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Biomedical subjects

D R Chettle

Publications and source records attributed to D R Chettle.

At least 73 records · Page 4Linked to original sources

In vivo measurements of bone lead--a comparison of two x-ray fluorescence techniques used at three different bone sites.

In vivo bone lead measurements have been made on a group of about 120 people, most of whom were lead exposed workers. Two different x-ray fluorescence (XRF) techniques were used to make measurements at three bone sites. Finger lead was measured using 57Co sources, and lead measurements were made in both tibia and calcaneus with a technique based on 109Cd sources. The results of the bone lead measurements correlated strongly with each other and with the index of cumulative exposure, thus confirming the value and reliability of these in vivo measurements as a tool in the study of chronic lead exposure. Measurement precision, +/- 1 standard deviation, was highest for tibia +/- 7.4 micrograms (g bone mineral)-1, +/- 16.6 micrograms (g bone mineral)-1 for the calcaneus and lowest for phalangeal lead +/- 25.0 micrograms (g bone mineral)-1. Maximum absorbed doses to the skin were comparable for all three measurements (1-3 mGy). The mean whole body dose equivalents were all low, but that for the finger measurement, 0.1 microSv, was significantly less than for the calcaneus and tibia measurements 3-5 microSv.

Bone and Bones↗

Cadmium fume inhalation and emphysema.

Lung function and chest radiographs of 101 men who had worked for 1 or more years manufacturing copper-cadmium alloy were compared with those of a referent group matched for age, sex, and employment status. Cigarette consumption was similar in the two groups. The cadmium workers had an excess of abnormalities of lung function and of radiographic changes consistent with emphysema. Classification of the cadmium workers by exposure categories based on either estimated cumulative cadmium exposure or liver cadmium measured by neutron activation analysis showed that abnormalities of lung function were greatest in those with the highest cumulative cadmium exposure or liver cadmium. The difference in the transfer coefficient (KCO) between cadmium workers and referents increased linearly with increasing cumulative exposure without evidence for a threshold. The estimated mean decrement in KCO for a cadmium worker employed 5 or more years with a cumulative exposure of 2000 yr.microgram.m-3 (exposure to the current UK control limit of 50 micrograms.m-3 for a working lifetime of 40 yr) lies between 0.05 and 0.3 mmol.min-1.kPa-1.l-1 (95% confidence interval). This decrement is consistent with the functional and radiological changes of emphysema observed in this group of workers.

Aged↗

Relations between liver cadmium, cumulative exposure, and renal function in cadmium alloy workers.

Detailed biochemical investigations of renal function were made on 75 male workers exposed to cadmium and an equal number of referents matched for age, sex, and employment status. The exposed group consisted of current and retired workers who had been employed in the manufacture of copper-cadmium alloy at a single factory in the United Kingdom for periods of up to 39 years and for whom cumulative cadmium exposure indices could be calculated. In vivo measurements of liver and kidney cadmium burden were made on exposed and referent workers using a transportable neutron activation analysis facility. Significant increases in the urinary excretion of albumin, retinol binding protein, beta 2 microglobulin, N-acetylglucosaminidase (NAG), alkaline phosphatase, gamma-glutamyl transferase and significant decreases in the renal reabsorption of calcium, urate, and phosphate were found in the exposed group compared with the referent group. Measures of glomerular filtration rate (GFR) (creatinine clearance, serum creatinine, and beta 2 microglobulin) indicated a reduction in GFR in the exposed population. Many of these tubular and glomerular function indicators were significantly correlated with both cumulative exposure index and liver cadmium burden. Using cumulative exposure index and liver cadmium as estimates of dose, a two phase linear regression model was applied to identify an inflection point signifying a threshold level above which changes in renal function occur. Many biochemical variables fitted this model; urinary total protein, retinol binding protein, albumin, and beta 2 microglobulin gave similar inflection points at cumulative exposure levels of about 1100 y.micrograms/m3 whereas changes in the tubular reabsorption of urate and phosphate occurred at higher cumulative exposure indices. Measures of GFR, although fitting the threshold model did not give well defined inflection points. Fewer variables fitted the two phase model using liver cadmium; those that did gave threshold levels in the range 20.3-55.1 ppm. When cadmium workers with cumulative exposure indices of less than 1100 y.micrograms/m3 were compared with their respective referents only serum beta 2 microglobulin and urinary NAG were significantly increased in the exposed group and these differences were not related to the degree of cadmium exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

Alloys↗

In vivo tibia lead measurements as an index of cumulative exposure in occupationally exposed subjects.

