Faculty Bibliography

PURPOSE: Perineural invasion (PNI) in oral squamous cell carcinoma (SCC) is recognized as a significant predictor of outcome. PNI is associated with locoregional recurrence and decreased survival of patients with head and neck SCC. Nerve growth factor (NGF) has been shown to be involved in PNI in several malignancies, including breast, prostate, and pancreatic cancers. We investigated the hypothesis that NGF and its high-affinity receptor tyrosine kinase A (TrkA) are highly expressed in cases of oral SCC that have histologic evidence of PNI. MATERIALS AND METHODS: We performed immunohistochemistry on archived oral tongue SCC specimens from the established oral and general pathology databases at the University of California, San Francisco. The following groups were evaluated: 1) 21 T1/T2 oral tongue SCC cases with PNI and 2) 21 T1/T2 oral tongue SCC cases without histologic evidence of PNI. RESULTS: Strong homogeneous cytoplasmic staining for NGF and TrkA was detected in the malignant cells in the PNI-positive group of tumors. In group II (PNI negative) NGF and TrkA were detected in the stroma cells or were very weakly expressed by the malignant cells. We were able to show the presence of NGF and TrkA in the cytoplasm of malignant squamous cells in tumors with histologic evidence of PNI. Immunostaining for NGF (P = .0001) and TrkA (P = .039) was significantly higher in the PNI-positive oral SCC group than in the PNI-negative oral SCC group. CONCLUSION: This study shows that oral SCC with evidence of PNI shows increased expression of NGF and TrkA and suggests that NGF and TrkA are involved with the mechanism leading to PNI. Further investigations are warranted to determine the potential for use of NGF and TrkA as candidate biomarkers to predict progression and outcome

Rodent pain models play an important role in understanding the mechanisms of nociception and have accelerated the search for new treatment approaches for pain. Creating an objective metric for orofacial nociception in these models presents significant technical obstacles. No animal assay accurately measures pain-induced orofacial dysfunction that is directly comparable to human orofacial dysfunction. We developed and validated a high throughput, objective, operant, nociceptive animal assay, and an instrument to perform the assay termed the dolognawmeter, for evaluation of conditions known to elicit orofacial pain in humans. Using the device our assay quantifies gnawing function in the mouse. We quantified a behavioral index of nociception and demonstrated blockade of nociception in three models of orofacial pain: (1) TMJ inflammation, (2) masticatory myositis, and (3) head and neck cancer. This assay will be useful in the study of nociceptive mediators involved in the development and progression of orofacial pain conditions and it will also provide a unique tool for development and assessment of new therapeutic approaches

OBJECTIVES: To observe the extent of nasal polyposis endoscopically in a cystic fibrosis population before the first surgical intervention and to grade the extent using a modified Malm scale, to observe patients prospectively and record the need for revision endoscopic sinus surgery (ESS), and to compare this among the individual polyp grading groupings. DESIGN: Retrospective medical record review of data collected prospectively. SETTING: Tertiary care hospital. PATIENTS: Forty-nine consecutive patients with a clinical preoperative diagnosis of cystic fibrosis and sinusitis. MAIN OUTCOME MEASURES: Using a modified Malm scale, the extent of polyps was prospectively graded into 3 groups before the first surgical intervention. The number of patients needing revision ESS and the mean time to revision ESS were compared among the 3 groups. RESULTS: Forty-nine consecutive patients underwent ESS between 1992 and 2007. We used a 3-stage system for extent of polyposis: 16 patients were noted to have no polyps (grade A), 14 had mild polyposis (grade B), and 19 had extensive polyposis (grade C). During the study, 14 patients required revision surgery: 3 with mild polyps and 11 with extensive polyps. Mean time to revision surgery was 39.7 months for those with grade B and 23.8 months for those with grade C. In the overall statistical analysis, the rate of revision ESS was significantly different among the 3 groups (P < .001). In pairwise comparisons, there were significant differences between those with grades A and C (P < .001) and between those with grades B and C (P = .04) and a trend toward significance between those with grades A and B (P = .052). There were no complications from ESS. CONCLUSION: Preoperative grading of nasal polyposis in patients with cystic fibrosis can help assess the future likelihood of revision ESS

