Updated on 2025/03/27

写真a

 
Hato Naohito
 
Organization
Graduate School of Medicine Program for Medical Sciences Professor
Title
Professor
Contact information
メールアドレス
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Degree

  • 医学博士 ( 愛媛大学 )

Research Interests

  • age-related hearing loss

  • 鼓室形成術

  • 骨導インプラント

  • 水素治療

  • herpes virus

  • nerve regeneration

  • Bell's palsy

  • artificial nerve

  • facial nerve

  • Hunt syndrome

  • ヘルペスウイルス

  • 人工神経

  • ハント症候群

  • 人工聴覚器

  • 神経再生

  • 顔面神経

  • ベル麻痺

Research Areas

  • Life Science / Otorhinolaryngology

Education

  • スタンフォード大学   医学部   耳鼻咽喉科

    1999.2 - 2001.4

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    Country: United States

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  • Ehime University

    1992.4 - 1996.3

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    Country: Japan

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  • Ehime University   Graduate School, Division of Medicine

    - 1996

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  • Ehime University   School of Medicine   Faculty of Medicine

    1983.4 - 1989.3

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    Country: Japan

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  • Ehime University   Faculty of Medicine

    - 1989

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Research History

  • Ehime University   Graduate School of Medicine

    2014

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  • - Ehime University Graduate School of Medicine

    2009

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  • Ehime University   Hospital

    2008 - 2013

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  • Ehime University   Hospital

    2001 - 2008

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  • Ehime University

    2001

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  • - Ehime University Hospital

    2001

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  • Ehime University   Hospital

    1996 - 1999

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  • Ehime University

    1996 - 1999

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  • Matsuyama Red Cross Hospital

    1991 - 1992

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  • Matsuyama Red Cross Hospital

    1990 - 1991

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  • Ehime University   Hospital

    1989 - 1991

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  • Ehime University

    1989 - 1990

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Professional Memberships

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Qualification acquired

  • medical doctor

Papers

  • Case-control study of IL23R rs76418789 polymorphism, smoking, and ulcerative colitis in Japan. International journal

    Yoshihiro Miyake, Keiko Tanaka, Chisato Nagata, Shinya Furukawa, Akira Andoh, Tetsuji Yokoyama, Naoki Yoshimura, Kenichiro Mori, Tomoyuki Ninomiya, Yasunori Yamamoto, Eiji Takeshita, Yoshio Ikeda, Mitsuru Saito, Katsuhisa Ohashi, Hirotsugu Imaeda, Kazuki Kakimoto, Kazuhide Higuchi, Hiroaki Nunoi, Yuji Mizukami, Seiyuu Suzuki, Sakiko Hiraoka, Hiroyuki Okada, Keitarou Kawasaki, Masaaki Higashiyama, Ryota Hokari, Hiromasa Miura, Teruki Miyake, Teru Kumagi, Hiromasa Kato, Naohito Hato, Koji Sayama, Yoichi Hiasa

    Cytokine   183   156743 - 156743   2024.11

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    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: Interleukin (IL)-23 is involved in the pathogenesis of ulcerative colitis (UC). A genome-wide significant association between IL23R p.G149R (rs76418789) and UC was previously identified in Japan and Korea. This case-control study aims to examine this association within the Japanese population. METHODS: The study included 384 cases diagnosed with UC within the past 4 years and 661 control subjects. Adjustment was made for sex, age, and smoking. RESULTS: The frequency of the AA genotype of rs76418789 was 0.0 % in cases and 0.5 % in control subjects. In comparison to study subjects with the GG genotype of rs76418789, those with the GA or AA genotype had a significantly reduced risk of UC, with an adjusted odds ratio of 0.67 (95 % confidence interval: 0.44-0.999). A significant multiplicative interaction was observed between rs76418789 and having ever smoked influencing UC (p for interaction = 0.03). A significant positive association was found between having ever smoked and UC in individuals with at least one A allele, while no such positive relationship was observed in those with the GG genotype. CONCLUSION: IL23R SNP rs76418789 showed a significant association with UC. This study provides new evidence regarding the interaction between rs76418789 and smoking in relation to UC.

