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PubMed1985

Selection, follow-up, and analysis in the Atomic Bomb Casualty Commission Study.

More is known about ionizing radiation as a cause of human cancer than about any other carcinogen. Most of this knowledge is derived from the studies conducted by the Atomic Bomb Casualty Commission and Radiation Effects Research Foundation on about 100,000 Japanese survivors of the atomic bombing in 1945. The importance of these studies is based on the large size of the exposed population and the fact that individual estimates of radiation dose were possible. These factors and the combined excellence of the centralized vital statistics reporting and population registration systems in Japan have made feasible the continuing longitudinal studies of cancer mortality by site in relation to radiation dose over a span of more than 30 years. Excellent voluntary cooperation by the survivors has enabled the continuation of a biennial physical examination program which has made possible the acquisition of blood for studies of radiation-induced chromosomal aberrations and mutations at the level of specific genes. Similarly, with the cooperation of local universities, hospitals, and physicians, tumor and tissue registries necessary for the study of cancer incidence have been developed. An autopsy pathology program has enabled study of the accuracy of cause of death certification.

Aged↗
PubMed1983

Immune function in aging atomic bomb survivors residing in the United States.

Immunologic parameters were studied among survivors of the 1945 atomic bombs who now reside in the United States. Of all known survivors living in the U.S., about 40% (n = 189) participated in this study. Of those survivors on whom radiation exposure information was available (n = 168), 96% were exposed to less than 50 rad at the time of the bomb (ATB). Survivors were divided into two groups; those exposed to varying low doses of radiation (S+ group, exposed at less than or equal to 2500 m from the hypocenter) were compared with those exposed to "O rad" (S0 group, exposed at greater than 2500 m from the hypocenter). Of the former group, 92% were exposed to less than 100 rad and 89% to less than 50 rad ATB. Cellular immune responses, including natural cell-mediated cytotoxicity (NCMC), interferon production, and the mitogenic response to PHA, tended to be higher among S+ individuals, although only the difference for NCMC was statistically significant. This was suggestive of a trend which was consistent with the higher serum interferon levels and lower frequencies of detectable immune complexes and antimitochondrial antibodies among the S+ group, although these differences were not statistically significant. Other immunologic parameters which showed no trend included frequency of antinuclear antibodies, rheumatoid factor, levels of serum immunoglobulins, levels of isoantibodies and heteroantibodies, and the magnitude of the mixed lymphocyte reaction.

Adolescent↗
PubMed1984

An analysis of various aspects of atomic bomb dose estimation at RERF using data on acute radiation symptoms.

The dose-response curves for acute radiation symptoms reported by atomic bomb survivors are compared by dose estimation method (the method used to calculate the transmission factor), shielding category, and city. Circular symmetry is also investigated. It is found that response rates for acute symptoms differ considerably by dose estimation method and shielding category even after controlling for both gamma and neutron exposure as well as for city, sex, and age at the time of the bomb. One explanation of these results is that the doses of survivors in Japanese type houses estimated by the nine parameter method are subject to less random measurement error, while doses of those survivors who were in the open and shielded by terrain, who were totally shielded by concrete buildings, and who were in factories are subject to especially large random errors. The degree to which systematic bias contributes to these differences could not be determined. These results have important implications for comparisons between cities since Nagasaki includes a far greater proportion of survivors in shielding categories showing weak dose-response relationships than does Hiroshima. The hypothesis that doses might be higher in the westerly direction in Hiroshima is not supported by acute effects analyses, but excess acute effects are found in the north of Hiroshima.

Alopecia↗
PubMed1983

Acute lymphoblastic leukemia with monosomy 7 in a Hiroshima survivor 37 years after the bomb.

Acute lymphoblastic leukemia (ALL) developed in a 53-year-old survivor of the Hiroshima bomb blast. Chromosomal analysis disclosed a single abnormality, deletion of chromosome 7. This deletion has been reported in patients with radiation exposure, but it is uncommon in adults with ALL. The karyotypic abnormality suggests that our patient's leukemia may be related to prior radiation exposure despite a 37-year hiatus. The findings raise further questions about the persistent risk of leukemia among atomic bomb survivors.

Aneuploidy↗
PubMed1994

Evidence of radiation-induced reduction of height and body weight from repeated measurements of adults exposed in childhood to the atomic bombs.

