It is no easy task to identify a causal association between an environmental hazard and a health effect. The task can be aggravated by society's lack of familiarity with the rigorous criteria that must be applied before an appropriate epidemiological study is undertaken. Extensive coverage of claims that particular agents induce unusual health events is often given before the definitive studies can be undertaken.

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The Multicenter AIDS Cohort Study (MACS) includes the following: Baltimore: The Johns Hopkins University School of Hygiene and Public Health: Alfred J. Saah, Principal Investigator; Homayoon Farzadegan, Neil Graham, Joseph Margolick, Justin McArthur. Chicago: Howard Brown Memorial Clinic-Northwestern University Medical School: John P. Phair, Principal Investigator, Joan S. Chmiel, Bruce Cohen, Steven M. Wolinsky. Los Angeles: University of California, Los Angeles-Schools of Public Health and Medicine and the UCLA Jonsson Comprehensive Cancer Center: Roger Detels, Principal Investigator; Barbara R. Visscher, John L. Fahey, Jan Dudley, Janis V. Giorgi, David T. Imagawa, Otoniel Martinez-Maza, Jeremy Taylor. Pittsburgh: University of Pittsburgh Graduate School of Public Health: Charles R. Rinaldo, Jr., Principal Investigator; Lawrence Kingsley, Phalguni Gupta, James Becker, Monto Ho. Data Coordinating Center: The Johns Hopkins School of Hygiene and Public Health: Alvaro Munoz, Principal Investigator; Noya Galai, Donald Hoover, Lisa P. Jacobson, Curtis Meinert, Sol Su, Steve Piantadosi. NIH: National Institute of Allergy and Infectious Diseases: Lewis Schrager, Project Officer, Richard A. Kaslow, Sten Vermund, Mark J. VanRaden; National Cancer Institute: Iris Obrams, Daniela Seminara

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Although such tragedies as the atomic bombings in Hiroshima and Nagasaki in 1945 should never be repeated, these unfortunate experiences have greatly enhanced our knowledge of the health effects due to ionizing radiation.
Studies on the late health effects of ionizing radiation among the atomic bomb survivors have been conducted since 1947 by the Atomic Bomb Casualty Commission (ABCC) and its successor, the Radiation Effects Research Foundation (RERF) which is equally funded by the two governments of Japan and the United States.
The results thus far obtained up to the present can be classified into the following three categories:
(1) The effects for which a clear increase has been found include malignant neoplasms, cataracts, chromosomal aberrations, small head size and mental retardation among the in utero exposed.
(2) A suggestive increase has been found in the several sites of cancers and immunological abnormalities.
(3) No difference has been observed between the exposed and the non-exposed in some types of leukemia, osteosarcoma, accelerated aging, sterility and hereditary effects.

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The chemical composition of SS, MS and US (used smoke originating in MS exhaled in the air) are similar. However, significant quantitative differences exist among these sources. Although nicotine is unique to ETS, it cannot trace a change at interval of a minute. We succeeded in monitoring the trends of ETS in the cabin of an aircraft with a combination of nicotine and SPM. Urinary cotinine and/or the self-reported method according to Jarvis's categories are generally used to estimate exposure to ETS. We maintain with examples that the urinary HOP ratio is also useful for this purpose. Epidemiological studies on ETS unavoidably involve various biases in measurement of ETS, such as the epidemiological step. Meta-analysis and so forth. For example, because the relative risk of ETS for lung cancer should be so far than that of smoking, such a bias may lead a final conclusion astray.

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265, 118 adults aged 40 and above in 6 Prefectures in Japan were followed up for 17 years and age standardized mortality rates from each cause of death were compared by life style variables studied at the time of enrollment. Multifactor-multidisease risk matrix thus constructed revealed that out of 44 causes of death 65.9% and 0% of them showed significantly higher and lower risk respectively in daily cigarette smokers while 2.3% and 34.1% of them showed significantly higher and lower risk respectively in daily consumers of green-yellow vegetables. Possible mechanisms of such associations and effective strategies achieving healthy aging were discussed based on these results.

