Faculty Bibliography

Recent developments in gene therapy have shown promise in the treatment of soft-tissue repair, bone formation, nerve regeneration, and cranial suture development. This special topic article reviews commonly used methods of gene therapy and discusses their various advantages and disadvantages. In addition, an overview of new developments in gene therapy as they relate to plastic surgery is provided

BACKGROUND: We present a case of partial facial duplication in a male infant. METHODS: The clinical, radiological, and laboratory findings for this patient are described, followed by a review of the literature. RESULTS: Craniofacial duplication is a rare form of conjoined twinning and presents in a wide spectrum, from dicephalus to diprosopus to partial facial duplication. Many of these cases can be diagnosed prenatally. Prenatal assessment of our patient revealed only agenesis of the corpus callosum. CONCLUSIONS: The pathogenesis is believed to involve duplication of the notochord. Where there are more severe associated anomalies, the prognosis is poor. Partial facial duplication, as in our case, is associated with fewer anomalies, and the prognosis is better. Symmetry and an excess of tissue, rather than deficiency, favor a positive result

An overly elevated preauricular hairline, a flat malar region, and a shallow sternomandibular trough are examples of undesirable postoperative results in rhytidectomy. The author describes 10 preoperative decisions that will help to avoid such pitfalls. (Aesthetic Surg J 2002;22:551-553.)

Asthma is now the leading cause of school absence among children of color in impoverished urban neighborhoods. Environmental interventions have the potential to augment clinical approaches to asthma management by directly reducing exposure to environmental triggers (e.g., cockroaches, rodents, and mold). We implemented an apartment-based intervention to reduce exposures to indoor allergens among children living with asthma in 2 areas in New York City with rates of asthma morbidity and mortality that rank among the highest in the United States. Although the intervention phase of the present study is not yet complete, timely reporting of our field experiences may prove useful to other groups engaged in environmental intervention trials in urban communities

PURPOSE: The purpose of this project was to evaluate a novel technique for inducing osteogenesis through periosteal distraction in a rabbit model. MATERIALS AND METHODS: A periosteal distraction device was rigidly fixed to the lateral surface of the mandible in 10 adult rabbits. Periosteal distraction was started 7 days after placement of the periosteal distraction device. The periosteum was distracted 7 mm over 15 days. The unoperated, contralateral side of the mandible served as the control. The animals were killed at postoperative days 28, 35, 42, and 56. The specimens were then fixed, decalcified, and stained with hematoxylin and eosin. Histologic examination and histomorphometric analysis were performed on all specimens. RESULTS: Nine of 10 periosteal distraction devices remained rigidly fixed to the lateral surface of the mandible. On postoperative day 28, the histologic specimen from the experimental side showed periosteal proliferation and an increase in the number of osteoblasts. On postoperative days 35, 42, and 56, the experimental side showed an increase in the number of osteocytes per unit area, collagen fibers parallel to the vector of distraction, islands of osteoblasts surrounded by newly formed bone, and maturation of bone. An average of 2.86 +/- 0.56 mm of new bone height was formed. CONCLUSION: We report on a novel technique for generating bone by periosteal distraction. Our histologic analysis showed proliferation of the periosteum, an increase in the number of osteoblasts and osteogenesis

We investigated the effect of chronic administration of morphine on noxious stimulus-induced antinociception (NSIA) produced by intraplantar capsaicin injection. In the untreated (naive) rat, we previously found that NSIA depends on activation of dopamine, nicotinic acetylcholine, and mu- and delta-opioid receptors in nucleus accumbens. Rats chronically implanted with subcutaneous morphine pellets demonstrated tolerance to the antinociceptive effects of acute systemic morphine administration but did not show cross-tolerance to NSIA. Morphine pretreatment, however, significantly reduced NSIA dependence on intra-accumbens opioid receptors but not on dopamine or nicotinic acetylcholine receptors. As observed in naive rats, intra-accumbens microinjection of either the dopamine receptor antagonist flupentixol or the nicotinic receptor antagonist mecamylamine blocked NSIA in rats tolerant to the antinociceptive effects of morphine, but, in contrast to naive rats, intra-accumbens microinjection of either the mu-receptor antagonist Cys2,Tyr3,Orn5,Pen7 amide or the delta-receptor antagonist naltrindole failed to block NSIA. These findings suggest that although NSIA is dependent on nucleus accumbens opioid receptors in the naive state, this dependence disappears in rats tolerant to the antinociceptive effects of morphine, which may account for the lack of NSIA cross-tolerance. In separate experiments, intra-accumbens extracellular dopamine levels were measured using microdialysis. Dopamine levels increased after either capsaicin or systemic morphine administration in naive rats but only after capsaicin administration in morphine pretreated rats. Thus, intra-accumbens dopamine release paralleled antinociceptive responses in naive and morphine pretreated rats

