Faculty Bibliography

BACKGROUND: Osteoradionecrosis is a serious complication of head and neck radiotherapy. Advanced cases are not amenable to periodic debridement, systemic antibiotics, or hyperbaric oxygen therapy. The authors sought to describe a cost-effective approach for patients with advanced craniofacial osteoradionecrosis. METHODS: Fifteen consecutive patients with craniofacial osteoradionecrosis were treated with radical resection and immediate microvascular free flap reconstruction at Johns Hopkins Hospital or R Adams Cowley Shock Trauma Center from 2002 to 2008. Demographic data were reviewed, and procedure costs were used to compare treatment options. RESULTS: All patients presented with intractable osteoradionecrosis, and most failed conservative therapy. Most cases (60 percent) involved the mandible, and the fibula was the flap of choice (73 percent). The median follow-up was 14 months, with 13 percent complications. Relative cost analysis for hyperbaric oxygen, surgical debridement, and a hospital stay was $25,010; simultaneous resection-microvascular free flap reconstruction and 7-day hospital stay were $30,030. The majority of patients, however, had prior attempts at conservative therapy followed by simultaneous resection and reconstruction; therefore, the average total relative cost per patient was $55,040 ($25,010 + $30,030). CONCLUSION: Definitive treatment of advanced or intractable osteoradionecrosis with simultaneous resection and microvascular composite flap reconstruction is not only definitive but financially sound.

Hedgehog signaling is often activated in tumors, yet it remains unclear how GLI2, a transcription factor activated by this pathway, acts as an oncogene. We show that GLI2 is a pleiotropic oncogene. The overexpression induces genomic instability and blocks differentiation, likely mediated in part by enhanced expression of the stem cell gene SOX2. GLI2 also induces transforming growth factor (TGF)B1-dependent transdifferentiation of foreskin and tongue, but not gingival fibroblasts into myofibroblasts, creating an environment permissive for invasion by keratinocytes, which are in various stages of differentiation having downregulated GLI2. Thus, upregulated GLI2 expression is sufficient to induce a number of the acquired characteristics of tumor cells; however, the stroma, in a tissue-specific manner, determines whether certain GLI2 oncogenic traits are expressed

Among dental implant design alterations, surface modifications have been by far the most investigated topic. Regarding implant surface research, the lack of hierarchical approaches relating in vitro, in vivo, clinical trials, and ex vivo analyses has hindered biomaterials scientists with clear informed rationale guidelines for implant surface design. This manuscript provides a critical hierarchical overview of the in vitro, laboratory in vivo, clinical, and ex vivo methodologies used to investigate the performance of novel biomaterials aiming to allow dental professionals to better evaluate the past, present, and future dental implant surface research. This manuscript also contains an overview of the commercially available surface texture and chemistry modifications including novel nanotechnology-based fabrication processes. Over the last decade, surface texturing has been the most utilized parameter for increasing the host-to-implant response. Recently, dental implant surfaces utilizing reduced length scale physico/chemical features (atomic and nanometric) have shown the potential to synergistically use both texture and the inclusion of bioactive ceramic components on the surface. Although surface modifications have been shown to enhance osseointegration at early implantation times, information concerning its long-term benefit to peri-implant tissues is lacking due to the reduced number of controlled clinical trials. Given the various implants/surfaces under study, the clinician should ask, founded on the basic hierarchical approach described for the in vitro, laboratory in vivo data, as well as the results of clinical studies to effectiveness before use of any dental implant

BACKGROUND: Widespread application of composite tissue allotransplantation has been impeded by risks of rejection and conventional immunosuppression. The authors have developed a nonhuman primate composite tissue allotransplantation model that demonstrated reliable and long-term success necessary to progress to preclinical studies. METHODS: Composite facial subunits (e.g., skin, muscle, and bone) were transplanted between mismatched cynomolgus monkeys. Vascular supply was based on the common carotid artery and external and internal jugular veins. Facial allografts were heterotopically transplanted to the recipient's lower abdomen with end-to-side anastomoses of the common carotid artery to the common femoral artery and of both the internal and external jugular veins to the common femoral vein. Animals received tacrolimus monotherapy. Grafts were inspected daily, submitted to biopsy regularly, and studied with magnetic resonance imaging. RESULTS: Thirteen transplants were performed. Two grafts based on the common carotid artery and only the internal jugular vein failed within 3 to 5 days because of venous thrombosis not related to rejection. Subsequent transplants included anastomoses of both the internal and external jugular veins to the common femoral vein without thromboses. Immunosuppression consisted of tacrolimus monotherapy and was tolerated without complications. Long-term success was achieved with rejection-free graft survival (60 to 177 days). CONCLUSIONS: The authors have developed the first successful model of facial composite tissue allotransplantation in a nonhuman primate. Technical requirements include preservation of both internal and external jugular venous outflow. Tacrolimus monotherapy permitted prolonged rejection-free graft survival without early complications. This model provides a platform for further investigation of composite tissue allotransplantation tolerance and requirements for indefinite survival.

