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Biomedical subjects

D Price

Publications and source records attributed to D Price.

At least 55 records · Page 3Linked to original sources
PubMed2000

Photosynthetic parameters of leaves of wild type and Cyt b6/f deficient transgenic tobacco studied by CO2 uptake and transmittance at 800 nm.

Parallel measurements of CO2 assimilation and 800 nm transmission were carried out on intact leaves of wild type and cytochrome b6/f deficient transgenic tobacco grown at different light intensities and temperatures, with the aim to diagnose rate-limiting processes in photosynthesis and investigate their adaptations to growth conditions. Maximum CO2- and light-saturated photosynthetic rate, mesophyll conductance, assimilatory charge and specific carboxylation efficiency were determined from CO2 fixation measurements and postillumination P700 rereduction time constant was measured from the transient of the 800 nm signal. Results show that growth conditions continue to modulate the expression of genes in transgenic plants, interfering with the antisense modulation, but under all environmental conditions the antisense treatment to decrease Cyt b6/f complexes ensured that the control of electron/proton transport rate by proton backpressure on the PSI donor side was stronger than the control by electron backpressure on the PSI acceptor side. Coordinated control of gene expression and enzyme activation ensures that different parts of the photosynthetic machinery--components of the electron transport chain, ribulose-1,5-bisphosphate carboxylase/oxygenase, enzymes of the sucrose and starch synthesis chains-are synthesized more or less proportionally under different environmental conditions and in case of mild genetic interference.

Carbon Dioxide↗
PubMed2000

Choices without reasons: citizens' juries and policy evaluation.

Citizens' juries are commended as a new technique for democratising health service reviews. Their usefulness is said to derive from a reliance on citizens' rational deliberation rather than on the immediate preferences of the consumer. The author questions the assertion of critical detachment and asks whether juries do in fact employ reason as a means of resolving fundamental disagreements about service provision. He shows that juries promote not so much a critically detached point of view as a particular evaluative framework suited to the bureaucratic idiom of social welfare maximisation. Reports of jury practice reveal a tendency among juries to suppress by non-rational means the everyday moral language of health care evaluation and substitute for it a system of thought in which it can be deemed permissible to deny treatment to sick people. The author concludes that juries are chiefly concerned with non-rational persuasion and because of this they are morally and democratically irrelevant. Juries are no substitute for voting when it comes to protecting the public from zealous minorities.

Community Participation↗
PubMed2000

Tolerability of montelukast.

The tolerability of a medication, especially in children with asthma, is linked to a number of key factors. These include clinical effectiveness, adverse effects, frequency of drug regimen, ease and route of administration. and taste. Montelukast is unusual in that, in most countries, a licence for children aged > or =6 years was granted at the same time as the adult licence. This is related to a variety of evidence. which includes pharmacological and adult studies suggesting the specificity and safety of the drug at many times the licensed dose, and a tolerability profile similar to that with placebo or inhaled corticosteroids in both adult and paediatric studies. The most common adverse effects in paediatric studies were headache, asthma and upper respiratory tract infection at rates not statistically significantly different from those with placebo. Up to July 1999, more than 2 million patients worldwide have received montelukast, of whom nearly 220,000 have received the paediatric formulation. In the UK, one prescribing database suggests that, of children who commenced montelukast therapy, less than 25% discontinued the drug. This implies that montelukast is effective and well tolerated in most children. Adverse effect monitoring by regulatory bodies has revealed little that would not be expected on the basis of the results of clinical trials. Montelukast has been associated with Churg-Strauss syndrome in a very small number of adults. In most. the syndrome was associated with corticosteroid withdrawal, which may have unmasked the condition. Churg-Strauss syndrome has not been reported in children. Its clinical effectiveness, lack of major adverse effects, oral route of administration, palatability and the once-daily regimen combine to make montelukast a generally well tolerated medication in children.

Acetates↗
PubMed2000

Patient desire and reasons for specialist referral in a gatekeeper-model managed care plan.

OBJECTIVE: To describe patient desire and reasons for specialist referrals in a gatekeeper-model managed care plan. STUDY DESIGN: Cross-sectional prospective study. PATIENTS AND METHODS: We developed a patient questionnaire to gather demographic data and to gauge patients' desire for specialist referral and their reasons for seeking such referral. The survey was administered at 2 sites--an ambulatory care facility of a university hospital and an internal medicine clinic in a suburban ambulatory care site. Patients asked to complete the questionnaire at the university hospital site were enrolled in a gatekeeper-model managed care plan (called CU Gold); those seen at the internal medicine clinic were enrolled in a group-model health maintenance organization. Patients were asked to complete the 1-page questionnaire in the waiting room before being seen by their primary care physician. RESULTS: Among the 860 CU Gold patients who met the inclusion criteria during the 3-month study period (September to December 1997), 112 (13%) reported a definite desire to see a specialist and 274 (32%) indicated a possible desire to see a specialist at the time of their primary care visit. Compared with the CU Gold patients, significantly fewer patients in the health maintenance organization indicated a definite desire to see a specialist (3% versus 13%), but a similar percentage expressed a possible desire to see a specialist (30% versus 32%). The difference in definite desire for referral between the 2 groups could not be explained by patient or primary care physician characteristics. The principal health concerns for which patients sought referral were musculoskeletal, genitourinary or gynecologic, or dermatologic problems. Need for reassurance (cited by 67% of patients), seeing a specialist before (56%), and believing the primary care physician lacked expertise (49%) were the primary reasons patients sought referral. Seventy-four percent of patients referred by their primary care provider and 54% of those not referred agreed it was a good idea to see their primary care physician first before seeing a specialist. CONCLUSIONS: Patients have a significant desire for specialist referral, driven by their need for reassurance, previous specialist referral, and belief that their primary care physician does not have the requisite expertise. Patients' expectations for referral varied significantly, depending on the healthcare system (academic primary care clinic or health maintenance organization) in which they were enrolled.

