Faculty Bibliography

The discipline of limb lengthening has undergone numerous advances over the last few years. The neurologic complications surrounding this procedure are well established and described in the clinical setting, and can be deleterious for the patients in distraction osteogenesis protocols. The specific aims of the reported project were: 1) to determine the ability of IGF-I to enhance nerve regeneration in repaired nerves that are subjected to distraction only 4 weeks after nerve repair, and 2) to determine if a low dose of IGF-I applied at the time of the repair is neuroprotective to repaired nerves at this early time window. Forty adult male Sprague-Dawley rats were randomized into eight groups (n=5). Four groups (Groups A to D) underwent distraction of the femoral bone following sciatic nerve repair, and four groups served as controls (Groups E to H). Nerve reconstruction was achieved by end-to-end nerve repair (four groups, two with distraction [A, B] and two without [E, F]) and by interposition nerve grafting (four groups, two with distraction [C, D] and two without distraction [G, H]). A low dose of IGF-I was administered at the time of nerve microreconstruction. Distracted groups, despite the administration of IGF-I, demonstrated no signs of nerve regeneration, as assessed by sciatic functional index (SFI), electrophysiologic studies, and quantitative and qualitative histologic studies. Non-distracted groups showed signs of nerve regeneration. The 4-week time interval between nerve repair and distraction did not provide enough time for nerve regeneration to be completed, even if the repair was exposed to a low dose of IGF-1

The authors previously established an in vitro palate nonfusion model on the basis of a spatial separation between prefusion embryonic day 13.5 mouse palates (term gestation, 19.5 days). They found that an interpalatal separation distance of 0.48 mm or greater would consistently result in nonfusion after 4 days in organ culture. In the present study, they interposed embryonic palatal mesenchymal tissue between embryonic day 13.5 mouse palatal shelves with interpalatal separation distances greater than 0.48 mm in an attempt to 'rescue' this in vitro palate nonfusion phenotype. Because no medial epithelial bilayer (i.e., medial epithelial seam) could potentially form, palatal fusion in vitro was defined as intershelf mesenchymal continuity with resolution of the medial edge epithelia bilaterally. Forty-two (n = 42) palatal shelf pairs from embryonic day 13.5 CD-1 mouse embryos were isolated and placed on cell culture inserts at precisely graded distances (0, 0.67, and 0.95 mm). Positive controls consisted of shelves placed in contact (n = 6). Negative controls consisted of shelves placed at interpalatal separation distances of 0.67 mm (n = 6) and 0.95 mm (n = 7) with no interposed mesenchyme. Experimental groups consisted of embryonic day 13.5 palatal shelves separated by 0.67 mm (n = 11) and 0.95 mm (n = 12) with interposed lateral palatal mesenchyme isolated at the time of palatal shelf harvest. Specimens were cultured for 4 days (n = 19) or 10 days (n = 23), harvested, and evaluated histologically. All positive controls at 4 and 10 days in culture showed complete histologic palatal fusion. All negative controls at 4 days and 10 days in culture remained unfused. Five of six palatal shelves separated at 0.67 mm interpalatal separation distance with interposed mesenchyme were fused at 4 days, and all five were fused at 10 days. At an interpalatal separation distance of 0.95 mm with interposed mesenchyme (n = 12), no palates (zero of four) were fused at 4 days, but seven of eight were fused at 10 days. These data suggest that nonfused palatal shelves can be 'rescued' with an interposed graft of endogenous embryonic mesenchyme to induce fusion in vitro

The endothelium is a metabolically active secretory tissue, capable of responding to a wide array of environmental stimuli. Hypoxia and vascular endothelial growth factor (VEGF) are two components of the putative fracture microenvironment. This study investigated the role of hypoxia and VEGF on endothelial cell activation as it relates to the bone repair process. It was hypothesized that endothelial cells may have an important osteogenic role in fracture healing through the production of bone morphogenetic protein-2 (BMP-2), an osteogenic cytokine at the fracture site. Therefore, BMP-2 mRNA and protein expression in endothelial cells under hypoxia and/or VEGF treatment was studied. The authors observed a 2-fold to 3-fold up-regulation of BMP-2 mRNA expression in bovine capillary endothelial cells and human microvascular endothelial cells stimulated with hypoxia or rhVEGF. Furthermore, the combined effects of hypoxia and rhVEGF appeared to be additive on BMP-2 mRNA expression in bovine capillary endothelial cells. Actinomycin D and cycloheximide studies suggested that the increased mRNA expression was transcriptionally regulated. BMP-2 protein expression was up-regulated after 24 and 48 hours of treatment with either hypoxia or rhVEGF in bovine capillary endothelial cells. Surprisingly, the data suggest that endothelial cells may play not only an angiogenic role but also an osteogenic role by a direct stimulation of the osteoblasts, through the enhanced expression of a potent osteogenic factor, BMP-2, at the fracture site

