Faculty Bibliography

The analysis of saliva has been proposed as a potentially rapid, non-invasive method to monitor and diagnose patients with oral disease. In this study we measured salivary endothelin-1 (ET-1) levels in patients diagnosed with oral squamous cell carcinoma (SCC) prior to treatment. We demonstrate significantly elevated salivary ET-1 levels in the oral SCC group (4.37+/-1.35pg/ml), relative to the control group (1.16+/-0.29pg/ml). ET-1 and ET-1 mRNA were also measured in oral SCC tissue specimens and compared to normal oral epithelial controls. The concentration of ET-1 in the oral SCC specimens was 17.87+/-4.0pg/ml and in the normal epithelial controls the concentration of ET-1 was 5.43+/-2.5pg/ml. ET-1 mRNA was significantly overexpressed in 80% (8/10) of the oral SCC specimens. Our results demonstrate the potential utility of salivary analysis for ET-1 levels to monitor patients at risk for oral SCC

BACKGROUND: Trauma patients with high-energy injuries often present with severe tissue damage that extends beyond the immediate zone of injury and requires recruitment of vascularized tissues from distant sites. The objective of this study was to evaluate the utility of the anterolateral thigh (ALT) flap for reconstruction of the traumatically injured lower extremity. METHODS: Prospective data were collected on all patients who underwent lower extremity reconstruction with an ALT flap during a 3.5-year period at a primary adult resource center (PARC). Demographics captured included age, gender, Injury Severity Score, mechanism of injury, and size of defect and complications. RESULTS: Fifty-six patients underwent a total of 59 ALT flap harvests during the study period. The majority of patients were male (75%) and sustained blunt injury (95%). The mean age was 37 +/- 14 years with a mean Injury Severity Score of 17.9 +/- 8. The mean flap size was 20.7 x 8.4 cm, with 64% harvested from the injured limb. Total flap success rate was 91.5%, with four total (6.7%) and one partial flap failure (1.7%). CONCLUSION: The ALT flap is a useful tool for trauma reconstruction in lower extremity salvage. We have shown that the ALT flap can be performed successfully in the traumatically injured patient even when harvested from the ipsilateral lower extremity.

BACKGROUND: Diabetics suffer from vascular dysfunction with increased risks of coronary artery disease and peripheral vascular disease secondary to an impaired ability to respond to tissue ischemia. Because endothelial progenitor cells are known to home to sites of ischemia and participate in new blood vessel growth, the authors examined the effects of diabetes on human endothelial progenitor cell function and peripheral tissue signaling in hypoxia, and determined whether these cells might be a useful cell-based therapy for diabetic vascular complications. METHODS: Circulating human endothelial progenitor cells from type 2 diabetic patients and controls were isolated and subjected to in vitro adhesion, migration, and proliferation assays (n = 5). Cell mobilization and recruitment were studied in vivo in diabetic and nondiabetic environments (n = 6). Exogenous human diabetic and normal cells were analyzed for therapeutic efficacy in a murine ischemia model (n = 6). RESULTS: Adhesion, migration, and proliferation of human diabetic endothelial progenitor cells in response to hypoxia was significantly reduced compared with controls. In diabetic mice, cell mobilization from the bone marrow and recruitment into ischemic tissue was significantly reduced compared with controls. Normal cells injected systemically as replacement therapy in a diabetic mouse increased but did not normalize ischemic tissue survival. CONCLUSIONS: These findings suggest that diabetes causes defects in both the endothelial progenitor cell and peripheral tissue responses to hypoxia. These changes in endothelial progenitor cell function and signaling offer a novel explanation for the poor clinical outcome of type 2 diabetics following ischemic events. Based on these findings, it is unlikely that endothelial progenitor cell-based cellular therapies will be able to prevent diabetic complications

