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Biomedical subjects

D R Chettle

Publications and source records attributed to D R Chettle.

At least 37 records · Page 2Linked to original sources
PubMed1998

Lead concentrations in tibial and calcaneal bone in relation to the history of occupational lead exposure.

OBJECTIVES: This study tested a simple model of the relationship between the lead concentration in bone (bone-Pb), exposure time, and lead in plasma (P-Pb) and whole blood (B-Pb) to make it possible to use bone-Pb as a retrospective exposure index. METHODS: Seventy-seven active lead workers and 24 referents were studied. The bone-Pb in tibia (T-Pb) and calcaneus (C-Pb) was measured by in vivo X-ray fluorescence. P-Pb was calculated from B-Pb by use of the nonlinear relationship between these variables. Cumulative B-Pb (cumB-Pb) and P-Pb (cumP-Pb) were calculated to the time of the bone-Pb measurements. In addition, cumP-Pb was adjusted by applying varying rate constants for the transfer of lead from bone to plasma. RESULTS: There were close linear associations between the lead concentrations in tibia (proportion of variance explained, R2 = 0.78) and calcaneus (R2 = 0.80), on one hand and the cumB-Pb on the other. The best fit of bone-Pb to the adjusted cumP-Pb (0.79 for T-Pb; 0.82 for C-Pb) was obtained for the terminal phase half-times of 13 and 12 years, respectively. CONCLUSIONS: The combined data on bone-Pb and exposure time make it possible to estimate previous mean P-Pb and B-Pb. Such estimates will be valuable in studies of toxic effects on long-term exposed lead workers when data on the intensity of previous exposure are lacking. The use of P-Pb in modeling bone-Pb kinetics is physiologically relevant, but the use of adjusted cumP-Pb, as compared with cumB-Pb, did not significantly change the variance in the relation to bone-Pb.

Adolescent↗
PubMed1997

Further experience with bone lead content measurements in residents of southern Ontario.

Bone lead content of the mid-tibia was measured by in vivo fluorescence excitation in 90 females and 59 males aged between 6 and 81. The cross-sectionally derived rate of increase of tibia lead content was 0.24 +/- 0.03 microgram [g mineral]-1 yr-1. In 93 adult women, the corresponding rate of increase for calcaneus lead content was 0.12 +/- 0.11 microgram [g mineral]-1 yr-1. Comparison with European values show that, in Canada, the rates of lead accumulation are greater than those found in N. Sweden and Finland, similar to those of S. Sweden and less than values measured in England.

Adolescent↗
PubMed1997

The feasibility of measuring bone uranium concentrations in vivo using source excited K x-ray fluorescence.

X-ray fluorescence (XRF) has been demonstrated to be an extremely useful technique for measuring trace quantities of heavy metals in various tissues within the body. This study investigates the applicability of XRF to the measurement of bone uranium concentration. The factors affecting the accuracy and minimal detectable concentration of bone uranium in vivo are discussed. The system chosen employs a 57Co source to excite the uranium K x-rays, with the source and detector in an approximate 180 degrees backscatter geometry relative to the sample position. It is demonstrated, with experiment and Monte Carlo simulation, that the x-ray to coherent peak ratio is linearly related to concentration and is independent of variations in source-sample geometry, thickness of overlying tissue and tibia size. Preliminary in vivo measurements indicate that this system has a minimum detectable concentration of approximately 20 micrograms U/g bone mineral which may not be sufficiently precise for a monitoring system for occupational workers. Future work will involve attempts to enhance this precision through the use of alternative sources for the excitation of uranium x-rays as well as possible modifications to the detector and electronics.

Biophysical Phenomena↗
PubMed1997

Accumulated body burden and endogenous release of lead in employees of a lead smelter.

Bone lead levels for 367 active and 14 retired lead smelter workers were measured in vivo by X-ray fluorescence in May-June 1994. The bone sites of study were the tibia and calcaneus; magnitudes of concentration were used to gauge lead body burden. Whole blood lead readings from the workers generated a cumulative blood lead index (CBLI) that approximated the level of lead exposure over time. Blood lead values for 204 of the 381 workers were gathered from workers returning from a 10-month work interruption that ended in 1991; their blood level values were compared to their tibia and calcaneus lead levels. The resulting relations allowed constraints to be placed on the endogenous release of lead from bone in smelter works. Calcaneus lead levels were found to correlate strongly with those for tibia lead, and in a manner consistent with observations from other lead industry workers. Relations between bone lead concentration and CBLI demonstrated a distinctly nonlinear appearance. When the active population was divided by date of hire, a significant difference in the bone lead-CBLI slope emerged. After a correction to include the component of CBLI existing before the workers' employment at the smelter was made, this difference persisted. This implies that the transfer of lead from blood to bone in the workers has changed over time, possibly as a consequence of varying exposure conditions.

