The 1998 APHA Annual Lecture. What the UK can teach the US about health care.
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Economic Competition↗
Biomedical subjects
D Light
Publications and source records attributed to D Light.
CC chemokine receptor 5-mediated signaling and HIV-1 Co-receptor activity share common structural determinants. Critical residues in the third extracellular loop support HIV-1 fusion.
There is a close correspondence between the ability of RANTES and macrophage inflammatory proteins 1alpha and 1beta to activate CC chemokine receptor 5 (CCR5) and the ability to inhibit CCR5-dependent membrane fusion mediated by the envelope glycoprotein of human immunodeficiency virus (HIV), type 1. This finding suggests that some of the structural determinants for CC chemokine/CCR5 interactions and CCR5 HIV-1 fusion co-receptor activity may be shared. Recent studies using human CCR5/CCR2B chimeras have suggested that the determinants of CCR5 co-receptor activity are complex and may involve multiple extracellular receptor domains and that viral co-receptor activity is dissociable from ligand-dependent signaling responses. However, conclusive evidence demonstrating an important role for the second and third extracellular regions of human CCR5 is lacking. Furthermore, to determine whether the determinants for CCR5 co-receptor activity overlap with those required for agonist activity, studies that compare the chemokine specificity for inhibition of envelope-mediated cell fusion and the agonist profile of chimeric receptors are necessary. In the present report, using a series of CCR5/CCR2B chimeras we ascribe an important role for the second and third extracellular loop of CCR5 in supporting the co-receptor activity of CCR5. We also provide evidence that the intracytoplasmic tail of CCR5 does not play an important role in supporting HIV-1 entry. The hypothesis that the structural determinants for CC chemokine/CCR5 interactions and CCR5 HIV-1 fusion co-receptor activity may be shared was confirmed by two novel observations: first, the fusion activity supported by two hybrid receptors could be inhibited by both RANTES and monocyte chemoattractant protein-1, chemokines specific to CCR5 and CCR2B, respectively; and second, the chemokine specificity for inhibition of envelope-mediated cell fusion matched the agonist profile of these hybrid receptors. These data shed new light on the structural determinants involved in these distinct activities of CCR5 and may have important implications for the development of CCR5-targeted anti-viral compounds.
3T3 Cells↗
A massive gas leak: missing O-ring and a plastic band.
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Aged↗
Joint commissioning. Born in the USA.
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Budgets↗
Recombinant soluble human thrombomodulin: a randomized, blinded assessment of prevention of venous thrombosis and effects on hemostatic parameters in a rat model.
UNLABELLED: Thrombomodulin is an endothelial surface receptor that binds thrombin and accelerates the activation of protein C. We compared the effects of a recombinant thrombomodulin analog (TME), recombinant hirudin (r-HIR), heparin sodium (HEP), and normal saline (Control) on thrombus formation, activated partial thromboplastin time (APTT), thrombin time (TT), platelet aggregation and tail transection bleeding time (BT) in a rat model of vena cava thrombosis. RESULTS: TME, r-HIR and HEP prevented venous thrombosis in this model in a dose-dependent manner. At the dose required to reduce vena cava thrombosis by 50% (ED50), TME did not prolong the APTT or TT as did HEP and r-HIR. Platelet aggregation in response to thrombin was not effected by TME but was inhibited by both r-HIR and HEP. BT did not differentiate the agents tested. CONCLUSION: TME inhibited venous thrombosis in a rat vena cava model with less effect on hemostatic variables than HEP or r-HIR.
Animals↗
Intravenous recombinant soluble human thrombomodulin prevents venous thrombosis in a rat model.
Thrombomodulin is an endothelial surface thrombin receptor. Thrombin bound to thrombomodulin loses all procoagulant activity and instead activates the protein C anticoagulant pathway. We developed a recombinant thrombomodulin analog and compared the effects of recombinant thrombomodulin (100 micrograms/ea), saline (controls), recombinant hirudin (1.0 mg/kg), and heparin (100 units/kg) on thrombus formation, activated partial thromboplastin time, and tail transection bleeding time in a rat model of stasis-induced venous thrombosis. Results showed that thrombus was detected in the vena cava in six of the six rats treated with saline solution, in zero of the six rats treated with recombinant thrombomodulin (p less than 0.05), in one of six rats treated with recombinant hirudin (p less than 0.05), and in zero of six rats treated with heparin (p less than 0.05). The activated partial thromboplastin time in rats receiving recombinant thrombomodulin was slightly longer than controls (22 +/- 8 vs 37 +/- 6, p less than 0.05). The bleeding times in rats receiving recombinant thrombomodulin were approximately twice as long as controls (215 +/- 68 vs 545 +/- 173, p = 0.037). In all rats treated with recombinant hirudin or heparin, activated partial thromboplastin times were greater than 120 seconds and bleeding times were greater than 1200 seconds. We conclude that recombinant thrombomodulin inhibits venous thrombosis in a rat model with less prolongation of activated partial thromboplastin time and bleeding time than heparin or hirudin.
