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1.
Muscle Nerve ; 64(1): 104-108, 2021 07.
Article in English | MEDLINE | ID: mdl-33961288

ABSTRACT

INTRODUCTION/AIMS: Temporary vocal fold injection (VFI) is a common treatment for acute and subacute vocal fold paralysis (VFP). Laryngeal electromyography (LEMG) is useful for diagnosing neurogenic causes of VFP. This study evaluated whether the presence of VFI material prevents interpretation of LEMG in patients with acute and subacute VFP. METHODS: Patients with acute and subacute unilateral VFP (onset ≤6 mo) who underwent temporary VFI within 3 mo preceding LEMG were evaluated. A matched control group that did not undergo VFI was also studied. The LEMG team (laryngologist and electromyographer) performed and interpreted LEMG using a pre-specified protocol, including qualitative and quantitative motor unit analysis. RESULTS: Eighteen patients with VFI underwent LEMG successfully with interpretation of spontaneous activity and motor unit recruitment. Fourteen patients were seen in follow-up to determine accuracy of established LEMG prognosis. Seven of seven subjects with poor LEMG prognosis did not recover vocal fold motion. Five of seven subjects with fair LEMG prognosis recovered vocal fold motion. Findings were similar for the control group. DISCUSSION: VFI augmentation material did not prevent interpretation of meaningful LEMG data in patients with acute and subacute VFP, and accurate prognoses of vocal fold motion recovery were established.


Subject(s)
Cellulase/administration & dosage , Electromyography/methods , Vocal Cord Paralysis/diagnosis , Vocal Cord Paralysis/physiopathology , Vocal Cords/drug effects , Vocal Cords/physiopathology , Adult , Aged , Female , Humans , Larynx/drug effects , Larynx/physiopathology , Male , Middle Aged , Young Adult
2.
Clin Otolaryngol ; 46(1): 131-137, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32558170

ABSTRACT

OBJECTIVES: We assessed fibroblast growth factor (FGF) regenerative efficacy in an aged vocal fold rat model and confirmed it in a prospective clinical trial. DESIGN, SETTING, AND PARTICIPANTS: For animal experiments, 48 Sprague-Dawley rats were divided into two groups: 24 six-month-olds (young group) and 24 twenty-four-month-olds (old group). FGF was injected once a week thrice into the left vocal fold of the old group, dividing them into two sub-groups (injected [left] and uninjected [right]). Additionally, we conducted a prospective clinical trial for 38 patients with aged atrophic vocal fold. MAIN OUTCOME MEASURES: A month post-injection, excised larynx from the three groups was subjected to comparative histopathological (ratio of relative lamina propria to total vocal fold) and mRNA expression analysis (of procollagen I, hyaluronic acid synthase (HAS)-2 and matrix metalloproteinase (MMP)-2) by real-time PCR. We performed perceptual, stroboscopic, acoustic aerodynamic test and Voice Handicap Index survey prior to and 1, 6 and 12 months after FGF injection. RESULTS: In rats, the relative lamina propria ratio increased after FGF injection. Procollagen I mRNA level decreased, whereas that of HAS-2 and MMP-2 increased significantly in the injected compared to the uninjected old group. Enrolled patients showed improved subjective and objective voice parameters after FGF injection, and these were maintained for a year. Potential side effects were not observed. CONCLUSIONS: Animal experiments and prospective clinical trial suggest that FGF injection to vocal fold can significantly improve voice quality until one year, without complications, and is effective for aged atrophic vocal fold treatment.


Subject(s)
Aging/pathology , Dysphonia/prevention & control , Fibroblast Growth Factors/therapeutic use , Vocal Cords/drug effects , Vocal Cords/pathology , Aged , Animals , Atrophy , Disease Models, Animal , Dysphonia/etiology , Dysphonia/pathology , Female , Humans , Male , Middle Aged , Prospective Studies , Rats , Rats, Sprague-Dawley
3.
Mar Drugs ; 18(2)2020 Jan 24.
Article in English | MEDLINE | ID: mdl-31991543

ABSTRACT

Here, we investigated the effects of sex hormones on extracellular matrix (ECM)-related gene expression in the vocal fold lamina propria of ovariectomized (after ovary removal) rats and verified whether echinochrome A (ECH) exerts any therapeutic effects on ECM reconstitution after estrogen deficiency in ovariectomized rats. Sprague-Dawley female rats (9 weeks old) were acclimatized for a week and randomly divided into three groups (n = 15 each group) as follows: group I (sham-operated rats, SHAM), group II (ovariectomized rats, OVX), group III (ovariectomized rats treated with ECH, OVX + ECH). Rats from the OVX + ECH group were intraperitoneally injected with ECH at 10 mg/kg thrice a week after surgery for 6 weeks. And rats were sacrificed 6 weeks after ovariectomy. Estradiol levels decreased in OVX group compared with the SHAM group. ECH treatment had no effect on the levels of estradiol and expression of estrogen receptor ß (ERß). The evaluation of ECM components showed no significant changes in elastin and hyaluronic acid levels between the different groups. Collagen I and III levels were lower in OVX group than in SHAM group but increased in OVX + ECH group. The mRNA levels of matrix metalloproteinase (MMP)-1, -2, -8, and -9 were significantly higher in the OVX group than in the SHAM group, but decreased in the OVX + ECH group. Thus, changes were observed in ECM-related genes in the OVX group upon estradiol deficiency that were ameliorated by ECH administration. Thus, the vocal fold is an estradiol-sensitive target organ and ECH may have protective effects on the ECM of vocal folds in ovariectomized rats.


