Biomedical subjects
Publications and source records attributed to M C Scott.
Acute vaginal bleeding secondary to uterine myomas can be a devastating event. We report the use of a combined therapeutic approach in a patient who presented with protracted bleeding of a myomatous uterus that was equivalent in size to a 38 week gestation. This patient's course was further complicated by her refusal of blood or blood products.
A Monte Carlo program has been written to model the in vivo x-ray fluorescence of lead in the kidney, to aid the choice of one of four candidate fluorescing source/measurement geometry combinations: 109Cd/180 degrees, 57Co/90 degrees and 99Tcm at both 180 degrees and 90 degrees. Computational studies and practical considerations led to the choice of 99Tcm in a backscatter geometry for the measurement system.
In-air and in-phantom neutron spectra have been measured between 10 and 60 MeV for two field sizes on the Clatterbridge cyclotron by unfolding the response of a specially built NE213 scintillator. The in-phantom measurements show distinct spectral hardening with depth, which is reflected in changes in the spectrum-averaged mean neutron energy. These findings are confirmed using Monte Carlo calculations.
Lead in bone can be measured in vivo using gamma-rays from a 109Cd source to excite lead K X-rays. Normalization of lead X-ray amplitudes to that of the elastically backscattered 88 keV gamma-rays produces a determination of the concentration of lead in bone mineral that is accurate and insensitive to variations in measurement or bone geometry. For in vivo tibia measurements, a typical precision (1 SD) of +/- 5 micrograms lead (g bone mineral)-1 is achieved for an effective dose equivalent of 2.1 microSv. Measurement can be made of any superficial bone site, but precision will vary approximately as the inverse of the square root of the mass of bone mineral sampled. The apparatus required for this technique is readily transportable, and mobile laboratory facilities are easily established.
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An in vivo neutron activation system for measuring kidney cadmium has been redesigned, firstly to reduce ambient dose levels and, secondly, to improve the cadmium signal to neutron dose ratio by modifying the neutron spectrum from 238Pu/Be, by interposing a beryllium premoderator. The ambient dose was reduced by a factor of seven. The overall system performance (lower limit of detection for a given dose) was improved by 40-50%. This 238Pu/Be based system now performs as well as or better than analogous 252Cf systems, without the drawback of the relatively short half life of 252Cf.
The effects of lead exposure on serum 1,25-dihydroxyvitamin D levels and calcium homeostasis have been studied in 63 males occupationally exposed to the metal in the UK. The exposure indices used were blood lead, reflecting short-term exposure, and an in vivo X-ray fluorescence measurement of tibia lead which reflects cumulative lead exposure. Serum 1,25-dihydroxyvitamin D levels were higher than those in a referent population, who were non-occupationally exposed to lead, and were correlated with both blood lead and tibia lead. Multiple regression analysis suggested that blood lead was the variable responsible for the increase in serum 1,25-dihydroxyvitamin D. There were no other abnormalities in calcium metabolism associated with the degree of lead exposure.
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.
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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.
Histamine N-methyltransferase (HNMT) catalyzes the N tau-methylation of histamine. HNMT is present in many human tissues, including the red blood cell (RBC). Our study evaluated the possible role of inheritance in the regulation of individual variations in human RBC HNMT activity. HNMT activity was measured in RBC lysates from 241 members of 51 nuclear families. After correction for the gender-specific effects of age, the frequency distribution of RBC HNMT activities was unimodal, and activities varied threefold within 2 SDs of the mean. The correlation of HNMT activities in RBCs from 45 pairs of spouses was only 0.070, indicating that shared environment did not result in similar activities among genetically unrelated individuals. Correlation coefficients were also calculated for pairs of genetically related individuals. All of these correlations were significant except the mother-oldest son correlation. The majority of the correlations did not differ significantly from those predicted for a trait with a heritability of 1.0 (100%). Our results demonstrate a significant familial aggregation of human RBC HNMT activity and suggest that inheritance may play an important role in the regulation of variation in the activity of this N-methyltransferase enzyme in the human RBC.
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)
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.
This paper describes a method for measurement of dopamine 3-O-sulfate (DA3S) and dopamine 4-O-sulfate (DA4S) in dog and human plasma and dog cerebrospinal fluid. C18 solid-phase extraction columns were utilized for sample preparation. DA3S and DA4S were separated by high-performance liquid chromatography and then quantified by dual-electrode electrochemical detection. [3H]Dopamine O-sulfate (DAS) was used as internal standard. Recovery of authentic DAS added to dog plasma and carried through the entire procedure was 49.9 +/- 6.3% for DA3S (n = 9) and 42.2 +/- 4.3% for DA4S (n = 8). The lower limit of detection (signal-to-noise ratio of 3) was 20 fmol for each DAS isomer. The within-assay coefficient of variation for DA3S in dog plasma averaged 5.8% (range 2.0-12%, n = 5). The between-assay coefficient of variation for DA3S in dog plasma was 3.8% (n = 3). DAS levels in plasma of conscious dogs were 20.3 +/- 6.9 pmol/ml DA3S and 5.91 +/- 3.5 pmol/ml DA4S (n = 5). Cerebrospinal fluid levels were 3.06 +/- 3.22 pmol/ml DA3S and 0.10 +/- 0.18 pmol/ml DA4S in dogs anesthetized with methoxyflurane and nitrous oxide (n = 3). This procedure is also appropriate for use with human plasma; DAS levels were 24.3 +/- 12.8 pmol/ml DA3S and 9.07 +/- 3.9 pmol/ml DA4S (n = 6).
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High performance liquid chromatography with radioactive flow detection was used to examine the accumulation and sulfoconjugation of dopamine by human and dog platelets. Platelets from both species accumulated similar amounts of dopamine from the incubation medium, but only human platelets were found to convert 3H-dopamine to 3-H-dopamine sulfate. This difference between the two species was associated with a relative absence of phenol sulfotransferase activity in dog platelets as compared to human platelets. Dog platelets did not appear to contain an inhibitor of phenol sulfotransferase activity. Despite the apparent difference in the ability of platelets to form dopamine sulfate, conc concentrations of dopamine-3-O-sulfate and dopamine-4-O-sulfate were similar in dog and human plasma. These data suggest that platelets may represent a potential source of at least some of the dopamine sulfate found in human plasma, but not in dog plasma.
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.