Objectives/Hypothesis 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. Study Design Prospective animal study. Methods Six New Zealand white breeder rabbits weighing 3 to 5 kg were used in this study. A rigid endoscope and camera were used to document glottal configuration. Acoustic signals of modal and raised phonation were recorded and digitized. Two separate one-way repeated measures analysis of variance (ANOVA) tests were used to investigate within subject differences in phonation intensity and fundamental frequency between modal and raised phonation. Results Phonation intensity was 54.19 dB SPL (6.21 standard deviations [SD]) during modal phonation, and 60.31 dB SPL (5.68 SD) during raised phonation. Endoscopic images revealed a convergent glottis, with greater separation of the vocal folds during raised phonation. Results of ANOVA revealed a significant within subjects effect for phonation intensity (P = .011). Pairwise comparisons revealed that phonation intensity increased significantly during raised phonation, compared to modal phonation (P = .008). No differences in mean fundamental frequency were observed between phonation conditions. Conclusions Improved understanding of factors that control phonation output in the in vivo rabbit model will result in improved capabilities to match phonation dose across animals and provide immediate direction to future biochemical studies.
Objectives 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 PCR was performed to investigate the mRNA expression of Interleukin-1beta (IL-1β), Transforming Growth Factor beta-1 (TGFβ-1), 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 .016 to control for type I error. Significant main effects were further examined using Fisher’s Least Significant Difference. Results ANOVA revealed that there were differences for IL-1β, TGF-β1, and COX-2 between sham-control, modal phonation, and raised intensity phonation (p < .0001). Pairwise comparisons revealed that the expression of IL-1β, COX-2, and TGF-β1 increased significantly during raised intensity phonation, compared to modal phonation and sham-control (p < .0001). Conclusions 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.
Curcumin is a promising compound that can be used as a theranostic agent to aid research in Alzheimer’s disease. Beyond its ability to bind to amyloidal plaques, the compound can also cross the blood brain barrier. Presently, curcumin can be applied only to animal models, as the formulation needed for iv injection renders it unfit for human use. Here, we describe a novel technique to aerosolize a curcumin derivative, FMeC1 and facilitate its safe delivery to the brain. Aside from the translational applicability of this approach, a study in the 5XFAD mouse model suggested that inhalation exposure to an aerosolized FMeC1 modestly improved the distribution of the compound in the brain. Additionally, immunohistochemistry data confirms that following aerosol delivery, FMeC1 binds amyloidal plaques expressed in the hippocampal areas and cortex.
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 Ͻ .0001). Pairwise comparisons revealed that the expression of IL-1B increased significantly during raised intensity phonation, compared to modal phonation and sham-control (p Ͻ .0001); TGF-B1 increased significantly during raised intensity phonation, compared to modal phonation (p Ͻ .0001) and shamcontrol (p ϭ .002); and COX-2 increased significantly during raised intensity phonation, compared to modal phonation and sham-control (p Ͻ .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.
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.
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