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Biomedical subjects

K E McDonald

Publications and source records attributed to K E McDonald.

At least 19 recordsLinked to original sources
PubMed1998

Lowland gorillas and seed dispersal: the importance of nest sites.

Lowland gorillas eat the fruit and disperse the seeds of many tree species in the Lopé Reserve, Gabon. This study aimed to show whether deposition of seeds at gorilla ground nest sites conferred any advantage for germination and seedling establishment as compared to the fate of seeds deposited in gorilla dung on trails or under parents. Four tree species were chosen for study, which had a range of fruit types and fruiting patterns but which were all important foods for gorillas. Data showed that gorillas removed significant quantities of seeds from all four species and deposited them in dung at nest sites or on trail. Nest sites were not always favorable for germination, but the most favorable sites permitted the best survival and growth of any of the seedlings, including those deposited in dung on trail or scatter-dispersed under or away from parent canopies. Initial performance in the first few weeks after deposition was not always indicative of long-term survival and growth, so data collection over 1-2 years was absolutely essential. The main factors affecting seedling fate at nest sites appeared to be vegetation cover and desiccation. It is suggested that the nesting habits of gorillas are an additional factor encouraging the successful establishment of seedlings over and above the obvious advantages of large body size, gut capacity, and extended day ranges.

Animals↗
PubMed1993

Lifespan studies in rats exposed to 239PuO2 aerosol. III. Survival and lung tumours.

Female, young adult, Wistar rats were given a single inhalation exposure to a submicron sized aerosol of high-fired 239PuO2 and observed during their lifespan for primary lung tumours. Rats were distributed among sham-control (n = 1052) and exposed (n = 2105) groups. Survival was significantly reduced only in rats with lung doses > 30 Gy. A total of 99 primary lung tumours were found, of which 92% were malignant and 80% were carcinomas. Of malignant lung tumours, 49 were squamous cell carcinoma, 23 adenocarcinoma, nine hemangiosarcoma, seven adenosquamous carcinoma, and three fibrosarcoma. One adenocarcinoma was found in controls and only four adenomas were seen in the exposed rat at lung doses < 1.5 Gy. The lowest doses at which lung tumours appeared in exposed rats were 1.5 Gy for squamous cell carcinoma, 3.1 Gy for adenocarcinoma. 4.1 Gy for hemangiosarcoma, and about 9 Gy for adenosquamous carcinoma and fibrosarcoma. Pulmonary squamous metaplasia was not seen in controls and was first seen in exposed rats only at lung doses > 1 Gy. Primary lung tumours were the presumed cause of death (fatal) in 60% of rats with malignant lung tumours; causes of death were equally distributed among all tumour types and doses. The incidence of all lung tumours was 0.095% in control rats, 0.21% in 1877 rats with lung doses < 1 Gy, and 41% in 228 rats with doses > 1 Gy. Lung tumour incidence increased in a linear manner from 6.9% at 2.3 Gy to an incidence of 64-88% at 16-44 Gy. Absolute malignant lung tumour risk averaged 270 lung tumours per 10(4) rat-Gy above a lung dose of 1 Gy. All types of malignant lung tumours induced by inhaled 239PuO2 exhibited a threshold at a lung dose > 1 Gy.

Adenocarcinoma↗
PubMed1993

Lifespan studies in rats exposed to 239PuO2 aerosol.

