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Biomedical subjects

L Walters

Publications and source records attributed to L Walters.

At least 19 recordsLinked to original sources
PubMed1997

Alterations in carbohydrate metabolism in dogs with nonhematopoietic malignancies.

OBJECTIVE: To determine whether alterations in carbohydrate metabolism exist in dogs with nonhematopoietic malignancies but without evidence of weight loss or cachexia. ANIMALS: 90 dogs with nonhematopoietic malignancies and 18 control dogs. PROCEDURE: An intravenous glucose tolerance test was done in 90 dogs with previously untreated nonhematopoietic malignancies and in 18 clinically normal dogs. These dogs also had no evidence of unrelated diseases that would affect glucose metabolism. None of the dogs had evidence of cachexia. Samples were assayed for glucose, lactate, and insulin concentrations. This procedure was repeated for 45 of the tumor-bearing dogs from which all gross evidence of tumor was completely excised and evidence of diseases that would alter carbohydrate metabolism did not exist. RESULTS: The mean of all time points during the intravenous glucose tolerance test (ie, 0, 5, 15, 30, 45, and 60 minutes) for lactate (12.9 +/- 6.7 mg/dl) and insulin (69.1 +/- 44.9 microU/ml) concentrations in untreated dogs with nonhematopoietic malignancies were significantly higher than values for controls (lactate, 9.7 +/- 4.3 mg/dl; and insulin, 31.7 +/- 11.5 microU/ml). This increase in lactate and insulin values did not return to normal when the dogs were rendered free of all observable evidence of cancer after surgery. CONCLUSIONS: Carbohydrate metabolism is altered in dogs with a variety of nonhematopoietic malignancies and these abnormalities do not abate when dogs are rendered free of gross evidence of malignant disease after surgery. CLINICAL RELEVANCE: Alterations in carbohydrate metabolism may result in decreased quality of life and may be associated with the paraneoplastic syndrome, cancer cachexia.

Animals↗
PubMed1996

Analysis of paediatric prescribing profiles in two health-funding systems.

OBJECTIVE: To investigate the adequacy of two large South African medical administrative databases in providing prescribing profiles for paediatricians and general practitioners (GPs) respectively. DESIGN: Statistical analysis of data captured during 1994. Data were analysed retrospectively with frequency analysis and non-parametric tests. SETTING: Two industry databases, one covering a prepaid health maintenance organisation (HMO), the other providing a chronic medication programme for medical schemes and their members. MAIN OUTCOME MEASURES: Comparison of prescribing profiles of specialists and GPs. MAIN RESULTS: Data from the HMO revealed that referrals to paediatricians were mainly for gastro-intestinal and respiratory problems. Paediatricians' prescriptions for treatment of gastro-oesophageal reflux and/or abdominal pain represented 15.5% of all items prescribed and accounted for 40.7% of total paediatric medicine costs. GPs used formulary items more frequently, and cost per prescription was two-thirds that of specialists. Data from the chronic medication programme were used to compare treatment of asthma by the two provider groups. There were significant differences in the prescribing profiles of the two groups, with specialists using more in the way of "third-line agents' and newer, expensive products. Significant numbers of prescriptions did not conform to national guidelines for treatment of asthma. CONCLUSIONS: Industry databases provide a viable and valuable source of information; however, some problems were experienced in extracting the required data. Prescribing profiles revealed certain practices that require review, in particular the relatively low use of generic products, the early resorting to drug therapy for gastrooesophageal reflux, and non-conformity with national guidelines for management of childhood asthma.

Asthma↗
PubMed1996

Formulary and funding implications of the gap between the national Essential Drugs List and current prescribing in a large health maintenance organisation.

