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Parathyroid tumors in atomic bomb survivors in Hiroshima: first report of surgical cases, 1956-1988.

Seventeen patients with parathyroid gland tumors underwent surgical resection at the Hiroshima University Hospital between 1956 and 1988. Three of them where born after the atomic bomb explosion, and 6 of the remaining 14 patients (42.9% of the total- a high proportion) were atomic bomb survivors. Because parathyroid gland tumors and hyperparathyroidism are assumed to develop in patients who have been exposed to radiation after a long latent period, it is necessary to anticipate the possible occurrence of these diseases in atomic bomb survivors. The present paper is the first to report surgically extirpated parathyroid gland tumors in atomic bomb survivors.

Adolescent↗

The observed relationship between the occurrence of acute radiation effects and leukemia mortality among A-bomb survivors.

In an analysis of a follow-up study of a fixed population of 73,330 atomic bomb survivors in Hiroshima and Nagasaki, the slope of an estimated dose response between ionizing radiation and leukemia mortality was found to be steeper (P less than 0.002), by a factor of 2.4, among those who reported epilation within 60 days of the bombings, compared to those who did not experience this sign of acute radiation exposure. The strength of this empirical finding as evidence of biological association in individual radiosensitivity for these two end points is studied here. The major factor complicating the interpretation of this finding as evidence of such an association is the degree of imprecision of the radiation dosimetry system used in assignment of radiation doses to the A-bomb survivors. Using models recently suggested for dealing with dosimetry errors in epidemiological analysis of the A-bomb survivor data, the sensitivity of the apparent association between leukemia mortality and severe epilation to the assumed level of dosimetry error is investigated.

Acute Disease↗

[Incidence of multiple myeloma in Nagasaki City, with special reference to those subjected to atomic bomb exposure].

In order to observe the incidence of multiple myeloma in the population of Nagasaki City from 1973 to 1982, and to assess any influence caused by A-bomb exposure, 85 cases of myeloma have been collected and analysed. Informatively, 48 cases of this number were A-bomb survivors. Among the middle-aged cases, the crude incidence rates of myeloma in the exposed group were found to be higher than those in the non-exposed group. Further, the relative risk of myeloma was higher in A-bomb survivors and this tendency become more pronounced in the those who were within 2 km of the epicenter of the blast. The age-adjusted relative risk in male and female A-bomb survivors was 1.59 and 1.68 respectively, but no significant differences were noted.

Adult↗

Mortality of registered A-bomb survivors in Nagasaki, Japan, 1970-1984.

A follow-up study of A-bomb survivors registered in Nagasaki was conducted from 1970 to 1984 by the Scientific Data Center of A-Bomb Disaster at Nagasaki University, which has collected medical and administrative data on A-bomb survivors with the help of Nagasaki City Hall and other organizations. The purpose of this study was to investigate the following two points. (1) Has the health screening program for A-bomb survivors reduced the mortality rate? (2) If so, how much has it reduced it, and what would the life-shortening effect of radiation be without the health screening program? The results revealed that the effect of radiation on mortality would be underestimated if the health screening factor were ignored. The estimated effect of radiation dose was compared with that estimated by the Radiation Effects Research Foundation (RERF).

Aged↗

Yale and the Atomic Bomb Casualty Commission.

This is a description, based largely on personal discussions, of the contributions of men from the Yale University School of Medicine to the saga of the immediate and long-term studies on the medical effects of the atomic bombs at Hiroshima and Nagasaki. They played key roles in the immediate studies of bomb effects, in the creation of long-term studies of delayed effects, and in elevating the Atomic Bomb Casualty Commission after 1955 to a position of excellence in its studies and relations with the Japanese. The accumulation of the information presented in this paper derives from research for the preparation of the history of the Atomic Bomb Casualty Commission. In 1975, the commission was passed to Japanese leadership as the Radiation Effects Research Foundation.

Connecticut↗

Prevalence of hepatitis B surface antigen, hepatitis B e antigen and antibody, and antigen subtypes in atomic bomb survivors.

