Neurocognitive Function in Aged Survivors Exposed to Atomic Bomb Radiation In Utero: The Radiation Effects Research Foundation Adult Health Study.

Although some adverse effects on neurocognitive function have been reported in children and adolescents irradiated prenatally during the atomic bombings and the Chernobyl nuclear accident, little information is available for effects on the elderly. Here we evaluate the effects of prenatal exposure to atomic bomb radiation on subjective neurocognitive function in aged survivors. To evaluate neurocognitive impairment, we mailed the Neurocognitive Questionnaire (NCQ), a self-administered scale, to prenatally exposed survivors, including clinic visitors and non-visitors at the time of the 2011 and 2013 Adult Health Study (AHS) examinations. We received replies from 444 individuals (mean age, 66.9 ± 0.6 years). After adjusting for sex, city, and educational background, we found no significant effects of radiation, clinic visit, or interaction between radiation and clinic visit on the scores of the 4 NCQ factors of metacognition, emotional regulation, motivation/organization, and processing speed. Even in analyses considering gestational age at the time of the bombings, none of the 4 NCQ factor scores was related to maternal uterine dose. There remains the limitation that this study consisted of healthy survivors, but we found no significant radiation effect on late-life cognition in people prenatally exposed to atomic bomb radiation.

Radiation Effects on Late-life Neurocognitive Function in Childhood Atomic Bomb Survivors: A Radiation Effects Research Foundation Adult Health Study.

High-dose radiation in childhood such as is used in radiation therapy causes cognitive decline, but there is insufficient research on the cognitive effects of low- to medium-dose radiation. We aimed to reveal the association between atomic bomb radiation exposure in childhood and late-life neurocognitive function. In 2011 and 2013, we mailed the Neurocognitive Questionnaire (NCQ) to subjects who were 12 years old or younger at the time of the atomic bombing. We converted the four NCQ subscales (metacognition, emotional regulation, motivation/organization, and processing speed) to T scores and defined the highest 10% of the controls (exposure dose < 5 mGy) as impaired. We used a generalized linear mixed model to evaluate the effect of radiation exposure on T scores and percentage impaired. We enrolled 859 participants. At the time of the bombing, the mean (SD) age was 6.7 (3.8) years for the control (N = 390) and 6.1 (3.8) years for the exposed (N = 469). At the time of replying to the questionnaire, the mean age of all the participants was 73.7 (3.8) years of age. After adjusting for cofactors, older age was related to the decline of all neurocognitive subscales. Sex and education level had relevance to some of the subscales. For neurocognitive function, exposure dose was not related except to percentage impaired, motivation/organization. Late-life neurocognitive function in atomic bomb survivors exposed as children was associated with age, but not clearly with radiation dose. More studies are needed to evaluate the effect of low-dose radiation during childhood on long-term neurocognitive function.

Incidence of Diabetes in the Atomic Bomb Survivors: 1969-2015.

CONTEXT: Recent epidemiological studies have shown increased risk of diabetes among childhood cancer survivors who received high therapeutic doses of radiation, particularly to the total body or to the abdomen. However, the effect of low-to-moderate dose radiation (<4 Gy) on the risk of diabetes is still unknown. OBJECTIVES: To investigate the radiation effect on diabetes incidence among atomic bomb (A-bomb) survivors, and whether the dose response is modified by other factors including city, sex, and age at time of bombing (ATB). METHODS: 9131 participants without diabetes at baseline were observed through biennial clinical exams from 1969 to 2015. A Cox proportional hazards model was used to estimate hazard ratios (HR) to evaluate the dose response for diabetes incidence. RESULTS: During the study period, 1417 incident diabetes cases were identified. The overall crude incidence rate was 7.01/103 person-years. Radiation dose was significantly associated with diabetes incidence, with effect modification by city and age ATB. In Hiroshima, at ages 10 and 30 ATB, the HRs at 1 Gy of pancreatic radiation dose were 1.47 (95% CI, 1.31-1.66) and 1.13 (95% CI, 0.97-1.31), respectively. However, no significant radiation dose response was observed at these ages in Nagasaki. The HR for radiation dose was higher among those who were younger ATB and decreased 1% for each additional year of age. CONCLUSIONS: Among A-bomb survivors, a radiation association was suggested for incidence of diabetes. Results were inconsistent by city and age ATB, which could indicate potential confounding of the radiation association with diabetes.