Subject(s)
Estradiol/deficiency , Extracellular Matrix/drug effects , Naphthoquinones/administration & dosage , Vocal Cords/drug effects , Vocalization, Animal/drug effects , Animals , Disease Models, Animal , Extracellular Matrix/metabolism , Female , Humans , Ovariectomy/adverse effects , Rats , Rats, Sprague-Dawley , Vocal Cords/cytology , Vocal Cords/physiology , Vocalization, Animal/physiology
4.
ORL J Otorhinolaryngol Relat Spec ; 82(4): 188-200, 2020.
Article in English | MEDLINE | ID: mdl-32268330

ABSTRACT

OBJECTIVE: Vocal fold scarring and laryngeal stenosis are major clinical challenges. Current drugs do not efficiently reduce scarring. We examined the antiproliferative and antifibrotic effects of cisplatin on primary human vocal fold fibroblasts (HVFFs). METHODS: HVFFs were cultured in vitro and identified by immunocytochemistry. The relative viability of HVFFs was analyzed by Cell Counting Kit-8 assays (CCK-8). The fibrogenic phenotype was induced by transforming growth factor-ß1 (TGF-ß1) and reversed by cisplatin as shown by immunocytochemistry. Real-time PCR and Western blotting assessed collagen III and I. Western blotting for Smad2, p-Smad2, Smad-3, p-Smad3 and caspase-3 were performed. RESULTS: CCK-8 results showed that cisplatin decreased the relative viability of HVFFs, and Western blots revealed elevation of the apoptosis-related protein caspase-3 in HVFFs. Cisplatin treatment reduced α-smooth muscle actin staining intensity in the presence of TGF-ß1. Real-time PCR revealed the downregulation of collagen III and I in cisplatin-treated HVFFs. The TGF-ß1-induced increased fibrogenic protein levels were decreased by cisplatin. Reduced levels were detected at late time points. CONCLUSIONS: Cisplatin induces antiproliferative and antifibrotic alterations in HVFFs. Cisplatin may prevent postoperative vocal fold scarring and laryngeal stenosis in patients treated with CO2 laser microsurgery and undergoing delayed wound healing.


Subject(s)
Antineoplastic Agents/pharmacology , Cisplatin/pharmacology , Fibroblasts/drug effects , Vocal Cords/drug effects , Vocal Cords/metabolism , Carcinoma, Squamous Cell , Cell Differentiation/drug effects , Cells, Cultured , Cicatrix , Collagen , Fibroblasts/pathology , Humans , Laryngectomy , Male , Middle Aged , Vocal Cords/pathology
5.
Int J Mol Sci ; 21(18)2020 Sep 10.
Article in English | MEDLINE | ID: mdl-32927894

ABSTRACT

Particulate matter (PM) is an environmental exposure factor that adversely affects human health. PM is a risk factor for various diseases. However, the mechanism by which PM affects the vocal folds (VF) has not yet been evaluated. Thus, we investigated the cytotoxic effects of PM on human vocal fold fibroblasts (hVFF) and the underlying signaling pathways. hVFF were isolated from human VF. The effect of PM on hVFF, and the underlying mechanism, were analyzed using Western blot, quantitative real-time polymerase chain reaction, and flow cytometry. In addition, a histological evaluation was performed in animal experiments. Cell proliferation decreased after the PM treatment. PM increased the expression of interleukin (IL)-6 and IL-1ß. The generation of reactive oxygen species (ROS) in PM-treated hVFF and subsequent activation of the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways were confirmed. Furthermore, PM increased the expression of fibrosis-related markers and induced the accumulation of collagen in the extracellular matrix. As a result, PM exposure significantly enhances the inflammatory response on VF through the ROS-mediated activation of the MAPK and NF-κB signaling pathways. In addition, PM promotes differentiation into myofibroblasts and induces fibrosis. These results suggest that PM triggers an inflammatory reaction through ROS production and causes VF fibrosis.


