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Papers - Ogawa, Kaoru

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Inflammatory and immune responses in the cochlea

Fujioka Masato, Okano Hideyuki, Ogawa Kaoru

Frontiers in Pharmacology 5 ( DEC ) 2014

The inner ear was previously assumed to be an "immune-privileged" organ due to the existence of its tight junction-based blood-labyrinth barrier. However, studies performed during the past decade revealed that the mesenchymal region of the cochlea, including its lateral wall, is a common site of inflammation. Neutrophils do not enter this region, which is consistent with the old dogma; however, bone marrow-derived resident macrophages are always present in the spiral ligament of the lateral wall and are activated in response to various types of insults, including noise exposure, ischemia, mitochondrial damage, and surgical stress. Recent studies have also revealed another type of immune cell, called perivascular melanocyte-like macrophages (PVM/Ms), in the stria vascularis. These dedicated antigen-presenting cells also control vascular contraction and permeability. This review discusses a series of reports regarding inflammatory/immune cells in the cochlear lateral wall, the pathways involved in cochlear damage and their potential as therapeutic targets.

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A study on thyroid nodules without preoperative malignant features

Nishiyama Takanori, Sakamoto Koji, Ito Fumihiro, Shinden Seiichi, Ogawa Kaoru

Practica Oto-Rhino-Laryngologica 107 ( 9 ) 729 - 734 2014

ISSN 0032-6313

When a thyroid nodule has malignant features found by some examinations (e.g. Echo, FNAC, CT), we perform surgical resection. But if the thyroid nodule does not have malignant feature, there is still the possibility of malignancy, especially when the nodule is large. In the case of large pre-operatively benign thyroid nodules, we therefore consider a diagnostic lobectomy. There is, however, no definite recommendation how large a nodule should be before a lobectomy is performed, and how many malignancies exist in pre-operatively benign nodules. In our hospital, we consider surgical resection when the diameter of the thyroid nodule is over 3 cm. In this study, we analyze pre-operatively benign thyroid nodules in which surgical resection was performed in our hospital, how many malignant nodules there were and what the characteristics were between benign or malignant nodule. From 2005 April to 2012 June, 351 patients underwent a lobectomy in our hospital, 70 of which were pre-operatively benign thyroid nodules with diameters of over 3 cm. We analyzed the pathological findings and compared the nodule diameters, serum thyroglobulin, FNAC's classification and some characteristics of echography between pathologically benign and malignant cases. Fifty-eight patients (83%) had pathologically benign nodules, and 12 patients (17%) had malignant nodules. In 58 benign nodules, 33 nodules (47%) were adenomatous goiter, 24 patients (34%) had follicular adenomas and 1 nodule (1%) was an atypical adenoma. In the 12 malignant patients, 8 patients (11%) had papillary adenocarcinoma and 4 patients (6%) had follicular adenocarcinoma. Almost no significant characteristics were found concerning malignancy, in diameter, serum thyroglobulin, class of FNAC and features of echography. As for complications after surgery, hypothyroidism occured in 4 patients (6%), and neither hypoparathyroidism nor vocal fold paralysis occurred. We concluded that pre-operatively benign thyroid nodule that were over 3 cm in diameter had about a 17% possibility of malignancy. Examinations may not distinguish whether such pre-operatively benign tumors are benign or malignant before surgical resection. We should therefore consider whether to perform therapeutic surgery or not in such patients.

Successful treatment of relapsed ménière's disease using selective serotonin reuptake inhibitors

Goto Fumiyuki, Tsutsumi Tomoko, Ogawa Kaoru

Experimental and Therapeutic Medicine 7 ( 2 ) 488 - 490 2014

ISSN 1792-0981

Patients with Ménière's disease who have relapsed following endolymphatic sac surgery (EDS) or intratympanic gentamicin injection are occasionally treated with intratympanic gentamicin injections or revision surgery. However, there is a potential link between Ménière's disease and anxiety or depression. The use of serotonin selective reuptake inhibitors (SSRIs) is likely be beneficial in the treatment of patients with Ménière's disease. The aim of this report is to describe the benefits of SSRIs in patients with relapsed Meniere's disease. Over the course of two years, three patients were treated for symptoms associated with Ménière's disease with an SSRI (sertraline), with the complete resolution, or significant improvement, of symptoms. In these cases, the SSRI may have treated the associated morbidity and not Ménière's disease itself. Ménière's disease that appears to be resistant to typical otological treatment may not be just Ménière's disease. Ménière's disease may co-exist with three other conditions that are able to cause vestibular symptoms and respond to SSRIs: migraine-associated vertigo (MAV), panic disorders and chronic subjective dizziness (CSD).

