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Biomedical subjects

R L Kathren

Publications and source records attributed to R L Kathren.

At least 37 records · Page 2Linked to original sources

Radiation protection and medical practice with special reference to health physicists and the Health Physics Society.

This paper broadly examines the historical development of radiation protection in medical practice through an examination of the interactions of those concerned with radiation protection and medical practice with emphasis on the last half century and on the role played by health physicists and the Health Physics Society. Included is a brief discussion of the relevant activities of various federal agencies and other organizations including the Atomic Energy Commission and successors and the U.S. Public Health Service; the National Council on Radiation Protection and Measurements and International Commission on Radiological Protection; and the Health Physics Society, American Board of Health Physics, American Association of Physicists in Medicine, Society of Nuclear Medicine, and Conference of Radiation Control Program Directors and related scientific and professional bodies.

Government Agencies↗

Diurnal urinary volume and uranium output in uranium workers and unexposed controls.

Volume and uranium content were determined in individual urine voids over a 76-h (3.25-d) period from six unexposed normal male subjects and three male uranium workers. Uranium analyses were accomplished by a newly developed high-precision kinetic phosphorescence analysis technique with a lower level of detection of 0.007 ng mL-1. Urinary uranium concentrations in individual voids varied by a factor of 2 or less for any one unexposed subject, although there was an order of magnitude variation among the group of unexposed men. The fractional urinary volume excreted in the "standard" so-called simulated 24-h sample was the same for both the unexposed and exposed groups and averaged 0.42 +/- 0.13 of the total daily urine volume. The fraction of uranium in the simulated 24-h samples was 0.43 +/- 0.15 in the unexposed group but only 0.31 +/- 0.13 in the uranium worker group, suggesting that the use of the simulated 24-h urine sample would underestimate the total daily urinary uranium output by approximately a factor of 2 in the uranium workers. Daily urinary excretion relative to intake from drinking water (essentially equal to the gastrointestinal uptake fraction) among the unexposed group ranged from 0.002-0.028, averaging 0.011 +/- 0.008, with an indication that the gastrointestinal uptake factor was inversely proportional to total intake via drinking water.

Adult↗

Soft tissue concentrations of plutonium and americium in occupationally-exposed humans.

Human tissues, obtained at autopsy from 82 volunteer donors with a history of occupational exposure, were analyzed for 238Pu, 239 + 240Pu, and 241Am by chemical separation and subsequent alpha spectrometry. Concentrations of these actinide nuclides in soft tissues (testes, thyroid gland, spleen, kidneys, heart, and skeletal muscle) were compared to those of the livers in the same subjects. Tissue:liver concentration ratios were essentially constant over a wide range of liver concentrations. The spleen had consistently high actinide concentrations relative to liver; however, the heart had the greatest concentration ratio for 241Am. Testes had relatively high concentration ratios of the plutonium nuclides but low concentrations of 241Am. Skeletal muscle had low concentrations of plutonium relative to liver but high concentrations of 241Am. In the tissues studied, concentration ratios of 241Am were greater than those of the plutonium nuclides, most likely a result of more rapid excretion of that nuclide than the plutonium nuclides by the liver.

Americium↗

Plutonium in south-central Washington State autopsy tissue samples--1970-1975.

Results are presented of postmortem human tissue sampling and analysis for plutonium of Hanford Site workers, residents of the nearby Tri-Cities, and individuals residing farther away from the Hanford Site for the period 1970-1975. The majority of Hanford Site workers and nearby residents coming to autopsy had tissue concentrations of plutonium no larger than those who lived farther away from Hanford and whose likely source of plutonium was limited to nuclear weapons testing fallout. Thus, Hanford operations up to that time apparently had made no significant addition to plutonium in those individuals sampled postmortem.

Autopsy↗

Comprehensive evaluation of a Thorotrast patient: an overview.

For several decades, thousands of people received Thorotrast during the course of angiography and other radiologic procedures. Eventually, as the hazards of this radioactive, radiographic contrast agent became apparent, research was initiated to further evaluate its associated adverse effects. In 1988 and 1989, Charles W. Mays, together with colleagues at a variety of sites, developed a detailed protocol for the comprehensive postmortem evaluation of one subject who had been administered Thorotrast 36 y previously. This case represents the first holistic approach to the analysis of Thorotrast in a whole body, simultaneously assembling clinical and autopsy findings with dosimetric, radiochemical, autoradiographic, and molecular evaluations.

Aged↗

Alteration of the c-fms gene in a blood sample from a Thorotrast individual.