Reduction of growth from exposure to atomic bomb radiation has been examined using individuals under 10 years old at the time of the bombing (ATB) and a growth curve analysis based on measurements of height and weight made in the course of the 4th-7th cycles of the Adult Health Study examinations (1964-1972). As expected, the largest difference in growth to emerge is between males and females. However, a highly significant reduction of growth associated with dose (DS86) was observed among those survivors for whom four repeated measurements of height and weight were available. Longitudinal analysis of a more extended data set (n = 821), using expected values based on simple linear regression models fitted to the three available sets of measurements of height and weight on the 254 individuals with a missing measurement, also indicates a significant radiation-related growth reduction. The possible contribution of such factors as poor nutrition and disruption of normal family life in the years immediately after the war is difficult to evaluate, but the effects of socioeconomic factors on the analysis of these data are discussed.

Adult↗
PubMed1994

Thyroid diseases among atomic bomb survivors in Nagasaki.

OBJECTIVE: To elucidate the current thyroid disease status for the Nagasaki Adult Health Study cohort of the Radiation Effects Research Foundation. DESIGN: Survey study. SETTING: Nagasaki, Japan. PARTICIPANTS: Cohort members of the Nagasaki Adult Health Study who received biennial health examinations from October 1984 to April 1987 (n = 2856). A total of 2587 subjects remained after exclusion of persons exposed in Hiroshima or in utero and those who were not in Nagasaki at the time of the bombing. Thyroid radiation dose by the dosimetry system established in 1986 was available for 1978 of the 2587 subjects. MAIN OUTCOME MEASURES: Thyroid diseases were diagnosed using uniform procedures including ultrasonic scanning. The relationship of the prevalence of each thyroid disease with thyroid radiation dose, sex, and age was analyzed using logistic models. RESULTS: A significant dose-response relationship was observed for solid nodules, which include cancer, adenoma, adenomatous goiter, and nodules without histological diagnosis, and for antibody-positive spontaneous hypothyroidism (autoimmune hypothyroidism) but not for other diseases. The prevalence of solid nodules showed a monotonic dose-response relationship, yet that of autoimmune hypothyroidism displayed a concave dose-response relationship reaching a maximum (+/- SE) level of 0.7 +/- 0.2 Sv. CONCLUSIONS: The present study confirmed the results of previous studies by showing a significant increase in solid nodules with dose to the thyroid and demonstrated for the first time a significant increase in autoimmune disease among atomic bomb survivors. A concave dose-response relationship indicates the necessity for further studies on the effects of relatively low doses of radiation on thyroid disease.

Cohort Studies↗
PubMed1994

Immune responses to Epstein-Barr virus in atomic bomb survivors: study of precursor frequency of cytotoxic lymphocytes and titer levels of anti-Epstein-Barr virus-related antibodies.

Precursor frequencies of cytotoxic lymphocytes to autologous Epstein-Barr virus-transformed B cells and serum titers of anti-Epstein-Barr virus-related antibodies were measured in 68 atomic bomb survivors to clarify the immune mechanism controlling Epstein-Barr virus infection. The precursor frequency was negatively correlated with the titer of anti-early antigen IgG, which is probably produced at the stage of viral reactivation. A positive correlation between the precursor frequency and titer of anti-Epstein-Barr virus-associated nuclear antigen antibody was also observed, indicating that the precursor frequency reflects the degree of in vivo destruction by T cells of the virus-infected cells. These results suggest that T-cell memory specific to Epstein-Barr virus keeps the virus under control and that the precursor frequency assay is useful for the evaluation of immune responses to Epstein-Barr virus. However, no significant effect of atomic bomb radiation on the precursor frequency was observed in the present study, probably due to the limited number of participants.

B-Lymphocytes↗
PubMed1994

Ultrasonographic abdominal screening of atomic bomb-exposed subjects.

