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school:SOM

Department/Unit:Plastic Surgery

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Inhibition of Smad3 expression in radiation-induced fibrosis using a novel method for topical transcutaneous gene therapy

Lee, Judy W; Tutela, John P; Zoumalan, Richard A; Thanik, Vishal D; Nguyen, Phuong D; Varjabedian, Leon; Warren, Stephen M; Saadeh, Pierre B
OBJECTIVE: To attempt to mitigate the effects of irradiation on murine skin after high-dose radiation using a novel transcutaneous topical delivery system to locally inhibit gene expression with small interfering RNA (siRNA) against Smad3. DESIGN: Laboratory investigation. SETTING: University laboratory. SUBJECTS: Twenty-five wild-type C57 mice. INTERVENTION: In an isolated skin irradiation model, the dorsal skin of C57 wild-type mice was irradiated (45 Gy). Just before irradiation, Smad3 and nonsense siRNA were applied to 2 separate dorsal skin areas and then reapplied weekly. Skin was harvested after 1 and 4 weeks. Smad3 expression were assessed by immunohistochemistry, and collagen deposition and architecture was examined using picrosirius red collagen staining. MAIN OUTCOME MEASURES: Epidermal thickness was measured semiquantitatively at 4 weeks. Radiation-induced fibrosis was measured quantitatively via tensiometry. The Young modulus, a measure of cutaneous rigidity inversely related to elasticity, was determined, with normal irradiated skin serving as a control specimen. RESULTS: Murine skin treated with topical Smad3 siRNA demonstrated effective Smad3 inhibition at 1 week and persistent suppression at 4 weeks. Collagen deposition and epidermal thickness were significantly decreased in skin treated with Smad3 siRNA compared with control irradiated skin. Tensiometry demonstrated decreased tension in Smad3 siRNA-treated skin, with a Young modulus of 9.29 MPa (nonirradiated normal skin, 7.78 MPa) compared with nonsense (control) siRNA-treated skin (14.68 MPa). CONCLUSIONS: Smad3 expression can be effectively silenced in vivo using a novel topical delivery system. Moreover, cutaneous Smad3 inhibition mitigates radiation-induced changes in tissue elasticity, restoring a near-normal phenotype
PMID: 20644068
ISSN: 1538-361x
CID: 111363

Blink restoration in adult facial paralysis

Terzis, Julia K; Karypidis, Dimitrios
BACKGROUND: Impaired eyelid function in facial paralysis patients is a serious disability that can even threaten vision. Eye reanimation techniques and specifically blink restoration reinstates the cornea's protective mechanism and recovers a more natural appearance and eye function. Both dynamic and static procedures have been used to augment eye closure, but only dynamic procedures can lead to blink restoration. In this study, the experience of a single surgeon (J.K.T.) with dynamic procedures addressing the challenge of blink restoration is presented. METHODS: A retrospective review of 95 adult patients who underwent dynamic procedures for blink restoration was performed. The patients were divided into two groups. Group A (n = 75) included patients who underwent nerve transfers, including cross-facial nerve grafting and subsequent microcoaptations, mini-hypoglossal nerve transfers, and direct orbicularis oculi muscle neurotization. Group B (n = 20) included patients who underwent eye sphincter substitution procedures, including pedicled frontalis or mini-temporalis transfers, free platysma, occipitalis, gracilis subunits, extensor digitorum brevis, and a slip of adductor longus transfer. Objective blink ratios were measured according to a protocol established by the senior author (J.K.T.). RESULTS: The patients included 34 men and 61 women. Mean age was 34.9 +/- 9.8 years. Denervation time ranged from 7 months to 42.12 years, and the mean denervation time was 13.02 years. Blink improvement was noted in all of the patients. Blink scores and ratios were consistently better in group A than in group B. CONCLUSION: Dynamic procedures provide the functional substrate on which subsequent static procedures can be performed and aid blink return
PMID: 20595863
ISSN: 1529-4242
CID: 115113

A simple approach of tubularizing the supraclavicular flap for circumferential pharyngoesophageal defects [Letter]

Henderson, Megan M; Chiu, Ernest S; Jaffer, Azul S
PMID: 20595837
ISSN: 1529-4242
CID: 169969

Role of a new orthognathic surgery in maxillomandibular reconstruction by free flaps

Gennaro, Paolo; Torroni, Andrea; Leonardi, Alessandra; Aboh, Ikenna Valentine; Ramieri, Valerio; Valentini, Valentino
PURPOSE: The objective of this study was to describe the orthognathic surgery techniques for the treatment of occlusal anomalies in those patients who underwent complex maxillomandibular reconstruction with bony free flap. MATERIALS AND METHODS: The authors describe their personal technique developed over years of experience with reconstruction of mandibular defects with bony free flaps. RESULTS: The outcomes in these patients who were treated according to our surgical planning were completely satisfying, with a 100% stability of the treated bones. CONCLUSIONS: Orthognathic procedure on bony free flaps for the reconstruction of mandibular defects is nowadays accepted. Patients who underwent major mandibular destruction due to oncologic disease or trauma outcomes can now benefit from this technique.
PMID: 20613587
ISSN: 1536-3732
CID: 1770052