Adult↗
PubMed2000

Observed changes in the lipid profile and calculated coronary risk in patients given dietary advice in primary care.

BACKGROUND: Dietary advice is usually the first-line treatment for increased blood cholesterol in primary care with a reduction in levels as the expected response. In practice, the diet adopted by the patient may lead to changes in blood lipids characterised by a greater decrease in high-density lipoprotein (HDL) than total cholesterol. The ratio of total cholesterol to HDL cholesterol is an important factor in calculated coronary risk using the Framingham model, from which most risk tables currently in use have been derived. This suggests that either coronary risk may increase after dietary advice or that risk should always be assessed on measurements made before any intervention has taken place. AIM: To report observed changes in blood lipids and calculated coronary risk following dietary advice in primary care. METHOD: Subjects with at least one coronary risk factor and baseline cholesterol above 5.2 mmol/l from an inner-city general practice had cardiovascular risk factors, including fasting lipids, recorded before receiving dietary advice. At follow-up several months later, risk factor measurements were repeated. Ten-year coronary risk was calculated using the Framingham model. Lipid levels and coronary risk at baseline and follow-up were compared. RESULTS: There was a significant decrease in both total cholesterol and HDL cholesterol in both sexes. However, in 56% of subjects, HDL decreased by a greater proportion than the total cholesterol. These subjects showed a highly significant increase in the total cholesterol/HDL cholesterol ratio (median = 0.8 [semi-interquartile range = 1.5], P < 0.001, which was correlated with a change in triglycerides (rs = 0.309, P < 0.001). In those who had an increase in the total cholesterol/HDL cholesterol ratio, calculated coronary risk increased from 5.45% (13.2) at baseline to 7.25% (15.5) (P < 0.001). In all subjects, the change in calculated coronary risk associated with dietary advice ranged from -15% to 15%. CONCLUSIONS: Low fat dietary advice in this primary care setting was frequently associated with undesirable changes in the lipid profile. The majority of subjects showed an increase in the total cholesterol/HDL cholesterol ratio, owing primarily to a decrease in HDL. Consequently, calculated coronary risk increased in over one-half of the subjects. Owing to our incomplete understanding of HDL metabolism, it is unclear whether the fall in HDL is actually detrimental; however, it seems prudent to give dietary advice to patients to avoid excess simple carbohydrate as a fat substitute. This helps avoid a rise in triglycerides, which appears to be associated with an increase in the ratio. These results confirm that coronary risk should always be calculated using measurements made before intervention.

Adult↗
PubMed1999

How the World Trade Organisation is shaping domestic policies in health care.

High up on the agenda of the World Trade Organisation (WTO) is the privatisation of education, health, welfare, social housing and transport. The WTO's aim is to extend the free market in the provision of traditional public services. Governments in Europe and the US link the expansion of trade in public services to economic success, and with the backing of powerful medico-pharmaceutical, insurance, and service corporations, the race is on to capture the share of gross domestic product that governments currently spend on public services. They will open domestic European services and domestic markets to global competition by government procurement agreements, dispute-settlement procedures, and the investment rules of global financial institutions. The UK has already set up the necessary mechanisms: the introduction of private-sector accounting rules to public services; the funding of public-sector investment via private-public partnerships or the private finance initiative; and the change to capitation funding streams, which allows the substitution of private for public funds and services. We explain the implications of these changes for European public-health-care systems and the threat they pose to universal coverage, solidarity through risk-pooling, equity, comprehensive care, and democratic accountability.

Delivery of Health Care↗
PubMed1999

Cell death in age-related macular degeneration.