On the basis of previous studies showing an association between hepatitis B surface antigen (HBsAg) positivity and radiation exposure in atomic bomb (A-bomb) survivors, we investigated further the active state of hepatitis B virus (HBV) infection by incorporating tests for hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) and HBsAg subtypes into our biennial health examinations. Among 6548 A-bomb survivors for whom HBsAg was assayed between July 1979 and July 1981, 129 persons were HBsAg positive. HBeAg and anti-HBe were measured in 104 of these persons and subtypes of HBsAg in 98 persons. Among those exposed to radiation (average liver dose 0.58 Sv), the odds ratio of HBsAg positivity tended to increase with radiation dose (P for trend = 0.024). The P values for association between the prevalence of HB e antigen and radiation dose and between the prevalence of anti-HBe and radiation dose were 0.094 and 0.17, respectively. The HB antigen subtype adr was predominant over other subtypes in both Hiroshima and Nagasaki, but the distribution of subtypes did not seem to differ in relation to radiation dose. These results suggested that A-bomb survivors remain in an active state of HBV infection and that the mechanism(s) of seroconversion may be impaired.

Adolescent↗

Bomb-related injuries.

Between 1980 and 1990 there were 12,216 bombing incidents in the United States, the majority involving pipe-bomb type devices. Victims of such devices may suffer a combination of blast, penetrating, and thermal injuries requiring special surgical approaches. A series of cases is presented which illustrates the management dilemmas faced in such situations. Given the nationwide incidence of bombings, both local emergency medical systems and trauma surgeons should be prepared to deal with blast injuries, be aware of their regional incidence of bombings, and have a planned response that is coordinated with law enforcement agencies.

Adult↗

[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.

Follow-Up Studies↗

Radiation therapy among atomic bomb survivors, Hiroshima and Nagasaki.

As a follow-up to the two previous surveys of radiation therapy among the atomic bomb survivors, a large-scale survey was performed to document (1) the number of radiation therapy treatments received by the atomic bomb survivors and (2) the types of radiation treatments conducted in Hiroshima and Nagasaki. The previous two surveys covered the radiation treatments among the Radiation Effects Research Foundation Adult Health Study (AHS) population, which is composed of 20,000 persons. In the present survey, the population was expanded to include the Life Span Study (LSS), including 93,611 atomic bomb survivors and 26,517 Hiroshima and Nagasaki citizens who were not in the cities at the times of the bombings. The LSS population includes the AHS population. The survey was conducted from 1981 to 1984. The survey teams reviewed all the medical records for radiation treatments of 24,266 patients at 11 large hospitals in Hiroshima and Nagasaki. Among them, the medical records for radiation treatments of 1556 LSS members were reviewed in detail. By analyzing the data obtained in the present and previous surveys, the number of patients receiving radiation therapy was estimated to be 4501 (3.7%) in the LSS population and 1026 (5.1%) in the AHS population between 1945-1980. During 1945-1965, 98% of radiation treatments used medium-voltage X rays, and 66% of the treatments were for benign diseases. During 1966-1980, 94% of the radiation treatments were for malignant neoplasms. During this period, 60Co gamma-ray exposure apparatus and high-energy electron accelerators were the prevalent mode of treatment in Hiroshima and in Nagasaki, respectively. The mean frequency of radiation therapy among the LSS population was estimated to have been 158 courses/year during 1945-1965 and 110 courses/year during 1966-1980. The present survey revealed that 377 AHS members received radiation therapy. The number was approximately twice the total number of cases found in the previous two surveys. Thus the data on radiation therapy in the AHS members have been updated well by this survey, and will provide information for more precise dose-response analyses of radiation effects in the AHS population. The information extracted from the medical records of the hospitals consisted of hospital names, treatment periods, body sites treated, diagnoses, treatment doses, radiation sources, the field sizes of the exposures and the data for identification of the patients. These data will be essential in estimating the organ doses from scattered radiation and in evaluating the effects of therapeutic radiation.

Adolescent↗

Flow cytometry measurements of subsets of T, B and NK cells in peripheral blood lymphocytes of atomic bomb survivors.

