Disclosure of sexual preferences and lesbian, gay, and bisexual practitioners.
Explore the source record for details and available documents.
Attitude to Health↗
Biomedical subjects
David Hughes
Publications and source records attributed to David Hughes.
Preservation of porcine non-heart-beating donor livers by sequential cold storage and warm perfusion.
BACKGROUND: Normothermic perfusion has been shown to resuscitate and maintain viability of non-heart-beating donor (NHBD) livers that have undergone significant warm ischemic injury. However, the logistics of clinical organ retrieval are complex, and a period of cold storage before warm preservation would simplify the process. We have investigated the effects of short duration of cold preservation before normothermic preservation on the function of porcine NHBD livers. METHODS: Porcine livers were subjected to 60 minutes of warm ischemia and then assigned to the following groups: group W (n=5), normothermic preservation for 24 hours; and group C (n=4), cold preservation in University of Wisconsin solution for 4 hours followed by normothermic preservation for 20 hours (total preservation time 24 hours). Outcome parameters that were measured included bile production, serum transaminases and hyaluronic acid levels (cellular damage), and base deficit and glucose use (metabolic function). RESULTS: Group W livers had superior bile production, metabolic activity (base deficit and greater glucose use), and less evidence of hepatocellular damage (alanine aminotransferase, aspartate aminotransferase), and sinusoidal endothelial cell dysfunction (hyaluronic acid). Group C livers showed greater necrosis and destruction of architecture on histology. CONCLUSION: Normothermic perfusion failed to resuscitate porcine livers after 60 minutes of warm ischemia and 4 hours of cold preservation. Even a short period of cold ischemia is significantly deleterious to the function of ischemically damaged (NHBD) livers.
Acid-Base Equilibrium↗
Acute renal failure associated with Gemella haemolysans pneumonia.
We describe a 13-year-old boy who developed acute renal failure associated with Gemella haemolysans pneumonia. At presentation he was found to have macroscopic hematuria associated with lobar pneumonia. Gemella haemolysans was isolated from blood cultures. Renal failure was detected on admission, progressed and dialysis was required until day 18. Renal impairment had resolved by 3 months after the initial presentation. Histopathology of a renal biopsy showed focal proliferative glomerulonephritis, but the predominant abnormality was tubular damage associated with erythrocyte casts in tubular lumina. We believe that tubular damage due to hematuria rather than the glomerular changes was the most likely cause of renal failure.
Acute Kidney Injury↗
Evaluation and treatment of familial globozoospermia in five brothers.
OBJECTIVE: To document the pathology of five siblings with complete globozoospermia and to report the effectiveness of repeated intracytoplasmic sperm injection (ICSI) treatment as therapy. DESIGN: Case report. SETTING: A tertiary center for assisted reproduction. PATIENTS(S): Five siblings with globozoospermia. INTERVENTION(S): Twenty cycles of repeated ICSI treatment. Detailed light and electron microscopy studies were performed on three of the globozoospermic brothers. MAIN OUTCOME MEASURE(S): Clinical pregnancy and live birth after ICSI treatment. RESULT(S): Light and electron microscopy showed that all spermatozoa had round heads and no acrosome. Of 129 metaphase-II oocytes injected, 49 fertilized normally, giving an overall fertilization rate of 38% (range, 0-100%). No pregnancies resulted from 13 cycles in brothers 1-3. Brothers 4 and 5 had three pregnancies after seven ICSI cycles, with one live birth and two first-trimester losses. CONCLUSION(S): Despite variable fertilization rates, pregnancies and a live birth can be achieved after repeated ICSI treatment cycles in globozoospermic siblings. No apparent pattern was manifest that reflected the true pathology or determined the outcome of ICSI treatment.
Abortion, Spontaneous↗
CD20-induced lymphoma cell death is independent of both caspases and its redistribution into triton X-100 insoluble membrane rafts.