Subject(s)
Laryngeal Diseases/chemically induced , MAP Kinase Signaling System/drug effects , NF-kappa B/metabolism , Particulate Matter/adverse effects , Vocal Cords/drug effects , Cell Differentiation/drug effects , Extracellular Matrix/metabolism , Fibrosis , Humans , Laryngeal Diseases/metabolism , Laryngeal Diseases/pathology , Myofibroblasts , Primary Cell Culture , Reactive Oxygen Species/metabolism , Vocal Cords/metabolism , Vocal Cords/pathology
6.
Turk J Med Sci ; 49(5): 1577-1581, 2019 Oct 24.
Article in English | MEDLINE | ID: mdl-31652040

ABSTRACT

Background/aim: Phenytoin is an anticonvulsant drug which causes fibroblast proliferation, collagen synthesis, and an increase in epidermal growth factor. Therefore, the aim of the present study is to evaluate the effect of phenytoin injection on the wound healing process in rats with vocal cord injury by histopathological methods. Materials and methods: The vocal cords of 10 albino Wistar rats were damaged bilaterally; the left vocal cord was kept as the control group. Phenytoin was injected in the right vocal cord. Ten rats were sacrificed. The thickness of the lamina propria and density of the fibroblast and collagen were evaluated histopathologically. Results: Thickness of the lamina propria was 18.0 ± 7.1 µm in the control group, 65.5 ± 10.7 µm in the phenytoin group. The density of fibroblast and collagen were statistically lower in the control group compared the phenytoin group (P < 0.05). Conclusion: Phenytoin injection in rats after vocal cord injury significantly increased the thickness of the lamina propria and density of fibroblast and regular and mature collagen in the lamina propria. The findings in our study provide a feasible scientific view for adding phenytoin treatment to vocal cord surgeries in otolaryngology practice, but further studies are needed in order to evaluate the use of phenytoin in preventing the formation of scar tissue and possible effects on vocal cord vibration in humans after vocal cord injury.


Subject(s)
Phenytoin/administration & dosage , Vocal Cords/injuries , Wound Healing/drug effects , Animals , Injections, Intralesional , Phenytoin/pharmacology , Phenytoin/therapeutic use , Rats , Rats, Wistar , Vocal Cords/drug effects , Wounds and Injuries/drug therapy
7.
Arch Toxicol ; 92(5): 1741-1749, 2018 05.
Article in English | MEDLINE | ID: mdl-29445839

ABSTRACT

Mammalian attachment behaviors, such as crying, are essential for infant survival by receiving food, protection, and warmth from caregivers. Ultrasonic vocalization (USV) of infant rodents functions to promote maternal proximity. Impaired USV emission has been reported in mouse models of autism spectrum disorder, suggesting that USV is associated with higher brain function. In utero and lactational dioxin exposure is known to induce higher brain function abnormalities in adulthood; however, whether perinatal dioxin exposure affects behavior during infancy is unclear. Therefore, we studied the impact of dioxin exposure on USV emission in infant mice born to dams treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 0.6 or 3.0 µg/kg) on gestational day 12.5. On postnatal days 3-9, USVs of the offspring were recorded for 1 min using a microphone in a sound-attenuated chamber. The total USV and mean call durations in infant mice exposed to 3.0 µg/kg, but not 0.6 µg/kg, were shorter than those in the control mice. In addition, the percentages of complicated call types (i.e., chevron and wave) in mice exposed to 3.0 µg/kg were decreased. Dioxin-induced gene expression changes occurred in the brains of mice exposed to 3.0 µg/kg; however, body weight, motor activity, and vocal fold structure were not significantly affected. These results suggest that infant USV is a useful behavioral endpoint in developmental neurotoxicity assessment that may be used to evaluate effects of chemical exposure on the infant-caregiver interaction.


Subject(s)
Brain/drug effects , Polychlorinated Dibenzodioxins/toxicity , Vocalization, Animal/drug effects , Animals , Animals, Newborn , Basic Helix-Loop-Helix Transcription Factors/genetics , Brain/physiology , Dietary Exposure , Female , Gene Expression Regulation/drug effects , Lactation , Mice, Inbred C57BL , Motor Activity/drug effects , Pregnancy , Prenatal Exposure Delayed Effects , Receptors, Aryl Hydrocarbon/genetics , Ultrasonics , Vocal Cords/drug effects , Vocal Cords/pathology
8.
J Craniofac Surg ; 29(3): e322-e325, 2018 May.
Article in English | MEDLINE | ID: mdl-29485564

ABSTRACT

OBJECTIVE: To investigate effects of smoking cigarette on male and female larynges and compare them. METHOD: Eighteen adult Wistar Albino rats were included to study; 9 were male and 9 female. The exposure groups each contained 6 rats, and the control groups 3 rats. Six male constituted group 1 and 6 female constituted group 2. Group 1 and 3 were exposed to smoke. Group 2 and 4 were composed of 3 males and 3 females, respectively. Smoke from 10 cigarettes was delivered in each of the morning and afternoon daily for 1 month. At the end of 4 weeks, all rats were sacrificed and their larynges were evaluated histopathologically. RESULTS: Microscobic evaluation of epithelium of vocal folds revealed no significant difference between study groups. There was also no difference between study and control groups. Subepitelial tissue showed no difference between study groups but angiogenesis and inflammation were higher in study groups. Epithelial analysis of false vocal folds showed significant difference between study groups. Female epithelium showed more hyperplastic and metaplastic changes. CONCLUSION: Cigarette smoke damaged both the vocal folds and false vocal folds. The female false vocal folds were more susceptible to damage than the males.


