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Biomedical subjects

D P Myburgh

Publications and source records attributed to D P Myburgh.

At least 19 recordsLinked to original sources

A comparative study of atenolol, nifedipine and their combination in the treatment of hypertension.

The antihypertensive effects, as assessed by clinical and ambulatory blood pressure measurement, of nifedipine slow-release (SR), atenolol and the two in combination were evaluated in 28 known hypertensives in a placebo-controlled, double-blind, randomised cross-over trial. Clinical blood pressure was significantly lower on combination therapy (P less than 0.025) than on either agent alone, although all therapeutic agents reduced blood pressure significantly when compared with placebo (P less than 0.01). All ambulatory blood pressure measurements obtained on any therapeutic agent were significantly lower than those obtained on placebo (P less than 0.01). The mean daytime (08h00-17h00) ambulatory blood pressure measurement as well as the percentage of this monitoring period during which patients were hypertensive were significantly lower (P less than 0.01) on combination therapy than on nifedipine SR. A similar pattern was observed for 24-hour ambulatory blood pressure measurements. Headache was the most significant adverse effect. This was most common with nifedipine SR, less common with combination therapy and least common with atenolol. Combination therapy with nifedipine SR and atenolol is therefore a viable therapeutic alternative in the treatment of patients with benign essential hypertension.

Adult

Observer accuracy and confirmation of the important role of abnormal ST/T time course behavior in the evaluation of stress electrocardiograms.

Routine exercise electrocardiography has been criticized for yielding too many so-called "false-positive" results. Recent studies in our institution indicate that evaluation of the time course behavior of ST segment and T wave (ST/T) changes after cessation of exercise differentiates ischemic from non-ischemic ("false-positive") stress electrocardiograms (SEs). Our method of assessing time course behavior is clarified. The principal aim of this study was to determine the accuracy of experienced observers in making this differentiation. Records of consecutive patients undergoing coronary arteriography over a 2 year period were reviewed and 30 with SEs judged positive for ischemia by the widely accepted ST/T configurational criteria alone were selected at random for the investigation. Sixteen subjects had normal coronary angiograms and had therefore previously been regarded as having false-positive SEs. Fourteen patients had at least one significantly (> 70%) stenosed coronary artery which was our yardstick for ruling that true myocardial ischemia, due to epicardial coronary artery disease (CAD), was present. Five observers, familiar with post-exercise ST/T time course patterns, independently and "blindly" analyzed all 30 configurationally abnormal SEs. Observers were informed only of the patient's age and sex; they were thus unaware of symptoms, exercise variables, coronary anatomy and the number of patients in the 2 groups. The observer consensus for ischemia of SEs using time course analysis was: total test accuracy 87%, sensitivity 79%, specificity 94%, positive predictive value 92% and negative predictive value 83%. Because all 30 patients had ST/T abnormalities, results of the sample for ischemia based on configurational criteria alone were sensitivity 100%, specificity 0% and positive predictive value 47%. We concluded that time course analysis plays a crucial role in evaluating SEs and that exercise electrocardiography remains a safe, cost-effective and reliable method of screening many asymptomatic, as well as symptomatic, subjects for CAD.

Coronary Angiography

Post-exercise time-course analysis of ST segment and T wave changes: an important contribution to the role of stress electrocardiography in aircrew.

Flight surgeons recognize that ongoing vigilance is necessary to detect coronary artery disease (CAD) in aircrew. Regular physical examinations with only a resting electrocardiogram, albeit having a very low predictive value for detection of CAD in asymptomatic subjects, are now widely practised. Routine stress electrocardiography has been criticized for yielding too many so-called "false positive" results because ST/T changes that develop during and after exercise are prevalent. Recent studies in our institution indicate, however, that the time-course behavior patterns of these ST/T configurational "abnormalities" after exercise are different from those reflecting myocardial ischemia due to epicardial CAD. Time-course analysis increases the predictive value of exercise testing and has dramatically decreased the number of asymptomatic aircrew being subjected to coronary arteriography in our institution. Routine exercise electrocardiography provides a reliable, cost-effective means of detecting aircrew with CAD and a baseline for comparison at subsequent examination, and we strongly recommend that it be universally reinstated.

