John V. White

Chronic Venous Insufficiency

Chronic venous insufficiency, characterized by the retrograde flow of blood in the lower extremity, is a common, debilitating disorder that is increasing in prevalence. An estimated 25 million people in the United States have varicose veins, 2 to 6 million have more advanced forms of chronic venous insufficiency (swelling, skin changes), and nearly 500,000 have painful venous ulcers. Although varicose veins are more likely to develop in women, men more commonly have venous ulcers. Regardless of gender, the disorder is associated with a significant reduction in quality of life. Although initiating events, such as deep vein thrombosis and muscle pump failure, may lead to chronic venous insufficiency, vein valve dysfunction appears to be the common final pathway in the development of this problem. Recent studies have determined that the basal state of veins valves is coaptation, with the prevention of retrograde flow. Failure of this mechanism results in increases in retrograde flow and distal venous pressure, which can begin to alter the structure and function of the downstream vein wall. The diagnosis is established by history, physical examination, and functional venous testing with duplex imaging or phlebography. Classification systems have been developed that stratify according to the severity of the disorder and help guide therapeutic endeavors. Treatment is directed toward controlling the retrograde flow of blood, venous pooling, and the complications associated with these pathophysiologic processes. When appropriate therapy is instituted, response is generally excellent.

Abdominal Aortic Aneurysm Is a Specific Antigen‐Driven T Cell Disease

Abstract:u2002 To determine whether monoclonal/oligoclonal T cells are present in abdominal aortic aneurysm (AAA) lesions, we amplified β‐chain T cell receptor (TCR) transcripts from these lesions by the nonpalindromic adaptor (NPA)‐polymerase chain reaction (PCR)/V‐β‐specific PCR followed by cloning and sequencing. Sequence analysis revealed the presence of substantial proportions of identical β‐chain TCR transcripts in AAA lesions in 9 of 10 patients examined, strongly suggesting the presence of oligoclonal populations of αβ TCR+ T cells. We have also shown the presence of oligoclonal populations of γδ TCR+ T cells in AAA lesions. Sequence analysis after appropriate PCR amplification and cloning revealed the presence of substantial proportions of identical VγI and VγII TCR transcripts in 15 of 15 patients examined, and of Vδ1 and Vδ2 TCR transcripts in 12 of 12 patients. These clonal expansions were very strong. All these clonal expansions were statistically significant by the binomial distribution. In other studies, we determined that mononuclear cells infiltrating AAA lesions express early‐ (CD69), intermediate‐ (CD25, CD38), and late‐ (CD45RO, HLA class II) activation antigens. These findings suggest that active ongoing inflammation is present in the aortic wall of patients with AAA. These results demonstrate that oligoclonal αβ TCR+ and γδ TCR+T cells are present in AAA lesions. These oligoclonal T cells have been clonally expanded in vivo in response to yet unidentified antigens. Although the antigenic specificity of these T cells remains to be determined, these T cells may play a significant role in the initiation and/or the propagation of the AAA. It appears that AAA is a specific antigen‐driven T cell disease.

Aneurysmal Lesions of Patients with Abdominal Aortic Aneurysm Contain Clonally Expanded T Cells

Abdominal aortic aneurysm (AAA) is a common disease with often life-threatening consequences. This vascular disorder is responsible for 1–2% of all deaths in men aged 65 years or older. Autoimmunity may be responsible for the pathogenesis of AAA. Although it is well documented that infiltrating T cells are essentially always present in AAA lesions, little is known about their role in the initiation and/or progression of the disease. To determine whether T cells infiltrating AAA lesions contain clonally expanded populations of T cells, we amplified β-chain TCR transcripts by the nonpalindromic adaptor–PCR/Vβ-specific PCR and/or Vβ-specific PCR, followed by cloning and sequencing. We report in this article that aortic abdominal aneurysmal lesions from 8 of 10 patients with AAA contained oligoclonal populations of T cells. Multiple identical copies of β-chain TCR transcripts were identified in these patients. These clonal expansions are statistically significant. These results demonstrate that αβ TCR+ T lymphocytes infiltrating aneurysmal lesions of patients with AAA have undergone proliferation and clonal expansion in vivo at the site of the aneurysmal lesion, in response to unidentified self- or nonself Ags. This evidence supports the hypothesis that AAA is a specific Ag–driven T cell disease.

Cost-Effectiveness of New Cardiac and Vascular Rehabilitation Strategies for Patients with Coronary Artery Disease

Objective Peripheral arterial disease (PAD) often hinders the cardiac rehabilitation program. The aim of this study was evaluating the relative cost-effectiveness of new rehabilitation strategies which include the diagnosis and treatment of PAD in patients with coronary artery disease (CAD) undergoing cardiac rehabilitation. Data Sources Best-available evidence was retrieved from literature and combined with primary data from 231 patients. Methods We developed a Markov decision model to compare the following treatment strategies: 1. cardiac rehabilitation only; 2. ankle-brachial index (ABI) if cardiac rehabilitation fails followed by diagnostic work-up and revascularization for PAD if needed; 3. ABI prior to cardiac rehabilitation followed by diagnostic work-up and revascularization for PAD if needed. Quality-adjusted-life years (QALYs), life-time costs (US

Response to Comment on “Aneurysmal Lesions of Patients with Abdominal Aortic Aneurysm Contain Clonally Expanded T Cells”

), incremental cost-effectiveness ratios (ICER), and gain in net health benefits (NHB) in QALY equivalents were calculated. A threshold willingness-to-pay of

Impact of Claudication and Its Treatment on Quality of Life

75 000 was used. Results ABI if cardiac rehabilitation fails was the most favorable strategy with an ICER of

Progress in the Endovascular Treatment of Intermittent Claudication: Rationale for Changes in the TASC Classification

44 251 per QALY gained and an incremental NHB compared to cardiac rehabilitation only of 0.03 QALYs (95% CI: −0.17, 0.29) at a threshold willingness-to-pay of

Chronic Subcritical Limb Ischemia: A Poorly Recognized Stage of Critical Limb Ischemia

75 000/QALY. After sensitivity analysis, a combined cardiac and vascular rehabilitation program increased the success rate and would dominate the other two strategies with total lifetime costs of

Determination and Importance of Clinical and Patient-Based Measures in Outcome Assessment of Peripheral Arterial Occlusive Disease

30 246 a quality-adjusted life expectancy of 3.84 years, and an incremental NHB of 0.06 QALYs (95%CI:−0.24, 0.46) compared to current practice. The results were robust for other different input parameters. Conclusion ABI measurement if cardiac rehabilitation fails followed by a diagnostic work-up and revascularization for PAD if needed are potentially cost-effective compared to cardiac rehabilitation only.

Aortic aneurysm: Search for the trigger

We appreciate Dr. Kroon and Dr. Taanman’s interest and comments on our manuscript demonstrating the presence of clonally expanded T cells in aneurysmal lesions of patients with aortic abdominal aneurysm (AAA) ([1][1]). The current treatment modalities for AAA involve surgical treatment which