Published papers

Fibrocytes of the spiral limbus are thought to play a significant role in maintaining ion homeostasis in the cochlea. The present study measured physiological and morphological changes in spiral limbus of mice in response to noise exposure. 6-week-old male C3H/HeJJcl mice were exposed to octave-band noise (120 dB SPL) for 2 h and evaluated at a series of times thereafter, up to 8 weeks. Permanent hearing loss resulted in the mice, as assessed by auditory brainstem response (ABR) recordings. The fibrocytes loss was found in the spiral limbus of the apical turn, which has been proved to be induced by apoptosis. These results suggest that noise exposure might result in apoptosis of fibrocytes in spiral limbus, which suggest a mechanism for noise-induced hearing loss.

Conclusion: Pure tone auditory thresholds can change according to duration of interrupted tones in patients with mild to severe psychogenic hearing loss (PHL). Objectives: To examine how the duration of stimulus tones affects the hearing thresholds of patients with PHL. Methods: Twelve patients with PHL (21 ears) were enrolled in this study. We initially measured their hearing thresholds using interrupted tones with a duration of 2 s and equal length of on-time and off-time, 225 ± 35 ms, respectively. After a 10 min interval, we measured their hearing thresholds using the same interrupted tones conditions lasting 5 s. The average threshold gains (2 s thresholds minus 5 s thresholds) were compared to those of 15 control subjects with normal hearing (25 ears), 15 patients with cochlear hearing loss (23 ears), and 4 patients with retrocochlear lesions (4 ears). Patients with profound PHL (4 patients, 6 ears) were analyzed separately. Results: The average threshold gain of PHL patients (excluding profound PHL patients) at all frequencies was 18.3 dB, which was significantly larger than that of other groups: 0.3 dB (profound PHL patients), 3.8 dB (controls with normal hearing), 3.0 dB (patients with cochlear hearing loss), and 3.2 dB (patients with retrocochlear lesions).

Objective: There is compelling evidence that tinnitus is associated with functional alterations in the central nervous system. Repetitive transcranial magnetic stimulation (rTMS) is a potent tool for modifying neural activity at the stimulated area and at a distance along the functional anatomical connections. Depending on the stimulation parameters, cortical networks can be functionally disturbed or modulated in their activities. Low-frequency rTMS has been shown to result in a decrease in cortical excitability. The technique can alleviate tinnitus by modulating the excitability of neurons in the auditory cortex. We aimed to investigate the effects of low-frequency rTMS in patients and determine the factors that predict a beneficial outcome with rTMS treatment. Methods: Sixteen patients (male 10, female 6) with chronic tinnitus underwent low-frequency (1. Hz) rTMS (intensity: 110% motor threshold; number of stimuli: 1200) to the left auditory cortex. The treatment outcome was assessed with a visual analog scale (VAS) of loudness, annoyance and duration, loudness balance test, and tinnitus handicap inventory (THI). Therapeutic success was studied according to the patients' clinical characteristics. Results: A significant reduction in the VAS (loudness and annoyance) occurred immediately after rTMS, with a gradual return to pretreatment levels after 7 days. The tinnitus patients with sudden deafness were significant resistant to rTMS treatment compared with those diagnosed with age-related hearing loss. Conclusion: These results support the potential of rTMS as a new therapeutic tool for the treatment of chronic tinnitus. Because this study was performed with a small sample size and showed high interindividual variability in treatment effects, further development of the technique is needed before it can be recommended for clinical applications.

Conclusion: Both the symptoms score and quality of life (QOL) score increased in patients with seasonal allergic rhinitis as pollen dispersed, and nasal congestion, which had a strong effect on sleep, had the largest effect on the decrease in 'total QOL' in all the groups of patients. Objectives: To assess QOL scores in patients with Japanese cedar (JC) pollinosis in relationship to timing of pollen dispersal. Methods: A multicenter, inter-group, cross-sectional study was conducted in 905 adult symptomatic patients with JC pollinosis to investigate the Japanese Allergic Rhinitis Standard QOL Questionnaire (JRQLQ).. The subjects were divided into five groups based on the timing of their responses to the questionnaire. JRQLQ scores were analyzed and compared among the patient groups. Results: Both the symptoms score and JRQLQ score increased in patients as pollen dispersed. Among the symptoms of pollinosis, nasal congestion had the largest effect on the decrease in QOL, and had a strong effect on sleep, which may influence daytime activities and reduce QOL.

