Barriers to implementation of placental transfusion of babies at birth in Zambia.

Delayed cord clamping (DCC) and umbilical cord milking (CM) have many benefits. However, a previous study done in Zambia showed that it was not a common practice among midwives. This study investigated possible barriers to DCC and CM, at the University Teaching Hospital in Lusaka. This was a qualitative study. A convenience sample was chosen, and snowball sampling was used. The midwives were interviewed using semi-structured interviews. Burnard's method of thematic content analysis was used. Through 14 interviews it became clear that the midwives were aware of DCC and used it whenever possible. The participants reported that the main barriers were the high workload and a variation in knowledge. A lack of facilities, such as heaters and resuscitation equipment in the delivery room also led to earlier cord clamping. The midwives were motivated to continue improving the routines. They expressed a need for more training as well as equipment and resources to facilitate DCC.

The EWA (estrogen in women with atherosclerosis) study: a randomized study of the use of hormone replacement therapy in women with angiographically verified coronary artery disease. Characteristics of the study population. Effects on lipids and lipoproteins.

OBJECTIVES: To evaluate the effects of hormone replacement therapy (HRT) on lipids and lipoproteins in postmenopausal women with coronary artery disease. SETTING: In this single-centre, controlled and randomized study taking place in a tertiary referral clinic, patients were examined at baseline, and after 3 and 12 months. All analyses were performed examiner-blind. SUBJECTS: Postmenopausal women (n = 118) with angiographically verified coronary artery disease were recruited consecutively from patients referred for investigational procedures due to coronary artery disease. INTERVENTIONS: The women were randomized to HRT, i.e. transdermal application of continuous 17-beta oestradiol with cyclic medroxyprogesterone actetate tablets every 3rd month for 14 days, or to a control group. MAIN OUTCOMES: Effects on lipids and lipoproteins. RESULTS: After 3 months of unopposed oestradiol, triglycerides decreased significantly compared to the control group (P = 0.006). Sequential administration of medroxyprogesterone caused a decrease in HDL cholesterol (P = 0.01), concomitantly with a decrease in ApoA1 lipoproteins (P = 0.007). No other changes in lipids or lipoproteins were observed. After 12 months of therapy, no significant differences were observed between the two groups in lipid or lipoprotein levels. Concomitant statin treatment did not alter the main findings. CONCLUSIONS: In postmenopausal women with established coronary artery disease in whom the majority is treated with statins, no additional effect of HRT on lipids or lipoproteins could be observed except for a transient decrease in triglycerides in the initial unopposed oestradiol phase. No deleterious effect could be observed during medroxyprogesterone administration except for a small transient decrease in HDL cholesterol and ApoA1 lipoproteins.

Amlodipine versus slow release metoprolol in the treatment of stable exertional angina pectoris (AMSA).

OBJECTIVES: To compare the effects of amlodipine and slow release metoprolol on subjective symptoms and signs of ischaemia during bicycle ergometric exercise tests in patients with stable angina pectoris. DESIGN: A randomized double-blind comparison of the two drugs in patients with documented coronary disease required to have at least three attacks of angina per week and to perform a symptom-limited exercise test with significant signs of ischaemia in the ECG. RESULTS: Out of 127 patients, 117 completed the study. Both amlodipine and metoprolol significantly increased total exercise time, total workload, time to onset of angina and time to 1 mm ST-depression with no significant differences between the drugs. Amlodipine was significantly more efficient than metoprolol in reducing ST-depression at maximum workload. Diary data revealed no differences in patients' self-rating of drug effects. CONCLUSIONS: Judged by suppression of subjective symptoms and performance on exercise tolerance tests amlodipine represents a useful alternative to metoprolol as monotherapy in stable angina pectoris.

[An overview of hypertension studies with calcium antagonists]. / Oversikt over hypertensjonsstudier med kalsiumantagonister. ASCOT. Anglo-Scandinavian Cardiac Outcomes Trial.

