Identification of Diarylurea Inhibitors of the Cardiac-Specific Kinase TNNI3K by Designing Selectivity Against VEGFR2, p38α, and B-Raf.

A series of diarylurea inhibitors of the cardiac-specific kinase TNNI3K were developed to elucidate the biological function of TNNI3K and evaluate TNNI3K as a therapeutic target for the treatment of cardiovascular diseases. Utilizing a structure-based design, enhancements in kinase selectivity were engineered into the series, capitalizing on the established X-ray crystal structures of TNNI3K, VEGFR2, p38α, and B-Raf. Our efforts culminated in the discovery of an tool compound (GSK329), which exhibited desirable TNNI3K potency and rat pharmacokinetic properties as well as promising kinase selectivity against VEGFR2 (40-fold), p38α (80-fold), and B-Raf (>200-fold).

Nonenhanced arterial spin labeled carotid MR angiography using three-dimensional radial balanced steady-state free precession imaging.

Purpose: To optimize and preliminarily evaluate a three-dimensional (3D) radial balanced steady-state free precession (bSSFP) arterial spin labeled (ASL) sequence for nonenhanced MR angiography (MRA) of the extracranial carotid arteries.

Materials And Methods: The carotid arteries of 13 healthy subjects and 2 patients were imaged on a 1.5 Tesla MRI system using an undersampled 3D radial bSSFP sequence providing a scan time of ∼4 min and 1 mm(3) isotropic resolution.

Complications of indwelling retrievable versus permanent inferior vena cava filters.

Objective: Retrievable inferior vena cava (IVC) filters are appealing because they are designed for either retrieval or long-term use. However, the long-term safety of indwelling retrievable compared with permanent filters is largely unknown. This study was undertaken to compare complication rates and types associated with indwelling retrievable and permanent filters.

Resection of intracaval leiomyomatosis using abdominal approach and venovenous bypass.

Background: Intravenous leiomyomatosis is the venous involvement of a histologically benign uterine tumor. This uncommon tumor can present contemporaneously with the primary uterine tumor or in a delayed fashion. Tumor extends up the venous system, via the iliac or ovarian veins, and can involve portions or all of the inferior vena cava and can extend into the heart as well.

Is atherectomy the best first-line therapy for limb salvage in patients with critical limb ischemia?

Objective: To determine the efficacy of atherectomy for limb salvage compared with open bypass in patients with critical limb ischemia.

Methods: Ninety-nine consecutive bypass and atherectomy procedures performed for critical limb ischemia between January 2003 and October 2006 were reviewed.

Results: A total of 99 cases involving TASC C (n = 43, 44%) and D (n = 56, 56%) lesions were treated with surgical bypass in 59 patients and atherectomy in 33 patients.

Local and systemic consequences of large retroperitoneal clot burdens.

Background: There is a paucity of data regarding the impact of retroperitoneal hematoma (RPH) volumes, as detected by computed tomography (CT) scanning, on patient morbidity and mortality. Therefore, we wanted to determine the natural history of RPHs and the effect of size on local and systemic outcomes.

Methods: We performed a volumetric analysis of CT-documented RPHs managed at our institution between 1985 and 2006 along with a retrospective chart review.

The use of arterial closure devices for incidental arterial injury.

Incidental arterial injury is one of the main mechanical complications associated with central venous catheter placement. These injuries can result in significant morbidity and mortality. The use of arterial closure devices to repair these injuries offers a less invasive alternative than open repair and a safer approach than manual compression.

Reappraisal of velocity criteria for carotid bulb/internal carotid artery stenosis utilizing high-resolution B-mode ultrasound validated with computed tomography angiography.

Objective: Reliability of the most commonly used duplex ultrasound (DUS) velocity thresholds for internal carotid artery (ICA) stenosis has been questioned since these thresholds were developed using less precise methods to grade stenosis severity based on angiography. In this study, maximum percent diameter carotid bulb ICA stenosis (European Carotid Surgery Trial [ECST] method) was objectively measured using high resolution B-mode DUS validated with computed tomography angiography (CTA) and used to determine optimum velocity thresholds for > or =50% and > or =80% bulb internal carotid artery stenosis (ICA).

