Faculty Bibliography

Transverse mandibular distraction osteogenesis involves moving the osteotomized segments of the mandible in either a varus or valgus direction. This maneuver allows for widening of the bigonial distance or for a lateral shift of an asymmetric mandibular midline. During this process, a significant amount of torque is placed on the mandibular condyles, because they act as the pivot point for the mandibular translation. Although standard linear distraction osteogenesis induces transient, reversible changes in the temporomandibular joint, it is not known what effect the varus and valgus stresses of transverse distraction have on the temporomandibular joint. We therefore designed a study to document the temporomandibular joint changes following various degrees of transverse distraction.Bilateral transverse mandibular distraction was performed on 10 adult, female mongrel dogs using an external, multiplanar mandibular distraction device. The distraction protocol was as follows: (1) complete osteotomy at the angle of the mandible, (2) 5-day latency period, (3) distraction rate of 1 mm/day, (4) rhythm of one turn per day, (5) linear activation 16 to 30 mm bilaterally, and (6) 8-week consolidation period. A variety of varus and valgus distraction vectors were applied to the mandible only after 10 mm of initial linear distraction had been achieved. Posteroanterior and lateral cephalograms were performed throughout the entire process. Pre-distraction and post-consolidation computed tomographic scans were also performed. Changes in mandibular conformation, axis of rotation, temporomandibular joint structure, and glenoid fossa changes were directly assessed by evaluating the postmortem craniofacial skeleton. The findings were compared with those of normal, age-matched mongrel dog skulls.Significant remodeling changes were observed in the temporomandibular joints of all animals involved in the study. The mandibular condyles demonstrated varying degrees of flattening and erosion at all contact points with the craniofacial skeleton. In some cases, the condyle became part of the distraction regenerate process and was hypertrophied in all dimensions. The condyles were frequently displaced out of the glenoid fossa, particularly on the side in the direction of varus distraction. When the latter occurred, a new fossa was created on the undersurface of the zygomatic arch. Varying degrees of mandibular rotation in the sagittal plane were also observed, which led to abnormal torquing of the condyles in the coronal plane, depending on whether the axis of rotation occurred primarily around the condyle or around the distraction regenerate zone.In conclusion, transverse mandibular distraction is an effective means of producing a varus or valgus shift in the gonion relative to the midsagittal plane. However, unlike linear or angular mandibular distraction, transverse distraction has a multitude of nontransient effects on the temporomandibular joint. Therefore it must be emphasized that in clinical practice, transverse distraction should be used cautiously. One must also be aware that such a maneuver in distraction can have negative effects on the temporomandibular joint

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

Bannayan-Zonana syndrome (BZS) is a genetic disorder with autosomal dominant inheritance characterized by macrocephaly and multiple hamartomas of mesodermal origin. Here we present a patient with BZS manifested by many of the classic features, as well as a high-flow upper extremity arteriovenous malformation (AVM). Although this rare syndrome was initially described in 1971, to our knowledge, this is the first report showing an association of AVM with BZS and the first report of this syndrome in the radiologic literature

OBJECTIVE: To determine if fine needle aspiration (FNA) can preclude the requirement for diagnostic open biopsy in suspicious pediatric head and neck masses. METHODS: The records of 40 children presenting to an inner city tertiary care hospital who underwent a total of 50 FNA biopsies during the years 1988-1999 were reviewed. From these 40 patients, 17 children, aged 3 months to 18 years, underwent both clinically indicated FNA biopsy and subsequent open surgical biopsy or excision. Outcome measurements included clinical resolution or surgical pathologic diagnosis. RESULTS: The 17 patients who underwent open surgical biopsy subsequent to the FNA had a total of 21 FNAs performed. Three of these patients had more than one needle biopsy prior to surgery. The histologic diagnosis of the surgical excision confirmed the FNA biopsy cytologic diagnosis in all but two cases. FNA cytologic diagnostic categories included reactive lymph node/non-specific inflammation (25 biopsies), benign cystic process (four), granulomatous disease (eight), malignant neoplasm (three), and benign neoplasm (one). Eight of nine FNAs initially non-diagnostic had either complete resolution of the mass or a diagnosis obtained by subsequent FNA or open biopsy. CONCLUSIONS: FNA is a valuable diagnostic tool in the management of children with the clinical presentation of a suspicious neck mass. The technique reduces the need for more invasive and costly procedures. Early surgical biopsy, however, should be considered in rapidly enlarging masses, in the presence of persistent systemic symptoms, and when repeated FNA cytology is non-diagnostic

