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Biomedical subjects

D M Reid

Publications and source records attributed to D M Reid.

At least 127 records · Page 7Linked to original sources
PubMed1995

Extracellular epitopes of platelet glycoprotein Ib alpha reactive with serum antibodies from patients with chronic idiopathic thrombocytopenic purpura.

Glycoproteins (GPs) IIb/IIIa and Ib/IX are principal targets of autoantibodies (autoAbs) in idiopathic thrombocytopenic purpura (ITP). Platelet-associated Abs against GPIIb/IIIa primarily recognize discontinuous or nonlinear epitopes (Fujisawa et al, Blood 81:1284, 1993). This study focused on whether Abs against the extracellular domain of GPIb/IX might react with short linear amino acid (aa) sequences of GPIb alpha. Complementary DNAs (cDNAs) coding for two overlapping fragments of GPIb alpha were amplified, cloned into pFLAG.2 plasmids, and expressed in Escherichia coli DH5 alpha competent cells as FLAG fusion proteins, which were purified by anti-FLAG immunoaffinity chromatography. Of 16 selected ITP sera containing anti-GPIb/IX, 6 reacted in microtiter radioimmunoassays (RIAs) with recombinant protein fragment 2 (aas 240 to 485); 1 also with fragment 1 (aas 1 to 247). When synthetic peptides corresponding to 4 segments of fragment 2 with high antigenic indices (P1 to P4) were used as targets in RIAs, all 6 sera reacted with P2 (aas 326 to 346); 1 also reacted with P4 (aas 389 to 412). P2 was shown to be present on the surface of intact platelets by adsorption studies, and anti-P2 was detected in direct eluates of platelets from ITP patients. Glycocalicin in solution effectively competed with immobilized P2 for anti-P2; P2 in solution was a less effective competitor. Epitope scanning with a panel of synthetic 15-mer peptides localized the P2 epitope to the sequence, TKEQTTFPP. Epitope definition may offer insight into the pathophysiology of and more specific treatments for ITP.

Amino Acid Sequence↗
PubMed1995

Hormone replacement therapy: compliance and cost after screening for osteoporosis.

OBJECTIVE: To assess HRT compliance and cost 1 year after population screening for low bone density. DESIGN: Postal questionnaire sent out to women 1 year after having a bone density scan. MAIN OUTCOME MEASURES: Compliance with HRT, type of HRT and cost. RESULTS: Compliance with HRT after screening for women with low bone density was 48% for postmenopausal women and 59% for women with a simple hysterectomy. The most often used form of HRT was Estraderm (49%) for women with a hysterectomy, whilst for women with an intact uterus Prempak-C (54%) was the most popular. The average annual cost of treating women who had had a hysterectomy was 67 pounds whilst for women with an intact uterus it was 61 pounds, a non-significant difference. CONCLUSIONS: Approximately 50% of women with low bone density had started HRT within 1 year of having a densitometry examination. Previous reports of the cost advantage of treating women who had had a hysterectomy relative to those who had not has been overstated.

Bone Density↗
PubMed1995

Carboxylation of osteocalcin in post-menopausal osteoporotic women following vitamin K and D supplementation.

The effect of vitamin supplements on bone metabolism indices in patients with osteoporosis has received scant attention in the literature. Over a 2-week period, vitamin supplements of K and K+D were given to 20 post-menopausal osteoporotic women with previous Colles fractures. Osteoporosis was confirmed by bone mass measurements that demonstrated that broadband ultrasound attenuation (os calcis) was almost as discriminatory as dual energy X-ray absorptiometry (spine and hip) in Colles fracture patients compared with matched controls. Vitamin K corrected the carboxylation defect in osteocalcin and while less marked 4 weeks later, the improvement was still detectable. The result after K+D was similar. The level of carboxylation became the same as in premenopausal women. Total osteocalcin level (bound) osteocalcin. While there was vitamin K correctable undercarboxylation of osteocalcin, simultaneously there was no evidence of undercarboxylation of prothrombin.

Absorptiometry, Photon↗
PubMed1995

Life-style, environmental and medical factors influencing peak bone mass in women.

