Third generation oral contraceptives and the risk of venous thromboembolism: management of the uncertainty.
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Biomedical subjects
Publications and source records attributed to T J Maling.
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We have defined the effect and acceptability of a locally developed general practice programme for the modification of prescribing. This voluntary programme consisted of prescription analysis and feedback, followed by visits from a pharmacist, a therapeutic bulletin on benzodiazepine prescribing, and use of a locally compiled preferred medicines list. A 3-month prescription sample from 26 general practitioners (GPs) fulfilling a stable practice definition was used to compare prescribing pre-project and mid-project. For 20 out of 26 GPs, prescribing of medicines on the preferred medicines list had increased significantly 8 months after the intervention programme had been introduced. Total prescription numbers and total medicines expenditure decreased by 8.3 and 4.9%, respectively, from 1988 to 1989. The decrease in benzodiazepine prescribing was marked (mean -22.2%, range -50.3 to +4%). The cooperative multimodel approach was highly successful in modifying prescribing in general practice.
1. Haematologic parameters were measured in untreated borderline hypertensive (BHT) men, and weight and age matched with normotensive men to determine whether previously described increased haematocrit (Hct) in established hypertension is evident in borderline hypertension. 2. Haematocrit was significantly increased in BHT men (mean 0.46, s.d. 0.032) compared with normotensive men (mean 0.43, s.d. 0.014) and correlated significantly with mean arterial pressure in this group (r = 0.67, P = 0.036) independent of weight. 3. The correlation of blood pressure with Hct in BHT men supports the concept that increased Hct may contribute to increased blood viscosity and thus to raised arterial pressure.
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1. Erythrocytic sodium-lithium (Na-Li) countertransport (CT) was measured in normotensive Maori and non-Maori by in vitro and in vivo methods to determine its relationship to erythrocytic hypernatraemia previously identified in Maori. 2. In vivo and in vitro CT rates were correlated within race and were similar between races. Countertransport rate was correlated with erythrocytic sodium concentration only in Maori. 3. The findings suggest the possibility of a genetically determined alteration in CT stoichiometry in Maori.
OBJECTIVE: To assess the efficacy of simvastatin in a large patient cohort. DESIGN: In an open multicentre study, after a four week placebo phase, patients were treated with simvastatin for 24 weeks; a subgroup continued therapy for a further 24 weeks. Efficacy of simvastatin (a) with prolonged use over three years, and (b) in combination with bezafibrate was assessed in an open single site study. SETTING: Lipid or cardiology specialist hospital outpatient clinics. PATIENTS: For the open multicentre study, 228 patients with primary hypercholesterolaemia (total cholesterol level greater than 6.5 mmol/L) were recruited, of whom 224 met entry criteria and completed the study. Forty-seven of these patients continued therapy for one year. In the open single site study, 22 patients (with low density lipoprotein [LDL] cholesterol levels greater than 4.3 mmol/L) participated in studies of long term use (n = 9) or of combined therapy (n = 13). INTERVENTION: Therapy in the open multicentre study began with 10 mg of simvastatin per day, doubling to 20 mg after six weeks and then 40 mg after 12 weeks of therapy if total cholesterol levels persisted above 5.2 mmol/L. In the study of long term use, simvastatin (40 mg daily) was taken continuously over three years. In the study of combination therapy, bezafibrate (600 mg daily) was taken in addition to simvastatin (40 mg daily) for 10 months. MAIN OUTCOME MEASURES: Plasma lipid and lipoprotein concentrations. RESULTS: In the multicentre study, total plasma cholesterol levels were reduced by 32.8% from 9.11 +/- 1.84 (in mmol/L, mean +/- SD) to 6.12 +/- 1.25 (P less than 0.001), and LDL cholesterol levels by 41.4% from 6.90 +/- 1.92 to 4.04 +/- 0.31 (P less than 0.001). The effect of therapy was sustained in those patients continuing therapy to 48 weeks. The study of long term use found no significant attenuation of effect over three years of monotherapy. Combined simvastatin/bezafibrate therapy reduced the LDL cholesterol concentration by a further 19.9% (P less than 0.001) from levels achieved on simvastatin alone. CONCLUSIONS: Simvastatin is an effective, well tolerated lipid lowering drug, without significant attenuation of effect with prolonged use. Simvastatin plus bezafibrate appears to be a potentially useful drug combination.
