Faculty Bibliography

Gene therapy has moved from the promise of laboratory investigation to the reality of clinical practice in just the last decade. Various methods for delivery of genes to host cells have been developed and utilized both in vitro and in vivo. From the perspective of the plastic surgeon, gene therapy holds the promise to augment healing in clinical situations that remain difficult to treat, such as chronic wounds, osteoradionecrosis, or possibly to expedite current clinical practices, such as distraction osteogenesis. The authors chose to investigate the potential for gene therapy in osseous tissues using a replication-deficient adenovirus vector to deliver the marker transgene beta-galactosidase. An adenovirus vector is ideal for use in situations in which transgene expression is desired for only a relatively short period of time, such as wound and fracture healing. Utilizing a rat mandibular osteotomy model, they demonstrated that, using an adenoviral vector, foreign genes can be delivered in a simple fashion and can be expressed in a reliable manner within and around the osteotomy site for at least 10 days. Furthermore, there was no evidence of transfection of distant tissues associated with local application of the adenovirus vector. With this information, clinicians may now attempt to deliver osteogenic and angiogenic genes in a site-specific fashion to improve and expedite osseous healing

BACKGROUND: The closure of any circular or asymmetric wound results in puckering or excess of tissue known as dog-ears. OBJECTIVE: Facility in managing dog-ears is an invaluable tool in cutaneous surgery due to its common presentation. METHODS: Methods for correcting dog-ears are extensively detailed in both the plastic and dermatologic surgery literature. This review provides a practical outline of nine methods of dog-ear correction along with pertinent schematic and clinical illustration. RESULTS: A comprehensive approach to dog-ears requires knowledge of tissue dynamics, adherence to proper surgical technique, and strategies for the management of dog-ears. CONCLUSIONS: A thorough understanding of dog-ear formation and correction allows the surgeon to choose the most appropriate management for dog-ears in any clinical setting

The deep nasolabial fold and other facial furrows and wrinkles have challenged the facial plastic surgeon. A variety of techniques have been used in the past to correct these troublesome defects. Advances in the last five years in new materials and design have created a subcutaneous implant that has excellent properties. This article reviews the development and use of Softform facial implant

The well-described detrimental effects of ionizing radiation on the regeneration of bone within a fracture site include decreased osteocyte number, suppressed osteoblast activity, and diminished vascularity. However, the biologic mechanisms underlying osteoradionecrosis and the impaired fracture healing of irradiated bone remain undefined. Ionizing radiation may decrease successful osseous repair by altering cytokine expression profiles resulting from or leading to a change in the osteoblastic differentiation state. These changes may, in turn, cause alterations in osteoblast proliferation and extracellular matrix formation. The purpose of this study was to investigate the effects of ionizing radiation on the proliferation, maturation, and cytokine production of MC3T3-E1 osteoblast-like cells in vitro. Specifically, the authors examined the effects of varying doses of ionizing radiation (0, 40, 400, and 800 cGy) on the expression of transforming growth factor-beta1 (TGF-beta1), vascular endothelial growth factor (VEGF), and alkaline phosphatase. In addition, the authors studied the effects of ionizing radiation on MC3T3-E1 cellular proliferation and the ability of conditioned media obtained from control and irradiated cells to regulate the proliferation of bovine aortic endothelial cells. Finally, the authors evaluated the effects of adenovirus-mediated TGF-beta1 gene therapy in an effort to 'rescue' irradiated osteoblasts. The exposure of osteoblast-like cells to ionizing radiation resulted in dose-dependent decreases in cellular proliferation and promoted cellular differentiation (i.e., increased alkaline phosphatase production). Additionally, ionizing radiation caused dose-dependent decreases in total TGF-beta1 and VEGF protein production. Decreases in total TGF-beta1 production were due to a decrease in TGF-beta1 production per cell. In contrast, decreased total VEGF production was secondary to decreases in cellular proliferation, because the cellular production of VEGF by irradiated osteoblasts was moderately increased when VEGF production was corrected for cell number. Additionally, in contrast to control cells (i.e., nonirradiated), conditioned media obtained from irradiated osteoblasts failed to stimulate the proliferation of bovine aortic endothelial cells. Finally, transfection of control and irradiated cells with a replication-deficient TGF-beta1 adenovirus before irradiation resulted in an increase in cellular production of TGF-beta1 protein and VEGF. Interestingly, this intervention did not alter the effects of irradiation on cellular proliferation, which implies that alterations in TGF-beta1 expression do not underlie the deficiencies noted in cellular proliferation. The authors hypothesize that ionizing radiation-induced alterations in the cytokine profiles and differentiation states of osteoblasts may provide insights into the cellular mechanisms underlying osteoradionecrosis and impaired fracture healing

