Faculty Bibliography

Even though total absence of elbow flexion in obstetric brachial plexus palsy (OBPP) is rare, weakness is a frequent problem. Numerous procedures for elbow flexion restoration in late obstetric brachial plexus palsy have been described. In this study, children with OBPP who underwent secondary reconstruction for elbow flexion restoration were studied. A retrospective review of 15 patients (16 elbows) who underwent 16 pedicled and eight free-muscle transfers for elbow flexion restoration was conducted. The mean follow-up period was 8.4 +/- 2.9 years (range, 25 months to 12.2 years). The mean age at operation (elbow surgery) was 5.4 +/- 1.9 years. The total arc of elbow motion was the result of the active elbow flexion less the flexion contracture. There was significant improvement in biceps muscle power from an average grading of 2.49 +/- 0.80 preoperatively to 3.64 +/- 0.46 postoperatively (p < 0.001). Thirteen of 16 elbows (81%) achieved good and excellent results (>/=M3+); and three elbows (19%) fair results (M3- or M3). The average arc of motion was significantly improved from 36 degrees +/- 25 degrees preoperatively to 94 degrees +/- 26 degrees postoperatively (p < 0.001). The preoperative and postoperative average elbow flexion contracture was 10.9 degrees +/- 8.9 degrees and 20 degrees +/- 12.2 degrees , respectively. Pedicled and/or free-muscle transfers can significantly improve elbow flexion in late obstetric brachial plexus palsy. Choice of the procedure should be individualized and determined on the basis of the type of paralysis, availability of donor muscles, previous reconstruction, and experience of the surgeon.

In a crown system, core fracture requires replacement of the restoration. Understanding maximum principal stress concentration in the veneered core of a tooth-crown system as a function of variations in clinically relevant parameters is crucial in the rational design of crown systems. This study evaluated the main and interacting effects of a set of clinical variables on the maximum principal stress (MPS) in the core of an anatomically correct veneer-core-cement-tooth model. A 3D CAD model of a mandibular first molar crown was generated; tooth preparation was modeled by reducing the proximal walls by 1.5 mm and the occlusal surface by 2.0 mm. A cemented veneered core crown was modeled on the preparation. This 'crown system' permitted finite element model investigation of the main and interacting effects of proximal wall height reduction, core material, core thickness, cement modulus, cement thickness, and load position on the maximum stress distribution in a factorial design. Analysis of variance was used to identify the main and interacting influences on the level of MPS in the crown core. Statistical significance was set at p<0.05. MPS levels varied as a function of two-way interactions between the following: core thickness and load position; cement thickness and load position; cement modulus and load position; cement thickness and core thickness; and cement thickness and cement modulus; and also three-way interactions among the load position, core material, and proximal wall height reduction, and among the core thickness, cement thickness, and cement modulus. MPS in the crown-tooth system is influenced by the design parameters and also by the interaction among them. Hence, while the geometry of molar crowns is complex, these analyses identify the factors that influence MPS and suggest levels that will minimize the core MPS in future studies of crown design

The human homologue of the Drosophila segment polarity gene PTCH1, a tumor suppressor gene within the Sonic Hedgehog pathway has been implicated as the mutation responsible for nevoid basal cell carcinoma syndrome (NBCCS) as well as many other sporadic neoplasms. The calcifying epithelial odontogenic tumor (CEOT) is a rare and aggressive tumor of the jaws. The objective of this study was to investigate the role of the Sonic hedgehog pathway in the pathogenesis of the CEOT. We evaluated the protein distribution of PTCH and the transcription factors Gli1 and Gli2 within seven cases using immunohistochemistry. We also sought to confirm the findings by sequencing the PTCH1 gene from DNA extracted from the paraffin-embedded tissue of these cases. Seven cases of paraffin-embedded CEOT specimens were analyzed with immunohistochemistry. Immunoreactivity for Sonic hedgehog pathway proteins was evaluated using antibodies to the receptor PTCH as well as to the transcription factors Gli1 and Gli2. A keratocystic odontogenic tumor (KOT) from a 12year-old with NBCCS served as our positive control. Normal salivary gland tissue served as our negative control. PTCH gene sequencing was completed using PCR. Immunoreactivity to PTCH was seen in 6/7 cases, to Gli1 in 6/7 cases and to Gli2 in 6/7 cases. All three proteins were positive in the syndromic KOT and all proteins were negative in normal salivary tissue. Gene sequencing revealed five single-nucleotide polymorphisms (SNPs) of which two resulted in missense mutations. A missense mutation was also detected in the KOT. This study is the first to implicate the Sonic hedgehog pathway in the pathogenesis of the CEOT through sequencing. Similar to other odontogenic neoplasms gene mutations in PTCH1 are present in the CEOT

