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The Gemini-AALA (Australia, Asia, Latin America, Africa/Middle East) study evaluated the efficacy and safety of single-pill amlodipine/atorvastatin (Caduet) for the treatment of patients of diverse ethnicity with concomitant hypertension and dyslipidaemia. This was a 14-week, open-label study including patients from 27 countries across the Middle East, Asia-Pacific, Africa and Latin America. Eight dosage strengths of single-pill amlodipine/atorvastatin (5/10, 10/10, 5/20, 10/20, 5/40, 10/40, 5/80 and 10/80 mg) were titrated to improve blood pressure and lipid control. Blood pressure and lipid goals were determined according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) and National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP ATP III) guidelines, respectively (blood pressure,140/90 or130/80 mm Hg; low-density lipoprotein cholesterol (LDL-C),4.1 to2.6 mmol l(-1) (160 to100 mgdl(-1))). Overall, 1649 patients received study medication. Most patients (91.4%) hador=1 cardiovascular risk factor (as defined by NCEP ATP III guidelines) in addition to hypertension/dyslipidaemia, and 61.7% had coronary heart disease/risk equivalent. At baseline, mean blood pressure was 146.6/88.3 mm Hg and LDL-C was 3.4 mmol l(-1) (130.2 mgdl(-1)). At week 14, 55.2% of patients reached both blood pressure and lipid goals, 61.3% reached blood pressure goal and 87.1% reached lipid goal (34.0% were at lipid goal at baseline). Mean blood pressure reduction was 20.2/11.4 mm Hg. For patients who were lipid-lowering drug naive at baseline, mean reduction in LDL-C was 41.0%. Treatment-related adverse events led to the discontinuation of 3.6% of patients. Single-pill amlodipine/atorvastatin therapy was well tolerated and effective for the reduction of blood pressure and lipids to recommended goals in patients from diverse ethnic backgrounds.

To examine the effects of dietary isoflavone supplementation with an extract from red clover on cognitive function in postmenopausal women.Thirty postmenopausal women aged greater than 60 years received either two tablets of an extract of aglycone isoflavones from red clover (each containing formononetin 25 mg, biochanin 2.5 mg and less than 1 mg of daidzein and genistein) for 6 months in a randomized, controlled clinical trial. Cognitive function tests were performed at baseline and at the end of isoflavone or placebo therapy.Isoflavone supplementation was associated with an apparent improvement in block design (a test of visual-spatial intelligence) compared to placebo (isoflavone +12%, placebo -3%; p = 0.03), no improvement in verbal memory compared to an improvement on placebo (isoflavone +1%, placebo +29%; p = 0.023) and a deterioration in digit recall compared to placebo (isoflavone -6%, placebo +12%; p = 0.029). However, these findings were not statistically significant when corrections were made for potential chance findings due to multiple comparisons.Isoflavone supplementation does not appear to have major short-term effects on cognitive function in postmenopausal women. However, further clinical trials are required to determine whether small effects or long-term effects on cognitive function occur during isoflavone supplementation.

Objectives: To assess the acceptability of the delivery of an isoflavone supplementation in the form of a powdered drink, and whether the supplementation of dietary isoflavones in this manner decreased the incidence of menopausal flushes. The secondary aims included assessment of other symptoms or parameters of estrogen deficiency and responses to isoflavones. Methods: A randomized, double-blind, placebo-controlled, parallel-group trial comprising 24 postmenopausal women with symptoms of estrogen deficiency was performed over a 12-week period. The women were randomized to receive a dietary beverage containing isoflavones or an isoflavone-free, isocaloric placebo preparation. Results: Although there was a high compliance rate among individual patients, there was a 25% withdrawal rate from the study in the active group. The incidence of complaints of bad taste tended to be higher in the active group (p = 0.07), and the total number of adverse events was significantly higher in this group (p < 0.001). There ...

