Faculty Bibliography

We studied the effects of LEX032, a novel serine protease inhibitor, on N(G)-nitro-L-arginine methyl ester (L-NAME) induced leukocyte-endothelium interactions in vivo, utilizing intravital microscopy of the rat mesentery. Superfusion of the rat mesentery with 50 microM L-NAME, a nitric oxide (NO) inhibitor, for 90 min resulted in a significant and time-dependent increase in leukocyte rolling, leukocyte adherence, and transmigration of leukocytes, compared to control rats superfused with Krebs-Henseleit (K-H) solution. However, systemic administration of LEX032 (15 mg/kg bolus injection followed by a 15 mg/kg per hour infusion) to L-NAME superfused rats significantly attenuated leukocyte rolling and adherence along the venular endothelium of the rat mesentery, and also inhibited transmigration of leukocytes through the microvascular endothelial wall. Moreover, no significant changes were observed in mean arterial blood pressure or local venular shear rates following systemic administration of LEX032. Our data demonstrate that systemic inhibition of serine proteases by LEX032 reduces enhanced leukocyte-endothelium interactions provoked by inhibition of NO synthesis. These results also explain some of the beneficial effects exerted by serine protease inhibitors in ischemia-reperfusion and other inflammatory states.

The growing strength of managed care has diminished the financial and clinical autonomy of many orthopaedic surgeons. In part to offset these negative trends, new relationships are being developed to define doctors' methods of contracting with health-maintenance organizations. These include physician practice management companies (PPMs), independent practice associations, management service organizations, and physician-sponsored organizations. Each entity offers distinct advantages and disadvantages. While the PPM is the most popular new vehicle to offset adverse market trends, it carries with it some of the greatest potential pitfalls. In every case, before negotiating to join one of these new entities, it is important for a physician to have a solid understanding of the competing claims made by each entity, as well as insight into the fiscal health of the particular company in question. For some doctors, these arrangements offer a solution to current woes. For others, PPMs interpose another meddlesome intermediary in a market already bloated by layers of bureaucracy.

OBJECTIVE: To assess the effect of a screen for problem drinking on medical residents and their patients. DESIGN: Descriptive cohort study. SETTING: Veterans Affairs Medical Clinic. PATIENTS: Patients were screened 2 weeks before a scheduled visit (n = 714). Physicians were informed if their patients scored positive. MEASUREMENTS AND MAIN RESULTS: Physician discussion of alcohol use was documented through patient interview and chart review. Self-reported alcohol consumption was recorded. Of 236 current drinkers, 28% were positive for problem drinking by the Alcohol Use Disorders Identification Test (AUDIT). Of 58 positive patients contacted at 1 month, 78% recalled a discussion about alcohol use, 58% were advised to decrease drinking, and 9% were referred for treatment. In 57 positive patient charts, alcohol use was noted in 33 (58%), and a recommendation in 14 (25%). Newly identified patients had fewer notations than patients with prior alcohol problems. Overall, 6-month alcohol consumption decreased in both AUDIT-positive and AUDIT-negative patients. The proportion of positive patients who consumed more than 16 drinks per week (problem drinking) decreased from 58% to 49%. Problem drinking at 6 months was independent of physician discussion or chart notation. CONCLUSIONS: Resident physicians discussed alcohol use in a majority of patients who screened positive for alcohol problems but less often offered specific advice or treatment. Furthermore, residents were less likely to note concerns about alcohol use in charts of patients newly identified. Finally, a screen for alcohol abuse may influence patient consumption.

David M. Oshinsky reviews the book "The Children" by David Halberstam