We analyzed six different tissue DNA samples from a leukemic individual who received an injection of Thorotrast for alterations in proto-oncogene or tumor-suppressor gene structure. Our examination of the DNA indicated an alteration of the c-fms gene in the blood sample from this individual. This locus showed a deletion in which the 3' end of the deleted region maps between exons 11 and 12. In this particular case, the type of leukemia is unknown but myeloid leukemia is a neoplasm associated with individuals injected with Thorotrast. It is possible that the alteration in the c-fms gene of this individual is a consequence of the radiation exposure. No apparent alterations in the c-mos gene were observed in any of the tissues from the individual. This is in contrast to previous studies that described alterations in methylation patterns associated with the c-mos locus in radium-exposed individuals. A number of the individuals exposed to radium also had alterations of the retinoblastoma gene while no such alterations were observed in any tissue DNA samples from this Thorotrast case. It is possible that our inability to detect alterations of the c-mos and retinoblastoma gene may be attributable to the nature of alpha-emitting radionuclides or their distribution, or to the limited set of tissues available for analysis.

Aged↗

Microdistribution and microdosimetry of thorium deposited in the liver.

The distribution of thorium in the liver of a patient 36 y after injection with Thorotrast was examined with autoradiographic and scanning electron microscope backscatter image techniques. Autoradiographic examination of randomly selected histologic sections of the liver showed a total alpha activity calculated at 33.7 Bq g-1, with the highest concentration of alpha activity sequestered in subcapsular scare tissue. Subcapsular scare tissue received 4.8 cGy d-1 of alpha radiation, periportal areas were accumulating 1.4 cGy d-1, and the hepatic cord areas 0.09 cGy d-1 of alpha radiation at the time of death. The concentration of dose in periportal areas correlates with higher incidence of bile duct tumors (than hepatocellular carcinomas) found in patients exposed to Thorotrast. The backscatter technique was demonstrated as useful for identifying thorium in liver specimens.

Aged↗

The distribution of Thorotrast in human bone marrow: a case report.

Samples of bone containing cellular and fatty bone marrow were removed at autopsy from the body of a woman who, following an automobile accident, had been injected with approximately 25 mL of the radiographic contrast medium Thorotrast. The woman survived for 36 y after the accident and died at age 72 y following bone marrow failure. The samples were analyzed to determine their thorium content by x-ray fluorescence and by image analysis. In addition, Thorotrast was visualized in the different bones examined by light microscopy and by backscattered electron imaging with a scanning electron microscope. The results showed Thorotrast to be largely restricted to areas of cellular bone marrow. In such regions, Thorotrast was present throughout the marrow tissue and was also concentrated within cells that were commonly aggregated within focalized areas of the marrow. Overall the results suggest a rather uniform pattern of Thorotrast uptake by the red bone marrow at different skeletal sites. Significant deposits of Thorotrast were not found in fatty yellow marrow. We conclude that Thorotrast-derived risk estimates for human leukemia following high LET, alpha irradiation may be used for calculating the risks of alpha exposure, but with caution.

Aged↗

Distribution and dosimetry of Thorotrast in USUR case 1001.

The distribution of radioactivity and the associated doses were evaluated postmortem for USUR Case 1001, a female who had been injected with Thorotrast some 36 y prior to death. The distribution was determined for four nuclides: 232Th and its decay products, 228Ra and 228Th; and 230Th, a contaminant associated with Thorotrast. More than 90% of the activity was associated with the reticuloendothelial system. Approximately 32% of the total activity was found in the total skeleton (mineral bone and bone marrow), which is somewhat higher than expected from the literature. The 44% found in the liver and 12% in the spleen were somewhat lower than expected. This difference may be attributable, in part, to the initial deposition as influenced by colloidal particle size and to the radiation-induced hyposplenism, splenic atrophy, and slight hepatic atrophy observed at autopsy. In addition, roughly 3% of the activity was found in the Thorotrastoma and surrounding carotid artery tissue. Estimated lifetime absorbed doses from the 232Th series were 15 Gy to the liver, 121 Gy to the spleen, 4 Gy to the skeleton, and 16 Gy to the Thorotrastoma. Comparable dose equivalents to these tissues are 300, 2420, 80, and 320 Sv, respectively, assuming a quality factor of 20 for alpha irradiation.

Aged↗

Cancer risk following exposure to Thorotrast: overview in relation to a case report.

Radioactive measurements and histopathologic findings are described in a patient administered Thorotrast, a radiographic contrast agent, 36 y prior to death and compared with cancer risks noted in epidemiologic studies. This person [designated as U.S. Uranium Registry (USUR) Case 1001] had prearranged for donation of her body to the USUR and the National Cancer Institute for study. Elevated levels of radioactivity were noted in those organs in which excess cancers have been reported in epidemiologic surveys of Thorotrast-exposed subjects. Hepatic tissue in USUR Case 1001 was estimated to have received an average lifetime absorbed dose of 16.2 Gy, based on radiochemical analyses, consistent with the high risks for liver tumors reported in all studied populations. Thorotrast was present throughout the bone marrow of USUR Case 1001, who died secondary to complications of refractory anemia with excess blasts (RAEB). Elevated risks for acute myeloid leukemia have been noted in Thorotrast patients, and more recently, cases of RAEB and RAEB in transformation have been reported. The thorium decay series includes the bone-seeking radionuclides 224Ra and 228Ra, which have been associated with high risks for osteosarcomas, although the association between Thorotrast and bone cancer is not as convincing. The skeleton of USUR Case 1001, however, contained significant levels of radioactivity. Other tissues evaluated in USUR Case 1001 included lung, eye, kidney, and breast, which did not contain elevated levels of radioactivity.