Calcium antagonists are widely used in the treatment of hypertension. However, few endpoint studies with calcium antagonists have been done to prove reduction in hypertensive complications. Results of the STONE, SYST-EUR and SYST-CHINA studies show that long-acting calcium antagonists are effective compared to placebo, especially in patients with isolated systolic hypertension and diabetes. Ongoing prospective and randomized trials like STOP II, INSIGHT, NORDIL, ALLHAT and ASCOT will clarify whether calcium antagonists are more effective than well-proven diuretics and betablockers. ASCOT will test the hypothesis that amlodipine is more efficacious than atenolol in preventing cardiac complications in 18,000 hypertensive patients with high coronary risk including diabetes (among them, 2,000 in Norway). The study is also randomizing the patients in a factorial design to either atorvastatin or placebo, testing the so-called lipid hypothesis.

Serum N-terminal pro-atrial natriuretic factor 1-98 before and during thyroxine replacement therapy in severe hypothyroidism.

Decreased plasma concentrations of atrial natriuretic factor (ANF) and of its N-terminal prohormones have been demonstrated in severely hypothyroid patients compared with control subjects, and shown to normalize with thyroxine (T4) replacement therapy. Whether this depends on thyroid hormone deficiency exclusively or is secondary to hemodynamic changes that result from it remains a matter of debate. In a recent investigation dose-related increases in both ANF and N-terminal prohormones of ANF by T4 replacement therapy in incremental doses increased at 4-week intervals were demonstrated. It was suggested that thyroid hormones may enhance synthesis rather than release of atrial peptide hormones. The aim of the present study was to confirm this assumption in hypothyroid patients with normal cardiac performance. Serum N-terminal amino acids 1-98 (ie, pro-ANF 1-98) of pro-ANF was determined in 11 severely hypothyroid patients without pericardial effusion and with normal cardiac left ventricular function. Mean pro-ANF 1-98 concentration before T4 replacement therapy remained unchanged after 10 days on T4 (p = .12). After 2 months of therapy, mean pro-ANF 1-98 was significantly increased compared with pretreatment values (p < .003). A significant correlation to the increase in free T4 (r = 0.48, p < .01) but not to the decrease in thyrotropin (TSH) (r = -0.32, p = .09) was found. The present results indicate that thyroid hormones directly increase pro-ANF 1-98 independently of cardiac hemodynamics in the hypothyroid state.

Silent myocardial ischemia in hypothyroidism.

In some patients with severe hypothyroidism thyroxine replacement therapy precipitates or aggravates angina pectoris, whereas in other patients angina pectoris is ameliorated or even disappears. The reason for this paradox is unknown. It has been attributed either to reversible endocrine cardiomyopathy in the form of asymmetric septal hypertrophy (ASH) or reversible anatomical narrowing of the coronary arteries. The results of a recent investigation, in which myocardial performance was surveyed by radionuclide ventriculography throughout early thyroxine replacement therapy in severe hypothyroidism, were compatible with the presence of reversible coronary dysfunction rather than of ASH. The aim of the present investigation was to confirm these findings. In six severely hypothyroid patients, without echocardiographic evidence of ASH or evidence of concomitant coronary artery disease (CAD), exercise and redistribution tomographic myocardial thallium-201 imaging (SPECT) was performed before thyroxine replacement therapy and repeated after 10 days and again after 2 months during therapy. In four patients substantial regional perfusion defects were demonstrated after exercise that were normalized at rest both before, and in one subject also after 10 days, on thyroxine. With restoration of euthyroidism, exercise and redistribution SPECT were normal in every patient. Determination of exact confidence limits reveals that the proportional incidence of myocardial perfusion defects in hypothyroidism, indicating myocardial ischemia, will at least be 22% with 95% probability. Despite the relatively low specificity of SPECT it seems pertinent to conclude that impaired myocardial perfusion as assessed by SPECT probably is due to reversible coronary dysfunction inherent in the hypothyroid state, and that this is not an infrequent manifestation of severe hypothyroidism.

Incidence of hypertrophic cardiomyopathy in hypothyroidism.

In 13 consecutive severely hypothyroid patients no sign of endocrine cardiomyopathy in the form of asymmetric septal hypertrophy (ASH) could be disclosed by M-mode and two-dimensional (2D) echocardiography on examination prior to thyroxine replacement therapy. In previous investigations ASH was demonstrated to be almost invariably present in untreated hypothyroidism irrespective of thyrotropin levels. Consequently application of positive inotropic and afterload reducing agents that may invoke deleterious effects in ASH has been considered hazardous in hypothyroidism even when indicated by concurrent other heart disease. Determination of exact confidence limits reveals that the proportional incidence of hypothyroid hypertrophic cardiomyopathy could not exceed 24.7% with 95% probability. We conclude that ASH is not necessarily inherent in hypothyroidism.

