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Biomedical subjects

L G Howes

Publications and source records attributed to L G Howes.

At least 19 recordsLinked to original sources
PubMed2005

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.

Acetylcholine↗
PubMed2004

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.

Cognition↗
PubMed2003

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.

Aged↗
PubMed2002

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.

Aged↗
PubMed2001

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.

Adult↗
PubMed2001

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.

Adult↗
PubMed2001

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.

Beverages↗
PubMed2000

The effects of hormone replacement therapy on plasma lipids in type II diabetes.

OBJECTIVES: The effects of hormone replacement therapy on cardiovascular risk factors in postmenopausal women with non-insulin dependent diabetes mellitus (type II diabetes) is uncertain. METHODS: The effects of estrogen replacement therapy (ERT, conjugated equine estrogen0.625mg orally daily), combined estrogen and continuous progestogen therapy (HRT, 0.625 mg of conjugated equine estrogens plus medroxyprogesterone acetate 5 mg daily) or placebo was compared in 20 postmenopausal type II diabetic women and 20 normal postmenopausal women in a double blind, randomised, crossover study. Patients receiving insulin were excluded from the study and all lipid modifying drugs were ceased at least 4 weeks prior to randomisation. Other medication including oral hypoglycaemics was kept constant for the duration of the study. RESULTS: Women with type II diabetes were a similar age (58.7+/-1.3 years) to the non-diabetic women (59.6+/-1.6 years) but they had a significantly greater body mass index, a higher incidence of treated hypertension, higher fasting plasma glucose levels, higher triglycerides and lower HDL cholesterol levels than non-diabetic women. ERT reduced total cholesterol and LDL cholesterol by a similar extent (8.9-12.3%) in normal and type II diabetic women and increased HDL cholesterol to a similar extent in both groups (11.0 and 8.9% respectively). ERT did not significantly alter fasting triglyceride levels in either group. The addition of medroxyprogesterone acetate 5 mg daily abolished the increase in HDL cholesterol associated with ERT in both groups but did not significantly affect any of the other lipid measurements. ERT and HRT did not significantly alter fasting insulin levels nor alter fasting glucose levels in either non-diabetic women or women with type II diabetes. CONCLUSIONS: ERT and HRT have similar effects on lipids in women with type II diabetes and non-diabetic women after 1 month of therapy.

Cholesterol, HDL↗
PubMed2000

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.

Aged↗
PubMed2000

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.

Adult↗
PubMed2000

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.

Animals↗
PubMed1999

Outcomes from treatment. Clinical applications from recent trials.

BACKGROUND: Several recent studies have addressed issues including the optimum blood pressure target and differences between antihypertensive drug classes in reducing cardiovascular morbidity and mortality. OBJECTIVE: To review the results of several recent and topical hypertension trials. DISCUSSION: There is remaining uncertainty about the optimal blood pressure target with the exception of diabetics in whom aggressive blood pressure reduction has been shown to be more effective in reducing morbidity and mortality than less aggressive reduction. It remains unclear whether there are differences between antihypertensive drug classes in their ability to reduce cardiovascular events. At least two studies have demonstrated that it is possible to achieve good blood pressure control in the majority of hypertensive patients if two or more antihypertensive drugs are used.

Aged↗
PubMed1998

The prevalence of isolated systolic hypertension in patients 60 years of age and over attending Australian general practitioners.

AIMS: To determine the prevalence of isolated systolic hypertension (ISH) in patients 60 years of age and over attending general practitioners, and the proportion of patients in whom blood pressure (BP) remains within the ISH range when measured on three successive occasions and when using home BP monitoring. METHODS: BP was measured in 38 832 patients. Patients categorized as having ISH were reviewed after one week. Patients who had BPs in the ISH range at the second visit were provided with a home BP monitor and attended again in one week's time for further clinic blood pressure measurements. RESULTS: 8.6% of all patients were classified as having ISH and 31.4% as having borderline ISH at the first clinic visit. ISH was twice as prevalent in patients receiving antihypertensive therapy (12.4%) than in those not on antihypertensive therapy (6.2%). Of the patients initially categorized as having ISH, and who attended all three clinic visits and completed the home BP monitoring, 52.3% were confirmed as having ISH, 34.0% fell into the borderline ISH range and only 7.0% had a normal BP reading at the third clinic visit. The use of home BP monitoring produced similar results. CONCLUSION: ISH is present on first screening in approximately 8% of elderly Australian patients. This prevalence falls by about 50% when BP is measured on two further occasions, with most patients subsequently falling into the borderline ISH range. Home BP monitoring does not reduce the percentage of patients classified as having ISH on the basis of three clinic measurements.