Relationship Between Radiation Exposure and Incident Atrial Fibrillation Among Atomic Bomb Survivors.

Background: Atrial fibrillation (AF) is a common arrhythmia. Although radiation exposure is associated with an elevated risk of cardiovascular disease, the effects of radiation on arrhythmia, especially AF, are unclear. We evaluated the relationship between radiation and AF in a cohort of atomic bomb survivors. Methods and Results: From a baseline enrollment period (1967-1969) to 2009, 7,379 Hiroshima and Nagasaki atomic bomb survivors (mean baseline age 50.6 years, 65.8% women, 72.9% from Hiroshima) without AF and who had been exposed to estimated radiation doses between 0 and 3.614 Gy were followed-up once every 2 years. AF was identified by 12-lead electrocardiograms and medical records. Treating age as the time scale, AF incidence was modeled with Cox proportional hazards models adjusting for demographics, AF risk factors, and radiation. We modeled radiation as both a continuous variable and categorized according to radiation dose (Control [<0.005 Gy] and 5 equal-sized groups based on radiation dose quintiles in the cohort). Over 4 decades of follow-up, we identified 276 AF cases in 176,687 person-years, for an incidence rate of 1.56 per 1,000 person-years. After adjusting for sex and city, neither categorized, linear, nor linear-quadratic models showed substantive evidence of radiation effects. Similar results were obtained after adjusting for AF risk factors. Conclusions: There were no clear positive associations between radiation dose and AF risk, rather null or non-significant inverse associations.

Association of human T-cell leukemia virus type 1 with prevalent rheumatoid arthritis among atomic bomb survivors: A cross-sectional study.

ABSTRACT: Previous studies have suggested that human T-cell leukemia virus type 1 (HTLV-1) might act as a pathogen in rheumatoid arthritis (RA), but epidemiological evidence of an association is scarce. We measured anti-HTLV-1 antibodies among Nagasaki atomic bomb survivors to determine whether HTLV-1 is related to RA and whether radiation exposure is associated with HTLV-1 and RA prevalence.This is a cross-sectional study among atomic bomb survivors who participated in biennial health examinations from 2006 to 2010. Serum levels of anti-HTLV-1 antibodies were measured using a chemiluminescent enzyme immunoassay and confirmed by Western blotting. Association between HTLV-1 and RA was analyzed by a logistic regression model.Of 2091 participants (women 61.5%; median age, 73 years), 215 (10.3%) had anti-HTLV-1 antibodies. HTLV-1 prevalence was higher among women (13.1% vs 5.8%; P < .001). Twenty-two participants (1.1%) were diagnosed with RA. HTLV-1 prevalence among RA participants was significantly higher than that among non-RA participants (27.3% vs 10.1%; P = .020). After adjustment for age, sex, and hepatitis C virus infection, HTLV-1 was significantly associated with prevalent RA (odds ratio, 2.89; 95% confidence interval, 1.06, 7.03). There was no association between radiation dose and either the prevalence of HTLV-1 or RA.This study, among a well-defined group of atomic bomb survivors, suggests that HTLV-1 is associated with RA.

Radiation effects on atherosclerosis in atomic bomb survivors: a cross-sectional study using structural equation modeling.