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National Nutrition Survey has been done every year since 1946. About seven thousand households in 300 randomly selected districts participated this survey. The food intake in each household by weight was recorded on three consecutive days in mid November. In 1989 survey, energy, proteinand fat intake per day per capita were 2, 061 Kcal, 80.2 g, and 42.4, respectively. All nutrient, except calcium exceeded Japanese R.D.A. The proportion of fat in energy was 25.7%. Sodium intake (presented as salt) per day per capita was 12.2 g. It showed regional difference. After the World War II, nutritional condition remarkably improved. Our recent problem is increasingfat intake, positive balance of energy and slow curve of decreasing salt intake. National Nutrition Survey has done its big role of monitoring Japanesenutrition and health condition.

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A specific type of lymphoid malignancy, adult T-cell leukemia/ lymphoma(ATL), which is caused by human T-cell leukemia virus type I (HTLV-I), is highly prevalent and there are also many healthy carriers of HTLV-I in the same areas. Three main routes of HTLV-I transmission are recognized: 1) vertical transmission from mother to child mainly through breast milk, 2) horizontal transmission from man to woman through semen, and, 3) parenteral transmission from carrier donor to non-carrier recipient. The annual incidence rate of ATL among HTLV-I carriers is estimated at 2.0 in males and 0.5 in females, and the cumulative risk for ATL in HTLV-I carriers during a 70-year life span is 2-5%. Possible risk factors for ATL in addition to HTLV-Iinfection were considered, i.e. genetic factors, environmental factors, nutritional condition, thymus involution and so on. ATL in Japan is an important subject for study in the field of cancer epidemiology, and several trial intervention programs for the prevention of ATL, such as controls of vertical transmission from mother to child through breast milk, are now in progress in ATL-endemic areas in Japan.

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The tuberculosis situation in 46 countries in Asia is reported. TB is still prevalent in Asia and more than 5 million or 60% of new TB patients in the world occur in Asia annually. Prevalence of TB is high in rural and urban areas, the young and the aged, female as well as males. Because of high prevalence of TB and delay in case-finding, annual risk of TB infection is still 1.5% or more in almost all countries. The cure rate by standard chemotherapy is often less than 50%, so that the prevalence of initial drug resistance is very high in many countries. As a result, TB is not decreasing to a satisfactory degree in almost all the developing countries of Asia. To improve this situation, WHO Headquarters presented a new TB controlstrategy recently. Priority is given to curing 85% of detected smear positive cases in all the developing countries by the introduction of short-course chemotherapy including rifampicin, and to detecting 65% of existing smear positive cases. The author stresses the importance of improvement and activation of the TB control program in Asian countries for TB control in the world.

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A retrospective cohort study among tuberculosis patients registered in Shanghai TB Registry since 1972 was carried out during 1987-89 for testing the hypothesis on association of lung cancer with pulmonary tuberculosis. A total of 30, 373 cases (male: 19, 709 and female: 10, 664) of pulmonary tuberculosis patients born before 1 January 1957 and resided in Shanghai urban were followed up until 1986. The SMRs for lung cancer were 1.38 and 2.73 in males and females, respectively, both of which were statistically significant. When the risk was adjusted by smoking, the adjusted SMRs for lung cancer were 1.72 (95% CI: 1.11-2.53) in males and 2.79 (95% CI: 1.79-4.14) in females. The elevated risk of lung cancer among tuberculosis patients was irrelevant to smoking. INH treatment and X-ray exposure can not be explained for this higher risk.

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A total of 3, 580 pulmonary TB patients newly registered in Nagoya TB registry in 1979-81 were followed-up until the end of 1983. 489 patients (13.7%) died in the period of observation.
O/E ratio of dying from TB was very high, being 15.1 per 100, 000 for males and 40.0 for females, and also higher O/E ratio of cancer, heart dis- eases, pneumonia/bronchitis were shown for both sexes, the risks ranged 1.7 to 3.2. The risk of liver diseases except cancer was high in females only. Lung cancer death showed high O/E ratio of 3.8 for males and 6.4 for females. Observed higher risk of malignant neoplasms related to bone marrow suggest some immune disorders of the patients. Causative factors were discussed.

