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Biomedical subjects

D M Reid

Publications and source records attributed to D M Reid.

At least 109 records · Page 6Linked to original sources
PubMed1997

Osteoporosis.

Clearly osteoporosis is a major scourge of Western society but interest in the condition has risen exponentially in the last 10 years partly because of advances in our understanding of the disease process, the ability to predict its onset, to reverse the process of bone loss and to measure the consequences of treatment, but also in part due to increased public awareness. Further advances are likely, especially in our understanding of the genetic background of the disorder and our ability, not only to reduce bone resorption, but also to enhance bone formation. The challenge will be how to target our improved therapies at the expanding elderly population to reduce the impact and costs of fracture.

Absorptiometry, Photon↗
PubMed1997

Bone density variation and its effects on risk of vertebral deformity in men and women studied in thirteen European centers: the EVOS Study.

In Europe there is a 3-fold variation, according to geographical center, in risk of vertebral deformity in men and women over the age of 50. We investigated the relationship between bone density, as assessed by dual-energy X-ray absorptiometry (DEXA) of the spine and hip and prevalent vertebral deformities in 13 of the 36 centers participating in the European Vertebral Osteoporosis Study (EVOS). Each center recruited an age-stratified sample of men and women aged 50 years and over, and of those who agreed to densitometry, 288/2088 women and 233/1908 men were found to have one or more deformities of the vertebrae between T4 and L4 as assessed by the McCloskey algorithm. DEXA was in each case performed on L2-L4, the proximal femur, or both. Bone densitometry results were cross-calibrated between centers using the European Spine Phantom prototype and results expressed as bone mineral density (BMD, g/cm2). In both genders, subjects with deformities involving loss of anterior vertebral body height alone comprised over 20% of the total with deformities and these related poorly to BMD. Other classes of deformity were found by logistic regression to relate significantly to BMD in one or both genders, with odds ratios for the risk of any of these ranging from 1.67 to 2.11 for a 1 SD reduction in bone density at spine, femoral neck, or trochanter (p < 0.001). Adjusting for anthropometric variables and BMD did not remove the effect of age on risk which rose 1.67- to 1.78-fold per decade according to gender. The greater unadjusted rate of increase in deformity risk with age in women was attributable to their faster rate of bone loss with age; after adjusting for age, body mass index (BMI), and BMD at the trochanter in grams per square centimeter, men had a 2-fold higher risk of deformity than women. Analysis of the relationship between mean bone density and the prevalence of deformity in each center demonstrated no significant differences between centers in either gender, after adjusting for BMD, age, and BMI together with an a posteriori statistical adjustment for imperfect cross-calibration of densitometers. It is concluded that BMD is an important determinant of deformity risk in both genders. Together with age, BMD explains much of the differences in risk both between the sexes and between individual geographical centers in Europe.

Aged↗
PubMed1997

The economics of osteoporosis and its prevention. A review.

A systematic review of all published economic evaluations of treatments for the prevention of osteoporosis since 1980 was undertaken. 21 published studies were identified. The majority of the studies were set in the context of the US healthcare system. Non-US studies were heavily influenced by the methodologies of 1 US research group. All studies published before 1990 only considered the use of hormone replacement therapy (HRT) at the menopause for osteoporosis prevention. Since 1990 a number of studies have looked at other therapies as well as HRT in older women. All studies that have made a direct comparison between using HRT at the menopause with HRT in older women have suggested that it is more cost effective to initiate therapy in older non-perimenopausal women. However, there is a paucity of evidence from randomised controlled trials on which to base assumptions on costs and effectiveness. Large randomised trails with hip fracture as the main outcome measure are required to answer key economic and clinical questions.

Female↗
PubMed1996

Human thrombopoietin levels are high when thrombocytopenia is due to megakaryocyte deficiency and low when due to increased platelet destruction.