Objective Oral antibiotic use may have changed the incidence and microbiology of otitic intracranial complications. We reviewed cases of acute mastoiditis to document: (1) incidence of intracranial complications; (2) risk factors; and (3) identify pathologic organisms. Methods: A retrospective study of children at a tertiary care children's hospital with acute mastoiditis from July, 1986 through June, 1998. Results: 118 children with acute mastoiditis were identified. Eight patients (6.8%), ages 20 months to 14 years, had intracranial complications related to acute mastoiditis. Three children had a sigmoid sinus thrombosis, two children had an epidural abscess, and two children had both complications of sigmoid sinus thrombosis and epidural abscess, and a sigmoid sinus thrombosis and meningitis was present in one child. Pre-admission oral antibiotics were administered for an average of 10 days in seven of the eight patients. Persistent otorrhea and/or otalgia were present in all patients. Intraoperative cultures were negative in four cases (50%). Organisms isolated included. Streptococcus pneumoniae (2); Proteus mirabilis (I); Pseudomonas aeruginosa (1); and coagulase negative Staphylococcus (I). Multi-drug resistant organisms were documented in only one case. All patients underwent a contrast enhanced CT of the temporal bones and brain. Surgical management included complete mastoidectomy in all patients and a pressure equalization tube in seven of the eight cases. Conclusions: Our review did not document an increase in the incidence of otitic intracranial complications. Persistent otalgia or otorrhea while on oral antibiotics with associated neurologic symptoms are ominous signs suggestive of a complication. Multi-drug resistant organisms are uncommon whereas negative intraoperative cultures are common. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved

The purpose of this study was to determine the solidification rates for BoneSource (hydroxyapatite cement) mixed with sterile water versus BoneSource mixed with 0.25 ml of sodium phosphate. The average time for cure for BoneSource mixed with sterile water was 99 minutes, with a SD of 5.3 minutes. The average time for cure for BoneSource and sodium phosphate was 43 minutes, with a SD of 3.6 minutes (P < 0.0003). The average temperature for BoneSource in sterile water was 19.1 degrees C with a SD of 0.082, and the average temperature of BoneSource in sodium phosphate was 20.1 degrees C, with a SD of 0.1. Therefore, sodium phosphate shows that there is a significantly decreased amount of time required to solidify BoneSource and it remains isothermic throughout this reaction

The ultrastructure of the early regenerative response in an end-to-side neurorrhaphy rat model was studied using transmission electron microscopy. The ipsilateral saphenous nerve was grafted to the sciatic nerve under the following conditions: Group 1, the epineurium and perineurium of the sciatic nerve remained intact; Group 2, an epineurial and perineurial window was created at the site of the lateral neurorrhaphy; Group 3, the same as in Group 2 and, in addition, the sciatic nerve sustained a partial neurectomy. Rats were perfused through the heart with fixative containing 2 percent paraformaldehyde and 2.5 percent glutaraldehyde in 0.1 M cacodylate buffer (pH 7.4) at 4, 8, 12, 24 and 48 hr after surgery. In Group 1, no regenerating axons were observed and the myelin sheath in the donor nerve did not demonstrate any degenerative changes through 48 hr. In Group 2, an increased diameter of the unmyelinated axons and growth cones was observed in the donor nerve proximal to the coaptation site after 12 hr. Degenerative changes in the myelin sheath were observed after 12 hr within the several layers under the coaptation site. In Group 3, many growth cone-like structures were observed in the area proximal to the coaptation site after 12 hr. After 24 hr, proximal regenerating axons elongated to the coaptation site and, at 48 hr, many regenerating nerves grew inside the Schwann cell basement membrane of the graft nerve. These results indicate that the perineurial window and nerve graft are the critical conditions for inciting nerve regeneration in the donor nerve