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Biomedical subjects

A Edwards

Publications and source records attributed to A Edwards.

At least 145 records · Page 8Linked to original sources

In vitro and in vivo biodurability of a compliant microporous vascular graft.

Polyurethanes have unique mechanical and biologic properties that make them ideal for many implantable devices. However, certain polyurethanes are affected by some in vivo degradation mechanisms. For example, poly(ester)urethanes are subject to hydrolytic degradation and are no longer used in long-term implanted devices. Poly(ether)urethanes while hydrolytically stable, are subject to oxidative degradation in several forms, including environmental stress cracking and metal ion oxidation. We have developed a second-generation poly(carbonate)urethane with superior biostability. This material has been fabricated by our patented method into small diameter microporous vascular grafts. We evidenced the biodurability of our vascular graft by in vitro qualification tests which compared the poly(carbonate)urethane with a traditional poly(ether)urethane. This poly(carbonate)urethane graft has also proven to be biodurable in in vivo experimental implants up to twenty months duration with no evidence of hydrolysis or environmental stress cracking (ESC).

Animals↗

The use of specialist palliative care services by patients with human immunodeficiency virus-related illness in the Yorkshire Deanery of the northern and Yorkshire region.

To examine the use of palliative care services by patients affected by human immunodeficiency virus (HIV) in hospices which do not specialize in the care of HIV patients, a tape-recorded, semistructured interview was carried out in 12 hospices in the UK. The interview explored concerns about such provision, as well as actual issues encountered. The study revealed that all 12 hospices accepted referrals for people affected by HIV and had clear working practices on infection control. between 1990 and 1996, 48 individuals affected by HIV had contact with the hospices. The number of referrals was not related to the size of the hospice. Thirty-nine individuals had a total of 655 days of inpatient care (range 1-35 days); mean length of stay 12.7 days. Twenty-four (62%) died during their first admission. Referrals came from disparate sources and this affected the amount and type of specialist HIV support available to the hospice. The paucity of referrals raised concerns in most of the units as to how to maintain skills. Issues about maintaining confidentiality of diagnosis in a multiprofessional team, and after death were highlighted. All units expressed concerns about the impact on fundraising of HIV-related admissions. Overall it was felt that the hospice units were failing to meet the palliative care needs of the majority of people affected by HIV or acquired immunodeficiency syndrome (AIDS) in the region. Possible reasons for this are given.

Advance Directives↗

Criteria for evaluating alternative MEDLINE search engines.

With so many options available for searching MEDLINE on the World Wide Web or as a component of an online service, evaluation criteria are suggested as a means of assisting librarians in determining the positive and negative aspects of alternative MEDLINE sites. A set of searches was utilized to systematically compare MEDLINE sites. Sites evaluated included Avicenna, America Online, HealthGate, PubMed, Medscape, and Physicians' Online. Some features used to evaluate these sites were: default fields; operators (default); access to MeSH; subheadings; stop words protected in MeSH; truncation; and stemming. This article will describe the group process used to arrive at the evaluation criteria, as well as some general conclusions which will help librarians in directing their users to a particular MEDLINE site.

Abstracting and Indexing↗

Improved detection of familial hypercholesterolemia by determining low density lipoprotein receptor expression in mitogen-induced proliferating lymphocytes.

In view of the presence of some 190 mutations in the low density lipoprotein receptor (LDL-R) gene and a lack of simple detection methods, we have developed an improved assay system for detecting familial hypercholesterolemia (FH) using mitogen-induced proliferating lymphocytes. Freshly isolated mononuclear cells were cultured for 3 days in RPMI 1640 supplemented with 10% human lipoprotein-deficient serum (LPDS) and 1% phytohemagglutinin (PHA). LDL-R expression was measured by flow cytometry using a monoclonal anti-LDL-R antibody or DiI-LDL. Mitogenic responses were monitored by cell size (FSC), interleukin-2 receptor (IL2-R) expression, and stimulation index (SI). The LDL-R expression in PHA-stimulated lymphocytes was significantly higher than lymphocytes or monocytes cultured without PHA (15.2- and 3.6-fold, respectively). The gradation of the LDL-R expression was highly correlated to FSC, IL2-R expression, and SI (r > 0.9 in each case). However, no difference in FSC, IL2-R expression, or SI existed between 30 clinically diagnosed FH and 42 normolipemic control subjects. The significantly lower LDL-R expression in the FH group (45.2 +/- 15.3% versus 100 +/- 14.1%; unpaired t test, P < 0.0001) indicated the presence of genetic defects. Normocholesterolemic first degree relatives and non-FH hypercholesterolemic subjects demonstrated normal LDL-R expression as did the controls. The assay carries an efficiency of 97% and both sensitivity and specificity of 98.5%. Measurement of low density lipoprotein receptor expression in phytohemagglutinin- and lipoprotein-deficient serum-stimulated lymphocytes offers a simple method for detecting familial hypercholesterolemia with improved sensitivity.

