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Biomedical subjects

A H Maslowski

Publications and source records attributed to A H Maslowski.

At least 19 recordsLinked to original sources

Aspirin does not improve early arterial patency after streptokinase treatment for acute myocardial infarction.

OBJECTIVE: To investigate the hypothesis that the magnitude of the life saving effect of aspirin in the second international study of infarct survival (ISIS-2) trial cannot be explained solely by prevention of late reocclusion of the infarct related artery. The aim of this study was to discover whether or not aspirin in combination with streptokinase had an adjuvant thrombolytic effect. DESIGN: Aspirin (150 mg) or placebo was given at the start of streptokinase infusion to 200 patients seen within six hours of the start of prolonged ischaemic cardiac pain and ST segment elevation. All patients received active aspirin at three hours. Patency of the infarct related artery was assessed non-invasively by the normalised rise of creatine kinase activity at three hours after starting streptokinase in these 200 patients and in a further 52 patients who had already taken aspirin within one week of the start of infarction. MAIN OUTCOME MEASURE: Rise in creatine kinase activity from baseline to > or = 20% or < 20% of the peak rise of activity in blood taken at three hours after starting infusion of streptokinase. This correlates with patency or occlusion of the infarct related coronary artery at about 2.5 hours after starting streptokinase. RESULTS: Assessed in this way, patency of the infarct related artery was 60% in patients given aspirin, 63% in those given placebo, and 62% in patients who had already taken aspirin within one week of infarction. CONCLUSION: The magnitude of the life saving effect of aspirin remains unexplained. Further investigation is needed into the mechanism of action of antiplatelet treatment in relation to thrombolytic treatment.

Aged↗

Clinical experience with doxazosin in general medical practice in New Zealand.

This study investigated the safety and efficacy of doxazosin treatment in a large population of patients (n = 336) with essential hypertension and assessed the effect of doxazosin on the serum lipid profile and the calculated risk of developing coronary heart disease. Patients were assigned to two groups: those with a baseline diastolic blood pressure greater than or equal to 95 mm Hg (group 1) and those with a baseline diastolic blood pressure less than 95 mm Hg (group 2) that was controlled by previous antihypertensive therapy. Doxazosin treatment (monotherapy in 76.2% of patients) significantly (p less than 0.05) reduced the blood pressure of patients in group 1 (-23/-17 mm Hg) after 10 weeks and maintained the control of blood pressure for patients in group 2. Heart rate was essentially unchanged in both groups. Mean final daily doses of 3.6 and 3.2 mg were achieved in groups 1 and 2, respectively. Treatment with doxazosin improved the severity category of hypertension for 88.4% of patients in group 1; 87.3% of patients were considered a therapy success. Doxazosin had a favorable effect on the serum lipid profile in both groups of patients. The majority of lipid changes achieved statistical significance and resulted in a significant 27% decrease in the calculated risk of developing coronary heart disease. Doxazosin was well tolerated; only 24.1% of patients had side effects that were related or possibly related to treatment. In nine (2.7%) patients the dose of doxazosin was reduced and 26 (7.7%) patients withdrew from doxazosin therapy because of side effects.

Antihypertensive Agents↗

Effect of intravenous streptokinase as compared with that of tissue plasminogen activator on left ventricular function after first myocardial infarction.

In a double-blind trial comparing two thrombolytic agents as treatment for acute myocardial infarction, we randomized 270 consecutive patients an average (+/- SD) of 2.5 +/- 0.6 hours after the onset of chest pain from a first myocardial infarction--135 to receive intravenous streptokinase (1.5 million units over 30 minutes) and 135 to receive intravenous recombinant tissue plasminogen activator (rt-PA) (100 mg over three hours). The primary end point was left ventricular function as assessed by cineangiography performed three weeks after infarction. The effects of the two agents on left ventricular function were similar. The ejection fraction was identical (58 +/- 12 percent) in both groups. The end-systolic volume was 61 +/- 29 ml in the streptokinase group and 66 +/- 31 ml in the rt-PA group (P not significant). Patency rates at three weeks for the infarct-related artery were also similar (75 percent in the streptokinase group and 76 percent in the rt-PA group). Reinfarction rates at 30 days were the same (5 percent) in both groups. One patient had a fatal intracerebral hemorrhage 13 hours after receiving rt-PA, and another had a fatal cerebellar hemorrhage 21 hours after receiving rt-PA for reinfarction nine days after treatment with streptokinase. An intention-to-treat analysis revealed that mortality at 30 days was 3.7 percent in the rt-PA group as compared with 7.4 percent in the streptokinase group (P greater than 0.2). Follow-up for a mean of 9.0 months revealed no significant difference in survival; we observed 12 deaths (8.9 percent) in the streptokinase group and 8 deaths (5.9 percent) in the rt-PA group (P = 0.34). We conclude that rt-PA and streptokinase, in the doses given, have similar effects on left ventricular function after a first myocardial infarction. Because of the small number of deaths, it is not possible to determine whether their effects on mortality are similar.

