PubMed Health⌕ Search

Biomedical subjects

R D Lloyd

Publications and source records attributed to R D Lloyd.

At least 55 records · Page 3Linked to original sources
PubMed1994

Eye tumors and other lesions among beagles given 90Sr or 226Ra.

Analysis of eye tumors and other eye lesions among beagles given either 90Sr or 226Ra, and among control animals, indicated that intraocular tumors in excess of the rate for our control animals were not associated with radiation from incorporated 90Sr + 90Y. It is unequivocal that eye melanomas were produced by injected 226Ra. Intraocular neoplasia, hyperplasia, hyperpigmentation, and melanosis in the eye all occurred in our control beagles given no radioactivity; however, tumor experience as currently reported for different beagle colonies may not be directly comparable because of differing rates of discovery, nonuniform nomenclature, and varying criteria for classification of lesions with their discordant interpretation by different pathologists.

Animals↗
PubMed1994

Distribution of skeletal malignancies in beagles injected with 239Pu citrate.

The distribution of skeletal malignancies among our beagles injected with 239Pu as young adults roughly seems to follow the distribution of skeletal mass and skeletal 239Pu. These findings are similar to those we reported previously for a group of dogs given 26Ra. Although there were differences in tumor distribution between the animals given 226Ra and those given 239Pu, most of them were not statistically significant; however, the radium dogs seemed to show a greater sensitivity to bone tumor origin in the tibia, while there may have been a tendency among the plutonium dogs toward increased relative sensitivity in the scapula, lumbar vertebrae, sacrum, and ribs. In contrast, the most common site for the formation of naturally-occurring bone malignancy in the dog is the distal radius. Perhaps there were too few tumors and too few dogs to establish statistical significance. A correlation between tumor location and at least two anatomical-physiological factors in the skeleton indicated that these two factors (site-specific bone turnover rate and percent of red marrow at the site, which is correlated with vascularity) may influence the appearance of malignancies both individually and in combination. Except for the femur, there appeared to be no difference between the relative distribution of skeletal malignancies of low-level (30 Bq-2 Bq kg-1 injected) and high-level (3-122 kBq kg-1) dogs. Distribution of bone tumors between the axial and appendicular skeleton was 50% vs. 50% for 239Pu (42 and 42), but it was 39% axial vs. 61% appendicular (22 and 35, respectively) for dogs given 226Ra. This difference was not significant (p > 0.2).

Animals↗
PubMed1994

Relative effectiveness of 239Pu and some other internal emitters for bone cancer induction in beagles.

The toxicity ratio (relative effectiveness per gray of average skeletal dose) has been estimated for bone cancer induction in beagles injected as young adults for a number of bone-seeking internal emitters. These experiments yielded calculated toxicity ratios (+/- SD) relative to 226Ra = 1.0 of 239Pu = 16 +/- 5 (single exposure to monomeric Pu) and 32 +/- 10 (continuous exposure from an extraskeletal deposit in the body), 224Ra = 16 +/- 5 (chronic exposure) and approximately 6 +/- 2 (single exposure), 228Th = 8.5 +/- 2.3, 241Am = 6 +/- 0.8, 228Ra = 2.0 +/- 0.5, 249Cf = 6 +/- 3, 252Cf = 4 +/- 2, 90Sr = 1.0 +/- 0.5 (for high doses) and 0.05 +/- 0.03 (for low doses) and 0.01 +/- 0.01 (for extremely low doses). Because no skeletal malignancies were observed among beagles given only 253Es, the toxicity ratio is undefined.

Animals↗
PubMed1994

Occurrence of mammary tumors in beagles given radium-226.

