Greetings: 50 years of Atomic Bomb Casualty Commission-Radiation Effects Research Foundation studies.

The Atomic Bomb Casualty Commission was established in Hiroshima in 1947 and in Nagasaki in 1948 under the auspices of the U.S. National Academy of Sciences to initiate a long-term and comprehensive epidemiological and genetic study of the atomic bomb survivors. It was replaced in 1975 by the Radiation Effects Research Foundation which is a nonprofit Japanese foundation binationally managed and supported with equal funding by the governments of Japan and the United States. Thanks to the cooperation of the survivors and the contributions of a multitude of scientists, these studies flourish to this day in what must be the most successful long-term research collaboration between the two countries. Although these studies are necessarily limited to the effects of acute, whole-body, mixed gamma-neutron radiation from the atom bombs, their comprehensiveness and duration make them the most definitive descriptions of the late effects of radiation in humans. For this reason, the entire world relies heavily on these data to set radiation standards. As vital as the study results are, they still represent primarily the effects of radiation on older survivors. Another decade or two should correct this deficiency and allow us to measure definitively the human risk of heritable mutation from radiation. We look to the worldwide radiation and risk community as well as to the survivors who have contributed so much to what has been done already to accomplish this goal.

Epidemiology in Japan and future problems.

A brief history of epidemiology in Japan is presented for the sake of convenience in three stages; the period of birth extending to the early 1940s, the period of growth from 1945 to 1964 and the period of development from 1965. The future problems facing epidemiology are also described. Even in the Meiji period, outstanding epidemiological studies were conducted by Dr. Kanehiro Takaki and Dr. Masakiyo Ogata, but it was only in 1938 that the first epidemiological research laboratory was formally established. Epidemiology at that time was confined to studies on epidemics of infectious diseases, but in the period of growth from 1945 there began to appear epidemiolgoical studies on non-infectious diseases such as adult diseases and diseases caused by environmental pollution. From the period of development commencing in 1965, the sphere of epidemiological studies was further expanded to include intractable diseases, and with the introduction of information science, epidemiology became actively involved in health services research. There are a number of problems facing epidemiology in Japan, including refinement of risk factors, improved measurements of exposure doses, emphasis on individual characterization aimed at health prediction, and development of new health indices.

A long-term cohort study of the atomic-bomb survivors.

The Atomic Bomb Casualty Commission (ABCC), the predecessor of the Radiation Effects Research Foundation (RERF), was established in 1947 to conduct long-term, comprehensive epidemiological and genetic studies of the atomic-bomb (A-bomb) survivors. Today this study still depends upon the voluntary cooperation of several tens of thousands of survivors of the bombings of Hiroshima and Nagasaki. An in-depth follow-up study of mortality in the study population of 120,000 persons, including A-bomb survivors and controls, has continued since 1950. The study of tumor incidence was initiated through record linkage with a tumor registry system in Hiroshima and Nagasaki in 1958. In the same year, biennial medical examinations of 20,000 individuals began. Follow-up studies also have been conducted on in-utero-exposed persons and first-generation offspring of the survivors. On the basis of these studies spanning nearly half a century, we know that the occurrence of leukemia and cancers associated with A-bomb radiation is higher than among the non-exposed. Among the A-bomb survivors, radiation cataracts, hyperparathyroidism, delayed growth and development, and chromosomal aberrations also occur more often. However, to date no evidence exists of genetic effects in the children of A-bomb survivors. It should be kept in mind that such study results could never be obtained without the cooperation of A-bomb survivors.

Profiles of non-cancer diseases in atomic bomb survivors.