Thrombopoietin (TPO), the ligand for c-mpl, stimulates proliferation of committed megakaryocytic progenitors and induces maturation of megakaryocytes. To better understand factors regulating TPO levels, we measured blood levels of TPO in patients with impaired platelet production due to aplastic anemia (AA) and with platelet destructive disorders, including idiopathic thrombocytopenic purpura (ITP), posttransfusion purpura (PTP), drug purpura (DP), and X-linked thrombocytopenia (XLTP). The TPO receptor capture enzyme immunoassay (EIA) used had a detection limit of integral of approximately-150 to 200 pg/mL. TPO was undetectable in 88 of 89 normal individuals. Eighteen of 19 patients with AA and a mean platelet count (MPC) of 18,000/microliters (2,000 to 61,000/microliters) had markedly elevated TPO levels (mean, 1,467 pg/mL; range, 597 to 3,834 pg/mL). Eight AA patients who responded to immunosuppressive therapy with their MPC increasing to 140,000/microliters (92,000 to 175,000/microliters) had substantial decreases in TPO (mean, 440 pg/mL; range, 193 to 771 pg/mL). Initial TPO levels did not differ significantly between responders and nonresponders. In contrast, all 21 patients with ITP and an MPC of 16,000/microliters (1,000 to 51,000 /microliters) had undetectable TPO levels, as did 6 patients with acute PTP or DP and 2 patients with XLTP. Megakaryocyte mass, reflected in the rate of platelet production, appears to be the major determinant of TPO levels in thrombocytopenic patients rather than circulating platelet levels per se. Measurement of serum TPO may be useful in differentiating thrombocytopenias due to peripheral destruction from those due to thrombopoietic failure.

Adolescent↗
PubMed1996

Elevated nitric oxide production in rheumatoid arthritis. Detection using the fasting urinary nitrate:creatinine ratio.

OBJECTIVE: To develop a simple method for assessing endogenous nitric oxide (NO) production applicable to routine clinical practice in rheumatology. METHODS: NO production was assessed in patients with rheumatoid arthritis (RA) as serum nitrate levels and as the urinary nitrate:creatinine ratio in morning samples of urine following an overnight fast. The influence of dietary intake of nitrate on these measurements was investigated in healthy volunteers. The clinical value of the urinary nitrate:creatinine ratio was validated in patients with infectious gastroenteritis, in whom its production is known to be increased. RESULTS: Urinary nitrate:creatinine ratios were significantly elevated in patients with RA (average 3-fold elevation over controls; P < 0.005) or infectious gastroenteritis (average 10-fold elevation, P < 0.001). Serum nitrate was significantly elevated only in patients with infectious gastroenteritis (P < 0.001). Dietary intake of nitrate had no significant influence on the fasting morning urinary nitrate:creatinine ratio in the healthy volunteers, showing that this parameter is a useful indicator of endogenous NO production.

Adult↗
PubMed1996

Prediction of perimenopausal fractures by bone mineral density and other risk factors.

In a prospective population-based cohort study, we assessed whether bone mineral density (BMD) measurements of perimenopausal women and other risk factors for osteoporosis are predictive of subsequent fracture. Women aged 47-51 years chosen randomly from a population register who underwent a bone density measurement 2 years previously were followed up by questionnaire to assess the 2-year incidence of any self-reported fractures. We found that 44 women, out of 1857 who completed the questionnaire, sustained at least one fracture within a 2-year follow-up period. After adjustment for covariates, the odds ratio of sustaining a fracture was 1.6 (95% confidence interval [CI] 1.16-2.34) for every standard deviation reduction in BMD at the spine, for women with a prior history of fracture the odds ratio of a subsequent fracture was approximately 2 (95% CI 1.31-3.03), a family history of hip fracture (maternal grandmother) carried an odds ratio of 3.7 (95% CI 1.55-8.85), while being postmenopausal or having a hysterectomy resulted in an odds ratio of 1.98 (1.02-3.56). This study has shown that BMD measurements at the hip and spine and other risk factors predict any nonhip and nonspine perimenopausal fractures. Further follow-up is required to assess the predictive performance of BMD measurements and other risk factors for hip and spine fractures.

Bone Density↗
PubMed1996

Light- and temperature-entrained circadian regulation of activity and mRNA accumulation of 1-aminocyclopropane-1-carboxylic acid oxidase in Stellaria longipes.

