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Estimation of thyroid radiation doses for the hanford thyroid disease study: results and implications for statistical power of the epidemiological analyses.

Residents of eastern Washington, northeastern Oregon, and western Idaho were exposed to I released into the atmosphere from operations at the Hanford Nuclear Site from 1944 through 1972, especially in the late 1940's and early 1950's. This paper describes the estimated doses to the thyroid glands of the 3,440 evaluable participants in the Hanford Thyroid Disease Study, which investigated whether thyroid morbidity was increased in people exposed to radioactive iodine from Hanford during 1944-1957. The participants were born during 1940-1946 to mothers living in Benton, Franklin, Walla Walla, Adams, Okanogan, Ferry, or Stevens Counties in Washington State. Whenever possible someone with direct knowledge of the participant's early life (preferably the participant's mother) was interviewed about the participant's individual dose-determining characteristics (residence history, sources and quantities of food, milk, and milk products consumed, production and processing techniques for home-grown food and milk products). Default information was used if no interview respondent was available. Thyroid doses were estimated using the computer program Calculation of Individual Doses from Environmental Radionuclides (CIDER) developed by the Hanford Environmental Dose Reconstruction Project. CIDER provided 100 sets of doses to represent uncertainty of the estimates. These sets were not generated independently for each participant, but reflected the effects of uncertainties in characteristics shared by participants. Estimated doses (medians of each participant's 100 realizations) ranged from 0.0029 mGy to 2823 mGy, with mean and median of 174 and 97 mGy, respectively. The distribution of estimated doses provided the Hanford Thyroid Disease Study with sufficient statistical power to test for dose-response relationships between thyroid outcomes and exposure to Hanford's I.

Adolescent↗

Regional blood flow with first circulation time-indicator curves: a simplified, physiologic method of interpretation.

Dynamic computed tomography, digital subtraction angiography, and radionuclide angiography can all be used to evaluate regional blood flow noninvasively. In each case an indicator is injected intravenously and time-indicator curves are generated from regions of interest during the first circulation. Although regional blood flow cannot be determined uniquely from first circulation time-indicator curves, relative transit time to and through the regions of interest and relative regional blood volume in the regions of interest can be measured and related to relative regional blood flow using a modified Stewart-Hamilton equation. However, for precise mathematical calculation, extrapolation of the first circulation data beyond the point of recirculation is required. This extrapolation is inconvenient and difficult to perform accurately and reproducibly. Indices of transit time and regional volume that do not require extrapolation were evaluated in an experimental model. The correlation coefficients between the indices of transit time and volume and the more mathematically precise measurements were 0.99 and 0.95, respectively (p less than 0.01). It is suggested that these indices, which can also be evaluated visually, are useful in interpreting first circulation time-indicator curves in a physiologic manner.

Blood Circulation Time↗

[A new strain of rat osteogenic sarcoma].

The report deals with a newly-developed strain of rat osteogenic sarcoma which has passed through 64 generations. The strain was obtained from rat primary osteogenic sarcoma induced by 32P treatment. It may be used in testing chemotherapeutic preparations and new drugs for radionuclide diagnosis of tumors.

Animals↗

Definition of myocardial perfusion by continuous infusion of krypton-81m.

Krypton-81m, a radionuclide emitting a 190 kev gamma ray, has a half-life of 13 seconds. It is a radioisotope of an inert water-soluble noble gas and is produced at a constant rate by spontaneous decay of rubidium-81 in an 81Rb-81mKr generator-delivery system. Delivery is through a minibore Teflon catheter that can be threaded through a standard no. 7 or 8F angiographic catheter. The generator is eluted by 5 percent dextrose-in-water, delivered by infusion pump at 1.5 ml/min, and the eluate is infused intraarterially directly into any organ. Delivery and decay reach equilibrium within 2 minutes, producing a heterogeneous distribution that is proportional to the perfusibility of the tissue concerned and the time required to reach it. The ultrashort halflife of the radionuclide rapidly eliminates activity when delivery ceases; thus, experiments can be sequentially repeated at brief intervals. The radiation hazard for easily imaged doses is negligible. Preliminary studies in open chest dogs were visualized by scintillation camera, stored on digital data disk, processed, and displayed in dual channel, dual color mode on a video system. Images of myocardial perfusion defined relative levels of perfusion, collateral circulation between coronary arterial branches, equilibrium time of diffusible perfusion of the myocardium, focal defects in induced occlusion, collateral circulation to occlusion, and reactive hyperemia after release of induced coronary occlusion. The system and technique appear applicable to human subjects.

Animals↗

Transgenerational accumulation of radiation damage in small mammals chronically exposed to Chernobyl fallout.