Past reports indicated that total-body irradiation at low to moderate doses could be responsible for cardiovascular disease risks, but the mechanism remains unclear. The purpose of this study was to investigate the association between radiation exposure and atherosclerosis, an underlying pathology of cardiovascular diseases, in the Japanese atomic bomb survivors. We performed a cross-sectional study measuring 14 clinical-physiological atherosclerosis indicators during clinical exams from 2010 to 2014 in 3274 participants of the Adult Health Study cohort. Multivariable analyses were performed by using a structural equation model with latent factors representing underlying atherosclerotic pathologies: (1) arterial stiffness, (2) calcification, and (3) plaque　as measured with indicators chosen a priori on the basis of clinical-physiological knowledge. Radiation was linearly associated with calcification (standardized coefficient per Gy 0.15, 95 % confidence interval: CI [0.070, 0.23]) and plaque (0.11, 95 % CI [0.029, 0.20]), small associations that were comparable to about 2 years of aging per Gy of radiation exposure, but not with arterial stiffness (0.036, 95 % CI [- 0.025, 0.095]). The model fitted better and had narrower confidence intervals than separate ordinary regression models explaining individual indicators independently. The associations were less evident when the dose range was restricted to a maximum of 2 or 1 Gy. By combining individual clinical-physiological indicators that are correlated because of common, underlying atherosclerotic pathologies, we found a small, but significant association of radiation with atherosclerosis.

Modifying Effect of Chronic Atrophic Gastritis on Radiation Risk for Noncardia Gastric Cancer According to Histological Type.

The findings from previously published studies have suggested that radiation exposure is associated with increased mortality and incidence of gastric cancer. However, few cohort studies have incorporated risk factors such as Helicobacter pylori (H. pylori) infection or chronic atrophic gastritis (CAG). The current study is aimed at evaluating the modifying effect of CAG on radiation risk of noncardia gastric cancer by histological type, by reanalyzing data from a nested case-control study conducted within the longitudinal clinical cohort of atomic bomb survivors. The analysis was restricted to 297 intestinal- or diffuse-type noncardia cases and 873 controls rematched to the cases on gender, age, city, and time and type of serum storage, and countermatched on radiation dose. Multivariable-adjusted relative risks [95% confidence interval (CI)] of noncardia gastric cancer were 3.9 (2.1-7.2) for H. pylori IgG seropositivity with cytotoxin-associated gene A (CagA) IgG low titer, 2.6 (1.9-3.6) for CAG, 1.9 (1.3-2.8) for current smoking, and 1.4 (1.1-1.9) for 1 Gy irradiation. Among subjects without CAG, the relative risk (95% CI) of noncardia gastric cancer at 1 Gy was 2.3 (1.4-3.7), whereas relative risk (95% CI) at 1 Gy was 1.1 (0.8-1.5) among subjects with CAG (for the overall interaction, P = 0.012). By histological type, the risk at 1 Gy was high for diffuse type without CAG, with adjusted relative risk (95% CI) of 3.8 (2.0-7.6), but was not high for diffuse type with CAG or for intestinal-type irrespective of CAG status. The results indicate that radiation exposure is associated with increased risk of diffuse-type noncardia gastric cancer without CAG, and this association exists despite adjustment for H. pylori infection and smoking habit.

Association between radiation, glaucoma subtype, and retinal vessel diameter in atomic bomb survivors.

We examined the relationship between glaucoma subtype and retinal vascular caliber as markers of ocular circulation. Subjects were Japanese atomic bomb survivors in Hiroshima and Nagasaki. After a screening examination, potential cases were subjected to further definitive examination. The diameters of central retinal artery and vein equivalents (CRAE and CRVE) on digitized retinal photographs were measured using an established method. Generalized linear regression analyses were used to examine the associations among vessel diameters, radiation exposure, and prevalence of glaucoma subtypes among the study subjects. We identified 196 cases of glaucoma (12%) based on optic disc appearance, perimetry results, and other ocular findings. The main subtypes were primary angle-closure glaucoma, primary open-angle glaucoma and normal-tension glaucoma (NTG). NTG was the dominant subtype (78%). NTG was negatively associated with CRAE and CRVE, and positively associated with radiation dose. CRVE was negatively associated with radiation dose and the association was unclear for CRAE. The smaller retinal vessel caliber in NTG patients than in subjects without glaucoma may indicate an association between ocular blood flow and the pathogenesis of NTG. However, significant relationships among vessel calibers, NTG and radiation exposure were not clear.

Radiation exposure and longitudinal changes in peripheral monocytes over 50 years: the Adult Health Study of atomic-bomb survivors.

