Patient-specific polyetheretherketone facial implants in a computer-aided planning workflow.

PURPOSE: In the present study, we report an innovative workflow using polyetheretherketone (PEEK) patient-specific implants for esthetic corrections in the facial region through onlay grafting. The planning includes implant design according to virtual osteotomy and generation of a subtraction volume. The implant design was refined by stepwise changing the implant geometry according to soft tissue simulations. MATERIALS AND METHODS: One patient was scanned using computed tomography. PEEK implants were interactively designed and manufactured using rapid prototyping techniques. Positioning intraoperatively was assisted by computer-aided navigation. Two months after surgery, a 3-dimensional surface model of the patient's face was generated using photogrammetry. Finally, the Hausdorff distance calculation was used to quantify the overall error, encompassing the failures in soft tissue simulation and implantation. RESULTS: The implant positioning process during surgery was satisfactory. The simulated soft tissue surface and the photogrammetry scan of the patient showed a high correspondence, especially where the skin covered the implants. The mean total error (Hausdorff distance) was 0.81 ± 1.00 mm (median 0.48, interquartile range 1.11). The spatial deviation remained less than 0.7 mm for the vast majority of points. CONCLUSIONS: The proposed workflow provides a complete computer-aided design, computer-aided manufacturing, and computer-aided surgery chain for implant design, allowing for soft tissue simulation, fabrication of patient-specific implants, and image-guided surgery to position the implants. Much of the surgical complexity resulting from osteotomies of the zygoma, chin, or mandibular angle might be transferred into the planning phase of patient-specific implants.

Crestal Sinus Floor Augmentation Using Hydraulic Pressure and Vibrations: A Retrospective Single Cohort Study.

PURPOSE: To evaluate the sinus membrane perforation and implant survival rate after crestal minimally invasive sinus floor augmentation using hydraulic pressure and vibrations. MATERIALS AND METHODS: In this retrospective single cohort study, all patients who underwent minimally invasive sinus floor augmentation between 2007 and 2015 using hydraulic pressure and vibrations were included. The sinus membrane is elevated by physiologic saline at 1.5 bar. The fluid is then set into vibration to further separate the sinus membrane from the bony floor. The endpoints were sinus membrane perforation and the survival rate of implants. RESULTS: The hydraulic pressure and vibration technique was applied in 156 patients. Seven patients with perforations of the sinus membrane were treated with the lateral window approach and excluded from the follow-up analysis. In the remaining 149 patients, 184 crestal sinus floor augmentations were performed and 184 implants were placed. In 10 of these 184 cases, a perforation was suspected in the postoperative computed tomography (CT) scan. In total, the perforation rate was 8.9% (17/191). Nineteen implants were lost during the follow-up period ranging from 0.2 to 8.4 years with a median of 2.3 years. The cumulative implant survival rates after 1, 3, and 5 years were 94.4%, 87.7%, and 87.7%, respectively. No severe perioperative complications were noted. CONCLUSION: The hydraulic pressure and vibration technique allows a minimally invasive crestal sinus augmentation with a perforation rate less than 10% and implant survival rates of approximately 90%.

Expression patterns of Ets2 protein correlate with bone-specific proteins in cell-seeded three-dimensional bone constructs.

The transcription factor Ets2 and its transcriptional targets osteopontin (OPN) and osteocalcin (OC) are expressed in tissue-engineered bone constructs in vitro. Up to now little is known about the role of Ets2 in tissue-engineering applications. This study was intended to investigate the hypothesis that protein expression of Ets2 is correlated with the expression of bone-specific proteinsin tissue-engineeredbone constructs. Cell-seeded three-dimensional bone constructs manufactured with osteoblastic cells and poly(lactic-co-glycolic acid) polymer fleeces over a period of 21 days were analyzed by SDS-PAGE and Western blotting. The protein expression of OPN, OC, osteonectin and collagen type I was analyzed. Cellularity, alkaline phosphatase-specific activity and histology confirmed the osteoblastic phenotype of the constructs. Correlations between Ets2 expression and OPN and Ets2 and collagen type I expression could be detected during the phase of late osteoblastic differentiation between days 9 and 21. The correlation between OC and collagen type I was significant in this late stage of osteoblastic differentiation. These results suggest that there is a strong interplay of Ets2 with bone-specific proteins in cell-seeded three-dimensional bone constructs. This study is a crucial step to elucidate the complex interplay of bone-related proteins in the application of bone tissue engineering.

