Search PubMed⌕ Search

Biomedical subjects

B R Scott

Publications and source records attributed to B R Scott.

At least 37 records · Page 2Linked to original sources
PubMed1995

Posterior interosseous nerve palsy in a machine gunner.

We report the case of a 19-year-old Infantryman who developed posterior interosseous nerve palsy and a transient sensory deficit in a radial distribution after prolonged carrying of an M60 machine gun. Posterior interosseous nerve palsy has been reported in association with a variety of activities involving forceful, repetitive pronation and supination; however, to our knowledge, no previous cases of this palsy have been reported in association with use of a military weapon.

Adult↗
PubMed1995

Pulmonary carcinogenicity of repeated inhalation exposure of rats to aerosols of 239PuO2.

To study the long-term biological effects of repeated inhalation exposure to 239PuO2, 84-day-old rats were exposed to aerosols of 239PuO2 to re-establish desired 239Pu lung burdens of 26, 80 or 250 Bq every other month for 1 year (seven exposures). Other rats were exposed once at 84 or 450 days of age to achieve desired initial lung burdens of 30, 90, 280 or 850 Bq. The incidences of lung tumors were not significantly different (Fisher's exact test; P > 0.05) in groups of rats with similar lifetime mean alpha-particle doses to the lungs of 0.90 +/- 0.39 to 4.4 +/- 1.8 (+/- SD) Gy, whether exposed once or repeatedly. Among rats with mean alpha-particle doses of 12 +/- 2.4 to 10 +/- 2.1 Gy to the lungs after single or repeated exposures, respectively, the crude incidence of lung tumors was significantly less (Fisher's exact test; P < 0.05) in the rats exposed repeatedly. Times to death of rats with lung tumors were compared among groups with similar alpha-particle doses to the lungs after single or repeated exposure to 239PuO2. Those that died with lung tumors after repeated exposures died at times similar to (Mantel-Cox statistic; P > 0.05) or later than (Mantel-Cox statistic; P < 0.05) those for 84-day-old rats exposed once. The risk of lung tumors in rats per unit dose to the lungs was less in the rats exposed repeatedly than in those exposed once. It was concluded that alpha-particle doses to the lung of rats exposed repeatedly to aerosols of 239PuO2 were not more carcinogenic and possibly were less carcinogenic than the dose after a single inhalation exposure when rats with similar lifetime alpha-particle doses to the lungs were compared. The relative biological effectiveness in rats of the alpha-particle dose to the lungs from inhaled 239PuO2 relative to beta-particle doses to the lungs from inhaled 144CeO2 was 21 +/- 3.

Administration, Inhalation↗
PubMed1993

Effect of cumulative exposure on nasal response to ozone.

To assess the potential health risks associated with exposure to low levels of ozone, it is essential to know if the ozone-induced responses are dependent on cumulative exposures or on the peak concentrations. To answer this question female F344/N rats, 11-13 weeks of age, were exposed to a matrix of equal concentration x time values that included exposures to 0, 0.12, 0.24, and 0.48 ppm ozone for 3, 6, 12, or 24 hr. the response of the nasal epithelium was measured as induced DNA synthesis determined by the uptake of bromodeoxyuridine (a thymidine analog) into epithelial cells lining the nasal anterior maxilloturbinates. No increased DNA synthesis was observed in rats exposed to 0.12 ppm ozone for any of the time periods. For exposures higher than 0.12 ppm ozone, the response of the nasal epithelium was similar for equal cumulative exposures. The responses, however, were not linearly related to the cumulative (concentration x time) exposures. It appeared that some mitigating factor was present which decreased the responses at the higher cumulative exposures. No frank toxicity or cellular necrosis was observed, indicating that sublethal cell damage was sufficient to induce DNA synthesis. A simple mathematical model was developed to describe the relationship between ozone exposure and the induction of DNA synthesis in the nasal epithelium. The model predicted that the threshold concentration of ozone for inducing DNA synthesis in the nasal epithelium was 0.1 +/- 0.1 ppm. For one measure of ozone toxicity (induced DNA synthesis) at a sensitive site in the respiratory tract (maxilloturbinates), the effects of ozone were dependent on cumulative exposures at concentrations > 0.12 ppm and within the time and concentration ranges used in this study.

Administration, Inhalation↗
PubMed1990

The combined effects of alpha-particles and X-rays on cell killing and micronuclei induction in lung epithelial cells.

