Yoshihiko Kumai

Kumamoto University, Kumamoto-shi, Kumamoto Prefecture, Japan

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Publications (29)37.36 Total impact

  • Article: Postdeglutitive residue in idiopathic unilateral vocal fold paralysis: A quantitative videofluoroscopic study.
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    ABSTRACT: OBJECTIVES/HYPOTHESIS: To quantitate postdeglutitive residue and determine its association with paralysis duration (≤6 vs. ≥6 months) in patients with idiopathic unilateral vocal fold paralysis (UVFP). STUDY DESIGN: Primary institutional retrospective review. METHODS: Twenty patients (mean age, 72 years) with idiopathic UVFP and 13 patients (mean age, 66 years) with isolated recurrent laryngeal nerve paralysis (RLNP) who underwent videofluoroscopic swallow studies (VFSSs) were included. Vallecular and pyriform sinus (PS) residues in the anteroposterior view were analyzed quantitatively. In both regions, the symmetry of the affected versus nonaffected sides between patients with idiopathic UVFP and RLNP were compared. Residual differences between short- versus long-term paralysis duration in idiopathic UVFP patients alone were also evaluated. RESULTS: The affected PS of the idiopathic group demonstrated significantly increased residue (P = .007) as compared with the nonaffected PS, but with no significant difference with respect to the vallecula (P = .183). There was no significant difference in the RLNP group. When compared with RLNP patients, the idiopathic group showed significantly increased residue on the affected PS (P = .002), but differences in the vallecular residue were nonsignificant. Pharyngeal residue and the duration of paralysis in idiopathic UVFP patients were not significantly different. CONCLUSIONS: Idiopathic UVFP patients were more likely to demonstrate increased residue and asymmetry toward the involved region as compared with RLNP patients, suggesting that nerve involvement in idiopathic UVFP may not be exclusive to the RLN. Laryngoscope, 2013.
    The Laryngoscope 05/2013; · 1.75 Impact Factor
  • Article: Recurrent laryngeal nerve regeneration through a silicone tube produces reinnervation without vocal fold mobility in rats.
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    ABSTRACT: We established an animal model of recurrent laryngeal nerve reinnervation with persistent vocal fold immobility following recurrent laryngeal nerve injury. In 36 rats, the left recurrent laryngeal nerve was transected and the stumps were abutted in a silicone tube with a 1-mm interspace, facilitating regeneration. The mobility of the vocal folds was examined endoscopically 5, 10, and 15 weeks later. Electromyography of the thyroarytenoid muscle was performed. Reinnervation was assessed by means of a quantitative immunohistologic evaluation with anti-neurofilament antibody in the nerve both proximal and distal to the silicone tube. The atrophy of the thyroarytenoid muscle was assessed histologically. We observed that all animals had a fixed left vocal fold throughout the study. The average neurofilament expression in the nerve both distal and proximal to the silicone tube, the muscle area, and the amplitude of the compound muscle action potential recorded from the thyroarytenoid muscle on the treated side increased significantly (p < 0.05) over time, demonstrating regeneration through the silicone tube. Recurrent laryngeal nerve regeneration through a silicone tube produced reinnervation without vocal fold mobility in rats. The efficacy of new laryngeal reinnervation treatments can be assessed with this model.
    The Annals of otology, rhinology, and laryngology 01/2013; 122(1):49-53. · 1.05 Impact Factor
  • Article: An asymptomatic intraorbital foreign body for 30 years.
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    ABSTRACT: Intraorbital foreign bodies (IOFBs) are usually accompanied by notable skin wounds and/or ocular wounds, and often there is a clear history of a penetrating object. We report herein on a patient who had an asymptomatic IOFB for 30 years. To the best of our knowledge, there is only one other case of a patient with an IOFB for a longer asymptomatic period after the injury. IOFBs may be overlooked because a small penetrating wound may be accompanied by no signs of inflammation for many decades as in this patient's clinical course.