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A cohort study is one of the most important methods of investigating epidemiologically the etiological significance of possible risk factors on the occurrence of stroke. The Adult Health Study of the Radiation Effects Research Foundation, which began in 1958 under the aegis of the Atomic Bomb Casualty Commission, is one of a series of epidemiologic studies of the late effects of exposure to ionizing radiation on the atomic bomb survivors in Hiroshima and Nagasaki. This cohort study provides a wealth of information on changes in the incidence over time in cardiovascular diseases, including ischemic heart disease and stroke.
When the study began, the population at risk of a stroke was about 16, 500 individuals who were free of cerebrovascular disease at the time of their first medical examination. During 26 years of follow-up, 865 cases of definite or probable strokes have been ascertained. When the cases were classified into strokes arising from cerebral hemorrhage, on the one hand, and cerebral infarction, on the other, age-adjusted incidence rates revealed a declining trend for both types, but especially for cerebral hemorrhage. The results of a multivariate analysis of risk factors showed that hypertension was the most significant predictor of stroke. It appears, however, that stroke occurrence in Japan varies with life style changes in accordance with the results from a comparative study of Japanese men living in Japan and in Hawaii.

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Incidence and risk factors for cerebral stroke and its changing pattern with time were studied in a prospective population survey which has been conducted in a Japanese rural community, Hisayama. Cerebral infarction was more frequent than intracerebral hemorrhage among Hisayama residents, however, the incidence of intracerebral hemorrhage would actually have been higher in Hisayama residents than in western populations especially in 1960's or 1970's. Incidence of both intracerebral hemorrhage and cerebral infarction decreased in the recent Hisayama population, and among the types of cerebral infarction perforating infarcts most prominently decreased. The reduced prevalence of hypertension and successful management of hypertension were considered to contribute to the reduction in cerebral stroke. It is expected, however, that characteristics or patterns of cerebral stroke would change in the future with increasing prevalence of atherogenic factors among the.Japanese population.

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To test a hypothesis that Japanese traditional dietary habits may be associated positively with risk of stroke and inversely with that of ischemic heart disease, a 13.5-year prospective study was conducted among residents aged 40 years and over in A-I district, Shibata City, Niigata Prefecture, Japan. Their baseline intake of nutrients and foods was assessed in July, 1977, by a food frequency method which was newly developed by the authors.
Even during the follow-up period when Japanese dietary habits were considerably westernized, neither hypercholesterolemia nor obesity was re- lated to development of stroke or ischemic heart disease.
The risk of ischemic heart disease had a tendency to be low among the persons whose vegetable intake was high, and the risk of cerebral hemorrhage tended to be low among those whose intake of animal foods was high, although these relations did not reach statistical significance. This may be due to residual effects from the national privation period to the present day.

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To relate the morbidity trends with changes in risk factors for stroke and coronary heart disease between the 1960's and the 1980's, the data of disease surveillance and population surveys of risk characteristics in a northeast rural community of Japan (1965 census population 7, 030) are combined. Between 1964 and 1987, the incidence of all stroke declined about 70% for both men and women aged 40-69. A decline in the stroke incidence was also observed for men and women aged 70 and over in the 1980's. There was about a 50% decline in the prevalence of stroke patients and the number of “bed-ridden” patients with severe disability among men and women aged 40 and over between the 1970's and the 1980's. The incidence of coronary heart disease did not change significantly and was lower than that for stroke. There was an over 10 mmHg systolic and 4 mmHg diastolic blood pressure decline for men and women aged 40-69, primarily in the second decade. The blood pressure decline may have been in part due to increased use of antihypertensive medication which was observed from the first decade. However, part of the blood pressure decline may be attributed to changes in related behaviors and environmental factors such as decreased salt intake and the improvement of working conditions, since the substantial decline occurred in the second decade. Between the 1960's and the 1980's, daily average salt intake decreased from 20 g to 14 g for men aged 40-59. Animal fat intake doubled from 4.5% to 9.6%. The most of the increase of fat intake was seen in the first decade due to an increased intake of meat, eggs and dairy products. Mean serum cholesterol increased 22 mg/dl to the 1980's mean level of 179 mg/dl in men aged 40-69, and 29 mg/dl to 192 mg/dl in women age 40-69. The increase of serum cholesterol level paralleled the increased intake of animal fat. A cohort of men and women aged 40-69 were followed from 1963-1966 to 1973 (2, 257 persons) to examine risk factors of stroke. According to multivariate regression analyses, blood pressure levels and end organ effects in the electrocardiogram and fundus photographs were significantly associated with the incidence of cerebral hemorrhage and infarction. Serum total cholesterol was inversely associated with cerebral hemorrhage. Reliable estimates of risk factors for coronary heart disease in this population was not obtained because of the small number of cases. Surveillance and risk factor surveys are continuing in order to clarify trends in cardiovascular diseases in the rural Japanese population in the future.