Subject(s)
Cigarette Smoking/adverse effects , Vocal Cords/drug effects , Animals , Female , Hyperplasia , Larynx/pathology , Male , Metaplasia , Rats , Rats, Wistar , Sex Factors , Vocal Cords/pathology
9.
J Acoust Soc Am ; 142(4): EL401, 2017 10.
Article in English | MEDLINE | ID: mdl-29092550

ABSTRACT

This pilot study used acoustic speech analysis to monitor patients with heart failure (HF), which is characterized by increased intracardiac filling pressures and peripheral edema. HF-related edema in the vocal folds and lungs is hypothesized to affect phonation and speech respiration. Acoustic measures of vocal perturbation and speech breathing characteristics were computed from sustained vowels and speech passages recorded daily from ten patients with HF undergoing inpatient diuretic treatment. After treatment, patients displayed a higher proportion of automatically identified creaky voice, increased fundamental frequency, and decreased cepstral peak prominence variation, suggesting that speech biomarkers can be early indicators of HF.


Subject(s)
Acoustics , Edema/diagnosis , Heart Failure/complications , Phonation , Speech Acoustics , Speech Production Measurement , Vocal Cords/physiopathology , Voice Disorders/diagnosis , Voice Quality , Aged , Aged, 80 and over , Diuretics/therapeutic use , Edema/drug therapy , Edema/etiology , Edema/physiopathology , Female , Heart Failure/diagnosis , Heart Failure/drug therapy , Heart Failure/physiopathology , Humans , Lung/physiopathology , Male , Middle Aged , Phonation/drug effects , Pilot Projects , Predictive Value of Tests , Respiration , Treatment Outcome , Vocal Cords/drug effects , Voice Disorders/drug therapy , Voice Disorders/etiology , Voice Disorders/physiopathology , Voice Quality/drug effects
10.
J Surg Res ; 197(1): 32-8, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25818979

ABSTRACT

BACKGROUND: The goal of vocal fold wound healing is the reconstitution of functional tissue, including a structurally and functionally intact epithelium. Mechanisms underlying reepithelialization in vocal folds are not known, although it is suspected that healing involves the interplay between several growth factors. We used a three-dimensional human embryonic stem cell-derived model of vocal fold mucosa to examine the effects of one growth factor, exogenous epidermal growth factor (EGF), on wound healing. MATERIALS AND METHODS: A scratch wound was created in the in vitro model. Rate of wound healing, epidermal growth factor receptor (EGFR) activation, and cell proliferation after injury were analyzed with and without application of both exogenous EGF and an EGFR inhibitor, gefitinib. RESULTS: Wound repair after injury was significantly hastened by application of exogenous EGF (13.3 µm/h, ± 2.63) compared with absence of exogenous EGF (7.1 µm/h ± 2.84), but inhibited with concurrent addition of Gefitinib (5.2 µm/h, ± 2.23), indicating that EGF mediates wound healing in an EGFR-dependent manner. Immunohistochemistry revealed that EGFR activation occurred only in the presence of exogenous EGF. Although not statistically significant, increased density of Ki67 staining in the epithelium adjacent to the scratch wound was observed after treatment with EGF, suggesting a tendency for exogenous EGF to increase epithelial cell proliferation. CONCLUSIONS: Exogenous EGF increases the rate of wound healing in an EGFR-dependent manner in a three-dimensional stem cell-derived model of vocal fold mucosa. This model of wound healing can be used to gain insight into the mechanisms that regulate vocal fold epithelial repair after injury.


Subject(s)
Epidermal Growth Factor/pharmacology , Laryngeal Mucosa/injuries , Vocal Cords/injuries , Wound Healing/drug effects , Biomarkers/metabolism , Cell Line , Cell Proliferation/drug effects , Embryonic Stem Cells , Epidermal Growth Factor/administration & dosage , Epidermal Growth Factor/metabolism , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Humans , Immunohistochemistry , In Vitro Techniques , Laryngeal Mucosa/drug effects , Laryngeal Mucosa/physiology , Vocal Cords/drug effects , Vocal Cords/physiology , Wound Healing/physiology
11.
Ann Otol Rhinol Laryngol ; 124(7): 572-8, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25667215

ABSTRACT

OBJECTIVE: Corticosteroids may be beneficial in treating vocal fold scarring. Current drug delivery methods do not permit controlled corticosteroid release. Here we investigate the effects of poly-lactic-co-glycolic acid (PLGA) microparticles loaded with the corticosteroid dexamethasone in reducing collagen synthesis and inflammation in vocal fold fibroblasts treated with and without TGF-ß1. STUDY DESIGN: Experimental, in vitro study. METHODS: PLGA microparticles of differing molecular weight and terminating moieties were synthesized using a hydrogel template method. The release of dexamethasone was characterized from these microparticles over 4 days. Based on the release studies, ester-terminated low molecular weight PLGA microparticles were loaded with dexamethasone and applied to TGF-ß1 treated vocal fold fibroblasts for 4 days. Quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assays (ELISAs) were used to assess the effects of released dexamethasone on collagen synthesis and inflammatory mediators. RESULTS: COL3A1 and COL1A2 were significantly down-regulated after exposure to ester-terminated low molecular weight PLGA microparticles loaded with dexamethasone. The loaded microparticles also reduced interleukin-6 synthesis. CONCLUSION: These data show promise in using a PLGA microparticle-based delivery system to control dexamethasone release over 4 days. Our findings lay the groundwork for developing more effective treatments for vocal fold scarring.


