Faculty Bibliography

AlloDerm has been used as a tissue supplement in conjunction with the pectoralis major muscle to provide full coverage over an implant in breast reconstruction. While this method of reconstruction has shown promising results there is little known on the relationship of AlloDerm size and potential immediate expansion volume. A retrospective chart review was completed evaluating all tissue expander or primary implant reconstructions using AlloDerm. Data recorded included: The type/size of implant/expander, dimensions of the AlloDerm used, initial fill volume, number of expansions and time period of expansion. Statistical analysis was completed with a linear regression model. AlloDerm was used on 49 patients (72 reconstructions). Thirty-four patients (50 reconstructions) underwent reconstruction with a tissue expander and 15 patients (22 reconstructions) underwent a single stage reconstruction with a permanent implant. The tissue expander volume filled (cc) could be predicted by 5 x surface area of AlloDerm (cm(2)) - 12 (R(2) = 0.62) and 80 x height of AlloDerm (cm) - 15 (R(2) = 0.59). The tissue expanders could be filled to an average of 75% of total size and required three to four injections in the postoperative period to reach full expansion. Obviously, a requirement for maximal implant expansion is an appropriate skin sparing mastectomy. There is a mathematical relationship between fill volume and surface area as well as height of AlloDerm used in breast reconstruction. This analysis provides a guideline for immediate implant expansion to surgeons using AlloDerm in reconstructive breast surgery

We previously reported that topically applied calreticulin (CRT), a calcium-binding ER chaperone protein comprising N, P, and C domains, markedly enhances diabetic murine (db/db) and porcine cutaneous wound healing. Consistent with the potent wound healing effects, we further showed, in vitro, that exogenous CRT stimulated proliferation of keratinocytes and fibroblasts, induced concentration-dependent migration of these cells and monocytes and macrophages, and upregulated protein expression of collagen, fibronectin, and TGF-beta-3 in fibroblasts. Notably, all these broad-ranging effects purport novel non-ER functions for CRT that act from outside the cell inward. The current studies address: 1) whether the ER chaperone function of CRT is required for its extracellular functions, 2) the molecular structure(s) of CRT that function in its biological activities and 3) the in vitro effects of CRT on diabetic compared to normal mouse and human fibroblasts. Using CRT null mouse embryo fibroblasts (K42) compared to wild type (K41) in proliferation and migration assays (scratch plate and chamber), we show that exogenous CRT stimulates proliferation of null K42 cells to a similar extent as K41 cells (2-fold at 10 pg/ml). However, K42 cells require 100 times more CRT for a peak migratory response (1 vs 100 ng/ml), with a 20% decreased response. We also show that the C domain stimulates fibroblast proliferation to the same extent and peak response as the entire molecule. Finally, we show that fibroblasts isolated from db/db mouse skin and human fibroblasts cultured in high glucose, to simulate type II diabetes, respond to CRT by migration and proliferation albeit with 1/3 less robust response requiring 10-fold more CRT for peak responses compared to controls. The breath of novel non-ER functions of CRT, structure-function relationships, and effects on diabetic cells in vitro underscore this molecule as a potential potent agent for the topical treatment for healing diabetic wounds

BACKGROUND/AIMS: Neovascularization involves angiogenesis and vasculogenesis mediated by cytokines and soluble chemokines. The predominant stimulus is ischemia, however, recent data suggest that ionizing radiation (IR) has angiogenic potential. In this study we evaluated whether IR increases vascularity and perfusion in vivo. METHODS: In wild-type mice, a full-thickness, pedicled skin flap was created and isolated for localized irradiation at a dose of 5 Gy. Serial Doppler analysis of the flap was performed. The skin flaps were then harvested at various time points for vascularity and histologic analysis. Blood was concurrently harvested for serum and hematopoietic progenitor cell population analysis. RESULTS: IR to an ischemic flap augmented the angiogenic cytokines SDF-1 and VEGF. Serum MMP-9 and s-kit levels, which are critical for progenitor cell mobilization, were also increased. When hematopoietic progenitor cells were evaluated by Sca1+/Flk1+ cells, a correlate 2-fold increase was seen compared to controls. When the flaps were examined, both vascularity and perfusion were increased. CONCLUSION: In this study we demonstrate that local, low-dose IR upregulates angiogenic chemokines and results in progenitor cell mobilization to the systemic circulation. There is a resultant increase in the vascularity of the irradiated flap, suggesting that the pro-angiogenic effects of IR can be harnessed locally

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

Pathologic resections involving the maxilla/hemimaxilla offer a unique reconstructive challenge to the maxillofacial reconstructive surgeon. Traditionally, reconstruction and replacement of lost tissues have been achieved with a variety of methods including obturators, local/regional flaps, and microvascular free tissue transfer. All these techniques have distinct disadvantages. We present a novel approach to palatomaxillary reconstruction using a combination of free tissue transfer and zygomaticus implants. To our knowledge, this specific technique has not been previously reported.

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