The purpose of this investigation has been the analysis of the long-term development of biological damage in natural populations of a model mammalian species, the bank vole (Clethrionomys glareolus, Schreber), which were chronically exposed to low doses of ionizing radiation over 22 animal generations within 10 years following the Chernobyl accident. The time course of the biological end-points (chromosome aberrations in bone marrow cells and embryonic lethality) was compared with the time course of the whole-body absorbed dose rate from external and internal exposure in the studied populations inhabiting monitoring sites in Belarus with different ground deposition of radionuclides. The yield of chromosome aberrations and, in lesser degree, embryonic lethality was associated with the radionuclide contamination of the monitoring areas in a dose-dependent manner. As a main feature of the long-term development of biological damage under low dose rate irradiation, permanently elevated levels of chromosome aberrations and an increasing frequency of embryonic lethality have developed over 22 animal generations. This contrasts with the assumption that the biological damage would gradually disappear since in the same period of time the whole-body absorbed dose rate decreased exponentially with a half-value time of about 2.5-3 years. Furthermore, gravid females were captured, and their offspring, born and grown up under contamination-free laboratory conditions, showed the same enhanced level of chromosome aberrations. Therefore the authors suggest that, along with the biological damage attributable to the individual exposure of each animal, the observed cellular and systemic effects reflect the transgenerational transmission and accumulation, via genetic and/or epigenetic pathways, of damage attributable to the chronic low-dose rate exposure of the preceding generations of animals. They also suggest that the level of the accumulated transmissible damage in the investigated populations will decrease in future due to the further recession of the chronic exposure and as a consequence of selection processes.

Animals↗

Determination of dose rates from natural radionuclides in dental materials.

Different types of materials used for dental prosthetics restoration, including feldspathic ceramics, glass ceramics, zirconia-based ceramics, alumina-based ceramics, and resin-based materials, were investigated with regard to content of natural radionuclides by means of thermoluminescence beta dosimetry and gamma spectrometry. The gross beta dose rate from feldspathic and glass ceramics was about ten times higher than the background measurement, whereas resin-based materials generated negligible beta dose rate, similarly to natural tooth samples. The specific activity of uranium and thorium was significantly below the levels found in the period when addition of uranium to dental porcelain materials was still permitted. The high-beta dose levels observed in feldspathic porcelains and glass ceramics are thus mainly ascribable to (40)K, naturally present in these specimens. Although the measured values are below the recommended limits, results indicate that patients with prostheses are subject to higher dose levels than other members of the population. Alumina- and zirconia-based ceramics might be a promising alternative, as they have generally lower beta dose rates than the conventional porcelain materials. However, the dosimetry results, which imply the presence of inhomogeneously distributed clusters of radionuclides in the sample matrix, and the still unsuitable structural properties call for further optimization of these materials.

Ceramics↗

Treatment of radioactive liquid waste by sorption on natural zeolite in Turkey.

Liquid radioactive waste has been generated from the use of radioactive materials in industrial applications, research and medicine in Turkey. Natural zeolites (clinoptilolite) have been studied for the removal of several key radionuclides ((137)Cs, (60)Co, (90)Sr and (110m)Ag) from liquid radioactive waste. The aim of the present study is to investigate effectiveness of zeolite treatment on decontamination factor (DF) in a combined process (chemical precipitation and adsorption) at the laboratory tests and scale up to the waste treatment plant. In this study, sorption and precipitation techniques were adapted to decontamination of liquid low level waste (LLW). Effective decontamination was achieved when sorbents are used during the chemical precipitation. Natural zeolite samples were taken from different zeolite formations in Turkey. Comparison of the ion-exchange properties of zeolite minerals from different formations shows that Gordes clinoptilolite was the most suitable natural sorbent for radionuclides under dynamic treatment conditions and as an additive for chemical precipitation process. Clinoptilolite were shown to have a high selectivity for (137)Cs and (110m)Ag as sorbent. In the absence of potassium ions, native clinoptilolite removed (60)Co and (90)Sr very effectively from the liquid waste. In the end of this liquid waste treatment, decontamination factor was provided as 430 by using 0.5 mm clinoptilolite at 30 degrees C.

Adsorption↗

Comparison of SPECT aerosol deposition data with a human respiratory tract model.

