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Biomedical subjects

M J Woods

Publications and source records attributed to M J Woods.

At least 19 recordsLinked to original sources

International guidance on the establishment of quality assurance programmes for radioactivity measurement in nuclear medicine.

A new guidance document for the implementation of quality assurance (QA) programmes for nuclear medicine radioactivity measurement, produced by the International Atomic Energy Agency, is described. The proposed programme is based on the principles of ISO 17025 and will enable laboratories, particularly in developing countries, to provide consistent, safe and effective radioactivity measurement services to the nuclear medicine community.

Guidelines as Topic↗

Comparison of strontium-89 solution sources in UK hospitals, 2003.

Concerns have been raised within the nuclear medicine field about the accuracy of measurements of 89Sr. The 85Sr impurity present in the 89Sr solution has a significant effect on the response of radionuclide calibrators used in hospitals. A comparison was conducted between the National Physical Laboratory (NPL) and the UK hospital physics community. Only 58% of the results were within 5% of the NPL value. Work at NPL has resulted in correction factors for the NPL secondary standard radionuclide calibrator and for Capintec calibrators, which will produce a significant improvement in performance.

Hospitals↗

Some results of a simulated test for administration of activity in nuclear medicine.

This paper describes the results obtained using a simulated test for administration of activity in nuclear medicine between 2002 and 2004. Measurements in the radionuclide calibrator are made during the different stages of the procedure. The test attempts to obtain supplementary information on the quality of the measurement, with the aim of evaluating in a more complete way the accuracy of the administered activity value compared with the prescribed one. The participants' performance has been assessed by means of a statistical analysis of the reported data. Dependences between several attributes of the simulated administration tests results are discussed. Specifically, the proportion of satisfactory results in the 2003-2004 period was found to be higher than in 2002. It reveals an improvement of the activity administration in the Cuban nuclear medicine departments since 2003.

Calibration↗

Comparison of radioactivity measurements with radionuclide calibrators in the Republic of Korea.

Recognizing the importance of comparisons of radionuclide calibrators in nuclear medicine and the need to provide access to activity standards that are traceable to the international measurement system, the Korea Food & Drug Administration (KFDA) as a national secondary standard dosimetry laboratory (SSDL), started a comparison program in 2002. The first two comparisons were conducted with (131)I (71 participants) and (99m)Tc (72 participants). The results indicated that only 61% of reported activities for (131)I and 65% for (99m)Tc were within +/-5% of the correct value. These numbers increased to 84% for (131)I and 83% for (99m)Tc when a +/-10% limit was applied. Follow-up action on those calibrators with results outside the +/-10% limits only produced a small improvement. There was also a marked difference in performance between the various calibrator types used. The results have shown that such comparisons are necessary to improve the quality of the measurements and to identify those radionuclide calibrators that are not functioning correctly.

Calibration↗

Nuclear data used in the analysis of thorium in the workplace.

The analysis of thorium in the workplace can be achieved using a variety of metrological techniques. The uncertainty on the final measured values will include components that arise from the uncertainties in the nuclear data that are used. These data include half-lives, branching ratios and gamma ray emission probabilities. It is important that a common, consistent and reliable data set is used in order to minimise the potential differences between analytical results. With particular reference to the problems associated with thorium analysis, some of the various sources of nuclear data are discussed and a recommended set of data is proposed.

Databases as Topic↗

Thorium in the workplace: the preparation and validation of comparison samples for a European-based measurement comparison project.

The quality of any comparison exercise depends critically on the quality. accuracy and fitness for purpose of the comparison samples. The comparisons were designed to move progressively from the testing of the analysis capabilities for relatively simple. aqueous solutions through to the more complex natural matrix materials encountered in the workplace. In each case, it was imperative that the comparison samples were prepared and validated in such a way as to ensure traceability of their activity values to national and international standards of radioactivity, to enable a reasonable estimate to be made of the uncertainty on those values and to ensure homogencity both within and between samples. The processes involved are discussed.

Alpha Particles↗

Thorium in the workplace: results from a European-based measurement comparison project.