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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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Clinical outcome and clinicopathological prognostic factors in adenoid cystic carcinoma of the head and neck

Shigetomi Seiji, Imanishi Yorihisa, Shimoda Masayuki, Tomita Toshiki, Ozawa Hiroyuki, Sakamoto Koji, Fujii Ryoichi, Habu Noboru, Otsuka Kuninori, Yamashita Taku, Fujii Masato, Ogawa Kaoru

Journal of Otolaryngology of Japan 117 ( 5 ) 658 - 665 2014

ISSN 0030-6622

We retrospectively reviewed the records of the 30 patients with adenoid cystic carcinoma of the head and neck (ACCHN) who had undergone initial treatment in the Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine between 1988 and 2007. The primary tumor site was the parotid gland in 10 patients and the submandibular gland in 4 patients, which account for about a half of the subjects. Thirty patients underwent surgical resection with curative intent as the primary treatment, of which 10 patients had post-operative radiotherapy. The 5- and 10-year disease-specific survival (DSS) was 73.9% and 62.4%, respectively, whereas the 5- and 10-year disease-free survival (DFS) was 64.3% and 59.7%, respectively. A univariate analysis revealed that DSS was significantly correlated with perineural invasion (p = 0.010) and lymphatic invasion (p = 0.036), while DFS was significantly correlated with higher T-stage (p = 0.044), a positive surgical margin (p = 0.012) and perineural invasion (p = 0.019). A multivariate analysis demonstrated that perineural invasion (/> = 0.034, risk ratio = 9.530) was the independent prognostic factor for DSS, whereas for DFS it was a positive surgical margin (p = 0.038, risk ratio = 8.897). The histological grade classification, defined specifically for ACC, showed no correlation with the survival. Extended resection with wider margin and additional resection in cases with positive margin may improve treatment results, however, surgical resection alone can prevent neither the development of local recurrence mainly attributed to undetectable perineural invasion, nor that of delayed distant, metastasis. Therefore, the roles of adjuvant radiotherapy and effective systemic therapies are also significant in ACCHN, although a reliable regimen for the latter has not yet been established. Development of a personalized strategy for the adjuvant therapy, which should be based on the accurate prediction of the long-term prognosis in combination with dependable molecular biomarkers, would be indispensable in the future to improve the clinical outcome of the patients with ACCHN.

Primary dural closure and anterior cranial base reconstruction using pericranial and nasoseptal multi-layered flaps in endoscopic-assisted skull base surgery

Tomio Ryosuke, Toda Masahiro, Tomita Toshiki, Yazawa Masaki, Kono Maya, Ogawa Kaoru, Yoshida Kazunari

Acta Neurochirurgica 156 ( 10 ) 1911 - 1915 2014

ISSN 0001-6268

Introduction: Dural and anterior cranial base reconstruction is essential in the surgical resection of a craniofacial tumor that extends from the paranasal sinuses to the subdural space. Watertight reconstruction of vascularized tissue is essential to prevent postoperative liquorrhea, especially under conditions that prevent wound healing (e.g., postoperative irradiation therapy).Method: We successfully treated two cases of olfactory neuroblastoma by endoscopic-assisted craniotomy with primary dural closure and anterior cranial base reconstruction using a multi-layered flap technique. Dural defects were closed using temporal fascia or fascia lata in a conventional fashion, immediately after detaching the subdural tumor, in order to isolate and prevent contamination of subdural components and cerebrospinal fluid (CSF) from the tumor and nasal sinuses. Tumor removal and anterior cranial base reconstruction were performed without any concern of CSF contamination after dural closure by craniotomy and endoscopic endonasal approach (EEA). Vascularized pericranial flaps (PCF) and nasoseptal flaps (NSF) were used simultaneously as doubled-over layers for reconstruction.Results: The tumor was completely removed macroscopically and the anterior cranial base was reconstructed in both cases. CSF leak and postoperative meningitis were absent. Postoperative and irradiation therapy courses were successful and uneventful.Conclusions: This multi-layered anterior cranial base reconstruction consisted of three layers: a fascia for dural plasty and double-layered PCF and NSF. This surgical reconstruction technique is suitable to treat craniofacial tumors extending into the subdural space through the anterior cranial base dura mater.