Three-dimensional (3D) radionuclide imaging provides detailed information on the distribution of inhaled aerosol material within the body. Analysis of the data can provide estimates of the deposition per airway generation. In this study, two different nebulizers have been used to deliver radiolabeled aerosols of different particle size to 12 human subjects. Medical imaging has been used to assess the deposition in the body. The deposition pattern has also been estimated using the International Commission on Radiological Protection (ICRP) empirical model and compared to values obtained by experiment. The results showed generally good agreement between model and experiment for both aerosols for the deposition in the extrathoracic and conducting airways. However, there were significant differences in the fate of the remainder of the aerosol between the amount deposited in the alveolar region and that exhaled. The inter-subject variability of deposition predicted by the model was significantly less than that measured, for all regions of the body. The model predicted quite well the differences in deposition distribution pattern between the two aerosols. In conclusion, this study has shown that the ICPR model of inhaled aerosol deposition shows areas of good agreement with results from experiment. However, there are also areas of disagreement, which may be explained by hygroscopic particle growth and individual variation in airway anatomy.

Administration, Inhalation↗

Experimental approaches for exposure to sized glass fibers.

A number of studies have shown that glass fibers induce both malignant mesothelioma and fibrosis in rats and that these reactions may be primarily a function of the physical properties of the fiber. However, these studies were carried out with fibers having broad size distributions and used methods of administration which bear little resemblance to the way man is exposed. To better characterize the health effects of glass fibers, techniques have been developed to expose rats to glass fibers of defined sizes by intratracheal instillation of aqueous suspensions and by "nose only" inhalation exposure, and to determine the deposition, translocation, and ultimate fate of these fibers in the rat. The fibers have known size distributions with geometric mean diameters of 1.5 micrometers (sigma g = 1.1) and lengths of either 5 micrometers (sigma g = 1.49) or 60 micrometers (sigma g = 3.76). The fibers have been activated with neutron irradiation. Of the several resulting radionuclides, 65Zn appeared to be the most suitable for long-term clearance studies by use of in vivo whole body radioassay techniques. A fluidized bed aerosol generator has been developed to expose rats by "nose only" inhalation to approximately 500 fibers/cm3. The generator and exposure system permits reuse of fibers which pass through the exposure chamber and produces no significant alteration of the fiber size distribution. Rats were exposed by intratracheal instillations to 20 mg of the longer fibers and to equal numbers (2 mg) and equal mass (20 mg) of the shorter fibers. Through approximately 19 weeks little difference was observed in the whole rat clearance rate of long versus short fibers in the initial exposure group. Histopathology, however, showed differences at this time with the short fibers apparently successfully phagocytized by alveolar macrophages and cleared to the lymph nodes, while the long fibers were not.

Aerosols↗

[Expression of genomic instability in lymphocytes from children living under conditions of long term exposure to radioactive factors].

An experimental study of expression of genomic instability was carried out with the use of testing irradiation in peripheral blood lymphocytes of 15 children (born in 1986-1998) living on territories with radionuclide contaminations (over 15 Ci/km2, 137Cs, Novozybkov district, Bryansk region). In 5 children exposed to intrauterine irradiation in 1986 this phenomenon was studied in 3 successive cell generations (mitoses). The data obtained suggest the reality of expression of induced genomic instability in the offsprings of repeatedly divided cells of a growing organism exposed to prolonged action of low radiation levels.

Cesium Radioisotopes↗

Noninvasive assessment of hemodynamic effects of mitral valve commissurotomy during rest and exercise in patients with mitral stenosis.

Noninvasive radionuclide angiocardiography (RNA) provides simple and accurate assessment of parameters of cardiac function during rest and during maximal exercise. Left ventricular function was assessed by RNA in nine patients with isolated mitral stenosis before and approximately 6 months after mitral commissurotomy. Before operation, the mean mitral valve gradient was 14.0 +/- 2.8 mm Hg, and the mean mitral valve area was 1.20 +/- 0.3 cm2. Each patient was evaluated at rest and during maximal exercise on an isokinetic bicycle ergometer before and after commissurotomy. Heart rate, ejection fraction, end-diastolic volume, stroke volume, pulmonary transit time, cardiac output, and diastolic ventricular filling rate were determined by the radionuclide technique. Before operation, patients with mitral stenosis had characteristic changes from rest to exercise which supported restriction to diastolic ventricular filling as the primary limitation in generating a cardiac output during exercise. The stroke volume was unchanged from rest to exercise. Thus the cardiac output during exercise was heart rate dependent. However, after commissurotomy the stroke volume increased from rest to exercise. Therefore, cardiac output during exercise was achieved by heart rate and an augmented stroke volume. Moreover, the pulmonary transit time was reduced during rest and exercise after operation. The maximum ventricular ejection and filling rates were markedly increased during rest and exercise after commissurotomy. These differences in hemodynamic parameters at rest and during exercise document the mechanics of increased exercise tolerance in patients with mitral stenosis after mitral commissurotomy.

Adult↗

Radionuclides in the Great Lakes basin.

