The Research Initiatives Meeting and the National Institutes of Health
1996; Elsevier BV; Volume: 23; Issue: 6 Linguagem: Inglês
10.1016/s0741-5214(96)70223-9
ISSN1097-6809
Autores Tópico(s)Aortic Thrombus and Embolism
ResumoIn the 1980s it became apparent that a closer liaison with the National Institutes of Health (NIH) and one of its major branches, the National Heart, Lung, and Blood Institute (NHLBI), would be of great benefit to the members of The Society for Vascular Surgery. In addition, if an interchange of ideas could evolve, it could be of importance to those interested in research devoted to vascular problems. It was during this time that I was serving on the Cardiology Advisory Committee of the NHLBI. This committee was charged to deal with matters related to both the heart and the peripheral vascular system. There was a feeling on the committee that the area of peripheral vascular disease had not been properly addressed by the Institute over the years. We were fortunate to have Dr. Robert W. Barnes precede me on the committee and help set the stage for a more comprehensive collaboration. During my tenure, discussions were begun with Dr. John Watson, the Chief of the Devices and Technology Branch of NHLBI, about the possibility of putting together a workshop on vascular disease to be held in Bethesda, Md. The idea behind such an effort was to try to stimulate interest in the scientific community about this area that had been underserved in the past. This workshop was supported by NHLBI. It was also the intent of the program to attract the best scientific minds available in the research community to provide insight into the status of vascular research in this country. This new information could then be taken back to the Cardiology Advisory Committee and the NIH to inform the leadership about the areas that needed more work. This in turn could lead to the development of and dissemination of initiatives to the research community for possible funding. The topics for this first workshop were broad in scope but provided a framework for the subsequent programs that evolved from this experience. Some of the topics covered in the first meeting included the scope of the problem of vascular disease, the nature of atherosclerotic plaque, venous thromboembolism, vasospastic disorders, the available diagnostic methods, the status of cellular and molecular biology, blood flow, vascular healing, vascular grafts, and the pathophysiology of acute venous disorders. The proceedings of this conference resulted in a book entitled Vascular Diseases: Current Research and Clinical Applications, which appeared in 1987.1Strandness Jr, DE Didisheim P Clowes AW Watson JT Vascular diseases: current research and clinical applications. : Grune and Stratton, Orlando1987Google Scholar Because of the success of this initial venture, negotiations were held with Dr. Claude Lenfant, the director of NHLBI, about the feasibility of joint sponsorship of future meetings of this type. The joint council approved this proposal, and we began to move forward. The collaborative effort was agreed to, and the first announcement about this effort went out to the membership in January 1988. Although it was not certain at that time whether this program would become an annual event, subsequent history and the success of the endeavor left little doubt about its future. This success led to the establishment of what became known as the Research Initiatives Meetings (appendix). These meetings have been held annually for the past 10 years. The meeting format and topics have been under the guidance of members of The Society for Vascular Surgery and have been approved by them. The efforts in this regard have been led by me, Dr. Frank LoGerfo, Dr. Patrick Claggett, and Dr. Alexander Clowes. The meetings have been held in Bethesda, Md., in February or March of each year. The first jointly sponsored meeting was held February 19 and 20, 1988. The opening lecture was given by Dr. John Watson from NHLBI, who reviewed the perspectives on research in vascular diseases from the standpoint of the Institute. This lecture was followed by papers on hemodynamics and the arterial wall, diagnostic approaches, new strategies in intervention, adaptive responses of arteries, the arterial wall response to injury, mechanisms of graft failure, aneurysmal disease, atherosclerosis, lipids, and the arterial wall. At the time of this meeting, the topics were again of broad and general interest to the medical community. As will be noted, future conferences became much more focused. After this initial conference, Dr. Frank LoGerfo