Evaluation of levocetirizine in beagle dog and cynomolgus monkey telemetry assays: Defining the no QTc effect profile by timepoint and concentration-QTc analysis.

In prior clinical studies, levocetirizine (LEVO) has demonstrated no effect on ventricular repolarization (QTc intervals), therefore it is a relevant negative control to assess in nonclinical assays to define low proarrhythmic risk. LEVO was tested in beagle dog and cynomolgus monkey (nonhuman primate [NHP]) telemetry models to understand the nonclinical-clinical translation of this negative control. One oral dose of vehicle, LEVO (10 mg/kg/species) or moxifloxacin (MOXI; 30 mg/kg/dog; 80 mg/kg/NHP) was administered to instrumented animals (N = 8/species) using a cross-over dosing design; MOXI was the in-study positive control.

Evaluation of moxifloxacin in canine and non-human primate telemetry assays: Comparison of QTc interval prolongation by timepoint and concentration-QTc analysis.

The in vivo correct QT (QTc) assay is used by the pharmaceutical industry to characterize the potential for delayed ventricular repolarization and is a core safety assay mentioned in International Conference on Harmonization (ICH) S7B guideline. The typical telemetry study involves a dose-response analysis of QTc intervals over time using a crossover (CO) design. This method has proven utility but does not include direct integration of pharmacokinetic (PK) data.

Survival Prolongation Index as a Novel Metric to Assess Anti-Tumor Activity in Xenograft Models.

A single efficacy metric quantifying anti-tumor activity in xenograft models is useful in evaluating different tumors' drug sensitivity and dose-response of an anti-tumor agent. Commonly used metrics include the ratio of tumor volume in treated vs. control mice (T/C), tumor growth inhibition (TGI), ratio of area under the curve (AUC), and growth rate inhibition (GRI).

The Need for Accreditation of Office-Based Interventional Vascular Centers.

The rise in office-based interventional vascular laboratories in recent years was prompted in part by expedient ambulatory patient experience and favorable outpatient procedural reimbursement. While studies have shown that clinical safety and treatment efficacy can be achieved in office-based vascular facilities, critics have raised various concerns due to inconsistent patient care standards and lack of organizational oversight to ensure optimal patient outcome. Available literature showed widely varied clinical outcomes which were partly attributable to nonuniform standards in reporting clinical efficacy and adverse events.

Glycolytic oscillations and limits on robust efficiency.

Both engineering and evolution are constrained by trade-offs between efficiency and robustness, but theory that formalizes this fact is limited. For a simple two-state model of glycolysis, we explicitly derive analytic equations for hard trade-offs between robustness and efficiency with oscillations as an inevitable side effect. The model describes how the trade-offs arise from individual parameters, including the interplay of feedback control with autocatalysis of network products necessary to power and catalyze intermediate reactions.

Changing pattern of surgical revascularization for critical limb ischemia over 12 years: endovascular vs. open bypass surgery.

Objective: This study is a review and evaluation of our 12-year experience of revascularization for critical limb ischemia (CLI) with angioplasty/stenting and bypass surgery to identify specific trends of procedure volume and outcomes in this particular group.

Methods: Endovascular and open bypass procedures done for CLI by a single surgeon between 1993 and 2004 were evaluated retrospectively. Thrombolysis and thrombectomy procedures done as the only revascularization procedure were excluded from analysis.

The influence of the ipsilateral superficial femoral artery on iliac angioplasty.

Our objective was to evaluate the impact of the ipsilateral superficial femoral artery (SFA) on percutaneous transluminal angioplasty (PTA) of the iliac arteries. From 1993 to 2005, 183 iliac lesions (179 stenoses, 4 occlusions; 37 common, 35 external, and 111 both iliac arteries) in 127 patients with disabling claudication [94 (52%)], rest pain [43 (23%)], and ulcer/gangrene [46 (25%)] were treated by PTA. TransAtlantic Inter-Society Consensus (TASC) iliac lesion types were A in 48 limbs (26%), B in 92 (50%), C in 38 (21%), and D in 5 (3%).

Long-term outcomes and predictors of iliac angioplasty with selective stenting.

Objective: To review our 11-year experience of iliac angioplasty with selective stenting and to evaluate the safety, short- and long-term patency, clinical success rates, and predictive risk factors in patients with iliac artery occlusive disease.

Methods: From August 1993 to November 2004, 151 iliac lesions (149 stenoses, 2 occlusions) in 104 patients were treated by percutaneous transluminal angioplasty (PTA). The patients had chronic limb ischemia described as disabling claudication (the Society for Vascular Surgery clinical category 2 or 3) in 76 (50%), rest pain (category 4) in 38 (25%), and ulcer/gangrene (category 5) in 37 (25%).

Thoracic outlet syndrome: pattern of clinical success after operative decompression.

Objective: To evaluate the pattern of clinical results in patients with neurogenic thoracic outlet syndrome (N-TOS) after operative decompression and longitudinal follow-up.

Methods: From May 1994 to December 2002, 254 operative sides in 185 patients with N-TOS were treated by the same operative protocol: (1) transaxillary first rib resection and the lower part of scalenectomy for the primary procedure with or without (2) the subsequent upper part of scalenectomy with supraclavicular approach for patients with persistent or recurrent symptoms. This retrospective cohort study included 38 men and 147 women with an age range of 19 to 80 years (mean, 40 years).

The effectiveness of percutaneous transluminal angioplasty for the treatment of critical limb ischemia: a 10-year experience.

Objective: To determine the efficacy, safety, and long-term results, including continued clinical improvement and limb salvage, of percutaneous transluminal angioplasty (PTA) in patients with critical limb ischemia (CLI).

Methods: From August 1993 to March 2004, 138 limbs in 111 patients with CLI (rest pain in 62 [45%] and ulcer/gangrene in 76 [55%]) were treated by PTA. In iliac lesions, stents were placed selectively for primary PTA failure: residual stenosis (>30%) or pressure gradient (>5 mm Hg).