Showing papers by "John P. Boehmer published in 2005"

A Multicenter, Prospective, Randomized, Double-Blind Trial of Basiliximab in Heart Transplantation

Abstract: Background The role and pharmacokinetics of interleukin-2 (IL-2) monoclonal antibodies (mAbs) in heart transplantation remain unclear. This 1-year double-blind, randomized, placebo-controlled study evaluated safety, tolerability, and pharmacokinetics of the IL-2 mAb basiliximab with cyclosporine, mycophenolate mofetil, and steroids in adult de novo heart transplant recipients. Methods Fifty-six patients received either basiliximab (20 mg) or placebo on Days 0 and 4 post-transplantation. Safety assessments included adverse events, serious adverse events, and infections. The time to and severity of biopsy-proven acute rejection (BPAR) were also assessed. Results Basiliximab was generally well tolerated. There were no significant differences between treatment groups with respect to adverse event profiles, serious adverse events (84.0% vs 61.3%), or infections (84% vs 74.2%). The mean number of days to first BPAR was longer with basiliximab (73.7 ± 59.68) than placebo (40.6 ± 53.30) at 6 months, but not statistically significant (trend). The duration that basiliximab concentrations exceeded the CD25 saturation threshold averaged 38 ± 13 days. Patients with rejection did not clear basiliximab faster or have shorter durations of saturation than rejection-free patients. None of the patients screened had detectable anti-idiotype antibodies. Conclusions These pilot results describe the pharmacokinetics of basiliximab and show that basiliximab appears to be tolerated with a similar safety profile to placebo in adult de novo heart transplant recipients. Larger scale clinical trials are feasible and warranted.

Renal vascular response to static handgrip exercise: Sympathetic vs. autoregulatory control

Abstract: Static exercise causes activation of the sympathetic nervous system, which results in increased blood pressure (BP) and renal vascular resistance (RVR). The question arises as to whether renal vasoconstriction that occurs during static exercise is due to sympathetic activation and/or related to a pressure-dependent renal autoregulatory mechanism. To address this issue, we monitored renal blood flow velocity (RBV) responses to two different handgrip (HG) exercise paradigms in 7 kidney transplant recipients (RTX) and 11 age-matched healthy control subjects. Transplanted kidneys are functionally denervated. Beat-by-beat analyses of changes in RBV (observed via duplex ultrasound), BP, and heart rate were performed during HG exercise in all subjects. An index of RVR was calculated as BP/RBV. In protocol 1, fatiguing HG exercise (40% of maximum voluntary contraction) led to significant increases in RVR in both groups. However, at the end of exercise, RVR was more than fourfold higher in control subjects than in the RTX group (88 vs. 20% increase over baseline; interaction, P < 0.001). In protocol 2, short bouts of HG exercise (15 s) led to significant increases in RVR at higher workloads (50 and 70% of maximum voluntary contraction) in the control subjects (P < 0.001). RVR did not increase in the RTX group. In conclusion, we observed grossly attenuated renal vasoconstrictor responses to exercise in RTX subjects, in whom transplanted kidneys were considered functionally denervated. Our results suggest that renal vasoconstrictor responses to exercise in conscious humans are mainly dependent on activation of a neural mechanism.