Spatial-temporal dose-distribution patterns in the lung continually change following inhalation of radionuclides. Lung clearance, microdosimetry, and radiation dose were examined in female Wistar rats exposed to high-fired 169Yb2O3-239PuO2 aerosols. Whole-body counting for 169Yb at 14 d postexposure provided an accurate (r = 0.99) estimate of 239Pu lung content. Alpha irradiation of tracheal epithelium was at least 50 times less than for bronchiolar epithelium due principally to preferential retention of 239PuO2 in peribronchiolar alveoli as compared to other alveolar regions. The formation of large aggregates (> 25 particles) increased linearly with initial lung burden starting at 0.4 kBq; mean dose rate to these focal alveolar regions was 120 Gy d-1. Concentration of 239PuO2 in pulmonary macrophages and in aggregates, along with the limited penetration of alpha particles in tissue, resulted in a highly nonhomogeneous dose distribution pattern. Alveolar clearance was best represented by a biphasic clearance curve comprised of a rapid early phase (80% initial lung burden) and a slow late phase (20% initial lung burden). Studies with intratracheally instilled 237PuO2-239PuO2 and with inhaled 239PuO2 showed that alveolar clearance was inversely proportional to initial lung burden. A single clearance function was derived from experimentally determined clearance curves for inhaled 239PuO2 that was used to accurately estimate lung dose at all initial lung burden levels. Lung doses were calculated for 2,105 exposed lifespan rats based on individually determined initial lung burden, survival time, and individually computed clearance function.

Administration, Inhalation↗
PubMed1991

Retrospective review of chemotherapy for small cell lung cancer in the elderly: does the end justify the means?

Between 1978 and 1983, 72 patients aged 70 years or older (median 72, range 70-80) were treated for biopsy-proven, small cell lung cancer (SCLC). Intercurrent disorders were common, including ischaemic heart disease, peripheral vascular disease, chronic airflow limitation and second malignancies. 26 patients (36%) had limited extent of disease, and 46 (64%) had extensive disease. "Intensive" chemotherapy incorporating vincristine, cyclophosphamide and doxorubicin (OCA regimen) was administered to 32 patients [complete response (CR) + partial response (PR) = 84%]; less rigorous regimens (e.g. single agent chemotherapy, planned dose reductions, radiotherapy only) were used in 34 cases (CR + PR = 52%); and 6 received no active treatment. In the intensively treated group, there were 3 treatment-related deaths and 26 episodes of WHO grade 3-4 toxicity. In the less intensively treated group, there were no treatment-induced deaths and only 1 episode of severe toxicity. The overall median survival was 25 weeks (36 weeks for intensive treatment, 16 weeks with less intense treatment). For patients with limited disease only, the median survival in each group was 43 and 26 weeks, respectively. Intensive treatment for elderly patients with small cell lung cancer is associated with substantially increased toxicity and higher response rates than for gentle treatment, but without a major survival benefit.

Age Factors↗
PubMed1990

Pulmonary carcinogenesis in rats given implants of shale oil in beeswax pellets.

Pellets of crude shale oil, neutral, basic, or polynuclear aromatic fractions of shale oil, or crude petroleum were implanted in the lungs of rats through a thoracotomy. The pellets had a beeswax-tricaprylin vehicle that allowed the slow release of material into the surrounding parenchyma. A dose-related incidence of lung cancer was observed with each of the materials studies. A greater risk for lung cancer was not demonstrated for crude shale oil compared to crude petroleum.

Animals↗
PubMed1989

Quantitative scanning electron microscopic autoradiography of inhaled 239PuO2.

We have applied the scanning electron microscope (SEM) to obtain autoradiographs of particles of 239PuO2 deposited in rat lung. The technique was used to obtain quantitative information on the clearance rates of particles from the alveoli, bronchioles and trachea up to 240 d after exposure. At all times, the concentration of particles on the surface of the bronchioles was an order of magnitude greater than on the tracheal surface. The clearance of Pu from both regions followed a biphasic pattern, similar to that obtained by radiometric analysis of the whole lung. Most of the radiation dose to the bronchiolar epithelium originated from Pu particles in peribronchiolar alveoli in which they were preferentially retained, compared to other alveolar regions. The prolonged retention of particles in the peribronchiolar alveoli may be a significant factor in the induction of lung carcinomas.

Administration, Inhalation↗
PubMed1989

Tritiated thymidine-labeled bronchioloalveolar cells and radiation dose following inhalation of plutonium in rats.