Subject(s)
Dexamethasone/administration & dosage , Lactic Acid , Polyglycolic Acid , Transforming Growth Factor beta1/drug effects , Vocal Cord Dysfunction/drug therapy , Vocal Cords/pathology , Biocompatible Materials , Cells, Cultured , Cicatrix/drug therapy , Cicatrix/metabolism , Cicatrix/pathology , Collagen/biosynthesis , Collagen/genetics , Cytokines/biosynthesis , Cytokines/genetics , Delayed-Action Preparations , Drug Carriers , Enzyme-Linked Immunosorbent Assay , Fibroblasts/drug effects , Fibroblasts/metabolism , Gene Expression Regulation , Glucocorticoids/administration & dosage , Humans , Polylactic Acid-Polyglycolic Acid Copolymer , Polymerase Chain Reaction , Transforming Growth Factor beta1/metabolism , Vocal Cord Dysfunction/metabolism , Vocal Cord Dysfunction/pathology , Vocal Cords/drug effects , Vocal Cords/metabolism
12.
Am J Otolaryngol ; 36(2): 303-5, 2015.
Article in English | MEDLINE | ID: mdl-25481299

ABSTRACT

A 67-year old male underwent uneventful robotic-assisted thoracoscopic resection of a solitary pulmonary fibrous tumor. Immediately following extubation at the completion of the surgical procedure, the patient developed respiratory distress that did not resolve with treatment. Benadryl provided only temporary relief. Midazolam and hydromorphone were given for anxiolysis and analgesia respectively, which provided transient relief of symptoms. Propofol was given to decrease upper airway reflexes. Adequate reversal from nondepolarizing neuromuscular blockade was confirmed with nerve stimulator. A flexible laryngoscope was introduced nasally to visualize the vocal cords, which revealed intermittent tremulousness of the vocal cords, adduction of bilateral vocal cords to the midline, and minimal to absent opening with inspiration, without any apparent injury or blood, saliva, or vomit noted in or around the glottic opening. The patient was then given diazepam and reintubated. Given the patient's history of difficulty breathing after previous surgery and the lack of vocal cord movement, dystonic reaction to propofol was suspected. The patient remained intubated for two hours in the post-anesthesia care unit before being extubated uneventfully.


Subject(s)
Cholinergic Antagonists/administration & dosage , Propofol/adverse effects , Respiratory Insufficiency/etiology , Vocal Cord Dysfunction/chemically induced , Vocal Cords/drug effects , Acute Disease , Aged , Airway Extubation , Anesthetics, Intravenous/adverse effects , Dystonia/chemically induced , Dystonia/therapy , Follow-Up Studies , Humans , Intubation, Intratracheal , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Propofol/administration & dosage , Respiratory Insufficiency/physiopathology , Respiratory Insufficiency/therapy , Risk Assessment , Robotic Surgical Procedures/methods , Thoracic Surgery, Video-Assisted/methods , Treatment Outcome , Vocal Cord Dysfunction/diagnosis , Vocal Cord Dysfunction/therapy
13.
J Neurosci ; 33(14): 6070-80, 2013 Apr 03.
Article in English | MEDLINE | ID: mdl-23554488

ABSTRACT

Somatosensation plays an important role in the motor control of vocal functions, yet its neural correlate and relation to vocal learning is not well understood. We used fMRI in 17 trained singers and 12 nonsingers to study the effects of vocal-fold anesthesia on the vocal-motor singing network as a function of singing expertise. Tasks required participants to sing musical target intervals under normal conditions and after anesthesia. At the behavioral level, anesthesia altered pitch accuracy in both groups, but singers were less affected than nonsingers, indicating an experience-dependent effect of the intervention. At the neural level, this difference was accompanied by distinct patterns of decreased activation in singers (cortical and subcortical sensory and motor areas) and nonsingers (subcortical motor areas only) respectively, suggesting that anesthesia affected the higher-level voluntary (explicit) motor and sensorimotor integration network more in experienced singers, and the lower-level (implicit) subcortical motor loops in nonsingers. The right anterior insular cortex (AIC) was identified as the principal area dissociating the effect of expertise as a function of anesthesia by three separate sources of evidence. First, it responded differently to anesthesia in singers (decreased activation) and nonsingers (increased activation). Second, functional connectivity between AIC and bilateral A1, M1, and S1 was reduced in singers but augmented in nonsingers. Third, increased BOLD activity in right AIC in singers was correlated with larger pitch deviation under anesthesia. We conclude that the right AIC and sensory-motor areas play a role in experience-dependent modulation of feedback integration for vocal motor control during singing.


