Faculty Bibliography

While the plasticity of excitatory synaptic connections in the brain has been widely studied, the plasticity of inhibitory connections is much less understood. Here, we present recent experimental and theoretical findings concerning the rules of spike timing-dependent inhibitory plasticity and their putative network function. This is a summary of a workshop at the COSYNE conference 2012.

Background MEN-2B syndrome is comprised of the association of MTC, PHEOs and multiple mucosal neuromas. The latter is a phenotype pathognomonic of this syndrome, but expressivity of the mucosal neuroma phenotype is less than 100%. The RET genotype-phenotype correlations are well recognized. MEN-2B is transmitted as an autosomal dominant trait. The germline point mutations are gain-of-function, causing RET activation. Most cases of MEN-2B have a codon 918 mutation (exon 16) of the intracellular tyrosine kinase domain of RET proto-oncogene. Recently, classification based on the pathogenesis and molecular correlation of the mutations involved in MEN-2A and MEN-2B places these mutations into a cluster 2 (kinase receptor signaling) and its downstream pathway: the mutated protein RET interacts with and alters the activity of several effector proteins of the receptor kinase intracellular signaling pathway. Case presentation 9 year old female presenting with 2 weeks of neck pain and left anterior neck mass. No history of radiation exposure to the head or neck; no family history of thyroid cancer or pheochromocytoma. VS: BP 90/60 mm Hg, HR 85 bpm, height 130 cm (-1.1 SD). Phenotype: long faces, lingual mucosal neuromas with involvement of the lips, pectus excavatum, and arachnodactyly. Thyroid exam: left, firm ~ 2cm x 2cm-sized thyroid nodule, not fixed. Laboratory studies: Calcitonin: 226 pg/mL (0-5)- high; Chromogranin A: 8 nmol/L (0 - 5) elevated; CEA: 4.4 ng/ml (0 - 4.7) borderline high. Thyroid US: left thyroid lobe hypoechoic complex nodule 1.5 x 1.8 x 2.8 cm with coarse calcifications. US-guided FNAB, cytology: atypical cells, salt/pepper chromatin, amyloid (+). Immunohistochemical staining (+) for calcitonin. Diagnosis: MTC (Medullary Thyroid Carcinoma). Pheochromocytoma screen: plasma free metanephrine: 33 pg/mL (0-62), pelvic MRI with/without contrast and I-123 MIBG were normal. Genetic study: germline mutation, RET M918T (highest aggressiveness). Total thyroidectomy with central compartment lymph node dissection was performed. Pathology: pT1b (> 1 cm, < 2 cm), no nodal extension. Postoperative Calcitonin: < 2.0 pg/mL. Conclusions Identification of the mucosal neuroma phenotype in a child should alert the clinician to the diagnosis of MTC, a rare aggressive cancer syndrome. The diagnosis of MTC is made from calcitonin measurements and FNAB. Confirmation by positive immunostaining of tumor tissue for calcitonin is necessary with exclusion of pheochromocytoma. The finding of a germline mutation (sporadic/hereditary) in the RET gene in proband necessitates genetic testing in all first-degree relatives. After surgical intervention (in accordance to genotype-phenotype stratification), surveillance with calcitonin levels (as a marker of persistent/recurrent disease), CEA, Chromogranin A, and thyroid US along with plasma free metanephrines is recommended

Traditional upper blepharoplasty typically involves resection of excess upper eyelid skin and muscle with or without fat excision. Well-established concepts in periorbital aging have been challenged by newer morphologic and histologic studies that have characterized the changes that occur in the various periorbital soft tissue components. Several modified or adjunctive techniques have recently emerged to improve esthetic outcomes in upper blepharoplasty. The authors review surgical technique in detail: nasal fat repositioning, orbicularis oculi preservation, increasing lateral upper eyelid fullness, lacrimal gland resuspension, internal brow elevation, and glabellar myectomy, along with complications and aftercare involved with procedures.

OBJECTIVES: To describe our technique of using septal bone grafts for correction and stabilization of caudal septal deviation and to evaluate the effectiveness of this technique in the treatment of the deviated caudal septum. METHODS: A retrospective review of 81 patients who underwent open septorhinoplasty using septal bone grafts for correction of a caudal septal deviation or deformity and nasal obstruction. We reviewed medical records to determine postoperative outcomes in nasal obstruction and caudal septal position. RESULTS: Of the 81 patients, we included 66 with adequate follow-up information in the analysis. Follow-up duration ranged from 1 to 72 (mean, 8) months. Postoperative examination revealed a midline septum in 55 of the 66 patients (83%). Fifty-seven patients (86%) reported resolution of nasal obstruction; 49 (74%) had a midline septum and resolved nasal obstruction at the longest follow-up. Nine patients (14%) reported postoperative nasal obstruction, of whom only 3 required revision surgery. CONCLUSION: Nasal septal bone grafts can be an effective tool in stabilizing severe cartilaginous deformities or deviations and correcting caudal septal deviation.

IMPORTANCE: Understanding age-related changes is important when considering cartilage-based implants or grafts during rhinoplasty and nasal reconstructive surgery. OBJECTIVE: To characterize the cellular and architectural changes in human nasal cartilage with aging. DESIGN: Laboratory study. PARTICIPANTS: Nasal septal cartilage was harvested from 50 consecutive patients undergoing septoplasty, rhinoplasty, or septorhinoplasty. INTERVENTION: Cartilage specimens were stained with hematoxylin-eosin (H&E) and safranin O for cartilage. MAIN OUTCOME MEASURES: A modified Mankin histologic grading scale was used to analyze each cartilage sample for H&E findings and safranin O staining. Higher H&E scores indicated more degenerative changes, while higher safranin O scores indicated reductions in proteoglycan content within the cartilage matrix, representing decreased active chondrocyte activity. Correlation between H&E and safranin O scores and patient age was determined. RESULTS: There was positive correlation between safranin O staining scores and age, with higher scores seen with advancing age (P = .01). A linear regression best-fit equation was determined to calculate a potential safranin O staining score for a given age. CONCLUSIONS AND RELEVANCE: We have quantitatively determined that advancing age is positively correlated with reductions in cartilage proteoglycan content and active cartilage growth. This finding not only enhances our current understanding of the natural changes that occur in cartilage with aging but may also affect surgical decision making when cartilage grafting is considered during functional, reconstructive, and aesthetic rhinoplasty. LEVEL OF EVIDENCE: NR.