Faculty Bibliography

The well-described detrimental effects of ionizing radiation on the regeneration of bone within a fracture site include decreased osteocyte number, suppressed osteoblast activity, and diminished vascularity. However, the biologic mechanisms underlying osteoradionecrosis and the impaired fracture healing of irradiated bone remain undefined. Ionizing radiation may decrease successful osseous repair by altering cytokine expression profiles resulting from or leading to a change in the osteoblastic differentiation state. These changes may, in turn, cause alterations in osteoblast proliferation and extracellular matrix formation. The purpose of this study was to investigate the effects of ionizing radiation on the proliferation, maturation, and cytokine production of MC3T3-E1 osteoblast-like cells in vitro. Specifically, the authors examined the effects of varying doses of ionizing radiation (0, 40, 400, and 800 cGy) on the expression of transforming growth factor-beta1 (TGF-beta1), vascular endothelial growth factor (VEGF), and alkaline phosphatase. In addition, the authors studied the effects of ionizing radiation on MC3T3-E1 cellular proliferation and the ability of conditioned media obtained from control and irradiated cells to regulate the proliferation of bovine aortic endothelial cells. Finally, the authors evaluated the effects of adenovirus-mediated TGF-beta1 gene therapy in an effort to 'rescue' irradiated osteoblasts. The exposure of osteoblast-like cells to ionizing radiation resulted in dose-dependent decreases in cellular proliferation and promoted cellular differentiation (i.e., increased alkaline phosphatase production). Additionally, ionizing radiation caused dose-dependent decreases in total TGF-beta1 and VEGF protein production. Decreases in total TGF-beta1 production were due to a decrease in TGF-beta1 production per cell. In contrast, decreased total VEGF production was secondary to decreases in cellular proliferation, because the cellular production of VEGF by irradiated osteoblasts was moderately increased when VEGF production was corrected for cell number. Additionally, in contrast to control cells (i.e., nonirradiated), conditioned media obtained from irradiated osteoblasts failed to stimulate the proliferation of bovine aortic endothelial cells. Finally, transfection of control and irradiated cells with a replication-deficient TGF-beta1 adenovirus before irradiation resulted in an increase in cellular production of TGF-beta1 protein and VEGF. Interestingly, this intervention did not alter the effects of irradiation on cellular proliferation, which implies that alterations in TGF-beta1 expression do not underlie the deficiencies noted in cellular proliferation. The authors hypothesize that ionizing radiation-induced alterations in the cytokine profiles and differentiation states of osteoblasts may provide insights into the cellular mechanisms underlying osteoradionecrosis and impaired fracture healing

This retrospective study evaluated tumour volume, estimated by computed tomography (CT), as a predictive factor in carcinoma of the tongue. Tumour volume was measured from pretreatment CT scans of 20 consecutive patients, followed up for at least 3 years, and this measurement was compared with tumour volume estimated from pathological specimens. T-stage and CT-derived tumour volume were compared with the clinical and pathological status of the nodes, and with the outcome of treatment.The measurement of tumour volume derived from CT correlated well with measurements derived from pathological examination, and tumour volume also predicted overall treatment failure. The disease-specific survival rate was 100% for patients with low-volume tumours (<13 cc) compared with 79% for those with stage T1 and T2 tumours.CT is a reliable way of measuring the volume of tumours in carcinoma of the tongue, and tumour volume is useful adjunct to the clinical tumour-node-metastases staging system.