BACKGROUND: The Department of Health has prepared an Essential Drugs List (EDL) for public sector implementation in 1996 and future extension to the private sector. Stakeholders have been consulted to ensure that the EDL achieves its objectives of safety, efficacy and quality at the lowest possible cost, while providing coverage for 90-95% of the common and important conditions in the country. This study was undertaken to gain insight into the current use of EDL products by 200 general practitioners (GPs) servicing a large health maintenance organisation (HMO). METHODS: Approximately 120,000 prescriptions were reviewed and the use of specified EDL medicines, other forms of EDL medicines and non-EDL medicines was analysed for several pharmacological groups. These included antibiotics and medicines for the cardiovascular, musculoskeletal, central nervous, respiratory and gastro-intestinal systems. To gauge potential savings to the private sector through the purchase of EDL products at state tender prices, current prices of a random sample of EDL products were compared. RESULTS: In the areas reviewed, only 22.4% of current GP prescriptions included EDL items; a further 19.6% included 'other forms of EDL' items. Simply obtaining those EDL products that are currently prescribed at state tender prices would reduce costs by almost 20%, while extending the use of EDL products might save in excess of 70% on private sector GP prescriptions. CONCLUSIONS: Assuming that all prescriptions were clinically indicated, the 'gap' between the EDL and medicines prescribed indicates that debate will be.

Drug Prescriptions↗
PubMed1994

Pharmaco-economic assessment of the HMG-CoA reductase inhibitors.

OBJECTIVE: To perform a comparative pharmaco-economic assessment of two HMG-CoA reductase inhibitors. DESIGN: A cost-effectiveness analysis was employed using comparative efficacy data from selected clinical trials. A comprehensive international literature search formed the basis for this selection. Criteria for inclusion of clinical trial results in the analysis were set a priori. Acquisition costs used were the recommended reimbursement prices as at September 1994. MAIN OUTCOME MEASURES: Two outcome measures are reported: (i) the comparative cost-effectiveness in lowering blood lipid concentrations; and (ii) the comparative cost-effectiveness of the medicines when used to achieve a predetermined therapeutic goal. RESULTS: The average cost per 1% decrease in total cholesterol is 21.9% higher on 10 mg pravastatin daily than on 10 mg simvastatin daily. Similarly the average cost per 1% decrease in low-density lipoprotein (LDL) cholesterol is 23.1% higher on 10 mg pravastatin than on 10 mg simvastatin daily. This difference is consistent throughout the dosage range. The use of incremental doses of simvastatin monotherapy in order to reach a predetermined therapeutic goal (LDL < or = 4.14 mmol/l) is more cost-effective than an equivalent pravastatin dosage regimen. Total treatment costs for simvastatin-treated patients are 3.5% less than for pravastatin-treated patients. More patients on simvastatin are successfully treated; the difference in overall treatment costs per successfully treated patient is 27.9% in favour of simvastatin. Sensitivity analysis shows these results to be stable under extreme scenarios. CONCLUSIONS: This analysis employed objective comparative efficacy data obtained from peer-reviewed sources to compare the economic and clinical outcomes of simvastatin and pravastatin in the treatment of hypercholesterolaemia. The acquisition cost of simvastatin is 10.3-22.8% higher than an equivalent milligram dose of pravastatin, depending on the dosage used. However, because of the greater milligram potency of simvastatin, it is a more cost-effective alternative. Simvastatin therefore provides better value for money than pravastatin in lowering lipid levels in clinical practice.

Anticholesteremic Agents↗
PubMed1994

Aspects of roaccutane prescription in South Africa.

A nationwide postmarketing surveillance study on the use and outcomes of use of isotretinoin has been conducted in South Africa. A representative sample of prescribers of the drug was identified from drug utilisation data and the overall doctor response rate was 90.1%. A total of 766 patients was enrolled in the study, of which 728 were analysable for safety and efficacy. More than half the patients prescribed isotretinoin were women, of whom only 48.25% were practising some form of contraception. The mean overall dosage prescribed was 0.64 mg/kg/day and the mean overall duration of therapy prescribed was 15.5 weeks. The mean dose and duration of therapy prescribed by dermatologists was significantly higher than that prescribed by general practitioners. Potentially dangerous drug interactions involving the concomitant use of isotretinoin with tetracyclines, vitamin A and oral contraceptives together with antibiotics were noted. Mucocutaneous drying effects were the most common adverse events and the incidence of these effects decreased with continuation of therapy. The known effectiveness of the drug was confirmed by the results of the study.

Acne Vulgaris↗
PubMed1993

Germ-line gene modification and disease prevention: some medical and ethical perspectives.