Stem and leaf tissues of Stellaria longipes Goldie (prairie ecotype) exhibit circadian rhythmicity in the activity and mRNA abundance for 1-aminocyclopropane-1-carboxylic acid oxidase (EC 1.4.3). The steady-state mRNA levels and enzymatic activity levels fluctuated with a period of approximately 24 h and reached their maxima by the middle of the light phase and minima by the middle of the dark phase. The oscillations showed damping under constant light, constant dark and constant temperature conditions, indicating that the rhythm is entrained by an external signal. The results indicate that light/dark cycles have greater entraining effects than temperature cycles. A 15-min red light pulse, but not a blue light pulse, could reset rhythm in continuous darkness, suggesting the possible role of a red-light signal transduction pathway in the circadian regulation of 1-aminocyclopropane-1-carboxylic acid oxidase.

Amino Acid Oxidoreductases↗
PubMed1996

Vitamin D receptor polymorphism, bone mineral density, and osteoporotic vertebral fracture: studies in a UK population.

Bone mineral density is under strong genetic control and polymorphisms of the vitamin D receptor (VDR) have been suggested to account for some of the genetic variation in bone mass. However, the relationship between VDR polymorphisms and bone density is controversial and has not been confirmed by all workers. Since there is little information on the association between VDR genotype and bone mass in the UK, we studied VDR genotype, bone mineral density, and osteoporotic fracture in a cohort or pre- and postmenopausal women from the Northeast of Scotland. We found a highly significant "inverse" association between the VDR genotype and bone mineral density at the hip such that individuals of "bb" genotype had a femoral neck bone density of 0.79 standard deviation lower than individuals of BB genotype (p < 0.02). This contrasts with most previous studies in which the "bb" genotype has been associated with high bone density. A similar, but nonsignificant trend was seen for lumbar spine BMD. To study the clinical significance of this observation, we examined the distribution of VDR genotypes in a subgroup of patients with severe osteoporosis who had vertebral compression fractures (n = 44) as compared with with age-and gender-matched controls (n = 44). Despite the differences in BMD between genotypes, there was no significant excess of any specific VDR genotype in osteoporotic fracture patients, indicating that VDR genotyping may be of limited practical value in identifying patients at risk of vertebral fracture. This study confirms that there is a significant association between VDR genotype and bone mass in our population. The "inverse" relationship between VDR genotype noted in this, as compared with previous studies, would be consistent with a model whereby VDR polymorphisms are not the cause of reduced BMD, but rather, are in linkage disequilibrium with a disease-causing locus nearby.

Absorptiometry, Photon↗
PubMed1996

Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type I alpha 1 gene.

Osteoporosis is a common disease with a strong genetic component, characterized by reduced bone mass and increased fracture risk. Current evidence suggests that the inheritance of bone mass is under polygenic control but the genes responsible are poorly defined. Type I collagen is the major protein of bone encoded by the COLIA1 and COLIA2 genes. While these are strong candidates for the genetic regulation of bone mass, no abnormality of either gene has so far been defined in osteoporosis. In this study, we describe a novel G-->T polymorphism in a regulatory region of COLIA1 at a recognition site for the transcription factor Sp1(7) that is significantly related to bone mass and osteoporotic fracture. G/T heterozygotes at the polymorphic Sp1 site (Ss) had significantly lower bone mineral density (BMD) than G/G homozygotes (SS) in two populations of British women and BMD was lower still in T/T homozygotes (ss). The unfavourable Ss and ss genotypes were over-represented in patients with severe osteoporosis and vertebral fractures (54%), as compared with controls (27%), equivalent to a relative risk of 2.97 (95% confidence interval 1.63-9.56) for vertebral fracture in individuals who carry the 's' allele. While the mechanisms that underlie this association remain to be defined, the COLIA1 Sp1 polymorphism appears to be an important marker for low bone mass and vertebral fracture, raising the possibility that genotyping at this site may be of value in identifying women who are at risk of osteoporosis.

Binding Sites↗
PubMed1996

Allele-specific restriction analysis of human platelet antigen system 4.

BACKGROUND: Diagnosis, and occasionally treatment, of disorders involving platelet-specific alloimmunization, including neonatal alloimmune thrombocytopenia and posttransfusion purpura, requires platelet allotyping. Allele-specific restriction analyses for convenient genotyping are available for the major human platelet antigen (HPA) systems except HPA-4. STUDY DESIGN AND METHODS: An allele-specific restriction analysis for HPA-4 was developed by designing a polymerase chain reaction primer containing a single-base substitution (A for T) at glycoprotein IIIa cDNA position 529. The resulting mismatch did not interfere with DNA amplification. Digestion of the polymerase chain reaction product with BsmI allowed differentiation of HPA-4a and HPA-4b alleles. RESULTS: A 126-bp polymerase chain reaction product was amplified with the novel primer. BsmI endonuclease cleaved product encoding HPA-4a into 104- and 22-bp fragments and left DNA encoding HPA-4b intact. CONCLUSION: This rapid allele-specific restriction analysis for genotyping the HPA-4 system complements similar methods for other platelet alloantigenic determinants.