took over the responsibility for the subject, content, and design of the conferences. The second Research Initiatives Meeting was devoted to a consideration of NIH-funded research in vascular surgery and a wide variety of research topics. These topics included mechanisms of smooth muscle cell proliferation, the role of smooth muscle function in intimal hyperplasia, and the role of the macrophage in intimal hyperplasia. The regulation of growth factors by the endothelium and the contribution of mechanical stress to this entire process was reviewed. The topics then focused on the overall problem of intimal hyperplasia, its prevalence, and its impact from a clinical standpoint. The importance of intimal hyperplasia in vein grafts was covered, as was the progress being made in inhibiting this process experimentally. The third conference was held in February 1990 and was devoted to the problems of “Thrombosis, Thrombolysis, and Antithrombotic agents.” In addition, the current knowledge relating to hypercoaguable states was reviewed. Representatives from NHLBI presented information on the status of the Academic Awards in Systemic and Pulmonary Vascular Disease. The current initiatives in the Cardiac Diseases Branch were also presented. This was the first conference in which papers on endothelial function and gene therapy were presented. The problems related to gene transfer were reviewed. Finally, the issue of blood and materials interaction was covered. This is an area of great importance to all vascular surgeons. In 1991 the entire conference was devoted to problems related to “Prosthetic Grafts in the Arterial System.” Because prosthetic grafts have been used in vascular surgery nearly from its inception as a specialty, they is a topic of great importance. The role of the surface covering of the grafts and the prospects for endothelial seeding were reviewed. A major problem with prosthetic grafts relates to the compliance mismatch present and the intimal hyperplasia that develops at the anastomoses. Although these problems remain largely unsolved, the current state of our knowledge in these areas was reviewed. Because prosthetic graft infection is always a challenge in management, an entire session was devoted to the problem. The 1992 conference was devoted entirely to the rapidly expanding field of “Molecular Biology and Vascular Surgery.” Although molecular biology is an area of great interest to basic scientists, it was also clear from this conference that vascular surgeons were also beginning to play a role in this challenging field. The fundamental concepts necessary to understand the use of these new tools were reviewed. There was a major session devoted to genetic vascular disease. The one area of immediate interest to vascular surgeons was the abdominal aortic aneurysm and its relationship to genetic factors. A great deal of time was devoted to gene expression in endothelial and smooth muscle cells. The final session was devoted to the potential role for gene therapy and genetic engineering. In 1993 the conference was designed to review the progress being made in “Ischemia/Reperfusion.” This issue is of great interest to vascular surgeons, who have to deal with the problem of acute ischemia in many different vascular beds. The clinical relevance of the problems and the contributing factors were reviewed in a single session. Another session was devoted to the problems related to skeletal muscle and the splanchnic bed. The review not only touched on the clinical aspects but also the basic pathophysiology involved in the generation of the clinical problems. In 1994 the symposium highlighted the emerging area of “Transluminally Placed Endovascular Prostheses.” This was a very timely topic that, with time, has been shown to be of great interest and importance. NIH representatives brought the participants up to date on the activities of the devices and technology branch of NHLBI. In addition, the newly established programs in vascular biology, medicine, and surgery at NHLBI were reviewed. Finally, the new initiatives from the Division of Heart and Vascular Diseases were reviewed. The topics reviewed included some basic considerations of atherosclerosis, with particular emphasis on the advantages and shortcomings of animal models. The role of thrombosis in the atherosclerotic models and humans was also reviewed in a session devoted to this problem. The mechanisms of healing of prosthetic grafts was also reviewed, followed by a session devoted to intimal hyperplasia. A minisymposium on NIH funding opportunities for vascular surgeons was held. This included