    DOI: 10.1016/j.cyto.2024.156743

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  • Summary of Japanese clinical practice guidelines for Bell's palsy (idiopathic facial palsy) - 2023 update edited by the Japan Society of Facial Nerve Research. International journal

    Takashi Fujiwara, Naohito Hato, Takashi Kasahara, Daichi Kasuya, Kenji Shida, Makito Tanabe, Haruki Nakano, Shin-Ichi Haginomori, Masashi Hamada, Ayato Hayashi, Yasushi Furuta, Ken Matsuda, Naohito Morishima, Takechiyo Yamada, Takashi Nakagawa

    Auris, nasus, larynx   51 ( 5 )   840 - 845   2024.7

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    OBJECTIVE: The "Summary of Japanese clinical practice guidelines for Bell's palsy (idiopathic facial palsy) - 2023 update edited by the Japan Society of Facial Nerve Research" aims to review the latest evidence regarding the treatment of Bell's palsy and to provide appropriate recommendations. METHOD: Regarding the treatment of Bell's palsy, a guideline panel identified key clinical questions using an analytic PICO framework. The panel produced recommendations following the standards for trustworthy guidelines and the GRADE approach. The panel considered the balance of benefits, harm, and preferences when making recommendations. RESULTS: The panel identified nine key clinical questions: systemic (high/standard dose) corticosteroids, intratympanic corticosteroids, systemic antivirals, decompression surgery, acupuncture, physical therapy, botulinum toxin, and reanimation surgery. CONCLUSION: These guidelines strongly recommend systemic standard-dose corticosteroids for the clinical management of Bell's palsy. Other treatments are weakly recommended due to insufficient evidence. The absolute risk reduction of each treatment differed according to the disease severity. Therefore, physicians and patients should decide on treatment based on the disease severity.

    DOI: 10.1016/j.anl.2024.07.003

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  • Simultaneous disturbance of NHE1 and LOXL2 decreases tumorigenicity of head and neck squamous cell carcinoma. International journal

    Yuji Hayashi, Shoko Miyoshi, Itaru Watanabe, Nagomi Yano, Kodai Nagashio, Mihiro Kaneko, Teppei Kaminota, Tomoyoshi Sanada, Yuki Hosokawa, Takashi Kitani, Sohei Mitani, Mohammed E Choudhury, Hajime Yano, Junya Tanaka, Naohito Hato

    Auris, nasus, larynx   51 ( 3 )   472 - 480   2024.6

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    OBJECTIVE: Although there have been brilliant advancements in the practical application of therapies targeting immune checkpoints, achieving success in targeting the microenvironment remains elusive. In this study, we aimed to address this gap by focusing on Na+ / H+ exchanger 1 (NHE1) and Lysyl Oxidase Like 2 (LOXL2), which are upregulated in head and neck squamous cell carcinoma (HNSCC) cells. METHODS: The malignancy of a metastatic human HNSCC cell line was assessed in a mouse tongue cancer xenograft model by knocking down (KD) NHE1, responsible for regulating intracellular pH, and LOXL2, responsible for extracellular matrix (ECM) reorganization via cross-linking of ECM proteins. In addition to assessing changes in PD-L1 levels and collagen accumulation following knockdown, the functional status of the PD-L1 / PD-1 immune checkpoint was examined through co-culture with NK92MI, a PD-1 positive phagocytic human Natural Killer (NK) cell line. RESULTS: The tumorigenic potential of each single KD cell line was similar to that of the control cells, whereas the potential was attenuated in cells with simultaneous KD of both factors (double knockdown [dKD]). Additionally, we observed decreased PD-L1 levels in NHE1 KD cells and compromised collagen accumulation in LOXL2 KD and dKD cells. NK92MI cells exhibited phagocytic activity toward HNSCC cells in co-culture, and the number of remaining dKD cells after co-culture was the lowest in comparison to the control and single KD cells. CONCLUSION: This study demonstrated the possibility of achieving efficient anti-tumor effects by simultaneously disturbing multiple factors involved in the modification of the tumor microenvironment.