The goal of this study is to show the relationship of inhaled Pu particle distribution and alveolar-bronchiolar target-cell response with respect to the formation of pulmonary carcinoma. The proliferation of type 2 alveolar epithelium and nonciliated bronchiolar epithelium appears critical in the induction of lung tumors associated from inhaled 239PuO2. Female, Wistar rats were either sham-exposed (40 rats) or given a single inhalation to 169Yb-239PuO2 (99 rats, ILB, 3.9 +/- 1.2 kBq) and examined at 20 time intervals from 1 day to 700 days postexposure for Pu particle distribution in airways by SEM quantitative autoradiography and for cell labeling with tritiated thymidine. Initially, deposited Pu particles were rapidly cleared from the surface of the trachea, bronchi, and bronchioles within a few days. Thereafter, about 5 times more alpha track exposure to the bronchiolar epithelium was delivered from Pu particles found in peribronchiolar alveoli than from Pu particles being cleared from bronchiolar surfaces. Exposure of bronchiolar epithelium at later times was due mostly to the formation of peribronchiolar Pu particle aggregates. A maximal increase in labeled alveolar wall cells was seen at 60 days after exposure, decreasing gradually to control levels by 400 days. Cell labeling in focal alveolar regions of Pu aggregation was about 5 fold higher. Increased bronchiolar epithelium labeling appeared in two phases. The first phase was seen 15 days after exposure, associated with initial deposition and clearance of Pu particles. The second phase slowly reached a maximum at 250 days and was associated with peribronchiolar Pu aggregate formation. The temporal-spatial dose-distribution pattern for inhaled Pu particles is an important aspect of Pu-induced pulmonary carcinogenesis.

Administration, Inhalation↗
PubMed1989

Scanning electron microscopy of lung following alpha irradiation.

Pulmonary aggregation of inhaled 239PuO2 particles leads to a cellular evolution of focal inflammation, fibrosis, epithelial dysplasia and lung tumor formation. Female Wistar rats were exposed to an aerosol of high-fired 239PuO2 (initial lung burden, 3.9 kBq) and the lungs examined at intervals from 1 day to 700 days after exposure by light and scanning electron microscopy and autoradiography. Peribronchiolar Pu particle aggregation increased with time, resulting in well-defined focal inflammatory lesions after 120 days and fibrotic lesions after 180 days. A generalized hypertrophy and hyperplasia of nonciliated bronchiolar cells was seen at 15 days and type II cell hyperplasia by 30 days after exposure. Focal dysplastic changes in type II alveolar epithelium and terminal nonciliated bronchiolar epithelium preceded carcinoma formation. Alveolar bronchiolarization was first noted at 120 days, squamous metaplasia at 210 days, squamous carcinoma at 270 days and adenocarcinoma at 600 days after exposure.

Alpha Particles↗
PubMed1988

SEM autoradiography: aggregation of inhaled 239PuO2.

Aggregation of inhaled 239PuO2 particles in the pulmonary region of the lung may be required for promotion of pulmonary carcinogenesis in rats. Female Wistar rats were exposed to an aerosol of 239PuO2 and their lungs examined by scanning electron microscopic (SEM) autoradiography. SEM autoradiography provides a rapid and inexpensive method for viewing a large lung tissue volume for alpha tracks. Evidence of particle aggregation was seen by 28 days postinhalation and was marked by 90 to 150 days post-inhalation. Subpleural plutonium particles resulted in exposure into the pleural cavity. Peribronchiolar, alveolar plutonium particles and particle aggregates gave the greatest radiation dose to the bronchiolar epithelium. High-dose, overlapping, alpha-track, radiation zones in bronchiolar epithelium may be required for maximum development of lung tumors.

Administration, Inhalation↗
PubMed1988

Lung tumor response to inhaled Pu and its implications for radiation protection.

