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Biomedical subjects

D M Reid

Publications and source records attributed to D M Reid.

At least 73 records · Page 4Linked to original sources
PubMed2000

Early asthma prophylaxis, natural history, skeletal development and economy (EASE): a pilot randomised controlled trial.

OBJECTIVES: (1) To establish recruitment rates of newly presenting asthmatic children. (2) To establish acceptability of study protocols. (3) To pilot age-specific quality of life (QoL) assessment. (4) To assess short-term (6 months) outcomes of inhaled corticosteroids (ICS) treatment. (5) To refine sample size calculations for a definitive study. DESIGN: A randomised pragmatic longitudinal trial design was used, with no blinding or placebo, to examine early ICS introduction similar to its use in practice. Subjects were assessed at entry, 3 and 6 months. SETTING: Subjects were recruited from six general practices. Children under 6 years were assessed at the Craig Research and Investigation Unit, Royal Aberdeen Children's Hospital, or their family home, and subjects 6 years and over were assessed at their general practice. SUBJECTS: Children (aged 6 months-16 years) with symptoms suggestive of asthma/wheeze that had commenced no longer than 12 months before were identified retrospectively and prospectively from general practices. Subjects were also required to be naïve to prophylactic therapy with no other lung disease/concomitant illness. INTERVENTIONS: Subjects were randomised to ss2-agonist (ss2-only group) or ss2-agonist and ICS (ICS group) for 6 months. Physicians could later prescribe ICS in controls if needed. MAIN OUTCOME MEASURES: (1) Pulmonary function. (2) Asthma symptom diary. (3) Symptomatic health status questionnaire. (4) Caregiver's and child's QoL. (5) Growth. (6) Bone mass. (7) Bone turnover. (8) Economic issues. RESULTS: Of over 15,000 children yielded from general practice records, 11% had symptoms suggestive of asthma/wheeze, and two-thirds of these already used ICS. Of the remaining, 141 subjects met the criterion of early asthma, and 86 were randomised. Two-thirds of those randomised were < 6 years old, the males:females ratio was 2:1, and 67% had a family history of atopy. RESULTS - PHYSIOLOGICAL DEVELOPMENT: Pulmonary function did not significantly improve in the older children. Although tidal breathing measures in the pre-school children were significantly higher at 6 months in the ss2-only group, there was great variability. Incidence of wheeze and night-time cough reduced equally in both groups. Reduction of night-time symptom score and reliever use, and increase in symptom-free days were only significant in the ss2-only group. No significant differences were found in growth and bone mass between the two groups, but bone metabolism was significantly reduced at 6 months in the ICS group. RESULTS - PSYCHOLOGICAL DEVELOPMENT: The caregiver's QoL questionnaire was sensitive to child symptom changes over 3 months, but absolute impact of child symptoms on their QoL varied, whereas the child-centred questionnaire was not sensitive to change. RESULTS - ECONOMICS: There were no significant differences in medical consultation costs between the groups, but, as expected, prescription costs in the ICS group were higher over 6 months. Combined healthcare costs were significantly higher for patients assigned to ICS, but there were no significant differences in any effectiveness measures between the groups. CONCLUSIONS: Most (96%) of the proposed sample was recruited, and the low drop-out rate (8%) demonstrated acceptability of the study protocol. Most children first presenting with symptoms suggestive of asthma were < 6 years old and represented a group biased towards mild to moderate asthma, or virally induced wheeze. The caregiver's QoL questionnaire was found to better reflect a child's symptom changes than a child-centred instrument. In the short term, no adverse effects were seen on growth, but ICS treatment significantly reduced bone metabolism. Most of the young children with asthma/wheeze improved over time with ss2-agonist treatment alone, and clinical benefits of early ICS intervention amongst these children were not detected; however, there was inadequate power in this pilot study to establish this. (AB

Adolescent↗
PubMed1999

Radial bone mineral density and estimated rates of change in normal Scottish women: assessment by peripheral quantitative computed tomography.

