Diabetes is associated with poor outcomes following acute vascular occlusive events. This results in part from a failure to form adequate compensatory microvasculature in response to ischemia. Since vascular endothelial growth factor (VEGF) is an essential mediator of neovascularization, we examined whether hypoxic up-regulation of VEGF was impaired in diabetes. Both fibroblasts isolated from type 2 diabetic patients, and normal fibroblasts exposed chronically to high glucose, were defective in their capacity to up-regulate VEGF in response to hypoxia. In vivo, diabetic animals demonstrated an impaired ability to increase VEGF production in response to soft tissue ischemia. This resulted from a high glucose-induced decrease in transactivation by the transcription factor hypoxia-inducible factor-1␣ (HIF-1␣), which mediates hypoxia-stimulated VEGF expression. Decreased HIF-1␣ functional activity was specifically caused by impaired HIF-1␣ binding to the coactivator p300. We identify covalent modification of p300 by the dicarbonyl metabolite methylglyoxal as being responsible for this decreased association. Administration of deferoxamine abrogated methylglyoxal conjugation, normalizing both HIF-1␣/p300 interaction and transactivation by HIF-1␣. In diabetic mice, deferoxamine promoted neovascularization and enhanced wound healing. These findings define molecular defects that underlie impaired VEGF production in diabetic tissues and offer a promising direction for therapeutic intervention.deferoxamine ͉ HIF-1 ͉ hyperglycemia ͉ ischemia

Background-Cells from the bone marrow contribute to ischemic neovascularization, but the identity of these cells remains unclear. The authors identify mesenchymal stem cells as a bone marrow-derived progenitor population that is able to engraft into peripheral tissue in response to ischemia.

Background Over a two-decade period the senior author (P.G.C.) has had extensive experience with two-stage implant-based breast reconstruction with total musculofascial coverage. During this time period the approach has evolved substantially. The evolution has been based on changes in breast cancer treatment, available technology and most importantly, on yearly evaluation of surgical outcomes. Methods This paper describes changes in the conceptual approach to breast reconstruction, and the resulting evolution of surgical techniques. The evolution of concepts and current techniques are described as they relate to each consecutive stage of implant-based breast reconstruction. Results For the first stage of breast reconstruction, i.e. placement of the tissue expander, key concepts and techniques described are the vertical mastectomy defect, the point of maximal expansion, the musculofascial pocket, and the inferior fasciotomy. For the second stage of breast reconstruction, i.e. the exchange procedure, key concepts and techniques described are implant selection, setting the inframammary fold, defining the inferolateral shape of the breast, and circumferential capsulotomy. Conclusions The purpose of this article is to relay the lessons learned from this long experience and to provide conceptual and technical framework to two-stage implant-based breast reconstruction.

Distal replantation performed at institutions that specialize in microsurgery and specifically tailored to the level of injury is associated with good survival, function, and patient satisfaction and superior aesthetic outcome. More prospective data are needed to evaluate the cost of treatment, psychological outcomes, and functional outcomes of distal replantation compared with revision amputation.

The natural history of inherited epidermolysis bullosa (EB) varies significantly across subtypes. When confronted with an infant suspected to have EB, rapidly determining the type and subtype is critical in counselling families accurately about the infant's diagnosis and prognosis. Although transmission electron microscopy (TEM) has been considered the criterion standard for EB diagnosis, immunofluorescence microscopy (IFM) using monoclonal antibodies (mAbs) to EB-specific basement membrane zone proteins has several advantages, but few studies have evaluated the diagnostic utility of IFM. We sought to evaluate the clinical utility of IFM using an expanded panel of EB-specific mAbs. This was a retrospective review of pathology reports from infants younger < 1 year old with suspected EB primarily analyzed with IFM by the Stanford Dermatopathology service. Seventy-seven cases were identified for analysis, of which 20 were suboptimal for IFM analysis. Fifty-five cases were diagnosed with EB and classified as follows: EB simplex (n = 5), junctional EB (n = 31), dystrophic EB (n = 19). TEM was available in 36 of 55 cases (65%). IFM with an expanded panel of EB-specific mAbs should be considered the first-line diagnostic test to evaluate infants with clinically suspected EB.