Since 1976, experimental and clinical studies have suggested the superiority of vascularized nerve grafts. In this study, a 27-year experience of the senior author is presented regarding vascularized nerve grafts and fascia for complex upper extremity nerve reconstruction. The factors influencing outcomes as well as a comparison with conventional nerve grafts is presented. Since 1981, 21 vascularized nerve grafts, other than vascularized ulnar nerve, were used for reconstruction of nerve injuries in the upper extremity. Indications were prolonged denervation time, failure of the previously used conventional nerve grafts, and excessive scar in the recipient site. Injury was in the hand/wrist area (n = 5), in the forearm (n = 4), in the elbow (n = 2), in the arm (n = 4), or in the plexus (n = 6). Vascularized sural (n = 9), saphenous (n = 8), superficial radial (n = 3), and peroneal (superficial and deep) nerves were used. The mean follow-up was 31.4 months. Vascularized nerve grafts for upper extremity injuries provided good to excellent sensory return in severely scarred upper extremities in patients in whom conventional nerve grafts had failed. They have also provided relief of causalgia after painful neuroma resection and motor function recovery in selective cases even for above the elbow injuries. Small diameter vascularized nerve grafts should be considered for bridging long nerve gaps in regions of excessive scar or for reconstructions where conventional nerve grafts have failed

PURPOSE: The purpose of the present study was to assess the safety and efficacy of oral diclofenac potassium liquid-filled soft gelatin capsule (DPSGC) that uses ProSorb dispersion technology (Xanodyne Pharmaceuticals, Inc, licensed from AAIPharma, Wilmington, NC), to treat adult patients with acute pain after third molar extraction. PATIENTS AND METHODS: In the present multicenter, randomized, double-blind, placebo-controlled trial, patients experiencing a baseline level of pain (>/= 50 mm on a 100-mm visual analog scale within 4 hours after surgery) were randomized to receive a single dose of DPSGC at 25, 50, or 100 mg or placebo. Pain intensity and relief were assessed for 6 hours after dosing. The efficacy endpoints included the summed pain intensity difference, total pain relief, and the median time to the onset of perceptible and meaningful pain relief (using the 2-stopwatch method). RESULTS: A total of 249 randomized patients had a significant increase in the summed pain intensity difference and total pain relief values at 3 and 6 hours across all DPSGC-treated groups compared with the placebo group (P < .0001). The onset of perceptible and meaningful pain relief was significantly faster in all DPSGC groups than in the placebo group, including the DPSGC 25-mg group (25 minutes [P = .0002] and 52 minutes [P < .0001] for perceptible and meaningful pain relief, respectively). Significantly fewer patients in the DPSGC groups required rescue medication compared with those in the placebo group (P < .0001). The global evaluation scores were significantly greater for the patients who received DPSGC than for those who received placebo (P < .0001), and more than 65% of DPSGC-treated patients rated the medication as good, very good, or excellent compared with 18% of the placebo-treated patients. DPSGC was generally well tolerated, and no serious adverse events were reported. CONCLUSIONS: The results from the present single-dose study of postoperative dental pain suggest that DPSGC offers significant pain relief compared with placebo and that the study medication provided was well tolerated by patients who required pain relief after third molar extraction

Summary form only given. This study aims to evaluate the potential of atmospheric pressure non-thermal plasma technology (NPT) to enhance the adhesive bond strength on normative dentin substrates. Two different microplasma jets were used in our experiments, a direct-current driven microhollow cathode discharge jet operated in air and a rf-driven jet operated in Ar. Other gas mixtures, e.g. He/O2 are also being explored.Initial experiments were carried out using fresh, non-carious third molars obtained under a protocol approved by the New York University College of Medicine Institutional Review Board. The occlusal enamel of each tooth was removed perpendicular to the long axis of the tooth to expose a flat dentin surface, which was subsequently polished. The specimens were randomly assigned to 3 groups for bonding and NPT applications. For the control group, three teeth were etched with phosphoric acid etched, the dentin bonding agent (DBA) was applied and the teeth were restored with a 4 mm thick resin composite. Another group of 3 teeth was treated with an Ar plasma and a third group was exposed to an air plasma. For the plasma-treated groups, the dentin substrates were etched for 15 s, rinsed for 10s and treated by the plasma for 20 s followed by DBA application and resin composite placement. All specimens were stored in water for 24 h prior to a microtensile bonding test. Preliminary data indicate that the bond strength values were not significantly affected by the Ar or air plasma treatment. We observed that teeth treated with the Ar plasma exhibited an enhanced premature failure rate (-50%) during the cutting or specimen mounting phases. This was not observed for the control or for the air plasma treated groups. Extensive surface characterization studies using various microscopy techniques, XPS, and micro-Raman are underway to assess the effect of the plasma on the surface. Optical emission spectroscopy is used to monitor the presence of reactive spe- - cies (eg. OH, O) in the plasma for various operating conditions and feed gases or gas mixtures. The results of these studies will be presented and discussed in detail at the Conference