consideration of the importance of research training and its availability. The Harvard-Longwood Training Program in Vascular Surgical Research was presented by Dr. Frank LoGerfo. Finally, a review of how, why, and what grants get funded was presented by Dr. Paul Parakkal from the Scientific Review Branch of NIH. A session was devoted to aortic aneurysms, with particular emphasis on experimental models and how they might apply to human beings. This session was followed by a symposium on the current status of transluminally placed endovascular prostheses. This was one of the first scientific sessions devoted entirely to this new and important field. It was clear from this session what some of the problems were likely to be and how they might be approached. The early clinical experience and problems being encountered were also reviewed. In 1995 the conference was taken over by Dr. Alexander W. Clowes, who devoted the conference to “Atherosclerosis and Restenosis: The Failure of Conventional Wisdom.” Problems related to the use of animal models were reviewed. The limitations of these models were covered in great detail. Another session was devoted to available and new techniques for studying vascular disease in human beings. Because thrombosis is a prominent feature found in atherosclerosis, the question as to why some lesions lead to thromboembolic symptoms was addressed in a session. The issues related to plaque progression and the problems associated with abnormalities of vasomotor function were addressed in a single session. Finally, the mechanisms of restenosis as they relate to vascular reconstructions was reviewed in some depth. The tenth anniversary of this conference was held March 7 and 8, 1996. Dr. Alexander W. Clowes organized a conference devoted to the issue of “Vascular Gene Transfer: Models of Disease and Therapy,” an in-depth examination of one of the more exciting areas in biologic research. This program provided A-to-Z coverage of the subject, which should be of great interest to those who have interests in this field. Another worthwhile effort on the part of the Society was to have the proceedings of these conferences published in the Journal of Vascular Surgery. This policy was important to those who were unable to attend these important meetings. After 50 years for The Society for Vascular Surgery and the 10th Anniversary of the Research Initiatives Meetings, one must fairly ask to what extent this collaborative effort has been a success. It is my view that it has succeeded in many different ways. First, and perhaps most importantly, it has provided a forum for an interchange of ideas and in-depth discussion of important problems. In addition, because it is held annually, most topics that are discussed are timely and up-to-date. Both the NIH and the scientific community have benefited from this type of exposure. Has it in any way increased the flow of funds to our colleagues? I do not know, but I think that that issue is in many respects irrelevant to the goals of the conference. As one will note from the programs over the years, the topics reviewed at the meetings have been of increasing complexity. This is in a sense a mirror of what is happening in real life. In addition, these conferences do provide a forum for “science,” which is often put aside these days because of our concerns over health care delivery and cost containment. Although there is no argument over concerns related to health care delivery, the solutions to many of our problems in the future will come from the basic science community. It is my view that the leadership of The Society for Vascular Surgery should be commended for urging this kind of collaborative effort. Opening Lecture. Research in Vascular Disease: Perspectives of NHLBI. John T. Watson, PhD Hemodynamics and the Arterial Wall. Frank W. LoGerfo, MD, Don P. Giddens, PhD Diagnostic Approaches. D. E. Strandness, Jr., MD, Henry D. Berkowitz, MD New Strategies In Intervention. Rodney A. White, MD, Thomas Fogarty, MD Panel Discussion. Moderator: John T. Watson, PhD. Panelists: Frank W. LoGerfo, MD, Don P. Giddens, PhD, D. E. Strandness, Jr., MD, Henry D. Berkowitz, MD, Rodney A. White, MD, Thomas Fogarty, MD, Alan S. Berson, PhD Adaptive Responses of Arteries. Christopher K. Zarins, MD, William M. Abbott, MD Arterial Wall Response to Injury and Healing. Seymour Glagov, MD, Alexander W. Clowes, MD Mechanisms of Graft Failure. Harry L. Bush, Jr., MD, Dennis F. Bandyk, MD Panel Discussion. Moderator: James C. Stanley, MD. Panelists: Christopher K. Zarins, MD, William M. Abbott, MD, Seymour Glagov, MD, Alexander