The aim of this study was to assess which life-style factors were associated with peak bone mass. One-thousand-two-hundred-and-twenty-seven pre-menopausal women aged between 45 and 49 yr had their bone density measured at the hip and spine. In addition, these women were given a postal questionnaire asking about life-style factors that may be associated with bone mineral density (BMD). Using stepwise multiple linear regression analysis we found that life-style or environmental factors explained a small but significant proportion of the variation in BMD. Statistically significant associations between anthropometric measures, exercise levels, fracture history and BMD were found. We also observed a positive association between self-reported numbers of miscarriages and BMD. This work supports the conclusions of smaller studies that risk factor analysis explains only a small amount of the variance in BMD.

Anthropometry↗
PubMed1995

Minocycline-associated lupus erythematosus.

We report a patient who developed symptoms of lupus erythematosus which was apparently related to minocycline therapy for acne vulgaris. To our knowledge, this is only the second reported case of minocycline-associated lupus erythematosus.

Acne Vulgaris↗
PubMed1995

Measuring sexual functioning in premenopausal women.

OBJECTIVE: To assess the validity and reliability of a measure of sexual function for premenopausal women. DESIGN: A self-administered sexual function questionnaire, derived from the Sabbatsberg Sexual Self-Rating Scale, and other health measures were given to women who were randomly sampled from the community health index. SUBJECTS: One hundred and forty-eight premenopausal women aged between 45 and 49 years. MAIN OUTCOME MEASURES: The content validity, internal consistency and construct validity of the revised sexual rating scale. RESULTS: One hundred and thirty-seven women (92%) responded to the main questionnaire and 89 (60%) completed the sexual rating scale, which possessed a high level of internal consistency; scores on the sexual rating scale, which possessed a high level of internal consistency; scores on the sexual ratings scale had small to moderate correlations with the measures of health, two of which (depression and role limitations attributable to emotional problems) were sufficient to explain 25% of the variation in the sexual functioning scores. CONCLUSION: Questions derived from the Sabbatsberg sexual self-rating scale have been used to construct a simple, acceptable, valid and reliable measure of sexual functioning for women in the 45 to 49 years of age group. Such a measure could be widely used as an adjunct to clinical and more general measures of health in order to assess the impact of interventions on sexual functioning within clinical trials.

Female↗
PubMed1995

Steroid induced osteoporosis: an opportunity for prevention?

OBJECTIVE: To determine the frequency with which osteoporosis prophylaxis is given to corticosteroid treated hospital inpatients. METHODS: All patients receiving systemic corticosteroids in a large teaching hospital over a three month period were identified through routine prescription monitoring by hospital ward pharmacists. Coprescription of antiosteoporotic therapy was recorded, along with other relevant details such as steroid dose, actual, or intended duration of therapy, and indication for therapy. RESULTS: Corticosteroids were prescribed to 214 patients over the study period, giving an average rate of 2.5 new prescriptions each day. Indications included: chest disease (n = 84; 39.2%), cancer (n = 17; 7.9%), inflammatory bowel disease (n = 16; 7.5%), rheumatoid arthritis/connective tissue disease (n = 16; 7.5%), and renal diseases (n = 7; 3.3%). One hundred and twelve patients (52.3%) were receiving short term steroid therapy (less than four months); 66 (37%) were receiving medium/long term steroid therapy (four months or more). In 36 cases (16.8%) the duration of therapy was unknown. Only 12 of the 214 patients (5.6%) received any form of osteoporosis prophylaxis. The prevalence of prophylaxis was similarly low in postmenopausal women (six of 93; 6.4%) and in patients receiving high dose long term steroid therapy (two of 25; 8%). CONCLUSIONS: Systemic corticosteroids are used frequently in hospital practice for a wide range of indications, but few patients receive co-prescription of prophylaxis against osteoporosis. This is true even in high risk groups such as postmenopausal women and those on high dose long term steroid therapy. Identification of individuals by the mechanism used in this study provides an opportunity by which all corticosteroid treated patients could be detected and offered osteoporosis prophylaxis before serious loss of bone density has occurred.

Adolescent↗
PubMed1995

Fall frequency and incidence of distal forearm fracture in the UK.

