Faculty Bibliography

PURPOSE: This study evaluated the use of enucleation and cryosurgery in the management of odontogenic keratocysts. PATIENTS AND METHODS: This study involved a retrospective review of 26 patients. All of the patients received a combination of enucleation and cryosurgery. Postoperative follow-up consisted of clinical and radiographic examinations. RESULTS: Before enucleation and cryotherapy, 22 of the 26 patients had received previous treatment consisting of enucleation alone. The average time from initial treatment to recurrence was 6.2 years. Twenty-three cases occurred in the mandible, 22 in the posterior (proximal to the canine), and 1 in the anterior mandible. Three cases involved the maxilla. Three of the 26 patients (11.5%) developed a recurrence after treatment. The average time from treatment to recurrence in these 3 patients was 1.6 years (range, 1.2 to 1.9 years). The remaining 23 patients (88.5%) had no evidence of clinical or radiographic recurrence. The average time of follow-up was 3.5 years (range, 2.0 to 10.0 years). CONCLUSIONS: Based on these results, the combination of enucleation and liquid nitrogen cryotherapy may offer patients improved therapy in the management of odontogenic keratocysts

HYPOTHESIS: Increased cell motility is a hallmark of cancer cells. Proteins involved in cell motility may be used as molecular markers to characterize the malignant potential of tumors. METHODS: Molecular biology and immunohistochemistry techniques were used to investigate the expression of a selected panel of motility-related proteins (Rho A, Rac 2, Cdc42, PI3K, 2E4, and Arp2) in normal, premalignant, and squamous cell cancer cell lines of human head and neck origin. To assess the clinical potential of these proteins as molecular markers for cancer, immunohistochemistry was performed on paraffin-fixed head and neck cancer specimens (n = 15). RESULTS: All six motility-associated proteins were overexpressed in the premalignant and squamous cell cancer cell lines relative to normal keratinocytes. Immunohistochemistry with Rho A and Rac 2 showed increased staining in areas of cancer but not in normal tissue. CONCLUSION: Proteins involved in cell motility can be used as markers for head and neck squamous cell carcinoma. The head and neck cell lines used in this study may be used as a model to further investigate cell motility. Molecular markers of motility could have a significant impact on the diagnosis and staging of cancers originating from differentiated non-motile cells

Facial paralysis (FP) remains today one of the most disturbing cranial nerve disorders. The present study utilized the rat model of FP and examined a dual approach of combining the current microsurgical treatment of cross-facial nerve graft (CFNG) with local administration of insulin-like growth factor-I (IGF-I). The efficacy of this combined treatment approach was assessed by motor end-plate analysis of the reinnervated orbicularis oculi muscle (OOM). Local administration of IGF-I (50 microg/ml) to the CFNG demonstrated a 61 percent increase in the number of end-plates in the reinnervated OOMs, compared to the OOMs reinnervated with CFNG plus vehicle. These results indicate that the local therapeutic augmentation of IGF-I levels at the coaptation site(s) of the CFNG may, in fact, enhance reinnervation of muscle and recovery of function in general

Vascular disruption secondary to fracture creates a hypoxic gradient of injury wherein the oxygen tension at the center of the wound is very low. In vivo this hypoxic microenvironment stimulates the expression of a variety of cytokines from inflammatory cells, fibroblasts, endothelial cells, and osteoblasts. In order to begin to dissect this complex system, we have examined the effects of hypoxia on isolated osteoblast gene expression in vitro. Understanding gene expression in this system may facilitate the development of targeted therapeutic modalities designed to accelerate fracture repair and reduce complications. Using an established model of in vitro hypoxia, we have analyzed the expression of genes involved in bone matrix production and turnover. Subconfluent neonatal rat calvarial osteoblasts were exposed to hypoxia (pO(2) = 35-40 mm Hg) and total cellular RNA was collected at 0, 3, 6, 24, and 48 h. Northern analysis was used to analyze the expression patterns of (1) transforming growth factors (TGFs)-beta1, -beta2, and -beta3 and their type I receptor; (2) collagens I and III; and (3) tissue inhibitor of metalloproteinase-1. We have demonstrated a marked elevation of TGF-beta1 gene expression within 3 h of hypoxia. Although neither TGF-beta2 nor TGF-beta3 expression was affected by hypoxia, the TGF-beta type I receptor was substantially upregulated within 6 h. In addition, extracellular matrix scaffolding molecules (collagens I and III) were markedly, but differentially, upregulated. Finally, we have demonstrated that the expression of an inhibitor of extracellular matrix turnover, the tissue inhibitor of metalloproteinase-1, was strikingly decreased in response to hypoxia. These results imply that hypoxia can affect osseous healing by altering the expression of cytokines, bone-specific extracellular matrix molecules, and their regulators

