advertisement
Browse Health
Cardiologist (heart)
36 years of experience
Video profile
Accepting new patients

Credentials

Education ?

Medical School Score Rankings
Duke University (1975)
  •  
Top 25%

Awards & Distinctions ?

Awards  
Castle Connolly's Top Doctors™ (2012 - 2013)
Patients' Choice Award (2014)
Compassionate Doctor Recognition (2014)
Top 10 Doctor - Metro Area (2014)
Greater San Jose
Cardiologist
On-Time Doctor Award (2014)
Appointments
Stanford Hospital & Clinics
Associations
American Board of Internal Medicine

Affiliations ?

Dr. Rockson is affiliated with 2 hospitals.

Hospital Affiliations

Score

Rankings

  • Stanford Hospital and Clinics *
    Cardiology
    300 Pasteur Dr, Stanford, CA 94305
    •  
    Top 50%
  • Lucile Salter Packard Children's Hospital @ Stanford
    Cardiology
    725 Welch Rd, Palo Alto, CA 94304
    •  
  • * This information was reported to Vitals by the doctor or doctor's office.

    Publications & Research

    Dr. Rockson has contributed to 83 publications.
    Title Temporal and Spatial Patterns of Endogenous Danger Signal Expression After Wound Healing and in Response to Lymphedema.
    Date July 2011
    Journal American Journal of Physiology. Cell Physiology
    Excerpt

    While acute tissue injury potently induces endogenous danger signal expression, the role of these molecules in chronic wound healing and lymphedema is undefined. The purpose of this study was to determine the spatial and temporal expression patterns of the endogenous danger signals high-mobility group box 1 (HMGB1) and heat shock protein (HSP)70 during wound healing and chronic lymphatic fluid stasis. In a surgical mouse tail model of tissue injury and lymphedema, HMGB1 and HSP70 expression occurred along a spatial gradient relative to the site of injury, with peak expression at the wound and greater than twofold reduced expression within 5 mm (P < 0.05). Expression primarily occurred in cells native to injured tissue. In particular, HMGB1 was highly expressed by lymphatic endothelial cells (>40% positivity; twofold increase in chronic inflammation, P < 0.001). We found similar findings using a peritoneal inflammation model. Interestingly, upregulation of HMGB1 (2.2-fold), HSP70 (1.4-fold), and nuclear factor (NF)-κβ activation persisted at least 6 wk postoperatively only in lymphedematous tissues. Similarly, we found upregulation of endogenous danger signals in soft tissue of the arm after axillary lymphadenectomy in a mouse model and in matched biopsy samples obtained from patients with secondary lymphedema comparing normal to lymphedematous arms (2.4-fold increased HMGB1, 1.9-fold increased HSP70; P < 0.01). Finally, HMGB1 blockade significantly reduced inflammatory lymphangiogenesis within inflamed draining lymph nodes (35% reduction, P < 0.01). In conclusion, HMGB1 and HSP70 are expressed along spatial gradients and upregulated in chronic lymphatic fluid stasis. Furthermore, acute expression of endogenous danger signals may play a role in inflammatory lymphangiogenesis.

    Title Stress-induced Cardiomyopathy Associated with a Transfusion Reaction: A Case of Potential Crosstalk Between the Histaminic and Adrenergic Systems.
    Date July 2011
    Journal Experimental and Clinical Cardiology
    Excerpt

    The adrenergic and histaminergic systems have been reported to have analogous effects on the heart. A case of transient ventricular dysfunction with echocardiographic findings characteristic of stress-induced cardiomyopathy (also known as takotsubo cardiomyopathy) in a patient who had an urticarial transfusion reaction is described. The effect of histamine on ventricular function and its interaction with the adrenergic system are discussed.

    Title Secondary Lymphedema: is It a Primary Disease?
    Date October 2008
    Journal Lymphatic Research and Biology
    Title Diagnosis and Management of Lymphatic Vascular Disease.
    Date September 2008
    Journal Journal of the American College of Cardiology
    Excerpt

    The lymphatic vasculature is comprised of a network of vessels that is essential both to fluid homeostasis and to the mediation of regional immune responses. In health, the lymphatic vasculature possesses the requisite transport capacity to accommodate the fluid load placed upon it. The most readily recognizable attribute of lymphatic vascular incompetence is the presence of the characteristic swelling of tissues, called lymphedema, which arises as a consequence of insufficient lymph transport. The diagnosis of lymphatic vascular disease relies heavily upon the physical examination. If the diagnosis remains in question, the presence of lymphatic vascular insufficiency can be ascertained through imaging, including indirect radionuclide lymphoscintigraphy. Beyond lymphoscintigraphy, clinically-relevant imaging modalities include magnetic resonance imaging and computerized axial tomography. The state-of-the-art therapeutic approach to lymphatic edema relies upon physiotherapeutic techniques. Complex decongestive physiotherapy is an empirically-derived, effective, multicomponent technique designed to reduce limb volume and maintain the health of the skin and supporting structures. The application of pharmacological therapies has been notably absent from the management strategies for lymphatic vascular insufficiency states. In general, drug-based approaches have been controversial at best. Surgical approaches to improve lymphatic flow through vascular reanastomosis have been, in large part, unsuccessful, but controlled liposuction affords lasting benefit in selected patients. In the future, specifically engineered molecular therapeutics may be designed to facilitate the controlled regrowth of damaged, dysfunctional, or obliterated lymphatic vasculature in order to circumvent or mitigate the vascular insufficiency that leads to edema and tissue destruction.

    Title The Lymphatic Continuum Revisited.
    Date July 2008
    Journal Annals of the New York Academy of Sciences
    Title Animal Models for the Molecular and Mechanistic Study of Lymphatic Biology and Disease.
    Date July 2008
    Journal Annals of the New York Academy of Sciences
    Excerpt

    The development of animal model systems for the study of the lymphatic system has resulted in an explosion of information regarding the mechanisms governing lymphatic development and the diseases associated with lymphatic dysfunction. Animal studies have led to a new molecular model of embryonic lymphatic vascular development, and have provided insight into the pathophysiology of both inherited and acquired lymphatic insufficiency. It has become apparent, however, that the importance of the lymphatic system to human disease extends, beyond its role in lymphedema, to many other diverse pathologic processes, including, very notably, inflammation and tumor lymphangiogenesis. Here, we have undertaken a systematic review of the models as they relate to molecular and functional characterization of the development, maturation, genetics, heritable and acquired diseases, and neoplastic implications of the lymphatic system. The translation of these advances into therapies for human diseases associated with lymphatic dysfunction will require the continued study of the lymphatic system through robust animal disease models that simulate their human counterparts.

    Title Estimating the Population Burden of Lymphedema.
    Date July 2008
    Journal Annals of the New York Academy of Sciences
    Excerpt

    Lymphedema is a complex, regional edematous state that ensues when lymph transport is insufficient to maintain tissue homeostasis. The disorder is remarkably prevalent, but the population implications of lymphatic dysfunction are not well-studied. Prevalence estimates for lymphedema are relatively high, yet its prevalence is likely underestimated. The ability to estimate the burden of disease poses profound implications for current and future lymphedema patients, but the challenge to correctly surmise the incidence and prevalence of lymphedema is complex and the relevant medical literature is scanty. In the absence of the highly desired, prospectively designed and rigorously performed relevant epidemiologic studies, it is instructive to look at the existing studies of lymphedema disease burden. In the current review, the extant literature is examined in the context of the disease setting in which tissue edema is encountered. Incidence or prevalence estimates are provided or inferred, and, where feasible, the size of the subject population is also identified. It is extremely attractive to contemplate that future approaches will entail formal, prospectively designed studies to objectively quantitate incidence and prevalence statistics for individual categories, as well as for the global lymphedema population.