Correlations of exercise test and quality of life variables with clinical improvement in effort angina.

The value of the exercise test has been challenged in connection with assessments of the effects of drugs on angina. Therefore, a series of test variables were correlated with clinical improvement in 30 patients with effort-related angina and coronary stenoses proved by angiography. The patients had two bicycle tests with an interval of 1 year. They were also clinically graded by a combined score of drug consumption and self-assessment of physical fitness on those two occasions, and classified as deteriorated or unchanged, improved, or without symptoms. Sixteen patients had an aortocoronary bypass during the time between the tests. The highest coefficient of correlation was between differences in heart rate at 1 mm ST depression and changes in clinical grading (r = 0.78, p = 0.001). Fairly good correlations were found when changes in total exercise time and changes in maximum double product were related to changes in clinical grading. Differences in maximum ST depression and in blood pressures at 1 mm ST depression did not correlate with clinical improvement; neither did changes in estimates of quality of life.

Primary prevention potential of the calcium antagonists. Effects on blood pressure and lipid pattern.

Untreated hypertension has a variety of serious consequences, such as stroke, congestive heart failure and coronary heart disease, the incidences of which escalate sharply in the presence of other risk factors. Traditional antihypertensive therapy has been associated with reductions in the frequency of strokes, congestive heart failure and kidney failure, but a corresponding decline in myocardial infarctions has not been observed. Deleterious changes in lipid metabolism that are induced by these agents may counteract the beneficial effects of blood pressure reduction. Calcium antagonists have been used successfully in the management of hypertension for more than a decade. To define the impact of the calcium antagonist verapamil on metabolic parameters, 45 hypertensive patients were treated with verapamil monotherapy and followed up for 4 to 8 years. After a mean treatment period of 5.3 years, total cholesterol and triglycerides were unchanged, whereas mean high density lipoprotein (HDL) cholesterol increased significantly, from 1.17 +/- 0.41 to 1.39 +/- 0.36 mmol/L (p less than 0.05). Other important biochemical parameters were unaffected by verapamil therapy. The primary target organs of hypertension are the arterial system and the myocardium. Accumulating literature now suggests that the calcium antagonists may represent an effective therapeutic approach to hypertension that controls both the pressure-related and atherosclerotic complications.

Cardiac left ventricular function before and during early thyroxine treatment in severe hypothyroidism.

In some patients with severe hypothyroidism, thyroxine replacement therapy precipitates or aggravates angina pectoris, whereas in other patients angina pectoris is ameliorated or even cured. Cardiac function in eight severely hypothyroid patients was studied by means of radionuclide ventriculography (RNV) at rest and during supine bicycle exercise before thyroxine treatment, and repeated during treatment before and after administration of 160 mg of oral verapamil. There was an exercise-induced fall in left ventricular ejection fraction (LVEF) in two patients before therapy, and in two additional subjects after 17 d on suboptimal doses of thyroxine. Verapamil attenuated the fall and induced a significant increase in LVEF during exercise (P less than 0.014). No abnormal regional cardiac wall movement (RWM) was observed. After 2 months of thyroxine treatment, LVEF increased significantly during exercise both before and after verapamil (P less than 0.012 and P less than 0.005). These findings are indicative of reversible coronary artery dysfunction. We recommend that, if feasible, thyroxine should be supplemented with verapamil during the early phase of treatment.

Effects of long-term verapamil therapy on serum lipids and other metabolic parameters.

Calcium antagonists have been used successfully in the management of hypertension for more than a decade, but less is known about their long-term metabolic effects. To define the impact of one calcium antagonist, verapamil, on serum lipids and other metabolic parameters, we placed 45 hypertensive patients on verapamil monotherapy and followed them for 4 to 8 years. After a mean treatment period of 5.3 years, total cholesterol and triglyceride levels were not significantly different from baseline, whereas the mean high-density lipoprotein cholesterol value increased significantly from 1.17 +/- 0.41 mmol/L at the initiation of treatment to 1.39 +/- 0.36 mmol/L at 5.3 years (p less than 0.05). Other important biochemical parameters, including serum glucose, potassium and uric acid levels were unaffected by verapamil therapy. No serious side effects or adverse cardiovascular events occurred during verapamil therapy, and there were no study dropouts. It therefore seems likely that this agent will become increasingly useful in the long-term management of essential hypertension.