STUDY OBJECTIVE: This analysis aimed to determine the frequency of falls in men and women aged 50 years and over and to explore whether age variation in fall frequency may explain variation in the incidence of distal forearm fracture in women. DESIGN: This was a cross sectional survey. SETTING: Primary care based registers in four UK areas. PARTICIPANTS: Altogether 501 men and 702 women age 50-79 years participated. MAIN RESULTS: A total of 131 (26.1%) men and 181 (25.8%) women reported falling in the previous year. In women, the frequency of falls rose with age (chi 2 test for trend 4.33; p = 0.04), with no obvious early post-menopausal peak or subsequent decline. Men aged 50-54 years had a significantly increased risk of falls compared with women of this same age group, (odds ratio (OR) = 2.4; 95% confidence interval (CI) 1.3, 4.6), though above this age, the risk of falling was greater in women (OR = 1.2; 95% CI 0.9, 1.5). CONCLUSION: There are important differences in the frequency of falls in relation to age and sex. The data suggest that variation in fall frequency per se does not explain age variation in the incidence of distal forearm fracture in women.

Accidental Falls↗
PubMed1995

Vertebral fractures in men and women: how discriminative are bone mass measurements?

Vertebral fractures are associated with osteoporosis. This study examined men and women with vertebral deformation/fractures, as defined by vertebral morphometry. These were compared with a population derived group measured contemporaneously who were defined as having no vertebral deformation/fracture by the radiographs. All patients underwent a dual energy X-ray absorptiometry (DXA) scan of the spine and hip, and a broadband ultrasound attenuation (BUA) scan of their os calcis. The abilities of these two techniques were compared for their discriminatory powers in this type of fracture. The results showed that DXA hip and spine had a better discriminatory power in the female vertebral group compared with BUA. In males none of the bone measurements could discriminate between the fracture and non-fracture groups.

Absorptiometry, Photon↗
PubMed1995

Comparisons between three dual-energy X-ray absorptiometers used for measuring spine and femur.

Lunar, Hologic and Norland dual-energy X-ray absorptiometry scanners have been compared for measurements of spine and femur bone density. Precision was not greatly different in realistic phantoms and volunteer subjects. Most clinical therapeutic trials are concerned with measuring changes of bone mineral, and interchangeability in this context was examined using phantoms of spine and femur in which changes of bone mineral density (BMD) were simulated. With each instrument the measured changes were closely linear. For the spine the biggest difference of slope between instruments was 15%. For the femur, in all areas of interest, the differences of slope were less than 10%. It is concluded that the three instruments can be satisfactorily used in multicentre clinical trials to investigate changes in bone mineral. 12 volunteers were measured with each scanner. There were significant mean differences between each pair of instruments, suggesting different calibration criteria. More importantly, those mean differences had appreciable standard deviations (SDs), in proportional terms from 3% to 10%. When the measurements were related to reference ranges and expressed in terms of age-matched normal values the mean biases disappeared, but the SDs did not improve. Results from different manufacturers' apparatus are not interchangeable for studying individual patients. Measurements from the phantoms were used to cross-calibrate the scanners. Those from the variable spine phantom predicted the in vivo ratio within 4%, but this was no better than measurements of the unmodified phantom alone. Results using the European Spine Phantom were less satisfactory. No phantom provided an adequate cross-calibration for femur measurements.

Absorptiometry, Photon↗
PubMed1995

Decreased axial and peripheral bone density in patients taking long-term warfarin.

Impaired vitamin K metabolism is associated with under-carboxylation of the non-collagenous bone-matrix protein osteocalcin, which is required in its fully carboxylated state for normal bone formation. Post-menopausal women have under-carboxylation of osteocalcin which increases with age and is marked in the elderly. A similarly marked degree of impaired carboxylation occurs during coumarin therapy, and a key question is whether this may lead to accelerated loss of bone mass which is clinically important. We measured axial and peripheral bone mineral density (BMD) in 40 male patients on warfarin and 40 controls individually matched for age, disease and other drug therapy. A consistent trend for reduced BMD at all sites was observed in the warfarin-treated patients. This was particularly marked in the cancellous bone at the distal radius (9% reduction, p = 0.023) and at the cancellous rich lumbar spine site (10.4% reduction, p < 0.004). No significant relationship was observed between warfarin dose, International Normalized Ratio (INR) or duration of therapy and bone density. Because of the biochemical similarity, this study provides a new lead on post-menopausal osteoporosis, and supports the hypothesis that impaired carboxylation of osteocalcin plays a role in the pathogenesis of bone loss in the elderly through deficiency in vitamin K metabolism.