A total of 128 primary mammary tumors (66 of them malignant) occurred in 35 female beagles injected with 226Ra at eight dose levels ranging from 0.2 to 440 kBq/kg body mass as young adults, while a total of 156 mammary tumors (57 of them malignant) were seen in 46 female control beagles not given any radioactivity. Sixty-three of 65 control dogs and 59 of 61 dogs given 226Ra survived the minimum age for diagnosis of mammary tumors of 3.75 years. Based on the observed age-dependent tumor incidence rates in the controls and on the corresponding number of dog-years at risk, the total number of observed malignant tumors in the radium group was statistically greater than the number of expected malignant tumors (66 observed vs 34 expected, P < 0.005). There was no such difference for the benign tumors. Cox regression analysis indicated no increased risk for the first tumor occurrence in irradiated dogs. Cox regression analysis of the multivariate risk sets showed no significantly increased risk for the occurrence of benign tumors but a statistically higher risk of 1.66 with a confidence interval of 1.15-2.40 for the occurrence of malignant tumors. The increased risk was dependent on dose, but a dependence on the frequency of previous occurrence of mammary tumors could not be confirmed. Censoring ovariectomized dogs at time of surgery decreased the relative risks slightly but did not alter the significance. Exposure to diagnostic X rays with cumulative exposures below 0.2 Gy had no effect on tumor formation. It is unknown whether the increased risk for malignant mammary tumors was due to some initial deposition of radium in sensitive tissue, a possible irradiation of fatty mammary tissue from transient radon-->polonium deposition, or a general effect of the overall radium deposition on the immune system of the dogs that lowered their resistance to formation of mammary tumors. Results of this study are potentially useful in understanding risks of radium-induced breast cancers in humans.

Age Factors↗
PubMed1993

A cohort study of thyroid disease in relation to fallout from nuclear weapons testing.

OBJECTIVE: To estimate individual radiation doses and current thyroid disease status for a previously identified cohort of 4818 schoolchildren potentially exposed to fallout from detonations of nuclear devices at the Nevada Test Site between 1951 and 1958. DESIGN: Cohort analytic study. SETTING: Communities in southwestern Utah, southeastern Nevada, and southeastern Arizona. PARTICIPANTS: Individuals who were still residing in the three-state area (n = 3122) were reexamined in 1985 and 1986, and information on the subjects' and their mothers' milk and vegetable consumption during the fallout period was obtained by telephone interview (n = 3545). After exclusions to eliminate missing data and confounding factors, 2473 subjects were available for analysis. MAIN OUTCOME MEASURES: Individual radiation doses to the thyroid were estimated by combining consumption data with radionuclide deposition rates provided by the US Department of Energy and a survey of milk producers. Relative risk models adjusted for age, sex, and state were fitted using maximum likelihood to period prevalence data for thyroid carcinomas, neoplasms, and nodules. RESULTS: Doses ranged from 0 mGy to 4600 mGy, and averaged 170 mGy in Utah. There was a statistically significant excess of thyroid neoplasms (benign and malignant; n = 19), with an increase in excess relative risk of 0.7% per milligray. A relative risk for thyroid neoplasms of 3.4 was observed among 169 subjects exposed to doses greater than 400 mGy. Positive but nonsignificant dose-response slopes were found for carcinomas and nodules. CONCLUSIONS: Exposure to Nevada Test Site-generated radioiodines was associated with an excess of thyroid neoplasms. The conclusions are limited by the small number of exposed individuals and the low incidence of thyroid neoplasms.

Adolescent↗
PubMed1993

Bone cancer occurrence among beagles given 239Pu as young adults.

