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Biomedical subjects

William B White

Publications and source records attributed to William B White.

At least 19 recordsLinked to original sources
PubMed2007

Ambulatory blood pressure monitoring as an investigative tool for characterizing resistant hypertension and its rational treatment.

Ambulatory blood pressure (BP) monitoring has matured into a useful methodology that obtains automated measurements of brachial artery BP during a 24-hour period. Cardiovascular outcomes in the treated patient with hypertension are often better predicted by ambulatory BP than by office pressures. Consensus guidelines have advocated lower goals of treated office BP in the majority of patients with hypertension; guidelines for the goal of ambulatory BP are needed as well. Recently, prospective cohort studies have shown that individuals whose clinic pressure is relatively normal but whose 24-hour BP is elevated are more likely to have a cardiovascular event than individuals with both normal clinic BP and ambulatory BP. Along with the knowledge gained from analyses of higher-risk hypertension patients, recommendations can now be made for how to use ambulatory BP monitoring in clinical practice. For example, ambulatory BP monitoring may be useful in verifying 24-hour control in high-risk patients whose office BP appears to be normal at rest or during the peak effect time of their antihypertensive agents. Evidence is mounting from studies that support the use of ambulatory BP monitoring in patients with resistant hypertension at the time of diagnosis and following clinically guided therapy.

Antihypertensive Agents↗
PubMed2006

Risk of cardiovascular events in patients receiving celecoxib: a meta-analysis of randomized clinical trials.

Some nonsteroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-2 selective inhibitors, have been associated with increased cardiovascular (CV) events in recent clinical trials or observational studies. To determine whether the cyclooxygenase-2 selective inhibitor celecoxib affects CV risk, the incidence of CV events was analyzed in patients treated with celecoxib, placebo, or nonselective NSAIDs in the clinical trial database for celecoxib using defined Antiplatelet Trialists' Collaboration end points of nonfatal myocardial infarction, nonfatal stroke, and CV death. Patient data were derived from studies in osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, low back pain, and Alzheimer's disease. This meta-analysis included (1) 7,462 patients exposed to celecoxib 200 to 800 mg/day for 1,268 patient-years compared with 4,057 patients treated with placebo for 585 patient-years, and (2) 19,773 patients treated with celecoxib 200 to 800 mg/day for 5,651 patient-years compared with 13,990 patients treated with nonselective NSAIDs (diclofenac, ibuprofen, naproxen, ketoprofen, and loxoprofen) for 4,386 patient-years. CV events were adjudicated by a 3-member expert end point committee (WBW, JSB, PBG) blinded to treatment group and study. The incidence rates of the combined CV events were not significantly different between patients treated with celecoxib and placebo or between those treated with celecoxib and nonselective NSAIDs. Event rates were similar for adjudicated and nonadjudicated data. Dose of celecoxib, the use of aspirin, or the presence of CV risk factors did not alter these results. In conclusion, these analyses failed to demonstrate an increased CV risk with celecoxib relative to placebo and demonstrated a comparable rate of CV events with celecoxib treatment compared with nonselective NSAIDs.

Administration, Oral↗
PubMed2006

What controls deposition rate in electron-beam chemical vapor deposition?

The key physical processes governing electron-beam-assisted chemical vapor deposition are analyzed via a combination of theoretical modeling and supporting experiments. The scaling laws that define growth of the nanoscale deposits are developed and verified using carefully designed experiments of carbon deposition from methane onto a silicon substrate. The results suggest that the chamber-scale continuous transport of the precursor gas is the rate controlling process in electron-beam chemical vapor deposition.

Journal Article↗
PubMed2006

Effects of a new hormone therapy, drospirenone and 17-beta-estradiol, in postmenopausal women with hypertension.

Drospirenone (DRSP), a progestin with antialdosterone activity, has been developed for hormone therapy in combination with 17-beta-estradiol (E2) in postmenopausal women. We evaluated the antihypertensive efficacy and safety of various doses of DRSP and E2 and estradiol alone in postmenopausal women with hypertension using ambulatory and clinic blood pressure (BP) monitoring. This was a randomized, double-blind clinical trial of 3 doses of DRSP combined with estradiol, estradiol alone, and placebo in 750 postmenopausal women with stage 1 to 2 hypertension between 45 to 75 years. Ambulatory and clinic BPs, potassium, aldosterone, and lipid measurements and adverse events were evaluated in postmenopausal women with stages 1 to 2 hypertension during 8 weeks of double-blind therapy. DRSP and E2 induced dose-related reductions in the ambulatory and clinic systolic BP with physiological increases in serum aldosterone. Significant decreases in 24-hour systolic pressure were observed at doses of 2 and 3 mg of DRSP combined with estradiol but not by estradiol alone or 1 mg of DRSP with estradiol. There were no significant changes from baseline in potassium in any treatment group. Small, significant reductions in total and low-density lipoprotein cholesterol occurred on all of the active treatments, and serum triglycerides did not change. Adverse event rates were low and similar across treatment groups. In conclusion, these data show that DRSP combined with E2 significantly reduces BP in postmenopausal women with hypertension and did not induce significant increases in serum potassium. These characteristics may lead to a new benefit for this novel hormone therapy in postmenopausal women with hypertension.

