Ion transport its regulation in the endolymphatic sac: suggestions for clinical aspects of Meniere's disease.

Ion transport and its regulation in the endolymphatic sac (ES) are reviewed on the basis of recent lines of evidence. The morphological and physiological findings demonstrate that epithelial cells in the intermediate portion of the ES are more functional in ion transport than those in the other portions. Several ion channels, ion transporters, ion exchangers, and so on have been reported to be present in epithelial cells of ES intermediate portion. An imaging study has shown that mitochondria-rich cells in the ES intermediate portion have a higher activity of Na+, K+-ATPase and a higher Na+ permeability than other type of cells, implying that molecules related to Na+ transport, such as epithelial sodium channel (ENaC), Na+-K+-2Cl- cotransporter 2 (NKCC2) and thiazide-sensitive Na+-Cl- cotransporter (NCC), may be present in mitochondria-rich cells. Accumulated lines of evidence suggests that Na+ transport is most important in the ES, and that mitochondria-rich cells play crucial roles in Na+ transport in the ES. Several lines of evidence support the hypothesis that aldosterone may regulate Na+ transport in ES, resulting in endolymph volume regulation. The presence of molecules related to acid/base transport, such as H+-ATPase, Na+-H+ exchanger (NHE), pendrin (SLC26A4), Cl--HCO3- exchanger (SLC4A2), and carbonic anhydrase in ES epithelial cells, suggests that acid/base transport is another important one in the ES. Recent basic and clinical studies suggest that aldosterone may be involved in the effect of salt-reduced diet treatment in Meniere's disease.

Presence of adrenergic receptors in rat endolymphatic sac epithelial cells.

Intravenous application of catecholamines produces a depression in the endolymphatic sac direct current potential (ESP) and increases endolymphatic pressure via the ß-adrenergic receptor (AR) in guinea pigs, suggesting that catecholamines play a role in the endolymphatic system. However, the localization of ARs in the endolymphatic sac (ES) is still undetermined. The presence of ARs in the rat ES was investigated by reverse transcriptase-polymerase chain reaction using laser capture microdissection (LCM) and immunohistochemical analysis. Expression of α(1A)-, α(1B)-, α(2A)-, α(2B)-, ß(1)-, ß(2)- and ß(3)-ARs was observed in LCM samples of ES epithelia. Immunohistochemical analysis using specific antibodies showed immunofluorescence of ß(2)- and ß(3)-ARs in epithelial cells of the ES intermediate portion, and no specific staining results were obtained for α(1)-, α(2A)-, α(2B)- and ß(1)-ARs. The presence of ß(2)-AR with no clear immunostaining of ß(1)-AR in ES epithelial cells is in accordance with previous electrophysiological and pharmacological results, which suggests that ß(2)-AR mediates the action of catecholamines on the ESP. The presence of ß(3)-AR in the ES epithelial cells and its absence in the stria vascularis implies that ß(3)-AR plays a specific role in the ES.

Temporal Adjusters Can Reduce Pain During the Video Head Impulse Test for Patients With Mongoloid Facial Features, Without Increasing the Slippage-Induced Artifacts.

BACKGROUND: The aim of this study was to determine whether the extent and intensity of pain caused by wearing goggles during the video head impulse test (vHIT) could be reduced by adjusting the direction in which the band pulls the goggles, without increasing the number of artifacts recorded during vHIT. METHODS: vHIT tests were performed in 65 healthy adult subjects, and the Visual Analog Scale (VAS) and Numerical Rating Scale (NRS) were used to evaluate pain intensity. Temporal adjusters were used to adjust the direction in which the band pulls the goggles, without decreasing the tightness of the temple straps. Artifacts were compared by calculating the instantaneous gains at 40 ms, 60 ms, and 80 ms of head movement. RESULTS: Maximum VAS and NRS of pain were significantly reduced from 22.0 ± 2.3 to 13.0 ± 1.7 and from 3.0 ± 0.2 to 2.0 ± 0.2 (both P < .0001). The VAS score without adjusters was significantly correlated with the improvement of the VAS score with temporal adjusters (P < .0001, r = 0.61). The higher the VAS score without adjusters, the greater the improvement in the VAS score with temporal adjusters. The instantaneous gains were close to 1.0 under both conditions. CONCLUSION: The pain induced by the goggle was significantly mitigated with temporal adjusters in the bilateral temple strap. Using temporal adjusters is a useful and easy solution to reduce discomfort during vHIT, while maintaining the tightness of the strap to decrease the slippageinduced artifacts.