    DOI: 10.1016/j.anl.2024.01.006

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  • Role of Oxidative Stress in Sensorineural Hearing Loss. International journal

    Masato Teraoka, Naohito Hato, Haruhiko Inufusa, Fukka You

    International journal of molecular sciences   25 ( 8 )   2024.4

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    Hearing is essential for communication, and its loss can cause a serious disruption to one's social life. Hearing loss is also recognized as a major risk factor for dementia; therefore, addressing hearing loss is a pressing global issue. Sensorineural hearing loss, the predominant type of hearing loss, is mainly due to damage to the inner ear along with a variety of pathologies including ischemia, noise, trauma, aging, and ototoxic drugs. In addition to genetic factors, oxidative stress has been identified as a common mechanism underlying several cochlear pathologies. The cochlea, which plays a major role in auditory function, requires high-energy metabolism and is, therefore, highly susceptible to oxidative stress, particularly in the mitochondria. Based on these pathological findings, the potential of antioxidants for the treatment of hearing loss has been demonstrated in several animal studies. However, results from human studies are insufficient, and future clinical trials are required. This review discusses the relationship between sensorineural hearing loss and reactive oxidative species (ROS), with particular emphasis on age-related hearing loss, noise-induced hearing loss, and ischemia-reperfusion injury. Based on these mechanisms, the current status and future perspectives of ROS-targeted therapy for sensorineural hearing loss are described.

    DOI: 10.3390/ijms25084146

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  • Dysphagia in patients with severe COVID-19: a retrospective study. International journal

    Rie Asayama, Kaori Tanaka-Nishikubo, Masahiro Okada, Naoki Mukai, Suguru Annen, Hironori Matsumoto, Jun Takeba, Norio Sato, Naohito Hato

    Scientific reports   14 ( 1 )   6829 - 6829   2024.3

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    To investigate dysphagia after extubation in patients with severe coronavirus disease 2019 (COVID-19). We retrospectively examined patients with severe COVID-19 treated in our hospital between August 2021 and March 2022. Feeding outcomes were categorized into two groups-(1) total oral intake, and (2) difficulty in oral intake. To assess the feeding outcome, we used modified water-swallowing test (MWST) for all patients. However, in cases where aspiration or recurrent laryngeal nerve palsy was suspected, we conducted the fiberoptic endoscopic evaluation of swallowing after MWST. Patient data were collected from medical records. Forty-six patients with severe COVID-19 were included. Among the 46 patients, 14 (30.4%) experienced difficulties with oral intake. Older age, longer length of hospitalization, duration of mechanical ventilation, tracheostomy, diabetes, and higher serum levels of C-reactive protein (CRP) and procalcitonin (PCT) at the time of intubation were associated with difficulty in oral intake. The rate of difficulty with oral intake in patients with severe COVID-19 was 30.4%, which is not as high as reported in previous studies. Older age, longer duration of mechanical ventilation, tracheostomy, diabetes, and higher levels of CRP and PCT were associated with the prevalence of oral intake difficulty, suggesting that early attention should be paid to high-risk patients who have preexisting deterioration of swallowing function due to aging and comorbidities, or who have prolonged intubation or tracheostomy to prevent aspiration pneumonia.

