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Stanley G Rockson

Publications and source records attributed to Stanley G Rockson.

32 records · Page 2Linked to original sources
PubMed2003

Endothelial cell diversity revealed by global expression profiling.

The vascular system is locally specialized to accommodate widely varying blood flow and pressure and the distinct needs of individual tissues. The endothelial cells (ECs) that line the lumens of blood and lymphatic vessels play an integral role in the regional specialization of vascular structure and physiology. However, our understanding of EC diversity is limited. To explore EC specialization on a global scale, we used DNA microarrays to determine the expression profile of 53 cultured ECs. We found that ECs from different blood vessels and microvascular ECs from different tissues have distinct and characteristic gene expression profiles. Pervasive differences in gene expression patterns distinguish the ECs of large vessels from microvascular ECs. We identified groups of genes characteristic of arterial and venous endothelium. Hey2, the human homologue of the zebrafish gene gridlock, was selectively expressed in arterial ECs and induced the expression of several arterial-specific genes. Several genes critical in the establishment of left/right asymmetry were expressed preferentially in venous ECs, suggesting coordination between vascular differentiation and body plan development. Tissue-specific expression patterns in different tissue microvascular ECs suggest they are distinct differentiated cell types that play roles in the local physiology of their respective organs and tissues.

Cells, Cultured↗
PubMed2003

Endothelial dysfunction: clinical strategies for treating oxidant stress.

BACKGROUND: A growing body of evidence has demonstrated that oxidants play a critical role in the pathogenesis of endothelial dysfunction. Pathologic processes fundamental to development and progression of endothelial dysfunction such as the oxidation of LDL, the loss of bioavailable nitric oxide, and the vascular inflammatory response are all modulated by oxidant stress. Therapeutic strategies to reverse endothelial dysfunction have begun to focus on agents with the ability to ameliorate oxidant stress. METHODS: Preclinical and clinical studies evaluating the actions of antioxidants as well as traditional cardiovascular therapies in ameliorating oxidative stress and endothelial dysfunction were reviewed through the use of a MEDLINE search of English language articles published between the years of 1992 and 2002. RESULTS: Antioxidants appear to be an attractive candidate therapy, yet despite compelling preclinical evidence supporting their benefits, efforts to validate the use of vitamins C and E in a clinical setting have been conflicting. In contrast, conventional cardiovascular therapies such as ACE inhibitors, statins, insulin-sensitizing agents, and estrogens have been shown to alleviate endothelial dysfunction, often independent of their effects on systemic disease processes. CONCLUSIONS: These agents restore endothelial function through their salutary effects on pathologic vascular oxidative processes.

Angiotensin Receptor Antagonists↗
PubMed2003

Coronary restenosis: a review of mechanisms and management.

Percutaneous coronary interventions represent an attractive alternative to surgical revascularization; nevertheless, these techniques continue to be characterized by their propensity to elicit restenosis. Despite an exhaustive search for an effective pharmacotherapy to treat or prevent restenosis, hundreds of clinical trials have failed to identify an agent with proven therapeutic benefit. Recently, however, the Food and Drug Administration approved intracoronary radiation (brachytherapy) as a viable therapeutic option for in-stent stenosis. In addition, recent randomized trials have shown encouraging results for drug-eluting stents. This article reviews the pathophysiology of restenosis, along with current and future treatment options.

Atherectomy, Coronary↗
PubMed2003

Animal models for the study of lymphatic insufficiency.

Lymphedema is the term commonly employed to describe the spectrum of pathological states that arise as a consequence of functional lymphatic insufficiency. These human disease entities currently lack an effective cure. Satisfactory therapeutic strategies for both primary and secondary lymphedema will require additional insight into the complex cellular mechanisms and responses that comprise both normal lymphatic function and its regional derangement in states of pathologic dysfunction. Such insights must, initially, be derived from suitable animal models of the chronic human disease process. Historically, efforts to replicate the untreated disease of human lymphedema in animals, through surgery, irradiation, and toxicology, have been fraught with difficulty. The major impediments to the creation of satisfactory animal models have included an inability to reproduce the chronic disease in a stable, reproducible format. Recently, with the promise of potentially successful growth factor-mediated therapeutic lymphangiogenesis, and with the enhanced availability of investigative tools to assess therapeutic responses to molecular therapies, there has been a resurgence of interest in the development of viable animal models of lymphatic insufficiency. Current research has led to the development of genetic and postsurgical models of lymphedema that closely simulate the human conditions of primary and secondary lymphatic insufficiency, respectively. Such models will help to refine the assessment of various therapeutic approaches and their potential applicability to human disease interventions.

