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Biomedical subjects

P R Edwards

Publications and source records attributed to P R Edwards.

At least 37 records · Page 2Linked to original sources
PubMed1998

Second-order kinetic analysis of IAsys biosensor data: its use and applicability.

The kinetic analysis of IAsys biosensor association data usually relies upon the assumption of constant ligate concentration. In certain circumstances this assumption may no longer be valid. In a similar vein, the analysis of the dissociation phase assumes the concentration of ligate to be negligible in the liquid phase-an assumption that may not be sustainable for high-affinity interactions. In this paper we derive analytical solutions of the second-order differential kinetic equations for the association and dissociation phases, together with a binding isotherm that also allows for changes in concentration of both the ligand and the ligate. Using these equations it is possible to determine the conditions under which the pseudo-first-order assumption ceases to be valid. It is found that the effect of ligate depletion on the association rate constant becomes significant only when binding low ligate concentrations to ligand on surfaces with high binding capacities or high affinities. Similarly, the rebinding in the dissociation phase is dependent upon the affinity and the ligand capacity together with the starting dissociation response compared to the capacity. Finally, depletion also affects the form of the binding isotherm, particularly in situations involving high matrix capacities for ligate and high-affinity interactions.

Biosensing Techniques↗
PubMed1998

New approaches for the analysis of molecular recognition using the IAsys evanescent wave biosensor.

Trends in the analysis of molecular recognition using the IAsys evanescent wave biosensor are outlined. Diversification of sensor surface chemistry, an open cuvette format and the advent of robotics controlled by intelligent software are widening the range and throughput of applications. Analyses of binding and dissociation are now carried out across a wide spectrum of biomolecules, including protein, nucleic acid, carbohydrate and lipid. Determinations are obtained from a range of experimental formats. These include qualitative 'yes/no' screening assays, through semi quantitative ranking of kinetic association, dissociation and equilibrium constants for a family of binding partners, to deriving constants comparable with those which would be obtained in free solution. A dependence of the initial rate of biomolecular association on concentration allows analyte concentration to be measured--an increasingly common application class. This is often employed in situations where a rapid determination is required The ability to recover bound analyte from the sensor surface in sufficient amounts for subsequent characterization is opening up new routes to the parallel analysis of structure and function.

Animals↗
PubMed1998

Hypertension care at a Cape Town community health centre.

OBJECTIVES: To describe the demographic profile of hypertensive patients and the quality of care for hypertension at a Cape Town community health centre (CHC). DESIGN: Prospective, descriptive study. SETTING AND SUBJECTS: Medium-sized CHC, attended by 1,098 hypertensive patients during a 1-year period from 1 January 1992. OUTCOME MEASURES: Default rate--proportion of due visits not attended. Loss to follow-up--proportion of patients persistently defaulting or not responding to recall. Frequency of blood pressure measurement--per 12 due visits. Compliance--proportion of patients collecting > or = 75% of antihypertensive drugs. Blood pressure control--mean blood pressure of aggregated readings; and proportion controlled (< 160/95 mmHg) on the basis of all blood pressure readings and mean blood pressures of individual patients with two or more readings during the study period. RESULTS: More than half (51.6%) of the hypertensive patients were aged > or = 65 years; 81.7% were female. The default rate was between 11.9% and 19.4%. Compliance was high (76.9%). Loss to follow-up was 8.1%. Blood pressure was recorded a mean of 4.0 times per 12 due visits. There were no significant gender differences with regard to these measures. Mean blood pressure was 158.3/89.6 mmHg. Over half (56.7%) of all individual readings over the year were uncontrolled and 51.4% of patients were found to be uncontrolled when categorised by their mean blood pressure. Control was significantly poorer among women > or = 65 years. CONCLUSION: We found better compliance, more frequent blood pressure measurement, and lower defaulting and loss to follow-up compared with previous South African studies in similar settings. Despite this, blood pressure control was mediocre. Possible explanations for this are discussed. The low proportion of male hypertensives attending the CHC suggests that the accessibility or acceptability of care is poor for this group. The study illustrates the potential for research in this setting and for the use of computers to monitor the quality of primary care.