A Series of comparisons were conducted to test the capabilities of a range of metrological techniques and analytical laboratories engaged in the assay of thorium in the workplace. The results of these exercises are presented together with the decision criteria used to determine whether results are significantly different from the true value. The discussion highlights those aspects which warrant closer and further attention.

Europe↗

The EC Thematic Network on the Analysis of Thorium and its isotopes in Workplace Materials.

Accurate measurements of workplace exposure to 232Th and its progeny are required to estimate internal radiation doses received by persons working with thorium-containing materials. However, a small intercomparison carried out in the mid-nineteen nineties raised doubts about the reliability of results obtained by methods available for measurement of thorium. An EC-funded thematic network was therefore established to bring together experts in the field of thorium analysis in order to coordinate research activity and identify best analytical practice. requirements for reference materials. etc. This network has now successfully completed its work programme. which included a survey to determine future research needs; a series of intercomparisons to test the performance of methods for measuring thorium in workplace materials, and a workshop held to promote best practice and transfer information to regulatory authorities and industry. Results of the work have been used to make various recommendations concerning future needs in this field.

Humans↗

Multiple forms and locations for the peripheral-type benzodiazepine receptor.

The pharmacological effects of benzodiazepines are mediated through a class of recognition sites associated with the neuronal gamma-aminobutyric acidA (GABAA) receptor. A second class of benzodiazepine binding sites is found in virtually all mammalian peripheral tissues, in blood cells, and in glial cells in the brain, but its functions remain unclear. Although these peripheral-type benzodiazepine binding sites (PBBS) have been localized to the mitochondrial outer membrane in many tissues, a growing body of evidence suggests that they may also exist on the plasma membrane. Plasma membrane PBBS have been described in heart, liver, adrenal, and testis and on hemopoietic cells. In rat liver, the two subcellular forms of PBBS are found separately in two different subpopulations of cells. The discovery of a plasma membrane fraction of PBBS clearly has implications for some of its putative functions, including steroidogenesis, mitochondrial respiration, heme metabolism, calcium channel modulation, cell growth, and immunomodulation. This commentary reviews the evidence for two locations for the PBBS and discusses the relevance of mitochondrial and plasma membrane forms with regard to structure, molecular biology, and proposed roles.

Animals↗

Synthesis, biological activity, and SARs of pyrrolobenzoxazepine derivatives, a new class of specific "peripheral-type" benzodiazepine receptor ligands.

The "peripheral-type" benzodiazepine receptor (PBR) has been reported to play a role in many biological processes. We have synthesized and tested a novel series of PBR ligands based on a pyrrolobenzoxazepine skeleton, in order to provide new receptor ligands. Several of these new compounds proved to be high affinity and selective ligands for PBR, and benzoxazepines 17f and 17j were found to be the most potent ligands for this receptor to have been identified to date. The SAR and the molecular modeling studies detailed herein delineated a number of structural features required for improving affinity. Some of the ligands were employed as "molecular yardsticks" to probe the spatial dimensions of the lipophilic pockets L1 and L3 in the PBR cleft and to determine the effect of occupation of L1 and L3 with respect to affinity, while other C-7 modified analogues provided information specifically on the hydrogen bonding with a putative receptor site H1. The new pyrrolobenzoxazepines were tested in rat cortex, a tissue expressing high density of mitochondrial PBR, and exhibited IC50 and Ki values in the low nanomolar or subnanomolar range, as measured by the displacement of [3H]PK 11195 binding. A subset of the highest affinity ligands was also found to have high affinities for [3H]PK 11195 and [3H]Ro 5-4864 binding in rat adrenal mitochondria. All the ligands in this subset are stimulators of steroidogenesis having similar potency and extent of stimulation as PK 11195 and Ro 5-4864 of steroidogenesis in the mouse Y-1 adrenocortical cell line.

Animals↗

Two cellular and subcellular locations for the peripheral-type benzodiazepine receptor in rat liver.