This study examines normative bone mineral density (BMD) data, as measured by peripheral quantitative computed tomography of the ultradistal radius, in 332 Scottish women aged 18-90 years, comparing it to a recently reported normal German population. The normative Scottish data were higher in almost all decades compared with German counterpart, percentage differences being +0.002%-+21.6% for total (Qtot), and -0.06%-+31.9% for trabecular (Qtrab) BMD. Differences in calibration of the Stratec XCT-960 and XCT-900 systems are thought to be largely responsible for these differences. Estimated age-related changes were determined in the Scottish population. A cubic regression model best fitted age-related changes in the whole population, and changes as a function of years postmenopause in the postmenopausal subgroup, for Qtot, subcortical (Qscort), and cortical (Qcort) BMD, whereas a parabolic regression model best fitted corresponding changes in Qtrab BMD. Percentage age-related changes (5 years: 10 years postmenopause) in Qtot (-0. 79%-1.12%/year) and Qscort (-0.72%-1.12%/year) were greater than Qtrab (-0.53%-0.56%/year) in the early postmenopausal years. Maximum age-related changes were found at 20 years postmenopause for Qtot (-1.36%/year), Qscort (-1.39%/year), and Qcort (-1.39%/year). This study has highlighted variation in normative data derived by different Stratec pQCT systems. The estimated age-related changes suggest that early postmenopausal bone loss preferentially affects subcortical rather than trabecular bone at the radius.

Adolescent↗
PubMed1999

Cervical and trochanteric hip fractures: bone mass and other parameters.

We examined 310 hip fracture patients (55 men, 255 women) to identify differences in those patients who had suffered a cervical fracture compared with those with a trochanteric fracture of the hip. Patients underwent a dual-energy X-ray absorptiometry (DXA) scan of their hip and total body and quantitative ultrasound (QUS) scans of their heel. Other measurements included medical/drug history. Significant differences were found for broadband ultrasound attenuation (BUA) and DXA total-body measurements, with those with a cervical fracture having a higher bone mass. Those with a trochanteric fracture showed a significantly higher incidence of stroke (12.8% vs. 6.3%, p = 0.05), while high blood pressure/antihypertensive therapy was significantly more common in the cervical fracture group (11.6% vs. 4.3%, p < 0.03). Therefore, it is not only bone parameters that differ in these patients. In the presence of certain medical conditions, preventative therapy may be directed to managing co-existing conditions as well as improving bone density.

Absorptiometry, Photon↗
PubMed1999

Predicting a second hip fracture.

In an attempt to identify a high-risk cohort of patients, who could be offered preventive therapy, we assessed patients who had suffered one hip fracture. A total of 394 patients were prospectively followed to determine those who had suffered a second fracture. Entry bone mass of the unfractured hip and total body was examined by dual X-ray absorptiometry (DXA) and of the os calcis, by quantitative ultrasound (QUS), along with various clinical parameters. The relative risks in the QUS parameters did not reach significance, except for broadband ultrasound attentuation as measured by the McCue CUBA Clinical, whereas femoral neck and total body bone mineral density also reached significance. Lowest quartile body weight was also a significant risk factor as were occurrence of a new fall and poor mobility score. Using Receiver Operator Characteristic curves, we found no significant differences between DXA trochanter or for the Mini Mental State Examination score in predicting those who sustained a second hip fracture. In this elderly group risk factors are almost as good as bone mass at predicting those who will sustain a second hip fracture. Low body weight and poor mobility could be used as triggers for the use of preventive therapy without the use of bone mass measurements and to target expensive preventive therapy to reduce fracture risk.

Absorptiometry, Photon↗
PubMed1999

Osteoporosis and its management.

Osteoporosis is a common systemic disease leading to premature fractures. This article reviews the state of the art of assessing the risk of future osteoporotic fracture and summarizes the prevention and treatment of the condition.

Adrenal Cortex Hormones↗
PubMed1999

Evidence for a pathogenic role of nitric oxide in inflammation-induced osteoporosis.