Oral squamous cell carcinoma (SCC) is characterized by invasive growth and the propensity for distant metastasis. The expression of specific adhesion receptors promotes defined interactions with the specific components found within the extracellular matrix (ECM). We previously showed that the alpha v beta 6 fibronectin receptor is highly expressed in oral SCC. Here we forced expression of the beta 6 subunit into poorly invasive SCC9 cells to establish the SCC9 beta 6 cell line and compared these two cell lines in several independent assays. Whereas adhesion to fibronectin was unaffected by the expression of beta 6, migration on fibronectin and invasion through a reconstituted basement membrane (RBM) were both increased. Function-blocking antibodies to alpha v beta 6 (10D5) reduced both migration on fibronectin and invasion through an RBM, whereas anti-alpha 5 antibodies were effective only in suppressing migration on fibronectin, not invasion. Expression of beta 6 also promoted tumor growth and invasion in vivo and modulated fibronectin matrix deposition. When grown as a co-culture with SCC9 cells, peritumor fibroblasts (PTF) organized a dense fibronectin matrix. However, fibronectin matrix assembly was decreased in co-cultures of SCC9 beta 6 cells and PTF and this decrease was reversed by the addition of function-blocking anti-alpha v beta 6 antibodies. The expression of beta 6 also resulted in increased levels of matrix metalloproteinase 3. Addition of the general MMP inhibitor GM6001 to SCC9 beta 6/PTF co-cultures dramatically increased fibronectin matrix assembly in a similar fashion as incubation with anti-alpha v beta 6 antibodies. These results demonstrate that expression of beta 6 (1) increases oral SCC cell motility and growth in vitro and in vivo; (2) negatively affects fibronectin matrix assembly; and (3) stimulates the expression and activation of MMP3. We suggest that the integrin alpha v beta 6 is a key component of oral SCC invasion and metastasis through modulation of MMP-3 activity

We previously demonstrated that noxious peripheral stimulation (e.g. subdermal capsaicin injection in the hind paw) produces antinociception that is mediated by opioid receptors in nucleus accumbens. The current study used the trigeminal jaw-opening nociceptive reflex responses in the rat to assess the role of intra-accumbens mu-, delta- and kappa-opioid receptors in the antinociceptive effect of noxious stimulation and intra-accumbens opioid agonism. Whilst intra-accumbens injection of either the mu-receptor-selective antagonist Cys2,Tyr3,Orn5,Pen7amide (CTOP) or the delta-receptor-selective antagonist naltrindole blocked capsaicin-induced antinociception, neither the selective mu-agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO; 150 or 300 ng) nor the selective delta-agonist D-Pen2,5-enkephalin (DPDPE; 150 or 300 ng) alone induced antinociception. Simultaneous injection of DAMGO and DPDPE (150 ng each), however, produced significant antinociception. Capsaicin-induced antinociception was not blocked by the selective kappa-receptor antagonist nor-binaltorphimine, but was blocked by the kappa-agonist U69,593. U69,593 also antagonized the antinociceptive effect of the DAMGO/DPDPE combination. Thus, in nucleus accumbens, mu- and delta- but not kappa-opioid receptors contributed to capsaicin-induced antinociception; selective activation of individual receptor subtypes was insufficient, but coactivation of mu- and delta-opioid receptors induced antinociception, and kappa-receptors appeared to play an antianalgesic role in nucleus accumbens