Enhanced inflammatory responses have been suggested decades after radiation exposure in atomic-bomb survivors, but cellular and molecular alterations related to prolonged inflammation remain unclear. This study, utilizing longitudinal haematological data over 50 years for 14 000 persons, investigated whether radiation exposure promoted the relative increase in peripheral myeloid cells, known as an aging-associated indicator of low-grade inflammation. Statistical modelling was performed with a linear mixed-effects model for leucocyte subsets, together with a proportional hazards regression model for all-cause mortality. We found that age trends in lymphocyte, neutrophil and monocyte percentages or counts differed before versus after age 60 years. Radiation dose was associated with monocyte percentages and counts, but not with the lymphoid-myeloid cell ratio. Radiation effects on monocytes were stronger after versus before age 60 years. Increases in monocyte percentages and counts were associated with higher risk of all-cause mortality. Studies of chromosomal aberrations have shown a clonal expansion of haematopoietic stem cells among atomic-bomb survivors. Therefore, radiation exposure might accelerate aging-associated clonal haematopoiesis, which could result in a long-lasting elevation of circulating monocytes.

Epidemiological studies of atomic bomb radiation at the Radiation Effects Research Foundation.

Epidemiological studies of people who were exposed to atomic bomb radiation and their children who were conceived after parental exposure to radiation (F1) have investigated late health effects of atomic bomb radiation and its transgenerational effects. Those studies were initiated by the Atomic Bomb Casualty Commission (ABCC) in the 1950s. ABCC was reorganized to the Radiation Effects Research Foundation (RERF) in 1975, which continued the work of the ABCC. Follow-up of vital status and cause of death is performed for all RERF cohorts, including the atomic bomb survivors (the Life Span Study: LSS), in utero survivors, and the children of the survivors (F1). Cancer incidence is investigated for accessible subpopulations of the cohorts. Health examinations for subcohorts of the LSS and in utero survivors are conducted as the Adult Health Study (AHS); a program of health examinations for a subcohort of the F1 study is called the F1 Offspring Clinical Study (FOCS). Participants of all clinical programs are asked to donate their blood and urine for storage and future biomedical investigations. Epidemiological studies have observed increased radiation risks for malignant diseases among survivors including those exposed in utero, and possible risks for some noncancer diseases. No increased risks due to parental exposure to radiation have been observed for malignancies or other diseases in F1, but continuing investigations are required.

Association Between Prevalence of Peripheral Artery Disease and Radiation Exposure in the Atomic Bomb Survivors.

Background Past reports suggested that total-body irradiation at 0.5 to 1.0 Gy could be responsible for atherosclerosis. Peripheral artery disease ( PAD ) is a manifestation of systematic atherosclerosis. Whether the consequences of a low-to-moderate dose of radiation include increased risk of PAD remains to be determined. The purpose of this study was to examine the association between radiation exposure and prevalence of PAD among Japanese atomic bomb survivors. Methods and Results Radiation exposure from the atomic bombing was assessed in 3476 participants (41.1% men, mean age 74.8 years with SD 6.4 years) with a cross-sectional survey in 2010 to 2014. Left- and right-side ankle-brachial indexes and upstroke time ( UT ) were obtained using oscillometric VP -2000. PAD was defined as an ankle-brachial index of 1.0 or less or a prior history related to revascularization. UT was considered a sensitive marker of early-stage PAD . Association between radiation exposure and PAD or UT was assessed using multivariable regression analyses with adjustment for potential confounding factors. Of 3476 participants, 79 (2.3%) were identified as having prevalent PAD . Multivariate logistic regression analysis indicated that radiation dose was unrelated to PAD prevalence (odds ratio, 0.83; 95% confidence interval [0.57-1.21]). UT appeared to increase with radiation dose, but the increase was not statistically significant (1.09 ms/Gy; 95% confidence interval [-0.17 to 2.36]). Conclusions We found no clear association of radiation dose with PAD , but it remains to be determined whether UT is associated with radiation dose.

THYROID DISEASES AMONG ATOMIC BOMB SURVIVORS.