No metabolic side effects of long-term treatment with verapamil in hypertension.

In a prospective, open study 45 patients (mean age fifty-three years) with essential hypertension were treated with verapamil for four to eight years (mean 5.3 years). Blood pressure was satisfactorily controlled (from 160/104 to 145/91) and the side effects were infrequent, mild, and often transient. Verapamil did not exert any unfavorable metabolic or hematologic effects over the years. HDL-cholesterol was moderately increased (mean 24%) and the other plasma lipids were unaffected. These data suggest that the calcium channel blocker verapamil is a metabolically safe drug to use as monotherapy in essential hypertension.

Circulatory effects of intravenous and oral atenolol in acute myocardial infarction.

The hemodynamic dose-response effects of intravenous (0.05 and 0.10 mg/kg) and oral (50 and 100 mg) atenolol were compared in a randomized between-group study of 24 men within seventeen hours of an acute uncomplicated myocardial infarction; 6 subjects were evaluated in each of the four groups. Hemodynamic variables were determined over a one-hour control period, following which the randomized dose of atenolol was administered and measurements repeated at 15 (intravenous therapy only), 30, 60, 90, 120, 180, 240, 300, and 360 minutes. The peak hemodynamic effect was similar and independent of either the dosage or route of administration. In all groups atenolol reduced heart rate and cardiac and stroke volume indices. The pulmonary artery occluded pressure and systemic vascular resistance index were transiently increased. Mean arterial pressure was significantly reduced only in the oral group with the highest pretreatment pressure. Maximum changes developed between fifteen and thirty minutes after intravenous dosing and between two and three hours after oral dosing. However, substantial reductions in cardiac index (-0.6 L/min/m2; p less than 0.05) were already achieved at sixty minutes following oral dosing. The duration of pharmacodynamic activity was for two to three hours following intravenous and for the study duration (four to six hours) after oral dosing. These data confirm the hemodynamic safety of atenolol after acute myocardial infarction.

Serum ionized calcium--a predictor of therapeutic response to slow calcium channel blockade in essential hypertension.

In 20 patients with mild to moderate essential hypertension, serum ionized calcium was determined before and after four weeks of treatment with 240 mg verapamil sustained release bid. Pretreatment systolic blood pressure was inversely correlated to serum ionized calcium (r = -0.44, p = 0.05). Mean blood pressure was significantly (p less than 0.001) reduced (from 161/100 to 145/88 mm Hg), but mean serum ionized calcium did not change during treatment (from 1.23 to 1.24 mmol/L). A significant inverse correlation (r = -0.56, p = 0.01) was found between pretreatment serum ionized calcium and reduction in systolic blood pressure during verapamil treatment. Thus serum ionized calcium in untreated essential hypertensive patients may predict the blood pressure response to the slow calcium channel blocker verapamil.

Oral verapamil and calcium infusion in patients with sick sinus syndrome.

Electrophysiologic and circulatory effects of a single oral dose of verapamil (120 mg) were evaluated in 8 patients with symptomatic sick sinus syndrome. Ninety min. after verapamil, calcium gluconate (1375 mg) was infused in an attempt to reverse the depressor actions of the drug. Verapamil significantly increased sinus node recovery time (P less than 0.05) and atrioventricular conduction time (P less than 0.01), and decreased both systolic (P less than 0.01) and diastolic blood pressure (P less than 0.05) and spontaneous heart rate (P less than 0.01). Intravenous calcium significantly reversed blood pressure reduction (P less than 0.001) and further lowered heart rate (P less than 0.05) without affecting sinus node recovery time and atrioventricular conduction significantly. There was no significant correlation between plasma verapamil concentrations and any of the cardiovascular parameters. These data confirm that verapamil is principly contraindicated in patients with sinus node dysfunction and demonstrate that the actual calcium dose, although partly reversing blood pressure reduction, cannot reverse the depressant action of the drug on the sinus and atrioventricular node in such patients.

Comparative hemodynamic dose-response effects of five slow calcium channel-blocking agents in coronary artery disease.