Understanding how cellular damage produced by high-linear energy transfer (LET) radiation interacts with that produced by low-LET is important both in radiation therapy and in evaluating risk. To study such interactions, rat lung epithelial cells (LEC) were grown on Mylar films and exposed to both X-rays and alpha-particles, separately or simultaneously. Cell killing, and the numbers of binucleated cells and micronuclei, were measured as indicators of damage. X-rays and alpha-particles given separately caused dose-related increases in cell cycle time, with alpha-particles producing greater mitotic delay than X-rays. Damage from alpha-particles and X-rays given simultaneously did not interact to alter further the cell cycle. Cell survival data following exposure to X-rays and alpha-particles, combined or individually, were fitted by linear-quadratic models. Survival curves following exposure to alpha-particles only, or to 1.0 Gy alpha-particles plus graded X-ray doses, were adequately described using only the linear (alpha) term of a linear-quadratic model with alpha coefficients of 0.9 +/- 0.04 and 1.03 +/- 0.18 Gy-1, respectively. Survival following exposure to X-rays only or to 0.06 Gy alpha-particles combined with X-rays was best fitted using both alpha and beta terms of the linear-quadratic model (0.12 +/- 0.03)D + (0.007 +/- 0.002)D2 and (0.57 +/- 0.08)D + (0.3 +/- 0.02)D2, respectively. The numbers of micronuclei produced by exposure to alpha-particles or X-rays alone increased linearly with dose, with slopes of 0.48 +/- 0.07 and 0.19 +/- 0.05 micronuclei/binucleated cell per Gy for alpha and X-rays, respectively. Simultaneous exposure to graded levels of X-rays and a constant alpha dose of either 1.0 or 0.06 Gy increased micronuclei frequency, with a slope of 0.74 +/- 0.05 or 0.58 +/- 0.04 micronuclei/binucleated cell per Gy, respectively. These slopes are similar to that produced by alpha-particles alone. These studies demonstrated that both cell killing and the induction of micronuclei were increased by combined exposures compared with that predicted for separate exposures.

Alpha Particles↗
PubMed1990

Predicted and observed early effects of combined alpha and beta lung irradiation.

The nonstochastic radiobiological effects of combined alpha and beta irradiation of the lungs of rats from inhaled radionuclides were studied. Both respiratory functional morbidity at 18 mo and mortality from radiation pneumonitis within 18 mo after exposure were examined for rats exposed to the beta-emitter 147Pm, the alpha-emitter 238Pu, or both combined. The results were used to validate hazard-function models that were developed (1) for respiratory functional morbidity at 18 mo and (2) for lethality from radiation pneumonitis within 18 mo. Both models were found to adequately predict the experimental observations for chronic alpha plus beta irradiation of the lung. Based on this 18-mo study, a relative biological effectiveness of approximately seven was obtained for 238Pu alpha radiation compared to 147Pm beta radiation for both respiratory functional morbidity and lethality from radiation pneumonitis. However, the relative biological effectiveness for the alpha radiation is likely to increase with longer follow-up.

Administration, Inhalation↗
PubMed1990

A model for hematopoietic death in man from irradiation of bone marrow during radioimmunotherapy.

There are numerous institutions worldwide performing clinical trials of radioimmunotherapy (RIT) for cancer. For RIT, an exponentially decaying radionuclide is attached by using a chelating agent to a specific monoclonal or polyclonal tumour antibody (e.g. antiferritin IgG). The major limitation to RIT is toxicity to normal tissue in organs other than the one containing the tumour (e.g. bone marrow). The focus of this manuscript is on modelling the risk (or probability) of hematopoietic death in man for exponentially decaying patterns of high-energy beta irradiation (e.g. 90Y) of bone marrow by radioimmunoglobulin injected into the blood. The analytical solutions presented are only applicable to protocols for which significant uptake of radioactivity by the bone marrow does not occur, and only for high energy beta emitters. However, the generic equation used to obtain the analytical solutions is applicable to any continuous pattern of high energy beta irradiation. A model called the "normalized dose model" was used to generate calculated values for the LD50 as a function of the effective half-time for the radioimmunoglobulin in the blood. A less complicated empirical model was used to describe the calculated values. This model is presumed to be valid for effective half-times in blood of up to about 20 days. For longer effective half-times, the LD50 can be estimated using the normalized-dose model presented. In this manuscript, we also provide a modified Weibull model that allows estimation of the risk of hematopoietic death for single or multiple injections (in one cycle) of radioimmunoglobulin, for patients with normal susceptibility to irradiation and for patients with heightened susceptibility. With the modified Weibull model, the risk of hematopoietic death depends on the level of medical treatment provided to mitigate radiation injuries.

