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The QUO VADIS (the effects of QUinapril On Vascular Ace and Determinants of ISchemia) study was a randomized, double-blind, placebo-controlled trial designed to evaluate the effects of long-term angiotensin-converting enzyme (ACE) inhibition on angiotensin II formation in human vasculature. Patients (n = 187) scheduled for coronary artery bypass surgery used study medication 27 +/- 1 days before surgery. Segments of internal mammary arteries were exposed to increasing doses (0.1 nM-1 microM) of angiotensin I and II in organ baths. The rate of local angiotensin II formation is a function of the reciprocal of the difference between the pEC50's of the dose response curves to angiotensin I and II (-log/mol) and of the area between the curves (units). Quinapril (40 mg) and captopril (3 x 50 mg) similarly and significantly reduced mean blood pressure compared with placebo (p = 0.04). Difference between pEC50's was 0.90 +/- 0.08 in quinapril patients compared with 0.60 +/- 0.08 for placebo (p = 0.01); the area between curves was 91 +/- 8 for quinapril patients compared with 67 +/- 8 for placebo (p = 0.03). Angiotensin II formation was decreased to a lesser extent with captopril and was not statistically different from placebo (p = 0.3); the difference between pEC50's was 0.83 +/- 0.15; the area between curves was 84 +/- 12. This is the first randomized study to demonstrate that long-term oral treatment with an ACE inhibitor reduces vascular angiotensin II formation in humans.

This pilot study investigated the efficacy of high-dose gemfibrozil (2400 mg/day) in treating patients with elevated lipoprotein (a) [Lp(a)]. Lp(a) has been shown to be an independent risk factor for the development of coronary heart disease (CHD).Eleven patients with serum Lp(a)/=45 mg/dl participated in this 12-week study. Initially, all patients received oral gemfibrozil 600mg twice daily. At 4-week intervals, the dose was increased by 600mg for patients able to tolerate the increase up to a maximum of 2400 mg/day.Eight patients completed the study. Three of these patients met the predetermined criterion of a clinically meaningful Lp(a) reduction of 33%. The mean percentage change in Lp(a) was not statistically significant with values of -18.3 +/- 15.4% (p = 0.14, 1-tailed). All patients demonstrated a significant decrease in plasma triglycerides. The mean percentage change was -62.5 +/- 1.8% (p0.001, 1-tailed). The mean percentage change in total cholesterol was -12.4 +/- 3.8% (p = 0.007, 1-tailed). Gemfibrozil was considered suspect in five of 16 adverse events reported, but only one of these (dyspepsia) caused withdrawal from the study. For all patients participating in the study no adverse event was characterised as severe.While the small number of patients does not allow any definitive conclusion on effectiveness to be drawn, the results suggest that further randomised studies utilising larger patient numbers appear warranted.

Procainamide is a class IA antiarrhythmic drug indicated for the treatment of life-threatening or symptomatic ventricular arrhythmias. The current sustained-release formulation requires 6-hour dosing (qid). To improve patient compliance, a new sustained-release formulation for twice-daily (bid) administration has been developed (Procanbid, Parke-Davis). This study assesses the pharmacologic equivalence of the bid and qid formulations in the suppression of symptomatic ventricular premature depolarizations (VPDs). Fourteen centers enrolled a total of 99 patients with frequent symptomatic VPDs (average ≥20 VPDs/hr) who previously responded to and tolerated the procainamide qid formulation. During the first week of the double-blind phase, patients were randomized to either placebo or procainamide dosages of 1000, 2000, or 4000 mg/d (bid or qid formulations). In the second week, the patients were crossed over to the alternate formulation. Seventy-seven patients qualified for the primary activity analysis. The bid and qid formulations showed comparable effectiveness in the suppression of mean VPDs with a linear dose-response relationship. The VPD suppression was not attenuated towards the end of the dosing interval for either formulation. Sixty-eight of these patients entered an optional 1-year extension to receive the bid formulation. Thirty-seven (54%) patients had adverse effects. Of those, 15 (22%) had side effects considered treatment related. Most of the adverse events occurred during the first 6 weeks of treatment. Only a few patients (8%) withdrew as a consequence of treatment with the bid formulation. The overall safety profile of the bid formulation was similar to other formulations, and the procainamide bid formulation has a low proarrhythmic rate (`3%). In conclusion, the effectiveness of the twice-daily formulation of procainamide in the suppression of VPDs is comparable to the currently available qid formulation.

THE substrate surface characteristics are known to affect the hysteresis properties, the reproducibility, and the development of a uniaxial anisotropy in vacuum or electro-deposited permalloy thin ( < 2000 A) films. The primary requisites of a satisfactory substrate for development of uniaxial anisotropy in magnetic thin films are: (1) extreme smoothness; and (2) an amorphous or micro-crystalline structure. Electroless nickel (chemical deposition) has been reported, to be amorphous1 as well as micro-crystalline2 in character. Consequently, chemically (electroless) deposited films of nickel were evaluated as substrates for electro-deposited permalloy films. The electroless nickel was deposited in a manner suggested by Brenner3 on to a polyester film base.