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Biomedical subjects

R D Lloyd

Publications and source records attributed to R D Lloyd.

At least 73 records · Page 4Linked to original sources
PubMed1991

Radium-226 dose to a boy from playing on mill tailings.

Two boys born in September 1949 played on uranium mill tailings from about ages 8 to 12. One of these boys was diagnosed as having leukemia at age 15.5. The 226Ra body burden of the survivor was measured at age 38. The whole-body 226Ra content measured by counting in vivo was 0 +/- 17 Bq and independently by Rn breath analysis as 4.3 +/- 2.1 Bq. At the same time, a control subject with no known exposure to 226Ra, matched in age, height, and weight, was also measured. The whole-body content was estimated as 4 +/- 15 Bq and independently by Rn breath analysis as 5.5 +/- 3.7 Bq. The body burden of the control subject was not significantly different from that of the exposed person. The radiation dose to the marrow-free skeleton assuming a constant 226Ra:Ca ratio since birth was 0.49 and 1.33 mGy at ages 14 and 38, respectively. The radiation dose to the marrow-free skeleton assuming 226Ra intake only between ages 8 to 12 was 1.4 and 2.8 mGy at ages 14 and 38, respectively. The best estimate is the mean of these two estimates: 0.9 and 2.1 mGy at ages 14 and 38, respectively. The alpha-particle dose to the red marrow from 226Ra and its decay products was 0.05 mGy at age 14 and 0.10 mGy at age 38. Since no excess was found for the radium dial painters whose doses were much higher, the induction of leukemia by doses of this magnitude would seem quite unlikely.

Body Burden↗
PubMed1991

Plutonium- or americium-induced liver tumors and lesions in beagles.

Plutonium-239 or 241Am administered intravenously in the monomeric citrate form was initially deposited in beagle livers principally in the hepatocytes and to a much lesser extent in the sinusoidal macrophages and connective tissues. The initial distribution was quite uniform throughout the hepatic parenchyma; however, at later postinjection intervals, depending on the amount of injected activity, the liver burden became increasingly more focal due to: (1) a progressive shift of the radionuclide from the hepatic epithelium to the macrophages; (2) the movement of such macrophages toward the portal or central regions of the lobule; and (3) the displacement of the older more radioactive tissue by regenerating hepatocytes, which generally have a much lower radionuclide content. The hepatic lesions produced by Pu or Am included: (1) necrosis and degenerative changes that were clinically serious or fatal in some of the animals injected with approximately 107 kBq kg-1; (2) marked structural and circulatory changes resulting from necrosis and focal hepatocyte hyperplasia; (3) a significant incidence of both benign and malignant primary liver tumors. In both Pu- and Am-treated dogs, the most frequently appearing neoplasm was the bile duct adenoma, followed by the cholangiocarcinoma. The most obvious difference between Pu- and Am-induced liver neoplasia was the greater frequency of fibrosarcomas and mast cell sarcomas in the Am-treated groups. Hepatomas were of relatively low frequency in animals with Pu or Am burdens. Although the incidence of bone neoplasia was high among the dogs in these studies, the risk of liver tumors, especially in the Am-treated animals, exceeded that of the skeleton in some of the lower dosage levels where the survival times were long. A risk coefficient of approximately 1200 fatal liver malignancies (10(4) beagle Gy)-1, derived from the dosage groups with long survival times, was calculated for combined Pu and Am animals. The prominence of the liver syndromes in beagles with burdens of Pu or Am indicates that humans with body burdens of 239Pu, 241Am, or other actinide elements may be at risk from radiation effects in the liver, including neoplasia development.

Adenoma↗
PubMed1991

The influence of age at time of exposure to 226Ra or 239Pu on distribution, retention, postinjection survival, and tumor induction in beagle dogs.