The Great Lakes basin is of radiologic interest due to the large population within its boundaries that may be exposed to various sources of ionizing radiation. Specific radionuclides of interest in the basin arising from natural and artificial sources include 3H, 14C, 90Sr, 129I, 131I, 137Cs, 222Rn, 226Ra, 235U, 238U, 239Pu, and 241Am. The greatest contribution to total radiation exposure is the natural background radiation that provides an average dose of about 2.6 mSv/year to all basin residents. Global fallout from atmospheric nuclear weapons tests conducted before 1963 has resulted in the largest input of anthropogenic radioactivity into the lakes. Of increasing importance is the radionuclide input from the various components of the nuclear fuel cycle. Although the dose from these activities is currently very low, it is expected to increase if there is continued growth of the nuclear industry. In spite of strict regulations on design and operation of nuclear power facilities, the potential exists for a serious accident as a result of the large inventories of radionuclides contained in the reactor cores; however, these risks are several orders of magnitude less than the risks from other natural and man-made hazards. An area of major priority over the next few decades will be the management of the substantial amounts of radioactive waste generated by nuclear fuel cycle activities. Based on derived risk coefficients, the theoretical incidence of fatal and weighted nonfatal cancers and hereditary defects in the basin's population, attributable to 50 years of exposure to natural background radiation, is conservatively estimated to be of the order of 3.4 x 10(5) cases. The total number of attributable health effects to the year 2050 from fallout radionuclides in the Great Lakes basin is of the order of 5.0 x 10(3). In contrast, estimates of attributable health effects from 50 years of exposure to current nuclear fuel cycle effluent in the basin are of the order of 2 x 10(2). Although these are hypothetical risks, they show that the radiologic impact of man-made sources is very small compared to the effects of normal background radiation.

Environmental Exposure↗

Bystander effect produced by radiolabeled tumor cells in vivo.

The bystander effect, originating from cells irradiated in vitro, describes the biologic response(s) of surrounding cells not directly targeted by a radiation insult. To overcome the limitations of in vitro tissue culture models and determine whether a bystander effect that is initiated by the in vivo decay of a radionuclide can be demonstrated in an animal, the ability of 5-[(125)I]iodo-2'-deoxyuridine ((125)IUdR)-labeled tumor cells to exert a damaging effect on neighboring unlabeled tumor cells growing s.c. in nude mice has been investigated. When mice are injected with a mixture of human colon LS174T adenocarcinoma cells and LS174T cells prelabeled with lethal doses of DNA-incorporated (125)I, a distinct inhibitory effect on the growth of s.c. tumor (derived from unlabeled cells) is observed. Because (i) the (125)I present within the cells is DNA-bound, (ii) approximately 99% of the electrons emitted by the decaying (125)I atoms have a subcellular range (<0.5 microm), and (iii) the overall radiation dose deposited by radiolabeled cells in the unlabeled cells within the growing tumor is <10 cGy, we conclude that the results obtained are a consequence of a bystander effect that is generated in vivo by factor(s) present within and/or released from the (125)IUdR-labeled cells. These in vivo findings significantly impact the current dogma for assessing the therapeutic potential of internally administered radionuclides. They also call for reevaluation of the approaches currently used for estimating the risks to individuals and populations inadvertently exposed internally to radioactivity as well as to patients undergoing routine diagnostic nuclear medical procedures.

Animals↗

Significance of the pericardium in human subjects: effects on left ventricular volume, pressure and ejection.

To assess the effect of the pericardium, left ventricular systolic function and diastolic compliance were studied in 15 patients before and after pericardiotomy during coronary artery surgery. Using first pass radionuclide angiography, curves for left ventricular systolic function (stroke work versus end-diastolic volume) and a measure of diastolic compliance (pulmonary capillary wedge pressure versus end-diastolic volume) were generated by changing body position to alter venous return. Left ventricular end-diastolic volume ranged from 41 to 111 ml/m2 and pulmonary capillary wedge pressure from 0 to 24 mm Hg. No significant changes were found in blood pressure (150/83 to 148/82 mm Hg), heart rate (66.7 to 67.1 beats/min), cardiac index (2.38 to 2.41 liters/min per m2), ejection fraction (0.56 to 0.54), end-systolic volume index (31.4 to 32.2 ml/m2), end-diastolic volume index (65.9 to 69.5 ml/m2) or pulmonary capillary wedge pressure (7.5 to 7.3 mm Hg). The pericardium did not affect the curves relating stroke work and end-diastolic volume or those relating pulmonary capillary wedge pressure and end-diastolic volume. Thus, when filling pressure and volume are normal or only moderately elevated, the pericardium does not appear to affect left ventricular systolic function or diastolic compliance in patients.

Adult↗