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[The present state of atomic bomb survivors, with special reference to biological late-effects of radiation].

Atomic bombs were dropped on Hiroshima and Nagasaki in August 1945. Within a few months, the bomb blast, heat and radiation emitted by the atomic explosions led to approximately 114,000 fatalities in Hiroshima and about 70,000 in Nagasaki. The radiation in particular continued to exert effects on the human body over a long period of time, resulting in the development of tumors and functional abnormalities in various organs. This paper briefly outlines the diseases caused by radiation as well as the biological late-effects on the survivors without any specific diseases, and stresses the necessity of our enthusiastic opposition to the use of any kind of nuclear weapons.

Antibodies, Viral↗

Studies of the mortality of A-bomb survivors. 9. Mortality, 1950-1985: Part 3. Noncancer mortality based on the revised doses (DS86).

Deaths in the RERF Life Span Study (LSS) sample have been determined for the years 1950-1985 and an analysis of cancer mortality with the revised DS86 doses has been described separately. In this report, we examine the relationship to dose of deaths from all diseases other than cancer. Although the evidence is still limited, there seems to be an excess risk from noncancer death at high doses (2 or 3 Gy and over). Statistically, a pure quadratic or a linear-threshold model [the estimated threshold dose is 1.4 Gy (0.6-2.8 Gy)] is found to fit better than a simple linear or linear-quadratic model. This increase in noncancer mortality is statistically demonstrable, generally, after 1965 and among the younger survivors (less than 40 at the time of the bombing), suggesting a sensitivity for this age group. For specific causes of death, an excess in relative risk at the high dose level, that is, 2 Gy or more, is seen in circulatory and digestive diseases. The relative risk is, however, much smaller than that for cancer. These findings, based as they are on death certificates, have their limitations. Most significant, perhaps, is the possible erroneous attribution of radiation-related cancer deaths to other causes. At present, the contribution such errors may make to the apparent increase in non-cancer deaths at the higher doses cannot be estimated as rigorously as is obviously desirable. However, even now, this increase does not appear to be fully explicable in terms of errors in classification. Further follow-up of mortality in this LSS cohort as well as disease revealed by the biennial physical examinations of the morbidity subsample (Adult Health Study) of the LSS cohort will be needed to confirm this suggestion of a radiation-related increase in mortality from causes other than cancer, and to determine whether it results in a demonstrable life shortening among the heavily exposed A-bomb survivors.

Age Factors↗

Lessons in posttraumatic stress disorder from the past: Venezuela floods and Nairobi bombing.

Identification and treatment of posttraumatic stress disorder (PTSD) are important following a disaster. Insights into how these aims can be achieved may be obtained from previous disasters. This article describes mental health initiatives following the 1999 flooding in Vargas State, Venezuela, and the 1998 U.S. Embassy bombing in Nairobi, Kenya. Following the Vargas State floods, a specialist mental health center devoted to the diagnosis, treatment, and follow-up of PTSD was established. Awareness and acceptance of the clinic was promoted by media campaigns and community-based activities. After 18 months, approximately 5000 people had been screened, of whom 62% were diagnosed with PTSD and treated. Moreover, the clinic's activities had expanded to include treatment of other medical conditions and assistance with nonmedical needs. Following the Nairobi bombing, a mass media campaign was initiated to create awareness of PTSD symptoms and help victims come to terms with their experience. This campaign was found to be well received and helpful. In addition, counselors were trained to support people living or working close to the blast. These examples show that mental health initiatives are feasible after a disaster and highlight a number of issues: (1) The intervention should be tailored to the needs of the target population; (2) Communication should be simple and appropriate; (3) Community-based activities are valuable in promoting awareness and acceptance of mental health initiatives; (4) Reducing the stigma often associated with mental health problems is important; and (5) The mass media can be helpful in promoting awareness of mental health issues following major trauma.

Community Mental Health Centers↗

[A peculiar speech disorder due to bomb injury of the brain].

