Dipyridamole-induced headache and lower recurrence risk in secondary prevention of ischaemic stroke: a post hoc analysis.

Background And Purpose: Our objective was to investigate the association between recurrent stroke risk and headache induced by extended-release dipyridamole (ER-DP) when administered alone or with low-dose aspirin (ASA+ER-DP).

Methods: This was a post hoc analysis of prospectively collected data on recurrent stroke risk and headache as an adverse event or reason for treatment discontinuation from the PRoFESS (N = 20,332) and ESPS2 (N = 6602) trials. Hazard ratios (HRs) for recurrent stroke were calculated using the Cox model.

Telmisartan effects on insulin resistance in obese or overweight adults without diabetes or hypertension.

Angiotensin receptor blockers (ARBs) are antihypertensive agents associated with reduced risk of new-onset diabetes mellitus. The ARB telmisartan is a partial agonist of peroxisome proliferator-activated receptor-gamma (PPAR-γ). This study evaluated the effect of telmisartan on insulin resistance, a known target of PPAR-γ agonism.

Safety, efficacy, and pharmacokinetics of telmisartan in pediatric patients with hypertension.

Objective: To assess the safety, pharmacokinetics (PKs), and blood pressure (BP)-lowering efficacy of telmisartan in pediatric (6 to <18 years) patients with hypertension.

Study Design: Patients with diagnosed hypertension were randomized to 4 weeks of treatment with placebo, or with 1 of 2 nominal telmisartan dose levels (1 mg/kg/d or 2 mg/kg/d). The primary end point was change in seated systolic BP (SBP) from baseline to study end.

Telmisartan in migraine prophylaxis: a randomized, placebo-controlled trial.

We evaluated telmisartan 80 mg for migraine prophylaxis. Migraine patients (n = 95) with three to seven migraine attacks in 3 months were randomized, double-blind to telmisartan or placebo. The primary end-point was the reduction in the number of migraine days (i.

Telmisartan is more effective than losartan in reducing proteinuria in patients with diabetic nephropathy.

In patients with diabetic nephropathy, lowering blood pressure and reducing proteinuria by over 30% correlates with a slower progression to kidney failure. We compared two different angiotensin receptor-blockers in a double blind, prospective trial of 860 patients with type 2 diabetes whose blood pressure levels was over 130/80 mmHg or who were receiving antihypertensive medication(s) and who had a morning spot urinary protein to creatinine ratio of 700 or more. Patients were randomized to telmisartan (a highly lipophilic agent with a long half-life) or losartan (with low lipophilicity and short half-life).

Effects of the angiotensin II receptor blockers telmisartan versus valsartan in combination with hydrochlorothiazide: a large, confirmatory trial.

In 2004-2005, the antihypertensive effects of telmisartan 80 mg versus valsartan 160 mg combined with hydrochlorothiazide 25 mg were assessed in a large placebo-controlled trial in patients with stages 1 and 2 hypertension and demonstrated that both agents were highly effective in lowering blood pressure (BP) compared with placebo and that telmisartan lowered BP significantly greater than valsartan. To confirm this finding according to Food and Drug Administration guidelines, we performed a second large trial using the same design in an entirely separate patient population. The trial was double-blind with a 4 : 4 : 1 randomization scheme to compare once daily telmisartan 80 mg plus hydrochlorothiazide 25 mg versus once daily valsartan 160 mg plus hydrochlorothiazide 25 mg versus once daily placebo on reductions in seated clinic BP in patients with stages 1 and 2 hypertension.

The effect of telmisartan and ramipril on early morning blood pressure surge: a pooled analysis of two randomized clinical trials.

Objectives: The period of early morning blood pressure surge is associated with a higher incidence of cardiovascular events than at other times of the day. Antihypertensive medication given once daily in the morning may not protect against this surge if its duration of action is too short. We compared telmisartan, an angiotensin II receptor blocker with a trough-to-peak ratio >90%, with ramipril, an angiotensin-converting enzyme inhibitor with a trough-to-peak ratio of around 50%.

Novel pharmacological targets for the treatment of Parkinson's disease.

Dopamine deficiency, caused by the degeneration of nigrostriatal dopaminergic neurons, is the cause of the major clinical motor symptoms of Parkinson's disease. These symptoms can be treated successfully with a range of drugs that include levodopa, inhibitors of the enzymatic breakdown of levodopa and dopamine agonists delivered by oral, subcutaneous, transcutaneous, intravenous or intra-duodenal routes. However, Parkinson's disease involves degeneration of non-dopaminergic neurons and the treatment of the resulting predominantly non-motor features remains a challenge.