Abdominal ultrasonographic screening for cancer was performed in 6,001 Hiroshima and Nagasaki A-bomb exposed and comparison subjects, all members of the Adult Health Study of the Radiation Effects Research Foundation, formerly the Atomic Bomb Casualty Commission. This study yielded 20 cancers, including 7 hepatocellular, 3 gastric, 3 renal and 2 urinary bladder cancers; one cancer each of the ovary, pancreas, colon and ureter; and one cancer metastatic to the liver, whose primary was unknown. Seventeen of these 20 subjects manifested no symptoms or signs of their disease. A variety of additional tumors, unproven and probably benign, including uterine myomata, and other abnormalities were also detected. Abdominal ultrasonographic screening greatly assisted in the detection of cancers, most of which neither the patients nor their physicians were aware. In this screened fixed population sample the cancer detection rate was 0.33%, exceeding any such rates previously reported in the medical literature.

Abdominal Neoplasms↗
PubMed1994

Incidence of female breast cancer among atomic bomb survivors, 1950-1985.

An incidence survey among atomic bomb survivors identified 807 breast cancer cases, and 20 second breast cancers. As in earlier surveys of the Life Span Study population, a strongly linear radiation dose response was found, with the highest dose-specific excess relative risk (ERR) among survivors under 20 years old at the time of the bombings. Sixty-eight of the cases were under 10 years old at exposure, strengthening earlier reports of a marked excess risk associated with exposure during infancy and childhood. A much lower, but marginally significant, dose response was seen among women exposed at 40 years and older. It was not possible, however, to discriminate statistically between age at exposure and age at observation for risk as the more important determinant of ERR per unit dose. A 13-fold ERR at 1 Sv was found for breast cancer occurring before age 35, compared to a 2-fold excess after age 35, among survivors exposed before age 20. This a posteriori finding, based on 27 exposed, known-dose, early-onset cases, suggests the possible existence of a susceptible genetic subgroup. Further studies, involving family histories of cancer and investigations at the molecular level, are suggested to determine whether such a subgroup exists.

Adult↗
PubMed1993

Analysis of somatic cell mutations at the glycophorin A locus in atomic bomb survivors: a comparative study of assay methods.

The glycophorin A (GPA) assay for in vivo somatic cell mutations was performed on blood samples from 39 survivors of the atomic bomb at Hiroshima. Parallel analyses were performed at two laboratories using three different GPA assay methods to enumerate cells lacking expression of either the M- or N-allele of GPA. All assay methods yielded significant dose-dependent increases in hemizygous GPA variant cell frequencies (VFs) and smaller increases in homozygous VFs. The slopes of the fitted linear dose-response functions did not differ significantly among assay methods used in the present study, or from slopes obtained in a study reported previously. The version of the assay described most recently (BR6) appears best suited for future studies because the assay has a higher precision than earlier methods. Variant frequencies from different assay methods measuring the same variant cell type agreed with each other better than with the estimated dose, suggesting that the imprecision in the assay is not primarily responsible for VFs that differ from the fitted dose response. Consistent deviations from the dose response were seen for some individuals, suggesting either errors in dose estimates for these individuals or interindividual differences in susceptibility or other exposures. For the study population as a whole, however, discrepancies between assays for M-loss and N-loss variants suggest stochastic factors may have an important effect on individual VFs for A-bomb survivors.

Chromosome Mapping↗
PubMed1994

Autoantibodies and immunoglobulins among atomic bomb survivors.

The purpose of this study was to determine if exposure to atomic bomb radiation affects immune responsiveness, such as the occurrence of autoantibodies and levels of immunoglobulins. Rheumatoid factor, antinuclear antibody, antithyroglobulin antibody, anti-thyroid-microsomal antibody and immunoglobulin levels (IgG, IgM, IgA and IgE) were measured among 2,061 individuals exposed to atomic bomb radiation in Hiroshima and Nagasaki whose estimated doses ranged from 0 to 5.6 Gy. The prevalence and titers of rheumatoid factor were found to be increased in the individuals exposed to higher radiation doses. The IgA level in females and the IgM level in both sexes increased as radiation dose increased, although the effects of radiation exposure were not large. No effect of radiation was found on the prevalence of antinuclear antibody, antithyroglobulin antibody and anti-thyroid-microsomal antibody or on the levels of IgG and IgE.

Adult↗
PubMed1994

Levels of parathyroid hormone and calcitonin in serum among atomic bomb survivors.

