Extremely metal-poor stars from the cosmic dawn in the bulge of the Milky Way.

The first stars are predicted to have formed within 200 million years after the Big Bang, initiating the cosmic dawn. A true first star has not yet been discovered, although stars with tiny amounts of elements heavier than helium ('metals') have been found in the outer regions ('halo') of the Milky Way. The first stars and their immediate successors should, however, preferentially be found today in the central regions ('bulges') of galaxies, because they formed in the largest over-densities that grew gravitationally with time. The Milky Way bulge underwent a rapid chemical enrichment during the first 1-2 billion years, leading to a dearth of early, metal-poor stars. Here we report observations of extremely metal-poor stars in the Milky Way bulge, including one star with an iron abundance about 10,000 times lower than the solar value without noticeable carbon enhancement. We confirm that most of the metal-poor bulge stars are on tight orbits around the Galactic Centre, rather than being halo stars passing through the bulge, as expected for stars formed at redshifts greater than 15. Their chemical compositions are in general similar to typical halo stars of the same metallicity although intriguing differences exist, including lower abundances of carbon.

Impact of age and gender on blood pressure and low-density lipoprotein cholesterol reduction: results of a pooled analysis.

OBJECTIVES: To compare the simultaneous reduction of blood pressure (BP) to below 150 mmHg and low-density lipoprotein cholesterol (LDL-C) after treatment with single-pill amlodipine/atorvastatin (SPAA) among younger (<65 years), older (≥65 years) and elderly (≥75 years) men and women with hypertension and dyslipidemia. METHODS: Data from five, 14-20-week, open-label, multi-national studies (GEMINI US, GEMINI-Australia, Asia, Latin-America, Africa/Middle-East [AALA], JEWEL 1, JEWEL 2, and the Clinical Utility of Caduet in Simultaneously Achieving Blood Pressure and Lipid End Points [CAPABLE]) were pooled. In these studies, SPAA (5/10 to 10/80 mg/mg) was electively titrated to achieve study-specific targets. Reductions in BP and LDL-C, and changes in renal and liver function tests, fasting glucose and adverse event (AE) rates were compared across the three age groups. RESULTS: A total of 3613 patients (65%) were <65 years, 1946 (35%) were ≥65 years and 441 (8%) were ≥75 years. Baseline mean systolic BP tended to increase with age and diastolic BP and LDL-C decreased, p<0.001. Final mean SPAA dose was similar (7.2/23.9, 7.1/24.3, 7.1/24.0 mg/mg). Final mean BP in the younger/older/elderly groups was 128.1/79.9, 131.3/75.0, 132.8/73.4 mmHg (adjusted BP reductions -20.2/-10.4, -18.6/-12.7, -17.7/-13.2 mmHg, p<0.001). Final mean LDL-C was 91, 87, 87 mg/dl (2.4, 2.3, 2.3 mmol/l) p<0.001; adjusted %LDL-C reductions -27.1, -26.8, -26.4, p<0.001. Estimated glomerular filtration rate increased in the younger group but decreased in the older and elderly groups (p=0.005). Small increases in liver function tests and fasting glucose were observed. Discontinuations due to AEs tended to increase with age but were low in all groups (6.2%, 7.9%, 8.8%, p=0.045). Study limitations include post hoc analysis and short duration of follow-up. CONCLUSIONS: Simultaneous reduction of BP to below 150 mmHg and LDL-C using SPAA is both effective and well-tolerated among younger and older men and women, including those aged≥75 years. Clinicians may be reassured by the low proportion of AEs that led to discontinuation in all groups suggesting that older patients were not disadvantaged by this treatment.

Predictors of inotropic and chronotropic effects of NG-monomethyl-L-arginine.