W. Clowes, MD, Harry L. Bush, Jr., MD, Dennis F. Bandyk, MD, Paul Didisheim, MD Aneurysmal Disease. M. David Tilson, MD, Philip Dobrin, MD, PhD Thrombosis and Thrombolysis. Patrick G. Claggett, MD, John M. Porter, MD Atherosclerosis, Lipids, and the Arterial Wall. William Lands, PhD, Joseph H. Rapp, MD Panel Discussion. Moderator: John M. Porter, MD. Panelists: M. David Tilson, MD, Phillip Dobrin, MD, Patrick G. Claggett, MD, William Lands, PhD, Gardiner C. McMillen, MD, Joseph H. Rapp, MD Introductory Comments. Frank W. LoGerfo, MD NIH Funded Research in Vascular Surgery. Paul Didishem, MD Mechanisms of Smooth Muscle Proliferation—The Rule of Cytokines and Growth Factors. Russell Ross, MD Smooth Muscle Cell Function in Intimal Hyperplasia. Peter Libby, MD The Role of Macrophage in Intimal Hyperplasia. Howard Greisler, MD Regulation of Growth Factor by Endothelium. Paul DiCorleto, MD Mechanical Stress and Cell Growth. Bauer Sumpio, MD Panel Discussion. Moderator: Russell Ross, MD. Panelists: Paul Didisheim, MD, Peter Libby, MD, Howard Greisler, MD, Paul DiCorleto, MD, Bauer Sumpio, MD What is Intimal Hyperplasia? Seymour Glagov, MD Morphology of Intimal Hyperplasia. Christian C. Haudenschild, MD Endarterectomy-Induced Intimal Hyperplasia. Harry L. Bush, Jr., MD Panel Discussion. Moderator: Christopher K. Zarins, MD. Panelists: Seymour Glagov, MD, Christian C. Haudenschild, MD, Harry L. Bush, Jr., MD Intimal Hyperplasia and Restenosis Following Carotid Endarterectomy. G. Patrick Claggett, MD Intimal Hyperplasia and Restenosis Following Coronary Angioplasty. Wade McBride, MD Biomechanics of Anastomotic Hyperplasia. Frank W. LoGerfo, MD Panel Discussion. Moderator: Jerry Goldstone, MD. Panelists: G. Patrick Claggett, MD, Wade McBride, MD, Frank W. LoGerfo, MD Vein Grafts: Clinical Aspects of Intimal Hyperplasia. Jonathan B. Towne, MD Vein Grafts: Pathobiology of Intimal Hyperplasia. Jerome I. Brody, MD Vein Grafts: Implantation Injury. Gayle D. Adcock, PhD Panel Discussion. Moderator: Frank W. LoGerfo, MD. Panelists: Jonathan B. Towne, MD, Jerome I. Brody, MD, Gayle D. Adcock, PhD Heparin Inhibition of Intimal Hyperplasia. Alexander W. Clowes, MD Inhibition of Adhesive Receptors. Jack Hawiger, MD, PhD Intimal Hyperplasia: In Vivo Mechanisms (Im-munologic, Mitogenic, and Eicosanoid), Lipo-protein Peroxidation, and Treatment with OMEGA-3 Fatty Acids. D. Craig Miller, MD Panel Discussion. Moderator: Jack L. Cronenwett, MD. Panelists: Alexander W. Clowes, MD, Jack Hawiger, MD, PhD, D. Craig Miller, MD Welcome. Frank W. LoGerfo, MD NHLBI Academic Award in Systemic and Pulmonary Vascular Disease. John C. Hoak, MD Initiatives in Cardiac Diseases Branch. Constance Weinstein, MD New Developments in Thrombolytic Therapy. Desire Collen, MD Thrombin After Clot Formation. John W. Fenton, II, MD Thrombolytic Agents in Venous Thrombosis. Alexander G. G. Turpie, MD Intraoperative Thrombolysis. Anthony J. Comerota, MD, FACS Thrombolytic Therapy in Perspective. John M. Porter, MD Hirudin: A Thrombin Inhibitor. James Chesebro, MD Thromboxane Inhibition. Jack L. Cronenwett, MD Prostaglandins as Antithrombotic Agents. V. Paul Adonizio, MD Clinical Aspects of Hypercoagulable States. Jonathan B. Towne, MD Hypercoagulability in Arterial Thrombosis: New Perspectives from Epidemiologic Studies. Kenneth K. Wu, MD Antithrombin III: Clinical Trials in Hip and Knee Replacement. Charles W. Francis, MD Endothelial Cell Fibrinolytic Assembly. Ralph L. Nachman, MD Gene Transfer into Endothelial Cells. W. French Anderson, MD Endothelial Cell Gene Transfer: Experimental Realities, Therapeutic Possibilities. Louis K. Birinyi, MD Moderator: Frank W. LoGerfo, MD Blood Contact Activation During Cardiopulmonary Bypass. L. Henry Edmunds, Jr., MD Platelet Materials Interaction. Laurence Harker, MD The Role of Plasma Protein in Platelet Activation by Artificial Surfaces. Jack Lindon, PhD Welcome. Frank W. LoGerfo, MD NHLBI Programs and Initiatives. Paul Didisheim, MD, John L. Fakunding, PhD Endothelial Biology Applied to Materials and Devices. Una S. Ryan, PhD Quantitative Studies of Endothelial Adhesion Using Confocal Image Analysis. Peter Davies, PhD Endothelial Seeding. Malcolm B. Herring, MD Microvessel Derived Endothelial Cells Isolation, Adherence, and Monolayer Formation for Vascular Grafts. Bruce E. Jarrell, MD Graft Endothelialization: The Role of Angiogenic Mechanisms. Alexander W. Clowes, MD Genetic Manipulation of Seeded Endothelial Cells in Vascular Prostheses. James C. Stanley, MD Relationship Between Anastomotic Hemodynamics and Intimal Thickening. Christopher K. Zarins, MD The Blood/Materials