Adult↗
PubMed1996

Partition of circulating lead between serum and red cells is different for internal and external sources of lead.

Serum lead, whole blood lead, and lead in both tibia and calcaneus were measured in each of 49 active lead workers. Serum lead correlated more strongly with both in vivo bone lead measurements than did whole blood lead. The ratio of serum lead to whole blood lead varied from 0.8% to 2.5% and showed a positive correlation with tibia, and an even stronger correlation with calcaneus lead. This implies that lead released from bone (endogenous exposure) results in a higher proportion of whole blood lead being in serum than is the case for exogenous exposure. This observation needs to be confirmed, and the relationships amongst the parameters must be studied further, particularly in former or retired lead workers. If confirmed, since at least a portion of lead in serum is readily diffusible and thus toxicologically more immediately significant than lead bound to red cells, the health implications of endogenous exposure may have to be reassessed.

Adult↗
PubMed1995

Hormone replacement therapy may reduce the return of endogenous lead from bone to the circulation.

Hormone replacement therapy (HRT) in postmenopausal women suppresses the increase in bone resorption expected as circulating levels of endogenous estrogen decline. We tested the hypothesis that bone lead content might remain elevated in women on HRT. Fifty six women who at recruitment were on average 35 years postmenopausal were placed on calcium supplementation. Six months later 33 of these women were prescribed either low dose or moderate dose hormone replacement in addition to the calcium supplementation. After approximately 4 years of hormone replacement, lead content was measured at the tibia and calcaneus by in vivo fluorescence excitation, and lead concentrations were measured in serum, whole blood, and urine. Women not taking hormones had significantly lower lead concentrations in cortical bone compared to all women on HRT (p = 0.007). Tibia lead content (mean +/- SD) for women on calcium only was 11.13 +/- 6.22 microgram/g bone mineral. For women on HRT, tibia bone lead was 19.37 +/- 8.62 micrograms/g bone mineral on low-dose HRT and 16.87 +/- 11.68 micrograms/g bone mineral on moderate-dose HRT. There were no differences between groups for lead concentrations measured in trabecular bone, whole blood, serum or urine. Hormone replacement maintains cortical bone lead content. In women not on HRT, there will be a perimenopausal release of lead from bone.

Bone and Bones↗
PubMed1994

The use of multiple parameters to characterize cadmium-induced renal dysfunction resulting from occupational exposure.

Renal function has been examined in a group of 77 subjects occupationally exposed to cadmium fume and dust, together with a referent group of 103 age- and socioeconomically matched subjects. Fourteen biochemical parameters were measured on each subject. Three different ways of combining the information from all 14 tests were used to identify those subjects with renal dysfunction. These were first to count the number of parameters in which a subject recorded an abnormal test result. Second, the z value was computed for each parameter for each person by comparison with the mean and standard deviation of a derived normal population; these z scores were then summed. Lastly a multivariate distance measure, Mahalanobis D2, was determined for each subject from the distribution of normal subjects. The three approaches showed a considerable degree of agreement in identifying subjects with renal dysfunction, but they also displayed complementary strengths and weaknesses. The consensus of the three techniques was then taken to define truly dysfunctional subjects and each of the 14 parameters, and some combinations of pairs of parameters were tested as to their sensitivity and specificity. For this group of subjects, it was not possible to improve greatly on the use of retinol binding protein on its own. Were a second parameter to be chosen, it would be desirable to choose one reflecting the glomerular filtration rate, but the absence of a suitable sensitive biological monitoring parameter precludes a firm recommendation.

Blood Proteins↗
PubMed1994

In vivo measurements of bone lead content in residents of southern Ontario.

In 111 subjects not occupationally exposed, bone lead content increased steadily with age in both men and women. Higher than expected bone lead levels were observed in two-thirds of 27 subjects working in occupations with potential for lead exposure. Five of 8 patients who displayed symptoms which might have been due to lead poisoning had increased bone lead levels. In vivo bone lead measurements reflect the cumulative extent of exposure to environmental and occupational sources of lead and allow the assessment of abnormal exposures.