Adult

Evaluation of the post-exercise time-course behaviour of ST-segment and T-wave changes in the elimination of the false-positive stress ECG.

Routine stress ECG has been criticised for yielding too many so-called false-positive results because ST-segment and T-wave (ST/T) changes that develop during and after exercise are prevalent. Recent studies in our institutions indicate that the time-course behaviour patterns of ST/T configurational abnormalities after exercise reflecting myocardial ischaemia are different from those that do not. The epicardial coronary arteries of 111 patients, who had positive stress tests for ischaemia based on ST/T configurational changes alone but were considered non-ischaemic when the ST/T time-course behaviour was analysed, were assessed. Of these patients, 102 had normal coronary arteries, 7 had insignificant stenoses and only 2 had significant coronary artery diseases. ST/T abnormalities on stress testing with a non-ischaemic time-course pattern should be regarded in the same category as ST segments that remain normal as far as the detection of myocardial ischaemia due to epicardial coronary artery disease is concerned. This policy has resulted in an improved predictive value of exercise testing and has considerably decreased the number of patients subjected to coronary arteriography in our institutions. The assessment of the post-exercise stress ECG remains the most practical and cost-effective method for detecting ischaemic heart disease.

Adolescent

Left anterior hemiblock in South African aircrew.

Serial ECGs and clinical records were examined to determine the prevalence, associated ECG abnormalities and outcome of left anterior hemiblock (LAH) in 13,037 airmen. The prevalence of LAH was 0.72% and it was not related to underlying cardiac disease. LAH should be regarded as a benign finding in healthy individuals.

Adolescent

Bezafibrate and simvastatin (MK-733) in the treatment of primary hypercholesterolaemia.

Simvastatin, a new 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitor, was compared to bezafibrate, a fibric acid derivative, in an open cross-over placebo-controlled study. Bezafibrate was administered as a 200 mg dose 3 times daily, while simvastatin dosage ranged from 10 mg to 40 mg once daily at night. Bezafibrate produced a non-significant 13.1% (P = 0.113) decrease in total cholesterol (TC), a 20.7% (P less than 0.05) decrease in low-density lipoprotein cholesterol (LDL-C), an increase of 26.5% (P less than 0.01) in high-density lipoprotein cholesterol (HDL-C) and an improvement in the HDL:LDL ratio of 77.3% (P less than 0.01). Simvastatin 10 mg and 20 mg daily reduced TC by 18.6% and 22.6%, respectively, and LDL-C by 23.9% and 28.6% respectively (P less than 0.01), while no significant increase was noted in HDL-C. Simvastatin 40 mg daily reduced TC and LDL-C by 27.1% and 37.6%, respectively (P less than 0.01), increased HDL-C by 32.0% (P less than 0.05) and improved on the HDL:LDL ratio by 130.8% (P less than 0.01). This showed improvements over bezafibrate of 13.5% for TC, 18.9% for LDL-C, 6.0% for HDL-C and 55.8% for HDL:LDL ratio. It was concluded that simvastatin was well tolerated and had significant hypocholesterolaemic effects when taken once daily.

Adult

Safety, tolerability and efficacy of acipimox in type II hyperlipidaemia.

Twenty-one patients with type II hyperlipidaemia were treated with the nicotinic acid analogue, acipimox (Olbetam; Farmitalia), for 6 months. Total cholesterol decreased by 10% and the high-density lipoprotein: low-density lipoprotein cholesterol ratio increased by 13%. Triglycerides were unaltered. Two patients stopped the drug after developing gastro-intestinal side-effects. Acipimox therapy warrants ongoing use and further investigation.

Cholesterol

Effects of therapy with diet and simvastatin on atherosclerosis in hypercholesterolemic patients.