Age Factors↗
PubMed1998

Effects of glibenclamide on blood pressure and cardiovascular responsiveness in non-insulin dependent diabetes mellitus.

OBJECTIVE: To compare the effects of chronic glibenclamide therapy and placebo on blood pressure and cardiovascular responsiveness in patients with non-insulin-dependent diabetes. DESIGN AND METHODS: Fourteen patients with non-insulin-dependent diabetes mellitus, seven of whom were receiving angiotensin converting enzyme inhibitor therapy, received glibenclamide or placebo for 1 month in a double-blind, randomized crossover study. At the end of each treatment period patients attended for studies of forearm vascular responsiveness to intra-brachial arterial infusions of angiotensin II, acetylcholine, sodium nitroprusside and noradrenaline, responses of blood pressure to intravenous infusions of noradrenaline and angiotensin II and 24 h ambulatory blood pressure monitoring. RESULTS: Administration of glibenclamide produced significantly better glycaemic control than placebo (fasting blood glucose level 8.5 +/- 2.4 versus 13.5 +/- 4.5 mmol/l, P < 0.001) and plasma insulin levels were significantly higher during glibenclamide treatment than they were with placebo (12.9 +/- 4.4 versus 9.2 +/- 4.1 mU/l, P < 0.05). Body weights at the ends of the glibenclamide treatment and placebo phases were similar (92.1 +/- 14.3 versus 91.1 +/- 14.3 kg, P = 0.085). Night-time systolic blood pressures were significantly higher during glibenclamide treatment than they were with placebo (128 +/- 17 versus 118 +/- 10 mmHg, P < 0.05) due to there being a smaller day-night difference in systolic blood pressure during glibenclamide treatment that appeared to occur mainly in patients receiving angiotensin converting enzyme inhibitors. Responses of diastolic blood pressure to intravenous infusion of angiotensin II and forearm vascular responses to intra-brachial arterial infusion of angiotensin II were significantly greater during glibenclamide treatment than they were with placebo (P < 0.05). However, the enhancement of forearm vascular responses during glibenclamide treatment appeared to be restricted to patients receiving angiotensin converting enzyme inhibitors. Responses of blood pressure to intravenous infusion of noradrenaline and forearm vascular responses to infusions of noradrenaline, acetylcholine and nitroprusside did not differ between glibenclamide treatment and placebo; neither did basal forearm vascular resistance. CONCLUSIONS: Glibenclamide therapy is associated with greater responses of blood pressure and forearm vascular responses to infusion of angiotensin and higher nocturnal blood pressures. This effect appears to be influenced by concomitant angiotensin converting enzyme inhibition.

Acetylcholine↗
PubMed1998

Acute effects of oral glibenclamide on blood pressure and forearm vascular resistance in diabetics.

1. To determine the effects of an acute oral dose of glibenclamide on blood pressure (BP), basal forearm vascular resistance (FVR) and FVR responses to the K+(ATP) channel activating vasodilator diazoxide, a placebo-controlled, double-blind cross-over study was performed in eight male volunteers with non-insulin-dependent diabetes mellitus. 2. Changes in vascular responses to progressively increasing concentrations of diazoxide (3.75-30 mg/kg per min) and noradrenaline (25-100 ng/kg per min) were measured by venous occlusion plethysmography. 3. Glibenclamide significantly lowered plasma glucose levels compared with placebo (P < 0.02) and attenuated the decrease in FVR (P < 0.05) and the decrease in systolic BP (P < 0.05) that followed a meal. However, vasodilator responses to diazoxide were potentiated by the administration of oral glibenclamide (P < 0.01). 4. Acute administration of oral glibenclamide attenuates the normal decrease in FVR and systolic BP that follows a meal and potentiates rather than inhibits forearm vasodilator responses to intra-arterial diazoxide, probably via indirect humoral effects. These results suggest that glibenclamide has direct or indirect vasoconstrictor effects that antagonize the normal increase in forearm blood flow that follows a meal and that the inhibition of vascular K+(ATP) channels following acute oral glibenclamide administration is clinically insignificant compared with other indirect vascular effects of the drug.

Adult↗