Functional outcomes of virtually planned free fibula flap reconstruction of the mandible.

BACKGROUND: The free fibula osteocutaneous flap has become the criterion standard for reconstruction of complex mandibular defects. The authors present their institutional experience with optimization of flap contouring and inset using virtual planning and prefabricated cutting jigs. METHODS: All free fibula-based mandible reconstructions performed at the authors' institution using virtual planning technology between 2009 and 2012 were retrospectively analyzed. The authors evaluated a variety of patient and procedural variables and outcomes. A series of cases performed before virtual planning was reviewed for comparison purposes. RESULTS: Fifty-four reconstructions were performed in 52 patients. Patients were divided evenly between a private university-affiliated medical center and a large county hospital. The most common indications were malignancy (43 percent), ameloblastoma (26 percent), and osteonecrosis/osteomyelitis (23 percent). Thirty percent of patients had irradiation of the recipient site and 38 percent had previous surgery. Sixty-three percent of patients received dental implants, with 47 percent achieving functional dentition. Twenty-five percent of patients had immediate dental implant placement, and 9 percent had immediate dental restoration. Postoperative imaging demonstrated excellent precision and accuracy of flap positioning. Comparison with cases performed before virtual planning demonstrated increased complexity of flap design along with reduced operative time in the virtually planned group. CONCLUSIONS: Preoperative virtual planning along with use of prefabricated cutting jigs allows for precise contouring and positioning of microvascular fibula free flaps in mandibular reconstruction. Using this technique, the authors have achieved unprecedented rates of dental rehabilitation along with reduced operative times. The authors believe that virtual planning technologies are an emerging criterion standard in mandible reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Virtual surgical planning in orthognathic surgery.

Computer-aided surgical simulation has greatly enhanced the efficiency and accuracy of orthognathic surgery for correction of dentofacial deformities. Virtual surgical planning (VSP) improves the efficiency of the presurgical work-up and provides an opportunity to illustrate the multidimensional correction at the dental and skeletal level. VSP provides preoperative insight into the surgical intervention and the fabrication of cutting jigs/guides and templates can help decrease intraoperative surgical inaccuracies. VSP is rapidly becoming the standard of care for surgical treatment planning of dentofacial deformities.

Ten-year evolution utilizing computer-assisted reconstruction for giant ameloblastoma.

BACKGROUND: The authors describe our current practice of computer-aided virtual planned and pre-executed surgeries using microvascular free tissue transfer with immediate placement of implants and dental prosthetics. METHODS: All patients with ameloblastomas treated at New York University (NYU) Medical Center during a 10-year period from September 2001 to December 2011 were identified. Of the 38 (36 mandible/2 maxilla) patients that were treated in this time period, 20 were identified with advanced disease (giant ameloblastoma) requiring aggressive resection. Reconstruction of the resultant defects utilized microvascular free tissue transfer with an osseocutaneous fibular flap in all 20 of these patients. RESULTS: Of the patients reconstructed with free vascularized tissue transfer, 35% (7/20) developed complications. There were two complete flap failures with consequent contralateral fibula flap placement. Sixteen patients to date have undergone placement of endosteal implants for complete dental rehabilitation, nine of which received immediate placement of the implants at the time of the free flap reconstruction. The three most recent patients received immediate placement of dental implants at the time of microvascular free tissue transfer as well as concurrent placement of dental prosthesis. CONCLUSIONS: To our knowledge, this patient cohort represents the largest series of comprehensive computer aided free-flap reconstruction with dental restoration for giant type ameloblastoma.

A suppressor analysis of residues involved in cation transport in the lactose permease: identification of a coupling sensor.