Subject(s)
Biofeedback, Psychology/physiology , Brain Mapping , Cerebral Cortex/physiology , Functional Laterality/physiology , Music , Singing/physiology , Adult , Anesthetics, Local/pharmacology , Cerebral Cortex/blood supply , Feedback , Female , Humans , Image Processing, Computer-Assisted , Lidocaine/pharmacology , Magnetic Resonance Imaging , Male , Oxygen , Pitch Perception/physiology , Regression Analysis , Time Factors , Vocal Cords/drug effects , Vocal Cords/physiology
14.
J Membr Biol ; 247(5): 441-50, 2014 May.
Article in English | MEDLINE | ID: mdl-24648011

ABSTRACT

The vocal fold epithelium is exposed to inhaled particulates including pollutants during breathing in everyday environments. Yet, our understanding of the effects of pollutants on vocal fold epithelial function is extremely limited. The objective of this study was to investigate the effect of the pollutant acrolein on two vocal fold epithelial mechanisms: ion transport and mucin (MUC) synthesis. These mechanisms were chosen as each plays a critical role in vocal defense and in maintaining surface hydration which is necessary for optimal voice production. Healthy, native porcine vocal folds (N = 85) were excised and exposed to an acrolein or sham challenge. A 60-min acrolein, but not sham challenge significantly reduced ion transport and inhibited cyclic adenosine monophosphate-dependent, increases in ion transport. Decreases in ion transport were associated with reduced sodium absorption. Within the same timeline, no significant acrolein-induced changes in MUC gene or protein expression were observed. These results improve our understanding of the effects of acrolein on key vocal fold epithelial functions and inform the development of future investigations that seek to elucidate the impact of a wide range of pollutant exposures on vocal fold health.


Subject(s)
Acrolein/toxicity , Air Pollutants/toxicity , Mucins/metabolism , Vocal Cords/drug effects , Vocal Cords/metabolism , Animals , In Vitro Techniques , Mucins/genetics , Swine
15.
Respirology ; 19(4): 531-7, 2014 May.
Article in English | MEDLINE | ID: mdl-24655302

ABSTRACT

BACKGROUND AND OBJECTIVE: Abnormal vocal cord movement may coexist with asthma and cause additional upper/middle airway obstruction. The condition may be a form of muscular dystonia that could contribute to asthma resistant to optimised treatments. Botulinum toxin causes temporary paralysis of muscle and may be an effective local treatment that improves asthma control. METHODS: In an observational study, we evaluated the benefits of unilateral vocal cord injection with botulinum toxin in 11 patients (total 24 injections). Subjects had asthma resistant to optimised treatment and abnormal vocal cord movement. Responses after botulinum toxin treatment were assessed using asthma control test (ACT) scores, vocal cord narrowing quantified by computerised tomography (CT) of the larynx and spirometry. Side-effects were recorded. RESULTS: ACT scores improved overall (9.1 ± 2.4 before and 13.5 ± 4.5 after treatment; difference 4.4 ± 4.2; P < 0.001). There was also an improvement in airway size on CT larynx (time below lower limit of normal at baseline 39.4 ± 37.63% and improved to 17.6 ± 25.6% after injection; P = 0.032). Spirometry was not altered. One patient experienced an asthma exacerbation but overall side-effects were moderate, chiefly dysphonia and dysphagia. CONCLUSIONS: Although a placebo effect cannot be ruled out, local injection of botulinum toxin may be an effective treatment for intractable asthma associated with abnormal vocal cord movement. Further mechanistic studies and a double-blind randomised controlled trial of botulinum toxin treatment are merited.


Subject(s)
Anti-Asthmatic Agents/therapeutic use , Asthma , Botulinum Toxins , Vocal Cord Dysfunction , Vocal Cords/drug effects , Acetylcholine Release Inhibitors/administration & dosage , Acetylcholine Release Inhibitors/adverse effects , Aged , Asthma/complications , Asthma/diagnosis , Asthma/diagnostic imaging , Asthma/drug therapy , Asthma/physiopathology , Botulinum Toxins/administration & dosage , Botulinum Toxins/adverse effects , Drug Resistance , Female , Humans , Injections, Intramuscular/methods , Male , Middle Aged , Respiratory Function Tests/methods , Tomography, X-Ray Computed/methods , Treatment Outcome , Vocal Cord Dysfunction/complications , Vocal Cord Dysfunction/diagnosis , Vocal Cord Dysfunction/drug therapy , Vocal Cord Dysfunction/physiopathology , Vocal Cords/diagnostic imaging , Vocal Cords/physiopathology
16.
Ann Otol Rhinol Laryngol ; 123(1): 71-6, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24574427

