Faculty Bibliography

A 37-year-old woman who underwent a parotidectomy for acinic cell carcinoma was referred for correction of the resulting defect. As an assistant principal, the patient was often in public and, because she was somewhat self-conscious about her facial deformity, she sought reconstruction. Physical examination revealed a pre-auricular soft-tissue defect that measured approximately 5 x 5 cm. After consultation with the patient, microsurgical transfer of fat from the lower abdomen based on branches of the deep inferior epigastric vessels, rather than the deep inferior epigastric artery and vein itself, was planned. A vertical skin ellipse measuring 6 x 5 cm was raised from the right lower abdomen with a pedicle consisting of only a branch of the deep inferior epigastric artery and vein. The donor vessels were then microsurgically anastomosed to the superficial temporal artery and vein on the left side of the face. Two weeks postoperatively the flap was defatted, with removal of the skin-monitoring island. The patient continues to do well with a normal contour of the face and decreased anxiety secondary to correction of her facial deformity.

The ultrastructure of the early regenerative response in an end-to-side neurorrhaphy rat model was studied using transmission electron microscopy. The ipsilateral saphenous nerve was grafted to the sciatic nerve under the following conditions: Group 1, the epineurium and perineurium of the sciatic nerve remained intact; Group 2, an epineurial and perineurial window was created at the site of the lateral neurorrhaphy; Group 3, the same as in Group 2 and, in addition, the sciatic nerve sustained a partial neurectomy. Rats were perfused through the heart with fixative containing 2 percent paraformaldehyde and 2.5 percent glutaraldehyde in 0.1 M cacodylate buffer (pH 7.4) at 4, 8, 12, 24 and 48 hr after surgery. In Group 1, no regenerating axons were observed and the myelin sheath in the donor nerve did not demonstrate any degenerative changes through 48 hr. In Group 2, an increased diameter of the unmyelinated axons and growth cones was observed in the donor nerve proximal to the coaptation site after 12 hr. Degenerative changes in the myelin sheath were observed after 12 hr within the several layers under the coaptation site. In Group 3, many growth cone-like structures were observed in the area proximal to the coaptation site after 12 hr. After 24 hr, proximal regenerating axons elongated to the coaptation site and, at 48 hr, many regenerating nerves grew inside the Schwann cell basement membrane of the graft nerve. These results indicate that the perineurial window and nerve graft are the critical conditions for inciting nerve regeneration in the donor nerve

Poorly healing mandibular fractures and osteotomies can be troublesome complications of craniomaxillofacial trauma and reconstructive surgery. Gene therapy may offer ways of enhancing bone formation by altering the expression of desired growth factors and extracellular matrix molecules. The elucidation of suitable candidate genes for therapeutic intervention necessitates investigation of the endogenously expressed patterns of growth factors during normal (i.e., successful) fracture repair. Transforming growth factor beta1 (TGF-beta1), its receptor (Tbeta-RII), and the extracellular matrix proteins osteocalcin and type I collagen are thought to be important in long-bone (endochondral) formation, fracture healing, and osteoblast proliferation. However, the spatial and temporal expression patterns of these molecules during membranous bone repair remain unknown. In this study, 24 adult rats underwent mandibular osteotomy with rigid external fixation. In addition, four identically treated rats that underwent sham operation (i.e., no osteotomy) were used as controls. Four experimental animals were then killed at each time point (3, 5, 7, 9, 23, and 37 days after the procedure) to examine gene expression of TGF-beta1 and Tbeta-RII, osteocalcin, and type I collagen. Northern blot analysis was used to compare gene expression of these molecules in experimental animals with that in control animals (i.e., nonosteotomized; n = 4). In addition, TGF-beta1 and T-RII proteins were immunolocalized in an additional group of nine animals killed on postoperative days 3, 7, and 37. The results of Northern blot analysis demonstrated a moderate increase (1.7 times) in TGF-beta1 expression 7 days postoperatively; TGF-beta1 expression returned thereafter to near baseline levels. Tbeta-RII mRNA expression was downregulated shortly after osteotomy but then increased, reaching a peak of 1.8 times the baseline level on postoperative day 9. Osteocalcin mRNA expression was dramatically downregulated shortly after osteotomy and remained low during the early phases of fracture repair. Osteocalcin expression trended slowly upward as healing continued, reaching peak expression by day 37 (1.7 times the control level). In contrast, collagen type IalphaI mRNA expression was acutely downregulated shortly after osteotomy, peaked on postoperative days 5, and then decreased at later time points. Histologic samples from animals killed 3 days after osteotomy demonstrated TGF-beta1 protein localized to inflammatory cells and extracellular matrix within the fracture gap, periosteum, and peripheral soft tissues. On postoperative day 7, TGF-beta1 staining was predominantly localized to the osteotomized bone edges, periosteum, surrounding soft tissues, and residual inflammatory cells. By postoperative day 37, complete bony healing was observed, and TGF-beta1 staining was localized to the newly formed bone matrix and areas of remodeling. On postoperative day 3, Tbeta-RII immunostaining localized to inflammatory cells within the fracture gap, periosteal cells, and surrounding soft tissues. By day 7, Tbeta-RII staining localized to osteoblasts of the fracture gap but was most intense within osteoblasts and mesenchymal cells of the osteotomized bone edges. On postoperative day 37, Tbeta-RII protein was seen in osteocytes, osteoblasts, and the newly formed periosteum in the remodeling bone. These observations agree with those of previous in vivo studies of endochondral bone formation, growth, and healing. In addition, these results implicate TGF-beta1 biological activity in the regulation of osteoblast migration, differentiation, and proliferation during mandibular fracture repair. Furthermore, comparison of these data with gene expression during mandibular distraction osteogenesis may provide useful insights into the treatment of poorly healing fractures because distraction osteogenesis has been shown to be effective in the management of these difficult clinical cases

