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Department/Unit:Plastic Surgery

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Effect of peripheral endothelin-1 concentration on carcinoma-induced pain in mice

Pickering, Victoria; Jay Gupta, R; Quang, Phuong; Jordan, Richard C; Schmidt, Brian L
In this study, we investigated the role of the peripheral endothelin-1 (ET-1) concentration in a cancer pain model. To test the hypothesis that the concentration of ET-1 in the tumor microenvironment is important in determining the level of cancer pain we used two cancer pain mouse models that differed significantly in production of ET-1. The two mouse cancer models were produced by injection of cells derived from a human oral squamous cell carcinoma (SCC) and melanoma into the hind paw of female mice. Pain, as indicated by reduction in withdrawal thresholds in response to mechanical stimulation, was significantly greater in the SCC group than the melanoma group. The peripheral concentration of ET-1 within the cancer microenvironment was significantly greater in the SCC group. Intra-tumor expression of both ET-1 mRNA and ET-1 protein were significantly higher in the SCC model compared to the melanoma model. ET receptor antagonism was effective as an analgesic for cancer pain in the SCC model only. To address the potential confounding factor of tumor volume we evaluated the contribution of tumor volume to cancer pain in the two models. The mean volumes of the tumors in the melanoma group were significantly greater than the tumors in the SCC group. In both groups, the pain level correlated with tumor volume, but the correlation was stronger in the melanoma group. We conclude that ET-1 concentration is a determinant of the level of pain in a cancer pain mouse model and it is a more important factor than tumor volume in producing cancer pain. These results suggest that future treatment regimens for cancer pain directed at ET-1 receptor antagonism show promise and may be tumor type specific
PMCID:2771221
PMID: 17664075
ISSN: 1532-2149
CID: 132022

Oral maxillary squamous cell carcinoma: management of the clinically negative neck

Montes, David M; Schmidt, Brian L
PURPOSE: Squamous cell carcinomas of the hard palate, maxillary gingiva, and maxillary alveolus occur at relatively low rates compared with squamous cell carcinomas in other oral sites. There is little within the surgical literature to guide treatment for maxillary squamous cell carcinoma. To date, only 1 other group has addressed neck management in the oral maxillary squamous cell carcinoma patient presenting with a clinically negative neck. Adequate characterization of maxillary gingival carcinoma behavior with respect to regional cervical metastasis is wanting. PATIENTS AND METHODS: We present a retrospective review of our own clinical experience as well as a review of the existing literature. RESULTS: In our University of California San Francisco patient group, cervical disease was detected in 20% of those individuals with maxillary squamous cell carcinoma presenting for initial consultation. After ablative surgery, those individuals who presented with clinically negative necks had a 21.4% rate of regional node metastasis. Ultimately, 50% of our patients with squamous cell carcinomas of the palate, maxillary gingiva, and maxillary alveolus developed regional or metastatic distant disease; 42.9% of the patients manifested disease to the cervical lymph nodes alone. CONCLUSIONS: The cases of oral maxillary squamous cell carcinomas reviewed herein exhibit aggressive regional metastatic behavior comparable to that of such carcinomas of the tongue, floor of the mouth, and mandibular gingiva. Based on the findings presented herein, we recommend selective neck dissection in the setting of a clinically negative neck as a primary management strategy for patients with oral maxillary squamous cell carcinomas involving the palate, maxillary gingiva, and maxillary alveolus
PMID: 18355602
ISSN: 1531-5053
CID: 132023