Endothelin-1 (ET-1) produced by various cancers is known to be responsible for inducing pain. While ET-1 binding to ETAR on peripheral nerves clearly mediates nociception, effects from binding to ETBR are less clear. The present study assessed the effects of ETBR activation and the role of endogenous opioid analgesia in carcinoma pain using an orthotopic cancer pain mouse model. mRNA expression analysis showed that ET-1 was nearly doubled while ETBR was significantly down-regulated in a human oral SCC cell line compared to normal oral keratinocytes (NOK). Squamous cell carcinoma (SCC) cell culture treated with an ETBR agonist (10(-4)M, 10(-5)M, and 10(-6) M BQ-3020) significantly increased the production of beta-endorphin without any effects on leu-enkephalin or dynorphin. Cancer inoculated in the hind paw of athymic mice with SCC induced significant pain, as indicated by reduction of paw withdrawal thresholds in response to mechanical stimulation, compared to sham-injected and NOK-injected groups. Intratumor administration of 3mg/kg BQ-3020 attenuated cancer pain by approximately 50% up to 3h post-injection compared to PBS-vehicle and contralateral injection, while intratumor ETBR antagonist BQ-788 treatment (100 and 300microg/kg and 3mg/kg) had no effects. Local naloxone methiodide (500microg/kg) or selective mu-opioid receptor antagonist (CTOP, 500microg/kg) injection reversed ETBR agonist-induced antinociception in cancer animals. We propose that these results demonstrate that peripheral ETBR agonism attenuates carcinoma pain by modulating beta-endorphins released from the SCC to act on peripheral opioid receptors found in the cancer microenvironment

Mediators involved in the generation of pain in patients with cancer are poorly understood. Using a combined molecular, pharmacologic, behavioral, and genetic approach, we have identified a novel mechanism of cancer-dependent allodynia induced by protease-activated receptor 2 (PAR2). Here we show that human head and neck carcinoma cells have increased levels of proteolytic activity compared to normal human cell controls. Supernatant from human carcinoma cells, but not controls, caused marked and prolonged mechanical allodynia in mice, when administered into the hindpaw. This nociceptive effect was abolished by serine protease inhibition, diminished by mast cell depletion and absent in PAR2-deficient mice. In addition, non-contact co-culture of trigeminal ganglion neurons with human head and neck carcinoma cells increased the proportion of neurons that exhibited PAR2-immunoreactivity. Our results point to a direct role for serine proteases and their receptor in the pathogenesis of cancer pain. This previously unrecognized cancer pain pathway has important therapeutic implications wherein serine protease inhibitors and PAR2 antagonists may be useful for the treatment of cancer pain

BACKGROUND: Critical defects of the craniomaxillofacial region are often treated with vascularized osteocutaneous free flaps. These lengthy operations may be associated with considerable donor-site morbidity and suboptimal functional and aesthetic results. To overcome these issues, this study investigates an engineered vascularized bone flap using allograft bone, adipose-derived stem cells, and recombinant human bone morphogenic protein (rhBMP)-2 and compares two alternative blood supplies. METHODS: Edentulous porcine hemimandibles were commercially sterilized, packed with rhBMP-2-soaked absorbable collagen sponge and autologous, culture-expanded adipose-derived stem cells, and implanted into two locations within 10 pigs: (1) an intercostal-based periosteal envelope (thoracic) and (2) within the rectus abdominis muscle with insertion of the superficial inferior epigastric vascular pedicle into the medullary cavity (abdominal). The constructs were incubated in vivo for 7 to 8 weeks and harvested to assess de novo bone formation. RESULTS: Radiographic, micro-computed tomographic, and histologic assessments of harvested constructs were performed. Abdominal constructs had a thin rim of new, cancellous bone surrounding a fibrotic core with little allograft remaining. Thoracic allografts were absorbed completely and replaced with new, full-thickness, cancellous bone. Calcitic tissue content was significantly higher in thoracic (474.16 +/- 75.93 ml) compared with abdominal (143.20 +/- 46.39 ml) constructs (p < 0.006). New bone in both groups contained Haversian systems, but only thoracic constructs contained marrow elements and blood vessels resembling normal bone. CONCLUSIONS: These data demonstrate revitalization of large-volume allograft bone, and have positive implications for bone tissue engineering. Allograft revitalization in thoracic but not abdominal constructs reinforces the critical role of the periosteum in the process.