Inflammatory disease is associated with increased production of nitric oxide (NO) and activation of the inducible nitric oxide synthase (iNOS) pathway. Several studies have addressed the role of NO as a mediator of cytokine effects on bone cell activity in vitro. Stimulatory and inhibitory actions have been found, however, depending on the concentrations produced and model system used. In view of this, it has been difficult to predict whether increased production of NO during inflammation is likely to increase bone loss or prevent it. We have investigated the pathogenic role of NO in an animal model of inflammation-induced osteoporosis (IMO). NO production was increased in IMO when compared with controls (+344%; p < 0.01), and this was accompanied by activation of inducible NOS (iNOS) in the bone marrow space. Bone mineral density (BMD) was reduced in IMO when compared with controls (-64%; p < 0.01), and this was found to be associated with reduced osteoblast numbers (-44%; p < 0.05) and increased osteoclast numbers (+38%; p < 0.01). The NOS inhibitor L-NMMA reversed the deleterious effects of IMO on bone mass and bone turnover, but L-NMMA had no effect on bone mass in control animals. This study has important implications for many inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, and inflammatory bowel disease which are associated with increased NO production and osteoporosis. Our data not only suggest that iNOS activation and increased NO production contribute to the pathogenesis of osteoporosis in these situations, but also suggest that NOS inhibitors could be of therapeutic value in the prevention and treatment of such bone loss.

Animals↗
PubMed1999

A comparison of radial peripheral quantitative computed tomography, calcaneal ultrasound, and axial dual energy X-ray absorptiometry measurements in women aged 45-55 yr.

Perimenopausal bone loss is considered to affect trabecular bone preferentially. Peripheral quantitative computed tomography (pQCT) quantifies trabecular bone mineral density (BMD) independently at the ultradistal radius. This article examines differences in pQCT BMD between late premenopausal and early postmenopausal women, comparing the differences with calcaneal ultrasound and axial dual energy X-ray absorptiometry measurements. One hundred nineteen normal perimenopausal women aged 45-55 yr who attended a randomized osteoporosis screening program were stratified by menopausal status into premenopausal (PRE: n = 79) and postmenopausal (POST: n = 40) groups. All measurements were lower in the postmenopausal group with the exception of ultrasonic velocity (PRE vs POST: 1397 +/- 53.8 vs 1421 +/- 58.5 m/s, p = 0.037). Total (391.8 +/- 52.9 vs 366.3 +/- 68.6 g/cm(3), p = 0.013) and subcortical (533.6 +/- 59.4 vs 504.3 +/- 79.8 g/cm(3) p = 0.018), but not trabecular (187.5 +/- 38.8 vs 173.2 +/- 46.6 g/cm(3), p = 0. 098) or cortical (561 +/- 53.4 vs 551.2 +/- 66 g/cm(3), p = 0.174), pQCT BMD measurements were significantly lower in the POST group, as were ultrasonic attenuation (79.4 +/- 16 vs 72.3 +/- 18.0 dB/Mz, p = 0.034), DXA spine (1.032 +/-16 vs 0.959 +/- 0.2 g/cm(2), p = 0.003), and all hip (p </= 0.001) measurements. Although body mass index (BMI) was positively and menopausal status and age negatively correlated with most bone mass measurements, adjusting for BMI did not alter the relative deficits in postmenopausal compared with premenopausal women. This study suggests that early postmenopausal bone loss at the radius preferentially affects subcortical, rather than trabecular, bone in the appendicular skeleton, which suggests preferential trabecular bone loss in the axial skeleton.

Absorptiometry, Photon↗
PubMed1999

The pharmacoeconomics of hormone replacement therapy.

Hormone replacement therapy (HRT) is a highly cost-effective treatment for symptoms of the menopause such as hot flushes (flashes). A number of economic evaluations have indicated that it may also be a cost-effective therapy for the prevention of cardiovascular disease and osteoporosis. However, these evaluations are based on the premise that HRT will reduce cardiovascular disease by 30 to 50%. Recent evidence casts doubt on its effectiveness at preventing cardiovascular disease, certainly as a secondary preventive therapy. Furthermore, HRT is likely to increase the incidence of breast cancer. If the effect of HRT on the cardiovascular system is slight or nonexistent, but its effect on breast cancer is modest or strong, then HRT is unlikely to be a cost-effective treatment for asymptomatic women at low risk of osteoporosis. However, the unwanted effects of HRT on the breast may be significantly reduced by targeting therapy to those women with low bone mass and who have other risk factors for fracture. Such a strategy is likely to be more cost effective than a strategy which allows asymptomatic women with low fracture risk to take HRT in the long term. As selective estrogen receptor modulators (SERMs) aggravate menopausal symptoms they are not likely to be an alternative for most perimenopausal women. Therefore, SERMs are more likely to be a competitor to existing and forthcoming bisphosphonates rather than HRT.