With complex nasal sinus anatomy difficult to understand, we designed a three-dimensional (3D) cubic paper sinus model for ENT residents. Seven subjects then put the model together and took it apart. Their understanding of sinus anatomy was assessed in multiple-choice questionnaires before and after training. All subjects' scores improved through training (167%, p=0. 005)-particularly identification of anatomical parts in the axial plain schema (308%, p=0. 007). These results show that 3D anatomical understanding improved dramatically. Training with the 3D cubic paper model thus proved cost-effective for ENT residents.

In the middle ear, a chain of three tiny bones (ie, malleus, incus, and stapes) vibrates to transmit sound from the tympanic membrane to the inner ear. Little is known about whether and how bone-resorbing osteoclasts play a role in the vibration of auditory ossicles. We analyzed hearing function and morphological features of auditory ossicles in osteopetrotic mice, which lack osteoclasts because of the deficiency of either cytokine RANKL or transcription factor c-Fos. The auditory brainstem response showed that mice of both genotypes experienced hearing loss, and laser Doppler vibrometry revealed that the malleus behind the tympanic membrane failed to vibrate. Histological analysis and X-ray tomographic microscopy using synchrotron radiation showed that auditory ossicles in osteopetrotic mice were thicker and more cartilaginous than those in control mice. Most interestingly, the malleal processus brevis touched the medial wall of the tympanic cavity in osteopetrotic mice, which was also the case for c-Src kinase-deficient mice (with normal numbers of nonresorbing osteoclasts). Osteopetrotic mice showed a smaller volume of the tympanic cavity but had larger auditory ossicles compared with controls. These data suggest that osteoclastic bone resorption is required for thinning of auditory ossicles and enlargement of the tympanic cavity so that auditory ossicles vibrate freely.

A meta-analysis showed that chemoradiotherapy (CCRT) improved survival in patients with advanced head and neck squamous cell carcinoma (HNSCC). CCRT has become widely used in treating such patients. The purpose of CCRT in the treatment of resectable HNSCC is to improve survival while preserving organs and functions, and so CCRT is a potential alternative to surgery. However, problems regarding CCRT were revealed such as severe dysphasia and difficulty of salvage surgery. Recently, induction chemotherapy has attracted attention again, the purpose of which is to predict the response of subsequent CCRT or to improve outcomes. Moreover, chemotherapy is concurrently used with postoperative radiotherapy or definitively used for recurrent or metastatic HNSCC. In this article, we review the current state of chemotherapy for HNSCC and consider the problems in Japan.

The aim of this study was to examine differences of susceptibility to oxidative stress of Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) established from Meniere's disease (MD) patients and to examine the effect of ATP treatment in the prognosis and treatment MD. LCLs were established from 10 patients with MD and 10 healthy donors by EBV. Cell viabilities were calculated after treatment of H2O2 with or without ATP. The relationship between the sensitivity of H2O2-treated LCLs to ATP and the staging scale of MD was examined. The nuclear morphological changes of Hoechst 33258-stained LCLs after H2O2-treatment were observed under a fl uorescence microscope. LCLs from MD were significantly more sensitive (p < 0.001) to H2O2 than LCLs from healthy donors after 3 h of H2O2 treatment. All of the ATP-sensitive LCLs were categorized as Stage 1 or 2, while others categorized as Stage 3 or 4 were not sensitive to ATP. There were significant differences (p < 0.01) of cell viabilities after addition of ATP between H2O2-treated LCLs classifi ed as Stage 1 or 2 and as Stage 3 or 4 in MD. Both chromatin condensation and swelling of the cell body were observed in H2O2-treated LCLs. Our findings indicate that LCLs established from MD patients might be used as a unique model to detect susceptibility to oxidative stress and ATP treatment in MD patients. Also, the difference of the sensitivity of H2O2-treated LCLs to ATP might relate to prognosis and treatment of MD. This system may form the basis of tailor-made therapy for MD.

