Zachary S. Peacock

Immunogenicity and Protective Immunity Induced by Synthetic Peptides Associated with Putative Immunodominant Regions of Streptococcus mutans Glucan-Binding Protein B

ABSTRACT Glucan-binding protein B (GbpB) from Streptococcus mutans has been shown to induce protective immunity to dental caries in experimental models. Having recently sequenced the gbpB gene, our objective in this study was to identify immunogenic regions within the GbpB sequence for use in subunit vaccines. Potential regions of immunogenicity were sought by use of a matrix-based algorithm (EpiMatrix) to estimate the binding characteristics of peptides derived from the GbpB sequence by using a database of known major histocompatibility complex class II binding alleles. Screening the entire sequence revealed several peptides with estimated high binding probabilities. Two N-terminal 20-mer peptides (SYI and QGQ) subtending two of these regions were synthesized. A preliminary experiment, in which these peptides were synthesized in the multiple antigenic peptide format and were used to subcutaneously immunize Sprague-Dawley rats twice at a 21-day interval, revealed that the SYI peptide induced a higher percentage of responses to the inciting peptide as well as to intact GbpB, as measured by enzyme-linked immunosorbent assay. The effect of immunization with the SYI peptide construct on the cariogenicity of S. mutans was then investigated by immunizing weanling Sprague-Dawley rats twice at a 9-day interval with SYI or with phosphate-buffered saline. All rats were then orally infected with S. mutans strain SJ. After a 78-day infection period, the SYI-immunized groups had significant reductions in dental caries on both smooth and occlusal surfaces compared with the sham-immunized group. Thus, these experiments indicated that at least one linear sequence, derived from the N-terminal third of GbpB, was sufficiently immunogenic to induce a protective immune response in this experimental rat model for dental caries.

Percutaneous dilatational tracheostomy: review of technique and evidence for its use.

Tracheostomy is a technique for airway management commonly used by surgeons who care for critically ill patients. Patients with traumatic facial injuries, severe odontogenic infections, and head and neck malignancies are often recipients of tracheostomies. As such, the oral and maxillofacial surgeon who frequently treats such patients should be well-trained in tracheostomy placement. For decades, the standard technique for tracheostomy was the open surgical technique. However, during the past 20 years, the use of percutaneous dilatational tracheostomy has increased. The purpose of the present report is to review the percutaneous dilatational tracheostomy technique, describe the use of intensive care units as proxies for the operating room, and review the available evidence comparing percutaneous dilatational tracheostomy to open tracheostomy.

Le Fort-based maxillofacial transplantation: current state of the art and a refined technique using orthognathic applications.

Abstract Following encouraging results from the first 6 maxillofacial allotransplants, there has been a dramatic rise in interest worldwide. Numerous groups are now devoting resources to increase the frequency of these complex procedures, and with this, the craniomaxillofacial surgeon should become familiar with the emerging state of the art. This article reviews the evolution of Le Fort–based cadaveric studies pertaining to maxillofacial allotransplantation, briefly describes the clinical reports through 2010, and introduces a refined technique applying orthognathic applications. Preliminary studies over the last 5 years have highlighted the challenges associated with transplanting skeletal components, and clinical results presented thus far have been extremely promising. However, a notable area for improvement is suboptimal facial-skeletal harmony and profile in the context of sagittal skeletal projection and maxillomandibular relation. To our knowledge, orthognathic planning as applied to osteocutaneous face transplantation has not been described. Many recipients seen thus far demonstrate some degree of malocclusion and suboptimal harmony, as expected, given the donor-to-recipient skeletal/jaw discrepancies. Given that the goal is to improve function as well as form, the importance of orthognathic planning cannot be overstated with respect to optimizing harmony, profile, and occlusion. Preoperative planning, including generation of donor/recipient dental cast models, as described herein for the first time, is essential.

Quantifying Temporomandibular Joint Synovitis in Children With Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) frequently affects the temporomandibular joints (TMJs) and is often undetected by history, examination, and plain imaging. Qualitative assessment of gadolinium‐enhanced magnetic resonance images (MRIs) is currently the standard for diagnosis of TMJ synovitis associated with JIA. The purpose of this study is to apply a quantitative analysis of synovial enhancement to MRIs of patients with and without JIA to establish a disease threshold and sensitivity and specificity for the technique.