Cardiac autonomic function was studied in 23 alcohol dependent men by standard tests of autonomic function and measurement of 24 hour heart rate variability. In all there was peripheral or central nervous system damage or both. Standard tests of autonomic function showed vagal neuropathy in seven. The remainder had normal autonomic function tests. Twenty four hour heart rate variability was measured as the standard deviation of the successive differences between RR intervals from an ambulatory electrocardiogram recording. Twenty four hour heart rate variability was significantly lower in both alcohol dependent groups than in controls, but the results in the two alcohol dependent groups were not significantly different from each other. The results of standard tests of autonomic function did not distinguish between the alcohol dependent men with normal autonomic function and controls. The differences in heart rate variability between this group and the controls may have been the result of the ability of this method to detect small changes in autonomic integrity. Cardiomyopathy may also account for some of these differences and such abnormalities should be excluded before results are to be regarded as a reflection of vagal function. Twenty four hour measurement of heart rate variability may be a more useful index of cardiac vagal neuropathy than currently available tests of autonomic function.
The Nelson general practice prescribing project has been set up to develop a model for cost effective prescribing in general practice. A pilot audit of regional prescribing patterns and trends for February 1989 was conducted to test data acquisition and presentation for the project, based on 12,690 scripts. There was marked variation in medicines choice, cost and number of scripts between general practitioners. The cost of prescriptions ranged from $2.20 to $127.70, median $10.77. Cardiovascular medicines were most frequently prescribed and most costly. Extemporaneous prescribing accounted for 20% of the February inventory and was highly individually variable. Benzodiazepine prescribing was not in line with current guidelines and was high, mean 6.7% of all prescribing, indicating an urgent need for unbiased drug information. Audited prescription data allows definitions of educational and pricing strategies.
A special format is described for individualised feedback of audited prescribing information to practitioners. The format has been developed for general practitioners participating in the Nelson prescribing project (part I), and has been successfully trialed in conjunction with a preferred medicines list, specifically compiled for the Nelson region. The unbiased, reliable information is seen as a practical means of regular prescribing update and modification of medicine choice, as yet unexploited.
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The cost effectiveness of antihypertensive therapy is increasingly called into question. Minimising the prescribed dose of antihypertensive medications is one potentially effective method of improving cost effectiveness. The minimum effective dose of an antihypertensive medication is defined as that dose above which any further increase is unlikely to result in significant additional lowering of blood pressure. A review of the available clinical trials was undertaken to determine the minimum effective dosages for commonly prescribed beta blockers. These minimum effective dosages were then compared with the average dosages currently prescribed in New Zealand general practices, as determined by a random national survey of prescriptions. The comparison indicated that several beta blockers--including atenolol, metoprolol, propranolol and oxprenolol--are probably being prescribed at excessively high doses. These findings were supported by the results of a general practice based prospective study of beta blocker dose reduction. Seventy-three hypertensive patients on a range of beta blockers were monitored for three months, following a halving of their medication dosage. The results of this study indicated that despite 50% reduction in dosage, there was no loss of antihypertensive effect in this patient population, although heart rate increased. Together, these two studies demonstrate the clinical relevance of the concept of a minimum dosage for beta blockers. A strategy is outlined for reducing the doses for several beta blockers in a significant proportion of hypertensive patients with major cost savings.
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Differences in erythrocyte sodium-lithium countertransport rate and erythrocyte potassium concentration were found between 0900 h and 2100 h in ten healthy individuals. Sodium-lithium countertransport rates were lowest at 0900 h (x: 0.34 mmol/l per h; SD: 0.15) and highest at 1200 h (x: 0.42 mmol/l per h; SD: 0.16). Erythrocyte potassium concentrations increased progressively during the day, while erythrocyte sodium concentrations did not change significantly during the day. For comparative and epidemiological studies of erythrocyte sodium-lithium countertransport rate blood samples should be taken at the same time of the day.
In 83 healthy normotensive males aged 20-55 years the platelet count is positively correlated with the red cell count (r = 0.371; P = 0.0006), the white cell count (r = 0.358; P = 0.0009), and with weight (r = 0.252; P = 0.0269). The red cell count is also positively related with the white cell count (r = 0.242; P = 0.0278) and with weight (r = 0.326; P = 0.0039); while the white cell count is slightly correlated with weight (r = 0.210; P = 0.067). These findings provide further indirect evidential support for a haemopoetic growth factor acting on a single pluripotent stem cell.
