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Biomedical subjects

A Gray

Publications and source records attributed to A Gray.

At least 19 recordsLinked to original sources
PubMed1992

HRT: an analysis of benefits, risks and costs.

A cost-effectiveness analysis of hormone replacement therapy (HRT) was undertaken to assess the relative benefits of different treatment strategies, and to identify which factors most influence cost-effectiveness. The current lack of conclusive evidence on the effects of HRT, especially in relation to combined therapy and cardiovascular disease, necessitated the use of a large number of assumptions in our model. In terms of net health benefits, the potential reduction in cardiovascular disease would have greatest impact, and would overshadow any small increase in breast cancer risk possibly associated with long-term use. Net expenditure by the NHS will depend critically on the direct costs of treatment, rather than on any indirect costs incurred or averted as a result of side-effects. In terms of cost-effectiveness, long-term prophylactic treatment of hysterectomised women and treatment of symptomatic women with a uterus compare favourably with other accepted health care interventions.

Breast Neoplasms↗
PubMed1992

Isolation and biochemical characterization of the human sperm tail fibrous sheath.

The isolation and biochemical characterization of the human sperm tail fibrous sheath (FS) is described for the first time. Initially, the solubilization properties of the FS were assessed immunocytochemically using GDA-J/F3 and RT97 monoclonal antibodies (MoAbs) and morphologically by electron microscopy. Following extensive investigations to optimize the conditions for the FS isolation, a simple method was developed which involved sequential extraction of the flageller components with Triton-dithiothreitol (DTT) and urea-DTT. The procedure was monitored by phase contrast microscopy and the purity of the FS preparations was confirmed by electron microscopy. SDS-PAGE of the isolated FS revealed seven major protein bands with mol. wt of 97, 76, 62, 55, 33, 28 and 25 kDa. In Western blotting, the reaction of RT97 MoAb with supernatants from the various extraction steps and the isolated FS indicated that its target antigen (AJ-p97) was an integral FS product and that disulphide bonding was probably involved in its stabilization. The reactivity of normal and aprotruded sperm tails with GDA-J/F3 and RT97 MoAbs was not affected by Triton while the GDA-J/F3 staining of the cytoplasmic matrix of other abnormal spermatids was abolished, thus suggesting variation in the biochemical properties of GDA-J/F3 in normal and abnormal germ cells. These and other data indicate that the FS could be a modified form of intermediate filament.

Antibodies, Monoclonal↗
PubMed1992

Milk.

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Animals↗
PubMed1992

Signal enhancement in fluorescence microscopy and flow cytometry using fluorescent liposome-antibody conjugates as second layer reagents.

We have developed small unilamellar liposomes (SUV) containing carboxyfluorescein for indirect immunophenotyping of cells by fluorescent microscopy and flow cytometry. Covalently coupled to anti-mouse Ig and anti-human Ig with mouse monoclonal antibodies and human typing antisera respectively, these conjugates can increase sensitivity by a factor of 10 compared to fluorescein isothiocyanate (FITC) conjugates. No increase in background fluorescence was observed. The reagents have been used to detect a low density antigen, the interleukin-2 receptor, on resting T-cells and to overcome the quenching effect of haemoglobin in fluorescent phenotyping of red cells. This has allowed to accurately estimate blood grouping in mixed fields and with small numbers of cells. We have determined the blood group of fetal red cells obtained from a chorionic villous sample at 10 weeks gestation and predicted severe hemolytic disease. This was confirmed by fetal sampling at 19 weeks and several intra-uterine transfusions were undertaken before a successful delivery at 36 weeks. Applications of the method in leucocyte phenotyping and transfusion medicine are discussed.

Animals↗
PubMed1991

Liposomes in haematology.

Liposomes were first described nearly a quarter of a century ago and have been useful models for studying the physical chemistry of lipid bilayers and the biology of the cell membrane. It was also realised that they might be used as vehicles for the delivery of drugs but clinical applications have been slow to emerge. Proposed clinical uses have included vaccine adjuvancy, gene transfer and diagnostic imaging but the major effort has been in the development of liposomes as targetable drug carriers in the treatment of malignancy. Although based on good in vitro data and animal studies, the strategies have been mostly impractical due to the predominant but unwanted uptake by the reticuloendothelial system and the limited extent of extravasation. The same features have nonetheless been turned to advantage in the case of amphotericin B which has recently become the first liposomally formulated agent to be licensed for parenteral use. Liposomal doxorubicin is currently also being evaluated in clinical trials. The early evidence suggests that while liposomal encapsulation may not greatly enhance their efficacy the toxicity of these agents is greatly attenuated.