The bioavailability of and pharmacodynamic responses to doxazosin, administered with and without food, were examined in a crossover study in 12 hypertensive subjects. The administration of doxazosin with food delayed its absorption by approximately 1 hour, reduced the maximum (peak) plasma drug concentration after single dose administration (Cmax) by 18%, and reduced the area under the plasma concentration-time curve (AUC) by 12%; however, these effects were not statistically significant. The acute fall in blood pressure following doxazosin administration was not significantly affected by food; however, there was a trend towards a lower incidence of complaints in this group. The effect of coadministration of food on the pharmacokinetic and pharmacodynamic responses to doxazosin are unlikely to be of clinical significance.

We have previously reported a strong positive association between average day time and nighttime heart rate measured during 24 hour ambulatory blood pressure monitoring and usual alcohol intake.1 Acute alcohol consumption has been previously described to reduce ECG indices of vagal activity, and men who are severely dependent on alcohol have been reported to have significantly lower indices of cardiac vagal nerve activity than normal volunteers.2–5 We performed 24 hour ambulatory ECG monitoring and power spectral analysis of heart rate variability in apparently healthy middle aged men to examine the association between alcohol consumption, heart rate, and indices of heart rate variability. Twenty eight men aged 50 (9) years (range 33–68 years) who were free from clinically apparent alcohol related or cardiovascular diseases and receiving no medication were selected from volunteers responding to an advertisement in a local newspaper. The subjects’ blood pressures (128 (12)/75 (9) mm Hg), heart rate (72 (9) beats/min), body weight, and height were measured and their demographic details recorded. A detailed alcohol consumption history was taken by an experienced alcohol and other drugs nurse counsellor (JR). The information obtained included the duration that they had been consuming their current alcohol intake, the days of the week that they usually drank, and the amount of alcohol consumed …

Reserpine (Fig. 1), an alkaloid derived from the roots of certain species of Rauwolfia, was isolated in 1952, and about 50 Rauwolfia alkaloids are known. Extracts of Rauwolfia, a plant genus belonging to the Apocynaceae family, were used by the Hindus for a variety of diseases including snake bites because of the resemblance of the roots to a snake (Rauwolfia serpentina). It was also used for the treatment of cardiovascular diseases, insomnia, and insanity (Weiner 1985). Reference to the medical use of Rauwolfia alkaloids appeared in the Western literature as early as 1563 (Bein 1956). In 1931 Sen and Bose reported in the Indian Medical Journal that the whole root could be used for the treatment of hypertension and psychosis. Widespread interest in their use for the treatment of hypertension, however, was aroused much later after Vakil (1949) published his findings on the use of Rauwolfia alkaloids in the British Heart Journal. Parental usage became popular for hypertensive emergencies but has a tendency to produce excessive sedation.

Guanethidine and related compounds have collectively been called adrenergic blocking drugs because their major pharmacological action is to prevent the release of noradrenaline from postganglionic neurons in response to sympathetic nerve stimulations. Guanethidine has other actions on catecholamine metabolism (see Sect. 2) and can cause significant tissue depletion of catecholamines. It does not, however, interfere with release of catecholamines from the adrenal medulla and does not produce parasympathetic blockade.

In chronic cardiac failure, various neurohumoral mechanisms are activated to sustain blood volume, blood pressure, and organ perfusion. Using the coronary artery ligation model of heart failure in the rat, we have measured changes in vasoactive hormone secretion and related these changes to salt and water status during a 1-month period. When compared with controls, rats with infarction had a marked rise in plasma atrial natriuretic peptide (294 +/- 59 vs. 79 +/- 10 pg/ml, p less than 0.001) although there was no increase in total exchangeable body sodium. Plasma renin activity and plasma aldosterone concentrations were the same for both rats with infarction and controls. Similarly, there were no significant differences in plasma arginine vasopressin, plasma osmolality, or plasma sodium concentration in rats with infarction. Ventricular norepinephrine levels were reduced in animals with infarction (p less than 0.01). Plasma atrial natriuretic peptide levels were raised in this model of chronic left ventricular failure. However, there was no salt retention and little stimulation of the renin-angiotensin-aldosterone system or vasopressin. The results suggest that high circulating atrial natriuretic peptide levels may prevent or limit salt and water retention, either directly or indirectly, by inhibiting the renin-angiotensin-aldosterone system.