Immediate breast reconstruction has important advantages over delayed reconstruction, including a shorter operative time and decreased psychological distress for the patient. However, the authors' experiences with the deep inferior epigastric perforator flap demonstrate variable aesthetic outcomes among patients who undergo radiation postoperatively. To establish an association between radiation and poor postoperative results, a matched-pairs analysis was conducted. Thirty irradiated patients were paired with 30 nonirradiated patients, according to age and body mass index. For each group, the incidence of fat necrosis, fibrosis/shrinkage, and flap contracture was recorded. In addition, an aesthetic evaluation was conducted to compare before-and-after images of 10 irradiated patients with those of 10 nonirradiated patients from similar time periods. The images were randomized and blindly evaluated by a panel of eight judges. A five-point scale was used to evaluate symmetry, aesthetic proportion, and the appearance of the superior pole. Statistical analysis demonstrated a significant difference in the score changes for irradiated and nonirradiated patients, according to all three criteria. Nonirradiated patient scores increased by one-half point, and irradiated patient scores decreased by one-half point. In addition, the incidences of fat necrosis, fibrosis, and flap contracture were all significantly higher among the irradiated group. These results suggest that when possible, reconstruction should be delayed until after radiation therapy is complete. Persons who smoke or are obese may be at particular risk for complications following radiation therapy

A long-term follow-up study of patients who underwent bilateral mandibular distraction is presented, and the results of patients with Treacher Collins syndrome and Nager syndrome are compared with results for other forms of congenital micrognathia. It was hypothesized that the factors responsible for the predetermined, syndrome-specific shape of the mandible in patients with Treacher Collins and Nager syndromes would alter the long-term results of linear (uniplanar) distraction of the mandible. Thus, over time, the mandibles would remodel to preoperative form while maintaining the increase in volume. To investigate this hypothesis, all patients treated with bilateral mandibular distraction who had at least 1.5 years of follow-up, including satisfactory cephalometric examinations, were retrospectively reviewed. Two groups were identified. Group 1 (n = 6) were Treacher Collins and Nager syndrome patients (ages, 2 to 13 years; mean, 5.2 years) and group 2 (n = 6) included other forms of bilateral, congenital micrognathia (ages, 1.5 to 19 years; mean, 8.4 years). Serial cephalometric measurements were recorded before distraction, after distraction, and at least 18 months after distraction. Mandibular mean linear distraction distance (as recorded on the device) averaged 24.5 mm in group 1 and 26.2 mm in group 2. In group 1, the antegonial angle (angle from the mandibular plane to the top of the antegonial notch) decreased after distraction by 3.8 degrees, and the antegonial notch height was reduced by 1.6 mm. The posttreatment morphologic change was modified significantly over time, with a 3.7-degree increase of the antegonial angle and a 1.2-mm deepening of the antegonial notch. In group 2, the immediate reduction in height of the antegonial notching was subtler; however, long-term recurrence of the antegonial notching was also observed. At the end of distraction, the mean group 1 gonial angle became 8 degrees more obtuse. In contrast, patients in group 2 developed a more acute angle (mean, 8 degrees). The mandibles of the Treacher Collins syndrome patients (group 1) maintained their more obtuse postdistraction gonial angle during the period of follow-up, whereas over time this change was reversed in group 2 patients. In conclusion, experience with bilateral mandibular distraction has demonstrated that long-term determination of mandibular form is more complex than either the amount of distraction or the direction of the distraction vector. The underlying genotype and the musculoskeletal milieu must be taken into account when planning distraction, as these factors tend to remodel the mandible into its preoperative shape over time, despite the fact that the increased mandibular volume and projection are maintained