BACKGROUND: The haemodynamic effects of intravenous infusion of the non-selective nitric oxide synthase (NOS) L-omega monomethyl arginine (L-NMMA) have previously been characterized in humans. Its effect of reducing cardiac index (CI) is an important reason for the increase in mortality in patients with septic shock receiving L-NMMA in a pivotal outcome trial for this indication. The mechanism for the reduction in CI however, is uncertain. METHODS: In this study, we investigated the haemodynamic and arterial stiffness response to a bolus intravenous infusion of L-NMMA (3 mg kg(-1) over 5 min) in 26 healthy human volunteers to clarify the likely cause of L-NMMA induced negative inotropic and chronotropic effects. Digital photoplethysmography (MicroMedical Pulse Trace) was used to derive two measures of arterial stiffness: stiffness index, a measure of large arterial stiffness, and reflection index (RI), a measure of small- to medium-sized arterial stiffness. Haemodynamic measurements of systolic blood pressure, diastolic blood pressure, heart rate, systemic vascular resistance index (SVRI), stroke index and CI were made using a bioimpedance monitor (BioZ Cardiodynamics). RESULTS: We found that changes in CI during L-NMMA are closely related to changes in RI and SVRI. CONCLUSION: The negative inotropic effect of L-NMMA may be a result of an increase in coronary vascular resistance and a resultant decrease in myocardial perfusion. The reduction in CI may also result from a direct reduction of the normal positive inotropic effect of NO by L-NMMA which is closely correlated with its effects on SVRI.

Single-pill amlodipine/atorvastatin helps patients of diverse ethnicity attain recommended goals for blood pressure and lipids (the Gemini-AALA study).

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 or <130/80 mm Hg; low-density lipoprotein cholesterol (LDL-C), <4.1 to <2.6 mmol l(-1) (<160 to <100 mgdl(-1))). Overall, 1649 patients received study medication. Most patients (91.4%) had >or=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.

Evidence for functional expression of vascular angiotensin II type 2 receptors in patients with insulin resistance.

AIM: Angiotensin II type 2 (AT2) receptors are believed to become over-expressed in response to cardiovascular damage and to mediate beneficial effects (e.g. vasodilation). It is unknown whether AT2 receptors are functionally expressed in patients with insulin resistance (INSR). In this study, we investigated the role of the highly selective AT2 receptor antagonist, PD123319, on arterial stiffness and haemodynamic parameters in patients with INSR, compared with an age- and gender-matched control (N) group to determine whether there is functional expression of vascular AT2 receptors in patients with INSR. METHODS: We studied 10 subjects with INSR [mean age 28 +/- 5 years, body mass index (BMI) 30.4 +/- 5.4 kg/m(2), mean cholesterol level 4.7 +/- 0.7 mmol/l, mean homeostasis model assessment 2.78 +/- 0.84] and 10 age- and gender-matched normal subjects (mean age 27 +/- 7 years, BMI 23.6 +/- 2.5 kg/m(2), mean cholesterol level 3.9 +/- 0.6 mmol/l). All were normotensive, non-smokers and on no medications. Subjects received a 3-min infusion of PD123319 (10 microg/min). At the end of the infusion, arterial stiffness indices [stiffness index (SI) and reflective index (RI)] and haemodynamic parameters [cardiac index, systemic vascular resistance index (SVRI) and stroke index (ZI)] were measured. RESULTS: RI (mean % change: INSR 13.8 +/- 15.5%, N -0.2 +/- 4.6, p = 0.04) and SVRI (mean % change: INSR 13.5 +/- 9.7%, N -1.5 +/- 5.7, p = 0.005) increased significantly in response to PD123319 infusion in patients with INSR compared with controls. There were no significant changes in SI, systolic blood pressure, diastolic blood pressure and ZI. CONCLUSION: The results suggest the functional expression of AT2 receptors in small vessels that determine the inflection of the digital volume pulse wave in patients with INSR, possibly as an indicator of early vascular damage.

Effects of cerivastatin on forearm vascular responses, blood pressure responsiveness and ambulatory blood pressure in type 2 diabetic men.

