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Biomedical subjects

Ray D Lloyd

Publications and source records attributed to Ray D Lloyd.

9 recordsLinked to original sources
PubMed2005

Efficacy of orally administered amphipathic polyaminocarboxylic acid chelators for the removal of plutonium and americium: comparison with injected Zn-DTPA in the rat.

Chelators are used to promote excretion of actinides and some other metals, but few are orally effective. The relative efficacies of orally administered triethylenetetraminepentaacetic acids (TT) with varying lipophilic properties on the removal of 241Am and 239Pu and comparison with parenteral Zn-DTPA was determined. The actinides were administered to adult rats 2 weeks prior to initiation of 30 d of chelation treatment. The TT compounds were given orally while Zn-DTPA was given twice weekly by injection. Total body content of 241Am was measured before and during the treatment period and organ contents of 241Am and 239Pu were measured at the end of the study. Significant reductions in 241Am occurred within the first week, with Zn-DTPA being the most effective. By 3 weeks, the most lipophilic chelator, C22TT was as effective as Zn-DTPA. After 30 d, reductions in organ content of 239Pu and 241Am directly correlated with increasing lipophilicity of the TT chelators. Oral C22TT was as effective as injected Zn-DTPA in liver and bone, the major organs of actinide deposition. The removal of 239Pu from the liver and reduction of redeposition of 239Pu in newly formed bone by C22TT was confirmed by neutron-induced autoradiographs. The amphipathic TT chelators may be useful as orally administered alternatives to current parenteral DTPA for the removal of actinide elements from the body, particularly for longer-term therapeutic applications.

Acetates↗
PubMed2005

Does the severity of radionuclide-induced skeletal malignancy depend upon radiation dose?

The severity of effect as a function of skeletal radiation dose for induced skeletal malignancy was investigated among a relatively large group of beagle dogs singly injected as young adults with soluble radionuclide. Bone-seeking radionuclides considered were 239Pu, 226Ra, 228Ra, 224Ra, 228Th, and 90Sr. Variables included skeletal radiation dose, tumor growth rate, maximum tumor volume, sex of the animals, growth period of the tumor, degree of calcification of the tumor, skeletal location of the tumor, year of death, and occurrence of metastases. Except for a significant relationship between tumor volume and metastatic process and for growth rate and tumor volume, no significant dependence of any two of these factors could be established. It is concluded from available data on skeletal malignancies among beagles exposed to bone-seeking radionuclides that the severity of the disease is not dependent upon skeletal radiation dose.

Animals↗
PubMed2004

Does malignant hematopoietic disease result from internal exposure to 239Pu?

Neither Fisher's Exact Test nor linear regression analysis (dose-response relationship) using average skeletal dose from 239Pu as a surrogate for marrow dose could establish a statistically significant association between malignant hematopoietic disease (MHD including leukemia and aleukemia) and exposure to 239Pu among dogs in the Utah beagle colony. In addition, when dog-years at risk was the parameter used to estimate the rate of expected malignant hematopoietic tumors in dogs exposed to 239Pu, the estimate was within the range of the 95% confidence limits of the control dogs for six cases (and also within the 95% confidence limits for five cases when the single case of lymphoma was omitted). It was concluded that if there was an effect of 239Pu exposure on the occurrence of MHD in this beagle experiment, it was not very meaningful. These data could not establish a significant susceptibility to neoplasia of either myeloid or lymphoid tissue of 239Pu exposure.

Age Distribution↗
PubMed2004

Does low dose internal radiation increase lifespan?

No significant differences in lifespan could be established between control dogs and dogs given 241Am, 228Th, 90Sr, 228Ra, 226Ra or monomeric 239Pu at low dosage levels that induced less than 10% skeletal malignancies (low dose animals) in the Utah beagle colony when all dogs surviving at least 1 y were included in the analysis and dogs given individual radionuclides were considered separately or together. Censoring or exclusion of dogs from these groups that were diagnosed with skeletal malignancies or that died in a gran mal epileptic seizure made no important difference to these results. Therefore, an enhanced lifespan of low dose dogs as compared with controls could not be established. It is concluded that low doses from internal (mainly skeletal) deposits of these radionuclides probably do not benefit the survival of individuals so exposed.

Animals↗
PubMed2003

Does soft tissue cancer affect the development of radionuclide-induced skeletal malignancy?

Data in the archives of the beagle project at the University of Utah were used to determine whether there might have been an association between the occurrence of soft tissue cancer and bone tumor (skeletal malignancy) among the dogs injected with bone-seeking radionuclides. In addition to comparing the numbers of animals with and without bone tumors and with and without soft tissue cancers, data on bone sarcomas and soft tissue sarcomas were compared. Longevity (postinjection survival) of the dogs was investigated. It appeared that survival (time between radionuclide injection and death) was important in the eventual expression of malignancies. There could not be established a possible susceptibility to skeletal malignancy associated with the occurrence of soft tissue cancer (or soft tissue sarcoma). We concluded that, although the literature reports an increased susceptibility for subsequent malignancies for individuals with naturally-occurring or radiation-induced cancer, the data derived from this study do not confirm the concept that the appearance of soft tissue cancer is strongly associated with an increased risk of developing a radionuclide-induced skeletal malignancy.

Animals↗
PubMed2003

Comparisons of the skeletal locations of putative plutonium-induced osteosarcomas in humans with those in beagle dogs and with naturally occurring tumors in both species.

Osteosarcomas occur from exposures to bone-seeking, alpha-particle-emitting isotopes, particularly plutonium. The skeletal distribution of putative 239Pu-induced osteosarcomas reported in Mayak Metallurgical and Radiochemical Plutonium Plant workers is compared with those observed in canine studies, and these are compared with distributions of naturally occurring osteosarcomas in both species. In the Mayak workers, 29% and 71% of the osteosarcomas were in the peripheral and central skeleton, respectively, with the spine having the most tumors (36%). An almost identical distribution of plutonium-induced osteosarcomas was reported for dogs injected with 239Pu as young adults. This distribution of osteosarcomas is quite different from the distributions of naturally occurring osteosarcomas for both species. In the Cooperative Osteosarcoma Study Group in humans (1,736 osteosarcomas from all ages), over 91% of the tumors occurred in the peripheral skeleton. In the Mayo Clinic group of older individuals (>40 years old), over 60% of the osteosarcomas appeared in the peripheral skeleton. The distribution of naturally occurring osteosarcomas in the canine is similar to that in the adult human. The similarities of the distributions of plutonium-associated osteosarcomas in the Mayak workers with those found in experimental studies suggest that many of the reported osteosarcomas may have been associated with plutonium exposures. These results also support the experimental paradigm that plutonium osteosarcomas have a preference for well vascularized cancellous bone sites. These sites have a greater initial deposition of plutonium, but also greater turnover due to elevated bone remodeling rates.

Adolescent↗