To examine the potential causes of increased levels of calcium in serum with increasing dose of atomic bomb radiation, which was obtained from the previous preliminary analysis, levels of parathyroid hormone (PTH) and calcitonin in serum were examined among 1459 subjects in Hiroshima and Nagasaki. A significant effect of radiation on levels of calcium, PTH and calcitonin in serum was found, even after patients with hyperparathyroidism were excluded. The level of calcium in serum increased with radiation dose; this can be explained partly by the increase in the level of PTH with radiation dose. However, the dose effect on calcium remained even after adjustment for PTH, calcitonin and confounding factors such as renal function, serum albumin level and medication. Parathyroid hormone increased initially by 6.8% per gray, but the dose response leveled off after about 1 Gy. The level of calcitonin increased with radiation dose, probably in part due to feedback mechanisms stimulated by the increase in calcium. However, after adjustment for the level of calcium, the increase in the level of calcitonin with dose was still found. Although the etiological mechanisms of the effect of radiation on serum levels of calcium, PTH and calcitonin are unclear, radiation exposure may affect secretion of PTH and calcitonin and regulation of calcium a long time after atomic bomb exposure.

Adult↗
PubMed1993

Radiation-associated lung cancer: a comparison of the histology of lung cancers in uranium miners and survivors of the atomic bombings of Hiroshima and Nagasaki.

A binational panel of Japanese and American pulmonary pathologists reviewed tissue slides of lung cancer cases diagnosed among Japanese A-bomb survivors and American uranium miners and classified the cases according to histological subtype. Blind reviews were completed on slides from 92 uranium miners and 108 A-bomb survivors, without knowledge of population, sex, age, smoking history, or level of radiation exposure. Consensus diagnoses were obtained with respect to principal subtype, including squamous-cell cancer, small-cell cancer, adenocarcinoma, and less frequent subtypes. The results were analyzed in terms of population, radiation dose, and smoking history. As expected, the proportion of squamous-cell cancer was positively related to smoking history in both populations. The relative frequencies of small-cell cancer and adenocarcinoma were very different in the two populations, but this difference was accounted for adequately by differences in radiation dose or, more specifically, dose-based relative risk estimates based on published data. Radiation-induced cancers appeared more likely to be of the small-cell subtype, and less likely to be adenocarcinomas, in both populations. The data appeared to require no additional explanation in terms of radiation quality (alpha particles vs gamma rays), uniform or local irradiation, inhaled vs external radiation source, or other population difference.

Adenocarcinoma↗
PubMed1993

[A stink bomb in an office environment. Sick building syndrome with toxic rhinitis after exposure to fusel].

In 1983 WHO, defined "The Sick Building Syndrome". Various conditions influence the indoor climate, among others the degassing of chemicals. An epidemic of sick building syndrome is described in a two year old office building. The symptoms appeared after exposure to toxic chemicals released by a stink bomb--a form of exposure not previously described in the literature. Gas chromatographic analysis of the content of the stink bomb revealed 22 different chemicals likely to be remains from an alcoholic fermentation process. Twenty-four employees were exposed. A questionnaire investigation of the employees revealed that seven had symptoms related to the exposure. A clinical investigation of those who claimed to have symptoms took place. Six of the seven patients were investigated. They all had toxic rhinitis with bleeding. Owing to an unsystematic procedure it took more than two months before the indoor climate was normalized. The toxic rhinitis and other symptoms gradually decreased over more than four months. In order to minimize potential health damage due to the sick building syndrome, we recommend that experts should be consulted within this particular field.

Adult↗
PubMed1993

Monoclonal gammopathy in atomic bomb survivors.

An analysis of monoclonal gammopathy in relation to radiation exposure was conducted on atomic bomb survivors examined between October 1979 and September 1981 and between June 1985 and May 1987. There was no overall increase in the relative risk of monoclonal gammopathy and only a suggestive increase in benign monoclonal gammopathy in the second survey which did not achieve statistical significance (P = 0.17). Thirty-one cases were detected among 8796 individuals studied in the first survey, whereas 68 cases were found among 7350 people in the second survey. Among the 31 cases found in the first survey, 9 individuals (29%) died before the second survey: 4 of cancer, 4 of vascular disease, and 1 of infection. Among the 8 individuals with benign monoclonal gammopathy examined in both surveys, 4 developed suppression of residual immunoglobulin(s), suggesting the progression of monoclonal gammopathy. The overall relative risks of monoclonal gammopathy in atomic bomb survivors in the two surveys were not significantly increased with increasing radiation dose. Only benign monoclonal gammopathy in 1985-1987 showed a suggestive increase with radiation exposure. The relative risk of benign monoclonal gammopathy in 1985-1987 was 2.64 in the group exposed to 0.01-0.49 Gy and 2.14 in the > or = 0.50-Gy group (95% confidence intervals = 0.90-8.82 and 0.69-7.31, respectively).

