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Papers - Oishi, Naoki

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Auditory resting-state functional connectivity in tinnitus and modulation with transcranial direct current stimulation

Minami Shujiro B., Oishi Naoki, Watabe Takahisa, Uno Kimiichi, Kaga Kimitaka, Ogawa Kaoru

Acta Oto-Laryngologica 135 ( 12 ) 1286 - 1292 2015.12

ISSN 0001-6489

Conclusions: The functional connectivity (FC) between the right and left auditory cortex is weak in tinnitus patients. Transcranial direct current stimulation (tDCS) over the auditory cortex has potential as a tool to modulate auditory-based FC. Objective: This study investigated the effects of applying tDCS in tinnitus patients, and searched for modulation of brain networks in resting-state functional magnetic resonance imaging (rs-fMRI) through an analysis of FC with the stimulated brain region. Subjects and methods: Nine male patients with chronic tinnitus and 10 male volunteers with normal hearing were enrolled. The subjects were evaluated with rs-fMRI immediately before and after tDCS. The tinnitus patients filled out the self-evaluation questionnaires designed to measure tinnitus conditions before tDCS treatment and 1 week afterwards. Results: The FC between the right and left auditory cortex was significantly weaker in tinnitus patients than in controls. After tDCS treatment, in the tinnitus group, the primary auditory cortex showed a reduction in the amount of statistically significant connectivity with the somatosensory area and motor area, but maintained strong significant connectivity (p < 0.005) with the auditory area and insular cortex. In contrast, in the control group, there remained strong significant connectivity between the primary auditory cortex and the somatosensory area, motor area, insular cortex, and auditory area.

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Metformin protects against gentamicin-induced hair cell death in vitro but not ototoxicity in vivo

Oishi Naoki, Kendall Ann, Schacht Jochen

Neuroscience Letters 583 65 - 69 2014.11

ISSN 0304-3940

Metformin (N,N-dimethylbiguanidine) is a widely employed oral hypoglycemic agent for the management of type 2 diabetes mellitus. Its antioxidant properties and safe clinical use raise the possibility of preventing gentamicin-induced hearing loss in patients. Therefore, we screened the usefulness of metformin against gentamicin toxicity in murine cochlear explants and in the guinea pig in vivo. We confirmed in organ culture that metformin blocks the gentamicin-induced translocation of endonuclease G into the nucleus of outer hair cells and attenuates hair cell loss. In vivo, gentamicin treatment with 80, 100, or 130 mg/kg body weight for 14 days induced significant threshold shifts as determined by auditory brain stem responses. Metformin (30, 75, or 100 mg/kg for 14 days) was well tolerated without any indication of auditory side effects. However, co-administration of metformin with gentamicin in various permutations did not prevent loss of auditory function. On the contrary, combined treatment at higher dosages aggravated the gentamicin-induced threshold shifts and caused additional adverse reactions including body weight loss and premature deaths in some animals. These results caution against the use of metformin co-treatment with aminoglycosides and confirm the need for in vivo studies in order to evaluate potentially protective agents selected by in vitro screens.

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A case of intractable suspected perilymph fistula with severe depression

Goto Fumiyuki, Oishi Naoki, Tsutsumi Tomoko, Ogawa Kaoru

Psychiatry Investigation 11 ( 4 ) 499 - 501 2014

ISSN 1738-3684

A 68-year-old woman presented dizziness whenever she put her finger into the right ear and also complained of water-streaming tinnitus, which indicated she would have been suffering from perilymph fistula. An exploratory tympanotomy was conducted. Leakage of perilymph from the round window was suspected, although the cochlin-tomoprotein (CTP) results were negative. After the procedure, the patient’s finger-induced dizziness, tinnitus, and vertigo spells disappeared completely. However, her dizzy symptom did not improve. The patient also complained of general fatigue, weight loss, and insomnia, which led us to suspect comorbid depression. Antidepressants and vestibular rehabilitation treatment resulted in a significant improvement in her dizziness. Although it is not apparent whether the patient had a perilymph fistula, this case demonstrates the importance of evaluating not only physical symptoms but also psychological comorbidity, especially when the physical symptoms are intractable despite treatment.

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Long-term effects of tinnitus retraining therapy involving monaural noise generators

Inagaki Yozo, Oishi Naoki, Kanzaki Sho, Wakabayashi Satoko, Fujioka Masato, Watabe Takahisa, Watanabe Reiko, Wasano Koichiro, Yamada Hiroyuki, Kojima Takashi, Shinden Seiichi, Ogawa Kaoru

Journal of Otolaryngology of Japan 117 ( 2 ) 116 - 121 2014

ISSN 0030-6622

We have previously reported on the effects of tinnitus retraining therapy (TRT) involving monaural noise generators (NGs) up to 24 months after the start of treatment (Eur Arch Otorhinolaryngol. 2013 Feb; 270(2): 443-8.) but very few reports exist about the long-term effects of TRT for periods of over 2 years. The aim of this study was to report the effects of TRT involving monaural NGs more than 24 months after the start of treatment. Thirty-three patients with chronic tinnitus were included in this study. All received directive counseling and monaural NGs without any other combination treatment. Effects were evaluated with the Tinnitus Handicap Inventory (THI) at their final visits to our clinic (average 31 months after the start of treatment). The average THI scores significantly improved from 55.3 ± 19.7 at baseline to 33.5 ±23.3 at their final visits. Seventeen patients (52%) improved by more than 20 points from the baseline. Eleven patients who were treated with TRT for more than 3 years were individually observed in a detailed manner. Some of them experienced aggravation of their symptoms after 2 years' successful treatments. This study suggests that, although TRT seems effective more than 2 years after the start of treatment, the clinical course of each patient can vary and we need to follow them periodically depending on their situations and symptoms.