Effects of the angiotensin II receptor blockers telmisartan vs valsartan in combination with hydrochlorothiazide 25 mg once daily for the treatment of hypertension.

To attain recent goals of blood pressure (BP) control, multiple drug therapy combinations are required, including higher doses of thiazide diuretics in combination with other classes of antihypertensive drug therapy. Thus, the authors evaluated the antihypertensive effects of telmisartan vs valsartan when combined with hydrochlorothiazide (HCTZ) 25 mg in a large (N=1066), placebo-controlled trial in patients with stage 1 or 2 hypertension. The primary end points were the changes from baseline in seated diastolic and systolic BP at the end of the 8-week treatment period.

Efficacy and safety of tamsulosin for benign prostatic hyperplasia: clinical experience in the primary care setting.

Objective: This study evaluated the efficacy and safety of the alpha(1A)/alpha(1D) subtype-selective blocker tamsulosin for the increasingly common treatment of benign prostatic hyperplasia (BPH) in the primary care setting.

Methods: A total of 493 men (age > or = 45 years), 99.6% of whom had moderate or severe BPH at baseline, were given tamsulosin 0.

An effectiveness study comparing algorithm-based antihypertensive therapy with previous treatments using conventional and ambulatory blood pressure measurements.

Effectiveness trials in hypertension enable the efficacy and safety of new drugs to be compared with previous therapy. Since these open-label trials could inadvertently be influenced by observer bias, this study has used ambulatory blood pressure monitoring (ABPM) to provide a rigorous blinded end point to validate the study conclusions. The study was performed in 675 patients with stage 1 or 2 hypertension despite receiving single-agent or fixed-dose combination therapy.

A multicenter, 14-week study of telmisartan and ramipril in patients with mild-to-moderate hypertension using ambulatory blood pressure monitoring.

Background: Blood pressure (BP) has a circadian pattern with a morning surge that is associated with an increased risk of acute coronary and cerebrovascular events. In a prospective, randomized, open-label, blinded-endpoint, parallel-group, multicenter, forced-titration study of telmisartan and ramipril, the efficacy of both drugs on mean ambulatory diastolic BP (DBP) and systolic BP (SBP) during the last 6 h of a 24-h dosing interval was evaluated.

Methods: After screening and a single-blind run-in phase, 812 adults with mild-to-moderate hypertension (defined as a mean seated DBP > or =95 mm Hg and < or =109 mm Hg and a 24-h ABPM mean DBP 7 > or = 85 mm Hg) were randomized to the open-label, 14-week, forced-titration, active-treatment phase as follows: telmisartan 40 mg/80 mg/80 mg (n = 405) or ramipril 2.

Measuring the efficacy of antihypertensive therapy by ambulatory blood pressure monitoring in the primary care setting.

Background: Traditional clinical trials in hypertension measure the efficacy of antihypertensive drugs but may not fully assess their effectiveness in clinical practice. Community-based trials can provide this information but are limited because usually they are of open-label design and potentially subject to observer bias. Therefore, we used ambulatory blood pressure monitoring (ABPM), an automated and objective measure of blood pressure (BP) to overcome these shortcomings in a large community-based trial.

Comparative antihypertensive efficacy of angiotensin receptor blocker-based treatment in African-American and white patients.

Blood pressure (BP) reductions with agents that block the renin-angiotensin system are regarded as less effective as monotherapy in African Americans than other ethnic groups. This practice-based study compares the efficacy of an angiotensin receptor blocker-based regimen in African-American and Caucasian patients. Included in the 10-week study were 173 African-American and 1296 Caucasian patients.

Ambulatory blood pressure monitoring in the primary care setting: assessment of therapy on the circadian variation of blood pressure from the MICCAT-2 Trial.

Background: We conducted a large-scale, practice-based trial (MICCAT-2) to evaluate the effects of telmisartan alone and in combination with a diuretic on 24-h blood pressure (BP) profiles, including the early morning period, a time when cardiovascular risk is excessive.

Methods: Patients with hypertension, either untreated or currently on treatment, were started on, or switched to, the angiotensin receptor blocker telmisartan 40 mg daily; after 2 weeks, if office blood pressure (BP) remained > or =140/85 mmHg, the dose was increased to 80 mg; and if necessary, hydrochlorothiazide 12.5 mg was added after a further 4 weeks and continued for a final 4-week period.

Acetaminophen in the treatment of headaches associated with dipyridamole-aspirin combination.

The authors assessed the prevalence of headaches following extended-release dipyridamole/aspirin combination (DAC), and the efficacy of acetaminophen in the treatment of these headaches. Following DAC, 38.7% of the participants developed headaches.

Sustained antihypertensive activity of telmisartan compared with valsartan.

