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Biomedical subjects

G M Angleton

Publications and source records attributed to G M Angleton.

18 recordsLinked to original sources

Ultraviolet radiation, solar dermatosis, and cutaneous neoplasia in beagle dogs.

Beagle dogs that were part of a life span study of the effects of low-level ionizing radiation during development were evaluated for the incidence of skin neoplasia and solar dermatosis. A total of 991 dogs up to 14 years of age were examined. The dogs were housed in gravel-based, outdoor pens with doghouses in a high-altitude, high-sunshine level environment. Solar dermatosis was restricted to the sparsely haired, nonpigmented abdominal skin. Skin neoplasms were either removed surgically or found at necropsy. Solar dermatosis was diagnosed in 363 of the 991 dogs, an incidence of 36.6%. There were 175 hemangiomas, hemangiosarcomas, or squamous cell carcinomas of the skin in the 991 dogs. Of these, 129 tumors occurred in dogs with, and only 46 in dogs without, solar dermatosis. Of the dogs with solar dermatosis, 93 (26%) had at least one of the three tumor types, compared to only 44 (7%) of dogs without solar dermatosis. Thirty-two dogs had multiple tumor types and solar dermatosis, compared to only two dogs with multiple tumor types and no solar dermatosis. There was a highly significant correlation (P less than 0.001) between the occurrence of these tumor types and solar dermatosis in the unpigmented abdominal skin. This correlation was strongest for the malignant neoplasms. Whole-body gamma-radiation exposures were delivered at one of three prenatal or three postnatal ages up to 1 year of age. There appeared to be an increased risk for hemangiosarcomas and squamous cell carcinomas in dogs with solar dermatosis and given gamma-ray exposures at 1 year of age. This suggests an interaction between exposures to ionizing and ultraviolet radiation.

Animals

Radiation carcinogenesis in dogs irradiated during prenatal and postnatal development.

To evaluate the lifetime hazards of ionizing radiation exposure, 1680 beagles received whole-body, 60-Cobalt gamma exposures or sham-exposures during development. Eight groups of 120 dogs each received mean doses of 16 or 83 cGy at 8 (preimplantation), 28 (embryonic), or 55 (late fetal) days postcoitus (dpc), or 2 (neonatal) days postpartum (dpp). One group of 120 dogs received 83 cGy at 70 dpp (juvenile), and one group of 240 dogs received 83 cGy at 365 dpp (young adult). Sham-irradiations were delivered to 360 controls. Sexes were equally represented. Young dogs, up to 4 years of age, had an increase in benign and malignant neoplasms after irradiation in the perinatal period at 55 dpc or 2 dpp. Among these, 4 fatal cancers were observed. No malignancies occurred in comparably-aged controls. The increase in both fatal neoplasms and all neoplasms in the perinatally-exposed groups were statistically significant. Over the full lifetime, dogs irradiated in the perinatal period also had the strongest evidence for an increased risk for fatal malignancies of all types. Though not as strong, there was a trend for increased risk for fatal cancer in dogs irradiated at all other ages. The risk of fatal malignancy after irradiation was greater in females than in males. Dogs exposed at 55 dpc had a significant increase in lymphoid neoplasia and dogs exposed at 8 and 55 dpc had increased risk for hemangiosarcoma. There was no evidence for an increased risk for mammary carcinoma in irradiated females. Dogs exposed as juveniles at 70 dpp had a significant increase in all benign and malignant thyroid neoplasms, including fatal thyroid carcinoma.

Aging

Perinatal radiation-induced renal damage in the beagle.

The developing perinatal kidney is particularly sensitive to radiation. The pathogenesis of the radiation-induced lesion is related to the destruction of outer cortical developing nephrons and direct radiation injury with secondary hemodynamic alterations in remnant nephrons. In this study, which is part of a life span investigation of the effects of whole-body gamma radiation during prenatal and early postnatal life, dogs were given 0, 0.16, 0.83, or 1.25 Gy irradiation at either 55 days postcoitus or 2 days postpartum and were examined morphometrically and histopathologically at 70 days of age. Although irradiated dogs showed no reduction in the total number of nephrons per kidney, there was a significant increase in the total number and relative percentage of immature, dysplastic glomeruli. In addition, deeper cortical glomeruli of irradiated kidneys exhibited mesangial sclerosis similar to that associated with progressive renal failure in our previous studies. These findings are in accord with those reported at doses of 2.24 to 3.57 Gy and demonstrate that the perinatal kidney is affected by radiation doses much lower than previously demonstrated.