Determination of ligand binding properties of the peripheral benzodiazepine receptor (PBBS) in liver, in hepatocytes, and in nonparenchymal cells demonstrated the presence of receptor-specific high-affinity binding in both hepatocyte and nonhepatocyte cells. Density gradient centrifugation showed that the high-affinity receptor in hepatocytes was localised to mitochondria, whereas in nonhepatocytes it was not mitochondrial, but with a possible biliary epithelial cell plasma-membrane location. Both receptors showed the peripheral-type specific high-affinity binding of PK 11195 and Ro5 4864 and could be photolabelled as 18 kDa proteins with [3H]PK 14105. Immunocytochemistry showed the presence of acyl-CoA binding protein, a putative endogenous ligand for the receptor, in both cell locations. Some other properties of the PBBS were investigated in liver. Diphosphatidyl glycerol had a strong inhibitory effect on receptor binding in both liver and adrenal, with Ro5 4864 more sensitive to inhibition than PK 11195. However, whereas soybean lipid and phosphatidyl serine increased the binding of both ligands to adrenal receptor, these lipids had no effect on liver, suggesting that liver PBBS may differ from the well-characterised adrenal PBBS in some of its protein conformation. Modulators of mitochondrial respiration that also influence intermembrane contact site formation were found to elicit no marked stimulatory or inhibitory effects on PBBS ligand binding in liver, a result also found for adrenal mitochondria, suggesting that the extent of contact site formation does not influence ligand binding and that the hepatocyte receptor may not play a role in regulating mitochondrial respiration. These two cellular and subcellular locations of the PBBS in liver and the different effect of phospholipids compared to other peripheral tissues may be important for the role(s) of PBBS in liver and also for the multiple roles ascribed to the receptor and to peripheral-type benzodiazepine ligands.

Adrenal Glands↗

Calibration of the NPL secondary standard radionuclide calibrator for 192Ir brachytherapy sources.

Safe and effective treatment with brachytherapy sources requires an accurate knowledge of the local tissue absorbed dose rate derived from the source reference air kerma rate. It is desirable that these air kerma rate measurements be traceable to national standards. The NPL has embarked on a programme that will enable the user to assay brachytherapy sources in a convenient manner prior to treatment. Calibration figures have been derived for the NPL secondary standard radionuclide calibrator for 192Ir brachytherapy sources manufactured by Amersham International plc. The calibration figures enable the user to accurately estimate the reference air kerma rate and activity of such sources by measuring the ionization chamber response. Calibration figures for other brachytherapy sources are also being derived.

Brachytherapy↗

The fate of circulating megakaryocytes during cardiopulmonary bypass.

Megakaryocytes with intact cytoplasm normally leave the bone marrow, enter central venous blood, and are filtered in the lungs. During cardiopulmonary bypass, large megakaryocytes are not filtered by the lungs and may not be removed in the extracorporeal circuit by arterial line filters. In such circumstances, they could enter the systemic circulation and block smaller cerebral vessels, resulting in neurologic impairment. To investigate the fate of circulating megakaryocytes during cardiopulmonary bypass, central venous blood and oxygenated blood samples before and after arterial line filtration (40 microns polyester screen filter) were obtained from 10 patients undergoing cardiopulmonary bypass. Megakaryocytes were isolated by whole blood filtration and identified by their characteristic structure after May-Grunwald-Giemsa staining. In preliminary studies, megakaryocyte identification was verified by immunolabeling. All samples contained megakaryocytes with copious cytoplasm. Their frequencies in central venous blood and oxygenated blood before and after the arterial line filtration (corrected for hemodilution) were 23.4 +/- 9.3 per milliliter (mean +/- standard error of the mean, range 3.1 to 89.7 per milliliter), 21.0 +/- 8.2 per milliliter (2.0 to 84.2 per milliliter) and 17.1 +/- 7.4 per milliliter (3.1 to 80.4 per milliliter), respectively. Megakaryocytes with scant or no visible cytoplasm were also observed. The results confirm that circulating megakaryocytes are a normal physiologic component. During cardiopulmonary bypass, megakaryocytes with copious cytoplasm (mean diameter 42.7 microns, range 22 to 78 microns) can pass through the extracorporeal circuit. In the absence of filtration by the lungs, these large cells have access to the systemic circulation. This study supports a possible role for circulating megakaryocytes in the development of cerebral dysfunction after cardiopulmonary bypass.