Drug Carriers↗
PubMed1991

An examination of research design effects on the association of testosterone and male aging: results of a meta-analysis.

The study of testosterone is likely to be prominent in future epidemiological work on endocrine function and the clinical treatment of age-related diseases. Thus, understanding the hormonal changes involved in the normal male aging process will be critical. Using techniques of meta-analysis, the authors examined 88 published studies of the age-testosterone relation in men. These studies reported conflicting results: age-testosterone correlations ranged from -0.68 to +0.68. In cross-study comparisons, certain research design characteristics (e.g. time of day of blood sampling) and various sample characteristics (e.g. volunteers vs patients as subjects) were related to both mean testosterone level and the slope of the age-testosterone relation. For example, for subgroups of subjects that did not exclude ill men, the mean testosterone levels were low, and did not decline with age. Subgroups that included only healthy subjects, in contrast, had higher overall testosterone levels and showed a decline of testosterone with age. Implications of these results for design, analysis and reporting of future epidemiologic studies will be discussed. These results also illustrate the utility of meta-analysis for research with the aged.

Adult↗
PubMed1991

The estimation of whole blood viscosity by a porous bed method.

A significant impediment in determining the relative contribution of whole blood viscosity to the pathogenesis of cardiovascular and cerebrovascular disease has been the lack of an uncomplicated method to measure whole blood viscosity. To address this problem, a simplified porous bed viscometer has been developed to measure whole blood viscosity. Whole blood is passed through a porous bed of branching channels with a mean pore diameter of 69.6 +/- 20.2 microns and an estimated mean shear rate of 19.6 seconds-1. The effects of sample collection, sample storage, and temperature are described. The mean whole blood viscosity of 242 healthy persons was 22.7 +/- 5.3 seconds, which, when corrected to centipoise using Darcy's equation, corresponds to an apparent viscosity of 5.7 +/- 1.3 cp. There was a significant difference in the whole blood viscosity of normal men and women related to their different packed cell volumes. Platelets and granulocytes influenced whole blood viscosity in proportion to their contribution to the total packed cell volume. Fibrinogen levels did not significantly influence measured whole blood viscosity, which is consistent with the disaggregating conditions and the mean shear rate of the instrument. The porous bed viscometer is a convenient means to measure whole blood viscosity and it should be useful as a screening test for clinical and epidemiologic studies.

Anticoagulants↗
PubMed1991

Patterns of mortality in sickle cell disease in the United Kingdom.

Eighteen of 384 patients entered on the Brent sickle cell disease register died between 1974 and 1989, a mortality of one per 128 years of follow up. Two children died from acute splenic sequestration and a third died from fulminant pneumococcal septicaemia: none was taking prophylactic penicillin. Acute chest syndrome was the cause of death in eight young adults and one child. Three deaths occurred after surgery. Cerebrovascular accidents contributed to the cause of death in three cases and there were two sudden unexplained deaths. Ten of the deaths occurred at home or within 24 hours of admission to hospital. Post mortem examinations were made in 14 cases, but the histological appearances of acute chest syndrome were often not recognised. In most cases for whom information was available, the cause of death (chest syndrome, pneumococcal sepsis, postoperative complications) could have been prevented.

Acute Disease↗
PubMed1991

Influence of initial flaw size on crack growth in air-tempered porcelain.

Tempering of dental porcelain by forced convective cooling in air has been shown previously to inhibit the sizes of cracks induced in porcelain surfaces. However, the depth of compressive stress that is produced by tempering of feldspathic porcelain has not been determined. It can be assumed that the potential of tempered specimens to inhibit crack formation is reduced as the flaw size exceeds some critical value, since the compressive stress decreases with distance from the surface. The objective of this study was to test the hypothesis that the effectiveness of tempering stress in porcelain decreases with the increasing size of initial surface flaws. Body porcelain discs, 16 mm in diameter and 2 mm in thickness, were tempered (T) by forced convective cooling in air from an initial temperature of 982 degrees C at a pressure of 0.34 MPa for 90 s. Nontempered control discs (NT) were slowly cooled by termination of power to the furnace. The half crack-lengths (c) of surface cracks induced by a Vickers microhardness indenter at loads ranging from 2.0 to 39.2 N were determined initially and over a period of 24 h. The initial half crack-lengths, co, for the tempered specimens were significantly smaller (p less than 0.05) than the corresponding values for the slow-cooled specimens. The mean value of the stress corrosion susceptibility coefficient (n), which is inversely related to the slope of log crack size vs. log time, was only slightly smaller for the NT specimen groups (15.3), compared with the mean value for the T groups (17.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Air↗
PubMed1991

Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study.

