Search PubMed⌕ Search

Biomedical subjects

D C Lloyd

Publications and source records attributed to D C Lloyd.

At least 19 recordsLinked to original sources
PubMed2001

In vitro transmission of chromosomal aberrations through mitosis in human lymphocytes.

Stable and unstable chromosome aberrations in human lymphocytes exposed to 2 and 4Gy of X-rays in G(0) were analyzed in M1 and M2 cells harvested at 72h to investigate how the scoring protocol influences the yields of aberrations transmitted through one mitosis. Metaphase chromosomes 2, 3, and 5 were painted using fluorescence in situ hybridization (FISH) whole chromosome probes, together with a pan-centromeric probe and stained by the harlequin-FISH method, to allow the cell cycle status of each cell to be determined as it was scored. A strict scoring criterion was adopted so that each metaphase had to contain 46 centromeres and each dicentric/centric ring had to have an acentric present. In addition to scoring the painted material, unstable aberrations in the whole genome were also recorded. The yield of complete dicentrics decreased by more than a factor of 2 in going from M1 to M2. The decrease was greater at the lower dose. Two-way translocations appeared stable, but one-way translocations decreased. This suggests that if translocation yields are to be used for biological dosimetry purposes, then the two-way type should be used.

Adult↗
PubMed2001

Prescribing at the Primary Care Group level: census data and prescribing indicators.

OBJECTIVE: To examine the relationship between prescribing and morbidity, mortality and deprivation for the 481 Primary Care groups set up on 1 April 1999, by examining the prescribing of their constituent practices in the year 1998/99, i.e. the year before. DESIGN: Cross-sectional study. OUTCOME MEASURES: Set of 11 prescribing indicators taken from the Prescription Pricing Authority 'Toolkit' system; census measures of morbidity and deprivation and Standardized Mortality Ratio for those aged 75 and under. SETTING: All practices in England belonging to a Primary Care Group. RESULTS: Several of the indicators showed strong correlation with morbidity, mortality and, to a weaker extent, with deprivation. There was a negative correlation between the census-based measures and choice of more expensive alternatives or greater duration prescriptions for antibiotic prescribing and with the use of hormone replacement therapy (HRT). Conversely, there was a positive correlation with use of premium products and drugs of limited therapeutic value. CONCLUSION: Practices in areas of greater need (as measured by permanent sickness and Standardized Mortality Ratio) seem to be trying to hold down costs by the way they prescribe antibiotics. Conversely, their use of premium price products pushes up their costs in the absence of clear evidence concerning compliance. The use of HRT is low in areas of high overall need.

Anti-Bacterial Agents↗
PubMed2001

A study to verify a reported excess of chromosomal aberrations in blood lymphocytes of Namibian uranium miners.

This report describes a study to verify an earlier report of excess chromosomal damage in the blood lymphocytes of uranium miners. Coded blood samples from 10 miners and 10 controls were analyzed conventionally for unstable aberrations and by FISH for translocations. Conventional analysis, scoring 1000 metaphases per subject, showed no significant difference between miners and controls in the frequencies of chromosome- and chromatid-type aberrations. Investigators at two laboratories undertook FISH analyses, each scoring 4000 metaphases per subject. When the data from each laboratory were examined separately, one found slightly more translocations in the miners while the other found fewer. In neither case was the difference significant at the 95% level of confidence. Combining the data likewise showed no significant excess of damage in the miners. This applied to simple one- and two-way translocations and to cells with complex exchanges. There was no correlation between levels of translocations and total lifetime doses from occupational and/or background irradiation. A borderline significant excess of rogue cells was found in the miners. This may be a chance observation, as these rare, highly abnormal cells are considered to be unrelated to radiation exposure and are probably due to a virus. The overall conclusion is that the frequency of chromosomal damage in the miners did not exceed that in the controls. Therefore, the result of the earlier study was not confirmed.

Chromosome Aberrations↗
PubMed2001

Lymphocyte chromosomal aberrations and their complexity induced in vitro by plutonium-239 alpha-particles and detected by FISH.