The critical length of 30 mm beyond which nerve regeneration was not possible limited up to now the use of tubulization. In this pilot study, a novel animal model is introduced using tubulization techniques for long-nerve defects (40 mm) in brachial plexus surgery. Twelve Sprague-Dawley rats were divided into 3 groups. A poly-DL-lactide-epsilon-caprolactone tube (group 1), a collagen tube (group 2), and a nerve graft (group 3) were, respectively, used to bridge a 40-mm gap between the right C7 root and the left musculocutaneous nerve. Animals were euthanized on day 30. Evaluation consisted of behavioral assessment, needle electromyography studies, biceps muscle weight measurements, qualitative, and quantitative morphometry. Only group 3 demonstrated axon regeneration and reinnervation potentials. There was statistical significant difference for biceps weight left/right ratio (P = 0.010) but not for behavioral results (P = 0.10) between group 3 and groups 1 and 2. This study introduced a novel rat model for the studying of nerve regeneration along long-nerve gaps (4 cm). Although using an autologous nerve graft regeneration achieved, the use of synthetic conduits failed to show regeneration. This may be attributed to gap length; duration of follow-up; and to no administration of a neurotrophic factor

BACKGROUND: Today's breast augmentation (BA) patient obtains information from a variety of sources that may positively or negatively influence her decision. OBJECTIVES: The authors evaluate the decision-making process of patients undergoing BA, including how they seek information regarding the procedure, potential complications, the medical device itself, referral sources, and surgeon(s). METHODS: A written 36-item, blinded survey developed for this study was administered to all patients who underwent aesthetic primary BA by the senior author (JW) over a 12-month period in her metropolitan private practice. Patients were included only if they had undergone surgery after Food and Drug Administration approval of silicone implants and had at least four months of follow-up. Patients were excluded if they underwent reconstruction, revision, augmentation/mastopexy, or implant exchange. Data were analyzed utilizing descriptive statistics; frequencies of responses were calculated with SPSS (version 16). RESULTS: Of 153 mailed surveys, 100 respondents returned completed questionnaires (65%). Mean age was 30 years (range, 20-50 years). Eighty-eight patients were in the workforce, eight were students, and three were homemakers. Thirty-three percent had completed some graduate work or had a graduate degree, and 41% had a college degree. In terms of how patients began their informational searches, 41% began with Google, 18% began with a BA portal Web site, and 1% went through referral from a primary care provider (PCP)/OB-GYN. The primary influence in a patient's decision to have BA was her own desire to change her appearance (36%), and second was her plastic surgeon's Web site (16%). On a graded scale of 10 factors ranking importance (1 = not at all and 5 = extremely), 52% said that their plastic surgeon's Web site very much or extremely influenced their decision. Of respondents, 82% had silicone implants (18% saline). The most influential factor in choosing implant filler was the feel of the silicone versus saline implants (for 41%), followed by the plastic surgeon's explanation of the difference (29%) and recent FDA approval (13%). Primary sources of information for possible complications were the plastic surgeon and BA portal sites. When asked what the worst complication could be, patients reported capsular contracture (37%), implant rupture or leak (22%), and infection (20%). The most powerful influence on choice of surgeon for BA was the plastic surgeon's Web site (49%); meeting the doctor in consultation was next (14%), followed by BA portal sites (9%). Thirty-six percent of respondents consulted with a psychiatrist or psychologist at some point in their lives, with depression, anxiety, and stress management as top-ranked reasons (in that order). CONCLUSIONS: The Internet (specifically Google, the plastic surgeon's Web site, and portal Web sites) is very important to patients ages 20 to 50 in their search for information on BA. Educational and reality TV may have less influence on this particular group than was previously thought. Patients are well educated, are part of the workforce, and seem to be independent and private thinkers when it comes to their decision making. Referral sources such as the PCP assume a much smaller role in the search for information than in days past