Aged↗

U.S. Transuranium Registry report on the 239Pu distribution in a human body.

The distribution of 239Pu in a human whole body is reported. The body contained 246 Bq of 239Pu of which 130 Bq (52.8%) was found in the lungs and associated lymph nodes. Of the remaining 116 Bq (47.2%) that constituted the systemic deposition, 51.2 Bq (44%) were in the skeleton, 48.6 Bq (42%) in the liver, and the remainder (14%) in the rest of the body exclusive of the lungs and associated lymph nodes. An unexpectedly high concentration was observed in the pituitary. The systemic distribution of Pu in this case, when combined with the exposure history, is suggestive of an initial partitioning ratio of 239Pu between skeleton and liver of less than unity, and a tentative initial distribution from the transfer compartment of 25% to the skeleton, 50% to the liver, and 25% to the rest of the body and early excretion is proposed for this case. Older biokinetic models, when used with the available urinalysis data for this case, typically overestimated the deposition when compared with the tissue analysis results, but more recent models provided estimates in close agreement with the autopsy results.

Actinoid Series Elements↗

Modified biokinetic model for uranium from analysis of acute exposure to UF6.

Urinalysis measurements from 31 workers acutely exposed to uranium hexafluoride (UF6) and its hydrolysis product UO2F2 (during the 1986 Gore, Oklahoma UF6-release accident) were used to develop a modified recycling biokinetic model for soluble U compounds. The model is expressed as a five-compartment exponential equation: yu(t) = 0.086e-2.77t + 0.0048e-0.116t + 0.00069e-0.0267t + 0.00017 e-0.00231t + 2.5 x 10(-6) e-0.000187t, where yu(t) is the fractional daily urinary excretion and t is the time after intake, in days. The excretion constants of the five exponential compartments correspond to residence half-times of 0.25, 6, 26, 300, and 3,700 d in the lungs, kidneys, other soft tissues, and in two bone volume compartments, respectively. The modified recycling model was used to estimate intake amounts, the resulting committed effective dose equivalent, maximum kidney concentrations, and dose equivalent to bone surfaces, kidneys, and lungs.

Accidents, Occupational↗

Comparison of systemic plutonium deposition estimates from urinalysis and autopsy data in five whole-body donors.

The systemic deposition of (239 + 240)Pu was determined by postmortem radiochemical analysis of the tissues from five whole-body donors to the United States Transuranium Registry (USTR). All were males with intakes typically occurring many years prior to death. The postmortem radiochemical results were compared with estimates of systemic deposition made with 13 different biokinetic models using urinary excretion data obtained during life. In general, estimates made with older biokinetic models were severalfold greater than those obtained from radiochemical analysis of the tissues. For all five cases, agreement within a factor of two with the tissue analysis results was obtained with two of the biokinetic models evaluated: the Langham power function model as modified by Leggett and Eckerman and the two compartment exponential model proposed in ICRP Publication Nos. 19 and 30.

Aged↗

Units and terminology of radiation measurement: a primer for the epidemiologist.

The utility and even the validity of radiation epidemiology studies rest upon the quality of the underlying radiologic data and the correctness of their interpretation. To ensure meaningful and comparable results, radioepidemiologic studies need to properly and consistently use radiologic quantities and units, and to evaluate and fully discuss the radiologic measurements and their interpretation, recognizing that experts in health physics may differ in their assessments. As succinctly stated by Polya Two persons presented with the same evidence and applying the same patterns of plausible inference may honestly disagree.

Epidemiology↗

Uranium in the tissues of an occupationally exposed individual.

Uranium concentrations were radiochemically determined in samples of lung, kidney, liver and bone collected at autopsy from an occupationally exposed individual. Levels of U in these tissues were clearly in excess of those expected from environmental exposure. Deposition followed the pattern: skeleton greater than liver greater than kidney, with ratios of 63:2.8:1. The data suggest there is an important long-term storage depot in the skeleton, but the fraction transferred to this compartment, as proposed by ICRP 30, may be too small. In vivo chest counts obtained over about a 10-y period prior to death indicated about a factor of 2 greater in total U content and 235U enrichment than deposition estimates made at autopsy for the lungs and associated lymph nodes.

Bone and Bones↗

Comparative skeletal distribution of Am and Pu in man, monkey, and baboon.

The skeletal distribution of Am and Pu in four human cases was compared with the skeletal distributions of these radioelements in baboons and monkeys. Excellent agreement was noted among the four human cases; data were available for Am in all four and Pu in three. A statistically significant correlation was found between the 241Am and 239Pu + 240Pu skeletal distributions in the humans and those in nonhuman primates. Trabecular bone had the highest concentrations of 241Am and 239+240Pu in humans, baboons, and monkeys. Scaling factors are proposed to convert the percentages of skeletal activity in animal bones to the corresponding percentages in the bones of the human skeleton.

Americium↗