Multistage models of cancer induction have been accepted in chemical and radiation carcinogenesis for many years. Most models assume that both initiating and promoting events are required for greatest expression of tumor incidence. The sequence of events is important in determining the shape of the dose-response curve. A total of 1058 female, SPF, Wistar, sham-exposed rats and 2134 rats given a single inhalation to 169Yb, 239PuO2 are being studied for lung tumor formation in a life-span study. Histopathological analyses have been completed on 1149 rats. Similar dose-response curves are seen for pulmonary fibrosis pulmonary metaplasia and lung tumor formation. Lung tumor incidences were: 0.6% (0 Gy), 0.5% (0.06 Gy), 0% (0.11 Gy), 0% (0.23 Gy), 4.5% (0.46 Gy), 0% (0.84 Gy), 13.8% (1.9 Gy), 18.6% (3.5 Gy), 72.5% (7.4 Gy), and 84.9% (15 Gy). The dose lung-tumor curve was best fit by a quadratic function and was not well fit by a linear function. It is proposed that the low-dose portion of the quadratic curve represents promotion event(s) due to increasing 239PuO2 particle clustering in subpleural regions, leading to a cellular evolution of focally intense inflammation, fibrosis, epithelial metaplasia and carcinoma formation. A defined, practical threshold dose may be useful with respect to setting radiation protection guidelines for lung tumor induction.

Administration, Inhalation↗
PubMed1988

Scanning electron microscopic autoradiography of lung.

Scanning electron microscopic (SEM) autoradiography of the lung is being used to determine the distribution of inhaled, alpha particle-emitting, plutonium dioxide particles. SEM autoradiography provides high visual impact views of alpha activity. Particles irradiating the bronchiolar epithelium were detected both on the bronchiolar surface and in peribronchiolar alveoli. The technique is being used to obtain quantitative data on the clearance rates of plutonium particles from bronchi and bronchioles.

Animals↗
PubMed1988

Promotion of pulmonary carcinogenesis by plutonium particle aggregation following inhalation of 239PuO2.

Promotion of lung tumor formation from inhaled 239PuO2 in rats may be associated with aggregation of plutonium particles near bronchioles. The relationship of plutonium particle aggregation in the lung and the development of lung tumors after inhalation of 239PuO2 was studied in 664 life span rats with mean lung doses ranging from 0.35 to 20 Gy. Plutonium particle concentration and aggregation were determined from autoradiographic sections of the left lung lobe. The increase in particles/cm2 and mean number of particles per aggregate up to 20 Gy were directly proportional to lung dose. Aggregates with greater than 25 particles increased linearly with dose from 0.2% at 1.4 Gy to 8.2% at 20 Gy, in a pattern similar to increasing severity of pulmonary fibrosis and incidence of lung tumors. Lung tumor incidence increased from about 6% at 1.4 Gy to 83% at 8 Gy; no further increase in lung tumors was seen at doses greater than 8 Gy. Maximum lung tumor incidence at 8 Gy corresponded to a particle concentration of 130/cm2 and four particles/aggregate with 4% of aggregates having greater than 25 particles. Aggregation of inhaled plutonium particles in clusters of greater than 25 particles resulted in daily doses of only a few centigray to focal tissue regions containing clustered particles, yet these doses appeared sufficient to cause pulmonary fibrosis and promotion of pulmonary carcinogenesis.

Administration, Inhalation↗
PubMed1984

Experimental pulmonary emphysema induced in the rat by intratracheally administered elastase: morphogenesis.

Emphysema was produced experimentally in rats by administration of porcine pancreatic elastase at dose levels of 75, 100, 125, and 150 units elastase activity/100 g body wt. All doses studied were equally effective in producing emphysema. Dose levels of over 75 units activity/100 g offered no advantage in terms of degree or severity of emphysema produced; however, such doses exacerbated hemorrhage and edema, resulting in relatively high post-instillation mortality. Lesion morphogenesis at all doses tested paralleled those described in this and in other species by other investigators. The 75-unit activity produced a quantifiable degree of emphysema which was relatively constant among animals. Results suggest that because of group differences in susceptibility to elastase (or variations in batches of elastase), dose-range studies should be performed on each new group of animals.

Animals↗
PubMed1983

Pathologic effects in rodents exposed to sodium combustion products.

Three species of rodents exhibited respiratory distress when exposed to aerosols of sodium combustion products, the major constituent of which was shown to be sodium carbonate. At the higher doses, animals died during or shortly after 2 hr exposures. Lesions, primarily involving the pharynx and larynx, included accumulation of mucus, vesiculation, and mucosal edema. Other lesions included edema and vesiculation of the anterior trachea, hemorrhage in the lungs, and severe gastric tympany. Basal epithelial cells of the posterior pharynx and anterior trachea had enlarged mitochondria following exposures of 1 hr or more.