This article summarizes the results of a recent study of atomic bomb radiation and non-cancer diseases in the AHS (Adult Health Study) population by the RERF (Radiation Effects Research Foundation) along with a general discussion of previous studies. The association of atomic bomb radiation and CVD was examined by incidence studies and prevalence studies of various endpoints of atherosclerosis, such as MI, stroke, aortic arch calcification, isolated systolic hypertension, and pulse wave velocity, and, although the excess was small, all endpoints indicated an increase of CVD in the heavily exposed group. Because of the consistency of the results, it is almost certain that CVD is higher among atomic bomb survivors. However, all CVD risk factors associated with lifestyle had not necessarily been adjusted for in studies to date, and it is difficult at present to conclude that the increase in CVD among survivors was a direct effect of radiation. Recent studies have demonstrated almost certainly that uterine myoma is more frequent among atomic bomb survivors. It cannot, at present, be concluded that uterine myoma is caused by radiation, because there are no reported studies of other exposed populations. Further analyses including the role of confounding factors as well as molecular approaches are needed to verify this radiation effect. The relationship between atomic bomb radiation exposure and hyperparathyroidism can now be said to have been established in view of the strong dose response, the agreement with results of studies of other populations, the high risk in the younger survivors, and the biological plausibility. Future studies by molecular approaches, etc., are needed to determine the pathogenic mechanism. Among other benign tumours, a dose response has been demonstrated for tumours of the thyroid, stomach and ovary. Although fewer studies have been conducted than for cancer, a clear association between radiation and various benign tumours is emerging. Concerning the association between atomic bomb radiation exposure and chronic liver diseases, the recent incidence study of members of the AHS population demonstrated a significant dose response. Both chronic hepatitis and cirrhosis were suggested as being associated with exposure. The possibility that the increased occurrence of chronic liver diseases among the survivors may be due to hepatitis virus infection cannot be excluded, and the results of the ongoing hepatitis C virus antibody titre studies are awaited.

Mortality study of atomic-bomb survivors: implications for assessment of radiation accidents.

To determine the possible late effects of atomic-bomb radiation, the Life Span Study (LSS) cohort of about 120,000 individuals, including 93,000 atomic bomb survivors and 27,000 non-exposed controls, was established by the Radiation Effects Research Foundation (RERF). Mortality in this cohort has been under study since 1950. Deaths are routinely identified through the family registry system and ascertainment is virtually complete. Cancer incidence data for the LSS cohort are also available from the Hiroshima and Nagasaki population-based tumour registry established in 1958. The central finding of the LSS is an increase in cancer risk. Besides the well-known increase in leukaemia, increases in solid cancer such as cancers of the lung, breast, stomach and thyroid have also been demonstrated. Radiation-induced leukaemia occurred 2 to 3 years after exposure, reached its peak within 6 to 8 years after the bombing, and has since declined steadily. However, this has not been true of solid cancer. Radiation-induced solid cancer begins to appear at later ages than such cancer is normally prone to develop, and continues to increase proportionally with the increase in mortality or incidence in the control group as it ages. Survivors who were exposed in the first or second decade of life have just entered the cancer-prone age and have so far exhibited a high relative risk in association with radiation dose. Whether the elevated risk will continue or will fail with time is not yet clear. It is important to continue long-term follow-up of this cohort to document the changes with time since exposure. Beyond cancer risk, increased risk of non-cancer mortality is also suggested, although it is not conclusive.

Childhood thyroid diseases around Chernobyl evaluated by ultrasound examination and fine needle aspiration cytology.