Cost-Benefit Analysis↗
PubMed1999

Bone density and bone turnover in patients with osteoarthritis and osteoporosis.

OBJECTIVE: Osteoarthritis (OA) and osteoporosis (OP) are reported to be rare in the same patient. We examined bone mass, bone turnover, and radiological presence of OA in a group of patients with OA with previous hip fractures and age matched controls. METHODS: Bone mass was assessed by bone mineral density (BMD), using dual energy x-ray absorptiometry (DEXA) of the hip and total body, and quantitative ultrasound of the os calcis, measuring broadband ultrasound attenuation and velocity of sound. Bone turnover was assessed by measuring urinary pyridinium crosslinks and serum osteocalcin. RESULTS: There were differences in bone density, the patients with OP having lower bone density, while patients with OA had similar or increased bone density compared to controls, Serum osteocalcin showed no significant differences among the 3 groups of patients. Urinary pyridinium crosslinks excretion was significantly elevated in the OA group but not in the OP group compared with controls. CONCLUSION: Increased bone turnover was restricted to the OA group.

Absorptiometry, Photon↗
PubMed1999

The distribution, determinants, and clinical correlates of vertebral osteophytosis: a population based survey.

OBJECTIVE: Vertebral osteophytes are a characteristic feature of intervertebral disc degeneration. There are, however, few population data concerning the occurrence of and clinico-biological correlates of vertebral osteophytes in both the dorsal and lumbar spine. Our purpose was to determine the frequency and distribution of anterior osteophytes in the thoracic and lumbar spine, and their relationship with both various putative risk factors, including physical activity and obesity, and self-reported back pain. METHODS: Men and women aged 50 years and over were recruited from primary care based registers in 5 UK centers. They were invited to attend for an interviewer administered lifestyle questionnaire, assessment of height and weight, and lateral spinal radiographs. Lateral spinal radiographs were evaluated by a single observer for the presence of osteophytes from T4 to L5 using a semiquantitative score (grade): 0 = none, 1 = doubtful, 2 = mild, 3 = moderate, 4 = severe. Based on these data 2 summary statistics were derived: the maximum osteophyte grade at any vertebral level (MAX), and the sum of the osteophyte grades at the individual vertebral levels (TOT). RESULTS: In total, 681 women, mean age 63.3 years, and 499 men, mean age 63.7 years, were studied; 84% of men and 74% of women had at least one vertebral level with a grade 1 or higher osteophyte. Both the sum of the individual grades (TOT) and the proportion of subjects with MAX > or =2 were greater in men than in women in both the dorsal and lumbar spine, and both increased with age. The pattern of spinal involvement was similar in the sexes, with osteophytes occurring most frequently at T9-10 and L3. Increasing body mass index was associated with more frequent osteophytes at both dorsal and lumbar spine, although the relationship was stronger at the dorsal spine. Heavy physical activity, particularly in young adult life, was associated with osteophytosis in men. Self-reported back pain, both ever and in the past year, was linked with lumbar osteophytes in men. CONCLUSION: The distribution within the spine in our study and the relationship with heavy physical activity points to mechanical factors being important in pathogenesis of vertebral osteophytosis. Prospective studies are needed to explore the types of physical activity that increase susceptibility to vertebral osteophytosis. In men, osteophytes affecting the lumbar spine are associated with back pain.

Aged↗
PubMed1998

Thiopurine methyltransferase genotype predicts therapy-limiting severe toxicity from azathioprine.

