Erik R. Swanson

Effects of raised-intensity phonation on inflammatory mediator gene expression in normal rabbit vocal fold.

OBJECTIVE: To investigate the hypothesis that a transient episode of raised-intensity phonation causes a significant increase in vocal fold inflammatory messenger RNA (mRNA) expression in vivo. STUDY DESIGN: Prospective animal study. SETTING: Laboratory. SUBJECTS AND METHODS: Ten New Zealand White breeder rabbits received 30 minutes of experimentally induced modal or raised-intensity phonation, followed by a 30-minute recovery period. A separate group of five rabbits served as sham controls. Real-time polymerase chain reaction was performed to investigate the mRNA expression of interleukin 1β (IL-1β), transforming growth factor β (TGFβ1), and cyclooxygenase-2 (COX-2). Separate one-way analysis of variance (ANOVA) tests were used to investigate differences in gene expression across groups, with an appropriate alpha correction of 0.016 to control for type I error. Significant main effects were further examined using Fishers least significant difference. RESULTS: ANOVA revealed that there were differences for IL-1β, TGFβ1, and COX-2 between sham control, modal phonation, and raised-intensity phonation (P < 0.0001). Pairwise comparisons revealed that the expression of IL-1β, COX-2, and TGFβ1 increased significantly during raised-intensity phonation, compared to modal phonation and sham control (P < 0.0001). CONCLUSION: Results provided support for the hypothesis that a transient episode of raised-intensity phonation causes a significant increase in vocal fold inflammatory mRNA expression. Future studies will investigate the signal transduction pathways and mechanisms regulating the vocal fold inflammatory response. The long-term goal of these studies is to advance understanding of the molecular and cellular events underlying phonation-related tissue alterations.

Regenerative effects of basic fibroblast growth factor on extracellular matrix production in aged rat vocal folds.

Objectives We investigated acute changes in extracellular matrix (ECM) gene expression and histologic changes in the deposition of collagen and hyaluronan (hyaluronic acid; HA) after basic fibroblast growth factor (bFGF) treatment of the aged rat vocal fold. Methods For the polymerase chain reaction (PCR) experiments, we divided ten 18-month-old Sprague-Dawley rats into two groups that received serial injections of sham (saline solution) or bFGF (2 ng/uL) and euthanized them 2 weeks after the initial injection to investigate acute changes in ECM gene expression. We treated a separate group of 5 animals unilaterally and sacrificed them 4 weeks after the initial injection to investigate histologic changes in the deposition of collagen and HA. Results Real-time PCR revealed significantly up-regulated HA synthase (HAS)-2, HAS-3, matrix metalloproteinase (MMP)-2, and procollagen type I gene expression in the bFGF treatment group as compared to the sham treatment group. Histologic staining revealed significantly increased deposition of HA in the bFGF-treated vocal fold as compared to the sham-treated vocal fold. No differences in ECM collagen levels were observed between treatment sides. Conclusions Basic fibroblast growth factor induced the up-regulation of HAS-2, HAS-3, MMP-2, and procollagen type I. Histologically, aged vocal folds treated with bFGF revealed increased deposition of HA as compared to sham-treated vocal folds.

Regeneration of Aged Rat Vocal Folds using Hepatocyte Growth Factor Therapy

We investigated acute changes in extracellular matrix gene expression and histologic changes in the deposition of collagen and hyaluronan (HA) from hepatocyte growth factor (HGF) treatment of the aged rat vocal fold. We hypothesized that: 1) HGF induces matrix metalloproteinase gene expression, which might contribute to the downregulation of collagen; and 2) HGF induces hyaluronan synthase (HAS) gene expression, which might play a role in the upregulation of extracellular matrix HA.

Characterization of raised phonation in an evoked rabbit phonation model.

Our laboratory has developed an in vivo rabbit model to investigate the effects of phonation on expression and turnover of the vocal fold extracellular matrix. As a logical outgrowth of this research to include phonotrauma in the present study, we investigated the hypothesis that an increase in airflow rate delivered to the glottis produces a change in glottal configuration and an increase in mean phonation intensity.

Spontaneous otogenic posterior fossa pneumocephalus

Few cases of spontaneous pneumocephalus originating from the temporal bone are reported in the literature. We report a patient who presented to us with a sixto eight-week history of gradual decline in neurologic status. The patient had no past medical history that would put her at risk for the development of pneumocephalus; however, computerized tomography (CT) of the head revealed a 5by 3-cm collection of air in the right posterior fossa with an appreciable dehiscence of bone superior to the vestibular aqueduct. The patient underwent transmastoid retrolabyrinthine approach to the cerebellopontine angle (CPA) to allow for release of this pneumatocele. The patient subsequently demonstrated improvement in neurologic status, and postoperative CT revealed near complete resolution of pneumocephalus.

