PubMed Health⌕ Search

Biomedical subjects

M Price

Publications and source records attributed to M Price.

At least 55 records · Page 3Linked to original sources

Developmental expression of GABA(A) receptor subunit mRNAs in individual hippocampal neurons in vitro and in vivo.

The GABA(A) receptor is a heterooligomeric protein complex composed of multiple receptor subunits. Developmental changes in the pattern of expression of 11 GABA(A) receptor subunits in individual rat embryonic hippocampal neurons on days 1-21 in culture and acutely dissociated hippocampal neurons from postnatal day (PND) 5 rat pups were investigated using the technique of single-cell mRNA amplification. We demonstrate that multiple GABA(A) receptor subunits are expressed within individual hippocampal neurons, with most cells simultaneously expressing alpha1, alpha2, alpha5, beta1, and gamma2 mRNAs. Further, relative expression of several GABA(A) receptor subunit mRNAs changes significantly in embryonic hippocampal neurons during in vitro development, with the relative abundance (compared with beta-actin) of alpha1, alpha5, and gamma2 mRNAs increasing 2.3-, 2.7-, and 3.8-fold, respectively, from days 1 to 14, and beta1 increasing 5-fold from days 1 to 21. In situ hybridization with antisense digoxigenin-labeled alpha1, beta1, and gamma2 RNA probes demonstrates a similar increase in expression of subunit mRNAs as embryonic hippocampal neurons mature in vitro. Relative abundances of alpha1, beta1, and gamma2 subunit mRNAs in acutely dissociated PND 5 hippocampal neurons are also significantly greater than in embryonic day 17 neurons on day 1 in vitro and exceed the peak values seen in cultured neurons on days 14-21, suggesting that GABA(A) receptor subunit mRNA expression within individual hippocampal neurons follows a similar, if somewhat delayed, developmental pattern in vitro compared with in vivo. These findings suggest that embryonic hippocampal neuronal culture provides a useful model in which to study the developmental regulation of GABA(A) receptor expression and that developmental changes in GABA(A) receptor subunit expression may underlie some of the differences in functional properties of GABA(A) receptors in neonatal and mature hippocampal neurons.

Age Factors↗

The management of diabetes at primary level in South Africa: the results of a facility-based assessment.

Diabetes is a widespread condition in South Africa and is often managed at primary level health facilities. This study aimed to assess the quality of diabetes management using a rapid assessment approach, focusing on three indicators as proxy measurements of quality: the regularity of blood glucose level (BGL) measurement; the percentage of patients whose BGLs were within 'acceptable' limits (under 10.0 mmol/l) on at least 75% of visits; the rate at which action was taken in response to high BGLs. Five sites were included in the study, including public and private, doctor- and nurse-based facilities. A total of 128 records were examined. Only 33% of all records were found to be well-managed according to the study criteria. None of the individual facilities were found to have more than 40% of patients achieving BGLs within the study limits. Some obstacles to good glycaemic control were costs to patients, transport problems, a lack of health education and shortcomings in clinical expertise. Policy implications and recommendations are suggested.

Blood Glucose↗

The cost implications of participatory research. Experience of a health services review in a rural region in South Africa

OBJECTIVES: The study objectives were to estimate the total costs incurred by a comprehensive review of primary health care services in a rural region in South Africa, and to determine which of these costs were incurred because of the participatory research techniques employed by the review. DESIGN: The costing study estimated the direct and indirect costs of each component of the review in order to determine total costs. Costs that were linked to participatory research activities were aggregated separately. SETTING: The review that was costed was conducted in an area that included the former 'homeland' KaNgwane and the adjacent areas of 'white' South Africa, in part of what is now known as Mpumalanga Province. SUBJECTS: Not relevant. OUTCOME MEASURES: Direct, indirect, total, research and participation costs were used as outcome measures. RESULTS: Expenditure generated by participatory research techniques was estimated to be almost 14% of the total (direct and indirect) costs. CONCLUSIONS: Despite these costs, participatory research techniques are invaluable in terms of the many benefits they have for a research project. However, because of these costs, it is important that the financing of participatory research should be carefully planned. Projects must budget for the direct costs of participatory techniques, participating organisations and individuals must be committed to bearing the indirect costs of participation, and, increasingly, funders must consider funding these indirect costs. This is important in the South African situation, where public health research relies increasingly on the participation of relevant stakeholders.

Journal Article↗

Evaluation of rural ambulance services.

The evaluation of ambulance services in a rural area of South Africa is described. The approach is affordable and could be applied in other countries. As well as providing valuable information it involves health workers in planning, motivates them to improve service delivery, and lends support to their requests for increased resources.

Ambulances↗

Burden and outcomes of hospitalisation for congestive heart failure.

