Faculty Bibliography

BACKGROUND: Cryolipolysis provides a method for noninvasive fat reduction that significantly reduces subcutaneous fat in a pig model without apparent damage to skin and surrounding structures. This study aimed to determine whether fat reduction in humans caused by cold exposure is associated with alteration in local sensory function or nerve fibers. METHODS: In this study, 10 subjects were treated with a prototype cooling device. Fat reduction was assessed in 9 of the 10 subjects via ultrasound before treatment and at the follow-up visit. Sensory function was assessed by neurologic evaluation (n = 9), and biopsies (n = 1) were collected for nerve staining. RESULTS: Treatment resulted in a normalized fat layer reduction of 20.4% at 2 months and 25.5% at 6 months after treatment. Transient reduction in sensation occurred in six of nine subjects assessed by neurologic evaluation. However, all sensation returned by a mean of 3.6 weeks after treatment. Biopsies showed no long-term change in nerve fiber structure. There were no lasting sensory alterations or observations of skin damage in any of the subjects evaluated. CONCLUSION: Noninvasive cryolipolysis results in substantial fat reduction within 2 months of treatment without damage to skin. The procedure is associated with modest reversible short-term changes in the function of peripheral sensory nerves

BACKGROUND: Infection in severe pressure ulcers can lead to sepsis with a 6-month mortality as high as 68%. METHODS: Operative records of 142 consecutive operative debridements on 60 patients in a dedicated wound healing inpatient unit were reviewed, from the Wound Electronic Medical Record, for identification of key steps in debridement technique, mortality, unexpected returns, and time to discharge following debridement. RESULTS: The mean age of the patients was 73.1 years, and 45% were men. Most wounds (53%) were located on the hip (ischial or trochanteric); others were on the sacrum (32%) and the heels (14%). The mean initial wound area prior to debridement was 14.0 cm(2), and 83% of debridements were performed on stage IV pressure ulcers. The postoperative hospital stay averaged 4.1 days. Key steps in the technique included (1) exposure of areas of undermining by excising overlying tissue; (2) removal of callus from wound edges; (3) removal of all grossly infected tissue; and (4) obtaining a biopsy of the deep tissue after debridement of all nonviable or infected tissue for culture and pathology to determine the presence of infection, fibrosis, and granulation tissue. There was one death 9 days post-debridement of a sacral ulcer and one unplanned return to the operating room for bleeding 8 days post-debridement. CONCLUSIONS: Operative debridement of pressure ulcers is safe, despite the medical co-morbidities in patients with severe pressure ulcers. Proper debridement technique may prevent sepsis and death in patients with multiple co-morbid conditions

BACKGROUND: The technical success of facial composite tissue allotransplantation demands full understanding of superficial and deep perfusion for reliable microvascular transfer. Candidates with composite midface defects require an appreciation of the circulatory patterns to design a composite midface allotransplant. METHODS: External carotid vascular territories were evaluated in 10 cadavers to determine the reliability of facial soft-tissue flaps based on a single vascular pedicle. The right common carotid artery was injected with red latex and the left was injected with blue latex. Dual perfusion was confirmed by purple, following two-color mixing. Vascular pedicles included the superficial temporal, transverse facial, and facial arteries. In five additional cadavers, the midface segment was isolated by Le Fort III osteotomy after two-color latex injection with inclusion of the internal maxillary vascular pedicle. Cadavers were imaged with three-dimensional computed tomographic reconstructions following latex injection to confirm perfusion patterns. RESULTS: In soft-tissue facial flaps, unilateral carotid dominance was seen in the nasal dorsum and tip, confirming reliable supply by a single external carotid artery. In midface flaps, bilateral perfusion was seen in the maxilla. Ipsilateral perfusion was observed at the zygomaticomaxillary complex without any contralateral contribution. CONCLUSIONS: Dual soft-tissue perfusion was confirmed in most specimens at the nasal, central face, and maxilla. The inclusion of the maxilla in the design of a facial composite allotransplant demands bilateral vascular pedicles based on the internal maxillary arteries. The authors highlight a procurement strategy for design of such flaps.

In end-to-side neurorrhaphy, 'noninjury' models of the donor nerve do not seem to offer worthwhile functional outcomes. The role of donor nerve injury distal to the coaptation site remains unclear. End-to-side neurorrhaphy was studied in a rat model in which the proximal stump of the transected musculocutaneous nerve was sutured to the median nerve by end-to-side coaptation. Twenty Sprague-Dawley rats were randomized to four groups of five animals each, in which three different types of donor injury (crush, ligation, or transection injury) distal to the coaptation site were executed; findings were compared with a similar end-to-side model without donor nerve injury (control). Behavioral analysis, electrophysiological studies, muscle morphometric studies, and nerve fibers counts showed no significant differences among groups. However, there was a significant difference regarding mean myelin area (P = 0.0362) and mean fiber diameter (P = 0.0159) for the crush injury group as compared with the control group. No significant differences were found among the other groups. These data suggest that donor crush injury distal to the coaptation site may increase the rate of myelin formation in regenerating axons across an end-to-side model; however, at 4 weeks of follow-up, there was no significant behavioral or functional significance in this treatment group