Previous studies of blood cells from atomic bomb survivors have shown that frequencies of chromosome aberrations and somatic mutations are elevated in heavily exposed survivors and that T-cell functions and the number of mature T cells are decreased in the survivors who were exposed to radiation as adults. Current progress in flow cytometry allows a sophisticated analysis of various subsets of T, B and NK cells. In the present study, proportions of such subsets in peripheral blood lymphocytes from atomic bomb survivors (159 survivors estimated to be exposed to > or =1.5 Gy) and 252 controls were measured using multiple combinations of monoclonal antibodies to lymphocyte differentiation antigens to investigate whether the previous radiation exposure had altered the composition of the subsets. Among T-cell subsets, the proportion of CD4+ T-cell subsets was decreased significantly in the heavily exposed survivors; this tendency was apparent for the CD4+CD45RA+ naive T-cell subset. However, there were no significant differences in the proportions of CD8+ T-cell subsets between the exposed survivors and controls. As for the B-cell subsets, the proportion of both CD5+ and CD5 B cells as well as CD23+ and CD23- B cells increased in the heavily exposed survivors. Further, no effect of radiation was found in the proportion of NK-cell subsets. These results strongly suggest that previous radiation exposure altered the composition of T and B cells in the peripheral blood of atomic bomb survivors, and they raise the possibility that atomic bomb radiation may have affected the developmental processes of T and B cells.

Adult↗

Can external signs of trauma guide management?: Lessons learned from suicide bombing attacks in Israel.

BACKGROUND: Following a suicide bombing attack, scores of victims suffering from a combination of blast injury, penetrating injury, and burns are brought to local hospitals. OBJECTIVE: To identify external signs of trauma that would assist medical crews in recognizing blast lung injury (BLI) and effectively triaging salvageable and nonsalvageable victims. DESIGN: Retrospective analysis of all 15 suicide bombing attacks that occurred in Israel from April 1994 to August 1997. SETTING: National survey. PATIENTS: One hundred fifty-three victims died and 798 were injured as a result of 15 attacks. Medical records were reviewed for external signs of trauma, such as burns and penetrating injuries, and the presence of BLI. Main Outcome Measure The odds ratio for BLI and death. RESULTS: Three settings were targeted: buses, semiconfined spaces, and open spaces. Sixty survivors (7.5%) suffered from BLI, which was more common in buses (37 of 260) than semiconfined spaces (14 of 279) and open spaces (9 of 259) (P<.001). Victims with BLI were more likely to suffer from penetrating injury to the head or torso, burns covering more than 10% of the body surface area, and skull fractures (odds ratios, 4, 11.6, and 55.8, respectively; P<.001). Victims who died at the scene were more likely to suffer from burns, open fractures, and amputations in comparison with survivors (odds ratios, 6.5, 18.6, and 50.1, respectively; P<.001). CONCLUSIONS: Following a suicide bombing attack, external signs of trauma should be used to triage victims to the appropriate level of care both at the scene and in the hospital. Triage of salvageable and nonsalvageable victims should take into account the presence of amputations, burns, and open fractures.

Adolescent↗

Salivary gland tumors in atomic bomb survivors, Hiroshima, Japan. I. Epidemiologic observations.

An epidemiologic investigation was undertaken in Hiroshima to study the relationship of salivary gland tumors to exposure to ionizing radiation. Two hundred and eleven cases examined between 1953-1971 were confirmed by a review of histologic specimens. Of these, 66 cases occurred in residents of Hiroshima City who were born before the A-bomb: 30 among A-bomb-exposed, and 36 in non-exposed individuals. The incidence of salivary gland tumors among the exposed individuals was significantly higher, 2.6 times greater than that among the nonexposed individuals for all tumors, and 10 times greater for malignant tumors. The incidence increased with proximity to the hypocenter for the directly exposed. An increased incidence was also found among early entrants, particularly those entering the city within 3 days of the A-bomb.

Adolescent↗

Hepatocellular carcinoma among atomic bomb survivors: significant interaction of radiation with hepatitis C virus infections.