BACKGROUND: Substantial hematologic toxicity limits the use of azathioprine. OBJECTIVE: To evaluate 1) polymorphic inactivation of azathioprine by thiopurine methyltransferase and 2) clinical toxicity. DESIGN: Prospective cohort study. SETTING: Two rheumatology units. PATIENTS: 67 patients for whom azathioprine was prescribed as second-line therapy for rheumatic disease. MEASUREMENTS: Polymerase chain reaction-based assays were used to detect mutations in thiopurine methyltransferase. The primary end point was discontinuation of azathioprine therapy because of toxicity. RESULTS: Six of 67 patients (9%) were heterozygous for mutant thiopurine methyltransferase alleles. Five of the 6 patients discontinued therapy within 1 month of starting treatment because of low leukocyte counts. The sixth patient did not adhere to treatment. Patients with wild-type thiopurine methyltransferase alleles received therapy longer than did patients with mutant alleles (median duration of therapy, 39 weeks [range, 6 to 180 weeks] and 2 weeks [range, 2 to 4 weeks], respectively; P = 0.018). CONCLUSION: Analysis of thiopurine methyltransferase genotype is a quick way to identify patients at risk for acute toxicity from azathioprine.

Adult↗
PubMed1998

Structure-function relationships and localization of the Na/Ca-K exchanger in rod photoreceptors.

The structural and functional properties of the bovine rod photoreceptor Na/Ca-K exchanger and its distribution in vertebrate photoreceptor cells were studied using a panel of monoclonal antibodies. Antibodies that bind to distinct epitopes along the large hydrophilic N-terminal segment of the exchanger labeled the extracellular surface of the rod outer segment plasma membrane, whereas antibodies against a large hydrophilic loop between the two membrane domains labeled the intracellular side. Enzymatic deglycosylation studies indicated that the exchanger primarily contains O-linked sialo-oligosaccharides located within the N-terminal domain. Removal of the extracellular domain with trypsin or the large intracellular domain with kallikrein did not alter the Na+- or K+-dependent Ca2+ efflux activity of the exchanger when reconstituted into lipid vesicles. Anti-exchanger antibodies were also used to visualize the distribution of the exchanger in the retina by light and electron microscopy. The exchanger was localized to the plasma membrane of rod outer segments. No labeling was observed in the disk membranes, cone photoreceptor cells, or other retinal neurons, and only faint staining was seen in the rod inner segment. These results indicate that the O-linked glycosylated rod Na/Ca-K exchanger is specifically targeted to the plasma membrane of rod photoreceptors and has a topological organization similar to that reported for the cardiac Na/Ca exchanger. The large intracellular and extracellular domains do not directly function in the transport of ions across the rod outer segment plasma membrane, but instead may play a role in protein-protein interactions that maintain the spatial organization of the exchanger in the plasma membrane or possibly regulate transport activity of the exchanger.

Animals↗
PubMed1998

Mortality associated with vertebral deformity in men and women: results from the European Prospective Osteoporosis Study (EPOS).

Clinically apparent vertebral deformities are associated with reduced survival. The majority of subjects with radiographic vertebral deformity do not, however, come to medical attention. The aim of this study was to determine the association between radiographic vertebral deformity and subsequent mortality. The subjects who took part in the analysis were recruited for participation in a multicentre population-based survey of vertebral osteoporosis in Europe. Men and women aged 50 years and over were invited to attend for an interviewer-administered questionnaire and lateral spinal radiographs. Radiographs were evaluated morphometrically and vertebral deformity defined according to established criteria. The participants have been followed by annual postal questionnaire--the European Prospective Osteoporosis Study (EPOS). Information concerning the vital status of participants was available from 6480 subjects, aged 50-79 years, from 14 of the participating centres. One hundred and eighty-nine deaths (56 women and 133 men) occurred during a total of 14,380 person-years of follow-up (median 2.3 years). In women, after age adjustment, there was a modest excess mortality in those with, compared with those without, vertebral deformity: rate ratio (RR) = 1.9 (95% confidence interval (CI) 1.0,3.4). In men, the excess risk was smaller and non-significant RR = 1.3 (95% CI 0.9,2.0). After further adjusting for smoking, alcohol consumption, previous hip fracture, general health, body mass index and steroid use, the excess risk was reduced and non-significant in both sexes: women, RR = 1.6 (95% CI 0.9,3.0); men RR = 1.2 (95% CI 0.7,1.8). Radiographic vertebral deformity is associated with a modest excess mortality, particularly in women. Part of this excess can be explained by an association with other adverse health and lifestyle factors linked to mortality.