OBJECTIVES: To compare the reliability of the disto-facial (DF) and mesio-lingual (ML) cusps of an anatomically correct zirconia (Y-TZP) crown system. The research hypotheses tested were: (1) fatigue reliability and failure mode are similar for the ML and DF cusps; (2) failure mode of one cusp does not affect the failure of the other. METHODS: The average dimensions of a mandibular first molar crown were imported into CAD software; a tooth preparation was modelled by 1.5 mm marginal high reduction of proximal walls and occlusal surface by 2.0 mm. The CAD-based tooth preparation was milled and used as a die to fabricate crowns (n=14) with porcelain veneer on a 0.5 mm Y-TZP core. Crowns were cemented on composite reproductions of the tooth preparation. The crowns were step-stress mouth motion fatigued with sliding (0.7 mm) a tungsten-carbide indenter of 6.25 mm diameter down on the inclines of either the DF or ML cusps. Use level probability Weibull curve with use stress of 200 N and the reliability for completion of a mission of 50,000 cycles at 200 N load were calculated. RESULTS: Reliability for a 200 N at 50,000 cycles mission was not different between tested cusps. SEM imaging showed large cohesive failures within the veneer for the ML and smaller for the DF. Fractures originated from the contact area regardless of the cusp loaded. CONCLUSION: No significant difference on fatigue reliability was observed between the DF compared to the ML cusp. Fracture of one cusp did not affect the other

OBJECTIVES: This study compared the reliability and fracture patterns of zirconia cores veneered with pressable porcelain submitted to either axial or off-axis sliding contact fatigue. METHODS: Forty-two Y-TZP plates (12mm x 12mm x 0.5mm) veneered with pressable porcelain (12mm x 12mm x 1.2mm) and adhesively luted to water aged composite resin blocks (12mm x 12mm x 4mm) were stored in water at least 7 days prior to testing. Profiles for step-stress fatigue (ratio 3:2:1) were determined from single load to fracture tests (n=3). Fatigue loading was delivered on specimen either on axial (n=18) or off-axis 30 degrees angulation (n=18) to simulate posterior tooth cusp inclination creating a 0.7mm slide. Single load and fatigue tests utilized a 6.25mm diameter WC indenter. Specimens were inspected by means of polarized-light microscope and SEM. Use level probability Weibull curves were plotted with 2-sided 90% confidence bounds (CB) and reliability for missions of 50,000 cycles at 200N (90% CB) were calculated. RESULTS: The calculated Weibull Beta was 3.34 and 2.47 for axial and off-axis groups, respectively, indicating that fatigue accelerated failure in both loading modes. The reliability data for a mission of 50,000 cycles at 200N load with 90% CB indicates no difference between loading groups. Deep penetrating cone cracks reaching the core-veneer interface were observed in both groups. Partial cones due to the sliding component were observed along with the cone cracking for the off-axis group. No Y-TZP core fractures were observed. CONCLUSIONS: Reliability was not significantly different between axial and off-axis mouth-motion fatigued pressed over Y-TZP cores, but incorporation of sliding resulted in more aggressive damage on the veneer

This study evaluated the stress levels at the core layer and the veneer layer of zirconia crowns (comprising an alternative core design vs. a standard core design) under mechanical/thermal simulation, and subjected simulated models to laboratory mouth-motion fatigue. The dimensions of a mandibular first molar were imported into computer-aided design (CAD) software and a tooth preparation was modeled. A crown was designed using the space between the original tooth and the prepared tooth. The alternative core presented an additional lingual shoulder that lowered the veneer bulk of the cusps. Finite element analyses evaluated the residual maximum principal stresses fields at the core and veneer of both designs under loading and when cooled from 900 degrees C to 25 degrees C. Crowns were fabricated and mouth-motion fatigued, generating master Weibull curves and reliability data. Thermal modeling showed low residual stress fields throughout the bulk of the cusps for both groups. Mechanical simulation depicted a shift in stress levels to the core of the alternative design compared with the standard design. Significantly higher reliability was found for the alternative core. Regardless of the alternative configuration, thermal and mechanical computer simulations showed stress in the alternative core design comparable and higher to that of the standard configuration, respectively. Such a mechanical scenario probably led to the higher reliability of the alternative design under fatigue