Aged↗
PubMed2006

Dispersion of SiO2-based nanocomposites with high performance liquid chromatography.

Core-shell structured Ag/SiO2 nanocomposite has been synthesized by a cyclohexane/Igepal/water reverse micelle system. The spherical nanocomposite particles were washed and concentrated with high performance liquid chromatography (HPLC) to remove the surfactant added during synthesis. Spherical SiO2 micrometer-scale particles were packed in the HPLC column as a stationary phase for the washing and dispersing of Ag/SiO2 nanocomposite particles. Surface modification of Ag/SiO2 nanocomposite particles and SiO2 microspheres with silane coupling agent enhanced the surface charge of the particles and improved the efficiency of washing with HPLC. Well-dispersed Ag/SiO2 stable suspensions were successfully attained in ethanol/water mixed solvents after HPLC washing. The state of dispersion for the Ag/SiO2 nanocomposite suspension was systematically assessed using dynamic light scattering (DLS) and transmission electron microscope (TEM) and spin coat/atomic force microscope (AFM) analyses. The mechanism of the enabling HPLC washing protocol for SiO2-based nanoparticles is discussed.

Journal Article↗
PubMed2006

Effects of tyramine administration in Parkinson's disease patients treated with selective MAO-B inhibitor rasagiline.

Rasagiline is a novel, potent, and selective MAO-B inhibitor shown to be effective for Parkinson's disease. Traditional nonselective MAO inhibitors have been associated with dietary tyramine interactions that can induce hypertensive reactions. To test safety, tyramine challenges (50-75 mg) were performed in 72 rasagiline-treated and 38 placebo-treated Parkinson's disease (PD) patients at the end of two double-blind placebo-controlled trials of rasagiline. An abnormal pressor response was prespecified as three consecutive measurements of systolic blood pressure (BP) increases of >or= 30 mm Hg and/or bradycardia of < 40 beats/min. In the first study involving 55 patients with early PD on rasagiline monotherapy, no patients randomized to rasagiline (1 mg/2 mg; n = 38) or placebo (n = 17) developed systolic BP (SBP) or heart rate changes indicative of a tyramine reaction. In the second trial involving 55 levodopa-treated patients, 3 of 22 subjects on rasagiline 0.5 mg/day and 1 of 21 subjects on placebo developed asymptomatic, self-limiting SBP elevations >or= 30 mm Hg on three measurements. No subject on 1 mg/day rasagiline (0/12) experienced significant BP or heart rate changes following tyramine ingestion. These data demonstrate that rasagiline 0.5 to 2 mg daily is not associated with clinically significant tyramine reactions and can be used as monotherapy or adjunct to levodopa in PD patients without specific dietary tyramine restriction.

Administration, Oral↗
PubMed2006

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. 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 BP remained > or = 140/85 mm Hg, the dose was increased to 80 mg, and if necessary, hydrochlorothiazide 12.5 mg was added after a further 4 weeks and continued for the final 4-week period. Baseline and treatment ABPM measurements were completed in 940 previously untreated patients and 675 previously treated patients. RESULTS: The average reduction of the entire cohort was -10.7/-6.5 mm Hg (P < .0001; mean 24-hour BPs were reduced by 12/8 and 8/5 mm Hg in the untreated and previously treated patients, respectively). In contrast, the office BPs fell by an average of 23/12 and 17/10 mm Hg in previously untreated and treated patients. In 401 patients whose baseline 24-hour BP was > or = 130/85 mm Hg, the mean decrease in 24-hour BP was 16.8/11.4 mm Hg. Based on ABPM criteria, the BP was fully controlled (< 130/85 mm Hg) in 70% of patients, and based on office measurement criteria (< 140/90 mm Hg), in 79%. CONCLUSIONS: Ambulatory BP monitoring demonstrated excellent control rates by telmisartan monotherapy or in combination with hydrochlorothiazide. Observer and measurement bias was substantial based on the changes from baseline by clinical measurements in contrast to ambulatory BP recordings. The successful use of this procedure in primary care research will create further opportunities to define the effectiveness of treatment in the environment in which it is customarily prescribed.