Oslo was bombed by British bombers 6 September 1941, and a 28-year-old woman was hit on the head by a bomb fragment. She was seriously wounded with a large defect in the cranium frontally on the left side, and it was believed that she was not going to survive. She was unconscious for 3-4 days, and when she woke up she had right-sided hemiplegia and complete aphasia. She gradually recovered, and two months later she was discharged from hospital. Remarkably, the brain damage had altered her melody of language, and she spoke with a German-like accent. This led to problems for her during the war: she was for example not served in shops. The case story was published after the war by the Norwegian neurologist Georg Herman Monrad-Krohn (1884-1964), and it is the best known case of the so-called foreign accent syndrome. In this paper, this rare syndrome is presented, emphasising Monrad-Krohn's patient and based on his writings and the patient's medical record.

Adult↗

Malignant tumors during the first 2 decades of life in the offspring of atomic bomb survivors.

The risk of cancer (incidence) prior to age 20 years has been determined for children born to atomic bomb survivors and to a suitable comparison group. Tumor ascertainment was through death certificates and the tumor registries maintained in Hiroshima and Nagasaki. The rationale for the study stemmed from the evidence that a significant proportion of such childhood tumors as retinoblastoma and Wilms tumor arise on the basis of a mutant gene inherited from one parent plus a second somatic cell mutation involving the allele of this gene. Gonadal radiation doses were calculated by the recently established DS86 system, supplemented by an ad hoc system for those children for one or both of whose parents a DS86 dose could not be computed but for whom an ad hoc dose could be developed on the basis of the available information. The total data set consisted of (1) a cohort of 31,150 live-born children one or both of whose parents received greater than 0.01 Sv of radiation at the time of the atomic bombings (average conjoint gonad exposure 0.43 Sv) and (2) two suitable comparison groups totaling 41,066 children. Altogether, 43 malignant tumors were ascertained in the children of exposed parents, and 49 malignant tumors were ascertained in the two control groups. A multiple linear regression analysis revealed no increase in malignancy in the children of exposed parents. However, examination of the data suggested that only 3.0-5.0% of the tumors of childhood that were observed in the comparison groups are associated with an inherited genetic predisposition that would be expected to exhibit an altered frequency if the parental mutation rate were increased. There is thus far no confirmation of the positive findings that Nomura found in a mouse system.

Adolescent↗

Chromosome aberrations in B lymphocytes of atomic bomb survivors.

Although chromosome aberrations in T lymphocytes and bone marrow cells have been reported in atomic bomb survivors, the presence of chromosome abnormalities has not been demonstrated in B lymphocytes because of the technical difficulties involved in B-lymphocyte separation. A method for detecting chromosome aberrations in B lymphocytes was established by "stimulation" of B lymphocytes with Epstein-Barr virus (EBV) instead of "separation" of B lymphocytes by rosette formation. The EBV-stimulated lymphocytes were isolated as single colonies in soft agar and transferred to liquid culture for further cell growth. The EBV-stimulated B lymphocytes of two heavily exposed survivors showed 50% and 12.5% chromosome abnormalities 30 yr after exposure to the effects of the atomic bomb. The former patient seemed to have a karyotypically abnormal clone of B lymphocytes in vivo. The method used in this study and the evidence of chromosome aberrations in B lymphocytes for long periods after radiation exposure will be useful and important in elucidating the malignant processes of acute lymphocytic leukemia, B-cell lymphoma, and multiple myeloma among high-risk groups having a history of accidental or therapeutic exposure to radiation or radiomimetic drugs.

Adolescent↗

Radiation-related posterior lenticular opacities in Hiroshima and Nagasaki atomic bomb survivors based on the DS86 dosimetry system.