G0 human lymphocytes were exposed in vitro to plutonium-239 alpha-particles, with doses ranging from 0 to 1.62 Gy, to provide a dose response curve and to compare complex rearrangements produced by high LET radiation with low LET data from previous work. Metaphase chromosomes 1 and 2 were painted using fluorescence in situ hybridization (FISH) whole chromosome probes. All unstable and stable aberrations involving the painted chromosomes were scored. The whole genome corrected alpha-coefficient for dicentrics was 0.244 +/- 0.023 and for total translocations 0.346 +/- 0.032, when considering simple and complex exchanges. The ratio of bicoloured total translocations to bicoloured dicentrics was 1.21 +/- 0.15 and the ratio of 2-way to 1-way translocations was 1.73 +/- 0.27 for apparently simple exchanges only. A correlation was noted between the distributions of dicentrics and translocations and this applied even when the complex rearrangements were removed. 20% of the observed rearrangements were complex and this observation was independent of dose. Qualitatively, following irradiation with alpha-particles the complex rearrangements observed were of a greater complexity than seen after X- or gamma-rays. Using the Savage and Simpson system to classify the complex rearrangements, the higher order complexes were found to be the most common type observed. However the insertion type increased while the 2F + 2G types decreased when complex rearrangements induced by alpha-particles were compared to those formed after X- or gamma-irradiation.

Alpha Particles↗
PubMed2000

Derivation of a needs based capitation formula for allocating prescribing budgets to health authorities and primary care groups in England: regression analysis.

OBJECTIVE: To develop a weighted capitation formula for setting target allocations for prescribing expenditures for health authorities and primary care groups in England. DESIGN: Regression analysis relating prescribing costs to the demographic, morbidity, and mortality composition of practice lists. SETTING: 8500 general practices in England. SUBJECTS: Data from the 1991 census were attributed to practice lists on the basis of the place of residence of the practice population. MAIN OUTCOME MEASURES: Variation in age, sex, and temporary resident originated prescribing units (ASTRO(97)-PUs) adjusted net ingredient cost of general practices in England for 1997-8 modelled for the impact of health and social needs after controlling for differences in supply. RESULTS: A needs gradient based on the four variables: permanent sickness, percentage of dependants in no carer households, percentage of students, and percentage of births on practice lists. These, together with supply characteristics, explained 41% of variation in prescribing costs per ASTRO(97)-PU adjusted capita across practices. The latter alone explained about 35% of variation in total costs per head across practices. CONCLUSIONS: The model has good statistical specification and contains intuitively plausible needs drivers of prescribing expenditure. Together with adjustments made for differences in ASTRO(97)-PUs the model is capable of explaining 62% (35%+0.65% (41%)) of variation in prescribing expenditure at practice level. The results of the study have formed the basis for setting target budgets for 1999-2000 allocations for prescribing expenditure for health authorities and primary care groups.

Budgets↗
PubMed2000

The role of cytogenetics in early triage of radiation casualties.

Preliminary dose estimates by chromosomal analysis can be made rapidly in order to supplement early triage of radiation casualties based on clinical signs. An in vitro simulation of an accident with many casualties receiving whole or partial body exposure in the range 0-8 Gy is described. Faced with an urgent need for rapid results, confirmation of clinical triage can generally be obtained from scoring 20 metaphases per subject. Scoring should be increased to 50 cells where there is disagreement with the initial assessments or evidence of significantly inhomogeneous exposure.

Chromosome Aberrations↗
PubMed1999

The 60Co gamma ray dose-response for chromosomal aberrations in human lymphocytes analysed by FISH; applicability to biological dosimetry.

PURPOSE: To investigate the in vitro dose-response for 60Co irradiated human lymphocytes assayed by FISH, and to consider how this may be applied to retrospective dosimetry. METHOD: Blood was irradiated with doses in the range 0.25-4.0 Gy. Cultured lymphocytes were scored for all stable and unstable aberrations involving painted chromosomes 2, 3 and 5 and, in addition, all unstable aberrations in the counterstained chromosomes. A pancentromeric probe was included. RESULTS: The relative numbers of painted and full genome dicentrics agreed well with the Lucas hypothesis for calculating genome equivalence. The involvement of each painted chromosome in exchanges agreed with their relative arm lengths. The dose-response relationship fitted well to the linear quadratic model; Y=(0.9 x 10(-2))D+(6.5 x 10(-2))D2 where D is the dose in Gy for the incidence Y, of all one plus two-way translocations in all cells corrected for genome equivalence. Complex rearrangements also became more frequent with increasing dose. A correlation was noted between the distributions of dicentrics and translocations among the cells and this was entirely due to complexes. CONCLUSIONS: For retrospective dosimetry it is recommended to use an in vitro dose-response for apparently simple translocations in stable (Cs) cells. To date, acute linear yield coefficients from FISH data carry statistical uncertainties too large for useful application to retrospective dosimetry of persons exposed to chronic or low doses. As an interim measure it is suggested that one may derive a linear term from full genome dicentrics corrected by a factor representing the translocation to dicentric ratio.