    Title The Clinical Spectrum of Lymphatic Disease.
    Date July 2008
    Journal Annals of the New York Academy of Sciences
    Excerpt

    Lymphatic disease is quite prevalent, and often not well clinically characterized. Beyond lymphedema, there is a broad array of human disease that directly or indirectly alters lymphatic structure and function. The symptomatic and objective presentation of these patients can be quite diverse. In this review, we have attempted to provide a systematic overview of the subjective and objective spectrum of lymphatic disease, with consideration of all of the categories of disease that primarily or secondarily impair the functional integrity of the lymphatic system. Lymphedema is discussed, along with chromosomal disorders, lymphangioma, infectious diseases, lymphangioleiomyomatosis, lipedema, heritable genetic disorders, complex vascular malformations, protein-losing enteropathy, and intestinal lymphangiectasia.

    Title Gorham's Disease: an Osseous Disease of Lymphangiogenesis?
    Date July 2008
    Journal Annals of the New York Academy of Sciences
    Excerpt

    Gorham's disease, also known as massive osteolysis, Gorham-Stout disease, vanishing bone disease, or, phantom bone disease is a rare disorder of the musculoskeletal system. The disease is characterized by osteolysis in bony segments, with localized proliferation of lymphatic channels. The presence of abundant, leaky systemic lymphatic vessels is often accompanied by chylous ascites. There is no standardized treatment available for Gorham's disease, and its molecular mechanisms remain unclear. Future strategies for understanding Gorham's disease should emphasize its apparent identity as a disease of disordered lymphangiogenesis. Breakthroughs in lymphatic research have identified several lymphangiogenic pathways that may play a relevant role in Gorham's disease.

    Title A Population-based Assessment of the Problem of Lymphatic Disease.
    Date June 2008
    Journal Lymphatic Research and Biology
    Title Molecular Insights into the Microvascular Regulation of Lymph Formation.
    Date March 2008
    Journal Lymphatic Research and Biology
    Title Reinforcing a Continuum of Care: In-hospital Initiation of Long-term Secondary Prevention Following Acute Coronary Syndromes.
    Date February 2008
    Journal Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy
    Excerpt

    INTRODUCTION: Patients with a history of acute coronary syndrome are particularly susceptible to further vascular or ischemic events. Effective secondary prevention following acute coronary syndrome requires multiple medications targeting the different mechanisms of atherothrombosis. The 2002 American College of Cardiology/American Heart Association guidelines for the management of unstable angina and non ST-segment myocardial infarction and the 2004 guidelines for ST-segment myocardial infarction assign priority to the long-term administration of four critical classes of drugs: antiplatelet agents, in particular aspirin and clopidogrel, beta-blockers, angiotensin-converting enzyme inhibitors, and statins. CONCLUSIONS: Despite clinical trial evidence demonstrating their ability to reduce cardiovascular morbidity and mortality, available preventive pharmacotherapies remain underutilized. Suboptimal compliance with current recommendations, as with other management guidelines, arises from a host of entrenched physician, patient, and system-related factors. Optimal management of acute coronary syndrome acknowledges a continuum of care in which acute stabilization represents a single important component. Early, in-hospital implementation of secondary preventive measures reinforces the continuum of care approach, promoting a successful transition from treatment to prevention, inpatient to outpatient management, and, when appropriate, subspecialist to generalist care.

    Title Biomarkers of Lymphatic Function and Disease: State of the Art and Future Directions.
    Date October 2007
    Journal Molecular Diagnosis & Therapy
    Excerpt

    Substantial advances have accrued over the last decade in the identification of the processes that contribute to lymphatic vascular development in health and disease. Identification of distinct regulatory milestones, from a variety of genetic models, has led to a stepwise chronology of lymphatic development. Several molecular species have been identified as important tissue biomarkers of lymphatic development and function. At present, vascular endothelial growth-factor receptor (VEGFR)-3/VEGF-C/VEGF-D signaling has proven useful in the identification of clinical lymphatic metastatic potential and the assessment of cancer prognosis. Similar biomarkers, to be utilized as surrogates for the assessment of inherited and acquired diseases of the lymphatic circulation, are actively sought, and will represent a signal advance in biomedical investigation.

    Title A Novel Vegfr3 Mutation Causes Milroy Disease.
    Date August 2007
    Journal American Journal of Medical Genetics. Part A
    Excerpt

    Milroy disease, also known as primary congenital lymphedema, is a hereditary form of lymphedema with autosomal dominant inheritance. Individuals with Milroy disease are typically characterized by congenital onset of lymphedema of the lower limbs due to hypoplasia of the lymphatic vessels. The genetic basis of most cases of Milroy disease has not been established, although mutations in the vascular endothelial growth factor receptor VEGFR3 (FLT-4) are responsible for some cases with 17 mutations described to date. In this report, we describe a novel VEGFR3 mutation in exon 22 in a four-generation family in which congenital lymphedema segregates in an autosomal dominant manner. In addition to lymphedema, affected family members had other clinical manifestations associated with Milroy disease including hydrocele, ski jump toenails, large caliber veins, and subcutaneous thickening. We screened VEGFR3 for mutations which revealed a novel 3059A>T transversion in exon 22 resulting in Q1020L missense mutation in the second tyrosine kinase domain of VEGFR3. This mutant allele segregated with lymphedema among affected individuals with incomplete penetrance. This is the first report of an exon 22 mutation in Milroy disease.

    Title Lymphatics and the Heart: the Importance of Visceral Lymphatic Function in Health and Disease.
    Date July 2007
    Journal Lymphatic Research and Biology
    Title Rapid Diagnosis of Myocardial Injury with Troponin T and Ck-mb Relative Index.
    Date June 2007
    Journal Molecular Diagnosis & Therapy
    Excerpt

    BACKGROUND: Current hospital practice involves protracted observation of chest-pain patients to rule out myocardial infarction. Concurrent measurement of multiple biomarkers may increase sensitivity and make rapid diagnosis feasible. OBJECTIVE: We sought to determine the optimal biomarker strategy for highly sensitive, early diagnosis of myocardial injury. STUDY DESIGN: A prospective evaluation of 171 acute coronary syndrome patients admitted to a single university medical center was performed. Blood tests for creatine kinase (CK), CK myocardial band isoenzyme (CK-MB), and troponin T were obtained at 0, 3, 6, 8, and 16 hours after presentation to the emergency department. Myocardial injury was defined as a troponin T level of >or=0.03 ng/mL. RESULTS: Troponin T had sensitivities of 79.7%, 95.7%, and 98.4% at the time of initial presentation, 3 and 6 hours after presentation, respectively. Using a combination of troponin T and CK-MB relative index, sensitivity on presentation was increased to 90.6%. The sensitivity was improved to 97.9% and 100% at 3 and 6 hours, respectively. CONCLUSION: This study demonstrates that the diagnosis of myocardial injury can be accurately excluded within 6 hours of admission with high sensitivity using troponin T. The combination of troponin T and CK-MB relative index provided the largest improvement in diagnostic sensitivity at patient arrival. These results support the feasibility of rapid, efficient triage for the emergent presentation of patients with chest pain.