OBJECTIVE: The objective of the study was to investigate the effects of cerivastatin therapy on forearm endothelial dependent acetylcholine (ACH) and independent (nitroprusside) vasodilator responses, blood pressure (BP) responses to intravenous infusions of angiotensin II (AII) and noradrenaline (NA) and on 24-h ambulatory BP recordings in type 2 diabetic men. DESIGN: Eleven type 2 diabetic men aged 59 +/- 9 years with total cholesterol levels of 5.0 +/- 1.26 mmol/l, triglycerides of 2.23 mmol/l and high-density lipoprotein cholesterol levels of 1.24 mmol/l completed a double-blind, randomized, crossover trial comparing 8 weeks of cerivastatin therapy (800 microg of nocte) with placebo. Forearm vascular resistance (FVR) responses to intrabrachial-arterial infusions of ACH (3-24 microg/min), nitroprusside (2-16 microg/min), the nitric oxide(NO) synthase inhibitor l-nitro-mono-methyl arginine (l-nmma) (8 micromol/min), ACH during l-NMMA infusion and BP responses to intravenous infusions of AII (12.5-50 ng/min) and NA (20-400 ng/min) were measured at the end of each treatment period. Twenty-four-hour ambulatory BP recordings were also performed. RESULTS: FVR responses to ACH during l-NMMA infusion were significantly (p = 0.026) greater during cerivastatin than during placebo therapy. In contrast, FVR responses to ACH in the absence of NO synthase inhibition did not differ significantly between cerivastatin and placebo therapies (p = 0.81). FVR increased by 31.4 +/- 57.3% in response to l-NMMA infusion during cerivastatin therapy compared with 6.1 +/- 41.2% during placebo therapy (p = 0.20). FVR responses to nitroprusside did not differ between cerivastatin and placebo therapies (p = 0.28), nor did BP responses to AII (systolic BP, p = 0.99; diastolic BP, p = 0.98) or NA (systolic BP, p = 0.21; diastolic BP, p = 0.48). Mean 24-h BP was similar during cerivastatin (123 +/- 10 or 70 +/- 7 mmHg) and placebo therapies (129 +/- 11 or 74 +/- 7 mmHg) (systolic BP, p = 0.26; diastolic BP, p = 0.41). CONCLUSION: Cerivastatin increases FVR responses to ACH in type 2 diabetic men with mild dyslipidaemia but only following NO synthase inhibition. This may indicate an improvement in endothelium-derived hyperpolarizing factor-mediated responses.

The effects of dietary supplementation with isoflavones from red clover on cognitive function in postmenopausal women.

OBJECTIVE: To examine the effects of dietary isoflavone supplementation with an extract from red clover on cognitive function in postmenopausal women. DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Effects of dietary supplementation with isoflavones from red clover on ambulatory blood pressure and endothelial function in postmenopausal type 2 diabetes.

OBJECTIVE: The aim of this study was to determine whether dietary supplementation with isoflavones from red clover affected ambulatory blood pressure and forearm vascular endothelial function in postmenopausal type 2 diabetic women. DESIGN: Sixteen postmenopausal type 2 diabetics treated with diet or oral hypoglycaemic therapy completed a randomized double-blind crossover trial of dietary supplementation with isoflavones from red clover (approximately 50 mg/day) for 4 weeks compared to placebo. Twenty-four-hour ambulatory blood pressure recordings and forearm vascular responses to acetylcholine, nitroprusside and L-nitromonomethylarginine (L-NMMA) were measured at the end of each treatment period. RESULTS: Mean daytime systolic and diastolic blood pressures were significantly lower during isoflavone therapy compared to placebo (-8.0 +/- 3.4 and -4.3 +/- 1.9 mmHg respectively, p < 0.05). The increase in forearm vascular resistance following L-NMMA was significantly greater during isoflavone supplementation (20.9 +/- 6.5) than placebo (3.7 +/- 2.9 arbitrary units, p < 0.05), suggesting an improvement in basal endothelial function. Plasma lipoproteins, glycated haemoglobin and forearm vascular responses to acetylcholine and nitroprusside did not differ significantly between isoflavone and placebo therapy. CONCLUSION: Isoflavone supplementation from red clover may favourably influence blood pressure and endothelial function in postmenopausal type 2 diabetic women.

Nocturnal blood pressure predicts left ventricular mass index in normotensive elderly.