The cellular and molecular mechanisms underlying the death of photoreceptors and other retinal cells in age-related macular degeneration (AMD) remain poorly understood. Some of the questions for which answers need to be sought, and which are explicitly or implicitly addressed in this article include: (1) how do patterns of cell death in AMD compare, qualitatively and quantitatively, with "normal" cell death in aging retinas, and with cell death in retinitis pigmentosa (RP) and its animal models; (2) is apoptosis involved in AMD; (3) is there any evidence that rods are necessary for cone survival; (4) if the answer is yes, is there evidence that rods produce one or more survival-promoting factor(s) that act directly on cones; (5) are the effects of rods upon cones exclusively mediated by diffusible factors, or do they also involve contact-mediated interactions; (6) is there any evidence that photoreceptors regulate the survival and/or function of RPE and Müller cells, as well as the interactions between these cells and cones; (7) are trophic factors and their receptors in the macula different from those in other parts of the retina; and (8) are toxic mechanisms involved in the onset and progression of cell death in AMD? Clear cut answers to most of these (and related) questions about cell death in AMD are not yet available. The goal of this article is to summarize discussion that should help in the formulation of suitable hypotheses, amenable to experimental analysis. To provide a platform for such discussion, we present an overview of progress made in recent years in the analysis of other retinal degenerations and of neuronal degenerations in other regions of the CNS. We conclude with an overview of concepts and speculation derived from our current research.

Aging↗
PubMed1999

Insulin activates protein kinases C-zeta and C-lambda by an autophosphorylation-dependent mechanism and stimulates their translocation to GLUT4 vesicles and other membrane fractions in rat adipocytes.

In rat adipocytes, insulin provoked rapid increases in (a) endogenous immunoprecipitable combined protein kinase C (PKC)-zeta/lambda activity in plasma membranes and microsomes and (b) immunoreactive PKC-zeta and PKC-lambda in GLUT4 vesicles. Activity and autophosphorylation of immunoprecipitable epitope-tagged PKC-zeta and PKC-lambda were also increased by insulin in situ and phosphatidylinositol 3,4,5-(PO(4))(3) (PIP(3)) in vitro. Because phosphoinositide-dependent kinase-1 (PDK-1) is required for phosphorylation of activation loops of PKC-zeta and protein kinase B, we compared their activation. Both RO 31-8220 and myristoylated PKC-zeta pseudosubstrate blocked insulin-induced activation and autophosphorylation of PKC-zeta/lambda but did not inhibit PDK-1-dependent (a) protein kinase B phosphorylation/activation or (b) threonine 410 phosphorylation in the activation loop of PKC-zeta. Also, insulin in situ and PIP(3) in vitro activated and stimulated autophosphorylation of a PKC-zeta mutant, in which threonine 410 is replaced by glutamate (but not by an inactivating alanine) and cannot be activated by PDK-1. Surprisingly, insulin activated a truncated PKC-zeta that lacks the regulatory (presumably PIP(3)-binding) domain; this may reflect PIP(3) effects on PDK-1 or transphosphorylation by endogenous full-length PKC-zeta. Our findings suggest that insulin activates both PKC-zeta and PKC-lambda in plasma membranes, microsomes, and GLUT4 vesicles by a mechanism requiring increases in PIP(3), PDK-1-dependent phosphorylation of activation loop sites in PKC-zeta and lambda, and subsequent autophosphorylation and/or transphosphorylation.

Adipocytes↗
PubMed1999

High-level expression of rat class I alcohol dehydrogenase is sufficient for ethanol-induced fat accumulation in transduced HeLa cells.

The mechanisms by which ethanol causes fatty liver are complex. Reducing equivalents generated during ethanol oxidation inhibit tricarboxylic acid cycle activity and fatty acid oxidation. In addition, ethanol inhibits lipoprotein export and increases fatty acid uptake and lipid peroxidation. To test the role that alcohol metabolism by alcohol dehydrogenase (ADH) has on cellular lipid metabolism, a cell line expressing rat ADH was generated by transducing HeLa cells with an ADH-expressing retrovirus. The cells expressed high levels of ADH protein and had ADH activity similar to that of liver. Exposure of the cells to 20 mmol/L ethanol for 24 hours led to substantial accumulation of free fatty acids and triacylglycerol in the transduced, but not wild-type, HeLa cells. The rate of synthesis of saponifiable lipid was increased significantly by ethanol under these conditions. Ethanol exposure also promoted triacylglycerol accumulation when the cells were incubated with linoleic acid. This was associated with a decrease in the rate at which the cells oxidized 1-[14-C]-linoleic acid. Fat accumulation was not prevented by including alpha-tocopherol in the medium, arguing against a role for lipid peroxidation. However, the presence of methylene blue completely prevented the fat accumulation. This was associated with a return of the elevated lactate/pyruvate ratio toward normal. These data suggest that generation of reducing equivalents by ADH was sufficient to cause fat accumulation in this cell model.

Acetaldehyde↗
PubMed1999

Present and future management of asthma and COPD: proceedings from WONCA 1998.

On 15 June 1998, a workshop on asthma and chronic obstructive pulmonary disease (COPD) was held at the WONCA conference in Dublin. Based on the current guidelines for diagnosis and treatment of asthma and COPD, new developments and present and future research projects were discussed. Based on these guidelines and the research findings, new developments were positioned. The final conclusion of this workshop was that there is a need to continue exchanging ideas at an international level. So an initiative to start a Scientific Group of Primary Care Research within the European Respiratory Society has been taken.

Asthma↗