The influence of age at injection of 226Ra or 239Pu on skeletal deposition and local distribution, the pattern of bone tumor formation, and postinjection survival was assessed in parallel short-term studies of mechanisms and lifetime toxicity. Beagles received a single intravenous injection of 226Ra or 239Pu at 3 months (juveniles), 17-19 months (young adults) or 60 months (mature). Data from short-term studies of mechanisms and dosimetry and from one dosage level (41 kBq 226Ra/kg or 11 kBq 239Pu/kg body mass) of each of the toxicity experiments were compared. Skeletal growth and turnover produced differential initial deposition and distribution patterns typical for each age group. At 1 week after injection, skeletal retention of 226Ra or 239Pu was 68 and 68%, respectively, in the juveniles, 32 and 46% in the young adults, and 31 and 43% in the mature dogs. Comparing individual bones in the juveniles, gradients in the concentration of 239Pu were small since all bones were actively growing, but substantial gradients, corresponding to centers of ossification, were present within individual bones. In other age groups, local concentration gradients were less pronounced, but much larger differences were present among the various bones. In the toxicity study all animals injected with either 41 kBq 226Ra/kg or 11 kBq 239Pu/kg have died. The cumulative average skeletal doses to the presumed time of start of tumor growth (1 year before death) were 25 and 4 Gy, respectively, for the juveniles, 22 and 5 Gy for the young adults, and 15 and 4 Gy for the mature dogs. The highest bone tumor incidence was seen in the young adult groups. Differences were observed in location of bone tumors between dogs in the same age group given radium or plutonium and among age groups injected with either radionuclide, some of which could be explained by differences in local dose distributions. Median postinjection survival assessed by the Kaplan-Meier nonparametric method ranged from 2513 and 2592 days for the juveniles to 2099 and 1617 for the young adults to 2086 and 1421 in the mature groups. Cox regression analysis indicated no significant differences in postinjection survivals (uncorrected for the different preinjection periods) of groups injected with radium, but there was a statistically significant difference among the groups injected with plutonium. It was demonstrated that differences in the effects of 239Pu in the three groups were due primarily to the age- and time-dependent local distribution of the radionuclide.

Aging↗
PubMed1991

A comparison of the natural survival of beagle dogs injected intravenously with low levels of 239Pu, 226Ra, 228Ra, 228Th, or 90Sr.

The natural survival, relative to properly chosen controls, of 26 beagle dogs injected once intravenously with an average of 0.58 +/- 0.04 kBq 239Pu/kg, 23 dogs injected with 2.31 +/- 0.43 kBq 226Ra/kg, 13 dogs injected with 1.84 +/- 0.26 kBq 228Ra/kg, 12 dogs injected with 0.56 +/- 0.030 kBq 228Th/kg, and 12 dogs injected with 21.13 +/- 1.74 kBq 90Sr/kg was evaluated statistically. The amounts of these radionuclides are related directly to the estimated maximum permissible body burdens for humans suggested in ICRP II (1959). They constitute a level of exposure that initially was assumed to cause no deleterious effects in dogs. This study had two objectives: (1) identification of homogeneous control groups against which to evaluate the survival of the irradiated groups and (2) comparison of the survival characteristics and estimation of mortality or hazard rate ratios for control dogs vs dogs injected with the baseline dosages given above. It was shown, by goodness-of-fit plots, that the Cox proportional hazards model was an appropriate method of analysis. Therefore, covariates that possibly could influence survival were tested for significance. Only the effects of grand mal seizure, which is caused in epileptic dogs by an external stimulus and can be fatal if untreated, were significant (P less than 0.0001). Consequently, in the final model, death from grand mal seizure was considered as accidental. After censoring the dogs dying from grand mal seizure, it was established that the data for the control groups from previous and contemporary experiments could be pooled. The change in hazard rates relative to controls resulting from exposure to the baseline radionuclide level was modest, 1.6 times for 239Pu (P = 0.033), 1.0(4) for 226Ra (P = 0.86), 1.9 for 228Ra (P = 0.035), 2.5 for 228Th (P less than 0.001), and 0.52 for 90Sr (P = 0.041). Bone tumor induction was clearly elevated in dogs injected with 239Pu and 228Th. When the effect of these bone tumors on survival was removed by censoring, the dogs injected with 239Pu were indistinguishable from the controls. In contrast, the effects of bone tumor on group survival of the 228Ra and 228Th dogs were not significant. Thus, no additional life-shortening effects beyond those attributable to bone tumor were suggested by these data for 239Pu, but other, as yet unspecified, confounders are suggested for 228Ra and 228Th.

Analysis of Variance↗
PubMed1990

Leukemia in Utah and radioactive fallout from the Nevada test site. A case-control study.