Aged↗
PubMed2006

Primary hyperaldosteronism associated with hypertensive emergencies.

There is growing awareness of primary hyperaldosteronism as a cause of secondary hypertension. Usually, it manifests as hypertension and hypokalemia, or as resistant hypertension. Much less often, primary hyperaldosteronism may be detected after a hypertensive emergency has developed. We highlight this association by reporting on eight patients with a clinical diagnosis of primary hyperaldosteronism whose course was complicated by a hypertensive crisis. In all patients, an elevated serum aldosterone, was accompanied by a suppressed plasma renin activity despite the presence of a hypertensive crisis. A good outcome was obtained either with laparoscopic adrenalectomy (1 patient) or with an antihypertensive drug regimen that included an antialdosterone agent (7 patients). The differential diagnosis of hypertensive emergencies should include primary hyperaldosteronism.

Acute Disease↗
PubMed2006

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. After baseline ABPM, the previous treatment was replaced by telmisartan 40 mg daily; if control (office blood pressure <140/90 mm Hg) was not achieved in 2 weeks, the dose was increased to 80 mg, and if necessary, a fixed combination with hydrochlorothiazide 12.5 mg was used after a further 4 weeks. ABPM was repeated after 4 weeks on final therapy. Overall, 50% of patients finished on monotherapy and 50% on combination therapy. By office measurements, there was a decrease (mean +/- SEM) of 16.8+/-0.5/10.3+/-0.3 mm Hg (p<0.001) when telmisartan-based treatment replaced previous treatment; by ABPM, the decrease was 8.2+/-0.4/5.0+/-0.2 mm Hg (p<0.001). The decreases were significant for comparisons with each of the prior drug classes. A treatment algorithm based on the angiotensin receptor blocker, telmisartan, was confirmed by the blinded end point of ABPM as an efficacious alternative to other antihypertensive regimens in clinical practice.

Aged↗
PubMed2006

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. Safety end points included adverse events, changes in laboratory parameters, and pulse rate. Changes from baseline in BP following telmisartan-HCTZ (-24.0/-17.6 mm Hg) were significantly greater than both placebo (-4.4/-6.8 mm Hg) and valsartan-HCTZ (-21.2/-16.1 mm Hg) (vs placebo, P<.001 for systolic and diastolic BP; vs valsartan-HCTZ, P=.004 for systolic BP and P=.019 for diastolic BP). The total number of patients with at least 1 adverse event reported were similar among the 3 treatment groups (placebo, 49%; telmisartan-HCTZ, 43%; and valsartan-HCTZ, 38%). In conclusion, telmisartan-HCTZ at doses of 80/25 mg lowered both systolic and diastolic BP to a greater extent than valsartan-HCTZ at doses of 160/25 mg. These data support using a higher dose of a thiazide diuretic (25 mg) with a long-acting angiotensin receptor blocker as a useful strategy for improving hypertension control.

Adult↗
PubMed2005

Antihypertensive effects of drospirenone with 17beta-estradiol, a novel hormone treatment in postmenopausal women with stage 1 hypertension.

BACKGROUND: Drospirenone (DRSP) is a novel progestin with antimineralocorticoid activity that has been developed for hormone therapy in combination with 17beta-estradiol (E2) in postmenopausal women. In prior studies with DRSP in postmenopausal women that were focused on relief of menopausal symptoms, DRSP/E2 yielded significant reductions in blood pressure (BP). METHODS AND RESULTS: The effects of 3 mg DRSP/1 mg E2 on clinic and 24-hour ambulatory BP as well as potassium homeostasis were evaluated in postmenopausal women with stage 1 hypertension (systolic, 140 to 159 and/or diastolic, 90 to 99 mm Hg) in a 12-week, multicenter, double-blind, randomized, placebo-controlled study. Clinic BPs were measured at baseline and at 2, 4, 6, 8, and 12 weeks of therapy, whereas potassium was measured at 2, 6, and 12 weeks of therapy. Ambulatory BP was performed in a substudy at baseline and at the end of the trial. In the intention-to-treat population of 213 women, the clinic BP was reduced significantly on DRSP/E2 (clinic BP, -14.1/-7.9 for DRSP/E2 versus -7.1/-4.3 mm Hg for placebo, P<0.0001). In the subgroup of 43 women with ambulatory BP monitoring, the 24-hour BP fell by -8.5/-4.2 mm Hg versus -1.8/-1.6 mm Hg on placebo (P=0.002/0.07). There were no significant changes from baseline in potassium levels or in the incidence of hyperkalemia (> or =5.5 meq/L) on DRSP/E2 compared with placebo. CONCLUSIONS: Combination therapy with DRSP/E2 significantly lowered both clinic and 24-hour systolic BP in postmenopausal women with stage 1 systolic hypertension. This characteristic may lead to benefit for cardiovascular risk reduction in this population.

