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Biomedical subjects

R Glazer

Publications and source records attributed to R Glazer.

13 recordsLinked to original sources
PubMed1999

Dose-response efficacy of valsartan, a new angiotensin II receptor blocker.

OBJECTIVE: To study the efficacy and tolerability of a range of valsartan doses in patients with mild-to-moderate hypertension. DESIGN: 122 adult out-patients were randomised in equal numbers to receive valsartan 10 mg, 40 mg, 80 mg, 160 mg or placebo once daily (OD) for 4 weeks in this multicentre, double-blind, fixed-dose, parallel trial. Patients were assessed at 0, 2 and 4 weeks. MAIN OUTCOME MEASURES: The primary efficacy variable was change from baseline in trough mean supine diastolic blood pressure (MSuDBP). Other variables included change from baseline in trough mean supine systolic blood pressure (MSuSBP), responder rates and trough/peak ratio. RESULTS: All treatments significantly reduced MSuDBP and MSuSBP at 4-week end-point compared to baseline (P < 0.001). The magnitude of blood pressure lowering was greater with increasing doses of valsartan (least square mean change from baseline for placebo, valsartan 10 mg, 40 mg, 80 mg, 160 mg respectively: MSuDBP -4.4 mm Hg, -4.9 mm Hg, -6.5 mm Hg, -8.2 mm Hg, -9.1 mm Hg; MSuSBP -1.3 mm Hg, -3.6 mm Hg, -7.0 mm Hg, -11.1 mm Hg, -11.9 mm Hg). A fitted quadratic curve, to predict relationship between dose and change from baseline in trough MSuDBP, indicated a positive dose response. Responder rates were 16%, 24%, 33%, 46%, 54% for placebo, valsartan 10 mg, 40 mg, 80 mg, 160 mg respectively, which also indicated a positive dose response in the dose range of 10 mg to 160 mg. Greater than 50% of the antihypertensive effect measured at peak persisted at trough for each of the four active treatment groups, confirming efficacy over a 24-h period. No dose-related adverse experiences were observed, with overall incidence (regardless of relationship to trial medication) of 44% with placebo and 44%, 36%, 22%, 21% for valsartan 10 mg, 40 mg, 80 mg, 160 mg respectively. The most common adverse experience reported was headache which occurred most frequently with placebo (12%). No trial drug-related cough was observed. Treatment with valsartan did not produce clinically significant orthostatic changes in diastolic or systolic blood pressure. One case of symptomatic orthostatic hypotension was observed on placebo. CONCLUSIONS: The results of this trial show valsartan to effectively lower blood pressure in patients with mild-to-moderate hypertension, and demonstrate that the reduction in blood pressure increases with increasing dose levels.

Adolescent↗
PubMed1996

Effects of benazepril and hydrochlorothiazide, given alone and in low- and high-dose combinations, on blood pressure in patients with hypertension.

OBJECTIVE: To assess the efficacy and safety of several combinations of benazepril, an angiotensin-converting enzyme inhibitor, and hydrochlorothiazide, as compared with placebo, in the treatment of patients with essential hypertension. DESIGN: A 6-week, randomized, double-blind, parallel study conducted at 24 centers. A placebo run-in period of 1 to 4 weeks preceded the double-blind phase. PARTICIPANTS AND SETTING: Male and female outpatients, aged 18 years and older, were eligible to participate if their sitting diastolic blood pressure was between 95 and 114 mm Hg at the last two consecutive visits during the placebo phase. Among the 334 patients who entered the double-blind phase, 17% were aged 65 years or older and 26% were black. Eleven patients withdrew because of adverse experiences, including two patients receiving placebo. INTERVENTIONS: Patients received placebo; benazepril, 20 mg; hydrochlorothiazide, 25 mg; or combination therapy with benazepril/hydrochlorothiazide, 5/6.25 mg, 10/12.5 mg, 20/25 mg, 20/6.25 mg, or 5/25 mg, once daily for 6 weeks. MAIN OUTCOME MEASURES: The mean change from baseline in sitting diastolic blood pressure at end point (last postrandomization measurement carried forward) in the double-blind phase. Combination therapy with benazepril/hydrochlorothiazide, 20/25 mg, was compared with benazepril, 20 mg alone, and hydrochlorothiazide, 25 mg alone. Sitting systolic blood pressure and the effect of race and age on treatment efficacy were also evaluated. RESULTS: Compared with placebo, all benazepril/hydrochlorothiazide combinations produced statistically significant reductions from baseline in sitting diastolic and systolic blood pressures at study end point. In the benazepril/hydrochlorothiazide, 20/25 mg, group, the adjusted mean changes in sitting diastolic blood pressure at end point were statistically significantly greater than those in the monotherapy treatment groups (benazepril, 20 mg, P < or = .05; hydrochlorothiazide, 25 mg, P < or = .001) alone. All therapies were generally well tolerated. Decreases in mean serum potassium level with hydrochlorothiazide monotherapy were reduced or eliminated with combination therapy. CONCLUSION: Benazepril in combination with hydrochlorothiazide, including a low-dose combination of 5/6.25 mg, is effective in reducing sitting diastolic and systolic blood pressure in patients with hypertension.

