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Biomedical subjects

D M Reid

Publications and source records attributed to D M Reid.

At least 163 records · Page 9Linked to original sources

Methods of measurement of bone turnover and clinical evaluation of osteoporosis: relevance to asthma and corticosteroid therapy.

Bone turnover can be assessed by measurements of biochemical markers. Serum alkaline phosphatase and osteocalcin can be used as indices of bone formation, and hydroxyproline and pyridinium crosslinks in urine can be used to assess bone resorption. These markers are able to detect changes induced by high-dose corticosteroid therapy given by the oral or inhaled route. However, a clinical diagnosis of osteoporosis requires, in addition, the presence of at least one relatively atraumatic fracture. Fracture risk may be assessed by in vivo measurement of bone density, for which a number of new techniques, including single-photon absorptiometry, dual-photon absorptiometry, dual-energy X-ray absorptiometry, and quantitative computed tomography, have been developed and are now in clinical use.

Absorptiometry, Photon↗

Falling and perimenopausal women.

The relationships between falling, fracture and bone density in perimenopausal women have not previously been explored. As part of a population-based screening programme for osteoporosis examining historical risk factors and bone mineral density, we have investigated risk factors for falling in 45-49-year-old women. Our results indicate that the risk of falling may be related to menopausal status, increased body weight, use of diuretics, self-reported arthritis and absence of car ownership.

Accidental Falls↗

Recruitment methods for screening programmes: trial of a new method within a regional osteoporosis study.

OBJECTIVE: To estimate the response rates and operating costs of three recruitment methods within a regional osteoporosis screening programme. DESIGN: Randomised trial of three types of invitation letter: one offering fixed appointments with option to change time, one offering fixed appointments but requiring telephoned confirmation of intention to attend, and one inviting recipient to telephone to make an appointment. SETTING: Osteoporosis screening unit, Aberdeen. SUBJECTS: 1200 women aged 45-49 years living within 32 km of Aberdeen and randomly selected from the community health index. 400 women were randomised to each appointment method. MAIN OUTCOME MEASURES: Numbers attending for screening; default rate among women who confirmed appointments; social class of attenders; cost per appointment slot and per completed scan. RESULTS: 299 (75%), 277 (69%), and 217 (54%) women were scanned after fixed, confirmable, and open invitations respectively. Women who attended were given a questionnaire, and 694 (87.5%) returned it. No significant differences were found in the social class of attenders among the three methods. Of the 514 women who made or confirmed appointments, 494 attended for a scan. Total costs per scan were 25.00 pounds, 21.40 pounds, and 21.00 pounds for fixed, confirmable, and open invitations respectively. CONCLUSIONS: The offer of a fixed appointment requiring telephoned confirmation has the potential to reduce the costs of scanning without exaggerating any social bias or significantly reducing response rates provided that empty appointments can be rebooked at short notice.

Appointments and Schedules↗

Characterization and application of an in vitro detection system for studying the binding and phagocytosis of rod outer segments by retinal pigment epithelial cells.

Direct and indirect radioactivity and fluorescent assays have been developed to study the interaction of rod outer segments (ROS) with retinal pigment epithelial (RPE) cells. In the direct assays ROS labelled with 125I or fluorescein isothiocyanate (FITC) have been used to measure total phagocytosis, i.e. surface binding and ingestion. In the indirect assays RPE cells were first treated with unlabelled ROS or biotinylated ROS and subsequently probed with [125I]Rho 4D2 antirhodopsin antibody or [125I]streptavidin for radioactivity measurements or with the Rho 4D2 antibody and FITC-goat anti-mouse Ig or FITC-streptavidin for fluorescent counting. In these indirect methods the number of surface bound ROS were distinguished from the number of ingested ROS by comparative labelling of non-permeabilized and permeabilized ROS-treated RPE cells. Using these assays, we have studied the binding and ingestion of bovine ROS with cultured bovine RPE cells. As in the case of newborn cultured rat RPE cells [Hall and Abrams (1987) Exp. Eye Res. 45, 907-22], binding and ingestion of bovine ROS by bovine RPE cells was saturable with respect to ROS concentration and time. At 37 degrees C ROS binding reached a saturating concentration at 1 x 10(7) ROS per well; the number of bovine ROS ingested by bovine RPE cells, however, was less than the number of rat ROS ingested by rat RPE cells. When 1 x 10(7) ROS per well was used, maximal surface binding of bovine ROS to bovine RPE cells was obtained after 2-3 hr, whereas after an initial delay, ingestion rapidly increased to a maximum at 1-2 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Bone density in asthmatic patients taking high dose inhaled beclomethasone dipropionate and intermittent systemic corticosteroids.

