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Biomedical subjects

N D Priest

Publications and source records attributed to N D Priest.

At least 19 recordsLinked to original sources
PubMed2006

Relative toxicity of chronic irradiation by 45Ca beta particles and 242Cm alpha particles with respect to the production of lung tumors in CBA/Ca mice.

Approximately 1800 female CBA/Ca mice were exposed by inhalation at three dose levels to beta particles from (45)Ca-labeled fused aluminosilicate particles (FAP), to alpha particles from (242)Cm-labeled FAP, or to carrier control FAP. Another group of mice inhaled no FAP and were designated as untreated cage controls. The FAP in combination with these radionuclides was used to achieve the same spatial and temporal distribution of alpha- and beta-particle dose within the irradiated mice. Some mice were killed to determine the clearance of radiolabeled FAP from their lungs, and the remainder were allocated to a life-span study. All animals were subjected to a detailed necropsy. To facilitate the identification of small tumors, the lungs were rendered transparent in methyl salicylate and examined under back illumination for the presence of lesions. Lung nodules and other microscopic lesions were excised for histological examination. The median survival of mice in all groups was approximately 910 days. The control animals lived longer than those that were irradiated, but it was difficult to determine a dose-response relationship for survival among the exposed mice. Benign adenomas and, less frequently, malignant adenocarcinomas were identified in all animal groups. The prevalence of these tumors was approximately 28.8% in the control mice, which is consistent with the results of other studies using the same strain of mouse. After exposure to radionuclide-labeled FAP, there was a significant dose-related increase in the prevalence of lung tumors in (242)Cm- (peak prevalence 55%) and (45)Ca-exposed (peak prevalence 48.6%) mice. The prevalence of tumors in the mice that received (242)Cm-labeled FAP was approximately twice that in the mice that inhaled (45)Ca-labeled FAP within the range of doses employed (0.55-4.69 Gy). Using the ratio of the slope of the linear component of the dose-response curves, the toxicity of the alpha particles relative to the beta particles was 1.5 (90% CI: 0.7, 9.0) for all adenomas and 9.4 (90% CI: 5.0, 23.0) for the less frequent adenocarcinomas. The relative toxicity for adenocarcinomas was found to decrease with increasing dose.

Adenocarcinoma↗
PubMed2004

The biological behaviour and bioavailability of aluminium in man, with special reference to studies employing aluminium-26 as a tracer: review and study update.

Until 1990 biokinetic studies of aluminium metabolism and biokinetics in man and other animals had been substantially inhibited by analytical and practical difficulties. Of these, the most important are the difficulties in differentiating between administered aluminium and endogenous aluminium-especially in body fluids and excreta and the problems associated with the contamination of samples with environmental aluminium. As a consequence of these it was not possible to detect small, residual body burdens of the metal following experimental administrations. Consequently, many believed aluminium to be quantitatively excreted within a short time of uptake in all, but renal-failure patients. Nevertheless, residual aluminium deposits in a number of different organs and tissues had been detected in normal subjects using a variety of techniques, including histochemical staining methods. In order to understand the origins and kinetics of such residual aluminium deposits new approaches were required. One approach taken was to employ the radioisotope (67)Ga as a surrogate, but this approach has been shown to be flawed-a consequence of the different biological behaviours of aluminium and gallium. A second arose from the availability, in about 1990, of both (26)Al-a rare and expensive isotope of aluminium-and accelerator mass spectrometry for the ultra-trace detection of this isotope. Using these techniques the basic features of aluminium biokinetics and bioavailability have been unravelled. It is now clear that some aluminium is retained in the body-most probably within the skeleton, and that some deposits in the brain. However, most aluminium that enters the blood is excreted in urine within a few days or weeks and the gastrointestinal tract provides an effective barrier to aluminium uptake. Aspects of the biokinetics and bioavailability of aluminium are described below.

Administration, Oral↗
PubMed2001

Human biokinetics of injected bismuth-207.

A healthy male volunteer received an intravenous injection of 207Bi as citrate. Levels of the tracer in blood and in excretion samples, and its retention and distribution within the body, were investigated by appropriate radioactivity measurements. Levels in blood fell very rapidly, with only 1% of the injection remaining at 7 h and only ca. 0.1% at 18 days. There was rapid initial excretion, with 55% lost during the first 47 h, principally in urine; however, longer-term losses were much slower and 0.6% remained in the body at 924 days, when the contemporary rate of loss implied a half-life of 1.9 years. Integration of the retention pattern suggested that steady exposure to bismuth compounds could lead ultimately to a body content of approximately 24 times the daily systemic uptake. The largest organ deposit was in the liver, which after 3 days contained ca. 60% of the contemporary whole body content, consistent with reports of hepatotoxicity. These findings differ markedly from the metabolic model for bismuth proposed by the International Commission on Radiological Protection, which envisages a terminal half-life in the body of only 5 days and kidney as the site of highest deposition.