Accuracy of treatment planning based on stereolithography in computer assisted surgery.

Three-dimensional stereolithographic models (SL models), made of solid acrylic resin derived from computed-tomography (CT) data, are an established tool for preoperative treatment planning in numerous fields of medicine. An innovative approach, combining stereolithography with computer-assisted point-to-point navigation, can support the precise surgical realization of a plan that has been defined on an SL model preoperatively. The essential prerequisites for the application of such an approach are: (1) The accuracy of the SL models (including accuracy of the CT scan and correspondence of the model with the patient's anatomy) and (2) the registration method used for the transfer of the plan from the SL model to the patient (i.e., whether the applied registration markers can be added to the SL model corresponding to the markers at the patient with an accuracy that keeps the "cumulative error" at the end of the chain of errors, in the order of the accuracy of contemporary navigation systems). In this study, we focus on these two topics: By applying image-matching techniques, we fuse the original CT data of the patient with the corresponding CT data of the scanned SL model, and measure the deviations of defined parameter (e.g., distances between anatomical points). To evaluate the registration method used for the planning transfer, we apply a point-merge algorithm, using four marker points that should be located at exactly corresponding positions at the patient and at connective bars that are added to the surface of the SL model. Again, deviations at defined anatomical structures are measured and analyzed statistically. Our results prove sufficient correspondence of the two data sets and accuracy of the registration method for routine clinical application. The evaluation of the SL model accuracy revealed an arithmetic mean of the relative deviations from 0.8% to 5.4%, with an overall mean deviation of 2.2%. Mean deviations of the investigated anatomical structures ranged from 0.8 mm to 3.2 mm. An overall mean (comprising all structures) of 2.5 mm was found. The fiducial registration error of the point-merge algorithm ranged from 1.0 mm to 1.4 mm. The evaluated chain of errors showed a mean deviation of 2.5 mm. This study verifies that preoperative planning on SL models and intraoperative transfer of this plan with computer assisted navigation is a suitable and sufficiently reliable method for clinical applications.

Bone morphogenetic proteins 5 and 6 stimulate osteoclast generation.

Bone regeneration is required for fracture-healing, and different procedures have been used to promote osteogenesis. Recently, BMP-2 has been shown to induce bone formation in vivo and has been tested in clinical trials. A recent in vitro study evaluated the osteogenic activity of 14 BMPs on osteoblastic progenitor cells with an osteogenic hierarchical model in which BMP-2 and BMP-6 may play an important role in inducing osteoblast differentiation. Although the relative osteoinductive activity of each BMP is important, bone regeneration is a process consisting of bone formation and bone resorption. Therefore, it remains unclear which effects BMP-5 and -6 have on the generation of osteoclasts and by which mechanism osteoclastogenesis is stimulated. To compare osteoclastic potency of each BMP, primary murine bone marrow cells were treated with human recombinant BMP-2, BMP-5, or BMP-6 and 1,25-(OH)2 vitamin D3 and stained for the TRAP enzyme. Osteogenic activity of BMP-5 was determined by measuring induction of ALP-activity and proliferation after incubation with primary murine osteoblasts. For elucidating the molecular mechanism, primary bone marrow cells with various concentrations of OPG were added to the TRAP assay and mRNA levels of RANKL and OPG were measured after stimulation with BMP-5. The presented data show that BMP-5 and BMP-6, unlike BMP-2, enhanced the formation of murine TRAP+/MNCs in a biphasic curve. BMP-5 and -6 were less potent in stimulating osteoclastogenesis compared to BMP-2. Concerning the effects of BMP-5 on osteoblasts, there was a dose-dependent increase of ALP activity and proliferation up to a maximum dose of 300 ng/mL. At the mRNA level, BMP-5 increased the RANKL/OPG ratio. In conclusion, this study demonstrates that in contrast to BMP-2, BMP-5 and -6 influences the generation of osteoclasts in a biphasic mode. Both proteins might be very important regulators of bone homeostasis, and therefore, potent candidates for future treatment strategies of bone regeneration.