This paper investigates the quantitative relationship of ionizing radiation to the occurrence of posterior lenticular opacities among the survivors of the atomic bombings of Hiroshima and Nagasaki suggested by the DS86 dosimetry system. DS86 doses are available for 1983 (93.4%) of the 2124 atomic bomb survivors analyzed in 1982. The DS86 kerma neutron component for Hiroshima survivors is much smaller than its comparable T65DR component, but still 4.2-fold higher (0.38 Gy at 6 Gy) than that in Nagasaki (0.09 Gy at 6 Gy). Thus, if the eye is especially sensitive to neutrons, there may yet be some useful information on their effects, particularly in Hiroshima. The dose-response relationship has been evaluated as a function of the separately estimated gamma-ray and neutron doses. Among several different dose-response models without and with two thresholds, we have selected as the best model the one with the smallest x2 or the largest log likelihood value associated with the goodness of fit. The best fit is a linear gamma-linear neutron relationship which assumes different thresholds for the two types of radiation. Both gamma and neutron regression coefficients for the best fitting model are positive and highly significant for the estimated DS86 eye organ dose.

Cataract↗

[Trends in the incidence of uterine cancer in Nagasaki city, with special reference to previous atomic bomb exposure, 1973-1982].

An epidemiological study has been conducted to elucidate the trend in the incidence of uterine cancer, a with a reference also to previous A-bomb exposure. Studied were 783 cases (345 exposed and 438 nonexposed) of uterine cancer that were handled from 1973 to 1982. The incidence rate of cervical cancer was significantly higher among the population who came into Nagasaki city within two weeks after exposure. A comparison between the incidence rate of '73-'77 and '78-'82 revealed a decreasing trend of cervical cancer and an increasing trend of corpus cancer. The increasing rate of corpus cancer was higher in the younger group of a-bomb survivors (less than 59 years old) than in the other survivors.

Adult↗

Radiosensitivity of skin fibroblasts from atomic bomb survivors with and without breast cancer.

Fibroblasts were established in vitro from skin biopsies obtained from 55 women and 1 man with or without breast cancer and with or without exposure to radiation from the atomic bomb explosion in Hiroshima. The radiosensitivity of these cells was evaluated by clonogenic assays after exposure to X-rays or to fission neutrons from a 252Cf source. Data were fitted to a multitarget model, S/S0 = A [1 - (1 - ekD)N], for both X-ray and neutron dose-survival curves. A single hit model, S/S0 = AekD, fits the neutron dose-survival responses as well. There were no differences in the means or variances of radiosensitivity between exposed and nonexposed groups or between patients with or without breast cancer. Hence, although the sample is not large, it provides no support for the hypothesis that atomic bomb radiation preferentially induces breast cancer in women whose cells in vitro are sensitive to cell killing by radiation.

Adolescent↗

Cancer risk among atomic bomb survivors. The RERF Life Span Study. Radiation Effects Research Foundation.

This article summarizes the risk of cancer among the survivors of the atomic bombing of Hiroshima and Nagasaki. We focus primarily on the risk of death from cancer among individuals in the Life Span Study sample of the Radiation Effects Research Foundation from 1950 through 1985 based on recently revised dosimetry procedures. We report the risk of cancer other than leukemia among the atomic bomb survivors. We note that the number of excess deaths of radiation-induced malignant tumors other than leukemia increases with age. 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 fall with time is not yet clear, although some evidence suggests that the risk may be declining. It is important to continue long-term follow-up of this cohort to document the changes with time since exposure and to provide direct rather than projected risks over the lifetime of an exposed individual.

Acute Disease↗

Immunological responses of aging Japanese A-bomb survivors.

Immune response parameters were studied on 1341 A-bomb survivors residing in Hiroshima, Japan. Mononuclear cells were isolated from venous blood and tested for interleukin-2 production; lymphocytes were purified and tested for natural killer (NK) cell activity and interferon (IFN) production; and serum was tested for IFN and circulating immune complex (CIC) levels. Statistical analyses were performed for each type of assay using a linear models procedure including sex, age at the time of the bomb, radiation exposure, all the interaction variables, and the categorical variable day-of-assay in the model. The findings showed that (1) none of the immunologic variables were significantly affected by radiation exposure; (2) NK activity and CIC levels were positively associated with age; and (3) NK activity was on average higher for males than females. The data exemplify the difficulty in reaching firm conclusions concerning associations with radiation exposure when the dependent variable exhibits a large degree of interindividual and day-of-assay variability.