    Title The Lymphatic Continuum Continues.
    Date June 2007
    Journal Lymphatic Research and Biology
    Title Addressing the Unmet Needs in Lymphedema Risk Management.
    Date June 2007
    Journal Lymphatic Research and Biology
    Title Literature Watch.
    Date June 2007
    Journal Lymphatic Research and Biology
    Title An Experimental Model for the Study of Lymphedema and Its Response to Therapeutic Lymphangiogenesis.
    Date June 2007
    Journal Biodrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
    Excerpt

    BACKGROUND: Evaluation of the efficacy of molecular treatment strategies for lymphatic vascular insufficiency requires a suitable preclinical animal model. Ideally, the model should closely replicate the untreated human disease in its pathogenesis and pathological expression. OBJECTIVE: We have undertaken a study of the time course of the development and resolution of acquired, experimental lymphedema and of its responses to vascular endothelial growth factor (VEGF)-C lymphangiogenesis in the mouse tail model. STUDY DESIGN: We provoked post-surgical lymphedema in the mouse tail model and assessed the effects of exogenously administered human recombinant VEGF-C. Quantitative assessment of immune traffic function was performed through sequential in vivo bioluminescent imaging. RESULTS: In untreated lymphedema, tail edema was sustained until day 21. Exogenous administration of human recombinant VEGF-C produced a significant decrease in volume. Untreated lymphedema in the mouse tail model was characterized by the presence of dilated cutaneous lymphatics, marked acute inflammatory changes, and hypercellularity; VEGF-C produced a substantial reversion to the normal pattern, with notable regression in the size and number of cutaneous lymphatic vessels that express lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1). In vivo imaging confirmed the presence of an impairment of immune traffic in lymphedema that was ameliorated after VEGF-C administration. CONCLUSION: The post-surgical murine tail model of lymphedema closely simulates attributes of human lymphedema and provides the requisite sensitivity to detect therapeutically induced functional and structural alterations. It can, therefore, be used as an investigative platform to assess mechanisms of disease and its responses to candidate therapies, such as therapeutic lymphangiogenesis.

    Title A Roadmap for the Lymphatics.
    Date May 2007
    Journal Lymphatic Research and Biology
    Title Indirect Magnetic Resonance Lymphangiography to Assess Lymphatic Function in Experimental Murine Lymphedema.
    Date May 2007
    Journal Lymphatic Research and Biology
    Excerpt

    BACKGROUND: Recently, indirect magnetic resonance lymphangiography with gadolinium (Gd) has been demonstrated to offer the potential for safe, high-resolution visualization of the lymphatic vessels, in addition to the lymph nodes. In this study, the potential utility of indirect Gd contrast magnetic resonance imaging of lymphatic vascular function was investigated in the murine tail. Functional imaging of healthy mice is contrasted with the findings in experimentally-induced lymphatic vascular insufficiency. METHODS: Postsurgical lymphedema was experimentally created in the murine tail. Normal and lymphedematous mouse tails were imaged following direct subcutaneous administration of Gadolinium-DTPA, 0.1 mmol/kg. Images were obtained in axial and coronal planes with a T1-weighted spin echo inversion-recovery sequence. RESULTS: In the normal tail, both of the bilateral major collecting lymphatics were clearly visualized as the Gd tracer was cleared from the interstitial compartment. In contrast, the Gd tracer accumulated at the prior surgical site in the lymphedematous tail. Quantitative assessment of Gd clearance demonstrates that accumulation of Gd correlates with the impedance to lymph flow proximal to the site of surgical lymphatic ablation. CONCLUSION: Magnetic resonance is a feasible and reliable method to be applied to quantitative functional imaging of the lymphatic vasculature in experimental models of lymphedema.

    Title Inflammatory Manifestations of Experimental Lymphatic Insufficiency.
    Date February 2007
    Journal Plos Medicine
    Excerpt

    BACKGROUND: Sustained lymph stagnation engenders a pathological response that is complex and not well characterized. Tissue inflammation in lymphedema may reflect either an active or passive consequence of impaired immune traffic. METHODS AND FINDINGS: We studied an experimental model of acute post-surgical lymphedema in the tails of female hairless, immunocompetent SKH-1 mice. We performed in vivo imaging of impaired immune traffic in experimental, murine acquired lymphatic insufficiency. We demonstrated impaired mobilization of immunocompetent cells from the lymphedematous region. These findings correlated with histopathological alterations and large-scale transcriptional profiling results. We found intense inflammatory changes in the dermis and the subdermis. The molecular pattern in the RNA extracted from the whole tissue was dominated by the upregulation of genes related to acute inflammation, immune response, complement activation, wound healing, fibrosis, and oxidative stress response. CONCLUSIONS: We have characterized a mouse model of acute, acquired lymphedema using in vivo functional imaging and histopathological correlation. The model closely simulates the volume response, histopathology, and lymphoscintigraphic characteristics of human acquired lymphedema, and the response is accompanied by an increase in the number and size of microlymphatic structures in the lymphedematous cutaneous tissues. Molecular characterization through clustering of genes with known functions provides insights into processes and signaling pathways that compose the acute tissue response to lymph stagnation. Further study of genes identified through this effort will continue to elucidate the molecular mechanisms and lead to potential therapeutic strategies for lymphatic vascular insufficiency.

    Title Validation of a New Technique for the Quantitation of Edema in the Experimental Setting.
    Date December 2006
    Journal Lymphatic Research and Biology
    Excerpt

    BACKGROUND: An inherent limitation to the study of in vivo animal models of lymphedema is the potential inaccuracy or unreliability of existing methods for the quantification of edema volume as a surrogate functional measure of lymphatic transport capacity. Circumference-based techniques have been proposed and validated as a suitable alternative to volume displacement measurements in human clinical studies; accordingly, we have elaborated a new application of this approach that can be applied to small animal studies. METHODS: Acute postsurgical lymphedema was created experimentally in the murine tail. Both normal and lymphedematous murine tails were examined. Tail volume was quantitated both by water displacement and by a digital photographic technique. In selected mice, after sacrificed on postsurgical day 7, a 6 cm segment was resected from the midportion of the tail and cauterized to create a closed space. Known incremental volumes of saline (20-100 microL) were injected for subsequent digital photographic volumetry. RESULTS: The coefficients of variation for volume assessment by water displacement and by digital imaging were 0.08+/-0.09 and 0.01+/-0.009, respectively. The two techniques were poorly correlated: while serial water displacement analysis yielded highly variable measurements within the same tail, concurrent digital imaging of the tail circumference was quite reproducible. Furthermore, after parenteral injection of known incremental volumes of saline, the correlation between the injectate volumes and the digitally measured increases in volume was high, both in the normal and the lymphedematous tail. CONCLUSION: In the murine tail, when compared to water displacement volumetry, digital photography yields highly reproducible data. We can conclude that the lack of correlation between the two methods, with the relatively flat slope of the linear regression relationship, reflects inherent inaccuracies of the water displacement method.

