Search PubMed⌕ Search

Biomedical subjects

R A Guilmette

Publications and source records attributed to R A Guilmette.

At least 19 recordsLinked to original sources
PubMed2001

Effect of flow rate on particle deposition in a replica of a human nasal airway.

Charge-coupled device (CCD) imaging technology was used to observe how the spatial deposition patterns of inhaled aerosols changed as a function of rate of airflow through the airway. This technology allows the experimenter to measure local particle deposition patterns of different sized fluorescent particles at different flow rates in a full-scale multisection replica of a human nasal airway. Total particle deposition efficiencies and particle deposition patterns were measured in the nasal airway for 5.5-microm-diameter particles at constant flow rates of 10, 20, 30, and 40 L/min. Images of fluorescing particles on each plate of the exposed model were taken with a CCD camera and combined to form three-dimensional particle deposition patterns. Total particle deposition efficiency as measured with the model was found to be consistent with in vivo data. Impaction was found to be the dominant mechanism by which 5.5-microm-diameter particles deposit within the model, in agreement with published inhalation data.

Aerosols↗
PubMed1999

Review and critical analysis of available in vitro dissolution tests.

The procedures recommended in Publications 30 and 66 by ICRP for calculating radiation doses from inhaled or ingested radionuclides include classification of material on the basis of different parameters, among which transportability plays a major role, The allocation of transportable Classes or absorption Types should, whenever possible, be based on animal or human data. However, when such in vivo data are unavailable, it becomes appropriate to consider the use of other approaches, among which in vitro dissolution techniques are reasonable alternatives. This paper reviews and critically analyzes in vitro dissolution techniques that have been described historically and recommends methods shown to be useful in estimating the in vivo solubility of radioactive particles.

Administration, Inhalation↗
PubMed1999

Comparative stochastic effects of inhaled alpha- and beta-particle-emitting radionuclides in beagle dogs.

The stochastic effects of inhaled, insoluble particles of alpha- or beta-particle-emitting radionuclides were compared in dogs. Male and female beagle dogs were exposed briefly by nasal inhalation to relatively insoluble aerosols of (239)PuO(2) or (144)Ce in fused aluminosilicate particles (FAP) and observed for cancer for their lifetimes. The initial lung burden and retention of each radionuclide was determined by whole-body counting of the emissions from (144)Ce-(144)Pr- or (169)Yb-labeled (239)PuO(2). Lung doses were calculated for each dog from these data. The lung doses ranged from 0.21 to 1200 Gy for (144)Ce FAP and 1.6 to 58 Gy for (239)PuO(2). Dogs with doses to the lung of about 60 Gy or greater from (144)Ce or about 2 Gy or greater from (239)PuO(2) had an increased incidence of lung carcinomas. In dogs exposed to (144)Ce FAP, three organs were targets for neoplasia: lung, tracheobronchial lymph nodes, and heart. The insoluble FAP carried to the lymph nodes draining the lung delivered high radiation doses to the nodes and adjacent heart, resulting in hemangiosarcomas of these organs. In the lung, high radiation doses induced hemangiosarcomas and carcinosarcomas. At lower doses, carcinomas of various histological patterns were induced in the lung. In dogs exposed to (239)PuO(2), the lung was the sole target organ for neoplasia. Nearly all of these neoplasms were carcinomas of various histological patterns. These results indicated that relatively low doses of alpha-particle radiation can induce pulmonary cancers, but relatively large doses of beta-particle radiation are required. In addition, inhaled beta-particle emitters can also induce cancers in lung-associated lymph nodes and heart at these larger absorbed radiation doses.

Administration, Inhalation↗
PubMed1999

Comparative deterministic effects of inhaled, insoluble alpha- and beta-particle-emitting radionuclides in dogs.