A prospective, randomized study compared the hemodynamic effects of equivalent doses of five slow calcium channel blockers (verapamil, diltiazem, nicardipine, nisoldipine, and amlodipine) in 50 patients with ischemia. After a stable control period, dose-response curves were constructed for each drug with hemodynamics measured 10 minutes after intravenous boluses. Each drug reduced mean systemic arterial pressure (P less than 0.01) and systemic vascular resistance index (P less than 0.01). The heart rate increased after nicardipine, nisoldipine, and amlodipine (P less than 0.01) but was unchanged after verapamil and reduced after diltiazem (P less than 0.01). The left ventricular filling pressure increased after amlodipine (P less than 0.05) and verapamil (P less than 0.01) but was unchanged with the other compounds. Cardiac index increased substantially after the dihydropyridines (P less than 0.01), with little change after verapamil or diltiazem. Cardiac double product fell only after verapamil and diltiazem. These studies provide quantitation of the comparative actions of acute intravenous calcium channel blockade in coronary disease.

Can blood pressure reduction induced by slow calcium channel blockade (verapamil) be reversed by calcium infusion?

The pressor effects of a single infusion of calcium gluconate (1375 mg) were measured in 20 patients, aged 31-63 years, with mild and moderate essential hypertension, being on long-term treatment with the slow calcium channel blocker verapamil. The calcium load induced a significant (P less than 0.001) increase in mean serum ionized calcium (from 1.24 +/- 0.01 to 1.40 +/- 0.2 mmol/l). This did not alter mean blood pressure or mean heart rate, although the individual patients responded differently to the mild hypercalcaemia; a significant fall in blood pressure being observed in a few patients. These results demonstrate the unpredictable effects of an increase in extracellular calcium on vascular smooth muscle cells and suggest that an intravenous bolus of 1375 mg calcium gluconate is not effective in counteracting the hypotensive action of verapamil.

Depressor effects of ionized calcium infusion in essential hypertension.

The circulatory effects of an acute increase in serum ionized calcium were assessed in 27 patients with mild to moderate hypertension. Following a control period of fifteen minutes with confirmed circulatory variables, 1,375 mg calcium gluconate was infused over three minutes. Systemic mean arterial blood pressure and heart rate were recorded before, at one-minute intervals during, and for five minutes following the infusion. There was a brief increase of serum ionized calcium concentration (from 1.28 +/- 0.06 mmol/liter to 1.42 +/- 0.07 mmol/liter; p less than 0.001) maximum by one minute after infusion with return toward control by a further four minutes. This was accompanied by a significantly decreased mean arterial blood pressure (from 117 +/- 8 mmHg to 110 +/- 9 mmHg at three minutes; p less than 0.05) and heart rate (from 70 +/- 11 min-1 to 63 +/- 10 min-1 at three minutes; p less than 0.01). There was a significant correlation between the change in ionized calcium and that of the systemic arterial blood pressure (r = 0.68; p less than 0.01). No major side effects were recorded. The blood pressure reduction may theoretically be related to increased membrane stabilization of vascular smooth muscle cells, the acute increase in extracellular ionized calcium impairing calcium ions influx.

A haemodynamic and radionuclide assessment of diltiazem in coronary heart disease.

To obtain multiple dose-response haemodynamic and radionuclide data on i.v. diltiazem, 12 ischaemic patients were studied during routine catheterization. At rest, following a 20 min stable control period, the effects of four doses (0.0625, 0.0625, 0.125 and 0.25 mg kg-1 diltiazem at 5 min intervals) were measured in the 3-5 min following i.v. injection. The exercise effects of the cumulative 0.5 mg kg-1 dosage were assessed by comparing a control and post drug period of supine bicycle exercise. The increase in plasma diltiazem levels correlated linearly with the administered dose and achieved therapeutic levels. There were significant dose-related reductions in systemic arterial blood pressure and vascular resistance index; the heart rate fell and cardiac stroke index increased. The calculated double-product (heart rate X systolic blood pressure) was significantly reduced. The left ventricular filling pressures, ejection fraction and cardiac volumes were unaltered. During supine bicycle exercise, the systemic diastolic blood pressure, heart rate and calculated double-product were reduced without change in other parameters. Over the dose range 0.0625-0.5 mg kg-1, diltiazem acutely increased cardiac stroke index and reduced resting heart rate. These haemodynamic data, taken together with its described coronary vasodilator activity suggest that its role in acute vasospastic angina and during angiographic procedures ought to be explored further.