Absorptiometry, Photon↗
PubMed1994

Spectrum of Ig classes, specificities, and titers of serum antiglycoproteins in chronic idiopathic thrombocytopenic purpura.

The characteristic decreased recovery and survival of transfused platelets in nonalloimmunized patients with idiopathic thrombocytopenic purpura (ITP) suggest that plasma antiplatelet autoantibodies (autoAbs) are present in almost all cases. Studies emphasizing reactions of IgG autoAbs with platelet glycoprotein (GP) IIb/IIIa indicate that less than 50% of ITP patients have detectable serum Abs, and that many of these Abs may not be pathogenic because they are directed against epitopes in the cytoplasmic domain of GPIIIa (Fujisawa et al, Blood 77:2207, 1991 and 79:1441, 1992). We evaluated the contribution of Ig classes other than IgG to the overall incidence of serum Abs in 47 patients with chronic ITP and the frequency of reactions with GPs IIb/IIIa, Ib/IX, IV, and Ia/IIa. Abs were further characterized by their reactions with cytosolic or exosolic GP epitopes and their titers and apparent affinities. Using immunobead techniques we found (1) anti-GPs in 85% of sera; (2) IgA and IgG Abs each in 68%, together in 51%; (3) IgM agglutinins in 15%, always with another Ab class; (4) GP Ib/IX, IIb/IIIa, IV, and Ia/IIa targets in 83%, 81%, 38%, and 28% of cases, respectively; (5) 93% of positive sera reactive with more than one GP; but GP IV or Ia/IIa never the sole target; (6) Abs against cytosolic epitopes on one or more of GPs IIIa, Ib alpha, and IIb beta in 66% of sera, always accompanied by Abs against exosolic epitopes of the same or a different GP; (7) autoAbs against cytosolic GP epitopes in 38% of 16 patients recovered from posttransfusion purpura and drug purpura; and (8) evidence that serum ITP Abs, often high-titered, saturate platelets less than alloAbs against the same GPs. Whereas Abs against external GP epitopes are a distinctive marker for ITP in 80% of patients, Abs against internal GP epitopes are likely a secondary phenomenon of platelet destruction and not pathogenic. Anti-GPs against exosolic epitopes were also found in eluates of patient's platelets, suggesting that they have pathogenic significance.

Amino Acid Sequence↗
PubMed1994

Biology of the mononuclear phagocyte system of the central nervous system and HIV infection.

Infection of the central nervous system by HIV-1 results in widespread neuropathology and neurological symptoms. The cells infected in the brain belong to the mononuclear phagocyte lineage. We review aspects of the biology of the macrophage populations associated with the central nervous system and consider their distribution, phenotype, and kinetics in relation to HIV pathology.

Central Nervous System↗
PubMed1994

Broadband ultrasound attenuation and dual energy X-ray absorptiometry in patients with hip fractures: which technique discriminates fracture risk.

There is considerable interest in predicting risk of hip fracture in order to allow targeting of preventive care. This study aimed to determine which of two methods best discriminates a hip fracture population from controls. Fifty women with fractured neck of femur, and 50 control subjects were scanned using dual energy X-ray absorptiometry (DXA) of the spine and hip and broadband ultrasound attenuation (BUA) of the os calcis. Significant differences between the two populations could be found for both DXA and BUA, with BUA showing the largest percentage difference (27%). The mean z-scores showed that BUA had the lowest, with the exception of DXA trochanter. However, no significant difference between BUA and DXA trochanter Z-scores was found. A receiver operator characteristic (ROC) analysis showed that BUA has a superior sensitivity and specificity compared with DXA measurements, with DXA of the hip being better than the spine. This retrospective study shows that BUA is a better discriminator of hip fracture than DXA lumbar spine or DXA hip, which may have important implications for predicting those at risk of future hip fracture.

Absorptiometry, Photon↗