Antibodies, Monoclonal↗
PubMed1988

A radiation protection approach to assessing population risk for threshold-type radiobiological effects.

The potential harm to a population exposed to radiation from a nuclear accident, such as the one that recently occurred at the Chernobyl plant in the Soviet Union, is of concern to many individuals. The average dose to a population is a useful index of harm (IH) only for linear, nonthreshold-type, quantal (i.e., all-or-none) effects. For such radiobiological effects, the expected harm to the population is linearly related to the average dose. However, for nonstochastic effects, it is not. An IH is proposed for threshold-type nonstochastic effects which is based on a form of the Weibull model where, at low to moderate doses, the individual risk at dose X = D/D50 is given by the approximation Risk = ln(2)XV; where D50 is the absorbed radiation dose that produces the specified effect in one-half the population, D is the absorbed radiation dose, and V is a positive parameter. The dose, X, is in units of the D50. Use of this form of the Weibull model is limited to doses such that X is small in comparison to 1. An IH for the population can be obtained by defining a new variable, P = XV, in dimensionless units, because the individual risk is linearly related to P at low and moderate doses. The average value for P (given by [P]) for an exposed population can be used as an IH for the population when the maximum value for P does not exceed 1. Both P and [P] can be regarded as theoretical doses. The average risk for the population in terms of the average dose [P] is given by ln(2)*[P], and the expected cases of nonstochastic effects among N individuals by N*ln(2)*[P]. As an example of the application of the average dose [P], the expected cases of temporary sterility in males among the approximately 135,000 people evacuated within 30 km of the Chernobyl plant is calculated to be about 200. The cases of sterility would be expected to come from those males exposed to doses to the testes of about 0.35 Gy or higher. No cases of sterility would be expected for individuals exposed to lower doses.

Accidents↗
PubMed1988

Risk estimators for radiation-induced bone marrow syndrome lethality in humans.

This manuscript provides risk estimators for acute lethality from radiation-induced injury to the bone marrow of humans after uniform total-body exposure to low linear energy transfer (LET) radiation. The risk estimators are needed for nuclear disaster risk assessment. The approach used is based on the dose X, in units of D50 (i.e., the dose required for 50% lethality). Using animal data, it is demonstrated that the use of dose in units of D50 eliminates most of the variability associated with mammalian species, type of low-LET radiation, and low-LET dose rate. Animal data are used to determine the shape of the dose-effect curve for marrow-syndrome lethality in man and to develop a functional relationship for the dependence of the D50 on dose rate. The functional relationship is used, along with the Weibull model, to develop acute lethality risk estimators for complex temporal patterns of continuous exposure to low-LET radiation. Animal data are used to test model predictions.

Bone Marrow↗
PubMed1987

Chemical and biological characterization of hazardous industrial waste. II. Eukaryotic bioassay of a wood-preserving bottom sediment.

The eukaryotic haploid and diploid forms of Aspergillus nidulans were used to detect gene mutations and various types of chromosome damage, respectively, in the acid, base and neutral fractions of a wood-preserving bottom sediment. The corresponding response to prokaryotic mutagenicity assays and major chemical constituents of the 3 waste fractions were described by Donnelly et al. (1987). The haploid methionine system detected genotoxic compounds in all 3 primary waste fractions without metabolic activation. With metabolic activation, the maximum response observed in the gene mutation assay was induced by the base fraction. In the diploid assay without metabolic activation, the acid fraction induced the maximum number of major chromosome abnormalities, while the base fraction induced the maximum number of minor deletions or insertions. These results appear to reflect the different composition of the waste fractions since each fraction induced a different type of genetic damage in the two bioassays employed. Alternately, because exposure in the diploid assay was during a growth stage, the results may reflect a varying response at different points of the cell division cycle. The results obtained using eukaryotic bioassays indicate that the wood preserving waste contains compound(s) capable of inducing point mutations, chromosome damage, recombination, and compound(s) acting as spindle poisons.

Aspergillus nidulans↗
PubMed1987

Mixtures of toxic agents and attributable risk calculations.

Calculations of attributable risks have attracted increasing interest recently. However, these efforts have been limited to mostly one agent, radiation, and no interactions with effects of other toxic agents have been taken into account. This paper outlines a generic approach to the calculation of attributable risks for an exposure to several toxic agents and interaction effects associated with them. In this calculation, the partition of interaction terms between the agents responsible is of particular importance. At present, there are no rules on how to assign equitable shares, so one methodology will be proposed and others discussed briefly. For one example of an assignment, the standard errors of the attributable risks are determined in terms of the uncertainties of the input parameters, thus setting the stage for a comparison of the different shares of responsibility.