BACKGROUND: Asthmatic patients taking low to moderate doses of inhaled topical corticosteroids have been shown to have lower bone density than those taking bronchodilators only. There is little information on bone density in asthmatic patients taking high dose inhaled corticosteroids. METHODS: Bone mass was studied in three age matched groups of asthmatic patients. These comprised: 17 asthmatic patients who had never taken inhaled or systemic corticosteroids (group 1); 20 patients who had taken beclomethasone diproprionate in a dosage of 1000-2000 micrograms daily for at least a year, who had also received courses of systemic corticosteroids in the past (group 2); and 20 patients who were taking both high dose inhaled corticosteroids and regular low dose prednisolone, at a median dose of 7 mg daily (group 3). Vertebral bone density was measured by quantitative computed tomography. Biochemical indices of bone formation and resorption were also measured. RESULTS: Mean bone density in group 2 (127.5(22.6) mg/ml) was similar to that in group 3 (114.5 (36.0) mg/ml). Bone density was significantly lower in both of these groups than in group 1 (160.4 (27.4) mg/ml). There were no significant differences between groups for any of the markers of bone formation and resorption. CONCLUSIONS: Asthmatic patients receiving high dose inhaled beclomethasone and intermittent courses of systemic corticosteroids have reduced vertebral bone density. The bone loss is similar in degree to that seen in patients taking high dose inhaled topical corticosteroids and continuous low dose systemic corticosteroids.

Administration, Inhalation↗

Factors influencing medical interns trained at U.W.I. to work subsequently in a rural area in Jamaica.

Recognising the present paucity of doctors trained at the University of the West Indies who are working in rural government health facilities in Jamaica, and its impact on the health services, this study was done to determine the factors influencing the decision of UWI-trained interns to work in these facilities post-internship. A questionnaire was administered to 57 UWI-trained medical graduates presently doing their internship in Jamaica. The results showed that there was no significant difference in the choice of placement with respect to sex, or residential background of the intern, though the latter seemed to indicate a trend. Of those who thought they would work in a rural government health facility, two-thirds would do so immediately post-internship but 50% did not plan to work there for more than five years. Opportunities for postgraduate training and lack of equipment were the most important deterrents to working in a rural government health facility.

Choice Behavior↗

Ethylene-Mediated Regulation of Gibberellin Content and Growth in Helianthus annuus L.

Elongation of hypocotyls of sunflower can be promoted by gibberellins (GAs) and inhibited by ethylene. The role of these hormones in regulating elongation was investigated by measuring changes in both endogenous GAs and in the metabolism of exogenous [(3)H]- and [(2)H(2)]GA(20) in the hypocotyis of sunflower (Helianthus annuus L. cv Delgren 131) seedlings exposed to ethylene. The major biologically active GAs identified by gas chromatography-mass spectrometry were GA(1), GA(19), GA(20), and GA(44). In hypocotyls of seedlings exposed to ethylene, the concentration of GA(1), known to be directly active in regulating shoot elongation in a number of species, was reduced. Ethylene treatment reduced the metabolism of [(3)H]GA(20) and less [(2)H(2)]GA(1) was found in the hypocotyls of those seedlings exposed to the higher ethylene concentrations. However, it is not known if the effect of ethylene on GA(20) metabolism was direct or indirect. In seedlings treated with exogenous GA(1) or GA(3), the hypocotyls elongated faster than those of controls, but the GA treatment only partially overcame the inhibitory effect of ethylene on elongation. We conclude that GA content is a factor which may limit elongation in hypocotyls of sunflower, and that while exposure to ethylene results in reduced concentration of GA(1) this is not sufficient per se to account for the inhibition of elongation caused by ethylene.

Journal Article↗

Transport and Metabolism of 1-Aminocyclopropane-1-carboxylic Acid in Sunflower (Helianthus annuus L.) Seedlings.