    DOI: 10.1038/s41598-024-57508-x

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  • Effect of intranasal administration of concentrated growth factors on regeneration of the olfactory epithelium in an olfactory dysfunction-induced rat model. International journal

    Naruhiko Kai, Naoya Nishida, Kunihide Aoishi, Taro Takagi, Naohito Hato

    PloS one   19 ( 2 )   e0298640   2024

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    OBJECTIVE: The development of treatments that promote the regenerative capacity of the olfactory epithelium (OE) is desirable. This study aimed to evaluate the effects of intranasal administration of concentrated growth factors (CGFs) in a rat model of olfactory dysfunction. STUDY DESIGN: Animal study. METHODS: Nineteen male rats were used. Fourteen olfactory dysfunction models were created by intraperitoneal administration of 3-methylindole. We randomly divided the rats from the olfactory dysfunction model after 1 week into the CGF or saline group; CGFs were administered to seven animals and saline to seven animals. Behavioral assessments using the avoidance test were conducted until day 28 after CGF/saline administration. On day 28, histological evaluation was conducted to determine olfactory epithelial thickness and the olfactory marker protein (OMP)-positive cell count. Five animals were intraperitoneally injected with saline as the control group. RESULTS: The avoidance rate remained decreased until 28 days after CGF/saline administration, and there was no significant difference between the two groups. Olfactory epithelial thicknesses on day 28 were 38.64 ± 3.17 μm and 32.84 ± 4.50 μm in the CGF and saline groups, respectively. OE thickness was significantly thicker in the CGF group than in the saline group (P = 0.013). The numbers of OMP-positive cells were 40.29 ± 9.77/1.0 × 104 μm2 and 31.00 ± 3.69/1.0 × 104 μm2 in the CGF and saline groups, respectively. The number of OMP+ cells in the CGF group was significantly increased compared with that in the saline group (P = 0.009). Both groups showed no improvement compared with the control group (OE thickness: 54.08 ± 3.36 μm; OMP+ cell count: 56.90 ± 9.91/1.0 × 104 μm2). CONCLUSIONS: The CGF group showed improved olfactory epithelial thickness and OMP-positive cell numbers compared with that in the saline group.

    DOI: 10.1371/journal.pone.0298640

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  • Coffee and caffeine intake reduces risk of ulcerative colitis: a case-control study in Japan. International journal

    Keiko Tanaka, Hitomi Okubo, Yoshihiro Miyake, Chisato Nagata, Shinya Furukawa, Akira Andoh, Tetsuji Yokoyama, Naoki Yoshimura, Kenichiro Mori, Tomoyuki Ninomiya, Yasunori Yamamoto, Eiji Takeshita, Yoshio Ikeda, Mitsuru Saito, Katsuhisa Ohashi, Hirotsugu Imaeda, Kazuki Kakimoto, Kazuhide Higuchi, Hiroaki Nunoi, Yuji Mizukami, Seiyuu Suzuki, Sakiko Hiraoka, Hiroyuki Okada, Keitarou Kawasaki, Masaaki Higashiyama, Ryota Hokari, Hiromasa Miura, Teruki Miyake, Teru Kumagi, Hiromasa Kato, Naohito Hato, Koji Sayama, Yoichi Hiasa

    Journal of gastroenterology and hepatology   39 ( 3 )   512 - 518   2023.12

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    BACKGROUND AND AIM: Although diet is one of the potential environmental factors affecting ulcerative colitis (UC), evidence is not sufficient to draw definitive conclusions. This Japanese case-control study examined the association between the consumption of coffee, other caffeine-containing beverages and food, and total caffeine and the risk of UC. METHODS: The study involved 384 UC cases and 665 control subjects. Intake of coffee, decaffeinated coffee, black tea, green tea, oolong tea, carbonated soft drinks, and chocolate snacks was measured with a semiquantitative food-frequency questionnaire. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, body mass index, and intake of vitamin C, retinol, and total energy. RESULTS: Higher consumption of coffee and carbonated soft drinks was associated with a reduced risk of UC with a significant dose-response relationship (P for trend for coffee and carbonated soft drinks were <0.0001 and 0.01, respectively), whereas higher consumption of chocolate snacks was significantly associated with an increased risk of UC. No association was observed between consumption of decaffeinated coffee, black tea, green tea, or oolong tea and the risk of UC. Total caffeine intake was inversely associated with the risk of UC; the adjusted odds ratio between extreme quartiles was 0.44 (95% confidence interval: 0.29-0.67; P for trend <0.0001). CONCLUSIONS: We confirmed that intake of coffee and caffeine is also associated with a reduced risk of UC in Japan where people consume relatively low quantities of coffee compared with Western countries.

