Biomedical subjects
Publications and source records attributed to Fiona E McNeill.
Using a 50 W x-ray tube as the fluorescing source, an x-ray fluorescence system was designed to measure arsenic in superficial layers of tissue-simulating phantoms. The detection limit for arsenic in the phantoms at a setting of 35 kV and with 200 microm of a Mo filter was 0.40 +/- 0.06 microg As g(-1). This measurement results in an effective dose of 0.6 microSv.
The existence of radiation-induced bystander effects mediated by diffusible factors is now accepted, but the mechanisms and precise behavior at low doses remain unclear. We exposed cells to gamma-ray doses in the range 0.04 mGy-5 Gy, harvested the culture medium, and transferred it to unirradiated reporter cells. Calcium fluxes and clonogenic survival were measured in the recipients. We show evidence for a dose threshold around 2 mGy for the human skin cell line used with a suggestion of increased survival below that dose. Similar experiments using direct gamma irradiation showed no reduction in survival until the dose exceeded 7 mGy. Preliminary data for neutrons where the gamma-ray dose was kept below the bystander threshold do not show a significant bystander effect in the dose range 1-33 mGy. A lack of a bystander response with neutrons occurred at around 1 Gy, where significant cell killing from direct irradiation was observed. The result may have implications for understanding the role of bystander effects at low doses.
Long term lead metabolism in the human body has never been fully understood due to the lack of human data in this area. The technological improvement of bone lead measurement systems has made bone lead data of substantial populations available. In this study, a set of X-ray fluorescence bone lead data was used to test Leggett's lead metabolism model (R. W. Leggett, Environ. Health Perspect., 1993a, 101, 598-616), especially the model of metabolism in bone. The data set includes the bone lead concentration of 539 occupationally exposed workers, of whom 327 were measured twice in five years. The bone lead concentrations of both cortical bone (tibia) and trabecular bone (calcaneus) were obtained by Cd-109 gamma-ray induced XRF measurement. The histories of blood lead concentration for these workers were used to regulate the input file of the model. The results show that the bone lead concentrations predicted by Leggett's model greatly underestimate the measured values, especially for older workers. This data set was then organized into five age groups. A new simplified model was applied to estimate the lead transfer rates between blood and lead compartments for these age groups. The original transfer rates and the new transfer rates are compared, and the differences are discussed. When the transfer rates derived from measured bone lead data were put into the input file of the model to replace the existing parameters, the predicted values were much closer to the measured values for both cortical bone and trabecular bone.
An x-ray fluorescence measurement system has been developed with an 125I source to detect arsenic in superficial layers of phantoms and tissue. Based on in vivo measurements, in conjunction with Monte Carlo simulations, the detection limit for arsenic in skin ranges between 2.6+/-0.5 and 5.7+/-1.1 microg g(-1), depending on skin thickness and assuming that arsenic is uniformly distributed in the skin. The effect of skin arsenic distribution was also examined.
This paper describes a new metabolic model for lead in humans and a numerical method to solve the differential equations governing the transfer of lead between body compartments. The model includes 3 compartments-cortical bone, trabecular bone and blood-and accounts for absorption from external sources and release through excreta. Estimation of the lead kinetics parameters was performed using the grid search method. Grid search is a simple procedure that allows the fit of an arbitrary function to data. When applied to data from occupationally exposed populations, the method demonstrated the exposure dependence of the rate of lead uptake and release by the compartments in the model. The results confirm and refine previous observations of the significant decrease of the transfer rate of lead from cortical bone to blood with increasing exposure, as expressed by half-lives of (in years): 6.5 +/- 0.7, 13.6 +/- 1.0 and 47.5 +/- 2.3, in subgroups of low, intermediate and high long-term lead exposure. A similar trend was observed for the transfer rate from trabecular bone, which could be statistically supported for the first time. Reduction by a factor of 7 to 10 in the default values assigned to the fractional removal of lead from cortical bone to plasma in existing metabolic models was also predicted. These results can be used in the review of current metabolic models for lead, which are still based on the assumption of a constant rate of lead removal from bone, independently of the level of exposure.