Four amino acids critical for lactose permease function were altered using site-directed mutagenesis. The resulting Quad mutant (E269Q/R302L/H322Q/E325Q) was expressed at 60% of wild-type levels but found to have negligible transport activity. The Quad mutant was used as a parental strain to isolate suppressors that regained the ability to ferment the alpha-galactoside melibiose. Six different suppressors were identified involving five discrete amino acid changes and one amino acid deletion (Q60L, V229G, Y236D, S306L, K319N and DeltaI298). All of the suppressors transported alpha-galactosides at substantial rates. In addition, the Q60L, DeltaI298 and K319N suppressors regained a small but detectable amount of lactose transport. Assays of sugar-driven cation transport showed that both the Q60L and K319N suppressors couple the influx of melibiose with cations (H(+) or H(3)O(+)). Taken together, the data show that the cation-binding domain in the lactose permease is not a fixed structure as proposed in previous models. Rather, the data are consistent with a model in which several ionizable residues form a dynamic coupling sensor that also may interact directly with the cation and lactose.

Identification of histone deacetylase-3 domains that interact with the orphan nuclear receptor TR2.

The orphan nuclear receptor TR2 interacts directly with histone deacetylase HDAC3 and HDAC4. We now report that two domains of HDAC3 are involved in its interaction with TR2. GST pull-down assays show that both the N-terminal (residues 1-135) and the C-terminal (residues 210-428) segments of HDAC3 directly interact with TR2. The interaction is also demonstrated in coimmunoprecipitation experiments. The two TR2-binding sites of HDAC3 compete with each other for binding to TR2. The two receptor-interacting domains (RIDs) of HDAC3 were further dissected and mapped to amino acid residues 1-70 and 270-320. In vivo studies demonstrate that HDAC3 and TR2 can form a complex on the TR2 DNA target and this complex exhibits histone deacetylase activity. These data identify two RIDs of HDAC3 and the biological activity of the complex formed by TR2 and HDAC3 on the TR2 DNA target.

Interaction of nuclear receptor zinc finger DNA binding domains with histone deacetylase.

A direct interaction between the nuclear receptor TR2 and histone deacetylases (HDACs) 3 and 4 is mediated by the DNA binding domain (DBD) of TR2. To test if this interaction is common to members of the nuclear receptor family, the Cys2-Cys2 type zinc finger (ZF) DBDs were subcloned from several nuclear receptors (mRARalpha, mRXRbeta, mTR2, mTR4, RAR, mPPARdelta, and mPPARgamma2). Using GST pull-downs, both HDACs 3 and 4 were found to interact directly with the core DBD from each receptor. The three-dimensional structure of the ZF domains was essential for this interaction as disruption by zinc chelation precluded interaction with HDACs. The results suggest that the ZFs of nuclear receptors provide a general interaction interface for HDACs 3 and 4. Functional significance of this interaction was demonstrated using ChIP assays where a truncated TR2 protein (lacking the LBD) recruited HDACs 3 and 4 to the target DNA causing demonstrable histone deacetylation. GST pull-downs and mammalian two-hybrid interaction tests were then used to define the interaction domains of HDAC3 with TR2. Both the N- and C-terminal portions of HDAC3 showed interaction with the TR2 DBD. Thus, multiple domains of HDAC3 form the interaction surface for the DBD of nuclear receptors.

Effects of retinoid ligands on RIP140: molecular interaction with retinoid receptors and biological activity.

Receptor interacting protein 140 (RIP140) interacts with retinoic acid receptor (RAR) and retinoid X receptor (RXR) constitutively, but hormone binding enhances this interaction. The ligand-independent interaction is mediated by the amino and central regions of RIP140 which contain a total of nine copies of the LXXLL motif, whereas the agonist-induced interaction is mediated by its carboxyl terminus which contains a novel motif (1063-1076, LTKTNPILYYMLQK). The ligand-independent interaction could be enhanced slightly by agonists, whereas the ligand-dependent interaction was strictly agonist dependent for both RAR and RXR. In the context of heterodimers, ligand occupancy of RXR played a more dominant role for both molecular interaction and biological activity of RIP140. Competition and mutation studies demonstrated an essential role for (1067)Asn and (1073)Met for a ligand-dependent interaction. A model was proposed to address the constitutive and agonist-dependent interaction of RIP140 with RAR/RXR.