Transport and metabolism of [2,3-(14)C] 1-aminocyclopropane-1-carboxylic acid (ACC) from roots to shoots in 4-day-old sunflower (Helianthus annuus L.) seedlings were studied. [(14)C]ACC was detected in, and (14)C(2)H(4) was evolved from, shoots 0.5 hours after [(14)C]ACC was supplied to roots. Ethylene emanation from the shoots returned to normal levels after 6 hours. The roots showed a similar pattern, although at 24 hours ethylene emanation was still slightly higher than in those plants that did not receive ACC. [(14)C]N-malonyl-ACC (MACC) was detected in both tissues at all times sampled. [(14)C]MACC levels surpassed [(14)C]ACC levels in the shoot at 2 hours, whereas [(14)C]MACC levels in the root remained below [(14)C]ACC levels until 6 hours, after which they were higher. Thin-layer chromatography analysis identified [(14)C] ACC in 1-hour shoot extracts, and [(14)C]MACC was identified in root tissues at 1 and 12 hours after treatment. [(14)C]ACC and [(14)C] MACC in the xylem sap of treated seedlings were identified by thin-layer chromatography. Xylem transport of [(14)C]ACC in treated seedlings, and transport of ACC in untreated seedlings, was confirmed by gas chromatography-mass spectrometry. Some evidence for the presence of [(14)C]MACC in xylem sap in [(14)C]ACC-treated seedlings is presented. A substantial amount of radioactivity in both ACC and MACC fractions was detected leaking from the roots over 24 hours. A second radiolabeled volatile compound was trapped in a CO(2)-trapping solution but not in mercuric perchlorate. Levels of this compound were highest after the peak of ACC levels and before peak MACC levels in both tissues, suggesting that an alternate pathway of ACC metabolism was operating in this system.

Journal Article↗

Evaluation of urinary hydroxypyridinium crosslink measurements as resorption markers in metabolic bone diseases.

Analyses of the urinary concentration relative to creatinine of the collagen crosslinks, pyridinoline (Pyd) and deoxy-pyridinoline (Dpd) were made in 47 patients with metabolic bone diseases to assess the validity of these assays as indicators of bone resorption. The mean values for patients with Paget's disease of bone, primary hyperparathyroidism and osteomalacia were significantly higher (P less than 0.001) than those for age-matched healthy individuals. During treatment of Paget's disease with bisphosphonates, there was a steady decline in the urinary concentration of the crosslinks to the normal range; this change occurred earlier than for serum alkaline phosphatase. There were significant correlations (P less than 0.01) between the concentrations of both crosslinks and the corresponding values for hydroxyproline. At lower crosslink concentrations, however, these relationships were less marked due to large variations in hydroxyproline values. The results show that measurements of urinary Pyd and Dpd provide clinically applicable indices of bone resorption that are more specific than other markers.

Aged↗

Breast vasculitis in association with breast gigantism in a pregnant patient with systemic lupus erythematosus.

A 24 year old woman with systemic lupus erythematosus (SLE) developed widespread necrotic skin ulceration and gigantism of both breasts during an exacerbation of SLE in the last trimester of her second pregnancy. Over the remainder of the pregnancy the ulceration was only controlled by high dose corticosteroids. After parturition, however, it was possible to reduce the steroid dose without recurrence of the ulceration.

Adult↗

The pattern of rheumatoid arthritis in West Africa and comparison with a cohort of British patients.

Inadequate information is available on the care burden and severity of rheumatological diseases such as rheumatoid arthritis in West Africa. We therefore studied patients with rheumatoid arthritis presenting to a rheumatology unit in Nigeria and compared these with patients presenting to a British rheumatology unit. The West African patients were younger at onset of disease, less frequently had a family history, showed fewer extra-articular features and erosions and were less commonly rheumatoid factor positive. The overall mildness of the disease in the West Africans was striking.

Adolescent↗

Randomized, double-blind trial of deflazacort versus prednisone in juvenile chronic (or rheumatoid) arthritis: a relatively bone-sparing effect of deflazacort.

Thirty-four children with juvenile chronic (rheumatoid) arthritis were recruited to a randomized, double-blind study of deflazacort (an oxazolone derivative of prednisone) vs prednisone. All had been receiving glucocorticoid therapy for at least 1 year and required at least 5 mg/d of prednisolone (usually as 10 mg every 2 days). Thirty-one children completed the study. Bone density trends were measured in the spine by dual photon absorptiometry and in the forearm by single photon quantitative computed tomography at 3-monthly intervals. Trends (velocities) in bone and soft tissue growth were calculated. In the spine, bone growth correlated well with indices of soft tissue growth, but covariance analysis showed a significant advantage (P less than .007) of deflazacort when spinal bone mineral growth was compared to body surface area and weight. In part this was due to a temporary interruption in weight by children receiving deflazacort, whose gain in height was comparable with that of the prednisone group. Some children in both groups improved clinically and showed catch-up growth; in these children relative spinal bone mineral growth velocities were about twice those observed for height and weight. It is concluded that during the first year of deflazacort, their spinal bone mineral content at a level that was appropriate for their height and weight. Further observations are required to establish whether this advantage can be maintained subsequently. The anti-inflammatory effects of the two glucocorticoids appeared similar.