Adult↗
PubMed1995

Superactive lipophilic peptides discriminate multiple vasoactive intestinal peptide receptors.

To distinguish vasoactive intestinal peptide (VIP) receptors in the brain-mediating neurotransmission and neurotrophism, potent VIP analogues were designed. Using a single amino acid substitution and the addition of a fatty acyl moiety, an analogue was devised that exhibited both a 100-fold greater potency than VIP and specificity for a VIP receptor associated with neuronal survival. This VIP agonist increased neuronal survival via a cAMP-independent mechanism. Identical chemical modification of a prototype VIP antagonist (Met-Hybrid, Neurotensin6-11-VIP7-28) also resulted in a 100-fold greater potency in blocking VIP-mediated increases in neuronal survival. Blockade of circadian activity rhythms was limited to VIP antagonists that could inhibit VIP-mediated increases in cAMP. These lipophilic peptides provide novel tools in receptor discrimination and drug design.

Amino Acid Sequence↗
PubMed1994

Diurnal oscillation in vasoactive intestinal peptide gene expression independent of environmental light entraining.

Vasoactive intestinal peptide (VIP) is a neuromodulator and secretagogue for neuronal survival factors. Moreover, in the suprachiasmatic nucleus (SCN) of mature animals, where the circadian clock resides, day-night cycles are paralleled by rhythmical alteration in the levels of the mRNA encoding VIP. We now show, for the first time, that diurnal oscillation in VIP mRNA occurred in animals reared in the dark and also preceded eye opening. Thus, by Northern blot hybridization elevated levels of VIP mRNA were measured at night time as compared to day time. Furthermore, diurnal oscillation in VIP mRNA were more pronounced in rats reared in the dark. These observations suggested an endogenous as well as exogenous (environmental) control of VIP gene expression in the SCN and implicated VIP as an integral part of the circadian clock.

Aging↗
PubMed1983

Physician turnover in eight New England prepaid group practices: an analysis.

The objectives of this questionnaire study of all primary care physicians (N = 154) who had ever worked in eight New England prepaid group practices (PGPs) include 1) calculation of turnover rates, 2) comparison of those who stayed in (stayers) versus those who left (leavers) the PGPs, and 3) description of reasons given for leaving. An annual turnover rate of 3.9 to 6.3 per cent, depending upon the measure, was within the range reported by others. Factors associated with stayer-leaver status were experiences before and during the physician's PGP tenure. Leavers reported pre-PGP experience in fee-for-service, hospital-based, and academic positions, and while in the PGPs, they reported constraints on autonomy, independence, and professional development. Leavers reported higher incomes and longer working hours in their new practices. They cited the potential for greater autonomy as the reason for leaving. The findings and study limitations are discussed.

Attitude of Health Personnel↗
PubMedDate not supplied

Complete avulsion of the triceps tendon: MRI diagnosis.

Avulsion of the triceps tendon is a rare injury. We report a case of complete avulsion of the triceps tendon diagnosed by magnetic resonance imaging (MRI) and confirmed surgically. The excellent soft tissue contrast and multiplanar imaging capability of MRI makes it an ideal tool to diagnose this disorder. To our knowledge, this is the first reported case of MRI diagnosis of complete avulsion of the triceps tendon.

