Gender-related differences of hyaluronic acid distribution in the human vocal fold

OBJECTIVE: To quantify the distribution of hyaluronic acid (HA) within the normal human vocal fold and evaluate gender- and age-related differences. STUDY DESIGN: Prospective, cross-sectional study by age and gender groups using cadaveric vocal folds to study hyaluronic acid differences. METHODS: Twenty-five vocal fold halves obtained at autopsy were evaluated from nine adult male (age range, 34-52 y), seven adult female (age range, 21-41 y), four geriatric male (age range, 65-77 y), and five geriatric female (age range 65-82 y) subjects. Midmembranous vocal fold sections were stained for HA using the Muller-Mowry colloidal iron (acid mucopolysaccharide) stain with and without hyaluronidase. Digital imaging software was used to quantify the distribution of HA across the lamina propria at the vocal fold edge from superficial (subepithelial) to deep (vocalis muscle). RESULTS: A significant gender difference (P =.03) was noted in distribution when controlled for age. Combined, male subjects had a relatively constant distribution pattern throughout the depth of lamina propria. Female subjects showed relatively less HA in the first 15% of depth (most superficial) but showed more HA in the deeper 40% to 100% (toward vocalis muscle) than in male subjects. CONCLUSIONS: Important clinical implications may be extrapolated from our findings. First, relatively less HA in the most superficial area implies less protection from vibratory trauma and overuse and may explain in part why more female than male patients have phonotrauma to phonotraumatic lesions. Second, evaluating the distribution of HA in the normal human vocal fold allows more direction in our application of HA as a therapeutic lamina propria substitute in patients with voice disorders.     

Characteristics of age-related changes in cultured human vocal fold fibroblasts

Objectives/Hypothesis: Normal human vocal fold fibroblast (hVFF) primary cell lines are unavailable commercially and are very difficult to acquire, subsequently little is known about their characteristics. The purpose of this study was to compare the morphological and proliferation characteristics and gene expression of hVFFs from different aged donors. Study Design: In vitro. Methods: We developed three normal hVFF primary cell lines from donors aged 21 (21T), 59 (59T) and 79 (79T) years. We characterized their morphological features, proliferative abilities, telomere lengths, and their functional gene expression by quantitative real-time PCR. Results: The 21T line maintained a typical spindle shape until passage 14 whereas 59T and 79T changed morphology to wider, shorter cells at passage 7. Proliferation rates were constant for the 21T through passage 14; 59T's proliferative half-life was passage 9, whereas 79T maintained lower proliferation rates from passage 4. Gene expression levels for fibronectin, collagen I, collagen VI, procollagen I and elastin demonstrated similar patterns for all lines, however, relative amounts decreased with the age of donor. Telomere lengths did not show differences related with donor age. Conclusions: hVFF primary cultures have limited proliferative capacity. The morphology, proliferation, differentiation, and gene expression levels of VFF can be affected by age, but senescence patterns were similar across the ages.     

Acute vocal fold hemorrhage caught on video during office exam

This article presents a unique video of a laryngeal exam during which a vocal fold hemorrhage occurs. This patient had likely been suffering from intermittent vocal fold hemorrhages for the last decade due to a persistent vascular lesion and an underlying chronic cough. Laryngoscope, 2009     

Roles of hepatocyte growth factor and transforming growth factor beta1 in production of extracellular matrix by canine vocal fold fibroblasts

BACKGROUND/OBJECTIVES: When the lamina propria of the vocal fold is replaced by fibrosis after wound healing, it is difficult to restore an appropriate viscoelasticity of the vocal fold. To treat fibrotic scarring, material that reduces collagen deposition and increases soft amorphous substances, such as hyaluronic acid, is required. The potential use of hepatocyte growth factor (HGF) is intriguing. In this study, the authors examined canine vocal fold fibroblasts to determine how HGF contributes to the production of extracellular matrix. More specifically, the authors describe how the productions of hyaluronic acid, collagen type I, and fibronectin are associated with administration of HGF and transforming growth factor beta1. STUDY DESIGN: In vitro. METHODS: Fibroblasts were collected from the lamina propria of the vocal folds of five Beagles and were cultured with and without HGF or transforming growth factor beta1. The productions of hyaluronic acid, collagen type I, and fibronectin in supernatants culture were examined using ELISA. RESULTS: Hepatocyte growth factor stimulated hyaluronic acid production, reduced collagen type I production, and did not affect fibronectin production, while transforming growth factor beta1 stimulated the productions of all components. CONCLUSIONS: Collagen type I appears to be a major contributor in creation of fibrosis, and excessive fibronectin may stiffen the tissue. Since HGF reduced collagen type I production from fibroblasts and increased hyaluronic acid, HGF is considered to have therapeutic potential in prevention and treatment of the fibrosis of the vocal fold.