Background: Ectopic beats are frequently associated with morphologic repolarization alterations of ensuing sinus beats. Less is known about repolarization duration alterations of post-ectopic sinus beats. In one patient who developed long QT and torsades de pointes upon exposure to a class III antiarrhythmic drug, and was later genotyped as being a carrier for long QT syndrome (LQTS) type 1, review of a pre-drug Holter monitor study revealed marked QT prolongation of post-ectopic sinus beats. In wondering whether this might be a common clue to "concealed" unexpressed LQTS, we realized that we must first characterize the range of post-ectopic QT prolongation present in normals. Prolongation beyond the upper limit of this range might then raise suspicion of possible LQTS and alter the antiarrhythmic drug selection process for the suppression of atrial fibrillation or other arrhythmias. Methods: Accordingly, we assessed the presence/degree of repolarization prolongation following premature ectopic impulses in 166 subjects with normal conduction intervals and normal repolarization on their resting 12-lead ECG, 75 of whom had no known associated cardiovascular disorder of any kind. That is, in our subjects, the maximal prolongation of the QT interval of the sinus beat following isolated ventricular and atrial premature complexes was characterized. Results: QT prolongation is common in post ectopic sinus beats. However, in our subjects the uncorrected QT interval of post-ectopic sinus beats never exceeded 480 ms in duration [which was much shorter than that seen (510-590 ms) in our gene carrier]. CONCLUSIONS: The QT interval in normal subjects may prolong following premature complexes but not to a value in excess of 480 ms.

BACKGROUND: Radioprotective modalities such as dose fractionation and pharmacologic agents such as amifostine have been used to protect bone and other types of normal tissue from the damaging effects of ionizing radiation without significantly impacting tumor kill. To better understand the cellular mechanism of radioprotection of osseous tissue, the authors sought to determine the effect of dose fractionation and amifostine on isolated osteoblasts. METHODS: Isolated primary rat calvarial osteoblasts were exposed to single or fractionated doses of ionizing radiation both with and without amifostine pretreatment. Endpoints included cell growth (n = 4), vascular endothelial growth factor production as measured by enzyme-linked immunosorbent assay (n = 3), and early osteodifferentiation as measured by a quantitative alkaline phosphatase assay (n = 3). RESULTS: Both dose fractionation and amifostine protect osteoblasts from the growth inhibitory effects of ionizing radiation. Fractionation but not amifostine was protective for hypoxia-induced vascular endothelial growth factor production (used as a surrogate marker of normal osteoblast function). Neither fractionation nor amifostine could prevent the inhibitory effect of ionizing radiation on normal osteoblast osteodifferentiation as measured by alkaline phosphatase production. CONCLUSIONS: Both dose fractionation and amifostine have valid roles as radioprotectants for osteoblasts and can act in an additive fashion. Radioprotection of cell growth and viability does not necessarily correlate with preservation of normal cellular function. Combination protocols involving dose fractionation and amifostine may be effective in radioprotection of osteoblasts and normal osseous tissue.

The aim of this collaborative public health study was to engage families, agencies, and programs in reducing secondhand smoke exposure in Central Harlem, New York City. Baseline interviews (n=657) and focus groups (n=4) were conducted with adult members of households with children who had asthma and asthma-like symptoms in the Harlem Children's Zone Asthma Initiative. The interviews concerned the prevalence and determinants of exposure of enrolled children to secondhand smoke. Key findings were that participants: (1) were generally aware of the hazards of secondhand smoke; (2) used strategies to reduce exposure to secondhand smoke in their homes; (3) believed that outdoor pollutants are sometimes just as bad for the health of their children as secondhand smoke; and (4) used smoking to provide stress relief and help diffuse otherwise volatile situations in their homes. The Harlem Smoke-Free Home Campaign was launched in October 2007 based in part on these findings.