Chimerism analysis following nonmyeloablative stem cell transplantation.

Molecular monitoring of hematopoietic chimerism has become a routine diagnostic approach in patients after allogeneic stem cell transplantation. Chimerism testing permits the documentation and surveillance of engraftment and facilitates early detection of impending graft rejection. In patients transplanted for treatment of malignant hematological disorders, monitoring of chimerism can provide an early indication of incipient disease relapse. The investigation of chimerism has therefore become an indispensable tool for the management of patients during the posttransplant period. Growing use of nonmyeloablative conditioning, which is associated with prolonged duration of mixed hematopoietic chimerism, has further increased the clinical importance of chimerism analysis. At present, the most commonly used technical approaches to the investigation of chimerism include microsatellite analysis by polymerase chain reaction and, in the gender-mismatched transplant setting, fluorescence in situ hybridization analysis of sex chromosomes. The investigation of chimerism within specific leukocyte subsets isolated from peripheral blood or bone marrow samples by flow-sorting or magnetic bead-based techniques provides more specific information on processes underlying the dynamics of donor/recipient chimerism. Moreover, cell subset-specific analysis permits the assessment of impending complications at a significantly higher sensitivity, thus providing a basis for earlier treatment decisions.

Van Der Woude syndrome: variable penetrance of a novel mutation (p.Arg 84Gly) of the IRF6 gene in a Turkish family.

Van der Woude syndrome (VWS) is an autosomal dominant disorder characterized by clefts of the lip and/or palate (CL+/-P), lip pits, bifid uvula and hypodontia. Mutations of the interferon regulatory factor 6 gene (IRF6) have been recently described in patients with VWS. The entire 9 exons of the IRF6 gene in two brothers of Turkish origin clinically diagnosed with Van der Woude syndrome and four healthy family members were screened for mutations using a newly established denaturing gradient gel electrophoresis (DGGE) method. A novel heterozygous mutation in exon 2 (DNA binding region) of the IRF6 gene, p.Arg84Gly, was found in both brothers with VWS and in their clinically asymptomatic mother. Our results suggest a dominant negative effect of the p.Arg84Gly mutation in the VWS of both patients. Non-penetrance of this mutation is suggested in the mother of the patients.

Mutation analysis of CLPTM 1 and PVRL 1 genes in patients with non-syndromic clefts of lip, alveolus and palate.

INTRODUCTION: Non-syndromic cleft lip with or without cleft palate (CL/P), is one of the most common birth defects, but its aetiology is largely unknown. The aim of this study was to determine the sequence changes of the Cleft Lip and Palate Transmembrane Protein 1 (CLPTM 1) and Poliovirus Receptor Related 1 (PVRL 1) genes in patients with non-syndromic complete clefts of lip, alveolus and palate and to correlate these findings with clinical features. PATIENTS AND METHODS: 25 patients were analysed (14 male and 11 female, aged 4-10 years) of European descent (9 patients with right, 9 with left and 7 patients with bilateral CLAP) and 25 controls, respectively. Exons 2-14 of the CLPTM1 and exons 1-6 of the PVRL1 gene were analysed by a direct sequencing method using DNA extracted from whole blood. RESULTS: A novel in frame Glu441-Gly442 ins Glu mutation of the PVRL 1 gene in combination with novel exon mutations Gly331Gly, Ala88Ala, Pro309Pro and intron change IVS7-10G/A of the CLPTM 1 gene were found in 9 patients. The Glu441-Gly442 ins Glu mutation and the intron change IVS7-10G/A were not detected in 25 controls. CONCLUSION: These results suggest that a simultaneous occurrence of PVRL1 and CLPTM 1 gene mutations in cleft patients does not correlate with the type of cleft (left, right, bilateral) or the gender of the patients. If a combination of the intron change IVS7-10G/A, exon changes Gly331Gly, Ala88Ala and Pro309Pro of the CLMPT 1 gene and Glu441-Gly442 ins Glu mutation of the PVRL 1 gene could be a genetic factor for non-syndromic clefts of the primary and the secondary palates, it is important to investigate more patients and controls.