Blood pressure (BP) predictors of left ventricular mass index (LVMI) were studied in 40 healthy normotensive (71.4 +/- 4.4 years) and 31 hypertensive (73.5 +/- 4.8 years) elderly community-dwelling subjects using short-axis cardiac cine magnetic resonance imaging and 24-h ambulatory BP monitoring. Mean night-time BPs were calculated from the average of readings during sleep and mean daytime BPs were calculated from the remaining recordings. The hypertensive subjects were all receiving anti-hypertensive therapy with angiotensin-converting enzyme (ACE) inhibitors, calcium-channel blockers, beta-blockers or diuretics. Nocturnal systolic BP was a strong predictor of LVMI in both normotensive (beta = 0.38, p = 0.02) and treated hypertensive (beta = 0.39, p = 0.03) subjects. By contrast, daytime systolic BP was a weaker predictor of LVMI in the treated hypertensives (beta = 0.36, p = 0.04) and did not predict LVMI in the normal subjects (beta = 0.27, NS). Nocturnal BP may partly explain the increase in LVMI with ageing in subjects thought to be normotensive on the basis of daytime clinic BP recordings.

Role of angiotensin type 2 receptors in human forearm vascular responses of normal volunteers.

1. It has been hypothesized that the expression of angiotensin (Ang) II type 2 (AT(2)) receptors may become important in vascular disease; however, the functional existence of AT(2) receptors in normal adult humans remains to be established. 2. Vascular responses to AngII after the administration of the specific AT(2) receptor antagonist PD 123319 were determined in the forearm circulation of normal volunteers. 3. PD 123319 (8 microg/min) did not alter basal forearm blood flow, or forearm blood flow or forearm vascular resistance responses to AngII. 4. These results suggest that AT(2) receptors do not play a significant role in the regulation of forearm blood flow or forearm vascular resistance of normal volunteers, but do not preclude a role for AT(2) receptors in other vascular beds or in patients with cardiovascular disease.

Relationship between alcohol consumption, ambulatory blood pressure recordings and left ventricular mass.

The relationship between alcohol consumption, blood pressure and left ventricular mass remains uncertain. A detailed alcohol intake history, clinic blood pressure measurements, 24-h ambulatory blood pressure recordings and measurements of left ventricular mass using magnetic resonance imaging (MRI) were performed in 98 males aged 47.9 +/- 9.7 years, 20 of whom were receiving antihypertensive monotherapy. Alcohol consumption (median intake 315 g/week, range 0-2050) was significantly related to supine systolic clinic blood pressures (beta = 0.20, p = 0.05) but not to clinic supine diastolic blood pressures (beta = 0.12, p = 0.25), 24-h blood pressures (systolic: beta = -0.03, p = 0.75; diastolic beta = -0.05, p = 0.60), awake blood pressures or sleeping blood pressures. Alcohol consumption was not related to left ventricular mass index (beta = -0.05, p = 0.59). Left ventricular mass was strongly related to mean 24-h systolic blood pressures (beta = 0.28, p = 0.01), mean awake and sleeping systolic blood pressures, and less strongly to clinic systolic blood pressures (beta = 0.23, p = 0.03). These results were not significantly altered by adjusting for age, smoking, body mass index or alcohol intake, or by excluding the 20 men who were receiving antihypertensive therapy. The results of this study suggest that alcohol consumption at levels commonly encountered in the community is not an important predictor of left ventricular mass index in men, either via direct effects or by indirect effects on blood pressure.

Effects on menopausal symptoms and acceptability of isoflavone-containing soy powder dietary 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 was no statistically significant difference in the incidence of flushes between the groups. There was no difference between the groups in Greene Menopause Symptom Scores, vaginal maturation value, levels of follicle stimulating hormone (FSH) or sex hormone-binding globulin (SHBG), or bone turnover markers. CONCLUSIONS: Powdered energy drinks are not commonly consumed in Australia and were poorly tolerated in this study. The high withdrawal rate and reporting of side-effects suggests that other methods of isoflavone delivery may be more appropriate in this culture, in future trials. At the dose used no benefit was seen in relief from menopausal symptoms, although for the sample size, the study could only have been expected to detect major differences between the groups.

Emergency response to raccoon rabies introduction into Ontario.