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Self-reported symptoms in patients with idiopathic sudden sensorineural hearing loss

Sano Hajime, Okamoto Makito, Ohhashi Kentaro, Ino Takeshi, Iwasaki Satoshi, Ogawa Kaoru

Otology and Neurotology 34 ( 8 ) 1405 - 1410 2013.10

ISSN 1531-7129

Objective: This study evaluated self-reported symptoms in patients with idiopathic sudden sensorineural hearing loss (ISSHL). Study Design: Cross-sectional study. Setting: Multicenter clinical investigation in 9 university hospitals. Patients: In total, 140 patients with ISSHL and 24 patients with unilateral sensorineural hearing loss (USHL; control) were included. Main Outcome Measures: A questionnaire on symptoms of ISSHL was distributed and the Short-Form Health Survey (Version 2) was used for assessing the quality of life. Results: In response to questions on hearing difficulty, many of patients in both groups experienced symptoms. In response to questions on hearing-related discomfort, a significantly higher number of patients with ISSHL experienced symptoms compared with those with USHL. Compared with a high incidence of tinnitus in patients with ISSHL, very low incidence of tinnitus was observed in those with USHL.In the multiple linear regression analysis, hearing-related discomfort was the sole significant factor on the Mental Component Summary scores of the Short-Form Health Survey (Version 2). Conclusion: Many patients with ISSHL experience several symptoms such as hearing difficulty, hearing-related discomfort, tinnitus, and anxiety. Hearing-related discomfort strongly affected the quality of life in patients with ISSHL.

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Age-Related Hearing Loss and the Factors Determining Continued Usage of Hearing Aids among Elderly Community-Dwelling Residents

Mizutari Kunio, Michikawa Takehiro, Saito Hideyuki, Okamoto Yasuhide, Enomoto Chieko, Takebayashi Toru, Ogawa Kaoru, Nishiwaki Yuji

PLoS One 8 ( 9 ) 2013.09

While hearing aids are recommended for people with age-related hearing loss, many with impaired hearing do not use them. In this study, we investigated how many elderly people in the study area needed hearing aids, and the factors that determined continued wearing of the devices. The study area was Kurabuchi Town, Japan, where 1,437 residents (those aged 65 years or over) were eligible for participation in the study; 1,414 participated, of whom, 103 (7.3%) were already using hearing aids at the start of the study. After the primary screening, hearing aids were lent to 68 participants (4.8%) who did not already have one, 38 of whom (60.3% of the borrowers, representing 2.7% of the total aged population) went on to wear the hearing aid continuously. The Hearing Handicap Inventory for the Elderly (HHIE) score was significantly elevated among these 38 participants. This study indicated that hearing aids are of potential benefit to many local residents. Multivariate logistic regression revealed that HHIE scores were associated with the extent of HA usage. The adjusted odds ratio for a 1-unit increase in HHIE score was 1.08 (95% confidence interval: 1.02-1.14). Programs like this, in which people with impaired hearing are identified at the local level and given appropriate assistance, are useful models for future use in societies with aging populations.

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Survival analysis and immunohistochemical study of HER-2 and AR (androgen receptor) expression in salivary duct carcinoma

Otsuka Kuninori, Imanishi Yorihisa, Habu Noboru, Sato Yoichiro, Shigetomi Seiji, Fujii Ryoichi, Sakamoto Koji, Tomita Toshiki, Fujii Masato, Kameyama Kaori, Ogawa Kaoru