Rituximab is routinely used for the treatment of neoplasia, although the mechanism of action remains uncertain. In the current study, CD20-induced apoptosis was investigated with a panel of anti-CD20 monoclonal antibodies (mAb) in a wide range of cell lines. A hierarchy of mAb activity was apparent, with the B1 mAb generally the most potent. Apoptosis through CD20 was dependent on the nature of mAb binding and correlated with the extent of homotypic cell adhesion induced. However, using anti-CD20 mAb, which vary in the extent to which they redistribute wild-type and mutant CD20 molecules to membrane rafts, we showed that CD20-induced apoptosis was independent of translocation to TX-100 insoluble rafts. Using crmA-transfected cells and caspase inhibitors, we showed that phosphatidylserine translocation and mitochondrial permeability transition evoked during CD20-induced apoptosis appeared caspase independent. Furthermore, in cytoplasts which lack mitochondria and in Bcl(2)-transfected cells, phosphatidylserine was still translocated to the cell surface after CD20 stimulation. Together, these data imply that CD20 can evoke apoptosis without the involvement of mitochondria and caspases and irrespective of redistribution into TX-100 insoluble membrane rafts.
Antibodies, Monoclonal↗
Low-dose valaciclovir prophylaxis against cytomegalovirus disease in renal transplant recipients.
High-dose valaciclovir at up to 8 g/day has been shown to be effective in prophylaxis against cytomegalovirus (CMV) disease in renal transplant recipients. We report our experience with low-dose valaciclovir prophylaxis of up to 3 g/day, adjusted to creatinine clearance. A group of patients at high risk of developing CMV disease who received prophylaxis were selected as the study group. This included all CMV-positive patients who received antilymphocyte therapy (R+, n=20) and all CMV-negative recipients of CMV-positive organs (D+R-, n=15). D+R- patients receiving antilymphocyte therapy were excluded, as most of the patients in the control group had received ganciclovir prophylaxis. A historical control group was used, which consisted of patients who did not receive prophylaxis. Low-dose valaciclovir prophylaxis resulted in a statistically significant decrease (8.5 vs 37%, P=0.004) in CMV disease in the study group at 6 months. On subgroup analysis the decrease was statistically significant only in the R+ group (5 vs 45%, P=0.003), not in the D+R- group (13.3 vs 26.6%, P=0.651). Low-dose valaciclovir prophylaxis seems to be adequate for R+ patients receiving antilymphocyte therapy. The role of low-dose valaciclovir prophylaxis needs to be assessed further in a prospective trial.
Acyclovir↗
Stochastic demand, production responses and hospital costs.
This paper considers the production responses to demand uncertainty within the hospital sector. It is noted that such responses have an impact on hospital cost structures. An empirical model is specified. Estimation is undertaken on a sample of UK hospitals over the period 1993-1995, differentiating between hospital output which arises from uncertain demand (emergency treatment) and output considered to be predictable (elective treatment). The model estimates that the cost of an elective admission is approximately 45% of the cost of an emergency admission. Demand uncertainty imposes a direct cost equivalent to around 5% of the total cost of emergency admission.
Elective Surgical Procedures↗
Going public: references to the news media in NHS contract negotiations.
This paper considers how middle-level managers in British Health Authorities and hospital Trusts orient to media reportage in the process of negotiating and monitoring contracts for clinical services. Although they sometimes produce media representations aimed at influencing the general public, local policy actors on both sides of the purchaser/provider split also use media messages as part of their negotiations with each other. We examine how they seek to manage negative publicity, and what happens when one side threatens to 'go public'. Managers must strike a balance between negotiating advantage and maintaining organisational relationships. Thus the powerful, but potentially double-edged, weapon of public disclosure was usually broached in indirect terms, and approached with some ambivalence. In rare cases, parties resorted to hostile press releases as relationships deteriorated. Arguably, these interactions reflect more general tensions that arise when managerial discourses, emphasising concepts such as adversarial contracting, markets and competition, are imported into professional organisations with a public service mission.
Attitude to Health↗
Staff reports of setting events associated with challenging behavior.
This study identified the setting events reported by caregivers as more and less likely to be associated with challenging behaviors of people with intellectual disabilities. Sixty-five staff working with 22 individuals were interviewed using a setting event inventory. Some setting events (e.g., being in a crowded room) were reported as strongly associated with challenging behavior, some (e.g., one-to-one support) as strongly associated with its absence. Some (e.g., day of week) were reported to be largely "inert"; many were idiosyncratically associated with occurrence, absence, or inertness. Different categories of setting events contributed different amounts to reported variation in challenging behavior. The inventory described here, or modified versions, may help identify relationships between setting events and challenging behaviors. The relationships reported in this study suggest ways in which service provision might be modified to help prevent challenging behavior.