    Auris, nasus, larynx 11/2012; · 0.58 Impact Factor
  • Article: Glottal configuration in unilaterally paralyzed larynx and vocal function.
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    ABSTRACT: Abstract Conclusions: Three different types of glottal configuration in unilaterally paralyzed larynx were proposed by utilizing three-dimensional computed tomographic (3DCT) images. This new classification might facilitate understanding of the behavior of the affected vocal fold in terms of vocal function. Objectives: To develop a classification of glottal configuration in unilateral vocal fold paralysis (UVFP) based on the thickness and location of the vocal folds utilizing 3DCT and to compare each type of configuration with vocal function. Methods: Thirty-seven consecutive patients with UVFP underwent CT during phonation and inhalation. 3D endoscopic and coronal images on two occasions were produced. Maximum phonation time and mean airflow rate were also measured. Results: Three types of glottal configuration were proposed. The thickness of the affected vocal fold during phonation was equal to or slightly thinner than the healthy fold in 10 patients (type A). The affected fold of the remaining 27 was thin during phonation; they were further classified into types B and C. In type B, the affected fold remained thin during phonation and inhalation (n = 12). Type C was allocated to those showing one or two paradoxical movements of the affected fold (n = 15). Those with type A showed significantly better vocal function.
    Acta oto-laryngologica 11/2012; · 0.98 Impact Factor
  • Article: The impact of nimodipine administration combined with nerve-muscle pedicle implantation on long-term denervated rat thyroarytenoid muscle.
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    ABSTRACT: OBJECTIVES/HYPOTHESIS: To evaluate the impact of nimodipineon reinnervation of the long-term denervated rat thyroarytenoid (TA) muscle following nerve-muscle pedicle flap (NMP) implantation. STUDY DESIGN: Quantitative histologic and physiologic assessments. METHODS: Using 120 Wistar rats, we performed NMP implantation at different times after transection of the left recurrent laryngeal nerve (RLN). Sixty animals received nimodipine treatment (NIMO [+] group), and the remaining 60 animals received no nimodipine treatment (NIMO [-] group). As a control, an additional 28 animals were subjected only to transection of the left RLN (DNV group). Subgroups were assigned based on the period after RLN transection (0 [immediate], 8, 16, and 32 weeks). In the DNV group, we assessed histologically the muscle area, axons, neuromuscular junctions (NMJs), and myosin heavy chains (MyHC) type IIA and IIB in the TA muscle. In the NIMO (-) and NIMO (+) groups, histologic assessments and evoked electromyography were performed on the TA muscle at 10 weeks post-NMP implantation. RESULTS: In 8-week interval subgroups, the muscle fiber area and the number of NMJs in the NIMO (+) group were significantly greater than in the NIMO (-) group (P < 0.05, each). In the 0-week and 32-week interval subgroups, the muscle fiber subtype changed significantly, from IIA to IIB (P < 0.01 and P < 0.05, respectively); and, at all time-points the muscle fiber area, number of NMJs, and action potentials in the TA muscle tended to be greater in the NIMO (+) group than in the NIMO (-) group. CONCLUSIONS: Nimodipine expedited the effects of NMP implantation on reinnervation of the long-term denervated TA muscle. Laryngoscope, 2012.
    The Laryngoscope 09/2012; · 1.75 Impact Factor
  • Article: Videolaryngoscopic assessment of laryngeal edema after arytenoid adduction.
