研究者詳細 - 小川　郁

論文 - 小川　郁

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Effects of tinnitus treatments on sleep disorders in patients with tinnitus

Wakabayashi Satoko, Saito Hideyuki, Oishi Naoki, Shinden Seiichi, Ogawa Kaoru

International Journal of Audiology 1 - 5 2017年09月

ISSN 1499-2027

Objective: To assess the effects of tinnitus treatments on sleep disorders in patients with tinnitus. Design: Subjects completed the Pittsburg Sleep Quality Index (PSQI), Tinnitus Handicap Inventory (THI), Self-rating Depression Scale (SDS), and State Trait Anxiety Inventory (STAI). The questionnaire results and the patients’ sex, age, time since the onset of tinnitus, and mean hearing level were examined, and differences between a sleep disorder group and a normal sleep group were examined. Patients completed the questionnaires again after initiating tinnitus treatments (counselling and use of sound generators), and the change in questionnaire scores at follow-up was evaluated. Study sample: Patients (N = 100) with tinnitus who visited Keio University Hospital and started treatment without medication between 2005 and 2008. Results: Sixty-six percent of the patients had sleep disorders. Compared with patients without sleep disorders, patients with sleep disorders had significantly higher SDS and STAI scores at the first visit. The mean PSQI scores showed significant improvement at follow-up. Conclusions: Sleep disorders in patients with tinnitus improved after tinnitus treatments. Complex interactions between depressive symptoms and anxiety may occur in these patients. The improvement in sleep disorders at follow-up was correlated with improvements in tinnitus severity and state anxiety.

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Clinical characteristics of patients with tinnitus evaluated with the Tinnitus Sample Case History Questionnaire in Japan

Kojima Takashi, Kanzaki Sho, Oishi Naoki, Ogawa Kaoru

PLoS ONE 12 （ 8 ） 2017年08月

ISSN 1932-6203

Background: The Tinnitus Sample Case History Questionnaire was determined as a standardized questionnaire for obtaining patient case histories and for characterizing patients into subgroups at the Tinnitus Research Initiative in 2006. In this study, we developed a Japanese version of this questionnaire for evaluating the clinical characteristics of patients with tinnitus. The Japanese version of the questionnaire will be available for evaluating treatments for tinnitus and for comparing data on tinnitus in research centers. Aims/Objectives: To evaluate the clinical characteristics of patients with tinnitus in Japan using a newly developed Japanese version of Tinnitus Sample Case History Questionnaire. Study design: This was a prospective study based on patient records. Setting: University hospitals, general hospitals, and clinics. Subjects and methods: We collected patient data using a Japanese translated version of the Tinnitus Sample Case History Questionnaire. In total, 584 patients who visited our institutions in Japan between August 2012 and March 2014 were included (280 males and 304 females; age 13–92 years; mean age, 60.8). We examined patients after dividing them into two groups according to the presence or absence of hyperacusis. The collected results were compared with those from the Tinnitus Research Initiative database. Results: Compared with the TRI database, there were significantly more elderly female patients and fewer patients with trauma-associated tinnitus. There was a statistically lower ratio of patients with hyperacusis. We found that patients with tinnitus in addition to hyperacusis had greater tinnitus severity and exhibited higher rates of various complications. Conclusion: The Japanese version of the Tinnitus Sample Case History Questionnaire developed in this study can be a useful tool for evaluating patients with tinnitus in Japan. The results of this multicenter study reflect the characteristics of patients with tinnitus who require medical care in Japan. Our data provides a preliminary basis for an international comparison of tinnitus epidemiology.

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Clinical outcomes of transoral videolaryngoscopic surgery for hypopharyngeal and supraglottic cancer

Imanishi Yorihisa, Ozawa Hiroyuki, Sakamoto Koji, Fujii Ryoichi, Shigetomi Seiji, Habu Noboru, Otsuka Kuninori, Sato Yoichiro, Watanabe Yoshihiro, Sekimizu Mariko, Ito Fumihiro, Tomita Toshiki, Ogawa Kaoru

BMC Cancer 17 （ 1 ） 2017年06月

ISSN 1471-2407

Background: Transoral videolaryngoscopic surgery (TOVS) was developed as a new distinct surgical procedure for hypopharyngeal cancer (HPC) and supraglottic cancer (SGC) staged at up to T3. However, long-term treatment outcomes of TOVS remain to be validated. Methods: Under a straight broad intraluminal view provided by combined use of a distending laryngoscope and a videolaryngoscope, we performed en bloc tumor resection via direct bimanual handling of the ready-made straight-form surgical instruments and devices. We retrospectively analyzed functional and oncologic outcomes of 72 patients with HPC (n = 58) or SGC (n = 14) whose minimum follow-up was 24 months or until death. Results: The cohort comprised nine patients of Tis, 23 of T1, 33 of T2, and 7 of T3. Among 36 patients (50%) who underwent neck dissection simultaneously, all but one were pathologically node-positive. Twelve patients underwent postoperative concurrent chemoradiation (CCRT) as adjuvant treatment, and another four patients underwent radiation or CCRT for second or later primary cancer. The endotracheal tube was removed in an operation room in all but two patients who underwent temporary tracheostomy. Pharyngeal fistula was formed transiently in two patients. The median time until patients resumed oral intake and could take a soft meal was 2 and 5 days, respectively. Eventually, 69 patients (96%) took normal meals. The 5-year cause-specific survival (CSS), overall survival (OS), larynx-preserved CSS, and loco-regional controlled CSS were 87.3%, 77.9%, 86.0%, and 88.0%, respectively. Multivariate analysis revealed N2-3 as an independent prognostic factor in both CSS (hazard ratio [HR] = 25.51, P = 0.008) and OS (HR = 4.90, P = 0.022), which indirectly reflected higher risk of delayed distant metastasis. Conclusions: Considering its sound functional and oncological outcomes with various practical advantages, TOVS can be a dependable, less invasive, and cost-effective surgical option of an organ-function preservation strategy for HPC and SGC.

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Characterization of slow-cycling cells in the mouse cochlear lateral wall

Li Yang, Watanabe Kotaro, Fujioka Masato, Ogawa Kaoru

PLoS ONE 12 （ 6 ） 2017年06月

ISSN 1932-6203

Cochlear spiral ligament fibrocytes (SLFs) play essential roles in the physiology of hearing including ion recycling and the generation of endocochlear potential. In adult animals, SLFs can repopulate after damages, yet little is known about the characteristics of proliferating cells that support SLFs’ self-renewal. Here we report in detail about the characteristics of cycling cells in the spiral ligament (SL). Fifteen P6 mice and six noise-exposed P28 mice were injected with 5-bromo-2′-deoxyuridine (BrdU) for 7 days and we chased BrdU retaining cells for as long as 60 days. Immunohistochemistry revealed that the BrdU positive IB4 (an endotherial marker) negative cells expressed an early SLF marker Pou3f4 but negative for cleaved-Caspase 3. Marker studies revealed that type 3 SLFs displayed significantly higher percentage of BrdU⁺ cells compared to other subtypes. Notably, the cells retained BrdU until P72, demonstrating they were dividing slowly. In the noise-damaged mice, in contrast to the loss of the other types, the number of type 3 SLFs did not altered and the BrdU incorporating- phosphorylated Histone H3 positive type 3 cells were increased from day 1 to 14 after noise exposure. Furthermore, the cells repopulating type 1 area, where the cells diminished profoundly after damage, were positive for the type 3 SLF markers. Collectively, in the latral wall of the cochlea, type 3 SLFs have the stem cell capacity and may contribute to the endogenous regeneration of lateral wall spiral ligament. Manipulating type 3 cells may be employed for potential regenerative therapies.

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Assessment of hyperacusis with a newly produced Japanese version of the Khalfa hyperacusis questionnaire

Oishi Naoki, Yamada Hiroyuki, Kanzaki Sho, Kurita Akihiro, Takiguchi Yoichiro, Yuge Isamu, Asama Yoji, Masuda Masatsugu, Ogawa Kaoru

Acta Oto-Laryngologica 1 - 5 2017年04月

ISSN 0001-6489

Objectives: The purpose of this study was to determine the validity and reliability of a Japanese version of the Khalfa hyperacusis questionnaire (KHQ) and proposed a threshold KHQ score for classifying hyperacusis. Methods: In total, 112 patients with hyperacusis (group A) and 103 patients without hyperacusis (group B). The patients in group A were further classified into the following subgroups: subjects with hyperacusis as their chief complaint (n = 26, group A1) and subjects with hyperacusis accompanied by chief complaints of tinnitus and/or hearing loss (n = 86, group A2). Results: The average total questionnaire score for patients in group A was 11.8 ± 9.7, which was statistically significantly higher than that of patients in group B, 5.7 ± 4.8. Cronbach’s coefficients for internal consistency were high for the total score (0.92). The average total scores for groups A1 and A2 were 18.1 ± 11.1 and 9.9 ± 8.4, respectively, and the difference between the groups was statistically significant. Conclusions: We developed a Japanese version of the KHQ. It showed high reliability and validity; suggesting its usefulness in clinical practice. We propose that a total KHQ score of 16 is an appropriate cutoff for classifying hyperacusis

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A nationwide multicenter study of the Cochlin tomo-protein detection test

Matsuda Han, Sakamoto Kei, Matsumura Tomohiro, Saito Shiho, Shindo Susumu, Fukushima Kunihiro, Nishio Shin ya, Kitoh Ryosuke, Shibasaki Osamu, Ito Akinori, Araki Ryuichiro, Usami Shin ichi, Suzuki Mamoru, Ogawa Kaoru, Hasegawa Tomonori, Hagiwara Yoshiaki, Kase Yasuhiro, Ikezono Tetsuo

Acta Oto-Laryngologica 1 - 7 2017年03月

ISSN 0001-6489

Objective: To investigate the positive rate for the Cochlin tomo-protein (CTP: an inner ear-specific protein) detection test among patients with inner ear-related clinical manifestations and evaluate the clinical characteristics of definite perilymphatic fistula (PLF). Methods: We have performed an ELISA-based CTP detection test using middle ear lavage (MEL) samples from 497 cases of suspected PLF enrolled from 70 clinical centers nationwide between 2014 and 2015. In addition to the CTP-positive rate, audio-vestibular symptoms were compared between CTP-positive and -negative cases. Results: 8–50% of patients in category 1 (trauma, middle and inner ear disease cases), and about 20% of those in categories 2, 3 and 4 (external origin antecedent events, internal origin antecedent events, and without antecedent event, respectively) were positive for CTP. In category 1 cases, the earlier tested samples showed a higher CTP-positive rate, whereas no differences were observed in categories 2, 3 or 4. The characteristic clinical features in the earlier tested cases were nystagmus and fistula sign in CTP test-positive cases in category 1, and streaming water-like tinnitus in those in categories 2, 3 and 4. Conclusion: The present study clarified that CTP detection test-positive patients exist at considerable rates among patients with inner ear-related manifestations.

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Mitochondrial mutations in maternally inherited hearing loss

Mutai Hideki, Watabe Takahisa, Kosaki Kenjiro, Ogawa Kaoru, Matsunaga Tatsuo

BMC Medical Genetics 18 （ 1 ） 2017年03月

ISSN 1471-2350

Background: Although the mitochondrial DNA (mtDNA) mutations m.1555A > G and m.3243A > G are the primary causes of maternally inherited sensorineural hearing loss (SNHL), several other mtDNA mutations are also reported to be associated with SNHL. Methods: Screening of m.1555A > G and m.3243A > G mutations was performed for 145 probands. Nine probands fulfilled the following criteria: 1) bilateral and symmetric SNHL, 2) ≥ 4 family members with SNHL with a maternal trait of inheritance in ≥ 2 generations, 3) onset of SNHL before the age of 40 years, 4) high-frequency SNHL, and 5) no record of environmental factors related to SNHL. Sequencing of additional mtDNA regions was performed for five subjects meeting the clinical criteria, but the screening results were negative. Results: Among the nine cases meeting the five clinical criteria detailed above, three had the m.1555A > G mutation in MTRNR1, one had a m.3243A > G mutation in MTTL1, and one case had a m.7511T > C mutation in MTTS1. In the family with the m.7511T > C mutation, penetrance of SNHL among maternally related subjects was 9/17 (53%). The age at onset varied from birth (congenital) to adulthood. Hearing levels varied from normal to moderately impaired, unlike previously reported subjects with this mutation, where some maternal family members presented with profound SNHL. Family members with the m.7511T > C mutation and SNHL did not exhibit any specific clinical characteristics distinct from those of other individuals with SNHL and different mtDNA mutations. Among the 136 probands who did not meet the criteria detailed above, one case had the m.1555A > G mutation, and three cases had the m.3243A > G mutation. Conclusions: Since five of nine probands with the clinical criteria used in this study had mtDNA mutations, these criteria may be helpful for identification of candidate patients likely to have mtDNA mutations.

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Utility of clinico-biological data for long-term prognosis of head and neck terminal cancer

Kawasaki Taiji, Wasano Koichiro, Yamamoto Sayuri, Tomisato Shuta, Ogawa Kaoru

Acta Oto-Laryngologica 1 - 4 2017年03月

ISSN 0001-6489

Objective: The prognosis of terminal head and neck cancer is traditionally determined using indices such as the palliative prognosis index. We aimed to develop an alternative prognosis index using clinico-biological data. Methods: This retrospective case-series study included 33 head and neck cancer patients whose cancer recurred despite receiving radiation therapy between April 2010 and April 2014. Clinico-biological data were collected the day patients were diagnosed as terminal. Bivariate correlation analyses were performed on survival times and clinico-biological data. For multivariate regression analyses, patients were divided into two groups: (1) patients who survived >120 days, and (2) those who survived <120 days. Group clinico-biological data were used to determine survival-time cutoff points for the prognosis index. Results: Bivariate analyses revealed significant correlations between survival time and BMI, hemoglobin, albumin, C-reactive protein (CRP), Onodera’s Prognostic Nutritional Index (O-PNI), modified Glasgow Prognostic Score (mGPS), and Performance Status (PS). Multivariate analyses showed a strong correlation between survival time and BMI. The two groups differed significantly in BMI, albumin, CRP, O-PNI, and mGPS. In multivariate analyses BMI, CRP, and O-PNI differed significantly in the two groups. Conclusion: BMI ≤16.4, CRP ≥1.01, and O-PNI ≤33.4 are significant predictors of long-term survival in terminal cancer patients.

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Epidemiological survey of acute low-tone sensorineural hearing loss

Sato Hiroaki, Kuwashima Shigeru, Nishio Shin Ya, Kitoh Ryosuke, Fukuda Satoshi, Hara Akira, Hato Naohito, Ikezono Tetsuo, Ishikawa Kotaro, Iwasaki Satoshi, Kaga Kimitaka, Matsubara Atsushi, Matsunaga Tatsuo, Murata Takaaki, Naito Yasushi, Nakagawa Takashi, Nishizaki Kazunori, Noguchi Yoshihiro, Ogawa Kaoru, Sano Hajime, Sone Michihiko, Shojaku Hideo, Takahashi Haruo, Tono Testuya, Yamashita Hiroshi, Yamasoba Tatsuya, Usami Shin Ichi

Acta Oto-Laryngologica 137 S34 - S37 2017年03月

ISSN 0001-6489

Objectives: A nationwide epidemiological survey involving 23 hospitals in Japan was conducted and the predictive values of demographic data were examined statistically. Methods: A total of 642 patients from 23 hospitals, including 20 university hospitals, in Japan were enrolled in the study. Age ranged from 8 to 87 years, and all were diagnosed with acute low-tone sensorineural hearing loss (ALHL) between 1994 and 2016. Demographic data for the patients, such as symptoms, gender, mean age, and distribution of ALHL grading, were collected and analyzed in relation to prognosis using Student’s t-test, χ ² test and logistic regression. Results: Female gender (p <.013), younger age (p <.001), low-grade hearing loss (p <.001), and shorter interval between onset and initial visit (p <.004) were significantly predictive of a good prognosis. The prognosis for definite ALHL was significantly better than that for probable ALHL (p <.007). Conclusions: The severity of initial hearing loss, interval between onset and initial visit and age were important prognostic indicators for ALHL, while female gender was an important prognostic indicator peculiar to ALHL.

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Idiopathic sudden sensorineural hearing loss and acute low-tone sensorineural hearing loss

Yoshida Tadao, Sone Michihiko, Kitoh Ryosuke, Nishio Shin Ya, Ogawa Kaoru, Kanzaki Sho, Hato Naohito, Fukuda Satoshi, Hara Akira, Ikezono Tetsuo, Ishikawa Kotaro, Iwasaki Satoshi, Kaga Kimitaka, Kakehata Seiji, Matsubara Atsushi, Matsunaga Tatsuo, Murata Takaaki, Naito Yasushi, Nakagawa Takashi, Nishizaki Kazunori, Noguchi Yoshihiro, Sano Hajime, Sato Hiroaki, Suzuki Mikio, Shojaku Hideo, Takahashi Haruo, Takeda Hidehiko, Tono Testuya, Yamashita Hiroshi, Yamasoba Tatsuya, Usami Shin Ichi

Acta Oto-Laryngologica 137 S38 - S43 2017年03月

ISSN 0001-6489

Objectives: The aim of this study was to investigate the differences between idiopathic sudden sensorineural hearing loss (SSNHL), and acute low-tone sensorineural hearing loss (ALHL) using the results of a nationwide survey database in Japan and to analyze the variables associated with their clinical features and the severity of hearing impairment, treatment, and prognosis. Methods: Participants were patients registered between April 2014 and March 2016 in a multicenter epidemiological survey database involving 30 university hospitals and medical centers across Japan. Statistical analysis was performed to clarify the factors associated with their clinical characteristics and the severity of hearing impairment, treatment, and prognosis. Results: Idiopathic SSNHL and ALHL differed significantly in terms of male-to-female ratio, age distribution, and time from onset to start of treatment. The treatment methods and hearing prognosis also differed markedly between the two diseases. A majority (92%) of idiopathic SSNHL patients were administered some type of corticosteroid, while half of the ALHL patients received corticosteroids and a diuretic agent. Conclusion: The results suggested that idiopathic SSNHL and ALHL belonged to different categories of inner ear disease.

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Nationwide epidemiological survey of idiopathic sudden sensorineural hearing loss in Japan

Kitoh Ryosuke, Nishio Shin Ya, Ogawa Kaoru, Kanzaki Sho, Hato Naohito, Sone Michihiko, Fukuda Satoshi, Hara Akira, Ikezono Tetsuo, Ishikawa Kotaro, Iwasaki Satoshi, Kaga Kimitaka, Kakehata Seiji, Matsubara Atsushi, Matsunaga Tatsuo, Murata Takaaki, Naito Yasushi, Nakagawa Takashi, Nishizaki Kazunori, Noguchi Yoshihiro, Sano Hajime, Sato Hiroaki, Suzuki Mikio, Shojaku Hideo, Takahashi Haruo, Takeda Hidehiko, Tono Testuya, Yamashita Hiroshi, Yamasoba Tatsuya, Usami Shin Ichi

Acta Oto-Laryngologica 137 S8 - S16 2017年03月

ISSN 0001-6489

Objectives: Using a large-scale nationwide survey database, we investigated the epidemiological characteristics for idiopathic SSNHL in Japan. Methods: The subjects for this analysis were patients registered in a Japanese multicentre database between April 2014 and March 2016. A total of 3419 idiopathic SSNHL patients were registered in the database, and the clinical characteristics of the idiopathic SSNHL patients were obtained. Several factors associated with the severity of hearing impairment and prognosis were then investigated. Statistical analysis was performed to clarify the factors associated with the severity of hearing impairment and prognosis. Results: There were significant correlations between the severity of hearing loss and diabetes mellitus, kidney disease, past history of brain infarction, heart disease, age (under 16 years/elderly), and symptoms of vertigo/dizziness. We also analyzed the prognostic factors for idiopathic SSNHL, and found that the severity of hearing loss (Grade 3 or 4), heart disease, aged 65 years or over, time from onset to treatment (over 7 days), and symptoms of vertigo/dizziness were all significantly related to poor prognosis. Conclusion: The present large-scale clinical survey revealed current epidemiological trends for idiopathic sudden sensorineural hearing loss (SSNHL) and various factors associated with the severity of hearing impairment and prognosis.

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Relationships among drinking and smoking habits, history of diseases, body mass index and idiopathic sudden sensorineural hearing loss in Japanese patients

Umesawa Mitsumasa, Kobashi Gen, Kitoh Ryoshuke, Nishio Shin Ya, Ogawa Kaoru, Hato Naohito, Sone Michihiko, Fukuda Satoshi, Hara Akira, Ikezono Tetsuo, Ishikawa Kotaro, Iwasaki Satoshi, Kaga Kimitaka, Kakehata Seiji, Matsubara Atsushi, Matsunaga Tatsuo, Murata Takaaki, Naito Yasushi, Nakagawa Takashi, Nishizaki Kazunori, Noguchi Yoshihiro, Sano Hajime, Sato Hiroaki, Suzuki Mikio, Shojaku Hideo, Takahashi Haruo, Takeda Hidehiko, Tono Tetsuya, Yamashita Hiroshi, Yamasoba Tatsuya, Usami Shin Ichi

Acta Oto-Laryngologica 137 S17 - S23 2017年03月

ISSN 0001-6489

Objectives: To present the cardiovascular risk factors in idiopathic sudden sensorineural hearing loss (SSNHL) patients enrolled in a nationwide epidemiological survey of hearing disorders in Japan. Materials and methods: We compiled the cardiovascular risk factors in 3073 idiopathic SSNHL subjects (1621 men and 1452 women) and compared their proportions with controls as part of the National Health and Nutrition Survey in Japan, 2014. The cardiovascular risk factors consisted of drinking and smoking habits, a history of five conditions related to cardiovascular disease and body mass index. Results: The proportion of current smokers was significantly higher among men aged 50–59, 60–69 and 70+ and among women aged 30–39, 40–49 and 60–69. The proportion of patients with a history of diabetes mellitus was significantly higher among men aged 50–59, 60–69 and 70+, but not in women. In addition, male and female SSNHL subjects aged 60–69 showed lower proportions of current drinking; and female SSNHL subjects aged 60–69 showed higher proportions of overweight (BMI ≥25 kg/m²). Conclusions: The present cross-sectional study revealed showed significantly higher proportions of current smokers among both men and women as well as those with a history of diabetes mellitus among men across many age groups in patients with idiopathic SSNHL compared with the controls.

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The effect of initial treatment on hearing prognosis in idiopathic sudden sensorineural hearing loss

Okada Masahiro, Hato Naohito, Nishio Shin Ya, Kitoh Ryosuke, Ogawa Kaoru, Kanzaki Sho, Sone Michihiko, Fukuda Satoshi, Hara Akira, Ikezono Tetsuo, Ishikawa Kotaro, Iwasaki Satoshi, Kaga Kimitaka, Kakehata Seiji, Matsubara Atsushi, Matsunaga Tatsuo, Murata Takaaki, Naito Yasushi, Nakagawa Takashi, Nishizaki Kazunori, Noguchi Yoshihiro, Sano Hajime, Sato Hiroaki, Suzuki Mikio, Shojaku Hideo, Takahashi Haruo, Takeda Hidehiko, Tono Tetsuya, Yamashita Hiroshi, Yamasoba Tatsuya, Usami Shin Ichi

Acta Oto-Laryngologica 137 S30 - S33 2017年03月

ISSN 0001-6489

Objective: To investigate the hearing prognosis of idiopathic sudden sensorineural hearing loss (SSNHL) treated with different initial therapies. Methods: Subjects consisted of patients diagnosed with idiopathic SSNHL within 7 days from onset and showing severe hearing loss (≥60 dB), who were registered in a Japanese multicenter database between April 2014 and March 2016. Subjects were divided into four groups according to initial therapy: (1) steroids, (2) steroids + Prostaglandins (PGs), (3) intratympanic steroids (ITS), and (4) no steroids. Hearing outcomes were compared among the groups. Results: In total, 1305 patients were enrolled. The final hearing level and hearing gain of patients treated with steroids + PGs were significantly higher than those of patients treated with steroids alone or no steroids. The ratio of good prognosis (complete recovery or marked improvement) in patients treated with steroids + PGs was higher than that in patients treated with steroids alone or no steroids. There was no difference in the prognosis of patients treated with steroids alone or no steroids. Conclusion: A large number of patients with idiopathic SSNHL were registered in a multicenter database. PG use in combination with steroid administration was associated with a good hearing prognosis in patients with severe hearing loss.

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The clinical features and prognosis of mumps-associated hearing loss

Morita Shinya, Fujiwara Keishi, Fukuda Atsushi, Fukuda Satoshi, Nishio Shin ya, Kitoh Ryosuke, Hato Naohito, Ikezono Tetsuo, Ishikawa Kotaro, Kaga Kimitaka, Matsubara Atsushi, Matsunaga Tatsuo, Murata Takaaki, Naito Yasushi, Nishizaki Kazunori, Ogawa Kaoru, Sano Hajime, Sato Hiroaki, Sone Michihiko, Suzuki Mikio, Takahashi Haruo, Tono Tetsuya, Yamashita Hiroshi, Yamasoba Tatsuya, Usami Shin ichi

Acta Oto-Laryngologica 1 - 4 2017年02月

ISSN 0001-6489

Conclusions: The majority of hearing loss due to mumps presents as unilateral profound sensorineural hearing loss, which is refractory to treatment. In rare cases of bilateral total deafness, cochlear implants were beneficial for speech perception. Vaccination against mumps is recommended to prevent mumps-associated hearing loss. Objective: The objective of this study is to investigate the clinical characteristics of hearing loss due to mumps and to evaluate hearing outcomes. Subjects and methods: The clinical parameters were analyzed under a retrospective multi-institutional study design in patients diagnosed with hearing loss due to mumps at the Otolaryngology departments of 19 hospitals between 1987 and 2016. Results: Sixty-seven patients with hearing loss due to mumps were enrolled. The study population consisted of 35 males and 32 females, ranging in age from 1 to 54, with a median age of 9.5 years. Sixty-three patients presented with unilateral, and 4 with bilateral hearing loss. Profound hearing loss was observed in 65 ears. Only one ear with severe hearing loss showed complete recovery. Four patients with bilateral hearing loss received cochlear implant surgery. Most of the patients with hearing loss due to mumps had no history of vaccination.

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Hochuekkito, a Japanese Herbal Medicine, Restores Metabolic Homeostasis between Mitochondrial and Glycolytic Pathways Impaired by Influenza A Virus Infection

Takanashi Keita, Dan Katsuaki, Kanzaki Sho, Hasegawa Hideki, Watanabe Kenji, Ogawa Kaoru

Pharmacology 240 - 249 2017年02月

ISSN 0031-7012

Background: Hochuekkito (HKT), a traditional Japanese herbal medicine (Kampo), has been used to treat symptoms of several diseases. In a recent clinical study, HKT was shown to be protective against the influenza virus infection. However, the underlying mechanism of the prophylactic effect is not clear. Mitochondrial and glycolytic pathways play important roles in cellular energy metabolism to maintain biological functions. These metabolic pathways are affected by the influenza virus infection. In this study, we examined the relationship between the preventive effects of HKT against the influenza virus infection and cellular energy metabolism in mitochondria and glycolysis using Madin-Darby canine kidney cells and influenza A/PR/8/34 (H1N1) virus (IAV). Methods: Mitochondrial and glycolytic metabolic pathways were evaluated on the basis of the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), respectively, using the XF24 Extracellular Analyzer. Results: The OCR/ECAR ratio in IAV-infected cells was lower than that in control cells. Cells that were treated with HKT before IAV infection showed a metabolic pattern similar to that in the control cells (increase in both OCR and ECAR). Conclusions: Our results suggest that HKT not only activates both mitochondrial and glycolytic energy metabolism in IAV-infected cells but also helps maintain metabolic homeostasis similar to that in noninfected cells.

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Cochlear Cell Modeling Using Disease-Specific iPSCs Unveils a Degenerative Phenotype and Suggests Treatments for Congenital Progressive Hearing Loss

Hosoya Makoto, Fujioka Masato, Sone Takefumi, Okamoto Satoshi, Akamatsu Wado, Ukai Hideki, Ueda Hiroki R., Ogawa Kaoru, Matsunaga Tatsuo, Okano Hideyuki

Cell Reports 18 （ 1 ） 68 - 81 2017年01月

ISSN 2211-1247

Hearing impairments are the most common symptom of congenital defects, and they generally remain intractable to treatment. Pendred syndrome, the most frequent syndromic form of hereditary hearing loss, is associated with mutations in the anion exchanger pendrin. Loss of pendrin function as an anion exchanger is thought to be causative, but rodent models do not exhibit progressive deafness. Here, we report a degenerative phenotype exhibiting mutant pendrin aggregates and increased susceptibility to cellular stresses in cochlear epithelial cells induced from patient-derived induced pluripotent stem cells (iPSCs). These degenerative phenotypes were rescued by site-specific gene corrections. Moreover, low-dose rapamycin and metformin reduced aggregation and cell death. Our results provide an unexpected, comprehensive understanding of deafness due to “degenerative cochlear disease” and may contribute to rational therapeutic development. This iPSC-based disease model provides an approach to the study of pathogenesis and therapeutic development for hereditary hearing loss.

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Phonosurgical resection using submucosal infusion technique for precancerous laryngeal leukoplakia

Kono Takeyuki, Saito Koichiro, Yabe Haruna, Ogawa Kaoru

Laryngoscope 127 （ 1 ） 153 - 158 2017年01月

ISSN 0023-852X

Objectives/Hypothesis: This study was designed to assess the feasibility of the submucosal infusion technique combined with microflap dissection as a radical therapeutic and diagnostic option for precancerous laryngeal leukoplakia. Study Design: Retrospective study. Methods: Severe dysplasia or carcinoma in situ was diagnosed after phonomicrosurgical dissections in 25 patients with unilateral laryngeal leukoplakia. Of these, 15 patients preferred no additional surgery (observation group), whereas 10 patients underwent further laser subligamental cordectomy (additional surgery group). The relationship between the initial surgical margin and histopathological characteristics of additionally excised tissues was assessed to evaluate diagnostic reliability. Disease control was assessed to determine the oncologic efficacy of the therapeutic procedure. Comparative multidimensional vocal assessments were performed in both groups to evaluate functional advantages of one-stage excision. Results: After the initial phonomicrosurgical resection, three patients had residual dysplastic lesions near the vocal process and anterior commissure, whereas three other patients had lesions suspicious for recurrence. No postoperative malignant transformation was observed in any patient. Although well-preserved vocal function was observed in the observation group, vocal quality deteriorated shortly after laser surgery in the additional surgery group. Regarding acoustics, aerodynamics, and quality-of-life evaluations, statistically equivalent scores were observed between the observation and control groups, whereas scores were inferior in the additional surgery group than in the control group. Conclusions: Phonomicrosurgical resection may be a therapeutic option with oncologic efficacy against precancerous laryngeal leukoplakia. This radical management might achieve more satisfactory postoperative vocal function. Level of Evidence: NA Laryngoscope, 127:153–158, 2017.

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Novel pre-therapeutic scoring system using patient and haematological data to predict facial palsy prognosis

Wasano K., Ishikawa T., Kawasaki T., Yamamoto S., Tomisato S., Shinden S., Minami S., Wakabayashi T., Ogawa K.

Clinical Otolaryngology 2017年

ISSN 1749-4478

Objectives: We describe a novel scoring system, the facial Palsy Prognosis Prediction score (PPP score), which we test for reliability in predicting pre-therapeutic prognosis of facial palsy. We aimed to use readily available patient data that all clinicians have access to before starting treatment. Design: Multicenter case series with chart review. Setting: Three tertiary care hospitals. Participants: We obtained haematological and demographic data from 468 facial palsy patients who were treated between 2010 and 2014 in three tertiary care hospitals. Patients were categorised as having Bell's palsy or Ramsey Hunt's palsy. Main outcome measures: We compared the data of recovered and unrecovered patients. PPP scores consisted of combinatorial threshold values of continuous patient data (eg platelet count) and categorical variables (eg gender) that best predicted recovery. We created separate PPP scores for Bell's palsy patients (PPP-B) and for Ramsey Hunt's palsy patients (PPP-H). Results: The PPP-B score included age (≥65 years), gender (male) and neutrophil-to-lymphocyte ratio (≥2.9). The PPP-H score included age (≥50 years), monocyte rate (≥6.0%), mean corpuscular volume (≥95 fl) and platelet count (≤200 000 /μL). Patient recovery rate significantly decreased with increasing PPP scores (both PPP-B and PPP-H) in a step-wise manner. PPP scores (ie PPP-B score and PPP-H score) ≥2 were associated with worse than average prognosis. Conclusions: Palsy Prognosis Prediction scores are useful for predicting prognosis of facial palsy before beginning treatment.

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Current status and problems associated with tinnitus treatment at municipal hospitals

Inagaki Yozo, Mashino Kenji, Oishi Naoki, Kanzaki Sho, Ogawa Kaoru, Shinden Seiichi

Practica Oto-Rhino-Laryngologica 110 （ 3 ） 163 - 169 2017年

ISSN 0032-6313

Based on a series of studies including brain function tests, we reinforced and improved treatment for tinnitus by developing a tinnitus retraining therapy (TRT) that incorporates the "tinnitus pain model"; our laboratory subsequently introduced this therapy in 2013. This model provides a clinical explanation that tinnitus manifests and worsens through nerve synchronization of the auditory path and the non-auditory path with the pain network. Therefore, the target of tinnitus therapy based on this model is the auditory path generating the tinnitus and the pain network that worsens the tinnitus. The therapy mainly uses "acoustic therapy" and "directive counseling", which are the same as the original TRT. What characterizes this method is the central use of a hearing aid in the "acoustic therapy" targeting tinnitus patients with hearing loss. TRT incorporating the "tinnitus pain model" would be ideal for the establishment of an outpatient department dedicated to hearing loss and tinnitus. In actual practices, however, many hospitals avoid offering "directive counseling", as it is often difficult to provide sufficient counseling in a general outpatient setting. This report examined the tinnitus treatment practice of a municipal hospital with two otolaryngologists. The hospital administered TRT incorporating the "tinnitus pain model" to 62 cases (average age: 68.7 years, prevalence period: 16 months [median]). All the cases were treated with "directive counseling", while 32 cases used hearing aids as a part of "acoustic therapy". The tinnitus handicap inventory (THI) score showed a statistically significant reduction after treatment from 49.3±23.0 to 24.8±21.1. The improvement rate, based on an "improvement of 20 THI points or above" and "16 or lower final THI points" as the statistical criteria, was 62.9%. The proactive involvement of municipal hospitals in tinnitus treatment may reduce the frequency of doctor shopping by tinnitus patients and could help to break the "vicious circle" of tinnitus treatment practices.

Surgical Outcome of Endoscopic Endonasal Surgery for Non-Functional Pituitary Adenoma by a Team of Neurosurgeons and Otolaryngologists Adenoma by a Team of Neurosurgeons and Otolaryngologists

Kikuchi Ryogo, Toda Masahiro, Tomita Toshiki, Ogawa Kaoru, Yoshida Kazunari

Turkish neurosurgery 27 （ 1 ） 1 - 7 2017年

ISSN 1019-5149

AIM: This study aimed to assess the efficacy of endoscopic endonasal surgery, conducted by a team of neurosurgeons and otolaryngologists.MATERIAL AND METHODS: We studied 40 patients who were undergoing surgery for primary non-functional pituitary adenomas with Knosp grades 1 to 3, at Keio University Hospital between 2005 and 2012. We compared the endoscopic endonasal transsphenoidal approach (team-eTSS; T-eTSS), with a microscopic transsphenoidal approach (mTSS). Analyses were conducted for differences between the two groups in tumor resection rates, operating durations, and complications from the non-functional pituitary adenomas. We also compared the heminostril and binostril approaches for T-eTSS.RESULTS: Tumor resection rates were higher when the surgeries were conducted by T-eTSS than mTSS. In particular, when the maximum tumor diameter was more than 25 mm, resection rates were significantly higher for T-eTSS than for mTSS. There were no unexpected complications in either group. There was no significant difference in resection rates between the heminostril and binostril approaches when T-eTSS was performed.CONCLUSION: T-eTSS is an efficacious surgical option for non-functional pituitary adenomas, particularly when the adenoma is of large size. Benefits of the heminostril approach are evident.

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Febrile neutropenia in patient with head and neck cancer treated with docetaxel, cisplatin and 5-fluorouracil (TPF protocol) - A comparison before and after the introduction of pegfilgrastim

Wasano Koichiro, Kawasaki Taiji, Hiraga Yoshihiko, Yamamoto Sayuri, Tomisato Shuta, Hashimoto Yosuke, Ogawa Kaoru

Practica Oto-Rhino-Laryngologica 110 （ 4 ） 287 - 293 2017年

ISSN 0032-6313

The TPF protocol composed of docetaxel, cisplatine and 5-fluorouracil, is the most commonly used chemotherapy regimen for the treatment of head and neck cancer. Recently, the importance of maintaining a relative dose-intensity (RDI) has been shown. Therefore, the treatment and prevention of febrile neutropenia, which can reduce the RDI of the TPF protocol, are important. Here, we compare patient outcomes before and after the introduction of pegfilgrastim for primary prophylaxis. The first group is consisted of 60 patients (88 chemotherapy courses) treated between January 2011 and October 2014 who did not receive prophylaxis. The second group consisted of 14 patients (20 chemotherapy courses) treated between November 2014 and July 2016 using pegfilgrastim. We examined the frequency of neutropenia (grade 3 and 4), febrile neutropenia (FN) and treatment-related death, the amount of granulocyte-colony stimulating factor (G-CSF) used, the cost for FN treatment and the hospitalization period. In the first group, there were 74 neutropenia events, 34 cases of FN and 2 treatment-related deaths; the average hospitalization period was 18.5 days. In the second group, there were 74 neutropenia events, 34 case of FN, and 0 treatment-related death; the average hospitalization period was 18.5 days. The frequency of adverse events, the amount of G-CSF used, the cost for FN and the hospitalization period were all significantly reduced by the introduction of pegfilgrastim. In conclusion, the administration of pegfilgrastim for the primary prophylaxis of FN was effective when included in the TPF protocol for the treatment of head and neck cancer.

Retrospective analysis of olfactory neuroblastoma cases treated with endoscopic endonasal approach

Ozawa Hiroyuki, Tomita Toshiki, Watanabe Yoshihiro, Sekimizu Mariko, Ito Fumihiro, Ikari Yuichi, Saito Shin, Sato Yoichiro, Toda Masahiro, Ogawa Kaoru

Japanese Journal of Head and Neck Cancer 43 （ 1 ） 1 - 7 2017年

ISSN 1349-5747

We retrospectively reviewed nine cases of olfactory neuroblastoma in Keio University School of Medicine from 2010 to 2015. The surgical approach was the endoscopic endonasal approach, either alone or in combination with craniotomy, performed by a team of head and neck surgeons and a neurosurgeon. The distribution of patients according to the modified Kadish classification （A/B/C/D) and Dulguerov classification （T1/T2/ T3/T4) was 1/4/4/0 and 1/4/2/2. Tumors of six cases were removed by the endoscopic endonasal approach alone; three cases needed craniotomy to resect intra-dual tumors. Three-layered skull base reconstruction using fascia, pericranial flap and nasoseptal flap was used for five cases. None of the cases experienced cerebrospinal fluid leakage postoperatively. Seven patients received postoperative radiotherapy. Three cases experienced tumor recurrence, and underwent salvage surgery or radiotherapy. All cases remained alive, though the average observation time was less than 3 years. Recent reports have demonstrated that the endoscopic endonasal approach has a comparable control rate to the open approach for olfactory neuroblastoma. We believe that endoscopic endonasal skull base surgery should play a key role in the treatment of olfactory neuroblastoma in the years ahead.

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Efficacy and objective evaluation of non-echo-planar diffusion-weighted MRI by the PROPELLER technique in the diagnosis of cholesteatoma

Yamada Hiroyuki, Oishi Naoki, Kanzaki Sho, Ogawa Kaoru

Nihon Jibiinkoka Gakkai kaiho 120 （ 5 ） 714 - 721 2017年

ISSN 0030-6622

In the diagnosis of cholesteatoma, non-echo-planar diffusion-weighted MRI using the PROPELLER(periodically rotated overlapping parallel lines with enhanced reconstruction)technique has been reported to be useful. However, interpretation of positive findings is subjective and the decision criteria remain unclear. It is necessary to establish an objective standard for evaluation of the signal intensity. The aim of this study was to establish whether diffusion MRI using the PROPELLER technique is effective for the diagnosis of cholesteatoma. Furthermore, we investigated whether objective evaluation is possible by comparing the signal intensities and determining which region of brain is the most suitable for such comparison. We evaluated 35 ears with a postoperative diagnosis of cholesteatoma for which preoperative evaluation had been performed by MRI using the PROPRLLER technique. We determined a lesion as positive if it showed a higher intensity than the cerebellar white matter. Furthermore, for objective evaluation, we set regions of interest and compared the highest signal intensity of the target lesion with that of the following parts of the brain ; cerebellum, cerebellar white matter, temporal lobe, temporal lobe white matter. The sensitivity/positive-predictive value were 85.7%, and the specificity/negative-predictive value was 42.9%. The smallest lesion observed was 3.8 mm in diameter. In addition, in 4 of the 35 ears, no lesion could be detected. Objective evaluation by comparison of the highest signal intensities of the regions of interest matched with the diagnosis after surgery in 26 of the 31 ears. The findings suggested that the cerebellar white matter was the most suitable among the 4 regions evaluated for such comparison. This method is thought to be useful, especially in cases where macroscopic evaluation of the lesions is difficult.

A clinical study of pharyngeal small cell carcinoma

Ito Fumihiro, Ozawa Hiroyuki, Sekimizu Mariko, Watanabe Yoshihiro, Tomita Toshiki, Imanishi Yorihisa, Ogawa Kaoru

Nihon Jibiinkoka Gakkai kaiho 120 （ 6 ） 825 - 832 2017年

ISSN 0030-6622

Extrapulmonary small cell carcinoma arising from the pharynx is rare. We have experienced 4 cases of pharyngeal small cell carcinoma. All the patients were male, and the mean age was 66 years old. The primary site was the oropharynx in 2 cases and the hypopharynx in 2 cases. All the patients initially underwent surgical resection, followed by chemotherapy or chemoradiotherapy. Three patients died because of distant metastasis. One patient is still alive without disease. Twentyfour cases of pharyngeal small cell carcinoma have been reported to date. An analysis of these 28 cases, including our 4 cases, revealed that 20 of the cases had died because of pharyngeal small cell carcinoma. Thus, pharyngeal small cell carcinoma appears to be associated with a relatively poor prognosis similar to that of pulmonary small cell carcinoma. Patients with T3/4 or metastatic diseases have an especially poor prognosis. When the primary site is resectable with minimum invasion, surgery followed by chemotherapy or chemoradiotherapy might offer a better chance of inhibiting local recurrence, compared with other strategies.

Endonasal endoscopic approach for a giant cavernous sinus meningioma that extended to the middle cranial fossa with preoperative embolization

Tamura Ryota, Toda Masahiro, Kohno Maya, Ozawa Hiroyuki, Tomita Toshiki, Akiyama Takenori, Ogawa Kaoru, Yoshida Kazunari

Interdisciplinary Neurosurgery: Advanced Techniques and Case Management 6 20 - 22 2016年12月

ISSN 2214-7519

Background Transcranial surgery is considered more appropriate than an endonasal endoscopic approach (EEA) for a large cavernous sinus meningioma with lateral extension. Case presentation A 6-cm-diameter hypervascular meningioma around cavernous sinus invaded the orbital apex and infratemporal fossa. 80% of the tumor was removed without too much blood loss via endoscopic endonasal transpterygoidal-infratemporal approach. Preoperative embolization from some feeding arteries was done, and 80% of the tumor staining disappeared. Discussion Tumor removal rates for giant meningioma are worse with EEA than with the transcranial approach because of various anatomical limitations and blood control. Recently, EEA has become more widely used with approaches such as the transpterygoidal approach. The operation can be done safely with preoperative embolization because the operative view is clear without bleeding. Conclusion Preoperative embolization for a large hypervascular tumor makes EEA more effective. A giant meningioma can be removed by EEA if the anatomical limitations can be identified and approached safely and effectively.

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The Preventive Effect of the Traditional Japanese Herbal Medicine, Hochuekkito, against Influenza A Virus via Autophagy in vitro

Takanashi Keita, Dan Katsuaki, Kanzaki Sho, Hasegawa Hideki, Watanabe Kenji, Ogawa Kaoru

Pharmacology 99 - 105 2016年10月

ISSN 0031-7012

Background: Hochuekkito (HKT), a traditional Japanese herbal medicine, enhances the immunity of elderly or weak individuals. It is also known to have preventive effects against influenza clinically. However, the detailed mechanisms of the preventive effects have not been clarified. We examined the relationship between the preventive effects of HKT and autophagy, a known stress response and quality control mechanism, using Madin-Darby canine kidney cells and influenza A/PR/8/34 (H1N1) virus. Methods: The effect of HKT on autophagy in influenza A virus (IAV)-infected cells was assessed by Western blotting and fluorescence microscopy using an RFP-GFP-LC3B sensor kit. Results: In Western blotting, treatment with HKT before IAV infection (pre-HKT) tended to induce autophagy in IAV-infected cells at an early stage of infection, eventually suppressing IAV-induced autophagy. Moreover, several autolysosomes, indicative of normal autophagosome-lysosome fusion, were observed in Pre-HKT cells transduced with RFP-GFP-LC3B but not in untreated IAV-infected cells. Conclusions: These findings indicated that IAV-mediated inhibition of the fusion of autophagosomes with lysosomes was prevented by HKT treatment before infection. According to these results, we propose that this phenomenon is one of the preventive effects of HKT against IAV.

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Pretreatment Hematologic Findings as Novel Predictive Markers for Facial Palsy Prognosis

Wasano Koichiro, Kawasaki Taiji, Yamamoto Sayuri, Tomisato Shuta, Shinden Seiichi, Ishikawa Toru, Minami Shujiro, Wakabayashi Takeshi, Ogawa Kaoru

Otolaryngology - Head and Neck Surgery (United States) 155 （ 4 ） 581 - 587 2016年10月

ISSN 0194-5998

Objective To examine the relationship between prognosis of 2 different facial palsies and pretreatment hematologic laboratory values. Study Design Multicenter case series with chart review. Setting Three tertiary care hospitals. Subjects and Methods We examined the clinical records of 468 facial palsy patients who were treated with an antiviral drug in combination with either oral or intravenous corticosteroids in participating hospitals between 2010 and 2014. Patients were divided into a Bell's palsy group or a Hunt's palsy group. We used the Yanagihara facial nerve grading system to grade the severity of facial palsy. "Recovery" from facial palsy was defined as achieving a Yanagihara score ≥36 points within 6 months of onset and having no accompanying facial contracture or synkinesis. We collected information about pretreatment hematologic findings, demographic data, and electrophysiologic test results of the Bell and Hunt group patients who recovered and those who did not. We then compared these data across the 2 palsy groups. Results In the Bell's palsy group, recovered and unrecovered patients differed significantly in age, sex, electroneuronography score, stapedial muscle reflex, neutrophil rate, lymphocyte rate, neutrophil-to-lymphocyte ratio, and initial Yanagihara score. In the Hunt's palsy group, recovered and unrecovered patients differed in age, electroneuronography score, stapedial muscle reflex, monocyte rate, platelet count, mean corpuscular volume, and initial Yanagihara score. Conclusions Pretreatment hematologic findings, which reflect the severity of inflammation and bone marrow dysfunction caused by a virus infection, are useful for predicting the prognosis of facial palsy.

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Pre-therapeutic nutritional assessment for predicting severe adverse events in patients with head and neck cancer treated by radiotherapy

Kono Takeyuki, Sakamoto Koji, Shinden Seiichi, Ogawa Kaoru

Clinical Nutrition 2016年08月

ISSN 0261-5614

Background & aims: Malnutrition is common in patients with head and neck cancer (HNSCC). It may be related to severe adverse toxicity as a result of radiotherapy. The aim was to investigate nutritional screening factors for severe adverse events. Methods: A retrospective chart review of 101 patients who underwent radiotherapy from 2009 to 2013 was performed. The relationships among severe adverse events and pretreatment nutritional parameters, including static variables (serum albumin, total protein, total lymphocyte counts, body mass index), dynamic variables (retinol-binding protein, transferrin, pre-albumin), and nutritional screening tools (Onodera's Prognostic Nutrition Index [O-PNI]; Nutrition Risk Index; Controlling Nutritional Status [CONUT] score; Nutritional Risk Screening 2002) were evaluated in addition to patient and treatment factors. Results: According to the static parameters, approximately 30% of patients were malnourished before treatment. Twenty-four patients exhibited severe adverse events. On univariate analysis, combined chemotherapy, advanced staging, O-PNI <40, and CONUT score ≥5 were significant predictors of severe adverse events. Multivariate analysis revealed that O-PNI <40 and combined chemotherapy independently predict severe adverse events. Conclusions: O-PNI is considered a useful nutritional factor for predicting severe adverse events in HNSCC patients undergoing chemoradiotherapy and facilitates the planning of aggressive nutritional interventions prior to treatment.

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Expression pattern of wolframin, the WFS1 (Wolfram syndrome-1 gene) product, in common marmoset (Callithrix jacchus) cochlea

Suzuki Noriomi, Hosoya Makoto, Oishi Naoki, Okano Hideyuki, Fujioka Masato, Ogawa Kaoru

NeuroReport 27 （ 11 ） 833 - 836 2016年08月

ISSN 0959-4965

Wolfram syndrome is an autosomal recessive disorder of the neuroendocrine system, known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness) syndrome, and considered an endoplasmic reticulum disease. Patients show mutations in WFS1, which encodes the 890 amino acid protein wolframin. Although Wfs1 knockout mice develop diabetes, their hearing level is completely normal. In this study, we examined the expression of wolframin in the cochlea of a nonhuman primate common marmoset (Callithrix jacchus) to elucidate the discrepancy in the phenotype between species and the pathophysiology of Wolfram syndrome-associated deafness. The marmoset cochlea showed wolframin immunoreactivity not only in the spiral ligament type I fibrocytes, spiral ganglion neurons, outer hair cells, and supporting cells, but in the stria vascularis basal cells, where wolframin expression was not observed in the previous mouse study. Considering the absence of the deafness phenotype in Wfs1 knockout mice, the expression of wolframin in the basal cells of primates may play an essential role in the maintenance of hearing. Elucidating the function of wolframin protein in the basal cells of primates would be essential for understanding the pathogenesis of hearing loss in patients with Wolfram syndrome, which may lead to the discovery of new therapeutics.