Peripheral cannabinoids attenuate carcinoma-induced nociception in mice

Guerrero, Andre V; Quang, Phuong; Dekker, Nusi; Jordan, Richard C K; Schmidt, Brian L
We investigated the cannabinoid receptor (CBr) agonists Win55,212-2 (non-selective) and AM1241 (CBr2 selective) and the peripheral receptor (CBr1) in carcinoma-induced pain using a mouse model. Tumors were induced in the hind paw of female mice by local injection of a human oral squamous cell carcinoma (SCC). Significant pain, as indicated by reduction in withdrawal thresholds in response to mechanical stimulation, began at 4 days after SCC inoculation and lasted to 18 days. Local administration of Win55,212-2 (10 mg/kg) and AM1241 (10 mg/kg) significantly elevated withdrawal thresholds, indicating an antinociceptive effect. Ipsilateral expression of CBr1 protein in L5 DRG was significantly upregulated compared to ipsilateral L4 DRG and in normal tissue. These findings support the suggestion that cannabinoids are capable of producing antinociception in carcinoma-induced pain
PMCID:2771220
PMID: 18242856
ISSN: 0304-3940
CID: 132024

Oral squamous cell carcinoma margin discrepancy after resection and pathologic processing

Cheng, Allen; Cox, Darren; Schmidt, Brian L
PURPOSE: Resecting oral squamous cell carcinoma (SCC) with an appropriate margin of uninvolved tissue is critical in preventing local recurrence and making the decision regarding postoperative radiation therapy. This task can be difficult due to the discrepancy between margins measured intraoperatively and those measured microscopically by the pathologist after specimen processing. The goal of this study is to quantify and compare the amount of margin discrepancy observed based on tumor location and staging. MATERIALS AND METHODS: Forty-one patients who underwent resective surgery with curative intent for primary oral SCC were included in this study. All patients underwent resection of the tumor with a measured 1 cm margin by one attending surgeon. Specimens were then submitted for processing and reviewing and histopathologic margins were measured. The closest histopathologic margin was compared with the in situ margin (1 cm) to determine percentage discrepancy. Percent discrepancies were grouped by locations (buccal mucosa, mandibular alveolar ridge, and retromolar trigone in group 1; maxillary alveolar ridge and palate in group 2; and oral tongue in group 3) and analyzed. Percent discrepancies grouped by stages T1/T2 or T3/T4 were compared. RESULTS: The mean discrepancy for all patients was a statistically significant 59.02% (P < .0001). The mean discrepancy was 71.90% for group 1, 53.33% for group 2, and 42.14% for group 3 (P = .0133). The mean discrepancy in T1/T2 tumors was 51.48% and in T3/T4 tumors was 75.00% (P = .0264). CONCLUSIONS: Oral SCC margin discrepancies after resection and specimen processing are highly significant. Tumors located in the buccal mucosa, retromolar trigone, and mandibular alveolar ridge show significantly greater discrepancies than tumors of the maxilla or oral tongue. Late stage tumors also show significantly greater margin discrepancies. These findings suggest that it might be prudent to consider oral site and staging when outlining margins to ensure adequacy of resection
PMID: 18280387
ISSN: 1531-5053
CID: 132025

Chin ptosis: classification, anatomy, and correction

Garfein, Evan S; Zide, Barry M
For years, the notion of chin ptosis was somehow integrated with the concept of witch's chin. That was a mistake on many levels because chin droop has four major causes, all different and with some overlap. With this article, the surgeon can quickly diagnose which type and which therapeutic modality would work best. In some cases the problem is a simple fix, in others the droop can only be stabilized, and in the final two, definite corrective procedures are available. Of note, in certain situations two types of chin ptosis may overlap because both the patient and the surgeon may each contribute to the problems. For example, in dynamic ptosis, a droop that occurs with smile in the unoperated patient can be exacerbated and further produced by certain surgical methods also. This paper classifies the variations of the problems and explains the anatomy with the final emphasis on long-term surgical correction, well described herein. This article is the ninth on this subject and a review of them all would be helpful (greatly) for understanding the enigmas of the lower face
PMCID:3052727
PMID: 22110784
ISSN: 1943-3875
CID: 146254

Assessment of teaching effectiveness in U.S. Dental schools and the value of triangulation