    Title Therapeutics for Lymphatic Disease: the Role of the Pharmaceutical and Biotechnology Sector.
    Date December 2006
    Journal Lymphatic Research and Biology
    Title Lymphedema.
    Date May 2006
    Journal Current Treatment Options in Cardiovascular Medicine
    Excerpt

    Aggressively applied decongestive measures (ie, manual lymphatic drainage, low-stretch bandaging, exercise, skin care, application of compressive elastic garments) are the mainstay of lymphatic therapy. Therapeutic regimens should differentiate between the sequential goals of acute volume reduction and maintenance of limb volume. Elastic garments should not be employed until maximal volume reduction has been attained through decongestive lymphatic techniques. It is my opinion that use of intermittent pneumatic compression devices can play an important adjunctive role to decongestive lymphatic therapy but should not be substituted for these techniques. At this time, I am not inclined to use pharmacologic therapy in these patients but anxiously await the results of studies that might demonstrate efficacy for molecular approaches. Surgical intervention is reserved for a small number of well-selected patients. Liposuction for volume reduction appears to be a very promising approach for specific patients.

    Title A Pilot, Prospective Evaluation of a Novel Alternative for Maintenance Therapy of Breast Cancer-associated Lymphedema [isrctn76522412].
    Date May 2006
    Journal Bmc Cancer
    Excerpt

    BACKGROUND: Prospective investigations of complete decongestive lymphatic physiotherapy (CDPT), including manual lymphatic drainage (MLD), have validated the efficacy of these interventions for the initial reduction of edema and long-term maintenance of limb volume in lymphedema. However, CDPT demands substantial time and effort from patients to maintain these benefits; the treatments are not always well-accepted, and patients may suffer from a deterioration in quality-of-life or a time-dependent loss of initial treatment benefits. A new device designed for home use by the patient, the Flexitouch, has been developed to mechanically simulate MLD. We have undertaken a prospective, randomized, crossover study of the efficacy of the Flexitouch, when compared to massage, in the self-administered maintenance therapy of lymphedema. METHODS: A prospective, randomized, crossover study of maintenance therapy was performed in 10 patients with unilateral breast cancer-associated lymphedema of the arm. Each observation phase included self-administered treatment with the Flexitouch or massage, 1 hour daily for 14 days, respectively, followed by crossover to the alternate treatment phase. Each treatment phase was preceded by a 1 week treatment washout, with use of garment only. The sequence of treatment was randomly assigned. The potential impact of treatment modality on quality of life was assessed with serial administration of the SF-36. RESULTS: Statistical analysis disclosed that the order of treatment had no outcome influence, permitting 10 comparisons within each treatment group. Post-treatment arm volume reduced significantly after the Flexitouch, but not after self-administered massage. The patients' mean weight decreased significantly with Flexitouch use, but not with massage. The Flexitouch device was apparently well-tolerated and accepted by patients. Serial SF-36 administration showed no deterioration in physical or psychosocial scores compared to baseline measurements; there were no statistical differences in scores when the two treatment modalities were compared. CONCLUSION: This short-term prospective evaluation of the Flexitouch suggests that the device may provide better maintenance edema control than self-adiminstered massage in breast cancer-associated lymphedema. The apparent ease of use and reliability of response to the device suggest that further broad-scale testing is warranted.

    Title Lymphedema Therapy in the Vascular Anomaly Patient: Therapeutics for the Forgotten Circulation.
    Date February 2006
    Journal Lymphatic Research and Biology
    Title Literature Watch. A Genetic Xenopus Laevis Tadpole Model to Study Lymphangiogenesis.
    Date February 2006
    Journal Lymphatic Research and Biology
    Title Treprostinil for the Treatment of Severe Digital Necrosis in Systemic Sclerosis.
    Date August 2005
    Journal Vascular Medicine (london, England)
    Excerpt

    We report a case of severe digital ulcerations associated with systemic sclerosis, successfully treated with treprostinil (Remodulin). There was improvement within days of the treatment initiation; complete healing was accomplished after 16 weeks of therapy. Patients with systemic sclerosis and peripheral small vessel disease have limited therapeutic options. Treprostinil is a prostacyclin analogue that can be delivered by subcutaneous infusion and is approved in the USA only for treatment of primary pulmonary hypertension. This report provides an impressive example of an alternative, complementary indication for the use of treprostinil.

    Title The Lymphatic Biology of Kaposi's Sarcoma.
    Date June 2005
    Journal Lymphatic Research and Biology
    Title Tumors, Wounds, and Lymph.
    Date May 2005
    Journal Lymphatic Research and Biology
    Title The Potential for Molecular Treatment Strategies in Lymphatic Disease.
    Date May 2005
    Journal Lymphatic Research and Biology
    Title The Elusive Adipose Connection.
    Date March 2005
    Journal Lymphatic Research and Biology
    Title Literature Watch. Cooke Cj, Nanjee Mn, Stepanova Ip, Olszewski Wl, Miller Ne. Variations in Lipid and Apolipoprotein Concentrations in Human Leg Lymph: Effects of Posture and Physical Exercise. Atherosclerosis 2004; 173:39-45.
    Date March 2005
    Journal Lymphatic Research and Biology
    Title Literature Watch. Hirakawa S, Hong Yk, Harvey N, Schacht V, Matsuda K, Libermann T, Detmar M. Identification of Vascular Lineage-specific Genes by Transcriptional Profiling of Isolated Blood Vascular and Lymphatic Endothelial Cells. Am J Pathol. 2003; 162:575-86.
    Date March 2005
    Journal Lymphatic Research and Biology
    Title How Can Lymphatic Research Influence Lymphatic Education?
    Date March 2005
    Journal Lymphatic Research and Biology
    Title Lymphatic Biology and Disease: is It Being Taught? Who is Listening?
    Date March 2005
    Journal Lymphatic Research and Biology
    Title Animal Models for the Study of Lymphatic Insufficiency.
    Date January 2005
    Journal Lymphatic Research and Biology
    Excerpt

    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.

    Title Immune Traffic: a Functional Overview.
    Date January 2005
    Journal Lymphatic Research and Biology
    Excerpt

    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.

    Title Comparing the Guidelines: Anticoagulation Therapy to Optimize Stroke Prevention in Patients with Atrial Fibrillation.
    Date April 2004
    Journal Journal of the American College of Cardiology
    Excerpt

    Atrial fibrillation (AF) is an important risk factor for stroke. According to a pooled analysis of controlled clinical trials with warfarin, anticoagulation therapy reduces stroke risk by 62%. However, clinicians must decide whether the benefit of long-term anticoagulation therapy with available agents outweighs the risk of bleeding for individual patients. Guidelines issued by the American College of Chest Physicians and by the joint American College of Cardiology, American Heart Association, and the European Society of Cardiology task force recommend antithrombotic therapy to protect AF patients from stroke based on risk-stratification algorithms. Risk factors for stroke AF patients include age > or =75 years; hypertension; thyrotoxicosis; diabetes; cardiovascular disease; congestive heart failure; and history of stroke, transient ischemic attack, or thromboembolism. Patients at high risk for stroke experience greater absolute benefit from anticoagulation therapy than patients at low risk. The guidelines are consistent in recommendations for high-risk patients (warfarin therapy, international normalized ratio 2.0 to 3.0) and low-risk patients (aspirin 325 mg), but differ for intermediate-risk patients with diabetes or heart disease. The guidelines continue to evolve, and future guidelines are likely to incorporate new clinical data, including the CHADS(2) algorithm for determining risk and the results of the Atrial Fibrillation Follow-up Investigation of Rhythm Management trial, the Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation study, and the Stroke Prevention Using an Oral Thrombin Inhibitor in Atrial Fibrillation II to V trials.