Alleles↗
PubMed1996

Prediction of fractures in perimenopausal women: a comparison of dual energy x ray absorptiometry and broadband ultrasound attenuation.

OBJECTIVE: To consider whether bone mineral density (BMD) measurements can predict traumatic fractures occurring in perimenopausal women. METHODS: One thousand perimenopausal women called up for screening underwent both dual energy x ray absorptiometry (DXA) of the spine and hip, and broadband ultrasound attenuation (BUA) of the heel. Two years later, they were sent a questionnaire to discover those who had since had a fracture, and compare them with those who had not. RESULTS: About 2% of the women had sustained a fracture in the two years since attendance for screening. Fractures in this age group can be predicted weakly, but significantly, by bone mass measurements using DXA and BUA (odds ratios from 1.4 to 2.1). The lumbar spine appeared to be one of the best predictive sites (odds ratio for 1 SD reduction in BMD 2.1 (95% confidence interval 1.2 to 3.8)), but no significant differences were found between the areas under the curve in receiver operator characteristic (ROC) analysis. CONCLUSION: In this preliminary study it appeared that bone mass measurements are predictive of perimenopausal traumatic fractures in addition to postmenopausal fractures related to osteoporosis. DXA of the lumbar spine did not perform significantly better than BUA. The number of fractures occurring was low, however, and further long term follow up is required to confirm the finding.

Absorptiometry, Photon↗
PubMed1996

Seasonal differences in biochemical parameters of bone remodelling.

AIMS: To compare bone remodelling parameters in late autumn and early spring in 20 post-menopausal women. METHODS: The parameters measured were serum osteocalcin and its apparent degree of carboxylation (measured by hydroxyapatite binding), total and bone specific alkaline phosphatase and urinary bone resorption markers, (pyridinoline and deoxypyridinoline). RESULTS: Serum osteocalcin concentrations were lower in autumn than in spring but the degree of carboxylation was similar. Total and bone specific alkaline phosphatase activities in serum were higher in autumn than in spring. These results support previous observations. However, notable and previously unreported changes in urinary bone resorption markers were observed. Pyridinoline concentrations were lower and deoxypyridinoline higher in autumn compared with spring. The ratio of pyridinoline:deoxypyridinoline was therefore very different between the seasons. CONCLUSIONS: The results clearly demonstrate that seasonal changes in these variables of bone remodelling must be taken into consideration when designing, reporting or analysing studies of bone metabolism in vivo.

Aged↗
PubMed1996

Estimating the point accuracy of population registers using capture-recapture methods in Scotland.

STUDY OBJECTIVE: To estimate the point accuracy of adult registration on the community health index (CHI) by comparing it with the electoral register (ER) and the community charge register (CCR). DESIGN: Survey of overlapping samples from three registers to ascertain whether respondents were living at the addresses given on the registers, analysed by capture-recapture methods. SETTING: Aberdeen North and South parliamentary constituencies. PARTICIPANTS: Random samples of adult registrants aged at least 18 years from the CHI (n = 1000), ER (n = 998), and CCR (n = 956). MAIN RESULTS: Estimated sensitivities (the proportions of the target population registered at the address where they live) were: CHI--84.6% (95% confidence limits 82.4%, 86.7%); ER--90.0% (87.5%, 92.5%), and CCR--87.7% (85.3%, 90.3%). Positive predictive values (the proportions of registrants who were living at their stated addresses) were: CHI--84.6% (82.2%, 87.0%); ER--94.0% (90.9%, 97.1%), and CCR--93.7% (91.7%, 95.7%). CONCLUSIONS: The CHI assessed in this study was significantly less sensitive and predictive than the corresponding ER and CCR. Capture-recapture methods are effective in assessing the accuracy of population registers.