Aging↗

Age and dose related alteration of in vitro mixed lymphocyte culture response of blood lymphocytes from A-bomb survivors.

The responsiveness of peripheral blood lymphocytes to allogenic antigens in mixed lymphocyte culture (MLC) was measured in 139 atomic-bomb survivors. The study revealed a significant decrease in MLC response with increasing dose of previous radiation exposure. This decline was marked in the survivors who were older than 15 at the time of the bomb (ATB). The results suggest a possible relationship between the recovery of T-cell-related function and the thymic function which processes mature T cells for the immune system. Thus it may be that in the advanced age ATB group, the thymus function had started to involute, allowing less recovery of T-cell function compared to young survivors who had adequate processing T-cell activity.

Aged↗

Risk of cancer among children exposed to atomic bomb radiation in utero: a review.

We have examined the risk for cancer (incidence) over a period of 40 years, 1945-1984, among 1829 persons exposed in utero to the atomic bombing of Hiroshima and Nagasaki. This report adds eight years of follow-up to a previous report which was confined to mortality. Only two cases of childhood cancer were observed among these survivors in the first 14 years of life; both had been heavily exposed. Subsequent cancers have all been of the adult type. Not only did these latter cancers occur earlier in persons exposed to greater than 0.30 Gy than in unexposed (0 Gy) but the incidence continues to increase, and the crude cumulative incidence rate 40 years after the bombing is 3.9-fold greater in persons exposed to greater than 0.30 Gy. In the observation period 1950-1984, the relative risk for cancer at 1 Gy, based on the absorbed dose to the mother's uterus as estimated by the Dosimetry System 1986 (DS86), is 3.77 with a 95% confidence interval of 1.14-13.48. For all persons exposed to greater than 0.01 Gy, the average excess risk per 10(4) person-year-Gy is 6.57 (0.07-14.49), and the estimated attributable risk is 40.9% (2.9-90.2%). These results, when viewed in the perspective of fetal doses, suggest that susceptibility to radiation-induced cancers is higher in survivors exposed prenatally than in those exposed postnatally (at least, those exposed as adults). However, definitive conclusions must await further follow-up studies.

Female↗

[A review of colorectal cancer in atomic bomb survivors--treated cases at Nagasaki Genbaku Hospital from 1971-1984].

Clinical and pathological characteristics of patients with colorectal cancer amongst atomic bomb survivors, who had undergone operations from 1971-1984, have been reviewed and compared with that of a control group. The survival rate of the atomic bomb survivors over the age of 60 years was statistically better than that of the same age group in the controls. In this age bracket, the control group were in a more advanced stage of the disease than were the survivors, this accounting for the reason why the survivors had a better prognosis. Further, the fact that the survivors continually have received more medical attention than have the aged in the control group affects this statistic.

Adenocarcinoma↗

Studies of the mortality of A-bomb survivors. 9. Mortality, 1950-1985: Part 1. Comparison of risk coefficients for site-specific cancer mortality based on the DS86 and T65DR shielded kerma and organ doses.

As a result of the reassessment of the A-bomb dosimetry, new (DS86) doses were calculated in 1986. In this paper, site-specific estimates of cancer mortality in the years 1950-1985, based on these new doses, are compared with those using the T65DR doses. The subjects of the study are 75,991 members of the Life Span Study sample for whom DS86 doses have been calculated. This reevaluation of the exposures does not change the list of radiation-related cancers. Most differences in dose response between Hiroshima and Nagasaki are no longer significant with the DS86 doses. The dose-response curve is closer to linear with the DS86 than the T65DR doses even for leukemia in the entire dose range, though, statistically, many other models cannot be excluded. However, in the low-dose range, the risk of leukemia remains nonlinear. Assuming a linear model at an RBE of 1, and using organ-absorbed doses, the risk coefficients derived from the two dosimetries are very similar, whereas those based on shielded kerma are about 40% higher with the new dosimetry. If RBE values larger than 1 are assumed, the disparity between the two dosimetries increases because the neutron dose is much greater in the T65DR. At an RBE of 10, for the five specific cancers, i.e., female breast, colon, leukemia, lung, and stomach, the increase in excess number of deaths per 10(4) PYSv under the DS86 varies from 12% (colon) to 133% (female breast). The magnitude of the effects of such modifiers of radiation-induced cancer as age at time of bomb and sex do not differ between the two dose systems.