Objective: The aim was to evaluate the oxidative stress and the angiitis in patients with BPPV. Method: Patients with benign paroxysmal positional vertigo (BPPV) within 14 days of onset were analyzed. The level of diacron reactive oxygen metabolites (d-ROM) and circulating soluble vascular cell adhesion molecule 1 (VCAM-1), were evaluated. As a treatment the patients were taught to perform the Brandt-Daroff exercise at home by themselves. The prognosis of BPPV, which is measured as the time until the disappearance of positional nystagmus by a physician during the outpatient visit each week, the relation among the level of oxygen metabolites, vascular molecule and the duration until remission were analyzed. Results: The patients who required longer time for the disappearance of positional nystagmus showed high d-ROM and VCAM levels, whereas those who required shorter time for remission showed lower d-ROM and VCAM levels. Conclusion: There is an increased expression of VCAM-1 and d-ROM confirming the existence of an angiitis and supporting the vascular involvement in BPPV. The identification of the high levels of d-ROM and VCAM-1 can open the way to selective pharmacological treatments able to correct the oxidative stress and activation of endothelial cells.

We have translated the dizziness handicap questionnaires (DHI), which were one of the dizziness questionnaires of a few years ago, confirmed the reliability and applied our results in our clinical research. However each of the sentences in the DHI is not always familiar to the individual dizzy patient. Some other type of questionnaires would therefore be better for some dizzy patients. A vertigo handicap questionnaire (VHQ) is one of the questionnaires for the quantitative evaluation of the degrees of handicap in the daily lives of patients with vestibular disorders. It consists of 25 questions. The aim of the present study was to examine the validity and reliability of the Japanese translation of the VHQ (VHQ-J). The VHQ-J was undergone by 110 patients suffering dizziness. The results were analyzed and are summarized as follows: (1) Cronbach's alpha coefficient, which measures the reliability based on the consistency of the questionnaire, was 0.78. (2) The VHQ-J components significantly correlated with the Dizziness handicap inventory (DHI-J) (p<0.05). (3) The VHQ-J results significantly correlated with the Hospital Anxiety and Depression Scale (HADS) (p<0.05). (4) The VHQ-J significantly correlated with the State-Trait Anxiety Inventory (STAI) (p<0.05). These results indicated that the VHQ- J is a valid and reliable questionnaire that can be used to assess the degree of handicap in the daily lives of patients with vestibular disorders.

Sho-saiko-to-ka-kikyo-sekko (TJ-109) is composed of 9 herbs (gypsum, Bupleurum root, Pinellia tuber, Scutellaria root, Platycodon root, jujube fruit, ginseng root, Glycyrrhiza root, and ginger rhizome). It is a folk medicine that has been used to treat pharyngitis or acute tonsillitis. The efficacy of TJ-109 for treating patients with chronic tonsillitis was investigated. Ten outpatients who experienced chronic tonsillitis for more than 2 years were recruited. TJ-109 was prescribed, and after one year of daily treatment the incidence of acute tonsillitis before and after the treatment was compared. The incidence of acute tonsillitis due to chronic tonsillitis decreased in all 7 patients who were followed up. No adverse events were observed in any of the patients. In conclusion, the herbal medicine TJ-109 effectively reduced the incidence of acute tonsillitis. In some cases, planned tonsillectomy was avoided.

Headaches is classified as primary and secondary, with secondary originating in head and neck conditions, the most important etiology being acute sinusitis. Headache due to mucosal contact, rarely encountered by otorhinolaryngologists, is an important secondary headache, whose criteria are defined by the International Classification of Headache Disorders to include intermittent pain localized in the periorbital and medial canthal or temporozygomatic regions, evidence that pain is attributable to mucosal contact and the presence of mucosal contact in the absence of acute rhinosinusitis, obtained using clinical examinations, nasal endoscopy, and/or computed tomography (CT). After mucosal contact is surgically corrected pain usually disappears permanently within 7 days. We reviewed mucosal contact headaches in 63 subjects undergoing nasal or paranasal surgery from April 2007 to March 2008. Of those 7 were diagnosed with headaches due to contact points in nasal mucosa, ranging from canthal to the temporozygomatic. The most common contact, between the middle turbinate and nasal septum, was seen in 6 of the 7. Surgery eliminated symptoms in 4 and ameliorated them in 3 indicating effective headache management. Subjects with severe headaches or localized periorbital and medial canthal pain regions, mucosal contact involvement is ruled out when CT allows no lesions. When mucosal contact headache is suspected, however surgery should be considered as a last resort.