Half-Life↗
PubMed1999

Accelerator mass spectrometry for the detection of ultra-low levels of plutonium in urine, including that excreted after the ingestion of Irish sea sediments.

Currently, most methods for the quantitative assessment of (239)Pu have minimum detection levels (25 microBq for alpha-particle spectrometry) that are much higher than the levels of this isotope in many human bioassay and environmental samples. Accordingly, a priority has existed to develop methods that are more sensitive. Fission-track and ICP-MS methods have been used, but these can suffer either from an uncertain level of removal and/or recovery of uranium or from isobaric mass interferences. Accelerator mass spectrometry (AMS) has no such disadvantages, and its demonstrated detection limits for plutonium isotopes approach levels of attograms, equivalent to about 500 nBq for (239)Pu. This paper describes the application of AMS to the measurement of (239)Pu in urine produced by youths living in London (3.5 microBq day(-1)) and by adults (approximately 2-260 microBq day(-1)), some of whom were exposed occupationally. In addition, an experiment was undertaken to measure the fasted absorbed fraction of ingested plutonium after the ingestion of 15 g of Irish Sea sediment by a volunteer. The measured absorbed fraction was 4.5 x 10(-5). It is concluded that accelerator mass spectrometry is a suitable method for the ultra-trace detection of plutonium.

Adult↗
PubMed1999

Revised organ partition of thorium-232 in thorotrast patients.

Risk estimates for internally deposited alpha particles in humans, such as those for alpha-particle-induced leukemia, have been derived from data on the toxicity of (232)Th in patients injected with Thorotrast. Their derivation requires both epidemiological data and organ doses calculated from the volume of Thorotrast injected and a knowledge of its pattern of deposition within the body. However, accumulating evidence suggests that the organ partition of (232)Th that has commonly been used for dosimetry (i.e. liver:spleen:red bone marrow: others tissues = 59:29:9:3) is inaccurate. In the present study, the organ distribution of (232)Th has been recalculated using a revised averaging method and both published data and our own unpublished data. For the three major organs of deposition (liver, spleen and bone marrow), activity concentration data were selected from 27 published papers and data sets including 140 newly compiled Japanese cases. For organs of minor storage, both published data for 38 German and 24 Japanese autopsy cases and new data were used. The revised estimate of the relative partition of (232)Th among the above organs was 53:14:25:8. It follows that doses calculated to date are essentially correct for the liver but are too high for the spleen and about three times too low for the red bone marrow. This suggests that the risk of alpha-particle-induced leukemia, per unit of alpha-particle dose, in Thorotrast patients is about three times lower than previously thought.

Bone Marrow↗
PubMed1998

Thorotrast distribution in monkey bone marrow at early and late times after injection.

Thorotrast, a 25% colloidal suspension of 232ThO2, was formerly used as a radiographic contrast medium. Although epidemiological studies have shown that alpha particles emitted from 232Th and its decay products incorporated in the bone marrow cause leukemia, the use of these data for alpha particle induced leukemogenesis risk estimation has been criticized mainly for inhomogeneity of Thorotrast distribution. Four monkeys were injected with Thorotrast to investigate the degree of inhomogeneity in the thorium content of different bone marrow sites and the cellular localization of Thorotrast. Two were injected via an artery and two via a vein and sacrificed either at 1 wk or 3 to 4 y after injection. Microscopic, solid state autoradiography and back scatter electron imaging methods were applied to several bone sites to determine the degree of inhomogeneity. Quantification was performed using x-ray fluorescence for trabecular bone and bone marrow and neutron activation analysis for compact bones. At 1 wk Thorotrast was found to be distributed evenly in the red marrow; by 3 and 4 y conglomerates were seen which were restricted to macrophages. The monkey was found to be a good model for humans. The choice of injection route did not noticeably affect the Thorotrast distribution in bones of the skeletal system. Considering the even distribution of Thorotrast within the red bone marrow at early times after its injection, the inevitable diffusion of thorium progeny from the particles, the mobility of bone marrow macrophages, and the well established correction factor of self-absorption within conglomerates, these results suggest that data derived from Thorotrast patients are useful for risk estimation of alpha particle induced leukemia.

Animals↗
PubMed1998

Uptake by man of aluminium in a public water supply.