Screening by ultrasound examination and fine-needle aspiration cytological biopsy (FNA) was conducted in five regions in Belarus, Ukraine, and Russia to investigate the prevalence of childhood thyroid diseases around Chernobyl. Gomel, Zhitomir, Kiev, and the western area of Bryansk are the administrative regions where severe radioactive contamination occurred. The subjects from Mogilev, where contamination was relatively low, served as controls. Among 55,054 subjects (26,406 boys and 28,648 girls), the prevalence of ultrasonographic thyroid abnormalities such as nodule, cyst, and abnormal echogenity was significantly higher in the regions with severe contamination than in Mogilev. Of the 1,396 children showing echographic thyroid abnormalities 197 were selected for FNA, and a sample was successfully obtained for diagnosis from 171 (51 boys and 120 girls) of the 197 subjects. The aspirate was insufficient for diagnosis in the remaining 26 subjects. Thyroid cancer was encountered in four children (2.3%) from the contaminated regions, two children being from Gomel. The other thyroid diseases were follicular neoplasm, 6.4%; adenomatous goiter, 18.7%; chronic thyroiditis, 31.0%; and cyst, 24.0%, suggesting that a major cause of thyroid nodularity is nonneoplastic changes, mainly chronic thyroiditis and cysts. These results will serve as an important data base for further analyses and suggest that childhood thyroid diseases, including both neoplasms and immunological disorders, are consequences of radioactive fallout.

[Health effects of atomic bomb radiation].

The health effects of atomic bomb radiation have been studied by the Atomic Bomb Casualty Commission (ABCC) and its successor, the Radiation Effects Research Foundation (RERF) based on a fixed population of atomic bomb survivors in Hiroshima and Nagasaki which had been established in 1950. The results obtained to the present can be classified into the following three categories: (1) The effects for which a strong association with atomic bomb radiation has been found include malignant neoplasms, cataracts, chromosomal aberrations, small head size and mental retardation among the in utero exposed. (2) A weak association has been found in the several sites of cancers, some non-cancer mortalities and immunological abnormalities. (3) No association has been observed in some types of leukemia, osteosarcoma, accelerated aging, sterility and hereditary effects.

A nationwide incidence survey of Kawasaki disease in 1985-1986 in Japan.

Nationwide epidemiological surveys of Kawasaki disease have been conducted nine times in Japan since 1970. By the end of 1986, 83,857 (male:female ratio, 1.4) cases were reported. We summarize the results of these surveys, especially the latest survey of cases from January 1985 to December 1986. There were three epidemic years - 1979, 1982, and 1986. The ratios of the number of patients diagnosed in each of those years to the number in the preceding year were 2.0, 2.4, and 1.7, respectively. The last epidemic started in a metropolitan area of Tokyo in December 1985 and propagated northwards and southwards to involve almost all of the country in six months. The age-specific incidence curve showed a unimodal peak at nine to 11 months of age. The proportion of sibling cases was approximately 2%. The epidemiological pictures suggested that the disease was caused by an unknown biologic agent that is common in the community and that spreads easily among very young children.

Mapas de mortalidad por diversas enfermedades / Maps that throw light on disease mortality

This article describes an atlas of disease mortality in the cities, towns and villages of Japan, based on data collected over a ten-year period. Copies have been distributed to medical schools, prefectural offices, and medical associations, where they are being used for the education of health workers and lay people, for planning purposes, and in epidemiological and other scientific studies

Nationwide survey on Kawasaki disease in Japan.

Results of the statistical analysis of a nationwide survey of patients with Kawasaki disease diagnosed within a 2-year 6-month period, from July 1982 to December 1984, are as follows. (1) The cumulative number of patients reported by the end of 1984 was 63,399 (36,891 boys and 26,508 girls; male to female ratio 1.4). (2) There were two epidemic years, 1979 and 1982, in which the numbers of patients were more than twofold that of the previous years. (3) A curve plotted for age-specific incidence rate showed a unimodal peak at age 1 year. (4) Steroid therapy was used for 6.3% of the patients, aspirin for 89.8%, antibiotics for 57.6%, and gamma-globulin for 11.4%. (5) The proportion of sibling cases was 1.4% and that of recurrent cases was 3.9% of all cases reported. (6) The incidence of cardiac sequelae in 1 month after disease onset was 17.2%.

Geographical distribution of cerebrovascular disease mortality and food intakes in Japan.