ABSTRACT

OBJECTIVES: Bicarbonate is critical for acid-base tissue homeostasis. In this study we investigated the role of bicarbonate ion transport in vocal fold epithelial defense to acid challenges. Acidic insults to the larynx are common in gastric reflux, carcinogenesis and metastasis, and acute inflammation. METHODS: Ion transport was measured in viable porcine vocal fold epithelium. First, 18 vocal folds were exposed to either the carbonic anhydrase antagonist acetazolamide or to vehicle. Second, 32 vocal folds were exposed to either a control buffer or a bicarbonate-free buffer on their luminal or basolateral surface or both. Third, 32 vocal folds were challenged with acid in the presence of bicarbonate-free or control buffer. RESULTS: The vocal fold transepithelial resistance was greater than 300 Ω*cm(2), suggesting robust barrier integrity. Ion transport did not change after exposure to acetazolamide (p > 0.05). Exposure to bicarbonate-free buffer did not compromise vocal fold ion transport (p > 0.05). Ion transport increased after acid challenge. This increase approached statistical significance and was the greatest for the control buffer and for the bicarbonate-free buffer applied to the basolateral surface. CONCLUSIONS: Bicarbonate secretion may contribute to vocal fold defense against acid challenge. Our data offer a potential novel role for bicarbonate as a therapeutic agent to reduce pH abnormalities in the larynx and prevent associated pathological changes.


Subject(s)
Acetazolamide/pharmacology , Bicarbonates/metabolism , Carbonic Anhydrase Inhibitors/pharmacology , Hydrochloric Acid/pharmacology , Laryngeal Mucosa/metabolism , Vocal Cords/metabolism , Animals , Homeostasis/drug effects , In Vitro Techniques , Ion Transport/drug effects , Laryngeal Mucosa/drug effects , Swine , Vocal Cords/drug effects
17.
Vopr Onkol ; 60(4): 510-3, 2014.
Article in Russian | MEDLINE | ID: mdl-25552074

ABSTRACT

The study included 62 patients with morphologically verified squamous cell carcinoma of laryngopharynx, stages T2-4N0-2M0. As a result of the treatment complete regression was recorded in 28.1 ± 7.9% of cases, partial regression--in 50.0 ± 8.8% of patients, and stabilization--in 21.9 ± 7.3% of cases. The total efficiency of therapy made up 78.1 ± 7.3%. Chemotherapy complications and radiation injuries did not exceed I-II grade by CTC-NCIC criteria and PTOG/EORTC scale, were easily stopped, did not affect the time periods of further treatment and had no considerable influence on the postoperative period. Conservative surgery was performed in 26% of cases. The total 5-year survival rate made up 65.4 ± 8.4%, relapse-free 5-year survival rate--60.6 ± 8.9%. The efficiency of the vocal function rehabilitation made up 73.9 ± 9.1%. Rehabilitation time was 21 ± 8.2 days.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/therapy , Head and Neck Neoplasms/therapy , Laryngeal Neoplasms/therapy , Laryngectomy , Neoadjuvant Therapy/methods , Pharyngeal Neoplasms/therapy , Pharyngectomy , Adult , Aged , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/rehabilitation , Chemoradiotherapy, Adjuvant/adverse effects , Disease-Free Survival , Female , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/rehabilitation , Humans , Kaplan-Meier Estimate , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/pathology , Laryngectomy/methods , Male , Middle Aged , Neoplasm Staging , Pharyngeal Neoplasms/mortality , Pharyngeal Neoplasms/pathology , Pharyngectomy/methods , Remission Induction , Speech , Squamous Cell Carcinoma of Head and Neck , Treatment Outcome , Vocal Cord Dysfunction/etiology , Vocal Cord Dysfunction/rehabilitation , Vocal Cords/drug effects , Vocal Cords/radiation effects , Vocal Cords/surgery
18.
Ann Otol Rhinol Laryngol ; 133(1): 87-96, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37497827

ABSTRACT

OBJECTIVES/HYPOTHESIS: Systemic glucocorticoids (GC)s are employed to treat various voice disorders. However, GCs have varying pharmacodynamic properties with adverse effects ranging from changes in epithelial integrity, skeletal muscle catabolism, and altered body weight. We sought to characterize the acute temporal effects of systemic dexamethasone and methylprednisolone on vocal fold (VF) epithelial glucocorticoid receptor (GR) nuclear translocation, epithelial tight junction (ZO-1) expression, thyroarytenoid (TA) muscle fiber morphology, and body weight using an established pre-clinical model. We hypothesized dexamethasone and methylprednisolone will elicit changes in VF epithelial GR nuclear translocation, epithelial ZO-1 expression, TA muscle morphology, and body weight compared to placebo-treated controls. METHODS: Forty-five New Zealand white rabbits received intramuscular injections of methylprednisolone (4.5 mg; n = 15), dexamethasone (450 µg; n = 15), or volume matched saline (n = 15) into the iliocostalis/longissimus muscle for 6 consecutive days. Vocal folds from 5 rabbits from each treatment group were harvested at 1-, 3-, or 7 days following the final injection and subjected to immunohistochemistry for ZO-1 and GR as well as TA muscle fiber cross-sectional area (CSA) measures. RESULTS: Dexamethasone increased epithelial GR nuclear translocation and ZO-1 expression 1-day following injections compared to methylprednisolone (P = .024; P = .012). Dexamethasone and methylprednisolone increased TA CSA 1-day following injections (P = .011). Methylprednisolone decreased body weight 7 days following injections compared to controls (P = .004). CONCLUSIONS: Systemic dexamethasone may more efficiently activate GR in the VF epithelium with a lower risk of body weight loss, suggesting a role for more refined approaches to GC selection for laryngeal pathology.