To evaluate the hypothesis that endocrine profiles change with aging independently of specific disease states, we examined the age trends of 17 major sex hormones, metabolites, and related serum proteins in 2 large groups of adult males drawn from the Massachusetts Male Aging Study, a population-based cross-sectional survey of men aged 39-70 yr conducted in 1986-89. Group 1 consisted of 415 men who were free of obesity, alcoholism, all prescription medication, prostate problems, and chronic illness (cancer, coronary heart disease, hypertension, diabetes, and ulcer). Group 2 consisted of 1294 men who reported 1 or more of the above conditions. Each age trend was satisfactorily described by a constant percent change per yr between ages 39-70 yr. Free testosterone declined by 1.2%/yr, and albumin-bound testosterone by 1.0%/yr. Sex hormone-binding globulin (SHBG), the major serum carrier of testosterone, increased by 1.2%/yr, with the net effect that total serum testosterone declined more slowly (0.4%/yr) than the free or albumin-bound pools alone. Among the major androgens and metabolites, androstane-3 alpha,17 beta-diol (androstanediol; 0.8%/yr) and androstanediol glucuronide (0.6%/yr) declined less rapidly than free testosterone, while 5 alpha-dihydrotestosterone remained essentially constant between ages 39-70 yr. Androstenedione declined at 1.3%/yr, a rate comparable to that of free testosterone, while the adrenal androgen dehydroepiandrosterone (3.1%/yr) and its sulfate (2.2%/yr) declined 2-3 times more rapidly. The levels of testosterone, SHBG, and several androgen metabolites followed a parallel course in groups 1 and 2, remaining consistently 10-15% lower in group 2 across the age range of the study. Subgroup analyses suggested that obese subjects might be responsible for much of the group difference in androgen level. Serum concentrations of estrogens and cortisol did not change significantly with age or differ between groups. Of the pituitary gonadotropins, FSH increased at 1.9%/yr, LH increased at 1.3%/yr, and PRL declined at 0.4%/yr, with no significant difference between groups 1 and 2.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

Simultaneous preparation of paired, syncytial, microvillous and basal membranes from human placenta.

A method for the simultaneous preparation of microvillous and basal membrane vesicles from human placental syncytiotrophoblast is described. Mg2(+)-aggregated basal membranes are separated from microvillous membranes by low-speed centrifugation after initial homogenization and centrifugation steps. Microvillous membranes (MVM) are obtained from the low speed supernatant while basal membranes (BM) contained in the Mg2(+)-aggregated material are resuspended and further purified on a sucrose step gradient. MVM and BM prepared by this method were enriched 20-fold and 11-fold as determined by the membrane marker enzymes, alkaline phosphatase (MVM) and adenylate cyclase (BM). There was minimal cross-contamination of the two isolated plasma membrane fractions and the yields obtained were 26% (MVM) and 21% (BM) compared to the initial homogenate. The MVM and BM fractions were free from contamination by mitochondrial or lysosomal membranes and showed only minor contamination by microsomal membranes. The two membrane fractions were also tested for the presence of non-syncytial plasma membranes by electrophoretic immunoblotting. Contamination of both MVM and BM by fibroblast, endothelial, macrophage and cytotrophoblast plasma membranes amounted to less than 15% of the total membrane protein as determined by immunoblotting. Vesicle orientation, determined from the latency of specific concanavalin A binding, was 88 +/- 4% right-side out for MVM and 73 +/- 12% right-side out for BM. This simple preparative procedure produces a high yield of both MVM and BM from human placenta. The analytical data demonstrates that 'paired' MVM and BM fractions derived from the same placental tissue have a high purity in terms not only of contamination by intracellular membranes, but also in terms of contamination by non-syncytial plasma membranes.

Alkaline Phosphatase↗
PubMed1990

Suspected adverse reactions to medicines during 1989.

There was an increase in reports of suspected adverse reactions to veterinary medicines in 1989 with 329 reports (compared with 206 in 1988), from veterinary surgeons, farmers and the public, comments the Veterinary Medicines Directorate (VMD). Suspected adverse reactions to clostridial/pasteurella vaccines in sheep were a dominant feature and important experience was gained both in terms of liaison with the farming press, and in handling large scale incidents involving PML products. The general trend towards increased reporting of adverse drug effects continues. The UK is the only EC member state to have a PML system and the VMD is looking with some urgency at ways of ensuring the more representative reporting of all categories of drug. Substantial liaison with the veterinary pharmaceutical industry occurred during the year and 204 product reports were requested from companies.

Analgesics↗