Adult↗
PubMed1998

Improving cost-effectiveness of hypertension management at a community health centre.

OBJECTIVES: To describe the pattern of prescribing for hypertension at a community health centre (CHC) and to evaluate the impact of introducing treatment guidelines and restricting availability of less cost-effective antihypertensive drugs on prescribing patterns, costs of drug treatment and blood pressure (BP) control. DESIGN: Before/after intervention study. SETTING: Medium-sized CHC in the Cape Flats area of Cape Town. SUBJECTS: 1,084 hypertensive patients attending the CHC, who had at least two prescriptions for antihypertensive drugs during a 1-year period starting on 1 January 1992. INTERVENTIONS: 1. Implementation of stepped-care guidelines for hypertension, specifying treatment with more cost-effective drugs and minimising drug treatment. 2. Reducing availability for routine prescribing by CHC doctors of 10 less cost-effective antihypertensive drugs or drug combinations. OUTCOME MEASURES: 1. Mean number of drugs prescribed per patient. 2. Proportion of prescriptions for: each major class of antihypertensive drug; restricted availability and freely prescribable drugs; and more and less cost-effective drugs. 3. Mean monthly cost of drugs prescribed per patient. 4. Mean blood pressure and proportion of BP readings controlled (< 160/95 mmHg) or uncontrolled (> or = 160/95 mmHg). RESULTS: A mean of 1.7 active drugs was prescribed per patient per visit. The most frequently prescribed drugs were thiazide-like diuretics (44.8%), centrally acting agents (28.4%) and b-blockers (13.2%). Mean monthly drug costs per patient decreased significantly by R1.99 (24.2%) from R8.24 to R6.25 between the first and last prescription for each patient (exclusive of any reduction due to withdrawal of treatment). This was attributable to reduced prescribing of more expensive drugs withdrawn from routine use and a 51.1% increase in prescribing of the most cost-effective drugs. The overall annual cost-saving of the changes in prescribing for this CHC are estimated at R75 150. Blood pressure control did not change significantly. CONCLUSION: The pattern of changes in prescribing and drug costs was consistent with a causal effect of the interventions. The study demonstrates the potential for improving cost-effectiveness of hypertension care in primary care in South Africa and the potential for research in this setting.

Antihypertensive Agents↗
PubMed1997

Determination of association rate constants by an optical biosensor using initial rate analysis.

We show that initial rate analysis can be successfully applied to analyze experimental binding data generated by an optical biosensor. The initial rates of binding obtained from linear regression are concentration dependent, and plots of initial rate against ligate concentration yield a straight line that passes through the origin. The slope of this graph is the product of the association constant times the maximal binding capacity of the immobilized ligand. This latter parameter is easily obtained from a single binding curve at high ligate concentration, allowing rapid determination of the association rate constant. The association rate constant obtained in this manner is found to be in good agreement with that obtained by the more customary method of nonlinear regression analysis of the entire binding profile. Initial rate analysis is more simple than fitting the full association profile and needs less data collection time. It also requires fewer assumptions about the functional form of the association profile. This can be advantageous when fitting biosensor-derived data, which often show complex association kinetics. Furthermore, it avoids the potential complication of second-order kinetics which may be found at low ligate concentrations with high-affinity interactions.

Biosensing Techniques↗
PubMed1996

Diminished thyroxine-binding globulin in pubertal diabetic children.