The present study focuses on an analysis of the relationship between cerebrovascular disease mortality and food intake. For this purpose, standardized mortality ratios(SMRs) from cerebrovascular disease were calculated for 3341 basic administrative units (wards, cities, towns and villages) between 1969 and 1978 in Japan. The major nutrient intakes and 30 selected food items were obtained from the 1974-1974 Ministry of Health and Welfare, National Nutrition Surveys in 1040 randomly sampled census tracts in 600 areas (18% of the nation). Our analysis demonstrates that the geographical pattern of cerebrovascular disease SMRs in Japan vary from higher in East Japan to lower in the West, and higher in the less urbanized areas, and lower in the more urban ones. Foods positively associated with cerebrovascular disease were rice and other starchy foods, pork, algae (seaweed), and salty foods such as miso (soybean paste), pickled vegetables, soy sauce and salted fish. All of these foods, with the exception of pork, are part of the traditional Japanese diet. On the contrary, mortality was negatively associated with intakes of wheat, butter and margarine, beef and eggs, items considered to be representative of a European diet. Using a stepwise multiple regression analysis, miso and salted fish were selected as positive, and beef and eggs as negative correlates of cerebrovascular disease mortality. According to these results, it is suggested that these four foods are useful as negative and positive indicators of improvement in dietary intakes as related to the reduction in the occurrence of cerebrovascular disease.

Nationwide epidemic of Kawasaki disease in Japan during winter of 1985-86.

Surveillance data on Kawasaki disease from 148 representative hospitals throughout Japan revealed a third nationwide epidemic of Kawasaki disease in Japan in November, 1985. The peak number of cases was at least 4.5 times greater than that observed in the preceding year. This epidemic wave spread from central Japan to the entire nation within six months.

Indoor infection in a modern building.

Outbreaks of tuberculosis (TB), which are of a type rarely experienced in the past, have recently increased in Japan. An example of such an outbreak, which occurred in a modern building with fixed sash windows, will be described. The occurrence of four TB cases, which had been found during the period between May 1979 and June 1980 among company employees working in the same building in downtown Tokyo, motivated the conduct of epidemiological and environmental surveys on this episode. The first case, a 36-year-old male with a positive smear and cavities in both lungs, was considered to have been in an infectious state for about one year before his admission to a TB hospital in June 1979. Follow-up investigation of 99 contacts until March 1982 revealed the occurrence of 16 secondary cases. The secondary attack rate was highest among those working on the same floor of the building as this first case, but no case was found among employees of another company that occupied this building. The desks of secondary cases were aggregated near and around that of the first case. Although this building had central air-conditioning, ventilation was often closed for energy conservation purposes. This resulted in the increase of carbon dioxide concentration in the air up to a level of more than 1,000 ppm during working hours and to as high as 2,000 ppm when the ventilation was closed. It was thus concluded that the indoor infection of TB in this episode was attributable to the insufficient ventilation in the building.

The epidemiological approach to cadmium pollution in Japan.

The study of health problems due to cadmium pollution in Japan originated from an endemic episode of Itai-itai disease in a rural area in north-central Japan after World War II. The disease was defined as osteomalacia with tubular changes in the kidney and considered to be associated with excess intake of cadmium. This episode motivated the Japanese Government to conduct health examinations on the general population in cadmium-polluted and non-polluted areas throughout the country since 1969. Although Itai-itai disease-like bone changes were rarely found, these studies revealed a higher prevalence of renal tubular dysfunction among elderly people in the cadmium-polluted areas. No significant difference was noted in cancer mortality, but mortality from cardiovascular diseases and all causes tended to be lower in cadmium-polluted areas. Clinical and pathological studies in man as well as experiments on primates have recently been made to elucidate the pathogenesis of Itai-itai disease and the health effects of cadmium. The lack of knowledge on the ecological and biological complex of cadmium resulted in the impediment of studies on this problem. The lesson from this experience is that basic research is essential for promoting the study of pollutants such as heavy metals, though pollution problems usually require urgent solutions.