Animals↗
Medical house arrest.
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Appointments and Schedules↗
Biting hard on the research bit.
Underfunding can be a major source of waste argues Donald Light in the fourth of a five part series of articles as he identifies some systemic inefficiencies.
Efficiency↗
Labelling waste as inefficiency.
In the third of a five part series of articles, Donald Light goes in search of justification for the sweeping changes affecting the NHS and finds that the current reforms ignore some basic problems.
Contract Services↗
Bending the rules.
It is naive to claim that competition leads to efficiency, warns Donald Light. In the second of five articles, he describes how sellers have manipulated the US healthcare market.
Economic Competition↗
Learning from their mistakes?
Embracing competition American style could turn out to be an expensive mistake, says Donald Light. In the first of a series of five articles he explains how bad advice and underfunding could turn the American dream into a British nightmare.
Economic Competition↗
The changing character of the medical profession: a theoretical overview.
Technological advances in medicine have greatly enhanced the ability of physicians to treat disease and disability, but, at the same time, changes in the organization and management of health care services in the United States have imposed constraints on their autonomy. How have these changes--medical advancement and professional decline--affected the theoretical concept of the medical profession? Challenging the prevailing model of professional dominance, the concepts of deprofessionalization, corporatization, and proletarianization emphasize the effects of recent social and economic developments on the changing status of the medical profession. There is evidence, however, that what the proponents of these concepts perceive as the profession's response to external forces are, in fact, the unanticipated consequences of the profession's campaign for autonomy.
Europe↗
Milk production characteristics of the Kenana breed of Bos indicus cattle in Sudan.
Data were analyzed on the Kenana, a Bos indicus breed of cattle indigenous to northern Sudan. Cattle were kept at Um Banein in a hot dry tropical environment 13 degrees .04' latitude north at an altitude of 435 m. Analyzed were lactation yield (1597 kg), lactation length (264), calving interval (530), and annual lactation yield (1225 kg). Between 1966 and 1980 all these traits except lactation length were significantly affected by lactation number and year. None was significantly influenced by the season in which lactation started. Kenana have considerable potential in the Sudan environment as a dairy breed, but further selection and an open nucleus system of breeding to introduce additional genetic material is required to express this potential.
Animals↗
The effect of the surface finish of alumina and stainless steel on the wear rate of UHMW polyethylene.
The effect of the surface finish of medical grade alumina and stainless steel on the wear rate of ultra-high molecular weight (UHMW) polyethylene was studied in a six station pin-on-plate wear screening device using bovine serum as lubricant. The wear rate decreased as the surface finish of alumina improved from 0.10 to 0.015 micron Ra, with no evidence of an increasing wear rate below a particular value of surface finish. Tests with surgical grade stainless steel showed a similar polyethylene wear rate around the 0.025 micron Ra level, but there was evidence of a higher wear rate with stainless steel than with alumina between approx. 0.035 and 0.075 micron Ra.
Aluminum↗
A comparison of RCH 1000 and Hi-Fax 1900 ultra-high molecular weight polyethylenes.
Hoechst RCH 1000 and Hercules Hi-Fax 1900 ultra-high molecular weight (UHMW) polyethylenes have been compared, for the first time, in tests, including wear, fatigue and creep, relevant to artificial human joints. In none of the tests was the behaviour of the Hercules material inferior to that of RCH 1000, and in the wear and creep tests it was superior.
Animals↗
Delayed pulmonary maturation in the fetus of the streptozotocin-diabetic rat.
Pulmonary maturation was studied in fetuses in streptozotocin-diabetic rats on the final four days of gestation. Diabetes was induced prior to conception by the intravenous injection of streptozotocin. Fetuses were hyperglycemic but did not manifest hyperinsulinemia. Whole lung total phospholipid, phosphatidylcholine, and disaturated phosphatidylcholine were significantly decreased in the diabetic group on day 21 (term = 22 days), but not prior to or after that point in gestation. Morphologic analysis also revealed a decreased number of type II cells and lamellar bodies per alveolar lining cell in the diabetic group only on day 21, coincident with the changes in phospholipid analysis. Activities of enzymes involved in fetal pulmonary phospholipid synthesis were measured to see if differences could account for the observed developmental delay. No significant differences between diabetic and control lungs were noted in any of the enzymes studied from days 20-22, with the exception of an increase in cholinephosphate cytidylyltransferase activity in the diabetic fetuses on day 22. Immaturity in both biochemical and morphologic indices of lung development was present at a specific time late in the diabetic rat gestation. This maturational delay could not be accounted for by changes in the activities of enzymes involved in phospholipid synthesis. The fetus of the streptozotocin-diabetic rat provides a useful model to study the effects of hyperglycemia on fetal lung development.
Animals↗