There has been considerable debate about the ethics of human germ-line gene modification. As a result of recent advances in the micromanipulation of embryos and the laboratory development of transgenic mice, a lively discussion has begun concerning both the technical feasibility and the ethical acceptability of human germ-line modification for the prevention of serious disease. This article summarizes some of the recent research on germ-line gene modification in animal models. Certain monogenic deficiency diseases that ultimately might be candidates for correction by germ-line intervention are identified. Several of the most frequently considered ethical issues relative to human germ-line gene modification are considered in the context of professional ethics, parental responsibility, and public policy. Finally, it is suggested that there is merit in continuing the discussion about human germ-line intervention, so that this technique can be carefully compared with alternative strategies for preventing genetic disease.

Animal Experimentation↗
PubMed1993

Data monitoring committees: the moral case for maximum feasible independence.

Since data monitoring committees (DMCs) began to be established in the 1970s, they have reviewed the clinical outcome data emerging from ongoing trials. The thesis of this essay is that DMCs most effectively promote the validity and credibility of randomized clinical trials when they perform this function with the maximum feasible independence. The essay argues that four types of individuals and groups should be excluded from the interim monitoring of outcome data: (1) investigators entering patients into a trial; (2) principal investigators or study chairs; (3) representatives of commercial firms connected with a trial; and (4) representatives of regulatory agencies. The role of statistical groups and officials of government funding agencies in the review of outcome data is also discussed.

Clinical Trials as Topic↗
PubMed1992

Fibulin is localized at sites of epithelial-mesenchymal transitions in the early avian embryo.

Fibulin is a 100-kDa calcium-binding, extracellular matrix (ECM), and plasma glycoprotein (Argraves et al., Cell 58, pp. 623-629, 1989; Argraves et al., J. Cell Biol. 111, 3155-3164). Immunoprecipitation analysis showed that antibodies against human fibulin react with an avian isoform (M(r) 100,000). The spatial and temporal distribution of fibulin was examined in the early avian embryo using immunofluorescence microscopy. In stage 15-22 quail embryos fibulin is a constituent of most basement membranes. Areas undergoing epithelial-mesenchymal transitions such as the endocardial cushions, developing myotomes, and neural crest display especially prominent immunostaining. In the early heart fibulin expression was most pronounced in the cardiac jelly at sites where endocardial cushion cells begin the migrations that lead to the formation of valvular and septal primordia. Laser scanning confocal microscopy showed extensive extracellular accumulations of fibulin on the surface of endocardial mesenchyme cells that were motile at the time of fixation (stage 19). These data suggest that enhanced deposition of fibulin at sites of epithelial-mesenchymal transitions may influence cell behavior.

Animals↗
PubMed1992

Zocor, the postmarketing experience.

The aim of this study was to develop and test a descriptive, intensive drug surveillance methodology in order to examine the effectiveness and safety of new drugs in the immediate postmarketing period. The HMG-CoA reductase inhibitor, simvastatin (Zocor), was chosen as the test drug. Data were collected from 100 randomly chosen cardiologists, specialist physicians and general practitioners practising in the six main centres of South Africa. A 66% doctor response rate was achieved and 438 patients were enrolled in the study. The overall effectiveness expressed as a percentage decrease (from baseline) in total cholesterol levels was 20.5% for the 251 patients who started on a 10 mg daily dose of the drug and 27.6% for the 42 patients who started on 10 mg but changed to 20 mg/d. The safety profile of simvastatin was comparable with the premarketing clinical trial data, and patient non-compliance appeared to be dose-related. The methodology employed was found to be suitable for the collection of safety and effectiveness data in the postmarketing period and simvastatin was shown to be effective with few adverse events reported.

Adult↗
PubMed1991

Human gene therapy: ethics and public policy.

The first three human gene transfer/therapy clinical protocols are now underway after having been subjected to an extensive review process by the Recombinant DNA Advisory Committee (RAC) and its Human Gene Therapy Subcommittee. The "Points to Consider" document developed by the RAC established the framework for evaluating genetic intervention protocols. This review process is taking place in a broader social context. Public attitude surveys in this country have indicated a general lack of knowledge in the area of genetic engineering but an acceptance of somatic-cell gene therapy as treatment for disease. Internationally, numerous policy statements on human genetic intervention have been published, all of which support the moral legitimacy of somatic-cell gene therapy for the cure of disease. The debate over the ethical issues related to somatic-cell gene therapy has evolved over a ten-year-period. The time has now come to begin a formal public process for the ethical assessment of germ-line genetic intervention.

Advisory Committees↗