OBJECTIVE: To describe the hospital burden and health outcomes associated with admission for congestive heart failure (CHF). DESIGN AND SETTING: Descriptive follow-up study in a tertiary-level metropolitan teaching hospital. PATIENTS: Acute adult inpatients with a clinical diagnosis of CHF for more than 24 hours admitted to Westmead Hospital, Sydney, during the four months from September 1993 to January 1994. At baseline, 122 patients were assessed; 88 patients were assessed at four-month follow-up. INTERVENTIONS: Usual clinical care. MAIN OUTCOME MEASURES: Length of stay; hospital bed-days; readmissions; mortality; health related quality of life (SF-36); patient knowledge. RESULTS: The average age of subjects was 73.4 years. Many were using informal domiciliary care before admission. Mean length of stay for the baseline admission was 13.8 days, accounting for 7.6% of hospital separations and 1683 hospital bed-days, or 4.2% of bed-days for all inpatients aged 65 years and over. Fifteen patients were readmitted for CHF during the following four months, with a total of 26 CHF-related admissions. Twenty-one patients (17.2%) died during the course of the study. Quality of life at baseline was poor compared with population normative data, with a slight improvement among survivors at four-month follow-up. Patient knowledge of CHF was poor in a subsample survey (n = 24). CONCLUSIONS: CHF represents a significant burden to patients (through morbidity and mortality), their carers (through provision of daily care), and hospitals (through multiple admissions for acute decompensation). It is difficult to monitor the hospital burden of CHF using routine data sources.

Adult↗

Iontophoresis of poly-L-lysines: the role of molecular weight?

PURPOSE: (1) To determine the extent of iontophoretic transport as a function of molecular weight (MW) of the penetrant; and (2) to visually and quantitatively characterize the iontophoretic transport pathways (follicular (F) versus nonfollicular (NF) of the fluorescently-labeled poly-L-lysines employed. METHODS: A series of fluorescently-labeled poly-L-lysines (FITC-PLLs) [4 KDa, 7 KDa and 26 KDa] were used to study the extent and distribution of iontophoretic skin penetration as a function of MW using laser scanning confocal microscopy (LSCM). RESULTS: It was found that, relative to the passive controls, and under the electrical conditions considered, iontophoresis greatly enhanced the penetration of the 4 KDa analog, slightly elevated the delivery of the 7 KDa FITC-PLL, but had no effect on the transport of the larger 26 KDa FITC-PLL. Quantitative analyses of LSCM images revealed that iontophoresis increased transport via F pathways only slightly more than that through NF pathways for the 4 KDa and 7 KDa FITC-PLL molecules. CONCLUSIONS: It is visually apparent that the iontophoretic transport pathways taken are importantly determined by the physicochemical properties (including size and charge) of the penetrant. The results presented here demonstrate an inverse dependence of iontophoretic delivery upon the MW of the penetrant.

Animals↗

Merkel cell carcinoma arising after therapeutic immunosuppression.

Azathioprine and cyclosporin have been used as immunosuppressants for many years, but long-term use has also been associated with neoplasia. We report three cases of rapidly fatal Merkel cell carcinoma in patients who had been treated with azathioprine for many years either for rheumatoid arthritis or following organ transplantation. Two of these patients had also received cyclosporin. We suggest that Merkel cell carcinoma may be seen more commonly in immunosuppressed patients than in the normal population and that the oncogenic potential of azathioprine and cyclosporin should be borne in mind when prescribing these drugs.

Aged↗

Clients entering drug abuse day treatment: 18-month outcomes.

Clients who entered and remained in day treatment for at least 2 weeks (N = 66) were interviewed at 6, 12, and 18 months after baseline. Follow-up rates for each time point ranged from 58% to 68%, and 30 clients (45%) were interviewed at every time point. Those who were consistently followed (N = 30) did not differ from those who were not consistently followed (N = 36) on demographics or on outcome variables measured at baseline. Comparison of mean outcome scores across time using MANOVA indicated significant changes from baseline to 6 months in the areas of alcohol, drug, legal, and social problem severity, and these changes were maintained up to 18 months postadmission. Outcomes reflecting psychiatric symptoms and employment also changed over time, but exhibited different patterns of change. Results are confounded by treatment received, since many respondents also participated in residential treatment during follow-up. Day treatment can serve clients having a range of substance abuse problems, and can act as a bridge to traditional residential treatment. Randomized clinical trials, where clients receive only one or the other type of treatment, are needed to assess the effectiveness of day treatment alone.

Adult↗

Nurse managed occupational health services without on-site clinical care delivery: a case example.

1. In this program management/community network model of occupational health services, the occupational health nurse is responsible for managing program development and implementation, with vendors providing the clinical services. 2. Occupational health nurses' primary areas of responsibility are occupational health, disability case management, ergonomics, and health promotion. 3. Successful management of program outcomes requires the occupational health nurse to continually assess employee/business needs, maintain communication with employees and management, and partner with the environmental, health, and safety team, other functional work groups, and vendors. 4. Effective management of contracts becomes critical to the process beginning with clear service requirements through the delivery of quality services.

Ambulatory Care Facilities↗

Assessment of five serum marker assays in patients with advanced breast cancer treated with medroxyprogesterone acetate.