The mechanism by which ethanol ingestion causes dermal vasodilation is unclear, but it may result from a direct action on central vascular control mechanisms. Forearm blood flow and peripheral skin temperatures were examined in five quadriplegics (lesions above T7) and five control subjects, before and after the ingestion of ethanol (0.75 ml/kg body wt). The lack of vasomotor efferent function was confirmed in the quadriplegics by the absence of vasodilation in response to radiant heating of the torso. There were no significant changes in peripheral temperatures or forearm blood flow after ethanol in the quadriplegics. The control subjects had a significant increase in forearm blood flow (1.12 +/- 0.2 ml.min-1.100 ml-1) and skin temperature (finger 2.4 +/- 0.4 degrees C, toe 3.4 +/- 0.3 degrees C) after ethanol. These data suggest that ethanol may induce peripheral vasodilation by modulation of central vasomotor control mechanisms.
Cardiac autonomic function was measured in 25 subjects with insulin-dependent diabetes mellitus and 11 control subjects. Autonomic integrity was assessed with standard tests of autonomic function and a new technique of measuring heart-rate variability (HRV) for 24 h. All of the diabetic subjects were selected on the basis of peripheral or autonomic neuropathy or long-term poorly controlled diabetes. They were divided into groups according to presence or absence of vagal neuropathy based on the results of standard tests of autonomic function. Thirteen diabetic subjects had normal autonomic function tests (group 1), and vagal neuropathy was detected in 12 diabetic subjects (group 2). All subjects were monitored by ambulatory electrocardiograph, and the recordings were played back through an analyzer that identified and timed successive pulse (R-R) intervals. HRV was measured from the standard deviation of the successive differences between R-R intervals. HRV was significantly reduced in group 1 (mean +/- SE 73 +/- 9 ms) and group 2 (65 +/- 12 ms) diabetic subjects compared with the control group (138 +/- 10 ms). The standard tests of autonomic function did not distinguish the vagal dysfunction noted with HRV monitoring in group 1 diabetic subjects compared with control subjects. Measurement of 24-h HRV can detect small changes in cardiac autonomic function compared with currently available tests.
The reported inverse relationship between fractional urinary clearance of lithium (FCLi) and erythrocyte sodium-lithium countertransport (Na-Li CT) in normotensive and hypertensive subjects suggests that Na-Li CT may be a marker of proximal tubular sodium reabsorption. We have refuted this hypothesis in a multiracial study of 57 Caucasian and 48 Maori normotensive and hypertensive males aged 20-40 years. Na-Li CT was measured in vitro by standard Li efflux methodology, and in vivo by the Li cell:plasma (Li C:P) ratio 24 h after a 1 g oral dose of lithium carbonate. The Na-Li CT and Li C:P ratio were not significantly different in the two races and were strongly correlated within race, confirming the validity of the Li C:P ratio as an in vivo index of in vitro Na-Li CT. There was no correlation in either race between in vitro or in vivo erythrocyte membrane sodium transport indices and FCLi.
The kinetic parameters Vmax and Km of erythrocyte sodium-lithium countertransport (Na-Li CT), and the lithium cell to plasma ratio (Li C:P) measured 24 h after a 1-g oral dose of Li2CO3, were determined in 14 normotensive (NT) and 14 untreated mild hypertensive (HT) males matched for age and weight. Li C:P and Na-Li CT were strongly correlated (r = -0.73), p less than 0.001), confirming the validity of Li C:P as an in vivo index of Na-Li CT. No differences in Li C:P (NT: 0.27 +/- 0.07; HT: 0.23 +/- 0.06), Na-Li CT (NT: 0.39 +/- 0.10 mmol/L/h; HT: 0.43 +/- 0.10 mmol/L/h), Vmax (NT: 0.58 +/- 0.16 mmol/L/h; HT: 0.68 +/- 0.20 mmol/L/h), or Km (NT: 1.5 +/- 0.4 mmol/L; HT: 1.6 +/- 0.9 mmol/L) were found between NT and HT. Our data do not support the marker concept of erythrocyte Na-Li CT in human hypertension.