A head-mounted operating binocular for augmented reality visualization in medicine--design and initial evaluation.

Computer-aided surgery (CAS), the intraoperative application of biomedical visualization techniques, appears to be one of the most promising fields of application for augmented reality (AR), the display of additional computer-generated graphics over a real-world scene. Typically a device such as a head-mounted display (HMD) is used for AR. However, considerable technical problems connected with AR have limited the intraoperative application of HMDs up to now. One of the difficulties in using HMDs is the requirement for a common optical focal plane for both the realworld scene and the computer-generated image, and acceptance of the HMD by the user in a surgical environment. In order to increase the clinical acceptance of AR, we have adapted the Varioscope (Life Optics, Vienna), a miniature, cost-effective head-mounted operating binocular, for AR. In this paper, we present the basic design of the modified HMD, and the method and results of an extensive laboratory study for photogrammetric calibration of the Varioscope's computer displays to a real-world scene. In a series of 16 calibrations with varying zoom factors and object distances, mean calibration error was found to be 1.24 +/- 0.38 pixels or 0.12 +/- 0.05 mm for a 640 x 480 display. Maximum error accounted for 3.33 +/- 1.04 pixels or 0.33 +/- 0.12 mm. The location of a position measurement probe of an optical tracking system was transformed to the display with an error of less than 1 mm in the real world in 56% of all cases. For the remaining cases, error was below 2 mm. We conclude that the accuracy achieved in our experiments is sufficient for a wide range of CAS applications.

Computer-enhanced stereoscopic vision in a head-mounted operating binocular.

Based on the Varioscope, a commercially available head-mounted operating binocular, we have developed the Varioscope AR, a see through head-mounted display (HMD) for augmented reality visualization that seamlessly fits into the infrastructure of a surgical navigation system. We have assessed the extent to which stereoscopic visualization improves target localization in computer-aided surgery in a phantom study. In order to quantify the depth perception of a user aiming at a given target, we have designed a phantom simulating typical clinical situations in skull base surgery. Sixteen steel spheres were fixed at the base of a bony skull, and several typical craniotomies were applied. After having taken CT scans, the skull was filled with opaque jelly in order to simulate brain tissue. The positions of the spheres were registered using VISIT, a system for computer-aided surgical navigation. Then attempts were made to locate the steel spheres with a bayonet probe through the craniotomies using VISIT and the Varioscope AR as a stereoscopic display device. Localization of targets 4 mm in diameter using stereoscopic vision and additional visual cues indicating target proximity had a success rate (defined as a first-trial hit rate) of 87.5%. Using monoscopic vision and target proximity indication, the success rate was found to be 66.6%. Omission of visual hints on reaching a target yielded a success rate of 79.2% in the stereo case and 56.25% with monoscopic vision. Time requirements for localizing all 16 targets ranged from 7.5 min (stereo, with proximity cues) to 10 min (mono, without proximity cues). Navigation error is primarily governed by the accuracy of registration in the navigation system, whereas the HMD does not appear to influence localization significantly. We conclude that stereo vision is a valuable tool in augmented reality guided interventions.

Interactive stereotaxic teleassistance of remote experts during arthroscopic procedures.