Aged↗
PubMed1998

Direct disclosure of bone density results to patients: effect on knowledge of osteoporosis risk and anxiety level.

If bone mineral density (BMD) screening is to achieve the aim of preventing the complications of osteoporosis, women with low BMD measurements must learn that they are at risk, and women at risk must know about and be willing to adopt and persist with measures that can prevent osteoporosis. In this paper we present the results of a randomized controlled trial designed to examine whether disclosing the results of a BMD scan directly to women, as well as through their general practitioners (GPs), improves their knowledge of their bone density results without adverse psychological sequelae. Direct disclosure resulted in 19% (59% vs 40%; 95% CI for difference in proportions: 9.8% to 27.8%) more women being aware of their BMD status at the spine and 22% (58% vs 36%; 95% CI for difference: 12.2% to 29.8%) at the hip. These differences were observed irrespective of risk status. There was no significant difference in anxiety levels between the randomized groups. We conclude, therefore, that direct disclosure of BMD results to women, as well as to their GPs, leads to increased knowledge of BMD status without increasing anxiety, and that BMD measurement services should consider informing women routinely of their results directly as well as through their GPs.

Anxiety↗
PubMed1998

Effects of menstrual history and use of medications on bone mineral density: the EVOS Study.

We have previously shown considerable between-center variation in bone mineral density (BMD) in the 13 EVOS centers that performed bone densitometry on their sex- and age-stratified population samples, after adjusting for weight and age. We have now investigated whether part of the between-center variability may be attributed to between-center variations in the use of medications. Information was collected from 2088 women and 1908 men at baseline on whether the subjects had ever been prescribed calcium, calcitonin, anabolic steroids, fluoride, vitamin D, or glucocorticoids and, for the women, whether they had ever used the oral contraceptive pill (OCP) or hormone replacement therapy (HRT). Each of these variables was fitted into a regression model adjusted for age, height, weight, and center. Only OCP and HRT significantly affected BMD. Those who had ever used OCPs had spinal BMD 0.029 g/cm2 greater than those who had never used them. Users of HRT had higher BMD than nonusers: 0. 037 g/cm2 at the spine, 0.018 g/cm2 at the trochanter, and 0.018 g/cm2 at the femoral neck. As expected, there was a great variation between centers in the use of OCP and HRT, but there were no significant correlations between mean BMD at any site in a given center and the prevalence of OCP or HRT use in that center. The between-center variance in BMD at all three sites remained highly significant after adjusting for treatment (P < 0.001). We conclude that HRT and OCP use are associated with moderate increases in BMD. The geographical variability of BMD in Europe was not explained by treatment with pharmaceuticals.

Absorptiometry, Photon↗
PubMed1998

Differential regulation of 1-aminocyclopropane-1-carboxylate synthase gene family and its role in phenotypic plasticity in Stellaria longipes.

Using degenerate oligonucleotides that correspond to conserved amino acid residues of known 1-aminocyclopropane-1-carboxylic acid (ACC) synthases, we cloned a genomic fragment that encodes ACC synthase in Stellaria longipes. Southern analysis suggests that ACC synthase is encoded by a small gene family comprising about 4 members. We isolated four unique ACC synthase cDNA clones under different growth conditions from alpine and prairie ecotypes of S. longipes. Northern analyses suggest that ACC synthase genes are differentially and synergistically regulated by photoperiod and temperature. Such differential regulation of ACC synthase genes positively correlate with the levels of ACC and ethylene. Since ethylene has previously been shown to partly control the stem elongation plasticity in S. longipes, we propose that differential regulation of ACC synthase genes may represent one of the underlying molecular mechanisms of phenotypic plasticity in S. longipes.

Acclimatization↗