    DOI: 10.1111/jgh.16439

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  • 喉頭摘出術後患者の合成音声を用いた代用音声の満足度調査

    飴矢 美里, 三谷 壮平, 勢井 洋史, 木谷 卓史, 西尾 直樹, 羽藤 直人

    喉頭   35 ( 2 )   148 - 154   2023.12

  • Oral Intake Difficulty and Aspiration Pneumonia Assessment Using High‐Resolution Manometry International journal

    Kaori Nishikubo‐Tanaka, Rie Asayama, Kazutaka Kochi, Masahiro Okada, Keiko Tanaka, Hiroyuki Yamada, Naohito Hato

    The Laryngoscope   134 ( 5 )   2127 - 2135   2023.11

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    OBJECTIVE: The sequential generation of swallowing pressure (SP) from the nasopharynx to the proximal esophagus is important for the bolus to pass from the oral cavity to the esophagus. The purpose of this study was to investigate the correlation of the SP sequence mode on high-resolution manometry (HRM) with oral intake difficulty and aspiration pneumonia. METHODS: Consecutive patients with dysphagia who were admitted to our dysphagia clinic between November 2016 and November 2020 were enrolled in this cross-sectional study. We classified the HRM pressure topography data according to the SP sequence mode into type A, normal; B, partially decreased; C, totally decreased; and D, sequence disappeared, and according to the upper esophageal sphincter (UES) during pharyngeal swallowing into type 1, flattening and 2, non-flattening. Clinical dysphagia severity was determined based on oral intake difficulty and aspiration pneumonia. RESULTS: In total, 202 patients with dysphagia (mean [standard deviation] age, 68.3 [14.5] years; 140 [69.8%] male) were enrolled. Type C (odds ratio [OR], 10.48; 95% confidence interval [CI], 2.89-51.45), type D (OR, 19.90; 95% CI, 4.18-122.35), and type 2 (OR, 6.36; 95% CI, 2.88-14.57) were significantly related to oral intake difficulty. Type C (OR, 3.23; 95% CI, 1.08-11.12) and type 2 (OR, 4.18; 95% CI, 1.95-9.15) were significantly associated with aspiration pneumonia. CONCLUSION: The failure of sequential generation of SP was associated with higher risk of oral intake difficulty and aspiration pneumonia. These assessments are useful in understanding the pathophysiology and severity of dysphagia and in selecting safety nutritional management methods. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2127-2135, 2024.

    DOI: 10.1002/lary.31155

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  • The Association Between Dehydration and the Prognosis of Sudden Sensorineural Hearing Loss International journal

    Yasunori Abe, Masahiro Okada, Keiko Tanaka, Kensuke Toyama, Yoshito Miyamoto, Naohito Hato

    Otology &amp; Neurotology Open   3 ( 4 )   e041 - e041   2023.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Ovid Technologies (Wolters Kluwer Health)  

    Background:

    There is an urgent need to identify undetermined risk factors for sudden sensorineural hearing loss (SSNHL) for the development of effective treatment strategies. SSNHL is likely associated with vascular insufficiency; however, no study has evaluated the relationship between dehydration and SSNHL.

    Objective:

    This study aimed to investigate the role of dehydration in the development and prognosis of sudden sensorineural hearing loss.

    Study Design:

    Retrospective case-control study.

    Setting:

    Secondary referral hospital.

    Patients and Interventions:

    This was a comparative study that compared dehydration parameters between healthy subjects without SSNHL (n = 94) and patients with SSNHL (n = 94). The study also evaluated the effect of dehydrated conditions on the prognosis of SSNHL.