Endolymphatic sac is involved in the regulation of hydrostatic pressure of cochlear endolymph.

To clarify the role of the endolymphatic sac (ES) in the regulation of endolymphatic pressure, the effects of isoproterenol, a beta-adrenergic receptor agonist, and acetazolamide, a potent carbonic anhydrase inhibitor, both of which decrease ES direct current potential on cochlear hydrostatic pressure, were examined in guinea pigs. When isoproterenol was applied intravenously, hydrostatic pressures of cochlear endolymph and perilymph were significantly increased with no change in endocochlear potential or the hydrostatic pressure of cerebrospinal fluid. Acetazolamide produced no marked change in the hydrostatic pressure of cochlear endolymph. In ears with an obstructed ES, the action of isoproterenol on the hydrostatic pressure of cochlear endolymph and perilymph was suppressed. These results suggest that the ES may regulate the hydrostatic pressure of the endolymphatic system via the action of the agents such as catecholamines on the ES.

Expression of thiazide-sensitive Na+-Cl- cotransporter in the rat endolymphatic sac.

The endolymphatic sac (ES) is a part of the membranous labyrinth and is believed to absorb endolymph. It has been well-established that the endolymph absorption is dependent on several ion transporters in a manner similar to that in the kidney, and the ES is regulated by hormones such as aldosterone and vasopressin that also affect on the kidney. The thiazide-sensitive Na(+), Cl(-) cotransporter (TSC) is an electroneutral cotransporter specific to the kidney that plays an important role in absorption of NaCl in renal tubules. In the inner ear, TSC expression has never been examined. The expression of TSC in the rat ES was examined by RT-PCR, in situ hybridization and immunohistochemistry. These analyses indicated that TSC genes and proteins were expressed in the rat ES. In contrast, it was not observed in the rat cochlea by RT-PCR. This is the first report confirming the expression of TSC in the ES.

A new approach for selective rat endolymphatic sac epithelium collection to obtain pure specific RNA.

The endolymphatic sac (ES) is an organ that is located in the temporal bone. Its anatomical location makes ES tissue collection without any contamination very difficult, and sometimes accurate molecular analyses of the ES are prevented due to this matter. In the present study, a new selective ES epithelial tissue collection method was attempted using laser capture microdissection to obtain pure ES RNA without any contamination. The validity of this method was demonstrated by RT-PCR with three specific primer pairs against osteocalcin, calponin H1, and NKCC2, which are specific proteins in bone, smooth muscle, and kidney/ES cells, respectively. From the RT-PCR results, the high specificity and sufficient sensitivity of the new method was indicated. It is considered that the new method is optimal for ES collection without contamination and it will be able to contribute to future analyses of the ES.

Tricellulin Expression and its Deletion Effects in the Endolymphatic Sac.