This article describes the technical setup for stereotaxic telesurgical assistance for arthroscopic procedures. It also outlines the current state, limitations, and feasibility of this technical development. Teleassistance or teleconsultation implemented in endoscopic or arthroscopic procedures have not yet been reported. In this study, 7 computer-assisted arthroscopies of the temporomandibular joint were supported by extramural experts via interactive stereotaxic teleconsultation from distant locations. The external experts were supplied with close to real-time video, audio, and stereotaxic navigation data directly from the operation site. This setup allows the surgeons and external experts to interactively determine portals, target structures, and instrument positions relative to the patient's anatomy and to discuss any step of the procedures. Optoelectronic tracking interfaced to computer- based navigation technology allowed precise positioning of instruments for single or multiple temporomandibular joint punctures. The average error of digitizing probe measurements was 1.3 mm (range, 0.0 to 2.5 mm) and the average standard deviation was 0.7 mm (range, 0.4 to 0.9 mm). Evaluation of the reliability and accuracy of this technique suggests that it is sufficient for controlled navigation, even inside the small temporomandibular joint, a fact that encourages further applications for arthroscopy in general. The minimum requirement for high-quality video transmission for teleassisted procedures are integrated services digital network (ISDN) connections. Conventional ISDN-based videoconferencing can be combined with computer-aided intraoperative navigation. Transmission control protocol/internet protocol (TCP/IP)-based stereotaxic teleassistance data transmission via ATM or satellite seem to be promising techniques to considerably improve the field of arthroscopy.

Rehabilitation of the severely atrophied maxilla by horseshoe Le Fort I osteotomy (HLFO).

OBJECTIVE: The purpose of this study was to determine the long-term outcome of the horseshoe Le Fort I osteotomy (HLFO) as a preprosthetic operation technique for implant insertion in the extremely atrophied maxilla. STUDY DESIGN: 36 patients (8 male, 28 female, average age 57.6 years) underwent HLFO combined with iliac crest bone grafting. They were divided into 2 groups: group A with 12 patients who simultaneously received 100 implants; group B with 24 patients where 176 implants were inserted in 18 patients in a second-stage procedure. Clinical and radiographic outcome with regard to implant osseointegration, alveolar bone height in the canine and molar regions, peri-implant bone loss and satisfaction of patients (esthetics, masticatory function, overall treatment) were investigated in all cases. RESULTS: The overall 2-year failure-free fraction of implants was 95.5%; the 5-year failure-free fraction was 89.3%. In the 1-step group the 2-year and 5-year failure-free fractions were 95.9% and 86.9%, respectively, in the 2-step group 95.0% and 91.3% (log rank test P=.57). A total of 27 implants were lost during the entire follow-up: 14 in 6 patients of the 1-stage and 13 in 9 patients of the 2-stage group. The mean loss of alveolar bone after augmentation in the canine and molar regions was almost equal in both groups (overall means for the 2 regions 3.67 +/- 2.77 and 4.42 +/- 2.72 mm, respectively). The relationship between the jaws and thereby the esthetic profile could be improved in all cases. All patients were satisfied with the dental rehabilitation and the achieved new esthetic appearance. CONCLUSIONS: HLFO combined with iliac bone grafting is a feasible preprosthetic technique prior to implant insertion in cases of severe atrophy of the maxillary alveolar ridge, leading to satisfying implant survival and rehabilitation of function.

Fixation of mandibular fractures with biodegradable plates and screws.

OBJECTIVE: Little data exist regarding the use of biodegradable plates and screws for the internal fixation of human mandibular fractures. The purpose of this study was to evaluate the stability of biodegradable, self-reinforced poly-L-lactide plates and screws for the internal fixation of fractures of the human mandible. STUDY DESIGN: Twenty-two individuals (14 male, 8 female; average age, 26.3 years) with a variety of fracture patterns of the mandible underwent management with a biodegradable fixation system. After surgery, maxillomandibular fixation was applied in 3 cases. Images (panoramic radiograph, computed tomographic scan) were taken immediately after surgery and at the 4-week, 8-week, 12-week, and 24-week intervals. The follow-up period averaged 49.1 weeks (range, 22 to 78 weeks). RESULTS: Mucosal dehiscences over the resorbable devices were present in 2 patients. In 1 of these 2 cases, the material had to be replaced with titanium plates. Mucosal healing and consolidation of the fracture were normal in all other patients. CONCLUSION: Self-reinforced biodegradable osteosynthesis materials provide a reliable and sufficient alternative to conventional titanium plate systems.