1. After overnight fasting, two young male adults each received a single oral dose of 100 Bq 26Al in tap water. Coincidence gamma-ray spectrometry and accelerator mass spectrometry were used to determine the 26Al content of excretion collections and of blood samples. 2. Close to 100% of the intake was recovered in faeces during the first 7 days. Gastro-intestinal uptake, determined by comparing urinary excretion with patterns previously established following intravenous administration of 26Al, averaged 0.22% in the two subjects. 3. Uptake fractions based on comparisons of blood concentration following ingestion and injection were much lower, but were judged to be unreliable. It is concluded that aluminium present in most water supplies is unlikely to contribute as much as 1% of a typical daily uptake of 10 microg from food.

Adult↗
PubMed1998

Partition of thorium between organs of monkeys injected with thorotrast: implications for alpha-particle dosimetry.

Risk estimates for alpha-particle-induced malignancies have been based mainly on studies of Thorotrast patients, but certain aspects of its deposition in the body have been at issue: the partition between the liver, spleen and red bone marrow, and the deposition at lower concentrations in other organs, such as muscle and fat, which may contribute to the risk. To supplement the existing data for humans, thorium concentrations were measured in the organs of two female monkeys 3-4 years after injection with Thorotrast. Relative deposits (liver:spleen:red bone marrow) were 54:6:41 and 75:4:21, in better agreement with the most recent observations in Thorotrast patients than with previous reports. Whereas the human testis had ranked among intermediate-level organs such as the adrenal glands and pancreas, the ovary of the monkey was among the organs with the lowest concentrations. The data suggest that risk factors for induction of malignancies by alpha-particle irradiation should be re-examined.

Animals↗
PubMed1997

Variations in the concentration of plutonium, strontium-90 and total alpha-emitters in human teeth collected within the British Isles.

Concentrations of plutonium-239, plutonium-240, strontium-90 and total alpha-emitters have been measured in children's teeth collected throughout Great Britain and Ireland. The concentrations of plutonium and strontium-90 were measured in batched samples, each containing approximately 50 teeth, using low-background radiochemical methods. The concentrations of total alpha-emitters were determined in single teeth using alpha-sensitive plastic track detectors. The results showed that the average concentrations of total alpha-emitters and strontium-90 were approximately one to three orders of magnitude greater than the equivalent concentrations of plutonium-239,240. Regression analyses indicated that the concentrations of plutonium, but not strontium-90 or total alpha-emitters, decreased with increasing distance from the Sellafield nuclear fuel reprocessing plant-suggesting that this plant is a source of plutonium contamination in the wider population of the British Isles. Nevertheless, the measured absolute concentrations of plutonium (mean = 5 +/- 4 mBq kg-1 ash wt.) were so low that they are considered to present an insignificant radiological hazard.

Adolescent↗
PubMed1996

The bioavailability of 26Al-labelled aluminium citrate and aluminium hydroxide in volunteers.

A study was undertaken to determine the fraction of ingested aluminium taken up by two male volunteers, following their ingestion of either aluminium citrate or aluminium hydroxide. In addition, the effects of simultaneous citrate ingestion on the gastrointestinal absorption of aluminium from its hydroxide was studied. Volunteers received three oral doses of 26Al-labelled aluminium compound in water. The doses were administered directly into the stomach using a paediatric feeding tube. Blood samples were collected from the volunteers at 1, 4 and 24 h after administration, and their daily output of urine and faeces was collected for 6 days. These samples were analysed for their 26Al content using either coincidence gamma-counting or accelerator mass spectrometry. The uptake of aluminium was greatest following its administration in the citrate form and was least following intake as the aluminium hydroxide suspension. The co-administration of citrate, with the aluminium hydroxide suspension, was found to enhance the levels of 26Al uptake in both volunteers. Using a urinary excretion factor based on the results of previous studies, the fractional aluminium uptake from each of the species was calculated: aluminium citrate, 5.23 x 10(-3); aluminium hydroxide, 1.04 x 10(-4); aluminium hydroxide with citrate, 1.36 x 10(-3).

Adult↗
PubMed1995

Histopathology and 241Am microdistribution in skeletal USTER Case 246.

Histopathology and qualitative autoradiography studies were undertaken on bone removed at autopsy from USTUR Case 246. The histopathology examination revealed extensive bone marrow peritrabecular fibrosis and decreased cellularity in most samples. In addition, histological indicators suggest that bone cell turnover was suppressed at most sites, although turnover was found to be essentially normal in a vertebral body sample. The autoradiographic studies showed that bone turnover that had occurred resulted in the redistribution of americium within bone. However, surface deposits of americium remained conspicuous at many sites, particularly those with low bone growth activity. A few percent of the americium was present in the bone marrow. The dosimetric and toxicology findings indicate that current assumptions about the metabolic behavior of bone-seeking radionuclides are likely to be unrealistically simplistic.

Aged↗
PubMed1995

Human metabolism of aluminium-26 and gallium-67 injected as citrates.