This report compares the deterministic effects from an alpha-particle-emitting radionuclide, (239)PuO(2), and a beta-particle emitter, (144)Ce in fused aluminosilicate particles (FAP). The studies were conducted in beagle dogs of both genders exposed by inhalation to aerosols of the radionuclides. The initial lung burdens of (239)Pu and (144)Ce were determined by whole-body counting of the (169)Yb added to the plutonium aerosol during its preparation or the (144)Ce and its progeny (144)Pr. In addition, organ retention data were obtained from parallel serial sacrifice studies with the same aerosols. After exposure, the dogs were observed for health effects over their lifetime. The deterministic effects observed for both of these relatively insoluble aerosols were lymphopenia, fibrosis, atrophy of the lung-associated lymph nodes, and radiation pneumonitis. Due to the longer half-life of plutonium, the lymphopenia was more prolonged and the clinical course of the radiation pneumonitis more chronic than that resulting from cerium. The greater tissue penetration of the beta-particle emissions from the cerium resulted in more uniform dose distribution over the lung and the atria of the heart than from the alpha-particle emissions from plutonium.

Administration, Inhalation↗
PubMed1999

Measurement of particle deposition patterns in a human nasal airway model using a Charge Coupled Device imaging system.

Charge Coupled Device (CCD) imaging technology is being applied to measure the spatial deposition patterns of inhaled aerosols in the nasal airway. The new technology allows the experimenter to measure local particle deposition patterns of different sized fluorescent particles at variable flow rates in a full-scale multi-section replica of a human nasal airway. Images of fluorescing particles on the exposed model have been taken with a CCD camera and combined to form three-dimensional particle deposition patterns. Total particle deposition efficiencies and particle deposition patterns have been measured in the nasal airway for 6 microns diameter particles and compared with published inhalation data.

Aerosols↗
PubMed1998

Statistical modeling of carcinogenic risks in dogs that inhaled 238PuO2.

Combined analyses of data on 260 life-span beagle dogs that inhaled 238PuO2 at the Inhalation Toxicology Research Institute (ITRI) and at Pacific Northwest National Laboratory (PNNL) were conducted. The hazard functions (age-specific risks) for incidence of lung, bone and liver tumors were modeled as a function of cumulative radiation dose, and estimates of lifetime risks based on the combined data were developed. For lung tumors, linear-quadratic functions provided an adequate fit to the data from both laboratories, and linear functions provided an adequate fit when analyses were restricted to doses less than 20 Gy. The estimated risk coefficients for these functions were significantly larger when based on ITRI data compared to PNNL data, and dosimetry biases are a possible explanation for this difference. There was also evidence that the bone tumor response functions differed for the two laboratories, although these differences occurred primarily at high doses. These functions were clearly nonlinear (even when restricted to average skeletal doses less than 1 Gy), and evidence of radiation-induced bone tumors was found for doses less than 0.5 Gy in both laboratories. Liver tumor risks were similar for the two laboratories, and linear functions provided an adequate fit to these data. Lifetime risk estimates for lung and bone tumors derived from these data had wide confidence intervals, but were consistent with estimates currently used in radiation protection. The dog-based lifetime liver tumor risk estimate was an order of magnitude larger than that used in radiation protection, but the latter also carries large uncertainties. The application of common statistical methodology to data from two studies has allowed the identification of differences in these studies and has provided a basis for common risk estimates based on both data sets.

Administration, Inhalation↗
PubMed1997

A biokinetic model for 137Cs.

An improved biokinetic model for 137Cs in humans was developed based on an analysis of data obtained from individuals internally contaminated during an accident in Goiania, Brazil, and other data. Seventeen children (ten girls and seven boys 1-10 y old), ten adolescents (four females and six males), and thirty adults, (fifteen females and fifteen males contaminated in the accident in Goiânia contributed to this study. 137Cs retention was determined through periodic measurements in a whole-body counter. In addition to the data on 137Cs retention from these individuals, data from a study on the metabolism of 137Cs in immature, adult, and aged Beagle dogs and data from the literature were used in the formulation of the 137Cs biokinetic model presented. Mathematically, the retention of cesium is described by three exponential terms, and the retention model is based on a step function of body weight. When the ICRP Publication 56 model for cesium was compared to the model suggested in this paper, it was determined that the ICRP model predicts lower effective doses in 5-y-old children and higher effective doses in infants, adolescents, and adults.