OBJECTIVE: To determine the effect of diabetes on thyroid hormone and thyroxine-binding globulin (TBG) concentrations during puberty. RESEARCH DESIGN AND METHODS: Total thyroxine (TT4), free thyroxine (FT4), and TBG levels of 171 thyroid microsomal antibody-negative subjects with normal thyroid-stimulating hormone (TSH) levels were measured and compared with those of nondiabetic adolescents. A random subset of 68 diabetic patients (40 boys and 28 girls) and 51 control subjects (24 boys and 27 girls) were analyzed for puberty-related changes. RESULTS: Most TT4 levels of diabetic subjects (80% of girls and 63% of boys) were below the 50th percentile for the normal range. TT4 increased with age in girls (r = 0.25, P < 0.04) but not in boys. FT4 was within normal limits in both sexes. TBG measurements were below the 50th percentile and 20% were below the 95% CI for both sexes; TT4 correlated with TBG in boys (r = 0.54, P < 0.001) and in girls (r = 0.58, P < 0.001). Duration of diabetes had no effect, whereas TT4 and FT4 levels were higher in girls with the lowest HbA1 levels (r = -0.29, P < 0.01 and r = -0.45, P < 0.01). Levels of TBG were reduced for all male pubertal stages (P < 0.01) and for early and late female pubertal stages (P < 0.01). There was no direct relationship between glucose control or the duration of diabetes and levels of TBG. CONCLUSIONS: Because TT4 levels are low and correlate with the low levels of TBG, it is important to measure free thyroid hormone and TSH levels in diabetic adolescents to establish euthyroidism.

Adolescent↗
PubMed1995

Kinetics of protein-protein interactions at the surface of an optical biosensor.

Methods based on the use of optical biosensors have recently become available to provide a convenient means of determining the rate and equilibrium constants for bimolecular interactions between immobilized ligands and soluble ligate molecules. However, the association data that these methods provide are not always accurately described by the expected pseudo-first-order reaction mechanism, particularly when the ligand is immobilized on a dextran matrix. We show that a better description of the association data, especially at higher ligate concentrations, is achieved with a double exponential function, indicating that at least two rate-limiting processes are involved. Various models are considered in order to explain these observations: the presence of two (or more) distinct populations of immobilized ligand; a change, possibly conformational, in the immobilized ligand before or after ligate binding; or the hindrance of ligate binding to immobilized ligand. We suggest that steric hindrance caused by ligate binding to the dextran-coated sensor surface seems the most likely explanation for the observed biphasic association kinetics and that the faster initial phase should be used in oder to determine association constants that can be compared to those in solution.

Antigen-Antibody Reactions↗
PubMed1993

Methods and prognosis of non-invasive ventilation in neuromuscular disease.

Ventilatory failure is the commonest terminal event in many neuromuscular disorders. Increasingly, non-invasive methods of ventilation, employing both negative and positive pressure techniques, have been used, with the aim of prolonging life and reducing morbidity. The use of non-invasive ventilation is reviewed in three main groups of neurological diseases, and the degree of success assessed. It is concluded that non-invasive methods can be effective in reducing morbidity in selected patients, especially those with more slowly progressive disorders. A reduction in mortality is suggested by comparison with historical controls. The institution of ventilatory support is a major undertaking for the medical team, patient and family, and should only be initiated after a full and frank discussion of the overall prognosis, in terms of both mortality and quality of life. The patient and principal caregivers can then make an informed decision as to the desirability of home ventilation.

Home Care Services↗
PubMed1992

In situ versus reversed femoropopliteal vein grafts: long-term follow-up of a prospective, randomized trial.

In a prospective, randomized trial, 226 patients undergoing femoropopliteal bypass for lower limb ischaemia were allocated to reversed (123 patients) or in situ (103) techniques. The groups were comparable for age, sex, incidence of diabetes, and indications for surgery. Eleven veins were rejected at operation, nine in the reversed group and two in the in situ group, leaving 114 reversed and 101 in situ grafts for study. Cumulative patency rates were not significantly different between reversed and in situ grafts at any time up to 6 years after operation, with primary patency rates at 1, 3 and 5 years of 84.8, 69.5 and 62.4 per cent for reversed grafts and 79.9, 71.2 and 63.5 per cent for in situ grafts. Small vein grafts (< 4 mm in diameter) were associated with patency rates at 1, 3 and 5 years of 63.5, 46.7 and 36.0 per cent compared with 93.9, 82.5 and 75.9 per cent for vein grafts > or = 4 mm in diameter (P < 0.002, log rank test). The patency rates of small veins employed in situ and reversed were similar. The in situ technique confers neither short- nor long-term advantage over reversed vein grafting for femoropopliteal bypass.