OBJECTIVES: Tricellulin is a tight junction (TJ)-forming protein that participates in the sealing function of tricellular TJs. Tricellulin-knockout (Tric-/-) mice show progressive hearing loss with degeneration of hair cells in the cochlea without physiological or physical disorders. In the present study, we investigated the tricellulin expression and its deletion effects in the endolymphatic sac (ES) using Tric-/- mice. MATERIALS AND METHODS: The ES epithelia from wild-type (WT) mice were laser-microdissected, and RT-PCR was performed. The ES sections from Tric-/- and WT mice were immunostained with an anti-tricellulin antibody. Hematoxylin and eosin staining was performed for morphological examination. The inner ear of Tric-/- mice was perfused with biotinylation reagents, and the ES sections were observed for tracer permeability assay after applying streptavidin-Alexa Fluor 488 conjugate. RESULTS: The tricellulin expression was confirmed by RT-PCR and by immunohistochemistry in the WT ES. The ES in Tric-/- mice showed normal morphology and revealed no biotin leakage from the lumen. CONCLUSION: The ES in Tric-/- mice showed no changes in morphology or disruption in macromolecular barrier function. The effects of solute leakages in the ES of Tric-/- mice may be very limited and compensatable, or that the ES epithelia may have other sealing system covering the lack of tricellulin.

The difference in endolymphatic hydrostatic pressure elevation induced by isoproterenol between the ampulla and the cochlea.

OBJECTIVE: The purpose of the study was to investigate the difference in the responses of endolymphatic hydrostatic pressure to isoproterenol, ß-adrenergic receptor agonist, between pars superior and pars inferior. METHODS: The hydrostatic pressure of endolymph and perilymph and endolymphatic potential in the ampulla and the cochlea during the intravenous administration of isoproterenol were recorded using a servo-null system in guinea pigs. RESULTS: The hydrostatic pressure of endolymph and perilymph in the ampulla and cochlea was similar in magnitude. Isoproterenol significantly increased hydrostatic pressure of ampullar and cochlear endolymph and perilymph with no change in the ampullar endolymphatic potential and endocochlear potential, respectively. The isoproterenol-induced maximum change of endolymphatic hydrostatic pressure in ampulla was significantly (p<0.01) smaller than that in the cochlea. In ears with an obstructed endolymphatic sac, the action of isoproterenol on endolymphatic hydrostatic pressure in the ampulla disappeared like that in the cochlea. CONCLUSION: Isoproterenol elevates endolymphatic hydrostatic pressure in different manner between the vestibule and the cochlea.

Hormonal changes following a low-salt diet in patients with Ménière's disease.

OBJECTIVE: A low-salt diet has been the main treatment modality for Ménière's disease (MD) since the 1930s, although the mechanisms behind this therapy have not yet been elucidated. Salt reduction is associated with a physiological increase in plasma aldosterone concentration. Several experimental reports have suggested that aldosterone may increase endolymph absorption in the inner ear, particularly in the endolymphatic sac. Therefore, aldosterone elevations due to a low-salt diet may increase endolymph absorption in the endolymphatic sac. In this study, urinary sodium excretion, plasma aldosterone, and other hormones were measured during low-salt diet therapy in patients with MD. METHODS: We included 13 patients with unilateral definite MD diagnosed at the Kagawa University Hospital. A national registered dietitian provided nutritional guidance initially for 14 enrolled patients with MD and prescribed them a low-salt diet (2g Na/day). Twenty-four hour urine was sampled at baseline, at 2, 4, 6, and 8 weeks, and at 6, 12, 18, and 24 months after initiating the low-salt diet. Urine osmotic pressure, and Na, K, and Cl levels were measured, and 24-h urinary Na, K, and Cl excretion was estimated. Aldosterone, cortisol, hormones (including anti-diuretic hormone), Na, K, and Cl in the blood were measured, alongside plasma osmotic pressure. A total of 13 patients followed the low salt diet therapy for more than 2 years, while one patient dropped out. RESULTS: Group 1 (n=7) included patients with a mean urinary sodium excretion amount lower than 3g/day and Group 2 (n=6) included those with more than 3g/day. Vertiginous states of all Group 1 patients comprised complete control (Class A, 100%), while Group 2 patients included Class A (four patients, 66%), Class C (one patient, 17%), and Class D (one patients, 17%). Plasma aldosterone concentrations significantly increased during the 2-year low-salt diet; concentrations in Group 1 tended to be higher than that in Group 2. Hearing improvements after 2 years in Group 1 were significantly better than that in Group 2. The plasma concentration of the hormones except aldosterone was not significantly changed during 2-year low-salt diet. CONCLUSION: A low-salt diet was an effective treatment for patients with Ménière's disease. This treatment will have a greater effect, when sodium intake is reduced to less than 3g/day. A low-salt diet may induce an increase in the plasma aldosterone concentration that can activate ion transport and absorbing endolymph in the endolymphatic sac.

