Use of Costal Perichondrium as an Interpositional Graft for Septal Perforation Closure.

IMPORTANCE: Closure of septal perforations remains a technically difficult procedure to perform. OBJECTIVE: To assess the use of costal perichondrium as an interpositional graft to enhance closure of septal perforations using bilateral mucosal flaps and the effectiveness of the procedure. DESIGN, SETTING, AND PARTICIPANTS: This case series included all 51 consecutive patients presenting with septal perforations from January 1, 2006, to August 31, 2014, at a single institution. Mean (SD) follow-up was 19 (18) months. Patients with subtotal perforations did not have their perforations closed but underwent rhinoplasty with improved form and function. All patients underwent evaluation for changes in postoperative symptoms. INTERVENTIONS: Bipedicled mucoperichondrial flaps with placement of costal perichondrium between the repaired flaps. MAIN OUTCOMES AND MEASURES: Success rate of septal perforation closures and the clinical impact of the success of closure as experienced by the patient using the validated Nasal Obstruction Symptom Evaluation (NOSE) questionnaire (range, 0-20; higher scores indicate greater obstruction). RESULTS: Of the 51 patients (14 male; 37 female; median age, 42.6 [range, 17-69] years), 44 underwent attempted closure of the perforation at the time of the procedure. Closure was successful in 42 of the 44 patients (95%).Two patients had persistent perforations, one of which was subsequently closed in a secondary procedure. Twenty-six of 51 patients with septal perforations completed preoperative and postoperative NOSE questionnaires. The mean (SD) preoperative and postoperative NOSE scores were 12.6 (4.2; range, 6-20) and 3.4 (3.8; range, 0-12), respectively (P < .001). A mean (SD) improvement of 9.0 (3.9) points in the NOSE score was observed from patients after closure of their septal perforation, and 10 patients reported no symptoms (NOSE score, 0). CONCLUSIONS AND RELEVANCE: Costal perichondrium is an effective interpositional graft to be used in conjunction with the bilateral mucoperichondrial flaps for closure of septal perforations. Costal perichondrium may be used to aid in closure rates of septal perforations. LEVEL OF EVIDENCE: 4.

Surgical Adhesives in Facial Plastic Surgery.

In facial plastic surgery, attaining hemostasis may require adjuncts to traditional surgical techniques. Fibrin tissue adhesives have broad applications in surgery and are particularly useful when addressing the soft tissue encountered in facial plastic surgery. Beyond hemostasis, tissue adhesion and enhanced wound healing are reported benefits associated with a decrease in operating time, necessity for drains and pressure dressings, and incidence of wound healing complications. These products are clinically accessible to most physicians who perform facial plastic surgery, including skin grafts, flaps, rhytidectomy, and endoscopic forehead lift.

Pediatric nasal valve surgery: short-term outcomes and complications.

OBJECTIVES: To examine the short-term outcomes and complications of open nasal valve surgery in children under 16 years of age. STUDY DESIGN: case series and chart review study setting: an urban, tertiary, pediatric otolaryngology practice. METHODS: Children under 16 years of age who had undergone nasal valve surgery with cartilage grafting for functional indications were identified. Patients with cleft-related nasal deformities were excluded. Charts were reviewed for indications and short-term outcomes (patient satisfaction and postoperative complications within the first 90 days). A literature review assessed prior outcomes in adult nasal valve patients. RESULTS: Fifteen pediatric patients, 15 years old or younger, were identified as having undergone open nasal valve repair utilizing septal or auricular cartilage grafts. Patient age ranged from 6 to 15 years. Surgical indications were nasal obstruction with nasal valve stenosis related to either previous trauma (n=10), congenital deformity (n=3), iatrogenic injury (n=1) or hemangioma of infancy (n=1). All patients noted improvement of symptoms at the 90 day interval or later. There was one episode of self-limited epistaxis, which occurred on postoperative day 7 following splint removal. CONCLUSIONS: In children, an obstructive nasal breathing pattern may be caused by nasal valve collapse, which can be addressed with nasal valve surgery. This small series suggests that short-term results in children may be similar to those observed in the adult population. Pediatric nasal valve surgery outcomes have not been described previously; studies focused on long-term outcomes following pediatric nasal valve surgery are needed. LEVEL OF EVIDENCE: 4.