Interaction and Downstream Effects in Prosthetic Conduits. Frank W. LoGerfo, MD PDGF Production Following Prosthetic Graft Implantation. Linda M. Graham, MD Modulation of Cell Growth by Mechanical Stretch. Bauer E. Sumpio, MD, PhD Elastic Protein-Based Polymers as Cell Attachment Matrices. Dan W. Urry, PhD Absorbable Materials and Macrophage Interactions. Howard P. Greisler, MD Human Blood Protein and Cellular Interactions in the Healing Responses of Vascular Protheses. James M. Anderson, MD, PhD NIH Grant Application Process and Guidelines: Session for New Grant Applicants. James S. T. Yao, MD, PhD, Paul Parakkal, PhD A Critical Analysis of Clinical Prosthetic Graft Infections. Vincent G. Pons, MD Utilizing Vascular Protheses for Drug Delivery. Ralph S. Greco, MD Pathogenesis of Graft Infections. Richard L. Simmons, MD Prosthetic Infections Due to Bacterial Laden Biofilms: Experimental and Clinical Observations. Dennis F. Bandyk, MD SMC Growth Inhibition: Experimental Data, Rationale and Future Directions. Fredrick J. Schoen, MD, PhD Antithrombotic Agents: Experimental Data, Rationale and Future Directions. Edwin W. Salzman, MD Clinical Trials: Current Status and Recommendations. G. Patrick Clagett, MD Opening Remarks. G. Patrick Clagett, MD, Claude Lenfant, MD Vascular Diseases: An Approach for the 1990s. David M. Robinson, PhD Training and Career Opportunities Supported by the National Heart, Lung, and Blood Institute. John Fakunding, PhD Fundamental Concepts in the Preparation and Analysis of DNA and RNA. Bauer E. Sumpio, MD Use of the Linked Reverse Transcription/Polymerase Chain Reactin for mRNA Phenotyping of Vascular Wall Cells. John B. Sharefkin, MD Cloning and Expression of Human Erythropoietin, a Paradigm. Carl W. Dieffenbach, PhD Molecular Biology—Vascular Health and Disease. Una S. Ryan, PhD Panel Discussion: Molecular Biology, Surgical Investigators, and Realistic Goals. Moderator: G. Patrick Clagett, MD. Panelists: John B. Sharefkin, MD, James C. Stanley, MD, Allan D. Callow, MD, PhD, Bauer E. Sumpio, MD, Louis K. Birinyi, MD, Alexander W. Clowes, MD. Regulation of Smooth Muscle Cell Function by Heparin. Alexander W. Clowes, MD Analysis of Local Gene Expression in Human Atherosclerotic Plaques. Josiah N. Wilcox, MD Inducible Gene Expression in Vascular Wall Cells and Lesional Leukocytes. Peter Libby, MD Vascular Smooth Muscle Cell Extracellular Matrix. David J. Carey, PhD Flow-Mediated Modulation of Selected Biologic and Molecular Determinants Related to Vascular Endothelial Activation. Eugene S. Sprague, PhD Drug Effects on Vascular Wall Cell Gene Expression: A Probe of the Molecular Biology of the Early Hyperplasia/Late Fibrosis Response to Large Vessel Injury. John B. Sharefkin, MD Analysis of the ELAM-1 and VCAM-1 Promoters—Tools to Target Gene Expression to Endothe-lium in Transgenic Animals. Tucker Collin, MD, PhD Panel Discussion. Alexander W. Clowes, MD, Josiah N. Wilcox, MD, Peter Libby, MD, David J. Carey, PhD, Eugene A. Sprague, PhD, John B. Sharefkin, MD, Tucker Collins, MD, PhD NIH Grant Application Process and Guidelines: Session for New Grant Applicants. James S. T. Yao, MD, PhD, Paul Parakkal, PhD Rational for Molecular Approaches to the Etiology of Abdominal Aortic Aneurysm Disease. M. David Tilson, MD Abnormalities in Collagen Biosynthesis and Abdominal Aortic Aneurysm Disease. Susan Deak, MD Molecular Biology of the Marfan Syndrome. Harry C. Dietz, MD DNA Sequencing as a Method to Identify Muta-tions in Patients with Familial Forms of Aneurysms. Gerard Tromp, MD, Helena Kuivanieme, MD Genetic Defects of Lipoprotein Metabolism. Helen H. Hobbs, MD Mapping Genes for Hypertension. Victor J. Dzau, MD Panel Discussion. M. David Tilson, MD, Susan Deak, MD, Harry C. Dietz, MD, Helen H. Hobbs, MD, Victor J. Dzau, MD Direct Gene Transfer into the Arterial Wall. Elizabeth G. Nabel, MD Repopulation of Injured Arteries with Genetically Modified Endothelial Cells. Louis K. Birinyi, MD Antisense Technology to Block Autocrine Growth Factor. Victor J. Dzau, MD Gene Transfer in the Treatment of Thrombosis and Other Focal Vascular Diseases. David A. Dichek, MD, NIH Gene Therapy and Molecular Pharmacology. Allan D. Callow, MD, PhD Panel Discussion. Elizabeth G. Nabel, MD, Louis K. Birinyi, MD, Victor H. Dzau, MD, David A. Dichek, MD, Allan D. Callow, MD, PhD Program Projects in Vascular Medicine and Academic Awards. David M. Robinson, PhD, NHLBI SCOR's in Cardiovascular Disease. Constance Weinstein, PhD, NHLBI Programs of Excellence in Molecular Biology. Stephen C. Mockrin, PhD. NIH
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