We evaluated the effect of cholesterol reduction on atherosclerotic coronary artery lesions using diet and simvastatin, a potent HMG CoA reductase inhibitor. Fifteen subjects aged 28-69 years (mean 44), each of whom demonstrated significant (greater than 50%) narrowing of a coronary artery and a baseline cholesterol level greater than 278 mg/dl, were studied. Coronary arteriography was performed prior to and after 20 +/- 2.5 months of therapy. A 42% reduction in total serum cholesterol, a 52% reduction in LDL cholesterol, and an 87% increase in the HDL/LDL cholesterol ratio (p less than 0.01) were achieved. Pretreatment and posttreatment angiograms were reviewed by three experienced angiographers with temporal order masked. Improvement in the overall status of coronary atherosclerotic lesions was demonstrated in two patients (13%), while deterioration occurred in one patient (7%). No overall change was found in the remaining 12 patients (80%). We conclude that a cholesterol-lowering regimen using a nonatherogenic diet and simvastatin therapy may at least stabilize coronary atherosclerosis.

Adult

The aeromedical implications of atrial fibrillation.

A retrospective study was undertaken to determine the incidence of spontaneous atrial fibrillation (AF) in a group of asymptomatic pilots. The electrocardiograms of 13,037 aircrew members accumulated between 1964 and 1986 were reviewed and those coded for AF were extracted. In each case an attempt was made to investigate factors relating to the onset, course, and prognosis of the AF. Eight subjects (mean age 50.1 years) were found to have AF. Of this group, two had a single isolated episode of AF for which a specific precipitating factor was implicated, three had recurrent paroxysmal AF of which one progressed to chronic persistent AF, and three had chronic persistent AF from the outset. The mean follow-up period for the eight subjects was 13.6 years. The two pilots who had isolated attacks of AF have thus far had no subsequent episodes of AF. Five of the remaining six have been completely well, while one required treatment for an embolus to his left leg. Concerning the aeromedical implications, we believe that pilots demonstrating single isolated episodes of AF in the presence of a normal heart, and in whom recovery is complete, should be allowed to return to full aviation duties on a waiver clause. Patients with chronic AF, lone AF, or paroxysmal AF should be excluded from all flying duties.

Adult

Comparison between a low-osmolar ionic (ioxaglate) and a low-osmolar non-ionic (iopamidol) contrast agent in cardiac imaging.

The aim of this study was to compare the subjective, haemodynamic and electrocardiographic changes associated with a low-osmolar ionic (ioxaglate) and a low-osmolar non-ionic (iopamidol) injection during routine ventriculography and coronary angiography. The double-blind study was terminated when 120 patients had been randomised to either ioxaglate or iopamidol. More patients (9) experienced nausea with ioxaglate than with iopamidol (2). One patient in each group developed urticaria during and immediately after the procedure. No patient in any group developed serious arrhythmias during dye injection. After left ventriculography the mean left ventricular end-diastolic pressure (LVEDP) increased significantly in the iopamidol group (P less than 0.001). The difference in the rise of LVEDP in the two groups was not significant. In both groups the systolic arterial pressure fell transiently after left ventriculography (P less than 0.001). The difference in the mean fall of the pressure was not significant. There was no significant change in heart rate with either left ventricular or selective right and left coronary artery injections in any of the groups. In the ioxaglate group with both right and left coronary artery injection, the mean QRS duration, mean Q-T interval and T-wave amplitude changed significantly (P less than 0.001). In the iopamidol group the QRS duration and Q-T interval were prolonged significantly only with left coronary artery injection (P less than 0.001). In all parameters no significant differences were noted in the two groups; only minor differences in the effects caused by the two contrast agents could be demonstrated.

Adult

Comparison of diltiazem and atenolol in young, physically active men with essential hypertension.