Drug Interactions↗
PubMed1985

Mutagenicity of three agricultural soils.

A chemical and biological testing protocol was employed to evaluate the mutagenic potential of the organic compounds extracted from three agricultural soils. The analytical procedures used included bioassays with Salmonella typhimurium and Aspergillus nidulans for the detection of point mutations and a gas chromatography/mass spectrometry/computer system to identify major organic constituents. The extracts of all three soils exhibited mutagenic response in the bioassays. At a dose level of 1000 micrograms per plate, the organic extract of the Bastrop clay induced 434 net revertants; while at the same dose level the Norwood sandy clay and the Sassafrass sandy loam induced 35 and 178 net revertants, respectively, in the Salmonella assay with metabolic activation. In the Aspergillus assay, the extract of the Norwood and Bastrop soils induced a positive response without metabolic activation; this effect was reduced or eliminated in the presence of metabolic activation. Chemical analysis identified a variety of initiators, promotors, inhibitors, and cocarcinogens; however, there were no mutagenic compounds identified in any of the soil extracts. The results of this combined testing protocol indicate that the agricultural soils tested had an inherent level of mutagenic activity, which was not detected by GC/MS analysis alone, and this activity may be related to the past history of agricultural practices, including biocide applications, fertilization, and cultivation.

Animals↗
PubMed1984

Methodologies for predicting the expected combined stochastic radiobiological effects of different ionizing radiations and some applications.

A methodology for predicting the expected combined stochastic radiobiological effects of sequential exposure to different ionizing radiations is used to arrive at a methodology for predicting the radiobiological effects of simultaneous exposure. Both methodologies require developing additive-damage dose-effect models. Additive-damage dose-effect models are derived assuming (a) each radiation comprised by the combined exposure produces initial damage called critical damage that could lead to the radiobiological effect of interest; (b) doses of different radiations that lead to the same level of radiobiological effect (or risk) can be viewed as producing the same amount of critical damage and being indistinguishable as far as the effects of subsequently administered radiation. Derived dose-effect functions that describe the risk per individual, conditional on radiation dose, are called risk functions. The methodologies allow the use of known radiation-specific risk functions to derive risk functions for combined effects of different radiations. The risk functions for combined exposure to different radiations are called global risk functions. For sequential exposures to different ionizing radiations, the global risk functions derived depend on how individual radiation doses are ordered. Global risk functions can also differ for sequential and simultaneous exposure. The methodologies are used to account for some previously unexplained radiobiological effects of combined exposure to high and low linear-energy-transfer radiations.

Alpha Particles↗
PubMed1983

Dose-response relationships for bone cancers from plutonium in dogs and people.

The risk of bone cancers developing from internally deposited plutonium must be estimated from studies in laboratory animals because no plutonium-induced cancers have been observed in people. Studies of the effects of 226Ra and 239Pu injected into beagle dogs at the University of Utah and 238PuO2 inhaled by beagle dogs at the Inhalation Toxicology Research Institute provide a key link to understanding the longterm effects of inhaled alpha-emitting radionuclides in people. Injected radium and plutonium are rapidly deposited in bone whereas plutonium deposited in lung by inhalation is translocated to bone more slowly, depending on its chemical form. The development of bone cancers is a late occurring effect seen after either injection of plutonium or radium or inhalation of plutonium. The incidence of bone cancers from alpha radiation to the skeletons of dogs was compared to bone cancer incidences in radium dial painters to estimate bone cancer risk from inhaled plutonium in people. A risk factor of 1200 bone cancers/10(6) rad to skeleton (average dose) was estimated.

Age Factors↗
PubMed1982

Method of analysis of monotone dose-response probabilities after long-term exposure to a toxicant.

A nonparametric hazard-function (HP) method for generating monotonically increasing incidence vs dose curves after long-term exposure to a toxic agent (e.g. radiation or chemical carcinogens) is described in detail in this paper. Here, incidence refers to the response-probability estimate that is adjusted for competing risks. The maximum likelihood principle was used to arrive at an appropriate point estimate of the cumulative hazard function (i.e. the negative natural logarithm of the proportion of the nonresponders) and the response probability for an array of doses that depends on the data set to be analyzed. The resultant point estimates can be used to develop or select an appropriate model for risk vs dose assessment. As an example of the application of the HF method, data for liver neoplasms caused by long-term exposure of mice to 2-acetylaminofluorene and data for radiation pneumonitis and pulmonary fibrosis caused by long-term exposure of dogs to ionizing radiation are analyzed.

2-Acetylaminofluorene↗