Adult↗
PubMed1994

In vivo X-ray fluorescence of lead in bone: review and current issues.

Bone lead measurements can assess long-term lead dosimetry because the residence time of lead in bone is long. Bone lead measurements thus complement blood and plasma lead measurements, which reflect more short-term exposure. Although the noninvasive, in vivo measurement of lead in bone by X-ray fluorescence (XRF) has been under development since the 1970s, its use is still largely confined to research institutions. There are three principal methods used that vary both in the how lead X-rays are fluoresced and in which lead X-rays are fluoresced. Several groups have reported the independent development of in vivo measurement systems, the majority adopting the 109Cd K XRF method because of its advantages: a robust measurement, a lower detection limit (compared to 57Co K XRF), and a lower effective (radiation) dose (compared to L XRF) when calculated according to the most recent guidelines. These advantages, and the subsequent widespread adoption of the 109Cd method, are primarily consequences of the physics principles of the technique. This paper presents an explanation of the principles of XRF, a description of the practical measurement systems, a review of the human bone lead studies performed to date; and a discussion of some issues surrounding future application of the methods.

Bone and Bones↗
PubMed1994

The reproducibility of 109Cd-based X-ray fluorescence measurements of bone lead.

We assessed the reproducibility of X-ray fluorescence-based lead measurements from multiple measurements made on a low-concentration plaster of paris phantom and in five subjects measured five times on two occasions. Over a 6-month period, 220 measurements of the same phantom were obtained and showed a standard deviation of 1.29 micrograms Pb (g plaster of paris)-1. The two sets of in vivo measurements were made 10 months apart and revealed a mean standard deviation of 3.4 micrograms Pb (g bone mineral)-1 and 5.1 micrograms Pb (g bone mineral)-1 for males and females, respectively. Our measured standard deviation exceeded by 20-30% the calculated standard deviation associated with a single measurement both in the phantom and in subjects. This indicates that some variance is introduced during the measurement process. Operator learning and consistency significantly minimized this increased variability. Measured lead concentrations of the left and right tibia in 14 subjects showed no significant differences between legs. As a result, either tibia can be sampled and compared over time. The levels of reproducibility we report here mean that X-ray fluorescence-based determinations of bone lead concentrations are reliable both over the short and long term. Thus, reasonably sized confidence intervals can be placed on detected changes in concentration and should permit acquisition of longitudinal data within a reasonable length of time.

Bone and Bones↗
PubMed1993

A pilot study using 99mTc to measure lead and platinum in the human kidney.

A pilot study has been conducted to investigate the hypothesis that the chemotherapeutic drug, cisplatinum, can mobilize skeletal lead. In vivo measurements of lead and platinum in the kidney of chemotherapy patients were performed with the technique of x-ray fluorescence, using 99mTc in a backscatter geometry. The results of the pilot study were inconclusive; the majority of patients exhibited no evidence of kidney lead at the level of system sensitivity, and negligible blood and urine lead levels.

Cisplatin↗
PubMed1993

An enhanced sensitivity K-shell x-ray fluorescence technique for tibial lead determination.

A novel irradiation-detection geometry capable of enhancing sensitivity for the measurement of tibial lead content by K-shell x-ray fluorescence (XRF) is described. The high-count-rate system comprised a small-area high-specific-activity (0.147 GBq mm-2) 109Cd source and a large-area (nominally 20 cm2) uncollimated detector, forming an axially symmetric back-scattering arrangement. Precisions in the range +/- 4.9 to +/- 14.2 micrograms Pb (g bone mineral)-1 have been obtained in a study of a cohort of 63 controls and 73 workers industrially exposed to lead. These precisions are comparable with those obtained in results using earlier systems, but at reduced source activities (less than 50% of the activity of other systems) and with significant reduction in measurement time (some 30% less than the measurement times of other systems). Subsequent investigation of detector collimation resulted in a marginal improvement in energy resolution, but the restriction in detected photon fluence meant that there was an insignificant change in detection sensitivity. For the resistive feedback preamplifier used in this study a maximum energy rate of the order of 7000 MeV s-1 was found to limit measurement precisions significantly. Higher-count-rate detector systems offer a basis for obtaining mean precisions down to +/- 3 micrograms Pb (g bone mineral)-1 at one standard deviation.

Humans↗