Double-Blind Method↗

Hormone, calcium and blood pressure relationships in primary hyperparathyroidism.

The cause of hypertension in primary hyperparathyroidism and its response to corrective surgery remains a matter of controversy. We therefore studied blood pressure, vasoactive hormones and plasma calcium responses to parathyroidectomy in six hypertensive and two normotensive patients with primary hyperparathyroidism. Twenty-four-hour intra-arterial pressure recordings, together with hourly blood sampling for plasma renin activity (PRA), aldosterone, cortisol, catecholamines and calcium levels, were undertaken in each patient before surgery and were repeated under identical conditions 3-6 months after parathyroidectomy. Mean plasma calcium was 3.03 +/- 0.1 before, and 2.35 +/- 0.02 mmol/l after, parathyroidectomy. Changes in arterial pressure were small and variable in individual patients. Group mean arterial pressures before and after surgery were identical. Plasma cortisol and PRA were significantly higher in the hypercalcaemic state (P less than 0.01 and P less than 0.05, respectively) but there was no significant difference in plasma aldosterone or catecholamine levels. No correlations between changes in plasma calcium or parathyroid hormone levels and concomitant changes in plasma concentration of other hormones were observed. Our findings show that correction of primary hyperparathyroidism has no systematic effect on arterial pressure in a heterogeneous group, including some patients with probable background essential hypertension, when evaluated 3-6 months after surgery. Compared with values after corrective surgery, mean levels of PRA and cortisol-but not aldosterone or catecholamines--are elevated in patients with primary hyperparathyroidism. These findings are consistent with an inhibitory effect of raised ionic calcium concentration on the response of the adrenal glomerulosa to angiotensin and adrenocorticotrophic hormone.

Aged↗

Hyponatraemic-hypertensive syndrome due to unilateral renal ischaemia in women who smoke heavily.

The hyponatraemic-hypertensive syndrome due to renal ischaemia is presumed to be uncommon. We describe four patients who presented with this syndrome over a period of 21 months. All were women who smoked heavily and had unilateral atherosclerotic renal ischaemia. Hypokalaemia was present in each patient, and in one case resulted in recurrent ventricular tachycardia. All had noted thirst, polyuria, and weight loss. Initiation of treatment with a converting-enzyme inhibitor reduced arterial pressure precipitously in two patients. Removal of the ischaemic kidney, or chronic therapy with a converting-enzyme inhibitor reversed the biochemical abnormalities and the presenting symptoms, and lowered arterial pressure. Detailed studies in two patients before and after treatment confirmed the central role of the renin-angiotensin system in the development of the hyponatraemic-hypertensive syndrome.

Aged↗

Blood-pressure response to moderate sodium restriction and to potassium supplementation in mild essential hypertension.

To determine whether moderate restriction of dietary sodium content or supplementation of potassium intake reduces blood-pressure in patients with mild essential hypertension, twelve patients were put on three different diets--a control diet (180 mmol sodium/day), a sodium restricted diet (80 mmol/day). Each diet was taken for at least 4 weeks and the sequence of the regimens was randomised. At the completion of each regimen intra-arterial pressure was recorded continuously, and vasoactive hormones were measured hourly, for 24 h, under standardised conditions, in hospital. Compared with the control diet, sodium restriction was associated with lower blood-pressure readings in seven patients, higher levels in five, and an overall reduction in mean pressures of only 4.0/3.0 mm Hg (not significant). Individual differences in blood-pressure between these two diets correlated closely with concomitant differences in plasma renin activity (r = 0.75). Potassium supplementation also resulted in variable changes in arterial pressure, and the mean difference in pressure recordings (0.1/0.8 mm Hg) was insignificant. The results show that moderate restriction of sodium intake or supplementation of dietary potassium has variable effects on arterial pressure in individuals with mild essential hypertension, and that overall the blood-pressure changes induced are very small. Responsiveness of the renin-angiotensin system may limit the fall in blood-pressure induced by sodium restriction.