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Successful continual intratympanic steroid injection therapy in a patient with refractory sensorineural hearing loss accompanied by relapsing polychondritis

Wasano Koichiro, Tomisato Shuta, Yamamoto Sayuri, Suzuki Noriomi, Kawasaki Taiji, Ogawa Kaoru

Auris Nasus Larynx 2016年05月

ISSN 0385-8146

Objective: To report the treatment efficacy of continual intratympanic steroid injection (ITSI) therapy in a patient with refractory sensorineural hearing loss accompanied by relapsing polychondritis. Patient: A 49-year-old female diagnosed with relapsing polychondritis at the age of 45 years and who had been treated with corticosteroids and immunosuppressants developed sensorineural hearing loss in the left ear. Intervention: Her unilateral hearing loss did not recover despite receiving one cyclophosphamide pulse treatment, one methylprednisolone pulse treatment, and weekly leukapheresis. Thus, we decided to initiate weekly ITSI therapy. Main outcome measure: Pure tone audiometry. Results: A week after the first ITSI treatment, the patient's hearing improved. We continued ITSI therapy and attempted to extend the interval between treatments, but her hearing worsened when ITSI therapy was delivered at 2- to 3-week intervals. Thus, we returned ITSI therapy to once per week for 21 months (total of 71 treatments). She experienced no adverse events, like tympanic perforation, and 1 year after terminating the therapy, her hearing remained stable and did not worsen. Conclusions: Continual, weekly ITSI therapy was effective in treating sensorineural hearing loss accompanied by relapsing polychondritis. ITSI therapy may be a promising treatment option for sensorineural hearing loss caused by autoimmune disease.

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Tympanoplasty for chondrodysplasia punctata

Hosoya Makoto, Kanzaki Sho, Wakabayashi Satoko, Ogawa Kaoru

Auris Nasus Larynx 2016年05月

ISSN 0385-8146

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Usefulness and Limitation of Thyroglobulin Measurement in Fine Needle Aspirates (FNA-Tg) for Diagnosis of Neck Lymph Node Metastasis from Thyroid Carcinoma

Sakamoto Koji, Imanishi Yorihisa, Tomita Toshiki, Ozawa Hiroyuki, Sato Yoichiro, Inagaki Yozo, Yamada Hiroyuki, Ito Fumihiro, Suzuki Noriomi, Kono Takeyuki, Saito Shin, Noguchi Masaru, Nishiyama Takanori, Nakamura Shintaro, Fujita Hiroko, Watabe Takahisa, Shinden Seiichi, Ogawa Kaoru

Nihon Jibiinkoka Gakkai kaiho 119 （ 5 ） 721 - 726 2016年05月

ISSN 0030-6622

BACKGROUND: Preoperative diagnosis of lymph node metastasis from thyroid carcinoma is usually confirmed by using fine needle aspiration cytology (FNAC) when thyroid carcinoma is suspected based on the clinical findings. However, the result of FNAC sometimes leads to a false negative, especially in cases of hypocellular lesions such as metastases with cystic change. Thyroglobulin measurement in fine needle aspirates (FNA-Tg) has been shown to be a useful technique to detect the protein specifically secreted by thyroid follicular cells. Elevated FNA-Tg levels in an extra-thyroidal lesion means that the lesion comprises thyroid-originated tissue, most of which suggests the metastasis from thyroid carcinoma. Thus, FNA-Tg is expected to improve the sensitivity of FNAC for the aforementioned purpose.PATIENTS AND METHODS: From 2008 to 2012, 49 extra-thyroidal lesions from 43 patients with thyroid carcinoma were examined using both FNAC and FNA-Tg, followed by surgical resection with a histopathological diagnosis. The results were retrospectively reviewed and analyzed.RESULTS: Among 49 lesions, 47 were metastatic lymph nodes from thyroid carcinoma (46 papillary carcinoma and one follicular carcinoma), one was a metastatic lymph node from submandibular gland adenocarcinoma, and one was an ectopic thyroid gland. In the 47 cases of thyroid carcinoma, the sensitivity of FNAC was 57.4% (27/47), whereas that of FNA-Tg was 76.6% (36/47). When both methods were combined, the sensitivity increased to 93.6% (44/47). Metastasis from submandibular gland adenocarcinoma was considered to be an example of a false positive from FNAC, whereas an ectopic thyroid gland was an FNA-Tg false positive. Three lesions were negative for both FNAC and FNA-Tg, although metastases were suspected by imaging studies and confirmed by histopathological diagnosis, which were consistent with examples of a false negative from both FNAC and FNA-Tg findings.CONCLUSIONS: FNAC reflects whether the lesion has malignant cells, whereas FNA-Tg reflects whether the lesion has thyroid-originated tissue that specifically secrets thyroglobulin. Therefore, FNAC and FNA-Tg are considered to be complementary to each other for the preoperative diagnosis of lymph node metastasis from thyroid carcinoma. FNA-Tg was validated to improve the preoperative diagnostic sensitivity especially when combined with FNAC, however, it is attended with the possibility of a false positive or negative finding, which requires caution in interpretation of the findings.

Vascularized middle turbinate flap for the endoscopic endonasal reconstruction of the anterior olfactory groove

Tamura Ryota, Toda Masahiro, Kohno Maya, Watanabe Yoshihiro, Ozawa Hiroyuki, Tomita Toshiki, Ogawa Kaoru, Yoshida Kazunari

Neurosurgical Review 39 （ 2 ） 297 - 302 2016年04月

ISSN 0344-5607

A vascularized middle turbinate flap (MTF) might be useful in the repair of lesions in the anterior olfactory groove. The sizes of the MTF and inferior turbinate flap (ITF) and these distances up to the frontal base were analyzed by computed tomography (CT) using a picture archiving and communication system (PACS) in 20 patients. The minimum flap measurement to reconstruct the skull base was defined as the distance from the basal plate to the medial slope or lateral slope edge of the MTF and the ITF on the coronal view. Next, we reviewed clinical data from three patients with dural deficits who underwent endoscopic vascularized MTF reconstruction. The distance to the frontal base from the ITF was significantly longer than that from the MTF. The minimum length of the MTF measured by coronal CT was similar to the distance to the frontal base. In contrast, the minimum length of the ITF was shorter than the distance to the frontal base. These results suggest that the MTF might be superior to the ITF for coverage of the anterior frontal base. Three patients who underwent MTF reconstruction for a defect in the anterior olfactory groove had good outcomes and no complications. The MTF is a good option for reconstruction of defects in the anterior part of the olfactory groove.

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Sustained effect of hyaluronic acid in subcutaneous administration to the cochlear spiral ganglion

Inagaki Yozo, Fujioka Masato, Kanzaki Sho, Watanabe Kotaro, Oishi Naoki, Itakura Go, Yasuda Akimasa, Shibata Shinsuke, Nakamura Masaya, James Okano Hirotaka, Okano Hideyuki, Ogawa Kaoru

PLoS One 11 （ 4 ） 2016年04月

The spatiotemporal distribution of drugs in the inner ear cannot be precisely evaluated because of its small area and complex structure. In the present study, we used hyaluronic acid (HA)-dispersed luciferin to image transgenic mice and to determine the effect of HA on controlled drug delivery to the cochlea. GFAP-luc mice, which express luciferase in cochlear spiral ganglion cells, were subcutaneously administered HA-luciferin (HA-sc) or luciferin dissolved in saline (NS-sc) or intraperitoneally administered luciferin dissolved in saline (NS-ip). The bioluminescence of luciferin was monitored in vivo in real time. The peak time and half-life of fluorescence emission were significantly increased in HA-sctreated mice compared with those in NS-sc- and NS-ip-treated mice; however, significant differences were not observed in peak photon counts. We detected differences in the pharmacokinetics of luciferin in the inner ear, including its sustained release, in the presence of HA. The results indicate the clinical potential of using HA for controlled drug delivery to the cochlea.

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A nationwide study on enlargement of the vestibular aqueduct in Japan

Noguchi Yoshihiro, Fukuda Satoshi, Fukushima Kunihiro, Gyo Kiyofumi, Hara Akira, Nakashima Tsutomu, Ogawa Kaoru, Okamoto Makito, Sato Hiroaki, Usami Shin ichi, Yamasoba Tatsuya, Yokoyama Tetsuji, Kitamura Ken

Auris Nasus Larynx 2016年03月

ISSN 0385-8146

Objective: To document the clinical features and associated pure-tone audiometry data in patients with enlargement of the vestibular aqueduct (EVA), and to identify risk factors for fluctuating hearing loss (HL) and vertigo/dizziness in EVA patients. Methods: In this nationwide survey in Japan, a first survey sheet was mailed to 662 board-certified otolaryngology departments to identify the ones treating EVA patients. A second survey sheet, which contained solicited clinical information and the results of the hearing tests, was mailed to all facilities that reported treating EVA cases. We analyzed clinical information, including age at the time of the most recent evaluation, gender, EVA side, age at onset, initial symptoms, precipitating factors, and etiology from survey responses, and assessed 4-frequency (500, 1000, 2000, and 4000. Hz) pure-tone average (PTA) from accompanying pure-tone audiometry data. A multivariate logistic regression analysis was utilized to identify the possible risk factors for fluctuating HL and vertigo/dizziness. Results: In total, 513 hospitals (response rate, 77.5%) responded to the first survey, and 113 reported treating patients with EVA. Seventy-nine out of the 113 hospitals (response rate 69.9%) responded to the second survey, and the data of 380 EVA patients were registered and analyzed. Of the 380 patients, 221 (58.2%) were female, suggesting female preponderance. The patient age ranged from 0 to 73 years (mean, 16.7 years; median, 13 years; interquartile range, 6-24 years). EVA was bilateral in 91.1% of the patients (346/380). The most prevalent initial symptom was HL (341/380), followed by vertigo/dizziness/imbalance (34/380). Sudden HL occurred secondary to head trauma in 5.3% of the patients and upper respiratory infection in 5.0%. Pure-tone audiometry showed profound HL (PTA >91. dB) in 316 (52.0%) of the 608 ears in the 304 patients tested, and asymmetric HL, defined as >10. dB, in 147 (48.4%) of the 304 patients. The mean PTA was 83.7. dB (median, 91.3. dB; interquartile range, 71.3-103.8. dB), and the severity in PTA did not correlate with age. Multivariate logistic regression identified age ≥10 years (compared to age of 0-9 years), bilateral HL (compared to unilateral HL/normal hearing), a history of head trauma, and Pendred syndrome (compared to the other EVA-associated disorders) as significant risk factors for fluctuating HL and/or vertigo/dizziness. Conclusion: The present nationwide survey of 380 EVA patients provided a more precise description of the clinical features, including risk factors for fluctuating HL and vertigo/dizziness.

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Late onset and high-frequency dominant hearing loss in a family with MYH9 disorder

Wasano Koichiro, Matsunaga Tatsuo, Ogawa Kaoru, Kunishima Shinji

European Archives of Oto-Rhino-Laryngology 1 - 6 2016年03月

ISSN 0937-4477

MYH9 disorder is a rare autosomal-dominant disorder. We previously reported that it is caused by mutations in the gene for nonmuscle myosin heavy chain IIA (NMMHC-IIA). MYH9 disorder causes congenital macrothrombocytopenia accompanied by progressive sensorineural hearing loss, nephropathy, and cataract. However, there are few reports that describe the audiological features of MYH9 disorder. The objective of this study was to characterize auditory and other phenotypes of patients with MYH9 disorder. We examined nine subjects from one Japanese family. Audiological, ophthalmological, hematological, and imaging examinations were used to assess clinical features. We carried out genetic analysis of the causative gene, MYH9. Five subjects exhibited macrothrombocytopenia and neutrophil cytoplasmic inclusion bodies. Immunofluorescence analysis of neutrophil NMMHC-IIA revealed abnormal type II localization. Two subjects had high-frequency dominant hearing loss, which was adult onset and progressive. Only one subject had cataract. MYH9 sequencing analysis of all thrombocytopenic subjects revealed a heterozygous c.4270G>A mutation in exon 30 (p.D1424N). We identified five patients with MYH9 disorder from the family. The hearing impairment associated with MYH9 disorder in this family was characterized as adult onset, progressive, and high-frequency dominant. Hematological manifestations of MYH9 disorder show complete penetrance, whereas extra-hematological manifestations show incomplete penetrance and variable expressivity in this family.

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Distinct Expression Patterns of Causative Genes Responsible for Hereditary Progressive Hearing Loss in Non-Human Primate Cochlea

Hosoya Makoto, Fujioka Masato, Ogawa Kaoru, Okano Hideyuki

Scientific Reports 6 2016年02月

Hearing impairment is the most frequent sensory deficit in humans. Deafness genes, which harbor pathogenic mutations that have been identified in families with hereditary hearing loss, are commonly expressed in the auditory end organ or the cochlea and may contribute to normal hearing function, yet some of the mouse models carrying these mutations fail to recapitulate the hearing loss phenotype. In this study, we find that distinct expression patterns of those deafness genes in the cochlea of a non-human primate, the common marmoset (Callithrix jacchus). We examined 20 genes whose expression in the cochlea has already been reported. The deafness genes GJB3, CRYM, GRHL2, DFNA5, and ATP6B1 were expressed in marmoset cochleae in patterns different from those in mouse cochleae. Of note, all those genes are causative for progressive hearing loss in humans, but not in mice. The other tested genes, including the deafness gene COCH, in which mutation recapitulates deafness in mice, were expressed in a similar manner in both species. The result suggests that the discrepancy in the expression between rodents and primates may account for the phenotypic difference. This limitation of the rodent models can be bypassed by using non-human primate models such as the marmoset.

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Overlapping expression of anion exchangers in the cochlea of a non-human primate suggests functional compensation

Hosoya Makoto, Fujioka Masato, Kobayashi Reona, Okano Hideyuki, Ogawa Kaoru

Neuroscience Research 2016年02月

ISSN 0168-0102

Ion homeostasis in the inner ear is essential for proper hearing. Anion exchangers are one of the transporters responsible for the maintenance of homeostasis, but their expression profile in the primate cochlea has not been fully characterized. However, species-specific overlapping expression patterns and functional compensation in other organs, such as the kidney, pancreas and small intestine, have been reported. Here, we determined the expression patterns of the anion exchangers SLC26A4, SLC26A5, SLC26A6, SLC26A7, SLC26A11, SLC4A2 and SLC4A3 in the cochlea of a non-human primate, the common marmoset (Callithrix jacchus). Although the pattern of expression of SLC26A4 and SLC26A5 was similar to that in rodents, SLC26A7, SLC4A2, SLC4A3 exhibited different distributions. Notably, five transporters, SLC26A4, SLC26A6, SLC26A11 SLC4A2 and SLC4A3, were expressed in the cells of the outer sulcus. Our results reveal a species-specific distribution pattern of anion exchangers in the cochlea, particularly in the outer sulcus cells, suggesting functional compensation among these exchangers. This "primate-specific" pattern may be related to the human-specific hearing loss phenotypes of channelopathy disorders, including the SLC26A4-related diseases Pendred syndrome/DFNB4.

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Sigmoid incision rescue nasoseptal flap technique for endoscopic endonasal skull base surgery

Ozawa Hiroyuki, Tomita Toshiki, Watanabe Yoshihiro, Sekimizu Mariko, Ito Fumihiro, Ikari Yuichi, Saito Shin, Toda Masahiro, Ogawa Kaoru

Acta Oto-Laryngologica 1 - 5 2016年02月

ISSN 0001-6489

Conclusion The sigmoid-incision (S-I) rescue flap technique has the advantage of both reduced-invasiveness and providing a sufficient surgical corridor for endoscopic endonasal skull base surgery (EESBS). Objective Skull base reconstruction with nasoseptal flap (NSF) is critically important in managing post-operative cerebrospinal fluid (CSF) leakage after tumor removal by EESBS. The NSF needs to be elevated before sphenoidotomy and posterior septectomy to preserve the pedicle. However, most extradural surgery without CSF leakage does not require NSF and, therefore, NSF preparation is often futile. As a result, a rescue flap technique to overcome this problem has been developed, whereby a new S-I rescue flap method is used that enables wide exposure of the sphenoidal rostrum and smooth manipulation of surgical instruments to preserve the NSF pedicle. Materials and methods Starting in April 2014, 19 cases underwent EESBS with S-I rescue flap. Results All patients underwent tumor resection under an adequate operative field with smooth manipulation of surgical instruments. Two complications were experienced. One patient had CSF leak after removal of the nasal packing, but the leakage was successfully closed by conventional NSF. Another patient had epistaxis from the septal wall, but this was controlled by electrocautery.

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The effects of cochlear implantation in Japanese single-sided deafness patients

Kitoh Ryosuke, Moteki Hideaki, Nishio Shinya, Shinden Seiichi, Kanzaki Sho, Iwasaki Satoshi, Ogawa Kaoru, Usami Shin ichi

Acta Oto-Laryngologica 1 - 5 2016年02月

ISSN 0001-6489

Conclusion Cochlear implantation (CI) for Japanese single-sided deafness patients resulted in improved speech perception, increased sound localization accuracy, and reduced tinnitus handicap. Objectives This study reports results for five adult SSD cases with CI, focusing on the benefits they obtained in terms of speech recognition, sound localization, and tinnitus handicap. Methods Five Japanese patients meeting the eligibility criteria were included in this study. All patients were implanted with a fully inserted MED-EL Concerto FLEX28® implant (MED-EL, Innsbruck, Austria). Speech perception outcomes in noise, as well as sound localization and tinnitus disturbance, were assessed pre-surgically and at 1, 3, 6, and 12 months after CI activation. Results The Japanese monosyllable test score in noise improved gradually after implantation. In some cases, speech perception ability appeared unstable, particularly in the first 1–6 months after implantation. The sound localization ability showed marked improvement in all cases, with the disturbance to daily life caused by tinnitus also decreasing in all cases from the early post-operative period.

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SOD1 gene polymorphisms in sudden sensorineural hearing loss

Kitoh Ryosuke, Nishio Shin Ya, Ogawa Kaoru, Okamoto Makito, Kitamura Ken, Gyo Kiyofumi, Sato Hiroaki, Nakashima Tsutomu, Fukuda Satoshi, Fukushima Kunihiro, Hara Akira, Yamasoba Tatsuya, Usami Shin ichi

Acta Oto-Laryngologica 1 - 5 2016年02月

ISSN 0001-6489

Conclusion The results suggest that SOD1 rs4998557 could be associated with susceptibility to SSNHL in the Japanese population. Objectives To assess the gene association with sudden sensorineural hearing loss (SSNHL). Methods A two-stage case control study was conducted to explore the relationship of the candidate genes to SSNHL. The 192 gene samples from SSNHL patients registered in the intractable inner ear disease gene bank were enrolled. As the candidate genes, 39 SNPs from 31 genes were selected for the first stage study. The second stage study examined whether the SOD1 gene polymorphisms, defined by significant differences between cases and controls in the first stage study, are associated with SSNHL. Results Significant differences were observed in four SNPs from three genes, Glutathione-S-transferase pai 1 (GSTP1), proteine kinase C heta (PRKCH), and superoxide dismutase 1 (SOD1), in terms of allele frequency between SSNHL patients and HapMap controls. In the SOD1 gene, a significant difference was observed in the dominant model study of the SNP rs4998557 in the second stage study. Furthermore, as a result of dividing SSNHL patients based on the clinical data, the difference was more apparent in the case of the over 60 dB group and the tinnitus–positive group.

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Clinical Outcomes and Prognostic Factors for Salivary Duct Carcinoma

Otsuka Kuninori, Imanishi Yorihisa, Tada Yuichiro, Kawakita Daisuke, Kano Satoshi, Tsukahara Kiyoaki, Shimizu Akira, Ozawa Hiroyuki, Okami Kenji, Sakai Akihiro, Sato Yuichiro, Ueki Yushi, Sato Yukiko, Hanazawa Toyoyuki, Chazono Hideaki, Ogawa Kaoru, Nagao Toshitaka

Annals of Surgical Oncology 1 - 8 2016年01月

ISSN 1068-9265

Background: Among salivary gland malignancies, the prognosis of salivary duct carcinoma (SDC) is assumed to be the poorest. However, because of its low incidence, reliable survival estimates and prognostic factors based on a large number of patients remain to be elucidated, thereby making it impossible to standardize the optimal treatment for SDC. Methods: We performed this multi-institutional, retrospective analysis by collecting the clinical information of 141 patients with SDC without distant metastasis who underwent curative surgery as the initial treatment to elucidate overall survival (OS) and disease-free survival (DFS) along with their prognostic factors. Results: The 3-year OS and DFS rates were 70.5 and 38.2 %, respectively. Multivariate analysis revealed that age ≥65 years (p <0.001) and N1 and N2 (p = 0.047 and

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Clinical review of globus patients with a focus on GERD cases

Uno Kosuke, Saito Koichiro, Yabe Haruna, Kono Takeyuki, Ogawa Kaoru

Journal of Otolaryngology of Japan 119 （ 11 ） 1388 - 1396 2016年

ISSN 0030-6622

Globus sensation is a common symptom seen daily in ear-nose-throat (ENT) clinics. Globus is affected by multiple factors, and of these, gastroesophageal reflux disease (GERD), has been recognized as a relatively more manageable cause of globus than the other causes. However, we still commonly encounter globus patients with unclear backgrounds who require multiple diagnostic and therapeutic modalities. To provide an appropriate treatment approach and create favorable situations for these patients, we developed and applied an intramural algorithm to manage globus considering GERD, laryngeal allergy, and psychological problems as major factors of this pathology. Twenty-six patients with globus sensation who visited our voice clinic from June 2012 to March 2015 were enrolled in this study. All these patients had undergone general ENT examinations, including naso-pharyngo-laryngeal endoscopies and cervicothoracic computed tomographic scans. Upper gastrointestinal endoscopy revealed 2 cancers. Further study classified 23 patients into the GERD group and 1 patient into the allergy group. Proton pump inhibitor (PPI) therapy was successful in 11 patients of the GERD group (response rate, 47.2%). Improvement in subjective symptoms of globus were measured by the scores of questionnaires, including the F scale and Reflux Symptom Index. Significant improvement in these scores were observed 1 month after PPI prescription in the PPI-responder group in this study. Further assessment of medical history as well as the scores of questionnaires to measure the severity levels of depression (Self-rating Depression Scale) and anxiety (State-Trait Anxiety Inventory-Form JYZ, STAI) proved that relatively longer lasting symptoms (≥4 months) or relatively higher anxiety scores (STAIS50 points) were predictive of PPI resistance. Our study results suggested that the pathology of globus is affected by multiple factors and that a multidisciplinary team approach is required for better management of this disease.

Modified endoscopic transnasal-transmaxillary-transpterygoid approach to parapharyngeal space tumor resection

Wasano Koichiro, Yamamoto Sayuri, Tomisato Shuta, Kawasaki Taiji, Ogawa Kaoru

Head and Neck 2016年

ISSN 1043-3074

Background: Conventional approaches for removing parapharyngeal space tumors require a cervical skin incision and resection of soft tissues between the skin and parapharyngeal space. The surgical visual field for this conventional approach is limited. Methods: To decrease invasiveness during removal of benign parapharyngeal space tumors and to enhance the visual field, we devised a new approach called the modified endoscopic transnasal-transmaxillary-transpterygoid approach (MENMAP). The "surgical corridor" to the parapharyngeal space consists of the maxillary sinus, submucous tunnel under the lateral nasal wall, and the space created by removing the pterygoid process. Results: We successfully performed en bloc removal of a parapharyngeal space tumor using the MENMAP approach. The only surgical complication was hypoesthesia of the right hard palate and maxillary gingiva, which gradually improved. Conclusion: The MENMAP approach is a viable alternative for removing parapharyngeal space tumors, as it is safe, feasible, and less invasive.

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Developmental disability and psychiatric conditions in 39 patients with stuttering

Tomisato Shuta, Oishi Naoki, Asano Kazumi, Watanabe Yoshihiro, Ogawa Kaoru

Japan Journal of Logopedics and Phoniatrics 57 （ 1 ） 7 - 11 2016年

ISSN 0030-2813

Stuttering may be related to developmental disability or mental diseases such as social anxiety disorder. However, there are few reports about these comorbid conditions in stuttering patients in Japan. In order to comprehend the relationship between stuttering and comorbid conditions, we conducted a chart review of 39 stuttering cases who sought consultation at Keio University Hospital in 2012 and 2013. Fifteen percent of the subjects had the following comorbid psychiatric conditions: mood disorder (depression and adjustment disorder), obsessive-compulsive disorder, epilepsy and tic disorder. Eighteen percent of the subjects had developmental disability, including definite or suspected developmental disability, and language development disorder. The age at which patients with developmental disability began stuttering was higher than that in patients without such disability. These findings suggest that clinical presentation of stuttering may be affected by comorbid developmental disability.

Comparative multidimensional assessment of laryngeal function and quality of life after radiotherapy and laser surgery for early glottic cancer

Kono Takeyuki, Saito Koichiro, Yabe Haruna, Uno Kosuke, Ogawa Kaoru

Head and Neck 2016年

ISSN 1043-3074

Background: This study was designed to comparatively assess laryngeal function and quality of life (QOL) of patients after laser surgery (LS) or radiotherapy (RT) for early glottic cancer. Methods: Sixty-four patients with T1 glottic cancer treated with RT or type II cordectomy underwent both subjective and objective vocal assessments. The LS group was divided into the following: (1) vaporization with defocused mode (laser surgery [LS]-Vap); and (2) excision with focused mode using lower power (LS-Ex). Results: Auditory-perceptual evaluation and videostroboscopic images in the LS-Ex group worsened shortly after treatment and time-dependent recovery was quicker than in the LS-Vap group. The LS-Ex group showed equivalent posttherapeutic vocal function with the RT group by acoustics, aerodynamics, and self-assessment questionnaire analysis, whereas the LS-Vap group showed statistically significant worse function. Conclusion: The multidimensional assessment showed that early glottic cancer could be successfully treated by either RT or LS-Ex with equivalent posttherapeutic laryngeal function and QOL.

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A case of middle ear implant VSB (Vibrant Soundbridge^®)

Inagaki Yozo, Kanzaki Sho, Yamada Hiroyuki, Watabe Takahisa, Oishi Naoki, Ogawa Kaoru, Iwasaki Satoshi

Practica Oto-Rhino-Laryngologica 109 （ 4 ） 239 - 246 2016年

ISSN 0032-6313

We participated in a clinical trial for a hearing aid system in Japan, "Verification of the efficacy and safety of the middle ear implant MVS (Medel Vibrant System) in conductive and mixed hearing loss". We present a report of a case that we encountered in our department. MVS is a Vibrant Soundbridge^® (VSB) middle ear implant device that is approved and is in wide use in Europe and the United States. It has been shown to have the potential to provide a high level of acoustic clarity and sound quality. Also, as compared to conventional hearing AIDS, there is no howling and the distortion frequency is lower. An additional advantage is the excellent transient response. The patient was a 33-year-old woman, with a history of bilateral hearing loss from birth, who was under observation whilst wearing a hearing aid. In an attempt to improve her hearing, we admitted her to our hospital. Based on the diagnosis of middle ear malformation and mixed hearing loss on both sides, we performed bilateral tympanoplasty. Since the hearing improvement following this procedure was poor on the right side, we prescribed a hearing aid. However, the patient did not adapt satisfactorily to this device. Four years after the initial diagnosis, we performed VSB middle ear implant surgery using the round window stimulation method, placing the transducer in the round window. The postoperative results were good. The speech inspection noise levels in both ears under a free-field, silent setting were 60 dBHL 85%, and 50 dBHL 100%. Thus, the postoperative course was good, the patient's satisfaction level improved and no adverse events occurred. VSB is likely to be a useful tool in rescue surgery for refractory middle ear cases. Also, it is useful as a standard rescue procedure in difficult hearing aid cases. In practice, otologic procedures are intended to improve the QOL and meet requirements in both diverse cases and individual patient conditions. Therefore, dissemination of VSB as one of the treatment choices for improving hearing loss is expected in the future.

Usefulness and limitation of thyroglobulin measurement in fine needle aspirates(FNA-Tg) for diagnosis of neck lymph node metastasis from thyroid carcinoma

Journal of Otolaryngology of Japan 119 （ 5 ） 721 - 726 2016年

ISSN 0030-6622

Preoperative diagnosis of lymph node metastasis from thyroid carcinoma is usually confirmed by using fine needle aspiration cytology(FNAC)when thyroid carcinoma is suspected based on the clinical findings. However, the result of FNAC sometimes leads to a false negative, especially in cases of hypocellular lesions such as metastases with cystic change. Thyroglobulin measurement in fine needle aspirates(FNA-Tg)has been shown to be a useful technique to detect the protein specifically secreted by thyroid follicular cells. Elevated FNA-Tg levels in an extra-thyroidal lesion means that the lesion comprises thyroid-originated tissue, most of which suggests the metastasis from thyroid carcinoma. Thus, FNA-Tg is expected to improve the sensitivity of FNAC for the aforementioned purpose. Patients and Methods : From 2008 to 2012, 49 extra-thyroidal lesions from 43 patients with thyroid carcinoma were examined using both FNAC and FNA-Tg, followed by surgical resection with a histopathological diagnosis. The results were retrospectively reviewed and analyzed. Results : Among 49 lesions, 47 were metastatic lymph nodes from thyroid carcinoma-46 papillary carcinoma and one follicular carcinoma-, one was a metastatic lymph node from submandibular gland adenocarcinoma, and one was an ectopic thyroid gland. In the 47 cases of thyroid carcinoma, the sensitivity of FNAC was 57.4%(27/47), whereas that of FNA-Tg was 76.6%(36/47). When both methods were combined, the sensitivity increased to 93.6%(44/47). Metastasis from submandibular gland adenocarcinoma was considered to be an example of a false positive from FNAC, whereas an ectopic thyroid gland was an FNA-Tg false positive. Three lesions were negative for both FNAC and FNA-Tg, although metastases were suspected by imaging studies and confirmed by histopathological diagnosis, which were consistent with examples of a false negative from both FNAC and FNA-Tg findings. Conclusions : FNAC reflects whether the lesion has malignant cells, whereas FNA-Tg reflects whether the lesion has thyroid-originated tissue that specifically secrets thyroglobulin. Therefore, FNAC and FNA-Tg are considered to be complementary to each other for the preoperative diagnosis of lymph node metastasis from thyroid carcinoma. FNA-Tg was validated to improve the preoperative diagnostic sensitivity especially when combined with FNAC, however, it is attended with the possibility of a false positive or negative finding, which requires caution in interpretation of the findings.

Distinct expression pattern of a deafness gene, KIAA1199, in a primate Cochlea

Hosoya Makoto, Fujioka Masato, Okano Hideyuki, Ogawa Kaoru

BioMed Research International 2016 2016年

ISSN 2314-6133

Deafness is one of the most common types of congenital impairments, and at least half of the cases are caused by hereditary mutations. Mutations of the gene KIAA1199 are associated with progressive hearing loss. Its expression is abundant in human cochlea, but interestingly the spatial expression patterns are different between mouse and rat cochleae; the pattern in humans has not been fully investigated. We performed immunohistochemical analysis of a nonhuman primate, common marmoset (Callithrix jacchus), cochlea with a KIAA1199-specific antibody. In the common marmoset cochlea, KIAA1199 protein expression was more widespread than in rodents, with all epithelial cells, including hair cells, expressing KIAA1199. Our results suggest that the primate pattern of KIAA1199 expression is wider in comparison with rodents and may play an essential role in the maintenance of cochlear epithelial cells.

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Frequency and specific characteristics of the incomplete partition type III anomaly in children

Kanno Ayako, Mutai Hideki, Namba Kazunori, Morita Noriko, Nakano Atsuko, Ogahara Noboru, Sugiuchi Tomoko, Ogawa Kaoru, Matsunaga Tatsuo

Laryngoscope 2016年

ISSN 0023-852X

Objectives/Hypothesis: To determine the frequency of the incomplete partition type III anomaly and the genetic and clinical features associated with POU3F4 mutations in children with hearing loss. Study Design: Retrospective case series from 2000 to 2014 at the National Hospital Organization Tokyo Medical Center and collaborating hospitals. Methods: A total of 1,004 patients (from 938 families) who had hearing loss by 10 years of age and had undergone computed tomography scanning of their temporal bones were enrolled in this genetic, clinical, and radiological study. Results: The incomplete partition type III anomaly was identified in six patients (0.6%), each of whom had an enlargement of the vestibular aqueduct at the end close to the vestibule. The six patients also had POU3F4 variants, and a genetic analysis revealed frameshift deletions in three patients, a missense variant in two patients of the same family, and a large deletion in one patient. Three of the six patients with POU3F4 variants were sporadic cases, and in one patient the genetic mutation occurred de novo. Conclusions: It was indicated that POU3F4 mutations can be predicted by incomplete partition type III anomaly by radiological examination of the inner ear. All six of the patients showed mixed hearing loss, but none showed fluctuations in hearing, which may be related to the lack of vestibular aqueduct enlargement at the operculum.

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Multidimensional vocal assessment after laser treatment for recurrent respiratory papillomatosis

Kono Takeyuki, Yabe Haruna, Uno Kosuke, Saito Koichiro, Ogawa Kaoru

Laryngoscope 2016年

ISSN 0023-852X

Objectives/Hypothesis: Recurrent respiratory papillomatosis (RRP) is a benign epithelial tumor that exhibits a high frequency of recurrence. This study assesses the vocal function after laser treatment for RRP, particularly in relation to the frequency of surgery. Study Design: Retrospective study. Methods: Thirty RRP patients who underwent laser surgery that controlled the tumor were included. Preoperative and postoperative Grade, Roughness, Breathiness, Asthenia, and Strain Scale, videostroboscopic findings, aerodynamic and acoustic parameters, and self-assessment questionnaires were measured and compared with an age- and sex-matched control group. Subsequently, to evaluate the association between postoperative voice quality and the number of surgeries, the patients were divided into three groups (group 1: single surgery, group 2: 2-5 surgeries, group3: >6 surgeries), and comparative multidimensional vocal assessments were performed. Results: The mean number of surgeries was 3.4 (range, 1-8). Although all patients exhibited poorer vocal function than the control group preoperatively, they showed improvement in postoperative subjective and objective parameters. However, four patients who underwent one surgery with relatively aggressive ablation exhibited vocal cord scarring and deteriorated objective parameters. All remaining patients showed voice quality that was on par with the control group. Subgroup analysis proved no association between post-therapeutic voice quality and the patient characteristics, including preoperative staging and the number of surgical treatments performed. Conclusions: RRP patients can achieve a close to normal voice with high satisfaction even after recurrent surgical treatment when ablation of a subepithelial lesion using sufficient laser energy is adequate.

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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年12月

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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Application of Kampo medicine on tinnitus and hearing loss

Ogawa Kaoru

Otolaryngology - Head and Neck Surgery (Japan) 87 （ 13 ） 1080 - 1084 2015年12月

ISSN 0914-3491

Novel in vivo imaging analysis of an inner ear drug delivery system

Kanzaki Sho, Watanabe Kotaro, Fujioka Masato, Shibata Shinsuke, Nakamura Masaya, Okano Hirotaka James, Okano Hideyuki, Ogawa Kaoru

Hearing Research 330 142 - 146 2015年12月

ISSN 0378-5955

Systemic application of drugs is commonly used in clinical situations. Some of these drugs are ototoxic. Since there are few studies on in vivo monitoring of drug delivery dynamics, the time course or bioavailability of drugs in the inner ear of live animals following systemic drug application remains unknown. For instance, it is unknown whether the volume of a drug delivered systemically correlates with its inner ear pharmacokinetics. We previously established a new in vivo imaging system to monitor drug delivery in live mice. In the present study, we used this system to compare drug concentration in the inner ear over time after systemic drug injections. We used transgenic GFAP-Luc mice that harbor a firefly luciferase gene expression cassette regulated by 12 kb of murine GFAP promoter and human beta-globin intron 2. Luciferin delivered into the inner ear of these mice reacts with luciferase, and the resulting signals are detected in GFAP-expressing cells in the cochlear nerve. Thus, we assessed in the inner ear the intensity and duration of luciferin/luciferase signals after systemic injections of different volumes of luciferin. An IVIS^® imaging system was used to observe signals, and these signals were compared to the drug dynamics of luciferin delivered through subcutaneous (sc) injections. The volume of sc-injected drug correlated significantly with photon counts measured in the inner ear. Photons were detected almost immediately after injection, peaking 20 min after injection. Drug concentration did not affect inner ear signals. Luciferin injected systemically appeared in the inner ear between highest and lowest concentration. Drug volume is an important parameter to know if the inner ear requires a higher level of the drug. We observed that it is the volume of a drug-not its concentration-that is the important factor. Indeed, the more volume of a drug injected systemically increased the concentration of that drug in the inner ear. This study provides a better understanding of in vivo drug delivery dynamics measured in the inner ear. Further studies will show whether a high dosage of drug is effective or not. This article is part of a Special Issue entitled .

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Expression of Oct3/4 and Nanog in the head and neck squamous carcinoma cells and its clinical implications for delayed neck metastasis in stage I/II oral tongue squamous cell carcinoma

Habu Noboru, Imanishi Yorihisa, Kameyama Kaori, Shimoda Masayuki, Tokumaru Yutaka, Sakamoto Koji, Fujii Ryoichi, Shigetomi Seiji, Otsuka Kuninori, Sato Yoichiro, Watanabe Yoshihiro, Ozawa Hiroyuki, Tomita Toshiki, Fujii Masato, Ogawa Kaoru

BMC Cancer 15 （ 1 ） 2015年10月

Background: The side population (SP) of cancer cells is reportedly enriched with cancer stem cells (CSCs), however, the functional role and clinical relevance of CSC marker molecules upregulated in the SP of head and neck squamous carcinoma (HNSCC) cells are yet to be elucidated. Patients with clinical stage I/II (T1-2N0M0) tongue squamous cell carcinoma (TSCC) typically undergo partial glossectomy; however, development of delayed neck metastasis (DNM) tends to reduce their survival. In the present study, we aimed to determine the CSC markers in the SP of HNSCC cells along with their functions in cellular behaviors, and to clarify the association of these markers with DNM. Methods: Flow cytometry was applied to isolate SP from main population (MP) in HNSCC cells. The expression of the CSC markers was examined by semi-quantitative RT-PCR and immunocytochemistry. In vitro proliferation, migration, and invasion assays were performed to assess cellular behaviors. Clinicopathological factors and immunohistochemical expressions of Oct3/4 and Nanog were evaluated using surgical specimens from 50 patients with stage I/II TSCC. Results: SPs were isolated in all three cell lines examined. Expression levels of Oct3/4 and Nanog were higher in SP cells than MP cells. Additionally, cell migration and invasion abilities were higher in SP cells than MP cells, whereas there was no difference in proliferation. Univariate analysis showed that expression of Oct3/4 and Nanog, vascular and muscular invasion, and mode of invasion were significantly correlated with DNM. Multivariate logistic regression revealed that Oct3/4 expression (risk ratio = 14.78, p = 0.002) and vascular invasion (risk ratio = 12.93, p = 0.017) were independently predictive of DNM. Regarding the diagnostic performance, Oct3/4 showed the highest accuracy, sensitivity, and NPV of 82.0%, 61.5%, and 86.8%, respectively, while vascular invasion showed the highest specificity and PPV of 94.6% and 71.4%, respectively. Conclusion: These results suggest that Oct3/4 and Nanog represent probable CSC markers in HNSCC, which contribute to the development of DNM in part by enhancing cell motility and invasiveness. Moreover, along with vascular invasion, expression of Oct3/4 can be considered a potential predictor for selecting patients at high risk of developing DNM.

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Closure of tracheoesophageal puncture with pedicled fascia flap of the sternocleidomastoid muscle

Wasano Koichiro, Suzuki Noriomi, Kawasaki Taiji, Yamamoto Sayuri, Minami Shujiro, Yamashita Taku, Ogawa Kaoru

Auris Nasus Larynx 42 （ 4 ） 318 - 321 2015年08月

ISSN 0385-8146

Objective: Closure of a tracheoesophageal puncture (TEP) formed during voice prosthesis implantation may sometimes be required. We report a new method of closure that we have termed the RESET method. Methods: We used the RESET method for four patients. An initial incision was made at the mucocutaneous junction of the tracheostoma, and the trachea and esophagus were separated. The TEP was sectioned, and the tracheal and esophageal sides were sutured into separate layers. A pedicled fascia flap lifted from the sternocleidomastoid muscle was sandwiched between the trachea and the esophagus, and subsequently secured. Results: The TEP was closed in all patients, and no complications were observed. Conclusion: The RESET method, using a pedicled fascia flap with stable perfusion, is a simple, reliable method of TEP closure.

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Magnetic resonance monitoring of superparamagnetic iron oxide (SPIO)-labeled stem cells transplanted into the inner ear

Watada Yukiko, Yamashita Daisuke, Toyoda Masashi, Tsuchiya Kohei, Hida Naoko, Tanimoto Akihiro, Ogawa Kaoru, Kanzaki Sho, Umezawa Akihiro

Neuroscience Research 95 21 - 26 2015年06月

ISSN 0168-0102

In the field of regenerative medicine, cell transplantation or cell-based therapies for inner ear defects are considered to be promising candidates for a therapeutic strategy. In this paper, we report on a study that examined the use of magnetic resonance imaging (MRI) to monitor stem cells transplanted into the cochlea labeled with superparamagnetic iron oxide (SPIO), a contrast agent commonly used with MRI. First, we demonstrated in vitro that stem cells efficiently took up SPIO particles. This was confirmed by Prussian blue staining and TEM. In MRI studies, T2 relaxation times of SPIO-labeled cells decreased in a dose-dependent manner. Next, we transplanted SPIO-labeled cells directly into the cochlea in vivo and then performed MRI 1. h, 2 weeks, and 4 weeks after transplantation. The images were evaluated objectively by measuring signal intensity (SI). SI within the ears receiving transplants was significantly lower (P < 0.05) than that of control sides at the 1-h assessment. This novel method will be helpful for evaluating stem cell therapies, which represents a new strategy for inner ear regeneration. To the best of our knowledge, this study is the first to demonstrate that local transplantation of labeled stem cells into the inner ear can be visualized in vivo via MRI.

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Neuroprotective effects of cutamesine, a ligand of the sigma-1 receptor chaperone, against noise-induced hearing loss

Yamashita Daisuke, Sun Guang wei, Cui Yong, Mita Shiro, Otsuki Naoki, Kanzaki Sho, Nibu Ken Ichi, Ogawa Kaoru, Matsunaga Tatsuo

Journal of Neuroscience Research 93 （ 5 ） 788 - 795 2015年05月

ISSN 0360-4012

The sigma-1 receptor, which is expressed throughout the brain, provides physiological benefits that include higher brain function. The sigma-1 receptor functions as a chaperone in the endoplasmic reticulum and may control cell death and regeneration within the central nervous system. Cutamesine (1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine dihydrochloride) is a ligand selective for this receptor and may mediate neuroprotective effects in the context of neurodegenerative disease. We therefore assessed whether cutamesine protects the inner ear from noise-induced or aging-associated hearing loss. Immunohistochemistry and Western blotting revealed that the sigma-1 receptor is present in adult cochlea. We treated mice with 0, 3, or 30 mg/kg cutamesine from 10 days before noise exposure until the end of the study. All subjects were exposed to a 120-dB, 4-kHz octave-band noise for 2 hr. We assessed auditory thresholds by measuring the auditory-evoked brainstem responses at 4, 8, and 16 kHz, prior to and 1 week, 1 month, or 3 months following noise exposure. For the aging study, measurements were made before treatment was initiated and after 3 or 9 months of cutamesine treatment. Damage to fibrocytes within the cochlear spiral limbus was assessed by quantitative histology. Cutamesine significantly reduced threshold shifts and cell death within the spiral limbus in response to intense noise. These effects were not dose or time dependent. Conversely, cutamesine did not prevent aging-associated hearing loss. These results suggest that cutamesine reduces noise-induced hearing loss and cochlear damage during the acute phase that follows exposure to an intense noise.

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Pico<inf>2</inf> monitoring of transferred jejunum perfusion using an air tonometry technique after hypopharyngeal cancer surgery

Ozawa Hiroyuki, Imanishi Yorihisa, Ito Fumihiro, Watanabe Yoshihiro, Kato Takashi, Nameki Hideo, Isobe Kiyoshi, Ogawa Kaoru

Medicine (United States) 94 （ 11 ） e632 2015年03月

ISSN 0025-7974

This study aimed to investigate the usefulness of intraluminal Pco 2 (Pico 2) monitoring by air tonometry for the assessment of the vascular condition of the transferred jejunum after surgery for hypopharyngeal cancer. Pico 2 in the transplanted jejunum of 24 patients was monitored using air tonometry after radical surgery for hypopharyngeal cancer from 2003 to 2010. All but 1 patient, who removed the catheter before monitoring began, were monitored safely. Pico 2 in the transferred jejunum correlated with arterial Pco 2 (Paco 2) that was measured concurrently, and dissociation of Pico 2 from Paco 2 was observed in cases with vascular complication. In those cases without postoperative vascular complication, the Pico 2 value gradually increased for 3 hours but then decreased by 12 hours after surgery. Three patients experienced major vascular complication. All 3 patients had continuous elevation of Pico 2 >100mm Hg, although vascular flow in 1 patient recovered by removal of a venous thrombosis and reanastomosis of the vein 7.5 hours after surgery. Four other patients who experienced elevation of Pico 2 had their skin suture released for decompression of their neck wound, resulting in a decrease in Pico 2 after treatment. The current results demonstrated that continuous monitoring of Pico 2 by air tonometry accurately reflects the vascular condition of the transferred jejunum, and this method is one of the best options for postoperative monitoring of jejunum blood perfusion.

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Usefulness of Clinicobiological Data Obtained Prior to Cervical Lymph Node Biopsy

Kawasaki Taiji, Wasano Koichiro, Suzuki Noriomi, Yamamoto Sayuri, Ogawa Kaoru

Nihon Jibiinkoka Gakkai kaiho 118 （ 3 ） 206 - 212 2015年03月

ISSN 0030-6622

INTRODUCTION: We commonly use data obtained prior to cervical lymph node biopsy for the diagnosis of malignant lymphoma. Based on such data, we can confirm whether a biopsy should be performed in some cases. Currently, the parameters used to indicate a presurgery examination prior to biopsy have been very few. So, we retrospectively analyzed cases of cervical lymph node biopsy. Moreover, we examined the usefulness of clinicobiological data obtained prior to cervical lymph node biopsy to evaluate various factors related to the diagnosis of malignant lymphoma.METHODS: This study included 77 patients for whom the initial diagnostic impression was malignant lymphoma before surgery. Of the 77 cases, 40 were diagnosed as having malignant lymphoma and 37 were diagnosed as having non-malignant lymphoma. We performed a case-controlled study to evaluate the differences in clinicobiological data between malignant and non-malignant lymphoma in terms of the following parameters: (1) age, (2) sex, (3) number of white blood cells, (4) white blood cell lymphocyte count, (5) percentage of white blood cell lymphocytes, (6) percentage of eosinophils (%), (7) percentage of monocytes (%), (8) atypical lymphocytes (%), (9) hemoglobin level, (10) lactate dehydrogenase level, (11) C-reactive protein level, (12) soluble interleukin-2 receptor (IL-2R) level, and (13) cytological findings. We used multivariate and univariate analyses to study the data statistically.RESULTS: The following 5 factors were found to be significant in a Wilcoxon t-test for malignant lymphoma: percentage of white blood cell lymphocytes, sIL-2R level, age, white blood cell lymphocyte count, and cytological findings; these factors were also significant when examined using a Pearson χ2 test. The other factors did not differ significantly between the malignant and non-malignant lymphomas. The percentage of white blood cell lymphocytes and the cytological findings were identified as significant independent factors for the diagnosis of malignant lymphoma in a multivariate analysis, whereas the other factors were not found to be significant.CONCLUSION: Based on the results of the univariate and multivariate analyses performed in the present study, the decline in the percentage of white blood cell lymphocytes and the cytological findings obtained prior to cervical lymph node biopsy are significant indicators of malignant lymphoma.

Usefulness of clinicobiological data obtained prior to cervical lymph node biopsy

Kawasaki Taiji, Wasano Koichiro, Suzuki Noriomi, Yamamoto Sayuri, Ogawa Kaoru

Journal of Otolaryngology of Japan 118 （ 3 ） 206 - 212 2015年03月

ISSN 0030-6622

Introduction: We commonly use data obtained prior to cervical lymph node biopsy for the diagnosis of malignant lymphoma. Based on such data, we can confirm whether a biopsy should be performed in some cases. Currently, the parameters used to indicate a presurgery examination prior to biopsy have been very few. So, we retrospectively analyzed cases of cervical lymph node biopsy. Moreover, we examined the usefulness of clinicobiological data obtained prior to cervical lymph node biopsy to evaluate various factors related to the diagnosis of malignant lymphoma. Methods: This study included 77 patients for whom the initial diagnostic impression was malignant lymphoma before surgery. Of the 77 cases. 40 were diagnosed as having malignant lymphoma and 37 were diagnosed as having non-malignant lymphoma. We performed a case-controlled study to evaluate the differences in clinicobiological data between malignant and non-malignant lymphoma in terms of the following parameters: (l) age, (2) sex, (3) number of white blood cells, (4) white blood cell lymphocyte count, (5) percentage of white blood cell lymphocytes, (6) percentage of eosinophils (%), (7) percentage of monocytes (%), (8) atypical lymphocytes (%), (9) hemoglobin level. (10) lactate dehydrogenase level. (11) C-reactive protein level. (12) soluble interleukin-2 receptor (IL-2R) level, and (13) cytologi- cal findings. We used multivariate and univariate analyses to study the data statistically. Results: 'Hie following 5 factors were found to be significant in a Wilcoxon /-test for malignant lymphoma: Percent-age of white blood cell lymphocytes, sIL-2R level, age, white blood cell lymphocyte count, and cytological findings; these factors were also significant when examined using a Pearson X2 test. The other factors did not differ significantly between the malignant and non-malignant lymphomas. The percentage of white blood cell lymphocytes and the cytological findings were identified as significant independent factors for the diagnosis of malignant lymphoma in a multivariate analysis, whereas the other factors were not found to be significant. Conclusion: Based on the results of the univariate and multivariate analyses performed in the present study, the decline in the percentage of white blood cell lymphocytes and the cytological findings obtained prior to cervical lymph node biopsy are significant indicators of malignant lymphoma.