This study concerns five different tumour marker assays examined in the context of 94 patients with advanced breast cancer treated in a prospectively randomised trial of different doses of medroxyprogesterone acetate (MPA). MPA was administered at doses of 500 or 1000 mg daily and clinical evaluation of patients was carried out according to UICC criteria. Carcinoembryonic antigen (CEA) was selected as a standard marker, with three assays for MUC1 mucins (epithelial mucin core antigens (EMCA), EMCA2 and BR-MA immunoradiometric assay) differing in antibody specificities for different mucin epitopes. An additional novel assay for soluble cytokeratin was also evaluated as an example of an independent marker with a different nature and biology. Sensitivity of individual assays ranged between 44 (EMCA2) and 69% (cytokeratin) and the use of two assays in combination led to sensitivities as high as 84% (cytokeratin+BR-MA). The proportion of patients found to be assessable by each assay ranged between 51 (EMCA2) and 76% (cytokeratin). Of those patients whose marker changes were assessable, those receiving the higher dose of MPA displayed significant falls in marker levels after 12 weeks of treatment. This effect was not observed in patients receiving 500 mg. The change in cytokeratin levels in patients undergoing high dose MPA therapy proved to be most marked. Using the cytokeratin assay, 91% (of 23 patients) of patients with progressive disease showed at least a 25% rise in serum marker levels. Of these, 66% showed increases before disease progression was detected clinically with a mean lead time of 14 weeks. There was very little difference between the responses of the five tumour marker assays in patients with stable or responding disease, the proportion of these patients with stable or falling tumour marker levels ranging between 58% (CEA) and 77% (EMCA). We conclude that the cytokeratin assay has an application in monitoring response to therapy and predicting tumour progression in advanced breast cancer patients with assessable tumour marker profiles, especially if used in combination with a MUC1 mucin assay.

Adult↗

Indicators and research methods for rapid assessment of a tuberculosis control programme: case study of a rural area in South Africa.

SETTING: An evaluation of the Tuberculosis Control Programme (TBCP) of KaNgwane, a rural, previously designated 'homeland' of South Africa, was performed in 1990. OBJECTIVE: The evaluation is presented as a case study to illustrate a proposed methodology for rapid, comprehensive, management oriented TBCP research. DESIGN: The components of the TBCP were categorised into direct TBCP activities, management processes and integration of the TBCP into Primary Health Care (PHC). The methods used to evaluate indicators for each of these components included: policy analysis, interviews with staff and patients, observation of in-patient and ambulatory patient care, record reviews and a household survey. RESULTS: The regional scope of the study yielded a wealth of useful information at a managerial level. Detailed, quantitative information was obtained, allowing for the identification of weaknesses in the TBCP and the targeting of appropriate action. Particularly problematic aspects were: the health information collection, case-finding and case-holding, health education and coordination and supervision. Comparative analyses between different health wards helped identify particular areas of weakness. Both illustrative results and methodological limitations are presented. The methodology used is related to previous South African TB health service research and to the emerging field of rapid assessment methods. CONCLUSIONS: A rapid but comprehensive review of a TBCP can be done if indicators and research methods are carefully selected and record systems are functional. If record systems are not functional, the non-record review methods still offer substantial information on many indicators and one or two quantitative indicators (e.g. case holding) could be selectively measured through reviewing a sample of records.

Adult↗

Selection of peptide ligands for the antimucin core antibody C595 using phage display technology: definition of candidate epitopes for a cancer vaccine.

Aims-To further define the specificity of the antimucin core antibody C595 by fitting it with a family of hexapeptide ligands by immunoselection of filamentous bacteriophage from a gene III display library of approximately 6.4 x 10(7) random hexapeptides.Methods-Three rounds of immuno-selection were used to enrich for C595 binding phage. DNA sequencing revealed the hexapeptides expressed. Bacteriophage and corresponding synthetic hexapeptides were used in ELISA assay to determine binding affinities.Results-Twenty nine clones from this selected population were analysed. Seven contained the natural epitope RPAP, encoded by two different DNA sequences; 17/29 contained the motif RLPP. In all, 28/29 clones contained the motif RXXP and one clone (RVRPAP) contained the motif RXXP in two peptidic registers; 24/28 clones (6/8 DNA sequences) contained a hydrophobic residue (V or I) at position 1 relative to the RXXP motif. In addition the proximity of RXXP to glycine (position 5) suggests that this contributes in the natural epitope to antibody/antigen binding, which was not detected by chemical synthetic methods. One clone, KSKAGV, bears no obvious relationship to the natural epitope and therefore qualifies as a weakly binding mimotope.Conclusions-This approach has rapidly defined the specificity of this antibody in unprecedented detail, and provides a more comprehensive molecular basis for exploring the immune recognition of the MUC1 mucin by the C595 antibody. Importantly, the novel but related epitopes seen provide peptide specificities and a strategy which may prove useful in generating cancer vaccine candidates.

Journal Article↗