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Tumor necrosis factor-alpha-mutant mice exhibit high frequency hearing loss

Oishi Naoki, Chen Jun, Zheng Hong Wei, Hill Kayla, Schacht Jochen, Sha Su Hua

JARO - Journal of the Association for Research in Otolaryngology 14 ( 6 ) 801 - 811 2013.12

ISSN 1525-3961

Exogenous tumor necrosis factor-alpha (TNF-α) plays a role in auditory hair cell death by altering the expression of apoptosis-related genes in response to noxious stimuli. Little is known, however, about the function of TNF-α in normal hair cell physiology. We, therefore, investigated the cochlear morphology and auditory function of TNF-α-deficient mice. Auditory evoked brainstem response showed significantly higher thresholds, especially at higher frequencies, in 1-month-old TNF-α^-/- mice as compared to TNF-α^+/- and wild type (WT); hearing loss did not progress further from 1 to 4 months of age. There was no difference in the gross morphology of the organ of Corti, lateral wall, and spiral ganglion cells in TNF-α^-/- mice compared to WT mice at 4 months of age, nor were there differences in the anatomy of the auditory ossicles. Outer hair cells were completely intact in surface preparations of the organ of Corti of TNF-α^-/- mice, and synaptic ribbon counts of TNF-α^-/- and WT mice at 4 months of age were similar. Reduced amplitudes of distortion product otoacoustic emissions, however, indicated dysfunction of outer hair cells in TNF-α^-/- mice. Scanning electron microscopy revealed that stereocilia were sporadically absent in the basal turn and distorted in the middle turn. In summary, our results demonstrate that TNF-α-mutant mice exhibit early hearing loss, especially at higher frequencies, and that loss or malformation of the stereocilia of outer hair cells appears to be a contributing factor. © 2013 Association for Research in Otolaryngology.

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Severe obstructive sleep apnea in loeys-dietz syndrome successfully treated using continuous positive airway pressure

Takenouchi Toshiki, Saito Hideyuki, Maruoka Ryo, Oishi Naoki, Torii Chiharu, Maeda Jun, Takahashi Takao, Kosaki Kenjiro

American Journal of Medical Genetics, Part A 161 ( 7 ) 1733 - 1736 2013.07

ISSN 1552-4825

Loeys-Dietz syndrome is a recently recognized connective tissue disorder characterized by severe craniofacial and skeletal abnormalities as well as arterial tortuosity with aggressive aneurysm formation. Marfan syndrome, a classic connective tissue disorder, is known to be associated with a risk of obstructive sleep apnea, but sleep-related breathing disorders have not been previously documented in Loeys-Dietz syndrome. The propositus had the prototypic features of Loeys-Dietz syndrome with a de novo mutation in TGFBR2. He developed severe obstructive sleep apnea during his infancy. Continuous positive airway pressure was introduced at age 7 years and provided significant improvement in his nocturnal apnea and sleep apnea-related symptoms, such as enuresis. Marfan syndrome is known to be associated with a high risk of sleep apnea because of its characteristic craniofacial and connective tissue abnormalities. Similarly, the severe craniofacial abnormalities in Loeys-Dietz syndrome may predispose patients to severe obstructive sleep apnea, even at a very young age. Despite the severity of obstructive sleep apnea in the propositus, the administration of continuous positive airway pressure was highly effective in alleviating his symptoms. In summary, severe obstructive sleep apnea was successfully treated using continuous positive airway pressure in a patient with Loeys-Dietz syndrome. Careful evaluation and aggressive intervention for the alleviation of obstructive sleep apnea is warranted in Loeys-Dietz syndrome. © 2013 Wiley Periodicals, Inc.