Background: Early morning blood pressure (BP) surge and 24 h mean BP are linked to target-organ damage and cardiovascular events. Antihypertensive agents should sustain BP control, particularly in the last 6 h of the dosing interval or if dosing is missed. The efficacies of the long half-life telmisartan compared with shorter half-life valsartan in the last 6 h of the dosing interval following active treatment and during 24 h after a missed dose were compared.

Effects of the angiotensin II receptor blockers telmisartan versus valsartan on the circadian variation of blood pressure: impact on the early morning period.

Background: Ambulatory blood pressure (BP) monitoring has shown that BP typically declines by 10% to 20% during sleep and increases fairly rapidly in the early morning period. Because the early morning period has been associated with both loss of hypertension control and increased rates of myocardial infarction and stroke, there has been interest in evaluating the effects of antihypertensive therapy at this particular time of the day. The purpose of this study was to assess the effects of a long half-life (telmisartan, 24 h) versus intermediate half-life (valsartan, 6 to 9 h) on early morning BP in two scenarios: after an active dose and after a missed dose of each agent.

Quality of life measured in a practice-based hypertension trial of an angiotensin receptor blocker.

Effectiveness of antihypertensive treatment depends not only on drugs that avoid or minimize symptomatic side effects but also on therapy that has a positive effect on quality of life. This study assessed the effect on quality of life of a contemporary agent (an angiotensin receptor blocker) and evaluated the validity and practicality of using a quality-of-life instrument in the practice-based setting. A total of 2716 hypertensive patients, either untreated or on single-agent therapy, were started on or switched to 40 mg telmisartan for 6 weeks; in patients whose blood pressures remained above 130/85 mm Hg after 2 weeks, the dose was increased to 80 mg for the remaining 4 weeks of treatment.

Defining the antihypertensive properties of the angiotensin receptor blocker telmisartan by a practice-based clinical trial.

Traditional randomized controlled clinical trials are designed to define the specific properties of individual antihypertensive drugs but do not provide full information about their use in clinical practice. To carry out a large-scale practice-based open-label trial to evaluate the safety and efficacy of an angiotensin receptor blocker (ARB) in controlling blood pressure (BP) in the community setting, 703 practitioners recruited 2705 hypertensive patients. There were three groups: untreated at the time of study entry with uncontrolled BP (>/=140/90 mm Hg) (N = 1957); treated but uncontrolled on current monotherapy (N = 685); and treated and controlled, but with unacceptable side effects (N = 63).

Change in trabecular architecture as measured by fractal dimension.

The objective of this work was to expose dried trabecular bone material to a decalcifying environment and to quantify the change in the spatial distribution of the bone with a fractal measure. Digitized radiographic images were produced from four separate slices of human vertebral bone as they dissolved within a solution of nitric acid. Pixel data from a region of interest (ROI) within the trabecular bone were used to estimate the time-dependent change in fractal dimension of the ROI as the bone dissolved.

Middle cerebral artery velocity correlates with nitroglycerin-induced headache onset.

Headache often accompanies treatment with nitroglycerin, but the cerebral hemodynamic effects and the exact mechanism of the headache are incompletely understood. Transcranial Doppler monitoring allows evaluation and monitoring of changes in blood flow velocity in the large intracranial arteries. The objective of this study was to assess middle cerebral artery (MCA) blood flow velocities with transcranial Doppler monitoring in subjects receiving continuous low-dose nitroglycerin intravenously or by patch, and correlate these with clinical headache.

Prostaglandin F2 alpha-induced mitogenesis in MC3T3-E1 osteoblasts: role of protein kinase-C-mediated tyrosine phosphorylation.

Prostaglandin F2 alpha (PGF2 alpha) stimulates DNA synthesis in osteoblasts through phospholipase-C-dependent increases in intracellular calcium and protein kinase-C (PKC) activity. We present evidence that stimulation of protein tyrosine phosphorylation by PKC is an additional component of the signaling pathways involved in PGF2 alpha-stimulated DNA synthesis in MC3T3-E1 osteoblast-like cells. Mitogenic doses of PGF2 alpha (42 nM) rapidly induced tyrosine phosphorylation of multiple substrates in these osteoblast-like cells.

PDGF induces tyrosine phosphorylation in osteoblast-like cells: relevance to mitogenesis.

We have studied the association between protein tyrosine phosphorylation and the mitogenic effect induced by platelet-derived growth factor (PDGF) in the osteoblast-like cell line MC3T3-E1. PDGF caused a dose-dependent increase in [3H]thymidine incorporation in MC3T3-E1 cells, reaching a plateau at 10 ng/ml. Vanadate, a potent phosphatase inhibitor, induced a twofold increase in thymidine incorporation.