Faculty Bibliography

The ability to avoid a subsequent bone graft makes the use of gingivoperiosteoplasty (GPP) at the time of cleft lip repair an attractive technique. The use of GPP, in combination with presurgical orthodontics, has been shown to result in successful bony union in the majority of patients. However, secondary bone grafting is still necessary in 30% to 40% of patients due to persistent alveolar bony defects. The elucidation of methods to improve the success rates of these procedures has been hampered by the lack of reproducible animal models. The purpose of this study was, therefore, to develop a rodent model of GPP that would facilitate the investigation of methods to improve osteogenesis in alveolar defects. We report a surgically produced rat model (9 x 5 x 3-mm alveolar defect) that is reproducible, inexpensive (relative to large-animal models), and simple technically. In addition, healing in this model occurs in a predictable manner during a 12-week period, thus enabling analysis of methods designed to accelerate or facilitate osseous regeneration

BACKGROUND: The role of cytokines in tumor regression is now well established. The major limitation for the clinical use of cytokines is the lack of a simple and effective protocol for the local and sustained delivery of cytokines to the tumor milieu. This study reports suppression of human head and neck squamous cell carcinoma (HNSCC) by human peripheral blood lymphocytes (HuPBL) following local, sustained delivery of interleukin-12 (IL-12) to tumors with biodegradable microspheres in a human/SCID mouse chimeric model. Materials and Methods Nondisrupted biopsy pieces (120 mg) of primary HNSCC were implanted s.c. into severe combined immunodeficient (SCID) mice and were expanded by serial passage in mice. Tumors were then titrated with different doses of allogeneic HuPBL by coengraftment of tumor pieces and HuPBL into the subcutis of SCID mice to determine whether the HuPBL possessed antitumor activity (the SCID/Winn model). The lymphocyte subsets that were responsible for the suppression of tumor engraftment were identified by selective depletion of the CD4+, CD8+, and CD56+ cells from the HuPBL prior to engraftment into mice. Attempts were then made to augment the antitumor activity of the HuPBL either by repeated intralesional bolus injections of recombinant human IL-12 (0.5 &mgr;g x 10 doses) or with a single dose of IL-12-loaded microspheres ( approximately 1.65 &mgr;g IL-12/mg microspheres, 2 mg microspheres/mouse). RESULTS: Successful engraftment of HNSCC was observed in 12 of 19 different patient samples. Normal histological architecture of tumor was maintained up to four serial passages in the SCID mice. After the first tumor engraftment, but not in subsequent passages, human immunoglobulin produced by plasma cells present in the tumor infiltrating lymphocyte population was detected in the mouse sera. Allogeneic human PBL displayed antitumor cytotoxic activity in a cell dose-dependent fashion when coengrafted with the tumors passaged in SCID mice. Lymphocyte subset depletion studies established that tumor suppression was dependent on both the CD8+ T lymphocytes and the CD56+ natural killer cells. Treatment of tumors with a single intralesional injection of IL-12-loaded microspheres was highly effective, resulting in the complete suppression of tumor engraftment in 50% of the mice. In contrast, treatment of tumors with repeated bolus IL-12 injections suppressed tumor engraftment only transiently and did not result in complete tumor rejection in any of the mice. CONCLUSION: The coengraftment of HNSCC and allogeneic lymphocytes into SCID mice provides a viable model with which to evaluate immunotherapeutic strategies for human cancer. The use of biodegradable microspheres for local sustained delivery of cytokines to augment lymphocyte mediated antitumor immunity within the tumor microenvironment provides a safer and simpler alternative to current cytokine immunotherapy protocols.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy with a high incidence of occult nodal metastases. MCC is believed to be similar in natural history to thick or ulcerated melanomas in its propensity for locoregional recurrence and early lymph node metastasis. Studies have shown that nodal status is statistically correlated to survival in MCC. Radiolocalization and superselective lymph node biopsy is a recent technique that has been proven to be of great value in evaluating the status of occult lymph node disease in malignant melanoma and breast cancer patients. OBJECTIVE: In previously untreated patients, an orderly progression of metastases is observed for both cutaneous carcinomas and malignant melanomas and is anticipated for MCC. METHODS/RESULTS. We present two patients with MCC of the head and neck who underwent simultaneous Mohs micrographic surgery and sentinel lymph node biopsy with intraoperative radiolocalization. CONCLUSION: Sentinel lymph node biopsy and intraoperative lymphoscintigraphy may prove to be a useful technique in evaluating occult nodal involvement and in limiting the potentially unnecessary morbidity of more comprehensive lymph node dissections in MCC patients who do not yet have metastatic involvement

This study was undertaken to evaluate whether 40 percent of the hypoglossal nerve, which showed optimal efficacy in restoring orbicularis oculi muscle (OOM) function after different percentages of partial neurectomy in a previous study would be effective after prolonged denervation time. Twenty Sprague-Dawley rats were divided into four groups. In first-stage surgery the left facial nerve of all animals was transected at the level of the stylomastoid foramen and main zygomatic branch. Group A (controls) consisted of animals with only left facial nerves transected (no repair). In Groups B, C, and D the facial nerve was transected and the facial musculature was denervated for a period of 4, 8, and 12 weeks respectively. During a second-stage procedure, a 40 percent neurectomy was performed on the hypoglossal nerve. Subsequently, a nerve transfer was performed by coaptations of a saphenous nerve graft to the neurectomized hypoglossal nerve and the main zygomatic branch of the facial nerve that innervated the OOM. Behavioral analysis of blink reflex, electrophysiology, and axon and motor end-plate counts in Groups B, C, and D showed superior results compared to Group A. There was no statistically significant difference observed among Groups B, C, and D (p > 0.05). Despite the diminished number of axons in the zygomatic branch and motor end-plates in the orbicularis oculi muscle after 12 weeks of denervation, there was still sufficient muscle target recovery to effect some eye closure in all groups except the controls. This study demonstrated in this model that the 40 percent partial neurectomy of the XII to VII component of the 'baby-sitter' procedure was effective even after prolonged denervation

Much has been written about the potential benefits in health promotion that are possible through partnerships between academic institutions and community-based organizations, but little practical advice has been provided on how to sustain these relationships when the original grant funds have been exhausted. Here we document our experiences in Harlem, New York City, a community with grave social, structural, and physical environmental inequities, and describe the successes and failings of a partnership now in its "adolescence" between researchers at the Joseph L. Mailman School of Public Health of Columbia University and community activists at West Harlem Environmental Action (WE ACT).

In this study, a simple protocol based on the rat femoral venous anastomosis was established to provide a quantitative representation of the progress. The learning curve is based on the patency rate in each consecutive group of five anastomoses. Two groups of surgeons were observed. The inexperienced group encountered a tough time in the first 25 anastomoses. However, the progress was fast and is represented by the steep slope of the curve. A plateau was reached whereby the avearge patency rate matches that of the experienced group. As expected, there was no learning curve for the experienced group. Despite every effort to attempt to maintain a perfect 100% patency on this model, the best achievable patency was only 88%. The results and its implication are discussed.

The deep nasolabial fold and other facial furrows and wrinkles have challenged the facial plastic surgeon. A variety of techniques have been used in the past to correct these troublesome defects. Advances in the last five years in new materials and design have created a subcutaneous implant that has excellent properties. This article reviews the development and use of Softform facial implant