The treatment of brachial plexus avulsion lesions invariably involves the use of neurotization procedures. Although some of these therapeutic strategies have been used for the past 20 years to restore selective function to the injured extremity, the individual efficacy of these nerve transfers has not been measured objectively, thereby rendering the prognostication of outcomes for these techniques a major problem. Using a true global avulsion model, the present study compares outcomes of the various neurotization procedures for the first time. The strength of this experimental model is that each nerve transfer tested leads to a common terminal pathway involving a single target-namely, the biceps muscle. Thus, quantitative measurements of biceps restoration will provide strong clues to the power of axonal regrowth of that particular motor pool. This study also introduces the Terzis grooming test, a modified behavioral test that can be quantified and that can provide an overall functional scale in the assessment of outcome. Thirty-five Sprague-Dawley rats were divided into seven groups, with each group testing a different motor donor for biceps reinnervation. The ipsilateral brachial plexus was globally avulsed in all animals, with the exception of the ipsilateral C7 group, and the respective motor donor coapted in an end-to-end fashion to the musculocutaneous nerve. Functional outcomes were measured by the Terzis grooming test, electromyography, biceps muscle force measurements, motor end plate counts, and quantitative axonal morphometry. The values of the different parameters were expressed as a standard score on a common scale. The relative standings of each group on each parameter were compared. Superior outcome was observed in the phrenic, the hypoglossal, and the ipsilateral C7 groups

Mandibular distraction osteogenesis (DO) has become an important technique to lengthen the hypoplastic mandible and to reconstruct osseous defects after ablative surgery. The hallmark of successful DO is the creation of new bone within the distraction gap. Several anecdotal reports have described alternating compressing and lengthening protocols (i.e., 'pumping the regenerate') to augment regenerate bone formation. The purpose of this experiment was to analyze formally the effects of an alternating compression/distraction protocol with a traditional distraction protocol. Ten adult male rats underwent unilateral mandibular osteotomy with placement of a custom distractor. After a latency period of 5 days, distraction was initiated at a rate of 0.25 mm twice daily. Animals in the control group (N = 5) were distracted to a length of 5.0 mm for 10 days at a rate of 0.25 mm twice daily. In contrast, animals in the experimental group (N = 5) were distracted to a length of 2.5 mm (at a rate of 0.25 mm twice daily) for 5 days, then compressed 1.0 mm for a 2-day period, and redistracted to a length of 5.0 mm. Regenerate cross-sectional area was evaluated by computed tomography performed after 5 weeks of consolidation. Gross examination and histological analysis were performed by a panel of experienced reviewers. Radiological as well as histological analysis of regenerate cross-sectional area demonstrated no significant differences between experimental (i.e., 'pumped') and control groups. Both groups demonstrated excellent regenerate bone formation with no evidence of fibrous union. This study represents the first attempt to investigate the anecdotal technique of pumping the mandibular regenerate. The authors have demonstrated that pumping the regenerate leads to no substantial differences in radiological or histological appearance of regenerate bone formation