    Main Outcome Measures:

    We compared dehydration parameters, such as the blood urea nitrogen-to-creatinine ratio (BUN/Cre) and plasma osmolality (Posm), between matched healthy subjects without SSNHL and patients with SSNHL. To evaluate the effect of dehydrated conditions on the SSNHL prognosis, the SSNHL patients were divided into 2 groups based on the cutoff value obtained from the receiver operating characteristic analysis: hydrated (n = 50; BUN/Cre &lt;21.4) and dehydrated (n = 44; BUN/Cre ≥21.4) groups. Subsequently, the severity and prognosis of SSNHL were analyzed.

    Results:

    The dehydration parameters, BUN/Cre and Posm, were significantly higher in patients with SSNHL than in healthy subjects. The initial hearing levels and SSNHL grades were worse in the dehydrated group than in the hydrated group. Moreover, a dehydrated condition (BUN/Cre ≥21.4) was associated with a poor SSNHL prognosis in all models of the multiple logistic regression analysis.

    Conclusions:

    The dehydration parameters of BUN/Cre and Posm were higher in patients with SSNHL than in healthy subjects. Additionally, a dehydrated condition (BUN/Cre ≥21.4) was an independent prognostic factor for SSNHL. Level of evidence: Level 4.

    DOI: 10.1097/ono.0000000000000041

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  • The Landscape of MYB/MYBL1- and Peri-MYB/MYBL1-Associated Rearrangements in Adenoid Cystic Carcinoma. International journal

    Kaori Ueda, Takayuki Murase, Daisuke Kawakita, Toshitaka Nagao, Kimihide Kusafuka, Masato Nakaguro, Makoto Urano, Hidetaka Yamamoto, Ken-Ichi Taguchi, Satoshi Kano, Yuichiro Tada, Kiyoaki Tsukahara, Kenji Okami, Tetsuro Onitsuka, Yasushi Fujimoto, Kazuo Sakurai, Nobuhiro Hanai, Toru Nagao, Ryo Kawata, Naohito Hato, Ken-Ichi Nibu, Hiroshi Inagaki

    Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc   36 ( 10 )   100274 - 100274   2023.10

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    Approximately 60% of adenoid cystic carcinoma (AdCC) cases are positive for MYB::NFIB or MYBL1::NFIB, whereas MYB/MYBL1 oncoprotein, a key driver of AdCC, is overexpressed in most cases. Juxtaposition of superenhancer regions in NFIB and other genes into the MYB/MYBL1 locus is an attractive oncogenic hypothesis for AdCC cases, either negative or positive for MYB/MYBL1::NFIB. However, evidence supporting this hypothesis is insufficient. We examined 160 salivary AdCC cases for rearrangements in MYB/MYBL1 loci and peri-MYB/MYBL1 areas (centromeric and telomeric areas of 10 Mb each) using formalin-fixed, paraffin-embedded tumor sections. For the detection of the rearrangements, we employed conventional fluorescence in situ hybridization split and fusion assays and a 5 Mb fluorescence in situ hybridization split assay. The latter is a novel assay that enabled us to detect any possible splits within a 5 Mb distance of a chromosome. We found MYB/MYBL1- and peri-MYB/MYBL1-associated rearrangements in 149/160 patients (93%). AdCC cases positive for rearrangements in MYB, MYBL1, the peri-MYB area, and the peri-MYBL1 area numbered 105 (66%), 20 (13%), 19 (12%), and 5 (3%), respectively. In 24 peri-MYB/MYBL1 rearrangement-positive cases, 14 (58%) were found to have a juxtaposition of the NFIB or RAD51B locus into the MYB/MYBL1 loci. On comparing with a tumor group positive for MYB::NFIB, a hallmark of AdCC, other genetically classified tumor groups had similar features of overexpression of the MYB transcript and MYB oncoprotein as detected by semiquantitative RT-qPCR and immunohistochemistry, respectively. In addition, clinicopathological and prognostic features were similar among these groups. Our study suggests that peri-MYB/MYBL1 rearrangements may be a frequent event in AdCC and may result in biological and clinicopathological consequences comparable to MYB/MYBL1 rearrangements. The landscape of MYB/MYBL1 and peri-MYB/MYBL1 rearrangements shown here strongly suggests that juxtaposition of superenhancers into MYB/MYBL1 or peri-MYB/MYBL1 loci is an alteration that acts as a key driver for AdCC oncogenesis and may unify MYB/MYBL1 rearrangement-positive and negative cases.