Animals

Transitional cell carcinomas of the urinary tract in a colony of beagle dogs.

Gross and light microscopic features of transitional cell carcinomas (TCC) of the urinary tract were examined in Beagle dogs used for the study of the long-term effects of low-dose, whole-body, 60Co gamma radiation. Thirty-eight cases of TCC occurred among 990 dogs that were from 0 to 14 years of age. There was no conclusive evidence of a radiation effect. The 38 TCC were equally divided between male and female dogs, but there was a significant difference in the sex distribution of urethra-origin TCC. Eleven males had a primary urethral TCC compared to only two females. There was no significant difference between the urethra-origin and bladder-origin TCCs in the number of tumors that caused clinical signs, metastasized, or that contributed to the death of the dog. All cases of urethral TCC in male dogs occurred in the prostatic urethra. The majority of these cases were not recognized to be neoplasms at gross necropsy, but microscopic examination revealed the TCC. Our findings differ from previous reports stating that TCC occurs more frequently in female than male dogs, and they especially differ from reports claiming that urethra-origin TCC is predominantly a disease of female dogs.

Animals

Hypodontia in the beagle after perinatal whole-body 60Co gamma irradiation.

As part of a long-term study to evaluate health effects of pre- and postnatal irradiation, dental development was examined. Beagles were irradiated in utero at 8, 28, or 55 days postcoitus or postnatally at 2, 70, or 365 days postpartum. Whole-body 60Co gamma radiation doses ranged from 0 to 3.8 Gy. There was an age-dependent dose-related increase in premolar hypodontia for animals irradiated at 55 days postcoitus or 2 days postpartum with doses of 0.83 Gy or higher and for those irradiated at 28 days postcoitus with 1.2 Gy or higher.

Animals

The effect of perinatal 60Co gamma radiation on brain weight in beagles.

Beagle dogs were given single, whole-body 60Co gamma-radiation exposures at one of three prenatal (8, 28, or 55 days postcoitus) or three postnatal (2, 70, or 365 days postpartum) ages to evaluate the relative radiosensitivity of various stages of brain development. A total of 387 dogs received mean doses ranging from 0.16 to 3.83 Gy, and 120 dogs were sham-irradiated. Groups of dogs were sacrificed at preselected times from 70 days to 11 years of age. Brain weight decreased significantly with increasing dose in dogs irradiated at 28 or 55 days postcoitus or at 2 days postpartum. Irradiations at 28 days postcoitus were dramatically more effective in causing a reduction in brain weight than those at 55 days postcoitus or 2 days postpartum. Among dogs given 1.0 Gy or more and followed for up to 4 years, there was a radiation effect evident at all three sensitive exposure ages. Among dogs given lower doses and followed for up to 11 years, there was a significant decrease in brain weight in dogs given 0.80-0.88 Gy at 28 days postcoitus. All decreases in brain weight were present after normalization for radiation-induced reductions in skeletal (body) size. No specific morphologic changes were noted in the brains which showed the radiation-related reductions in size.

Animals

Health effects of low-level irradiation during development: experimental design and prenatal and early neonatal mortality in beagles exposed to 60Co gamma rays.

As part of a long-term study of the effects of irradiation during development, prenatal and early neonatal mortality were evaluated for beagles exposed in utero at 8 days postcoitus (dpc), 28 dpc, 55 dpc, or 2 days postpartum. Mean doses used were 0,0.16, or 0.83 Gy. A decrease in whelping rates was observed for female breeders irradiated at 8 dpc. There was a significant decrease in litter sizes from female breeders irradiated at 8 and 28 dpc. Both of these findings are indicative of increased embryonic mortality. There was a significant decrease in the percentage of females born after exposures given at 28 dpc, indicating a differential radiosensitivity by sex. A significant increase in early neonatal mortality up to 14 days of age was observed for beagles exposed 8 or 28 dpc, again with an excess mortality in females.

Animals

Effects of body position and ventilation/compression ratios during cardiopulmonary resuscitation in cats.