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    ABSTRACT: Arytenoid adduction (AA) as surgical treatment for unilateral vocal fold paralysis (UVFP) is associated with higher morbidity from airway complications due to postoperative laryngeal edema compared with other laryngeal framework surgeries. The aim of this study was to evaluate postoperative laryngeal edema after AA using a new videolaryngoscopic (VL) scoring assessment. Prospective case series. Nineteen patients with UVFP (14 males and five females; mean age, 56 years) who were treated with AA alone or combined with ansa cervicalis (AA/AC) nerve anastomosis or nerve-muscle pedicle (AA/NMP) flap implantation were evaluated. Laryngeal edema was assessed by VL scoring for 10 days postoperatively. Degree of edema was scored in three subsites: the membranous vocal fold, arytenoid mound, and pyriform sinus on the operated side. Statistical significance was defined as P < .05. No patient experienced postoperative airway compromise. Interexaminer reliability was generally high (Spearman r > 0.75). The mean degree of edema increased steadily from postoperative day (POD) 1 to 3, peaking on POD 3 at all subsites. It then declined significantly from POD 3 to 7 (P < .05) and gradually through POD 10. The maximum degree of edema, maximum edema time, and operative time were not correlated significantly at any subsite. Maximum edema time and surgery type (AA vs. AA/AC or AA/NMP) were not correlated at any subsite. Inter-rater reliability for the proposed VL scoring was significant at all subsites. The VL findings suggest that AA alone or AA combined with reinnervation showed maximum laryngeal edema on POD 3 but added no significant morbidity.
    The Laryngoscope 03/2012; 122(5):1104-8. · 1.75 Impact Factor
  • Article: Nimodipine accelerates reinnervation of denervated rat thyroarytenoid muscle following nerve-muscle pedicle implantation.
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    ABSTRACT: To determine whether nimodipine, an L-type voltage-operated calcium channel antagonist that is an accelerator of axonal regeneration following peripheral nerve injury, can expedite reinnervation of denervated rat thyroarytenoid (TA) muscle following nerve-muscle pedicle (NMP) flap implantation. A quantitative histologic and physiologic assessment of the TA muscle following NMP flap implantation, with or without nimodipine treatment. Using 72 Wistar rats, we performed a transection on the left recurrent laryngeal nerve, followed by NMP flap implantation. Thirty-six animals received nimodipine treatment (NIMO [+] group), and the remaining 36 animals received no nimodipine treatment (NIMO [-] group). As a control, 18 animals were subjected only to transection of the left recurrent laryngeal nerve. We performed a histologic assessment for muscle area, axon, nerve terminals (NTs), and acetylcholine receptors (AchRs) in the TA muscle and electromyography at 2, 4, and 10 weeks after surgery. Muscle area, ratio of the number of NTs to that of AchRs (NT/AchR ratio), and evoked action potential in the TA muscle were significantly greater in the NIMO (+) group than in the NIMO (-) group (P < .05) at 4 weeks. At 10 weeks, the NT/AchR ratio was significantly greater in the NIMO (+) group than in the NIMO (-) group (P < .05). We found that nimodipine accelerated reinnervation of the denervated TA muscle following NMP flap implantation.
    The Laryngoscope 03/2012; 122(3):606-13. · 1.75 Impact Factor
  • Article: Vocal outcome after arytenoid adduction and ansa cervicalis transfer.
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    ABSTRACT: To evaluate the long-term efficacy of arytenoid adduction (AA) combined with ansa cervicalis-recurrent laryngeal nerve anastomosis (ACN-RLN) in the treatment of unilateral vocal fold paralysis. Retrospective review of clinical records. Institutional practice. Nine patients with severe paralytic dysphonia with large glottal gap were included. Voice outcome was followed up over 24 months postoperatively. One patient did not attend the 24-month evaluation. All patients underwent AA + ACN-RLN. The ansa cervicalis nerve to the sternohyoid muscle was used as the donor nerve. Maximum phonation time (MPT), pitch range, harmonics-to-noise ratio (HNR), and perceptual voice quality were evaluated preoperatively and postoperatively at 1 to 3 months, 6 to 8 months, 12 to 14 months, and 24 months. All parameters improved significantly after surgery and continued to improve over the 24-month period. The MPT continued to improve over time (P = .01, P = .006, and P = .001 when comparing the 1- to 3-month evaluation with the 6- to 8-month, 12- to 14-month, and 24-month evaluations, respectively). Also, pitch range and HNR showed significant, steady improvement over the 24-month duration of the study. Perceptual voice quality markedly improved at 24 months compared with the 1- to 3-month, 6- to 8-month, and 12- to 14-month follow-ups (P = .004, P = .005, and P = .02, respectively, for grade overall, and P = .004, P = .008, and P = .02, respectively, for breathiness grade). Treatment with AA + ACN-RLN provides near-normal vocal function in the 24-month follow-up. Therefore, this method could be a successful surgical treatment for severe paralytic dysphonia.