Usefulness of multislice-CT using multiplanar reconstruction in the preoperative assessment of the ossicular lesions in the middle ear diseases.

OBJECTIVE: The aim of the study is to evaluate the usefulness of multislice computed tomography (MSCT) using multiplanar reconstruction (MPR) in obtaining preoperative information on the ossicular lesions of middle ear diseases by comparing the ossicular findings of MPR images with the operative findings. METHODS: Sixty-two ears and 10 ears with preoperative middle ear diseases underwent 4- and 64-detector row CT of the temporal bone in Kagawa University Hospital, respectively. MPR images of three ossicles were created at the planes parallel to the long axis of ossicles. RESULTS: The findings of the three ossicles in MPR images were compatible with their operative findings in approximately 91% of 72 ears with various middle ear diseases. There was no significant difference in the coincidence rate of both findings between 4- and 64-detector row CT scanners. The ears with no soft tissue shadows around the ossicles had the coincidence rate of 96-100% in each ossicular part, whereas the coincidence rate was lower in the ears with soft tissue shadows around the ossicles. CONCLUSION: MPR imagings of the ossicles provide accurate preoperative information on the ossicular lesions in middle ear diseases. The 4-detector CT is still a useful device for imaging of the ossicles.

Clinical outcomes of nedaplatin and S-1 treatment with concurrent radiotherapy in advanced head and neck cancer.

CONCLUSION: Nedaplatin and S-1 treatment with concurrent radiotherapy was effective, with acceptable toxicities. This regimen does not require extensive intravenous hydration and continuous infusion. Nedaplatin and S-1 may contribute to better clinical outcomes and improve quality of life for patients. OBJECTIVES: We retrospectively analyzed the clinical efficacy and toxicity of concurrent chemoradiotherapy with nedaplatin and S-1 for head and neck squamous cell cancer. METHODS: Forty-six patients with oropharyngeal, hypopharyngeal, and laryngeal cancer were treated with S-1 on days 1 through 14 and nedaplatin on day 1 every 4 weeks for two cycles of radiotherapy. Therapeutic responses and adverse events were assessed. RESULTS: Primary site tumors and neck lymph nodes exhibited complete response rates of 91% and 64.3%, respectively. The 4-year relapse-free survival and overall survival rates were 76.2% and 85.3%, respectively. The main grade 3 and 4 toxicities were mucositis (30%), leukopenia (30%), anorexia (22%), dermatitis (15%), and thrombocytopenia (9%).

Deletion of Tricellulin Causes Progressive Hearing Loss Associated with Degeneration of Cochlear Hair Cells.

Tricellulin (also known as MARVELD2) is considered as a central component of tricellular tight junctions and is distributed among various epithelial tissues. Although mutations in the gene encoding tricellulin are known to cause deafness in humans (DFNB49) and mice, the influence of its systemic deletion in vivo remains unknown. When we generated tricellulin-knockout mice (Tric(-/-)), we found an early-onset rapidly progressive hearing loss associated with the degeneration of hair cells (HCs); however, their body size and overall appearance were normal. Tric(-/-) mice did not show any morphological change pertaining to other organs such as the gastrointestinal tract, liver, kidney, thyroid gland and heart. The endocochlear potential (EP) was normal in Tric(-/-) mice, suggesting that the tight junction barrier is maintained in the stria vascularis, where EP is generated. The degeneration of HCs, which occurred after the maturation of EP, was prevented in the culture medium with an ion concentration similar to that of the perilymph. These data demonstrate the specific requirement of tricellulin for maintaining ion homeostasis around cochlear HCs to ensure their survival. The Tric(-/-) mouse provides a new model for understanding the distinct roles of tricellulin in different epithelial systems as well as in the pathogenesis of DFNB49.