Adolescent↗
PubMed1997

Dose responses from inhaled monodisperse aerosols of 244Cm2O3 in the lung, liver and skeleton of F344 rats and comparison with 239PuO2.

The purpose of this study was to obtain information on the alpha-particle dose-response relationship of 244Cm in rats. Rats were exposed briefly by inhalation to graded levels of monodisperse aerosols of 244Cm2O3 heat-treated at 1150 degrees C. The initial lung burden (ILB) of each animal was determined by the use of the gamma-ray-emitting radionuclide 243Cm in the aerosols. Seven groups of 84-day-old F344/Crl rats (a total of 637 males and 645 females) were exposed once to 244Cm2O3 or sham-exposed to filtered ambient air. Mean ILBs of all rats per group ranged from 0.51 +/- 0.17 (+/-SD) to 240 +/- 82 kBq kg-1 body weight. Mean lifetime alpha-particle doses to the lungs per group ranged from 0.20 +/- 0.069 (+/-SD) to 36 +/- 6.5 Gy. After death, each rat was radiographed and necropsied. Dose-related increases occurred in incidences of benign and malignant lung neoplasms, except for the groups of rats with higher mean ILBs that were examined histologically (98 +/- 18 and 240 +/- 77 kBq kg-1 body weight) in which survival was markedly decreased. Also, average alpha-particle doses of 0.0014 +/- 0.00058 (+/-SD) to 0.17 +/- 0.091 Gy and 0.18 +/- 0.007 to 1.6 +/- 1.1 Gy were also absorbed by the liver and skeleton, respectively, in the rats in the different exposure groups. Primary liver neoplasms occurred in several rats. However, the incidence of these lesions was not related to dose. Increased incidences of bone neoplasms occurred only in rats receiving higher doses to the skeleton. Excess numbers of rats with lung neoplasms per 10(4) Gy to the lung per group ranged from 760 +/- 430 (+/- SE) at a mean dose of 0.48 Gy to 84 +/- 16 at a mean dose of 37 Gy. Risk factors for the lowest and highest ILB kg-1 body weight groups were not considered reliable because of large errors associated with these calculations and the life-span shortening in the highest ILB kg-1 group. Inhaled 244Cm2O3 appeared to be about 50% less effective as a lung carcinogen in rats compared to 239PuO2 at similar doses.

Aerosols↗
PubMed1996

Prussian Blue decorporation of 137Cs in beagles of different ages.

A 6-wk study was conducted using immature (4.7 mo), young adult (2.4 y), and aged (13.5 y) male beagles to determine the modifying effect of age on the effectiveness of Prussian Blue decorporation therapy for the removal of injected 137Cs. Whole-body clearance rates for injected 137Cs decreased with increasing age in the dogs. Treatment with Prussian Blue changed the ratio of fecal to urinary 137Cs excretion from 0.8 in untreated dogs to 2.2 in treated animals. The 137Cs concentrations in tissues of untreated and Prussian Blue-treated dogs at the end of the 6-wk study were similar, with the greatest concentrations in the skeletal muscle tissue, spleen, and kidneys. There was a lower concentration of 137Cs in the livers of the treated dogs. The reductions in the average total whole-body doses resulting from Prussian Blue treatment during the course of this study were 51% in the immature, 31% in the young adult, and 38% in the aged dogs. Because of the differences in the intake of Prussian Blue by the dogs in the different groups relative to their body weight, it is unclear as to the relative effectiveness of Prussian Blue in dogs of different ages.

Age Factors↗
PubMed1996

Toxicity of inhaled plutonium dioxide in beagle dogs.