Previous studies reported an association between leukemia rates and amounts of fallout in southwestern Utah from nuclear tests (1952 to 1958), but individual radiation exposures were unavailable. Therefore, a case-control study with 1177 individuals who died of leukemia and 5330 other deaths (controls) was conducted using estimates of dose to bone marrow computed from fallout deposition rates and subjects' residence locations. A weak association between bone marrow dose and all types of leukemia, all ages, and all time periods after exposure was found. This overall trend was not statistically significant, but significant trends in excess risk were found in subgroups defined by cell type, age, and time after exposure. The greatest excess risk was found in those individuals in the high-dose group with acute leukemia who were younger than 20 years at exposure and who died before 1964. These results are consistent with previous studies and with risk estimates for other populations exposed to radiation.

Acute Disease↗
PubMed1990

Development of a method to estimate thyroid dose from fallout radioiodine in a cohort study.

A cohort of 4831 persons aged 11-18 y in 1965 was identified among students in the schools of Washington County, UT; Lincoln County, NV; and Graham County, AZ. These children who had potentially been exposed to radioiodine from atomic weapons test fallout from the Nevada Test Site during 1951-1962 were selected for participation in a study of thyroid disease. The entire cohort was first examined during 1965-1968 for thyroid abnormalities. A total of 3,085 of these people were again reexamined during 1985-1986 to determine any subsequent occurrence of thyroid disease. In order to determine the relationship of the radiation dose to the thyroid with incidence of thyroid disease, we have developed a suite of models to calculate estimates of the internal dose received by the thyroid from fallout radioiodines. For completeness, the exposure to the thyroid from external radiation is also estimated. Dose estimates are made specific to each individual in the study using individual residential histories, the locality-specific exposure rate and radionuclide deposition, descriptions of dairy management for identified milk producers, and the subjects' sources of foods and intake rates of milk and leafy vegetables determined by interview. Other data such as the relationship of radioiodine deposition to measured exposure rate, environmental transfer parameters, and age-dependent factors for the conversion of radioiodine intake to thyroid dose were taken from work of other investigators. Dairy management information, milk distribution practices, the milk source for each study subject, as well as age-specific intake rates of milk and leafy vegetables, were determined by interview.

Adolescent↗
PubMed1990

Individual external exposures from Nevada Test Site fallout for Utah leukemia cases and controls.

External gamma-ray exposures from fallout originating at the Nevada Test Site (NTS) have been assigned to 6,507 individual subjects (1,177 leukemia cases and 5,330 control subjects) who died as Utah residents between 1952 and 1981. Leukemia cases were identified, confirmed, and classified by cell type from the Utah Cancer Registry, Utah State vital records, and medical records. Residential histories were obtained from the Deceased Membership File (DMF) of the Church of Jesus Christ of Latter-day Saints (LDS), supplemented by information from the LDS Church Census Records that were taken in 1950, 1955, and 1960-62. Control subjects were selected randomly within age strata from the DMF and were frequency-matched to the cases by age at death and for sex. Individual radiation exposures were assigned as a function of residence location and time interval for each residence during the fallout period (1951-1958) using geographic exposure data taken from the literature. Temporal distribution of exposure for subjects who resided in more than one locality or who were born or died during the fallout period was determined from data of other investigators. Calculated gamma-ray exposures for each place of residence were summed for each subject to yield the exposure to fallout from the NTS.

Case-Control Studies↗
PubMed1990

Kidney disease in beagles injected with polonium-210.

An unusually high incidence of kidney disease (tubular degeneration and necrosis with fibrous replacement) was observed among 24 beagles injected at about 5 years of age with 116 or 329 kBq 226Ra kg-1 but not among an additional 10 beagles given about 39 kBq 226Ra kg-1. This 226Ra solution also contained 210Pb, 210Bi, and 210Po. To determine whether the kidney disease was related to the radiation from 226Ra and its short-lived progeny or to the alpha radiation from 210Po, 2 beagles about 7 years of age were injected with 451 kBq 226Ra kg-1 of 210Po citrate. Measurements of polonium retention in the kidneys of 4 additional beagles given 210Bi citrate enabled us to model the retention of these emitters in the dog kidney and to estimate the kidney dose from the alpha radiation of 210Po following injection of either 226Ra + 210Bi + 210Po or 210Po only. Autoradiography revealed that almost equal concentrations of 210Po were in the tubular epithelium and/or its basement membrane and in the glomeruli, but very little of the 210Bi deposited in kidney tissue was present in the glomeruli. Radiation damage to the kidneys similar to that observed previously in beagles given 226Ra solutions that also contained 210Bi and 210Po was seen among the beagles given 210Po but not in the dogs given purified 226Ra. The analysis of these data indicated that the relatively high incidence of kidney disease among the mature beagles injected with 226Ra and its accompanying 210Bi and 210Po resulted from alpha irradiation of the kidneys by the substantial amount of 210Po that was in the injection solution.