The occurrence of skeletal malignancies has been documented among 234 young adult beagles given single intravenous injections of monomeric 239Pu citrate. Occurrence has also been documented among 132 comparable control group animals surviving the minimum latent time period of 2.79 y for radiation-induced bone cancer, who were maintained for lifespan observation. Injected amounts ranged from about 0.02-106 kBq kg-1 body mass with factors of 2 or 3 between dose levels. There were 84 radiographically apparent bone tumors in 76 plutonium-injected dogs and one tumor in a control group dog. Most of these were osteosarcomas except for seven chondrosarcomas, one liposarcoma, and one plasma cell myeloma of bone. The relationship between percent of dogs at any dose level with bone malignancy and average skeletal dose at the presumed time of tumor initiation of 1 y before death appeared to be linear below about 1.3 Gy average skeletal dose. The observed data can be approximated by the expression A = 0.76 + 75 D, where A = percent of dogs with bone cancer at any dose level, D = average skeletal dose in Gy (for doses up to 1.3 Gy) at tumor initiation, and 0.76 represents the percent tumor response in the control animals not given plutonium. Similar analysis of our corresponding data for beagles given 226Ra, excluding the two highest dose levels (approximately 100% occurrence), yielded the expression A = 0.76 + 4.7 D, where D = the average skeletal dose in Gy (for doses up to 20 Gy) at 1 y before death. The ratio of coefficients indicates the effectiveness for bone cancer induction of 239Pu relative to 226Ra, or [(75 +/- 22.5)(4.7 +/- 0.47)-1] = 16 +/- 5 for a single, brief intake of either nuclide into blood.

Animals↗
PubMed1993

Liver cancer induction by 239Pu, 241Am, and thorotrast in the grasshopper mouse, Onychomys leukogaster.

Forty young adult grasshopper mice (Onychomys leukogaster) of both genders were injected with either 129 or 44 kBq kg-1 of monomeric 239Pu and were maintained for lifetime observation. Average liver doses to death (mean times +/- standard deviation (SD) from injection to death = 405 +/- 133 and 756 +/- 189 d) were calculated as approximately 16 and 9 Gy, respectively. These animals developed a total of 18 primary liver tumors (neoplasms, malignant, and benign). Comparison of these mice to a previously published study involving 49 control animals of the same species, 70 mice given 241Am, and 73 given Thorotrast, indicated that the liver cancer induction of Thorotrast can be attributed almost exclusively to the effects of the radioactivity and not to its nonradiation properties. This suggests that projected risks of liver cancer induction from 239Pu, 241Am, or other liver-seeking actinides in humans probably can be estimated from the liver cancer experience in Thorotrast patients using the calculated radiation doses to liver. For this species, the linear risk coefficient for induction of liver neoplasia (percent of mice with liver tumor) by 241Am or Thorotrast was estimated to be about 14.6 +/- 5.4 times the average liver dose (in Gy) for groups of animals with average liver doses of 5 Gy or less. The lowest average liver dose among groups of these mice given 239Pu was about 9 Gy, the dose was not in the linear range, and it was too high to yield reliable results for determining a risk coefficient for low dose irradiation. However, the estimates for a risk coefficient were similar for the plutonium and americium mice with liver doses of approximately 9 Gy or 16 Gy.

Americium↗
PubMed1993

241Am-induced thyroid lesions in the beagle.

One of the features of 241Am metabolism in the beagle dog is a relatively high selective deposition in the thyroid glands, equal to approximately 0.06% of the injected dosage per gram. Retention is prolonged and principally in the interstitial connective tissue. The resulting average dose to the thyroid glands is about 1.42 and 0.76 times that delivered to the skeleton and the liver, respectively. This thyroid dose is much higher than has been reported in people. Although significant morphological changes and reductions in serum thyroxine occurred in this experiment, a significant increase in thyroid neoplasia was not observed.

Americium↗
PubMed1993

Duration and dose-related effects of an orally administered, partially lipophilic polyaminocarboxylic acid on the decorporation of plutonium and americium.