Journal of Otolaryngology of Japan 116 ( 9 ) 1024 - 1032 2013.09

ISSN 0030-6622

Background: Because of its low incidence, the clinical characteristics of the salivary duct carcinoma (SDC) based on a statistical analysis with a large number of patients remain to be elucidated, and thus it has been impossible to standardize the optimal treatments of SDC including adjuvant systemic therapy. Aims: The present study aimed to determine the prognostic factors along with the clinical outcomes of patients with SDC and to evaluate the expression of several receptor molecules as treatment targets. Methods: We performed a statistical analysis and immunohistochemical examination of 16 patients with SDC who had undergone initial treatment in the Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine from 1996 to 2010. Results: The 3-year disease-free survival (DFS) and cause-specific survival (CSS) rates were 29.2% and 72.7%, respectively. At the time of the analysis, 6 patients are alive without the disease, 2 patients are alive with distant metastasis, whereas 7 patients had died of distant metastasis, and 1 patient had died of another cause (pulmonary embolism). We examined the prognostic value of the clinico-pathological factors such as age, sex, T classification, N classification, clinical stage, primary site, histological pre-existence of pleomorphic adenoma. A univariate analysis revealed that DFS was significantly correlated with age (p = 0.049), T classification (p = 0.018), and clinical stage (p = 0.029), whereas no factor was found to be correlated with CSS. A multivariate analysis demonstrated that age (≥61 vs. ≤60, risk ratio (RR) = 5.423, p = 0.042) and T classification (3, 4 vs. 1, 2, RR= 1.087, p = 0.020) were the independent prognostic factors for DFS. Positive expressions of HER2, ER (estrogen receptor), PR (progesterone receptor), AR (androgen receptor), and MIB-1 (index<20%) were found in 50%, 6%, 13%, 100%, and 69%, respectively. However, none of them showed significant correlation with survival. Conclusion: Frequent expressions of HER-2 and AR in SDC suggest that these receptors can be suitable molecular targets of systemic therapy for patients with SDC in which distant metastasis seems to be the largest obstacle to improving survival. In order to assess the efficacy of anti-HER-2 therapy and anti-androgen therapy for each receptor-positive SDC, a multi-institutional joint research system should be organized.

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Long-lasting changes in the cochlear K⁺ recycling structures after acute energy failure

Takiguchi Yoichiro, Sun Guang wei, Ogawa Kaoru, Matsunaga Tatsuo

Neuroscience Research 77 ( 1-2 ) 33 - 41 2013.09

ISSN 0168-0102

Fibrocytes in the cochlear lateral wall and spiral limbus play an important role in transporting K⁺ and have the capacity of self-renewal. We showed that acute energy failure in the rat cochlea induced by local administration of the mitochondrial toxin 3-nitropropionic acid (3NP) caused hearing loss in a concentration-dependent manner, mainly due to degeneration of cochlear fibrocytes. We produced long-lasting profound cochlear damage in this model by modifying the 3NP administration protocol and observed morphological changes at 16 weeks after the administration. In the spiral ligament, severe degeneration of fibrocytes was observed in the basal turn, and the levels of the Na,K-ATPase alpha and beta1 subunits and of NKCC1 were decreased in these cells, whereas connexin 26 (Cx26) level increased in the type 1 fibrocytes adjacent to the stria vascularis. In the stria vascularis, levels of Kir4.1 and L-PGDS decreased. In the spiral limbus, severe degeneration of fibrocytes was observed in the middle and basal turns, but NKCC1 and Cx26 were still found in the center of the limbus in the middle turn. These results indicate long-lasting changes in the cochlear lateral wall and spiral limbus, which may compensate for damaged K⁺ recycling and protect cells from ATP shortage.

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Application of vestibular rehabilitation with an introduction session in patients with chronic dizziness

Goto Fumiyuki, Arai Motohiro, Ogawa Kaoru

Journal of Otolaryngology of Japan 116 ( 9 ) 1016 - 1023 2013.09

ISSN 0030-6622

Pharmacological and non-pharmacological approaches are the treatment options for dizzy patients. Vestibular exercises are a potential treatment option for intractable dizzy patients who do not respond to conventional drug therapy. The retention rate of exercises is quite important for a successful outcome. We organized vestibular exercise courses to improve the retention rate in the outpatient groups; these courses comprised introduction sessions with a clinical psychologist and rehabilitation sessions with a clinical technologist. It is unclear whether the effects of vestibular rehabilitation are based on the improvement of the psychological parameters of vestibular function. Therefore, we evaluated the functional mechanism of vestibular rehabilitation by using questionnaires and balance function tests. Our study comprised 16 patients with chronic dizziness. The patients performing the self-administered home-based vestibular exercise courses were supervised in small groups. The patients were taught that the exercises were to be performed 4 times a day at their respective homes. The symptoms of dizziness were evaluated using the Japanese version of the dizziness handicap inventory (DHI). Anxiety and depression levels were assessed using a set of psychological questionnaires. The static and dynamic balance function was assessed using static posturography and foam posturography and by measuring the time required for performing a certain series of eye-head movement protocols at the initial visit, before rehabilitation, and 2 and 3 months after rehabilitation. Of 16 patients, 15 could successfully complete the study (93.8%). The DHI score significantly improved 1 month after the rehabilitation, whereas anxiety and depression levels did not improve. The results of static and foam posturography as well as the time required for the eye-head movements also significantly improved. The improvement in the DHI scores was not associated with psychological changes, but with the improvement in the static and dynamic balance function.