Cystic fibrosis transmembrane conductance regulator in the endolymphatic sac of the rat.

OBJECTIVE: Na(+) and Cl(-) are dominant ions in the endolymphatic fluid in the endolymphatic sac and are important for volume regulation in the endolymphatic sac. An epithelial sodium channel (ENaC) and other Na(+) transporters have been identified in the endolymphatic sac epithelia, and they are involved in the regulation of endolymph. Although the presence of Cl(-) channels in the endolymphatic sac epithelia has been speculated, no Cl(-) channels have been identified. In this study, we confirmed the expression of cystic fibrosis transmembrane conductance regulator (CFTR) in the endolymphatic sac by reverse transcriptase polymerase chain reaction (RT-PCR) and by immunohistochemical staining. METHODS: Pure mRNA from endolymphatic sac epithelia was prepared using laser capture microdissection (LCM) and examined using RT-PCR. Localization of CFTR and ENaC in the endolymphatic sac was examined using immunohistochemistry. RESULTS: mRNA of the CFTR was expressed in the endolymphatic sac. Immunohistochemical analysis showed the expression of the CFTR on apical side of the endolymphatic sac epithelia and co-localization with the ENaC. CONCLUSION: RT-PCR and immunohistochemistry were used to identify the expression of CFTR in the endolymphatic sac epithelia, which gives us a clue for understanding Cl(-) transport in the endolymphatic sac. These results suggest a pathway for Cl(-), possibly through interaction with the ENaC, which may regulate the endolymph in the endolymphatic sac.

Detection of small fenestral otosclerotic lesions by high-resolution computed tomography using multiplanar reconstruction.

OBJECTIVE: The aim of this study was to assess the value of multislice computed tomography (MSCT) using multiplanar reconstruction (MPR) to detect the small fenestral lesions in patients with otosclerosis. METHODS: MSCT with MPR imaging was used to evaluate 27 ears of 17 patients with otosclerosis (3 male and 14 females) ranging in age from 33 to 69 years with a mean of 49.8 year. MSCT imaging was performed using Aquilion®. Axial spiral scans with a 0.5-mm slice thickness were obtained. The acquired high-resolution data were transferred to a workstation (ALATO VIEW). MPR images were created in the planes parallel to the stapedial crus and then analyzed on the monitor screen by two radiologists (Y.T. and N.K.). RESULTS: MPR images showed abnormal findings in 26 of 27 ears with otosclerosis (96%), whereas axial images showed abnormal findings in only 15 of 27 ears (56%). The similar classification between both images was shown only in 9 of 27 ears (33%). In 16 ears (67%) axial images under-evaluated the lesions compared with MPR images. MPR images detected smaller foci than axial images. Air-bone gap at 0.5-4kHz tended to increase dependently on the extension of fenestral lesions evaluated by MPR images. CONCLUSION: MPR images detected fenestral lesions in otosclerosis more frequently and more precisely than axial images. The extent of fenestral lesions observed on MPR images tends to be related to the degree of conductive hearing loss.

Changes in (18)F-fluorothymidine and (18)F-fluorodeoxyglucose positron emission tomography imaging in patients with head and neck cancer treated with chemoradiotherapy.