We conducted a nested case-control study within the cohort of Japanese survivors of the 1945 atomic bombings to study the joint effects of HBV and HCV with radiation on the risk of HCC. Among subjects who received autopsies during 1954-1988, we analyzed archival tissue samples for 238 pathologically confirmed HCC cases and 894 controls who died from diseases other than liver cancer. Using logistic regression and adjusting for potential confounders and other factors, we found a statistically significant, supermultiplicative interaction between A bomb radiation and HCV in the etiology of HCC. Compared to subjects who were negative for HCV and radiation, ORs of HCC for HCV-positive subjects showed a statistically significant, greater than multiplicative increase for liver irradiation exposures in the second (>0.018-0.186 Sv, p = 0.04) and third (>0.186 Sv, p = 0.05) tertiles of non-zero radiation exposure but not for first tertile exposure (>0-0.018 Sv, p = 0.86). Limiting analysis to subjects without cirrhosis, HCV-infected subjects were at 58.0-fold (95% CI 1.99- infinity ) increased risk of HCC per Sv of radiation exposure (p = 0.017), a supermultiplicative interaction between radiation and HCV that was not found among subjects with cirrhosis (p = 0.67). We found no evidence of interaction between HBV infection and radiation exposure in the etiology of HCC, regardless of cirrhosis status (p = 0.58). We conclude that among survivors of the nuclear bombings of Hiroshima and Nagasaki, subjects who were both HCV-positive and radiation-exposed were at a significantly, supermultiplicatively increased risk of HCC without concurrent cirrhosis.

Adult↗

Radiation-related mortality among offspring of atomic bomb survivors: a half-century of follow-up.

Our objective was to examine whether parental exposure to atomic bomb radiation has led to increased cancer and/or noncancer mortality rates among the offspring. We studied 41,010 subjects born from May 1946 through December 1984 (i.e., conceived between 1 month and 38 years after the bombings) and surviving for at least 1 year. One or both parents were in Hiroshima or Nagasaki at the time of the bombings and childbirth. We analyzed mortality data from 1946 to 1999 using the Japanese family registry system by Cox regression model and examined the effects of paternal and maternal irradiation with adjustment for city, sex, year of birth and parental age at childbirth. During follow-up, 314 cancer deaths and 1,125 noncancer disease deaths occurred. The mean age of living subjects was 45.7 years. Median doses were 143 mSv for 12,722 exposed fathers and 132 mSv for 7,726 exposed mothers. Cancer and noncancer mortality rates were no higher for subjects with exposed parents (5+ mSv or unknown dose) than for reference subjects (0-4 mSv), and mortality did not increase with increasing dose. For subjects with both parents exposed, the adjusted hazard ratios were 1.16 [95% confidence interval (CI) 0.92-1.46] for noncancer and 0.96 (95% CI 0.59-1.55) for cancer. This was true of deaths occurring both before and after 20 years of age. However, because of uncertainty due to the small number of deaths and relatively young ages of subjects, we cannot rule out an increase in disease mortality at this time.

Abnormalities, Radiation-Induced↗

PTSD and depression after the Madrid March 11 train bombings.

The March 11, 2004, train bombings in Madrid, Spain, caused the largest loss of life from a single terrorist attack in modern European history. We used a cross-sectional random digit dial survey of Madrid residents to assess the prevalence of posttraumatic stress disorder (PTSD) and major depression in the general population of Madrid 1 to 3 months after the March 11 train bombings. Of respondents 2.3% reported symptoms consistent with PTSD related to the March 11 bombings and 8.0% of respondents reported symptoms consistent with major depression. The prevalence of PTSD was substantially lower, but the prevalence of depression was comparable to estimates reported after the September 11 attacks in Manhattan. The findings suggest that across cities, the magnitude of a terrorist attack may be the primary determinant of the prevalence of PTSD in the general population, but other factors may be responsible for determining the population prevalence of depression.

Adolescent↗

The presence of BRAF point mutation in adult papillary thyroid carcinomas from atomic bomb survivors correlates with radiation dose.