Anxiety and depression greatly affect the prognosis of and burden on subjects seen for dizziness or vertigo, who usually report multiple somatic symptoms. We studied the prevalence of these symptoms in 145 subjects hospitalized for dizziness or vertigo and taking part in 4-day group vestibular rehabilitation. Questionnaires given to determine the prevalence of somatic symptoms assessed headache, insomnia, diarrhea, constipation, stomachache, chest pain, palpitations, dyspnea, general fatigue, and stress. Quantitation used aerical rating scale (NRS). Anxiety and depression were assessed using the hospital anxiety and depression scale (HADS). Disability due to dizziness was assessed using the dizziness handicap inventory (DHI). We conducted correlational analysis between dizziness and somatic symptoms. The top four average NRS scores for somatic symptoms were dizziness at 3.5 ± 2.8, general fatigue at 2.8 ± 2.6, insomnia at 2.4 ±2.6, and headache at 1.8 ±2.3. These symptoms resembled those reported for subjects with anxiety and depression. The correlation between headache and dizziness NRS scores was R = 0.48 (P<0.0001). The total HADS score was 13.9 ±8.1 points (anxiety 7.2 ±4.3, depression 6.7 ±4.3). The average DHI score was 36.3 ±24.1 points. These results indicate that those with dizziness reported several somatic symptoms related to anxiety and depression attributable to dizziness. This underscores the need to treat these somatic symptoms when treating subjects seen chiefly dizziness or vertigo.

Tinnitus and dizziness are symptoms of acute mountain sickness. We investigated the mechanism by which high altitude (i.e. hypobaric hypoxia) affects inner ear function by measuring transient evoked otoacoustic emissions (TEOAE) and distortion product otoacoustic emissions (DPOAE) under conditions of normobaric normoxia (1,013 hPa; 760 mm Hg) and hypobaric hypoxia (540 hPa; 405 mm Hg). The possibility that air pressure effects on the eustachian tube impacted our findings was excluded by the use of tympanograms. The nonphysiological effects of hypobaric hypoxia on TEOAE and DPOAE were also assessed using an ear simulator. Under conditions of hypobaric hypoxia, both TEOAE and DPOAE levels were reduced. The amount of reduction that occurred was approximately 4 dB in the total echo power and signal-to-noise ratio of the TEOAE, and in the 2f1 - f2 element level of the DPOAE. Stimulus levels that were measured using an ear simulator were also reduced by approximately 4 dB under conditions of hypobaric hypoxia. These results do not indicate that stimulus levels affected TEOAE and DPOAE levels because these levels were actually only slightly affected by changes in the stimulus level. Instead, this reduction was likely due to the nonphysiological hypobaric effects of the sound pressure emitted from the tympanic membrane. We conclude that the impact of hypobaric hypoxia on cochlear function was negligible up to pressures of 540 hPa.

Autonomic dysfunction is prevalent in dizzy patients. However, evaluating the autonomic nervous system is not very popular, since it is not easy to do. The Pulse Analyzer Plus® is a small device that measures a patient's pulse from his/her finger tip with a small probe, making it possible to evaluate autonomic nervous system function in as little as 5 minutes. The algorithm is identical to the one used in the frequency analysis of electrocardiograms. We report herein on our findings on the autonomic function of 25 dizzy patients who visited our department. Age-matched control data were obtained from healthy volunteers and patients not suffering from dizziness. The measurements were conducted in 5 minutes with the patient in the sitting position. Fast Fourier Transform (FFT) was used to calculate low frequency (LF) components, which mainly reflect sympathetic nervous system function, and high frequency (HF) components, which reflect parasympathetic nervous system (PNS) function. Natural logarithm (Ln) values were calculated for LF and HF components and used for conventional comparison. The ratio of LF/HF was also calculated. The results of the normal controls were LnLF = 5.2 ± 1.6 (mean ± SD), LnHF = 4.3 ± 1.2, LnLF/HF = 1.2 ± 0.3 whereas those of the dizzy patients were 4.4 ± 1.9, 3.5 ± 1.2 and 1.3 ± 0.5 respectively. The HF value of the dizzy patients was significantly smaller than that of the control subjects (P<0.05). These data indicate that PNS hypofunction was present in the dizzy patients. Future studies need to determine whether autonomic dysfunction results from the therapeutic interventions used to treat dizziness.