A recently developed, orally administered, partially lipophilic polyaminocarboxylic acid-based chelator, docosyl-triethylenetetraminepentaacetic acid (C22TT), was tested for its ability to promote decorporation of 239Pu and 241Am. The effects of dose and duration of treatment were determined in rats injected with 239Pu or 239Pu/241Am 2 weeks before the initiation of C22TT treatment and compared with untreated controls. In the dose-effects study, significant reductions in total body Am content were seen within 3 days after the initiation of C22TT treatment. After 30 days of treatment, there were dose-related reductions in the Pu and Am content of soft tissues and bones. All doses of C22TT resulted in substantial reductions in Pu and Am content of the liver. In the time-response study, there were rapid reductions in total body Am content in the C22TT-treated animals. The greatest reductions occurred within the first 30 days of treatment. Significant decreases in Pu content of soft and hard tissue were observed in the treated animals at 30, 60 or 90 days compared with untreated controls. The greatest reductions in organ Pu content occurred within the first 30 days of treatment, particularly in the liver, but it continued throughout the experiment. Neutron-induced autoradiography showed that C22TT greatly reduced the incorporation of Pu into new bone and substantially reduced the Pu content of the bone marrow. There was no evidence of overt toxicity in either experiment. This study demonstrates that orally administered C22TT is effective in reducing soft and hard tissue content of internally deposited Pu and Am.

Acetates↗
PubMed1992

Promotion of radiation-induced liver neoplasia by ethanol.

The risk of americium-induced liver cancer in beagle dogs that received long-term dietary ethanol was two to three times that of their nonalcoholic cohorts, even though the radionuclide retention time in hepatic tissue was shortened by the alcohol treatment. Liver malignancies did not occur in the ethanol-treated, nonirradiated controls. An ethanol-induced tumor-promoting effect was not observed in organs or tissues other than the liver.

Americium↗
PubMed1992

Decorporation of plutonium by oral administration of a partially lipophilic polyaminocarboxylic acid.

A new, orally administered, partially lipophilic polyaminocarboxylic acid chelator was tested for its ability to remove incorporated 239Pu deposits in rats. Animals were injected with 239Pu-citrate and 14 d later were treated for an additional 10 d with docosyl-triethylenetetraminepentaacetic acid (C22TT) added to the diet. There were significant reductions in the 239Pu content of selected organs in the chelated animals compared with controls. These results suggest that this class of chelators should be studied further for their ability to remove plutonium deposits from the body when given orally.

Acetates↗
PubMed1991

Effectiveness of DTPA treatments following the injection of particulate plutonium.

A limited long-term experiment has been completed in which the chronic toxicity resulting from a single intravenous injection of 31.4 kBq of a poly-disperse 239Pu colloid sol per kg of body weight was tested in Beagle dogs. The Pu deposited mostly in the phagocytic cells of liver, spleen and to a lesser degree in lung and bone marrow. Slow solubilization of the Pu particles by endogenous ligands caused translocation of the nuclide and redeposition mostly as monomeric Pu in the skeleton and in liver hepatocytes. Thus, the deposit behaved as expected from a pulmonary or wound contamination in humans with a moderately soluble depot of Pu such as Class W hot particles. Therefore, this type of deposit provided the basis for a practical model to study the ensuing radiation effects under various experimental conditions. The dogs were divided into three groups of four animals each, and the following conditions were applied: (a) no further treatment was given, allowing free translocation of the Pu to its secondary deposition sites; (b) interception of the Pu translocation by weekly injections of 30 mumol of Ca-DTPA/kg of body weight (Ca-chelate of diethylene-triaminepentaacetic acid); and (c) interception of translocation by daily injections of 30 mumol/kg body weight of Zn-DTPA. For each of the groups (b) and (c), three dogs were used in a lifetime study, and one was sacrificed for nuclide distribution studies. Free translocation and subsequent deposition in the skeleton resulted in the death of each of the non-chelated dogs from osteosarcoma between 1267 and 1594 days after injection. Weekly treatment with Ca-DTPA reduced the total Pu burden significantly, but these dogs also died with osteosarcoma between 1462 and 1783 days. Daily injections with Zn-DTPA reduced the total Pu burden more efficiently than Ca-DTPA and prevented continuous deposition of solubilized Pu on bone surfaces. The mean post-injection survival of these dogs was 3520 days or about 2.1 times that of the animals receiving Ca-DTPA, while the latent period for bone tumour induction was about 2.6 times longer. This treatment reduced the severity of liver lesions and eliminated the occurrence of persistent leukopenia, but it did not prevent the formation of bone cancer.

Animals↗