OBJECT: A relationship has been found between peripheral thermal injury and cerebral complications leading to injury and death. In the present study, the authors examined whether tumor necrosis factor-alpha (TNF-alpha) and matrix metalloproteinase-9 (MMP-9) play a causative role in blood-brain barrier (BBB) disruption after peripheral thermal injury. METHODS: Thirty-two male Sprague-Dawley rats were subjected to thermal injury. One hour later, 8 rats were injected with TNF-alpha neutralizing antibody, and 8 were injected with doxycycline, an inhibitor of the MMP family proteins; 16 rats did not receive any treatment. Brain tissue samples obtained 7 hours after injury in the treated animals were examined for BBB function by using fluorescein isothiocyanate-dextran and by assessing parenchymal water content. Protein expression of basement membrane components (collagen IV, laminin, and fibronectin) was quantified on Western blot analysis, and MMP-9 protein expression and enzyme activity were determined using Western blot and gelatin zymography. Thermally injured rats that did not receive treatment were killed at 3, 7, or 24 hours after injury and tested for BBB functioning at each time point. Histological analysis for basement membrane proteins was also conducted in untreated rats killed at 7 hours after injury. Results of testing in injured rats were compared with those obtained in a control group of rats that did not undergo thermal injury. RESULTS: At 7 hours after thermal injury, a significant increase in the fluorescein isothiocyanate-dextran and water content of the brain was found (p < 0.05), but BBB dysfunction was significantly decreased in the rats that received TNF-alpha antibody or doxycycline (p < 0.05). In addition, the components of the basal lamina were significantly decreased at 7 hours after thermal injury (p < 0.01), and there were significant increases in MMP-9 protein expression and enzyme activity (p < 0.05). The basal lamina damage was reversed by inhibition of TNF-alpha and MMP-9, and the increase in MMP-9 protein was reduced in the presence of doxycycline (p < 0.05). The authors found that MMP-9 enzyme activity was significantly increased after thermal injury (p < 0.01) but decreased in the presence of either TNF-alpha antibody or doxycycline (p < 0.01). CONCLUSIONS: The dual, inhibitory activity of both TNF-alpha and MMP-9 in brain injury suggests that a TNF-alpha and MMP-9 cascade may play a key role in BBB disruption. These results offer a better understanding of the pathophysiology of burn injuries, which may open new avenues for burn treatment beyond the level of current therapies

BACKGROUND: A chronic wound is tissue with an impaired ability to heal. This is often a consequence of one of the following etiologies: diabetes, venous reflux, arterial insufficiency sickle cell disease, steroids, and/or pressure. Healing requires granulation tissue depending on epithelialization and angiogenesis. Currently no growth factor is available to treat patients with impaired healing that stimulates both epithelialization and angiogenesis. The objective is to review is the multiple mechanisms of vascular endothelial growth factor (VEGF) in wound healing. MATERIALS AND METHODS: The authors reviewed the literature on the structure and function of VEGF, including its use for therapeutic angiogenesis. Particular attention is given to the specific role of VEGF in the angiogenesis cascade, its relationship to other growth factors and cells in a healing wound. RESULTS: VEGF is released by a variety of cells and stimulates multiple components of the angiogenic cascade. It is up-regulated during the early days of healing, when capillary growth is maximal. Studies have shown the efficacy of VEGF in peripheral and cardiac ischemic vascular disease with minimal adverse effects. Experimental data supports the hypothesis that VEGF stimulates epithelialization and collagen deposition in a wound. CONCLUSION: VEGF stimulates wound healing through angiogenesis, but likely promotes collagen deposition and epithelialization as well. Further study of the molecule by utilizing the protein itself, or novel forms of delivery such as gene therapy, will increase its therapeutic possibilities to accelerate closure of a chronic wound

In this work, a three-dimensional model for bone remodeling is presented, taking into account the hierarchical structure of bone. The process of bone tissue adaptation is mathematically described with respect to functional demands, both mechanical and biological, to obtain the bone apparent density distribution (at the macroscale) and the trabecular structure (at the microscale). At global scale bone is assumed as a continuum material characterized by equivalent (homogenized) mechanical properties. At local scale a periodic cellular material model approaches bone trabecular anisotropy as well as bone surface area density. For each scale there is a material distribution problem governed by density-based design variables which at the global level can be identified with bone relative density. In order to show the potential of the model, a three-dimensional example of the proximal femur illustrates the distribution of bone apparent density as well as microstructural designs characterizing both anisotropy and bone surface area density. The bone apparent density numerical results show a good agreement with Dual-energy X-ray Absorptiometry (DXA) exams. The material symmetry distributions obtained are comparable to real bone microstructures depending on the local stress field. Furthermore, the compact bone porosity is modeled giving a transversal isotropic behavior close to the experimental data. Since, some computed microstructures have no permeability one concludes that bone tissue arrangement is not a simple stiffness maximization issue but biological factors also play an important role.