Aged↗
PubMed2005

The Effects of cyclooxygenase-2 inhibitors and nonsteroidal anti-inflammatory therapy on 24-hour blood pressure in patients with hypertension, osteoarthritis, and type 2 diabetes mellitus.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors may attenuate the efficacy of antihypertensive agents in high-risk patients. Therefore, we conducted a double-blind, randomized trial to evaluate the effects of celecoxib, rofecoxib, and naproxen on 24-hour blood pressure (BP) in patients with type 2 diabetes, hypertension, and osteoarthritis. METHODS: Patients were randomly assigned to treatment with 200 mg of celecoxib once daily (n = 136), 25 mg of rofecoxib once daily (n = 138), or 500 mg of naproxen twice daily (n = 130) for 12 weeks. Twenty-four-hour ambulatory BP monitoring and validated arthritis efficacy assessments were conducted at randomization and at weeks 6 and 12 of treatment. The primary end point was the mean change from baseline in average 24-hour systolic BP at week 6. RESULTS: Reductions in osteoarthritis symptoms, including pain, mobility, and stiffness, were similar in all treatment groups. The mean +/- SE 24-hour systolic BP following 6 weeks of therapy was increased significantly by rofecoxib (from 130.3 +/- 1.2 to 134.5 +/- 1.4 mm Hg; P < .001) but not by celecoxib (132.0 +/- 1.3 to 131.9 +/- 1.3 mm Hg; P = .54) or naproxen (133.7 +/- 1.5 to 133.0 +/- 1.4 mm Hg; P = .74). The BP difference between rofecoxib and celecoxib was 3.78 mm Hg (95% confidence interval, 1.18-6.38; P = .005); between rofecoxib and naproxen, 3.85 mm Hg (95% confidence interval, 1.15-6.55; P = .005). The proportion of patients with controlled hypertension at baseline who developed ambulatory hypertension by week 6 (24-hour systolic BP>135 mm Hg) was significantly greater with rofecoxib (30%) than with celecoxib (16%) (P = .05) but not significantly greater than with naproxen (19%). CONCLUSIONS: At equally effective doses for osteoarthritis management, treatment with rofecoxib but not celecoxib or naproxen induced a significant increase in 24-hour systolic BP. However, destabilization of hypertension control occurred to some extent in all 3 treatment groups; this phenomenon was seen more often in patients treated with rofecoxib than with the other therapies.

Administration, Oral↗
PubMed2005

Effects of eplerenone versus losartan in patients with low-renin hypertension.

BACKGROUND: Sodium retention and volume expansion, mediated in part by aldosterone, are prominent features in low-renin hypertension. Agents that block aldosterone at its receptor sites, therefore, should have significant clinical benefit in patients with low-renin hypertension. METHODS: This 16-week, multicenter, double-blind, active-controlled, parallel-group, titration-to-effect trial compared the blood pressure and neurohumoral responses of the selective aldosterone blocker eplerenone (100-200 mg/d; n = 86) with those of the angiotensin receptor blocker losartan (50-100 mg/d; n = 82) in patients with low-renin hypertension (active renin < or = 25 pg/mL [< or = 42.5 mU/L]). Patients with diastolic blood pressure > or = 90 mm Hg after 8 weeks of monotherapy received add-on therapy with hydrochlorothiazide 12.5 to 25 mg daily. RESULTS: After 8 weeks of therapy, eplerenone reduced blood pressure to a greater extent than losartan (systolic blood pressure -15.8 vs -10.1 mm Hg, P = .017; diastolic blood pressure -9.3 vs -6.7 mm Hg, P = .05). After 16 weeks of therapy, significantly fewer eplerenone-treated patients (32.5%) than losartan-treated patients (55.6%) required add-on hydrochlorothiazide as allowed per protocol for blood pressure control (P = .003). Eplerenone consistently reduced blood pressure regardless of baseline active plasma renin levels whereas losartan reduced blood pressure more effectively in patients with higher baseline active renin levels. There were no differences between treatments in adverse events (reported by 62.8% of eplerenone patients and by 72.0% of losartan patients). CONCLUSIONS: These data show that eplerenone was more effective than losartan in reducing blood pressure in patients with low-renin hypertension. Further studies evaluating the efficacy of eplerenone in difficult-to-treat or resistant hypertension are needed.