Systematic epidemiological studies of Hiroshima and Nagasaki atomic bomb survivors have made substantial contributions to the understanding of radiation effects on human health. A recent study of atomic bomb survivors reported that an increased risk of thyroid cancer associated with childhood exposure might have persisted for more than 50 years after exposure. In analyses of non-cancer thyroid diseases, several cross-sectional studies, including the latest study focusing on survivors exposed in childhood, suggested that the risk of thyroid nodules increased, while risks of thyroid dysfunction and autoimmunity were not apparent several decades after radiation exposure. However, careful interpretations are needed because only limited data from cross-sectional studies are available. Further longitudinal studies are necessary to improve our understanding of the effect of radiation on the thyroid and its function.

Thyroid Dysfunction and Autoimmune Thyroid Diseases Among Atomic Bomb Survivors Exposed in Childhood.

Context: The risk of thyroid cancer increases and persists for decades among individuals exposed to ionizing radiation in childhood, although the long-term effects of childhood exposure to medium to low doses of radiation on thyroid dysfunction and autoimmune thyroid diseases have remained unclear. Objective: To evaluate radiation dose responses for the prevalence of thyroid dysfunction and autoimmune thyroid disease among atomic bomb survivors exposed in childhood. Design, Setting, and Participants: Hiroshima and Nagasaki atomic bomb survivors who were younger than 10 years old at exposure underwent thyroid examinations at the Radiation Effects Research Foundation between 2007 and 2011, which was 62 to 66 years after the bombing. Data from 2668 participants (mean age, 68.2 years; 1455 women) with known atomic bomb thyroid radiation doses (mean dose, 0.182 Gy; dose range, 0 to 4.040 Gy) were analyzed. Main Outcome and Measures: Dose-response relationships between atomic bomb radiation dose and the prevalence of hypothyroidism, hyperthyroidism (Graves' disease), and positive for antithyroid antibodies. Results: Prevalences were determined for hypothyroidism (129 cases, 7.8%), hyperthyroidism (32 cases of Graves' disease, 1.2%), and positive for antithyroid antibodies (573 cases, 21.5%). None of these was associated with thyroid radiation dose. Neither thyroid antibody-positive nor -negative hypothyroidism was associated with thyroid radiation dose. Additional analyses using alternative definitions of hypothyroidism and hyperthyroidism found that radiation dose responses were not significant. Conclusions: Radiation effects on thyroid dysfunction and autoimmune thyroid diseases were not observed among atomic bomb survivors exposed in childhood, at 62 to 66 years earlier. The cross-sectional design and survival bias were limitations of this study.

Cancer association as a risk factor for anti-HMGCR antibody-positive myopathy.

OBJECTIVE: To show cancer association is a risk factor other than statin exposure for anti-3-hydroxy-3-methylglutaryl coenzyme A reductase autoantibody-positive (anti-HMGCR Ab+) myopathy. METHODS: We analyzed the clinical features and courses of 33 patients (23 female and 10 male) with anti-HMGCR Ab+ myopathy among 621 consecutive patients with idiopathic inflammatory myopathies. RESULTS: Among the 33 patients, 7 (21%) were statin-exposed and 26 were statin-naive. In relation with cancer, there were 12 patients (statin-exposed, n = 4) with cancers detected within 3 years of myopathy diagnosis (cancer association), 3 patients (all statin-naive) with cancers detected more than 3 years before myopathy diagnosis (cancer history), 10 cancer-free patients followed up for more than 3 years (all statin-naive), and 8 patients without cancer detection but followed up for less than 3 years (statin-exposed, n = 3). Therefore, 12 patients with cancer association (36%) formed a larger group than that of 7 statin-exposed patients (21%). Among 12 patients with cancer association, 92% had cancer detection within 1 year of myopathy diagnosis (after 1.3 years in the remaining patient), 83% had advanced cancers, and 75% died of cancers within 2.7 years. Of interest, 1 patient with cancer history had sustained increase in creatine kinase level over 12 years from cancer removal to the development of weakness. CONCLUSIONS: Patients with cancer association formed a large group with poor prognosis in our series of patients with anti-HMGCR Ab+ myopathy. The close synchronous occurrence of cancers and myopathies suggested that cancer association is one of the risk factors for developing anti-HMGCR Ab+ myopathy.