Adult↗

Hormone and blood pressure relationships in primary aldosteronism.

We used continuous intra-arterial pressure monitoring and hourly venous hormone sampling over 24 hours in 5 patients with primary aldosteronism to study blood pressure and hormone regulation. Three patients were restudied under identical conditions of controlled diet electrolyte intake and body posture 3-7 months after removal of the aldosterone-secreting adrenal tumor. Prior to surgery there was no positive relationship of arterial pressure to renin or to aldosterone. Norepinephrine fluctuations showed positive correlations with arterial pressure but these 2 indices were more closely related after surgery. Plasma aldosterone levels paralleled those of cortisol both before and after cure of primary aldosteronism. Aldosterone/cortisol regression lines were steeper before surgery, and norepinephrine/renin regression lines were steepened in the post-operation studies. Our findings indicate that in established primary aldosteronism, fluctuations in arterial pressure are regulated in part by the sympathetic nervous system: the pattern of aldosterone secretion is controlled mainly by ACTH: aldosterone responsiveness to endogenous ACTH is enhanced: and sympathetic modulation of renin release in inhibited.

Adenoma↗

Bacterial endocarditis due to Kingella kingae.

A case of infective bacterial endocarditis due to Kingella kingae in a 26 year old male involving a prosthetic mitral valve is described. Microbiological features of this organism are outlined, and the treatment of this endocarditis is discussed with reference to the four previously reported cases.

Adult↗

Arterial pressure and hormone relationships in phaeochromocytoma.

To investigate the regulation of arterial pressure and vasoactive hormones in phaeochromocytoma, we measured intra-arterial pressure and hourly venous hormones (renin, angiotensin II, aldosterone, catecholamines and cortisol) for 24 h in two patients before and three months after removal of a catecholamine-secreting tumour. Before surgery, plasma catecholamines, renin and angiotensin II levels showed a weak inverse correlation with arterial pressure, whereas after surgery norepinephrine-blood pressure correlations were close and positive. Heart rate and arterial pressure fluctuations were reciprocal during short-term recordings but were parallel after removal of the tumour. Renin, angiotensin II and aldosterone levels, initially elevated, fell into the normal range after surgery. Circulating norepinephrine correlated in a positive fashion with renin before and after operation. Slopes of log renin (or angiotensin II)/aldosterone, and log cortisol/ aldosterone regression lines were steeper in the initial study compared to the second. We conclude that arterial pressure fluctuations measured hourly are not determined by concurrent levels of catecholamines or angiotensin II in phaeochromocytoma, although we surmise that minute-by-minute changes in blood pressure are catecholamine-related. Renin release is, at least in part, controlled by circulating catecholamines. Aldosterone responsiveness to angiotensin II and to ACTH is enhanced in phaeochromocytoma.

Adrenal Gland Neoplasms↗

Hemodynamic and hormonal responses during captopril therapy for heart failure: acute, chronic and withdrawal studies.

The hemodynamic and hormonal responses to acute and chronic captopril therapy and to its temporary withdrawal were studied in seven patients with congestive heart failure. Maximal hemodynamic and hormonal effects were reached with 25 to 50 mg doses of captopril. Since plasma angiotensin II levels were significantly higher 6 1/2 hours than 1 hour after administration of captopril, the drug should be given not less often than three times daily. No evidence of hormonal "escape" during long-term (mean 4 1/2 months) captopril therapy was observed, and initial hemodynamic responses were well maintained. Cessation of captopril administration resulted in abrupt increases in circulating angiotensin II levels, in arterial pressure, and in both pulse rate and plasma norepinephrine, but no decrease in cardiac function in the short-term was detected.

Aged↗

Haemodynamic and hormonal effects of captopril in primary pulmonary hypertension.

The treatment of primary pulmonary hypertension is unsatisfactory. Since, in animals, experimental pulmonary vasoconstriction may be mediated in part by angiotensin II, we treated five primary pulmonary hypertensive patients with captopril for four days. To ensure accuracy of haemodynamic and hormone data, the patients were studied under conditions of constant body posture, regulated dietary sodium and potassium intake, and unchanged diuretic therapy. Captopril reduced mean pulmonary arterial pressure in parallel with plasma angiotensin II levels. Right ventricular ejection fraction recordings increased considerably in three of four patients. Systemic arterial pressure fell, but there was no change in right atrial pressure, cardiac output, or heart rate. The decline in plasma (and urine) aldosterone levels presumably contributed to the positive cumulative potassium balance and the rise in plasma potassium (mean 0.7 mmol/1). These encouraging results suggest that converting enzyme inhibitors warrant a formal trial with prolonged follow up in the treatment of primary pulmonary hypertension.