Adult↗
PubMed2005

Effects of drospirenone/17-beta estradiol on blood pressure and potassium balance in hypertensive postmenopausal women.

BACKGROUND: Drospirenone (DRSP) is a novel progestin with aldosterone receptor antagonist activity developed for hormone therapy as DRSP /17-beta estradiol (DRSP/E2). Because of a significant aldosterone antagonist activity, we studied the effects of DRSP/E2 on serum potassium (K) and blood pressure (BP) in hypertensive postmenopausal women with and without diabetes mellitus. METHODS: This was a multicenter trial in postmenopausal women 44 to 70 years of age, either with type 2 diabetes mellitus (n = 82) or without type 2 diabetes mellitus (n = 148) and using an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor antagonist. Patients were randomized to 28 days of DRSP/E2 or placebo. Study endpoints were the number and percentage subjects who developed hyperkalemia (K >or= 5.5 mEq/L) and changes from baseline in clinic systolic and diastolic BP. To increase the likelihood of unmasking hyperkalemia, the nondiabetic group was also administered ibuprofen for 5 days. RESULTS: There were no statistical differences in the overall number and percentage of subjects with hyperkalemia for DRSP/E2 versus placebo. No subject had symptoms or electrocardiographic changes related to hyperkalemia. Blood pressure was reduced by -8.6/-5.8 mm Hg in patients receiving DRSP/E2 versus -3.7/-2.9 mm Hg in those receiving placebo (P < .01 for both SBP and DBP). CONCLUSIONS: In hypertensive postmenopausal women, treatment with DRSP/E2 was not associated with a greater incidence of hyperkalemia than with placebo in patients with and without type 2 diabetes mellitus and concomitant use of ACE inhibitors, angiotensin receptor antagonists, or ibuprofen. Furthermore, DRSP/E2 was found to have a significant antihypertensive effect in this high-risk population.

Administration, Oral↗
PubMed2005

Update on the drug treatment of hypertension in patients with cardiovascular disease.

The management of the high-risk patient with hypertension has become more challenging in recent years. Drug therapy should be initiated earlier and at lower blood pressure levels in patients with coexisting cardiovascular or kidney diseases. The blood pressure goals of drug therapy are substantially lower when patients have concomitant heart or kidney disease or diabetes mellitus. Numerous clinical trials in tens of thousands of hypertensive patients with increased cardiovascular risk have demonstrated that the calcium antagonists are as effective and safe as diuretics, beta-adrenergic blockers, and renin-angiotensin blocking agents to prevent heart attack and stroke but not heart failure. Several recent studies also demonstrate that angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers are effective in preventing stroke, progressive renal insufficiency, and heart failure in higher risk patients with hypertension. To achieve the aggressive blood pressure goals in patients with cardiovascular disease, thoughtful combinations of additive or synergistic agents improve efficacy and tolerability and have become an integral part of the modern management of hypertensive patients with coexisting cardiovascular disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

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. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) was performed at baseline and at the end of the treatment period. Baseline and treatment ABPM measurements were completed in 1619 patients. RESULTS: There were highly significant reductions in both the daytime (-11.8/-7.2 mmHg) and night-time (-9.6/-5.7 mmHg) mean BP following telmisartan alone or in combination with the diuretic. Evaluation of the 24-h profiles showed evidence for sustained pharmacodynamic effects of telmisartan over the entire dosing period. Ninety-five (6%) patients had a marked surge in early morning BP defined as >30 mmHg post-awakening change in systolic BP. The average reduction of in the early morning (post-awakening) BP in the entire cohort was -11.5/-7.0 mmHg (P<0.001; reductions were similar for monotherapy and combination therapy groups. The early morning post-awakening BPs fell by an average of -17.2/-10.1 mmHg in patients with large morning BP surges (P<0.05 versus non-surge patients). CONCLUSIONS: In a community based study using ambulatory BP monitoring, telmisartan-based therapy induced highly significant reductions in systolic and diastolic BP over 24 h and was particularly effective in reducing BP during the early morning period.

Aged↗