    Archives of otolaryngology--head & neck surgery 01/2012; 138(1):60-5. · 1.92 Impact Factor
  • Article: Modulation of nerve fibers in the rat thyroarytenoid muscle following recurrent laryngeal nerve injury.
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    ABSTRACT: Regeneration of nerve fibers in the thyroarytenoid (TA) muscle occurred actively after damage on the recurrent laryngeal nerve (RLN) compared with the vagus nerve (VN). However, remyelination did not occur after damage on the RLN. To determine the regeneration process of nerve fibers in the TA muscle following transection and immediate anastomosis of the RLN or VN. Three types of animal model were prepared: an RLN anastomosis model (RLNa), a VN anastomosis model (VNa), and a peroneal nerve anastomosis model (PNa). Animals were sacrificed at five time points following the procedure. The modulation of axons, myelin sheaths, Schwann cells (SCs), nerve terminals (NTs), and acetylcholine receptors (AchRs) in the TA or tibialis anterior muscles was examined by immunohistochemical analysis. The ratios of the expression areas in axons, myelin sheaths, and SCs, and the number of NTs and AchRs in the treated (T) and untreated (U) sides (T/U) were evaluated. At 18 weeks, the T/U ratios of expression in RLNa, VNa, and PNa were 68.5, 0, and 100.4%, respectively, in axons; 0, 0, and 97.6% in myelin sheaths; 53.7, 0, and 93.6% in SCs; 61.0, 0, and 96.4% in NTs; and 99.4, 67.0, and 101.2% in AchRs.
    Acta oto-laryngologica 12/2011; 132(3):305-13. · 0.98 Impact Factor
  • Article: Nerve-muscle pedicle implantation in the denervated thyroarytenoid muscle of aged rats.
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    ABSTRACT: Nerve-muscle pedicle (NMP) implantation was effective in the recovery of atrophic changes in the denervated thyroarytenoid (TA) muscle in aged rats. To evaluate the effects of NMP implantation on the denervated TA muscle in aged rats. Wistar rats aged 20 months and 8 weeks were respectively divided into two groups in which the left recurrent laryngeal nerve (RLN) was transected without (aged/young DNV group) or with (aged/young NMP group) NMP implantation. The aged DNV and NMP groups were further divided into two subgroups, based on the period after RLN transection (10 or 20 weeks). In the DNV groups, we assessed the area of muscle and the number of neuromuscular junctions (NMJs) histologically. In the NMP groups, we performed electromyography and histological assessments. For electromyography, we stimulated the transferred nerve and evaluated the muscle action potentials (MAPs) of the TA muscle. The muscle areas in the aged NMP groups were significantly larger than those in the aged DNV groups. More NMJs were found in aged NMP groups compared with aged DNV groups. MAPs were seen in all NMP animals. No significant differences were observed between the aged and young NMP groups in histological and physiological assessments.
    Acta oto-laryngologica 11/2011; 132(2):210-7. · 0.98 Impact Factor
  • Article: Assessment of canine vocal fold function after injection of a new biomaterial designed to treat phonatory mucosal scarring.
