Biomedical subjects

Nathan V Welham

Publications and source records attributed to Nathan V Welham.

8 recordsLinked to original sources

PubMed2006

Proteomic profiling of rat thyroarytenoid muscle.

PURPOSE: Proteomic methodologies offer promise in elucidating the systemwide cellular and molecular processes that characterize normal and diseased thyroarytenoid (TA) muscle. This study examined methodological issues central to the application of 2-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (2D SDS-PAGE) to the study of the TA muscle proteome using a rat model. METHOD: 2D SDS-PAGE was performed using 4 chemically skinned rat TA muscle samples. Gel images were analyzed and compared. Protein spot detection and matching were performed using computational image analysis algorithms only and computational image analysis followed by visual inspection and manual error correction. A synthetic master gel, constructed to control for uninteresting biological variation and technical artifact due to differences in protein loading and staining, was evaluated against its constituent gels. RESULTS: Manual error correction resulted in a consistent increase in the number of protein spots detected (between 5.8% and 40.9%) and matched (from 25.8% to 70.8%) across all gels. Sensitivity and specificity of the automatic (computational) spot detection procedure, evaluated against the manual correction procedure, were 74.1% and 97.9%, respectively. Evaluation of protein quantitation parameter values revealed statistically significant differences (p < .0001) in optical density, area, and volume for matched protein spots across gels. The synthetic master gel successfully compensated for these intergel differences. CONCLUSIONS: Valid and reliable proteomic data are dependant on well-controlled manageable variability and well-defined unmanageable variability. Manual correction of spot detection and matching errors and the use of a synthetic master gel appear to be useful strategies in addressing these issues. With these issues accounted for, 2D SDS-PAGE may be applied to quantitative experimental comparisons of normal and disease conditions affecting voice, speech, and swallowing function.

Algorithms↗

PubMed2004

Characterization of chronic vocal fold scarring in a rabbit model.

The purpose of the current study was to assess the histologic and rheologic properties of the scarred vocal fold lamina propria during a chronic phase of wound repair in a rabbit model. Eighteen rabbit larynges were scarred using a procedure that involved stripping the vocal fold lamina propria down to the thyroarytenoid muscle, using 3-mm microforceps. The approximate dimension of injury to the vocal fold was 3 x 1.5 x 0.5 mm [length x width x depth]. At 6 months postoperatively, histologic analysis of the scarred and control lamina propria in eight of these rabbits was completed for collagen, procollagen, elastin, and hyaluronic acid. Compared with control samples, scarred tissue samples revealed fragmented and disorganized elastin fibers. Additionally, collagen was significantly increased, organized, and formed thick bundles in the scarred vocal fold lamina propria. Measurements of the viscoelastic shear properties of the scarred and control lamina propria in the remaining 10 rabbits revealed increased elastic shear modulus (G') in 8 of 10 scarred samples and increased dynamic viscosity (eta') in 9 of 10 scarred samples. Although rheologic differences were not statistically significant, they revealed that on average, scarred samples were stiffer and more viscous than the normal controls. Histologic data are interpreted as indicating that by 6 months postinjury, the scarred rabbit vocal fold has reached a mature phase of wound repair, characterized by an increased, organized, and thick bundle collagen matrix. Rheologic data are interpreted as providing support for the potential role of increased, thick bundle collagen, and a disorganized elastin network on shear stiffness and dynamic viscosity in the chronic vocal fold scar. Based on these results, a 6-month postoperative time frame is proposed for future studies of chronic vocal fold scarring using the rabbit animal model.

Animals↗

PubMed2004

Vocal fatigue in young trained singers across a solo performance: a preliminary study.

This preliminary study aimed to measure changes in vocal function across a solo vocal performance task. Five participants, all trained singers, were required to complete a 10-min standard vocal warm-up, sing from a familiar repertoire for 40 min, and rest their voices for 10 min. Vocal function data were collected at 10-min intervals throughout the experimental session. Acoustic perturbation, sound pressure level and semitone pitch indices were employed as objective vocal function measures. A visual analogue scale and checklist of vocal fatigue symptoms were employed as self-report measures. Results revealed individual variation in vocal endurance, suggesting the importance of vocal history and repertoire factors in predisposing the onset of fatigue. Sound pressure level and pitch indices appeared more useful than perturbation indices in reflecting meaningful trends in vocal change.

Acoustics↗

PubMed2004

Hyaluronan levels in acute vocal fold scar.

OBJECTIVES/HYPOTHESIS: The objective was to measure the level of hyaluronan during the first 15 days after vocal fold biopsy in a rabbit model. STUDY DESIGN: Experimental, nonrandomized prospective study. METHODS: Twenty-eight rabbits underwent unilateral vocal fold biopsy. The contralateral vocal fold was preserved as a control sample. On days 3, 5, 10, and 15 after biopsy, hyaluronan levels in the injured and normal vocal folds were measured immunohistologically and with an ELISA assay. RESULTS: Hyaluronan levels in the injured vocal fold were lowest on day 3 and highest on day 5 after injury. Statistical analysis revealed that the injured vocal fold demonstrated significantly lower levels of hyaluronan on day 3 than on days 5, 10, and 15. On day 5, the injured vocal fold demonstrated significantly greater levels of hyaluronan than those observed on days 3, 10, and 15. Compared with the normal vocal fold, the injured vocal fold demonstrated significantly lower levels of hyaluronan on days 3, 10, and 15. No differences were observed between the injured and normal vocal fold on day 5, when the hyaluronan level was maximized in the injured vocal fold. CONCLUSION: Maximizing hyaluronan levels in the early stages of wound repair may have therapeutic potential for decreasing the incidence of vocal fold scar. Decreased hyaluronan levels may provide a less than optimal environment for normal tissue regeneration and may contribute to the formation of scar tissue in vocal fold lamina propria.