This study was conducted to determine the biological effects of inhaled 238PuO2 over the life spans of 144 beagle dogs. The dogs inhaled one of two sizes of monodisperse aerosols of 238PuO2 to achieve graded levels of initial lung burden (ILB). The aerosols also contained 169Yb to provide a gamma-ray-emitting label for the 238Pu inhaled by each dog. Excreta were collected periodically over each dog's life span to estimate plutonium excretion; at death, the tissues were analyzed radiochemically for plutonium activity. The tissue content and the amount of plutonium excreted were used to estimate the ILB. These data for each dog were used in a dosimetry model to estimate tissue doses. The lung, skeleton and liver received the highest alpha-particle doses, ranging from 0.16-68 Gy for the lung, 0.08-8.7 Gy for the skeleton and 0.18-19 for the liver. At death all dogs were necropsied, and all organs and lesions were sampled and examined by histopathology. Findings of non-neoplastic changes included neutropenia and lymphopenia that developed in a dose-related fashion soon after inhalation exposure. These effects persisted for up to 5 years in some animals, but no other health effects could be related to the blood changes observed. Radiation pneumonitis was observed among the dogs with the highest ILBs. Deaths from radiation pneumonitis occurred from 1.5 to 5.4 years after exposure. Tumors of the lung, skeleton and liver occurred beginning at about 3 years after exposure. Bone tumors found in 93 dogs were the most common cause of death. Lung tumors found in 46 dogs were the second most common cause of death. Liver tumors, which were found in 20 dogs but were the cause of death in only two dogs, occurred later than the tumors in bone and lung. Tumors in these three organs often occurred in the same animal and were competing causes of death. These findings in dogs suggest that similar dose-related biological effects could be expected in humans accidentally exposed to 238PuO2.

Administration, Inhalation↗
PubMed1995

Application of a canine 238Pu biokinetics/dosimetry model to human bioassay data.

Associated with the use of 238Pu in thermoelectric power sources for space probes is the potential for human exposure, primarily by inhalation and most likely as 238PuO2. Several models have been developed for assessing the level of intake and predicting the resulting radiation dose following human exposure to 239Pu. However, there are indications that existing models do not adequately describe the disposition and dosimetry of 238Pu following human exposure. In this study, a canine model that accounts for these differences has been adapted for use with human excretion data. The model is based on existing knowledge about organ retention of plutonium. An analysis of the sensitivity of the model to changes in aerosol-associated properties indicated that predictions of urinary excretion are most sensitive to changes in particle solubility and diameter and in the ratio of fragment:particle surface area. Application of the model to urinary excretion data from seven workers exposed to a 238Pu ceramic aerosol gave estimated intakes of 390-8,200 Bq and associated initial pulmonary burdens of 80-1,700 Bq. The resulting 50-y dose commitments to critical organs per Bq of 238Pu intake were estimated to be 0.5 mSv for the thoracic region, 0.2 mSv for the liver, and 1 mSv for the bone surfaces.

Animals↗
PubMed1993

Decorporation therapy for inhaled plutonium nitrate using repeatedly and continuously administered DTPA.

Decorporation therapy is the only known effective method of reducing the radiation dose to persons accidentally contaminated internally with radionuclides. Deposition of actinides in bone must be minimized because osteosarcoma appears to be the most likely pathological effect arising from systemic exposure. In previous studies, beagle dogs inhaled moderately soluble Am and Cm oxide aerosols and were then treated with diethylenetriaminepentaacetic acid (DTPA), either by repeated intravenous injection or by continuous infusion. The latter therapy was more effective in removing the actinides from the body. In this complementary study, dogs inhaled a polydisperse aerosol of 238Pu(NO3)4 and were treated as before using a single initial injection of CaDTPA (30 mumol kg-1) followed with either repeated intravenous injections of ZnDTPA (30 mumol kg-1 injection) or with subcutaneous infusion of ZnDTPA (30 or 120 mumol kg-1 day-1). Each treatment regimen commenced at 1 h after exposure and continued throughout 64 days, whereupon all animals were killed, and tissue samples and collected excreta samples were analysed radiochemically for their Pu contents. Unlike the results of previous studies with Am and Cm, in which the actinide dissolved in vivo over periods of many days to weeks, no significant differences in decorporation efficiency of 238Pu were noted for the three different DTPA-treated groups. All treatments removed about 85% of the initial pulmonary burden (IPB) of 238Pu compared with 24% IPB excreted by the saline-treated control dogs. The lack of additional effectiveness of the continuously infused DTPA was attributed to the high, initial in vivo solubility of the Pu nitrate aerosol used in this study. This resulted in a relatively rapid systemic uptake of Pu and translocation to liver, skeleton, and muscle/connective tissue, where it was less available to the longer-term action of DTPA.