Metabolic Profile as a Potential Modifier of Long-Term Radiation Effects on Peripheral Lymphocyte Subsets in Atomic Bomb Survivors.

Immune system impairments reflected by the composition and function of circulating lymphocytes are still observed in atomic bomb survivors, and metabolic abnormalities including altered blood triglyceride and cholesterol levels have also been detected in such survivors. Based on closely related features of immune and metabolic profiles of individuals, we investigated the hypothesis that long-term effects of radiation exposure on lymphocyte subsets might be modified by metabolic profiles in 3,113 atomic bomb survivors who participated in health examinations at the Radiation Effect Research Foundation, Hiroshima and Nagasaki, in 2000-2002. The lymphocyte subsets analyzed involved T-, B- and NK-cell subsets, and their percentages in the lymphocyte fraction were assessed using flow cytometry. Health examinations included metabolic indicators, body mass index, serum levels of total cholesterol, high-density lipoprotein cholesterol, C-reactive protein and hemoglobin A1c, as well as diabetes and fatty liver diagnoses. Standard regression analyses indicated that several metabolic indicators of obesity/related disease, particularly high-density lipoprotein cholesterol levels, were positively associated with type-1 helper T- and B-cell percentages but were inversely associated with naïve CD4 T and NK cells. A regression analysis adjusted for high-density lipoprotein cholesterol revealed a radiation dose relationship with increasing NK-cell percentage. Additionally, an interaction effect was suggested between radiation dose and C-reactive protein on B-cell percentage with a negative coefficient of the interaction term. Collectively, these findings suggest that radiation exposure and subsequent metabolic profile changes, potentially in relationship to obesity-related inflammation, lead to such long-term alterations in lymphocyte subset composition. Because this study is based on cross-sectional and exploratory analyses, the implications regarding radiation exposure, metabolic profiles and circulating lymphocytes warrant future longitudinal and molecular mechanistic studies.

Anti-TIF1-γ antibody and cancer-associated myositis: A clinicohistopathologic study.

OBJECTIVE: We aimed to analyze the clinical and histopathologic features of cancer-associated myositis (CAM) in relation to anti-transcriptional intermediary factor 1 γ antibody (anti-TIF1-γ-Ab), a marker of cancer association. METHODS: We retrospectively studied 349 patients with idiopathic inflammatory myopathies (IIMs), including 284 patients with pretreatment biopsy samples available. For the classification of IIMs, the European Neuromuscular Center criteria were applied. Patients with CAM with (anti-TIF1-γ-Ab[+] CAM) and without anti-TIF1-γ-Ab (anti-TIF1-γ-Ab[-] CAM) were compared with patients with IIM without cancers within and beyond 3 years of myositis diagnosis. RESULTS: Cancer was detected in 75 patients, of whom 36 (48%) were positive for anti-TIF1-γ-Ab. In anti-TIF1-γ-Ab(+) patients with CAM, cancers were detected within 1 year of myositis diagnosis in 35 (97%) and before 1 year of myositis diagnosis in 1. All the anti-TIF1-γ-Ab(+) patients with CAM satisfied the dermatomyositis (DM) criteria, including 2 possible DM sine dermatitis cases, and were characterized histologically by the presence of perifascicular atrophy, vacuolated fibers (VFs), and dense C5b-9 deposits on capillaries (dC5b-9). In contrast, 39 anti-TIF1-γ-Ab(-) patients with CAM were classified into various subgroups, and characterized by a higher frequency of necrotizing autoimmune myopathy (NAM). Notably, all 7 patients with CAM classified into the NAM subgroup were anti-TIF1-γ-Ab(-) and exhibited no dC5b-9 or VFs. CONCLUSIONS: CAM includes clinicohistopathologically heterogeneous disease entities. Among CAM entities, anti-TIF1-γ-Ab(+) CAM has characteristically shown a close temporal association with cancer detection and the histopathologic findings of dC5b-9 and VFs, and CAM with NAM is a subset of anti-TIF1-γ-Ab(-) CAM.