Osteocutaneous maxillofacial allotransplantation: Lessons learned from a novel cadaver study applying orthognathic principles and practice

Background: Osteocutaneous maxillofacial allotransplantation is an encouraging technique for reconstruction of complex midfacial injuries (i.e., Gordon type III composite tissue allotransplantation). Although clinical results have been promising, there are no published guidelines, to date, on how to establish a functional occlusion and class I skeletal relation between the donor maxilla and recipient mandible. The purpose of this study was to use orthognathic principles and practice to improve occlusal and facial skeletal outcomes in osteocutaneous maxillofacial allotransplantation. Methods: Three Le Fort III–based maxillofacial allotransplantations were performed, using six fresh cadavers. Each recipient was prepared bluntly simulating a massive, bilateral orbitozygomatic maxillofacial defect. The first transplant was completed according to published protocol. The second was planned using dental cast models, cephalometric analyses, model surgery, and occlusal splint fabrication. The third involved an edentulous scenario, with the donor alloflap fixated to the recipients mandible using a mimic Gunning splint to establish the vertical dimension of occlusion. Results: All three operations resulted in facial aesthetics comparable to those seen with autologous methods. Operative times ranged from 3.5 to 5.3 hours. The first allotransplant resulted in a class II malocclusion (overjet, 5 mm). The second recipient, with a preexisting class II skeleton, displayed a small anterior open bite of –1.7 mm, 1 mm of overjet, and a class I skeletal relationship (A-point–nasion–B-point angle, 2.3 degrees) following transplantation. The final transplant, consisting of an edentulous alloflap to an edentulous recipient, demonstrated an orthognathic profile. Conclusion: Use of orthognathic principles and practice in osteocutaneous maxillofacial allotransplantation resulted in improved occlusion, skeletal projection, and facial harmony relative to standard technique.

Preoperative Incisional and Intraoperative Frozen Section Biopsy Techniques Have Comparable Accuracy in the Diagnosis of Benign Intraosseous Jaw Pathology

PURPOSE To compare the accuracy of intraoperative frozen section (FS) and preoperative incisional biopsy (IB) techniques to diagnose benign intraosseous jaw lesions. MATERIALS AND METHODS This is a retrospective cohort study composed of subjects with benign intraosseous jaw lesions. The predictor variable was the technique for establishing a preliminary diagnosis of the lesion, preoperative IB or intraoperative FS. The outcome variable was the accuracy of the biopsy technique when compared with the final histologic diagnosis and was classified as concordant or discordant. The comparative diagnostic accuracy of the techniques was assessed with the χ(2) test. RESULTS A total of 71 subjects met inclusion criteria. The mean age was 39 years (range, 5 to 85 years), and 58% (41) were male patients. Of the subjects, 20 (28%) underwent IB. In 14 (70%) of these, the results of biopsy agreed with the final diagnosis. 51 (72%) underwent intraoperative FS and in 31 (62%) of these, the results of biopsy agreed with the final diagnosis. The difference in diagnostic accuracy between IB (70%) and FS (61%) was statistically insignificant (P = .48). Sources of biopsy error included sampling error (46%), insufficient epithelial tissue (15%), inflammation (15%), pathologists experience (8%), and artifact (4%). CONCLUSIONS Preoperative IB and intraoperative FS provide comparable accuracy of diagnosis in patients with benign intraosseous jaw pathology. Sampling error was the most common reason for discordant results.

Effects of mandibular distraction osteogenesis on three-dimensional airway anatomy in children with congenital micrognathia.