Adult↗
PubMed1996

Bone mineral density measurements: are they worth while?

Bone mineral density measurements have been criticized on the grounds that they are not a worth-while screening tool. In this paper we argue that bone mineral measurements can be an efficient diagnostic tool even if they are not of proven value for screening. There is complex relationship between the costs of a measurement, the intervention and the predictive value of the test all of which must be accounted for when assessing the value of a bone density measurement. For bone density measurements to be used for screening, a wider evaluation needs to be undertaken compared with that for their use as a diagnostic tool. We address some common objections, for example, that low compliance with screening would undermine efficiency, and show that these are not relevant. Evaluations of screening need to address issues that are likely to affect efficiency.

Aged↗
PubMed1996

Appendicular measurements in screening women for low axial bone mineral density.

Assessment of bone density at hip, spine, radius and calcaneus can predict fracture risk. This paper examines whether women with low bone mineral density (BMD) at the hip and spine can be identified by radial or calcaneal BMD assessment, thus enabling pre-selection of such women for further investigation. BMD in the lumbar spine (LS), femoral neck (FN), trochanter (FT) and Ward's area (FW) was measured by dual energy X-ray absorptiometry (DEXA). These measurements were compared with total (Qtot), trabecular (Qtrab), subcortical (Qscort) and cortical (Qcort) BMD of the ultradistal radius measured by peripheral quantitative computed tomography (pQCT), and ultrasound attenuation (BUA) and velocity (VOS) at the os calcis. Measurements were performed on 216 perimenopausal women aged between 45 and 55 years who attended a randomized osteoporosis screening programme. Correlations for pQCT and ultrasound with DEXA measurements were, at best, moderate (r = 0.05-0.53), being poorest for Qcort and VOS. Similar correlations were found between ultrasound and pQCT measurements (r = 0.05-0.31). None of the pQCT or ultrasound measurements predicted low DEXA measurements. 50-56% of women in the lowest quartile (QU4) of Qtot, Qtrab, Qscort and BUA were also in QU4 of LS; 45-57% were in QU4 of FT and FW, but only 22-33% were in QU4 of FN. To detect all women with osteopenia at FN or LS using pQCT or ultrasound, almost the entire population would have to be screened. In conclusion, pQCT and os calcis ultrasound measurements cannot successfully predict hip and spine osteopenia and could not be used to pre-select women for DEXA hip and spine assessment.

Absorptiometry, Photon↗
PubMed1996

Comparisons between fat measurements by dual-energy X-ray absorptiometry, underwater weighing and magnetic resonance imaging in healthy women.

OBJECTIVE: To compare the results of measurements of total and regional fat by dual-energy X-ray absorptiometry (DXA), underwater weighing (UWW) and magnetic resonance imaging (MRI) in women. DESIGN: 13 volunteer pre-menopausal women measured with a Norland XR26 HS DXA instrument, hydrodensitometry equipment and a 0.08 Tesla MRI scanner. SETTING: Aberdeen Royal Infirmary. RESULTS: There were high correlations between measurements of total-body fat by the different techniques, but poor agreement. The mean values of fat as a percentage of the total body mass were UWW = 28.6%, DXA = 40.0%, MRI = 23.0%, although the MRI excluded the head, forearms and feet, estimated from the DXA measurements to contain 8% of the body fat. Although the correlations were apparently linear in the ranges examined, those including the Norland DXA had high intercepts. Bland and Altman plots showed no dependence of the differences on the degree of fatness. Evidence was obtained from in vivo comparisons and phantom measurements that the fat calibration of the Norland DXA had changed during a three year period, suggesting that fat calibration errors contributed to the MRI/DXA differences. Previous comparisons between the Norland DXA and other brands indicate that Hologic and Lunar instruments would show a closer agreement with MRI and UWW. Profiles of fat distribution along the body showed variations in the DXA/MRI ratio, particularly in the chest, with the DXA pattern thought to be the less accurate. The DXA measurements of bone mineral, fat and lean tissue were used to demonstrate the variable proportion of bone in fat-free tissue, leading to errors in UWW. CONCLUSIONS: Each method has its assumptions, which are often not sufficiently appreciated. Each method may be useful for testing and improving the assumptions in the other methods. No method can yet be regarded as a satisfactory reference technique.

Absorptiometry, Photon↗