Background When kidney transplants fail, transplant medications are discontinued to reduce immunosuppression-related risks. However, retransplant candidates are at risk for allosensitization which prolonging immunosuppression may minimize. We hypothesized that for these patients, a prolonged immunosuppression withdrawal after graft failure preserves nonsensitization status (PRA 0%) better than early immunosuppression withdrawal. Methods We retrospectively examined subjects transplanted at a single center between 7/1/1999-12/1/2009 with a non-death related graft loss. Subjects were stratified by timing of immunosuppression withdrawal after graft loss: early (≤3 months) or prolonged (>3 months). Retransplant candidates were eligible for the main study where the primary outcome was nonsensitization at retransplant evaluation. Non-retransplant candidates were included in the safety analysis only. Results We found 102 subjects with non-death related graft loss of which 49 were eligible for the main study. Nonsensitization rates at retransplant evaluation were 30% and 66% for the early and prolonged immunosuppression withdrawal groups respectively (p=0.01). After adjusting for cofactors such as blood transfusion and allograft nephrectomy, prolonged immunosuppression withdrawal remained significantly associated with nonsensitization (adjusted odds ratio=5.78, 95% C.I. [1.37-24.44]). No adverse safety signals were seen in the prolonged immunosuppression withdrawal group compared to the early immunosuppression withdrawal group. Conclusions These results suggest that prolonged immunosuppression may be a safe strategy to minimize sensitization in retransplant candidates and provide the basis for larger or prospective studies for further verification.

Statins administered before invasive procedures significantly reduce the hazard of post-procedural MI. Additionally, statins reduce the risk of atrial fibrillation after CABG. The routine use of statins before invasive procedures should be considered.

Aim Increasing evidence demonstrates that circadian clock proteins are important regulators of physiological functions including blood pressure. An established risk factor for developing cardiovascular disease is the absence of a blood pressure dip during the inactive period. The goal of the present study was to determine the effects of a high salt diet plus mineralocorticoid on PER1-mediated blood pressure regulation in a salt-resistant, normotensive mouse model, C57BL/6J. Methods Blood pressure was measured using radiotelemetry. After control diet, wild type and Per1 knockout mice were given a high salt diet (4% NaCl) and the long-acting mineralocorticoid deoxycorticosterone pivalate. Blood pressure and activity rhythms were analyzed to evaluate changes over time. Results Blood pressure in wild type mice was not affected by a high salt diet plus mineralocorticoid. In contrast, Per1 knockout mice exhibited significantly increased mean arterial pressure in response to a high salt diet plus mineralocorticoid. The inactive/active phase ratio of mean arterial pressure in wild type mice was unchanged by high salt plus mineralocorticoid treatment. Importantly, this treatment caused Per1 knockout mice to lose the expected decrease or “dip” in blood pressure during the inactive compared to the active phase. Conclusion Loss of PER1 increased sensitivity to the high salt plus mineralocorticoid treatment. Italso resulted in a non-dipper phenotype in this model of salt-sensitive hypertension and provides a unique model of non-dipping. Together these data support an important role for the circadian clock protein PER1 in the modulation of blood pressure in a high salt/mineralocorticoid model of hypertension.

The aim of this study was to examine the controversial effects of experimental unilateral cryptorchidism and subsequent orchiopexy on the number of germ cells and other morphometric characteristics of testicular and epididymal structures in adult rabbits. Unilateral cryptorchidism was induced in 11 mature male New Zealand white rabbits by returning one testis, together with the ipsilateral epididymis, to the abdominal cavity via a surgical procedure. After 3 months, testes and epididymides were removed from six animals (and from six age-matched control animals that did not undergo the surgery). Orchiopexy was performed on the five remaining animals and the testes and epididymides of these animals (and an additional six age-matched control animals) were removed 7 weeks later. A contemporary, unbiased and efficient stereological tool, the optical disector, was used to estimate the number of nuclei in the testis and epididymis using methacrylate-embedded sections of 25 micron in thickness. Cryptorchidism resulted in severe testicular atrophy and spermatogenic arrest: type A spermatogonia and Sertoli cells only were seen in the seminiferous epithelium, and the number of type A spermatogonia per testis was reduced by 84%. After orchiopexy, the testis remained atrophied and the number of type A spermatogonia returned to the near-normal range in four of five animals, but spermatogenesis was recovered only partially at the stage of early primary spermatocytes (one animal), late primary spermatocytes (two animals) or spermatids (one animal). In conclusion, cryptorchidism caused severe spermatogenic arrest that was potentially recoverable (in view of the restoration of the number of type A spermatogonia), but orchiopexy failed to induce full recovery of spermatogenesis.

Background: Early studies of glycoprotein IIb/IIIa inhibitors (GPIs) demonstrated benefit during percutaneous coronary intervention for acute coronary syndromes (ACS). Since their introduction, the magnitude of benefit of GPIs has become unclear. Hypothesis: We hypothesized that adding a GPI to unfractionated heparin in ACS patients treated with stents and thienopyridines is beneficial. Methods: We searched the MEDLINE, Cochrane, and clinicaltrials.gov databases for randomized clinical trials that studied the use of GPIs during ACS. We required that patients be randomly assigned to unfractionated heparin plus a GPI versus unfractionated heparin plus placebo (or control). Additional inclusion criteria included the use of coronary stents and periprocedural thienopyridines. Outcomes were assessed at 30 days. Random effects DerSimonian-Laird summary risk ratios (RR) and 95% confidence intervals (CIs) were constructed. Results: Sixteen studies with 7611 patients were included. Myocardial infarction was 3.1% with GPI versus 4.4% with control (RR = 0.74; 95% CI, 0.59-0.94, P = 0.014); revascularization, 1.7% versus 2.7% (RR = 0.64; 95% CI, 0.46-0.89, P = 0.008); major bleeding, 2.5% versus 2.1% (RR = 1.21; 95% CI, 0.89-1.63, P = 0.22); minor bleeding, 5.5% versus 4.1% (RR = 1.37; 95% CI, 1.06-1.78, P = 0.016); and mortality, 2.2% versus 2.9% (RR = 0.79; 95% CI, 0.59-1.06, P = 0.12), respectively. Conclusions: Among ACS patients treated with stents and thienopyridines, GPIs were associated with reduced myocardial infarction and revascularization. Minor, but not major bleeding was increased with GPIs. Mortality was similar between the groups.