A pilot-study of a minimally invasive technique to elevate the sinus floor membrane and place graft for augmentation using high hydraulic pressure: 18-month follow-up of 20 cases.

OBJECTIVE: To evaluate medical efficacy and safety of crestal, minimally invasive sinus floor augmentation (MISFA) using an innovative method based on high hydraulic pressure. STUDY DESIGN: Twenty MISFA using the novel Jeder-System were performed in 18 patients at 2 study sites in Vienna, Austria. The Jeder-System consists of the Jeder-drill, the Jeder-pump, and a connecting tube-set. The pump generates high hydraulic pressure (1.5 bar) pushing back the sinus membrane from the drill at the first perforation. The pump also monitors the whole procedure by constantly measuring pressure and volume. RESULTS: Five percent membrane perforation rate (1/20) only detected in the postoperative computed tomography scan and without implication for implant placement. Height gain of 9.2 ± 1.7 mm achieved (from 4.6 ± 1.4 mm to 13.8 ± 2.3 mm). Average patient satisfaction was 9.82 on scale from 1 to 10 (10 = very satisfied). Mean duration of sick leave was 0.19 days. 18-month survival rate was 95% (1/20 implant lost). CONCLUSIONS: Within the limits of a prospective open cohort study with 20 cases, our data demonstrate the safety and medical efficacy of the novel method.

Sinus elevation with a cortical bone graft block: a patient-specific three-dimensional finite element study.

PURPOSE: The aim of the present study was to perform a finite element (FE) analysis of a modified sinus elevation procedure involving additional implantation of a cortical bone graft block for stabilization of an implant. A secondary aim was to compare the modified sinus augmentation with the standard technique and to determine whether the FE model to replace a dental implant can be simplified into a cylinder without compromising the accuracy of the outcome. MATERIALS AND METHODS: Based on computed tomography data, three-dimensional FE models of half of a maxilla were created. A basic model was generated to analyze a conventional sinus elevation procedure and another was created for the modified version, which involved insertion of a cortical bone graft block. Two implant models were used in the premolar region: a typical threaded endosseous dental implant and a simplified 4 x 10-mm cylinder. Occlusal loads were applied in axial, mediotrusive, and laterotrusive directions, and perfect bonding was assumed to be present at all interfaces. RESULTS: The maximum von Mises stresses were significantly lower for the sinus graft models with added cortical bone than for the conventional sinus elevation under all types of loads. No significant difference was observed between the use of threaded implants and the simplified implant cylinders. CONCLUSION: The addition of a cortical bone graft may be a useful approach to decrease stresses around implants placed into the grafted sinus.

Phenothiazine chloride and soft laser light have a biostimulatory effect on human osteoblastic cells.

OBJECTIVE: Low-level laser therapy (LLLT) is a well accepted tool to accelerate wound healing and to reduce inflammation after oral implant insertion. Since there are no in vitro data on a combination of LLLT with prior photosensitization, it was the aim of this study to investigate if photosensitization with phenothiazine chloride results in an alteration of the biostimulatory effect of low-level laser irradiation. BACKGROUND DATA: LLLT and antimicrobial photodynamic therapy are well established for the treatment of peri-implantitis. In vitro studies have shown a biostimulatory effect of LLLT on various cell types, including osteogenic cells. MATERIALS AND METHODS: SaOS-2 cells were treated with the photosensitizer phenothiazine chloride before irradiation with matched laser light. At 24-h intervals the viability and differentiation were analyzed in treated and untreated cells. RESULTS: While the biostimulatory effect of the LLLT could be observed for the lower irradiation dose, the pretreatment with phenothiazine chloride did not significantly affect the growth and differentiation of the SaOS-2 cells. CONCLUSION: It can thus be concluded that combined treatment with phenothiazine chloride and LLLT does not result in a synergistic enhancement of the biostimulatory effect of LLLT, but there was also no evidence for antagonizing effects on growth and differentiation of human osteoblasts.