Methods: B-mode DUS and CTA images of 74 bulb ICA stenoses were compared to validate accuracy of the DUS measurements.

WITHDRAWN: Reappraisal of internal carotid artery stenosis velocity thresholds utilizing high-resolution B-mode ultrasound validated with computed tomography angiography (CTA).

This article has been withdrawn consistent with Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).

Transperitoneal versus retroperitoneal suprarenal cross-clamping for repair of abdominal aortic aneurysm with a hostile infrarenal aortic neck.

Infrarenal abdominal aortic aneurysms (AAAs) with a hostile infrarenal aortic neck unfit for endovascular aneurysm repair (EVAR) are more likely to require open repair with suprarenal aortic cross-clamping. We compared the results of the transperitoneal versus retroperitoneal approaches for repair of infrarenal AAA requiring suprarenal cross-clamping and the relative frequency of such techniques after incorporating EVAR into our clinical practice. From January 1998 through September 2005, 478 elective infrarenal aortic aneurysms were repaired.

Effects of the CRF receptor antagonist D-Phe CRF(12-41) and the alpha2-adrenergic receptor agonist clonidine on stress-induced reinstatement of nicotine-seeking behavior in rats.

Tobacco dependence is a chronic disorder that is characterized by relapse after periods of abstinence. It has been hypothesized that the activation of brain stress systems mediates stress-induced relapse to smoking. The aim of these experiments was to investigate the role of corticotropin-releasing factor (CRF) and norepinephrine in stress-induced reinstatement of extinguished nicotine-seeking behavior.

B-mode ultrasonographic characterization of carotid atherosclerotic plaques in symptomatic and asymptomatic patients.

Objective: To identify features on B-mode ultrasonography (US) prevalent in symptomatic plaques and correlate these findings with histopathologic markers of plaque instability.

Methods: Carotid endarterectomy (CEA) plaques from symptomatic and asymptomatic patients with critical stenoses (>70%) were qualitatively assessed using preoperative B-mode US for echolucency and calcific acoustic shadowing. US echolucency was quantitated ex vivo using computerized techniques for gray-scale median (GSM) analysis.

Degree of carotid plaque calcification in relation to symptomatic outcome and plaque inflammation.

Objective: We undertook this study to quantitate differences in the degree of calcification between symptomatic and asymptomatic plaques removed at carotid endarterectomy (CEA) and to determine associated extent of plaque macrophage infiltration, a histopathologic feature of plaque instability.

Methods: CEA plaques (n = 48) were imaged at 1.25-mm intervals with spiral computed tomography (CT; 10-15 images per plaque).

Limb salvage after infrainguinal bypass graft failure.

Objective: The purpose of this study was to examine the outcome of patients in whom an infrainguinal bypass graft failed.

Methods: This was a retrospective analysis of consecutive patients undergoing infrainguinal bypass grafting in a single institution over 8 years.

Results: Six hundred thirty-one infrainguinal bypass grafts were placed in 578 limbs in 503 patients during the study period.

Redo infrainguinal bypass: factors predicting patency and limb salvage.

The increased complexity of redo infrainguinal bypass procedures can result in prolonged operative time and increased morbidity. This review was undertaken to compare outcomes from primary and redo bypass procedures and to identify factors predictive of graft failure and limb loss after redo bypass. All infrainguinal bypasses ( n = 468) from 1995 to 1999 were reviewed.

Long-term outcome of infrainguinal bypass grafting in patients with serologically proven hypercoagulability.

Objective: The purpose of this study was to test the hypothesis that the long-term outcome of infrainguinal bypass grafting in patients with congenital or acquired hypercoagulability is inferior to the results in patients without documented clotting disorders.