Adult↗
Advantages of normothermic perfusion over cold storage in liver preservation.
BACKGROUND: To minimize the ischemia-reperfusion injury that occurs to the liver with the current method of preservation and transplantation, we have used an extracorporeal circuit to preserve the liver with normothermic, oxygenated, sanguineous perfusion. In this study, we directly compared preservation by the standard method of simple cold storage in University of Wisconsin (UW) solution with preservation by perfusion. METHODS: Porcine livers were harvested from large white sows weighing between 30 and 50 kg by the standard procedure for human retrieval. The livers were preserved for 24 hr by either cold storage in UW solution (n=5) or by perfusion with oxygenated autologous blood at body temperature (n=5). The extracorporeal circuit used included a centrifugal pump, heat exchanger, and oxygenator. Both groups were then tested on the circuit for a 24 hr reperfusion phase, analyzing synthetic function, metabolic capacity, hemodynamics, markers of hepatocyte and reperfusion injury, and histology. RESULTS: Livers preserved with normothermic perfusion were significantly superior (P=0.05) to cold-stored livers in terms of bile production, factor V production, glucose metabolism, and galactose clearance. Cold-stored livers showed significantly higher levels of hepatocellular enzymes in the perfusate and were found to have significantly more damage by a blinded histological scoring system. CONCLUSIONS: Normothermic sanguineous oxygenated perfusion is a superior method of preservation compared with simple cold storage in UW solution. In addition, perfusion allows the possibility to assess viability of the graft before transplantation.
Animals↗
Large scale structures, symmetry, and universality in sandpiles.
We introduce a sandpile model where, at each unstable site, all grains are transferred randomly to downstream neighbors. The model is local and conservative, but not Abelian. This does not appear to change the universality class for the avalanches in the self-organized critical state. It does, however, introduce long-range spatial correlations within the metastable states. For the transverse direction d(perpendicular)>0, we find a fractal network of occupied sites, whose density vanishes as a power law with distance into the sandpile.
Journal Article↗
Randomized trial of tacrolimus versus cyclosporin microemulsion in renal transplantation.
This study was undertaken to compare the efficacy and safety of tacrolimus (Tac) with the microemulsion formulation of cyclosporin (CyA) in children undergoing renal transplantation. A 6-month, randomized, prospective, open, parallel group study with an open extension phase was conducted in 18 centers from nine European countries. In total, 196 pediatric patients (<18 years) were randomly assigned (1:1) to receive either Tac ( n=103) or CyA microemulsion ( n=93) administered concomitantly with azathioprine and corticosteroids. The primary endpoint was incidence and time to first acute rejection. Baseline characteristics were comparable between treatment groups. Tac therapy resulted in a significantly lower incidence of acute rejection (36.9%) compared with CyA therapy (59.1%) ( P=0.003). The incidence of corticosteroid-resistant rejection was also significantly lower in the Tac group compared with the CyA group (7.8% vs. 25.8%, P=0.001). The differences were also significant for biopsy-confirmed acute rejection (16.5% vs. 39.8%, P<0.001). At 1 year, patient survival was similar (96.1% vs. 96.6%), while 10 grafts were lost in the Tac group compared with 17 graft losses in the CyA group ( P=0.06). At 1 year, mean glomerular filtration rate (Schwartz estimate) was significantly higher in the Tac group (62+/-20 ml/min per 1.73 m(2), n=84) than in the CyA group (56+/-21 ml/min per 1.73 m(2), n=74, P=0.03). The most frequent adverse events during the first 6 months were hypertension (68.9% vs. 61.3%), hypomagnesemia (34.0% vs. 12.9%, P=0.001), and urinary tract infection (29.1% vs. 33.3%). Statistically significant differences ( P<0.05) were observed for diarrhea (13.6% vs. 3.2%), hypertrichosis (0.0% vs. 7.5%), flu syndrome (0.0% vs. 5.4%), and gum hyperplasia (0.0% vs. 5.4%). In previously non-diabetic children, the incidence of long-term (>30 days) insulin use was 3.0% (Tac) and 2.2% (CyA). Post-transplant lymphoproliferative disease was observed in 1 patient in the Tac group and 2 patients in the CyA group. In conclusion, Tac was significantly more effective than CyA microemulsion in preventing acute rejection after renal transplantation in a pediatric population. The overall safety profiles of the two regimens were comparable.