    Title Coronary Restenosis: a Review of Mechanisms and Management.
    Date December 2003
    Journal The American Journal of Medicine
    Excerpt

    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.

    Title Endothelial Cell Diversity Revealed by Global Expression Profiling.
    Date October 2003
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    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.

    Title Endothelial Dysfunction: Clinical Strategies for Treating Oxidant Stress.
    Date September 2003
    Journal American Heart Journal
    Excerpt

    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.

    Title Quantitative Radionuclide Lymphoscintigraphy Predicts Outcome of Manual Lymphatic Therapy in Breast Cancer-related Lymphedema of the Upper Extremity.
    Date June 2003
    Journal Nuclear Medicine Communications
    Excerpt

    Secondary lymphedema is a localized, acquired lymphatic microcirculatory disturbance that affects large numbers of patients after breast cancer therapy. There is a paucity of objective methods to quantitate lymphatic function and to anticipate the response to therapeutic interventions. We applied radionuclide lymphoscintigraphy to evaluate lymphatic transport and axillary lymph node visualization in women following breast cancer therapy to determine the utility of these data in these patients. Lymphoscintigraphy was performed after subcutaneous injection of 0.25 mCi of Tc-filtered sulfur colloid. Subcutaneous accumulation of radiotracer ('dermal backflow') and the visualization of axillary lymph nodes were graded using our own scoring system. The ratio of radioactivity within the affected to normal axillae (ARR) was also quantified. Nineteen patients with lymphedema after breast cancer therapy were evaluated. The disease severity was documented by serial measurements of the limb volume using the truncated cone formula. Responses to therapy were quantified after completion of the therapy. There was a correlation between the ARR and the percentage reduction in edema volume. The lymphoscintigraphic score correlated with the initial arm volume excess and with the durationof lymphedema. It can be concluded that quantitative and semi-quantitative assessment by radionuclide lymphoscintigraphy represents a potentially useful tool for the clinical assessment of upper extremity lymphedema.

    Title The Lymphatic Continuum: the Past, Present, and Exciting Future of Lymphatic Research.
    Date March 2003
    Journal Annals of the New York Academy of Sciences
    Title Preclinical Models of Lymphatic Disease: the Potential for Growth Factor and Gene Therapy.
    Date March 2003
    Journal Annals of the New York Academy of Sciences
    Excerpt

    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.

    Title Therapeutic Lymphangiogenesis with Human Recombinant Vegf-c.
    Date December 2002
    Journal The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology
    Excerpt

    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.

    Title Decongestive Lymphatic Therapy for Patients with Breast Carcinoma-associated Lymphedema. A Randomized, Prospective Study of a Role for Adjunctive Intermittent Pneumatic Compression.
    Date December 2002
    Journal Cancer
    Excerpt

    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.

    Title Diagnosis and Treatment of Concomitant Venous Obstruction in Patients with Secondary Lymphedema.
    Date September 2002
    Journal Journal of Vascular and Interventional Radiology : Jvir
    Excerpt

    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.

    Title The Role of Chemokines in Human Cardiovascular Pathology: Enhanced Biological Insights.
    Date April 2002
    Journal Atherosclerosis
    Excerpt

    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.

    Title Feasibility and Reliability of Rapid Diagnosis of Myocardial Infarction.
    Date January 2002
    Journal The American Journal of the Medical Sciences
    Excerpt

    BACKGROUND: Prevailing hospital practice dictates a protracted phase of observation for patients with chest pain to establish or exclude the diagnosis of myocardial infarction. Early diagnosis of acute myocardial infarction may improve patient care and reduce both complications and hospital costs. A study was performed to investigate the feasibility of early diagnosis of myocardial infarction within the first 9 hours of the hospital stay. METHODS: The records of all patients admitted with chest pain within one calendar year were analyzed. The timing of creatine kinase-MB (CK-MB) quantification was determined with reference to the initial phlebotomy (time 0). An enzymatic diagnosis of myocardial infarction was assigned if any determination of CK-MB exceeded the upper limit of normal, and the diagnosis of each patient at or before 9 hours (early diagnosis) was compared to the ultimate diagnosis at 14 to 24 hours (final diagnosis) beyond initial assessment. RESULTS: Of the 528 included patients, 523 patients (99.1%) had identical early and final diagnostic outcomes; 5 patients (0.9%) had conflicting results. An early diagnosis of myocardial infarction was assigned to 195 of the 528 patients (36.9%). Of these, 190 achieved the diagnosis within 9 hours (sensitivity 97.4%). The negative predictive value was 98.5%. CONCLUSION: Standard CK-MB mass measurements within 9 hours of arrival provided an accurate clinical assessment in > 99% of the cases. The high sensitivity and negative predictive values suggest that early diagnosis of myocardial infarction is feasible and reliable.

    Title Angiogenesis and the Ischaemic Heart.
    Date August 2001
    Journal European Heart Journal
    Title Benefits of Lipid-lowering Agents in Stroke and Coronary Heart Disease: Pharmacoeconomics.
    Date July 2001
    Journal Current Atherosclerosis Reports
    Excerpt

    Coronary heart disease remains the leading cause of death in the United States. Although coronary heart disease and stroke entail very expensive therapies and extensive hospital utilization, the cost of preventive measures is also quite expensive. In this review, the factors that determine the cost-effectiveness of statin therapy for the primary and secondary prevention of coronary heart disease are discussed. A risk-based strategy for the selection of patients seems to provide cost-effective utilization of this potent treatment strategy. Appropriate patient selection should be accompanied by aggressive measures to improve utilization and compliance through improved physician and patient education.

    Title Formulating Clinical Strategies for Angiotensin Antagonism: a Review of Preclinical and Clinical Studies.
    Date May 2001
    Journal The American Journal of Medicine
    Excerpt

    Extensive animal studies and a growing number of human clinical trials have now definitively demonstrated the central role of the renin-angiotensin-aldosterone system in the expression and modulation of cardiovascular disease. In contrast to the original hypothesis, the benefits of angiotensin antagonism do not emanate from the antihypertensive effect alone. Subsequent extensive investigations of angiotensin blockade suggest that the benefits of this approach may also result from the pharmacologic alteration of endothelial cell function and the ensuing changes in the biology of the vasculature. The more recent availability of direct antagonists of the AT(1) angiotensin receptor has introduced an element of doubt into this realm of clinical decision making. The receptor antagonists and the more widely studied converting-enzyme inhibitors share many endpoint attributes. Nevertheless, the partially overlapping mechanisms of action for the two classes of angiotensin antagonists confer distinct pharmacologic properties, including side effect profiles, mechanisms of action, and theoretic salutary effects upon the expression of cardiovascular disease. The current review will attempt to contrast the biology of angiotensin converting-enzyme inhibition with angiotensin II receptor antagonism. A discussion of the differential effects of these drug classes on endothelial cell function and on the modulation of vascular disease will be utilized to provide a theoretic framework for clinical decision making and therapeutics.

