Faculty Bibliography

Although clinical studies have identified scarring/fibrosis as significant risk factors for lymphedema, the mechanisms by which lymphatic repair is impaired remain unknown. Transforming growth factor -beta1 (TGF-beta1) is a critical regulator of tissue fibrosis/scarring and may therefore also play a role in the regulation of lymphatic regeneration. The purpose of this study was therefore to assess the role of TGF-beta1 on scarring/fibrosis and lymphatic regeneration in a mouse tail model. Acute lymphedema was induced in mouse tails by full-thickness skin excision and lymphatic ligation. TGF-beta1 expression and scarring were modulated by repairing the wounds with or without a topical collagen gel. Lymphatic function and histological analyses were performed at various time points. Finally, the effects of TGF-beta1 on lymphatic endothelial cells (LECs) in vitro were evaluated. As a result, the wound repair with collagen gel significantly reduced the expression of TGF-beta1, decreased scarring/fibrosis, and significantly accelerated lymphatic regeneration. The addition of recombinant TGF-beta1 to the collagen gel negated these effects. The improved lymphatic regeneration secondary to TGF-beta1 inhibition was associated with increased infiltration and proliferation of LECs and macrophages. TGF-beta1 caused a dose-dependent significant decrease in cellular proliferation and tubule formation of isolated LECs without changes in the expression of VEGF-C/D. Finally, the increased expression of TGF-beta1 during wound repair resulted in lymphatic fibrosis and the coexpression of alpha-smooth muscle actin and lymphatic vessel endothelial receptor-1 in regenerated lymphatics. In conclusion, the inhibition of TGF-beta1 expression significantly accelerates lymphatic regeneration during wound healing. An increased TGF-beta1 expression inhibits LEC proliferation and function and promotes lymphatic fibrosis. These findings imply that the clinical interventions that diminish TGF-beta1 expression may be useful in promoting more rapid lymphatic regeneration.

BACKGROUND: Although it is clear that radiation therapy can cause tissue injury, the degree of injury that is observed clinically can be highly variable. It is possible that variability in the methods by which ionizing radiation is delivered can contribute to some of the observed variability. Thus, the purpose of this study was to assess the effects of various fractionation schedules on the growth and differentiation potential of isolated mesenchymal stem cells in vitro. METHODS: Isolated mesenchymal stem cells (triplicate studies) were exposed to a dose of 12 Gy of ionizing radiation as a single dose, in two doses of 6 Gy, or in six doses of 2 Gy. Cellular proliferation and the potential for differentiation along the bone and fat lineage were assessed. Potential mechanisms for injury and protection were evaluated by analyzing the expression of p21 and manganese superoxide dismutase. RESULTS: Delivery of radiation in multiple doses confers significant radioprotection to mesenchymal stem cell proliferation and potential for differentiation. In contrast, delivery of 12 Gy of radiation as a single dose or as two equal doses of 6 Gy results in marked deficiencies in cellular proliferation and potential for multilineage cellular differentiation. CONCLUSIONS: The authors have demonstrated that even minor alterations in fractionation of radiation dose can result in significant effects on the potential of mesenchymal stem cells to differentiate. These findings imply that at least some of the variability in tissue damage after radiation therapy observed clinically may be attributable to differences in the delivery of ionizing radiation.

Hyperbaric oxygen (HBO) therapy is used in the treatment of osteoradionecrosis. Although HBO is thought to improve radiation-induced hypocellularity and bone tissue hypoxia, the precise effects of HBO on bone cells such as osteoblasts have not been described. In this study, our goal was to assess the effect of HBO on irradiated and nonirradiated primary osteoblast cultures and assess for changes in growth, apoptosis, cell cycle profile, differentiation, and gene expression. We found that daily HBO treatments caused a 24% decrease in cell growth after 9 days in culture. Hyperbaric oxygen negatively affects growth by inducing osteoblast apoptosis and cell cycle arrest. Hyperbaric oxygen leads to G1/S cell cycle arrest in unirradiated osteoblasts where as it causes G2/M arrest in cells that were previously irradiated with either 7 or 12 Gy of ionizing radiation. Although radiation was shown to have a dose-dependent inhibitory effect on early osteoblast differentiation as measured by alkaline phosphatase activity, HBO did not have a significant effect on osteoblast differentiation. Microarray analysis revealed that exposure to HBO leads to a differential expression of a variety of gene families including stress response pathways. In summary, although successive daily HBO treatments resulted in growth delay, osteoblast function as measured by the ability to produce alkaline phosphatase was not significantly affected. These data suggest that HBO does not have any positive effects on either normal or radiation-damaged osteoblasts in vitro.

