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Biomedical subjects

A Gray

Publications and source records attributed to A Gray.

At least 163 records · Page 9Linked to original sources

Myofibroblasts in hollow visceral myopathy: the origin of gastrointestinal fibrosis?

A patient with hollow visceral myopathy is reported in whom light microscopical studies of the small and large intestine showed typical features of degeneration, thinning, and fibrous replacement of smooth muscle of the gastrointestinal tract. Electron microscopy showed a striking increase in collagen with minimal fibroblast proliferation. Smooth muscle fibres had a range of ultrastructural abnormalities including myofilament disarray, electron lucency of the cytoplasm, and proliferation of the endoplasmic reticulum. Some fibres seemed to have typical ultrastructural characteristics of myofibroblasts, and others to be transition forms between typical smooth muscle cells and typical myofibroblasts. It seems likely that the fibrosis typical of this disorder has its origin in the transformation of smooth muscle fibres from a purely contractile to a myofibroblast collagen synthetic phenotype.

Adolescent↗

Supported arm exercise vs unsupported arm exercise in the rehabilitation of patients with severe chronic airflow obstruction.

OBJECTIVE: Compare unsupported (UAEx) vs supported (SAEx) arm exercise in training of patients with severe chronic airflow obstruction (CAO). DESIGN: Randomized trial of UAEx vs SAEx training added to a 10-week outpatient program of lower extremity (LE) exercise training, respiratory muscle training, breathing retraining, psychological support, and teaching. SETTING: The Lahey Clinic Medical Center, a tertiary referral center. PATIENTS: Forty patients with CAO entered the rehabilitation program with 32 completing training and testing. INTERVENTIONS: All underwent progressive bicycle ergometer and treadmill training and respiratory muscle training using a threshold inspiratory pressure trainer. Patients were randomized to progressive SAEx training (arm cycle ergometer, n = 17) or UAEx training (raising weighted dowel, n = 18). MAIN OUTCOME MEASURES AND RESULTS: There was no significant difference in disease severity or exercise capacity between the two groups. Twelve-min walk test, bicycle ergometer power output, and respiratory muscle function improved with no significant difference in improvement between the two groups. Both groups showed similar improvements in arm ergometer testing while those trained with UAEx showed greater improvement in dowel testing (UAEx > SAEx, p = 0.002). In 17 patients VO2isotime (time at which patient performed pre-training and post-training tests) was measured during dowel testing. Only those trained with UAEx showed decreases in VO2isotime (UAEx trained, p = 0.02; SAEx, p = 0.18). VO2 during the last minute of a 2-min period of simple arm elevation was also measured in 17 patients. Only those trained with UAEx showed decreases in VO2 (UAEx, p = 0.02; SAEx, p = 0.20). CONCLUSION: We confirm that a pulmonary rehabilitation program incorporating exercise training improves LE and respiratory muscle function. Arm exercise training improved arm activity with greater increases in unsupported arm activity seen in those trained with unsupported arm training. Metabolic cost of UAEx decreased only in those trained with UAEx. As UAEx is typical of activities of daily living in patients with CAO, the changes seen with UAEx training may be of greater clinical significance. Arm training should be incorporated in exercise training and a simple program of UAEx appears the optimal format.

Adult↗

Alzheimer's disease: the burden of the illness in England.

This paper reports the findings of a study that estimated the socioeconomic costs, both direct and indirect, of Alzheimer's Disease in England by using a 'burden of illness' framework. The burden of illness was calculated for all main areas of provision: hospital and residential care, general practice, day care, home care and informal care, including the calculations of costs by age-group and by service provider. The results show that the cost of this care amounted to around 1,039m pounds in 1990/91, establishing that spending associated with Alzheimer's Disease is a major area of care expenditure. Such burden of illness data should help those involved with health care decision-making, planning and priority setting, especially for health districts and social services establishing base plans for care in the community.

Aged↗

Infusion of stroma-free cross-linked hemoglobin during acute gram-negative bacteremia.

Twelve dogs were divided into two groups of six each, and were infused with bis-3,5-dibromosalicyl fumarate stroma-free hemoglobin (DBBF-Hb) or albumin. Their responses to an intravenous bolus of Escherichia coli were followed for 4 hr. Bacterial clearance from the blood stream was studied using standard colony counting methodology as well as blood counts, blood chemistries, and clotting factor analysis. There was a significant difference in mean arterial pressure (MAP) over time between DBBF-Hb-treated dogs and those treated with albumin (P < 0.02). While the DBBF-treated dogs had a higher MAP during the 10 min of bacteremia, after 1 hr, there were no longer any appreciable differences between septic dogs treated with DBBF-Hb vs. albumin. Consumption of clotting and natural anticoagulant factors was observed to be similar in both groups, as were endotoxin levels. Blood urea nitrogen (BUN) increased slightly in both groups, while white blood cell counts and clotting factor levels fell in both groups in a similar fashion. There was a more pronounced fall (P < 0.04) in platelet counts in the animals treated with DBBF-Hb. In the dogs treated with DBBF-Hb, there was also a late rise in pCO2 (P < 0.01), a more pronounced fall in pO2, and greater acidosis, which suggested that ventilation perfusion abnormalities may have been exacerbated by DBBF-Hb treatment. Since the exacerbation of respiratory abnormalities was not related to diminished bacterial or endotoxin clearance, the possibility is raised that DBBF-Hb interferes with compensatory respiratory changes during sepsis.

Acute Disease↗

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↗

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↗

Milk.

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Animals↗

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↗

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↗

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↗

Analysis of components of demographic change.

"There exist a number of approaches to analysis of the components of difference between demographic rates using standardization techniques. A generalization of some of these methods, for an arbitrary number of components and an arbitrary analytical function of them, is shown to be the theoretically best choice when the analytical function is linear in each of the components and when linear change is assumed for each of the components. Also, a very close approximation to an exact decomposition for the most general case can be obtained when dealing with change over time and time series data are available."

Demography↗

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↗

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↗

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↗

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↗