The autophagy pathway maintained signaling crosstalk with the Keap1-Nrf2 system through p62 in auditory cells under oxidative stress

Hayashi Ken, Dan Katsuaki, Goto Fumiyuki, Tshuchihashi Nana, Nomura Yasuyuki, Fujioka Masato, Kanzaki Sho, Ogawa Kaoru

Cellular Signalling 27 （ 2 ） 382 - 393 2015年02月

ISSN 0898-6568

The main purposes of our study were to consider the effect of autophagy on auditory cells under oxidative stress, and the function of possible crosstalk among p62, Keap1 and Nrf2 in autophagy-deficient auditory cells. First, we described how cell death was induced in auditory cell line (HEI-OC1) exposed to H₂O₂. We found that the decision for the cell death of auditory cells under oxidative stress depends on the balance between autophagy and necrosis due to ATP depletion, and autophagy plays a cytoprotective function in oxidative stress-induced necrosis. Our data clearly suggested that autophagy was a cell survival mechanism in H₂O₂-induced cell death, based on the observation that suppression of autophagy by knockdown of Atg7 sensitized, whereas activation of autophagy by rapamycin protected against H₂O₂-induced cell death. Next, our results regarding the relationship among p62, Nrf2 and Keap1 by siRNA paradoxically showed that p62 creates a positive feedback loop in the Keap1/Nrf2 pathway. Autophagy impaired by Atg7 knockdown degrades Keap1 in a p62-dependent manner, whereas Nrf2 is activated. As a result, the cell death induced by H₂O₂ was promoted in auditory cells. Taken together, these results suggested that the autophagy pathway maintained signaling crosstalk with the Keap1-Nrf2 system through p62 in auditory cells under oxidative stress.

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Supraclavicular artery island flap (SCAIF) in head and neck reconstruction

Wasano Koichiro, Suzuki Noriomi, Kawasaki Taiji, Ogawa Kaoru

Japanese Journal of Head and Neck Cancer 40 （ 4 ） 497 - 501 2015年01月

ISSN 1349-5747

Supraclavicular Artery Island Flap (SCAIF) is a pedicled fasciocutaneous flap based on the supraclavicular artery and vein. Originally, SCAIF had been used for surgery on post-burn scars. However, it gradually came to be used for reconstruction after head and neck cancer resection. Although it has been shown as useful in foreign countries, there were no reports in Japan.We used SCAIFs for reconstruction after head and neck cancer resection in four cases. The time for harvesting the flap was about one hour and the donor site could be primarily closed. Only head and neck surgeons participated in the surgery, but it was not so difficult to harvest SCAIFs for surgeons experienced in harvesting various flaps.As a result, there were no flap failures in this series; however, one case experienced salivary leak, but this was managed via DP flap onlay. All of the patients could resume an oral diet without gastric tube supplementation.Therefore, we consider that SCAIF can be one of the options available for reconstruction after head and neck cancer resection.

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Analysis of sphenoid sinus lateral pneumatization for endonasal endoscopic surgery

Kikuchi Ryogo, Toda Masahiro, Tomita Toshiki, Ogawa Kaoru, Yoshida Kazunari

Surgical Neurology International 6 （ 1 ） 2015年01月

ISSN 2152-7806

Background: The purpose of this study was to analyze sphenoid sinus lateral pneumatization (SSLP), especially in Asian populations, and to identify cautionary items when using the endoscopic endonasal approach (EEA) for parasellar/lateral lesions. Methods: We analyzed SSLP and the width of SS (SSW) in 121 patients who had undergone EEA from 2008 to 2013 at the Division of Neurosurgery, Keio University Hospital. SSLP was defined as the distance between the SS lateral edge and the medial aspect of the pterygoid process on coronal reconstruction computed tomography. SSW was defined as the distance between the midline and lateral wall. We recorded SSLP and SSW for 242 sides. Further, we present two characteristic cases. Results: The average SSLP and SSW were 7.0 mm (-10.0-25.8 mm) and 21.8 mm (6.0-40.2 mm), respectively. No correlation between pneumatization and age was observed at age 15 or more. Sphenoid pneumatization was significantly wider in male than in female patients. There was no relationship between lateral and sagittal plane pneumatization. In a patient with recurrent chordoma who had an undeveloped SSLP, the tumor was removed via the medial space in the internal carotid artery. In another patient who had a giant pituitary adenoma and average SSLP, the tumor was located in the middle cranial fossa and was removed via the lateral internal carotid space through the left SSLP. Conclusions: Wide variations were observed in SSLP and SSW. For EEA, pneumatization is an instrument corridor. Preoperative assessment of SSLP is important, especially for parasellar lesions.

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Auricular malformation treated by placement of an osseointegrated implant-supported epithesis using telenavigation and model simulation

Usuda Shin, Truppe Michael, Kaneko Tsuyoshi, Ogawa Kaoru, Asoda Seiji, Hatazawa Chika, Usuda Sho, Yamada Yuka, Ewers Rolf, Nakagawa Taneaki, Kawana Hiromasa

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 27 （ 1 ） 49 - 55 2015年01月

ISSN 2212-5558

We report a case of auricular malformation treated by placement of an osseointegrated implant-supported epithesis using telenavigation and model simulation. A 66-year-old male suffering from auricular malformation and atresia auris of his right ear since birth visited our department in October 2006. The patient desired placement of an ear epithesis supported by osseointegrated implants. Computed tomographic (CT) scans were obtained for use in the navigation system as a prerequisite for the telenavigation and the operative plan was designed in consultation with an overseas oral and maxillofacial surgeon having rich experience in telenavigation surgery. We also constructed a preoperative simulation model and a mirror model of the unaffected left ear based on laser lithography to produce successful operation and symmetrical form of a symmetrical ear epithesis as contrast with identical to that on the left side. The osseointegrated implant surgery was carried out under telenavigation guidance. As a result, safe and accurate positioning of the implants was achieved and a symmetrical and elaborate epithesis could be fabricated.

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Autophagy through 4EBP1 and AMPK regulates oxidative stress-induced premature senescence in auditory cells

Tsuchihashi Nana Akagi, Hayashi Ken, Dan Katsuaki, Goto Fumiyuki, Nomura Yasuyuki, Fujioka Masato, Kanzaki Sho, Komune Shizuo, Ogawa Kaoru

Oncotarget 6 （ 6 ） 3644 - 3655 2015年

The aim of this study was to determine whether autophagy and AMPK contribute to premature senescence in auditory cells. Incubating HEI-OC1 auditory cells with 5 mM H₂O₂ for 1 h induced senescence, as demonstrated by senescence-associated β-galactosidase (SA-β-gal) staining. H₂O₂ treatment significantly delayed populationdoubling time, leaving cell viability unchanged. Furthermore, the proportion of SA-β-gal-positive cells significantly increased. Autophagy-related protein expression increased, with Atg7 and LC3-II peaking 6 h and Lamp2 peaking 24 h after H₂O₂ treatment. The expression of these proteins decreased 48 h after treatment. Transmission electron microscopy revealed lipofuscin and aggregates within autolysosomes, which accumulated markedly in the cytoplasm of HEI-OC1 cells 48 h after treatment. Akt and P70S6 phosphorylation markedly decreased after H₂O₂ treatment, but 4EBP1 phosphorylation significantly increased 48 h after treatment. After RNAi-mediated knockdown (KD) of Atg7 and AMPK, H₂O₂-treated cells displayed dense SA-β-gal staining. Also, premature senescence was significantly induced. These suggest that a negative feedback loop may exist between autophagy and AMPK signaling pathways in HEI-OC1 cells. In our model, oxidative stress-induced premature senescence occurred due to impaired autophagy function through 4EBP1 phosphorylation. Our results also indicate that AMPK may regulate premature senescence in auditory cells in an autophagy-dependent and independent manner.

Petrous apex cholesterol granuloma

Shibao Shunsuke, Toda Masahiro, Tomita Toshiki, Saito Katsuya, Ogawa Kaoru, Kawase Takeshi, Yoshida Kazunari

Neurologia Medico-Chirurgica 55 （ 4 ） 351 - 355 2015年

ISSN 0470-8105

Recently, petrous apex cholesterol granulomas (CGs) have been treated via the endoscopic endonasal transsphenoidal approach (EEA) using a silicone tube, to prevent drainage route occlusion. Occlusion of the drainage route has led to problems with recurrence. The aim of this report is to describe the use of a surgical technique to prevent drainage route occlusion. In surgical technique, the posterolateral wall of the sphenoid sinus was opened by EEA. After cyst debridement, a vascularized nasoseptal flap with a width of approximately 4 cm was inserted into the lumen with a silicone T-tube with a diameter of 7 mm. This technique was used in two patients: the first patient during the second operation after recurrence following occlusion of the drainage route, and the second patient during the first operation. Opening of the cyst wall was confirmed endoscopically in both patients 12–24 months after surgery, even after removal of the T-tube. In conclusion, the use of a pedicled nasoseptal flap with a silicone tube is useful to prevent CG recurrence, by paranasal cavitization of the cystic cavity.

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Primary oropharyngeal herpes simplex virus infection in adults

Nakagawa H., Kusuyama T., Ogawa K.

Clinical Otolaryngology 40 （ 4 ） 393 - 396 2015年

ISSN 1749-4478

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A study on thyroid nodules without preoperative malignant features

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

Practica Otologica, Supplement 141 102 - 103 2015年

ISSN 0912-1870

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-opera-tively 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 four 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.

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Transoral vs. endoscopic endonasal approach for clival/upper cervical chordoma

Shidoh Satoka, Toda Masahiro, Kawase Takeshi, Nakajima Hideo, Tomita Toshiki, Ogawa Kaoru, Yoshida Kazunari

Neurologia Medico-Chirurgica 54 （ 12 ） 991 - 998 2014年12月

ISSN 0470-8105

The surgical results of 18 cases of clival/upper cervical chordoma treated in the last decade via the endoscopic endonasal approach (EEA, 9 cases) and the transoral-transpalatal approach (TO-TPA, 9 cases) were compared. Each group showed the same incidence of subdural invasion, with 5 cases each. The superior (frontal base) and lateral surgical fields were wider by EEA, but the inferior view lower than the cranio-vertebral junction (CVJ) was wider by TO-TPA. Gross total removal was achieved in 3 cases in the EEA group, but in only 1 case in the TO-TPA group. Differences in radicality might be due to the extent of the lateral and subdural overview. However for large tumors extending below the CVJ, TO-TPA was the only viable approach for surgical removal. Surgical complications were higher in the EEA (4 cases) than the TO-TPA group (1 case), and were mainly caused by aggressive management of subdural invasion in the EEA group. Post-operative oral intake was earlier and the operative time was shorter in the EEA group. The surgical results were more radical and less invasive in the EEA group than the TO-TPA group. However in tumors extending below the CVJ, the surgical field in EEA was limited, indicating the need to use the transoral route or a combination of routes. A higher complication rate following subdural management was a negative factor that requires improvement in the EEA group and two-staged EEA followed by a transcranial approach may be considered for the cases with subdural invasion.

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Analysis of the bacterial flora in the nasal cavity and the sphenoid sinus mucosa in patients operated on with an endoscopic endonasal transsphenoidal approach

Shibao Shunsuke, Toda Masahiro, Tomita Toshiki, Ogawa Kaoru, Yoshida Kazunari

Neurologia Medico-Chirurgica 54 （ 12 ） 1009 - 1013 2014年12月

ISSN 0470-8105

The aim of this study was to analyze the bacterial flora in the nasal cavity and sphenoid sinus and evaluate the sensitivity of these bacteria to antibiotics that can be used to prevent postoperative meningitis. Bacteria of the preoperative nasal cavity and intraoperative sphenoid sinus mucosa were cultured and analyzed in 40 patients (20 men and 20 women; mean age, 52.2 years) who underwent endoscopic transsphenoidal surgery. The sensitivity of these bacteria to cephalosporin, a representative prophylactic antibiotic, was examined. Staphylococcus epidermidis was the most frequently detected species in both spaces; 24 (38.7%) of 62 isolates in the nasal cavity and 26 (37.1%) of 70 isolates in the sphenoid sinus. In contrast, Corynebacterium species were found mainly in the nasal cavity, and anaerobic bacteria were found only in the sphenoid sinus. Bacteria that were resistant to cephalosporin were found in the nasal cavity in 3.2% of patients and in the sphenoid sinus in 20% of patients. In conclusion, the composition of bacterial flora, including bacteria that are resistant to prophylactic antibiotics, differs between the nasal cavity and the sphenoid sinus.

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Idiopathic sudden sensorineural hearing loss in Japan

Nakashima Tsutomu, Sato Hiroaki, Gyo Kiyofumi, Hato Naohito, Yoshida Tadao, Shimono Mariko, Teranishi Masaaki, Sone Michihiko, Fukunaga Yukari, Kobashi Gen, Takahashi Kunihiko, Matsui Shigeyuki, Ogawa Kaoru

Acta Oto-Laryngologica 134 （ 11 ） 1158 - 1163 2014年11月

ISSN 0001-6489

Conclusion: An epidemiological survey of hospitals and private clinics in Japan regarding idiopathic sudden sensorineural hearing loss (SSNHL) revealed that the incidence of SSNHL was 60.9 per 100 000 population. There were more females than males in the younger generation. Objective: The incidence of SSNHL varies largely by country. Because the Japanese criteria for diagnosing SSNHL have changed in accordance with those widely used in other parts of the world, a clinicoepidemiological study was undertaken using the new criteria. Methods: Ehime, Aichi, and Iwate Prefectures were selected from the western, central, and northeastern regions of Japan, respectively. The subjects for this study were patients who suffered SSNHL between April 1, 2012 and March 31, 2013. Questionnaires were mailed to all hospitals and private clinics in which ENT doctors were working. Initial and final audiograms were requested for 10% of the patients. Results: In all, 78 of 90 hospitals (87%) and 303 of 407 private clinics (74%) responded. It was reported that 1663 patients visited hospitals and 3090 patients visited only private clinics. It was estimated that 6205 SSNHL patients visited hospitals or private clinics in 1 year from a population of 10 145 000. Also, 23% of patients suffered acute low-tone SNHL (female to male ratio; 3:1 in definite cases).

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High fibrinogen in peripheral blood correlates with poorer hearing recovery in idiopathic sudden sensorineural hearing loss

Kanzaki Sho, Sakagami Masafumi, Hosoi Hiroshi, Murakami Shingo, Ogawa Kaoru

PLoS One 9 （ 8 ） 2014年08月

Objectives: We used hearing tests and peripheral blood sample analyses to characterize the pathology of idiopathic sudden sensorineural hearing loss (ISSNHL) and to identify possible prognostic factors for predicting recovery of hearing loss. Study Design: A retrospective, multicenter trial was conducted. Methods: Two hundred three patients examined within 7 days after the onset of ISSNHL received prednisone with lipoprostaglandin E1. Pure-tone auditory tests were performed before and after treatment with these drugs. Blood tests were performed on blood samples collected during the patients' initial visit to our clinic. Results: In all patients, elevated white blood cell (WBC) counts, fasting blood sugar levels, HgbA1c, and erythrocyte sedimentation rate (ESR) significantly correlated with high hearing threshold measurements obtained on the initial visit. High fibrinogen levels, WBC counts, ESR, and low concentrations of fibrinogen degradation products (FDP) were associated with lower hearing recovery rates. Additionally, different audiogram shapes correlated with different blood test factors, indicating that different pathologies were involved. Conclusions: High fibrinogen levels measured within seven days after ISSNHL onset correlated with poorer hearing recovery. This may be a consequence of ischemia or infections in the inner ear. The high WBC counts also observed may therefore reflect an immune response to inner ear damage induced by ischemic changes or infections. Our data indicate that therapeutic strategies should be selected based on the timing of initial treatment relative to ISSNHL onset.

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Restoration of E-cadherin expression by selective Cox-2 inhibition and the clinical relevance of the epithelial-to-mesenchymal transition in head and neck squamous cell carcinoma

Fujii Ryoichi, Imanishi Yorihisa, Shibata Katsushi, Sakai Nobuya, Sakamoto Koji, Shigetomi Seiji, Habu Noboru, Otsuka Kuninori, Sato Yoichiro, Watanabe Yoshihiro, Ozawa Hiroyuki, Tomita Toshiki, Kameyama Kaori, Fujii Masato, Ogawa Kaoru

Journal of Experimental and Clinical Cancer Research 33 （ 1 ） 2014年05月

ISSN 0392-9078

Background: The epithelial-to-mesenchymal transition (EMT) accompanied by the downregulation of E-cadherin has been thought to promote metastasis. Cyclooxygenase-2 (Cox-2) is presumed to contribute to cancer progression through its multifaceted function, and recently its inverse relationship with E-cadherin was suggested. The aim of the present study was to investigate whether selective Cox-2 inhibitors restore the expression of E-cadherin in head and neck squamous cell carcinoma (HNSCC) cells, and to examine the possible correlations of the expression levels of EMT-related molecules with clinicopathological factors in HNSCC. Methods. We used quantitative real-time PCR to examine the effects of three selective Cox-2 inhibitors, i.e., celecoxib, NS-398, and SC-791 on the gene expressions of E-cadherin (CDH-1) and its transcriptional repressors (SIP1, Snail, Twist) in the human HNSCC cell lines HSC-2 and HSC-4. To evaluate the changes in E-cadherin expression on the cell surface, we used a flowcytometer and immunofluorescent staining in addition to Western blotting. We evaluated and statistically analyzed the clinicopathological factors and mRNA expressions of Cox-2, CDH-1 and its repressors in surgical specimens of 40 patients with tongue squamous cell carcinoma (TSCC). Results: The selective Cox-2 inhibitors upregulated the E-cadherin expression on the cell surface of the HNSCC cells through the downregulation of its transcriptional repressors. The extent of this effect depended on the baseline expression levels of both E-cadherin and Cox-2 in each cell line. A univariate analysis showed that higher Cox-2 mRNA expression (p = 0.037), lower CDH-1 mRNA expression (p = 0.020), and advanced T-classification (p = 0.036) were significantly correlated with lymph node metastasis in TSCC. A multivariate logistic regression revealed that lower CDH-1 mRNA expression was the independent risk factor affecting lymph node metastasis (p = 0.041). Conclusions: These findings suggest that the appropriately selective administration of certain Cox-2 inhibitors may have an anti-metastatic effect through suppression of the EMT by restoring E-cadherin expression. In addition, the downregulation of CDH-1 resulting from the EMT may be closely involved in lymph node metastasis in TSCC.

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Pharmacological inhibition of cochlear mitochondrial respiratory chain induces secondary inflammation in the lateral wall

Fujioka Masato, Okamoto Yasuhide, Shinden Seiichi, Okano Hirotaka James, Okano Hideyuki, Ogawa Kaoru, Matsunaga Tatsuo

PLoS One 9 （ 3 ） 2014年03月

Cochlear lateral wall has recently been reported as a common site of inflammation, yet precise molecular mechanisms of the inflammatory responses remain elucidated. The present study examined the inflammatory responses in the lateral wall following acute mitochondrial dysfunction induced by a mitochondrial toxin, 3-nitropropionic acid (3-NP). Reverse-transcription (RT)-PCR revealed increases in the expression of the proinflammatory cytokines interleukin (IL)-1β and IL-6. Immunohistochemistry showed an increase in the number of activated cochlear macrophages in the lateral wall, which were in close proximity to IL-6-expressing cells. A genome-wide DNA microarray analysis of the lateral wall revealed that 35% and 60% of the genes showing >2-fold upregulation at 1 d and 3 d post-3-NP administration, respectively, were inflammatory genes, including CC- and CXC-type chemokine genes. High expression of CCL-1, 2, and 3 at 1 d, and of CCL-1, 2, 3, 4, and 5, CCR-2 and 5, and CX3CR1 at 3 d post-3-NP administration, coupled with no change in the level of CX3CL1 expression suggested that macrophages and monocytes may be involved in the inflammatory response to 3-NP-mediated injury. Quantitative (q)RT-PCR showed a transient induction of IL-1β and IL-6 expression within 24 h of 3-NP-mediated injury, followed by sustained expression of the chemoattractants, CCL-2, 4 and 5, up until 7 d after injury. The expression of CCL-2 and IL-6 was higher in animals showing permanent hearing impairment than in those showing temporary hearing impairment, suggesting that these inflammatory responses may be detrimental to hearing recovery. The present findings suggest that acute mitochondrial dysfunction induces secondary inflammatory responses in the lateral wall of the cochlear and that the IL-6/CCL-2 inflammatory pathway is involved in monocyte activation. Therefore, these secondary inflammatory responses may be a potential post-insult therapeutic target for treatments aimed at preventing the damage caused by acute mitochondrial dysfunction in the cochlear lateral wall.

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Bilateral congenital conductive hearing loss due to ossification of the stapedius tendon

Wasano Koichiro, Kanzaki Sho, Ogawa Kaoru

Otology and Neurotology 35 （ 3 ） 2014年03月

ISSN 1531-7129

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Keratinic amyloidosis of the external auditory canal

Wasano Koichiro, Saito Hideyuki, Kanzaki Sho, Ogawa Kaoru

Auris Nasus Larynx 41 （ 1 ） 97 - 100 2014年02月

ISSN 0385-8146

Objective: We present a rare case of keratinic amyloidosis of the external auditory canal. This is only the seventh case reported of localized cutaneous amyloidosis of the external auditory canal with no systemic symptoms. Patient: A 62-year-old man, who had complained of an itchy external auditory canal and left-side hearing loss, was referred to our hospital because of a bilateral external auditory canal mass. Intervention: Biopsy of the external auditory canal mass suggested a diagnosis of amyloidosis. However, total systemic examination failed to identify any disease due to systemic amyloidosis. This led us to diagnose him with localized cutaneous amyloidosis of the external auditory canal. Main outcome measure: We follow up periodically with systemic examination and local observation. Results: Thirty months after the initial diagnosis, he remains in follow-up and has not shown any significant aggravation of the disease. Conclusion: In previous cases, the chief complaints were itching sensations and pain in the external auditory canal as well as a sense of discomfort when wearing a hearing aid. This suggests that chronic stimulation and inflammation of the skin lining the external auditory canal induced amyloidosis.

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Isolated vagus nerve paralysis associated with internal carotid artery dissection

Nakagawa Hideki, Kusuyama Toshiyuki, Ogawa Kaoru

Auris Nasus Larynx 41 （ 1 ） 118 - 120 2014年02月

ISSN 0385-8146

Dysphagia and hoarseness caused by laryngopharyngeal paralysis associated with internal carotid artery (ICA) dissection is rare. We reported a case which recovered spontaneously. A 57-year old man visited our hospital complaining of dysphagia and hoarseness lasting for two weeks. Paralysis of right vocal fold and rotational movement of the posterior pharyngeal wall toward the left side during swallowing were observed. Magnetic resonance imaging was performed under diagnosis of isolated right vagus nerve paralysis, and dissection of the right ICA was revealed. He was treated conservatively, and both of laryngopharyngeal movement and the ICA dissection were improved completely. There is a possibility that laryngeal paralysis caused by ICA dissection has been misdiagnosed as an idiopathic paralysis.

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Subgroups of enlarged vestibular aqueduct in relation to SLC26A4 mutations and hearing loss

Okamoto Yasuhide, Mutai Hideki, Nakano Atsuko, Arimoto Yukiko, Sugiuchi Tomoko, Masuda Sawako, Morimoto Noriko, Sakamoto Hirokazu, Ogahara Noboru, Takagi Akira, Taiji Hidenobu, Kaga Kimitaka, Ogawa Kaoru, Matsunaga Tatsuo

Laryngoscope 124 （ 4 ） 2014年

ISSN 0023-852X

Objectives/Hypothesis To investigate possible association of hearing loss and SLC26A4 mutations with the subgroups of enlarged vestibular aqueduct (EVA) morphology in Japanese subjects with hearing loss. Study Design Retrospective multicenter study. Methods Forty-seven subjects who had vestibular aqueduct with midpoint diameter >1 mm by computed tomography of the temporal bone were enrolled at multiple sites across Japan, and DNA samples and clinical data were collected. EVA morphology was classified into four subgroups by the pattern of enlargement: aperture, aperture and midpoint, midpoint, and borderline enlargement. Venous blood DNA samples were subjected to polymerase chain reaction-based direct sequencing of all exons and exon-intron boundaries of the SLC26A4. Results Four novel SLC26A4 mutations were identified in the present study. SLC26A4 mutations were detected in almost all subjects with aperture, aperture and midpoint, and midpoint enlargement. In contrast, 71% of subjects with borderline enlargement had no SLC26A4 mutation. No significant difference was found in the distribution of truncating and nontruncating SLC26A4 mutations between the EVA subgroups. In addition, no significant correlation was observed between the EVA subgroups and hearing levels, incidence of hearing fluctuation, or progression of hearing loss. Conclusions Subgroups of EVA morphology were significantly correlated with the presence or absence of SLC26A4 mutation. In a subgroup analysis of subjects with SLC26A4 mutations, however, differences in the EVA subgroups were not correlated with SLC26A4 genotypes or characteristics of hearing loss. Level of Evidence NA. Laryngoscope, 124:E134-E140, 2014

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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年

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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Inflammatory and immune responses in the cochlea

Fujioka Masato, Okano Hideyuki, Ogawa Kaoru

Frontiers in Pharmacology 5 （ DEC ） 2014年

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年

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年

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年

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年

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年

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年10月

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年09月

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年09月

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年09月

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年09月

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年08月

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年06月

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年05月

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年05月

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年04月

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年03月

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年03月

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年02月

ISSN 1001-1781

Sudden onset hearing loss and vertigo just before posterior inferior cerebellar artery infarction (lateral medulla syndrome)

Kanzaki Sho, Suzuki Takafumi, Suzuki Shigeaki, Suzuki Norihiro, Ogawa Kaoru

Otology and Neurotology 34 （ 2 ） 2013年02月

ISSN 1531-7129

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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年02月

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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Quality of life reported by patients with idiopathic sudden sensorineural hearing loss

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

Otology and Neurotology 34 （ 1 ） 36 - 40 2013年01月

ISSN 1531-7129

OBJECTIVE: This study evaluated quality of life (QOL) in the patients with idiopathic sudden sensorineural hearing loss (ISSHL). STUDY DESIGN: Cross-sectional study. SETTING: Multicenter clinical investigation in ten university hospitals. PATIENTS: In total, 167 patients with ISSHL and 134 patients with bilateral sensorineural hearing loss (BSHL; control) were included. MAIN OUTCOME MEASURES: The Short Form Health Survey Version 2 was used to assess the health-related QOL. RESULTS: The average scores of 8 domains and 2 summary components were similar between the 2 groups. All scores except those for bodily pain (BP) in ISSHL patients and BP and vitality in BSHL patients were significantly lower than the Japanese average. Scores for the mental component summary (MCS) were especially low in ISSHL patients. MCS scores of ISSHL patients aged 40 to 49, 50 to 59, 60 to 69, and 70 years or older were significantly lower than the Japanese average for each age group. MCS scores of BSHL patients 70 years or older were significantly lower than the Japanese average. Two-way analysis of variance revealed no significant association of disease (ISSHL and BSHL) and age with MCS score. Interactions were also not significant. The effects of sex, age, hearing level, and time interval from the onset on MCS scores of ISSHL patients were evaluated using multiple regression analysis. Age and time interval from the onset were observed to be significant confounders. CONCLUSION: The QOL of patients with ISSHL deteriorated especially in terms of mental functioning. Similar deterioration was observed in BSHL patients.

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Treating pediatric psychogenic dizziness with a japanese herbal medicine

Goto Fumiyuki, Morimoto Noriko, Taiji Hidenobu, Tsutumi Tomoko, Ogawa Kaoru

Explore: The Journal of Science and Healing 9 （ 1 ） 41 - 43 2013年01月

ISSN 1550-8307

Objective: No conventional pharmacotherapy is available for the treatment of psychogenic dizziness in pediatric patients. Adults with psychogenic dizziness are treated with psychiatric medicines as the standard treatment. In children, this treatment is not widely accepted because of the potential for adverse reactions. Instead, Kampo, an alternative medicine, is probably the best choice of treatment. Design: We report herein three of four cases of pediatric psychogenic dizziness successfully treated with Yoku-kan-san-ka-chimpi-hange (YKCH), a traditional Japanese Kampo medicine known to ameliorate psychiatric symptoms. Subjects: YKCH was prescribed to four patients (two boys and two girls) with psychiatric dizziness whose ages ranged from 11 to 15 years. Four weeks after the initiation of treatment, clinical improvement was assessed by the Clinical Global impression-Improvement scale. Results: In three of the four patients, the drug showed some significant effects. The remaining patient could not continue the medication. It is reasonable to assume that YKCH was effective because of its serotonergic mechanism and the improvement of sleep in our patients. Conclusions: This report is the first to describe the beneficial effects of YKCH in the treatment of pediatric psychogenic dizziness. We conclude that administration of YKCH may be a suitable complementary therapy for pediatric psychogenic dizziness.

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Novel In Vivo Imaging Analysis of an Inner Ear Drug Delivery System in Mice

Kanzaki Sho, Fujioka Masato, Yasuda Akimasa, Shibata Shinsuke, Nakamura Masaya, Okano Hirotaka James, Ogawa Kaoru, Okano Hideyuki

PLoS One 7 （ 12 ） 2012年12月

Objective: Systemic steroid injections are used to treat idiopathic sudden-onset sensorineural hearing loss (ISSHL) and some inner ear disorders. Recent studies show that transtympanic (TT) steroid injections are effective for treating ISSHL. As in vivo monitoring of drug delivery dynamics for inner ear is lacking, its time course and dispersion of drugs is unknown. Here, we used a new in vivo imaging system to monitor drug delivery in live mice and to compare drug concentrations over time after TT and systemic injections. Methods: Luciferin delivered into the inner ears of GFAP-Luc transgenic mice reacted with luciferase in GFAP-expressing cells in the cochlear spiral ganglion, resulting in photon bioluminescence. We used the Xenogen IVIS® imaging system to measure how long photons continued to be emitted in the inner ear after TT or systemic injections of luciferin, and then compared the associated drug dynamics. Results: The response to TT and IP injections differed significantly. Photons were detected five minutes after TT injection, peaking at ~20 minutes. By contrast, photons were first detected 30 minutes after i.p. injection. TT and i.p. drug delivery time differed considerably. With TT injections, photons were detected earlier than with IP injections. Photon bioluminescence also disappeared sooner. Delivery time varied with TT injections. Conclusions: We speculate that the drug might enter the Eustachian tube from the middle ear. We conclude that inner-ear drug concentration can be maintained longer if the two injection routes are combined. As the size of luciferin differs from that of therapeutics like dexamethasone, combining drugs with luciferin may advance our understanding of in vivo drug delivery dynamics in the inner ear.

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Transoral anterior approach using median mandibular splitting in upper spinal tumor extirpation

Hiromasa Kawana, Shin Kato, Seiji Asoda, Akihiko Koike, Ryotaro Iwasaki, Morio Matsumoto, Kota Watanebe, Yorihisa Imanishi, Kaoru Ogawa, Taneaki Nakagawa

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 114 （ 5 ） 2012年11月

ISSN 2212-4403

Objective: Transoral approach from the anterior direction is necessary if an upper spinal tumor is too big to extirpate via the posterior approach alone. To obtain a good anterior view of the surgical field, the mandible, tongue, and soft palate have to be split, and we developed a criterion to select the surgical strategy. Study Design: We indicated a decision-making process of splitting techniques and indications with actual cases and review of literatures. Result: Tumors were located from the level of C1 to the lower part of C3. Computerized tomography and magnetic resonance imaging were important to decide approaches. The orthopedic surgical team invited oral and maxillofacial surgeons team to assist in all transoral anterior approach cases. Conclusions: Vertical splitting of the mandible, incising the skin of the mental region, and splitting the middle of the tongue were combined according to the position of the spinal tumor.

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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

Acta Oto-Laryngologica 132 （ 11 ） 1168 - 1171 2012年11月

ISSN 0001-6489

Conclusion: Increase in the average value of bilateral neck muscle tension (ANT) indicates the increase in neck muscle tension to stabilize static posture resulting from vestibular compensation. Asymmetry of neck muscle tension was closely related to postural imbalance. Objective: Patients with dizziness often complain of neck symptoms with stiff neck. This study was conducted to clarify the pathophysiological mechanism of neck symptoms in patients with dizziness. Methods: We objectively measured bilateral trapezius muscle tension in patients with chronic dizziness and determined its relationship with static postural perturbation. The study included 26 patients with chronic dizziness caused by unilateral vestibular deficit and 24 healthy controls. The tension of bilateral trapezius muscles was objectively measured using a neck muscle tension meter. ANT and the ratio (right/left) of the bilateral neck muscle tension (RNT) were calculated. Static posturography was performed to measure total length of path (LNG). Results: ANT was negatively correlated to LNG under the eyes closed (EC) condition only in the case of the patients (r 0.44, p < 0.05). In the case of both the controls and the patients with a unilateral vestibular deficit, RNT was positively correlated to LNG under the EC condition.

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Neurally mediated syncope presenting with paroxysmal positional vertigo and tinnitus

Goto Fumiyuki, Tsutsumi Tomoko, Nakamura Iwao, Ogawa Kaoru

Auris Nasus Larynx 39 （ 5 ） 531 - 533 2012年10月

ISSN 0385-8146

A 72-year-old man with positional vertigo and tinnitus was referred to us. He did not want to perform provoking test except once due to his fear. No positional nystagmus was provoked. He found that his attacks usually occurred when he lay on his right ear. From his clinical history, benign paroxysmal positional vertigo was suspected. Conventional pharmacotherapy as well as non-specific physical therapy did not have significant effect. His feeling of positional vertigo with pyrosis was actually presyncope. We suspected cardiovascular disorders, and referred him to a cardiologist. Portable cardiogram monitoring revealed paroxysmal bradycardia. He was diagnosed with neurally mediated syncope, and a pacemaker was implanted. His paroxysmal dizziness soon disappeared. It is important to study the clinical history of the patients in detail, as they are not always able to accurately explain their symptoms. We should carefully rule out cardiovascular disorders, especially when we see the patients with suspected BPPV without the characteristic positional nystagmus.

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Correlations of inflammatory biomarkers with the onset and prognosis of idiopathic sudden sensorineural hearing loss

Masuda Masatsugu, Kanzaki Sho, Minami Shujiro, Kikuchi Jun, Kanzaki Jin, Sato Hiroaki, Ogawa Kaoru

Otology and Neurotology 33 （ 7 ） 1142 - 1150 2012年09月

ISSN 1531-7129

HYPOTHESIS: We investigated whether inflammatory biomarkers and stress are involved in the pathophysiology of idiopathic sensorineural hearing loss (ISHL). STUDY DESIGN: Individual cohort study. SETTING: Two tertiary centers. PATIENTS: Forty-three ISHL and 10 non-ISHL patients seen in our ENT departments from 2004 to 2010 within a week from the onset of new symptoms and without steroid administration before visiting our departments. INTERVENTION: Multiple audiologic evaluations, blood tests including leukocyte counts, natural killer cell activity (NKCA), interleukin 6 (IL-6), tumor necrosis factor, high-sensitivity CRP (hCRP), and the General Health Questionnaire were used to evaluate the systemic stress and inflammatory response. MAIN OUTCOME MEASURES: Correlations between biomarkers and ISHL severity and prognosis were evaluated by statistical analysis. RESULTS: In the ISHL patients, a neutrophil count above the reference range was associated with severe hearing loss and poor prognosis, and was accompanied by low NKCA and high IL-6. In the non-ISHL patients, these associations were not present. The abnormal neutrophil count was independent of preexisting vascular diseases. The abnormal counts responded to treatment and decreased into the reference range. CONCLUSION: Neutrophil counts above the reference range of a facility will be a useful indicator of poor prognosis of ISHL. Synchronism of different types of NF-κB activation pathways could be required to cause severe ISHL. An NKCA decrease, an acute neutrophil count increase, and an IL-6 increase can induce NF-κB activation in the cochlea and cause severe ISHL. Further epidemiologic surveys should be conducted to evaluate whether stressful life events increase the risk of severe ISHL onset.

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Application of the endoscopic transsphenoidal approach to true type transsellar transsphenoidal meningoencephalocele in an adult

Saito Katsuya, Toda Masahiro, Sano Keisho, Tomita Toshiki, Ogawa Kaoru, Yoshida Kazunari

Acta Neurochirurgica 154 （ 8 ） 1511 - 1515 2012年08月

ISSN 0001-6268

Of the transsellar transsphenoidalmeningoencephaloceles (TTSMEs), the true type presents with the hernial sac extending from the intracranium to the epipharynx through the sellar floor. The true type is the most serious and difficult to manage, especially when the hernial sac contains vital structures, such as the anterior cerebral artery, pituitary gland, optic nerve, hypothalamus, and third ventricle. Surgical outcome for true type TTSME is reported to be poor. We describe a successful case of endoscopic repair for a 36-year-old man with true type TTSME. Our success with endoscopic repair for true type TTSME in an adult is the first reported case. We believe that the endoscopic transsphenoidal approach allows less invasive surgery and provides an acceptable operative outcome in comparison with other microsurgical approaches.

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Lateral semicircular canal plugging with endolymphatic sac decompression as new surgical treatment for intractable Meniere's disease

Goto Fumiyyuki, Tsutsumi Tomoko, Ogawa Kaoru

Acta Oto-Laryngologica 132 （ 8 ） 893 - 895 2012年08月

ISSN 0001-6489

Conclusion: Lateral canal plugging with endolymphatic sac decompression (LCPESD) is a new therapeutic approach to intractable Meniere's disease. Further clinical data will be required. Objective: The objective of this paper is to present a new surgical procedure, i.e. lateral canal plugging (LCP) with endolymphatic sac decompression (ESD), which we defined as LCPESD. Two cases of intractable Meniere's disease, a 48-year-old male and a 48-year-old female, were successfully treated by this method. Methods: LCPESD was performed under general anesthesia. First ESD was undertaken followed by LCP. The bone was drilled up to the 'blue line' in the central portion of the bony lateral canal; then a 2 mm segment of canal was skeletonized to create a fenestra. A plug comprising temporalis fascia, bone pate, and fibrinogen glue was inserted through the fenestra to compress the endosteum and membranous labyrinth. Results: The attack of Meniere's disease was completely controlled and the hearing threshold did not change after the surgery for 2 years. Obliteration of the horizontal canal was confirmed by MRI.

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Statistical analysis of 32 patients with nasopharyngeal Carcinoma

Fujii Ryoichi, Imanishi Yorihisa, Tomita Toshiki, Sakamoto Koji, Shigetomi Seiji, Habu Noboru, Ootsuka Kuninori, Sato Yoichiro, Ozawa Hiroyuki, Yamashita Taku, Fujii Masato, Shigematsu Naoyuki, Ogawa Kaoru

Journal of Otolaryngology of Japan 115 （ 8 ） 773 - 782 2012年08月

ISSN 0030-6622

In order to assess the clinical outcome and prognostic factors of patients with nasopharyngeal carcinoma (NPC) who were initially treated in the Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine between 1997 and 2006, statistical analyses were performed based on the patient medical records. Cause-specific survival (CSS) and disease-free survival (DFS) in all cases (stage I to IV, n = 32) and advanced cases (stage III and IV, n = 22) were estimated using the Kaplan-Meier method. The independent prognostic values of the clinical and therapeutic factors were determined using multivariate Cox proportional hazards models. Results: The 5-year CSS/DFS were 43.4%/34.8% in all cases and 34.596/29.8% in advanced cases. Multivariate analysis revealed that, in all cases, the independent prognostic factors for CSS were age ≥ 61 vs. ≤60, risk ratio (RR) =5.717, p = 0.006), T-stage (3/4 vs. 1/2, RR = 6.957, p = 0.004), and the use of platinum agents (unused vs. used, RR = 3.911, p = 0.012), whereas those for DFS were T-stage (3/4 vs. 1/2, RR=3.499, p = 0.019) and the use of platinum agents (unused vs. used, RR=2.947, p = 0.028). In advanced cases, the use of platinum agents alone was significant for both CSS (RR = 4.503, p = 0.023)and DFS (RR=4.218, p = 0.014). The patients who received neoadjuvant chemotherapy (NAC) showed better CSS and DFS than the patients who did not (p = 0.066 and p = 0.025, respectively) in a univariate analysis (Log-rank test), although no significant difference was seen between these groups in the multivariate analysis. Conclusion: The advantage of the administration of platinum agents in the treatment of NPC was statistically corroborated even in our study with its small sample size. As agents combined with chemoradiotherapy, the efficacy of do-cetaxel alone did not seem comparable to that of platinum agents. The docetaxel-CDDP-5-FU regimen applied as NAC was suggested to be possibly beneficial for advanced cases of NPC.

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Outcomes of autogenic training for patients with chronic subjective dizziness

Goto F., Tsutsumi T., Kabeya M., Ogawa K.

Journal of Psychosomatic Research 72 （ 5 ） 410 - 411 2012年05月

ISSN 0022-3999

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Surgical results of an endoscopic endonasal approach for clival chordomas

Saito Katsuya, Toda Masahiro, Tomita Toshiki, Ogawa Kaoru, Yoshida Kazunari

Acta Neurochirurgica 154 （ 5 ） 879 - 886 2012年05月

ISSN 0001-6268

Background The surgical approaches for clival chordomas remain controversial, although the extent of resection is one of the most important factors for long survival rates. Recently an endoscopic endonasal approach in good collaboration with otolaryngologists has attracted major attention as a surgical approach for clival chordomas. We describe our experience with the endoscopic endonasal approach and provide a review of the literature. Methods Between 2008 and 2011, six operations were performed via the endoscopic endonasal approach for clivus chordomas. The mean tumor size was 35 mm in diameter. The tumor location was mainly from the upper to middle clivus. The tumor extended into the cavernous sinus in five cases and intradurally in three cases. A binostril approach was performed in four cases, while a one nostril approach was performed in two cases. Results Gross total removal was achieved in three cases. The analysis of cases with incomplete resection suggested that residual tumors were observed epidurally and subdurally. The residual on the epidura was observed from the posterior clinoid to the posterior compartment of the cavernous sinus. On the other hand, the residual on the subdural was observed behind the upper part of the pituitary gland. There was no postoperative cerebrospinal fluid (CSF) leakage using vascularized nasoseptal flaps in any of the cases. Conclusions The endoscopic endonasal transclival approach allows an appropriate extent of resection with acceptable complication rates in comparison with other approaches. In our series, the accomplishment of gross total removal was associated with the relationship between the tumors and surrounding structures, such as the pituitary gland and the cavernous portion of the intracranial carotid artery (ICA).

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A new device for delivering drugs into the inner ear

Kanzaki Sho, Saito Hideyuki, Inoue Yasuhiro, Ogawa Kaoru

Auris Nasus Larynx 39 （ 2 ） 208 - 211 2012年04月

ISSN 0385-8146

Objectives: Intratympanic injection (ITI) of drugs into the inner ear is an attractive way to deliver therapy. However, if the round window membrane (RWM) cannot be visualized, adhesions need to be removed first before ITI can be performed. We developed and tested a novel otoendoscopy device that allows visualization of the RWM for the purpose of ITI. Methods: Our otoendoscope consists of a catheter channel for delivering drugs and a suction channel. Results: The novel otoendoscope for inner ear drug delivery has a fine needle with catheter, which can be used to remove or perforate round window niche (RWN) mucosal adhesions. The elliptical shape of the otoendoscope effectively captures the field in the light-guided area, resulting in bright images. Conclusions: Our otoendoscope can be used to apply drugs directly onto the surface of the RWM and to verify the correct placement of an inner ear drug delivery system, ensuring that it is safely in place.

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Various levels of plasma brain-derived neurotrophic factor in patients with tinnitus

Goto Fumiyuki, Saruta Juri, Kanzaki Sho, To Masahiro, Tsutsumi Tomoko, Tsukinoki Keiichi, Ogawa Kaoru

Neuroscience Letters 510 （ 2 ） 73 - 77 2012年02月

ISSN 0304-3940

Objective: Thus far, no objective measure has been developed to evaluate tinnitus severity. There is a close relationship between tinnitus and depression, in which brain-derived neurotrophic factor (BDNF) has a pathophysiological role. To determine whether BDNF levels could be used to evaluate tinnitus severity, we evaluated plasma BDNF levels in patients with tinnitus. Methods: Plasma BDNF levels were measured in 43 tinnitus patients and 30 healthy control patients. The severities of tinnitus, depression, and anxiety were measured using the tinnitus handicap inventory (THI) and the hospital anxiety and depression scale (HADS), respectively. Patients with tinnitus were divided into 2 groups depending on their THI scores: mildly handicapped (<36) and severely handicapped (>38). We also divided our subjects into 2 groups depending on the HADS score, which represents patient mood, including depression and anxiety. Results: Plasma BDNF levels were significantly higher in the mildly handicapped group than in the severely handicapped and control groups (P< 0.01). Patients with HADS scores of ≤14 had significantly lower THI scores (P< 0.05) and higher BDNF levels (P< 0.01). Conclusions: Our findings show for the first time that plasma BDNF levels vary with the severity of tinnitus, suggesting that plasma BDNF level is a useful tool for objective evaluation of tinnitus.

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Overexpression of SIP1 and downregulation of e-cadherin predict delayed neck metastasis in stage I/II oral tongue squamous cell carcinoma after partial glossectomy

Sakamoto Koji, Imanishi Yorihisa, Tomita Toshiki, Shimoda Masayuki, Kameyama Kaori, Shibata Katsushi, Sakai Nobuya, Ozawa Hiroyuki, Shigetomi Seiji, Fujii Ryoichi, Fujii Masato, Ogawa Kaoru

Annals of Surgical Oncology 19 （ 2 ） 612 - 619 2012年02月

ISSN 1068-9265

Background: Patients with clinical stage I/II (T1-2N0M0) oral tongue squamous cell carcinoma (TSCC) usually undergo partial glossectomy alone. However, 14-48% of them develop delayed neck metastasis (DNM), which may lead to an unfavorable course. Recently epithelial-to-mesenchymal transition (EMT) has been thought to play a crucial role in cancer metastasis. The present study aimed to examine the associations of EMT-involved molecular factors and clinicopathological factors with DNM in stage I/II TSCC. Methods: mRNA expression levels of E-cadherin and its transcriptional repressors (snail, SIP1, and twist) in 7 head and neck squamous cell carcinoma (HNSCC) cell lines were evaluated by quantitative real-time PCR. Clinicopathological parameters and immunohistochemical expressions of E-cadherin and its repressors were examined in surgical specimens of 37 stage I/II TSCC patients who underwent partial glossectomy alone. Results: In HNSCC cells, E-cadherin expression was inversely correlated with SIP1 expression (P = 0.023). Univariate analysis of immunohistochemistry showed that overexpression of SIP1 and loss of E-cadherin were significantly correlated with DNM, although no inverse correlation was found between E-cadherin and its repressors. Multiple logistic regression analysis including clinicopathological and molecular factors revealed that overexpression of SIP1 (P = 0.005), loss of E-cadherin (P = 0.046), and vascular invasion (P = 0.024) were independently correlated with DNM. Conclusions: These results suggest that development of DNM in stage I/II TSCC is closely related to induction of EMT in primary tumor cells. Especially, SIP1 and E-cadherin are considered to be the possible markers for selecting patients at high risk of DNM.

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Effects of a perilymphatic fistula on the passive vibration response of the basilar membrane

Koike Takuji, Sakamoto Chiaki, Sakashita Tasuku, Hayashi Ken, Kanzaki Sho, Ogawa Kaoru

Hearing Research 283 （ 1-2 ） 117 - 125 2012年01月

ISSN 0378-5955

In this study, a three-dimensional finite-element model of the passive human cochlea was created. Dynamic behavior of the basilar membrane caused by the vibration of the stapes footplate was analyzed considering a fluid-structure interaction with the cochlear fluid. Next, the effects of a perilymphatic fistula (PLF) on the vibration of the cochlea were examined by making a small hole on the wall of the cochlea model. Even if a PLF existed in the scala vestibuli, a traveling wave was generated on the basilar membrane. When a PLF existed at the basal end of the cochlea, the shape of the traveling wave envelope showed no remarkable change, but the maximum amplitude became smaller at the entire frequency range from 0.5 to 5. kHz and decreased with decreasing frequency. In contrast, when a PLF existed at the second turn of the cochlea, the traveling wave envelope showed a notch at the position of the PLF and the maximum amplitude also became smaller. This model assists in elucidating the mechanisms of hearing loss due to a PLF from the view of dynamics.

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[Application of antidepressant to treat patients in the department of otolaryngology].

Goto Fumiyuki, Tsutsumi Tomoko, Ogawa Kaoru

Nihon rinsho. Japanese journal of clinical medicine 70 （ 1 ） 115 - 121 2012年01月

ISSN 0047-1852

There are some patients complaining of somatic symptom who has depression. The use of antidepressant to these patients would be quite useful. Patients with dispersion have a variety sort of physical symptom. The evaluation of depression based on physical complaints may be difficult for otorhinolaryngologists, but it is important to do so where possible to increase the focus on the subject's physical illness. The prevalence of somatic complaints in hospitalized patients whose chief complaint was either dizziness or vertigo was very high. These patients were usually accompanied with depression. Then the effect of paroxetine to the patients with tinnitus was investigated. The paroxetine may be effective in treating distressed tinnitus patients with depression and anxiety by reducing their tinnitus severity as well as their depression and anxiety.

Comparative study between pre-seasonal and intra-seasonal treatment of allergic rhinitis using a new 808nm diode laser system

Sasaki Katsumi, Ohshiro Toshio, Ohshiro Takafumi, Kanzaki Sho, Ogawa Kaoru

Laser Therapy 21 （ 3 ） 209 - 214 2012年

ISSN 0898-5901

Background and Aims: Allergic rhinitis annually reaches epidemic proportions in Japan, and represents a major problem. The application of the CO2 laser in the treatment of allergic rhinitis was first successfully reported in 1982, but CO2 laser ablation is associated with side effects. The Ohshiro Clinic started using the conventional Nd: YAG laser for the treatment of allergic rhinitis in 1993, and from 2005 we started using a diode laser-pumped Nd: YAG laser with efficacy and safety at least equal to the others. Even more recently, we have adopted a novel 808 nm diode laser, and the present retrospective study examined the difference in of the efficacy rate between the preseasonal and intra-seasonal treatment of allergic rhinitis with this system. Subjects and methods: One thousand, two hundred and ten patients primarily presented to the Ohshiro Clinic with allergic rhinitis during the period from December 2010 to April 2011, of whom 531 were selected for blood tests to identify 13 kinds of Japanese allergens including cedar pollen. In the 2010-2011 season, huge clouds of cedar pollen appeared from February 26 ^th. The subjects were therefore divided into two groups depending on the treatment period, namely the preseasonal and intra-seasonal groups, December 1 ^st, 2010 to February 25 ^th, 2011 and February 26 ^th to April 6 ^th 2011, respectively. All patients were treated with the new 808 nm diode laser system. Results: A high success rate was achieved in both groups, with no significant difference seen regarding the symptoms of rhinorrhea, obstruction, sneezing, quality of life (QOL) or severity. Conclusions: The 808 nm diode laser offers an excellent solution for the uncomfortable symptoms of allergic rhinitis, and could be equally well applied before or during the Japanese cedar pollen dispersed season.

