Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria. European Microalbuminuria Captopril Study Group.

OBJECTIVES: To study the effect of angiotensin converting enzyme inhibition on the rate of progression to clinical proteinuria and the rate of change of albumin excretion rates in patients with insulin-dependent diabetes mellitus and persistent microalbuminuria. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled clinical trial of 2 years' duration at 12 hospital-based diabetes centers. PATIENTS: Ninety-two patients with insulin-dependent diabetes mellitus and persistent microalbuminuria but no hypertension. INTERVENTION: The patients were randomly allocated in blocks of two to receive either captopril, 50 mg, or placebo twice per day. MEASUREMENTS: Albumin excretion rate, blood pressure, glycosylated hemoglobin level, and fructosamine level every 3 months; urinary urea nitrogen excretion every 6 months; and glomerular filtration rate every 12 months. RESULTS: Twelve patients receiving placebo and four receiving captopril progressed to clinical proteinuria, defined as an albumin excretion rate persistently greater than 200 micrograms/min and at least a 30% increase from baseline (P = .05). The probability of progression to clinical proteinuria was significantly reduced by captopril therapy (P = .03 by log-rank test). Albumin excretion rate rose from a geometric mean (95% confidence interval) of 52 (39 to 68) to 76 (47 to 122) micrograms/min in the placebo group but fell from 52 (41 to 65) to 41 (28 to 60) micrograms/min in the captopril group, a significant difference (P < .01). Mean blood pressure was similar at baseline in the two groups and remained unchanged in the placebo group but fell significantly, by 3 to 7 mm Hg, in the captopril group. Glycosylated hemoglobin levels and glomerular filtration rate remained stable in the two groups. CONCLUSIONS: Captopril therapy significantly impeded progression to clinical proteinuria and prevented the increase in albumin excretion rate in nonhypertensive patients with insulin-dependent diabetes mellitus and persistent microalbuminuria.

Disk susceptibility studies with cefazolin and cephalothin.

Cefazolin and cephalothin disk susceptibility and minimal inhibitory concentration determinations were conducted on 591 clinical isolates. Cefazolin demonstrated superior activity, as shown by lower minimal inhibitory concentrations, and a greater percentage of isolates inhibited in the disk susceptibility test. The cephalothin antibiotic class disk by the standard Bauer-Kirby method failed to detect susceptibility to cefazolin in a significant percentage of Escherchia coli, Enterobacter species, and Enterococcus isolates. A separate cefazolin disk with a susceptibility cut-off point of 18 mm is recommended. An alternative to a separate cefazolin disk would be a reinterpretation of the cephalothin susceptibility disk zone diameters so that it would more adequately predict cefazolin activity.

Comparative serum levels and protective activity of parenterally administered cephalosporins in experimental animals.

Six cephalosporin antibiotics were administered subcutaneously to mice at a level of 20 mg/kg. The serum levels of each were determined at five time intervals ranging from 5 to 120 min after dosing. Urinary recovery and the presence of active metabolites in mouse urine were determined. The peak serum levels and serum half-lives in mice were found to be positively correlated with the mean effective dose values obtained after lethal challenge with Escherichia coli. The administration of cefazolin and cephanone resulted in the highest serum level and the best protection. Good protection was obtained with cephaloridine despite somewhat lower serum levels. The cephalosporins with the acetoxy side chain (cephalothin, cephapirin, and cephacetrile) showed lower serum levels and the poorest protection. Cefazolin, cephaloridine, and cephalothin serum levels were also determined in dogs, squirrel monkeys, and rabbits. A mixed response was obtained in these species, with cefazolin peak serum levels being highest in rabbits and cephaloridine peak highest in dogs.

Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD Investigators. Survival With Oral d-Sotalol.

BACKGROUND: Left ventricular dysfunction after myocardial infarction is associated with an increased risk of death. Other studies have suggested that a potassium-channel blocker might reduce this risk with minimal adverse effects. We investigated whether d-sotalol, a pure potassium-channel blocker with no clinically significant beta-blocking activity, could reduce all-cause mortality in these high-risk patients. METHODS: Patients with a left ventricular ejection fraction of 40% or less and either a recent (6-42 days) myocardial infarction or symptomatic heart failure with a remote (> 42 days) myocardial infarction were randomly assigned d-sotalol (100 mg increased to 200 mg twice daily, if tolerated) or matching placebo twice daily. FINDINGS: After 3121 of the planned 6400 patients had been recruited, the trial was stopped. Among 1549 patients assigned d-sotalol, there were 78 deaths (5.0%) compared with 48 deaths (3.1%) among the 1572 patients assigned placebo (relative risk 1.65 [95% CI 1.15-2.36], p = 0.006). Presumed arrhythmic deaths (relative risk 1.77 [1.15-2.74], p = 0.008) accounted for the increased mortality. The effect was greater in patients with a left ventricular ejection fraction of 31-40% than in those with lower (