Inhibiting HIV-1 entry with fusion inhibitors.

In recent years, tremendous progress has been made in understanding the HIV-1 entry process in which the viral and cellular membranes are fused, resulting in the subsequent delivery of the viral genome into the host cell. The mechanistic insight gained from these studies has led to the formulation of exciting new approaches for therapeutic intervention. One of the first and clinically most advanced drugs to emerge from this effort is the fusion inhibitor T20. T20 acts by freezing a transient structural intermediate of the HIV-1 fusion process, thus blocking an essential step in viral entry. With phase III clinical trials already well underway, the success of T20 indicates that targeting of the viral entry process will soon be an important component of antiretroviral therapy. This review addresses this rapidly developing area of HIV research, with a focus on the mechanistic role of fusion inhibitors targeted to the HIV-1 gp41 transmembrane glycoprotein. We will review the results of recent clinical trials with T20 and discuss possible mechanisms of viral escape through the evolution of drug-resistant HIV-1 variants. We will also discuss ongoing research on fusion inhibitor susceptibility testing and the development of new improved fusion inhibitors.

Reduced hospitalization cost for patients with pectus excavatum treated using minimally invasive surgery.

BACKGROUND: Currently, few data exist regarding the relative costs associated with open and minimally invasive pectus excavatum repair. The aim of this study was to compare the surgical and hospitalization costs for these two surgical techniques and to identify factors responsible for cost differences. METHODS: A retrospective review of hospital charts, patient and parent questionnaires, and hospital accounting records was performed for 68 patients who underwent surgical correction of pectus excavatum between June 1996 and December 1999. RESULTS: In this series, 25 patients underwent open repair, whereas 43 patients underwent minimally invasive repair of pectus excavatum (MIRPE). The patient ages ranged from 4 to 19 years. The average ages for open repair (12 years) and MIRPE (11 years) did not differ significantly. As compared with open repair, MIRPE was associated with a 27% lower overall cost of hospitalization ( p < 0.05). The operating room costs were 12% higher for the patients who underwent MIRPE ( p < 0.05). The mean operative time for open repair was 3 h 15 min, whereas MIRPE required 1 h 10 min ( p < 0.001). The hospital stay for open repair averaged 4.4 days, as compared with 2.4 days for MIRPE ( p < 0.001). In contrast to other published series, the postoperative analgesia after MIRPE in this series consisted of narcotics, ketorolac, and methocarbamol. No patient received epidural analgesia, regardless of the repair technique selected. The postoperative complication rate was 4% in the open group and 14% in the MIRPE group. Most of the patients treated with either open or MIRPE reported postoperative oral narcotic usage for 2 weeks or less and returned to routine activities within 3 weeks. The patients and parents alike reported good to excellent overall outcomes in 85% or more of the open repair cases and 90% or more of the MIRPE cases. CONCLUSIONS: These data demonstrate for the first time that the use of an alternate pain management strategy including, narcotics, NSAIDs, and methocarbamol, but without epidural catheters, results in reduced hospital length of stay and decreased overall hospitalization costs for MIRPE, as compared with open pectus repair. This cost benefit was achieved without compromising pain management or patient satisfaction with surgical care.

Neonatal renovascular hypertension - a complication of aortic monitoring catheters.

Two critically ill neonates with severe renovascular hypertension as a complication of aortic monitoring catheter are presented. They did not respond to intensive medical therapy for hypertension. In spite of their precarious general condition, nephrectomy was undertaken with complete relief of symptoms.