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Efficacy of a vibrotactile neurofeedback training in stance and gait conditions for the treatment of balance deficits

Basta Dietmar, Rossi-Izquierdo Marcos, Soto-Varela Andrés, Greters Mario Edwin, Bittar Roseli Saraiva, Steinhagen-Thiessen Elisabeth, Eckardt Rahel, Harada Tatsuhiko, Goto Fumiyuki, Ogawa Kaoru, Ernst Arne

Otology and Neurotology 32 （ 9 ） 1492 - 1499 2011年12月

ISSN 1531-7129

Objective: Vestibular rehabilitation strategies mostly require a long-lasting training in stance conditions, which is finally not always successful. The individualized training in everyday-life conditions with an intuitive tactile neurofeedback stimulus seems to be a more promising approach. Hence, the present study was aimed at investigating the efficacy of a new vibrotactile neurofeedback system for vestibular rehabilitation. Study Design: Double-blinded trial. Patients: One hundred five patients who experience one of the following balance disorders for more than 12 months were included in the study: canal paresis, otolith disorder, removal of an acoustic neuroma, microvascular compression syndrome, Parkinson's disease, and presbyvertigo. Interventions: Vibrotactile neurofeedback training was performed daily (15 min) over 2 weeks with the Vertiguard system in those 6 tasks of the Standard Balance Deficit Test with the most prominent deviations from the normative values. Main Outcome Measures Trunk and ankle sway, dizziness handicap inventory, and vestibular symptom score were measured in the verum and placebo group before the training, on the last training day and 3 months later. Results: A significant reduction in trunk and ankle sway as well as in the subjective symptom scores were observed in the verum group. Such an effect could not be found in any of the outcome parameters of the placebo group. Conclusion: The vibrotactile neurofeedback training applied in the present study is a highly efficient method for the reduction of body sway in different balance disorders. Because the rehabilitation program is easy to perform, not exhausting, and time saving, elderly patients and those with serious, long-lasting balance problems also can participate successfully.

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Thyroglobulin concentration measurement in fine-needle aspiration fluid from cystic cervical lymph node metastases of papillary thyroid carcinoma

Inagaki Yozo, Sakamoto Koji, Inoue Yasuhiro, Imanishi Yorihisa, Tomita Toshiki, Shinden Seiichi, Ozawa Hiroyuki, Fujii Ryoichi, Shigetomi Seiji, Watabe Takahisa, Yamada Hiroyuki, Ogawa Kaoru

Journal of Otolaryngology of Japan 114 （ 12 ） 912 - 916 2011年12月

ISSN 0030-6622

Background: Combining ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI) and fine-needle aspiration cytology (FNAC) usually results in the best preoperative diagnosis of cervical masses, including neoplasms. This may not be tnie, however, especially in occult papillary thyroid carcinoma (PTC) associated with single cystic cervical lymph node metastasis. We assessed the role of thyroglobulin measurement in FNA fluid (FNATg) in differentially diagnosing cystic cervical mass lesions, including PTC cystic lymph node metastasis. Methods: We reviewed the records of 17 subjects with cervical cystic masses undergoing both FNATg measure ment and surgery. FNA was done under ultrasonographic guidance. We also measured FNATg concentrations from extrathyroid lesions, consisting of cystic cervical lymph node metastases and benign cystic lesions. Results: Pathological diagnosis involved 5 PTC lymph node metastases, 3 lateral cervical cysts, 7 thyroglossal duct cysts, and 2 squamous cell carcinoma (lung and oropharynx) lymph node metastases. FNATg of PTC lymph node metastasis was much higher than the reference range of blood serum thyroglobulin, although much lower for the lateral cervical cyst detection threshold. FNAC and FNATg measurement are thought to be mutually complementary in the differential-diagnosis of PTC cystic lymph node metastasis. Conclusion : High concentrations of FNATg in a cystic cervical mass is considered specific to PTC lymph node metastasis, indicating its usefulness in distinguish PTC cystic metastasis from other cystic lesions. Including FNATg measurement with FNAC may thus improve preoperative diagnosis accuracy without additionally stressing subjects with PTC cystic lymph node metastasis.

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Late-phase recovery in the cochlear lateral wall following severe degeneration by acute energy failure

Mizutari Kunio, Nakagawa Susumu, Mutai Hideki, Fujii Masato, Ogawa Kaoru, Matsunaga Tatsuo

Brain Research 1419 1 - 11 2011年10月

ISSN 0006-8993

We previously reported a model of acute cochlear energy failure using a mitochondrial toxin, 3-nitropropionic acid (3-NP), to study mechanisms of inner ear disorders such as inner ear ischemia. In this model, the main cause of hearing loss is apoptosis of fibrocytes in the cochlear lateral wall. Here, we analyzed the time course of structural and hearing level changes in the cochlea from the acute phase to the chronic phase up to 2 months after surgery. Hearing levels as determined by auditory brainstem response (ABR) thresholds exceeded the maximum acoustic output (> 87 dBSPL) of the system at all frequencies 1 day after 3-NP treatment. Histology showed nearly complete loss of fibrocytes 2 weeks after 3-NP treatment. However, after 2 months, ABR showed significant recovery at low frequency (8 kHz) in four of five rats treated with 3-NP. ABR thresholds at 20 kHz occasionally showed some recovery. At 40 kHz, recovery of ABR thresholds was not observed. Histology of 3-NP-treated rats revealed partial recovery of the lateral wall and the regenerated fibrocytes in the spiral ligament expressed Na/K-ATPase in the cochlear basal turn 2 months after 3-NP treatment. These results indicate that ABR recovery is caused by regeneration of the cochlear lateral wall. Our findings demonstrate the recoverable capacity of the cochlear lateral wall that leads to functional recovery after severe damage.

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Effectiveness of home-based vestibular rehabilitation in chronic dizziness

Goto Fumiyuki, Tsutsumi Tomoko, Arai Motohiro, Ogawa Kaoru

Practica Oto-Rhino-Laryngologica 104 （ 10 ） 681 - 687 2011年10月

ISSN 0032-6313

Therapeutic options for vertigo may be pharmacological or non pharmacological. Intractable dizziness may require conventional drug therapy or vestibular exercises. We set up a single-group outpatient vestibular exercise course and evaluated its benefit. Subjects numbered 18 having chronic vertigo whose etiology included unilateral canal paresis following vestibular neuritis. Time from disease onset to the introduction of vestibular exercise was from 6 to 70 months (average ±std: 22.1±21.1). Small-groups home-based vestibular exercise consisted of a 2-hour lecture and practice in which subjects were taught exercises to be done 4 times a day at home. Symptoms of vertigo were obtained using Japanese version of the dizziness handicap inventory (DHI) and static posturography at the initial visit and before, 2 months, and 4 months after rehabilitation. The DHI score at the initial visit was 38. 6 ±26. 0 compared to 12. 3 ±10. 2 4 months after rehabilitation. The static posturography area did not change before or after therapy. We recommend that future studies objectively assess how the DHI score could be improved.

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Application of autogenic training in patients with Ménière disease

Goto Fumiyuki, Nakai Kimiko, Ogawa Kaoru

European Archives of Oto-Rhino-Laryngology 268 （ 10 ） 1431 - 1435 2011年10月

ISSN 0937-4477

Data are limited on the role of psychotherapy in the treatment of Ménière disease. We sought to document the effect of a psychotherapeutic technique known as autogenic training on clinical outcome in Ménière disease. Six patients with Ménière disease were studied. Retrospective chart review was conducted. All patients were refractory to conventional therapy and completed a course of autogenic training, which was offered as a complementary treatment. Autogenic training with initial psychological counseling was conducted by a clinical psychologist during 45-min sessions. Outcome measures assessed were the frequency of vertigo and functional levels 2 years after initiation of autogenic training. Functional levels were evaluated according to the 1995 guidelines of the American Academy of Otolaryngology-Head Neck Surgery (AAO-HNS). As a personality measure, we used the Maudsley Personality Inventory (MPI), devised by Eysenck, which measures neuroticism (N), extraversion (E), and propensity to lie (L). Five of six patients showed improved functional level after three to eight sessions of psychotherapy; hearing level did not change. The score of the N scale of the MPI was closely related to the number of psychotherapy sessions. Prognosis was evaluated based on the AAO-HNS reporting guidelines, as follows: A = 3, B = 1, C = 1, F = 1. The value of N in MPI was closely related to the number of psychological counseling sessions (R = 0.97, P < 0.05). In conclusion, autogenic training may enhance the mental well-being of patients with Ménière disease and improve clinical outcome.

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Thirteen-month-old boy with malignant lymphoma having symptoms mimicking acute otitis media and mastoiditis with facial palsy

Kanzaki Sho, Saito Hideyuki, Mori Tetsuya, Shimasaki Noriko, Mukai Makio, Ogawa Kaoru

ORL 73 （ 5 ） 266 - 270 2011年09月

ISSN 0301-1569

Non-Hodgkin diffuse large B-cell lymphomas of the mastoid that extend from the nasopharynx are extremely rare in children. Moreover, in lymphoproliferative diseases, the presence of otoneurological signs prior to systemic disease involvement is rare. Here, we present a rare case of non-Hodgkin B-cell lymphoma invading the middle ear and mastoid in a 1-year-old boy that mimicked acute mastoiditis with complete facial nerve palsy. As this case illustrates, physicians should consider a diagnosis of malignant lymphoma if a patient presents with otitis media and mastoiditis accompanied by facial palsy.

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The Japanese version of the dizziness handicap inventory as an index of treatment success

Goto Fumiyuki, Tsutsumi Tomoko, Ogawa Kaoru

Acta Oto-Laryngologica 131 （ 8 ） 817 - 825 2011年08月

ISSN 0001-6489

Conclusion: The Japanese version of the Dizziness Handicap Inventory (DHI) is a reliable, comprehensively validated, and clinically useful tool to measure self-perceived handicap associated with dizziness. Objectives: The DHI is a useful instrument to document the consequences of vestibular and/or balance impairment. A Japanese version of this self-assessment inventory is needed to evaluate the handicapping effects imposed by vestibular system disease in Japanese patients. The purpose of this study was to determine the internal consistency of the reliability of the Japanese version of the DHI. Methods: We recruited 176 patients between January and September 2008 from the outpatients of the Department of Otolaryngology, Hino Municipal Hospital, Japan. The DHI was translated into Japanese, and the test was independently completed by each subject. We used principal component analysis to evaluate the different dimensions of the DHI. The internal consistency of the retained factors was investigated by estimating Cronbach's alpha coefficients and corrected item-total correlations. Results: Cronbach's coefficients for internal consistency were high for the total scale (0.93) and good for the subscales: functional subscale (0.87), physical subscale (0.82), and emotional subscale (0.85). The correlation matrix demonstrated that the variables were suited for factor analysis. The determinant was 1.26E ⁶, which is slightly under the recommended value. Bartlett's test was highly significant (p < 0.0001), and the KaiserMeyerOlkin measure of sampling adequacy was 0.91.

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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年07月

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.

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Acoustic overstimulation-induced apoptosis in fibrocytes of the cochlear spiral limbus of mice

Cui Yong, Sun Guang Wei, Yamashita Daisuke, Kanzaki Sho, Matsunaga Tatsuo, Fujii Masato, Kaga Kimitaka, Ogawa Kaoru

European Archives of Oto-Rhino-Laryngology 268 （ 7 ） 973 - 978 2011年07月

ISSN 0937-4477

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.

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Expression and function of Sox21 during mouse cochlea development

Hosoya Makoto, Fujioka Masato, Matsuda Satoru, Ohba Hiroyuki, Shibata Shinsuke, Nakagawa Fumiko, Watabe Takahisa, Wakabayashi Ken Ichiro, Saga Yumiko, Ogawa Kaoru, Okano Hirotaka James, Okano Hideyuki

Neurochemical Research 36 （ 7 ） 1261 - 1269 2011年07月

ISSN 0364-3190

The development of the inner ear is an orchestrated process of morphogenesis with spatiotemporally controlled generations of individual cell types. Recent studies have revealed that the Sox gene family, a family of evolutionarily conserved HMG-type transcriptional factors, is differentially expressed in each cell type of the mammalian inner ear and plays critical roles in cell-fate determination during development. In this study, we examined the expression pattern of Sox21 in the developing and adult murine cochlea. Sox21 was expressed throughout the sensory epithelium in the early otocyst stage but became restricted to supporting cells during adulthood. Interestingly, the expression in adults was restricted to the inner phalangeal, inner border, and Deiters' cells: all of these cells are in direct contact with hair cells. Evaluations of the auditory brainstem-response revealed that Sox21^-/- mice suffered mild hearing impairments, with an increase in hair cells that miss their appropriate planar cell polarity. Taken together with the previously reported critical roles of SoxB1 families in the morphogenesis of inner ear sensory and neuronal cells, our results suggest that Sox21, a counteracting partner of the SoxB1 family, controls fine-tuned cell fate decisions. Also, the characteristic expression pattern may be useful for labelling a particular subset of supporting cells.

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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年06月

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).

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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年06月

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.

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Quality of life of Japanese seasonal allergic rhinitis patients is related to timing of pollen dispersal - Multicenter analysis

Kanzaki Sho, Ogawa Hiroshi, Ikeda Michiko, Masuda Takamasa, Ogawa Kaoru

Acta Oto-Laryngologica 131 （ 3 ） 290 - 297 2011年03月

ISSN 0001-6489

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.

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Impaired vibration of auditory ossicles in osteopetrotic mice

Kanzaki Sho, Takada Yasunari, Niida Shumpei, Takeda Yoshihiro, Udagawa Nobuyuki, Ogawa Kaoru, Nango Nobuhito, Momose Atsushi, Matsuo Koichi

American Journal of Pathology 178 （ 3 ） 1270 - 1278 2011年03月

ISSN 0002-9440

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.

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Learning sinus anatomy using 3D paper models

Araki Yasutomo, Kunihiro Takanobu, Saito Hideyuki, Ogawa Kaoru, Uno Kousuke, Yoshida Satoko, Satou Yasuo

Practica Oto-Rhino-Laryngologica 104 （ 3 ） 229 - 234 2011年03月

ISSN 0032-6313

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.

Editorial

Ogawa Kaoru

Auris Nasus Larynx 38 （ 1 ） 1 2011年02月

ISSN 0385-8146

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Clinical review and statistical analysis of tongue squamous cell carcinoma

Sakamoto Koji, Imanishi Yorihisa, Tomita Toshiki, Ozawa Hiroyuki, Tagawa Takamasa, Fujii Ryoichi, Shigetomi Seiji, Habu Noboru, Ootsuka Kuninori, Yamashita Taku, Kanke Minoru, Fujii Masato, Ogawa Kaoru

Japanese Journal of Head and Neck Cancer 37 （ 4 ） 529 - 535 2011年

ISSN 1349-5747

We reviewed 86 patients with oral tongue squamous cell carcinoma who were initially treated with curative intent in the Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine between 1996 and 2007. Statistical analysis was performed to examine the prognostic value of the clinical features. Eighty patients underwent surgery and six underwent radiotherapy as the initial treatment. The five-year disease-free survival (DFS) rates determined by the Kaplan-Meier method were as follows: 75.8% in all stages, 88.7% in stage I (n = 30), 82.6% in stage II (n = 24), 77.1% in stage III (n = 14), and 39.7% in stage IV (n = 18). Univariate analysis demonstrated that stage III/IV, T 3/4, and N2 were significantly correlated with poor prognosis, whereas multivariate analysis showed that only N2 was independently correlated with poor prognosis. Neoadjuvant chemotherapy (NAC) was applied for 24 patients. Although the DFS of the responders (CR+PR) was higher than that of the non-responders (NC+PD), the difference was not significant. Among 80 patients who received surgical treatment initially, neck dissection (ND) was performed in 42 patients. Five-year DFS was significantly higher in the patients with no or single node metastasis than in the patients with multiple node metastases (93.8% vs. 32.7%). These outcomes suggest that more aggressive postoperative therapy should be recommended for patients found to have pathologically multiple positive nodes.

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Unusual computed tomography findings of radionecrosis after chemoradiation of stage IV hypopharyngeal cancer

Baba Yuh, Kato Yasumasa, Ogawa Kaoru

Journal of Medical Case Reports 5 2011年

ISSN 1752-1947

Abstract. Introduction. Radionecrosis (post-radiotherapy laryngeal submucosal inflammation and necrosis) is a complication of (chemo) radiotherapy for hypopharyngeal cancer that is difficult to differentiate from tumor recurrence. Case presentation. A 67-year-old Japanese man presented with a condition extremely difficult to diagnose differentially as radionecrosis or tumor recurrence after radiotherapy for hypopharyngeal cancer. Although tumor recurrence was suspected from clinical conditions and computed tomography findings, pathologic analysis revealed no evidence of tumor recurrence, and successful therapy with steroids and antibiotics reduced the mucosal edema. Conclusion: Our findings emphasize the wide spectrum of radiographic presentation of radionecrosis after chemoradiation of stage IV hypopharyngeal cancer.

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Investigation of the reliability and validity of the vertigo handicap questionnaire (VHQ) translated into Japanese

Goto Fumiyuki, Arai Motohiro, Tsutumi Tomoko, Masuda Kanako, Ogawa Kaoru

Equilibrium Research 69 （ 6 ） 412 - 417 2010年12月

ISSN 0385-5716

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.

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Sho-saiko-to-ka-kikyo-sekko as an alternative treatment for chronic tonsillitis to avoid surgery

Goto Fumiyki, Asama Youji, Ogawa Kaoru

Complementary Therapies in Clinical Practice 16 （ 4 ） 216 - 218 2010年11月

ISSN 1744-3881

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.

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Surgical outcome in headache due to mucosal contact

Goto Fumiyuki, Yabe Haruna, Ogawa Kaoru

Practica Oto-Rhino-Laryngologica 103 （ 10 ） 915 - 920 2010年10月

ISSN 0032-6313

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.

Somatic symptoms in those hospitalized for dizziness or vertigo

Goto Fumiyuki, Tsutumi Tomoko, Arai Motohiro, Ogawa Kaoru

Journal of Otolaryngology of Japan 113 （ 9 ） 742 - 750 2010年09月

ISSN 0030-6622

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.

Physical and physiological effects on otoacoustic emissions in hypobaric hypoxia

Ide Rika, Harada Tatsuhiko, Kanzaki Sho, Saito Hideyuki, Hoshikawa Masako, Kawahara Takashi, Ogawa Kaoru

ORL 72 （ 4 ） 225 - 232 2010年08月

ISSN 0301-1569

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.

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Autonomic dysfunction in dizzy patients revealed by pulse analysis

Goto Fumiyuki, Mizutari Kunio, Kunihiro Takanobu, Ogawa Kaoru

Equilibrium Research 69 （ 4 ） 207 - 212 2010年08月

ISSN 0385-5716

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.

Vestibular dysfunction in a Japanese patient with a mutation in the gene OPA1

Mizutari Kunio, Matsunaga Tatsuo, Inoue Yasuhiro, Kaneko Hiroki, Yagi Hirotaka, Namba Kazunori, Shimizu Satoko, Kaga Kimitaka, Ogawa Kaoru

Journal of the Neurological Sciences 293 （ 1-2 ） 23 - 28 2010年06月

ISSN 0022-510X

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.

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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年06月

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.

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Objective evaluation of the therapeutic responses of patients with psychological dizziness by means of static posturography

Goto Fumiyuki, Hayashi Ken, Tsutsumi Tomoko, Ogawa Kaoru

Equilibrium Research 69 （ 3 ） 141 - 146 2010年06月

ISSN 0385-5716

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.

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Balance dysfunction resulting from acute inner ear energy failure is caused primarily by vestibular hair cell damage

Mizutari Kunio, Fujioka Masato, Nakagawa Susumu, Fujii Masato, Ogawa Kaoru, Matsunaga Tatsuo

Journal of Neuroscience Research 88 （ 6 ） 1262 - 1272 2010年05月

ISSN 0360-4012

Inner ear energy failure is associated with disorders such as inner ear ischemia. Recently, we used the mitochondrial toxin 3-nitropropionic acid (3-NP) to establish an animal model of inner ear energy failure that presents with auditory dysfunction. Here we investigated the mechanisms underlying balance disorders in the 3-NP animal model. Spontaneous nystagmus peaked 6 hr after treatment with either 300 mM or 500 mM 3-NP. The nystagmus attenuated gradually and disappeared 3 days after 3-NP treatment. A caloric test using ice water was performed to evaluate residual vestibular function 7 days after 3-NP treatment. The response to caloric stimulation was reduced to ∼40% of the response of the untreated ear following 300 mM 3-NP and was undetectable following 500 mM 3-NP. Structural changes in the peripheral vestibular organs were analyzed by light and electron microscopy. Severe loss of stereocilia was observed following 500 mM 3-NP, whereas disorganized and mildly reduced stereocilia were observed following 300 mM 3-NP. There was severe loss and degeneration of vestibular hair cells following 500 mM 3-NP but only slight loss and degeneration of hair cells following 300 mM 3-NP. These results indicate that acute inner ear energy failure causes balance dysfunction mainly by damaging hair cells in the vestibule, which is distinct from the mechanism underlying auditory disorders.

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Traditional Chinese medicine for treatment of laryngeal papillomatosis

Okubo Keisuke, Saito Koichiro, Fukuda Hiroyuki, Watanabe Kenji, Ogawa Kaoru, Shiotani Akihiro

Journal of Alternative and Complementary Medicine 16 （ 4 ） 427 - 433 2010年04月

ISSN 1075-5535

Objective: The objective of this study was to assess the clinical effectiveness of Traditional Chinese Medicine (TCM) as an adjuvant therapy for recurrent respiratory papillomatosis. Design: The design of this study was a case series. Location and subjects: Fifty-one (51) patients with laryngeal papillomatosis who were treated at Keio University Hospital between May 1981 and April 2008 were incorporated in this study. Interventions: Individually formulated TCM was orally administered postsurgically to 20 patients with aggressive laryngeal papillomatosis requiring multiple laser ablations (at least biannually) because of frequent recurrence. Eight (8) patients were excluded because of discontinued visits or medication (6 patients), or malignant transformation of the lesion (2 patients). The remaining 12 patients were enrolled in this study. Outcome measures: Retrospective chart review and review of the patients' recorded laryngeal images were performed. Clinical response to TCM was measured by the surgical necessity and Derkay's severity score for each patient, followed by statistical analyses. Results: Surgeries were required statistically less often (p= 0.0029) after TCM administration compared with the pre-TCM period. Furthermore, Derkay's severity score was significantly lower (p= 0.022) at the patients' last visit compared with the score before TCM administration. Conclusions: TCM may be a useful adjuvant therapy to treat aggressive laryngeal papillomatosis. Further studies are necessary to clarify the pharmacological mechanism of TCM in the treatment of laryngeal papillomatosis.

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Blockade of interleukin-6 signaling suppressed cochlear inflammatory response and improved hearing impairment in noise-damaged mice cochlea

Wakabayashi Kenichiro, Fujioka Masato, Kanzaki Sho, Okano Hirotaka James, Shibata Shinsuke, Yamashita Daisuke, Masuda Masatsugu, Mihara Masahiko, Ohsugi Yoshiyuki, Ogawa Kaoru, Okano Hideyuki

Neuroscience Research 66 （ 4 ） 345 - 352 2010年04月

ISSN 0168-0102

Hearing impairment can be the cause of serious socio-economic disadvantages. Recent studies have shown inflammatory responses in the inner ear co-occur with various damaging conditions including noise-induced hearing loss. We reported pro-inflammatory cytokine interleukin-6 (IL-6) was induced in the cochlea 6 h after noise exposure, but the pathophysiological implications of this are still obscure. To address this issue, we investigated the effects of IL-6 inhibition using the anti-IL-6 receptor antibody (MR16-1). Noise-exposed mice were treated with MR16-1 and evaluated. Improved hearing at 4 kHz as measured by auditory brainstem response (ABR) was noted in noise-exposed mice treated with MR16-1. Histological analysis revealed the decrease in spiral ganglion neurons was ameliorated in the MR16-1-treated group, while no significant change was observed in the organ of Corti. Immunohistochemistry for Iba1 and CD45 demonstrated a remarkable reduction of activated cochlear macrophages in spiral ganglions compared to the control group when treated with MR16-1. Thus, MR16-1 had protective effects both functionally and pathologically for the noise-damaged cochlea primarily due to suppression of neuronal loss and presumably through alleviation of inflammatory responses. Anti-inflammatory cytokine therapy including IL-6 blockade would be a feasible novel therapeutic strategy for acute sensory neural hearing loss.

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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年04月

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.

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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年03月

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.

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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年02月

ISSN 0032-6313

Inostamycin prevents malignant phenotype of cancer

Baba Yuh, Kato Yasumasa, Ogawa Kaoru

Cell Biology International 34 （ 2 ） 171 - 175 2010年02月

ISSN 1065-6995

Head and neck squamous cell carcinoma is the sixth most common type of neoplasm worldwide, but its prognosis has not improved significantly in recent years. Therefore, efforts need to be intensified to gain a better understanding of this disease and develop novel treatment strategies. Inhibition of cytidine 5'-diphosphate 1,2-diacyl-sn-glycerol: inositol transferase by inostamycin, an antibiotic isolated from Streptomyces sp. MH816-AF15, induces G1 cell cycle arrest accompanied by a decrease in cyclin D1 and phosphorylated RB protein levels, along with suppression of in vitro invasive ability through reduced production of matrix metalloproteinases (MMP-2 and MMP-9) and cell motility in head and neck cancer cell lines. Furthermore, inostamycin abrogated the stimulatory effect of VEGF (vascular endothelial growth factor) on growth and migration activities of endothelial cells by targeting extracellular signal-regulated kinase-cyclin D1 and p38 pathways, respectively. Because inostamycin has both antiproliferative and anti-invasive abilities, inhibition of phosphatidylinositol synthesis could be a potent therapeutic strategy for head and neck cancer as the 'cancer dormant therapy', i.e. a therapeutic concept to prolong 'time to treatment failure' or 'time to progression'.

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Hearing handicap predicts the development of depressive symptoms after 3 years in older community-dwelling Japanese

Saito Hideyuki, Nishiwaki Yuji, Michikawa Takehiro, Kikuchi Yuriko, Mizutari Kunio, Takebayashi Toru, Ogawa Kaoru

Journal of the American Geriatrics Society 58 （ 1 ） 93 - 97 2010年01月

ISSN 0002-8614

Objectives: To examine the association between hearing handicap and depressive symptoms in older community-dwelling Japanese. DESIGN: Community-based cohort study. Setting: Kurabuchi Town, Gunma Prefecture, Japan. Participants: Five hundred eighty residents (261 men, 319 women) aged 65 and older without depressive symptoms. Measurements: In a baseline examination performed in 2005/06, participants answered the 10-item screening version of the Hearing Handicap Inventory for Elderly (HHIE-S). They were divided into two groups according to their scores: a group with no hearing handicap (HHIE-S scores of ≤8) and a hearing handicap group (HHIE-S scores of ≥10). The Geriatric Depression Scale was used to identify depressive symptoms in face-to-face home visit interviews conducted in 2008, and the association between hearing handicap and depressive symptoms was assessed using logistic regression. Results: The incidence of depressive symptoms was 19.6% in the group with a hearing handicap and 8.0% in the group without a hearing handicap. When compared with the subjects without hearing handicap, subjects with a hearing handicap had a multiadjusted odds ratio of depressive symptoms of 2.45 (95% confidence interval=1.26-4.77). The association remained significant even when hearing impairment measured with pure-tone audiometry was added to the multiadjusted model. Conclusion: A hearing handicap can predict future depressive symptoms in older community-dwelling people.

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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年01月

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.

Chemotherapy for head and neck cancer

Tomita Toshiki, Imanishi Yorihisa, Ozawa Hiroyuki, Fujii Ryoichi, Shigetomi Seiji, Habu Noboru, Otsuka Kuninori, Ogawa Kaoru, Fukada Junichi, Shigematsu Naoyuki, Kogashiwa Yasunao, Yamauchi Kohichi, Kohno Naoyuki

Toukeibu Gan 36 （ 3 ） 273 - 277 2010年

ISSN 1349-5747

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.

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The possible contribution of angiitis to the onset of benign paroxysmal positional vertigo (BPPV)

Goto Fumiyuki, Hayashi Ken, Kunihiro Takanobu, Ogawa Kaoru

International Tinnitus Journal 16 （ 1 ） 25 - 28 2010年

ISSN 0946-5448

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.

A novel model for prognosis of meniere's disease using oxidative stress susceptibility of lymphoblastoid cell lines

Hayashi Ken, Kobayashi Ryo, Kitamura Koichi, Goto Fumiyuki, Ogawa Kaoru, Matsumoto Tetsuya

BioScience Trends 4 （ 2 ） 72 - 78 2010年

ISSN 1881-7815

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.

Differetial diagnosis of acute sensorineural hearing loss

Ogawa Kaoru

Otolaryngology - Head and Neck Surgery (Tokyo) 82 （ 1 ） 19 - 24 2010年

ISSN 0914-3491

Anxiety and depression levels measured using a hospital anxiety and depression scale in patients with an otolaryngological disorder

Goto Fumiyuki, Tsutumi Tomoko, Ogawa Kaoru

Practica Oto-Rhino-Laryngologica 102 （ 12 ） 1071 - 1075 2009年12月

ISSN 0032-6313

Introduction: Anxiety and depression are closely related to mental and physical disease prognosis. This makes it important to know anxiety and depression levels in patients with physical or mental disorders who visited the department of otorhinolaryngology. We evaluated the anxiety and depression levels in such patients using a hospital anxiety and depression scale (HADS). Methods: Subjects were 67 individuals whose degree of anxiety and depression was decided on HADS. Subjects were then divided into 4 groups-group I, no anxiety or depression; group II, depression alone, group III, anxiety alone, and group IV, both anxiety and depression. We then looked at the relationship between these results and their major perceived problems. Results: Groups I had 39 subjects II 7, III 8, and IV 13. Anxiety and depression were correlated (r= 0. 56; p<0. 0001). 90% of subjects reported dizziness, tinnitus, or throat discomfort. Those with throat discomfort had the highest anxiety score, while those with anxiety most commonly reported dizziness. Conclusions: Our results suggest that subjects may have anxiety and/or depression. The evaluation of anxiety and depression based on physical complaints may be difficult for otorhinolaryngologists, but it is important to do so where possible to increase the focus on the subject's physical illness and perceived problems.

Neuronal re-juvenilization in the nucleus ambiguus after vagal nerve injury

Takaoka Takuji, Shiotani Akihiro, Saito Koichiro, Tomifuji Masayuki, Mori Yuko, Fujimine Takekatsu, Okano Hideyuki, Ogawa Kaoru

Neuroscience Research 65 （ 4 ） 353 - 359 2009年12月

ISSN 0168-0102

Nestin is an intermediate filament expressed in immature cells in the CNS including neural stem/progenitor cells, reactive astrocytes and immature neurons in lesser amounts after injury. Nestin expression in the nucleus ambiguus following vagal nerve injury was studied using nestin-EGFP transgenic rats. We confirmed that EGFP immunoreactivity was evident at 6 h to 8 days in ipsilateral nucleus ambiguus after nerve transection. Properties of these cells were examined immunohistochemically. These EGFP-immunoreactive cells were immunoreactive for Tuj1 and Hu, and exhibited ChAT activity. However, no immunoreactivity for GFAP or CNPase was observed. In normal development, the level of KCC2 expression is known to increase with maturation of neurons. In our study, decreased KCC2 expression was observed in nestin-EGFP-positive cells within the nucleus ambiguus on the lesioned side compared with the contralateral side. These EGFP-immunoreactive cells were immunonegative for BrdU. This is the first study to demonstrate the expression of a neural stem/progenitor cell-enriched marker, Nestin, in the nucleus ambiguus after vagal nerve injury. The present findings suggest that mature motoneurons are an origin of these Nestin-positive cells, which are induced after injury. Mature neurons in the nucleus ambiguus may thus have the potential to juvenilize after vagal/recurrent laryngeal nerve injury.

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Electrocautery snare efficacy in head and neck lesion treatment

Saito Koichiro, Inagaki Koji, Naganishi Hideki, Takaoka Takuji, Isogai Yutaka, Ogawa Kaoru

Journal of Otolaryngology of Japan 112 （ 11 ） 739 - 746 2009年11月

ISSN 0030-6622

The electrocautery snare has been widely used in gastroenterology and to remove bronchial and urinary bladder lesions, but rarely in head and lesion electrocautery. Since October 2006, we have used this instrument to treat 17 head and neck granuloma, papilloma, cyst, and cancer lesions under local or general anesthesia. Lesions were localized in the larynx, oropharynx, hypopharynx, or tracheostoma. The snare was used through a rhinolaryngovideoscope in most cases with a current of 15-30 watts produced by an electrosurgical generator. All procedures were easy, quick and successful, with minimal bleeding. No severe adverse effects were seen in any of our cases. The electrocautery snare was extremely useful in treating pedunculated lesions and in removing epiglottic cysts with a clear margin after excision of the mass without bleeding. Our results indicate the electrocautery snare to be useful and safe in treating selected head and neck lesion cases.

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年11月

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).

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Inferior meatal antrostomy impairs dynamic stability of the orbital walls

Nagasao Tomohisa, Miyamoto Junpei, Tamaki Tamotsu, Kanazaki Sho, Ogawa Kaoru

Auris Nasus Larynx 36 （ 4 ） 431 - 437 2009年08月

ISSN 0385-8146

Objectives: The medial wall of the maxillary sinus, or the bony buttress, plays an important role in supporting the orbital floor. Since part of the bony buttress is removed in the inferior meatal antrostomy (IMA), it is expected that the IMA makes the orbital floor likely to develop serious fractures in traumatic situations. We conducted the present study to elucidate the effect of the IMA on the vulnerability of the orbital floor. Methods: After producing CAD (Computer Assisted Design) models simulating twelve skulls, we performed simulation antrostomy for each of the twelve CAD models in both the middle meatus and the inferior meatus. According to the site of the antrostomy, the models were categorized as the MMA (middle meatal antrostomy) or IMA groups. We then applied an impact on the orbital region of each model. Using the finite element method, we calculated the area of the orbital wall fracture induced by the impact. Then we compared the area of the orbital wall fractures between the MMA and IMA groups. Results: The orbital wall fracture areas were significantly greater in the IMA group than in the MMA group. Conclusions: The patients who underwent IMA are likely to develop serious orbital fractures if their orbits receive traumatic impacts. Hence, surgeons should be prudent in their indications for IMA.

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Promoted cell proliferation by connexin 30 gene transfection to head-and-neck cancer cell line

Ozawa Hiroyuki, Mutai Hideki, Matsunaga Tatsuo, Tokumaru Yutaka, Fujii Masato, Sakamoto Kouji, Tomita Toshiki, Ogawa Kaoru

Anticancer Research 29 （ 6 ） 1981 - 1985 2009年06月

ISSN 0250-7005

Background: There have been inconsistent results regarding the contribution of the connexin family of genes to tumor cell proliferation. Materials and Methods: We aimed to clarify the role of connexin 30 (Cx30), by transfecting three kinds of vectors that express either full length Cx30 (Cx30-Full), Cx30 devoid of C-terminal region (Cx30-DelC) or Cx30 C-terminal region (Cx30-CT), in HSC-4, a head-and-neck cancer cell line. Results: Transfected Cx30-Full was localized on the plasma membrane, while Cx30-DelC and Cx30-CT was expressed in the cytoplasm or circumnuclear sites. We studied the effect on the growth rate followed by immunostaining with anti-Ki-67 (MIB-1). The MIB indices of HSC-4 cells transfected with Cx30-Full and Cx30-DelC, but not Cx30-CT were shown to be significantly higher than that of the controls. Conclusion: Our results demonstrated that Cx30 enhanced the proliferation of HSC-4 cells and the proliferating activity was considered to be achieved without the transport of the protein onto the plasma membrane.

Heme oxygenase-1 expression in the guinea pig cochlea induced by intense noise stimulation.

Matsunobu Takeshi, Satoh Yasushi, Ogawa Kaoru, Shiotani Akihiro

Acta oto-laryngologica. Supplementum （ 562 ） 18 - 23 2009年06月

ISSN 0365-5237

CONCLUSION: These results suggest that noise induces free radical formation in the cochlea and that, in the guinea pig, heme oxygenase-1 (HO-1) may play an important role in the recovery from noise trauma in the organ of Corti. OBJECTIVE: Free radicals are involved in noise-induced hearing loss. It has been demonstrated that the induction of HO-1 may protect cells exposed to oxidative challenge. The present study was designed to investigate the effect of intense noise exposure on HO-1 induction. MATERIALS AND METHODS: A total of 25 adult guinea pigs (body weight 200-300 g) with a normal Preyers's reflex were used as subjects. Based on preliminary tests, the appropriate intensities and durations of noise were determined that were adequate to induce apparent threshold shifts and lead to various recovery patterns to initial thresholds. The sound was routed through a power amplifier to a speaker, which was positioned directly over the animals in a sound chamber. Auditory brainstem response (ABR) testing, Western blot analysis for HO-1, and immunohistochemical testing were done. RESULTS: Exposure of the guinea pigs to 115 dB SPL octave band noise for 5 h induced HO-1 expression in the organ of Corti. In the organ of Corti, HO-1 expression increased mainly in the outer hair cells. Some expression of HO-1 was observed before and after noise exposure in the supporting cells. HO-1 expression in the organ of Corti was definitely increased in guinea pigs with an intense noise exposure which causes a temporary threshold shift.

Laryngeal function after supracricoid laryngectomy

Saito Koichiro, Araki Koji, Ogawa Kaoru, Shiotani Akihiro

Otolaryngology - Head and Neck Surgery 140 （ 4 ） 487 - 492 2009年04月

ISSN 0194-5998

Objective: The purpose of this study was to assess laryngeal function after supracricoid laryngectomy. Study Design: Case series. Subjects and Methods: Supracricoid laryngectomy (SCL) has been performed in our institution for 24 selected patients with laryngeal cancer since December 2000. Reconstruction was performed through cricohyoidoepiglottopexy for 23 patients and cricohyoidopexy for 1 patient. Seven patients had ipsilateral arytenoid removal, and 15 patients underwent SCL as salvage surgery. A retrospective chart review was performed to assess postoperative speech and swallowing function. Stroboscopy and/or fiberscopy of the neoglottis were used to assess postoperative speech kinetics. Acoustic parameters were measured to evaluate vocal function, and several questionnaires were used to evaluate postoperative quality of life (QOL). Results: In the absence of postoperative complications, stoma closure and normal diet intake were achieved 1 month after surgery. The neoglottis comprises the arytenoid(s), epiglottis, and pyriform sinus mucosa. Several different combinations of vibrating regions were observed among patients during phonation. Although vocalization sounded rough and breathy, vocal communication was possible with little inconvenience. Conclusion: Acceptable functional recovery and tolerable QOL can be achieved after SCL.

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Survey of feeding and swallowing functions in patients recruited by the nutrition support team

Fujimine Takekatsu, Shiotani Akihiro, Saito Koichiro, Tomifuji Masayuki, Tsunoda Koichi, Fujii Masato, Ogawa Kaoru

Japan Journal of Logopedics and Phoniatrics 50 （ 2 ） 109 - 115 2009年04月

ISSN 0030-2813

In order to evaluate feeding and swallowing functions in patients recruited by the Nutrition Support Team (NST), we investigated their underlying diseases, primary departments, age distribution, nutrition administration routes, and feeding and swallowing, The survey was conducted on 66 cases determined to be suffering from malnutrition based on screening of all hospitalized patients. The elderly aged 65 or over accounted for 86 percent of all cases. Neurological disorders were the most prevalent type of disease, affecting 29 percent of all cases. Oral feeding accounted for 40 percent, and supplemental nutrition for 60 percent of all cases. The incidence of aspiration was 66 percent. Forty-two percent of all cases did not involve oral administration. Feeding and swallowing functions were more seriously affected in cases of respiratory and neuromuscular diseases as compared with other diseases. Our findings suggest that in order to carry out safe oral nutrition, medical staff must evaluate the individual patient's feeding and swallowing functions.

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Experimental evaluation of relapse-risks in operated zygoma fractures

Nagasao Maki, Nagasao Tomohisa, Imanishi Yorihisa, Tomita Toshiki, Tamaki Tamotsu, Ogawa Kaoru

Auris Nasus Larynx 36 （ 2 ） 168 - 175 2009年04月

ISSN 0385-8146

Objectives: Prevention of relapse, or postoperative dislocation, of the fixed zygoma is necessary to achieve optimal results in the treatment of zygoma fractures. Assuming that the occurrence of intensified stresses on mastication at the screw-bone interface (SBI) constitutes the essential cause of the relapse, we evaluated the stresses for three different fixation methods-fixation at the frontal process (FP), inferior orbital rim (IOR), and zygomatico-maxillary buttress (ZMB). Methods: We used 10 computer-aided design (CAD) models simulating zygoma fractures in the experiment. For each CAD model, we fixed the fractured zygoma with four screws and one mini-plate at the FP, IOR, or ZMB. After applying a 5.5 kg force simulating mastication, we calculated the intensity and distribution patterns of the stresses occurring at the SBIs of the fixation screws using the finite element method. Thereby, we evaluated dynamic stability of the fixed zygoma for each of the three fixation methods. Results: Greater stresses occur at the SBIs with IOR fixation than at those with FP and ZMB fixation. Although the stresses occurring at the SBIs on mastication demonstrated evenly distributed patterns with the FP and ZMB fixation, the stresses demonstrated concentration on one screw with the IOR fixation. Conclusions: The fixed zygoma is more likely to cause relapse with the IOR fixation than with the FP or ZMB fixation. Hence, in performing zygoma fixation at the IOR, care should be taken to minimize the likelihood of postoperative relapse that is caused by skewed distribution of the stresses on the fixation screws.

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Diagnosis and management of cervical sympathetic chain schwannoma

Tomita Toshiki, Ozawa Hiroyuki, Sakamoto Koji, Ogawa Kaoru, Kameyama Kaori, Fujii Masato

Acta Oto-Laryngologica 129 （ 3 ） 324 - 329 2009年03月

ISSN 0001-6489

Conclusions. Cervical sympathetic chain schwannoma (CSCS) sometimes mimics carotid body tumor (CBT). Differential diagnosis between these tumors is sometimes difficult using MRI alone. MRA, color Doppler ultrasonography, and fine needle aspiration (FNA) after imaging may be helpful to rule out CBT. Surgical resection of CSCS is relatively effortless, and Horner's syndrome is an expected but acceptable postoperative complication. Intratumoral hemorrhage and vasodilation may be the main reasons for significant enhancement on MRI. Objectives. CSCSs are rare and known to mimic carotid body tumors. We report 9 cases of CSCS with an emphasis on imaging, surgical management, and pathological findings. Moreover, we describe the differential diagnosis of CSCS and CBT, and speculate the reasons behind significant enhancement on MRI. Patients and methods. Nine cases of CSCS treated at a tertiary referral center between 1996 and 2008 were reviewed. Results. MRI revealed 3 of 9 cases (33%) splayed the carotid bifurcation and displayed marked contrast enhancement with gadolinium. All patients underwent surgical excision of the mass with minimal blood loss. Postoperative Horner's syndrome was encountered in all patients, which required no treatment. Marked gadolinium enhancement tended to be associated with histological findings such as intratumoral hemorrhage and vasodilation.

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Oxidative stress and Ménière's disease and benign paroxysmal positional vertigo

Goto Fumiyuki, Ide Rika, Yabe Haruna, Kunihiro Takanobu, Ogawa Kaoru

Equilibrium Research 68 （ 1 ） 9 - 13 2009年02月

ISSN 0385-5716

It is known that oxidative stress plays some role in inner ear diseases, such as sensorineural hearing loss due to aging. Free radicals are produced as a result of oxidative stress, such as reactive oxygen species (ROS) and nitric oxide. Radical scavengers and antioxidants play a role in the protection against oxidative stress. Although some basic data have indicated a relationship between oxidative stress and endolymphatic hydrops, no clinical data have been published from patients. Diacron reactive oxygen metabolites (d-ROM) were measured by the Free Radical Analytical system 4 (FRAS 4) from the blood of 39 patients. The subjects consisted of 16 controls, 13 patients with Ménière's disease, and 10 patients with benign paroxysmal positional vertigo. The d-ROM value of the controls was 307.3 ± 42.5 U Carr, compared with 350.1 ± 50.5 U Carr in BPPV and 352.2 ± 71.5 U Carr in Meniere's disease subjects. Although no statistically significant differences were seen among the groups, patients with BPPV and Ménière's disease had slightly higher values than the controls, suggesting that free radicals were being produced in patients with both Ménière's disease and benign paroxysmal positional vertigo. It may be useful to control dizziness or vertigo by reducing free radicals as a product of oxidative stress, and controlling oxidative stress may be a valuable approach in the treatment of patients with dizziness due to Méniè re's disease or benign paroxysmal positional vertigo.

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Bisphosphonate therapy ameliorates hearing loss in mice lacking osteoprotegerin

Kanzaki Sho, Takada Yasunari, Ogawa Kaoru, Matsuo Koichi

Journal of Bone and Mineral Research 24 （ 1 ） 43 - 49 2009年01月

ISSN 0884-0431

Three auditory ossicles including the malleus, incus, and stapes conduct sound in the middle ear from the tympanic membrane to the inner ear. Auditory ossicles are massively resorbed by osteoclasts in Opg^-/- mice, which lack osteoprotegerin (OPG), a soluble decoy receptor for the osteoclastogenic cytokine RANKL. Opg^-/- mice exhibit progressive hearing loss and are a model for juvenile Paget's disease. However, effects of antiresorptive treatment on auditory ossicles and on hearing function in Opg^-/- mice are unknown. We intraperitoneally injected Opg^-/- mice with bisphosphonate risedronate 5 d/wk for 9 wk. Morphology of auditory ossicles was examined microscopically, radiographically, and histologically. Hearing function was monitored by measuring the auditory brain stem response (ABR). Control Opg^-/- mice exhibited thinning of all three ossicles and tibia. In contrast, risedronate treatment significantly inhibited bone loss in auditory ossicles as well as in long bones of Opg^-/- mice. Bony fusion of the junction between the stapes and the otic capsule was reduced after treatment. Moreover, ABR measurement showed that hearing in Opg^-/- mice was significantly improved by risedronate treatment. These data suggest that hearing loss in pathologies characterized, by excessive resorption of the auditory ossicles may be prevented by bisphosphonates.

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Management of deep neck infection by a transnasal approach

Baba Yuh, Kato Yasumasa, Saito Hideyuki, Ogawa Kaoru

Journal of Medical Case Reports 3 2009年

ISSN 1752-1947

Introduction. Deep neck infection is a life-threatening condition, and intravenous antibiotic therapy is preferable in the early stages of the disease. However, in the advanced stages, surgical drainage should be performed. Although several surgical treatment strategies are available, it is necessary to standardize treatment according to the patient's general condition and history. Case presentation. We report the case of a 68-year-old man with a deep neck abscess and with severe diabetes mellitus and inflammation. Computed tomography identified a deep neck infection extending from the level of the epipharynx to that of the hyoid bone. We performed surgical drainage by transnasal endoscopy. The patient exhibited no evidence of either recurrent disease or post-surgical complications within 30 months of follow-up. Conclusions. This case report provides evidence that transnasal endoscopic drainage should be recommended as a standard approach in patients with a deep neck abscess and with a severe general condition, diabetes mellitus, and inflammation.

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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年

ISSN 0032-6313

Intractable depression successfully treated with a combination of autogenic training and high-dose antidepressant in department of otorhinolaryngology

Goto Fumiyuki, Nakai Kimiko, Murakami Masato, Ogawa Kaoru

Cases Journal 2 （ 8 ） 2009年

ISSN 1757-1626

Introduction: Patients suffering from ear discomfort are commonly encountered in the department of otolaryngology. If various clinical examinations do not reveal any objective findings, then the patients are referred to the department of internal medicine or psychiatry. Psychotherapy is recommended in some cases. This paper describes the successful administration of autogenic training in a patient suffering from ear discomfort due to major depression. Case presentation: We present a case of intractable depression that was successfully treated with a combination of psychotherapy, administered by a clinical psychologist, and high-dose antidepressant. The patient was a 36-year-old female with hearing discomfort in her left ear. In 2003, she experienced insomnia and an appetite loss, and her condition was diagnosed as major depression along with an avoidant personality disorder. Her depression has not been improved with antidepressant treatment for 3 years in department of psychosomatic medicine. She was referred to our department because of ear discomfort in her left ear. There was no abnormality in her physical examinations. She wanted to be treated in department of otorhinolaryngology. We increased the dose of fluvoxamine maleate up to 200 mg/day, and introduced cognitive therapy and autogenic training by a clinical psychologist. Eventually, her depressive state as well as the hearing complaint was markedly alleviated. Conclusions: Autogenic training can be a viable and acceptable treatment option for patients who fail to respond to other therapies. This case emphasizes the importance of autogenic training as a method to control physical symptom of depression.

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Pharmacological treatment for acute peripheral vertigo

Goto Fumiyuki, Yabe Haruna, Ogawa Kaoru

Practica Oto-Rhino-Laryngologica 102 （ 4 ） 315 - 320 2009年

ISSN 0032-6313

Introduction: Treatments for acute peripheral vertigo have not been well investigated. The most suitable drug for controlling acute vertigo should suppress both vertigo and accompanying nausea. The purpose of this study was to evaluate the effect of four different drugs on acute peripheral vertigo: (A) hydroxyzine hydrochloride (25 mg, i.v.); (B) 0. 5% metoclopramide (2 ml, i.v.); (C) sodium bicarbonate (40 ml, i.v.); and (D) a cocktail of diphenhydramine hydrochloride (30 mg) and dyprophylline (26 mg) (both i.m.). Methods: Forty-two patients with acute peripheral vertigo (average age: 59. 5 ±18.1 years) with spontaneous nystagmus were assigned to four treatment groups (A-D, above). Patients with central vertigo and vestibular neuritis were excluded. The number of patients in each group was as follows: A, n= 11; B, n=ll; C, n=ll; and D, n=9. Patients were instructed to evaluate their subjective symptoms of nausea and vertigo before and 30 minutes after drug treatment. They rated the severity of their symptoms on a 0-to-10 scale, with 10 representing the most severe symptoms and 0 a lack of symptoms. Results: Group A patients (hydroxyzine hydrochloride; 25 mg, i.v.) reported the highest level of relief from vertigo and nausea after drug treatment, whereas group C (sodium bicarbonate; 40 ml, i.v.) and D (diphenhydramine hydrochloride (30 mg)-dyprophylline (26 mg) cocktail; i.m.) patients reported only the slight relief of these symptoms. Group B patients (0. 5% metoclopramide; 2 ml, i.v.) experienced partial symptom relief; their vertigo remained unchanged. Thus, hydroxyzine hydrochloride (A) was the most effective in controlling both nausea and vertigo, whereas sodium bicarbonate (C) and diphenhydramine hydrochloride and dyprophylline (D) only slightly suppressed vertigo and nausea. Metoclopramide (B) only suppressed nausea. Conclusions: Hydroxyzine hydrochloride (A) was the most suitable for treating acute peripheral vertigo. Doctors should be familiar with the contraindications of these drugs. Some of these drugs may potentially be used in combination to control the symptoms of acute vertigo more effectively.