Importance of computer-aided design and manufacturing technology in the multidisciplinary approach to head and neck reconstruction [Case Report]

Sharaf, Basel; Levine, Jamie P; Hirsch, David L; Bastidas, Jairo A; Schiff, Bradley A; Garfein, Evan S
Head and neck reconstruction is a multidisciplinary field, requiring communication among various surgical and dental specialists. The free fibular flap is the standard method for reconstructing large mandibular defects after benign or malignant tumor ablation. The graft has to be precisely contoured to fit the three-dimensional defect to meet the functional and aesthetic goals.Virtual surgical planning using computed tomographic imaging and computer-aided design and manufacturing technology allows the surgeons to perform virtual surgery and generates templates and cutting guides that allow for the precise and expedient recreation of the plan in the operating room. The authors describe 2 cases where virtual planning was used for the extirpative and reconstruction phases to achieve precise reconstruction and decreased time under anesthesia.
PMID: 20613609
ISSN: 1049-2275
CID: 156182

Head and neck radiotherapy compliance in an underserved patient population

Sethi, Rajni A; Stamell, Emily F; Price, Leah; DeLacure, Mark; Sanfilippo, Nicholas
OBJECTIVES/HYPOTHESIS: Compliance to intensive multiweek radiation therapy (RT) regimens in head and neck cancer (HNC) patients is challenging, particularly among medically underserved patients with fewer financial and social resources. Treatment prolongation reduces local control and overall survival rates, making adherence to treatment a key factor in optimal outcome. We evaluated factors affecting compliance in medically underserved patients who received RT for HNC in a large municipal hospital setting in New York City. STUDY DESIGN: Retrospective review. METHODS: Treatment records of patients treated between July 2004 and August 2008 were reviewed. Number of and reasons for missed treatments were identified. Several demographic, toxicity, and treatment variables were analyzed for impact on compliance. RESULTS: Eighty consecutive HNC patients who underwent RT with a 5- to 7-week regimen were identified. Thirty-two patients (40%) missed no treatments, 36 (45%) missed one to six treatments, six (8%) missed seven to 14 treatments, two (3%) missed more than 14 treatments, and four (5%) did not complete treatment. Reasons for missed treatments were hospitalization (31% of events) and toxicity (20%). Patients with percutaneous endoscopic gastrostomy tube were more likely to miss treatments (P = .01, chi(2) test). No other variable showed a significant association with missed treatments (chi(2) test). CONCLUSIONS: Intensive RT for HNC can be delivered with very good adherence within a medically underserved population. Eighty-five percent of patients completed treatment with 0 to 6 days of interruption. Efforts to further improve adherence in this population are ongoing
PMID: 20564718
ISSN: 1531-4995
CID: 110686

The effect of a nanothickness coating on rough titanium substrate in the osteogenic properties of human bone cells

Moura, Camilla C G; Souza, Maria A; Dechichi, Paula; Zanetta-Barbosa, Darceny; Teixeira, Cristina C; Coelho, Paulo G
This study evaluated the effect of a bioactive ceramic coating, in the nanothickness range, onto a moderately rough surface on the osteogenic behavior of human bone cells. The cells were harvested from the mandibular mental region and were cultured over Ti-6Al-4V disks of different surfaces: as-machined (M), alumina-blasted/acid etched (AB/AE), and alumina-blasted/acid-etched + 300-500 nm thickness amorphous Ca- and P-based coating obtained by ion beam-assisted deposition (Nano). The culture was then evaluated regarding cell viability, adhesion, morphology, immunolocalization of osteopontin (OPN) and alkaline phosphatase (ALP). The results showed that the surface treatment did not interfere with cell viability. At 1 day, AB/AE and Nano showed higher adhesion than the M surface (p < 0.001). Higher adhesion was observed for the M than the Nano surface at 7 days (p < 0.005). The percentage of cells showing intracellular labeling for OPN at day 1 was significantly higher for the Nano compared to M surface (p < 0.03). The percentage of ALP intracellular labeling at 7 days was significantly higher for the AB/AE compared to the M surface (p < 0.0065); no differences were detected at 14 days. Our results suggest that the presence of a thin bioactive ceramic coating on a rough substrate did not favor the events related to in vitro osteogenesis. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.
PMID: 20128004
ISSN: 1549-3296
CID: 160722

Biomechanical evaluation of endosseous implants at early implantation times: a study in dogs