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The Akita pathology study was conducted to examine risk characteristics of stroke and myocardial infarction, and trends of atherosclerosis in brain and coronary arteries. The subjects were 845 men aged 30 and over, examined among autopsied men admitted to a local hospital of northeast Japan between 1966 and 1984. The overall autopsy rate was 88%. Blood pressure and serum cholesterol at admission was compared according to type of stroke. To elucidate risk characteristics of myocardial infarction in Akita, the infarction cases were compared with those in Osaka (the second largest city in Japan). Grades of atherosclerosis for basal cerebral arteries and coronary arteries and grade of arteriosclerosis for intracerebral small arteries were determined blindly by one pathologist using a method of cross-sectional stenosis scoring. As expected, blood pressure levels were higher in all types of stroke than nonstroke. Serum cholesterol was lower in cerebral hemorrhage than in nonstroke, and was higher in infarction in cortical artery regions than in nonstroke. Cerebral hemorrhage showed the lowest proportion of significant stenosis in both basal and intracerebral penetrating arteries. Myocardial infarction in Akita had a higher prevalence of hypertension and a lower prevalence of high serum cholesterol, the higher proportion of scattered type of infarction (mostly subendocardial infarction) compared with myocardial infarction in Osaka. Age-adjusted mean scores for atherosclerosis in the coronary arteries and basal cerebral arteries declined 30% and 42%, respectively, between 1966-1974 and 1975-1984. There was a decline in age-adjusted blood pressure levels at admission: 10 mmHg for systolic and 4 mmHg for diastolic blood pressure, whereas mean serum cholesterol rose 6 mg/dl. There results indicated that hypertension and low serum cholesterol levels were associated with cerebral hemorrhage, and mostly hypertension with myocardial infarction in Akita. The deline in blood pressure levels between the 1960's and 1980's may have contributed to the decreased atherosclerosis in both brain and coronary arteries. The effect of an increase in serum cholesterol for coronary atherosclerosis was overwhelmed by the large decrease in blood pressure levels.

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Breast cancer is the most frequent cancer in Singapore, which showed rapid increase in incidence in the last two decades. A case-control study consisted of 200 histologically confirmed cases and 420 controls was carried out between 1986 and 1988. The results were as follows; in premenopausal women, the increased risk was associated with high red meat intake and high animal protein intake and the decreased risk was associated with high polyunsaturated fatty acid (PUFA) intake, high soya protein and total soya intake, high PUFA: SFA (saturated fatty acids) ratio, and high soya/total protein. The significant factors after multiple regression analyses of dietary effects were predisposing effect of red meat and protective effect of high intake of PUFA, b-carotene and soya/total protein. In postmenopausal women no significant factors were found for any of dietary effects. The findings were mainly confined to younger premenopausal women who have exhibited major changes in their diet.