OBJECTIVE: This study compared change of (18)F-fluorothymidine (FLT) uptake with that of (18)F-fluorodeoxyglucose (FDG) in head and neck squamous cell cancer (HNSCC) patients during and after treatment and evaluated the utility for early monitoring of response to chemoradiotherapy. METHODS: Thirty patients with newly diagnosed HNSCCs treated with concurrent chemoradiotherapy underwent FLT and FDG PET in pre-treatment (PET1), mid-treatment (PET2) and post-treatment (PET3) stages. The PET images were evaluated quantitatively using maximum standardized uptake values (SUVs). Ratios between SUVs at PET2 and PET3 were also calculated. RESULTS: According to the SUVs, no significant differences were found with primary site location, cellular differentiation and T category in all PET scans. About a 78 % median decrease in FLT SUV was observed at the total dose (TD) of 30 Gy and no apparent change was observed thereafter. About a 40 % decrease in FDG SUV was observed at TD 30 Gy and significant decreases were then found at the 4- and 6-week time points after the therapy. FLT PET demonstrated no recurrence regions in patients with a PET3/PET2 ratio of <1.5. In comparison, FLT SUVs in PET3 with recurrence were increased more than three times. However, no significant difference was found between the values with recurrence and those with no recurrence in FDG PET. CONCLUSION: FLT PET signal change preceded FDG PET change and the increase of FLT uptake after the therapy can imply recurrence or a residual tumor. FLT PET seems promising for early evaluation of chemoradiation effects in HNSCCs.

Evaluation of the vestibular aqueduct in Ménière's disease using multiplanar reconstruction images of CT.

OBJECTIVE: Previous studies, in which the vestibular aqueduct (VA) was determined using axial CT, have indicated that the VA sizes in patients with Ménière's disease were smaller than those in the subjects of the control group and that 25-35% of ears with Ménière's disease were "non-visible type." In this study, in addition to obtaining the axial size, we measured the VA size along the vertical plane by using vertical multiplanar reconstruction (MPR) images. METHODS: The VA size of both ears of patients with unilateral Ménière's disease (n=34) and of subjects of the control group (n=30) was measured by using the vertical MPR and the axial CT images. RESULTS: The VA size was measured along the axial and vertical planes in all subjects. The parameters measured on the axial image of the VA correlated with each other; however, the parameters on the vertical MPR image did not correlate with those on the axial image. Values of parameters in the affected and nonaffected ears with Ménière's disease tended to be smaller than those in the control ear. The external aperture areas of the VA fenestra of the affected and nonaffected ears of patients with Ménière's disease were significantly smaller than that for the control ears. CONCLUSION: Our findings suggest that the vertical parameters of the VA yield information that is independent of that provided by the axial parameters. In both ears of patients with unilateral Ménière's disease, the VA tended to be thinner than those in the control ear.

The mRNA of claudins is expressed in the endolymphatic sac epithelia.

OBJECTIVE: Claudins are a family of membrane proteins which localize to tight junctions (TJs). Recent studies have shown that claudins can form pores for ions in the TJs and regulate the permeability of epithelial paracellular ion transport. The endolymphatic sac (ES) is a part of the inner ear, absorbing the endolymphatic fluid. ES dysfunction may result in endolymphatic hydrops. In this study, we focused on the paracellular transport and examined claudin mRNA expression in the ES epithelia. MATERIALS AND METHODS: Total RNA was isolated from whole ES epithelia of rats by laser capture microdissection. RT-PCR was used to evaluate the expression of claudins. The expression of each claudin mRNA in the epithelial cells of rat ES was confirmed by in situ hybridization. RESULTS: RT-PCR indicated the expression of cldn2, cldn4, cldn6, cldn7, cldn9, cldn11, cldn12, and cldn14. The expression of these claudin mRNAs in the epithelial cells of rat ES was confirmed by in situ hybridization. CONCLUSION: We demonstrated mRNA expression of multiple claudins in the rat ES epithelia. These results in the ES epithelia were consistent with a role of claudins in paracellular ion transport.

Comparison of ( 18 ) F-FLT PET and ( 18 ) F-FDG PET for detection of cervical lymph node metastases in head and neck cancers.