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

OBJECTIVE/HYPOTHESIS: To identify the significance of molecular markers in determining the risk of recurrence and distant metastases in nasopharyngeal carcinoma. STUDY DESIGN: In this retrospective case study, we evaluated archival nasopharyngeal carcinoma specimens for patterns of expression of E-cadherin, beta-catenin, c-erb-B2, and Ki-67, which have been demonstrated to be important in other tumors. METHODS: Fifty-four cases of nasopharyngeal carcinoma were identified, with a maximum follow-up of 13 years. The histopathological sections were stained using an automated immunohistochemical stainer (NexES, Ventana Medical Systems, Tucson, AZ) for E-cadherin (Zymed Laboratories [San Francisco, CA] and Transduction Laboratories [Lexington, KY] clones), beta-catenin (Zymed), c-erb-B2 (Ventana Medical Systems), and Ki-67 (Novocastra, Burlingame, CA). The numbers of positively staining cells were scored as follows: 0%, 1% to 33%, 34% to 66%, or greater than 67%. RESULTS: E-cadherin (Zymed) stained positively in only one case. The Transduction Laboratories clone demonstrated a spectrum of staining in all cases, from complete to disrupted to no identifiable membranous staining. The staining was consistently absent at the advancing tumor border, regardless of stage. The loss of beta-catenin expression did not correlate with that of E-cadherin or with clinical outcomes. No staining was identified for c-erb-B2. Ki-67 staining was variable and did not correlate with clinical outcomes. CONCLUSIONS: Altered expression or loss of E-cadherin, or both, may result in loss of function, particularly at the infiltrating edge, with resultant loss of cell polarity, cell migration, and eventual metastasis. The interpretation of E-cadherin staining depends on antibody source. In contrast to recent studies, beta-catenin expression is not altered and c-erb-B2 expression not identified, suggesting that these markers are not important in the prognosis of nasopharyngeal carcinoma

Distraction osteogenesis is a well-established method of endogenous tissue engineering. This technique has significantly augmented our armamentarium of reconstructive craniofacial procedures. Although the histologic and ultrastructural changes associated with distraction osteogenesis have been extensively described, the molecular mechanisms governing successful membranous distraction remain unknown. Using an established rat model, the molecular differences between successful (i.e., osseous union with gradual distraction) and ineffective (i.e., fibrous union with acute lengthening) membranous bone lengthening was analyzed. Herein, the first insight into the molecular mechanisms of successful membranous bone distraction is provided. In addition, these data provide the foundation for future targeted therapeutic manipulations designed to improve osseous regeneration. Vertical mandibular osteotomies were created in 52 adult male Sprague-Dawley rats, and the animals were fitted with customized distraction devices. Twenty-six animals underwent immediate acute lengthening (3 mm; a length previously shown to result in fibrous union) and 26 animals were gradually distracted (after a 3-day latency period, animals were distracted 0.25 mm twice daily for 6 days; total = 3 mm). Four mandibular regenerates were harvested from each group for RNA analysis on 5, 7, 9, 23, and 37 days postoperatively (n = 40). Two mandibular regenerates were also harvested from each group and prepared for immunohistochemistry on postoperative days 5, 7, and 37 (n = 12). In addition to the 52 experimental animals, 4 control rats underwent sham operations (skin incision only) and mandibular RNA was immediately collected. Control and experimental specimens were analyzed for collagen I, osteocalcin, tissue inhibitor of metalloproteinase-1, and vascular endothelial growth factor mRNA and protein expression. In this study, marked elevation of critical extracellular matrix molecules (osteocalcin and collagen I) during the consolidation phase of gradual distraction compared with acute lengthening is demonstrated. In addition, the expression of an inhibitor of extracellular matrix turnover, tissue inhibitor of metalloproteinase-1, remained strikingly elevated in gradually distracted animals. Finally, this study demonstrated that neither gradual distraction nor acute lengthening appreciably alters vascular endothelial growth factor expression. These results suggest that gradual distraction osteogenesis promotes successful osseous bone repair by regulating the expression of bone-specific extracellular matrix molecules. In contrast, decreased production or increased turnover of bone scaffolding proteins (i.e., collagen) or regulators of mineralization (i.e., osteocalcin) may lead to fibrous union during acute lengthening

