Prednisolone pharmacokinetics in patients with rheumatoid arthritis,polymyalgia rheumatica and asthma

Summary The pharmacokinetic profile of a single 10 mg oral dose of prednisolone was studied in three groups of six patients with rheumatoid arthritis (RA), polymyalgia rheumatica (PMR) and bronchial asthma (BA) who were already receiving steroid therapy. A fourth group of age and sex-matched normal controls was also studied. Kinetic parameters (including elimination half-life, area under the plasma concentration curve, apparent volume of distribution and total body clearance) were similar for all four groups but there was considerable intersubject variability. The correlations between these kinetic parameters and age, body weight and serum albumin were poor. The results suggest that any differences in the effects of corticosteroids in these inflammatory diseases are unlikely to be due to pharmacokinetic factors. The duration of steroid therapy and the reduction in patient mobility would appear to be more likely explanations for the reduction in bone mass observed in patients with RA.     

Studies of nonoxynol-9. I. The effect on the vaginas of rabbits and rats

A standard rabbit vaginal irritation test was used to evaluate the morphologic reaction to an aqueous solution of a nonionic spermicidal detergent, nonoxynol-9 (N-9). Various amounts of N-9, between 2.5 mg and 50 mg, were incorporated into cylindrical collagen sponges which were retained in the vagina for 10 days. Changes in the continuity of the epithelial lining, edema of the submucosal layer, and the inflammatory cell infiltrate of this layer were proportional to the amount of N-9 tested. An increase in semiquantitative score for the inflammatory changes in the vagina was noted for increasing amounts of N-9. In young adult female rats treated vaginally with 5 mg/100 gm body weight/day of aqueous N-9 for 5 to 20 days, the number of cells (DNA) was significantly increased on day 5. The collagen content in the vaginal wall (hydroxyproline) was significantly increased after 15 and 20 daily injections of the detergent. We conclude that both morphologic and chemical changes in the vagina are compatible with the inflammatory reaction induced by the detergent tested.     

Multicenter seroepidemiologic study of the impact of cytomegalovirus infection on renal transplantation

The effects of cytomegalovirus (CMV) infection on patient and allograft survival were determined in 1245 renal transplant recipients from 46 transplant centers. When an antilymphocyte preparation was administered to cadaveric allograft recipients, those at risk for primary CMV had a worse outcome than similar patients treated with prednisone and azathioprine (53.1% alive at 6 months with a functioning allograft vs. 70.8%, P = .05) or patients at risk for reactivation CMV (53.1% vs. 71.1%, P = .035). Patients at risk for reactivation CMV had a better outcome if they received an antilymphocyte preparation (71.1% vs. 60.8%, P less than .01). The type of immunosuppression had no effect on patients without CMV. Living-related donor transplantation was not significantly influenced by CMV or type of immunosuppression. We conclude that CMV infection is strongly influenced by the form of immunosuppression employed, and that both are important determinants of the outcome of cadaveric renal transplantation.     

Navy Hearing Conservation Program: threshold shifts in enlisted personnel, 1995-1999.

This study presents audiometric information from 54,057 Navy enlisted personnel in the Navy and Marine Corps Hearing Conservation Program database from 1995 to 1999. The purpose was to compare current threshold shift patterns for Navy enlisted population with historical literature and review programmatic effectiveness issues. The data suggest that 82% of the population did not display significant threshold shift (STS) on the "annual" and "termination" audiograms, which increased to 94% after the "follow-up 2" examination. Compared with historical data, STS rates were significantly lower for the most junior enlisted personnel (E1-E3) (odds ratio = 0.34, p = 0.00, 95% confidence interval = 0.30-0.39) but not significantly different for more senior enlisted personnel (odds ratio = 0.96, p = 0.22, 95% confidence interval = 0.90-1.03). STS rates did not appear to correlate with expected "high" and "low" noise exposure Navy enlisted occupations. This suggests further investigation to readdress the possible risk factors other than noise intensity/duration.     

Three-dimensional mapping of right atrial activation during sinus rhythm and its relationship to endocardial architecture

INTRODUCTION: Previous mapping studies of right atrial (RA) activation during sinus rhythm have been limited by the use of epicardial electrode plaques in open chest subjects or microelectrodes in the excised heart. This study describes global RA endocardial activation patterns using high-density mapping and compares the results with underlying endocardial architecture. METHODS AND RESULTS: Noncontact mapping of the RA was performed in 21 anesthetized swine. Isopotential and isochronal maps were superimposed upon three-dimensional reconstructions of RA geometry. Hearts were excised and endocardial dissection performed. Two patterns of RA activation were recorded. The site of earliest endocardial activation occurred either laterally at a position consistent with the terminal crest or superiorly at the junction between the superior caval vein and RA appendage. The subsequent spread of depolarization followed the longitudinal orientation of muscle fibers. Areas of conduction delay and block were seen at the junction between the terminal crest and posterior wall, the cavotricuspid isthmus, and around the margins of the triangle of Koch. Endocardial dissection at these sites demonstrated complex fiber orientation. A lateral site of earliest activation demonstrated a more prominent display of conduction delay or block. CONCLUSION: The spread of the sinus impulse follows endocardial myofiber orientation and is dictated by the site of earliest activation. Even during sinus rhythm, anisotropic conduction results in areas of conduction block or delay. These findings have implications in the development of reentrant arrhythmias and may influence surgical or electrophysiologic procedures.