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Daytime somnolence in an adult with smith-magenis syndrome

Takenouchi Toshiki, Saito Hideyuki, Oishi Naoki, Fukushima Hiroyuki, Kosaki Rika, Torii Chiharu, Takahashi Takao, Kenjiro Kosaki

American Journal of Medical Genetics, Part A 161 ( 7 ) 1803 - 1805 2013.07

ISSN 1552-4825

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Endoscopic investigation and evaluation of anxiety for the management of globus sensation

Oishi Naoki, Saito Koichiro, Isogai Yutaka, Yabe Haruna, Inagaki Koji, Naganishi Hideki, Kimura Hiroyuki, Ogawa Kaoru

Auris Nasus Larynx 40 ( 2 ) 199 - 203 2013.04

ISSN 0385-8146

Objective: To verify whether the severity of globus sensation would be affected by the results of investigations on possible underlying serious pathology in the head, neck and esophagus. Methods: Thirty-six patients with globus sensation were enrolled in this study. All the patients suffered relatively persistent globus sensation which remained after conventional laryngoscopy at their family doctors. These patients were investigated for possible underlying oropharyngeal and esophageal lesions using fiberoptic endoscopy. The severity of globus was evaluated by the visual analog scales (VAS), and the degree of anxiety was evaluated by the state section of State Trait Anxiety Inventory (STAI-s). The questionnaires were administered at their first visits, and 9.6. ±. 3.2 months after endoscopy. The follow-up data obtained from 22 patients were incorporated in the further evaluations. Multiple regression analysis was used to evaluate the relationship between the improvement of VAS scores and that of STAI-s scores. Afterwards, Pearson product-moment correlation coefficient was measured. The recorded images of fiberoptic endoscopy were retrospectively verified by an expert of upper gastrointestinal endoscopy. Results: No malignancies were observed in the endoscopic examination. Despite no treatment administered during the follow-up period, significant improvement of VAS scores was observed from the initial scores (40. ±. 21) to follow-up scores (27. ±. 27, p= 0.014) in the patients examined in this study. The multiple linear regression analysis proved that the improvement of STAI-s scores was the only factor significantly affected the improvement of VAS scores (p= 0.029) among the dependent valuables. The retrospective evaluation of the recorded images revealed comorbid esophagitis in 10 out of the 22 patients. When patients were stratified with the presence of comorbid esophagitis, significant improvement of VAS scores was observed only in the group without comorbid esophagitis at their follow up (17. ±. 20, p= 0.026) compared with their initial scores (36. ±. 17). The multiple linear regression analysis proved that the improvement of VAS scores was significantly affected by the improvement of STAI-s scores (p= 0.047) in this group. Moreover, significant positive relationship between the improvement of VAS scores and that of STAI-s scores was observed only in the group without comorbid esophagitis (r= 0.61, p= 0.047). Conclusion: Proper investigation to prove no underlying serious pathology may lead to the improvement of globus sensation in the patients without comorbid esophagitis through the reduction of their anxiety even when their symptoms are relatively persistent. Our results also indicated that some treatments against esophagitis may be helpful for the improvement of globus sensation in the patients with this comorbid disease. © 2012 Elsevier Ireland Ltd.

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Characteristic electroencephalographic findings by photic driving in patients with migraine-associated vertigo

Goto Fumiyuki, Oishi Naoki, Tsutsumi Tomoko, Ito Takao, Arai Motohiro, Ogawa Kaoru

Acta Oto-Laryngologica 133 ( 3 ) 253 - 256 2013.03

ISSN 0001-6489

Conclusions: Patients with migraine-associated vertigo (MAV) may have a higher incidence of photic-driven electroencephalography (EEG) response. The occurrence of photic-driven responses for stimulation at frequencies of 10, 12, and 15 Hz can be considered a positive indicator for MAV. Although photic driving is not specific to migraine, patients with MAV have a higher incidence of photic driving. The distinction between Ménière's disease and MAV by means of EEG would be another interesting topic of research. Objective: The objective of this study was to distinguish between patients with MAV and patients with other vestibulopathies (VPs) using EEG. Methods: EEG with intermittent photic stimulation (PS) at frequencies between 3 and 24 Hz was recorded to quantify photic driving in patients with MAV (n = 21) and VPs (n = 15). The presence or absence of photic driving was determined; a score of 1 was counted for response to a particular frequency. Results: Total scores were calculated for each patient for statistical comparison. There was a significant difference in the average total score between MAV and VP patients (p < 0.05), and photic-driven responses were observed for 10, 12, and 15 Hz stimulation. © 2013 Informa Healthcare.

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Intra-tympanic delivery of short interfering RNA into the adult mouse cochlea

Oishi Naoki, Chen Fu Quan, Zheng Hong Wei, Sha Su Hua

Hearing Research 296 36 - 41 2013.02

ISSN 0378-5955

Trans-tympanic injection into the middle ear has long been the standard for local delivery of compounds in experimental studies. Here we demonstrate the advantages of the novel method of intra-tympanic injection through the otic bone for the delivery of compounds or siRNA into the adult mouse cochlea. First, a fluorescently-conjugated scrambled siRNA probe was applied via intra-tympanic injection into the middle ear cavity and was detected in sensory hair cells and nerve fibers as early as 6 h after the injection. The fluorescent probe was also detected in other cells of the organ of Corti, the lateral wall, and in spiral ganglion cells 48 h after the injection. Furthermore, intra-tympanic delivery of Nox3 siRNA successfully reduced immunofluorescence associated with Nox3 in outer hair cells 72 h after injection by 20%. Drug or siRNA delivery via intra-tympanic injection does not compromise the tympanic membrane or interfere with noise-induced hearing loss, while trans-tympanic injections significantly altered the cochlear response to noise exposure. In summary, intra-tympanic injection through the otic bone into the middle ear cavity provides a promising approach for delivery of compounds or siRNA to cochlear hair cells of adult mice, relevant for the study of mechanisms underlying inner ear insults and, specifically, noise-induced hearing loss. © 2012 Elsevier B.V.