Female↗

Malignant breast tumors among atomic bomb survivors, Hiroshima and Nagasaki, 1950-74.

For 1950-74, 360 cases of malignant breast tumors were identified among the 63,000 females of the Radiation Effects Research Foundation's (Hiroshima and Nagasaki) Extended Life-Span Study sample of survivors of the 1945 atomic bombings of Hiroshima and Nagasaki; 288 of these females were residing in one of these two cities at the time of bombing (ATB). Two-thirds of all cases were classified as breast cancers on the basis of microscopic review of slides, and 108 cases received an estimated breast tissue dose of at least 10 rads. The number of cases of radiogenic breast cancer could be well estimated by a linear function of radiation dose for tissue doses below 200 rads. Excess risk estimates, based on this function, for women 10-19, 20-29, 30-39, and 50 years old or older ATB were 7.3, 4.2, 2.6, and 4.7 cases per million women per year per rad, respectively. Women irradiated in their forties showed no dose effect. Among all women who received at least 10 rads, those irradiated before age 20 years will have experienced the highest rates of breast cancer throughout their lifetimes. Separate excess risk estimates for Hiroshima and Nagasaki did not differ significantly, which indicates that for radiogenic breast cancer the effects of neutrons (emitted only in the Hiroshima explosion) and gamma radiation were about equal. Radiation did not reduce the latency period for the development of breast cancer, which was at least 10 years. The distribution of histologic types of cancers did not vary significantly with radiation dose. The data suggested that irradiation prior to menarche conferred a greater risk than irradiation after menarche.

Adolescent↗

Detection of somatic mutations at the glycophorin A locus in erythrocytes of atomic bomb survivors using a single beam flow sorter.

A modified method was developed for measuring the frequency of variant erythrocytes at the glycophorin A locus using a single beam cell sorter (SBS). Fluorescein- or phycoerythrin-labeled monoclonal antibodies specific for the M or N glycophorin A alleles were used for the SBS assay. To prevent contamination of nucleated cells in the sorting windows, the nucleated cells in the fixed erythrocyte sample were stained with propidium iodide before flow sorting. Blood samples were obtained from atomic bomb survivors who were heterozygous for the MN blood type, and the frequencies of the hemizygous and homozygous variant of the M or N glycophorin A allele were measured by the SBS. For the three types of variants, hemizygotes for M and N allele (Nø and Mø) and homozygotes for M allele (MM), the variant frequency measured by the SBS correlated well with that previously determined by a dual beam cell sorter. Variant frequencies of the Nø, Mø, and MM cell types in atomic bomb survivors determined by SBS measurements were found to increase with radiation dose (DS86, kerma) as well as with the frequency of chromosome aberrations in lymphocytes.

Alleles↗

Thermoluminescence dosimetry of gamma rays from the atomic bomb at Hiroshima using the predose technique.

Thermoluminescence dosimetry measurements of gamma rays produced by the atomic bomb in Hiroshima were made by the predose technique using eight ceramic samples collected from five buildings located at distances between 1271 and 2051 m from the hypocenter. The results of our measurements are compared to both the newer dose estimates (Dosimetry System 1986) and older dose estimates (Tentative 1965 Doses) for survivors of the Hiroshima atomic bomb. In comparison with the older estimates, our results are larger by a factor of 2.3 at 1271 m and 3.9 at 2051 m. Our results and the newer estimates for Hiroshima differ by a factor of only 1.14 +/- 0.16 on the average.

Ceramics↗