1. 26Al and 67Ga were given as citrates to a healthy male volunteer by intravenous injection. The retention of both tracers was studied by body radioactivity measurement. Levels in blood and excreta were determined by gamma-ray spectrometry and/or accelerator mass spectrometry. 2. More than half of the 26Al had left the blood after 15 min and the decline continued, leaving < 1% in blood after 2 d; the losses occurred both to renal excretion and through uptake by other compartments. Estimated excretion up to 13 d was 83% (urine) and 1.8% (faeces). Whole-body retention of 15% at 13 d declined to approximately 4% at 1178 d, when the daily reduction corresponded to a biological half-life of 7 y, suggesting that sustained intake of dietary aluminium may lead to a progressively increasing internal deposit. 3. The metabolism of 67Ga differed markedly from that of 26Al in all aspects studied.

Adult↗
PubMed1995

Inter-subject variability in the metabolism of aluminium following intravenous injection as citrate.

1. Six healthy male volunteers received intravenous injections of 26Al as citrate. Accelerator mass spectrometry and gamma-ray spectrometry were used to determine levels of the tracer in blood and excreta at times up to 5-6 d. 2. There was a rapid clearance from blood (mean 2% of injection remaining after 1 d) and major loss in urine (59% up to 1 d), but 27 +/- 7 (s.d.)% was retained in the body at 5 d. Faecal excretion was negligible (1% up to 5 d). 3. The mean results accord with the early metabolic pattern in the single subject of a previous, more extensive study, who had retained 4% of the injection after 3 y. Together, the two studies point to the likelihood of large inter-subject differences in the long-term accumulation of dietary aluminium by populations receiving a given level of daily intake.

Adult↗
PubMed1993

Systemic deposits of thorium in thorotrast patients with particular reference to sites of minor storage.

It is well established that injected Thorotrast is deposited in the liver, spleen, bone marrow, and lymph nodes, but accumulations in organs with lower macrophage activity have previously been given little attention. In this work, neutron activation analysis has been used to investigate concentrations of thorium in autopsy samples taken at sites of major and minor deposition in 24 Thorotrast patients. In the latter category, the highest values were found in the testis [40 x 10(-6) g/g(wet)], followed by those in the adrenal gland, gallbladder, lung, and pancreas. The resulting alpha-particle dose rates (mGy/year) are tentatively estimated to be 8.5 to the testis, 5.5 to the gallbladder, and 5.3 to the lung. These results may be relevant to the residual excess mortality among Thorotrast patients after diseases of the principal organs of deposition have been excluded; they also support previous indications that thorium deposited in pulmonary tissues is responsible for an important component of the total dose to the lung. In another context, our data may bear on the connection, postulated elsewhere, between exposure to alpha-particle emitters and elevated incidence of leukemia in the children of workers engaged in the reprocessing of nuclear fuel.

Adult↗
PubMed1992

The distribution of Thorotrast in human bone marrow: a case report.

Samples of bone containing cellular and fatty bone marrow were removed at autopsy from the body of a woman who, following an automobile accident, had been injected with approximately 25 mL of the radiographic contrast medium Thorotrast. The woman survived for 36 y after the accident and died at age 72 y following bone marrow failure. The samples were analyzed to determine their thorium content by x-ray fluorescence and by image analysis. In addition, Thorotrast was visualized in the different bones examined by light microscopy and by backscattered electron imaging with a scanning electron microscope. The results showed Thorotrast to be largely restricted to areas of cellular bone marrow. In such regions, Thorotrast was present throughout the marrow tissue and was also concentrated within cells that were commonly aggregated within focalized areas of the marrow. Overall the results suggest a rather uniform pattern of Thorotrast uptake by the red bone marrow at different skeletal sites. Significant deposits of Thorotrast were not found in fatty yellow marrow. We conclude that Thorotrast-derived risk estimates for human leukemia following high LET, alpha irradiation may be used for calculating the risks of alpha exposure, but with caution.

Aged↗
PubMed1989

Sensitivity testing of an age-related, multicompartment dosimetric model for bone-surface-seeking radionuclides in man.

The sensitivity testing of an age-related dosimetric model and its application to the dosimetry of 239Pu are described. The model is used to calculate the committed dose received by the skeleton and liver to age 70 y, following intakes of 239Pu by an adult aged 20 y and by children aged 0 and 10 y. The model is biologically based and takes account of the age-dependent transfer of Pu between the different organs of the body and between the different components of the skeleton. It consists of 22 compartments, 16 of which are skeletal, each connected by transfer pathways defined by age-dependent rate constants. The sensitivity of the predictions of the model, as applied to adults, to changes in the assumed values of rate constants were tested. The results of the tests applied suggested that the age-related model is relatively robust and is not particularly sensitive to changes in the assumed values of many of the rate constants used.

Adult↗