The epidermal growth factor receptor (EGFR) and the non-receptor protein tyrosine kinases Src and Pyk2 have been implicated in linking a variety of G-protein-coupled receptors (GPCR) to the mitogen-activated protein (MAP) kinase signaling cascade. In this report we apply a genetic strategy using cells isolated from Src-, Pyk2-, or EGFR-deficient mice to explore the roles played by these protein tyrosine kinases in GPCR-induced activation of EGFR, Pyk2, and MAP kinase. We show that Src kinases are critical for activation of Pyk2 in response to GPCR-stimulation and that Pyk2 and Src are essential for GPCR-induced tyrosine phosphorylation of EGFR. By contrast, Pyk2, Src, and EGFR are dispensable for GPCR-induced activation of MAP kinase. Moreover, GPCR-induced MAP kinase activation is normal in fibroblasts deficient in both Src and Pyk2 (Src-/-Pyk2-/- cells) as well as in fibroblasts deficient in all three Src kinases expressed in these cells (Src-/-Yes-/-Fyn-/- cells). Finally, experiments are presented demonstrating that, upon stimulation of GPCR, activated Pyk2 forms a complex with Src, which in turn phosphorylates EGFR directly. These experiments reveal a role for Src kinases in Pyk2 activation and a role for Pyk2 and Src in tyrosine phosphorylation of EGFR following GPCR stimulation. In addition, EGFR, Src family kinases, and Pyk2 are not required for linking GPCRs with the MAP kinase signaling cascade

Skin flaps from the medial aspect of the thigh have traditionally been based on the gracilis musculocutaneous unit. This article presents anatomic studies and clinical experience with a new flap from the medial and posterior aspects of the thigh based on the proximal musculocutaneous perforator of the adductor magnus muscle and its venae comitantes. This cutaneous artery represents the termination of the first medial branch of the profunda femoris artery and is consistently large enough in caliber to support much larger skin flaps than the gracilis musculocutaneous flap. In all 20 cadaver dissections, the proximal cutaneous perforator of the adductor magnus muscle was present and measured between 0.8 and 1.1 mm in diameter, making it one of the largest skin perforators in the entire body. Based on this anatomic observation, skin flaps as large as 30 x 23 cm from the medial and posterior aspects of the thigh were successfully transferred. Adductor flaps were used in 25 patients. On one patient the flap was lost, in one the flap demonstrated partial survival, and in 23 patients the flaps survived completely. The flap was designed as a pedicle island flap in 14 patients and as a free flap in 11. When isolating the vascular pedicle for free tissue transfer, the cutaneous artery is dissected from the surrounding adductor magnus muscle and no muscle is included in the flap. Using this maneuver, a pedicle length of approximately 8 cm is isolated. In addition to ample length, the artery has a diameter of approximately 2 mm at its origin from the profunda femoris artery. The adductor flap provides an alternative method for flap design in the posteromedial thigh. Because of the large pedicle and the vast cutaneous territory that it reliably supplies, the authors believe that the adductor flap is the most versatile and dependable method for transferring flaps from the posteromedial thigh region