Posttraumatic brachial plexus palsy is a severe injury primarily affecting young individuals at the prime of their life. The devastating neurological dysfunction inflicted in those patients is usually lifelong and creates significant socioeconomic issues. During the past 30 years, the surgical repair of these injuries has become increasingly feasible. At many centers around the world, leading surgeons have introduced new microsurgical techniques and reported a variety of different philosophies for the reconstruction of the plexus. Microneurolysis, nerve grafting, recruitment of intraplexus and extraplexus donors, and local and free-muscle transfers are used to achieve optimal outcomes. However, there is yet no consensus on the priorities and final goals of reconstruction among the various centers

OBJECT: The purpose of this study was to assess the efficacy, safety, associated complications, and outcome in patients with sagittal suture craniosynostosis in whom endoscopy-assisted wide-vertex craniotomy and 'barrel-stave' osteotomy were performed. METHODS: During a 4-year period, 59 patients with sagittal suture synostosis underwent endoscopy-assisted wide-vertex craniectomies, barrel stave-like osteotomies, and postoperatively were fitted with custom-made molding helmets. Data on operative time, blood loss, transfusion rates, hospital length of stay, complications, and hospital charges were collected prospectively. The mean patient age at the time of surgery was 3.7 months. The average blood loss was 31.8 ml; and only one patient required an intraoperative blood transfusion. Nine patients received transfusions of donor blood postoperatively. The mean operative time was 50 minutes, and all but three patients were discharged from the hospital the morning following surgery. There were no intraoperative complications. Normocephaly as well as normal cephalic indices were observed at latest follow up. CONCLUSIONS: The authors conclude that early treatment of infants with sagittal suture craniosynostosis by using minimally invasive, endoscopy-assisted wide-vertex craniectomies provides excellent results and a significantly lower morbidity rate than traditional calvarial vault reconstructive procedures

The purpose of this study was to determine the solidification rates for BoneSource (hydroxyapatite cement) mixed with sterile water versus BoneSource mixed with 0.25 ml of sodium phosphate. The average time for cure for BoneSource mixed with sterile water was 99 minutes, with a SD of 5.3 minutes. The average time for cure for BoneSource and sodium phosphate was 43 minutes, with a SD of 3.6 minutes (P < 0.0003). The average temperature for BoneSource in sterile water was 19.1 degrees C with a SD of 0.082, and the average temperature of BoneSource in sodium phosphate was 20.1 degrees C, with a SD of 0.1. Therefore, sodium phosphate shows that there is a significantly decreased amount of time required to solidify BoneSource and it remains isothermic throughout this reaction

The ability of immature animals and newborns to orchestrate successful calvarial reossification is well described. This capacity is markedly attenuated in mature animals and in humans greater than 2 years of age. Previous studies have implicated the dura mater as critical to successful calvarial reossification. The authors have previously reported that immature, but not mature, dural tissues are capable of elaborating a high expression of osteogenic growth factors and extracellular matrix molecules. These findings led to the hypothesis that a differential expression of osteogenic growth factors and extracellular matrix molecules by immature and mature dural tissues may be responsible for the clinically observed phenotypes (i.e., immature animals reossify calvarial defects; mature animals do not). This study continues to explore the hypothesis through an analysis of transforming growth factor (TGF)-beta3, collagen type III, and alkaline phosphatase mRNA expression. Northern blot analysis of total RNA isolated from freshly harvested immature (n = 60) and mature (n = 10) dural tissues demonstrated a greater than three-fold, 18-fold, and nine-fold increase in TGF-beta3, collagen type III, and alkaline phosphatase mRNA expression, respectively, in immature dural tissues as compared with mature dural tissues. Additionally, dural cell cultures derived from immature (n = 60) and mature dura mater (n = 10) were stained for alkaline phosphatase activity to identify the presence of osteoblast-like cells. Alkaline phosphatase staining of immature dural cells revealed a significant increase in the number of alkaline phosphatase-positive cells as compared with mature dural tissues (p < 0.001). In addition to providing osteogenic humoral factors (i.e., growth factors and extracellular matrix molecules), this finding suggests that immature, but not mature, dura mater may provide cellular elements (i.e., osteoblasts) that augment successful calvarial reossification. These studies support the hypothesis that elaboration of osteogenic growth factors (i.e., TGF-beta33) and extracellular matrix molecules (i.e., collagen type III and alkaline phosphatase) by immature, but not mature, dural tissues may be critical for successful calvarial reossification. In addition, these studies suggest for the first time that immature dural tissues may provide cellular elements (i.e., osteoblasts) to augment this process