Administration, Inhalation↗
PubMed1992

Long-term consequences of 239PuO2 exposure in dogs: persistent T lymphocyte dysfunction.

Young Beagle dogs were exposed by inhalation to aerosols of 239PuO2 and observed for their lifespans as part of a large, ongoing study of the biological effects of inhaled radionuclides. The purpose of our study was to compare certain immune responses of the 239PuO2-exposed dogs at middle age (7-10 years old) and old age (12-14 years old), with those of unexposed, age-matched or young (3-4 years old) animals. Some of the aged, exposed dogs had developed lung tumours. Lymphocyte proliferative responses to phytohaemagglutinin (PHA) were lower in aged control dogs than in either young or middle-aged control dogs. Both aged and middle-aged, radiation-exposed dogs had decreased responses to PHA when compared to age-matched controls. Responses to concanavalin A (Con A) were not affected by age in control dogs, but tended to decrease in the oldest group of radiation-exposed dogs. Responses to both PHA and Con A were severely depressed in tumour-bearing dogs. The cytolytic activity of natural killer cells was not affected by age, radiation exposure, or tumour presence. We concluded that inhalation of 239PuO2 by young Beagle dogs resulted in an earlier-than-normal decrease in the ability of T cells to respond to mitogenic stimulation. In other words the depressed responses to PHA that were observed might represent radiation-induced, accelerated ageing of the T cell response.

Administration, Inhalation↗
PubMed1992

Effectiveness of continuously infused DTPA therapy in reducing the radiation dose from inhaled 244Cm2O3 aerosols.

Radionuclide decorporation is the only effective method of reducing radiation dose for persons contaminated accidentally. In this study, dogs that had inhaled a moderately soluble aerosol of 244Cm2O3 were treated with either discrete intravenous injections of the chelating agent diethylenetriaminepentaacetic acid (Zn-DTPA) or with subcutaneous infusion of Zn-DTPA at either 30 or 120 mumol kg-1 d-1. Each treatment regimen was continued for 64 d, whereupon all animals were killed, and collected excreta and tissue samples were analyzed for curium. All DTPA treatment methods were effective. A total of 89% of the initial pulmonary burden (IPB) was removed by DTPA injection, whereas 94% IPB was removed by the low dose of infused DTPA and 97% by the high dose treatment. Thus, low and high infused doses of DTPA prevented the translocation of greater than 99.5% of curium to liver and 97-99% to bone and kidney. The resultant dose reductions to these organs were superior to those achieved by intravenous DTPA injections.

Administration, Inhalation↗
PubMed1992

In vitro dissolution of curium oxide using a phagolysosomal simulant solvent system.

Detailed study of actinide oxide behavior in alveolar macrophages (AM) in vitro is limited because of the short life span of these cells in culture. We created an in vitro dissolution system that could mimic the acidic phagolysosomal environment for the actinide and be maintained for an indefinite period so that dissolution of more insoluble materials could be measured. The dissolution system for this investigation, consisting of nine different solutions of HCl and the chelating agent diethylenetriamine pentaacetate (DTPA) in distilled water, is called the phagolysosomal simulant solvent (PSS). In this system, both the pH and the amount of DTPA were varied. We could observe the effect of altering pH within a range of 4.0-6.0 (similar to that of the phagolysosome) and the effect of the molar ratio of DTPA to curium at 1000:1, 100:1, or 10:1. We chose curium sequioxide (244Cm2O3) to validate the PSS for actinide dissolution versus that occurring in AM in vitro because it dissolves significantly in less than 1 week. The polydisperse 244Cm2O3) aerosol was generated, collected on filters, resuspended, and added to the PSS solutions and to cultured canine AM. By comparing dissolution in the two systems directly, we hoped to arrive at an optimum PSS for future dissolution studies. PSS and cell culture samples were taken daily for 7 days after exposure and tested for the solubilized curium. The amount of soluble material was determined by ultracentrifugation to separate the insoluble Cm2O3 from the soluble curium in the PSS solutions and filtration for the cell-containing material.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Distribution and biological effects of inhaled 239Pu(NO3)4 in cynomolgus monkeys.