The antihypertensive efficacy and effect on maximal exercise performance of diltiazem was evaluated and compared with atenolol in patients specifically selected on the basis of their being young and physically active. Diltiazem (sustained-release preparation, 90 mg twice daily) was administered to 14 patients (aged 33 +/- 2 years) and atenolol (50 mg once daily) to 13 patients (aged 30 +/- 2 years) with essential hypertension in a 16-week randomized, double-blind, parallel study. The 2 drugs had comparable antihypertensive effects at rest, with mean decreases of 18 and 17 mm Hg (p less than 0.001) for supine and standing diastolic blood pressure (BP), respectively, during diltiazem treatment, and mean decreases of 21 and 18 mm Hg (p less than 0.001) during atenolol treatment. During maximal graded exercise testing, systolic BP, diastolic BP, heart rate and heart rate-BP product were significantly reduced by both drugs. However, the reductions in systolic BP, heart rate and heart rate-BP product during exercise were considerably greater (p less than 0.001) with atenolol than with diltiazem. Maximal exercise performance was essentially unchanged with diltiazem and slightly (3%, p less than 0.05) reduced with atenolol. Thus, diltiazem is effective and well-tolerated single therapy for young patients with mild to moderate essential hypertension who lead a physically active life style and compares favorably with atenolol.

Adult

Effect of beta-adrenoceptor blockade and calcium antagonism, alone and in combination, on thermoregulation during prolonged exercise.

The effect of clinically used doses of propranolol, atenolol, nifedipine, propranolol plus nifedipine, and atenolol plus nifedipine on thermoregulatory responses of 11 healthy men was studied during 2-h block-stepping in heat. Drug intervention did not alter ventilation during exercise. In contrast, propranolol and atenolol produced equivalent reductions in exercise tachycardia, implying a similar level of beta 1-adrenoceptor blockade. The heart rate response to exercise was unaffected by nifedipine and during dual beta-adrenoceptor blockade and calcium antagonism was equivalent to that with beta-adrenoceptor blockade alone. While rectal temperature rises were not modified by drug ingestion, propranolol and, to a lesser degree, atenolol and combination therapy, but not nifedipine alone, attenuated skin temperature rises. Moreover, although atenolol, nifedipine, and their combination did not alter sweating, propranolol and its combination with nifedipine enhanced sweating during the 1st and 2nd h of exercise. This study concludes that nifedipine does not modify thermoregulation during exercise and allows for greater confidence of its use during cardiac rehabilitation. Furthermore, the present data confirm that propranolol does enhance sweating during exercise and demonstrate that this effect is not mediated simply by an earlier onset of rapid sweating nor abolished by concomitant calcium antagonism.

Adrenergic beta-Antagonists

Comparison of continuous and intermittent multistage maximal exercise testing during beta-adrenoceptor blockade in physically active men.

Cardiorespiratory responses of 11 healthy males were studied, with placebo and propranolol, during a continuous and an intermittent multistage maximal treadmill test. With placebo, equivalent maximal heart rates were attained for the disparate test modes, and the intermittent protocol yielded a slightly higher (2%, P less than 0.01) maximal O2 consumption. In contrast, during beta-adrenoceptor blockade, higher maximal heart rates (5.1%, P less than 0.01) and O2 consumptions (4.4%, P less than 0.02) were reached with intermittent compared with continuous testing. Values were, however, markedly lower (P less than 0.001) for both protocols than with placebo. These results demonstrate that the precise degree of attenuation of maximal heart rate and O2 consumption observed in physically active persons receiving propranolol is partly dependent upon the actual test protocol utilized. Furthermore, the present data suggest an advantage for intermittent testing when accurate evaluation of the maximal cardiorespiratory capacity is desired in such individuals.

Adrenergic beta-Antagonists

Placebo-controlled study of lisinopril in congestive heart failure: a multicentre study.