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    ABSTRACT: Most cases of irresolvable hoarseness are due to deficiencies in the pliability and volume of the superficial lamina propria of the phonatory mucosa. By using a US Food and Drug Administration-approved polymer, polyethylene glycol (PEG), we created a novel hydrogel (PEG30) and investigated its effects on multiple vocal fold structural and functional parameters. We injected PEG30 unilaterally into 16 normal canine vocal folds with survival times of 1 to 4 months. High-speed videos of vocal fold vibration, induced by intratracheal airflow, and phonation threshold pressures were recorded at 4 time points per subject. Three-dimensional reconstruction analysis of 11.7 T magnetic resonance images and histologic analysis identified 3 cases wherein PEG30 injections were the most superficial, so as to maximally impact vibratory function. These cases were subjected to in-depth analyses. High-speed video analysis of the 3 selected cases showed minimal to no reduction in the maximum vibratory amplitudes of vocal folds injected with PEG30 compared to the non-injected, contralateral vocal fold. All PEG30-injected vocal folds displayed mucosal wave activity with low average phonation threshold pressures. No significant inflammation was observed on microlaryngoscopic examination. Magnetic resonance imaging and histologic analyses revealed time-dependent resorption of the PEG30 hydrogel by phagocytosis with minimal tissue reaction or fibrosis. The PEG30 hydrogel is a promising biocompatible candidate biomaterial to restore form and function to deficient phonatory mucosa, while not mechanically impeding residual endogenous superficial lamina propria.
    The Annals of otology, rhinology, and laryngology 03/2011; 120(3):175-84. · 1.05 Impact Factor
  • Article: Effects of nerve-muscle pedicle on immobile rat vocal folds in the presence of partial innervation.
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    ABSTRACT: We investigated whether implantation of an ansa cervicalis nerve (ACN)-muscle pedicle into the thyroarytenoid (TA) muscle is efficacious in the presence of partial recurrent laryngeal nerve (RLN) innervation. We studied a total of 36 rats. Twelve of the rats served as positive and negative control animals. In the remaining 24 rats, the left RLN was transected, a 1-mm piece of nerve was removed, and the stumps were abutted in silicone tubes (STs), inducing partial RLN regeneration. Twelve of the ST-treated rats underwent this procedure alone, and the other 12 rats had a nerve-muscle pedicle (NMP) implanted into the left TA muscle 5 weeks after ST treatment. At 15 weeks, reinnervation was assessed by histologic evaluation of the TA muscle and by electromyography with stimulation of the RLNs and ACNs. The muscle area, the number of nerve terminals, the number of acetylcholine receptors, and the ratio of nerve terminals to acetylcholine receptors were significantly greater (p < 0.05) in the NMP group than in the ST group. Electromyography elicited TA muscle compound action potentials upon stimulation of the RLNs and ACNs. In rats, NMP implantation is efficacious for reducing atrophic changes in the TA muscle in the presence of partial RLN innervation.
    The Annals of otology, rhinology, and laryngology 12/2010; 119(12):823-9. · 1.05 Impact Factor
  • Article: External auditory canal stenting utilizing a useful rolled, tapered silastic sheet (RTSS) post middle ear surgery.
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    ABSTRACT: To overcome the demerits of conventional postoperative aural packing, we developed a useful protocol for postoperative stenting of the external auditory canal after middle ear surgery which enables transcanal drainage and simultaneously allows for visual inspection and treatment of the canal, as necessary. Twenty-four surgeries, 21 patients underwent tympanoplasty with a postaural incision. At the end of all surgical procedures, the external auditory canal was packed with a 0.3mm thickness rolled, tapered silastic sheet (RTSS) with antibiotic ointment applied to one surface. The inserted RTSSs were removed at 5-10 days postoperatively. We assessed the efficacy and the reliability of the RTSS. In 23 ear surgeries on 20 patients, we achieved successful postoperative ear packing utilizing our RTSS. With these patients, the tympanic membrane and the external auditory meatus were able to be observed immediately after the completion of the stenting during the surgery and the removal of the gauze over the operated ear at Day 1 to Day 3 postoperatively. During 4 surgeries with ventilation tube insertion to the tympanic membrane, there was secretion through the inserted ventilation tube which was easy to suction. In one surgery, on one patient, additional packing materials were utilized once only during a sandwich graft myringoplasty. No patients showed any harmful effects during the postoperative period. The useful and reliable RTSS, with antibiotic ointment applied to one surface, has several positive advantages that the conventional packing methods do not.