Animals↗
PubMed2003

Immune traffic: a functional overview.

The efficient function of the immune system necessitates the complex interaction of antigens, antigen-presenting cells, and cell populations that modulate, regulate and effectuate the immune response. In order to overcome the spatial limitations that are imposed by the constraints of the system, the immune system has evolved a dependence upon the lymphatic vasculature to serve the biological needs of immune trafficking. This review will focus upon useful ex vivo and intact animal models that possess the ability to provide valuable information about leukocyte trafficking.

Animals↗
PubMed2002

Decongestive lymphatic therapy for patients with breast carcinoma-associated lymphedema. A randomized, prospective study of a role for adjunctive intermittent pneumatic compression.

BACKGROUND: Disruption of the lymphatic circulation through breast carcinoma-associated axillary lymph node dissection, with or without radiation therapy, reportedly is the most common cause of lymphedema in developed countries. There is no cure for breast carcinoma-associated lymphedema. Although intermittent pneumatic compression (IPC) has been acknowledged as a potential component of the multidisciplinary therapeutic strategy in the treatment of patients with breast carcinoma-associated lymphedema, prospective study of its adjunctive safety and efficacy is required. METHODS: IPC was assessed as a component of the initial therapeutic regimen for newly treated patients with breast carcinoma-associated lymphedema. Twenty-three patients who had not previously been treated for lymphedema were randomized to receive either decongestive lymphatic therapy (DLT) alone or DLT with daily adjunctive IPC. Patients with stable, treated, breast carcinoma-associated lymphedema also were assessed in the maintenance phase of therapy. Twenty-seven patients were randomized either to DLT alone or to DLT coupled with daily IPC. In both studies, objective assessment included serial measurement of volume by water displacement, tissue tonometry to assess elasticity of the skin, and goniometry to measure joint mobility. RESULTS: During initial treatment, the addition of IPC to standard DLT yielded an additional mean volume reduction (45.3% vs. 26%; P < 0.05). During maintenance DLT alone, there was a mean increase in volume (32.7 +/- 115.2 mL); with DLT and IPC, there was a mean volume reduction (89.5 +/- 195.5 mL; P < 0.05). In both studies, IPC was tolerated well without detectable adverse effects on skin elasticity or joint range of motion. CONCLUSIONS: When IPC is used adjunctively with other, established elements of DLT, it provides an enhancement of the therapeutic response. IPC is well tolerated and remarkably free of complications.

Aged↗
PubMed2002

Therapeutic lymphangiogenesis with human recombinant VEGF-C.

Chronic regional impairments of the lymphatic circulation often lead to striking architectural abnormalities in the lymphedematous tissues. Lymphedema is a common, disabling disease that currently lacks a cure. Vascular endothelial growth factors C and D mediate lymphangiogenesis through the VEGFR-3 receptor on lymphatic endothelia. The purpose of this study was to investigate the therapeutic potential for lymphangiogenesis with VEGF-C. We developed a rabbit ear model to simulate human chronic postsurgical lymphatic insufficiency. Successful, sustained surgical ablation of the ear lymphatics was confirmed by water displacement volumetry. After complete healing, the experimental animals (n=8) received a single, s.c. 100 microg dose of VEGF-C in the operated ear; controls (n=8) received normal saline. Radionuclide lymphoscintigraphy was performed to quantitate lymphatic function. Immunohistochemistry (IHC) was performed 7-8 days following treatment. After VEGF-C, there was a quantifiable amelioration of lymphatic function. IHC confirmed a significant increase in lymphatic vascularity, along with reversal of the intense tissue hypercellularity of untreated lymphedema. This study confirms the capacity of a single dose of VEGF-C to induce therapeutic lymphangiogenesis in acquired lymphedema. In addition to improving lymphatic function and vascularity, VEGF-C can apparently reverse the abnormalities in tissue architecture that accompany chronic lymphatic insufficiency.

Animals↗
PubMed2002

The role of chemokines in human cardiovascular pathology: enhanced biological insights.