Eighteen cats were anesthetized and were randomly assigned to 2 groups (9 cats/group). Cardiopulmonary resuscitation (CPR) was performed on each cat, with the cat in dorsal (group 1) or lateral (group 2) recumbency, by administering 5 external cardiac compressions/1 interposed (diastolic) ventilation (American Heart Association [AHA] technique; n = 3 cats/technique), simultaneous compression and ventilation (SCV; n = 3 cats/technique), or SCV with 1 interposed (diastolic) ventilation every tenth compression (SCV/DV; n = 3 cats/technique). Fourteen of the 18 cats were resuscitated. Central aortic and venous pressures were determined concurrently with lead II electrocardiography. Arterial blood samples were collected during the base-line period (after pressure fluctuations had stabilized, with the cats spontaneously breathing room air), 2.5 minutes after the onset of arrest (defined as the cessation of aortic pressure fluctuations), and after 10 minutes of CPR. Arterial blood gas values during the base-line period or during the period of arrest were not significantly different between group-1 and group-2 cats. After CPR, arterial pH and bicarbonate values were not significantly different between groups or between technique categories. The PaCO2 values were significantly lower in cats resuscitated by SCV or by SCV/DV than in cats resuscitated by AHA (P less than 0.05). The PaO2 values were significantly (P less than 0.001) higher in group-2 cats than in group-1 cats and were significantly (P less than 0.001) different between each technique category, with cats resuscitated by AHA having the lowest PaO2 and cats resuscitated by SCV/DV having the highest PaO2. Body position, CPR technique, sex, weight, or arterial blood gas values after CPR were not predictors of successful resuscitation.

Animals

Neoplasms in young dogs after perinatal irradiation.

For a study of the life-time effects of irradiation during development, 1,680 beagles were given single, whole-body exposures to 60Co gamma-radiation at one of three prenatal (preimplantation, embryonic, and fetal) or at one of three postnatal (neonatal, juvenile, and young adult) ages. Mean doses were 0, 0.16, or 0.83 Gy. For comparison with data on childhood cancer after prenatal irradiation, examination was made of tumors occurring in young dogs in this life-span experiment. Up to 4 years of age, 18 dogs had neoplasms diagnosed, 2 of these being in controls. Four dogs that were irradiated in the perinatal (late fetal or neonatal) period died of cancers prior to 2 years of age. This risk was of significant increase compared to the risks for other experimental groups and for the canine population in general. Overall, 71% (5 of 7) of all cancers and 56% (10 of 18) of all benign and malignant neoplasms seen in the first 4 years of life occurred in 29% (480 of 1,680) of the dogs irradiated in the perinatal period. These data suggest an increased risk for neoplasia after perinatal irradiation in dogs.

Age Factors

Nodular hyperplasia of the liver in the beagle dog.

Gross and light microscopic features of focal nodular hyperplasia of the liver were investigated in beagle dogs used for the study of the long-term effects of low-dose, whole-body, 60Co gamma radiation. The nodules were morphologically similar in the irradiated and unirradiated dogs. Microscopically, and normal lobular architecture, although retained, often was distorted. Hepatocytes in the nodules often were vacuolated and the distribution of vacuolated cells varied from focal to diffuse. There were more hepatocytes per unit area within nodules than in the adjacent parenchyma. Nodule hepatocytes were more variable in size. A lower proportion were binucleate and a higher proportion were in mitosis. The cells in the nodules contained less hemosiderin. The incidence of hyperplastic nodules was directly related to age but not to sex, was higher in irradiated dogs than in controls. Nodular hyperplasia occurred in association with primary hepatocellular neoplasms in only two dogs.

Age Factors

A biometrical approach for determining the effects of treatment with a chemotherapeutic agent upon heart weight in the mature rabbit.

Changes in heart weight as attributable to treatments involving a chemotherapeutic agent (CTA) were studied using adult rabbits. CTA was administered to each subject three times a week until sacrifice. Dose level per administration was held constant with respect to mg of CTA per kgm of body weight. The level of treatment for a given animals was then determined by the length of time the animal was in the treatment program prior to sacrifice. At sacrifice, variations in heart weight were evaluated relative to sex, initial body weight, relative change in body weight and level of treatment. Regression techniques were used in the analysis of data. This procedures allowed for differentiation between the direct effects and indirect effects of treatment. The direct effect was shown to cause a significant increment in heart weight. The indirect effect as related to loss body weight was shown to lead to a significant decrement in heart weight.

Animals