During 15 July to 4 October, 1999, rabies control programs were implemented with the objective being to contain the first three confirmed cases of raccoon rabies in Canada. The strategy, called point infection control (PIC) involved the use of three tactics: population reduction (PR), trap-vaccinate-release (TVR) and oral rabies vaccination with baits (ORV), to control the spread of raccoon rabies. A total of 1,202 raccoons (Procyon lotor) and 337 skunks (Mephitis mephitis) were captured and euthanized using 24,719 trap-nights in the three PR zones around the location of the three rabies cases, near Brockville, Ontario. That represented an 83% to 91% reduction in the raccoon populations in an approximate 225 km2 area around the three rabies cases. Raccoon density in the PR zones declined from 5.1-7.1/km2 to 0.6-1.1/km2 following control. All tested specimens were negative for rabies by the fluorescent antibody test (FAT). In addition, 1,759 raccoons and 377 skunks were intramuscularly vaccinated against rabies and released using 27,956 trap-nights in an approximate 485 km2 TVR zone implemented outside of the PR zones. A total of 856 cats from both PR and TVR areas were also captured, vaccinated and released. Cost for the three PIC operations was $363,000.00 Cdn or about $500.00 Cdn/km2. To further contain the outbreak, about 81,300 baits containing Raboral V-RG oral rabies vaccine were aerially distributed on 8 and 27 September 1999, to create an 8 to 15 km wide buffer zone (1,200 km2 area) of vaccinated raccoons immediately beyond the PR and TVR zones. This was the first time that V-RG was used in Canada to orally vaccinate free ranging raccoons against rabies. Baiting costs were $241,000.00 Cdn or about $200.00 Cdn/km2 including post baiting assessment costs. As of 31 August, 2000, thirty-five additional cases (38 in total) of raccoon rabies have occurred in the control and vaccination zones. This number is far below the level of rabies prevalence in USA jurisdictions where raccoon rabies was epizootic. In the future, PIC methodologies will continue to be used in Ontario to contain isolated cases of raccoon rabies.

The effects of candesartan on vascular responses to angiotensin II and norepinephrine in normal volunteers.

The effects of chronic administration of candesartan, 16 mg once-daily, to normal volunteers on cardiovascular responses to angiotensin II (Ang II) and norepinephrine (NE) were examined. Fifteen healthy, non-smoking volunteers participated in a randomised, double-blind crossover study of two weeks of candesartan therapy, compared with two weeks of placebo. Blood pressure (BP) responses were measured to increasing infusion rates of intravenous Ang II and NE, along with forearm blood flow (FBF) responses into intra-brachial arterial Ang II, 2 and 24 hours after the last dose of candesartan or placebo. FBF responses to intra-brachial arterial NE were recorded approximately 2 hours following the final dose. Systolic and diastolic BP responses to intravenous infusions of Ang II during candesartan treatment were completely suppressed and significantly lower than during placebo treatment, 2 hours (candesartan 96+/-10/55+/-8 mmHg; placebo 105+/-5/64+/-8 mmHg) and 24 hours (candesartan 94+/-8/54+/-8 mmHg; placebo 103+/-7/64+/-7 mmHg) following the last dose. In contrast, FBF responses to intra-brachial arterial Ang II were significantly suppressed by candesartan compared with placebo in a subgroup of subjects 2 hours following the last dose (n=9), but not 24 hours after the last dose (n=8). FBF responses to NE were also suppressed by candesartan treatment 2 hours following the last dose, while BP responses to intravenous NE were unaltered. Chronic candesartan therapy, 16 mg once-daily effectively suppresses pressor responses to Ang II over the duration of the dosing interval.

White coat effect of alcohol.

Numerous studies have shown a relationship between alcohol intake and elevated clinic blood pressures (BP). However, there have been few studies on the relationship between alcohol consumption and 24-h ambulatory BP monitoring. This study aimed to determine the relationship between alcohol intake, clinic BP, and 24-h ambulatory BP recordings to determine to what extent a white coat effect may contribute to the relationship between alcohol consumption and BP. Clinical BP and 24-h ambulatory BP were measured in 121 male volunteers aged 50.6 +/- 9.8 years (range, 30-70 years) who consumed between 0 and 2050 g of alcohol per week (mean, 394 +/- 342 g; median, 385 g/week). Supine clinical systolic BP (SBP) was significantly related to alcohol intake (beta = 0.242; P = .007). Alcohol consumption was not related to 24-h mean SBP or diastolic BP (DBP), daytime SBP or DBP, or nighttime SBP or DBP (daytime SBP: beta = 0.02, P = .802). Alcohol intake was significantly related to the difference between clinic SBP and mean daytime SBP (beta = 0.260, P = .004). Twenty-four-hour mean heart rate (HR), daytime mean and nighttime mean HR were strongly associated with alcohol intake (24-h HR: beta = 0.455, P < .001). These results suggest that the association between alcohol consumption and elevated BP is contributed to by a significant white coat effect and that excessive alcohol consumption may be a significant factor in explaining differences between clinic and ambulatory BP measurements.