    Title Lymphedema.
    Date April 2001
    Journal The American Journal of Medicine
    Excerpt

    Lymphedema is a set of pathologic conditions that are characterized by the regional accumulation of excessive amounts of interstitial protein-rich fluid. These occur as a result of an imbalance between the demand for lymphatic flow and the capacity of the lymphatic circulation. Lymphedema can result from either primary or acquired (secondary) disorders. In this review, the pathophysiology, classification, natural history, differential diagnosis, and treatment of lymphedema are discussed.

    Title Photoangioplasty for Human Peripheral Atherosclerosis: Results of a Phase I Trial of Photodynamic Therapy with Motexafin Lutetium (antrin).
    Date November 2000
    Journal Circulation
    Excerpt

    BACKGROUND: In photoangioplasty, light activation of a photosensitive drug offers the potential for treatment of long segments of vascular disease. This is a brief description of a study designed to evaluate the safety and tolerability of a new photosensitizer, Antrin (motexafin lutetium), in the endovascular treatment of atherosclerosis. METHODS AND RESULTS: An open-label, single-dose, escalating drug- and light-dose study was performed in patients with atherosclerotic peripheral arterial insufficiency. Clinical evaluation, serial quantitative angiography, and intravascular ultrasonography were performed. Therapy was well tolerated, and only minor side effects were observed. Treatment produced no deleterious vascular effects. Although this study was not designed to examine clinical efficacy, several secondary end points suggested a favorable therapeutic effect. CONCLUSIONS: This phase I study demonstrates that photoangioplasty with motexafin lutetium is well tolerated and safe. Preliminary efficacy data suggest a future role for the treatment of flow-limiting atherosclerosis.

    Title Decongestive Lymphatic Therapy for Patients with Cancer-related or Primary Lymphedema.
    Date November 2000
    Journal The American Journal of Medicine
    Excerpt

    PURPOSE: A prospective evaluation was undertaken to assess the efficacy of intensive, short-term decongestive lymphatic therapy coupled with focused patient instruction in long-term self-care for the management of lymphedema. METHODS: The therapeutic responses of 79 patients with lymphedema were analyzed prospectively. Each patient received intensive, short-term decongestive lymphatic therapy, with quantification of the extent and durability of the clinical response. Decongestive lymphatic therapy was performed by therapists trained in these techniques. The mean (+/-SD) duration of therapy was 8+/-3 days. Instruction in self-management techniques was incorporated into the therapeutic regimen by day 3 of the patient's treatment. The mean period of follow-up was 38+/-52 days. Changes in the volume of the affected limb were assessed with a geometric approximation derived from serial measurements of circumference along the axis of the limb. RESULTS: The mean short-term reduction in limb volume was 44%+/-62% of the excess volume in the upper extremities and 42%+/-40% in the lower extremities. At follow-up, these results were adequately sustained: mean long-term excess volume reductions of 38%+/-56% (upper extremities) and 41%+/-27% (lower extremities) were observed. CONCLUSION: Decongestive lymphatic therapy, combined with long-term self-management, is efficacious in treating patients with lymphedema of the extremity.

    Title Photoangioplasty: An Emerging Clinical Cardiovascular Role for Photodynamic Therapy.
    Date August 2000
    Journal Circulation
    Excerpt

    Photodynamic therapy (PDT) has been studied and applied to various disease processes. The potential of PDT for selective destruction of target tissues is especially appealing in cardiovascular disease, in which other existing interventional tools are somewhat nonselective and carry substantial risk of damage to the normal arterial wall. Enthusiasm for photoangioplasty (PDT of vascular de novo atherosclerotic and, potentially, restenotic lesions) is fueled by more effective second-generation photosensitizers and technological advances in endovascular light delivery. This excitement revolves around at least 4 significant attributes of light-activated therapy: the putative selectivity and safety of photoangioplasty, the potential for atraumatic and effective debulking of atheromatous plaque through a biological mechanism, the postulated capability to reduce or inhibit restenosis, and the potential to treat long segments of abnormal vessel by simply using fibers with longer light-emitting regions. The available nonclinical data, coupled with the observations of a new phase I trial in human peripheral atherosclerosis, suggest a promising future for photoangioplasty in the treatment of primary atherosclerosis and prevention of restenosis.

    Title Images in Vascular Medicine. Complex Lower Extremity Edema in a Young Woman.
    Date January 2000
    Journal Vascular Medicine (london, England)
    Title Lymphoscintigraphic Manifestations of Hennekam Syndrome--a Case Report.
    Date January 2000
    Journal Angiology
    Excerpt

    Hennekam syndrome is a rare, recently described genetic disorder in which facial anomalies and mental retardation accompany congenital lymphedema and intestinal lymphangiectasia. Several other somatic abnormalities have variously been described, as have milder degrees of lymphatic dysfunction. The authors herein describe a case of Hennekam syndrome in which the diagnostic difficulties were partially overcome by the judicious use of radionuclide scintigraphy to verify the lymphedematous component of the patient's presentation.

    Title Fibroblast Growth Factor As Therapy for Critical Limb Ischemia: a Case Report.
    Date August 1999
    Journal Vascular Medicine (london, England)
    Excerpt

    In an attempt to avert impending, primary amputation, an 85-year-old woman with chronic critical leg ischemia was enrolled in an experimental protocol to induce therapeutic angiogenesis. Treatment consisted of six consecutive, weekly intravenous infusions of recombinant basic fibroblast growth factor (bFGF). Angiographic evaluation was performed before and after therapy. The patient's clinical response was monitored through serial measurements of the ankle/brachial index and by repetitive assessment of limb flow by mercury strain-gauge plethysmography. A beneficial clinical response was detectable by week 4 of therapy, which was characterized by an improved walking distance, relief of ischemic pain, a marked reduction in analgesic consumption, and healing of persistent, unresponsive, painful inflammation of the hallux. The clinical improvement was sustained throughout the remaining weeks of therapy and follow-up evaluation. Plethysmography documented improved blood flow; specifically, the augmentation of digital flow was sustained and correlated with the marked improvement in the patient's clinical status.

    Title Images in Vascular Medicine. Lymphoscintigraphy in Congenital Lymphedema.
    Date May 1999
    Journal Vascular Medicine (london, England)
    Title Precipitating Factors in Lymphedema: Myths and Realities.
    Date January 1999
    Journal Cancer
    Excerpt

    BACKGROUND: Lymphedema is an all too common occurrence following breast carcinoma therapy. Despite its prevalence, the predisposing factors to the development of this secondary form of lymphedema remain poorly understood. METHODS: Several studies have addressed these questions and are reviewed here. RESULTS: Treatment factors that appear to predispose to the late, subjective appearance of lymphedema include the extent of axillary surgery and exposure to high dose axillary radiotherapy, particularly when combined with surgical clearance of the axilla. Other pertinent patient factors may include the presence of hypertension and exposure to airline travel. Clinical features unrelated to the risk of lymphedema development include patient age; drug therapy; time interval to presentation, surgery, or radiotherapy to the breast; total dose of radiation; and menopausal status. The potential importance of concomitant venous abnormalities in these patients is worthy of consideration. CONCLUSIONS: Breast carcinoma-related secondary lymphedema is an important subjective and functional problem for affected patients. Additional research into the predisposing factors to this common problem is likely to foster enhanced patient education and to produce more efficacious measures to control this disease.