Cervical necrotizing fasciitis in children under two years of age.

We present two cases of life-threatening, necrotizing infections of the head and neck region, a rare infectious process in young children, that progressed to bacteremia and sepsis in two toddlers. To date there have been no reports of cervical necrotizing fasciitis in toddlers under two years of age. Immunocompromised children may be at higher risk for developing fulminent infections. Optimal management requires a combination of medical and surgical interventions. An aggressive surgical approach may be required to adequately clear the infection.

Identification of a molecular recognition role for the activation loop phosphotyrosine of the SRC tyrosine kinase.

A human cDNA phage display library screen, using a phosphopeptide designed to mimic the activation loop phosphotyrosine of the Src tyrosine kinase, has identified the N-terminal SH2 domain of the p85 regulatory subunit of phosphatidyl inositol-3 kinase (PI3K) as an interacting recognition domain. Activation loop phosphorylation is known to play a conformational role in kinase activation, but is largely not thought to play a role in protein/protein recognition. Affinity chromatography and biochemical evaluation in mouse fibroblast cells has confirmed the dependence of this interaction on both the Src activation loop phosphotyrosine and the N-terminal SH2 domain of PI3K.

Two-dimensional diversity: screening human cDNA phage display libraries with a random diversity probe for the display cloning of phosphotyrosine binding domains.

A random phosphopeptide probe (bio-pYZZZ) has been used for the isolation and identification of multiple SH2 domains from human cDNA-displaying phage libraries. In addition, on-phage analysis and quantification of binding affinities for these phage-displayed proteins has shown them to be functional domains, retaining the same characteristics as in their native state.

A dominant-negative thyroid hormone receptor blocks amphibian metamorphosis by retaining corepressors at target genes.

The total dependence of amphibian metamorphosis on thyroid hormone (T(3)) provides a unique vertebrate model for studying the molecular mechanism of T(3) receptor (TR) function in vivo. In vitro transcription and developmental expression studies have led to a dual function model for TR in amphibian development, i.e., TRs act as transcriptional repressors in premetamorphic tadpoles and as activators during metamorphosis. We examined molecular mechanisms of TR action in T3-induced metamorphosis by using dominant-negative receptors (dnTR) ubiquitously expressed in transgenic Xenopus laevis. We showed that T(3)-induced activation of T(3) target genes and morphological changes are blocked in dnTR transgenic animals. By using chromatin immunoprecipitation, we show that dnTR bound to target promoters, which led to retention of corepressors and continued histone deacetylation in the presence of T(3). These results thus provide direct in vivo evidence for the first time for a molecular mechanism of altering gene expression by a dnTR. The correlation between dnTR-mediated gene repression and inhibition of metamorphosis also supports a key aspect of the dual function model for TR in development: during T(3)-induced metamorphosis, TR functions as an activator via release of corepressors and promotion of histone acetylation and gene activation.

Chromatin disruption and histone acetylation in regulation of the human immunodeficiency virus type 1 long terminal repeat by thyroid hormone receptor.

The human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) controls the expression of HIV-1 viral genes and thus viral propagation and pathology. Numerous host factors participate in the regulation of the LTR promoter, including thyroid hormone (T(3)) receptor (TR). In vitro, TR can bind to the promoter region containing the NF-kappa B and Sp1 binding sites. Using the frog oocyte as a model system for chromatin assembly mimicking that in somatic cells, we demonstrated that TR alone and TR/RXR (9-cis retinoic acid receptor) can bind to the LTR in vivo independently of T(3). Consistent with their ability to bind the LTR, both TR and TR/RXR can regulate LTR activity in vivo. In addition, our analysis of the plasmid minichromosome shows that T(3)-bound TR disrupts the normal nucleosomal array structure. Chromatin immunoprecipitation assays with anti-acetylated-histone antibodies revealed that unliganded TR and TR/RXR reduce the local histone acetylation levels at the HIV-1 LTR while T(3) treatment reverses this reduction. We further demonstrated that unliganded TR recruits corepressors and at least one histone deacetylase. These results suggest that chromatin remodeling, including histone acetylation and chromatin disruption, is important for T(3) regulation of the HIV-1 LTR in vivo.