BACKGROUND: Bilateral cleft lip-cleft palate is associated with nasal deformities typified by a short columella. The authors compared nasal outcomes of cleft patients treated with banked fork flaps to those of patients who underwent nasoalveolar molding and primary retrograde nasal reconstruction. METHODS: A retrospective review of 26 consecutive patients with bilateral cleft lip-cleft palate was performed. Group 1 patients (n = 13) had a cleft lip repair and nasal correction with banked fork flaps. Group 2 patients (n = 13) had nonsurgical columellar elongation with nasoalveolar molding followed by cleft lip closure and primary retrograde nasal correction. Group 3 patients (n = 13) were age-matched controls. Columellar length was measured at presentation and at 3 years of age. The number of nasal operations was recorded to 9 years. The Kruskal-Wallis and Tukey-Kramer tests were used for statistical analysis. RESULTS: Initial columellar length was 0.49 +/- 0.37 mm in group 1 and 0.42 +/- 0.62 mm in group 2. Post-nasoalveolar molding columellar length was 4.5 +/- 0.76 mm in group 2. By 3 years of age, columellar length was 3.03 +/- 1.47 mm in group 1, 5.98 +/- 1.09 mm in group 2, and 6.35 +/- 0.99 mm in group 3. Group 2 columellar length was significantly greater (p < 0.001) than that of group 1 and not statistically different from that of group 3 (p > 0.05). All group 1 patients (13 of 13) needed secondary nasal surgery. No nasoalveolar molding patients (zero of 13, group 2) required secondary nasal surgery. CONCLUSION: Nonsurgical columellar elongation with nasoalveolar molding followed by primary retrograde nasal reconstruction restored columellar length to normal by 3 years and significantly reduced the need for secondary nasal surgery.

This study sought to evaluate the sealing capability of the implant abutment connection of different dental implant systems. Five Nobel Replace select, Straumann and Intra-lock implants of approximately 4.5 mm diameter with their respective abutments were provided by the manufacturers. A calibration curve was determined by placing toluidine blue (TB) increments of 0.1 microL into 1.5 mL of distilled water and recording its absorbance in a spectrophotometer until reaching 0.7 microL. Then, 0.7 microL of TB was placed in the deepest portion of each implant's internal screw, the abutments were adapted to the implant according to the manufacturer's instructions and the specimens were placed in vials with 1.5 mL of distilled water. Spectrophotometric analysis was performed at 1, 3, 6, 24, 48, 72, 96 and 144 h. Statistical analysis was performed by One-way anova at 95% level of significance. The calibration curve was linear with respect to the TB amount in 1.5 microL distilled water (R(2) = 0.9961). All implant abutment systems presented an increase in absorbance as a function of time. As time elapsed in vitro, significantly higher amounts of TB was released from the Straumann and Nobel Replace Select connection systems (P < 0.0001). Leakage was significant between the groups. Despite controlled torquing, the seal between the implant body and the abutment could not be maintained in all three of the systems tested.

BACKGROUND: Three-dimensional photography of the breast offers new opportunities to advance the fields of aesthetic and reconstructive breast surgery. The following study investigates the use of three-dimensional imaging to assess changes in breast surface anatomy, volume, tissue distribution, and projection following medial pedicle reduction mammaplasty. METHODS: Preoperative and postoperative three-dimensional scans were obtained from patients undergoing short-scar medial pedicle breast reduction. Three-dimensional models were analyzed by topographical color maps, changes in the lowest point of the breast, surface measurements, and the point of maximal projection. Total breast volume and percentage volumetric tissue distribution in the upper and lower poles were also determined. RESULTS: Thirty patients underwent reduction mammaplasty (mean postoperative scan, 80 +/- 5 days). Color maps highlighted the majority of spatial changes in the central, upper poles. Reduction mammaplasty resulted in a significant decrease in the anteroposterior projection of the breast (6.3 +/- 0.2 postoperatively compared with 8.1 +/- 0.2 cm preoperatively; p < 0.01). The point of maximal breast projection was elevated in the cranial-caudal direction (4.8 +/- 0.4 cm; p < 0.01), with a corresponding elevation in the lowest point of the breast (4.8 +/- 0.5 cm; p < 0.01). Volumetric three-dimensional measurements identified a significant change in percentage tissue distribution after reduction mammaplasty (45 +/- 2 percent above the inframammary fold preoperatively versus 76 +/- 2 percent postoperatively; p < 0.01). CONCLUSIONS: This study is the first to demonstrate the technical feasibility and clinical utility of three-dimensional geometric data in medial pedicle breast reduction surgery. This novel approach suggests new opportunities to define long-term operative changes following various breast procedures