Jahangiri, Leila; Mucciolo, Thomas W; Choi, Mijin; Spielman, Andrew I
The routine evaluation of teaching effectiveness is important in improving faculty, departmental, and institutional efforts. There are three main categories of assessments: those performed by students, peers, and self. Although each category is independently valid, a collection of data from all three categories leads to a more comprehensive outcome and a creation of a triangulation model. The purpose of this study was to identify commonly used methods of assessing teaching effectiveness and to suggest the use of a triangulation model, which has been advocated in the literature on performance assessment as an optimal approach for evaluating teaching effectiveness. A twelve-question survey was sent to all U.S. dental schools to identify evaluation methods as well as to find evidence of triangulation. Thirty-nine out of fifty-seven schools responded. The majority of the schools used student evaluations (81 percent) and peer reviews (78 percent). A minority of schools reported using self-evaluations (31 percent). Less than one in five dental schools reported using all three strategies to achieve triangulation (19 percent). The three most commonly used evaluation methods ('performed routinely') were all in the student evaluation category. Less than half of the schools routinely evaluated clinical teaching effectiveness by any means (42 percent). In conclusion, dental schools should implement a triangulation process, in which evaluation data are obtained from students, peers, and self to provide a comprehensive and composite assessment of teaching effectiveness
PMID: 18519601
ISSN: 0022-0337
CID: 153021

A model for an integrated predoctoral implant curriculum: implementation and outcomes

Jahangiri, Leila; Choi, Mijin
The implementation of an implant dental curriculum in U.S. dental schools has been consistently increasing from 33 percent in 1974 to 97 percent in 2004. Among these, only 51 percent have clinical components implemented. A survey of students conducted in 2004 at New York University College of Dentistry (NYUCD) showed an inadequacy in clinical implant restoration experience by graduation. This prompted the development of an extensive dental implant curriculum at NYUCD to meet the needs of the dental students. This report addresses the challenges in implementing such a curriculum and describes a step-by-step approach to develop a program that encompasses didactic, simulation, and patient care components. In 2005, a fully integrated predoctoral implant curriculum was initiated. In 2008, nearly all of the NYUCD students (91.8 percent) completed implant restorations/prosthesis on patients. An assessment revealed a 30 percent increase in students' positive perceptions of the implant curriculum. Based on our experiences at NYUCD, it is recommended that an implant curriculum become part of the core predoctoral curriculum and be integrated throughout the four years of dental education. This article reports on a model for a pre-doctoral implant curriculum, which includes planning, curriculum implementation, program management, and post-implementation stages. Using this model, dental schools can develop implant education for their students that is adapted to their institutional missions, priorities, and resources
PMID: 18981209
ISSN: 0022-0337
CID: 153410

Laboratory and FEA evaluation of dentin-to-composite bonding as a function adhesive layer thickness

Coelho, P G; Calamia, C; Harsono, M; Thompson, V P; Silva, N R F A
OBJECTIVE: The aim of this study was to test the hypothesis that microtensile bond strength values are inversely proportional to dentin-to-composite adhesive layer thickness through laboratory mechanical testing and finite element analysis. METHOD: Eighteen noncarious third molars were obtained, and occlusal enamel removed perpendicular to the tooth long axis. Two different adhesive systems were utilized as follows (n=3): (1) application of a single layer of Single Bond (3M ESPE Co.) and Clearfil SE Bond (Kuraray Co.) following the manufacturer's directions; (2) application of one layer of both adhesive systems followed by one additional layer; (3) application of one layer of both adhesive systems followed by two additional layers. A 4mm build up was fabricated in increments on each tooth sample (Z 100 composite, 3M ESPE). Section measurements were performed and specimens were separated into three adhesive thickness groups per material (40, 40-80 and 80-120 microm) for microtensile testing. The bond strength data (MPa) were analyzed by one-way ANOVA and Tukey test. Maximum principal stresses (MPS) were determined through FEA for three different adhesive layer thicknesses (20, 50 and 100 microm). RESULTS: The bond strength data obtained for Single Bond at 0-40 microm presented significantly higher values compared to higher adhesive layer thickness groups. There were no statistical differences among bond strength values for all Clearfil SE Bond adhesive layer thicknesses. FEA modeling indicated that MPS increased as adhesive layer increased. The hypothesis was accepted for the Single Bond only. SIGNIFICANCE: Correspondence (not tested statistically) between microtensile laboratory testing and FEA model was only observed for Single Bond as increased adhesive layer thickness did not reduce Clearfil SE Bond strength
PMID: 18374973
ISSN: 0109-5641
CID: 153093