Heme oxygenase-1 expression in the guinea pig cochlea induced by intense noise stimulation

Matsunobu Takeshi, Satoh Yasushi, Ogawa Kaoru, Shiotani Akihiro

Acta Oto-Laryngologica 129 （ SUPPL. 562 ） 18 - 23 2009年

ISSN 0001-6489

Conclusion: These results suggest that noise induces free radical formation in the cochlea and that, in the guinea pig, heme oxygenase-1 (HO-1) may play an important role in the recovery from noise trauma in the organ of Corti. Objective: Free radicals are involved in noise-induced hearing loss. It has been demonstrated that the induction of HO-1 may protect cells exposed to oxidative challenge. The present study was designed to investigate the effect of intense noise exposure on HO-1 induction. Materials and methods: A total of 25 adult guinea pigs (body weight 200-300 g) with a normal Preyers's reflex were used as subjects. Based on preliminary tests, the appropriate intensities and durations of noise were determined that were adequate to induce apparent threshold shifts and lead to various recovery patterns to initial thresholds. The sound was routed through a power amplifier to a speaker, which was positioned directly over the animals in a sound chamber. Auditory brainstem response (ABR) testing, Western blot analysis for HO-1, and immunohistochemical testing were done. Results: Exposure of the guinea pigs to 115 dB SPL octave band noise for 5 h induced HO-1 expression in the organ of Corti. In the organ of Corti, HO-1 expression increased mainly in the outer hair cells. Some expression of HO-1 was observed before and after noise exposure in the supporting cells. HO-1 expression in the organ of Corti was definitely increased in guinea pigs with an intense noise exposure which causes a temporary threshold shift.

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Meniere's disease in the elderly in Japan

Goto Fumiyuki, Yabe Haruna, Kunihiro Takanobu, Ogawa Kaoru

Equilibrium Research 67 （ 6 ） 500 - 505 2008年12月

ISSN 0385-5716

Introduction: Meniere's disease is generally observed in persons aged between 30 and 50 years old. However, with the aging of the population, one may expect an increase in the number of elderly patients with the disease. The current study was aimed at clarifying the prevalence and clinical characteristics of Meniere's disease in the elderly, especially in patients aged >65 years old at the onset of the disease. Methods: Statistical analysis was performed on the recorded data of patients with Meniere's disease who visited Hino Municipal Hospital from 2004 to 2007. Results: Our sample comprised 47 patients with Meniere's disease, with an average age of 54.9 ± 14.2 years. Patients who developed Meniere's disease at the age of ≥65 years were classified as de novo patients; the remaining patients were classified as non-de novo patients. There were 13 (27.7%) de novo patients (3 males and 9 females; average age: 73.4 ± 4.9 years). The observations showed that the worst hearing level exhibited by the de novo patients was significantly different from that exhibited by the non-de novo patients. As treatment for Meniere's disease, 6 (46.2%) of the de novo patients underwent tympanic tube insertion, while 4 of the 6 patients underwent middle ear pressure treatment with a Meniett device. Conclusion: De-novo patients were more frequently admitted, but there was no difference in the duration of hospitalization between the de novo and non-de novo patients. It can be quite stressful for elderly patients with Meniere's disease to call an ambulance to transport them to the hospital during a vertigo attack. Tympanic tube insertion was undertaken as treatment in many of the patients, but none of the patients received intratympanic gentamicin. It is important that physicians who care for elderly patients with Meniere's disease take special care of those experiencing vertigo. Early diagnosis of Meniere's disease should be made in the elderly.

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Long-term prognosis of steroid-dependent sensorineural hearing loss

Kanzaki Jin, Kanzaki Sho, Ogawa Kaoru

Audiology and Neurotology 14 （ 1 ） 26 - 34 2008年12月

ISSN 1420-3030

We report on the long-term follow-up of 15 patients with steroid-dependent sensorineural hearing loss (SDSNHL), which was steroid dose dependent. We classified the patients into 2 groups: group A consisted of 6 patients with systemic SDSNHL, and group B consisted of 9 patients with inner-ear-specific SDSNHL without systemic disease. Group B patients were further classified as patients with slowly or rapidly progressive hearing loss. The yearly rate of hearing deterioration was greater in group B than in group A. Thus, the long-term hearing prognosis of patients in group B was worse than those in group A. Although SDSNHL may have immune-related origins, we hypothesize that hearing deterioration may be caused by proinflammatory cytokines because many of our cases exhibited abnormal immunological laboratory values and because many of these cases responded favorably to steroid treatment.

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A case of delayed endolymphatic hydrops due to mumps viral infection treated with the Meniett device

Goto Fumiyuki, Yabe Haruna, Hayashi Ken, Kunihiro Takanobu, Ogawa Kaoru

Equilibrium Research 67 （ 6 ） 496 - 499 2008年12月

ISSN 0385-5716

Objective: We report a case of delayed endolymphatic hydrops due to complicating mumps virus infection that was treated with the Meniett device. Method: Case reports and a review of the world literature on delayed development of endolymphatic hydrops after mumps virus infection are presented. Results: The case of a woman who presented with unilateral, reversible sensorineural hearing loss following mumps infection and was successfully treated with the Meniett device is presented. This woman developed profound sensorineural hearing loss and intractable vertigo spells a few months after contracting mumps. In this case, the incubation period interval between the development of mumps infection and the diagnosis of DEH was only one year. DEH (Delayed endolymphatic hydrops) is a clinical entity characterized by profound sensorineural hearing loss in one ear during its early phase; after a prolonged period of time, DEH enters the late phase, which is characterized by different otologic symptoms. Although the most common causes of DEH are inflammation, trauma and other unidentified events during childhood, viral infections, including mumps, represent one of the known causes of DEH. Mumps infection sometimes represents a confirmed etiology of DEH Sometimes DEH can definitively be diagnosed as being caused by mumps infection. Conclusion: This is the first case report to demonstrate the efficacy of the Meniett device in the treatment of DEH due to complicating mumps infection.

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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年09月

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.

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Sentinel node concept in clinically N0 laryngeal and hypopharyngeal cancer

Tomifuji Masayuki, Shiotani Akihiro, Fujii Hirofumi, Araki Koji, Saito Koichiro, Inagaki Koji, Mukai Makio, Kitagawa Yuko, Ogawa Kaoru

Annals of Surgical Oncology 15 （ 9 ） 2568 - 2575 2008年09月

ISSN 1068-9265

Background: Sentinel nodes (SNs) are the lymph nodes that directly receive lymphatic flow from a primary cancer lesion. The SN concept implies that lymphatic metastasis initially occurs at SNs. SN navigation surgery can be introduced for cancers in which the SN concept is established. In SN navigation surgery, lymph node dissection beyond SNs can be omitted if SNs are metastasis free. Although the SN concept has been investigated frequently for oral and oropharyngeal cancer, it has so far been investigated less for laryngeal and hypopharyngeal cancer. In this study, we investigated whether the SN concept is applicable for laryngeal and hypopharyngeal cancer. Methods: Twenty patients with T2-T4 and clinically N0 laryngeal and hypopharyngeal cancer were recruited. ^99mTc-phytate was injected into several sites surrounding the tumor on the day before surgery. Lymphoscintigrams were acquired from at least two different viewpoints. SNs were surveyed intraoperatively, and neck dissections including at least levels II, III, and IV were performed. Results: SNs had occult metastases in five cases. In the remaining 15 cases, neither SNs nor other lymph nodes contained metastases, consistent with the SN concept. There was one false-negative case showing delayed nodal metastasis 2 years after initial surgery. The overall accuracy of the SN concept was 95%. Conclusion: Our study shows that SN biopsy is a reliable strategy to determine correct lymph node status in N0 laryngeal and hypopharyngeal cancer. SN detection was valuable in evaluating the need for neck dissection, whether ipsilaterally or bilaterally.

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Mucoepidermoid carcinoma of the head and neck

Ozawa Hiroyuki, Tomita Toshiki, Sakamoto Koji, Tagawa Takamasa, Fujii Ryoichi, Kanzaki Sho, Ogawa Kaoru, Kameyama Kaori, Fujii Masato

Japanese Journal of Clinical Oncology 38 （ 6 ） 414 - 418 2008年06月

ISSN 0368-2811

Objective: It is well known that mucoepidermoid carcinoma (MEC) displays a variety of biological behaviors. While the high-grade type is a highly aggressive tumor, its low-grade counterpart usually demonstrates a more benign nature and several systems have, therefore, been proposed to grade this neoplasm. Methods: This report analyzes 43 patients suffering from head and neck MEC, who were treated in our department during the period from 1989 to 2005. The relationship between clinical and pathologic characteristics and survival rate was investigated. Results: The 5-year overall and disease-free survival rate was 62.3 and 57.2%. Multivariate analysis demonstrated that the parameters that significantly affected survival were the patient's age (P = 0.040) and treatment method (P = 0.011). Conclusions: The patient's age and treatment method is the prognostic parameter in this study. Although complete surgical resection is the standard treatment for MEC, we should aggressively consider adjunctive radiotherapy in those cases that have a high risk of recurrence and poor prognosis.

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An anatomical study of the three-dimensional structure of the nasal septum in patients with alveolar clefts and alveolar-palatal clefts

Nagasao Tomohisa, Miyamoto Junpei, Yasuda Shohei, Ogata Hisao, Imanishi Yorihisa, Zhu Xiaohai, Jiang Hua, Ogawa Kaoru, Nakajima Tatsuo

Plastic and Reconstructive Surgery 121 （ 6 ） 2074 - 2083 2008年06月

ISSN 0032-1052

BACKGROUND: The present study was performed to quantitatively analyze the three-dimensional morphology of the nasal septa of patients with alveolar and alveolopalatal clefts. METHODS: Twenty-five unilateral complete cleft lip patients with alveolar clefts only (alveolar cleft group) and 35 unilateral complete cleft lip patients with alveolar and palatal clefts (alveolar and palatal cleft group) were included in the study. Although no patient in either group had undergone alveoloplasty, all patients had undergone palatoplasty. The degree of nasal septum deviation was studied for each patient at three different depths along the anteroposterior axis using three-dimensional computed tomographic data; the data were compared between the two groups to elucidate whether the difference in cleft type affects the morphologic patterns of the nasal septum. RESULTS: The nasal septa of the alveolar and palatal cleft group patients presented more uneven morphologic patterns than those of the alveolar cleft group patients. In the alveolar cleft group, the nasal septa did not present significantly different degrees of deviation at their anterior and posterior parts. In the alveolar and palatal cleft group, however, the posterior parts of the nasal septa presented greater deviation than the anterior parts. In the alveolar and palatal cleft group, furthermore, a significant correlation was observed between the severity of the cleft and the degree of the nasal septum deviation. CONCLUSIONS: The nasal septa present different three-dimensional morphologic patterns between the patients with alveolar clefts only and those with alveolopalatal clefts. This difference should be considered when performing surgical treatments for these patients.

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Migraine associated dizziness and treatment

Goto Fumiyuki, Yabe Haruna, Kunihiro Takanobu, Ogawa Kaoru

Equilibrium Research 67 （ 3 ） 205 - 210 2008年06月

ISSN 0385-5716

Introduction: The importance of the relationship between vertigo and headache, especially migraine, has been recognized. Vertigo has been found to be three times more common in patients with migraine than in controls, and migraine is found at a prevalence of 30%-50% in patients presenting with vertigo. Several authors have proposed different diagnostic criteria for defining migrainous vertigo and vestibular migraine. In this study, we attempted to clarify the current situation of migraine-related dizziness at our institute. Subjects and Methods: A retrospective review of 9 patients with migraine-related vertigo who visited our institute was conducted. We used the diagnostic criteria proposed by Neuhauser (2001). Results: Of the 9 patients, 1 was male and 8 were female; 6 patients had visited a neurosurgeon once, 3 patients had been diagnosed once as having Meniere's disease, although they had normal hearing. Calcium channel blockers, antidepressants, SSRIs (Selective Serotonin Reuptake Inhibitors) and anxiolytics had been prescribed as prophylactic agents. Of the 9 patients, 5 improved with the prophylactic treatment, 2 improved slightly, and 2 showed no change. The patients who showed improvement in the migraine with the prophylactic treatment also showed improvement of their vertigo at the same time. As acute-phase treatment NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) and triptans were prescribed. Three patients had a past history of BPPV (benign paroxysmal positional vertigo). Conclusion: The importance of diagnosis of migrane-associated vertigo was confirmed, since both prophylactic and acute-phase treatment were effective against both migraine and vertigo in these patients. To obtain further evidence for the treatment of migraine-associated vertigo, a more organized study should be conducted. The relationship between BPPV and migraine-associated vertigo should also be investigated in a future study.

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Neuroprotective effects of T-817MA against noise-induced hearing loss

Yamashita Daisuke, Shiotani Akihiro, Kanzaki Sho, Nakagawa Masaya, Ogawa Kaoru

Neuroscience Research 61 （ 1 ） 38 - 42 2008年05月

ISSN 0168-0102

Oxidative stress, including reactive oxygen species and other free radicals, is thought to play an important role in neuronal cell death, including noise-induced hearing loss. 1-{3-[2-(1-Benzothiophen-5-yl)ethoxy]propyl}azetidin-3-ol maleate (T-817MA), a novel neurotrophic agent, protects against oxidative stress-induced neurotoxicity. This study examines the effects of T-817MA in noise-induced ototoxicity in the cochlea. Guinea pigs received treatment with T-817MA-enhanced water (0.2, 0.7 mg/ml) or untreated water (control) beginning 10 days prior to noise exposure and continuing through this study. All subjects were exposed to 4-kHz octave-band noise at 120-dB SPL for 5 h. Auditory thresholds were assessed by sound-evoked auditory brainstem response at 4, 8, and 16 kHz, prior to and 10 days following noise exposure. Hair cell damage was analyzed by quantitative histology. T-817MA significantly reduced threshold deficits and hair cell death. These results suggest T-817MA reduces noise-induced hearing loss and cochlear damage, suggesting functional and morphological protection.

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Noninvasive in vivo delivery of transgene via adeno-associated virus into supporting cells of the neonatal mouse cochlea

Iizuka Takashi, Kanzaki Sho, Mochizuki Hideki, Inoshita Ayako, Narui Yuya, Furukawa Masayuki, Kusunoki Takeshi, Saji Makoto, Ogawa Kaoru, Ikeda Katsuhisa

Human Gene Therapy 19 （ 4 ） 384 - 390 2008年04月

ISSN 1043-0342

There are a number of genetic diseases that affect the cochlea early in life, which require normal gene transfer in the early developmental stage to prevent deafness. The delivery of adenovirus (AdV) and adeno-associated virus (AAV) was investigated to elucidate the efficiency and cellular specificity of transgene expression in the neonatal mouse cochlea. The extent of AdV transfection is comparable to that obtained with adult mice. AAV-directed gene transfer after injection into the scala media through a cochleostomy showed transgene expression in the supporting cells, inner hair cells (IHCs), and lateral wall with resulting hearing loss. On the other hand, gene expression was observed in Deiters cells, IHCs, and lateral wall without hearing loss after the application of AAV into the scala tympani through the round window. These findings indicate that injection of AAV into the scala tympani of the neonatal mouse cochlea therefore has the potential to efficiently and noninvasively introduce transgenes to the cochlear supporting cells, and this modality is thus considered to be a promising strategy to prevent hereditary prelingual deafness.

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Bcl-2 genes regulate noise-induced hearing loss

Yamashita Daisuke, Minami Shujiro B., Kanzaki Sho, Ogawa Kaoru, Miller Josef M.

Journal of Neuroscience Research 86 （ 4 ） 920 - 928 2008年03月

ISSN 0360-4012

Proteins of the Bcl-2 family have been implicated in control of apoptotic pathways modulating neuronal cell death, including noise-induced hearing loss. In this study, we assessed the expressions of anti- and proapoptotic Bcl-2 genes, represented by Bcl-xL and Bak following noise exposures, which yielded temporary threshold shift (TTS) or permanent threshold shift (PTS). Auditory brainstem responses (ABRs) were assessed at 4, 8, and 16 kHz before exposure and on days 1, 3, 7, and 10 following exposure to 100 dB SPL, 4 kHz OBN, 1 hr (TTS) or 120 dB SPL, 4 kHz OBN, 5 hr (PTS). On day 10, subjects were euthanized. ABR thresholds increased following both exposures, fully recovered following the TTS exposure, and showed a 22.6 dB (4 kHz), 42.5 dB (8 kHz), and 44.9 dB (16 kHz) mean shift on day 10 following the PTS exposure. PTS was accompanied by outer hair cell loss progressing epically and basally from the 4-kHz region. Additional animals were euthanized for immunohistochemical assessment. BcL-xL was robustly expressed in outer hair cells following TTS exposure, whereas Bak was expressed following PTS exposure. These results indicate an important role of the Bcl-2 family proteins in regulating sensory cell survival or death following intense noise. Bcl-xL plays an essential role in prevention of sensory cell death following TTS levels of noise, and PTS exposure provokes the expression of Bak and, with that, cell death.

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Case report

Goto Fumiyuki, Nakai Kimiko, Kunihiro Takanobu, Ogawa Kaoru

2008年01月

Background: Psychological stress plays an important role in the onset and course of Meniere's disease. Surgical therapy and intratympanic gentamicin treatment are options for cases that are intractable to conventional medical therapy. Psychotherapy, however, including autogenic training (AT), which can be used for general relaxation, is not widely accepted. This paper describes the successful administration of AT in a subject suffering from intractable Meniere's disease. Case presentation: A 51-year-old male patient has suffered from fluctuating right sensorineural hearing loss with vertigo since 1994. In May 2002, he was first admitted to our hospital due to a severe vertigo attack accompanied by right sensorineural hearing loss. Spontaneous nystagmus toward the right side was observed. Since April 2004, he has experienced vertigo spells with right-sided tinnitus a few times per month that are intractable to conventional medical therapy. After four months, tympanic tube insertion was preformed in the right tympanic membrane. Intratympanic injection of dexamethasone was ineffective. He refused Meniett therapy and intratympanic gentamicin injection. In addition to his vertigo spells, he suffered from insomnia, tinnitus, and anxiety. Tranquilizers such as benzodiazepines and antidepressants such as serotonin selective re-uptake inhibitors (SSRIs) failed to stop the vertigo and only slightly improved his insomnia. In December 2006, the patient began psychological counseling with a psychotherapist. After brief psychological counseling along with cognitive behavior therapy (CBT), he began AT. He diligently and regularly continued his AT training in his home according to a written timetable. His insomnia, tinnitus, and vertigo spells disappeared within a few weeks after only four psychotherapy sessions. In order to master the six standard formulas of AT, he underwent two more sessions. Thereafter, he underwent follow-up for 9 months with no additional treatment. He is now free from drugs, including tranquilizers, and has continued AT. No additional treatment was performed. When we examined him six and nine months later for follow-up, he was free of vertigo and insomnia. Conclusion: AT together with CBT can be a viable and palatable treatment option for Meniere's disease patients who are not responsive to other therapies.

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Caspase inhibitor facilitates recovery of hearing by protecting the cochlear lateral wall from acute cochlear mitochondrial dysfunction

Mizutari Kunio, Matsunaga Tatsuo, Kamiya Kazusaku, Fujinami Yoshiaki, Fujii Masato, Ogawa Kaoru

Journal of Neuroscience Research 86 （ 1 ） 215 - 222 2008年01月

ISSN 0360-4012

We recently showed that acute energy failure in the rat cochlea induced by local administration of the mitochondrial toxin 3-nitropropionic acid (3-NP) causes hearing loss mainly due to degeneration of cochlear lateral-wall fibrocytes. In the present study, we analyzed the effect of the pan-caspase inhibitor z-Val-Ala-Asp(Ome)-fluoromethylketone (Z-VAD-FMK) on 3-NP-induced hearing loss in a model showing temporary threshold shifts at low frequencies and permanent threshold shifts at high frequencies. The model rats received an intraperitoneal injection of either Z-VAD-FMK or vehicle for 3 days starting 1 day prior to 3-NP treatment. One day after the administration of 3-NP, the auditory brain-stem response (ABR) threshold at 20 kHz was elevated to 70 dB in the Z-VAD-FMK group and to 85 dB in controls. The Z-VAD-FMK group completely recovered to the preoperative level within 14 days, whereas in the controls, the ABR threshold remained elevated at 50 dB even 28 days after the administration of 3-NP. Treatment with Z-VAD-FMK also improved recovery of hearing at 8 kHz but did not change recovery at 40 kHz. Histological examination demonstrated that treatment with Z-VAD-FMK inhibited progressive degeneration of the lateral-wall fibrocytes in the cochlear basal turn, as well as apoptosis of these fibrocytes. These results clearly indicate that caspase-dependent apoptosis of fibrocytes in the cochlear lateral wall plays an important role in hearing loss in the present animal model. Moreover, the results of the present study suggest that systemic administration of a caspase inhibitor may be an effective therapy for sensorineural hearing loss caused by acute energy failure such as that observed in cochlear ischemia.

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Cost-Effectiveness of different treatment modalities for seasonal allergic rhinitis in japan — comparison of laser treatment with subcutaneous immunotherapy and oral medication —

Taniguchi Yuki, Fujii Shunji, Ohshiro Takafumi, Sasaki Katsumi, Ohshiro Toshio, Suzuki Takafumi, Kanzaki Sho, Ogawa Kaoru

Laser Therapy 17 （ 4 ） 193 - 197 2008年

ISSN 0898-5901

Allergic rhinitis is a condition which shows a high prevalence throughout the world. Once a person is sensitized to a specific allergen, spontaneous resolution of the allergy occurs only very rarely and this results in a steady accumulation of patient population. Worldwide attention to this affliction is being paid from both the medical and the economic perspectives. In Japan, the most typical seasonal allergic rhinitis is caused by cedar pollen during the spring months of late February to early May. Rough estimates of a 15 to 20% prevalence rate have been reported and hence Japanese cedar pollinosis is deemed as a national disease. The efficacy and cost-effectiveness of the treatment are of great concern to the social medical system of Japan. Previously there have been several reports regarding the cost-effectiveness of new medications and desensitization immunotherapy. The authors have previously reported their experience of treating allergic rhinitis with the Nd:YAG laser and its efficacy. However there are no reports, as of yet, on the cost-effectiveness of this procedure. The authors compared the costs of three typical treatment protocols for cedar pollenosis: Nd:YAG laser treatment, anti-histamine prescription and desensitization immunotherapy. The results revealed that the direct costs associated with the Nd:YAG laser treatment were less compared to the two other treatment protocols. The authors also believe that the indirect economical losses associated with allergic rhinitis such as loss of work force for hospital visits was also lessened with the Nd:YAG laser treatment.

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Phobic postural vertigo treated with autogenic training

Goto Fumiyuki, Nakai Kimiko, Kunihiro Takanobu, Ogawa Kaoru

Cases Journal 1 （ 1 ） 2008年

ISSN 1757-1626

Case presentation: We present a case of a patient who suffered from phobic postural vertigo. A 37-year-old female complained of dizziness. She had started experiencing dizziness almost 3 years She was intractable to many sort of conventional therapy. In the end, her symptom disappeared after introduction of autogenic training.Conclusion: Autogenic training can be a viable and acceptable treatment option for phobic postural vertigo patients who fail to respond to other therapies. This case emphasizes the importance of autogenic training as a method to control symptom of phobic postural vertigo.Background: Patients suffering from dizziness due to vertigo are commonly encountered in the department of otolaryngology. If various clinical examinations do not reveal any objective findings, then the patients are referred to the department of internal medicine or psychiatry. In many cases, the diagnosis is psychological dizziness. Phobic postural vertigo, which was first reported by Brandt T et al in 1994, is supposed to be a type of psychological dizziness. The diagnosis is based on 6 characteristics proposed by Brandt et al. Patients are usually treated with conventional medical therapy, but some cases may be refractory to such a therapy. Psychotherapy is recommended in some cases; however, psychotherapy including autogenic training, which can be used for general relaxation, is not widely accepted. This paper describes the successful administration of autogenic training in a patient suffering from phobic postural vertigo.

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A multidisciplinary approach to carotid body tumors. Report of five cases

Tomita Toshiki, Ozawa Hiroyuki, Tagawa Takamasa, Sakamoto Koji, Ogawa Kaoru

Journal of Otolaryngology of Japan 110 （ 12 ） 743 - 751 2007年12月

ISSN 0030-6622

We performed a retrospective review of five patients with carotid body tumors at our institution between 1997 and 2005. Out of the five patients, three patients were treated by surgical resection of the tumor, and 2 patients were observed. It would seem that it is difficult to suspect this disease based only on the clinical findings, because the disease was suspected in only one patient at the first medical examination. Imaging tests are important for establishment of the diagnosis. Color Doppler sonography and MR angiography in addition to MRI are useful. Angiography and balloon Matas test are important for selection of candidates for the operation. The resected tumors were all classified in Shamblin's group II. Delayed cerebral infarction was caused in one patient postoperatively, although the carotid artery was preserved. The dissection in a tumor-adventitial plane using the bipolar coagulation technique under the microscope was performed in the other two cases. Histological examination of the specimen revealed no tumor cells in the excision stump. Dissection in the tumor-adventitial plane using bipolar coagulation under the microscope is important for carotid artery preservation and radical resection of Shamblin's group I and II tumors. It is necessary to compare the risk of the operation with the problems of observation in the process of decision making and to achieve reliable informed consent. Moreover, it is necessary to examine the indications for operation in individual cases referring to the age, past history, expected Shamblin's classification, and result of the balloon Matas test. A multidisciplinary approach should be used, involving the fields of otolaryngology, radiology, neurosurgery and vascular surgery to treat these patients.

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"Ear popper®", new device to treat otitis media with effusion

Goto Fumiyuki, Yabe Haruna, Goto Kazuyoshi, Ogawa Kaoru

Oto-Rhino-Laryngology Tokyo 50 （ 5 ） 330 - 332 2007年10月

ISSN 0386-9687

Otitis media with effusion is a common disease and is the most common cause of hearing impairment among children. It is important to treat this condition in children to provide them a better quality of life. "Ear popper®" is a new device distributed in the US for non-surgical treatment of middle ear effusion. The device allows easy insufflation of the eustachian tube. We used the "Ear popper®" for the treatment of middle ear effusion in 18 patients. The patients ranged in age from 2 to 9 years old, and were composed of 8 males and 10 females. Successful insufflation without any problems was achieved in 17 out of the 18 patients at our hospital. This was confirmed by visual observation of the tympanic membrane, impedance audiometry and pure-tone audiometry. The new device is portable and easy to use. Although in this clinical trial, the use of this device was restricted only to doctors at the hospital, we are currently attempting to introduce the use of this device at home by the patients by themselves, just as in the U.S.A. We consider that the home treatment of persistent otitis media with effusion in children with "Ear popper®" is highly efficacious.

Development of solitary plasmacytoma in the internal auditory canal and inner ear after allogeneic hematopoietic stem cell transplantation for plasma cell leukemia

Masuda Masatsugu, Inoue Yasuhiro, Tanosaki Ryuji, Kanzaki Sho, Ogawa Kaoru

Japanese Journal of Clinical Oncology 37 （ 9 ） 701 - 703 2007年09月

ISSN 0368-2811

Here we report the first case of the development of intracranial solitary plasmacytoma in the inner ear after allogeneic stem cell transplantation (allo-SCT) in a 39-year-old Japanese female with primary plasma cell leukemia (PCL). A point to note is that this is not a case on multiple myeloma but on PCL. She was successfully treated with local irradiation and survived more than 6 years from the time of diagnosis and transplantation. This case elucidates the biology of PCL and stresses the need for an individual approach to the clinical management of patients with plasma cell neoplasm undergoing allo-SCT.

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Liposarcoma of the retropharyngeal space

Ozawa Hiroyuki, Soma Keiko, Ito Mari, Ogawa Kaoru

Auris Nasus Larynx 34 （ 3 ） 417 - 421 2007年09月

ISSN 0385-8146

Liposarcoma is a soft tissue malignant tumor that is common in adults, though the incidence of this type of tumor in the head and neck region is extremely low. Herein, we report a case of myxoid liposarcoma occurring in the retropharyngeal space. We were unable to make a proper diagnosis of this tumor prior to surgery because of the radiographic findings and the anatomical location resembled those of neurogenic tumor. Myxoid liposarcoma often recurs. So its excision must be carried out carefully and radical dissection is recommended. In the past, liposarcomas arising in the retropharyngeal space were not radically resected because the extent of resection in the head and neck area risked poor functional outcome. In the present case, functional resection and radiotherapy were performed and proved to be efficacious in that no recurrence was observed for 2 years.

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Clinical study of 28 cases of cervical lymph node metastasis from an unknown primary carcinoma

Tagawa Takamasa, Tomita Toshiki, Yamaguchi Hiroshi, Ozawa Hiroyuki, Sakamoto Koji, Ogawa Kaoru, Fujii Masato

Nippon Jibiinkoka Gakkai kaiho 110 （ 7 ） 506 - 512 2007年07月

ISSN 0030-6622

From 1989 to 2005, 28 patients--20 men and 8 women--with cervical lymph node metastasis from an unknown primary carcinoma were treated and studied retrospectively. In histological diagnosis, open biopsy was conducted in 11 patients and non-open biopsy (FNA or frozen section diagnosis during surgery) in 17. Blind biopsy under general anesthesia was conducted in 10 patients, showing one primary tumor in the nasopharynx. Tonsillectomy for diagnosis was not done. In region of maximum-size lymph node metastasis, the upper cervical region accounted for 22 cases (79%). The N stage of cervical lymph nodes was as follows: N2a in 4, N2b in 14, N2c in 3, and N3 in 7. The histopathological diagnosis of cervical lymph node was as follows: squamous cell carcinoma in 21, adenocarcinoma in 3, mucoepidermoid carcinoma in 2, and others in 2. Therapy was as follows: only neck dissection in 7, neck dissection with postoperative radiation therapy in 13, and irradiation and chemotherapy in 8. All patients treated with irradiation and chemotherapy had been judged to be inoperable. Seven patients were found to have a subsequent primary tumor. Primary tumor sites were as follows: tonsils in 3 and upper gingiva, base of tongue, lung, and nasopharynx in 1 each. FDG-PET was conducted in 7 patients but revealed no primary tumor. Overall 5-year survival in this study was 46%. We should pay particular attention to the tonsils for detecting primary tumors in patients with cervical metastasis from an unknown primary carcinoma.

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Decreased expression of connexin-30 and aberrant expression of connexin-26 in human head and neck cancer

Ozawa Hiroyuki, Matsunaga Tatsuo, Kamiya Kazusaku, Tokumaru Yutaka, Fujii Masato, Tomita Toshiki, Ogawa Kaoru

Anticancer Research 27 （ 4 B ） 2189 - 2195 2007年07月

ISSN 0250-7005

Background: The relation of connexins and carcinogenesis has been studied in various organs and cell lines, with connexins currently being considered tumor suppressors. Materials and Methods: The expression of connexin-26 (Cx26) and connexin-30 (Cx30) in human head and neck carcinomas, as well as in adjacent normal mucosa, was evaluated by immunohistochemistry. Furthermore, the expression of these connexins with regard to apoptosis and cell differentiation was investigated. Results: In the cancer tissues, Cx30 expression was drastically reduced compared to apparently normal mucosa while Cx26 expression was almost the same. The intracellular distribution patterns of Cx26 and Cx30 in cancer cells differed between cancer locations. In the cancer tissues, expression of Cx26 and Cx30 was not related to apoptosis assessed by TdT-mediated dUTP-biotin nick end labeling (TUNEL) reaction or to cell differentiation assessed by immunoreaction to involucrin. Conclusion: The present results suggest that connexins may play a role in the carcinogenesis of head and neck cancer.

Clinical study of 28 cases of cervical lymph node metastasis from an unknown primary carcinoma

Tagawa Takamasa, Tomita Toshiki, Yamaguchi Hiroshi, Ozawa Hiroyuki, Sakamoto Koji, Ogawa Kaoru, Fujii Masato

Journal of Otolaryngology of Japan 110 （ 7 ） 503 - 505 2007年07月

ISSN 0030-6622

From 1989 to 2005, 28 patients-20 men and 8 women-with cervical lymph node metastasis from an unknown primary carcinoma were treated and studied retrospectively. In histological diagnosis, open biopsy was conducted in 11 patients and non-open biopsy (FNA or frozen section diagnosis during surgery) in 17. Blind biopsy under general anesthesia was conducted in 10 patients, showing one primary tumor in the nasopharynx. Tonsillectomy for diagnosis was not done. In region of maximum-size lymph node metastasis, the upper cervical region accounted for 22 cases (79%). The N stage of cervical lymph nodes was as follows : N2a in 4, N2b in 14, N2c in 3, and N3 in 7. The histopathological diagnosis of cervical lymph node was as follows : squamous cell carcinoma in 21, adenocarcinoma in 3, mucoepidermoid carcinoma in 2, and others in 2. Therapy was as follows : only neck dissection in 7, neck dissection with postoperative radiation therapy in 13, and irradiation and chemotherapy in 8. All patients treated with irradiation and chemotherapy had been judged to be inoperable, Seven patients were found to have a subsequent primary tumor. Primary tumor sites were as follows : tonsils in 3 and upper gingiva, base of tongue, lung, and nasopharynx in 1 each. FDG-PET was conducted in 7 patients but revealed no primary tumor. Overall 5-year survival in this study was 46%. We should pay particular attention to the tonsils for detecting primary tumors in patients with cervical metastasis from an unknown primary carcinoma.

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A novel drug therapy for recurrent laryngeal nerve injury using T-588

Mori Yuko, Shiotani Akihiro, Saito Koichiro, Araki Koji, Ikeda Ken, Nakagawa Masaya, Watabe Kazuhiko, Ogawa Kaoru

Laryngoscope 117 （ 7 ） 1313 - 1318 2007年07月

ISSN 0023-852X

OBJECTIVES/HYPOTHESIS: We have previously shown that gene therapy using Insulin-like growth factor (IGF)-I, glial cell line-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF), or a combination of these trophic factors, is a treatment option for recurrent laryngeal nerve (RLN) palsy. However, there remain some difficulties preventing this option from becoming a common clinical therapy for RLN injury. Thus, we need to develop novel treatment option that overcomes the problems of gene therapy.R(-)-1- (benzothiophen-5-yl)-2-[2-N,N-diethylamino]ethoxy]ethanol hydrochloride (T-588), a synthetic compound, is known to have neuroprotective effects on neural cells. In the present study, the possibility of new drug treatments using T-588 for RLN injury was assessed using rat models. STUDY DESIGN: Animal study. METHODS: Animals were administered T-588 for 4 weeks. The neuroprotective effects of T-588 administration after vagal nerve avulsion and neurofunctional recovery after recurrent laryngeal nerve crush were studied using motoneuron cell counting, evaluation of choline acetyltransferase immunoreactivity, the electrophysiologic examination, and the re-mobilization of the vocal fold. RESULTS: T-588 administration successfully prevented motoneuron loss and ameliorated the choline acetyltransferase immunoreactivity in the ipsilateral nucleus ambiguus after vagal nerve avulsion. Significant improvements of motor nerve conduction velocity of the RLN and vocal fold movement were observed in the treatment group when compared to controls. CONCLUSION: These results indicate that oral administration of T-588 might be a promising therapeutic option in treating peripheral nerve injury.

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Phobic postural vertigo in Japan

Goto Fumiyuki, Yabe Haruna, Nakai Kimiko, Kunihiro Takanobu, Ogawa Kaoru

Equilibrium Research 66 （ 3 ） 123 - 129 2007年06月

ISSN 0385-5716

Introduction: Dizziness and vertigo are symptoms of various psychiatric conditions like major depression, somatoform disorder, anxiety disorders, and so on. Phobic postural vertigo (PPV) was first reported by Brandt T et al. in 1994. PPV occurs chiefly in patients with an obsessive-compulsive or narcissistic personality. The diagnosis is based on six characteristics proposed by Brandt et al. The key for a correct diagnosis is spontaneous (sometimes stimulus-induced) postural vertigo and unsteadiness in maintaining an upright position and walking. Methods: The characteristics of patients with PPV were reviewed in 16 patients from June 2002 to November 2006 in our hospital. Some psychological evaluations were preformed by a self-rating questionnaire. MAS (Manifest Anxiety Scale) was used to evaluate the level of anxiety, and the Japanese version of MOCI (Maudsley's Obsessional Compulsive Inventory) was employed to evaluate the obsessive-compulsive personality. Results: We encountered 16 PPV patients. Fourteen were female and 2 were male. The average age was 55±15.5 years old. Many of the patients showed depression and a high level of anxiety. The average MOCI score was 10.8, and this indicated an obsessive-compulsive or narcissistic personality. Treatment involved drug therapy with SSRI (Selective serotonin reuptake inhibitors), antidepressants, anxiolytics like benzodiazepine (BZD), and psychotherapy including cognitive behavior therapy and autogenic training. Conclusion: The diagnosis of PPV was important to improve the prognosis. The key for a correct diagnosis is not anxiety but the subjective dizziness itself. An obsessional personality is often observed.

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Temporal changes of subjective visual vertical in patients with vestibular neuritis

Goto Fumiyuki, Higashino Kazutaka, Kunihiro Takanobu, Hayashi Yujiro, Saito Akira, Masuda Kanako, Kanzaki Jin, Ogawa Kaoru

Equilibrium Research 66 （ 3 ） 116 - 122 2007年06月

ISSN 0385-5716

Introduction: During the acute phase, patients with vestibular neuritis suffer from severe vertigo. With time, the intensity of vertigo gradually decreases. The aims of the present study were: (1) to determine whether changes in the subjective visual vertical (SVV) system reflect how patients subjectively experience vertigo, and (2) to determine the relationship between changes in SVV and canal paralysis (CP). Methods: Our subjects comprised 23 patients with vestibular neuritis. We measured the SVV of each patient several times to evaluate the recovery of SVV and CP over time. The intensity of vertigo was graded numerically as follows: (1) 5 - very intense (patient cannot stand with eyes open), (2) 4 - intense (patient cannot stand with eyes closed), (3) 3 - moderate (patient can stand with eyes closed), (4) 2 - slight vertigo, and (5) 1 - no vertigo. We also evaluated CP in 10 patients using the thermal caloric test. Results: The temporal process of SVV recovery was grouped into three categories: (1) small fluctuation/rapid recovery (N=7); (2) small fluctuation/delayed recovery (N=8); and (3) large fluctuation (N=8). For CP recovery, we observed cases that failed to recover (N=4) and others that did recover (N=6). When tested 30 days and 1 year after the initial examination, the CP recovery group displayed larger SVV fluctuations accompanied by intense subjective vertigo, whereas the group that did not recover exhibited fewer fluctuations accompanied by weak vertigo. Conclusions: SVV represents the subjective perception of the direction of gravity. Fluctuations in SVV, rather than absolute SVV, correlate well with the subjective intensity of vertigo. This suggests that, during the recovery process, fluctuations in SVV, rather than the dysfunction itself, causes dizziness. Measuring SVV is very straightforward and quantifying SVV fluctuations is an effective measure of the intensity of vertigo.

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Laryngeal carcinoma presenting as a large anterior neck abscess

Nakagawa Hideki, Shiotani Akihiro, Araki Koji, Kusuyama Toshiyuki, Fukuda Hiroyuki, Ogawa Kaoru

Auris Nasus Larynx 34 （ 2 ） 249 - 251 2007年06月

ISSN 0385-8146

Laryngeal carcinoma presenting as a cervical abscess is rare, so that its diagnosis is not easy. We described a case of laryngeal squamous cell carcinoma presenting as a prelaryngeal large abscess. Markedly swollen false vocal fold inhibited fiberscopic examination of the vocal folds. CT scan indicated destruction of the thyroid cartilage. Although biopsies from the abscess did not reveal malignancy, laryngeal squamous cell carcinoma was confirmed by laryngomicrosurgery with laryngeal vestibulectomy. The patient was treated by total laryngectomy with neck dissection followed by radiotherapy. The abscess was thought to be formed not by direct extension and necrosis of the tumor, but by the leakage of air and mucus through the fistula on the destroyed thyroid cartilage. Precise observation and biopsy under directscopic vestibulectomy played an important role in diagnosis of malignancy inherent in severe inflammatory tissues.

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Appropriate diameter for screws to fix the maxilla following Le Fort I osteotomy

Nagasao Tomohisa, Miyamoto Junpei, Hikosaka Makoto, Nagasao Maki, Tokumaru Yutaka, Ogawa Kaoru, Nakajima Tatsuo

Journal of Cranio-Maxillofacial Surgery 35 （ 4-5 ） 227 - 233 2007年06月

ISSN 1010-5182

Background: After Le Fort I osteotomy, there is sometimes a secondary deformity (relapse), with the lower segment deviating from the intraoperatively fixed position. It is hyopothesized that the structural stability of the reconstructed maxilla is affected by the diameter of the fixation screws. The present study aims to elucidate the relationship between the diameters of the screws and the structural stability of the maxilla after Le Fort I osteotomy. Methods: 3D models were produced on a workstation from 20 dry skulls and a Le Fort I operation was simulated on them. The upper and lower segments of the divided maxilla in each of the 20 models were connected using four plates and 16 screws. Five different diameters of the fixation screws were tested. Thus altogether 100 models were produced. A 180 N load was applied to the molar region for each model. Using finite element analysis, the resultant stresses and deviations of the lower segments were calculated. Finally, referring to these values, the relationships between screw diameters and stability of the lower segment were evaluated. Result: The stability of the lower segment was greatest when the diameter of the fixation screws was equal to the thickness of the bone at each fixation site. Conclusion: In performing Le Fort I osteotomy, it is recommended that bone thickness is measured at each fixation site in advance, and the diameter of the fixation screws matched accordingly; thereby optimum stability of the reconstructed maxilla can be anticipated.

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Creatine and tempol attenuate noise-induced hearing loss

Minami Shujiro B., Yamashita Daisuke, Ogawa Kaoru, Schacht Jochen, Miller Josef M.

Brain Research 1148 （ 1 ） 83 - 89 2007年05月

ISSN 0006-8993

To define the role of free radical formation and potential energy depletion in noise induced hearing loss (NIHL), we measured the effectiveness of tempol (free radical scavenger) and creatine (enhances cellular energy storage) alone and in combination to attenuate NIHL. Guinea pigs were divided into four treatment groups: controls, 3% creatine diet (2 weeks prior to noise exposure), tempol (3 mM in drinking water 2 weeks prior to exposure), and creatine plus tempol and exposed to 120 dB SPL one-octave band noise centered at 4 kHz for 5 h. The noise-only control group showed frequency-dependent auditory threshold shifts (measured by auditory brainstem response, ABR) of up to 73 dB (16 kHz) on day 1, and up to 50 dB (8 kHz) on day 10. Creatine-treated subjects had significantly smaller ABR threshold shifts on day 1 and on day 10. Tempol alone significantly reduced ABR threshold shifts on day 10 but not on day 1. ABR shifts after combination treatment were similar to those in the creatine group. Hair cell loss on day 10 was equally attenuated by creatine and tempol alone or in combination. Our results indicate that the maintenance of ATP levels is important in attenuating both temporary and permanent NIHL, while the scavenging of free radicals provides protection from permanent NIHL.

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Role of salivary gland scintigraphy with Tc-99m pertechnetate in determining treatment of solitary parotid gland tumors

Nakahara Tadaki, Suzuki Takayuki, Hashimoto Jun, Shigematsu Naoyuki, Tomita Toshiki, Ogawa Kaoru, Kubo Atsushi

Clinical Nuclear Medicine 32 （ 5 ） 363 - 366 2007年05月

ISSN 0363-9762

PURPOSE OF THE REPORT: Although salivary gland scintigraphy has been useful for the diagnosis of Warthin's tumor (WT), there are no reports concerning the clinical impact of this scintigraphy. MATERIALS AND METHODS: We retrospectively investigated 127 patients with solitary parotid tumors who had undergone salivary gland scintigraphy. RESULTS: For patients who had surgery, the sensitivity, specificity, and accuracy of differentiating WT from non-WTs were 95%, 91%, and 92%, respectively. There was a significant correlation between scintigraphic results and the treatment decisions made for the 127 patients (χ = 16.5, P = 0.00026). The proportion of WT patients among those who underwent surgery was 19%, whereas 42% of those who were suspected to have WT from scintigraphy were followed without surgical intervention. The main reasons for clinical observation in these patients were comorbidity, refusal of surgery, and age. CONCLUSIONS: The high percentage of nonsurgical patients suspected to have WT can be explained by the high diagnostic accuracy of salivary gland scintigraphy, which is useful for determining further management when surgery is contraindicated or is refused by the patient.

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Evaluation of postural cerebral hemodynamics by near-infrared spectroscopy in patients with dizziness with or without orthostatic dysfunction

Goto Fumiyuki, Asama Youji, Ogawa Kaoru

Equilibrium Research 66 （ 2 ） 52 - 58 2007年04月

ISSN 0385-5716

Introduction: Using the near-infrared spectroscopy (NIRS), we evaluated the central circulation of patients with either dizziness and orthostatic dysfunction or dizziness alone. Methods: We used the NIRO-200 NIRS instrument to monitor bilateral oxygenation changes in cerebellar hemoglobin levels in 57 subjects during an orthostatic exam. Of the 46 patients with dizziness, 8 had orthostatic dysfunction. To determine whether NIRS is useful for evaluating patients with dizziness, we compared blood pressure changes with orthostatic dysfunction test scores. Diagnostic criteria for orthostatic dysfunction were as follows: (1) a greater than 21 mmHg reduction in systemic blood pressure, (2) a greater than 16 mmHg reduction in pulse pressure, and (3) a greater than 21 beats per minute increase in pulse rate. Results: We observed four different types of changes in oxy-hemoglobin during the orthostatic test. In type I, a rapid temporal decline of oxy-hemoglobin was followed by rapid recovery. In type II, the decline of oxy-hemoglobin was followed by recovery of oxy-hemoglobin levels above the initial levels. In type III, the decline of oxy-hemoglobin was followed by recovery of oxy-hemoglobin levels below the initial levels. In type IV, the decline of oxy-hemoglobin persisted without recovery. Most of the control patients displayed type I changes. Patients with orthostatic hypertension more frequently displayed type II and IV changes. Nine of the dizzy patients had a positive orthostatic test. Of these patients, 3 displayed type II changes and 6 displayed type IV changes. Conclusions: In normal subjects, cerebellar circulation remains stable, at least if orthostatically induced changes in blood pressure remain within normal ranges due to autoregulation. We suspect that dysfunctional autoregulation was responsible for the reduced cerebellar circulation in patients with orthostatic dysfunction. We propose that NIRS is an excellent, non-invasive tool for evaluating patients with dizziness that present with orthostatic dysfunction.

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Analysis of the orbital floor morphology

Nagasao Tomohisa, Hikosaka Makoto, Morotomi Tadaaki, Nagasao Maki, Ogawa Kaoru, Nakajima Tatsuo

Journal of Cranio-Maxillofacial Surgery 35 （ 2 ） 112 - 119 2007年03月

ISSN 1010-5182

Introduction: For the repair of large orbital floor defects due to blow-out fractures or those involved by tumours, it is necessary to understand the detailed morphology. The purpose of the present study was to elucidate how age and gender affect its three-dimensional morphology. Methods: The 3-D computer tomography data of 305 orbits of 182 patients were included in the study. Using the CT data, the orbital floor angle (the angle between the orbital floor and the horizontal plane) and the location of the most inferior point of the orbital floor were measured. Patients were classified into subgroups according to their gender and age. Data were compared among the subgroups. Results: The orbital floor angle was greater in males than in females, and in children than in adults. The location of the lowest point of the orbital floor moves postero-inferiorly with increasing age. Conclusion: The present study demonstrated that gender and age affects morphology of the orbital floor. These findings should be useful for reconstruction of the orbital floor.

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Planned neck dissection after weekly docetaxel and concurrent radiotherapy for advanced oropharyngeal cancer

Tomita Toshiki, Ozawa Hiroyuki, Sakamoto Koji, Fujii Ryoichi, Ogawa Kaoru, Fujii Masato, Yamashita Taku, Shinden Seiichi

Journal of Otolaryngology of Japan 110 （ 3 ） 95 - 102 2007年03月

ISSN 0030-6622

Small oropharyngeal carcinomas with advanced neck metastases (stage N2 or greater) are common. Patients with small T with large N oropharyngeal carcinoma have high rates of local control but lower rates of regional control when treated with chemoradiotherapy. Clinical assessment after chemoradiotherapy cannot ensure the absence of neck disease. In the last 5 years, we have treated patients with T1-2 with N2-3 oropharyngeal carcinoma with weekly docetaxel radiotherapy followed by planned neck dissection (PND). Our objectives were to clarify the pathologically complete response (CR) rate of neck metastasis after weekly docetaxel radiotherapy, to identify the clinical predictor of residual neck disease, and to determine the mobidity of planned neck dissection. After chemoradiotherapy, all 12 patients had a complete response at the primary site. We conducted 15 neck dissections. Of these, 6 (40%) had positive nodes. The pathological CR rate of neck metastasis was 58.3%, whereas overall 2-year neck control rate was 91.7%. These findings lend support to the role of PND after chemoradiotherapy in N2-3 neck disease. After chemoradiotherapy, clinical parameters including TN status, feasibility of chemoradiotherapy, largest lymph node size or size reduction in MRI, did not identify patients with residual neck disease. We conducted selective neck dissection (SND) in 80% of patients. SND as PND appears to be appropriate in this group of patients because of the low incidence of complications. A further cohort study including the comparison of PND nonenforcement group is necessary to clarify the validity of the addition of PND in weekly docetaxel radiotherapy.