Plastic surgery research affords tremendous opportunities in a variety of affluent mode systems. Only recently have researchers applied molecular biologic techniques to common plastic surgery problems. For example, investigating the fundamental biomolecular mechanisms of normal palate and cranial suture morphogenesis will improve the understanding of the etiopathogenesis of CLP and craniosynostosis and facilitate the development of biologically-based interventions. Furthermore, as interdisciplinary collaborations improve, surgeons can expect to see remarkable progress in de novo tissue synthesis, replacement, and repair. Ultimately, they may one day find that gene-modified endogenous tissue engineering will succeed today's biocompatible scaffolds and allogeneic or zenogeneic replacement strategies. In general, plastic surgeons can look forward to the development of highly effective biomolecular treatments for clinical problems such as complex wound repair, prolific scarring, bone deficits (or surpluses), and organ system replacement or repair. Researchers believe that biologically-based strategies like these will be combined with technical advances that harness minimally invasive approaches. Together, clinicians expect these new tactics will reduce morbidity and improve the results of clinical problems treated by plastic surgeons

The purpose of this study was to examine the effect of Lactosorb absorbable plates on bone healing across cranial bone defects in the rabbit skull. Two 10-mm diameter parietal skull defects were created in each of 20 rabbits, with one defect being placed on either side of the sagittal suture. In 10 rabbits, an absorbable plate was placed across both the inner and outer cortices of the left defect, and in the other 10 rabbits, an absorbable plate was placed across the outer cortex only of the left defect. The right defect always served as the control side, with no plate being placed across it. Rabbits were killed an average of 25 weeks postoperatively. Areas of reossification in the experimental and control defects of each rabbit were then measured, examined histologically, and compared. Growth across defects spanned by one plate was also compared with growth across defects spanned by two plates. Histologic and statistical analyses revealed no significant differences in reossification between the control and experimental defects in each animal and between the defects spanned by one versus two plates. This study suggests that these copolymer absorbable plates neither inhibit nor facilitate reossification across 10-mm diameter rabbit cranial defects

OBJECTIVE: The surgical excision of benign submucosal lesions of the larynx can be performed using a variety of techniques including direct laryngoscopy and external approaches. We propose that small submucosal lesions of the larynx can be removed via the external approach without a tracheotomy. STUDY DESIGN: Retrospective chart review. SETTING: Six patients at The Long Island Jewish Medical Center and at the New York University School of Medicine underwent an external approach for the removal of benign submucosal laryngeal lesions without tracheotomies. Lesions included a mixed laryngopyocele, an internal laryngopyocele, a mixed laryngocele, a paraganglioma, a neurilemmoma and a lymphoma. Follow-up ranged from 1 to 9 years. RESULTS: All patients were female with an average age of 72. No patient required a tracheotomy. One patient remained intubated for 24 hours postoperatively to ensure an adequate airway. Mild dysphagia was noted in all patients, but it was short-lived and did not require alternate methods of alimentation. There have been no recurrences of disease. CONCLUSION: The external approach without tracheotomy allows for good exposure with minimal functional disability for the removal of benign submucosal lesions of the larynx