    Title American Cancer Society Lymphedema Workshop. Workgroup Iii: Diagnosis and Management of Lymphedema.
    Date January 1999
    Journal Cancer
    Title Lymphedema: Classification, Diagnosis and Therapy.
    Date January 1999
    Journal Vascular Medicine (london, England)
    Excerpt

    This review presents the diagnostic features, the pathophysiology and the available therapies for lymphedema. This disease is often able to be diagnosed by its characteristic clinical presentation, yet, in some cases, ancillary tests might be necessary to establish the diagnosis, particularly in the early stages of the disease and in edemas of mixed etiology. These diagnostic modalities are also useful in clinical studies. Available modalities include isotopic lymphoscintigraphy, indirect and direct lymphography, magnetic resonance imaging, computed tomography and ultrasonography. Lymphedema may be primary or secondary to the presence of other disease and/or to the consequences of surgery. Primary lymphedema may occur at any phase of life but it most commonly appears at puberty. Secondary lymphedema is encountered more often. The most prevalent worldwide cause of lymphedema is filariasis, which is particularly common in south-east Asia. In the USA, postsurgical lymphedema of the extremity prevails. Complications of chronic limb lymphedema include recurrent cellulitis and lymphangiosarcoma. Most patients are treated conservatively, by means of various forms of compression therapy, including complex physical therapy, pneumatic pumps and compressive garments. Volume reducing surgery is performed rarely. Lymphatic microsurgery is still in an experimental stage, although a few centers consistently report favorable outcomes.

    Title Images in Vascular Medicine. Phlegmasia Coerulea Dolens--venous Gangrene.
    Date September 1998
    Journal Vascular Medicine (london, England)
    Title Lymphedema: Anatomy, Physiology and Pathogenesis.
    Date June 1998
    Journal Vascular Medicine (london, England)
    Excerpt

    The authors review the current understanding of lymphatic anatomy and physiology, and the pathophysiology of lymphedema. The skin lymphatic system consists of the initial lymphatics, which converge into lymphatic precollectors, collectors and lymphatic ducts; these in turn convey the lymph to the regional lymph nodes. Interstitial fluid and particles enter the initial lymphatics through interendothelial openings and by vesicular transport. Lymphatic uptake is enhanced by external compression. Lymphatic transport depends greatly on contraction of lymphangions, which generate the suction force that promotes absorption of interstitial fluid and expels lymph to collecting ducts. In lymphedema, various types of congenital and acquired abnormalities of lymphatic vessels and lymph nodes have been observed. These often lead to lymphatic hypertension, valvular insufficiency and lymphostasis. Accumulation of interstitial and lymphatic fluid within the skin and subcutaneous tissue stimulates fibroblasts, keratinocytes and adipocytes eventuating in the deposition of collagen and glycosaminoglycans within the skin and subcutaneous tissue together with skin hypertrophy and destruction of elastic fibers.

    Title Peripheral Arterial Insufficiency: Mechanisms, Natural History, and Therapeutic Options.
    Date April 1998
    Journal Advances in Internal Medicine
    Title A Novel Therapy for Lymphedema Complicated by Lymphorrhea.
    Date April 1998
    Journal Vascular Medicine (london, England)
    Excerpt

    Lymphorrhea is a rarely described complication of chronic lymphedema, in which the disrupted flow through diseased lymphatic channels gives rise to the external drainage of lymph, often heralded by the presence of an enlarging lymphocele. This report documents the applicability of the Reid sleeve, a novel, conservative form of therapy, in an unusually severe and protracted example of lymphorrhea.

    Title Myocardial Ischemia and Infarction Due to Multiple Coronary-cameral Fistulae: Two Case Reports and Review of the Literature.
    Date April 1998
    Journal Catheterization and Cardiovascular Diagnosis
    Excerpt

    The functional significance of coronary-cameral fistulae, and the effect of these arterial anomalies upon effective coronary blood flow, continue to be debated. Two cases of coronary cameral fistulae, each of which illustrates the likelihood of an ischemic substrate, are herein presented, along with a review of the relevant literature regarding this disorder.

    Title Pregnancy-associated Group B Streptococcal Endocarditis: a Report of Two Fatal Cases.
    Date September 1985
    Journal Obstetrics and Gynecology
    Excerpt

    Group B streptococci commonly colonize parturient women, yet pregnancy-associated endocarditis due to this organism is rare. Most reports of group B streptococcal endocarditis are from the preantibiotic era and occurred in women with rheumatic mitral valve disease. Reported herein are two cases of fatal group B streptococcal endocarditis involving the aortic valve of women with no preexisting heart disease. One had undergone a second-trimester abortion and the other had a normal pregnancy and uncomplicated vaginal delivery.

    Title Purification and Characterization of the Mammalian Beta 2-adrenergic Receptor.
    Date June 1983
    Journal Biochemistry
    Title An Antiidiotypic Antibody That Recognizes the Beta-adrenergic Receptor.
    Date June 1982
    Journal The Journal of Clinical Investigation
    Excerpt

    Antialprenolol rabbit antibodies were fractionated on an acebutolol affinity resin, followed by L-propranolol elution so as to separate a class of binding sites that mimic the beta-adrenergic receptor. Allotype-identicaL rabbits were immunized with this fraction. After 6 mo, antisera exhibited antiidiotypic activity inhibiting [3H]alprenolol binding to the original antibody and to rabbit antiacebutolol antibodies, which had a spectrum of ligand-binding properties identical to the original idiotype. Those antisera demonstrating the original idiotype. Those antisera demonstrating the most potent antiidiotypic activity also blocked [3H]alprenolol binding to the beta-adrenergic receptor of turkey membrane, canine pulmonary membrane, and rat reticulocyte. An idiotype affinity-purified fraction showed similar activity, inhibiting beta-receptor binding with a calculated dissociation constant (KD) of 53 nM. Isoproterenol-mediated adenylate cyclase activity was also inhibited in a competitive manner. The universality of recognition of these antiidiotypic antisera indicate that the three-dimensional structure of a receptor's binding site can be modeled by a subset of an elicited antibody population.

    Title Cellular Mechanisms of Impaired Adrenergic Responsiveness in Neonatal Dogs.
    Date April 1981
    Journal The Journal of Clinical Investigation
    Excerpt

    The myocardial responsiveness of conscious, instrumental dogs to exogenously administered isoproterenol and norepinephrine was investigated in neonatal, 6-wk-old, and adult animals. Comparable base-line values for peak left ventricular derivative of pressure with respect to time were observed in all age categories. However, when compared with adult responses, the sympathomimetic amine-induced increases in neonatal left ventricular dP/dt were significantly blunted at each concentration of adrenergic agonist examined, whereas the 6-wk-old puppies displayed an intermediate inotropic response. To investigate the cellular mechanisms of this blunted neonatal response, we correlated physiologic and biochemical measurements of the myocardial responses to catecholamines in each age category. When compared with adult myocardial membrane preparations, neonatal cardiac membranes were characterized in vitro by an increased density of beta-adrenergic binding sites, comparable affinity for adrenergic agonists and antagonists, and an enhanced coupling of adenylate cyclase activation to receptor occupancy. Simultaneous changes in either the serum catecholamine concentration or the membrane content of other intrinsic proteins failed to account for the observed neonatal increase in beta-adrenergic receptor density. These findings are most consistent with a compensatory mechanism of the cardiac cell membrane, whereby an inherent depression in the adrenergic responsiveness of the immature myocardium appears to induce the increase in receptor density and activation of adenylate cyclase.