Subject(s)
Glucocorticoids , Vocal Cords , Animals , Rabbits , Body Weight , Dexamethasone/pharmacology , Glucocorticoids/pharmacology , Injections, Intramuscular , Laryngeal Muscles , Methylprednisolone/pharmacology , Vocal Cords/drug effects , Vocal Cords/pathology
19.
Med Sci Monit ; 19: 276-82, 2013 Apr 17.
Article in English | MEDLINE | ID: mdl-23591165

ABSTRACT

BACKGROUND: Voice disorders resulting from glottic insufficiency are a significant clinical problem in everyday phoniatric practice. One method of treatment is injection laryngoplasty. Our study aimed to assess the voice quality of patients treated with hyaluronic acid injection into the vocal fold. MATERIAL AND METHODS: We studied 25 patients suffering from dysphonia, conducting laryngological and phoniatric examination, including videostroboscopy and acoustic voice analysis, before the operation and 1, 3, and 6 months later. RESULTS: In all cases there was complete or almost complete glottic closure after the operation. One month after the procedure, videostroboscopic examination revealed reappearance of vocal fold vibration in 8 cases; after 3 months this had risen to 15 cases. Perceptual voice quality (as assessed by the GRBAS scale) in patients with glottic insufficiency was improved. The most significant improvement was obtained 1 month after surgery (p=0.0002), and within the next months further statistically significant improvements (p=0.000002) were noted. Multidimensional voice analysis showed statistically significant and rapid improvement in frequency parameters, especially vFo. Other parameters were also improved 3 and 6 months after surgery. CONCLUSIONS: Injection of hyaluronic acid into the vocal fold improves phonatory functions of the larynx and the quality of voice in patients with glottic insufficiency. It may be a safe and conservative method for treatment of voice disorders. Hyaluronic acid injection to the vocal fold is an easy, effective, and fast method for restoration of good voice quality.


Subject(s)
Hyaluronic Acid/administration & dosage , Hyaluronic Acid/pharmacology , Vocal Cord Paralysis/drug therapy , Vocal Cords/drug effects , Voice Quality/drug effects , Acoustics , Adult , Aged , Female , Humans , Hyaluronic Acid/therapeutic use , Injections , Male , Middle Aged , Stroboscopy , Vocal Cord Paralysis/surgery , Vocal Cords/physiology , Vocal Cords/surgery
20.
Am J Otolaryngol ; 34(4): 331-6, 2013.
Article in English | MEDLINE | ID: mdl-23517569

ABSTRACT

PURPOSE: The purpose of this prospective study was to determine the effect of autologous transplantation of fascia into the vocal fold (ATFV) with controlled release of basic fibroblast growth factor (bFGF) on unilateral vocal fold paralysis (UVFP) in a rat model. MATERIALS AND METHODS: Unilateral recurrent laryngeal nerve (RLN) section was performed on 15 rats. Ten rats received an autologous fascia implant and gelatin hydrogel with or without bFGF (1 µg) to their larynxes (fascia only, "fascia group"; bFGF + fascia, "fascia + bFGF group"), while the rest underwent RLN transection ("RLN section group"). Four months later, evaluation of the laryngeal glottal gap and histological analysis were performed. RESULTS: The glottal gap was significantly reduced in the fascia + bFGF group, and fat volume increased significantly relative to the RLN section. The volume of the remaining fascia in the bFGF + fascia group was significantly greater than that of the fascia group. CONCLUSIONS: ATFV with controlled release of bFGF may compensate for diminished laryngeal volume in UVFP by reducing resorption of the implanted fascia and increasing fat volume. Our findings suggest that this modality may represent an attractive option for treating UVFP.


Subject(s)
Fascia/transplantation , Fibroblast Growth Factor 2/therapeutic use , Surgical Flaps/blood supply , Vocal Cord Paralysis/surgery , Animals , Disease Models, Animal , Male , Random Allocation , Rats , Rats, Sprague-Dawley , Plastic Surgery Procedures/methods , Recovery of Function , Statistics, Nonparametric , Transplantation, Autologous , Treatment Outcome , Vocal Cord Paralysis/pathology , Vocal Cords/drug effects , Vocal Cords/surgery
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