CONCLUSION: Despite low uptake of tracer, 3'-deoxy-3'-(18)F-fluorothymidine (FLT) PET could detect cervical lymph node metastases as well as 2-deoxy-2-(18)F-fluoro-d-glucose (FDG) PET. OBJECTIVE: The diagnostic efficacy of FLT PET was compared with that of FDG PET regarding nodal staging of head and neck squamous cell cancers. METHODS: Twenty-three patients were examined with FLT PET and FDG PET. PET images were evaluated qualitatively for regions of focally increased metabolism and maximum standardized uptake values (SUV) were calculated for semiquantitative analysis. RESULTS: The mean (± SD) FLT SUV in visualized metastatic lymph nodes was 4.8 ± 2.9 as compared with 6.9 ± 4.9 for FDG SUV (p < 0.001). Significant correlations were found between the area of metastatic lymph nodes and both FLT SUV (r = 0.8; p < 0.0001) and FDG SUV (r = 0.84; p < 0.0001). The false-positive (over-staged) and false-negative (under-staged) rates for lymph node staging by FLT PET were 4% (1/23) and 17% (4/23), respectively. Those for FDG PET were 9% (2/23) and 13% (3/23). All metastatic lymph nodes measuring more than 9 mm in short-axis diameter were correctly detected by FLT PET. However, both FLT and FDG PET had low sensitivity for detecting the lymph node metastases ≤ 9 mm in short-axis diameter and tumor deposits < 5 mm.

Presence of FXYD6 in the endolymphatic sac epithelia.

A homeostasis of the electrochemical properties and volume of the endolymph in the inner ear is essential for hearing and equilibrium sensing and is maintained by ion-transport across an epithelial tissue, the endolymphatic sac. One of the key proteins in the maintenance is Na(+), K(+)-ATPase. Although we previously found that the Na(+), K(+)-ATPase in the sac plays a pivotal role in the control of the endolymphatic volume, the mechanism remains unclear. Therefore, in this study, we examined the expression of FXYD6, a functional modulator of the Na(+), K(+)-ATPase, in the epithelial cells of the endolymphatic sac using various approaches. Laser capture microdissection RT-PCR was used to identify FXYD6 mRNA in the endolymphatic sac. Immunolabeling with the specific antibody showed that FXYD6 was predominantly expressed in the intermediate portion of the endolymphatic sac, and it was colocalized with the Na(+), K(+)-ATPase. Because the Na(+), K(+)-ATPase in this region is known to exhibit a high level of activity, an interaction of FXYD6 with this transporter may be critically involved in the regulation of the characteristics of the endolymph.

Tinnitus retraining therapy using portable music players.

OBJECTIVE: We aimed to perform acoustic analysis of environmental sounds used in sound therapy for tinnitus retraining therapy (TRT) and to evaluate the efficacy of TRT performed by using a portable music player (PMP) with recorded environmental sounds as the sound generator. METHODS: Acoustic analysis of environmental sounds was performed using a sound analyzer. The subjects were 23 patients with chronic tinnitus. Patients who had bilateral hearing loss and required hearing assistance were fitted with hearing aids (HAs). Patients with normal hearing or unilateral hearing loss were fitted with a tinnitus control instrument (TCI) or a PMP. The patients were divided into the PMP group, TCI group, and HA group. All subjects underwent audiometric evaluations prior to TRT and completed the tinnitus handicap inventory (THI). The THI scores were evaluated before treatment and 1 month, 3 months, 6 months, and 12 months after treatment. RESULTS: The sound spectrogram of the murmur of a stream showed a wide-frequency band with a constant strength, whereas that of a wave sound showed a wide-frequency band with variable strength. The THI score clearly decreased after 1 month, and this decrease tended to continue over 12 months. The TRT efficacy ratios in the PMP group, TCI group, and HA group at 12 months after treatment were 71%, 67%, and 70%, respectively. CONCLUSIONS: TRT using a PMP had efficacy similar to those of TCI and HA. The murmur of a stream was one of the most effective sounds in TRT. TRT using a PMP as the sound generator can provide the most cost-effective treatment option for tinnitus patients.