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Effects of tinnitus retraining therapy involving monaural noise generators

Oishi Naoki, Shinden Seiichi, Kanzaki Sho, Saito Hideyuki, Inoue Yasuhiro, Ogawa Kaoru

European Archives of Oto-Rhino-Laryngology 270 ( 2 ) 443 - 448 2013.02

ISSN 0937-4477

The aim of this study was to assess how tinnitus retraining therapy (TRT) employing monaural noise generators (NGs) affects tinnitus patients. Ninety-five patients with chronic tinnitus were included in this study. All received directive counseling and monaural NGs without any other combination treatment. Effects were evaluated with the Tinnitus Handicap Inventory (THI) 6, 12, and 24 months after the start of treatment. Multiple regression analysis was used to evaluate factors associated with improvement of THI scores. We observed a significant improvement in the average THI scores, which ranged from 59 at baseline to 36 after 6 months and were stable up to 24 months. Severely distressed (SD) patients experienced more benefits from the therapy than moderately distressed (MD) patients. Multiple regression analysis revealed that the presence of transient anxiety symptoms, measured by the state section of the State Trait Anxiety Inventory at the beginning of treatment, were associated the most to a decline in THI scores in SD patients. Pure-tone average at three mid frequencies was a negatively contributing factor. Analysis of MD patients did not provide a good model. In conclusion, TRT employing monaural NGs was an effective intervention especially for SD patients, although plateau of the effects after 6 months may be indicative of limitation of applying NGs monoaurally. Reducing the patients' hearing handicap may reinforce the effects of TRT in SD patients. Additional evaluation and interventions for both SD and MD patients might be needed. © 2012 Springer-Verlag.

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Ototoxicity in Dogs and Cats

Oishi Naoki, Talaska Andra E., Schacht Jochen

Veterinary Clinics of North America - Small Animal Practice 42 ( 6 ) 1259 - 1271 2012.11

ISSN 0195-5616

A variety of drugs in veterinary use have side effects that can potentially damage the senses of hearing or balance in animals. A large body of literature exists on the incidence and mechanisms of ototoxicity in experimental animals and in humans, but little is documented in domestic dogs and cats. However, the generality of these adverse actions across species allows one to extrapolate and provide the veterinarian with insight into possible complications of chemotherapy. © 2012 Elsevier Inc.

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Hidden depression in otolaryngology patients with medically unexplained symptoms

Goto Fumiyuki, Tsutsumi Tomoko, Oishi Naoki, Mimura Masaru

General Hospital Psychiatry 34 ( 2 ) 206 - 208 2012.03

ISSN 0163-8343

Objective: To investigate the prevalence of depression among otolaryngology patients with medically unexplained symptoms (MUS) and the outcome of treatment with selective serotonin reuptake inhibitors (SSRIs). Method: Ninety patients with MUS from a population of 983 consecutive otolaryngology outpatients were enrolled. The Self-Rating Depression Scale (SDS) was used to screen for depression. In addition to standard treatment, all depressed and nondepressed patients received SSRIs for 8 weeks. The Clinical Global Impression-Improvement (CGI-I) scale was used to evaluate clinical changes in patients with MUS. Results: There were 49 patients with depression among those with MUS, according to the SDS criteria. The patients with depression showed a better outcome than those without depression, demonstrating more significantly improved CGI-I scores. Conclusion: More than half of the individuals with otolaryngological MUS had depression, and their MUS were successfully treated withSSRIs. © 2012 Elsevier Inc..

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Two cases of acute mastoiditis requiring emergency mastoidectomy following treatment by pediatrician

Sato Tetsuya, Oishi Naoki, Takei Yasuhiko, Kohno Naoyuki

Practica Oto-Rhino-Laryngologica 104 ( 12 ) 859 - 863 2011.12

ISSN 0032-6313

Advances in broad-spectrum antibiotics are enabling general physicians and pediatricians to treat acute middle-ear infection without otolaryngologists' intervention. Most such subjects also recover without serious complications. Middle-ear infection remains potentially life-threatening, however, due to potential infectious intracranial complications, requiring surgery by otolaryngologists. We report two cases of acute pediatric mastoiditis following acute otitis media. Both had been initially treated by pediatricians and administered several antibiotics. One subject had masked mastoiditis when first seen and the other serious complications involving intracranial infection thought due to comorbid congenital cholesteatoma. Both were treated successfully with mastoidectomies followed by intravenous antibiotic therapy.