In vivo tibia lead measurements of 20 non-occupationally exposed and 190 occupationally exposed people drawn from three factories were made using a non-invasive x ray fluorescence technique in which characteristic x rays from lead are excited by gamma rays from a cadmium-109 source. The maximum skin dose to a small region of the shin was 0.45 mSv. The relation between tibia lead and blood lead was weak in workers from one factory (r = 0.11, p greater than 0.6) and among the non-occupationally exposed subjects (r = 0.07, p greater than 0.7); however, a stronger relation was observed in the other two factories (r = 0.45, p less than 0.0001 and r = 0.53, p less than 0.0001). Correlation coefficients between tibia lead and duration of employment were consistently higher at all three factories respectively (r = 0.86, p less than 0.0001; r = 0.61, p less than 0.0001; r = 0.80, p less than 0.0001). A strong relation was observed between tibia lead and a simple, time integrated, blood lead index among workers from the two factories from which blood lead histories were available. The regression equation from two groups of workers (n = 88, 79) did not significantly differ despite different exposure conditions. The correlation coefficient for the combined data set (n = 167) was 0.84 (p less than 0.0001). This shows clearly that tibia lead, measured in vivo by x-ray fluorescence, provides a good indicator of long term exposure to lead as assessed by a cumulative blood lead index.

Adolescent↗

Unexpected mobilisation of lead during cisplatin chemotherapy.

During an investigation by X-ray fluorescence of platinum uptake in the kidney after chemotherapy with cisplatin, lead was found to have accumulated in the kidney in four subjects. The average kidney lead burden in one case exceeded 800 micrograms/g. Although two of the subjects had been occupationally exposed to lead, the other two had not. The tibia lead burden was also high in the two subjects in whom it was measured. The origins of this mobilised lead and the implications for cisplatin nephrotoxicity are discussed.

Aged↗

Comparison of two in vitro methods of bone lead analysis and the implications for in vivo measurements.

Atomic absorption spectrometry and x-ray fluorescence have been used to determine the lead content of metatarsal and tibia bone samples. For a range of bone lead levels from 6.5 to 83 micrograms g-1 of ashed bone there is no evidence of a systematic difference between the two techniques of more than 1 microgram g-1. There is, however, some evidence that random differences between the two in vitro analyses applied to the same bone sample are larger than can be accounted for by known measurement uncertainties. Variations in bone composition could account for these differences. Because the x-ray fluorescence technique is applied in an identical way to in vivo analysis, it is concluded that the uncertainties in in vivo measurements are small.

Bone and Bones↗

In vivo elemental analysis in occupational medicine.

The application of in vivo measurement techniques, derived from nuclear and atomic physics, to problems encountered in occupational medicine is discussed. The main techniques, neutron activation and X-ray fluorescence, are described, and their use for in vivo measurements of cadmium and lead is explored in some detail. The extension of these and other, related, techniques to the possible measurement of other elements of importance in occupational medicine is considered. The use of in vivo measurements as a tool for research into the toxicological effects of cadmium, associated with occupational exposure is taken as an example of the way in which in vivo elemental analysis can contribute to research in occupational medicine.

Activation Analysis↗

In vivo measurement of lead in bone using x-ray fluorescence.

The factors affecting the accuracy and minimum detectable concentration of in vivo tibia lead measurement are discussed, and it is demonstrated that the use of a 109Cd source in a backscatter geometry and using the 88 keV coherently scattered photon for normalisation optimizes both criteria. The measurement is shown to be independent of variations in source-sample distance, thickness of overlying tissue and tibia size and shape. Applying the same technique in vitro to samples of human tibia and metatarsals, it is shown that the results are not significantly different (p approximately equal to 0.9) from atomic absorption spectrometry results from another laboratory. The results of Monte Carlo dose distribution calculations are presented and compared with measurements using thermoluminescent dosemeters: the mean absorbed dose to a 20 cm leg section is less than 0.1 mGy (10 mrad) and the maximum absorbed skin dose is 0.45 mGy (45 mrad). For this dose the minimum detectable lead concentration is 10 micrograms g-1. Finally, the technique has been applied to groups of normals and occupationally exposed workers, and the means have been shown to be significantly different, namely 10 and 31 micrograms g-1 respectively. In the normal subjects tibia lead correlated strongly with age (r = 0.63, p less than 0.001).