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Cholesterol granuloma surrounding the endolymphatic sac

Kanzaki Sho, Araki Yasutomo, Okamoto Yasuhide, Kurita Akihiro, Ogawa Kaoru

Auris Nasus Larynx 34 （ 1 ） 95 - 100 2007年03月

ISSN 0385-8146

We report a unique case of cholesterol granuloma (CG) surrounding the endolymphatic sac (ES). A 49-year-old man presented with the left side of sensorineural hearing loss, tinnitus, and vertigo. Magnetic resonance and computed tomography imaging revealed a CG surrounding the left ES. The patient initially underwent left transmastoid surgical resection of the tumor. At the time of surgery, brown fluid was aspirated from the tumor, but no other tumors were found. Histopathological examination revealed that the tumor contained cholesterol crystals, confirming the diagnosis of CG. At his 12-month postoperative follow-up, there was no evidence of recurrence. We discuss the radiology, pathology, and surgical removal of CGs surrounding ES.

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Sendai virus vector-mediated transgene expression in the cochlea in vivo

Kanzaki Sho, Shiotani Akihiro, Inoue Makoto, Hasegawa Mamoru, Ogawa Kaoru

Audiology and Neurotology 12 （ 2 ） 119 - 126 2007年02月

ISSN 1420-3030

We injected a recombinant Sendai virus (SeV) vector into the guinea pig cochlea using two different approaches - the scala media and scala tympani - and investigated which cell types took up the vector. The hearing threshold shift and distribution of transfected cells in animals using the scala media approach were different compared to those using the scala tympani approach. SeV can transfect very different types of cells, including stria vascularis, spiral ganglion neurons, and sensory epithelia of the organ of Corti, and fibrocytes of the scala tympani. Because SeV vectors can potentially deliver stimuli to the cochlea to induce hair cell regeneration, it may be a powerful tool for repairing the organ of Corti.

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A case of glossopharyngeal zoster diagnosed by detecting viral specific antigen in the pharyngeal mucous membrane

Nakagawa Hideki, Nagasao M., Kusuyama T., Fukuda H., Ogawa K.

Journal of Laryngology and Otology 121 （ 2 ） 163 - 165 2007年02月

ISSN 0022-2151

Glossopharyngeal nerve paralysis caused by varicella zoster virus reactivation is rare. We present a case of glossopharyngeal zoster confirmed by direct immunofluorescence staining for virus antigens. A 35-year-old man presented with right-sided, severe swallowing pain and dysgeusia. Physical examination showed a loss of ipsilateral gag reflex. White spots on the posterior wall of the right pyriform sinus were seen by laryngofibroscopy, and a loss of taste on the right posterior part of the tongue was confirmed by gustometry using the filter paper disc method. The varicella zoster virus antigen was revealed by direct immunofluorescence staining by fluorescein isothiocyanate labelled mouse monoclonal antibody specific for varicella zoster virus glycoprotein, using samples obtained from the mucosal lesion by abrasion with a cotton swab. The patient was treated by intravenous administration of acyclovir. His throat pain and dysgeusia completely resolved. We discuss the advantages of direct immunofluorescence staining for varicella zoster virus antigen for the diagnosis of glossopharyngeal zoster.

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Pulse-oximetery is useful in determining the indications for adeno-tonsillectomy in pediatric sleep-disordered breathing

Saito Hideyuki, Araki Kouji, Ozawa Hiroyuki, Mizutari Kunio, Inagaki Kouji, Habu Noboru, Yamashita Taku, Fujii Ryouichi, Miyazaki Soichiro, Ogawa Kaoru

International Journal of Pediatric Otorhinolaryngology 71 （ 1 ） 1 - 6 2007年01月

ISSN 0165-5876

Objective: Although first line therapy of sleep-disordered breathing (SDB) in children is adeno-tonsillectomy, the indications for this operation have not yet been clearly established. We investigated whether pulse-oximetry is useful for determining the optional treatment modality for pediatric SDB. Method: Two hundred and thirty-two children presenting with snoring and gasping had their oxygen saturation levels examined during sleep. Among them, 86 underwent on adeno-tonsillectomy and were evaluated pre- and post-surgery. We also examined 25 healthy children as controls. Results: Little desaturation was observed in healthy children. The difference in oxygen saturation levels of the patients between pre- and post-surgery was closely correlated with the pre-surgery levels. We examined the reaction operation characteristics and concluded that children with an oxygen desaturation index of 4% or more (ODI4) of more than 1.5 and/or ODI3 of more than 3.5 should undergo surgery. Conclusion: Pulse-oximetry is useful in determining the indications for adeno-tonsillectomy.

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Hypothyroidism after radiotherapy for patients with head and neck cancer

Ozawa Hiroyuki, Saitou Hideyuki, Mizutari Kunio, Takata Yasunori, Ogawa Kaoru

American Journal of Otolaryngology - Head and Neck Medicine and Surgery 28 （ 1 ） 46 - 49 2007年01月

ISSN 0196-0709

We report on 2 cases of hypothyroidism presenting clinical symptoms that occurred after radiotherapy for cancer of the head and neck and on the results of estimating thyroid function in patients with head and neck cancer who received radiotherapy. The first patient underwent total laryngectomy for laryngeal cancer without sacrificing the thyroid gland and partial gastrectomy for gastric cancer. Radiotherapy of the neck was carried out postoperatively. Two years later, the patient developed chest pain; pericardial effusion was detected, leading to a diagnosis of myxedema caused by hypothyroidism. The second patient received radiotherapy alone for laryngeal cancer. Two months later, low serum sodium concentration and anemia were detected in this patient. The cause of these changes was subsequently found to be hypothyroidism. Based on our experience with these 2 cases, we measured thyroid function in 35 patients who had undergone neck radiation for head and neck cancer at our hospital over the past 10 years. Hypothyroidism was observed in 13 of the 35 patients (37%). The prevalence of hypothyroidism was 46% (6/13) for patients treated with both radiation and surgery, as compared with 32% (7/22) for those who received radiation alone. The risk factors responsible for hypothyroidism were not evident from the statistical analysis of these cases. We believe that thyroid function should be evaluated periodically in patients who have undergone neck radiation because it is often difficult to diagnose hypothyroidism only from clinical symptoms.

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Malignant tumors of the parapharyngeal space

Tomita Toshiki, Sakamoto Koji, Fujii Ryoichi, Ozawa Hiroyuki, Ogawa Kaoru, Fujii Masato

Toukeibu Gan 33 （ 4 ） 493 - 498 2007年

ISSN 1349-5747

Most parapharyngeal space tumors are benign, and malignancies are rare. We report the results of a retrospective review of patients with primary parapharyngeal space malignant tumors treated at our institution from 1994 to 2007. During this period, 42 patients seen at our institution were found to have parapharyngeal space tumors. Six tumors (14.3%) were malignant and 36 (85.7%) were benign. Six of 21 (28.6%) prestyloid tumors were malignant, and malignant tumors were all found in the prestyloid region in MRI. There were three carcinoma ex pleomorphic adenomas and one each of salivary duct carcinoma and liposarcoma and chordoma. Four of the six tumors were diagnosed as benign preoperatively. Prestyloid parapharyngeal space tumors should be indicated for surgery even if they are asymptomatic, because preoperative diagnosis is difficult. It was difficult to deal with tumors that were revealed to be malignant postoperatively. Postoperative adjuvant therapy should be considered case by case by referring to the histology and surgical margin, because malignant parapharyngeal space tumors are heterogeneous. If tumors recur, it is important to follow up strictly to salvage them.

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Survey of patients wearing hearing aids applied with and without financial support from the hearing-handicapped approval law

Goto Fumiyuki, Yabe Haruna, Ogino Tamotsu, Ogawa Kaoru

Practica Oto-Rhino-Laryngologica 100 （ 8 ） 623 - 628 2007年

ISSN 0032-6313

In Japan, there is a government-mandated financial support system to help hearing-handicapped patients. In this welfare law, patients with severe hearing loss are categorized into three grades according to severity of hearing disturbance. Patients in each grade have the right to obtain financial support. Obtaining financial aid is a two-step process. First, the patient must apply for a certificate or license indicating that he/she is indeed hearing handicapped. It usually takes a few weeks to receive this license. Second, the patient must complete a financial support application form, which takes about one month for government approval. A doctor must sign both of these application forms. Between January 2005 and April 2006, we surveyed patients consulting our office for hearing aid counseling to assess the current situation and satisfaction of patients who bought hearing aids using governmental financial support. The patients graded their experience on a 5-point satisfaction scale. Among the eighty-nine patients who consulted our office, 22 (24.7%) patients applied for support; all 22 of these patients qualified as having a severe hearing-handicap. The average ages of patients certified as hearing handicapped and patients not certified as hearing handicapped were 80.9±7.7 years and 75.1±23.3 years, respectively. It took, on average, another 49 days to obtain financial support. Patients receiving governmental financial support rated their satisfaction significantly higher than did patients who did not receive support. The average amount of financial support was 40,736 yen ($340). A small amount of financial support can increase patient satisfaction. To promote the government-mandated financial support system for the hearing handicapped, doctors should show more interest in this law. Doctors should also actively guide and encourage certified patients in applying for governmental financial support for hearing aids, all with long-term goal of helping these patients achieve a better quality of life.

Treatment of four cases of intractable Meniere's disease with a new middle ear pressure device, Meniett®

Yabe Haruna, Goto Fumiyuki, Hayashi Ken, Kunihiro Takanobu, Ogawa Kaoru

Practica Oto-Rhino-Laryngologica 100 （ 6 ） 491 - 495 2007年

ISSN 0032-6313

It is not easy to treat patients with intractable Meniere's disease. Intratympanic injection of gentamicin or steroid is one option. The other is a surgical procedure like endolymphatic shunt surgery. Middle ear pressure treatment using the Meniett device, which has not been approved by the Japanese government is widely accepted in foreign countries. We had a chance to use this Meniett device under approval of the ethic's committee of Hino Municipal Hospital since September 2004. (Methods) Four patients with intractable Meniere's disease who suffered intensive vertigo attack for more than 5 months with conservative medical treatment were employed in the study. Ages ranged from 67 to 72, with 3 females and 1 male. After a ventilation tube was inserted under local anesthesia, treatment with the Meniett was performed 3 times a day at home. (Results) Two patients improved and 2 slightly improved concerning vertigo attacks. One showed no change, 1 experienced a worsening, and 2 showed slight improvement concerning the hearing level. (Conclusion) The Meniett device is less invasive and may be suitable for elderly patients who prefer conservative treatment. The mechanism involved in the reduction of vertigo attacks is not clear so far, but we speculate that middle ear pressure may suppress serum vasopressin (antidiuretic hormone) secretion and thereby reduce endolymphatic hydrops. It is necessary to accumulate treatment data with the Meniett in Japan to obtain official approval by the government.

Resorption of auditory ossicles and hearing loss in mice lacking osteoprotegerin

Kanzaki Sho, Ito Masako, Takada Yasunari, Ogawa Kaoru, Matsuo Koichi

Bone 39 （ 2 ） 414 - 419 2006年08月

ISSN 8756-3282

Bones conduct sound in the middle ear. The three ossicles-the malleus, incus, and stapes-form a chain that transmits vibrations from the tympanic membrane to the oval window of the inner ear. Little is known about bone remodeling events in these ossicles and about potential effects of osteoporosis on hearing loss. Osteoclastic bone resorption is enhanced in Opg^-/- mice lacking osteoprotegerin, which is a soluble decoy receptor for the osteoclastogenic cytokine RANKL. We asked whether auditory ossicles are resorbed in Opg^-/- mice, and whether these mice suffer from impaired auditory function. All three ossicles in Opg^-/- mice showed thinning, especially at the malleal manubrium and incus body. Most notably, unlike in the case in wild-type mice, the junction between the stapes and the otic capsule was fixed in Opg^-/- mice, and the stapedial footplate was thinner and broader. Radiological analyses revealed that malleal cortical thickness was positively correlated with tibial bone mineral density in Opg^-/- and control littermate mice. Furthermore, progressive hearing loss was detected in Opg^-/- mice starting at 6 to 15 weeks of age. These data suggest that osteoprotegerin plays a crucial role in hearing by protecting the auditory ossicles and otic capsule from osteoclastic bone resorption.

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Clinical experience with silicon pharyngeal tube for pharyngocutaneous fistula and cervical esophagus stenosis

Tomifuji Masayuki, Shiotani Akihiro, Takaoka Takuji, Mori Yuko, Fujimine Takekatsu, Ogawa Kaoru

Nippon Jibiinkoka Gakkai kaiho. 109 （ 6 ） 530 - 534 2006年06月

ISSN 0030-6622

Total laryngectomy or laryngopharyngectomy are commonly performed for the treatment of laryngeal cancer or hypopharyngeal cancer. However pharyngocutaneous fistula and cervical esophageal stenosis have been reported as postoperative complications of these procedures. We used a silicon pharyngeal tube in cases that developed pharyngocutaneous fistula and cervical esophageal stenosis. The pharyngeal tube was useful for controlling aspiration pneumonia and for starting oral feeding in a case of pharyngocutaneous fistula after a total laryngectomy. It was also helpful for starting oral feeding in a case with cervical esophageal stenosis after total laryngopharyngectomy and free jejunum interposition. This patient was able to maintain a good quality of life until re-operation. Adverse effects from the insertion of the tube included a foreign body sensation and pharyngeal pain that was tolerable with the use of NSAIDs for a short time. Silicon pharyngeal tubes are useful for the treatment of pharyngocutaneous fistula and cervical esophageal stenosis.

Adenoviral gene transfer of BDNF and GDNF synergistically prevent motoneuron loss in the nucleus ambiguus

Moro Kazuhisa, Shiotani Akihiro, Watabe Kazuhiko, Takeda Yasuo, Saito Koichiro, Mori Yuko, Ogawa Kaoru

Brain Research 1076 （ 1 ） 1 - 8 2006年03月

ISSN 0006-8993

We have previously shown that neuroprotective effects of an adenoviral glial cell line-derived neurotrophic factor (GDNF) gene transfer on the lesioned adult rat motoneurons in the nucleus ambiguus. In the present study, we examined neuroprotective effects of adenoviral gene transfer of brain-derived neurotrophic factor (BDNF) or/and GDNF to motoneurons in nucleus ambiguus using an adult rat vagal nerve avulsion model. The animals avulsed and inoculated with adenoviral vectors encoding BDNF (AxCAmBDNFME) or/and GDNF (AxCAhGDNF) showed immunolabeling for BDNF or/and GDNF in the nucleus ambiguus on the treated side, respectively, and expression of virus-induced BDNF or/and GDNF mRNA transcripts in the brainstem tissue that contained the nucleus ambiguus of the treated side. The treatment with AxCAhGDNF or AxCAmBDNFME significantly prevented the loss of vagal motoneurons in comparison to the control; the protective effect of AxCAmBDNFME was greater than that of AxCAhGDNF. The combined treatment with AxCAmBDNFME and AxCAhGDNF acted synergistically and significantly larger number of vagal motoneurons was preserved as compared to either AxCAmBDNFME treatment or AxCAhGDNF treatment. The treatment with AxCAmBDNFME or/and AxCAhGDNF after avulsion also suppressed the activity of nitric oxide synthase in lesioned motoneurons in the nucleus ambiguus. These results indicate that adenovirus-mediated BDNF and GDNF gene transfer may prevent the degeneration of motoneurons in humans after either vagal nerve injury or recurrent laryngeal nerve injury.

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Suitability of calcium phosphate cement for injection laryngoplasty in rabbits

Ikeda Asako, Shiotani Akihiro, Mori Yuko, Fujimine Takekatsu, Tomifuji Masayuki, Takaoka Takuji, Kameyama Kaori, Ogawa Kaoru

ORL 68 （ 2 ） 103 - 109 2006年03月

ISSN 0301-1569

Calcium phosphate cement (CPC) consists of powder and liquid, which become an injectable paste after mixing, self-hardening and recrystallizing to calcium hydroxylapatite (CaHA) after injection into a living body. In this study, we investigated the suitability of CPC as an injectable material for injection laryngoplasty using rabbits. All rabbits underwent left recurrent laryngeal nerve section and injection laryngoplasty with CPC. At 7 days, scanning electron microscopic findings revealed that complete recrystallization from CPC to CaHA was achieved in the larynx. At 1, 3, and 6 months, injected CPC stayed in the paraglottic space and did not migrate, and the average remaining CPC volume percentage was 91.7%. Focal foreign body reaction to injected CPC was almost the same as that of autologous fat for all time periods observed. These results indicated that CPC appears to be biocompatible, nonabsorbable, nonmigratory, and suitable for injection laryngoplasty.

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Proinflammatory cytokines expression in noise-induced damaged cochlea

Fujioka Masato, Kanzaki Sho, Okano Hirotaka James, Masuda Masatsugu, Ogawa Kaoru, Okano Hideyuki

Journal of Neuroscience Research 83 （ 4 ） 575 - 583 2006年03月

ISSN 0360-4012

Recent studies have showed that inflammatory responses occur in inner ear under various damaging conditions including noise-overstimulation. We evaluated the time-dependent expression of proinflammatory cytokines in noise-exposed rat cochlea. Among several detected cytokines, real-time RT-PCR showed that interleukin-1beta (IL-1β) and interleukin-6 (IL-6) were significantly induced 3 hr after noise exposure, and quickly downregulated to the basal level. Tumor necrosis factor-alpha (TNF-α) was also slightly upregulated immediately after noise exposure, Immunohistochemical analysis showed that IL-6 expression was distinctively induced within the lateral side of the spiral ligament. Sequential expression analysis showed that IL-6 immunoreactivity was initially found in the cytoplasm of lateral wall cells, including Type IV and III fibrocytes, and expanded broader throughout the lateral wall, finally to the stria vascularis. Because of the negative Iba-1 staining, IL-6 expression in the early-phase was not due to macrophage or microglia activation. IL-6 was also detected in spiral ganglion neurons at 12 and 24 hr after noise exposure. Our data demonstrates the production of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, in early phase of noise overstimulated cochlea. IL-6 expression was observed in the spiral ligament, stria vascularis, and spiral ganglion neurons. These cytokines, produced by the cochlear structure itself in response to noise exposure, may initiate an inflammatory response and have some role in the mechanism of noise-induced cochlear damage.

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Adenoviral GDNF gene transfer enhances neurofunctional recovery after recurrent laryngeal nerve injury

Araki K., Shiotani A., Watabe K., Saito K., Moro K., Ogawa K.

Gene Therapy 13 （ 4 ） 296 - 303 2006年02月

ISSN 0969-7128

To assess the possibility of gene therapy for recurrent laryngeal nerve (RLN) injury, we examined functional and histological recovery after glial cell line-derived neurotrophic factor (GDNF) gene transfer in a rat RLN crush model. Adenoviral vector encoding β-galactosidase gene (AxCALacZ) or human GDNF gene (AxCAhGDNF) was injected into the crush site of the RLN. Neurons in the nucleus ambiguus on the crushed side were labeled with X-gal or GDNF immnohistochemistry after AxCALacZ or AxCAhGDNF injection. Reverse transcription-polymerase chain reaction analysis revealed expression of human GDNF mRNA transcripts in brainstem tissue containing the nucleus ambiguus on the crushed side after AxCAhGDNF injection. Animals injected with AxCAhGDNF displayed significantly improved motor nerve conduction velocity of the RLN and recovery rate of vocal fold movement at 2 and 4 weeks after treatment as compared to controls. AxCAhGDNF-injected animals showed a significantly larger axonal diameter and improved remyelination in crushed RLN as compared to controls. Adenoviral GDNF gene transfer may thus promote laryngeal function recovery after RLN injury. Inoculation of adenoviral vector containing the GDNF gene at the site of damage soon after nerve injury may assist patients with laryngeal paralysis caused by nerve injury during head and neck surgery.

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Treatment of anxiety and depression-related vertigo and dizziness with SSRIs and SNRIs

Goto Fumiyuki, Araki Yasutomo, Saito Akira, Kunihiro Takanobu, Ogawa Kaoru

Equilibrium Research 65 （ 1 ） 17 - 23 2006年02月

ISSN 0385-5716

Recently, vertigo or dizziness has been linked to abnormal serotonin regulation in the hippocampus. According to the DSM-VI and ICD-10, vertigo or dizziness is a common symptom of anxiety disorder, somatoform disorder, and depression. In today's stressful society, we are now observing record increases in the number of patients with depression. Because of this increase, otolaryngologists are now encountering an increasing number of patients with depression-related dizziness or vertigo. We treated 41 patients with depression-related vertigo or dizziness with a selective serotonin reuptake inhibitor (SSRI: paroxetine or fluvoxamine) or a selective norepinephrine reuptake inhibitor (SNRI: milnacipran). We graded the effects of treatment according to three levels: outstanding, effective, or not effective. Besides dizziness, the chief complaints of patients we treated were problems with sleep, headache, heavy headedness, shoulder stiffness, and loss of motivation. Drug effectiveness or the overall recovery rate was defined as the ratio of the number of patients showing outstanding and effective improvements to the total number of patients treated with a particular drug. The overall recovery rate for patients treated with paroxetine was 82% (14/17), for patients treated with fluvoxamine it was 90% (10/11), and for patients treated with milnacipran it was 62% (8/13). Side effects were observed in 22% (9/41) of the patients. Symptoms disappeared in about 2 weeks after drug treatment began. SSRIs and SNRIs are now the drugs-of-choice for treating anxiety- or depression-related vertigo because they are associated with fewer adverse effects than traditional antidepressants. Moreover, when compared to tranquilizers, SSRIs and SNRIs tend to be less habit-forming. As an adjunct to psychological counseling, dizziness associated with psychiatric disorders can also be treated in otolaryngological outpatient clinics with relevant drugs. To effectively treat these dizzy patients, collaboration between the patients' otolaryngologists and psychiatrists or psychological counselors is also important.

Nuclear factor-kappa B nuclear translocation in the cochlea of mice following acoustic overstimulation

Masuda Masatsugu, Nagashima Reiko, Kanzaki Sho, Fujioka Masato, Ogita Kiyokazu, Ogawa Kaoru

Brain Research 1068 （ 1 ） 237 - 247 2006年01月

ISSN 0006-8993

There is increasing evidence to suggest that the expression of many molecules in the lateral wall of the cochlea plays an important role in noise-induced stress responses. In this study, activation of the nuclear transcription factor nuclear factor-kappa B (NF-κB) was investigated in the cochlea of mice treated with intense noise exposure (4 kHz, octave band, 124 dB, for 2 h). The present noise exposure led to remarkable auditory brainstem response threshold shifts and cochlear damage on surface preparations. To assess the effects of noise exposure on NF-κB/DNA binding activity in the cochlea, we prepared nuclear extracts from the cochlea at different time points after noise exposure and carried out an electrophoretic mobility shift assay using a probe specific to NF-κB. NF-κB/DNA binding was significantly enhanced in the cochlea 2-6 h after noise exposure and returned to basal levels after 12 h. Supershift analysis using antibodies against p65 and p50 proteins, which are components of NF-κB, demonstrated that enhancement of NF-κB/DNA binding was at least in part due to nuclear translocation of p65. An immunohistochemical study also showed that nuclear translocation of both p65 and p50 was observed in the lateral wall after noise exposure and that there may be a possible close association between p65 and enhanced inducible nitric oxide synthase expression. These results suggest that NF-κB may have a detrimental role in the response to acoustic overstimulation in the cochlea of mice.

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Surgical management of parapharyngeal space tumors

Tomita Toshiki, Ogawa Kaoru, Tagawa Takamasa, Fujii Masato, Nameki Hideo

Journal of Otolaryngology of Japan 109 （ 2 ） 88 - 95 2006年

ISSN 0030-6622

Despite its rarity, information on the diagnosis of parapharyngeal space tumors such as through imaging and aspiration biopsy cytology, is slowly accumulating. Little detailed examination has been conducted, however, on surgical approach, complications, and sequelae. We report the results of a retrospective review of 27 patients with primary parapharyngeal space tumors-25 with benign disease and 2 with malignant lesions-treated surgically. Surgical approach, postoperative complications, sequelae, and operative indications of parapharyngeal space tumors were examined in 28 operations on the 27 patients. Tumors found in the prestyloid region in CT or MRI are treated as salivary gland or malignant tumors. Those found in the poststyloid region are treated as shwannoma or paraganglioma. The transcervical approach is often used in patients with shwannoma, while a variety of approaches are selected for patients with salivary gland tumors. Complications occur in 50% of patients, however, bias based on pathological diagnosis has not been examined to the degree needed. Sequelae in our series occurred in 46.4% of our patients. Sequela in the patients with shwannoma, however, is 81.8%, compared to 9.1% in patients with salivary gland tumors. Prestyloid parapharyngeal space tumors seem to be "automatically" indicated for surgery, because the surgical risk is lower than the risk of inaction. In poststyloid parapharyngeal space tumors, however, it appears necessary to judge indication for surgery more carefully while considering the social background, age, and occupation of prospective surgical candidates.

Evaluation of 11 dacryocystorhinostomies

Saito Hideyuki, Ogawa Kaoru, Yamashita Taku, Fujii Ryouichi, Habu Noboru

Practica Oto-Rhino-Laryngologica 99 （ 3 ） 211 - 216 2006年

ISSN 0032-6313

We reviewed 11 patients (7 women and 4 men) with acquired dacryostenosis who underwent a dacryo-cysto-rhinostomy (DCR) at Saiseikai Utsunomiya Hospital between May 2000 and April 2004. The etiology was considered chronic inflammation in six, trauma in two and complications of paranasal sinus surgery in two. In addition to lacrymal probing and irrigation, we investigated all patients by anterior rhinoscopy and CT. One patient showed pneumatization in the lacrymal sac on CT and dacryoatresia was confirmed with irrigation. We diagnosed the common canaliculi as the site of atresia, and this was confirmed intraoperatively. We treated 7 cases by traditional extenal DCR (EXT-DCR) and 4 by endonasal endoscopic DCR (EE-DCR). We treated one case of relapsed obstruction with EE-DCR but treated well with the same method. The EXT-DCR cases have not show any recurrence to date. There were two cases of stenosis at the common canaliculi and both were improved after EE-DCR with silicone tube insertion. With EE-DCR, the duration of surgery was shorter and there was no scar formation or facial deformity. We suggest that ENT doctors should pay more attention to diseases of the naso-lacrymal system and cooperate with ophthalmologist when designing treatment regimens.

Infantile congenital petrosal cholesteatoma

Yamazaki Kazuharu, Sato Hiroaki, Murai Kazuo, Ogawa Kaoru

International Journal of Pediatric Otorhinolaryngology 69 （ 12 ） 1703 - 1707 2005年12月

ISSN 0165-5876

Congenital cholesteatoma of the middle ear is frequently seen in younger children including infant. By contrast, that of the petrous bone is rarely seen in younger children. We report an exceptional case occurring in 23-month-old infant who presented with unilateral facial nerve paralysis at about 18-month-old. Computed tomography and magnetic resonance imaging revealed congenital cholesteatoma measuring approximately 2 cm in the area of the right geniculate ganglion. The mass was completely eradicated via the middle fossa approach, which allowed for preservation of hearing. The facial nerve maintained intact during surgery and paralysis showed partial recovery after the operation. To our knowledge, the present case seems to be the youngest case of congenital petrosal cholesteatoma reported, and also demonstrates congenital petrosal cholesteatoma could exhibit facial nerve paralysis in early childhood.

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Isolated vagus nerve paralysis caused by varicella zoster virus reactivation

Nakagawa Hideki, Satoh Mami, Kusuyama Toshiyuki, Fukuda Hiroyuki, Ogawa Kaoru

Otolaryngology - Head and Neck Surgery 133 （ 3 ） 460 - 461 2005年09月

ISSN 0194-5998

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Permanent threshold shift caused by acute cochlear mitochondrial dysfunction is primarily mediated by degeneration of the lateral wall of the cochlea

Okamoto Yasuhide, Hoya Noriyuki, Kamiya Kazusaku, Fujii Masato, Ogawa Kaoru, Matsunaga Tatsuo

Audiology and Neurotology 10 （ 4 ） 220 - 233 2005年07月

ISSN 1420-3030

Mitochondrial dysfunction in the cochlea is thought to be an important cause of sensorineural hearing loss. Recently, we have established a novel rat model with acute hearing impairment caused by exposure to the mitochondrial toxin 3-nitropropionic acid (3-NP) to analyze the mechanism of cochlear mitochondrial dysfunction. Both permanent and temporary threshold shifts were observed in this model depending on the amount of 3-NP used to induce hearing impairment. In this study, we demonstrate cochlear morphological changes in the permanent threshold shift model. Marked degeneration was detected in type 2 fibrocytes in the spiral prominence, type 4 fibrocytes in the spiral ligament, marginal cells and intermediate cells in the stria vascularis 3 h after 3-NP administration; these changes were progressive for at least 14 days. Less prominent degeneration was detected in type 1 and type 3 fibrocytes in the spiral ligament. These results indicate that permanent threshold shift caused by acute cochlear mitochondrial dysfunction is primarily mediated by cellular degeneration in the lateral wall of the cochlea, and suggest that therapy of cochlear hearing loss due to acute energy failure may be achieved through protection and regeneration of the cochlear lateral wall.

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The relationship between subjective visual vertical and roll vection under visual stimulation

Kobayashi Hironari, Goto Fumiyuki, Kunihiro Takanobu, Ogawa Kaoru, Saito Akira, Kanzaki Jin

Equilibrium Research 64 （ 2 ） 57 - 63 2005年04月

ISSN 0385-5716

Previous experiments have established that visual stimulation in the roll plane causes people to feel roll vection. However, few experiments have been aimed at characterizing the relationship between changes in the subjective visual vertical (SVV) and the generation of vection. In this experiment we investigate the relationship between SVV, a quasi-subjective parameter, and vection, the visually induced perception of self-motion. We observed three different patterns of change in SVV. Even with fixed visual stimuli, in many cases SVV changed continuously. These results suggest that conflicts among different sensory inputs produce dynamic changes in the priority of these sensory inputs. The longer vection is perceived, the more predominant the visual sensory input becomes.

A case of cavernous hemangioma presenting acute hearing loss with vertigo

Asama Yohji, Goto Fumiyuki, Kunihiro Takanobu, Ogawa Kaoru

Equilibrium Research 64 （ 2 ） 71 - 75 2005年04月

ISSN 0385-5716

The origin of vertigo is difficult to identify since a similar symptom occurs in either central or peripheral impairment. An initial evaluation of the patient's clinical history, as well as his clinical manifestations are important for correct diagnosis. Final diagnosis typically depends on conventional imaging techniques, such as CT and MRI. Here, we describe a patients whose functional examination was quite helpful to identify the lesion. The patient was case a 44-year-old man with cavernous hemangioma in the brainstem presenting acute hearing loss with vertigo. Initially he was diagnosed as having peripheral vertigo by neurological examinations together with CT images. Later a rare cavernous hemangioma was identified by head MRI. In the process of diagnosis, the result of auditory brainstem response (ABR) strongly suggested brainstem impairment. This case reveals that conventional imaging procedures, such as CT, are inadequate for diagnosis, whereas functional exams, such as the auditory brain stem response (ABR), are quite helpful for clinical evaluation. ABR can work as a screening examination for patients with vertigo to rule out brainstem lesion even in patients with normal hearing.

Local complications in head and neck surgery and the diagnosis procedure combination/prospective payment system

Tomita Toshiki, Ogawa Kaoru

Toukeibu Gan 31 （ 3 ） 357 - 362 2005年

ISSN 1349-5747

The diagnosis procedure combination/prospective payment system (DPC/PPS) that was begun in university hospitals in fiscal 2003 is outlined. The DPC in the 2004 version concerning head and neck cancer was analyzed, and the handling of local complications in postoperative head and neck surgery patients in the DPC/PPS was examined. If major surgery of the head and neck cancer was performed, it often turned out to fall outside the scope of the inclusive evaluation. Moreover, it is understood that the presence of complication is not reflected in the classification in head and neck cancer even though it is common in other diseases to subdivide the diagnosis group classification by the presence of complication. The problem of local complication was examined in the case of oral cancer treatment by our department in 2004. It was clarified that the decision on whether complication was a negative factor of the DPC/PPS depended on the medical treatment expense concerning complication and the balance of the hospitalization period. Moreover, it seemed that cases which did not have complication and were quickly discharged from hospital were a minus in the DPC/PPS, and so improvement plans are necessary.

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Two cases of Meniere's disease with drop attacks

Goto Fumiyuki, Kunihiro Takanobu, Araki Yasutomo, Saito Akira, Ogawa Kaoru

Journal of Otolaryngology of Japan 108 （ 3 ） 222 - 225 2005年

ISSN 0030-6622

Drop attacks are sudden falls without concurrent vertigo whose etiology may be unknown. Drop attacks are also associated with cardiac, cerebrovascular, psychogenic, and vestibular disorders, in addition to seizures. Vestibular-based drop attacks without loss of consciousness can occur in patients with Meniere's disease. We present 2 cases of drop attack in patients with Meniere's disease. Case 1, a 65-year-old man, experienced 4 such attacks and case 2, a 55-year-old woman, experienced 20 within 2 years of Meniere's disease onset. Case 1 enjoyed spontaneous remission. In case 2, selective serotonin reuptake inhibitor (SSRI) administration suppressed attack frequency. Anxiety may predispose individuals to drop attack. Etiologically, inadequate stimulation of otolith organs may induce a sudden vestibule spinal reflex that, in turn, causes sudden falls. To correctly diagnose drop attacks, the patient must exhibit sudden falls, and transient ischemic attack should be carefully ruled out.

Evaluation of the quality of life in sudden deafness patients by HHIA (hearing handicap inventory) and questionnaire

Sato Minako, Ogawa Kaoru, Saito Hideyuki, Yamashita Daisuke, Yuge Isamu, Masuda Masatsugu, Okamoto Yasuhide, Kurita Akihiro

Journal of Otolaryngology of Japan 108 （ 12 ） 1158 - 1164 2005年

ISSN 0030-6622

After treatments, several patients with sudden deafness (SD) continued to have symptoms, including hearing loss, tinnitus and dizziness. These unresolved symptoms and their effect on the quality of life (QOL) in SD patients have not been studied. We evaluated QOL using the Hearing handicap inventory (HHIA) and an original questionnaire in SD patients who had been treated more than 6 months prior to the study. Compared to results in bilateral sensorineural hearing were significantly lower in SD patients (p<0.01). In bil-SNHL, this score peaked two to K) years after onset of disease and decreased thereafter. The score peaked more than 10 years after onset of disease in patients with SD. While hearing and test scores were correlated in bil-SNHL, this was not observed in SD. About half of patients were embarrassed by hearing loss and tinnitus after treatment. Among patients who scored more than 44 points on HHIA, all reported hearing loss and tinnitus. When asked about subjective changes in hearing after treatment, 27% believed their hearing had improved, 60% believed there was no change, and 13% believed their hearing had deteriorated. Cases believing deterioration in hearing also had high scores on HHIA. Sequelae of SD may worsen QOL, driving embarrassed patients to visit other medical facilities in to improve their QOL. Even though hearing may not improve after initial treatment in ears affected by SD, informed consent about the clinical course and audiological follow-up should be done.

Two cases of pulmonary embolism after head and neck surgery

Kanzaki Sho, Kunihiro Takanobu, Imanishi Tomohisa, Yamashita Daisuke, Ogawa Kaoru

Auris Nasus Larynx 31 （ 3 ） 313 - 317 2004年09月

ISSN 0385-8146

Pulmonary embolism (PE) is a prominent cause of morbidity and mortality in surgical patients. Here, we report two cases of PE following head and neck surgery: (1) in case 1, the patient underwent endoscopic sinus surgery (ESS), and (2) in case 2, the patient was suspected PE after resection of the parotid gland and radical neck dissection. Prophylactic compression devices were used during the operation in both cases. In case 1, PE was diagnosed 3 days following surgery after the patient complained of dyspnea while walking. PE was successfully treated by intravenous administration of heparin. In case 2, PE was strongly suspected 13 days following surgery after the patient experienced syncope and chest pain and exhibited abnormal findings on a cardiac echogram. This patient died 18 h after the onset of cardiac symptoms. Despite prophylactic measures taken during surgery, the prognosis was poor for this patient due to numerous high-risk factors (e.g., advanced age, obesity, prolonged immobilization). Although the incidence of postoperative PE in our department during the last 7 years is very low (0.04%), the frequency of postoperative PE in Japan has steadily increased in recent years. PE still is one of the most significant complications leading to morbidity and mortality following surgery. Given the gaining prominence of PE, we conclude that otolaryngologists including those in Japan should be reminded of high-risk factors associated with PE and be made aware of prophylactic treatments newly aimed at reducing the frequency of PE.

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Intramuscular myxoma of scalene muscle

Ozawa Hiroyuki, Fujii Masato, Tomita Toshiki, Ogawa Kaoru

Auris Nasus Larynx 31 （ 3 ） 319 - 322 2004年09月

ISSN 0385-8146

Intramuscular myxoma is a benign mesenchymal tumor that commonly occurs in the larger skeletal muscles, and is rare in the head and neck. A case of intramuscular myxoma in the scalene muscle is described. This is the first report of this tumor arising in that muscle. It is difficult to diagnose pre-operatively from clinical features, CT scan and ultrasonography of the neck because of the lack of characteristic manifestation or radiographic features. Intramuscular myxoma has an infiltrative tendency, so there are several reports of recurrence because of incomplete excision or enucleation. In our case no recurrence was observed for 4 years, since the tumor was removed with the muscle adherent to it.

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A case of Paget's disease presenting hearing loss and vertigo examined by continuous audiometry

Goto Fumiyuki, Kunihiro Takanobu, Ogawa Kaoru

Equilibrium Research 63 （ 3 ） 194 - 201 2004年06月

ISSN 0385-5716

We reported a case of Paget's disease presenting fluctuating hearing loss together with repeated dizziness and vertigo attacks. Pure tone audiometry in this patient was performed successively during follow-up periods. She visited our hospital 13 years ago with slight low tone sensorineural hearing loss in her left ear. Sensorineural hearing loss in her right ear and sensorineural and conductive hearing loss in left side deteriorated. Results of her latest examinations were as follows. Glycerol test was positive and inverted reflex was recorded in her right ear. CT showed severe calcification in skull bone and stenos of bilateral internal auditory canal. Endolymphatic hydrops, compression of VIII nerve in internal auditory canal, damage of cochlear hair cell and changes in middle ear conductive system were possible etiology of hearing loss and vertigo. Oral bisphosphonate is used to prevent deterioration of these symptoms. Evaluation of auditory and vestibular function should be continued.

Hypertrophic chronic pachymeningitis associated with chronic otitis media and mastoiditis

Kanzaki Sho, Inoue Yasuhiro, Watabe Takahisa, Ogawa Kaoru

Auris Nasus Larynx 31 （ 2 ） 155 - 159 2004年06月

ISSN 0385-8146

We describe the case history of a 70-year-old female patient presenting with bilateral hearing disturbance, facial paralysis, and vertigo. Radiological tests of temporal bone revealed soft tissue in the mastoid and tympanic cavities, and T1 weighted MRI revealed prominent Gd enhancement of the middle skull basal meninges. Middle ear inflammation appeared to induce pachymeningitis and to exacerbate associated symptoms, leading to a decline in the patient's overall condition. Bilateral mastoidectomies were effective in improving her general condition. Her hearing improved only on the right side because ossiculoplasty was performed only on that side. Her facial movement progressively improved and pachymeningitis diminished over time. We speculate that removal of the infectious granulation within the middle ears and mastoids ameliorated the acute inflammation. The etiology remains unknown in this case.

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Adaptation of Japanese version of the Hearing Handicap Inventory for Adults (HHIA)

Sato Minako, Ogawa Kaoru, Inoue Yasuhiro, Masuda Masatsugu

Nippon Jibiinkoka Gakkai kaiho 107 （ 5 ） 489 - 493 2004年05月

ISSN 0030-6622

We used social and emotional approaches to psychologically evaluate hearing disorders, translating the Hearing Handicap Inventory for Adults (HHIA) into Japanese and using it to evaluate Japanese adults with sensorineural hearing loss. The HHIA is a 25-item self-assessment scale composed of 2 subscales, emotional and social/situational, which has been used to evaluate adult patients with hearing disorders in Europe and North America. The test-retest reliability of the Japanese version and its screening version (HHIA-S) were excellent (kappa coefficients were 0.912 and 0.842). Due to the limitation of social/situational items, test-retest reliability was only good (0.6 < kappa coefficient < 0.8), possibly because of problems in translating these items. We discovered that the average of scores of the HHIA Japanese version was higher in bilateral hearing disorder patients than in those with unilateral hearing disorder. This score peaked in 2 to 10 years after onset and decreased thereafter in bilateral hearing disorder patients. The correlation coefficient between the average hearing level of 7 frequencies and scores of the test was highest among the 4 audiological evaluations. The HHIA Japanese version is thus useful for following up patients with hearing disorders.

Tracheoesophageal diversion versus total laryngectomy for intractable aspiration

Tomita Toshiki, Tanaka Kazuhito, Shinden Seiichi, Ogawa Kaoru

Journal of Laryngology and Otology 118 （ 1 ） 15 - 18 2004年01月

ISSN 0022-2151

This study evaluates the outcome and surgical stress associated with surgery for intractable aspiration. A retrospective review was conducted to compare the results between tracheoesophageal diversion and total laryngectomy. The operative time, intra-operative bleeding, time until drain removal, feeding conditions and surgical complications were compared between the two groups. Of the 19 patients, 31.6 per cent underwent tracheoesophageal diversion and 68.4 per cent received total laryngectomy. The operative time and drain insertion periods were statistically shorter in the tracheoesophageal diversion group, while the amount of intra-operative blood loss was smaller in the tracheoesophageal diversion group. The complication rate and the feeding conditions before and after surgery for the two groups did not show any statistically significant difference. Tracheoesophageal diversion was thus found to be a simple, safe, and reliable therapeutic modality for the control of intractable aspiration. Moreover, it induced less surgical stress than total laryngectomy.

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Cervical emphysema secondary to pneumomediastinum as a complication of childbirth

Nakagawa Hideki, Yamauchi Miwa, Kusuyama Toshiyuki, Fukuda Hiroyuki, Ogawa Kaoru

Ear, Nose and Throat Journal 82 （ 12 ） 948 - 951 2003年12月

ISSN 0145-5613

Pneumomediastinum and cervical emphysema usually occur following esophageal or chest trauma. Rarely do they occur as a complication of childbirth, and only approximately 200 such cases have been reported in the literature worldwide. We describe a new case, and we review the clinical picture, pathophysiology, and management of these conditions. In view of the head and neck symptoms of pneumomediastinum and cervical emphysema during labor - which include dyspnea, cough, sore throat, pain on swallowing, and dysphagia - otolaryngologists might be consulted and should therefore be aware of these conditions in order to recognize and treat them.

CCND1 Amplification Predicts Sensitivity to Chemotherapy and Chemoradiotherapy in Head and Neck Squamous Cell Carcinoma

Ishiguro Ryuichiro, Fujii Masato, Yamashita Taku, Tashiro Masatsugu, Tomita Toshiki, Ogawa Kaoru, Kameyama Kaori

Anticancer Research 23 （ 6 D ） 5213 - 5220 2003年11月

ISSN 0250-7005

Background: Cyclin D1 has been reported to be associated with poor prognosis in head and neck squamous cell carcinoma (HNSCC). Patients and Methods: FISH was performed on 58 patients. Thirty-two received neoadjuvant chemotherapy (NAC) as primary treatment and 21 with hypopharyngeal squamous cell carcinoma (HPC) received chemoradiotherapy. Results: CCND1 amplification was identified in 31 (53%) patients and the incidence was higher in HPC (p=0.0068). Four (31%) out of 13 patients with CCND1 amplification responded to NAC whereas the response rate in the non-amplified group was 79% (p=0.011). CCND1 amplification with a homogeneously staining region (HSR) was accompanied by cyclin D1 protein overexpression (p<0.0001). HPC showed HSR more frequently (p=0.033) and the survival rate of the subgroup with HSR was lower than that without (p<0.05). Conclusion: Detection of CCND1 amplification using FISH may be a useful marker of sensitivity to NAC and chemoradiotherapy for HNSCC.

Hearing improvement after tumor removal in a vestibular schwannoma patient with severe hearing loss

Inoue Y., Ogawa K., Kanzaki J.

European Archives of Oto-Rhino-Laryngology 260 （ 9 ） 487 - 489 2003年10月

ISSN 0937-4477

We herein report on the hearing improvement obtained after tumor removal in a vestibular schwannoma patient with preoperative severe hearing loss and good otoacoustic emission. Hearing recovery after tumor removal is an uncommon occurrence. As a result, hearing preservation surgery is usually not performed for patients with severe hearing loss. However, patients with a good OAE seem to have a better chance to recover their hearing than those with a poor OAE, even if they have severe hearing loss. As a result, the cochlear function should be evaluated, especially regarding the OAE, before determining the indications for hearing preservation surgery.

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Effect of single-drug treatment on idiopathic sudden sensorineural hearing loss

Kanzaki Jin, Inoue Yasuhiro, Ogawa Kaoru, Fukuda Satoshi, Fukushima Kunihiro, Gyo Kiyofumi, Yanagihara Naoaki, Hoshino Tomoyuki, Ishitoya Jun Ichi, Toriyama Minoru, Kitamura Ken, Murai Kazuo, Nakashima Tsutomu, Niwa Hideto, Nomura Yasuya, Kobayashi Hitome, Oda Makoto, Okamoto Makito, Shitara Tetuya, Sakagami Masafumi, Tono Tetsuya, Usami Shin Ichi

Auris Nasus Larynx 30 （ 2 ） 123 - 127 2003年05月

ISSN 0385-8146

Objectives: In order to evaluate the effect of a medical administration for the sudden deafness patients, single-drug treatment for idiopathic sudden sensorineural hearing loss (ISSHL) was assessed at multi-centers participating in the Acute Severe Hearing Loss Study Group sponsored by the Ministry of Health, Labor and Welfare of Japan. Methods: The subjects consisted of ISSHL patients who were (1) 20 years of age or older, (2) diagnosed within 2 weeks after the onset of hearing loss, (3) showing a mean hearing level of 40-90 dB at five frequencies from 250 to 4000 Hz, (4) previously untreated, and (5) with normal for age in hearing of the opposite ear. The drugs used in this study were ATP, alprostadil, hydrocortisone and amidotrizoate, which were administered intravenously, and beraprost sodium and betamethasone, which were given orally. Two drugs were assigned to each center, one of which was selected according to the code hidden in envelopes and administered for 1 week. The treatment after the single-drug administration was conducted at the discretion of each center. The hearing gain and recovery rate at 1 week after the initiation of single-drug treatment and at 1 month or over when the hearing level was fixed, were evaluated based on the criteria for hearing recovery prepared by the Acute Severe Hearing Loss Study Group. Results: There was no statistically significant difference in the recovery rate among drugs either at 1 week after the initiation of single-drug treatment or at the time of fixed hearing level. At the time when the hearing level was fixed, a statistically significant difference in the complete recovery rate was detected only between amidotrizoate and beraprost sodium. Conclusion: From these results, we could not find any specific drugs recommended for ISSNHL. In evaluating the effect of the drugs, however, several problems in the clinical trial for ISSHL should be considered.

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The inhibitory effect of matrix metalloproteinase inhibitor ONO-4817 on lymph node metastasis in tongue carcinoma

Yamashita Taku, Fujii Masato, Tomita Toshiki, Ishiguro Ryuichiro, Tashiro Masatsugu, Tokumaru Yutaka, Imanishi Yorihisa, Kanke Minoru, Ogawa Kaoru, Kameyama Kaori, Otani Yoshihide

Anticancer Research 23 （ 3 B ） 2297 - 2302 2003年05月

ISSN 0250-7005

Background: ONO-4817 is a novel matrix metalloproteinase (MMP) inhibitor which has a broad inhibitory spectrum for MMPs. We investigated the inhibitory effect of ONO-4817 on cervical lymph node metastasis of tongue carcinoma. Materials and Methods: HSC-3-M3, a cell line derived from human tongue carcinoma with high metastatic potential for lymph node, was used. The direct cytotoxicity of ONO-4817 was assessed by MTT assay and the gelatinolytic activity by gelatin zymography and film in situ zymography (FIZ). The inhibitory effect on lymph node metastasis was examined by orthotopic implantation model with nude mice. Results: ONO-4817 had no direct cyototoxicity on HSC-3-M3 cells. Gelatin zymography and FIZ demonstrated a suppression of MMP-9 activation and a marked inhibition of gelatinolysis. Additionally, a suppression of cervical lymph node metastasis was shown by therapeutic experiment. Conclusion: The MMP inhibitor, ONO-4817, is a candidate for adjunctive therapy of cervical lymph node metastasis in tongue carcinoma.

Adenoviral GDNF gene transfer prevents motoneuron loss in the nucleus ambiguus

Saito Kouichiro, Shiotani Akihiro, Watabe Kazuhiro, Moro Kazuhisa, Fukuda Hiroyuki, Ogawa Kaoru

Brain research 962 61-67 2003年03月

研究論文（学術雑誌）, 共著

Adenoviral GDNF gene transfer prevents motoneuron loss in the nucleus ambiguus

Saito Koichiro, Shiotani Akihiro, Watabe Kazuhiko, Moro Kazuhisa, Fukuda Hiroyuki, Ogawa Kaoru

Brain Research 962 （ 1-2 ） 61 - 67 2003年02月

ISSN 0006-8993

We examined neuroprotective effects of an adenoviral vector encoding glial cell line-derived neurotrophic factor (AxCAhGDNF) on the lesioned adult rat motoneurons in the nucleus ambiguus. After vagal nerve avulsion, AxCAhGDNF, AxCALacZ (adenovirus encoding β-galactosidase gene) or PBS was inoculated into the jugular foramen. Four days after the avulsion and treatment with AxCALacZ, the animals expressed β-galactosidase activity in the lesioned motoneurons in the nucleus ambiguus. The animals avulsed and inoculated with AxCAhGDNF showed immunolabeling for GDNF in the nucleus ambiguus on the treated side and expression of virus-induced human GDNF mRNA transcripts in the brainstem tissue that contained the nucleus ambiguus of the treated side. The treatment with AxCAhGDNF after avulsion prevented the loss of lesioned motoneurons in the nucleus ambiguus, ameliorated the choline acetyltransferase immunoreactivity, and also suppressed the activity of nitric oxide synthase in these neurons. These results indicate that adenovirus-mediated GDNF gene transfer may prevent the degeneration of motoneurons in humans after either vagal nerve injury or recurrent laryngeal nerve injury.