Twenty male cynomolgus monkeys were exposed by inhalation either to an aerosol of 239Pu(NO3)4 to produce projected initial lung burdens of either 40, 10, or 4 kBq or to a carrier aerosol as a control. Animals died or were sacrificed at 0.01, 1, 3, 6, 12, 24, 40, and 99 months after inhalation, and the distribution and biological effects of the 239Pu were determined. The 239Pu cleared efficiently from the lungs so that less than 0.05 kBq remained at 99 months after exposure to 40 kBq. Total skeletal 239Pu activity was nearly constant after the first year, but the fraction of the body burden in skeleton at sacrifice increased with time up to 99 months because of clearance from other organs. Plutonium in the liver increased to a peak at 1 year and then decreased to about 10% of the peak value at 99 months. Plutonium in the testes was localized in the interstitial tissue with only 0.01 to 0.002% of the projected lung burden remaining in testes at 99 months after inhalation. Three animals exposed to 40 kBq of 239Pu died of radiation-related pulmonary pneumonitis and fibrosis. A primary papillary adenocarcinoma of the lung was identified in one animal exposed to 40 kBq initial lung burden and sacrificed 99 months after inhalation. The frequency of chromosome aberrations in blood lymphocytes was significantly elevated only in monkeys with projected deposits of 40 kBq of 239Pu. There was no change in aberration frequency in other exposure groups as a function of inhaled activity, time after exposure, or calculated total dose to the lungs. Only in monkeys that had marked radiation-induced pathological changes in the lung did the frequency of chromosome-type aberrations increase significantly, to a value about twice the control level. In cynomolgus monkeys, chromosome aberration frequency in blood lymphocytes is not a good indicator of radiation dose or damage from inhaled soluble plutonium.

Administration, Inhalation↗
PubMed1992

Influence of dose rate on survival time for 239PuO2-induced radiation pneumonitis or pulmonary fibrosis in dogs.

Beagle dogs were exposed once or repeatedly to 0.75-microns-diameter monodisperse aerosols of 239PuO2 by pernasal inhalation. The dogs that were exposed once received alveolar depositions (+/- standard deviation) of 3.9 +/- 1.9 kBq/kg body mass and accumulated doses of 23 +/- 8 Gy to the lung before death at 5.4 +/- 1.7 years after exposure. Dogs exposed repeatedly received a total alveolar deposition of 5.3 +/- 0.9 kBq/kg body mass during 7 to 10 semiannual exposures and accumulated doses of 22 +/- 5 Gy to the lung before death at 4.9 +/- 0.7 years after first exposure. Clearance of the plutonium from the lung in the dogs exposed repeatedly was slower than in the dogs exposed once. All dogs in the repeated-exposure study and all but one dog in the single-exposure study died from radiation effects. Pulmonary fibrosis accounted for 72% of the radiation-related deaths in the single-exposure study and 87% in the repeated-exposure study. The remaining dogs died with pulmonary cancer. Based on total cumulative radiation dose, the times after exposure to death from radiation pneumonitis and pulmonary fibrosis were not significantly different for single and repeated exposures. Thus dose rate does not appear to be an important factor in predicting death from radiation pneumonitis or pulmonary fibrosis for dogs inhaling 239PuO2.

Administration, Inhalation↗