Acute Disease↗
Comparative study of enterostatin sequence in five rat strains and enterostatin binding proteins in rat and chicken serum.
Enterostatin, a pentapeptide derived from the precursor protein procolipase has been shown to inhibit dietary fat intake and to reduce body fat after chronic administration in rats. We repeat that the enterostatin amino acid sequence from the genomic DNA of 5 different rat strains is APGPR. 125I-APGPR bound to three proteins (300, 205 and 60 kDa) in rat serum and one 60 kDa protein in chicken serum. These serum binding proteins were also eluted by APGPR affinity chromatography. Western blot analysis of serum protein identified enterostatin-like immunoreactivity associated with the same molecular weight bands. Our results demonstrate the enterostatin sequence in rat is APGPR and suggest the presence of enterostatin binding proteins in rat and chicken serum.
Animals↗
What does 'access to health care' mean?
Facilitating access is concerned with helping people to command appropriate health care resources in order to preserve or improve their health. Access is a complex concept and at least four aspects require evaluation. If services are available and there is an adequate supply of services, then the opportunity to obtain health care exists, and a population may 'have access' to services. The extent to which a population 'gains access' also depends on financial, organisational and social or cultural barriers that limit the utilisation of services. Thus access measured in terms of utilisation is dependent on the affordability, physical accessibility and acceptability of services and not merely adequacy of supply. Services available must be relevant and effective if the population is to 'gain access to satisfactory health outcomes'. The availability of services, and barriers to access, have to be considered in the context of the differing perspectives, health needs and material and cultural settings of diverse groups in society. Equity of access may be measured in terms of the availability, utilisation or outcomes of services. Both horizontal and vertical dimensions of equity require consideration.
Health Care Rationing↗
Applying the Delphi technique in a study of GPs' information requirements.
This article describes some dilemmas and problems encountered in a Delphi study of general practitioners' (GPs) information requirements. The research involved a three-round Delphi administered to an expert panel of 50 GPs in one Welsh health authority area. The Delphi is generally perceived as a qualitative METHOD: However, we argue that the requirements of the technique make it difficult to sustain the kind of inductive analysis - faithfully reflecting respondents' perspectives - that is axiomatic to many of the theoretical approaches that underpin qualitative inquiry. We describe how our attempts to incorporate respondents' views in near-verbatim form in the first round were undermined by the need to classify and reduce statements for later rounds, and to impose judgments about what should count as consensus. The iterative 'consensus-building' process, that is so central to the Delphi, was difficult to take forward without active intervention by the research team, but this involved a re-ordering and reduction of the data, which moved the statements included in later rounds further and further from the verbatim responses on which they were based. Whilst the findings of the study were useful on one level, the final consensus statements took a general, virtually context-free form, which contained few references to background preoccupations (largely concerned with the recent NHS reforms) that were exercising GPs at this time. The method also coped badly with the polarized opinions that existed regarding the development of information systems for commissioning. We conclude that the Delphi is best used for large-scale research in areas where opinions are well established, where the problems and choices confronting the study group are well known, and where a major programme of organizational reform is not already underway.
Journal Article↗
"But if you look at the coronary anatomy...": risk and rationing in cardiac surgery.
Explore the source record for details and available documents.
Age Factors↗
Arthroscopic management of talar dome lesions using a transmalleolar approach.
Surgical treatment of posteromedial talar dome lesions is frequently necessary for Berndt and Harty grade IV osteochondral defects and nondisplaced osteochondral fragments resistant to conservative modalities. When operative intervention is indicated, the approach and management can be complicated by the location and extent of the injury. The operative technique we advocate allows direct exposure of the lesion and minimizes damage to healthy articular cartilage and surrounding soft tissue. Use of a drill guide assists the surgeon in precisely placing a transmalleolar portal through the tibia for subchondral drilling of osteochondral defects when the lesions are inaccessible through traditional arthroscopic portals.
Ankle Injuries↗