Aged↗
PubMed1992

The aetiology of vein graft strictures: a prospective marker study.

In a prospective series of 74 femoro-popliteal vein grafts (34 in situ and 40 reversed), 22 strictures were identified by duplex scanning in 18 grafts (24.3%). Thirteen strictures were identified in 10 of 40 reversed grafts and 9 strictures were identified in 8 of 34 in situ grafts. Grafts were marked at operation using surgical clips at sites of all valves, tributaries, clamps and venotomies, since these have all been suggested as potential sources of graft strictures. These were prospectively studied as part of a detailed graft surveillance programme by intravenous digital subtraction angiography and duplex scanning. A total of 377 valves, 681 tributaries, 15 clamps and 2 venotomies were identified. Twenty-two strictures were detected in 18 grafts, an incidence of 24.3%, but only one lesions coincided with a specific marked area (a valve site). Duplex examination in 34 in situ grafts identified 10 residual valve cusps in seven grafts. In none of these was there any evidence of turbulence or flow disturbance, and none progressed to form a stricture. It is concluded that there is no correlation between valve sites, tributaries, clamp sites or residual valve cusps and the development of vein graft strictures.

Angiography, Digital Subtraction↗
PubMed1991

The use of an adjuvant arterio-venous shunt in prosthetic femoro-crural bypass.

In limb threatening ischaemia the use of a long prosthetic graft to the distal calf vessels may be the only alternative to a primary amputation. Patency rates in these situations are relatively poor and the use of an adjuvant arteriovenous fistula (AVF) at the distal anastomosis to increase the velocity of flow above the thrombotic threshold seems logical. We present follow-up of up to 8 years in a series of 80 consecutive reconstructions to the distal crural vessels using human umbilical vein with an adjuvant AVF. The mean age of the patients was 68.3 years and 12 (15%) were diabetic. The indication for surgery was limb threatening ischaemia in all cases; 41 (51.2%) for established necrosis and the remaining 39 (48.8%) for severe ischaemic rest pain. The mean ankle:brachial index was 0.23. The common ostium (CO) configuration of AVF was used in 50 cases (62.5%) and pre-anastomotic in 30 cases (37.5%). The volume blood flow in 49 cases, measured peroperatively using an electromagnetic flowmeter, was 116 ml/min (+/- 62.5) with the shunt closed and 283 ml/min (+/- 132.2) with the shunt open (p less than 0.01, Student's t-test). Cumulative patencies of all grafts were 39% at 2 years and 29% at 4 years. The age of the patient and the type of AVF, common ostium or pre-anastomotic, had no significant effect on patency rates, but grafts under 70 cm in length had a cumulative patency at 2 years of 42.5% compared to 13.5% for those over 70 cm in length (p less than 0.01). Cumulative patencies were derived by life table analysis and compared using the log rank test. The size of the recipient vessels at the distal anastomosis is thought to be crucial to the outcome of these operations. An increase in velocity of flow produced by an AVF, increases the wall shear stresses at this site and may lead to an increased tendency for intimal hyperplasia. It may be possible to mitigate these effects by the use of additional surgical or pharmacological techniques and further studies are required.

Arteriovenous Shunt, Surgical↗
PubMed1990

Technical advantages of a ringed intra-luminal graft in the management of difficult aortic aneurysms.

The ringed intra-luminal graft has been designed for aortic repair with non-sutured anastomosis. The graft and technique of insertion are described. It is proposed that this type of prosthesis might have advantages over conventionally sutured grafts for the surgical management of thoraco-abdominal, suprarenal and dissecting aneurysms, and occasionally for infrarenal aneurysms when the neck is ectatic or excessively friable. This proposition is supported by reference to five patients with complex aneurysms which were repaired successfully with non-sutured grafts. The importance of appropriate patient selection and attention to technical detail is stressed.

Aged↗