Animals↗
PubMed1983

The flow-past chamber: an improved nose-only exposure system for rodents.

We have designed a nose-only inhalation exposure chamber in which fresh aerosol is flowed past each exposure port and exhaled air is immediately exhausted. This allows all animals in the chamber to be exposed to the same aerosol concentration. In tests comparing initial lung burdens (ILB) of animals exposed in a standard chamber with those of animals exposed in the flow-past chamber, coefficients of variation in ILBs were significantly smaller for the latter.

Aerosols↗
PubMed1978

Mechanism of effect of hypoxia on renal water excretion.

The effect of lowering the pressure of oxygen from 80 to 34 mm Hg was examined in anesthetized dogs that were undergoing a water diuresis. This degree of hypoxia was associated with an antidiuresis as urine osmolality (Uosm) increased from 107 to 316 mosmol/kg H(2)O (P < 0.001) and plasma arginine vasopressin increased from 0.06 to 7.5 muU/ml, (P < 0.05). However, hypoxia was not associated with significant changes in cardiac output (CO, from 4.2 to 4.7 liters/ min), mean arterial pressure (MAP, from 143 to 149 mm Hg), glomerular filtration rate (GFR, from 46 to 42 ml/min), solute excretion rate (SV, from 302 to 297 mosmol/min), or filtration fraction (from 0.26 to 0.27, NS). Hypoxia was associated with an increase in renal vascular resistance (from 0.49 to 0.58 mm Hg/ml per min, P < 0.01). The magnitude of hypoxia-induced antidiuresis was the same in innervated kidneys and denervated kidneys. To further examine the role of vasopressin in this antidiuresis, hypoxia was induced in hypophysectomized animals. The effect of hypoxia on CO, MAP, GFR, SV, and renal blood flow in hypophysectomized animals was the same as in intact animals. In contrast to intact animals, however, hypoxia did not induce a significant antidiuresis in hypophysectomized animals (Uosm from 72 to 82 mosmol/kg H(2)O). To delineate the afferent pathway for hypoxia-stimulated vasopressin release, hypoxia was induced in dogs with either chemo- or baroreceptor denervation. The effect of hypoxia on CO, MAP, GFR, SV, and renal blood flow in the denervated animals was the same as in nondenervated animals. Hypoxia resulted in an antidiuresis in chemoreceptor (Uosm from 113 to 357 mosmol/kg H(2)O, P < 0.001) but not in baroreceptor (Uosm from 116 to 138 mosmol/kg H(2)O, NS) denervated animals. To determine if hypoxia alters renal response to vasopressin, exogenous vasopressin was administered to normoxic and hypoxic groups of dogs. The antidiuretic effect of vasopressin was no different in these two groups. These results demonstrate that hypoxia induces an antidiuresis which is independent of alterations in CO, MAP, SV, filtration fraction, renal nerves, or renal response to vasopressin and occurs through baroreceptor-mediated vasopressin release. The nature of the baroreceptor stimulation remains to be elucidated.

Animals↗
PubMed1978

Pulmonary carcinogenesis in rats given implants of cigarette smoke condensate in beeswax pellets.

Lungs of inbred OM/NCR and outbred Sprague-Dawley rats were given implants, through a thoracotomy, of pellets of cigarette smoke condensate (CSC) suspended in a beeswax-tricaprylin vehicle. The pellets slowly released material into the surrounding parenchyma, which resulted in a dose-related increased incidence of lung cancer, predominantly invasive and metastasizing epidermoid carcinoma. A 42% prevalence of pulmonary carcinoma was present in the highest dosage group, which received 67 mg CSC, exposing approximately 1.65 cm2 bronchiolar epithelium. Squamous metaplasia associated with the implanted site preceded the appearance of the carcinomas and was more severe, with the larger pellets having more concentrated CSC. No difference was observed in incidence of pulmonary carcinomas with the use of CSC containing high or low concentrations of nicotine. The potential value of this bioassay system were discussed.

Animals↗