Alemtuzumab preconditioning with tacrolimus monotherapy - The impact of serial monitoring for donor-specific antibody

BACKGROUND. Antibody preconditioning with tacrolimus monotherapy has allowed many renal allograft recipients to be maintained on spaced weaning. METHODS. Of 279 renal allograft recipients transplanted between March 2003 and December 2004, 222 (80%) had spaced weaning (i.e., reduction of tacrolimus monotherapy dosing to every other day, three times a week, twice a week, or once a week) attempted. Routine monitoring for donor-specific antibody (DSA) was begun in September 2004. Mean follow-up is 34±6.5 months after transplantation and 26±8.1 months after the initiation of spaced weaning. RESULTS. One hundred and twenty-two (44%) patients remained on spaced weaning. One- and 2-year actual patient/graft survival was 99%/99%, and 97%/96%. Fifty-six (20%) patients experienced acute rejection after initiation of spaced weaning. One- and 2-year actual patient/graft survival was 100%/98%, and 94%/78%. Forty-two (15%) patients with stable renal function had spaced weaning stopped because of the development of DSA, which disappeared in 17 (40%). One- and 2-year actual patient and graft survival was 100% and 100%. CONCLUSION. Adult renal transplant recipients who are able to be maintained on spaced weaning have excellent outcomes. Patients with stable renal function who have reversal of weaning because of the development of DSA also have excellent outcomes. Routine monitoring for DSA may allow patients to avoid late rejection after spaced weaning. © 2008 Lippincott Williams & Wilkins, Inc

807-2 Effect of Age on Left Ventricular Diastolic Filling Patterns During Orthostatic Stress

Although numerous studies have demonstrated reduced early diastolic left ventricular (LV) peak filling velocity IE) and accentuated late filling velocity (A) with advancing age in the supine position, the effect of orthostatic stress on age-associated diastolic filling patterns is unknown. Accordingly, 30 healthy normotensive volunteers ages 19 to 90 years from the Baltimore Longitudinal Study of Aging underwent sequential Doppler echocardiography after 3 minutes each in the supine, seated, and standing positions. In the overall sample, standing was accompanied by an increase in heart rate (HR) of 8.8±1.7 beats/min, and decreases in E(20.6±2.7cm/sl. A 150±2.7cm/s)and LV diastolic dimension (LVDD) (7.8±0.8mm), x±SEM, each p<0.001 versus supine values. Systolic blood pressure (SBP) and atrial filling fraction (AFF) were unaffected by posture. Correlation coefficients versus age for relevant Doppler and hemodynamic variables are shown.EAE/AAFFHRSBPLVDDSupine-0.58†0.80†-0.78†0.84†0.010.56†-0.14Sit-0.360.77†-0.83†0.78†-0.040.37*-0.07Stand-0.240.60†-0.69†0.71†-0.320.47†0.09ΔSupine → Stand0.53†-0.46†0.56†-0.17-0.61†0.220.40**p<005†p<001Thus, orthostatic stress abolishes the reduction of E and attenuates the exaggerated A observed with advancing age in the supine position. probably because of the blunted standing-induced HR increase in older subjects. However, the supine age-associated increase in AFF is unaffected by orthostasis

The use of displacement damage dose to correlate degradation in solar cells exposed to different radiations

It has been found useful in the past to use the concept of 'equivalent fluence' to compare the radiation response of different solar cell technologies. Results are usually given in terms of an equivalent 1 MeV electron or an equivalent 10 MeV proton fluence. To specify cell response in a complex space-radiation environment in terms of an equivalent fluence, it is necessary to measure damage coefficients for a number of representative electron and proton energies. However, at the last Photovoltaic Specialist Conference we showed that nonionizing energy loss (NIEL) could be used to correlate damage coefficients for protons, using measurements for GaAs as an example. This correlation means that damage coefficients for all proton energies except near threshold can be predicted from a measurement made at one particular energy. NIEL is the exact equivalent for displacement damage of linear energy transfer (LET) for ionization energy loss. The use of NIEL in this way leads naturally to the concept of 10 MeV equivalent proton fluence. The situation for electron damage is more complex, however. It is shown that the concept of 'displacement damage dose' gives a more general way of unifying damage coefficients. It follows that 1 MeV electron equivalent fluence is a special case of a more general quantity for unifying electron damage coefficients which we call the 'effective 1 MeV electron equivalent dose'