Reduced 123I Ioflupane Binding in Bilateral Diabetic Chorea: Findings With 18F FDG PET, 99mTc ECD SPECT, and 123I MIBG Scintigraphy.

We report a 64-year-old man with diabetic chorea whom we investigated with dopamine transporter SPECT, F FDG PET, Tc ethylcysteinate dimer (ECD) SPECT, and I metaiodobenzylguanidine (MIBG) scintigraphy. Dopamine transporter SPECT revealed reduced I ioflupane binding in the bilateral striatum. F FDG PET showed metabolic dysfunction in the bilateral striatum, as shown in earlier studies. Tc ECD SPECT revealed reduced brain perfusion in the bilateral caudate nucleus and putamen. I MIBG scintigraphy revealed no cardiac sympathetic nerve dysfunction. Our case suggests a possible nigrostriatal presynaptic dopaminergic involvement in diabetic chorea.

Prognostic Significance of Premature Ventricular Contractions without Obvious Heart Diseases Determined by Standard 12-Lead Electrocardiography Considering their Morphology.

BACKGROUND: Although ventricular premature contraction (VPC) commonly arises in subjects with and without heart diseases, the prognosis of VPC has remained controversial and the effect of their morphology on mortality has not been fully determined in subjects without obvious heart diseases. The objective of this study was to assess the morphologic effect of VPC on mortality. METHODS: Japanese atomic bomb survivors (n = 6685) underwent baseline health examinations and standard 12-lead electrocardiogram (ECG) between January 1990 and December 1991. Of these, we extracted data from 5,685 (67.1% women) subjects who had neither heart diseases nor electrocardiographic abnormalities at baseline. Among them, we identified 131 VPC cases using standard 12-lead ECG and classified them into left bundle branch block (LBBB) type (n = 74), right bundle branch block (RBBB) type (n = 21), and undetermined type (n = 36) according to their morphology. These subjects were followed up until December 2008; we compared all-cause, cardiac and coronary heart disease (CHD) mortality rates using multivariate Cox regression analysis between those with and without VPC. RESULTS: No VPCs were associated with all-cause and cardiac mortality, but the LBBB type was significantly associated with CHD mortality (hazard ratio, 2.73; 95% confidence interval, 1.11-6.73) after controlling for age, sex, smoking status, alcohol consumption, and underlying diseases. CONCLUSIONS: Among Japanese atomic bomb survivors without obvious heart diseases, LBBB-type VPC was associated with increased CHD mortality. Larger studies are needed to confirm the effect of morphology as it might help to predict the risk.

Exposure to Atomic Bomb Radiation and Age-Related Macular Degeneration in Later Life: The Hiroshima-Nagasaki Atomic Bomb Survivor Study.

PURPOSE: To investigate the association between radiation exposure from the atomic bombings and the prevalence of age-related macular degeneration (AMD) among older residents of Hiroshima and Nagasaki. METHODS: The Adult Health Study is a cohort study of atomic bomb survivors living in Hiroshima and Nagasaki, comprising 2153 participants who underwent examinations with retinal fundus photographs in 2006-2008. The radiation dose to the eye for the analysis was estimated with the revised dosimetry system (DS02). The retinal photographs were graded according to the Wisconsin Age-Related Maculopathy Grading System modified for nonstereoscopic retinal images. Early and late AMD were defined according to the type of lesion detected in the worse eye of the participants. Person-specific data were analyzed by using a logistic regression model to assess the association between radiation dose and AMD. RESULTS: Among the 1824 subjects with gradable retinal images (84.7% of the overall participants), the estimated eye dose was widely distributed, with a mean of 0.45 Gy and standard deviation of 0.74 Gy. The prevalence of early and late AMD was 10.5% and 0.3%, respectively. There were no significant associations between radiation dose and AMD, with each 1-Gy increase in exposure, adjusted odds ratio was 0.93 (95% confidence interval [CI], 0.75-1.15) for early AMD and 0.79 (95% CI, 0.21-2.94) for late AMD. CONCLUSIONS: No significant associations were found between atomic bomb irradiation early in life and the prevalence of early or late AMD later in life among Japanese atomic bomb survivors.