Coelho, Paulo G; Granato, Rodrigo; Marin, Charles; Bonfante, Estevam A; Freire, Jose N O; Janal, Malvin N; Gil, Jose N; Suzuki, Marcelo
PURPOSE: This study tested the null hypothesis that differences in surgical instrumentation, macrogeometry, and surface treatment imposed by different implant systems do not affect early biomechanical fixation in a canine mandible model. MATERIALS AND METHODS: The lower premolars of 6 beagle dogs were extracted and the ridges allowed to heal for 8 weeks. Thirty-six (n = 12 each group) implants were bilaterally placed, remaining for 1 and 3 weeks in vivo. The implant groups were as follows: group 1, Ti-6Al-4V with a dual acid-etched surface with nanometer scale discrete crystalline deposition (Nanotite; Certain Biomet-3i, West Palm Springs, FL); group 2, Ti-6Al-4V with a titanium oxide-blasted fluoride-modified surface chemistry (Osseospeed 4.0 S; Astra Tech, Molndal, Sweden); group 3: Ti-6Al-4V with a bioceramic microblasted surface (Ossean; Intra-Lock International, Boca Raton, FL). Following euthanasia, implants were torqued to interface failure and histologically evaluated. General linear modeling (ANOVA) at 95% level of significance was performed. RESULTS: Histology showed that interfacial bone remodeling and initial woven bone formation were observed around all implant groups at 1 and 3 weeks. Torque values were significantly affected by time in vivo, implant group, and their interaction (P = .016, P < .001, and P = .001, respectively). Regarding torque values, group 3, group 2, and group 1 ranked highest, intermediate, and lowest, respectively. CONCLUSION: Early biomechanical fixation at 1 and 3 weeks was affected by surgical instrumentation, macrogeometry, and surface treatment present for one of the implant systems tested. The null hypothesis was rejected.
PMID: 20561471
ISSN: 0278-2391
CID: 160724

Le Fort III distraction: controlling position and path of the osteotomized midface segment on a rigid platform

Shetye, Pradip R; Grayson, Barry H; McCarthy, Joseph G
BACKGROUND: Precise control of the position of the midface through distraction with the rigid external distraction (RED) device has been a challenge. The present RED device with wire attachments to the intraoral dental splint and to the skeletal bone plates allows for flexibility in the vertical plane of the osteotomized Le Fort III segment. This tends to rotate the midface in a counterclockwise direction with inferior movement of the posterior nasal spine. OBJECTIVES: To report the development of a rigid distraction splint attachment to the RED device that permits precise control of the position of the midface during the latency period and through the activation and consolidation phases. METHODS: This paper describes the appliance design and the clinical application of a new device in controlling the position of the midface during distraction. Placement of the device and application of the desired force vectors are discussed. Patients treated by this modified device are illustrated to document the planned midface position after Le Fort III midface advancement. RESULTS: Examination of predistraction and postdistraction cephalograms of 2 patients treated with the new device showed advancement with minimum inferior displacement of the midface during all phases of the distraction process. CONCLUSIONS: The new device prevents undesired inferior movement of the posterior midface immediately after osteotomy and helps to stabilize the midface during the latency period. The device enables directional control of the distraction vectors, resulting in more predictable midface position at the end of treatment
PMID: 20613597
ISSN: 1536-3732
CID: 111356

Novel use of C7 spinal nerve for Moebius

Terzis, Julia K; Konofaos, Petros
BACKGROUND: The purpose of this study was to introduce the use of selective ipsilateral C7 spinal nerve transfer to the armamentarium of the dynamic procedures used for facial reanimation in Moebius patients. METHODS: Between 1991 and 2007, the selective ipsilateral C7 technique was used in four patients. In three patients with bilateral paralysis, both C7 spinal nerves were utilized as nerve donors. Thus, evaluation of outcomes was carried out in seven hemifaces. RESULTS: Short-term paresthesia on the index pulp of the donor upper extremity was observed in four limbs, which recovered spontaneously. Motor deficits were never noticed. Neurotization of the free-muscle transfer for smile was performed in five hemifaces, with good results in three hemifaces (p < 0.01, z = 2.61). Eye closure neurotization was made in six hemifaces, with good results in four hemifaces (p < 0.01, z = 2.88). Depressor neurotization was made in one case and resulted in improved depressor complex function. In two cases of free muscle transfer for masseter substitution, electromyographic interpretations revealed full motor activity after bilateral latissimus dorsi transfer. Tongue neurotization was performed in two instances. Postoperatively, the patients' speech intelligibility improved as well as tongue motility and bulk. CONCLUSION: The use of the C7 as a motor donor in Moebius cases with multicranial nerve involvement supplies the typical mask-like face with an abundance of motor fibers for facial reanimation and, if there is a coexisting twelfth nerve palsy, for speech restoration
PMID: 20595861
ISSN: 1529-4242
CID: 115114