In 1994, 207 women participated in a study designed to examine the effects of occupational exposure and various lifestyle factors on bone and blood lead levels. In vivo measurements of Pb concentrations in tibia were performed by X-ray fluorescence. All 108 former smelter employees and 99 referents provided blood samples and answered a questionnaire on lifestyle characteristics and the relevant medical history. Lead concentrations in tibia and blood were significantly higher in the exposed group. The difference in mean bone Pb concentrations of the two groups is markedly greater than the difference in the mean blood Pb concentrations, supporting the view that bone Pb measurements are a more reliable determinant of Pb body burden. Chronic exposure did not result in any statistically significant differences in adverse pregnancy outcomes. A significantly lower age at the onset of menopause in occupationally exposed women may suggest that Pb causes adverse changes in the pattern of estrus and menses. The exposed women had lower bone Pb concentrations than those found in most studies on predominantly male workers. Blood Pb concentrations remain increased in women long after the cessation of occupational exposure, reflecting the importance of the endogenous exposure. The endogenous exposure relation found for postmenopausal exposed women is consistent with data on male smelter workers, whereas the relation found for premenopausal women is significantly lower. This suggests that sex plays an important role in the metabolism of lead, and current models of exposure extrapolated from male data may be inappropriate for use on women.
Two sets of phantoms have been used to calibrate a 109Cd y-ray induced K-XRF bone-lead measurement system. Both sets of phantoms are made of plaster of Paris, but the calibration lines are significantly different. This results in a significant difference for the derived concentrations of bone lead for the same person using these two sets of phantoms. This study shows that the different calibration lines are due to the different compositions of the phantoms, which can then be accounted for by adjusting the parameters related to the phantom composition in spectral analysis. Bone-lead concentrations for ten lead-exposed smelter workers were computed before and after analysis modification, and the results show that the bone-lead concentrations for the same person calculated from two sets of phantoms are not significantly different, only after the modifications are incorporated. Through these investigations, it was discovered that a common practice of setting the ratio of the calcium edge amplitude to the coherent scatter amplitude as a constant is only valid when all spectra are acquired at the same system resolution. When there is a change in the resolution between spectra, it has been determined that the ratio of the calcium edge amplitude to the coherent area should instead be used as the constant factor in the analysis program.
Kondrashov and Rothenberg (Appl. Radiat. Isot. 55 (2001) 799) have published "a substantial correction for calculating estimates of lead concentration and uncertainty for in vivo X-ray fluorescent bone analysis with Cd-109 source" (sic). Our paper shows that their correction fails to consider two important points that render it (i) a correction to a superseded method and (ii) of limited effect. Also, their approach to a "crude" estimate produces measurement uncertainties that are implausibly small. In order that they not be propagated in the literature, our paper also corrects several misstatements and errors in Kondrashov and Rothenberg.
The aim of this paper was to assess the endogenous release of lead from bone to blood, in 204 exposed subjects. resuming their duties after a 10-month strike in a primary lead smelter in 1991. In vivo 109Cd K X-ray Fluorescence (109Cd K XRF) was used to measure the bone lead concentration in tibia and calcaneus in the smelter, in 1994 and five years later. The 1994 data were used to derive the post-strike bone lead concentrations retrospectively from the significant association between bone lead and the cumulative blood lead index (CBLI). When a linear model was used to predict the current blood lead upon the level of lead in bone, structural analysis of the data produced slopes for tibia (2.0, 95% CI 1.66-2.54) and calcaneus (0.19, 95% CI 0.16-0.23) that were significantly higher than those predicted by the commonly used simple linear regression method, for tibia (0.73, 95%, CI 0.58-0.88) and calcaneus (0.08, 95% CI 0.06-0.09). This suggests that more lead than previously predicted by regression is released from bone to blood. Furthermore, the structural analysis of the data produced an estimation of the contribution of the bone lead stores to the bloodstream that was more consistent with the 1999 epidemiological data than did the regression estimation. Moreover, a non-linear relationship between tibia lead and blood lead was suggested from the assumption checking procedures for regression. When a non-linear regression model was fit to the data, the method produced estimates of important parameters in human lead kinetics, namely the blood lead saturation constant, showing a good agreement with current knowledge of lead metabolism. Finally, the likelihood of a non-linear bone lead release seems to be supported by the recently described dependence of the half-life of lead in bone on age and intensity of occupational exposure.