Advanced hypopharyngeal cancer with amyotrophic lateral sclerosis

Kogashiwa Yasunao, Oishi Naoki, Yamauchi Kohichi, Kohno Naoyuki

Auris Nasus Larynx 38 ( 6 ) 750 - 752 2011.12

ISSN 0385-8146

We present a case of advanced hypopharyngeal cancer occurring in a patient with amyotrophic lateral sclerosis (ALS). A 58-year-old man diagnosed with ALS 2 years previously noticed a mass in his neck and dysphagia. We diagnosed him as having hypopharyngeal squamous cell carcinoma with the left cervical lymph node metastases (T3N2bM0) and treated with concurrent chemoradiotherapy. During and after the treatment, his neurological symptoms showed no worse signs. The patient has been cancer-free for 13 months after concurrent chemoradiotherapy. The influence of ALS on the patients' quality of life (QOL) and/or prognosis had to be taken into consideration when determining an appropriate treatment for the hypopharyngeal cancer. To the best of our knowledge, this may be the first case with ALS who was treated for hypopharyngeal cancer. © 2011 Elsevier Ireland Ltd.

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Influence of depressive symptoms, state anxiety, and pure-tone thresholds on the tinnitus handicap inventory in Japan

Oishi Naoki, Shinden Seiichi, Kanzaki Sho, Saito Hideyuki, Inoue Yasuhiro, Ogawa Kaoru

International Journal of Audiology 50 ( 7 ) 491 - 495 2011.07

ISSN 1499-2027

Objective: To assess factors that contribute to Tinnitus Handicap Inventory (THI) scores in Japan. Design: Case series with chart review. Study sample: Two hundred and eighty-five tinnitus patients at tertiary referral center, who completed the Japanese version of the THI, the Self-rating Depression Scale (SDS), and the State Trait Anxiety Inventory (STAI). Results: In multiple regression analysis, the SDS score contributed the most to the THI score. The state section of the STAI score and pure tone average (PTA) at four high frequencies also contributed significantly, but to lesser degrees. The other following factors were not statistically significant: age, gender, time from the onset of tinnitus to the first clinical visit, PTA at three mid frequencies, and trait section of the STAI score. This model may account for approximately 45% of THI score variability. Conclusions: The THI scores may be influenced by depressive symptoms, state anxiety, and pure tone thresholds in Japan. © 2011 British Society of Audiology, International Society of Audiology, and Nordic Audiological Society.

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Pure tone auditory thresholds can change according to duration of interrupted tones in patients with psychogenic hearing loss

Oishi Naoki, Inoue Yasuhiro, Hori Akemi, Yakushimaru Reiko, Kohno Naoyuki, Ogawa Kaoru

Acta Oto-Laryngologica 131 ( 6 ) 628 - 632 2011.06

ISSN 0001-6489

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). © 2011 Informa Healthcare.

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Severe progressive sensorineural hearing loss improved after removal of large jugular foramen schwannoma

Oishi Naoki, Kohno Naoyuki, Shiokawa Yoshiaki

Auris Nasus Larynx 38 ( 3 ) 398 - 401 2011.06

ISSN 0385-8146

We report a very rare case of hearing improvement after removal of the intracranial part of a jugular foramen schwannoma (JFS) presenting with chronic and severe progressive sensorineural hearing loss (SNHL). The patient presented with progressive hearing impairment in his right ear, lasting 2 years. The patient's pure tone audiogram revealed severe SNHL. His speech discrimination score (SDS) was 0%. Auditory-evoked brain responses (ABRs) comprised only I waves following 30-100. dB stimulation, although distortion-product otoacoustic emissions (DPOAEs) had good responses. These test results indicated that his hearing impairment was retrocochlear SNHL. Magnetic resonance imaging revealed within the right jugular foramen a large intracranial-extracranial tumor that compressed the brainstem. The intracranial part of the tumor was resected through retrosigmoidal craniotomy, and the tumor was pathologically diagnosed as a schwannoma. Several months after the operation, the patient's auditory thresholds improved to a level consistent with mild SNHL, ABR V waves emerged following 60-90. dB stimulation, and SDS improved significantly to 95%. This case demonstrates that hearing improvement can be achieved after surgery for JFS presenting with severe and chronic progressive SNHL, and that good DPOAE responses and the presence of ABR I waves may be predictors of postoperative hearing recovery in JFS. © 2010 Elsevier Ireland Ltd.

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Emerging treatments for noise-induced hearing loss

Oishi Naoki, Schacht Jochen

Expert Opinion on Emerging Drugs 16 ( 2 ) 235 - 245 2011.06

ISSN 1472-8214

Introduction: Approximately 5% of the population worldwide suffers from industrial, military or recreational noise-induced hearing loss (NIHL) at a great economic cost and detriment to the quality of life of the affected individuals. This review discusses pharmacological strategies to attenuate NIHL that have been developed in animal models and that are now beginning to be tested in field trials. Areas covered: The review describes the epidemiology, pathology and pathophysiology of NIHL in experimental animals and humans. The underlying molecular mechanisms of damage are then discussed as a basis for therapeutic approaches to ameliorate the loss of auditory function. Finally, studies in military, industrial and recreational settings are evaluated. Literature was searched using the terms 'noise-induced hearing loss' and 'noise trauma'. Expert opinion: NIHL, in principle, can be prevented. With the current pace of development, oral drugs to protect against NIHL should be available within the next 5 - 10 years. Positive results from ongoing trials combined with additional laboratory tests might accelerate the time from the bench to clinical treatment. © Informa UK, Ltd.