Female↗
PubMed1996

Direct biological evidence for a significant neutron dose to survivors of the Hiroshima atomic bomb.

In the past few years much physical evidence has accumulated that the A-bomb survivors at Hiroshima were exposed to significant doses of neutrons, in contrast to the predictions of the current DS86 dosimetry. We discuss some biological measurements of exchange-type chromosomal aberrations in survivors at Hiroshima, which also strongly imply that the survivors received a significant neutron dose. Specifically, the ratio of translocations (an interchromosomal aberration) to pericentric inversions (intrachromosomal interarm aberration), the F value, was significantly smaller than would be expected from a gamma-ray exposure, and was consistent with the majority of the effective dose coming from neutrons. If this biological evidence and the previous physical evidence are correct, the effective neutron dose at relevant locations at Hiroshima dominated the total effective dose, from which it may be concluded that (1) the risk coefficient for gamma rays may have been considerably overestimated, and (2) there is a possibility of deriving from the A-bomb data, with reasonable confidence limits, the relative biological effectiveness (RBE) for carcinogenesis by neutrons.

Chromosome Aberrations↗
PubMed1997

Salivary gland tumors among atomic bomb survivors, 1950-1987.

BACKGROUND: Malignant and benign tumors of the salivary glands have been associated with exposure to ionizing radiation from various sources, including the atomic bombings in Hiroshima and Nagasaki. However, questions remain unanswered regarding the nature and size of the risk and specific types of tumors involved. METHODS: The incidence and pathology of malignant and benign tumors of the salivary glands was studied in the Life Span Study cohort of atomic bomb survivors followed by the Radiation Effects Research Foundation (RERF) in Hiroshima and Nagasaki, Japan. Incident cases diagnosed during the period 1950-1987 were ascertained from the tumor and tissue registries of Hiroshima and Nagasaki and supplemented by additional case findings from autopsy, biopsy, and surgical specimens maintained at RERF and other institutions. Pathology slides and medical documents were reviewed by a panel of four pathologists who classified tumors using the World Health Organization classification scheme. Analyses were performed of histologic features associated with radiation exposure. RESULTS: Of 145 tumors of the salivary glands identified (119 of the major and 26 of the minor salivary glands), 120 (83%) were histologically confirmed by the current investigators. Among 41 malignant tumors, the frequency of mucoepidermoid tumor was disproportionately high at high radiation doses (P = 0.04); among 94 benign tumors, the frequency of Warthin's tumor increased with increasing radiation dose (P = 0.06). The nature of the tumor was undetermined for the remaining ten cases. Mortality from malignant tumors of the salivary gland was inversely related to radiation dose, reflecting the predominance of mucoepidermoid carcinoma at high dose levels in this series. In one case with high radiation exposure, mucoepidermoid carcinoma of the parotid gland was accompanied by a preexisting or coexisting Warthin's tumor. CONCLUSIONS: These findings, supported by population-based analyses in a companion study reported elsewhere, suggest a causal role for ionizing radiation in salivary gland tumorigenesis, particularly for mucoepidermoid carcinoma, and in the induction of one type of benign tumor (Warthin's tumor).

Adult↗
PubMed1997

The Oklahoma bombing. Lessons learned.

The Oklahoma City bombing experience in April of 1995 provided a unique opportunity to test the effectiveness of an existing disaster plan. The critical care nurses at Columbia Presbyterian Hospital learned valuable lessons about managing intense activity, equipment and supplies, staffing resources, and visitor issues. The degree to which the bombing affected the emotional state of personnel was unanticipated, and leaders learned that critical stress management interventions should be included in every emergency preparedness plan. Additionally, recommendations include using runners for communication; assigning specific roles (supplies, staffing, triage); keeping additional staff in reserve for shift relief; ensuring ample hospital staff members are available to coordinate visitors and media; and setting up record systems to preserve continuity. The unique lessons learned as a result of this terrorist attack can be used by other critical care nurses to understand and refine disaster plans.

Critical Care↗