Faculty Bibliography

AIM: The objective of this study was to evaluate the early healing of endosseous implants presenting various healing chamber configurations in a beagle dog mandible model. METHODS: The four premolars of 12 beagle dogs were extracted and allowed to heal for a period of 8 weeks. Implants allowing six different healing chamber configurations were placed in each dog (three per side, six configurations per dog). The animals were sacrificed after 3 and 5 weeks in vivo (n=6 per time in vivo), and the implants were non-decalcified processed to slides of approximately 30 microm thickness. Bone-to-implant contact (BIC) and bone area fraction occupied (BAFO) within the healing chamber were quantified. Statistical analysis was performed by a GLM ANOVA model at 5% significance level. RESULTS: Osseointegration and healing with woven bone filling throughout all healing chambers was observed. Replacement of woven bone by lamellar bone showing primary osteonic structures was observed at 5 weeks. BIC was significantly affected by healing chamber configuration (P<0.001) and was not affected by time in vivo (P>0.42) at 3 and 5 weeks in vivo. BAFO was not affected by healing chamber configuration (P>0.14) however significantly increased over implantation time (P<0.001). CONCLUSION: Regardless of healing chamber design and dimensions considered, healing allowed the devices osseointegration. However, healing chamber configuration significantly affected osseointegration measurable parameters such as BIC.

The purpose of this project was to study the effect of a subimmunosuppressive dose of FK506 (0.7 mg/kg per day) on nerve regeneration along a long nerve gap (4 cm), using the contralateral C7 nerve root transfer model for musculocutaneous nerve neurotization. Two types of tubes were applied to the nerve gap: a polycaprolactone tube and a collagen tube. Twenty adult male Sprague-Dawley rats were divided into 4 groups (n = 5). A polycaprolactone was used in groups 1 and 3 and a collagen tube in groups 2 and 4. Groups 1 and 2 were daily administered a subimmunosuppressive dose of FK506. Animals were euthanized on day 30. Evaluation consisted of behavioral assessment, needle electromyography studies, biceps muscle weight measurements, and qualitative and quantitative morphometry. Groups 1 and 2 showed higher mean values for fiber counts, axon diameters, myelin thickness and myelin area in C7, better functional evaluation results, and higher biceps weight left to right ratio than groups 3 and 4. There was no evidence of reinnervation potentials, and there were no axons detectable inside the tube lumen in any of the study groups. The present study demonstrated that there was nonsignificant improvement of the functional recovery, after systemic administration of a low dose of FK506. This was attributed to 3 factors: length of nerve gap; duration of follow up; and dose of FK506. However, FK506-treated animals tended to be in a more advanced stage of nerve regeneration compared with the control groups

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

OBJECTIVE: To evaluate the early bone response to plateau root form dental implants with 4 different surface treatments. STUDY DESIGN: Surface treatments comprised (n = 12 each): as-machined (M), alumina-blasted/acid-etched (AB/AE), alumina-blasted/acid-etched + nanothickness bioceramic coating (Nano), and plasma-sprayed calcium phosphate (PSCaP). Implants were placed in the radius diaphyses of 12 beagle dogs, remaining in vivo for 3 and 5 weeks. After euthanasia, the implants were subjected to torque to interface fracture and subsequently nondecalcified for histomorphology. Statistical analysis was performed by a GLM analysis of variance model at 5% significance level. RESULTS: Torque to interface fracture was significantly greater for the PSCaP group than for other groups (P < .001). Histomorphologic analysis showed woven bone formation around all implant surfaces at 3 weeks, and its replacement by lamellar bone at 5 weeks. Time in vivo did not affect torque measures. CONCLUSION: The PSCaP surface increased the early bone biomechanical fixation of plateau root form implants.

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