Adult↗

Isolation of circulating megakaryocytes in man.

Recovery of the small numbers of megakaryocytes (MKs) known to be present in normal blood is difficult because of their low frequency. Isolation of circulating MKs was achieved using a modified filtration system in which untreated blood was passed through 5 microns polycarbonate membranes. MKs were retained while most other blood cells passed through the membranes. Four groups of MKs were identified in May Grünwald-Giemsa stained filters of blood from peripheral, central and umbilical veins and umbilical arteries. Type 1 MKs were nuclei with no visible cytoplasm. Types 2, 3 and 4 were nuclei with increasing amounts of cytoplasm. Type 4 MKs, possessing copious cytoplasm, were rarely isolated from peripheral venous blood but were more regularly encountered in central venous and cord blood. Filtration of whole blood through polycarbonate membranes is a useful technique for the isolation of circulating MKs, which are a normal physiological occurrence. Their presence is consistent with the production of platelets in the placenta during intra-uterine life, and subsequently in the pulmonary circulation.

Hemofiltration↗

Two subcellular locations for peripheral-type benzodiazepine acceptors in rat liver.

Subcellular fractionation of rat liver by differential centrifugation showed the mitochondrial fractions to have the greatest enrichment of 'peripheral-type' benzodiazepine acceptor. Two peaks of acceptor sites were found on isopycnic density-gradient centrifugation, one peak (rho = 1.19 g/ml) corresponding to the peak of mitochondria as judged by marker enzyme distribution and by transmission electron microscopy, and the other peak (rho = 1.17 g/ml) which is not mitochondrial as judged by the lack of mitochondrial enzyme markers. Whereas the density of the mitochondrial acceptor was sensitive to sonication and was shown to have an outer-membrane location, the density of the non-mitochondrial acceptor was insensitive to sonication. The non-mitochondrial acceptor was shown not to be associated with Golgi, lysosomes, rough endoplasmic reticular microsomes, peroxisomes, or some types of plasma membranes, as judged by differences in the distribution of marker activities. No enrichment of benzodiazepine acceptor was found in the purified nuclear fraction. Both acceptors were shown to be peripheral-type high-affinity acceptors as judged by ligand specificities and by photoaffinity labelling.

Affinity Labels↗

Electrical impedance assessment of muscle changes following exercise.

Electrical impedance measurements have been assessed as a method of detecting changes in striated muscle following vigorous exercise. Transverse and longitudinal resistivities of the calf and thigh have been measured before and after four subjects ran a half marathon (21 km). No changes were observed in longitudinal resistivity but transverse resistivity rose by an average of 7% following the race. These results are consistent with changes in the muscle fibre membranes or interstitial fluid content.

Adult↗

Megakaryocyte ploidy in thrombocytosis: improved microdensitometric measurements with a new image analysis system.

Megakaryocyte (MK) nuclear deoxyribonucleic acid (DNA) content was measured on a new image analysis system. Feulgen-stained bone marrow aspirate smears were analysed from 9 patients with thrombocytosis. Average optical density (OD) of stained nuclei was evaluated by pixel discrimination over 128 grey levels. Projected nuclear area was delineated manually. The product of these two parameters gave an index of nuclear DNA content. Neutrophils were used as 2N reference cells. Reproducibility of OD, nuclear area and their product was excellent for individual cells (CV less than 2.0% for MKs, less than 4.0% for neutrophils). The average CV for DNA content of 18 groups of 10 neutrophils was 5.5% (range 3.0-9.7%). A significant linear regression existed between MK nuclear area and DNA content (p much less than 0.001) for 627 MKs in essential thrombocythaemia (ET) and 346 MKs in reactive thrombocytosis (RT). Compared with RT, more 8N and 64N MKs were seen in ET (p less than 0.05). 128N MKs were unique to ET. Image analysis of MK ploidy may assist the clinical discrimination between primary and secondary thrombocytosis.

DNA↗