and with 683 individually matched controls. All maximal SAR values were below 0.1 W kg-1, far lower than the level at which thermal effects may occur, the adjusted odds ratios (ORs) for regular mobile phone users being 1.22 (95% confidence interval (CI): 0.63-2.37) for glioma and 0.70 (0.42-1.16) for meningioma. When the maximal SAR value inside the tumour tissue was accounted for in the exposure indices, the overall OR was again not increased and there was no significant trend towards an increasing OR in relation to SAR-derived exposure indices. A non-significant increase in OR among glioma patients in the heavily exposed group may reflect recall bias. © 2008 Cancer Research UK.

Objectives: To identify the effects of indium on the lung and to assess exposure-effect and exposure-response relations between indium exposure and effects on the lungs. Methods: Ninety three male indium exposed and 93 male non-exposed workers from four ITO manufacturing or ITO recycling plants were analysed in a cross-sectional study. Indium in serum (In-S) was determined as a biological exposure index. Geometric means (GSD) of In-S were 8.25 ng/ml (4.55) in the exposed workers and 0.25 (2.64) in the non-exposed workers. The maximum concentration of In-S was 116.9 ng/ml. A questionnaire for respiratory symptoms and job histories, spirometry, high-resolution computerised tomography (HRCT) of the chest, serum KL-6, serum SP-A, serum SP-D and serum CRP were measured as the effect indices. Results: Spirometry, subjective symptoms and the prevalence of interstitial or emphysematous changes on lung HRCT showed no differences between exposed and non-exposed workers. Geometric means (GSD) of KL-6, SP-D and SP-A in the exposed workers were 495.4 U/ml (2.26), 85.2 ng/ml (2.02) and 39.6 ng/ml (1.57), and were significantly higher than those in the non-exposed workers. The prevalence (%) of the exposed and non-exposed workers exceeding the reference values were also significantly higher in KL-6 (41.9 vs 2.2), SP-D (39.8 vs 7.5), and SP-A (43.0 vs 24.7). Very sharp exposure-effect and exposure-response relations were discovered between In-S and KL-6 and between In-S and SP-D when the exposed workers were classified into seven groups by In-S. Conclusions: The study outcomes with regard to the basis of serum immunochemistry biomarkers and HRCT indicate that exposure to hardly soluble indium compound dust may represent a risk for interstitial lung damage.

Objectives: The prevalence of thoracic kyphosis is considered to increase as the population is ageing in Japan. However, little is known about the clinical and preventive significance of kyphosis. The purpose of the study is to assess the association of kyphosis with subjective poor health and functional activity in the community-dwelling Japanese elderly. The relation of kyphosis with blood pressure, as a subclinical indicator of arteriosclerosis, is also examined. Methods: The subjects consisted of 536 (male 241, female 295) elderly persons aged 65 years old and older. Trained examiners measured thoracic kyphosis using a flexicurve, and kyphosis index was calculated. Information on the subjects' subjective poor health and functional activity were collected through a face-to-face interview, and blood pressure was measured by a conventional method. Results: In females, their kyphosis index increased with age increased, whereas in males, there was no clear age-related change. An increased kyphosis index was associated with subjective poor health only among females. Compared with the lowest kyphosis index tertile, adjusted odds ratios for being in poor health were 5.4 (95% confidence interval: 1.1-27.4) in the middle tertile, and 6.4 (95% confidence interval: 1.3-32.1) in the highest tertile. Kyphosis index did not seem to be associated with functional activity score and blood pressure both in males and females even after adjustment. Conclusions: Kyphosis is associated with subjective poor health in the community-dwelling female elderly in this study population, but not with functional activity and blood pressure both in males and females.

The control banding method, or "control banding", is a simplified risk assessment system for chemical handling tasks. This system is supposed to provide assessment results of reasonable quality without expert involvement. The objective of this study was to evaluate the appropriateness of control banding judgment on the basis of workplace safety. A common approach for assessing workplace risk, which is called "comprehensive risk assessment" in this study, is to measure workers' exposure and compare it with relevant occupational exposure limits. Risk assessment was performed with control banding (COSHH Essentials, UK) at 12 workplaces of a petroleum company in Japan, where health risks had already been assessed separately through comprehensive risk assessment by experts and control technologies implemented accordingly. The obtained control banding judgments were then examined with regard to their adequacy by comparing them with existing control technologies. There was majority of cases (seven) where judgments by control banding were identified as "over-controlled"; there was no judgments identified as "under-controlled". Control banding also requested the seeking of expert advice in the majority of cases (eight). Thus, it was demonstrated that control banding tends to provide safe-sided judgment. A possible interpretation of this is that control banding is inherently designed to secure workplace safety by compensating for its insufficient exposure information with safe-sided judgment criteria and by requiring experts' intervention in high-risk cases. Control banding could be widely and effectively utilized in Japan, especially by employers in small enterprises, provided that the above characteristics are pre-acknowledged and health experts are made available. To this aim, it is essential to develop new local health experts and establish institutional mechanisms for facilitating employers' access to expert advice. It should however be noted that the number of workplaces evaluated in this study was small.