PURPOSE To assess the 3-dimensional (3D) computed tomography (CT) changes in airway size and shape in children with congenital micrognathia treated by mandibular distraction osteogenesis (DO). PATIENTS AND METHODS This was a retrospective study of patients with congenital micrognathia, treated by mandibular DO, who had pre- and postoperative 3D maxillofacial CT scans from the hard palate to the hyoid bone. Digital 3D-CT reconstructions were made before and after distraction. Demographic (age, gender, and diagnosis) and anatomic (airway size and shape) variables were recorded and analyzed. The pre-distraction measures of size and shape were compared with the post-distraction measures. P≤.05 was considered significant. RESULTS During the study period (1999 to 2010), 17 children with congenital micrognathia underwent mandibular DO. Of these patients, 11 (3 females) met the inclusion criteria. The mean age was 6.8 years (range 1.3 to 20.6). All subjects had first and second pharyngeal arch deformities. Nine were tracheostomy dependent before distraction. Postdistraction increases in the anteroposterior diameter (153%), lateral airway diameter (70%), airway volume (76%), minimal retroglossal (162%) and retropalatal (77%), and minimal cross-sectional areas (282%) were obtained. The mean airway length decreased after distraction by 4 mm DO also affected the airway shape: the airway surface area and airway compactness increased after distraction. Six subjects were decannulated or had their tracheostomies capped. Three subjects remained tracheostomy dependent after distraction. The reasons for continued tracheostomy included copious secretions, muscle hypotonia, hypopharnygeal stenosis, and mandibular hypomobility. CONCLUSIONS DO for congenital micrognathia increases airway size, decreases airway length, and alters the shape as measured using 3D-CT.

Involvement of PTCH1 mutations in the calcifying epithelial odontogenic tumor

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.

Giant cell lesions of the jaws: does the level of vascularity and angiogenesis correlate with behavior?

PURPOSE To compare vascularity and angiogenic activity in aggressive and nonaggressive giant cell lesions (GCLs) of the jaws. MATERIALS AND METHODS This is a retrospective study of 14 GCLs treated at the University of California, San Francisco. Immunohistochemistry was used to determine of the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), CD34, and CD31. VEGF and bFGF expression in giant cells (GCs) and surrounding mononuclear stroma was classified into 1) high immunoreactivity (>50% staining) and 2) low immunoreactivity (<50% staining). CD31- and CD34-stained vessels were counted at 200× magnification. Clinical and radiographic records were reviewed to classify lesions as aggressive or nonaggressive. RESULTS Of the lesions, 8 were aggressive and 6 were nonaggressive. High VEGF expression was found within the GCs in 4 of 8 aggressive lesions compared with 1 of 6 nonaggressive lesions. The stroma in both groups had low staining. High staining of the GCs for bFGF was found in 6 of 8 aggressive lesions compared with 3 of 6 nonaggressive lesions. The stroma of all aggressive cases showed high expression of bFGF compared with 3 of 6 nonaggressive cases. The aggressive group had a mean of 20.1 ± 5.4 vessels/high-powered field (hpf) stained for CD31 compared with 11.5 ± 5.6 vessels/hpf in the nonaggressive group. The aggressive group had 24.6 ± 7.0 vessels/hpf stained with CD34 compared with 18.5 ± 4.0 vessels/hpf in the nonaggressive group. CONCLUSIONS The vascularity and level of angiogenesis within aggressive GCLs are higher than those in nonaggressive lesions.

Role of computed tomographic angiography in treatment of patients with temporomandibular joint ankylosis.

PURPOSE To evaluate the use of preoperative computed tomographic angiography (CTA) and selective embolization as an ancillary tool for the treatment of patients with temporomandibular joint (TMJ) ankylosis. MATERIALS AND METHODS The present study was a case series of subjects with bilateral TMJ ankylosis who had undergone preoperative CTA and surgical release with immediate reconstruction. The indications for CTA were either an intimate association between the vessels and the ankylotic mass on the facial computed tomography (CT) scan or a history of multiple previous TMJ operations. In cases in which intimate anatomic association was present between the branches of the maxillary artery and the ankylotic masses, preoperative selective embolization was performed. All subjects underwent a standard approach to ankylosis release with immediate reconstruction and were followed up for up to 6 months postoperatively. The demographic and operative variables were recorded for each subject. RESULTS Five subjects (mean age, 36.4 years; 3 females) with bilateral TMJ ankylosis underwent release and had undergone preoperative CTA for vascular assessment. Three subjects underwent preoperative embolization. The total operating time ranged from 5.9 to 10.3 hours. The intraoperative blood loss ranged from 150 to 3,750 mL. One patient who had undergone unilateral embolization required an intraoperative transfusion because of bleeding on the nonembolized side. No adverse cardiac, renal, or neurologic events developed secondary to the blood loss. In all 5 subjects, the preoperative maximal incisor opening was less than 15 mm, increased to more than 35 mm intraoperatively, and was 30 mm or more at 6 months or longer of follow-up. CONCLUSIONS In select cases, CTA can be a useful adjunct in the treatment of patients with TMJ ankylosis.