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Robert J. Lederman

Other affiliations: Durham University, Duke University, University of Michigan  ...read more
Bio: Robert J. Lederman is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Interventional magnetic resonance imaging & Mitral valve replacement. The author has an hindex of 48, co-authored 256 publications receiving 8170 citations. Previous affiliations of Robert J. Lederman include Durham University & Duke University.


Papers
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Journal ArticleDOI
TL;DR: A single unilateral intramuscular administration of AdVEGF121 was not associated with improved exercise performance or quality of life in this study, and this study does not support local delivery of single-dose VEGF121 as a treatment strategy in patients with unilateral PAD.
Abstract: Background— “Therapeutic angiogenesis” seeks to improve perfusion by the growth of new blood vessels. The Regional Angiogenesis with Vascular Endothelial growth factor (RAVE) trial is the first major randomized study of adenoviral vascular endothelial growth factor (VEGF) gene transfer for the treatment of peripheral artery disease (PAD). Methods and Results— This phase 2, double-blind, placebo-controlled study was designed to test the efficacy and safety of intramuscular delivery of AdVEGF121, a replication-deficient adenovirus encoding the 121-amino-acid isoform of vascular endothelial growth factor, to the lower extremities of subjects with unilateral PAD. In all, 105 subjects with unilateral exercise-limiting intermittent claudication during 2 qualifying treadmill tests, with peak walking time (PWT) between 1 to 10 minutes, were stratified on the basis of diabetic status and randomized to low-dose (4×109 PU) AdVEGF121, high-dose (4×1010 PU) AdVEGF121, or placebo, administered as 20 intramuscular injec...

563 citations

Journal ArticleDOI
TL;DR: Intra-arterial rFGF-2 resulted in a significant increase in peak walking time at 90 days; repeat infusion at 30 days was no better than one infusion and the findings of TRAFFIC provide evidence of clinical therapeutic angiogenesis by intra-arteria infusion of an angiogenic protein.

505 citations

Journal ArticleDOI
TL;DR: IFP labeling of MSCs imparts useful MRI contrast, enabling ready detection in the beating heart on a conventional cardiac MR scanner after transplantation into normal and infarcted myocardium.
Abstract: Background— Delivery and tracking of endomyocardial stem cells are limited by the inability to image transplanted cells noninvasively in the beating heart. We hypothesized that mesenchymal stem cells (MSCs) could be labeled with a iron fluorophore particle (IFP) to provide MRI contrast in vivo to assess immediate and long-term localization. Methods and Results— MSCs were isolated from swine. Short-term incubation of MSCs with IFP resulted in dose-dependent and efficient labeling. Labeled cells remained viable for multiple passages and retained in vitro proliferation and differentiation capacity. Labeled MSCs (104 to 106 cells/150 μL) were injected percutaneously into normal and freshly infarcted myocardium in swine. One, 3, and 1 animals underwent serial cardiac MRI (1.5T) for 4, 8, and 21 days, respectively. MRI contrast properties were measured both in vivo and in vitro for cells embedded in agar. Injection sites containing as few as 105 MSCs could be detected and contained intact IFP-bearing MSCs on hi...

451 citations

Journal ArticleDOI
TL;DR: Clinical, radiographic, and genetic studies in three families with symptomatic arterial calcifications identified nine persons with calcifications of the lower-extremity arteries and hand and foot joint capsules, all five siblings in one family, three siblings in another, and one patient in a third family.
Abstract: Background Arterial calcifications are associated with increased cardiovascular risk, but the genetic basis of this association is unclear. Methods We performed clinical, radiographic, and genetic studies in three families with symptomatic arterial calcifications. Single-nucleotide-polymorphism analysis, targeted gene sequencing, quantitative polymerase-chain-reaction assays, Western blotting, enzyme measurements, transduction rescue experiments, and in vitro calcification assays were performed. Results We identified nine persons with calcifications of the lower-extremity arteries and hand and foot joint capsules: all five siblings in one family, three siblings in another, and one patient in a third family. Serum calcium, phosphate, and vitamin D levels were normal. Affected members of Family 1 shared a single 22.4-Mb region of homozygosity on chromosome 6 and had a homozygous nonsense mutation (c.662C→A, p.S221X) in NT5E, encoding CD73, which converts AMP to adenosine. Affected members of Family 2 had a ...

374 citations

Journal ArticleDOI
TL;DR: Precise targeted delivery of potentially regenerative cellular treatments to recent myocardial infarction borders is feasible with an MR catheter delivery system.
Abstract: Background— The local environment of delivered mesenchymal stem cells (MSCs) may affect their ultimate phenotype. MR fluoroscopy has the potential to guide intramyocardial MSC injection to desirable targets, such as the border between infarcted and normal tissue. We tested the ability to (1) identify infarcts, (2) navigate injection catheters to preselected targets, (3) inject safely even into fresh infarcts, and (4) confirm injection success immediately. Methods and Results— A 1.5-T MRI scanner was customized for interventional use, with rapid imaging, independent color highlighting of catheter channels, multiple-slice 3D rendering, catheter-only viewing mode, and infarct-enhanced imaging. MRI receiver coils were incorporated into guiding catheters and injection needles. These devices were tested for heating and used for targeted MSC delivery. In infarcted pigs, myocardium was targeted by MR fluoroscopy. Infarct-enhanced imaging included both saturation preparation MRI after intravenous gadolinium and wa...

218 citations


Cited by
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Journal ArticleDOI
TL;DR: The goals of this new consensus are to provide an abbreviated document to focus on key aspects of diagnosis and management, and to update the information based on new publications and the newer guidelines, but not to add an extensive list of references.

7,099 citations

Reference EntryDOI
31 Oct 2001
TL;DR: The American Society for Testing and Materials (ASTM) as mentioned in this paper is an independent organization devoted to the development of standards for testing and materials, and is a member of IEEE 802.11.
Abstract: The American Society for Testing and Materials (ASTM) is an independent organization devoted to the development of standards.

3,792 citations

Journal ArticleDOI
TL;DR: Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic) A Collaborative Report from the American Association for Vascular Surgery/Society for V vascular surgery,* Society for Cardiovascular Angiography and Interventions, Society forVascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines.
Abstract: Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic) A Collaborative Report from the American Association for Vascular Surgery/Society for Vascular Surgery,* Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease) Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation

3,239 citations

Book ChapterDOI
TL;DR: The physical principles underlying some current biomedical applications of magnetic nanoparticles are reviewed and the relevant physics of magnetic materials and their responses to applied magnetic fields are surveyed.
Abstract: The physical principles underlying some current biomedical applications of magnetic nanoparticles are reviewed. Starting from well-known basic concepts, and drawing on examples from biology and biomedicine, the relevant physics of magnetic materials and their responses to applied magnetic fields are surveyed. The way these properties are controlled and used is illustrated with reference to (i) magnetic separation of labelled cells and other biological entities; (ii) therapeutic drug, gene and radionuclide delivery; (iii) radio frequency methods for the catabolism of tumours via hyperthermia; and (iv) contrast enhancement agents for magnetic resonance imaging applications. Future prospects are also discussed.

2,815 citations

Journal ArticleDOI
TL;DR: The term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future and a quantitative method for cumulative risk assessment of vulnerable patients needs to be developed.
Abstract: Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document focuses on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.

2,719 citations