    Auris, nasus, larynx 12/2010; 37(6):680-4. · 0.58 Impact Factor
  • Article: Nerve-muscle pedicle flap implantation combined with arytenoid adduction.
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    ABSTRACT: To describe a new technique of nerve-muscle pedicle (NMP) flap implantation combined with arytenoid adduction (AA) to treat dysphonia due to unilateral vocal fold paralysis and to examine postoperative vocal function. Retrospective review of clinical records. Tertiary academic center. Twenty-two consecutive patients underwent NMP flap implantation with AA and were followed up short term over a period of 1 to 6 months (mean, 2.9 months) and long term over a period of 7 to 36 months (mean, 21.4 months). An NMP flap was made using an ansa cervicalis branch and a piece of the sternohyoid muscle. A window was opened in the thyroid ala at the level of the vocal fold. Then, AA was performed and the NMP flap was securely implanted onto the thyroarytenoid muscle through the window under microscopic guidance. The maximum phonation time, mean airflow rate, pitch range, and acoustic parameters (jitter, shimmer, and harmonics to noise ratio) were evaluated before surgery and twice after surgery. All parameters improved significantly after surgery (P < .01). The measurements for maximum phonation time, mean airflow rate, and harmonics to noise ratio were within normal ranges after surgery. Furthermore, the maximum phonation time and jitter were significantly improved after long-term follow-up compared with early postoperative measurements (P < .01 and P < .05, respectively). Precise harvest of an NMP flap and its placement directly onto the thyroarytenoid muscle combined with AA provided excellent vocal function. The NMP method may have played a certain role in the improvement of postoperative vocal function, although further study with electromyographic examination is required to clarify the innervation status of the thyroarytenoid muscle.
    Archives of otolaryngology--head & neck surgery 10/2010; 136(10):965-9. · 1.92 Impact Factor
  • Article: Modulation of vocal fold scar fibroblasts by adipose-derived stem/stromal cells.
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    ABSTRACT: To explore whether adipose-derived stem/stromal cells (ASCs) have therapeutic potential for treating scarred superficial lamina propria through the effects of secreted hepatocyte growth factor (HGF) on scar fibroblasts. In vitro study using coculture system. Scar fibroblasts (SFs) were isolated from ferret vocal folds electrocauterized 2 weeks previously. ASCs were isolated from ferret lipoaspirated subcutaneous abdominal fat. For coculture experiments, the two cell types were combined in Transwell plates for 6 days, followed by 1 or 3 days of monoculture after removing the upper chamber. Assays were then performed on cells and media from the bottom chamber. We measured: 1) the production of hyaluronic acid (HA), collagen and HGF via enzyme-linked immunosorbent assays, 2) the expression of alpha-smooth muscle actin (alpha-SMA), 3) cell proliferation, and 4) apoptosis of SFs (2, 3, and 4 via flow cytometry). Other experiments examined the effects of HGF on SFs and the effects of HGF neutralization in the coculture system. Coculture led to significant decreases in SF collagen production (P < .05), cell proliferation (P < .05), and alpha-SMA expression (P < .05), whereas HA production increased (P < .05). Coculture also increased HGF secretion from ASCs (P < .05). Neutralization of HGF abolished the inhibitory effects of ASCs on SF collagen synthesis (P < .05). ASCs influence SFs to adopt a less fibrotic profile. It appears that HGF is at least one of the soluble factors responsible for this effect. Implanted ASCs could potentially ameliorate vocal fold scar by acting as long-term, intrinsic sources of HGF.
    The Laryngoscope 12/2009; 120(2):330-7. · 1.75 Impact Factor
  • Article: Perspectives on adipose-derived stem/stromal cells as potential treatment for scarred vocal folds: opportunity and challenges.