Cells, Cultured↗
PubMed1999

Simple chromosome exchanges are not linear with dose.

PURPOSE: To check whether simple chromosome exchanges are linearly related to radiation dose. MATERIALS AND METHODS: Go-irradiated lymphocytes were cultured to produce metaphase preparations. Chromosomes 1 and 2 were painted different colours and the remaining chromosomes counterstained. Cells containing a colour junction involving both chromosomes 1 and 2 were scored fully, so that simple and complex rearrangements were distinguished. RESULTS: At doses of 2 Gy and below very few complex rearrangements were seen. About 90% of exchanges were simple. At these doses the linear component of the dose-effect curve accounts on average for only approximately 30% of the observed yield. CONCLUSIONS: There is a square-law dose component to the yield of simple exchanges in addition to the linear term.

Cells, Cultured↗
PubMed1999

Easy biodosimetry for high-dose radiation exposures using drug-induced, prematurely condensed chromosomes.

PURPOSE: To propose a practical method of biodosimetry for high-dose estimation. MATERIALS AND METHODS: Okadaic acid in the range 100 nM to 500 nM was given for 1-6 h to cultured lymphocytes that had been exposed in the range of 0 Gy to 40 Gy. The frequency of the cells with prematurely condensed chromosomes (PCC) was compared with that of metaphases accumulated by 0.05 microg/ml colcemid. The dose-response relationship of the yield of prematurely condensed ring chromosomes (PCC rings) in the irradiated lymphocytes was examined. RESULTS: The 0.05 microg/ml colcemid collected few metaphases when lymphocytes were irradiated to over 10 Gy. However, 500 nM okadaic acid produced a substantial number of analysable PCC in lymphocytes that had been exposed in the range of 0 Gy to 40 Gy. After 1 h of treatment, the 500 nM okadaic acid gave the most suitable chromosome morphology for the analysis. PCC rings were narrow, which facilitated their detection in Giemsa-stained preparations. The yield of PCC rings increased dose-dependently up to 20 Gy. CONCLUSION: PCC rings are a more suitable indicator than dicentrics at high doses over 10 Gy. This technique requires no particular equipment or exceptional skill. After a serious radiation accident, it can be easily performed in a short time in most medical facilities to obtain dose information to assist physicians.

Azure Stains↗
PubMed1999

Chromosomal analysis of peripheral lymphocytes of patients before and after radiation synovectomy with samarium-153 particulate hydroxyapatite.

OBJECTIVE: Radiation synovectomy may be indicated for the treatment of chronic synovitis. A number of factors may affect its current use, including availability, limited evidence for its efficacy compared to intra-articular glucocorticoid, and concerns regarding the potential long-term effects of radiation exposure, particularly in younger patients. Specific chromosome-type abnormalities in peripheral lymphocytes can be useful indicators of whole-body radiation exposure. The frequency of these aberrations has been shown to increase in patients who have had radiation synovectomy using yttrium-90 by up to five times compared to baseline levels. Samarium-153 particulate hydroxyapatite (Sm-153 PHYP) is a new radiopharmaceutical currently on trial which appears to have less extra-articular leakage than yttrium-90 compounds. The aim of this study was to identify any increase in specific chromosome-type abnormalities, using published criteria, in patients following Sm-153 PHYP synovectomy of the knee. The 10 patients (five men, five women) in whom the analyses were performed had a mean age of 47 yr (range 28-70 yr). RESULTS: There was no increase in scored chromosome-type abnormalities after Sm-153 PHYP synovectomy. CONCLUSION: This study further supports the relative safety of Sm-153 PHYP compared to other radiopharmaceuticals.

Adult↗
PubMed1998

Sonographic appearances of meniscal cysts.

