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Most recently endothelial dysfunction and thrombosis have been hypothesized to be contributing factors for this and other end-organ damage in SCD [10]. Current treatment options for leg ulcers are limited and outcome is unsatisfactory, with a high relapse rate and very slow rates of healing [1, 12]. Patients with sickle cell anemia have vascular dysfunction and develop related complications, such as stroke, pulmonary http://www.selleckchem.com/products/Cyclopamine.html hypertension, and renal dysfunction, at a higher rate than the nonsickle cell population. The potential role of vascular dysfunction in end-organ damage in sickle cell disease could be better investigated by physiological analysis of the regional microcirculation [12]. While this is virtually impossible to achieve in the intracranial or renal circulation, leg ulcers are more easily accessible and represent a unique opportunity to investigate blood flow and its alteration in patients with sickle cell disease. Laser speckle contrast imaging (LSCI) and infrared (IR) thermography are new, noninvasive techniques useful in the in vivo study of skin and wound perfusion in animal models and humans [13, 14]. The high http://www.selleckchem.com/products/BI-2536.html resolution of LSCI offers an advantage over traditional laser Doppler imaging techniques and can image the entire physiologic range of blood flow velocities within a small diameter vasculature to a depth of approximately 300 ?m [15]. These measurements reflect blood flow in capillaries, arterioles, venules, and dermal vascular plexuses and are sensitive to angiogenesis and vasodilation/constriction that occur during the different phases of wound healing [16]. IR measures tissue temperature up to 1 cm from the surface of the skin and its measurements correlate to forearm blood flow in patients with sickle cell disease [17]. We set out to study the regional blood flow of ulcer beds, and the immediate surrounding tissues compared to unaffected skin area in patients with SCD and chronic leg ulcers, http://www.selleck.cn/products/gsk126.html in order to understand its role in ulcer pathogenesis and perpetuation. We also evaluated prospectively histopathology, markers of thrombophilia and inflammation, and detailed ulcer and patients' clinical characteristics. All subjects were enrolled at the NIH Clinical Center on a clinical protocol approved by the institutional review board (ClinicalTrials.gov Identifier NCT01316796). Eligibility criteria required a subject to be at least 18 years old, have sickle cell disease, and have a leg ulcer of at least 4 weeks duration, between 2.5 and 100 cm2 in size and not acutely infected. All evaluated patients were screened with a detailed medical history, physical examination, and clinical blood and urine tests. An echocardiogram was obtained in all subjects, as previously described [1]. The wound ostomy continence nurse (WOCN) service assessed the leg ulcers and obtained a wound culture.