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    ABSTRACT: Regenerative therapy using stem cells for the treatment of vocal fold wound healing and fibrosis is a very active area of research in Otolaryngology. Although modern phonosurgical methods can deal with many types of vocal fold pathology, vocal fold scar remains a clinical challenge. Trauma (e.g. vocal abuse, phonosurgery) and inflammation (e.g. laryngitis) are the two main causes of the vocal fold scarring. Several recent reviews detail the problem of vocal fold scarring and the array of possible solutions under investigation. The search for solutions includes autologous tissues, biomaterial implants, growth factors, anti-fibrotic agents and stem cells. This review focuses on emerging research on stem cells for vocal fold regeneration and our own studies of interactions between adipose-derived stem/stromal cells and vocal fold fibroblasts using an in vitro model. While clearly an opportunity, the challenging approach of treating vocal scarring using ASCs has just started. For future in vivo studies, improvements in cell viability and markers of stem-cell differentiation into normal fibroblasts are needed. The roles of stem cell-derived cytokines in paracrine signaling need to be further explored at a cellular level in vitro, and then extended to in vivo experiments.
    Current Stem Cell Research & Therapy 11/2009; 5(2):175-81.
  • Article: 11.7 Tesla magnetic resonance microimaging of laryngeal tissue architecture.
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    ABSTRACT: High-resolution imaging of vocal folds that distinguishes vocal fold (VF) layered microstructure and VF implants would provide a key experimental tool for translational research investigating biomaterial-based interventions to treat vocal fold scar. To establish proof of concept, we studied whether 11.7 Tesla (T) magnetic resonance (MR) microimaging provides the needed resolution to resolve vocal fold tissue architecture. We performed ex vivo MR microimaging of fixed ferret and canine larynges to determine whether changes in the layered architecture can be detected in the presence of scar and subsequent to biomaterial injections into the vocal folds. Serial section histological analyses were done to corroborate MR microimaging findings. Multiple axial and transverse/coronal 300-microm slices were obtained using an 11.7 T MR spectrometer/500 MHz for proton with gradient-recalled echo and rapid acquisition with relaxation enhancement imaging sequences. High-resolution (39 microm/pixel) MR microimages distinguished VF epithelium, lamina propria, muscle, and cartilage in ferret and canine larynges. In ferret scarred VFs (n = 25), collagen-rich dense scar tissue was distinguishable from contralateral nonscarred VFs and from normal ferret VFs (n = 25), as confirmed on histology. MR microimaging accurately detected injected autologous fat, hyaluronic acid-based and polyethylene glycol (PEG)-based implants injected into both ferret and canine VFs. Importantly, MRI accurately showed resorption of PEG implants in ferrets and canines, as confirmed on histology. Additionally, ex vivo MR spectroscopy distinguished fat from PEG-based implants. Ex vivo 11.7 T MR microimaging provided high-resolution images of ferret and canine laryngeal tissue microstructure, although the superficial lamina propria could not be distinguished. Histology confirmed MR microimaging findings, indicating utility of MR microimaging of modeled scar, implant residence time, and tissue responses, thus providing integrative insight relevant to translational research.
    The Laryngoscope 10/2009; 119(11):2187-94. · 1.75 Impact Factor
  • Article: Crosstalk between adipose-derived stem/stromal cells and vocal fold fibroblasts in vitro.
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    ABSTRACT: To explore adipose-derived stem cell/fibroblast interactions as a potential remodeling pathway for vocal fold scar. Fibroblasts and adipose-derived stem/stromal cells (ASCs) were cultured alone and in combination in a cell-contact-independent paracrine system. Analyses of cell proliferation, and the production of hyaluronic acid (HA) and collagen were performed on samples collected on days 1, 3, and 7. Normal fibroblasts (NFs) were isolated bilaterally from the subepithelial lamina propria of two normal ferret vocal folds. Scar fibroblasts (SFs) were isolated from vocal folds that were electrocauterized 2 weeks before harvest. ASCs were isolated from lipoaspirated subcutaneous abdominal fat of two ferrets. A transwell cell-contact-independent cell communication culturing system was used for coculture experiments. Cells were seeded at 50,000/well in both monoculture and coculture experiments. In monoculture, SFs proliferated faster and produced less HA and more collagen than NFs at day 7 (P < .05). In SF/ASC coculture, SF proliferation was diminished and collagen production at day 7 decreased (P < .05). HA production did not differ between monoculture and coculture conditions. Normal and scar-tissue-derived vocal fold fibroblasts maintain phenotypic differences in culture, thus validating this in vitro scar model. In co-culture, contact-independent crosstalk occurs between SFs and ASCa, leading to less collagen secretion. The data support the hypothesis that ASCs can induce favorable remodeling of scarred vocal folds in vivo by their interactions with endogenous fibroblasts.