Analysis of Perturbation from Evoked Rabbit Phonation

OBJECTIVES: Adult idiopathic subglottic stenosis remains a rare entity. Fibrosis of the airway at the level of the cricoid results in narrowing of the airway and progressive dyspnoea. The aetiology remains uncertain but reflux and hormonal influences have recently been proposed. Multiple modalities including surgical excision, laser excision and balloon dilatation have been described. Additionally the adjunctive use of mitomycin or oestrogen has also been noted. From these options, cricotracheal resection and reconstruction for severe stenosis remains the modality providing the most favourable results. METHODS: We present our use of balloon dilatation in two cases as a management option with concomitant subglottic high frequency jet ventilation. Initially used in angioplasty, balloon dilatation has subsequently been successfully used for oesophageal dilatation and airway disorders. Control of ventilation during dilatation may be by endotracheal tube insertion and periodic removal, by supra-glottic jet ventilation, or our preferred modality of automated subglottic high frequency jet ventilation (Mistral model, Acutronic, Switzerland). RESULTS: The latter provides a clear visualisation of the stenotic region allowing sequential photodocumentation preand post-treatment with the additional ease of withdrawing and re-introduction of the catheter before and after dilation. The use of a hydrostatic balloon catheter (Cook Medical, USA) provides an optimal compliance curve that conforms to the stenotic region allowing radial dilation. CONCLUSIONS: Although this technique may not have the long-term efficacy of open surgical methods, it provides a non-invasive and relatively easily learned technique to manage this difficult condition.

Effects of raised phonation on vocal fold gene expression

OBJECTIVES: 1) Investigate the effects of modal and raised intensity phonation on messenger RNA (mRNA) expression of the vocal fold in an in-vivo rabbit model. 2) Collect preliminary data to provide direction to future biochemical studies. METHODS: Ten New Zealand white rabbits were assigned to receive experimentally induced modal or raised intensity phonation for 30 minutes. A separate control group of five rabbits received sham surgery. Vocal folds were harvested post-procedure and real-time PCR was used to investigate mRNA expression of Interleukin-1beta (IL-1B), Transforming Growth Factor-beta1 (TGF-B1), and Cyclooxygenase-2 (COX-2). One-way analysis of variance (ANOVA) tests were used to investigate differences in gene expression across groups. Alpha was adjusted to .016 to control for type I error. Significant main effects were further examined using Tukeys post-hoc tests. RESULTS: ANOVA revealed a significant main effect for IL-1B, TGF-B1, and COX-2 between groups (p .0001). Pairwise comparisons revealed that the expression of IL-1B increased significantly during raised intensity phonation, compared to modal phonation and sham-control (p .0001); TGF-B1 increased significantly during raised intensity phonation, compared to modal phonation (p .0001) and shamcontrol (p .002); and COX-2 increased significantly during raised intensity phonation, compared to modal phonation and sham-control (p .0001). CONCLUSIONS: Results provide preliminary data on the effects of raised intensity phonation on inflammatory mRNA expression in an in-vivo rabbit model. Ultimately, this model will be used to investigate clinical observations, such as toolong and too-loud, which are terms frequently used to describe the pathophysiology of dysphonia to patients.

R091: Stapedectomy Using the Nitinol Shape-Memory Prosthesis

PROBLEM: Complications associated with primary closure of persistent iatrogenic tracheocutaneous fistula (TCF). METHODS: A retrospective chart review was undertaken at a tertiary pediatric hospital between 1993 and 2005. The variables analyzed were the indications for tracheostomy, age at tracheostomy, length of cannulation and decannulation, associated comorbidities, and major and minor complications. Major complications required hospital admission and/or surgical intervention. Surgical repair involved fistulectomy with a three-layer primary closure and placement of a drain with 23-hour observation. All patients were extubated immediately following surgery. Drains were removed on the first postoperative day. RESULTS: Fifty patients were included in this study. The most common reasons for tracheostomy were prolonged intubation due to respiratory failure and subglottic stenosis. The mean patient age at closure was 4.7 years. The mean duration between decannualtion and fistula closure was approximately 1.2 years. There were one major and four minor complications. The major complication involved subcutaneous emphysema and mediastinal air requiring ICU admission. One patient with diabete mellitus developed a postoperative wound infection with dehiscence, which eventually closed by secondary intention. All complications presented no sooner than the seventh postoperative day. CONCLUSION: Excision and primary closure is a safe and effective procedure in the management of persistent TCF. Postoperative intubation is not routinely necessary when a passive drain is placed and the patient is observed for at least 23 hours. Delayed major and minor complications are still possible, however, necessitating close follow-up. Medical comorbidities at time of closure and original indication for tracheostomy are not related to the development of complications. SIGNIFICANCE: This represents one of the largest studies to evaluate the safety of primary closure of pediatric persistent TCF not utilizing postoperative intubation. This method of closure offers decreased recovery period and costs, and improved cosmesis.