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Repetitive transcranial magnetic stimulation (rTMS) for treatment of chronic tinnitus

Minami Shujiro B., Shinden Seiichi, Okamoto Yasuhide, Watada Yukiko, Watabe Takahisa, Oishi Naoki, Kanzaki Sho, Saito Hideyuki, Inoue Yasuhiro, Ogawa Kaoru

Auris Nasus Larynx 38 ( 3 ) 301 - 306 2011.06

ISSN 0385-8146

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. © 2010 Elsevier Ireland Ltd.

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Burow's solution-induced acute sensorineural hearing loss

Oishi Naoki, Inoue Yasuhiro, Saito Hideyuki, Ogawa Kaoru

Auris Nasus Larynx 37 ( 3 ) 369 - 372 2010.06

ISSN 0385-8146

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. © 2009 Elsevier Ireland Ltd.

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Long-term prognosis of low-frequency hearing loss and predictive factors for the 10-year outcome

Oishi Naoki, Inoue Yasuhiro, Saito Hideyuki, Kanzaki Sho, Kanzaki Jin, Ogawa Kaoru

Otolaryngology - Head and Neck Surgery 142 ( 4 ) 565 - 569 2010.04

ISSN 0194-5998

Objectives: To determine the long-term prognosis of low-frequency hearing loss and predictive factors for the 10-year outcome of low-frequency hearing loss. Study Design: Case series with chart review. Setting: Tertiary referral center. Subjects and Methods: From 1979 to 1998, 466 consecutive patients with low-frequency hearing loss received initial treatment at the Hearing and Tinnitus Clinic of Keio University Hospital. Of the 49 eligible patients, pure-tone threshold data obtained over a period of 10 years after onset of low-frequency hearing loss were available for analysis. To determine the progression of hearing loss, we analyzed audiometric pattern changes. We also examined how the following factors affected 10-year prognosis: sex, age, side of hearing loss, accompanying dizziness, pre-therapeutic hearing thresholds at low frequencies, initial therapy results, and fluctuation of hearing during the first year after onset. Results: High- and pan-frequency hearing loss increased as time progressed. About half of the cases developed high- or pan-frequency hearing loss within 10 years of onset. Audiometric patterns measured at 10 years significantly correlated with those measured at one (r = 0.57), three (r = 0.73), and five years (r = 0.85). The 10-year prognosis significantly correlated with only two factors: initial therapy results (r = 0.49) and fluctuation of hearing during the first year (r = 0.43). Conclusions: About half of the cases in our study developed high- or pan-frequency hearing loss within 10 years of onset of low-frequency hearing loss. The initial therapy results and fluctuation of hearing during the first year may indicate the long-term prognosis of patients presenting with low-frequency hearing loss. © 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation.

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Effects of selective serotonin reuptake inhibitor on treating tinnitus in patients stratified for presence of depression or anxiety

Oishi Naoki, Kanzaki Sho, Shinden Seiichi, Saito Hideyuki, Inoue Yasuhiro, Ogawa Kaoru

Audiology and Neurotology 15 ( 3 ) 187 - 193 2010.03

ISSN 1420-3030

We evaluated the effects of a selective serotonin reuptake inhibitor, paroxetine, on treating tinnitus.Tinnitus patients stratified for the presence of depression and anxiety were studied retrospectively. Fifty-six patients were observed for more than 6 months. They were initially treated with paroxetine only at a dose of 10 mg/day for 2-4 weeks; thereafter, the dose was increased to 20 mg/day. Tinnitus distress was evaluated with the Tinnitus Handicap Inventory (THI) and with visual analog scales (VASs) for tinnitus loudness and annoyance. Depression and anxiety were measured with the Self-Rating Depression Scale (SDS) and the trait section of the State-Trait Anxiety Inventory (STAI). The patients were grouped according to their SDS and STAI scores, and each variable was compared at baseline and the 6-month follow-up. Changes among these variables were also examined to determine whether reduced tinnitus distress was related to the improvement of depression or anxiety. Patients with both depression and anxiety showed better results (decrease in THI, VASs, SDS and STAI scores) than patients with anxiety alone, or patients without depression and anxiety. In patients with depression and anxiety, changes in tinnitus variables and changes in depression and anxiety scores were strongly correlated. In other patients, however, changes in tinnitus variables and changes in depression and anxiety scores were not correlated. These results suggest that paroxetine is effective in treating distressed tinnitus patients with depression and anxiety by reducing their tinnitus severity as well as their depression and anxiety. Copyright © 2009 S. Karger AG, Basel.

