Faculty Bibliography

BACKGROUND: The purpose of this study was to investigate the relationship between soft-tissue and underlying skeletal structures before and after unilateral mandibular distraction osteogenesis. METHODS: The sample consisted of 11 patients (three girls and eight boys) with an average age of 4.6 years at the time of treatment. All patients had unilateral craniofacial microsomia (four right-sided and seven left-sided unilateral craniofacial microsomia) and all underwent unilateral mandibular distraction osteogenesis. Measurements were performed on frontal medical photographs and posteroanterior cephalograms at predistraction (time 1) and postdistraction (time 2) periods. Left and right ramus heights, skeletal midline deviation, and transverse occlusal plane were measured on the posteroanterior cephalograms and compared with the linear distances between the lip commissures and the orbital plane, the circumference of both sides of the faces, and the angulation of the oral commissure plane as recorded on the medical photographs, respectively. To reduce magnification error, ratios of affected to less affected sides of the mandibles and soft-tissue facial structures were selected and studied. RESULTS: A similar relationship was observed between soft-tissue and skeletal components. However, there was no 1:1 relationship between the changes in ramus height and improvement in parallelism of lip commissures to the orbital plane. CONCLUSIONS: A significant improvement in soft- and hard-tissue anatomy has been observed following unilateral distraction osteogenesis of the mandible. The relationship between the soft-tissue and skeletal correction was different for all patients because of the large range in severity of the craniofacial malformation. Greater skeletal deficiency requires more correction to achieve symmetry of both hard and soft tissue

There is no doubt that reduction mammoplasty (RM) results in significant improvement in a myriad of patient macromastia-related symptoms and other macromastia-related quality of life factors. Whether this improvement is correlated with the amount of tissue resected remains unknown because no previous study of RM has stratified patients by the amount of breast tissue resected. In this study, all patients were given a custom-designed questionnaire designed to evaluate their macromastia-related symptoms and other macromastia-related quality of life issues. Patients were then provided the same questionnaire at their final postoperative visit between 3 and 12 months after surgery. A total of 188 patients completed pre- and postoperative surveys. Before the initiation of this study, patients were stratified by the total weight of breast tissue resected into the following cohorts: 1000 g or less (66 patients), 1001 to 1500 g (55 patients), 1501 to 2000 g (30 patients), and greater than 2000 g (37 patients). RM resulted in significant improvement in all macromastia-related symptoms and quality of life factors analyzed (P < 0.000001). There were no significant differences (P > 0.05) in pre- and postoperative macromastia-related symptoms across our 4 groups with the exception of lower back pain (preoperative P = 0.026), shoulder pain (preoperative P = 0.014), and painful bra strap grooves (preoperative P = 0.0059). Analysis of the symptomatic burden of macromastia on several quality of life factors showed no significant differences (P > 0.05) in either the pre- or postoperative symptom scores across all groups in any of the categories assessed. This study demonstrates that women seeking breast reduction have a similar preoperative symptom burden across a wide range of breast sizes. Furthermore, the symptomatic improvement derived from RM is not significantly different between women of different breast sizes

The Rag1 and Rag2 proteins initiate V(D)J recombination by introducing site-specific DNA double-strand breaks. Cleavage occurs by nicking one DNA strand, followed by a one-step transesterification reaction that forms a DNA hairpin structure. A similar reaction allows Rag transposition, in which the 3'-OH groups produced by Rag cleavage are joined to target DNA. The Rag1 active site DDE triad clearly plays a catalytic role in both cleavage and transposition, but no other residues in Rag1 responsible for transesterification have been identified. Furthermore, although Rag2 is essential for both cleavage and transposition, the nature of its involvement is unknown. Here, we identify basic amino acids in the catalytic core of Rag1 specifically important for transesterification. We also show that some Rag1 mutants with severe defects in hairpin formation nonetheless catalyze substantial levels of transposition. Lastly, we show that a catalytically defective Rag2 mutant is impaired in target capture and displays a novel form of coding flank sensitivity. These findings provide the first identification of components of Rag1 that are specifically required for transesterification and suggest an unexpected role for Rag2 in DNA cleavage and transposition

Tissue ischemia promotes vasculogenesis through chemokine-induced recruitment of bone marrow-derived endothelial progenitor cells (EPCs). Diabetes significantly impairs this process. Because hyperglycemia increases reactive oxygen species in a number of cell types, and because many of the defects responsible for impaired vasculogenesis involve HIF1-regulated genes, we hypothesized that HIF1 function is impaired in diabetes because of reactive oxygen species-induced modification of HIF1alpha by the glyoxalase 1 (GLO1) substrate methylglyoxal. Decreasing superoxide in diabetic mice by either transgenic expression of manganese superoxide dismutase or by administration of an superoxide dismutase mimetic corrected post-ischemic defects in neovascularization, oxygen delivery, and chemokine expression, and normalized tissue survival. In hypoxic fibroblasts cultured in high glucose, overexpression of GLO1 prevented reduced expression of both the EPC mobilizing chemokine stromal cell-derived factor-1 (SDF-1) and of vascular epidermal growth factor, which modulates growth and differentiation of recruited EPCs. In hypoxic EPCs cultured in high glucose, overexpression of GLO1 prevented reduced expression of both the SDF-1 receptor CXCR4, and endothelial nitric-oxide synthase, an enzyme essential for EPC mobilization. HIF1alpha modification by methylglyoxal reduced heterodimer formation and HIF1alpha binding to all relevant promoters. These results provide a basis for the rational design of new therapeutics to normalize impaired ischemia-induced vasculogenesis in patients with diabetes

BACKGROUND:: Restoration of eyelid animation and aesthetics is a major component of the surgical management of facial paralysis. The authors' experience with the minitendon graft (a piece of split palmaris tendon graft) for lower eyelid suspension is presented. The effect of age, cause, denervation time, and total number of procedures performed in the eye region are analyzed. METHODS:: Fifty-eight patients with facial paralysis presenting with paralytic ectropion received the minitendon graft for lower eyelid suspension. Twenty-eight patients with concurrent lagophthalmos received the eye spring (n = 14) or gold weight (n = 14). Scleral show and lagophthalmos were measured by the same investigator (S.A.K.) using the methodology established by Terzis and Bruno. Outcomes were graded as follows: grade 1, no change; grade 2, minimal change; grade 3, moderate change; grade 4, good (more than half decrease); and grade 5, excellent, no scleral show or lagophthalmos. RESULTS:: Seventy percent of the patients were female, and in 40 percent the cause was developmental. There was clear improvement in both scleral show and lagophthalmos (p < 0.001). More than 80 percent of the outcomes were graded as good to excellent for both scleral show and lagophthalmos. There was correlation between age and cause, but neither affected outcomes. Denervation time had no influence on the results (p = 0.942). CONCLUSION:: The minitendon graft for lower eyelid suspension is an effective technique for repositioning the paralyzed lower eyelid regardless of patient age, denervation time, or cause of injury, and may be effectively combined with the eye spring or gold weight in the presence of lagophthalmos