This is the report of rare cases to show the potential ototoxicity of Burow's solution in clinical use. We encountered two cases of acute sensorineural hearing loss occurring after the administration of 8% Burow's solution (pH 2.93) into the tympanic cavities. Prior to treatment, both cases presented with tympanic membrane perforations in the posterior and inferior portions and a small amount of serous discharge. Fortunately, hearing loss recovered almost completely except for high tones within a few weeks. These two case reports demonstrate that the ototoxicity of Burow's solution should be considered when it is used to treat otitis media accompanied by tympanic membrane perforation.

In our practice, we often encounter dizzy patients in whom organic and functional abnormalities are lacking, as assessed by a variety of clinical examinations. In these patients, anxiety and depression are strongly related to their clinical symptoms. We diagnose these patients as having "psychogenic dizziness" and treat them with antidepressants and anxiolytics. Although therapeutic evaluation of patients' subjective complaints and objective evaluation by doctors are usually performed, an objective measurement is necessary to determine whether the drug treatments are effective. In the present study, we used static posturography to objectively evaluate the therapeutic response to antidepressant and anxiolytic treatments in patients with psychogenic dizziness. Thirty-seven patients with psychogenic dizziness participated in this study. All patients were prescribed antidepressants and anxiolytics. We assessed each patient using static posturography before treatment and 4 weeks after treatment. Static posturography was performed for 60 seconds with the patients' eyes open and closed. The Clinical Global Impressions-Improvement (CGI-I) scale was used for global evaluation. On the basis of the CGI-I scores, the subjects were divided into two groups: I, improved (≦3), and N, not improved (≧4). The following static posturography measurements were used for comparison: length (LNG), environmental area (ENV), and LNG/ENV. For each of these parameters, we determined improvement rates by calculating the difference between before- and after-treatment measurements. We found that CGI-I scores correlated with LNG, ENV with eyes open, and ENV with eyes closed. The improvement rates of groups I and N were significantly different for all parameters. Data obtained from subjects that had lower improvement rates relative to control values were selected for further analysis. Control values were obtained from 2201 normal subjects. Group I subjects that had low LNG/ENV values (with eyes open) before treatment showed significantly increased LNG/ENV values (with eyes open) after treatment. Our analyses revealed statistically significant differences between groups I and N in some static posturography values obtained before and after treatment. Our findings indicate that static posturography values can be used to objectively evaluate psychogenic dizziness in future studies.

OPA1 mutations are known to cause autosomal dominant optic atrophy (ADOA), and some types of OPA1 mutations also cause auditory neuropathy. In the present study, we evaluated the vestibular dysfunction that accompanied auditory neuropathy in a patient with an OPA1 mutation. A caloric test failed to elicit nystagmus or dizziness in either ear. Vestibular evoked myogenic potentials (VEMPs) in the right ear were characterized by a normal biphasic waveform. In contrast, no VEMPs were evoked in the left ear. Model building suggested that the OPA1 mutation, p.R445H, indirectly distorts the catalytic structure of the GTPase reaction center and decreases GTPase activity. The patient complained of instability while walking or moving but thought these symptoms were caused by visual dysfunction. This is the first report of a detailed evaluation of vestibular dysfunction in a patient with an OPA1 mutation. This case suggests that vestibular dysfunction may be involved in motor instability in patients with an OPA1 mutation, even when patients do not complain of vestibular symptoms. Based on this case, we suggest that vestibular evaluation should be performed in auditory neuropathy patients carrying an OPA1 mutation, even if the patients are free of symptoms of vestibular dysfunction.