Animals↗
PubMed1989

Fission fragment RBE for bone sarcoma induction.

Thirty beagles and 277 mice were injected with 249Cf, and 30 beagles and 274 mice were injected with 252Cf. The skeletal dose (in Gy) from 252Cf was about half from fission fragments and half from alpha particles, whereas 249Cf emits alpha particles in 100% of its transformations. Bone sarcomas (mostly osteosarcomas) were the main radiation-induced cancer. The relative biological effectiveness (RBE) of fission fragment dose relative to alpha-particle dose for bone sarcoma induction was calculated from the ratio of 249Cf/252Cf doses at equal times to bone sarcoma in (a) beagles and (b) mice, and (c) from the ratio 252Cf/249Cf risk coefficients in mice. The average RBE +/- standard deviation of the three evaluations was 0.1 +/- 0.1. The very low RBE for bone sarcomas is supported by the data of A. L. Batchelor, T. J. Jenner, and L. M. Cobb [Phys. Med. Biol. 28, 475-483 (1983)] for lung cancer induction in rats and by that of A. L. Brooks, J. A. Mewhinney, and R. O. McClellan [Health Phys. 22, 701-706 (1972)] for producing chromosome aberrations in the liver cells of Chinese hamsters. The low effectiveness of fission fragments relative to alpha particles, per gray of absorbed dose, is ascribed primarily to the much larger number of cells traversed by the alpha particles. Consideration might be given to decreasing the quality factor of fission fragments by an order of magnitude below that for alpha particles.

Alpha Particles↗
PubMed1987

Cancer incidence and lifespan vs. alpha-particle dose in beagles.

Young adult beagles were injected with graded activities of 239Pu, 241Am, 228Th, 228Ra or 226Ra and observed throughout their lifespans. The vast majority of the dose was from alpha particles. The lifetime incidence of bone sarcoma increased with average skeletal dose, more or less linearly up to high incidence for 239Pu, 241Am, 228Th and 226Ra, but sigmoid fashion for 228Ra. Based on average skeletal dose, the toxicity of the emitters relative to 226Ra = 1.0 was 239Pu = 16.6 +/- 4.5, 241Am = 5.4 +/- 1.6, 228Th = 8.5 +/- 2.3 and 228Ra = 2.0 +/- 0.5. At the lowest doses, the average lifespans were 97% +/- 3% of that in the controls. If beneficial effects occurred, they may have been overwhelmed by the destructiveness of the densely ionizing alpha particles. A cell nucleus 5 micron in diameter receives a mean dose of about 1 Gy (100 rad) when traversed by a single alpha particle. We found no evidence that alpha-particle doses suppressed cancer or lengthened lifespan in beagles.

Alpha Particles↗
PubMed1986

Reducing the cancer risk of 239Pu by chelation therapy.

Groups of adult female C57BL/Do mice were injected intraperitoneally with graded activities of monomeric 239Pu(IV) citrate at 10 weeks of age. Beginning 3 days after plutonium injection, some mice received repeated subcutaneous injections of Zn Na3 diethylenetriaminepentaacetate (Zn-DTPA). Each injection was 37 mumol Zn-DTPA/kg body weight. To evaluate protection from bone sarcoma, brief, intermediate, or protracted chelation therapies were administered to groups of mice. The brief chelation therapy covered a 2-week period, the intermediate therapy 2 months, and the protracted therapy 1 year. The mice were followed throughout life and examined for bone sarcoma. Both skeletal dose and bone sarcoma risk were reduced by chelation. The bone sarcoma incidences in the mice given chelation treatments generally fell below the dose-response curve for the mice not given DTPA, indicating that the cancer risk was reduced more than that corresponding to the decreased skeletal dose. This results suggests that Zn-DTPA preferentially removed Pu from the most carcinogenic locations in the skeleton, such as on bone surfaces near living cells.

Animals↗