    The Laryngoscope 04/2009; 119(4):799-805. · 1.75 Impact Factor
  • Article: Nerve-muscle pedicle implantation facilitates re-innervation of long-term denervated thyroarytenoid muscle in rats.
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    ABSTRACT: Nerve-muscle pedicle (NMP) implantation was effective in the recovery from atrophic changes in long-term denervated thyroarytenoid (TA) muscle. Re-innervation occurred via the transferred nerve. However, the effectiveness of the NMP method may decline with increasing duration of denervation. To evaluate the effects of NMP implantation on long-term denervated rat TA muscle. Wistar rats (n=105) were divided into two groups in which the left recurrent laryngeal nerve (RLN) was transected without (DNV group) or with (NMP group) subsequent NMP implantation, and subgroups of each group were formed depending on the period after RLN transection (immediate to 48 weeks). In the DNV subgroups, we histologically assessed the area of muscle and the number of neuromuscular junctions. In the NMP subgroups, we performed electromyographic, videolaryngoscopic, and histologic assessments. The muscle area and muscle action potentials were evaluated by comparing the treated and untreated sides. The ratio of the number of nerve terminals to that of acetylcholine receptors was also assessed. The TA muscle area was significantly larger in most of the NMP subgroups compared with the DNV subgroups. Muscle action potentials were present in all NMP animals. All histologic and physiologic assessments revealed degradation as the denervation period in the five NMP subgroups.
    Acta oto-laryngologica 01/2009; 129(12):1486-92. · 0.98 Impact Factor
  • Article: Effects of long-term denervation on the rat thyroarytenoid muscle.
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    ABSTRACT: To determine the effects of long-term denervation on the rat thyroarytenoid (TA) muscle and neuromuscular junctions. A quantitative histologic assessment of the TA muscle after long-term denervation. Thirty Wistar rats were euthanized 10, 18, 26, 42, and 58 weeks after left recurrent laryngeal nerve resection. The areas of the entire muscle and individual muscle fibers were evaluated using hematoxylin-eosin staining, and neuromuscular junctions were detected by immunohistochemistry. Changes after denervation were evaluated by comparing the treated (T) and untreated (U) sides (T/U ratio). The ratio of the number of nerve terminals (NTs) to that of acetylcholine receptors (AChRs) (NT/AChR ratio) was also assessed. The average T/U ratio for the entire muscle area of the denervation groups ranged between 61.1% and 72.5% and did not differ significantly. Similarly, the T/U ratios for the individual muscle fiber area ranged between 45.0% and 51.9%, and the differences were not significant. The T/U ratio of AChRs at 58 weeks (35.3 +/- 20.2%) was significantly lower than that at 10 weeks (76.3 +/- 9.0%; P < .01). The NT/AChR ratios ranged between 30.3% and 35.6% and did not differ significantly among the denervation groups. The entire TA muscle area, individual muscle fiber area, and NT/AChR ratio did not decrease with long-term denervation. Thus, the TA muscle may retain an ability to receive regenerating nerve axons. However, the ability of the TA muscle to receive nerve axons may deteriorate after an excessively long denervation period because the T/U ratio of AChRs decreased with long-term denervation.
    The Laryngoscope 07/2008; 118(7):1318-23. · 1.75 Impact Factor