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The clinical features of migraine-associated vertigo

Goto Fumiyuki, Tsutsumi Tomoko, Ogawa Kaoru

Journal of Otolaryngology of Japan 116 ( 8 ) 953 - 959 2013.08

ISSN 0030-6622

Migraine-associated vertigo (MAV) is proposed as a new clinical entity on the basis of the assumption that the typical migraine and vertigo or dizziness have a common pathophysiology. Some of the patients with recurrent vertigo syndromes with unknown pathology may have MAV. We performed a retrospective study to clarify the clinical characteristics of MAV in the Japanese population. The following were considered as diagnostic criteria: (1) recurrent vestibular symptoms, (2) migraine headache as defined by the International Headache Society (IHS) criteria, (3) at least one instance of synchronization of a vertiginous attack with a migraine headache, (4) no associated unilateral hearing loss, and (5) absence of other diseases that may have caused vertiginous attacks. Of 552 patients with dizziness or vertigo, 46 (8.3%) were diagnosed as having MAV. A typical feature of this clinical entity is that migraine occurs before the onset of vertigo in women aged 30-40 years. Usually the attacks occur once in a year for 1 to 10 years. An attack lasts for 1-24 h and presents as vertigo and unsteadiness with simultaneous headache. The presence of hearing loss presents an important clinical dilemma. Whether the condition in patients experiencing hearing loss should be defined as MAV or not is still a matter for discussion.

Hearing handicap in adults with unilateral deafness and bilateral hearing loss

Iwasaki Satoshi, Sano Hajime, Nishio Shinya, Takumi Yutaka, Okamoto Makito, Usami Shin Ichi, Ogawa Kaoru

Otology and Neurotology 34 ( 4 ) 644 - 649 2013.06

ISSN 1531-7129

Objective: To assess the perception of hearing handicap in adult patients with unilateral sudden sensorineural hearing loss (SNHL) compared with those with bilateral SNHL or unilateral congenital SNHL. Study Design: Retrospective chart review. Setting: Multicenter department of otolaryngology referrals. Patients: Seventy-one subjects in the unilateral severe-profound (>70 dB) sudden SNHL group (Group 1), 17 subjects in the unilateral prelingual or congenital SNHL group (Group 2), and 121 subjects in the bilateral SNHL group (Group 3). Interventions: Questionnaire. Main Outcome Measures: Hearing Handicap Inventory for Adults (HHIA) and visual analogue scale (VAS) measurements of hearing handicap. Results: Average levels of hearing loss were 92 dB in Group 1, 109 dB in Group 2, and 67 dB in Group 3. The relative percentage scores ofHHIA andVAS compared with Group 3 were 72.6%and 81.0%in Group 1 and 25.4%and 50.3%in Group 2, respectively. A mild correlation between the HHIA subscale or VAS scores and degree of hearing loss could be found in Group 3. No significant correlation was found between the HHIA subscale or VAS scores and duration of hearing loss in Group 1 or Group 3. Higher scores were obtained in male subjects than in female subjects. Patients in Group 1 who were troubled by tinnitus scored significantly higher in the HHIA. In multiple logistic regression analysis, presence of tinnitus, older age, higher average hearing loss level, and group (bilateral SNHL>unilateral sudden SNHL>unilateral precongenital SNHL) revealed a significant positive association with high score (>42) of HHIA (odds ratio, 3.171, 1.021, 1.031, and 6.690, respectively). Conclusion: The results of HHIA and VAS suggest that not only patients with bilateral SNHL but also those with unilateral sudden SNHL, particularly those who have tinnitus, experience a hearing handicap.