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Adenoviral GDNF gene transfer prevents motoneuron loss in the nucleus ambiguus

Saitou Kouichirou, Shiotani Akihiro, Watabe Kazuhiko, Moro Kazuhisa, Fukuda Hiroyuki, Ogawa Kaoru

Brain research 962 （ 1 ） 61-67 2003年02月

研究論文（学術雑誌）, 共著

CHEP with the Total Removal of the Arytenoid on the Tumor-bearing Side

Shiotani Akihiro, Araki Koji, Moro Kazuhisa, Ikeda Asako, Okubo Keisuke, Saito Koichiro, Ogawa Kaoru

Journal of Otolaryngology of Japan 106 （ 11 ） 1100 - 1103 2003年

ISSN 0030-6622

A supracricoid laryngectomy with cricohyoidoepiglottopexy (CHEP) consists of the resection of the whole thyroid cartilage and paraglottic space, while preserving the cricoid cartilage, the hyoid bone, most of the epiglottis and the arytenoids. Laryngeal reconstruction is achieved be suturing the cricoid cartilage and the hyoid bone. This procedure is mainly indicated for large T2 glottic carcinomas and provides a complete resection and laryngeal preservation without requiring a permanent tracheostomy. Although bilateral arytenoids are usually preserved to ensure better laryngeal function after CHEP, we unavoidably had to remove the arytenoid on the tumor-bearing side during a complete resection performed in a 56-year-old male with a rT2 tumor who had undergone radiation and demonstrated impaired vocal fold motion. Despite the resection of one arytenoid, the final laryngeal function proved to be satisfactory. CHEP should be utilized as an alternative surgical modality for conventional vertical partial laryngectomies or total laryngectomies. CHEP with the total removal of the arytenoid on the tumor-bearing side may be a useful laryngeal preservation procedure for the treatment of patients with glottic carcinoma associated with an impaired vocal fold motion or a fixed vocal fold.

中耳手術の聴力改善判定基準をめぐって—耳硬化症の場合—

小川郁

Otology Japan 13 39797 2003年

研究論文（学術雑誌）, 単著

Adenoviral GDNF gene transfer prevents motorneuron loss in the nucleus ambiguus

Saito Kouichiro, Shiotani Akihiro, Watabe Kazuhiro, Moro Kazuhisa, Fukuda Hiroyuki, Ogawa Kaoru

Brain Reserch 962 （ 39449 ） 61-67 2003年

研究論文（学術雑誌）, 共著

A wearable sense of balance monitoring system towards daily health care monitoring

Matsushita Soichiro, Oba Toshihiko, Otsuki Kazuoki, Toji Masao, Otsuki Junichi, Ogawa Kaoru

176 - 183 2003年

We implemented a wearable system for detecting accelerations of the user's head while standing still for the purpose of developing a daily health care application. A 2- axis accelerometer was attached on the top of the user's head to separately detect faint accelerations in both the front to back and right to left directions. The total weight of the headset device is only 195 grams including a 9V NiMH battery. This paper presents the results of several experiments performed with the headset system. First, we observed healthy subjects under normal conditions and recorded typical accelerations in the range of 10-30 milli-Gs, which was sufficient to be detected by the system's sensitivity. We then performed numerical analysis on traces of acceleration patterns for a specific user in different conditions. From these analyses we found that the total length of 2-dimensional acceleration pattern trace and a high frequency spectrum (2Hz-10Hz) of right/left acceleration were related to the physical condition of the user. The wearable headset device can be carried to anywhere the user goes and the diagnosis of the wearer's physical condition only requires that the user stand still for 30 seconds, showing that this system can be used for daily health care monitoring.

Evidence-Based Therapeutic Strategy for Sudden Sensorineural Hearing Loss

Ogawa Kaoru

Otolaryngology - Head and Neck Surgery (Tokyo) 75 （ 12 ） 849 - 860 2003年

ISSN 0914-3491

頭頚部癌におけるSentinel node navigationの試み　―喉頭癌への応用―

塩谷彰浩，藤井博史，北川雄光，小川郁

癌の臨床 48 885-890 2002年12月

研究論文（学術雑誌）, 共著

耳鳴の心理的苦痛度・生活障害度の評価法に関する検討

新田清一，小川郁，井上泰宏，田副真美，浅野恭子

Audiology Japan 45 （ 6 ） 685-691 2002年12月

研究論文（学術雑誌）, 共著

小児喉頭乳頭腫　―手術療法および補助療法としての漢方療法―

塩谷彰浩，大久保啓介，福田宏之，小川郁

喉頭 14 69-73 2002年12月

研究論文（学術雑誌）, 共著

Effect of prostaglandin E1 on idiopathic sudden sensorineural hearing loss

Ogawa Kaoru, Takei Satoshi, Inoue Yasuhiro, Kanzaki Jin

Otology and Neurotology 23 （ 5 ） 665 - 668 2002年09月

ISSN 1531-7129

Objective and Study Design: The authors conducted a prospective, randomized, double-blinded clinical trial for the purpose of elucidating the effects of prostaglandin E1 (PGE1) on idiopathic sudden sensorineural hearing loss. Setting and Patients: With the approval of the institute ethics committee, a total of 57 consecutive patients with diagnoses of idiopathic sudden sensorineural hearing loss were included in the study. The patients in the PGE1 group received continuous infusion containing 60 μg PGE1 and 100 mg hydrocortisone for 7 days, and the patients in the placebo group were treated with continuous infusion containing an inactive placebo and 100 mg hydrocortisone. Results: No significant differences were observed in the improvements of pure-tone average and subjective symptoms between the PGE1 and the placebo groups. However, the hearing improvement at high frequencies (4 kHz and 8 kHz) was significantly higher in the PGE1 group than in the placebo group, especially in the patients with severe tinnitus. Conclusions: These results failed to prove a beneficial effect of PGE1 in the treatment of idiopathic sudden sensorineural hearing loss. Further studies will be needed to clarify the pharmacologic actions of PGE1 in the cochlea.

症例をどうみるか「一側性心因性難聴の1症例」

松延毅，橋口一弘，浅野恭子，井上泰宏，小川郁

JOHNS 18 （ 9 ） 1691-1695 2002年09月

研究論文（学術雑誌）, 共著

Effect of prostaglandin E1 on idiopathic sudden sensorineural hearing loss: a double-blinded clinical study

Ogawa Kaoru, Takei Satoshi, Inoue Yasuhiro, Kanzaki Jin

Otology neurotology 23 （ 5 ） 665-668 2002年08月

研究論文（学術雑誌）, 共著

Transgene expression in neonatal mouse inner ear explants mediated by first and advanced generation adenovirus vectors

Kanzaki Sho, Ogawa Kaoru, Camper SA, Raphael Yehoash

Hearing research 169 （ 1-2 ） 112-120 2002年07月

研究論文（学術雑誌）, 共著

人工中耳

小川郁

日本医師会雑誌「感覚器障害の臨床　update」 127 （ 9 ） 1497 2002年05月

研究論文（学術雑誌）, 単著

生涯教育シリーズ58，症候から診断へ第5集「耳漏」

小川郁

日本医師会雑誌 127 （ 8 ） 81-85 2002年04月

研究論文（学術雑誌）, 単著

急性低音障害型感音難聴の重症度分類

志津木健，小川郁，井上泰宏，泰地秀信，神崎仁

Audiology Japan 45 （ 2 ） 144-148 2002年04月

研究論文（学術雑誌）, 共著

Expression of c-Fos after noise-induced temporary threshold shift in the guinea pig cochlea

Shizuki Ken, Ogawa Kaoru, Matsunobu Takeshi, Kanzaki Jin, Ogita Kiyokazu

Neuroscience Letters 320 （ 1-2 ） 73 - 76 2002年03月

ISSN 0304-3940

c-Fos is known to be a component of a transcription factor, activator protein-1, which is induced by oxidative stress. Guinea pigs were exposed to 4 kHz band noise of 110 dB SPL for 1 or 5 h and the expression of c-Fos in the organ of Corti was determined using Western blotting analysis and immunocytochemistry. c-Fos was expressed only after the noise exposure. The c-Fos expression was mainly found in the Hensen's cells, Claudius' cells and Deiter's cells of the basal and second turns of the cochlea. Since the threshold shift was temporary, the expression of c-Fos is therefore considered to contribute to the survival or protective function of the organ of Corti.

耳鳴.　特集「お母さんへの回答マニュアル耳鼻咽喉科Q＆A」

小川郁

JOHNS 18 （ 3 ） 328-329 2002年03月

研究論文（学術雑誌）, 単著

自声強調.　特集「お母さんへの回答マニュアル耳鼻咽喉科Q＆A」

小川郁

JOHNS 18 （ 3 ） 330-331 2002年03月

研究論文（学術雑誌）, 単著

耳漏.　「症候から診断へ」　　127 (8): 81-85, 2002

小川郁

日本医師会雑誌 127 （ 8 ） 81-85 2002年02月

研究論文（学術雑誌）, 単著

The diagnostic significance of the 3D-reconstracted MRI in vestibular schwannoma surgery: prediction of tumor origin

Inoue Yasuhiro, Ogawa Kaoru, Momoshima Suketaka, Kanzaki Jin

European archives of oto-rhino-laryngology 259 （ 2 ） 73-76 2002年02月

研究論文（学術雑誌）, 共著

Expression of c-Fos after noise-induced temporary threshold shift in the guinea pig cochlea

Shizuki Ken, Ogawa Kaoru, Matsunobu Tuyoshi, Kanzaki Jin, Ogita K

Neuroscience Letter 320 （ 1-2 ） 73-76 2002年01月

研究論文（学術雑誌）, 共著

The diagnostic significance of the 3D-reconstracted MRI in vestibular schwannoma surgery: prediction of tumor origin

Inoue Yasuhiro, Ogawa Kaoru, Kanzaki Jin

European Archive of Otorhinolaryngology 259 （ 2 ） 73-76 2002年01月

研究論文（学術雑誌）, 共著

Transgene expression in neonatal mouse inner ear explants mediated by first and advanced generation adenovirus vectors

Kanzaki Sho, Ogawa Kaoru, Camper Sally A., Raphael Yehoash

Hearing Research 169 （ 1-2 ） 112 - 120 2002年

ISSN 0378-5955

The mouse serves as a valuable model for treatment leading to the prevention and therapy of inner ear disease. Transgenic correction of genetic inner ear disease in mice may help develop treatment for human genetic inner ear disease. In mutations involving hair cells (HCs) or supporting cells (SCs), it is necessary to insert the wild-type transgenes directly into these cells. We used inner ear explants to characterize the transgenic expression using adenovirus-mediated reporter genes (bacterial lacZ). The variable parameters were the age of the explants (P1-P5), the type of vector (first and advanced generation adenovirus) and the genotype of the mouse (wild-type versus shaker-2 mutant). Transduction of cochlear HCs was detected at P1 and in some of the P3 cochleae. Low efficiency transduction of SCs was observed in P1 explants, but the efficiency increased with age and reached high levels at P5. The pattern of transduction was similar regardless of the genotype and the type of vector used. The data demonstrate that differentiating HCs and SCs in mouse explants can be transduced by adenovirus vectors, suggesting that cultures of mouse ears are a valuable model for developing inner ear gene therapy protocols.

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Expression of c-Fos after noise-induced temporary threshold shift in the guinea pig cochlea

Shizuki Ken, Ogawa Kaoru, Matsunobu Takeshi, Kanzaki Jin, Ogita Keisuke

Neuroscience letters 320 73-76 2002年

研究論文（学術雑誌）, 共著

The diagnostic significance of the 3D-reconstructed MRI in vestibular schwannoma surgery

Inoue Y., Ogawa K., Momoshima S., Kanzaki J.

European Archives of Oto-Rhino-Laryngology 259 （ 2 ） 73 - 76 2002年

ISSN 0937-4477

In hearing preservation surgery for the treatment of vestibular schwannoma (VS), one of the important factors is the determination of the origin of VS. In this study, we investigated the diagnostic significance of using an MRI obtained by the three-dimensional Fourier transform fast spin-echo technique (3D-reconstructed MRI) in order to determine the origin of VS. The subjects consisted of 20 patients with mainly intra-canalicular sized VS who underwent tumor removal at our hospital. The origin of VS was determined from the 3D-reconstructed MRI findings and the results of the caloric test. These findings were then compared with the surgical findings. In 15 out of 20 patients, the MRI findings closely corresponded to the surgical ones, while the origin of VS hardly could be detected when a tumor filled up to the fundus acoustics on the MRI findings of the axial sections. On the other hand, 6 out of 15 patients (40%) whose tumor originated from the inferior vestibular nerve showed canal paresis. In conclusion, 3D-reconstructed MRI is considered to be helpful in obtaining more precise information regarding the origin of VS compared to the caloric test.

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The glutamate receptor agonist, AMPA, induces acetylcholine release in guinea pig cochlea; a microdialysis study

Hoya Noriyuki, Ogawa Kaoru, Inoue Yasuhiro, Takiguchi Yoichiro, Kanzaki Jin

Neuroscience Letters 311 （ 3 ） 206 - 208 2001年10月

ISSN 0304-3940

Acetylcholine (Ach) has been considered a major neurotransmitter in the inner ear efferent nerve endings. A bioassay analysis has shown that the electrical stimulation of the crossed olivocochlear bundle increased the Ach-like activity in the perilymph. Applying in vivo microdialysis techniques and high-performance liquid chromatography to the perilymph, the change of Ach level was thus measured before and after α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), a glutamate receptor agonist, was added to the perfusate. Ach was only detectable when the perfusate contained an acetylcholinesterase inhibitor. The level of Ach increased 2-3-fold immediately after AMPA was administered. Our data suggest that the afferent stimulation, such as the administration of AMPA, may therefore induce the release of Ach from the efferent nerve endings.

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耳鳴と心身医学.　トピックス「心身医学と耳鼻咽喉科」

小川郁，新田清一

耳鼻咽喉科・頭頸部外科 73 823-827 2001年10月

研究論文（学術雑誌）, 共著

耳鳴と心身医学.　トピックス「心身医学と耳鼻咽喉科」

小川郁

耳鼻咽喉科・頭頸部外科 73 823-827 2001年10月

研究論文（学術雑誌）, 単著

Effects of neuropepyide Y on cochlear blood flow in guinea pigs

Itou Mari, Ogawa Kaoru, Inoue Yasuhiro, Sato Minako, Kanzaki Jin

Acta Otolaryngologica 121 （ 5 ） 573-578 2001年06月

研究論文（学術雑誌）, 共著

Mechanisms of photoinduced cochlear ischemia in the guinea pig

Saito H., Ogawa K., Inoue Y., Kanzaki J., Harada T., Hoya N.

ORL 63 （ 3 ） 148 - 154 2001年05月

ISSN 0301-1569

An experimental model of cochlear ischemia using the photosensitization reaction of rose bengal (RB) is reported. Ischemia was induced by the systemic administration of RB solution and localized irradiation of the cochlea with a green light of specific wavelength for RB activation. After the RB solution was administered, the cochlear blood flow was temporarily increased and then decreased, and the latency of wave I of the auditory brainstem response increased and the amplitude of wave I decreased after RB injection and finally wave I disappeared completely. A histological study revealed thrombus formation in the vessels of the irradiated cochlea not only in the stria vascularis and the spiral ligament, but also in the modiolus. L-Histidine, a scavenger of singlet oxygen (¹O₂) and hydroxyl radical (^·OH), significantly prolonged cochlear dysfunction, but D-mannitol, a specific scavenger of ^·OH did not, suggesting that ¹O₂ has an important role in this reaction.

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Effect of tea cathekins on gastric submucosal circulation

Morishita T, Nagata H, Sekizuka E, Miyazaki, Nakamura A, Ogawa N, Mizushima H, Ihata A, Takemura S, Miyashita Y, Fujita H, Yoshitomi A, Murakami M, Nagahama T, Ishii H

Microcirculation Annual 2000 73-74 2001年05月

研究論文（学術雑誌）, 共著

Evaluation of hearing recovery and a grading system established by the Research Group on Sudden Deafness of the Japanese Ministry of Health and Welfare

Sato M., Matsunaga T., Kanzaki J., Ogawa K., Inoue Y., Houya N.

Journal of Otolaryngology of Japan 104 （ 3 ） 192 - 197 2001年03月

ISSN 0030-6622

A grading system for sudden deafness has been established by the Research Group on Sudden Deafness of the Japanese Ministry of Health and Welfare. According to this grading system, sudden deafness cases are classified according to the initial hearing level and the vestibular symptoms. Few clinical analyses of sudden deafness cases have been made using this grading system. In this study, 263 sudden deafness cases were classified into 6 groups based on the grading system. All of the cases presented with an initial hearing level of more than 40 dB and underwent treatment within 1 week of the onset of symptoms. The relationship between the grading system and hearing recovery is discussed. Fixed hearing levels with a good prognosis were grades 2b, 2a, 3b, 3a, 4b and 4a. To quantitatively evaluate hearing recovery, the average hearing recovery rate and the percentage of the complete recovery cases were analyzed for each group. Average hearing recovery was ranked into five levels, regardless of the evaluation method. Grades 2b and 3b were the best, and grade 4a was the worst. After grades 2b and 3b, grade 2a was the second best, grade 3a was the third, and grade 4b was the fourth. The cases included in grades 2 and 3 were more strongly effected by whether the cases had vestibular symptoms or not than by their initial hearing levels. When grade 4 cases were classified by their initial hearing level, a large difference existed among grade 4a cases with regard to whether they presented with an initial hearing level of under or more than 100 dB. The hearing recovery of grade 4a cases with an initial hearing level of less than 100 dB was almost the same as that of grade 3a. However, the hearing recovery of grade 4b cases varied only slightly. Consequently, some ranges of initial hearing level exhibited similar degrees of hearing recovery. In cases without vestibular symptoms, the range of initial hearing levels was 40-89 dB. These cases had a 60% chance of complete recovery, and the hearing recovery rate was 80% on average. In cases with vestibular symptoms, the range of initial hearing levels was 60-99 dB. These cases had a 40% possibility of complete recovery, with an average hearing recovery rate of 60%. After comparing the initial grades and the final grades using the same grading system, the majority of grade 2 and 3 cases attained a grade 1 fixed hearing level. However, most grade 4 cases had a grade 3 fixed hearing level.

耳硬化症における耳閉塞感の発症機序に関する検討

小川郁，神崎仁，井上泰宏，保谷則之

日本耳鼻咽喉科学会会報 104 （ 3 ） 187-191 2001年03月

研究論文（学術雑誌）, 共著

突発性難聴の重症度分類と予後との関係

佐藤美奈子，松永達雄，神崎仁，小川郁，井上泰宏，保谷則之

日本耳鼻咽喉科学会会報 104 （ 3 ） 192-197 2001年03月

研究論文（学術雑誌）, 共著

Pathogenesis mechanism in ear fullness in otosclerosis

Ogawa K., Inoue Y., Shinden S., Kumanomidou H., Ide R., Kanzaki J.

Journal of Otolaryngology of Japan 104 （ 3 ） 187 - 191 2001年03月

ISSN 0030-6622

To clarify the mechanism underlying ear fullness in otosclerosis, we studied the relationship between clinical features and examinations. Subjects were 116 otosclerosis patients (140 ears). The presence or absence of ear fullness was judged from a questionnaire in initial diagnosis or a chart description. Ear fullness was observed in 44 ears (31%) and absent in 96. The averaged air and bone conduction hearing levels (500 Hz-4 k Hz) in initial diagnosis were significantly lower in the group with ear fullness. The difference in averaged hearing was mainly apparent at 2 k Hz and 4 k Hz. The difference in hearing at lower frequencies (125 Hz, 250 Hz, and 500 Hz) and higher frequencies (2 k Hz, 4 k Hz, and 8 k Hz) was significantly larger in the group of ear fullness. From these results, we postulated that ear fullness in otosclerosis is caused by fixation of the stapes. The psychoacoustic abnormal sensation caused by lower input of lower-frequency sound or incomplete fixation of the stapes may cause ear fullness. Further study is needed to clarify the pathogenesis of ear fullness in different ear pathologies.

外リンパ圧異常と感音難聴

神崎仁，井上泰宏，小川郁

Otology Japan 11 （ 1 ） 33-38 2001年02月

研究論文（学術雑誌）, 共著

高度難聴まで進行した急性低音障害型感音難聴の2症例

小川郁，神崎仁，井上泰宏，志津木健

Audiology Japan 44 （ 1 ） 60-65 2001年02月

研究論文（学術雑誌）, 共著

The quality of life in vestibular schwannoma patients after surgery

Inoue Yasuhiro, Kanzaki Jin, Ogawa Kaoru

Acta Otolaryngologica 121 （ 1 ） 59-61 2001年01月

研究論文（学術雑誌）, 共著

Perilymph fistula -45 case analysis-

Goto Fumiyuki, Ogawa Kaoru, Kunihiro Takanobu, Kurashima Kazuhiro, Kobayashi Hironari, Kanzaki Jin

Auris Nasus Larynx 28 （ 1 ） 29-33 2001年01月

研究論文（学術雑誌）, 共著

Effects of changes in stimulus level on phases of distortion product otoacoustic emissions

Harada Tatsuhiko, Ogawa Kaoru, Inoue Yasuhiro, Kanzaki Jin

Hearing Research 152 （ 1-2 ） 152-158 2001年01月

研究論文（学術雑誌）, 共著

Quality of life of vestibular schwannoma patients after surgery

Inoue Y., Ogawa K., Kanzaki J.

Acta Oto-Laryngologica 121 （ 1 ） 59 - 61 2001年

ISSN 0001-6489

The quality of life of vestibular schwannoma (VS) patients after surgery was investigated. The subjects consisted of 236 unilateral VS patients who underwent tumor removal between 1990 and 1997. A questionnaire was sent to all patients regarding their hearing, tinnitus, dizziness and the changes in their daily life after surgery; 176 out of 204 patients (86%) who received the questionnaire completed and returned it. The answers were compared with recent data reported in other clinical studies. Ninety percent of the patients with postoperative class A hearing were satisfied with their hearing. However, only 30% of patients with postoperative class B hearing were satisfied. Tinnitus worsened after surgery more often in patients who underwent a labyrinthectomy than in those who did not. Dizziness improved after surgery in the majority of VS patients. However, 30% of patients had difficulty driving a car and 50% of patients could not enjoy activities such as playing sport after surgery.

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The learning curve in post-operative hearing results in vestibular schwannoma surgery

Kanzaki Jin, Inoue Yasuhiro, Ogawa Kaoru

Auris Nasus Larynx 28 （ 3 ） 209 - 213 2001年

ISSN 0385-8146

Purpose: We chronologically investigated whether the hearing preservation (HP) rate improved or not in vestibular schwannoma (VS) surgery. Subjects and methods: HP surgery has been attempted in 127 VS patients with pre-operative class A and B hearing from 1976 to 1999. The HP rate was chronologically compared with hearing level and tumor size. Results: The preservation rate of pre-operative class A hearing which was preserved post-operatively as class A has recently been increasing especially in patients with an intracanalicular (IC) tumor. This rate was improved to 67% from 1995, although this was 33% from 1989 to 1994. However, the preservation rate of pre-operative class B in patients with an IC tumor and that of pre-operative class A hearing which was preserved as class A in patients with a larger tumor extending into the posterior fossa, have not improved over the last 10 years. Conclusion: These results indicate that the improvement of the HP rate is mainly due to the increased number of patients with an IC tumor with class A pre-operative hearing. In patients with a tumor of 4-20 mm in size, especially in those showing pre-operative class B hearing, there may be histologically some limitations such as gliosis in the cochlear nerve in the preservation rate of good quality (class A or B) of hearing.

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Effects of neuropeptide Y on cochlear blood flow in guinea pigs

Itou M., Ogawa K., Inoue Y., Sato M., Kanzaki J.

Acta Oto-Laryngologica 121 （ 5 ） 573 - 578 2001年

ISSN 0001-6489

The aim of this study was to clarify the effects of neuropeptide Y (NPY) on cochlear blood flow (CBF) in pigmented guinea pigs. NPY was administered with or without noradrenaline (NA) by systemic perfusion or perilymphatic local perfusion, and CBF was measured using a laser Doppler flowmeter. The systemic and perilymphatic administrations of NPY with NA induced greater prolongation of the increase in and recovery of CBF than the administration of NA or NPY alone. Continuous reduction in CBF induced by NPY may play an important role in the pathogenesis of stress-induced sensorineural hearing losses, such as sudden deafness.

Effects of changes in stimulus level on phases of distortion product otoacoustic emissions

Harada Tatsuhiko, Ogawa Kaoru, Inoue Yasuhiro, Kanzaki Jin

Hearing Research 152 （ 1-2 ） 152 - 158 2001年

ISSN 0378-5955

Effect of changes in stimulus levels of both lower (f₁) and higher (f₂) stimulus tones on phases of 2f₁-f₂ component of the distortion product otoacoustic emission (DPOAE) was examined in five normal hearing adults. The f₂ was fixed at 4004 Hz in all of the measurements, and the stimulus frequency ratio (f₂/f₁) was varied from 1.15 to 1.3. Change of the level of lower stimulus tone (L₁) and the level of higher stimulus tone (L₂) showed different effects on the DPOAE phases. The phase lags increased with increasing L₁, when f₂/f₁ was above 1.22, whereas the phase gains increased with increasing L₁, when f₂/f₁ was below 1.22. On the other hand, the difference in L₂ minimally affected DPOAE phase at most f₁s. The previous studies about basilar membrane vibration revealed that phase lags increase with increasing stimulus level, when the stimulus frequency is below the best frequency, while phase gains increase with increasing stimulus level, when the stimulus frequency is above the best frequency, and the effect of phase change in stimulus level diminished, when the stimulus frequency was far above the best frequency. Based on the comparison between the results of the present study and the previous findings of others concerning basilar membrane vibration, the DPOAE generation site is assumed to be located at apical of the peak of the f₂ traveling wave.

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Heterogeneity of phospholipase C in the cochlea of the guinea pig

Oba Toshihiko, Ogawa Kaoru, Inoue Yasuhiro, Kanzaki Jin

ORL 63 （ 5 ） 272 - 279 2001年

ISSN 0301-1569

In the present study, we investigated the presence of phosphatidylinositol-specific phospholipase C (PLC) isoforms in the cochlea of the guinea pig using Western blot analysis and immunocytochemistry. By Western blotting, PLCβ1 and δ1 were expressed in the cochlear sensory epithelia (CSE) and PLCβ1, γ1 and δ1 were expressed in the cochlear lateral wall. By immunocytochemistry of the CSE, PLCβ1-like immunoreactivity was mainly expressed in the outer hair cells (OHCs), but not in the inner hair cells (IHCs). PLCγ1 and δ1 were expressed neither in the OHCs nor in the IHCs. In the cochlear lateral wall, PLCβ1, δ1 and γ1 were expressed in the stria vascularis and the spiral ligament. In addition, PLCβ1, δ1 and γ1 were also present in type I spiral ganglion cells. Based on these results, we discussed the function of these PLC isoforms in the cochlea.

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Perilymph fistula - 45 Case analysis

Goto Fumiyuki, Ogawa Kaoru, Kunihiro Takanobu, Kurashima Kazuhiro, Kobayashi Hironari, Kanzaki Jin

Auris Nasus Larynx 28 （ 1 ） 29 - 33 2001年

ISSN 0385-8146

Purpose of the study: Though perilymph fistula (PLF) is not a rare disease, preoperative diagnosis still remains to be established. Some new diagnostic methods are challenging, but there is still no established diagnostic method except exploratory tympanotomy that verifies the occurrence of leakage. Early diagnosis of PLF is fully depending on history taking and some clinical examinations. To know the clinical features of PLF is one of the greatest helps to make both earlier and accurate diagnosis. In spite of some innovations in clinical examinations classic diagnostic procedure is thought to be still reliable. Procedures: We investigated the clinical symptoms, basic tests results and therapeutic results in patients with PLF. Results: From 1983 to 1998 PLF was identified in 44 patients (45 ears) with exploratory tympanotomies in our hospital. With respect to clinical history the predisposing factors such as blowing the nose, lifting heavy goods, and landing in an airplane were found in almost half of the patients, while the rest of them had no clear inducing factors. Their major symptoms included hearing loss (93%), vertigo and dizziness (91%), tinnitus (76%), and aural fullness (31%). The patients who have a clear predisposing factor tended to make diagnosis easily; on the other hand the rest of the patients who do not have clear etiology had some diagnostic difficulty. Subjective positive fistula signs were observed in 71% of patients. Vestibular symptoms improved in 80% of patients after closure of PLF. Conclusions: These results suggest that the variety of clinical manifestation make diagnosis more difficult. At the moment meticulous clinical history taking and close follow-up applying repeating fistula tests are the most important for not only earlier but also accurate diagnosis.

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難聴，耳鳴，耳閉塞感の診断と治療

小川郁

日本医事新報（ 3998 ） 19-36 2000年12月

研究論文（学術雑誌）, 単著

術前鑑別診断が困難であった小脳橋角部腫瘍の経験

井上泰宏，小川郁，熊埜御堂浩，新田清一，井出里香，神崎仁

Otology Japan 10 （ 5 ） 593-597 2000年12月

研究論文（学術雑誌）, 共著

Hypoglossal neurinoma: Resport of two cases

Hoshi M, Yoshida K, Ogawa Kaoru, Kawase Takeshi

Neurol Med Chir 40 （ 9 ） 489-493 2000年09月

研究論文（学術雑誌）, 共著

Hypoglossal neurinoma- Two case reports-

Hoshi M, Yoshida K, Ogawa K, Kawase T

Neurologia medico-Chirurugica 40 （ 9 ） 489-493 2000年09月

研究論文（学術雑誌）, 共著

低音障害型感音難聴の診断基準に関する検討

志津木健，小川郁，井上泰宏，神崎仁

Audiology Japan 43 （ 4 ） 242-249 2000年08月

研究論文（学術雑誌）, 共著

Vestibular schwannoma presenting as sudden deafness -Hearing recovery and indication for hearing preservation surgery-

Inoue Yasuhiro, Kanzaki Jin, Ogawa Kaoru

Journal of Laryngology and Otology 114 （ 8 ） 589-592 2000年08月

研究論文（学術雑誌）, 共著

Creutzfelt-Jakob disease presenting hyperparathyroidism

Goto Fumiyuki, Kano Shigeru, Ogawa Kaoru

Auris Nasus Larynx 27 （ 3 ） 281 - 283 2000年07月

ISSN 0385-8146

We reported a 68-year-old female with Creutzfelt-Jakob disease (CJD) presenting hyperparathyroidism. She was suspected as Creutzfelt-Jakob like syndrome at her initial visit to our hospital because of progressive dementia and high level of serum calcium. Finally she was diagnosed as having CJD by the clinical symptoms including progressive dementia and myoclonus and the characteristic patterns of brain CT and electroencephalogram (EEG). CJD presents a variety of symptoms including progressive dementia, apathy and myoclonus. Hyperparathyroidism and toxicity of lithium, delirium and bismuth have been reported to induce similar symptoms of CJD, which are called Creutzfelt-Jakob like syndrome. Therefore, the diagnosis of CJD would be difficult in cases with CJD accompanied with Creutzfelt-Jakob like syndrome. It is rare for otolaryngologists to examine patients with dementia like CJD. However, we have to keep CJD in mind in the diagnosis of hyperparathyroidism. Copyright (C) 2000 Elsevier Science Ireland Ltd.

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聴神経腫瘍における耳閉塞感の検討

小川郁，井上泰宏，武井聡，志津木健，熊埜御堂浩，井出里香，神崎仁

Audiology Japan 43 （ 3 ） 196-200 2000年06月

研究論文（学術雑誌）, 共著

Creutzfelt-Jakob disease presenting hyperparathyroidism

Goto Fumiyuki, Kano Shigeru, Ogawa Kaoru

Auris Nasus Larynx 27 （ 3 ） 281-283 2000年06月

研究論文（学術雑誌）, 共著

耳下部に生じた結節性筋膜炎の一症例

井出里香，小川郁，熊埜御堂浩，松延毅，亀山香織，神崎仁

耳鼻咽喉科展望 43 （ 3 ） 199-203 2000年06月

研究論文（学術雑誌）, 共著

Photo-induced ischemia of guinea pig

Saito Hideyuki, Ogawa Kaoru, Inoue Yasuhiro, Kanzaki Jin, Harada Tatsuhiko, Hoya Noriyuki

ORL Journal of Otorhinolaryngol Related Spec 63 （ 3 ） 148-154 2000年03月

研究論文（学術雑誌）, 共著

乳幼児にみられる機能性難聴

小川郁

JOHNS 16 （ 2 ） 221-226 2000年02月

研究論文（学術雑誌）, 単著

錐体尖真珠腫に対する手術的アプローチ

小川郁

Otology Japan 10 （ 1 ） 4-9 2000年02月

研究論文（学術雑誌）, 単著

The long-term outcome of hearing preservation in vestibular schwannoma surgery

Inoue Yasuhiro, Kanzaki Jin, Ogawa Kaoru, Hoya Noriyuki, Takei Satoshi

Auris Nasus Larynx 27 （ 1 ） 9-13 2000年01月

研究論文（学術雑誌）, 共著

Vestibular schwannoma presenting as sudden deafness

Inoue Y., Kanzaki J., Ogawa K.

Journal of Laryngology and Otology 114 （ 8 ） 589 - 592 2000年

ISSN 0022-2151

In this study, we analysed the clinical and audiological features of 24 vestibular schwannoma patients presenting with sudden deafness who visited our hospital within 10 days after its onset. The relationships between the prognosis of hearing loss and the clinical and audiological features including the pure-tone average (PTA), the presence of dizziness and/or vertigo, the tumour size and the auditory brain stem response (ABR) findings were evaluated. Hearing recovery depended on the PTA and tumour size, but even a small tumour induced sudden deafness. Impaired hearing completely recovered in five our of 24 patients. ABR findings indicated that the aetiology of sudden deafness in the vestibular schwannowa patients might vary in each patient.

The long-term outcome of hearing preservation following vestibular schwannoma surgery

Inoue Y., Kanzaki J., Ogawa K., Hoya N., Takei S., Shiobara R.

Auris Nasus Larynx 27 （ 1 ） 9 - 14 2000年

ISSN 0385-8146

Objective: The aim of this study is to describe the long-term outcome of preserved hearing after vestibular schwannoma surgery.Methods: Subjects are 20 unilateral vestibular schwannoma patients whose class A hearing of the AAO-HNS classification was preserved successfully after tumor removal. Hearing preservation surgery was attempted via the middle cranial fossa (MCF) or the extended MCF approach. The follow-up periods ranged from 2 to 16 years. The outcome measures included the pure tone average (PTA) and speech discrimination score (SDS).Results: PTA was maintained in less than 30 dB in 11 out of 20 patients within 2 years follow-up, six out of 13 patients within 4 years follow-up, and two out of five patients within 6 years follow-up, respectively. SDS was maintained in more than 70% in 17 out of 20 patients within 2 years follow-up, ten out of 13 patients within 4 years follow-up, and three out of five patients within 6 years follow-up, respectively.Conclusions: The preserved hearing maintained about more than 40% of the patients with the class A hearing in every 2 years follow-up. From this result, we can conclude that the hearing preservation surgery could be one of the best treatments for vestibular schwannoma patients with class A hearing. However, further study will be needed to clarify the mechanism of the deterioration in hearing after hearing preservation surgery. Copyright (C) 2000 Elsevier Science Ireland Ltd.

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Hypoglossal neurinoma

Hoshi Michio, Yoshida Kazunari, Ogawa Kaoru, Kawase Takeshi

Neurologia Medico-Chirurgica 40 （ 9 ） 489 - 493 2000年

ISSN 0470-8105

Two patients presented with hypoglossal neurinoma extending both intra- and extracranially. A 63-year-old male presented with right trigeminal neuralgia and hypoglossal nerve paresis. The intracranial part of the tumor was removed totally via a suboccipital craniectomy. Over-coagulation of the venous collaterals, particularly the emissary veins, resulted in dural venous sinus thrombosis and cerebellar infarction. Unfortunately this patient died. A 48-year-old male presented with pareses of the VII, IX, X, XI, and XII cranial nerves and cerebellar sign. The tumor extended both extra- and intracranially, and was completely removed by opening the hypoglossal canal and the jugular foramen without over-coagulation of the venous collaterals. Preservation of the venous collaterals is very important for the prevention of postoperative venous complications.

Retroauricular nodular fasciitis—A case report

Ide Rika, Ogawa Kaoru, Kumanomido Hiroshi, Matsunobu Takeshi, Kanzaki Jin

Oto-Rhino-Laryngology Tokyo 43 （ 3 ） 199 - 203 2000年

ISSN 0386-9687

Nodular fasciitis has been generally considered as a benign and probably reactive fibroblastic growth originating from the subcutaneous fascia. In the present paper, we report a case with nodular fasciitis arising in the retroauricular region. The patient was a 23-year-old woman who had noticed a mass about 5 mm in diameter in the left retroauricular region. She was referred to our hospital because the mass was gradually growing and was tender to touch. At the initial examination, a pigmented mass about 1 cm in size was found in the left retroauricular region. The surface was smooth and the mass was freely mobile. Computed tomography (CT) revealed a mass-like tension which showed the same enhancement as a venous intensity. At operation, we found a white solid mass which had no capsule. The mass was easily removed, because it was not adherent to the surrounding tissues. The pathological diagnosis was nodular fasciitis which showed positive immunostaining for vimentin, HHF 35 (muscle actin), type III collagen and lysozyme, but negative immunostaining for desmin, S-100 protein and CD 34. This rare condition can be diagnosed only by pathological examination, however, it must be kept in mind in the differential diagnosis of retroauricular mass lesions.

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難聴・耳鳴・顔面神経麻痺

小川郁

JIM 9 （ 12 ） 1077-1080 1999年12月

研究論文（学術雑誌）, 単著

顔面に隆起性腫瘤として生じた悪性線維性組織球腫の1例

田島麻衣子，畑康樹，長坂武，大畑恵之，谷川瑛子，清水宏，小川郁，中嶋英雄，星野佳子，宮林徹

臨床皮膚科 53 （ 13 ） 1130-1132 1999年12月

研究論文（学術雑誌）, 共著

外耳・中耳の炎症性疾患

小川郁

JIM 9 （ 12 ） 1073-1076 1999年12月

研究論文（学術雑誌）, 単著

ストレスと耳鳴

小川郁

総合臨床 48 （ 9 ） 2239-2240 1999年09月

研究論文（学術雑誌）, 単著

Choristoma in the meddle ear: a case report

Morimoto Noriko, Ogawa Kaoru, Kanzaki Jin

American Journal of Otolaryngology 20 （ 4 ） 232-235 1999年08月

研究論文（学術雑誌）, 共著

Salivary gland choristoma in the middle ear

Morimoto Noriko, Ogawa Kaoru, Kanzaki Jin

American Journal of Otolaryngology - Head and Neck Medicine and Surgery 20 （ 4 ） 232 - 235 1999年07月

ISSN 0196-0709

Salivary gland choristoma (ectopic or heterotopic salivary gland tissue) is a rare condition that occurs in various locations within the head and neck regions. We present a 13-year-old boy with a salivary gland choristoma in the middle ear associated with congenital alopecia around the auricle in addition to facial nerve and ossicular chain abnormalities. Because the lesions commonly involve the facial nerve, intraoperative facial nerve monitoring is helpful in allowing safe biopsy without facial nerve damage.

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頭頸部領域における血管系腫瘍の診断と治療

井上泰宏，神崎仁，小川郁，保谷則之，武井聡

頭頸部外科 9 （ 1 ） 51-55 1999年06月

研究論文（学術雑誌）, 共著

小児心因性難聴の臨床像と治療結果

小川郁，神崎仁，井上泰宏，保谷則之，武井聡，志津木健，佐倉伸洋，浅野恭子，田副真美

Audiology Japan 42 （ 2 ） 131-136 1999年04月

研究論文（学術雑誌）, 共著

小児心因性難聴における心因の変化

浅野恭子，小川郁，井上泰宏，田副真美，神崎仁

Audiology Japan 42 （ 2 ） 94-99 1999年04月

研究論文（学術雑誌）, 共著

DPOAE位相情報の活用法

原田竜彦，井上泰宏，小川郁，神崎仁

Audiology Japan 42 （ 2 ） 94-99 1999年04月

研究論文（学術雑誌）, 共著

Aging does not alter phosphoinositide hydrolysis in the rat cochlear lateral wall

Ogawa Kaoru, Schacht Jochen

Auris Nasus Larynx 26 （ 1 ） 1 - 4 1999年01月

ISSN 0385-8146

We have previously reported that the inositol 1,4,5-trisphosphate (InsP₃) second messenger system is coupled to purinergic P2y receptors in the cochlear sensory epithelium and lateral wall. The tissues of the cochlear lateral wall (stria vascularis and spiral ligament) are responsible for maintaining the ionic composition of the cochlear endolymph. Both the endolymphatic potential and signal transduction processes are well known to be affected by aging. Furthermore, intracellular inositol concentrations decrease with age in the cochlear sensory epithelia. The present study compared the purinergic receptor-mediated release of inositol phosphates (InsPs) in the cochlear lateral wall of young (3 month-old) and aged (24 month-old) Fischer-344 rats. No differences were found in the incorporation of myo-[³H]inositol into phosphoinositide lipids. Likewise, the purinergic receptor-mediated release of InsPs remained unchanged. This suggests that the InsPs second messenger system in the cochlear lateral wall, in contrast to the sensory epithelium, may not be affected by aging.

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Aging does not affect phosphoinositide hydrolysis in the cochlear lateral wall

Ogawa Kaoru, Schacht Johen

Auris Nasus Larynx 26 （ 1 ） 1-4 1999年01月

研究論文（学術雑誌）, 共著

広範な凝固壊死を伴った耳下腺多形性腺腫の1例

山内友江，亀山香織，草刈悟，阿部仁，内田光子，小川郁，向井萬起男，秦順一

日本臨床細胞学会誌 38 （ 1 ） 89-92 1999年01月

研究論文（学術雑誌）, 共著

広範な凝固壊死を伴った耳下腺多型腺腫の1例

山内友江，亀山香織，草刈悟，阿部仁，内田光子，小川郁，向井萬起男，秦順一

日本臨床細胞学会雑誌 38 （ 1 ） 89-92 1999年01月

研究論文（学術雑誌）, 共著

聾型突発性難聴の臨床像

保谷則之，小川郁，井上泰宏，斎藤秀行，原田竜彦，佐藤美奈子，神崎仁

Audiology Japan 41 （ 6 ） 765-769 1998年12月

研究論文（学術雑誌）, 共著

Quality of hearing preservation in acoustic neuroma surgery

Kanzaki Jin, Ogawa Kaoru, Inoue Yasuhiro, Shiobara Ryuzo, Toya Shigeo

The American Journal of Otology 19 （ 5 ） 644-648 1998年09月

研究論文（学術雑誌）, 共著

Quality of hearing preservation in acoustic neuroma surgery

Kanzaki Jin, Ogawa Kaoru, Inoue Yasuhiro, Shiobara Ryuzo, Toya Shigeo

American Journal of Otology 19 （ 5 ） 644 - 648 1998年09月

ISSN 0192-9763

Objective: This study aimed to investigate the factors affecting the quality of postoperative hearing in acoustic neuroma. Study Design: The study was designed as a retrospective case review. Setting: The study was performed at the Department of Otolaryngology, School of Medicine, Keio University, Tokyo, Japan. Patients: The subjects were 94 patients with unilateral acoustic neuroma. Intervention: Hearing preservation surgery was performed in the subjects via the extended cranial fossa approach or the middle cranial fossa approach. Main Outcome Measures: The outcome measures included patient's age and gender, hearing level, speech discrimination score, tumor size, and surgical approach. The relationship between the qualities of preoperative and postoperative hearing and the long-term prognosis of preserved heating also was investigated. Results: In 94 subjects, there were 47 patients whose hearing was preserved (HP group) and 47 patients whose hearing was not preserved (non-HP group). Overall, hearing preservation rate was 50%. There were no significant differences in age, gender, and tumor size between the two groups. The heating preservation rate was significantly higher in patients with an intracanalicular tumor than that with a larger tumor. The better the preoperative quality of hearing was, the higher the postoperative one. Although the preserved hearing deteriorated after surgery in 4 patients, no significant hearing deterioration was observed in the other 43 patients. Conclusions: The results of this study indicated that the diagnosis for acoustic neuroma in the early stage with serviceable hearing is the most important to improve the quality of postoperative hearing.

明日の診療に役立つ画像診断・内耳道病変

小川郁

耳鼻と臨床 44 （ 5 ） 740-742 1998年05月

研究論文（学術雑誌）, 単著

高齢者の耳鳴

小川郁

耳鼻咽喉科・頭頚部外科 70 （ 5 ） 27-31 1998年04月

研究論文（学術雑誌）, 単著

New system for linear accelerator radiosurgery with a gantry-mounted video camera

Kunieda Etsuo, Kitamura Masayuki, Kawaguchi Osamu, Ohira Takayuki, Ogawa Kouichi, Ando Yutaka, Nakamura Kayoko, Kubo Atsushi

Int J Radiat Oncol Biol Phys 40 （ 3 ） 739-746 1998年03月

研究論文（学術雑誌）, 共著

Hearing in the MRL/lpr mouse as a possible model of immune-mediated sensorineural hearing loss

Inoue Y., Kanzaki J., Ogawa K., Hashiguchi K., Masuda M.

European Archives of Oto-Rhino-Laryngology 255 （ 5 ） 240 - 243 1998年

ISSN 0937-4477

In order to clarify the possible mechanism of hearing loss in immune-mediated sensorineural hearing loss, basic research needed includes animal model studies. In the present investigation, we examined hearing thresholds and cochlear histologies of the MRL/lpr mouse which is now well-known as a model for pathology consistent with systemic lupus erythematosis (SLE). Present findings demonstrated that there were no statistically significant differences in auditory brainstem response (ABR) thresholds between 4- to 6-week-old 'young' and 20- to 25-week-old 'old' MRL mice. These differences were not sex-dependent. Under light microscopy, there were no abnormal morphological findings in the cochleas of either young or old MRL mice. With immunohistochemistry, mouse IgG was detected around the capillary walls in the stria vascularis in both young and old MRL mice. Serum IgG level of the MRL mice significantly decreased after predonisolone (PSL) administration. However, expression of mouse IgG in the stria vascularis was not observed in the MRL mice after PSL administration. From these results, we speculate that the hearing of the MRL mouse does not always deteriorate, and the deposition of mouse IgG on the capillary wall in the stria vascularis is not a sufficient factor to induce hearing loss. At this point, we conclude that the MRL mouse should not be considered a useful model for immune-mediated sensorineural hearing loss.

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Hearing preservation surgery in acoustic neuroma patients with normal hearing

Kanzaki J, Ogawa K, Inoue Y, Shiobara R

Skull Base Surgery 7 109-113 1998年

研究論文（学術雑誌）, 共著

Quality of hearing preservation in acoustic neuroma surgery

Kanzaki J, Ogawa K, Inoue Y, Shiobara R

The American Journal of Otology 19 644-648 1998年

研究論文（学術雑誌）, 共著

Hearing of MRL/lpr mouse: Is it used as a model of immune-mediated sensorinoural hearing loss ?

Inoue Yasuhiro, Kanzaki Jin, Ogawa Kaoru, Hashiguchi Kazuhiro, Masuda Masazumi, Saito Hideyuki, Harada Tatsuhiko

European Archives of Otorhinolaryngology 255 240-243 1998年

研究論文（学術雑誌）, 共著

Hearing preservation surgery in acoustic neuroma patients with normal hearing

Kanzaki Jin, Ogawa Koru, Inoue Yasuhiro, Shiobara Ryuzo

Skull Base Surg 7 109-113 1998年

研究論文（学術雑誌）, 共著

Photo-induced cochlear ischemia of guinea pig

Saito Hideyuki, Ogawa Kaoru, Inoue Yasuhiro, Harada Tatsuhiko, Hoya Noriyuki, Kanzaki Jin

Proc Sendai Symposium 7 67-69 1997年12月

研究論文（学術雑誌）, 共著

DPPOAE latency measuremant using inverse FFT

Harada Tatsuhiko, Inoue Yasuhiro, Ogawa Kaoru, Saito Hideyuki, Hoya Noriyuki, Kanzaki Jin

Proc Sendai Symposium 7 113-114 1997年12月

研究論文（学術雑誌）, 共著

側頭骨内顔面神経鞘腫

原田竜彦，神崎仁，井上泰宏，小川郁，斎藤秀行

Facial Nerve Res 16 43-46 1997年12月

研究論文（学術雑誌）, 共著

パソコンによる統計解析

池田俊也，小川郁，松延毅

JOHNS 13 （ 12 ） 1809-1814 1997年12月

研究論文（学術雑誌）, 共著

プレゼンテーションの方法とその準備

志津木健，池田俊也，小川郁

JOHNS 13 （ 12 ） 1785-1791 1997年12月

研究論文（学術雑誌）, 共著

パソコンによる統計解析

池田俊也，小川郁，松延毅

JOHNS 13 （ 12 ） 1809-1814 1997年12月

研究論文（学術雑誌）, 共著

プレゼンテーションの方法とその準備

志津木健，池田俊也，小川郁

JOHNS 13 （ 12 ） 1785-1791 1997年12月

研究論文（学術雑誌）, 共著

プレゼンテーションの方法とその準備

志津木健，池田俊也，小川郁

JOHNS 13 （ 12 ） 1785-1791 1997年12月

研究論文（学術雑誌）, 共著

側頭骨内顔面神経鞘腫

原田竜彦，神崎仁，井上泰宏，小川郁，斎藤秀行

Facial N Res Jpn 17 43-46 1997年06月

研究論文（学術雑誌）, 共著

側頭骨縦骨折

小川郁

耳鼻・頭頸外科 69 （ 6 ） 56-59 1997年06月

研究論文（学術雑誌）, 単著

蝸牛内情報伝達機構とセカンドメッセンジャー

小川郁，神崎仁，井上泰宏，原田竜彦，斎藤秀行，保谷則之，大場俊彦

Otol Jpn 7 （ 2 ） 86-91 1997年05月

研究論文（学術雑誌）, 共著

聴神経腫瘍における聴力保存手術の適応について

井上泰宏，神崎仁，小川郁，斎藤秀行，原田竜彦

Otol Jpn 7 （ 2 ） 70-74 1997年05月

研究論文（学術雑誌）, 共著

Clinical application of transiently evoked otoacoustic emissions after glycerol administration for diagnosis of sensorineural hearing loss

Inoue Yasuhiro, Kanzaki Jin, O-Uchi Toshiaki, Ogawa Kaoru, Ogata Akira, Yoshihara Shigemitu, Satoh Yasuo

Auris Nasus Larynx 24 （ 2 ） 143 - 149 1997年04月

ISSN 0385-8146

Pure-tone audiometry and transiently evoked otoacoustic emission (TEOAE) measurements were made before and after glycerol administration in the ears of sensorineural hearing loss with three different clinical entities, i.e. Meniere's disease, cochlear Meniere's disease and unilateral sensorineural hearing loss of unknown cause without hearing fluctuation (SNHLWF). TEOAE was evoked after glycerol administration in several ears of Meniere's disease and cochlear Meniere's disease, in which it was not evoked before glycerol administration. Especially in patients with cochlear Meniere's disease, TEOAE was altered without an accompanying significant change in mean hearing level. The change in TEOAE after glycerol administration indicates that the active motile property of outer hair cells may be affected by endolymphatic hydrops.