Adolescent↗

Hindered transport of macromolecules in isolated glomeruli. I. Diffusion across intact and cell-free capillaries.

The filtrate formed by renal glomerular capillaries must pass through a layer of endothelial cells, the glomerular basement membrane (GBM), and a layer of epithelial cells, arranged in series. To elucidate the relative resistances of the GBM and cell layers to movement of uncharged macromolecules, we measured the diffusional permeabilities of intact and cell-free capillaries to narrow fractions of Ficoll with Stokes-Einstein radii ranging from 3.0 to 6.2 nm. Glomeruli were isolated from rat kidneys, and diffusion of fluorescein-labeled Ficoll across the walls of single capillary loops was monitored with a confocal microscopy technique. In half of the experiments the glomeruli were treated first to remove the cells, leaving skeletons that retained the general shape of the glomerulus and consisted almost entirely of GBM. The diffusional permeability of cell-free capillaries to Ficoll was approximately 10 to 20 times that of intact capillaries, depending on molecular size. Taking into account the blockage of much of the GBM surface by cells, the contribution of the GBM to the diffusional resistance of the intact barrier was calculated to be 13% to 26% of the total, increasing with molecular size. Thus, the GBM contribution, although smaller than that of the cells, was not negligible. The structure that is most likely to be responsible for the cellular part of the diffusional resistance is the slit diaphragm, which spans the filtration slit between epithelial foot processes. A novel hydrodynamic model was developed to relate the diffusional resistance of the slit diaphragm to its structure, which was idealized as a single layer of cylindrical fibers in a ladder-like arrangement.

Animals↗

Hindered transport of macromolecules in isolated glomeruli. II. Convection and pressure effects in basement membrane.

The filtration rates for water and a polydisperse mixture of Ficoll across films of isolated glomerular basement membrane (GBM) were measured to characterize convective transport across this part of the glomerular capillary wall. Glomeruli were isolated from rat kidneys and the cells were removed by detergent lysis, leaving a preparation containing almost pure GBM that could be consolidated into a layer at the base of a small ultrafiltration cell. A Ficoll mixture with Stokes-Einstein radii ranging from about 2.0 to 7.0 nm was labeled with fluorescein, providing a set of rigid, spherical test macromolecules with little molecular charge. Filtration experiments were performed at two physiologically relevant hydraulic pressure differences (delta P), 35 and 60 mmHg. The sieving coefficient (filtrate-to-retentate concentration ratio) for a given size of Ficoll tended to be larger at 35 than at 60 mmHg, the changes being greater for the smaller molecules. The Darcy permeability also varied inversely with pressure, averaging 1.48 +/- 0.10 nm2 at 35 mmHg and 0.82 +/- 0.07 nm2 at 60 mmHg. Both effects could be explained most simply by postulating that the intrinsic permeability properties of the GBM change in response to compression. The sieving data were consistent with linear declines in the hindrance factors for convection and diffusion with increasing pressure, and correlations were derived to relate those hindrance factors to molecular size and delta P. Comparisons with previous Ficoll sieving data for rats in vivo suggest that the GBM is less size-restrictive than the cell layers, but that its contribution to the overall size selectivity of the barrier is not negligible. Theoretical predictions of the Darcy permeability based on a model in which the GBM is a random fibrous network consisting of two populations of fibers were in excellent agreement with the present data and with ultrastructural observations in the literature.

Animals↗

Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS.

The precise role played by HIV-specific cytotoxic T lymphocytes (CTL) in HIV infection remains controversial. Despite strong CTL responses being generated during the asymptomatic phase, the virus persists and AIDS ultimately develops. It has been argued that the virus is so variable, and the virus turnover so great that escape from CTL recognition would occur continually, but so far there is limited evidence for CTL escape. The opposing argument is that evidence for CTL escape is present but hard to find because multiple anti-HIV immune responses are acting simultaneously during the asymptomatic phase of infection. We describe six donors who make a strong CTL response to an immunodominant HLA-B27-restricted epitope. In the two donors who progressed to AIDS, CTL escape to fixation by the same mutation was observed, but only after 9-12 years of epitope stability. CTL escape may play an important role in the pathogenesis of HIV infection.