A growing body of experimental evidence supports the pivotal role of chemokines in the pathogenesis of vascular disease. The endothelial expression of monocyte chemoattractant protein-1 (MCP-1) is apparently essential for the earliest cellular responses of atherogenesis. Many atherogenic and anti-atherogenic stimuli can be construed to exert their effects predominantly upon MCP-1 expression within the vascular wall. The atherogenic effects of interleukin-8 (IL-8) seem to be mediated through the down-regulation of the tissue inhibitor of metalloproteinase-1 (TIMP-1). Biological expression of these two important vascular chemokines is further modulated by NF-kappaB. The delineation of these molecular forces that drive atherogenesis increasingly underscores the pivotal role of various chemokines. It is anticipated that more precise delineation of these patterns of gene expression will help to identify molecular targets for the prevention and treatment of atherosclerosis.

Animals↗
PubMed2002

Diagnosis and treatment of concomitant venous obstruction in patients with secondary lymphedema.

PURPOSE: It has been proposed that concomitant iatrogenic venous obstruction substantially contributes to the appearance and severity of the secondary lymphedema that follows cancer surgery, radiation, and other traumas. The purpose of this study was to investigate the frequency of venous obstruction in the clinical presentation of patients with secondary lymphedema and to analyze the efficacy of interventional therapy in this patient population. MATERIALS AND METHODS: The experience of the university center for lymphatic and venous disorders with combined lymphaticovenous edema was retrospectively examined. The records and clinical course were reviewed for all patients referred to a university lymphedema center for evaluation between January 1996 and March 1999. During this interval, in 365 patients with lymphedema, 35 radiocontrast venograms were obtained to evaluate the suspected presence of mixed lymphaticovenous edema. Venographic evidence of venous stenosis (>50%) or occlusion was analyzed, as were the technical success of the intervention, determined by ability to cross the affected segment of the vein and perform venoplasty and place the stent, and the clinical success of the intervention assessed by relief of clinical symptoms (edema, pain) within 24 hours. RESULTS: The diagnosis of venous obstruction was confirmed in 17 patients (4.6% of all patients with lymphedema; 49% of patients studied with venography). Venography disclosed clinically relevant venous stenosis in five of seven patients with edema of the upper extremity and in six of 10 patients with leg lymphedema. Venous occlusion was found in two of seven patients with upper extremity edema and in four of 10 patients with leg lymphedema. Percutaneous endovascular venoplasty was attempted in all 17 patients and was successful in 16. Subsequent venous stent placement was performed in three patients with upper extremity edema and in all patients with lower extremity lymphedema. Clinical amelioration of edema was observed in 15 of these 17 patients. Amelioration was assessed by relief of symptoms, improvement in function, and reduction in limb girth. CONCLUSIONS: This study supports the clinical importance of concomitant venous obstruction in some patients with chronic secondary lymphedema. Edema can often be ameliorated through percutaneous catheter-based interventions.

Adult↗
PubMed2002

Preclinical models of lymphatic disease: the potential for growth factor and gene therapy.

The human disease states that are characterized by functional lymphatic insufficiency currently lack a cure. Molecular approaches may ultimately provide a therapeutic window to reverse the stigmata of both primary and secondary lymphatic insufficiency. To harness the potential therapeutic power of lymphangiogenesis, testing the safety and efficacy of the treatment response will be necessary. This, in turn, necessitates the availability of suitable preclinical animal models of the disease processes in question, along with suitable research tools to permit an assessment of the response to applied therapies. An ideal model would reproducibly and inexpensively replicate the untreated disease of human lymphedema. It would closely simulate the biology, as we understand it, of the human disease, and would replicate both the pathogenesis of the disease, including its natural history and the temporal patterns of its clinical expression. In this way, one might aspire to make valid predictions about the human applicability of therapy by extrapolation from observations in animal models. In addition to the availability of suitable animal models, the required investigative tools must also be available. In the context of lymphangiogenesis, to assess the therapeutic response, one must certainly possess the ability to recognize newly developed lymphatic vasculature. Sophisticated immunohistochemical and imaging techniques make this increasingly feasible. Initial experimental observations indicate that growth factor and gene therapy with VEGF-C holds promise for the treatment of both primary and secondary forms of lymphedema.

Animals↗