Adolescent↗

Western blot identification of platelet proteins that bind normal serum immunoglobulins. Characteristics of a 95-Kd reactive protein.

We have found that Western blots (WBs) of whole platelets exposed to normal autologous or homologous sera commonly have bands at 90 to 95 (95) Kd, and less often at 100 to 110, 80 to 85, 60 to 75, and 50 to 60 Kd when developed with antiglobulins. The percentages of normal sera producing a 95-Kd band with anti-immunoglobulin G (IgG), -IgA, and -IgM are 85, 50, and 30, respectively. Antiglobulin reagents alone also produce background bands on WBs that we have shown correspond to levels of platelet-associated Igs (PAIgs) or their derivatives. Titers of 95 Kd-reactive IgG in normal sera range from 10 to 1,280 (85% less than or equal to 50), and the reaction appears to be partially F(ab')2-mediated. The 95-Kd protein is internal and differs in many respects from surface glycoproteins IIIa, IV, and V of similar apparent molecular weight. In thrombocytopenic patients there was no correlation between severity of thrombocytopenia or PAIgG of platelet eluates and corresponding serum titers of 95 Kd-reactive IgG. Some WB reactions previously reported as evidence of autoimmunity may represent normal variations in reactions of Igs with internal platelet proteins. These reactions may be immunospecific or analogous to nonspecific, partially F(ab')2-dependent binding of Igs by certain bacterial proteins.

Blood Platelets↗

Identification of the sodium-calcium exchanger as the major ricin-binding glycoprotein of bovine rod outer segments and its localization to the plasma membrane.

After neuraminidase treatment the Na+/Ca2+ exchanger of bovine rod outer segments was found to specifically bind Ricinus communis agglutinin. SDS gel electrophoresis and Western blotting of ricin-binding proteins purified from rod outer segment membranes by lectin affinity chromatography revealed the existence of two major polypeptides of Mr 215K and 103K, the former of which was found to specifically react with PMe 1B3, a monoclonal antibody specific for the 230-kDa non-neuraminidase-treated Na+/Ca2+ exchanger. Reconstitution of the ricin affinity-purified exchanger into calcium-containing liposomes revealed that neuraminidase treatment had no significant effect on the kinetics of Na+/Ca2+ exchange activation by sodium. We further investigated the density of the Na+/Ca2+ exchanger in disk and plasma membrane preparations using Western blotting, radioimmunoassays, immunoelectron microscopy, and reconstitution procedures. The results indicate that the Na+/Ca2+ exchanger is localized in the rod photoreceptor plasma membrane and is absent or present in extremely low concentrations in disk membranes, as we have previously shown to be the case for the cGMP-gated cation channel. Previous reports describing the existence of Na+/Ca2+ exchange activity in rod outer segment disk membrane preparations may be due to the fusion of plasma membrane components and/or the presence of contaminating plasma membrane vesicles.

Animals↗

Anion channel blockers cause apparent inhibition of exocytosis by reacting with agonist or secretory product, not with cell.

Agents that act as anion channel blockers (ACBs) and do not permeate cells appear to inhibit exocytosis in platelets, parathyroid cells, and neutrophils. Based in large part on these observations, anion influx through plasma membrane channels has been considered a factor controlling cellular secretion, but there have been no direct anion influx measurements in cells or granules to support this concept. We have found that ACBs inhibit only thrombin-induced platelet secretion, not secretion induced by ADP, collagen, or A23187. ACBs inhibit thrombin esterolytic activity, binding of thrombin to platelets, and thrombin-stimulated platelet production of malondialdehyde in proportion to the degree of inhibition of thrombin-induced platelet secretion. Thus inhibition of platelet secretion by ACBs is due to inactivation of the stimulatory agonist, thrombin, and not to interference with cellular secretion per se. We have also found that previously reported inhibition of secretion of parathyroid cells and neutrophils by ACBs can be explained by the ability of ACBs to interfere with detection of the cellular secretory products that were measured to assess exocytosis. Our measurements of parathyroid hormone and beta-glucuronidase in the presence of ACBs were reduced to the same degree as the reported reduction in apparent cellular secretion produced by these agents. We conclude that plasma membrane anion channels of the type that can be blocked by ACBs such as 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid, suramin, and probenecid do not participate in cellular secretory processes. Whether other types of anion channels exist that are not affected by these ACBs and whether there are mechanisms of anion flux during secretion not dependent on channels remain open questions.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