The effects of dietary supplementation with isoflavones from red clover on the lipoprotein profiles of post menopausal women with mild to moderate hypercholesterolaemia.

The effects of dietary isoflavone supplementation using a purified extract of red clover containing approximately biochanin A 26 mg, formononetin 16 mg, daidzein 0.5 mg and genistein 1 mg per tablet at doses of one or two tablets per day were compared to placebo in a three-period, randomised, double blind, ascending dose study in 66 post menopausal women with plasma cholesterol levels between 5.0 and 9.0 mmol/l. Each treatment period lasted 4 weeks and a further nine women received placebo for the full 12-week period. All women consumed a low isoflavone diet for 2 weeks preceding the commencement of the study and for the 12-week study period. Urinary isoflavone excretion was very low in subjects receiving placebo but increased in a dose-dependent manner during therapy with one and two of isoflavone tablets. Dietary supplementation with isoflavones did not significantly alter total plasma cholesterol, LDL cholesterol, HDL cholesterol or plasma triglyceride levels. However, inverse correlations were found between urinary genistein excretion and plasma triglyceride levels and between urinary O-DMA excretion (an isoflavone metabolite) and plasma triglyceride levels in subjects receiving one isoflavone tablet, suggesting a weak relationship between isoflavone intake and plasma triglycerides which may be influenced by individual differences in isoflavone absorption or metabolism. The results suggest that isoflavone phytoestrogens from red clover in the proportions and quantities studied do not significantly alter plasma lipids in post menopausal women with moderately elevated plasma cholesterol levels.

Angiotensin receptor antagonists.

BACKGROUND: Angiotensin receptor antagonists are a relatively new class of cardiovascular drugs for which the clinical application has not yet been completely defined. OBJECTIVE: This article reviews the pharmacology of the various angiotensin receptor antagonists available in Australia, including their mode of action, side effects and potential drug interactions. DISCUSSION: Angiotensin receptor antagonists are effective drugs for the treatment of mild to moderate hypertension which have a side effect profile similar to placebo. Their role in the management of hypertension remains to be defined, but they are of particular use to patients who are intolerant of ACE inhibitors because of cough. It is uncertain at the present time whether the benefits of ACE inhibition in other disorders such as congestive heart failure and following myocardial infarction will be similar for angiotensin receptor blockers.

Effects of hormone replacement therapy on ambulatory blood pressure and vascular responses in normotensive women.

The effects of chronic oestrogen replacement therapy (ERT) (conjugated equine oestrogen 0.625 mg/day) and combined oestrogen and progestogen replacement therapy (HRT) (ERT plus continuous medroxyprogesterone acetate 5 mg/day) on 24-h ambulatory blood pressure recordings, forearm vascular resistance (FVR) and FVR responses to noradrenaline, angiotensin II, acetylcholine and nitroprusside were studied in 17 normotensive postmenopausal women in a 3-month randomized, double-blind, placebo-controlled crossover trial with 1 month of therapy in each treatment arm. During the last few days of each 1-month treatment period, the subjects underwent 24-h ambulatory blood pressure recordings and measurements of FVR responses. ERT and HRT reduced mean 24-h diastolic blood pressure by 4 and 5 mmHg, systolic blood pressure by 6 and 9 mmHg and mean 24-h heart rate by 5 and 3 beats/min, respectively for ERT and HRT (p < 0.05). Basal FVR was reduced by approximately 18% by ERT and HRT, but FVR responses to noradrenaline, angiotensin II, acetylcholine and nitroprusside were unaffected. ERT and HRT therapy for 1 month lowers blood pressure and basal FVR, but does not appear to influence FVR responses to acetylcholine, nitroprusside, noradrenaline and angiotensin II.