Phase 1 and preclinical profiling of ESM-HDAC391, a myeloid-targeted histone deacetylase inhibitor, shows enhanced pharmacology and monocytopaenia.

Aims: To improve the tolerability and therapeutic application of histone deacetylase inhibitors (HDACi), by application of an esterase-sensitive motif (ESM), to target pharmacological activity directly to mononuclear myeloid cells expressing the processing enzyme carboxylesterase-1 (CES1).

Methods: This first-in-human study comprised single and multiple ascending dose cohorts to determine safety and tolerability. Pharmacodynamic parameters included acetylation, cytokine inhibition and intracellular concentrations of processed acid metabolite in isolated monocytes.

Impact of Switching From Prasugrel to Clopidogrel Shortly After a Percutaneous Coronary Intervention Without a Loading Dose of Clopidogrel.

Objective: To determine the safety and efficacy of administering prasugrel at the time of percutaneous coronary intervention (PCI), and switching to clopidogrel, without reloading.

Background: Prasugrel has faster onset of action and appears to be of greater benefit than clopidogrel, particularly early after PCI. However, long-term prasugrel increases bleeding.

Does Preoperative Platelet Function Predict Bleeding in Patients Undergoing Off Pump Coronary Artery Bypass Surgery?

Objective: We sought to examine the relationship between preoperative platelet function and perioperative bleeding in patients undergoing CABG.

Background: There are many ways to measure platelet aggregability. Little is known about their correlations with one another, or with bleeding.

The effect of antiplatelet and anticoagulant therapy on the clinical outcome of patients undergoing ureteroscopy.

Objective: To determine if there is any difference in the clinical outcome for patients receiving aspirin, clopidogrel, and warfarin undergoing ureteroscopy and laser lithotripsy for urolithiasis compared with patients on no antithrombotic medication.

Methods: We retrospectively reviewed patients who underwent ureteroscopy for urolithaisis from July 1, 2005 to October 1, 2010. If patients continued aspirin, clopidogrel, or warfarin within 48 hours of surgery, they were considered to be on antithrombotic therapy.

Preoperative aspirin is safe in patients undergoing urologic robot-assisted surgery.

Purpose: To determine the impact of preoperative aspirin on bleeding and other complications in patients undergoing robot-assisted radical prostatectomy and nephrectomy.

Patients And Methods: We identified all patients who underwent robot-assisted radical prostatectomy or robot-assisted nephrectomy by a single surgeon between August 2008 and August 2010. We compared patients in whom aspirin had not been administered for 7 days with those who received aspirin the morning of surgery.

Allergic reactions to clopidogrel and cross-reactivity to other agents.

Clopidogrel is a widely used antiplatelet agent, particularly after coronary stent implantation. About 1% of patients have allergic or hematologic adverse reactions to clopidogrel. This has important therapeutic implications, as premature discontinuation of clopidogrel is the strongest risk factor for stent thrombosis.

Hormonal determinants of bone turnover before and after attainment of peak bone mass.

Introduction: Bone turnover decreases from adolescence into adulthood, but does not reach a nadir until the fourth decade. Biochemical markers of bone turnover reflect different processes before and after peak bone mass, so hormonal influences on bone turnover may differ before and after peak bone mass.

Objectives: To describe the changes in bone turnover and hormones relevant to bone metabolism from adolescence into adulthood, and to identify which hormones correlate with bone turnover before and after peak bone mass.

Attainment of peak bone mass at the lumbar spine, femoral neck and radius in men and women: relative contributions of bone size and volumetric bone mineral density.

The age at which peak bone mineral content (peak BMC) is reached remains controversial and the mechanism underlying bone mass "consolidation" is still undefined. The aims of this study were to investigate; (1) the timing of peak BMC by studying bone size and volumetric BMD (vBMD) as separate entities and (2) to determine the relative contributions of bone size and vBMD to bone mass "consolidation". A total of 132 healthy Caucasian children (63 boys and 69 girls, ages 11-19 years) and 134 healthy Caucasian adults (66 men and 68 women, ages 20-50 years) were studied.