PURPOSE: This study was conducted to define the sonographic appearances of cysts of the tibial menisci. METHODS: Thirteen cases of meniscal cyst, proven by magnetic resonance imaging (MRI), were assessed using high-resolution sonography, and results of the 2 imaging modalities were correlated. RESULTS: Seven meniscal cysts were lateral to the joint line, and 6 were located medially. MRI showed all 13 cysts to be associated with a tear of the adjoining meniscus. On sonograms, cyst size varied from 9 to 56 mm. Echotexture varied from uniformly hypoechoic or hypoechoic with echogenic septa to heterogeneously hyperechoic. Septated cysts were demonstrated by MRI and sonography. CONCLUSIONS: Because of their diverse echo patterns, meniscal cysts may be easily mistaken for soft-tissue tumors, ganglions, or other lesions, which may result in surgery being inappropriately recommended. This is particularly true in the case of echogenic cysts. The cardinal sonographic characteristic of a meniscal cyst is its continuity with the meniscus, not its echotexture.

Adult↗
PubMed1998

Magnetic resonance imaging of acute intraosseous disc herniation.

Schmorl's nodes, the result of previous intraosseous disc herniation (IODH), are a common incidental finding on plain radiographs, computed tomography (CT) and magnetic resonance imaging (MRI). Acute IODH can, however, cause severe back pain, and the radiological features may also lead to inappropriate suspicion of malignancy or infection. We present eight cases of acute IODH in order to illustrate how the correct diagnosis can be made by MRI. In six cases isotope bone scintigraphy had been performed, demonstrating focal increased activity at the site of IODH. MRI can reinforce the concern about serious underlying pathology by the demonstration of marrow oedema, which may be localized around the disc herniation or extensive, extending throughout the vertebral body and into the pedicles. The key to the correct diagnosis is the recognition of the endplate defect and disc herniation. In three cases the diagnosis may have been possible from plain radiographs in which disc calcification visible on previous radiographs had migrated into an intraosseous location.

Acute Disease↗
PubMed1998

Accidental intake of tritiated water: a cytogenetic follow-up case on translocation stability and dose reconstruction.

PURPOSE: To examine by fluorescence in situ hybridization (FISH) chromosomal translocations in a person who, 11 years previously, had accidentally incorporated tritiated water. To compare the resultant estimate of radiation dose with contemporary dosimetry made by urine analysis and dicentric chromosome scoring. MATERIALS AND METHODS: Blood lymphocytes were shared by two laboratories each performing the FISH analysis using different chromosome probe combinations. Doses were calculated by reference to an in vitro calibration curve produced in one of the laboratories. RESULTS: Good agreement in translocation yields was found by the two laboratories. Comparing the yields with the dicentric frequency obtained shortly after the accident and with a translocation frequency measured 6 years post exposure showed good agreement between all measurements. This indicates essentially perfect stability for translocations over an 11 year period in this individual. CONCLUSIONS: Dose reconstruction based on FISH-measured translocations showed good agreement with the dose estimated from initial dicentric measurements and from measurements of tritium in urine. Because of the extensive initial dosimetry performed on this individual, who received a uniform whole-body irradiation, the case serves as an excellent test for the use of FISH-measured translocations for retrospective biodosimetry.

Chromosomes, Human↗
PubMed1998

Risks from ionising radiation: deterministic effects.

This paper is a shortened version of an NRPB document that reviewed the deterministic effects on human health likely to arise from serious overexposure to ionising radiation. Little new primary information on deterministic effects has become available in recent years. However, advances in techniques for data analysis have been made, particularly in describing the sigmoid dose-effect relationships, effects of dose rate and radiation quality. These are presented in a form suitable for use in modelling the consequences to populations of serious radiological incidents.

Dose-Response Relationship, Radiation↗
PubMed1997

Chromosome aberrations in Syrian hamsters following very low radiation doses in vivo.

This paper addresses a report of a large increase (approximately 6- to 11-fold) in chromosome aberrations in lymphocytes of persons in Salzburg attributed to their exposure to fallout from the Chernobyl cloud. Their additional exposure, approximately 0.3 mGy in 1 year, comprised about a 30% increase in their normal background radiation dose. The report has attracted considerable attention because, if correct, it seriously challenges assumptions of linearity in the low-dose response for chromosomal damage and, by implication, the linear, no-threshold hypothesis for risk of induced cancer. An experiment has been carried out with Syrian hamsters treated with caesium-137 to produce a range of doses comparable with those calculated for the persons in Salzburg. No significant elevation in lymphocyte aberration yields was found in the hamsters, thus arguing against the conclusions of the Salzburg study.

Animals↗