Effect of water storage time and composite cement thickness on fatigue of a glass-ceramic trilayer system

Silva, Nelson R F A; de Souza, Grace M; Coelho, Paulo G; Stappert, Christian F J; Clark, Elizabeth A; Rekow, Elizabeth D; Thompson, Van P
AIM: Static Hertzian contact tests of monolayer glass-ceramics in trilayer configurations (glass-ceramic/cement/composite) have shown that thick cement layers lower strength. This study sought to test the hypothesis that thick resin cement layers lower mouth motion fatigue reliability for flat glass-ceramic/cement/composite trilayer systems and that aging in water reduces reliability. METHODS: Dicor plates (n > or = 12 per group) (10 x 10 x 0.8 mm(3)) were aluminum-oxide abraded (50 microm), etched (60 s), silanized, and bonded (Rely X ARC) to water aged (30 days) Z100 resin blocks (10 x 10 x 4 mm(3)). Four groups were prepared: (1) thick cement layer (>100 microm) stored in water for 24-48 h, (2) thick cement layer stored for 60 days, (3) thin cement layer (< or =100 microm) stored for 24-48 h, and (4) thin cement layer stored for 60 days. The layered structures were fatigued (2 Hz) utilizing mouth motion loading with a step-stress acceleration method. A master Weibull distribution was calculated and reliability determined (with 90% confidence intervals) at a given number of cycles and load. RESULTS: The aged group (60 d) with thick cement layer had statistically lower reliability for 20,000 cycles at 150 N peak load (0.11) compared with both nonaged groups (24-48 h) (thin layer = 0.90 and thick layer = 0.82) and aged group with thin cement layer (0.89). CONCLUSION: Trilayer specimens with thick cement layers exhibited significantly lower reliability under fatigue testing only when stored for 60 days in water. The hypothesis was accepted. These results suggest that diffusion of water into the resin cement and also to the glass-ceramic interface is delayed in the thick cement specimens at 24-48 h.
PMID: 17455281
ISSN: 1552-4973
CID: 153018

Hertzian contact response of dentin with loading rate and orientation

da Silva, Nelson Renato Franca Alves; Lalani, F; Coelho, Paulo G; Clark, Elizabeth A; Fernandes, Carlos Augusto de Oliveira; Thompson, Van P
OBJECTIVE: To test the hypothesis that dentin Hertzian contact response varies with loading rate and tubule orientation. DESIGN: Sound teeth (n=12) were cut either parallel or perpendicular to the axial direction to expose dentin (n=6 each). The cut specimens were embedded (poly-methyl-methacrylate (PMMA) and divided into two groups: (GL) load applied parallel to dentin tubule direction and (GP) load applied perpendicular to tubule direction. A 1.5mm diameter tungsten-carbide ball was used for Hertzian contact testing with a maximum load of 150 N load and loading rates of 0.1, 1, 100, and 1000 N/s on each specimen. Indented specimens were observed microscopically and photomicrographs acquired. Hertzian contact diameter and modulus were analysed (p<0.05) by one-way ANOVA and Tukey test. RESULTS: There were significant differences (p<0.05) in Hertzian response with respect to loading rate for GL (0.1N/s versus 1000 N/s, 0.1N/s versus 100 N/s, 1N/s versus 1000 N/s, and 1N/s versus 100 N/s), and GP (0.1N/s versus 1000 N/s, 0.1N/s versus 100 N/s, and 1N/s versus 1000 N/s). Contact modulus was higher for GL compared to GP at all loading rates (p<0.05). CONCLUSION: The results suggest that dentin contact modulus is loading rate dependent. Tubule orientation of dentin did not influence contact modulus values (p>0.05)
PMID: 18452892
ISSN: 0003-9969
CID: 153087