Pharmacokinetics of intravenous bepridil in patients with coronary disease

The pharmacokinetics of intravenous bepridil (1-[2-(N-benzylanilino)-1-(isobutoxymethyl)ethyl]pyrrolidine ) were studied in 16 patients undergoing cardiac catheterization for evaluation of coronary disease, all with normal base-line hemodynamic and renal functions. Ten patients received 3 mg/kg and six patients received 4 mg/kg of bepridil infused over a period of 30 min. Plasma bepridil concentrations were measured by HPLC and analyzed by model-dependent and model-independent methods. The mean (+/- SD) maximum plasma bepridil concentrations at the end of the infusion were 2047 +/- 820 ng/mL (3 mg/kg) and 2478 +/- 1426 ng/mL (4 mg/kg). Postinfusion bepridil concentrations were best described by a two-compartment open model. The model-dependent harmonic mean distribution and elimination half-lives were 1.7 h (range: 1.1-2.2 h) and 19.7 h (range: 8.0-61.9 h), respectively. The harmonic mean elimination half-life from model-independent analysis was 14.9 h (range: 7.4-64.0 h). The arithmetic means of other model-independent kinetic parameters were systemic clearance, 0.524 +/- 0.215 L X kg-1 X h-1; Vd, 15.3 +/- 10.9 L/kg; and Vdss, 10.1 +/- 6.0 L/kg. Model-dependent and model-independent estimates of half-life and clearance agreed reasonably well. Bepridil was well tolerated, effecting little or no change in central hemodynamics or EKG intervals. The extensive distribution and relatively slow clearance of bepridil account for its long elimination half-life. Intravenous bepridil appears to be a safe calcium (II) antagonist that is suitable for once-a-day dosing.     

Comparison of onset and steady-state responses of hearing aids: implications for use of the auditory brainstem response in the selection of hearing aids

Input-output (I/O) functions of hearing aids were measured in response to a 2000-Hz tone burst, having 0.5 ms rise/fall time and 10 ms duration. I/O functions, measured with a hearing-aid analyzer, served as reference conditions. Hearing-aid outputs at onset and during the steady-state portion of the waveform differed; these differences often depended upon stimulus rate. The relation between onset and steady-state estimates of output were not always predictable from hearing-aid attack and release times. These findings indicate that the steady-state output limitation characteristics of hearing aids cannot be estimated from their onset responses. In turn, this suggests that ABR measurements may not provide accurate estimates of the compressive characteristics of hearing aids.     

The incidence of AIDS among blacks and Hispanics

Compared with whites, the acquired immune deficiency syndrome (AIDS) has affected blacks and Hispanics disproportionately. The cumulative incidence (CI) for black men was 2.6, and for Hispanic men 2.5, times the rate for white men. Intravenous (IV) needle use alone does not account for this difference. Not counting IV needle-using cases, the CIs for black and Hispanic men were 1.7 times the CI for white men. Although there were fewer cases in women than men, the white-to-minority disparity was greater for women. The CIs for black and Hispanic women were 12.2 and 8.5 times, respectively, the CI for white women. Prevention programs are urgently needed and should focus on risky behavior (IV needle sharing and receptive anal intercourse), not just risk groups.     

Experimental demonstration of the immunogenicity of silicone-protein complexes

Although silicones, as a class, are nontoxic in animal and tissue studies, implanted silicone prostheses and medical devices are associated with various local and systemic host inflammatory reactions. They also have been associated with a form of autoimmune disease. To test the hypothesis that silicones may evoke an immunologically mediated inflammatory reaction, 10 guinea pigs were stimulated for 1 month with intraperitoneal injections of sterile medical-grade silicone oil admixed with homologous serum and complete Freund's adjuvant. Ten controls were stimulated with saline. Four additional animals were passively sensitized with splenic homogenates from four sensitized animals. Intradermal antigenic challenges consisted of silicone-homologous serum, pure silicone, saline-homologous serum, and purified protein derivative. Cutaneous reaction patterns were graded grossly and microscopically. Silicone-serum and purified protein derivative antigens evoked three to four times greater palpable lesions in all 10 actively and all 4 passively sensitized animals at approximately 24 h compared to controls. Biopsies showed a moderate to marked lymphocytic infiltrate. Control sites and naive animals showed only edema at the challenge sites. The data suggest that silicone-protein complexes are potentially immunogenic.     

Reduced prevalence of early preterm delivery in women with Type 1 diabetes and microalbuminuria--possible effect of early antihypertensive treatment during pregnancy.

AIMS: In normotensive women with Type 1 diabetes and microalbuminuria we previously found preterm delivery (< 34 weeks) in 23% of the pregnancies. Antihypertensive treatment was initiated in late pregnancy when preeclampsia was diagnosed and diastolic blood pressure > 90 mmHg. From April 2000 our routine was changed and early antihypertensive treatment with methyldopa was initiated if antihypertensive treatment was given prior to pregnancy, if urinary albumin excretion (UAE) was > 2 g/24 h, or blood pressure > 140/90 mmHg. The present study describes the impact of this more aggressive antiypertensive treatment in the prevalence of preterm delivery. METHODS: The old cohort (1995-1999) consisted of 26 and the new cohort (2000-2003) of 20 pregnant women with Type 1 diabetes and microalbuminuria. All were referred before gestational week 17. RESULTS: The cohorts were comparable with regard to age, diabetes duration, prepregnancy body mass index, HbA1c, blood pressure 121 (13)/71 (8) vs. 121 (14)/73 (8) mmHg [mean (sd)] and early UAE 69 (16-278) vs. 74 (30-287) mg/24 h (geometric mean and range). Antihypertensive treatment was initiated in the old cohort at 29 (20-33) weeks, n = 9, and in the new at 13 (0-34) weeks, n = 10. The prevalence of preterm delivery before 34 weeks was reduced from 23% to zero (P = 0.02), preterm delivery before 37 weeks from 62% to 40% (P = 0.15) and preeclampsia from 42% to 20% (P = 0.11). Perinatal mortality occurred in 4% vs. 0%. Birth weight was 3124 (767) g vs. 3279 (663) g. CONCLUSION: Introduction of early antihypertensive treatment with methyldopa in normotensive pregnant women with Type 1 diabetes and microalbuminuria resulted in a significant reduction in preterm delivery before gestational week 34.