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Migraine-associated vertigo with hearing loss and recurrent vertigo attack

Goto Fumiyuki, Tsutsumi Tomoko, Ogawa Kaoru

Journal of Otolaryngology of Japan 116 ( 5 ) 600 - 605 2013.05

ISSN 0030-6622

The clinical features of Ménière's disease and migraine-associated vertigo are quite similar. Both disorders are characterized by repeated vertigo spells. Several diagnostic criteria are used to diagnose migraine-associated vertigo. None of these criteria has been internationally defined,although the criteria proposed by Neuhauser are wieldy accepted. Hearing impairment is believed to be a key factor for diagnosing Meniere's disease. We report herein on a case of repeated vertigo spells with sensorineural hearing loss in the right ear. Initially,the condition was diagnosed as Meniere's disease. Treatment for improving endolymphatic hydrops did not have an effect on the vertigo spells. On careful questioning, we noted the coexistence of migraines without any aura. Treatment with Ca antagonists to prevent the migraine attacks successfully stopped the patient's vertigo spells. On the basis of this clinical course, it is safe to assume that the patient had migraine-associated vertigo with sensorineural hearing loss rather than Meniere's disease. For a patient experiencing migraines together with sensorineural hearing loss, an accurate diagnosis requires careful evaluation. The coexistence of migraines should be carefully ruled out, even if Meniere's disease with hearing loss is strongly suspected.

A psychometric validation of the Japanese versions of new questionnaires on tinnitus (THI-12, TRS, TRSw, TSS, and TSSw)

Wasano Koichiro, Kanzaki Sho, Sakashita Tetsushi, Takahashi Mariko, Inoue Yasuhiro, Saito Hideyuki, Fujioka Masato, Watabe Takahisa, Watanabe Reiko, Sunami Kishiko, Kato Shoko, Kabaya Kayoko, Shinden Seiichi, Ogawa Kaoru

Acta Oto-Laryngologica 133 ( 5 ) 491 - 498 2013.05

ISSN 0001-6489

Conclusion: The Japanese version of the Tinnitus Handicap Inventory-12 (THI-12), Tinnitus Rating Scale (TRS), TRS 1-week version (TRSw), Tinnitus Severity Scale (TSS), and TSS 1-week version (TSSw), which were developed in this study, showed high reliability and validity, suggesting their usefulness in clinical practice. Based on the THI severity grades, we propose that the severity grades of THI-12 (draft) are categorized into four groups: 0-4 points, 5-9 points, 10-14 points, and 15-24 points. Objectives: We developed Japanese versions of new questionnaires for evaluating the level of psychological distress and difficulty in activities of daily living due to tinnitus, and performed their psychometric validation to determine the reliability and validity. The THI-12 is an assessment consisting of 12 items, each of which is rated on a 3-point scale that was created by reducing the number of questions from the 25 items of the THI. The TRS, TRSw, TSS, and TSSw, which were self-evaluation questionnaires of tinnitus on an 11-grade integer Likert scale from 0 to10 points, were used as additional instruments to assess tinnitus severity and distress. Methods: The subjects were healthy adults, and patients with subjective tinnitus who were examined at the Otolaryngology Department of Keio University Hospital, Osaka City University Hospital, or Nagoya City University Hospital with a chief complaint of tinnitus between September 2010 and January 2011. In all, 38 healthy adult subjects and 113 patients with subjective tinnitus were included. We examined the reproducibility and the internal consistency for reliability. We also examined the relationship with the available scales (THI and Hospital Anxiety and Depression Scale, HADS) and group divergence for validity. Results: The psychometric validation showed high reliability and validity of the THI-12, TRS, TRSw, TSS, and TSSw.

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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.

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Moderate hearing loss associated with a novel KCNQ4 non-truncating mutation located near the N-terminus of the pore helix

Watabe Takahisa, Matsunaga Tatsuo, Namba Kazunori, Mutai Hideki, Inoue Yasuhiro, Ogawa Kaoru

Biochemical and Biophysical Research Communications 432 ( 3 ) 475 - 479 2013.03

ISSN 0006-291X

Genetic mutation is one of the causative factors for idiopathic progressive hearing loss. A patient with late-onset, moderate, and high-frequency hearing loss was found to have a novel, heterozygous KCNQ4 mutation, c.806_808delCCT, which led to a p.Ser260del located between S5 and the pore helix (PH). Molecular modeling analysis suggested that the p.Ser269del mutation could cause structural distortion and change in the electrostatic surface potential of the KCNQ4 channel protein, which may impede K+ transport. The present study supports the idea that a non-truncating mutation around the N-terminus of PH may be related to moderate hearing loss.

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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.

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[Objective evaluation of neck muscle tension and static balance in patients with chronic dizziness].

Asama Youji, Goto Fumiyuki, Tsutsumi Tomoko, Ogawa Kaoru

Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery 27 ( 3 ) 144 - 146 2013.02

ISSN 1001-1781

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.

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