The purpose of this study was to examine mandibular morphology and growth in patients with Crouzon, Pfeiffer, and Apert syndromes using posteroanterior cephalograms. Fifteen patients with Apert (n = 2), Crouzon (n = 11), and Pfeiffer (n = 2) (11 female, 4 male) syndrome were included in this study. All patients had serial posteroanterior cephalograms at 5, 10, and 15 years of age. The bicondylar width, bigonial width, bicondylar/bigonial ratio, and ramus to intercondylar plane angle for each patient were measured on the cephalograms and compared with age-match controls. An analysis of variance analysis was carried out to detect differences between patients and controls and sex differences between patients. In both male and female patients, there was a statistically significant reduction in bicondylar width compared with age-matched controls. Male patients also had a statistically significant increase in bigonial width compared with controls and female patients at 10 and 15 years. The resulting bicondylar/bigonial ratios were significantly reduced, and the ramus to intercondylar plane angles were significantly increased in both male and female patients compared with controls. Unlike previous reports of patients with syndromic synostosis, this study demonstrates that the mandible has significant morphologic and growth abnormalities, including constriction of bicondylar width with near normal bigonial width in female patients. These findings suggest a narrowing at the cranial base with resulting restriction of normal transverse mandibular growth at the condyle. The secondary nature of the mandibular finding is suggested by the near normal or increased transverse growth at the gonion in females and males, respectively. Consequently, the ramus appears torqued inward, forming a greater angle with the cranial base.

Chronic wounds, such as venous ulcers, are characterized by physiological impairments manifested by delays in healing, resulting in severe morbidity. Surgical debridement is routinely performed on chronic wounds because it stimulates healing. However, procedures are repeated many times on the same patient because, in contrast to tumor excision, there are no objective biological/molecular markers to guide the extent of debridement. To develop bioassays that can potentially guide surgical debridement, we assessed the pathogenesis of the patients' wound tissue before and after wound debridement. We obtained biopsies from three patients at two locations, the nonhealing edge (prior to debridement) and the adjacent, nonulcerated skin of the venous ulcers (post debridement), and evaluated their histology, biological response to wounding (migration) and gene expression profile. We found that biopsies from the nonhealing edges exhibit distinct pathogenic morphology (hyperproliferative/hyperkeratotic epidermis; dermal fibrosis; increased procollagen synthesis). Fibroblasts deriving from this location exhibit impaired migration in comparison to the cells from adjacent nonulcerated biopsies, which exhibit normalization of morphology and normal migration capacity. The nonhealing edges have a specific, identifiable, and reproducible gene expression profile. The adjacent nonulcerated biopsies have their own distinctive reproducible gene expression profile, signifying that particular wound areas can be identified by gene expression profiling. We conclude that chronic ulcers contain distinct subpopulations of cells with different capacity to heal and that gene expression profiling can be utilized to identify them. In the future, molecular markers will be developed to identify the nonimpaired tissue, thereby making surgical debridement more accurate and more efficacious

BACKGROUND: It is essential to critically assess bone deposition in midface distraction. The aim of this study was to characterize the quality and volume of bone deposition at specific osteotomy sites following midface distraction. METHODS: At approximately 6 months after distraction, computed tomographic scans with three-dimensional reconstruction were obtained on 10 craniosynostosis syndromal patients who had undergone LeFort III osteotomy and midface distraction. Patient age ranged from 37 to 109 months (mean, 63.7 months) and the distractions ranged from 7 to 15 mm. Both the reconstructed scans and axial cuts were independently evaluated by four blinded observers (two plastic surgeons, an orthodontist, and a radiologist) and graded for bone deposition in predetermined anatomical sites correlated to the osteotomy. RESULTS: The authors found that variable bony bridging occurred at all sites along the osteotomy, but bone deposition was most reliably seen at the pterygomaxillary buttress and nasofrontal junction. In addition, the medial orbital walls tended to show greater consistency in bone deposition than the lateral orbital walls, and deposition at the zygomatic arches was shown to be least likely to occur. The technique of evaluation and the clinically significant findings are discussed. CONCLUSIONS: Bony deposition occurs more reliably in the medial facial skeleton following LeFort III osteotomy, and osteotomy through the zygomatic body was more likely to result in deposition than one through the arch

Dapsone is a leprostatic agent commonly prescribed for the management of leprosy, malaria, and the immunosuppression-induced infections of Pneumocystis carinii and Toxoplasma gondii. In susceptible patients, methemoglobinemia, a potentially life-threatening event, can occur. We report a case of dapsone-induced methemoglobinemia which was observed during general anesthesia for the management of a fractured mandible. The pathophysiology, diagnosis, and management of dapsone-induced methemoglobinemia will be discussed.