Antilymphoid antibody preconditioning and tacrolimus monotherapy for pediatric kidney transplantation

Objective: Heavy post-transplant immunosuppression may contribute to long-term immunosuppression dependence by subverting tolerogenic mechanisms; thus, we sought to determine if this undesirable consequence could be mitigated by pretransplant lymphoid depletion and minimalistic post-transplant monotherapy. Study design: Lymphoid depletion in 17 unselected pediatric recipients of live (n = 14) or deceased donor kidneys (n = 3) was accomplished with antithymocyte globulin (ATG) (n = 8) or alemtuzumab (n = 9). Tacrolimus was begun post-transplantation with subsequent lengthening of intervals between doses (spaced weaning). Maintenance immunosuppression, morbidity, graft function, and patient/graft survival were collated. Results: Steroids were added temporarily to treat rejection in two patients (both ATG subgroup) or to treat hemolytic anemia in two others. After 16 to 31 months (mean 22), patient and graft survival was 100% and 94%, respectively. The only graft loss was in a nonweaned noncompliant recipient. In the other 16, serum creatinine was 0.85 ± 0.35 mg/dL and creatinine clearance was 90.8 ± 22.1 mL/1.73 m2. All 16 patients are on monotherapy (15 tacrolimus, one sirolimus), and 14 receive every other day or 3 times per week doses. There were no wound or other infections. Two patients developed insulin-dependent diabetes. Conclusion: The strategy of lymphoid depletion and minimum post-transplant immunosuppression appears safe and effective for pediatric kidney recipients. © 2006 Elsevier Inc. All rights reserved

Event Horizons in Numerical Relativity I: Methods and Tests

This is the first paper in a series on event horizons in numerical relativity. In this paper we present methods for obtaining the location of an event horizon in a numerically generated spacetime. The location of an event horizon is determined based on two key ideas: (1) integrating backward in time, and (2) integrating the whole horizon surface. The accuracy and efficiency of the methods are examined with various sample spacetimes, including both analytic (Schwarzschild and Kerr) and numerically generated black holes. The numerically evolved spacetimes contain highly distorted black holes, rotating black holes, and colliding black holes. In all cases studied, our methods can find event horizons to within a very small fraction of a grid zone.Comment: 22 pages, LaTeX with RevTeX 3.0 macros, 20 uuencoded gz-compressed postscript figures. Also available at http://jean-luc.ncsa.uiuc.edu/Papers/ Submitted to Physical Review

Event Horizons in Numerical Relativity II: Analyzing the Horizon

We present techniques and methods for analyzing the dynamics of event horizons in numerically constructed spacetimes. There are three classes of analytical tools we have investigated. The first class consists of proper geometrical measures of the horizon which allow us comparison with perturbation theory and powerful global theorems. The second class involves the location and study of horizon generators. The third class includes the induced horizon 2-metric in the generator comoving coordinates and a set of membrane-paradigm like quantities. Applications to several distorted, rotating, and colliding black hole spacetimes are provided as examples of these techniques.Comment: 23 double column pages including 28 figures. Higher quality figures (big size!) available upon request (jmasso OR [email protected]

The 3D Grazing Collision of Two Black Holes

We present results for two colliding black holes (BHs), with angular momentum, spin, and unequal mass. For the first time gravitational waveforms are computed for a grazing collision from a full 3D numerical evolution. The collision can be followed through the merger to form a single BH, and through part of the ringdown period of the final BH. The apparent horizon is tracked and studied, and physical parameters, such as the mass of the final BH, are computed. The total energy radiated in gravitational waves is shown to be consistent with the total mass of the spacetime and the final BH mass. The implication of these simulations for gravitational wave astronomy is discussed.Comment: 4 pages, 7 figures, revte