In papillary thyroid carcinogenesis, the constitutively activated mitogen-activated protein (MAP) kinase signaling pathway caused by a genetic alteration such as RET/PTC rearrangement or mutation of RAS and BRAF genes, is thought to be a major early event. Among these, the recently identified BRAF(V600E) mutation has been found at high frequency in adult patients with papillary thyroid carcinoma (PTC). However, the association between this mutation and radiation exposure in adult PTC is still unknown. In this study, we examined the BRAF(V600E) mutation in 64 PTCs among adult atomic bomb survivors in Hiroshima, Japan, comprising 17 nonexposed (0 mGy) and 47 exposed patients who developed the carcinoma after the bombing, and assessed the association of BRAF(V600E) mutation with clinico-pathological and epidemiological variables. The median radiation dose in PTCs with the BRAF(V600E) mutation was significantly lower than that without the mutation (18.5 vs.156.9 mGy, Wilcoxon rank-sum test, P=0.022). A significant difference was found in the median latency period (years elapsed from atomic bombing to diagnosis) between exposed patients with and without BRAF(V600E) mutation (29 vs. 21 yr, Wilcoxon rank-sum test, P=0.014). These findings were further confirmed by logistic regression analysis with BRAF(V600E) mutation status as a dependent variable and taking into account possible interactions between the variables. We found that the log-transformed radiation dose and latency period were independently associated with the BRAF(V600E) mutation (P=0.039 and P=0.010, respectively). These results suggest that involvement of BRAF mutation in thyroid carcinogenesis in exposed people may differ from that in the nonexposed people.

Adult↗

Possible selection effects for radiation risk estimates in Japanese A-bomb survivors: reanalysis of acute radiation symptoms data.

An earlier analysis examined the possibility of bias in the Life Span Study (LSS) cohort by studying Japanese A-bomb survivors with bomb-related acute injuries and those without such injuries. The authors reported significantly higher radiation risks, both for cancers and non-cancers, among those survivors with acute injuries compared with those without. The risks were reported to be particularly large among survivors aged <10 or > or =55 years of age at the time of bombings. The aim of this paper is to examine these findings more closely using the LSS acute effects data. All the analyses were carried out using Poisson regression. Relative risk models were fitted with adjustment for sex and other factors. Significant differences in relative risk between survivors with epilation and burns and those without epilation and burns are found for leukaemia. There is also some evidence for heterogeneity in the leukaemia risk between survivors with two or more acute injuries and those with no injuries, but the evidence is disappeared when survivors with one or more injuries are compared with those without injuries. For solid cancers, cardiovascular disease and all deaths combined, the risks do not differ to a statistically significant extent between survivors with and without injuries. There is no statistically significant heterogeneity in risk across age-at-exposure categories for survivors with injuries. For all deaths combined, relative risk estimates and their uncertainties are significantly higher for survivors exposed at ages <10 years when compared with other exposure ages, but risks are not significantly raised for survivors exposed at > or =55 years of age. With the exception of leukaemia, the findings from the present work are inconsistent with those of Stewart and Kneale.

Adult↗

Thyroid lymphoma of mucosa-associated lymphoid tissue with monoclonal gammopathy occurring in an atomic bomb survivor: report of a case.

We describe herein a case of thyroid lymphoma of the mucosa-associated lymphoid tissue (MALT) with monoclonal gammopathy (IgG kappa), occurring in a woman who was exposed to atomic-bomb (A-bomb) radiation 1.5 km from the explosion of the hypocenter when she was 31 years old. Her estimated radiation dose was 0.2 Gy. A total thyroidectomy resulted in the disappearance of monoclonal gammopathy, thus indicating extramedullary monoclonal gammopathy of the thyroid. Three patterns of protein electrophoresis, i.e., normal, the appearance of monoclonal immunoglobulins, and their disappearance after the total thyroidectomy, were consecutively recorded. The utility of checking of the monoclonal immunoglobulin levels after a thyroidectomy due to lymphoma of the MALT to monitor recurrence is therefore suggested. This lymphoma is most likely not related to the patient's A-bomb radiation exposure.

Aged↗