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A hospital-based case-control analysis was conducted to assess the relationship of life-style to breast cancer in Japan. The study population was selected among the outpatients of a hospital where information on life-style had been routinely collected prior to diagnosis since 1987. The ageadjusted risk to breast cancer significantly decreased with marital status, fullterm pregnancy history, number of fullterm pregnancies, number of breastfed children, and the average length of breastfeeding, while age at first fullterm pregnancy and family history of breast cancer were positively associated with the risk. The adjusted risk, controlling for potential confoundings, significantly decreased in alcohol drinkers. On the other hand, there was a significant dose-response gradient of increasing risk with smoking. No relationship of physical activity to the disease was observed. There were significant decreases in the risk with increasing intake of rice, bean curd, soy bean paste, and green vegetables. However, no evidence of increase in the risk was found with a high fat diet. These findings suggest that further study under the specific hypothesis in a different population should be followed to confirm the different risk factors of breast cancer in Oriental people from those in the Western countries.

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We carried out a case-control study of hepatocellular carcinoma (HCC) including 204 patients with HCC and 410 control subjects in Fukuoka prefecture, where HCC risk is among the highest in Japan. The possible risk factors examined were: a) chronic hepatitis B virus (HBV) infection, b) alcohol consumption and cigarette smoking, c) a past history of blood transfusion and hepatitis C virus (HCV) infection. Chronic HBV infection was strongly associated with the development of HCC (relative risk, RR = 14.6). Heavy drinkers experienced about a two-fold risk increase, yet a relationship between cigarette smoking and HCC was not evident. Blood recipients showed a significantly increased RR of 3.0. Serum antibodies to HCV (antiHCV) were detected by both enzyme-linked immunosorbent assay and recombinant immunoblot assay in 51% of HCCs and 3% of the controls; the RR (and 95% confidence interval) for positive anti-HCV was calculated as 52.3 (23.9-114.3). Among male patients with HCC, the anti-HCV rates were very high in blood recipients (68%), heavy drinkers (62%) and those who had no identifiable risk factors (75%), indicating the possible transmission of HCV via routes other than blood transfusion. We estimated the population attributable risk of HCC at 17% for chronic HBV infection, 13% for heavy drinking, and 49% for HCV infection in Fukuoka. Further investigations are still needed to identify the other infectious routes of HCV besides transfusion.

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Geophysical and socio-medical backgrounds including dietary habits between high risk and low risk areas of gastric cancer in Liaonin Province, China, were compared and analysed. Case-control study on psychobehavioral factors was carried out. The characteristics of high risk area was acid brown soil, drinking water with high nitrates, high rate of illiterates, unfavorable eating behavior and frequent intake of salty foods and foods with mutagens. Psychobehavioral factors may associate with higher incidence of gastric cancer.

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For studying lung cancer risk factor, we carried out a case-control study on female lung cancer in Liaonin Province. The study shows the smoking OR value was 2.42 (1.41-4.11, P < 0.01). There was marked correlation between female lung cancer and age of starting smoking, smoking amount, years of smoking, depth of inhalation and types of smoke (P < 0.01).

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This paper shows examples of the results of research projects of the Research Committee of Epidemiology of Intractable Diseases obtained in the fiscal years from 1988 to 1990.
The frequency and distribution of patients with intractable diseases were estimated from statistics of financially subsidized patients, national patient surveys and nation-wide hospital surveys. Descriptive epidemiology of some examples of the diseases are shown.
Case-control studies for six diseases have been conducted by the Research Committee in three recent years. As an example, results of a casecontrol study of 319 ulcerative colitis cases and controls are shown.
Pathologists and epidemiologists are exploring the possibility of applying autopsy registration data to epidemiological studies. An analysis on Creutzfeldt-Jacob disease is shown.

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The descriptive epidemiology of liver diseases in Yamanashi prefecture is reviewed with special emphasis on time trends. Age-adjusted death rates for liver cancer in males is increasing, but other data of SMR are showing gradual decreases. In the endemic area of schistosomiasis, SMR of liver cancer and cirrhosis in males are both increasing. The relationship between schistosome and liver cancer is also reviewed. The indirect theory seems to be accepted rather than the direct theory. However, further studies are necessary.