A double-blind randomised, parallel, placebo-controlled study was performed in patients with congestive heart failure, at 13 centres in 10 countries, to assess the efficacy and safety of lisinopril, a new angiotensin-converting enzyme inhibitor. After a 2-week run-in period, 130 patients receiving digoxin and/or diuretics were randomised to 12 weeks of treatment with lisinopril 5 mg daily (87 patients) or with placebo (43 patients), with an option to increase lisinopril dosage to 10 or 20 mg. Patients treated with lisinopril improved significantly more than placebo-treated patients (p less than 0.05) for all clinical parameters except oedema and paroxysmal nocturnal dyspnoea. Left ventricular ejection fraction rose by 8% in lisinopril patients compared to 2% in the placebo group, while the cardiothoracic ratio and echocardiographic end systolic diameter fell in the lisinopril group (p less than 0.01) but not in the placebo group. Exercise duration was greater in the lisinopril group at all timepoints, and the increase in exercise duration at 12 weeks was greater by more than 2 min in the lisinopril group as compared to the placebo group (p less than 0.01). Changes in clinical and noninvasive parameters such as the New York Heart Association status, were well correlated with changes in exercise duration. Four patients in the lisinopril group and three in the placebo group died in this study, and there were 31 adverse clinical experiences in the 87 lisinopril-treated patients compared to 13 in the 43 placebo-treated patients. We conclude that lisinopril in doses of 2.5-20 mg/day is well tolerated and effective in patients with heart failure who are receiving digitalis and diuretics.

Adolescent

Effect of dual beta-blockade and calcium antagonism on endurance performance.

The effect of oral clinically used doses of propranolol, atenolol, nifedipine, propranolol + nifedipine, and atenolol + nifedipine on endurance performance and ventilatory responses to graded treadmill testing was studied in 12 healthy physically active men. Maximal exercise duration was reduced by propranolol (8.5%, P less than 0.001) and its combination with nifedipine (11.1%, P less than 0.001), and to a lesser degree by atenolol (3.2%, 0.05 less than P less than 0.1), nifedipine (2.1%, P less than 0.05), and atenolol + nifedipine (3.9%, P less than 0.01). Exercise duration and heart rate (HR) and ventilatory responses to maximal exercise were equivalent with a beta-blocker and its combination with nifedipine. At submaximal exercise, beta-blockade reduced the HR and oxygen uptake, nifedipine accentuated the HR but did not alter ventilation, and all drugs modified the relative oxygen uptake corresponding to 85% of the maximal HR. Physiologic responses to submaximal exercise during combination therapy were similar to those during beta-blockade alone. This study concludes that, in physically active men, nifedipine induces a small impairment of maximal performance, but does not accentuate the reduction in effort tolerance resulting from beta-blockade. Furthermore, HR and ventilatory responses to exercise during combined beta-blockade and calcium antagonism can be predicted from those during beta-blockade alone.

Adrenergic beta-Antagonists

Effect of beta-blockade on exercise core temperature in coronary artery disease patients.

The effect of pharmacologic blockade of beta-adrenoceptors on the relationship between rectal (Tre) and pulmonary artery (Tpa) temperatures was studied in six coronary artery disease patients during 30 min of exercise. Exercise was performed at a set work rate (120 W) on a cycle ergometer before and 2 h after the ingestion of 80 mg propranolol. The heart rate on completion of exercise was reduced (P less than 0.001) from 140 +/- 5 to 108 +/- 3 beats.min-1 by propranolol demonstrating a considerable degree of beta-adrenoceptor blockade. At rest, neither Tre nor Tpa were modified by propranolol. Likewise, propranolol failed to modify the Tre response to exercise. However, propranolol induced an alteration of the normal relationship between Tre and Tpa during exercise. In particular, although Tre was essentially unchanged, propranolol accentuated both the initial fall (by 0.28 degrees C, P less than 0.001) and the subsequent rise (by 0.46 degrees C, P less than 0.01) in Tpa during exercise. The present data therefore demonstrate a considerable limitation to the use of Tre when assessing thermal homeostasis during acute beta-adrenoceptor blockade. Furthermore, although research with more chronic therapy is warranted, our study suggests an accentuated risk of hyperthermia and, by implication, its adverse physiologic consequences during prolonged exercise performed by coronary artery disease patients treated with propranolol.

Adult