Acquired Immunodeficiency Syndrome↗

The struggle to diagnose UTI in children under two in primary care.

BACKGROUND: The incidence of urinary tract infection (UTI) in childhood is highest in infancy and accounts for 5% of febrile infants. Reflux nephropathy following UTI in early childhood is the commonest preventable cause of chronic renal failure. Recent guidelines aim to improve the diagnosis and management of UTI in small children. OBJECTIVES: To assess management of febrile children and UTI in children under 2 years amongst GPs, and to identify some reasons for the difficulties in diagnosing UTI. METHOD: Questionnaire distributed by periodical journal. RESULTS: Eighty-two GPs responded, of whom 61 (74%) were unaware of the recent Royal College of Physicians guidelines on childhood UTI. Seventy-seven GPs (94%) would find guidelines helpful on when to send a urine sample for culture from a child under 2 years. Only 11 GPs (14%) regularly sent urine from febrile infants and toddlers; 48 GPs (63%) sent urine from only 0-10% of patients; 21 (26%) were unable to collect urine at all from these children. Several difficulties were identified by GPs regarding investigation for UTI in children. These related to practical difficulties in urine collection and culturing, lack of professional awareness of the importance of UTI and concerns about the costs of investigation. CONCLUSION: GPs frequently do not investigate for UTI in febrile children due to practical difficulties, lack of awareness and financial costs. National guidelines need to be disseminated and implemented effectively to reach target groups. Further scope for research into a simple, cheap method to collect and test urine has been highlighted as a priority to improve early diagnosis of UTI. Management of UTI in primary care can be improved with carefully evaluated strategies and this could lead to a reduction in the prevalence of renal scarring.

Family Practice↗

A urine analysis method suitable for children's nappies.

BACKGROUND: Urinary tract infection in infancy continues to be underdiagnosed, despite its association with renal scarring and thus hypertension, renal failure, and other sequelae. Low ascertainment of urinary tract infections reflects the many difficulties in establishing a diagnosis, some of which could be eliminated by a simple, reliable method for preliminary investigation of children's urine. AIM: To assess the accuracy of a new, simple method for testing urine for nitrite and leucocyte esterase, which could be applied to children in primary care. METHODS: An in vitro study was carried out to compare the results of conventional urine analysis with urine analysis on urine soaked on to panty-liners, and with the laboratory investigation. Two urine analysis stick types were used (Boehringer Mannheim Nephur sticks and Bayer Multistix 8SG) and two brands of panty-liners. Analysis examined evidence of agreement and bias for different methods in addition to sensitivity, specificity, and negative predictive values for urine analysis. RESULTS: Pressing urine analysis test sticks on to panty-liners soaked with urine achieved consistent results compared with the results of conventional dipstick urine analysis. At a prevalence of 21.8%, sensitivity and negative predictive values of urine analysis for laboratory confirmed urinary tract infection were 94% and 98%, respectively, for Boehringer sticks, and 76% and 93%, respectively, for Bayer sticks. At prevalences of 5% and 1% (prevalences that could be expected in primary care) Bayer sticks had negative predictive values of 98.7% and 99.7%, respectively, and Boehringer sticks had values of 99.6% and 99.9%, respectively. CONCLUSIONS: Testing urine on panty-liners is accurate compared with conventional urine analysis. It may be possible to apply this method to testing unwell children presenting in primary care to identify those who require microbiological urine culture to confirm or eliminate a diagnosis of urinary tract infection.

Adolescent↗

Facilitated transport in vasa recta: theoretical effects on solute exchange in the medullary microcirculation.

A new theoretical model describing the exchange of water and solutes between the renal medullary interstitium and the microcirculation was developed to account for the presence of water channels and urea transporters, both of which were recently identified in the descending vasa recta (DVR) of the renal medulla. Small solutes, which are excluded from the water channels, are freely exchanged through a parallel pathway shared with water. The transcapillary concentration gradients of sodium and urea across the water channels induce water efflux from DVR, whereas classic Starling forces across the shared pathway favor volume uptake by DVR. Because small solute concentration gradients are large in the inner medulla, the model predicts net water removal from DVR, in agreement with experimental observations. The descending and ascending vasa recta (AVR) function as a countercurrent exchanger, the efficiency of which is inversely related to the net amount of solute taken up by the medullary microcirculation. Our results indicate that net solute removal from the medulla is governed by convective uptake into AVR and thus depends predominantly on the parameters affecting AVR transcapillary volume flux. The simulations also suggest that the urea transporter significantly enhances the exchange of both sodium and urea and might serve to abrogate a reduction in exchanger efficiency imparted by water channels.

Animals↗