Genes proximal and distal to MYCN are highly expressed in human neuroblastoma as visualized by comparative expressed sequence hybridization.

MYCN amplification is associated with poor prognosis in neuroblastoma disease. To improve our understanding of the influence of the MYCN amplicon and its corresponding expression, we investigated the 2p expression pattern of MYCN amplified (n = 13) and nonamplified (n = 4) cell lines and corresponding primary tumors (n = 3) using the comparative expressed sequence hybridization technique. All but one MYCN amplified cell line displayed overexpression at 2p. Expression peaks were observed frequently at 2pter and less frequently at 2p24 (MYCN locus), 2p23.3-23.2, and/or 2p23.1. Importantly, cell lines and two corresponding primary tumors displayed expression peaks at similar loci. No significant 2p24 expression level was observed for those cell lines displaying a low amplification rate (n = 3) by comparative genomic hybridization. Only the cell lines with an enhanced peak at 2p23.2-23.3 displayed coamplification of the ALK gene (2p23.2), reported to be associated with unfavorable prognosis. Finally, two of four cell lines without MYCN amplification, both derived from patients with poor outcome, also showed an expression peak at 2p23.2. These data indicate that, besides MYCN, other genes proximal and distal to MYCN are highly expressed in neuroblastoma. The prognostic significance of expression peaks at 2p23.2-23.3, independent of MYCN and ALK status, remains to be investigated.

Accuracy of craniofacial measurements: computed tomography and three-dimensional computed tomography compared with stereolithographic models.

In a retrospective study, distance measurements of nine children with craniofacial malformation were analyzed. The accuracy of measurements was compared when measured on a workstation using a 16-slice multidetector spiral computed tomography and on a stereolithographic model. Three different methods of defining distances were investigated: 1) on the stereolithographic plastic models, 14 distances connecting landmarks were identified with a digitizer (Polaris Tracker); 2) the same distances were defined at axial, coronal, and sagittal reformats of the computed tomography data set and measured using a Philips MX View workstation; and 3) the same 14 distances were defined at three-dimensional virtual reality models of the skulls at the same workstation. All measurements were performed with all three methods by three different readers. The following conclusions could be drawn: stereolithographic models provide a highly exact reproduction of the skull in children with craniofacial malformations. They are a reliable basis for all analytic and probatory endeavors preparing complicated surgical corrections. Three-dimensional virtual reality display modes serve significantly better for exact distance measurements on the complex surface of the human skull than planar reformats of the same computed tomography data sets.

Potential involvement of MYC- and p53-related pathways in tumorigenesis in human oral squamous cell carcinoma revealed by proteomic analysis.

Oral squamous cellular carcinoma is a malignant tumor with poor prognosis. Discovery of early markers to discriminate between malignant and normal cells is of high importance in clinical diagnosis. Subcellular fractions from 10 oral squamous cell carcinoma and corresponding control samples, enriched in mitochondrial and cytosolic proteins, as well as blood from the tumor were analyzed by proteomics, two-dimensional gel electrophoresis, followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Three-hundred and fifty different gene products were identified. Twenty proteins showed deranged levels in oral squamous cell carcinoma in comparison with the control samples and are potentially involved in tumor growth and metastasis. Of these, 16 proteins were upregulated. By applying pathway analysis, we found 8 of the upregulated gene products to be linked to three main locus genes, p53, MYC, and MYCN, and could be candidate biomarkers for OSCC. The findings of this pilot study show that OSCC gene ontology combined with proteomic analysis is a powerful tool in systems biology for the elucidation of the complexity of expression profiles in cellular processes. Application of such pathway analysis has the potential to generate new insights into complex molecular mechanisms underlying disease related processes and could therefore significantly contribute to the efficient performance of the entire discovery process.