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Otosclerosis update (2) - Treatment and prevention

Ogawa Kaoru, Inoue Yasuhiro, Saito Hideyuki, Kanzaki Sho, Okamoto Yasuhide, Mizutari Kunio, Suzuki Takashi, Oishi Naoki, Watada Yukiko, Watabe Takahisa, Fujioka Masato

Practica Oto-Rhino-Laryngologica 103 ( 2 ) 103 - 112 2010.02

ISSN 0032-6313

Skull-base meningioma extending to the parapharyngeal space

Inagaki Yozo, Oishi Naoki, Fujimine Takekatu, Fujii Ryouichi, Saito Hideyuki, Ogawa Kaoru

Practica Oto-Rhino-Laryngologica 103 ( 1 ) 53 - 57 2010.01

ISSN 0032-6313

kull-base and parapharyngeal tumors require intricate treatments due to its anatomic complexity, variations in histological type, and the site often involves the presence of critical blood vessels and nerves. Diagnostic imaging and fine-needle aspiration cytology are thus essential. We report a case of skull-base meningioma extending to the parapharyngeal space in which we made a definitive diagnosis by biopsy (as grade I) and took a wait-and-see approach. A 52-year-old woman had complained of a headache since June 2006 and was seen in the neurology department at our hospital in July. A tumor from around the left jugular foramen to parapharyngeal space was revealed by magnetic resonance imaging (MRI) and she was referred for consultation to the neurosurgical department and our department. It was difficult to establish the diagnosis from the clinical manifestation and diagnostic images due to the tumor's complicated anatomy, therefore it was confirmed by biopsy instead of cytology. It can be said that biopsy is useful to determine therapeutic measures for the skull-base meningioma because it is less invasive and can verify a histological type compared with the complete removal of the tumor.

Acute-onset unilateral psychogenic hearing loss in adults

Oishi Naoki, Kanzaki Sho, Kataoka Chinatsu, Tazoe Mami, Takei Yasuhiko, Nagai Keiichi, Kohno Naoyuki, Ogawa Kaoru

ORL 71 ( 5 ) 279 - 283 2009.11

ISSN 0301-1569

We encountered 6 rare cases of acute-onset unilateral psychogenic hearing loss in adults. All were women in their 20s and 30s. Three cases had severe hearing impairment characterized by hearing loss at every frequency; 2 cases had profound hearing impairment, and 1 case had low-frequency hearing impairment. Of the 6 cases, 3 had a history of hearing loss, and 1 had a history of psychogenic visual disturbance. All 6 cases were initially diagnosed as having idiopathic sudden sensorineural hearing loss; all subsequently received steroid therapy. Three cases were not diagnosed as being psychogenic in origin until otoacoustic emissions and auditory brain responses were performed. Although the presence of distinctive clinical features (age, gender, and past history) is important for suspecting psychogenic hearing loss, objective audiological tests such as otoacoustic emissions are essential for diagnosing some cases. Compared to the existing reports of similar cases, our cases had a poorer prognosis (only 2 cases were cured). Copyright © 2009 S. Karger AG, Basel.

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Otosclerosis update (1) - Pathophysiology and diagnosis

Ogawa Kaoru, Inoue Yasuhiro, Saito Hideyuki, Kanzaki Sho, Okamoto Yasuhide, Mizutari Kunio, Suzuki Takashi, Oishi Naoki

Practica Oto-Rhino-Laryngologica 102 ( 3 ) 169 - 175 2009

ISSN 0032-6313

GFAP aggregates in the cochlear nerve increase the noise vulnerability of sensory cells in the organ of Corti in the murine model of Alexander disease

Masuda Masatsugu, Tanaka Kenji F., Kanzaki Sho, Wakabayashi Kenichiro, Oishi Naoki, Suzuki Takafumi, Ikenaka Kazuhiro, Ogawa Kaoru

Neuroscience Research 62 ( 1 ) 15 - 24 2008.09

ISSN 0168-0102

Outer hair cell (OHC) loss in the auditory sensory epithelium is a primary cause of noise-induced sensory-neural hearing loss (SNHL). To clarify the participation of glial cells in SNHL, we used an Alexander disease (AxD) mouse model. These transgenic mice harbor the AxD causal mutant of the human glial fibrillary acidic protein (GFAP) under the control of the mouse GFAP promoter. It is thought that GFAP aggregates compromise the function of astrocytes. In the auditory pathway, the formation of GFAP aggregates was observed only in GFAP-positive cells of the cochlear nerve. The presence of GFAP aggregates did not change auditory function at the threshold level. To assess the change in vulnerability to auditory excitotoxicity, both transgenic and control mice were treated with intense noise exposure. Auditory threshold shifts were assessed by auditory brainstem responses (ABR) at 1 and 4 weeks after noise exposure, and OHC damage was analyzed by quantitative histology at 4 weeks after exposure. Transgenic mice showed more severe ABR deficits and OHC damage, suggesting that cochlear nerve glial cells with GFAP aggregates play a role in noise susceptibility. Thus, we should focus more on the roles of cochlear nerve glial cells in SNHL. © 2008 Elsevier Ireland Ltd and the Japan Neuroscience Society.