Bone and Bones↗

Whole body cellular and collagen nitrogen in healthy and wasted man.

The classical literature shows that wasting of body protein takes place mainly from the cellular compartment leaving high proportions of extracellular collagen. Whole body nitrogen ( WBN ) is proportional to whole body protein (cellular + extracellular) while whole body potassium ( WBK ) is almost entirely intracellular. WBK might be an adequate index of cellular wasting. WBN was measured by neutron activation and WBK by counting 40K in 29 healthy males and 131 male and female patients with wide ranges of body composition. Our wasted patients with Crohn's disease or ulcerative colitis, had higher WBN / WBK ratios than matched healthy controls and the difference between the two groups was in the cellular ratio (23.6 mol of N/mol of K, 0.33 g of N/mmol of K, 3 mmol of K/g of N). A multiple regression model for all the subjects represented cellular nitrogen by a term in WBK and extracellular nitrogen by simple anthropometric measurements. The partial regression coefficient of WBN on WBK was 22.6 +/- 1.1 (SE) mol of N/mol of K; this was also similar to the cellular ratio. Our results were compatible with extracellular protein (mainly collagen, which is 35% of normal whole body protein) remaining resistant to wasting even when severe loss of cellular protein occurs. The high ratios of WBN / WBK in wasted patients can be explained by this disproportionate wasting of cellular substances and they do not imply alterations in the cellular N/K ratio. We suggested that the stable ratio of WBK to cellular protein makes it an effective index of cellular wasting. The resistance of collagen to wasting and the preponderance of extracellular mass in the fat-free mass of wasted subjects, make WBN and fat-free mass unreliable guides to the extent of wasting.

Activation Analysis↗

Renal dysfunction in cadmium smelters: relation to in-vivo liver and kidney cadmium concentrations.

Biochemical indicators of renal dysfunction have been compared with liver and kidney cadmium levels measured by neutron activation analysis in a group of 37 cadmium smelters. Higher than normal concentrations of cadmium in the liver reflect past exposure; they were associated with evidence of renal dysfunction in workers exposed to cadmium for more than 10 years. A small group of 6 workers exposed to cadmium for only a short time (mean = 4.6 years) had high hepatic cadmium concentrations but normal renal function. Longitudinal studies are required to establish the natural history of renal dysfunction following cadmium accumulation in industrial workers.

Cadmium↗

Effects of methandienone on the performance and body composition of men undergoing athletic training.

1. In a previous study of the effects of methandienone (Dianabol) on men undergoing athletic training, strength and performance increased, but not significantly more when the subjects were taking the drug than when they were taking placebo. The subjects did, however, gain more weight on the drug, with increases in total body potassium and muscle dimensions. It remained an open question whether the muscles had gained normal tissue or intracellular fluid. 2. In an attempt to distinguish between these possibilities the trial has been repeated, using as subjects seven male weight-lifters in regular training, and including measurements of total body nitrogen. As before, a dose of 100 mg of methandienone/day was given alternately with the placebo in a double-blind crossover experiment. The treatment periods lasted 6 weeks and were separated by an interval of 6 weeks. Body weight, potassium and nitrogen, muscle size, and leg performance and strength increased significantly during training on the drug, but not during the placebo period. 3. The finding of increased body nitrogen suggested that the weight gain was not only intracellular fluid. The increases in body potassium (436 +/- SEM 41 mmol) and nitrogen (255 +/- 69 g) were too large in proportion to the weight gain (2.3 +/- 0.4 kg) for this to be attributed to gain of normal muscle or other lean tissue, and imply gain of nitrogen-rich, phosphate-poor substance. Although this action of methandienone might be described as anabolic, the weight gain produced is not normal muscle.

Adult↗