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Osteoporosis is a major public health problem in industrialized countries because it is an underlying cause of fractures in postmenopausal women and elderly persons. In this study, we describe the epidemiology of osteoporotic fractures of the hip and vertebrae in Japan. The annual incidence of hip fracture was estimated by a nationwide survey as ranging between 41, 000 and 48, 000 in 1987. The incidence increased with increasing age in both sexes, and the incidence in females was about twice that in males. Regional differences were also found, in that the incidence of hip fracture in females was low in the eastern part of Japan and high in the west. A study of thoracic vertebral fracture incidence by the Radiation Effects Research Foundation (RERF) showed that it increased in all birth cohorts with increasing age in females but did not increase with age in males. The incidence was significantly lower in the younger birth cohorts in both sexes. Based on these descriptive epidemiological data, analytic and interventional studies of osteoporosis are ongoing at RERF to elucidate risk factors and to prevent bone loss and osteoporotic fractures.

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The present paper reviews a comprehensive study of elderly people carried out for 15 years in an urban community, Koganei City, Tokyo. The Koganei Study consisted of three types of study: longitudinal studies, cross-sectional studies, and case studies for the disabled. Each type of study has a particular purpose, and therefore, three types of study should be done complementarily to determine efficacious ways for successful aging.

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This paper described a case-control study on cleft lip and/or palate which aimed to disclose demographic and epidemiologic risk factors. Cases in this study were defined as the infants born with cleft lip and/or palate during the study period from April, 1978 to September, 1981, who visited two specified hospitals and lived in one of five cities. Controls were randomly selected from normal infants who were born in a major hospital in each city during the study period. Controls were matched to cases, with an allocation ratio of 1 : 1, for sex, birth order, residential area, and maternal age at birth to within one year. Routine demographic and numerous epidemiologic information were collected by direct interview of the study subject's mothers at home by one interviewer. Routine statistical analysis by odds ratio with 95% confidence interval was carried out on 194 cases, who comprized 55 cases with cleft lip alone, 87 with cleft lip and palate, and 52 with cleft palate alone, in comparison with 194 matched controls. Major findings are as follows: 1) A significantly elevated risk was associated with parental lower educational attainment, parental occupation of unskilled/ service workers, previous episode of artificial abortion, family history of cleft lip and/or palate, and maternal smoking habits at the first trimester, and maternal episodes at the first trimester of suffering from any diseases (common cold in particular), and of ingesting any drugs (cold remedies in particular). 2) A significantly reduced risk was linked with frequent maternal consumption at the first trimester of such animal proteins as meats, fishes and shells, eggs and milk. 3) Maternal episodes of spontaneous abortion/stillbirth, radiation exposure and frequent maternal consumption at the first trimester of fresh vegetables, fruits, Japanese tea, and black tea were not significantly associated. 4) Frequent maternal consumption of coffee at the first trimester significantly elevated the risk, but turned to be insignificant after statistical adjustment of maternal smoking habits. Causal implications were discussed on these epidemiologic factors which significantly enhanced or reduced the risk.Cleft lip and/or palate, Case-control study, Risk factors, Epidemiology, Japan

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In developing countries, local health authorities do improve health care delivery system based on the results from the studies conducted by the Institutes and Universities. This paper is to introduce an example of such project in East Malaysia. Project to promote child survival has been carrying out for one rural district in Sabah, East Malaysia. The phase I study is collection of baseline data or situational analysis, Phase II is intervention program (health education) and Phase III is evaluation of the intervention program. In Phase I study, five categories of variable for determinants of child survival were socioeconomic determinants, maternal factors, environmental factors, nutritional factors and health service utilization factors. Based on the findings from Phase I study, a number of intervention programs are now being implemented.

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The standardized mortality ratios (SMRs) of lung cancer and tuberculosis in males by area (city, town and village) in Japan during the periods 1969-78 and 1979-88 were calculated and illustrated by mapping of diseases. Changes in the SMRs for these two periods also were charted. Mortality from lung cancer increased in all areas during the two periods, but no remarkable increase in mortality was observed in metropolitan areas and industrialized districts in Japan. However, regional differences in mortality decreased in the latter period. Mortality from tuberculosis, on the other hand, decreased remarkably throughout Japan, but regional differences in mortality became more notable. No common rule was found in the pattern of changes in the SMRs. Correlation between the changing mortality rates for the two diseases - one is increasing and the other is decreasing - is under study.

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