Methods: The study was a retrospective analysis of consecutive patients from January 1994 to January 2001.

Results: Five hundred eighty-two infrainguinal bypass grafts were created in 456 patients.

Paravisceral aortic thrombus as a source of peripheral embolization--report of three cases and review of the literature.

Spontaneous embolization resulting in peripheral arterial occlusion remains a significant cause of morbidity and limb loss. Accurate localization and correction of the embolic source is paramount for the prevention of further episodes and for the preservation of long-term patency and limb salvage. Common well-recognized embolic sources include intracardiac thrombus or myxoma, and thrombus within arterial aneurysms or complex atherosclerotic plaques.

Operative intervention for recurrent stenosis after carotid stent angioplasty: a report.

Carotid artery angioplasty and stenting is gaining popularity, yet the natural history and optimal treatment for recurrent stenoses within stents are not known. Recurrent stenosis rates are not well characterized, with rates between 0 and 33% reported within the first year. Treatment of these lesions with repeat angioplasty may not be feasible or desirable, leading to operative interventions.

Long-term results of infrageniculate bypass grafting using all-autogenous composite vein.

Infrageniculate (below-knee) bypass using all-autogenous composite vein requires multiple incisions, venovenostomy, and prolonged operating time. The purpose of this study was to evaluate the long-term results of this procedure, with comparisons to grafts created from single-segment greater saphenous vein (GSV) or polytetrafluoroethylene (PTFE). A total of 362 consecutive infrainguinal bypass grafts with infrageniculate distal target arteries were created in 283 patients in a single institution between January 1995 and December 2000.

Spontaneous perforation of a non-aneurysmal visceral aorta.

A 77 year-old woman with mild osteoarthritis and Sjögren's Syndrome presented to an outside hospital with mild abdominal and back pain. The initial computed tomography (CT) scan was essentially negative. The repeat CT scan after 1 week of medical therapy was suspicious for a contained rupture of the visceral aorta.

Interleukin-6 causes endothelial barrier dysfunction via the protein kinase C pathway.

Background: Elevated levels of interleukin-6 (IL-6) have been identified in a variety of systemic inflammatory states that are associated with endothelial barrier dysfunction, but the specific effect of IL-6 on endothelial permeability and the mechanism of action have not been fully examined. The current study evaluated the effect of IL-6 on endothelial permeability and on the distribution of the tight junctional protein ZO-1 and cytoskeletal actin. We also assessed the role of protein kinase C (PKC) in this process.

Angiographic access site complications in the era of arterial closure devices.

Coronary and peripheral angiography is associated with a low but significant risk of access site complications. While percutaneous devices have been shown to permit more rapid puncture site closure, previous reports have suggested the incidence and severity of complications associated with these devices are greater than with manual compression. This study compares access site complications with and without closure devices in the current era.

Routine early postoperative duplex scanning is unnecessary following uncomplicated carotid endarterectomy.

Although early postoperative duplex scanning has become routine after carotid endarterectomy (CEA), it is unclear whether the results of these scans alter clinical management. The purpose of this study was to critically examine the usefulness of early postoperative duplex scans in evaluating the ipsilateral carotid artery (for technical perfection) as well as the contralateral carotid artery (for potential velocity changes after improvements in ipsilateral flow). Consecutive patients undergoing CEA between January 1995 and June 1999 in a tertiary hospital setting were studied.

Conduit choice for above-knee femoropopliteal bypass grafting in patients with limb-threatening ischemia.

Many surgeons consider PTFE to be the conduit of choice for above-knee femoropopliteal bypass grafting, since PTFE is relatively easy to implant and spares autogenous saphenous vein (ASV) for subsequent peripheral or coronary artery bypass grafting (CABG). This practice has recently been challenged, as some studies have suggested that ASV may exhibit superior patency in certain patient subgroups. The purpose of this retrospective study was to examine the contemporary outcome of above-knee femoropopliteal bypass grafting in patients with limb-threatening ischemia.