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The value of electroneurography in acute peripheral facial nerve palsy

Minami Shujiro, Shinden Seiichi, Yamashita Taku, Wasano Koichiro, Oishi Naoki

Practica Oto-Rhino-Laryngologica 101 ( 6 ) 435 - 439 2008

ISSN 0032-6313

Objective: To evaluate the use of electroneurography (ENoG) as a prognostic indicator in acute peripheral facial paralysis in a general hospital. Design: Retrospective study. Participants: The patients had been treated for a sudden onset unilateral facial paralysis during an 18 month period (2005. 7-2006.12). Main outcome measures: ENoG was performed 7 to 14 days after the onset facial palsy. The recovery of facial nerve function was documented by Yanagihara's grading system. All patients were followed monthly until recovery or up to 6 months after onset. Results: One-hundred ten patients with acute peripheral facial paralysis, including Bell's palsy (86%), Ramsay-Hunt Syndrome (6%), trauma (6%), and others (2%) underwent ENoG test. Patients were divided into 5 classes according to the ENoG value; [40%-] 41%, [20-40%] 24%, [10-20%] 9%, [0-10%] 11%, [0%] 15%. The recovery rate in each group was; [40%-] 98%, [20-40%] 96%, [10-20%] 90%, [0-10%] 58%, [0%] 24%. The patients whose ENoG values were greater than 10 % showed a 96 % chance of recovery (sensitivity 0. 88, specificity 0. 86). Patients with a greater ENoG value recovered significantly faster. Conclusion: ENoG provides accurate information predicting the prognosis and recovery rate of patients with facial palsy.

A clinical study of Bell's palsy and factors influencing its prognosis

Oishi Naoki, Shinden Seiichi, Yamashita Taku, Minami Shujiro, Ogura Mariko

Journal of Otolaryngology of Japan 110 ( 8 ) 592 - 598 2007.08

ISSN 0030-6622

We encountered 185 patients with Bell's palsy at our hospital between January 2003 and December 2005. Of these patients, 60% visited our department within 3 days of the onset, and 90% within 7 days of the onset ; the interval from onset to hospital visit showed no relation with the severity of the paralysis, Complete recovery was obtained in 85.0% of the patients with steroid or steroid + antiviral treatment. Preservation of the stapedius reflex was a statistically significant predictor of good prognosis, with a high positive predictive value (95.5%). Several factors influencing the prognosis were examined with a Cox's proportional hazards model. The factors considered were the sex of the patients, left / right localization, age, postauricular pain, eye symptoms, taste disorder, underlying diabetes, the Yanagihara facial grading system score, and use of antiviral drugs. The analysis revealed only the Yanagihara score and antiviral drug use as statistically important, with hazard ratios of 1.101 and 1.586, respectively. Although this study had several limitations, steroid + antiviral treatment could yield a better prognosis as compared to steroid treatment alone.

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Cerebral infarction presenting as sudden sensorineural hearing loss and vertigo - A case report

Oishi Naoki, Takei Satoshi

Oto-Rhino-Laryngology Tokyo 48 ( 5 ) 26 - 31 2005.10

ISSN 0386-9687

A 54-year-old man transferred to our emergency department due to sudden vertigo and left-side hearing impairment lasting several hours was found in clinical examination and audiovestibular tests to have profound sensorineural hearing loss and spontaneous right horizontal rotatory nystagmus. He had no other neurological deficits and was given intravenous steroids. On day 4, he reported mild numbness in the right hand. MRI showed infarctions in the left pons (basilar artery region) and in the left middle cerebellar penduncle (AICA region). These were followed by a right Babinski reflex, gait ataxia, and delayed left-sided facial palsy with newly left horizontal rotatory nystagmus. Antiplatelet agents and anticoagulation therapy were begun. He recovered completely except for the profound hearing loss.

Use of methylrosanilinium chloride for a post-operative MRSA-infected wound

Oishi Naoki, Takei Yasuhiko, Kiyota Sekiko, Yabe Haruna

Practica Oto-Rhino-Laryngologica 97 ( 11 ) 1021 - 1025 2004

ISSN 0032-6313

A 52-year-old male patient consulted our hospital with complaints of long lasting pain in the throat and swelling in the neck. Physical, pathological and X-ray examinations led to a diagnosis of carcinoma in the base of the tongue, which had already extended deeply into the tongue and epiglottis (oropharyngeal carcinoma, T4N2cM0). After chemoradiotherapy which did not successfully reduce the tumor, surgical removal of both the tongue and larynx, and reconstruction of the base of the oral cavity with a PM-MC flap were performed. Unfortunately, the operation was accompanied by a subcutaneous infection which occurred as a result of a surgical complication of a pharyngeal fistula. The germ culture examination revealed that the wound was infected with MRSA. Since povidone-iodine and general use of antibiotics were not effective in suppressing the inflammation, possibility arose for serious and critical complications such as MRSA pneumonia or rupture of a major neck artery. However, immediately after we started using methylrosanilinium chloride for the MRSA-infected wound, the inflammation began to disappear quickly without any serious side effect to surrounding tissue. We concluded that methylrosanilinium chloride was effective in the treatment of MRSA-infected wounds.

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