    Title Anti-alprenolol Antibodies in the Rabbit. A New Probe for the Study of Beta-adrenergic Receptor Interaction.
    Date August 1980
    Journal Circulation Research
    Excerpt

    We immunized rabbits with an antigen prepared by covalent linkage of alprenolol, a beta-adrenergic receptor antagonist, to bovine serum albumin. Competitive inhibition of [3H]dihydroalprenolol binding to antisera with a variety of unlabeled ligands revealed broad antibody specificity for beta-adrenergic antagonists and agonists. The antiserum was subjected to affintiy fractionation on hydroxybenzylpindolol-Sepharose 4B. Successive elution with 100 mM Tris HCl, 1M NaCl, 4 M LiBr, and 5 M guanidine yielded fractions with increasing affintiy for hydroxybenzylpindolol. The ligand-binding properties of these affinity-fractionated antibodies suggest that certain of these fractions recognize structural aspects of individual beta-adrenergic ligands which are irrelevant to their biological activity, whereas others can be used to distinguish shared functional properties, such as the ethanolamine side chain, within the structural heterogeneity of beta-adrenergic drugs. In particular, elution of hydroxybenzylpindolol-adsorbed antibody with (-)-propranolol allowed identification of an antibody fraction specific for the (-)-stereoisomer. Thus, affinity fractionation of antibodies raised against beta-adrenergic ligands can provide useful analogues for the further study of the recognition properties of the beta-adrenergic receptor.

    Title Plasma Dopamine-beta-hydroxylase in the Diagnosis of Neuroblastoma.
    Date April 1976
    Journal Cancer
    Excerpt

    An atypical case of neuroblastoma is described, in which the diagnosis was facilitated by the application of a new biochemical procedure, the assay of plasma dopamine-beta-hydroxylase activity. This laboratory tool is proposed as a useful adjunct to established techniques in the diagnosis of neural crest tumors.

    Title Plasma Dopamine-beta-hydroxylase Activity in Oral Contraceptive Hypertension.
    Date July 1975
    Journal Circulation
    Excerpt

    A prospective study was undertaken to evaluate the relative contribution of changes in sympathetic nervous system activity, as reflected by changes in dopamine-beta-hydroxylase (DBH) activity, to the pathogenesis of oral contraceptive-induced hypertension. Precontraceptive and serial post contraceptive determinations of blood pressure, plasma renin activity (PRA), DBH activity, and changes in body weight were obtained in twelve control patients and forty-one oral contraceptive users. Forty-four percent of oral contraceptive users had increases in blood pressure but remained normotensive and 17% became frankly hypertensive. The precontraceptive and average post contraceptive levels of mean arterial pressure (MAP), PRA and DBH activity in each patient were compared using paired group analysis. Control patients (group I) exhibited no significant changes in these variables, while the patients with contraceptive-induced increases in MAP (groups III and IV) underwent significant, parallel increases in DBH activity. Finally, the linear regression of changes in MAP on the percent change in DBH activity was examined. The positive slopes in groups III and IV differed significantly from the negative slope of the controls (group I). The data have been interpreted to reflect an inappropriate oral contraceptive-induced stimulus to sympathetic nervous system activity, leading to increases in MAP in susceptible individuals.

    Title Solitary Renal Cyst with Segmental Ischemia and Hypertension.
    Date January 1975
    Journal The Journal of Urology
    Title Lutetium Texaphyrin: A New Therapeutic Tool for Human Atherosclerosis.
    Date
    Journal Current Treatment Options in Cardiovascular Medicine
    Title Lymphedema.
    Date
    Journal Current Treatment Options in Cardiovascular Medicine
    Excerpt

    Aggressively applied decongestive measures (eg, manual lymphatic drainage, low-stretch bandaging, exercise, skin care, application of compressive elastic garments) are the mainstay of lymphatic therapy. Therapeutic regimens should differentiate between the goals of acute volume reduction and the maintenance of limb volume. Elastic garments should not be employed until maximal volume reduction has been attained through decongestive lymphatic techniques. It is my opinion that use of intermittent pneumatic compression devices can play an important adjunctive role to decongestive lymphatic therapy but should not be substituted for these techniques. At this time, I am not inclined to use pharmacologic therapy in these patients but anxiously await the results of studies that might demonstrate efficacy for molecular approaches. Surgical intervention is reserved for a small number of well-selected patients. Liposuction for volume reduction appears to be a very promising approach for specific patients.

    Title The Role of the Lymphatic Circulation in the Natural History and Expression of Cardiovascular Disease.
    Date
    Journal International Journal of Cardiology
    Excerpt

    The lymphatic vasculature is essential to fluid, protein and cellular transport, and to immune responsiveness. The last decade has witnessed a virtual renaissance of investigation into the function of the lymphatic microvasculature, prompting re-consideration of its role in the genesis and progression of cardiovascular pathology. The lymphatic microvasculature of the heart and vascular wall likely participate in atherogenesis, myocardial infarction, congestive heart failure, and cardiac transplantation. Intensive exploration of lymphatic mechanisms of cardiovascular disease is likely to lead to enhanced insights and novel therapeutic approaches.

    Title Blockade of Transforming Growth Factor-beta1 Accelerates Lymphatic Regeneration During Wound Repair.
    Date
    Journal The American Journal of Pathology
    Excerpt

    Lymphedema is a complication of cancer treatment occurring in approximately 50% of patients who undergo lymph node resection. Despite its prevalence, the etiology of this disorder remains unknown. In this study, we determined the effect of soft tissue fibrosis on lymphatic function and the role of transforming growth factor (TGF)-β1 in the regulation of this response. We determined TGF-β expression patterns in matched biopsy specimens collected from lymphedematous and normal limbs of patients with secondary lymphedema. To determine the role of TGF-β in regulating tissue fibrosis, we used a mouse model of lymphedema and inhibited TGF-β function either systemically with a monoclonal antibody or locally by using a soluble, defective TGF-β receptor. Lymphedematous tissue demonstrated a nearly threefold increase in the number of cells that stained for TGF-β1. TGF-β inhibition markedly decreased tissue fibrosis, increased lymphangiogenesis, and improved lymphatic function compared with controls. In addition, inhibition of TGF-β not only decreased TGF-β expression in lymphedematous tissues, but also diminished inflammation, migration of T-helper type 2 (Th2) cells, and expression of profibrotic Th2 cytokines. Similarly, systemic depletion of T-cells markedly decreased TGF-β expression in tail tissues. Inhibition of TGF-β function promoted lymphatic regeneration, decreased tissue fibrosis, decreased chronic inflammation and Th2 cell migration, and improved lymphatic function. The use of these strategies may represent a novel means of preventing lymphedema after lymph node resection.

    Similar doctors nearby

    Dr. David Lee

    Cardiovascular Disease
    19 years experience
    Stanford, CA

    Dr. Keane Lee

    Internal Medicine
    8 years experience
    Stanford, CA

    Dr. Robert Harrington

    Internal Medicine
    25 years experience
    Stanford, CA

    Dr. Ronald Witteles

    Internal Medicine
    11 years experience
    Stanford, CA

    Dr. Marco Perez

    Internal Medicine
    10 years experience
    Stanford, CA

    Dr. Francois Haddad

    Cardiology
    13 years experience
    Stanford, CA
    Search All Similar Doctors