Adult↗

Haemodynamic, hormonal, and electrolyte responses to withdrawal of long-term captopril treatment for heart failure.

To determine whether temporary cessation of captopril therapy compromises cardiac performance, haemodynamic, hormonal, and electrolyte indices were measured for 2 days before, and 4 days after discontinuation of long-term captopril treatment in 5 patients with heart failure. Captopril withdrawal resulted in a four-fold rise in plasma angiotensin II, higher levels of noradrenaline, and a 13.5mmHg increase in mean arterial pressure. Despite there changes, cardiac output at rest and during exercise was well maintained, and right-heart pressures were unaltered. Although plasma aldosterone levels increased three-fold, neither sodium retention nor potassium depletion occurred. Cortisol levels rose in parallel with angiotensin II levels. These results indicate that in the short term cardiac performance is not impaired and electrolyte balance is not adversely affected by the abrupt withdrawal of captopril.

Aged↗

Haemodynamic, hormonal, and electrolyte responses to captopril in resistant heart failure.

In five patients with resistant heart failure treated with the oral converting-enzyme inhibitor, captopril, standardised and intensive haemodynamic, hormone, and electrolyte monitoring showed significantly raised cardiac output and reduced arterial, pulmonary-wedge, and pulmonary-artery pressures which correlated closely with concomitant alterations in the activity of the renin-angiotensin system. These changes occurred in the absence of a natriuresis or diuresis. Clinical improvement was dramatic and paralleled the objective haemodynamic changes. Hyponatraemia and a rise in plasma-potassium were noted. Captopril is a major advance in the treatment of resistant heart failure, and its beneficial haemodynamic effects relate primarily to a blockade of the renin-angiotensin system, the activity of which is increased by conventional drug therapy.

Aged↗

The extent of reflux of unconjugated 14C-cholic acid from the liver in subjects with normal liver function.

An improved understanding of bile acid physiology is a prerequisite for the construction of an acceptable model for describing plasma clearance of bile acids. The aim of this study was to determine the extent of reflux unconjugated cholic acid from the liver to the plasma in subjects with normal liver function. The clearance of a bolus injection of unconjugated 14C-cholic acid was studied in four subjects using samples collected simultaneously from a peripheral and a hepatic vein. Hepatic extraction ratios calculated directly from the data were found to be essentially constant during the 20 min following injection, with average values of 0.60-0.72. This indicates that reflux did not occur significantly in the subjects investigated. These results are interpreted as favouring a model in which exchange of unconjugated 14C-cholic acid occurs between the plasma and a peripheral compartment with final removal from the plasma to the liver.

Carbon Radioisotopes↗

Haemodynamic effects of prostacyclin (PGI2) in pulmonary hypertension.

An infusion of prostacyclin (PGI2) in four patients with pulmonary hypertension resulted in a dose-related decrease in the systemic and pulmonary vascular resistance and an increase in cardiac output. No selectivity for the pulmonary vasculature was observed and the drug was not therapeutically beneficial.

Adult↗

Haemodynamic effects of dobutamine in patients with congestive heart failure receiving captopril.

Treatment with captopril has proved effective in some patients with resistant heart failure. Since cardiac output responses to captopril treatment are generally small, we infused the positive inotropic agent dobutamine in six patients already receiving captopril to determine whether cardiac output could be augmented without concomitantly increasing myocardial oxygen demands. At low infusion rates of dobutamine (2.5 and 5 microgram/kg per min), a substantial rise in cardiac output was observed yet myocardial oxygen uptake remained well below baseline (pre-captopril/dobutamine) levels. At higher rates of infusion (10 and 20 microgram/kg per min) the rise in cardiac output was accompanied by a pronounced increase in myocardial oxygen uptake, and the appearance of chest pain or multifocal ventricular extrasystoles in three patients. These data indicate that captopril treatment combined with low infusion rates of dobutamine can augment cardiac output in the short term, without increasing myocardial oxygen demand.

Aged↗