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Clinical application of transient evoked otoacoustic emissions after glycerol administration for diagnosis of sensorineural hearing loss

Inoue Yasuhiro, Kanzaki Jin, O-Uchi Toshiaki, Ogawa Kaoru, Ogata Akira, Yoshihara Shigemitsu, Satoh Yasuo

Auris Nasus Larynx 24 （ 2 ） 143-149 1997年04月

研究論文（学術雑誌）, 共著

メニエール病における誘発耳音響放射の臨床応用

井上泰宏，神崎仁，小川郁，斎藤秀行，原田竜彦

Audiology Japan 40 （ 2 ） 95-99 1997年04月

研究論文（学術雑誌）, 共著

脳幹インプラントの現状と将来

小川郁

BME 11 （ 4 ） 29-33 1997年04月

研究論文（学術雑誌）, 単著

Hearing preservation surgery in acoustic neuroma patients with normal hearing

Kanzaki Jin, Ogawa Kaoru, Inoue Yasuhiro, Shiobara Ryuzo

Skull Base Surgery 7 （ 3 ） 109 - 113 1997年

ISSN 1052-1453

Acoustic neuroma (AN) patients who had normal hearing accounted for 7% of all our AN cases. It is important to identify AN patients who have normal hearing but are suffering from tinnitus, dizziness, or vertigo, or a combination of these symptoms (without hearing loss), in order to make an early diagnosis. Patients who experience sudden hearing loss and recover completely should also be thoroughly examined in order to rule out AN. In this article, we describe an investigation of the clinical features and results of hearing preservation surgery in AN patients with normal hearing. The overall hearing preservation rate was 57%. The hearing preservation rate did not depend on the auditory brainstem response (ABR) pattern, tumor size, or the origin of the tumor. We think that patients must be properly informed concerning all aspects of the surgery, including the possibility that hearing and/or facial nerve function cannot be preserved.

Hearing preservation surgery in acoustic neuroma patients with normal hearing

Kanzaki Jin, Ogawa Kaoru, Inoue Yasuhiro, Shiobara Ryuzo

Skull Base Surg 7 109-113 1997年

研究論文（学術雑誌）, 共著

特発性内耳道狭窄の2症例

斎藤秀行，小川郁，井上泰宏，原田竜彦，神崎仁

Otol Jpn 6 （ 5 ） 556-561 1996年12月

研究論文（学術雑誌）, 共著

Heterogeneity of PLC in the cochlea

Ohba Toshihiko, Ogawa Kaoru, Lee Byung Don, Kanzaki Jin

Proc Sendai Symposium 6 11-13 1996年12月

研究論文（学術雑誌）, 共著

聴神経腫瘍における誘発耳音響放射について

井上泰宏，神崎仁，小川郁，小形章，吉原重光，佐藤靖夫

Audiology Japan 39 （ 4 ） 274-278 1996年08月

研究論文（学術雑誌）, 共著

耳鳴とは

小川郁

臨床と薬物治療 15 （ 6 ） 457-460 1996年06月

研究論文（学術雑誌）, 単著

突発性難聴発症直後における耳鳴の経時的変化

井上泰宏，神崎仁，大内利昭，小川郁，斎藤秀行，原田竜彦

Audiology Japan 39 （ 1 ） 84-89 1996年02月

研究論文（学術雑誌）, 共著

Electrocochleography during experimental cochlear ischemia of the guinea pig

Ogawa Kaoru, Kanzaki Jin, Ogawa Shigeo, Tsuchihashi Nobuaki, Inoue Yasuhiro, Sato Minako, Ikeda Shunya

Acta Oto-Laryngologica 116 （ 2 ） 253 - 256 1996年

ISSN 0001-6489

It has been postulated that impairment of cochlear blood flow (CoBF) is one of the most important causes of hearing loss occurring during acoustic neuroma (AN) surgery. However, it remains unclear how the degree of cochlear ischemia influences the evoked responses in electrocochleography (ECochG) which has been used for monitoring cochlear functions. In the present study, we investigated alterations in ECochG during cochlear ischemia of varying degree in the guinea pig. In order to induce cochlear ischemia, the anterior inferior cerebellar artery (AICA) was mechanically compressed via the transclival approach. The compression of AICA resulted in a reduction of CoBF in 55 out of 70 guinea pigs. A constant reduction of CoBF was maintained during the compression of AICA in 44 (63%) guinea pigs. CoBF abruptly decreased upon compressing AICA, and promptly recovered after releasing the compression. N1 and N2 in ECochG were also altered by compression. During 3-min ischemia, N1 and N2 disappeared in 36% and 41% of the cases, respectively. The residual CoBF in cases whose N1 and N2 disappeared was significantly lower that that in other cases whose N1 and N2 were sustained during 3-min ischemia. In addition, there was a tendency that the lower the residual CoBF was, the shorter the survival time of N1 and N2. In cases whose NI and N2 did not disappear, the prolongation of N1 and N2 latencies after 3-min ischemia was positively correlated to the residual CoBF. On the basis of these results, we discuss the mechanisms underlying the changes in CoBF and ECochG during cochlear ischemia, and conclude that the degree of cochlear ischemia during AN surgery can be estimated with ECochG.

Classification of hearing results after resection of acoustic neuromas. Extended Middle cranial fossa approach

Kanzaki Jin, Shiobara Ryuzo, Ogawa Kaoru, Inoue Yasuhiro, Satoh Yasuo, Yoshihara Shigemitsu, Toya Shigeo

Proceedings of the 2nd International Conference on Acoustic Neurma Surgery and 2nd European Skull Base Society Congress 227-230 1996年

研究論文（学術雑誌）, 共著

Facial nerve preservation in acoustic neuroma surgery with stimulus microinstruments. Extended middle cranial fossa approach

Kanzaki Jin, Shiobara Ryuzo, Ogawa Kaoru, Inoue Yasuhiro, Satoh Yasuo, Yoshihara Shigemitsu, Toya Shigeo

Proceedings of the 2nd International Conference on Acoustic Neuroma and 2nd European Skull Base Society Congress 131-136 1996年

研究論文（学術雑誌）, 共著

Electrocochleography during experimental cochlear ischemia of the guinea pigs

Ogawa Kaoru, Kanzaki Jin, Ogawa Shigeo, Tsuchihashi Nobuaki, Inoue Yasuhiro, Satoh Minako, Ikeda Shunya

Acta Otolaryngology 116 253-256 1996年

研究論文（学術雑誌）, 共著

免疫異常モデルマウス（MRL/lpr）における難聴と組織学的研究--柴苓湯の影響について--

井上泰宏，神崎仁，小川郁，斎藤秀行，原田竜彦

耳鼻臨補89 16-16 1996年

研究論文（学術雑誌）, 共著

Electrocochleography and cochlear blood flow during experimental cochlear ischemia of the guinea pig

Ogawa K, Kanzaki J, Ogawa S, Tsuchihashi N, Inoue Y, Sato M, Ikeda S

Acta Otolaryngol (Stockh) 116 253-256 1996年

研究論文（学術雑誌）, 共著

聴神経腫瘍における聴力保存の基礎と臨床

神崎仁，小川郁，松永達雄

耳鼻臨床 89 （ 3 ） 285-295 1996年

研究論文（学術雑誌）, 共著

Basic and clinical aspects of hearing preservation in acoustic neuroma surgery

Kanzaki Jin, Ogawa Kaoru, Matsunaga Tatsuo

Practica Otologica 89 （ 3 ） 285 - 295 1996年

ISSN 0032-6313

Hearing preservation is one of the ultimate goals of acoustic neuroma (AN) surgery. In this paper, we present the surgical results of hearing preservation surgery in our department, as well as our recent basic research on hearing preservation in AN surgery. Subjects consisted of 95 AN patients who underwent hearing preservation surgery via the extended middle cranial fossa approach and the middle cranial fossa approach. The overall hearing preservation rate was 51%. From the analysis of surgical results, we discussed the indications for hearing preservation surgery and the evaluation of pre- and post-operative hearing. In addition, we proposed a new classification system for pre- and post-operative hearing evaluation. We also present our basic research on "the relationship between cochlear blood flow and electrocochleographic findings during cochlear ischemia", and "the morphological studied of the VIII cranial nerve in AN patients". The changes in N1 and N2 in electrocochleography depended on the cochlear blood flow. Thus, we can estimate the degree of cochlear ischemia using the electrocochleography. Furthermore, the impairment of cochlear blood flow and cochlear nerve damage could be distinguished by the electrocochleographic findings. The morphological findings of the VIII cranial nerves of AN patients demonstrated tumor invasion in approximately 67% of the cochlear nerves, suggesting that total tumor removal together with hearing preservation could not be performed in these patients. In addition, gliosis in the transitional region of the cochlear nerve in AN patients was observed, which might lead to a change in capillary distribution. Angiogenesis was also found in tumor tissues from the cochlear nerve. These morphological findings indicated that the impairment of cochlear blood flow may be easily induced by manipulation during tumor removal, especially those around the transitional region.

メニエール病におけるグリセロール負荷後の耳鳴とEOAEの変化について

井上泰宏，神崎仁，大内利昭，小川郁，小形章，吉原重光，佐藤靖夫

Otol Jpn 5 （ 5 ） 603-607 1995年12月

研究論文（学術雑誌）, 共著

Purinergic receptor is coupled to inositol trisphosphate second messenger system in the cochlear lateral wall

Ogawa K, Kanzaki J, Schacht J

Proc Sendai Symposium 5 （ 1 ） 129-132 1995年12月

研究論文（学術雑誌）, 共著

P2y purinergic receptors coupled to phosphoinositide hydrolysis in tissues of the cochlear lateral wall

Ogawa K, Schacht J

NeuroReport 6 （ 11 ） 1538-1540 1995年07月

研究論文（学術雑誌）, 共著

蝸牛遠心性神経系の情報伝達とイノシトールリン酸・・生化学的アプローチから・・

小川郁

Otol Jpn 5 （ 2 ） 97-104 1995年05月

研究論文（学術雑誌）, 単著

P2y purinergic receptors coupled to phosphoinositide hydrolysis in tissues of the cochlear lateral wall

Ogawa K., Schacht J.

NeuroReport 6 （ 11 ） 1538 - 1540 1995年

ISSN 0959-4965

The tissues of the lateral wall of the cochlea, spiral ligament and stria vascularis, maintain homeostasis of the inner ear through the production of endolymph and regulation of cochlear blood flow. We examined the effects of purinergic agonists on the release of inositol phosphates (InsPs) in intact isolated lateral wall tissues of the Fischer-344 rat. After preincubation with myo-[³H]-inositol, stimulation with the P2 purinergic agonist ATP-γ-S resulted in a concentration-dependent increase in the formation of [³H]InsPs. The P2 purinergic agonist α,β-methylene ATP (AMP-CPP) was a weaker stimulant, and the P1 purinergic agonist adenosine was ineffective. These results are consistent;with the presence of P2y receptors and a purinergically controlled InsPs second messenger system in the cochlear lateral wall.

Hearing preservation by the extended and nonextended middle cranial fossa approach for acoustic neuroma

Kanzaki J., O-Uchi T., Ogawa K., Shiobara R., Toya S.

Skull Base Surgery 4 （ 2 ） 76 - 81 1994年

ISSN 1052-1453

The results of 248 cases of acoustic neuroma surgery carried out mainly by the extended middle cranial fossa approach during a 16-year period from 1976 to 1991 are analyzed. Hearing preservation was attempted in 69 cases and successfully achieved in 35 (51%) cases. Hearing was preserved in 24 (57%) of 42 cases in which a tumor was 20 mm or smaller in diameter, pure-tone hearing level was 50 dB or lower, and speech discrimination score was 50% or higher. The hearing preservation rate (76%) in the cases with a tumor extending 3 mm or less from the internal auditory canal was much higher than in cases with a larger tumor. Hearing was preserved in three of seven cases with a tumor of 21 mm or larger and in two of four cases of neurofibromatosis type 2. The evaluation of postoperative hearing is also discussed.

Evaluation of hearing recovery in patients with sudden deafness

Yamamoto Minako, Kanzaki Jin, Ogawa Kaoru, Ogawa Shigeo, Tsuchihashi Nobuaki

Acta Oto-Laryngologica 114 （ S514 ） 37 - 40 1994年

ISSN 0001-6489

It is still difficult to evaluate the efficacy of treatment of sudden deafness. Effective methods of therapy have been reported in some studies and other studies have reported spontaneous recovery. In The present study, we assessed the correlation between hearing recovery and various parameters measured during recovery. We used three parameters: hearing gain, relative hearing gain, and recovery rate. We found that the recovery rate during recovery and the parameters measured on the 7th treatment day demonstrated the greatest correlation. The recovery rate on the 7th day of treatment was found to be useful for predicting the final hearing recovery. Comparison of the recovery rate on the 7th day of treatment may be useful for the evaluation of the efficacy of treatment of sudden deafness.

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Aplastic anemia and sudden sensorineural hearing loss

Ogawa Kaoru, Kanzaki Jin

Acta Oto-Laryngologica 114 （ S514 ） 85 - 88 1994年

ISSN 0001-6489

In the present study, the clinical and audiological features of 3 patients with aplastic anemia who subsequently developed sudden sensorineural hearing loss are reported. These patients, for whom a diagnosis of aplastic anemia had previously been confirmed, suddenly developed profound or complete hearing loss accompanied by tinnitus and severe vertigo. In addition to erythrocytopenia and thrombocytopenia, serial hematological examinations revealed a marked drop in the platelet count prior to or just at the time of the acute episode of hearing loss. The prognosis for hearing recovery was poor in each patient. These findings suggest that intracochlear hemorrhage could be a mechanism underlying the sudden sensorineural hearing loss in these patients.

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Endoscopic diagnosis of idiopathic perilymphatic fistula

Ogawa Kaoru, Kanzaki Jin, Ogawa Shigeo, Tsuchihashi Nobuaki, Inoue Yasuhiro, Yamamoto Minako

Acta Oto-Laryngologica 114 （ S514 ） 63 - 65 1994年

ISSN 0001-6489

The usefulness of endoscopic examination for the diagnosis of idiopathic perilymphatic fistula (IPLF) was investigated. Eight patients presenting with unilateral sensorineural hearing loss and vertigo underwent endoscopic examination by the transtubal or transtympanic approach. In 5 out of the 8 patients, transtubal endoscopy was carried out using a superfine flexible endoscope. With this approach, no abnormal findings were visualized. A perilymphatic leak from the round window was observed in 2 patients by means of transtympanic examination using a needle scope. These findings were confirmed in both patients by microscopic observation during tympanotomy. In one patient who was finally diagnosed with IPLF, the transtympanic endoscopy failed to detect perilymphatic leakage. Although incision of the tympanic membrane is necessary for the examination, transtympanic endoscopy is useful for the diagnosis of IPLF. Further improvement of the superfine flexible fiberscope is necessary before transtubal observation of the tympanic cavity can be effectively conducted.

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Hearing recovery and vestibular symptoms in patients with sudden deafness and profound hearing loss

Yamamoto Minako, Kanzaki Jin, Ogawa Kaoru, Inoue Yasuhiro, Ikeda Shunya

Acta Oto-Laryngologica 114 （ S514 ） 41 - 44 1994年

ISSN 0001-6489

Audiometric data from 76 patients with unilateral sudden deafness and hearing loss of 80 dB or more were studied to statistically assess the relationship between vestibular findings (vertigo and/or dizziness, nystagmus, canal paresis) and hearing recovery in various frequency ranges. Hearing recovery in patients with vertigo and/or dizziness (V(+ was much poorer than in patients without such findings (V(-)). Concerning hearing recovery in the high frequency range, a significant statistical difference was evident between the V(+ and V(-) group. There were no statistically significant differences in hearing recovery between patients with spontaneous nystagmus or canal paresis and those without.

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Effect of aging on myo-inositol and phosphoinositide metabolism in the cochlear and vestibular sensory epithelia of the rat

Ogawa Kaoru, McLaren John, Schacht Jochen

Hearing Research 73 （ 2 ） 155 - 162 1994年

ISSN 0378-5955

Neurotransmission and transmembrane signaling are among the cellular mechanisms affected in the aging nervous system. In the inner ear, the phosphoinositide second messenger cascade is of particular interest as a target of the aging process. In both the cochlear (CSE) and vestibular sensory epithelia (VSE), the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdInsP₂) to the second messenger inositol 1,4,5-trisphosphate (InsP₃) is coupled to muscarinic cholinergic and P_2y purinergic receptors and may be linked to calcium homeostasis. The present study compared the turnover of phosphoinositides (PtdlnsPs), receptor-mediated release of inositol phosphates (InsPs), and concentrations of endogenous myo-inositol in the CSE and VSE of young (3 months) and aged (24 months) Fischer-344 rats. In the aged rat, there was a significant increase in [³H]inositol incorporation (per mass of protein) into PtdlnsPs plus InsPs in both sensory epithelia while the protein content remained unchanged. In contrast, no age-dependent differences were found when pre-labeled [³H]PtdInsPs were 'chased' with non-radiolabeled myo-inositol indicating that the turnover of these lipids was unaffected. The cholinergic receptor agonist carbamylcholine and the P₂ purinergic receptor agonist adenosine 5′-O-(3-thiotriphosphate) stimulated the release of [³H]InsPs two- to six-fold in both organs. This agonist-stimulated release of [³H]InsPs (per mass of protein) was significantly higher in aged animals. However, when the same stimulation was expressed as per cent of control values, there was no age-dependent difference. Finally, the concentration of endogenous myo-inositol decreased by 44% in the aged CSE and by 24% in the aged VSE. In contrast, levels of added myo-[³H]inositol were higher in aged tissues. These results suggest that the increased labeling of PtdlnsPs and InsPs in the aged CSE and VSE is a consequence of the increased specific radioactivity of the myo-[³H]inositol precursor pool. The activity of the phosphoinositide second messenger pathway thus appears unchanged. However, a decreased myo-inositol content may contribute to age-dependent pathology in these tissues, myo-inositol is an organic osmolyte and volume regulator. Changes in osmotic pressure or turgor of hair cells could alter micromechanical coupling on the basilar membrane and vestibular epithelium causing pathophysiological changes in sensory transduction.

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G-proteins coupled to phosphoinositide hydrolysis in the cochlear and vestibular sensory epithelia of the rat are insensitive to cholera and pertussis toxins

Ogawa Kaoru, Schacht Jochen

Hearing Research 74 （ 1-2 ） 197 - 203 1994年

ISSN 0378-5955

In the cochlear (CSE) and vestibular sensory epithelia (VSE), phosphoinositides are hydrolyzed in response to stimulation of phospholipase C (PLC) by cholinergic muscarinic and purinergic P_2y agonists. Such receptor-mediated activation of PLC is expected to be coupled through guanine nucleotide-binding proteins (G-proteins). Although several classes of G-proteins have been identified in the inner ear, nothing is known about the type of G-proteins associated with the phosphoinositide second messenger system in CSE and VSE. Phosphoinositide hydrolysis was determined by the release of radiolabeled inositol phosphates (InsPs). Ten mM NaF plus 10 μM AlCl₃ increased basal InsPs accumulation 2-fold in both CSE and VSE of the rat. Release of InsPs was also enhanced by guanosine 5'-O-(3-thiotriphosphate) (GTP-γ-S) in saponin-permeabilized tissues. Furthermore, release of InsPs stimulated by both carbamylcholine (CCh) and adenosine 5'-O-[3-thiotriphosphate](ATP-γ-S) was significantly inhibited by 100 μM guanosine 5'-O-[2-thiodiphosphate](GDP-β-S). These results strongly suggest the involvement of G-proteins in the receptor-PLC coupling in CSE and VSE. ADP-ribosylation in membrane fractions of CSE and VSE in the presence of cholera toxin (CTX) or pertussis toxin (PTX) indicated the existence of G_s- and G_i-type G-proteins. However, neither CTX nor PTX affected basal or agonist-stimulated release of InsPs. These observations suggest that muscarinic and P_2y purinergic receptors are coupled to PLC via CTX- and PTX-insensitive G-proteins in CSE and VSE.

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Receptor-mediated release of inositol phosphates in the cochlear and vestibular sensory epithelia of the rat

Ogawa Kaoru, Schacht Jochen

Hearing Research 69 （ 1-2 ） 207 - 214 1993年

ISSN 0378-5955

Various neurotransmitters, hormones and other modulators involved in intercellular communication exert their biological action at receptors coupled to phospholipase C (PLC). This enzyme catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdInsP₂) to inositol 1,4,5-trisphosphate (InsP₃) and 1,2-diacylglycerol (DG) which act as second messengers. In the organ of Corti of the guinea pig, the InsP₃ second messenger system is linked to muscarinic cholinergic and P₂y purinergic receptors. However, nothing is known about the the InsP₃ second messenger system in the vestibule. In this study, the receptor-mediated release of inositol phosphates (InsPs) in the vestibular sensory epithelia was compared to that in the cochlear sensory epithelia of Fischer-344 rats. After preincubation of the isolated intact tissues with myo-[³H] in-ositol, stimulation with the cholinergic agonist carbamylcholine or the P₂ purinergic agonist ATP-γ-S resulted in a concentration-dependent increase in the formation of [³H]InsPs in both epithelia. Similarly, the muscarinic cholinergic agonist muscarine enhanced InsPs release in both organs, while the nicotinic cholinergic agonist dimethylphenylpiperadinium (DMPP) was ineffective. The muscarinic cholinergic antagonist atropine completely suppressed the InsPs release induced by carbamylcholine, while the nicotinic cholinergic antagonist mecamylamine was ineffective. Potassium depolarization did not alter unstimulated or carbamylcholine-stimulated release of InsPs in either organ. In both tissues, the P₂ purinergic agonist α,β-methylene ATP also increased InsPs release, but the P₁ purinergic agonist adenosine did not. These results extend our previous observations in the organ of Corti of the guinea pig to the rat and suggest a similar control of the InsP₃ second messenger system in the vestibular sensory epithelia. In contrast to the cochlear sensory epithelia, atropine also significantly suppressed unstimulated InsPs release in the vestibular sensory epithelia. This suggests that the physiological mechanisms of the efferent nervous systems involving InsP₃ second messenger system might be different in vestibular versus cochlear sensory epithelia.

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Light and electron microscopic study of vestibular sensory epithelia in 17 cases with acoustic neurinoma

Matsunaga T., Kanzaki J., Shatari T., Ogawa K., O-Uchi T., Hosoda Y.

Auris Nasus Larynx 19 （ 4 ） 199 - 208 1992年

ISSN 0385-8146

Vestibular sensory epithelia were studied histologically and ultrastructurally in 17 cases with acoustic neurinoma (AN). The superior vestibular nerve (SVN) near the fundus was also histologically studied in 5 of these 17 cases. Histologically, severe fibrotic change of the vestibular sensory epithelia was found in 1 case, and severe fibrotic change of the SVN was also found in this case. Intra-epithelial cysts were found at the edge of the utricular sensory epithelia in 2 cases. The cysts consisted of the transitional epithelium and were filled with the darkly stained substances. Ultrastructurally, abnormal accumulation of darkly stained masses within the nerve ending and abnormal accumulation of the fibrillar material below the normal basal lamina were frequently observed. These morphological changes described above were regarded as the pathological changes due to AN. In addition, the relationship among the histologic changes, ultrastructural changes and clinical data were fully investigated, and some histologic and ultrastructural changes were regarded as artifacts or age-related changes.

A case of possible MS with the onset of vertigo and hemifacial palsy

Matsunaga T., Ogawa S., Ogawa K., Takahashi M., Kanzaki J.

Equilibrium Research 50 （ 2 ） 215 - 220 1991年

ISSN 0385-5716

Sudden deafness and vascular loop in the internal auditory canal

Ogawa K.

Otolaryngology - Head and Neck Surgery (Tokyo) 63 （ 9 ） 681 - 686 1991年

ISSN 0914-3491

Acoustic neuromas with normal hearing

Ogawa Kaoru, Kanzaki Jin, Ogawa Shigeo, Tsuchihashi Nobuaki, Yamamoto Minako

Acta Oto-Laryngologica 111 （ S487 ） 144 - 149 1991年

ISSN 0001-6489

We report on 10 patients with surgically proven acoustic neuroma (AN) who have normal hearing, and their clinical features have been investigated. The results obtained in this study were as follows: The clinical features of AN patients with normal hearing involved 1) predominance in younger adults, 2) predominance in small tumors with short duration after onset, 3) subjective hearing loss accompanied with tinnitus was the most common symptom, and 4) vertigo or dizziness without any cochlear symptoms was also a frequently seen symptom. We conclude that in order not to overlook AN among patients with normal hearing, transorbital X-ray and ABR tests should be performed on these patients for the screening purpose.

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Progression of hearing loss in acoustic neuromas

Ogawa Kaoru, Kanzaki Jin, Ogawa Shigeo, Tsuchihashi Nobuaki, Ikeda Shunya

Acta Oto-Laryngologica 111 （ S487 ） 133 - 137 1991年

ISSN 0001-6489

The progression of hearing loss and the factors influencing it are not well understood in patients with acoustic neuroma (AN). We investigated the relationships between the progression of hearing loss and the clinical findings in 42 patients with unilateral AN whose hearing could be examined for a period of 6 months or more. There was a tendency for hearing to deteriorate progressively in the patients with retrocochlear hearing loss, or with a small tumor. Based on these results, we conclude that an operation for hearing preservation should be performed as early as possible in these patients.

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Changes in clinical features of acoustic neuroma

Kanzaki Jin, Ogawa Kaoru, Ikeda Shunya

Acta Oto-Laryngologica 111 （ S487 ） 120 - 124 1991年

ISSN 0001-6489

During a 14-year period from 1976 to 1989, the authors experienced 160 cases of acoustic neuroma (AN). The clinical features were investigated in 132 of these cases (excluding those cases of recurrence and neurofibromatosis 2). The cases were divided into three periods for study. There were no significant differences in the patients' age, sex, or affected side among the three periods. The number of intracanalicular tumors have increased in recent years. The proportion of medium-sized and large tumors, however, has not changed, comprising about 70% of the total number of cases. Tumors of 20 mm or smaller in diameter were found in 24% of the cases in the early period, but increased to 58% in the most recent period. There was no difference among the periods in the length of time elapsed from the onset of symptoms to the first examination. A higher proportion of cases were diagnosed in otolaryngology departments in the middle and most recent periods than in the early period. Fewer cases in the most recent period presented initially with disequilibrium or trigeminal nerve symptoms. This was believed to be due to the increase in early stage cases. Patients are increasingly presenting with early stage AN. We feel that in order to support this favorable tendency, more emphasis needs to be placed on early diagnosis.

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The growth rate of acoustic neuromas

Ogawa Kaoru, Kanzaki Jin, Ogawa Shigeo, Yamamoto Minako, Ikeda Shunya, Shiobara Ryuzo

Acta Oto-Laryngologica 111 （ S487 ） 157 - 163 1991年

ISSN 0001-6489

Growth rate of acoustic neuromas (AN) was studied in 43 patients. The growth rate was analyzed using tumor increasing size (IS) and tumor volume doubling time (VDT). The growth rate of unilateral AN was lower than that of bilateral AN associated with neuroflbromatosis2 (NF2). The growth rate of recurrent tumors was higher than that of non-operative tumors. The relationships between growth rate and age and tumor size were also analyzed. The younger the patient or the greater the tumor size, the higher the growth rate. Several factors, i.e. age and sex of patients, tumor pathology and tumor size, should be considered together for predicting the growth rate on AN.

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Acoustic neuromas presenting as sudden hearing loss

Ogawa Kaoru, Kanzaki Jin, Ogawa Shigeo, Tsuchihashi Nobuaki, Inoue Yasuhiro

Acta Oto-Laryngologica 111 （ S487 ） 138 - 143 1991年

ISSN 0001-6489

Progressive hearing loss is well known as a usually existing complaint in patients with acoustic neuromas. However, sudden hearing loss is also a relatively frequent condition in acoustic neuroma patients. In our review of 132 patients with surgically proven unilateral acoustic neuromas, 29 (22.0% presented a history of sudden hearing loss. We investigated the clinical and audiological characteristics of these patients, and discuss the etiology of sudden hearing loss in patients with acoustic neuromas. The characteristics of patients with AN presenting sudden hearing loss were as follows: 1) a small tumor, 2) short duration after onset, 3) low incidences of vertigo, dizziness, facial and trigeminal nerve symptoms, 4) the trough type in the audiogram configuration, 5) normal caloric response. Based on the analysis of these results, we conclude that a conduction block of the cochlear nerve is likely to be the etiology of sudden hearing loss.

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Diagnostic procedure for acoustic neuroma

Kanzaki Jin, Ogawa Kaoru, Tsuchihashi Nobuaki, Yamamoto Minako, Ogawa Shigeo, O-uchi Toshiaki

Acta Oto-Laryngologica 111 （ S487 ） 114 - 119 1991年

ISSN 0001-6489

The authors' diagnostic procedure for unilateral acoustic neuroma and the reasoning behind it are explained. The actual methods involved will change with advances in methodology. At the present time, however, pure tone audiometry and simple radiographic imaging of the internal auditory canal (transorbital and Stenvers View) are first carried out. Then, if the hearing level (average hearing at 4 kHz and 8 kHz) is 70 dB or lower, auditory brain stem response audiometry is carried out. If it is 71 dB or higher, the patient is examined by MRI or CT. Contrast-enhanced CT is carried out when MRI is not available. Air CT is not necessary if MRI is available, but, in cases where hearing preservation is indicated, it may provide valuable information for identifying the tumor site within the internal auditory canal.

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Preoperative findings and hearing preservation in acoustic neuroma surgery

Ogawa Kaoru, Kanzaki Jin, O-uchi Toshiaki, Inoue Yasuhiro, Ikeda Shunya

Acta Oto-Laryngologica 111 （ S487 ） 30 - 35 1991年

ISSN 0001-6489

For the purpose of clarifying whether or not the possibility of hearing preservation can be predicted preoperatively, we compared clinical characteristics and preoperative test results between hearing preserved and hearing unpreserved patients. Based on an analysis of this study, we conclude that duration of symptoms, ABR findings and caloric test results, in addition to hearing level, speech discrimination score and tumor size should be considered as prognostic signs of hearing preservation. Although all factors do not suggest a definite possibility of hearing preservation, candidates for hearing preservation surgery should be selected according to these prognositc factors.

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Results of acoustic neuroma surgery by the extended middle cranial fossa approach

Kanzaki Jin, Ogawa Kaoru, Yamamoto Minako, Ikeda Toshiya, Shiobara Ryuzo, Toya Shigeo

Acta Oto-Laryngologica 111 （ S487 ） 17 - 21 1991年

ISSN 0001-6489

The results of surgery in 160 cases of AN are reported. Surgery was carried out by the extended middle cranial fossa (EMCF) approach in 138 cases and by the middle cranial fossa (MCF) approach in 22 cases. The tumor extended an average of 28.9 mm into the posterior cranial fossa; 42% of the tumors extended 31 mm or more. Mortality was 1.9% Of the 3 cases of death, two had large tumors of 45 mm and 52 mm each, and one was a case of recurrence. Total tumor removal was achieved in an average of 78.8% of the cases. When the cases were classified by date of operation, the total tumor removal rate in the 60 most recent cases was 93.3% The rate of facial nerve preservation was 82.4% on average and 93% in the recent cases. Hypoglossal-facial nerve anastomosis was performed in 33% of the cases in which facial nerve function failed to recover for an extended period of time. Among recent cases, however, anastomosis has been carried out in 22% of the cases. Hearing was preserved in 20 cases. Useful hearing was preserved in 8 (38% of 22 cases. Recurrence was confirmed through surgery in 3 cases. Recurrence was suspected but was unconfirmed in 3 cases.

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Surgical anatomy for the extended middle cranial fossa approach

Ogawa Kaoru, Inoue Yasuhiro, Yamamoto Minako, Ikeda Shunya, Kanzaki Jin

Acta Oto-Laryngologica 111 （ S487 ） 41 - 47 1991年

ISSN 0001-6489

The surgical anatomy of the temporal bone and the cerebellopontine angle was studied in cadavers, by performing simulated surgery via the extended middle cranial fossa approach. This approach is classified into 3 types according to extension of the drilling area of the temporal bone. In this paper, the surgical anatomy visualized by the EMCF type II and type III is described. In the EMCF type II, mastoidectomy and labyrinthectomy are performed completely through the middle cranial fossa, and in the EMCF type III permitting hearing preservation surgery, sections of the middle cranial fossa dura and the cerebellar tentorium are added to House's middle cranial fossa approach. The comprehension of these anatomical structures is essential for surgeons in performing acoustic neuroma surgery. We believe that this study will serve to expand our knowledge of surgical anatomy, and that as a result the EMCF approach for acoustic neuroma surgery will become more popular.

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Hearing preservation in acoustic neuroma surgery by the extended middle cranial fossa method

Kanzaki Jin, Ogawa Kaoru, O-uchi Toshiaki, Shiobara Ryuzo, Toya Shigeo

Acta Oto-Laryngologica 111 （ S487 ） 22 - 29 1991年

ISSN 0001-6489

The results of attempted hearing preservation were investigated in 160 cases of acoustic neuroma surgery carried out by a team of otologists and neurosurgeons at Keio University Hospital during a 14-year period from 1976 to 1989. Surgery was carried out by the middle cranial fossa (MCF) approach in the earlier cases and by the extended middle cranial fossa (EMCF) approach in the more recent cases. Measurable postoperative hearing was preserved in 20 of the 160 cases. Preoperatively, 22 cases had tumors of 20 mm or smaller in diameter, hearing levels (HL) of 50 dB or lower, and speech discrimination scores (SDS) of 50% or higher; 8 (36% met these conditions postoperatively. Among those cases with hearing preserved postoperatively, hearing was unchanged from the preoperative level in 9 cases and changed in 11 cases. Total tumor removal was achieved in 19 cases. In one case, part of the tumor was left in order to preserve hearing, but MRI and CT have revealed no change in hearing or tumor enlargement to date, at 4 12 years after surgery. Hearing was preserved but progressively deteriorated postoperatively in one case in which the tumor was believed to have been totally removed but there was recurrence and in another case of total resection of neurofibromatosis II. Postoperatively, there were increased incidences of absence of the stapedius reflex, Type V by Bekesy audiometry, and prolongation of the IT5, disappearance of Wave V, and no response in measurements of the ABR.

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Postoperative complications in acoustic neuroma surgery by the extended middle cranial fossa approach

Kanzaki Jin, Ogawa Kaoru, Tsuchihashi Nobuaki, Inoue Yasuhiro, Yamamoto Minako, Ikeda Shunya

Acta Oto-Laryngologica 111 （ S487 ） 75 - 79 1991年

ISSN 0001-6489

The complications of acoustic neuroma (AN) surgery by the extended middle cranial fossa approach were studied in 160 cases. Death during surgery occurred in 3 cases (1.9%; 2 of these involved large tumors and the third was a case of recurrence. Transient temporal lobe symptoms were seen in 24 cases (15.3%; the average tumor diameter in these cases was 36.0 mm. Beside symptoms of 7th and 8th nerve disturbance, hemiparesis was seen 7.6%; 3rd, 4th, and 6th cranial nerve symptoms in 7.0%; and cerebellar symptoms in 7.6% of the patients. The incidence of these disturbances increased with tumor size. Cerebrospinal fluid (CSF) leakage occurred in 20.4% of the cases and this necessitated surgical treatment in 5% of the cases.

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Audiological findings in acoustic neuroma

Kanzaki Jin, Ogawa Kaoru, Ogawa Shigeo, Yamamoto Minako, Ikeda Shunya, O-uchi Toshiaki

Acta Oto-Laryngologica 111 （ S487 ） 125 - 132 1991年

ISSN 0001-6489

Audiological examinations are vital in the diagnosis of acoustic neuroma. In interpreting their results, however, it is necessary to consider the patient's hearing level. The most sensitive audiological examination is auditory brain stem response (ABR) audiometry. Its most useful parameter is the IT5. A U-shaped audiometric configuration suggests AN, since it is seen in 10% of patients with small tumors. Psychological audiometric tests can be excluded from the battery of screening tests since they have low rates of positive diagnosis. The stapedius reflex (SR) test also has a low positive diagnostic rate in cases of small tumors. Even with the parameters of absence of reflex, elevated threshold, and decay combined, the overall SR test has a lower positive diagnostic rate than ABR audiometry. Nevertheless, the SR test can be employed as a screening device in cases in which the hearing level at 2 kHz and lower is 70 dB or lower, even if it is 71 dB or higher at 4 kHz and 8 kHz. At present, ABR audiometry is applicable in only about half of AN cases. Therefore, the need for early diagnosis must be further emphasized.

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Intracranial reconstruction of the facial nerve clinical observation

Kanzaki Jin, Kunihiro Takanobu, O-uchi Toshiaki, Ogawa Kaoru, Shiobara Ryuzo, Toya Shigeo

Acta Oto-Laryngologica 111 （ S487 ） 85 - 90 1991年

ISSN 0001-6489

Nine cases of intracranial facial nerve reconstruction are reviewed in this paper. All patients underwent this procedure for severe injury or disruption of the facial nerve during surgery for acoustic neruroma through the modified extended middle cranial fossa approach (1). Satisfactory recovery of facial function was obtained in 4 patients. Three patients underwent hypoglossal-facial nerve anastomosis 1.3-1.5 years later for no or poor recovery of the facial function. One patient refused any further surgical treatment despite unsatisfactory recovery. The remaining 1 patient, during a telephone interview, stated that facial function had not returned at all 1 year and 5 months postoperatively. Although some degree of associated movement or mass movement was unavoidable, facial movement and mimetic facial expression were better in the patients with satisfactory recovery, as compared with those after hypoglossal-facial nerve anastomosis (2). Fibrin glue, which we used in the latest 3 cases instead of suture, seemed to possibly solve the technical difficulty in placing a suture. Facial function after intracranial reconstruction with fibrin glue was as good or better than that after repair by suturing.

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Psychological aspects of psychogenic deafness in children

Yamamoto Minako, Kanzaki Jin, Ogawa Kaoru, Asano Kyoko

International Journal of Pediatric Otorhinolaryngology 21 （ 2 ） 113 - 120 1991年

ISSN 0165-5876

Twenty-nine children with psychogenic deafness were investigated from audiological and psychological aspects. ABR and Békésy audiometry were useful for diagnosing psychogenic deafness. The elapsed time from the start of treatment to audiometric recovery was significantly shorter in patients receiving psychological treatment, indicating that treatment by a team of otologists and counselors was able to hasten recovery in children with psychogenic deafness. The pattern of hearing recovery in the treated group was classified into 3 types and in the control group into 4 types. Counseling seemed to have a positive effect on patients with fluctuating improvement. In the patients in the treated group, the elapsed time to audiometric recovery from the beginning of psychological treatment was 7.5 months; however, in the control group recovery it took 17.1 months. Psychological treatment revealed that the clinical course of psychogenic deafness in children seemed to have some relation to the patient's personality and psychological stresses.

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Further investigation on loudness balance test for tinnitus

O-Uchi T., Fujii M., Kunihiro T., Okada Y., Satoh A., Ogawa K., Kanzaki J.

Audiology Japan 33 （ 1 ） 76 - 83 1990年

ISSN 0303-8106

We conducted the loudness balance test at 3 frequencies with the center at the pitch of tinnitus. The subjects were 68 tinnitus ears without hearing loss or associated with cochlear deafness, and their tinnitus pitch was simulated by pure tones. Results obtained were as follows; (1) There were no statistically significant differences among the values of loudness estimated at 3 test frequencies. (2) The values of loudness estimated at 3 test frequencies coincided in about 30% of the subjects. (3) The values of loudness estimated at neighboring 2 test frequencies coincided in about 50% of the subjects. (4) There was a slight negative correlation between the value of loudness and the hearing level at the pitch of tinnitus. (5) There was no clear correlation between the subjective scoring for loudness and the hearing level at the pitch of tinnitus. (6) There were positive correlations among the values of loudness estimated at 3 test frequencies. (7) Correlation coefficients were less than 0.260 between the subjective scoring for loudness and the values of loudness estimated at 3 test frequencies. (8) The optimal evaluating method of subjective scoring for loudness should be re-investigated.

Evoked otoacoustic emissions in patients with acoustic neuromas

O-Uchi T., Kanzaki J., Kunihiro T., Inoue T., Satoh A., Ogawa K., Koseki Y., Ogata A.

Audiology Japan 33 （ 2 ） 118 - 130 1990年

ISSN 0303-8106

Acute profound deafness related to immunological impairments

Tsuchihashi N., O-Uchi T., Ogawa K., Kunihiro T., Ogawa S., Ikeda S., Kanzaki J.

Audiology Japan 33 （ 4 ） 259 - 265 1990年

ISSN 0303-8106

Further investigation of subjective expression in tinnitus--relationship between subjective expression with onomatopoeias and pitch of tinnitus simulated by pure tones and band noise

O-Uchi T., Okada Y., Ogawa K., Fujii M., Kanzaki J.

Audiology Japan 33 （ 1 ） 48 - 55 1990年

ISSN 0303-8106

The standardized tinnitus test proposed by Tinnitus Study Group in 1984 presented 30 onomatopoeias and their corresponding frequency areas of pure tones and band noise of pure tone audiometer as an indicator to evaluate the pitch and the nature of tinnitus. In order to re-investigate the adequacy of these 30 onomatopoeias, we analysed the relationship between subjective expression with onomatopoeias and pitch of tinnitus simulated by pure tones and band noise of pure tone audiometer. The subject matter were 263 tinnitus ears without hearing loss or associated with cochlear deafness. The results obtained were as follows; 1) A total of 41 onomatopoeias was used for the subjective expression of tinnitus. However, among these 41 onomatopoeias, only 17 (41.5%) had been presented in the standardized tinnitus test in 1984. 2) Six onomatopoeias had not been presented in the standardized tinnitus test in 1984 although their frequency in use was more than 2% in this study. 3) As far as the relationship between onomatopoeias and their corresponding frequency areas of pure tones and band noise was concerned, discrepancies between the results obtained in this study and the proposals by the standardized tinnitus test in 1984 were found in 11 onomatopoeias out of 17 (64.7%). Based upon these results, we concluded that onomatopoeias as an indicator to evaluate the pitch and the nature of tinnitus should be re-investigated.

Subjectively estimated pitch of tinnitus and results of the pitch match test

O-Uchi T., Kunihiro T., Ogawa K., Satoh A., Kanzaki J.

Audiology Japan 33 （ 6 ） 759 - 766 1990年

ISSN 0303-8106

Stimulated oto-acoustic emission in normal hearing ears - Investigation of emission cochleogram -

Ogawa K., Kunihiro T., Inoue T., Kanzaki J., O-Uchi T., Koseki Y.

Audiology Japan 32 （ 3 ） 167 - 171 1989年

ISSN 0303-8106

Hearing preservation in acoustic neuroma surgery and postoperative audiological findings

Kanzaki J., Ogawa K., Shiobara R., Toya S.

Acta Oto-Laryngologica 107 （ 5-6 ） 474 - 478 1989年

ISSN 0001-6489

One hundred fifty-three cases of acoustic neuroma were treated surgically by the middle cranial fossa approach or extended middle cranial fossa approach. Attempts to preserve hearing were made in 30 cases with tumours extending 2.0 cm or less into the posterior fossa; successful hearing preservation was achieved in 12 cases. Among the 15 patients with preoperative hearing levels (HL) of 50 dB or lower and speech discrimination scores (SDS) of 50% or higher, hearing was preserved in 9 (60% patients. A similar rate of hearing preservation was achieved among the patients with normal or near-normal hearing. Compared with those patients in whom hearing could not be preserved, those with hearing preservation had better HL, higher SDS, and less abnormal ABR findings preoperatively. Postoperatively, the HL and SDS deteriorated slightly. In addition, there was a marked prolongation of the IT5, and the incidence of absence of the stapedius reflex increased. Compared with the preoperative HL, the postoperative HL was unchanged in 5 cases; deteriorated temporarily and then improved in 5 cases; and deteriorated, though with hearing preserved, in 2 cases. Intraoperative monitoring was conducted by recording the ABR and VIII nerve compound action potentials and by electrocochleography. However, postoperative hearing could not always be predicted from the findings obtained at the end of the operation.

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Oto-acoustic emissions by bone conduction stimulation in normal hearing ears

O-Uchi T., Ogawa K., Kunihiro T., Inoue T., Kanzaki J., Koseki Y.

Audiology Japan 32 （ 3 ） 200 - 206 1989年

ISSN 0303-8106

Hearing preservation in acoustic neurinoma surgery - The selection of patients and the findings of preoperative examinations

Ogawa K.

Otolaryngology - Head and Neck Surgery (Tokyo) 61 （ 5 ） 347 - 353 1989年

ISSN 0914-3491

Oto-acoustic emission evoked by air-conduction stimulation from the contralateral ear

O-Uchi T., Ogawa K., Kunihiro T., Inoue T., Kanzaki J., Koseki Y.

Audiology Japan 32 （ 2 ） 125 - 129 1989年

ISSN 0303-8106

Evaluation of hearing recovery and efficacy of steroid treatment in sudden deafness

Kanzaki J., Taiji H., Ogawa K.

Acta Oto-Laryngologica 105 （ S456 ） 31 - 36 1988年

ISSN 0001-6489

In cases of sudden deafness (SD), hearing recovery is generally assessed by classifying recovery into four degrees. To evaluate factors that may affect the prognosis for hearing recovery (e.g., hearing level at initial examination, days elapsed from onset of hearing loss to start of treatment) or drug efficacy, however, a quantitative method would be more advantageous. In the present study, therefore, the recovery rate was used as an index in investigating the prognosis and the efficacy of steroid treatment in 183 patients with SD first examined within 14 days after the onset of hearing loss during the period 1980-85. As with the degree of hearing recovery, the recovery rate was found to be favorable in those patients with good hearing at the initial examination, no vertigo, little difference in high-tone and low-tone hearing loss, and only a short lag between onset of symptoms and the initiation of treatment. This indicated that the recovery rate could be used as an index for the evaluation of hearing recovery in cases of sudden deafness. The efficacy of steroid treatment was evaluated in patients in whom the average of the hearing levels at five frequencies from 250 to 4000 Hz was 40-90 dB. No significant differences were found in either recovery rate or degree of recovery between those patients who received steroids and those who did not. This was believed to be attributable to the variety of pathological conditions involved in SD and to the influence of the other, non-steroidal drugs administered.

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Internal auditory canal vascular loops and sensorineural hearing loss

Kanzaki Jin, Ogawa Kaoru

Acta Oto-Laryngologica 105 （ S447 ） 88 - 93 1988年

ISSN 0001-6489

The relationship between vascular loops in the internal auditory canal and VIII nerve disorders was examined by performing pneumatic computerized tomographic (CT) cisternography in patients with idiopathic sudden deafness, idiopathic sensorineural hearing loss, and Meniere's disease. The incidence of vascular loops was higher in the diseased group than in the control group, viz. 19 of 61 cases (30% in the former, compared with only 6 of 88 cases (7% in the latter. The loops were classified as of Types I-IV according to the proximity to the fundus of the internal auditory canal. A large proportion of the loops found in the diseased group were classified as Type II or III. In most of the patients with vascular loops, the hearing loss was of the cochlear type, and in most cases, normal responses were obtained by the caloric test. Therefore, we concluded that vascular loops may be a possible cause of VIII nerve disorders and that this mechanism may involve circulatory disorder.

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Clinical Experience with Cefoperazone in the Field of Otorhinolaryngology

Kawaida Masahiro, Fukuda Hiroyuki, Taiji Hidenobu, Ogawa Kaoru, Ling Meiying, Kawasaki Yoshihisa, Saito Shigeji

Practica Oto-Rhino-Laryngologica 80 （ 12 ） 1905 - 1910 1987年

ISSN 0032-6313

The clinical usefulness of Cefoperazone for the treatment of post-operative infections or prophylaxis was studied in patients with head and neck tumors. In some cases in which local application of an antibiotic was considered to be useful, Polymyxin B Sulfate was used concomitantly. Cefoperazone administration was clinically useful in 17 of the 18 patients enrolled in this study (very useful in 10, useful in 7) and only one patient failed to respond to Cefoperazone therapy. Adverse reactions or laboratory abnormalities possibly related to the therapy were seen in three patients. However, in one case, the adverse reaction could be attributed to the concomitantly administered anticancer agent, and in the other two cases, reactions were mild and transient.

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Evaluation of tinnitus by loudness balance test

O Uchi T., Kanzaki J., Lin M., Ogawa K.

Audiology Japan 26 （ 2 ） 105 - 111 1983年

ISSN 0303-8106

In order to estimate the clinical values of the loudness balance test by pure tone audiometer as the objective method for evaluating tinnitus and to find out how we can use this method in the future, the results of the loudness balance test in 168 cases who complained of unilateral tinnitus were analyzed and presented in this study. Furthermore, in order to differentiate the tinnitus associated with endolymphatic hydrops and that of other causes, and to confirm the consistency and repeatability of the result of the loudness balance test by the pure tone audiometer, the loudness balance test was conducted before and after the oral administration of glycerol (glycerol loading tinnitus balance test). The test was performed in 44 confirmed cases of Meniere's disease and 10 of sensorineural hearing loss without fluctuation for a long duration. It was concluded that although by the loudness balance test with a pure tone audiometer the exact pitch of the tinnitus is not determined, much information about the tinnitus can be given. Also since there is no significant difference between the pitch of the tinnitus obtained by the pure tone audiometer and that by the Bekesy audiometer in most cases, and the loudness balance test by the pure tone audiometer is the easiest way to evaluate tinnitus clinically. This method has a meaningful and clinical value to evaluate the tinnitus objectively. After the glycerol administration several changes in the pitch and loudness of the tinnitus with or without changes of hearing were found in cases of Meniere's disease, but not in sensorineural hearing loss without fluctuation. The glycerol loading tinnitus balance test can be a good tool to differentiate the tinnitus associated with endolymphatic hydrops from that of the other causes, and therefore this test will be useful in the future as a new tinnitus test.

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