Animals↗

PubMed2004

Growth factor therapy for vocal fold scarring in a canine model.

Vocal fold scarring remains a therapeutic challenge. Hepatocyte growth factor (HGF) has strong antifibrotic activity and has proved to have therapeutic potential in restoration of scar tissues such as liver cirrhosis and lung fibrosis. The present study aimed to clarify the effects of HGF injection into scarred vocal folds in a canine model. Canine vocal folds were stripped unilaterally and treated with intracordal injection of saline solution (sham group), HGF (HGF group), or HGF with cultured autologous normal vocal fold fibroblasts (Fb/HGF group) 1 month after injury. The larynges were harvested 6 months after the initial injury and then subjected to vibratory and histologic examination. The results of vibratory examinations in the excised larynx setup revealed that phonation threshold pressure significantly increased and vocal efficiency was significantly reduced in all treated groups as compared to normal data obtained from normal canine larynges. However, the HGF group presented much better results than both the sham and Fb/HGF groups in terms of mucosal wave amplitude and incidence of vocal fold bowing, glottal incompetence, and phase asymmetry. The histologic data indicated a significant increase of collagen in both the sham and Fb/HGF groups, while normal levels of collagen were found in the HGF group. Tissue contraction of the lamina propria was also observed in both the sham and Fb/HGF groups, but was barely detectable in the HGF group. Although the HGF-treated vocal folds appeared to require more driving forces for vibration, HGF might prevent excessive collagen deposition and tissue contraction and thus reduce the effects of scarring on the vibratory properties of the vocal folds. From these data it is concluded that HGF has considerable potential in the treatment of vocal fold scarring.

Animals↗

PubMed2003

Vocal fatigue: current knowledge and future directions.

Vocal fatigue is a complex multifaceted clinical phenomenon. Several hypotheses exist concerning its underlying mechanism, and a range of empirical studies have examined its manifestation. This article reviews the literature pertaining to the nature, underlying processes, and salient features of vocal fatigue. First, vocal fatigue is defined, its major symptoms are discussed, and hypotheses concerning its primary physiological and biomechanical mechanisms are considered. Second, studies of experimentally induced vocal fatigue in humans are evaluated. Third, research investigating the clinical and occupational manifestations of vocal fatigue is discussed. Fourth, directions for ongoing research in this area are offered.

Biomechanical Phenomena↗

PubMed2003

Tracking outcomes after phonosurgery for sulcus vocalis: a case report.

Outcomes data after a surgical or behavioral intervention should be tracked until stability is reached. Often it is unclear how long patients should be followed and at what point an outcome can be considered stable. These issues have implications for treatment decision making, efficacy measurement, and the design of research studies. Vocal function data were collected 24 hours before and at 1, 6, and 12 months after phonosurgery for sulcus vocalis. One data series was collected daily during the first month after surgery, providing a unique opportunity to study voice changes in the immediate postoperative period. The different vocal function indices (acoustic, perceptual, videostroboscopic, aerodynamic, psychosocial) demonstrated a general pattern of improvement after intervention; however, they appeared to reach stability at different times. This report reinforces the value of following patients until complete outcome stability.

Adult↗

PubMed2003

Characterization of vocal fold scarring in a canine model.

OBJECTIVE: The objective was to assess the histological and viscoelastic shear tissue properties of the scarred vocal fold lamina propria at 2 and 6 months postoperatively in a canine model. STUDY DESIGN: Experimental, nonrandomized prospective study. METHODS: Six canine larynges were injured using a vocal fold stripping procedure. At 2 and 6 months postoperatively, histological analyses of the scarred and control lamina propria samples were completed for collagen, procollagen, elastin, and hyaluronic acid. RESULTS: In canines killed at 2 months, scarred tissue samples contained increased procollagen and decreased elastin. Elastin fibers in the scarred lamina propria were characteristically tangled and disorganized. In canines killed at 6 months, scarred tissue samples showed decreased elastin and increased collagen. Collagen fibers formed thick, disorganized bundles, and elastin fibers were disorganized throughout the entire scarred vocal fold lamina propria. Viscoelastic shear tissue measurements revealed increased stiffness and viscosity in one of three cases at 2 months and in all three cases at 6 months, indicating increased stiffness and resistance to shear flow during oscillatory shear deformation for scarred tissue samples. No differences were observed between the two postoperative times. CONCLUSIONS: Results indicated that viscoelastic tissue changes may take place before scar maturation in the scarred vocal fold lamina propria and that, although abundant collagen deposition may influence viscoelastic shear tissue properties, disorganization of collagen and elastin fibers, thick bundle collagen formation, or the interplay of several of these factors might also play a contributing role.

Animals↗