Faculty Bibliography

The Allen test is used to diagnose the relative contribution of the ulnar and radial arteries to each hand. We modified this test to investigate the relative vascular contributions to distal perfusion of the lower extremity. With the patient supine, a handheld Doppler is used to locate the first dorsal metatarsal artery. The posterior tibial artery (PT) and dorsalis pedis artery (DP) pulses are compressed. A persistent signal indicates collateral flow through the peroneal artery (PA). Sequential decompression is then used to evaluate the relative contribution of the PT and DP to distal circulation. We report a case in which angiography failed to predict reliance on the PT. In this case, performance of the lower-extremity Allen test (LEAT) led to an alternative recipient vessel choice. The LEAT is simple to perform and provides a valuable adjunct to angiographic data

Blood vessel growth is regulated by angiogenic and angiostatic CXC chemokines, and radiation is a vasculogenic stimulus. We investigated the effect of radiation on endothelial cell chemokine signaling, receptor expression, and migration and apoptosis. Human umbilical vein endothelial cells were exposed to a single fraction of 0, 5, or 20Gy of ionizing radiation (IR). All vasculogenic chemokines (CXCL1-3/5-8) increased 3-13-fold after 5 or 20Gy IR. 20Gy induced a marked increase (1.6-4-fold) in angiostatic CXC chemokines. CXCR4 expression increased 3.5 and 7-fold at 48h after 5 and 20Gy, respectively. Bone marrow progenitor cell chemotaxis was augmented by conditioned media from cells treated with 5Gy IR. Whereas 5Gy markedly decreased intrinsic cell apoptosis (0Gy=16%+/-3.6 vs. 5Gy=4.5%+/-0.3), 20Gy increased it (21.4%+/-1.2); a reflection of pro-survival angiogenic chemokine expression. Radiation induces a dose-dependent increase in pro-angiogenic CXC chemokines and CXCR4. In contrast, angiostatic chemokines and apoptosis were induced at higher (20Gy) radiation doses. Cell migration improved significantly following 5Gy, but not 20Gy IR. Collectively, these data suggest that lower doses of IR induce an angiogenic cascade while higher doses produce an angiostatic profile

BACKGROUND: Impaired diabetic wound healing is due, in part, to defects in mesenchymal progenitor cell tracking. Theoretically, these defects may be overcome by administering purified progenitor cells directly to the diabetic wound. The authors hypothesize that these progenitor cells will differentiate into endothelial cells, increase wound vascularity, and improve wound healing. METHODS: Lineage-negative progenitor cells were isolated from wild-type murine bone marrow by magnetic cell sorting, suspended in a collagen matrix, and applied topically to full-thickness excisional dorsal cutaneous wounds in diabetic mice. Application of lineage-positive hematopoietic cells or acellular collagen matrix served as comparative controls (n = 16 for each group; n = 48 total). Time to closure and percentage closure were calculated by morphometry. Wounds were harvested at 7, 14, 21, and 28 days and then processed, sectioned, stained (lectin/DiI and CD31), and vascularity was quantified. RESULTS:: Wounds treated with lineage-negative cells demonstrated a significantly decreased time to closure (14 days) compared with lineage-positive (21 days, p = 0.013) and collagen controls (28 days, p = 0.004), and a significant improvement in percentage closure at 14 days compared with the lineage-positive group (p < 0.01) and the collagen control (p < 0.01). Fluorescently tagged lineage-negative cells remained viable in the wound for 28 days, whereas lineage-positive cells were not present after 7 days. Lineage-negative, but not lineage-positive, cells differentiated into endothelial cells. Vascular density and vessel cross-sectional area were significantly higher in lineage-negative wounds. CONCLUSION: Topical progenitor-cell therapy successfully accelerates diabetic wound closure and improves wound vascularity