Arm Injuries↗
PubMedDate not supplied

Chronic moniliasis.

Explore the source record for details and available documents.

Adult↗
PubMedDate not supplied

Treatment of patients with essential hypertension: amlodipine 5 mg/benazepril 20 mg compared with amlodipine 5 mg, benazepril 20 mg, and placebo.

This multicenter, double-masked, randomized, parallel-group study compared the efficacy, tolerability, and safety of amlodipine 5 mg/benazepril 20 mg, amlodipine 5 mg, benazepril 20 mg, and placebo in patients with essential hypertension. After a placebo run-in period, 308 patients (all white) were randomized to treatment groups and took medication once daily for 8 weeks. Blood pressure was measured after 4 and 8 weeks of treatment in the 23- to 26-hour period after dosing. Patients wore a noninvasive blood pressure monitor for 24 hours before randomization and before the final visit. Investigators recorded adverse experiences at randomization and at study weeks 4 and 8, and obtained specimens for laboratory testing at randomization and at study week 8. Three hundred seven patients were evaluated for efficacy, and 308 for tolerability and safety. At end point (the last postrandomization measurement for each patient), the reduction in mean sitting diastolic blood pressure with the amlodipine 5 mg/benazepril 20 mg treatment was statistically significantly greater than with any comparative therapy. The results of 24-hour monitoring showed that the amlodipine/benazepril treatment, unlike monotherapy, maintained the hourly mean diastolic blood pressure at < or = 90 mm Hg. A responder rate of 87.0% was observed with amlodipine 5 mg/benazepril 20 mg versus 67.5%, 53.3%, and 15.8% with amlodipine, benazepril, and placebo, respectively. This difference between the amlodipine/benazepril treatment group and each comparative single-agent treatment group was statistically significant. Drug-related adverse events occurred in 15.6% of patients in the amlodipine/benazepril group and in 24.7%, 6.5%, and 11.7% of patients in the amlodipine, benazepril, and placebo groups, respectively. Edema occurred less often in the amlodipine/benazepril group than in the amlodipine group. Overall, once-daily therapy with amlodipine 5 mg/benazepril 20 mg provided an antihypertensive effect that was statistically and clinically superior to amlodipine 5 mg alone, benazepril 20 mg alone, and placebo, was well tolerated, and was associated with less edema than the amlodipine treatment.

Administration, Oral↗
PubMedDate not supplied

Dose-responsive antihypertensive efficacy of valsartan, a new angiotensin II-receptor blocker.

Predictable dose-related efficacy is considered to be an important attribute of any antihypertensive agent. To determine the magnitude of dose-responsive efficacy for valsartan, a highly selective angiotensin II-receptor blocker, we conducted an integrated analysis of efficacy data from nine double-masked, randomized, placebo-controlled, parallel studies of similar design and of at least 4 weeks' duration. The intent-to-treat analysis included 4067 patients with mild-to-moderate hypertension who had received valsartan (n = 2901) 10, 20, 40, 80, 160, or 320 mg once daily or placebo (n = 1166). Blood pressure was assessed at trough (24 hours after the last dose). In all nine studies, valsartan doses > or = 80 mg produced statistically significant reductions in supine or seated diastolic blood pressure (SDBP) and systolic blood pressure (SSBP) compared with placebo (P < 0.05). The integrated analysis demonstrated a clear increase in blood-pressure-lowering efficacy with increasing dose across the range 10 to 320 mg (placebo-subtracted mean changes from baseline to end point for valsartan 10, 20, 40, 80, 160, and 320 mg, respectively: SDBP, -0.8, -2.8, -2.6, -3.9, -5.1, and -6.4 mm Hg; SSBP, -1.3, -5.7, -5.3, -6.8, -8.6, and -9.0 mm Hg). The data demonstrate that valsartan provides dose-responsive antihypertensive efficacy across the therapeutic dose range, with clinically relevant blood-pressure lowering at doses > or = 80 mg once daily.

Adult↗