    DOI: 10.1016/j.modpat.2023.100274

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  • 3Dコンテンツを活用した新しい頸部郭清術教材の開発

    三谷 壮平, 木谷 卓史, 勢井 洋史, 佐藤 恵里子, 坂本 佳代, 向川 卓志, 鵜久森 徹, 脇坂 浩之, 羽藤 直人

    頭頸部外科   33 ( 2 )   177 - 183   2023.10

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    Language:Japanese   Publisher:(NPO)日本頭頸部外科学会  

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  • 3Dコンテンツを活用した新しい頸部郭清術教材の開発

    三谷 壮平, 木谷 卓史, 勢井 洋史, 佐藤 恵里子, 坂本 佳代, 向川 卓志, 鵜久森 徹, 脇坂 浩之, 羽藤 直人

    頭頸部外科   33 ( 2 )   177 - 183   2023.10

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    Language:Japanese   Publisher:(NPO)日本頭頸部外科学会  

    頸部郭清術は頭頸部外科医の登竜門的術式であるが,立体解剖の理解が要求され,その習得は若手医師にとって容易とはいえない。今回,学習者のニーズに対応した頸部郭清術教材を開発することを目的とした。ニーズ調査の結果に基づき,頸部の3Dモデルや3DVR動画を含む新しい教材を開発した。開発した教材は,耳鼻咽喉科頭頸部外科医20名によるアンケートで評価され,3Dで立体解剖をイメージできる点や,動画で手術の流れが確認できる点,ステップ分けして知識が解説されている点で,従来の教材と比較して優れているとされた。この教材は,頸部郭清術を学習する若手耳鼻咽喉科頭頸部外科医の新たな教育ツールとして価値があると思われた。(著者抄録)

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  • Prognostic scores for patients with salivary adenoid cystic carcinoma without lymph node metastasis. International journal

    Hikari Shimoda, Masanori Teshima, Takayuki Murase, Toshitaka Nagao, Kimihide Kusafuka, Masato Nakaguro, Makoto Urano, Ken-Ichi Taguchi, Hidetaka Yamamoto, Satoshi Kano, Yuichiro Tada, Kiyoaki Tsukahara, Kenji Okami, Tetsuro Onitsuka, Yasushi Fujimoto, Daisuke Kawakita, Kazuo Sakurai, Nobuhiro Hanai, Toru Nagao, Ryo Kawata, Naohito Hato, Ken-Ichi Nibu, Hiroshi Inagaki

    Oral oncology   145   106491 - 106491   2023.10

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    Adenoid cystic carcinoma (AdCC) of salivary gland grows relatively slowly, but occasionally develops distant metastasis. Although cervical lymph node metastasis (LNM) has been reported as a strong prognostic factor, most of AdCC do not have LNM. In this study, we investigated the prognostic factors to predict disease free survival (DFS), distant metastasis free survival (DMFS), and overall survival (OS) for 175 patients surgically treated for AdCC without LNM, and developed prognostic score (PS) determined as number of positive prognostic factors. The following emerged as significant prognostic factors: positive surgical margin in DFS, pT3/4 and positive surgical margin in DMFS, and positive surgical margin and high-histological grade in OS. 10-year DFS rates were 56.4% in PS0, and 19.1% in PS1 (p < 0.0001). 10-year DMFS rates were 86.3% in PS0, 56.4% in PS1, and 30.7% in PS2 (p < 0.0001). 10-year OS rates were 100% in PS0, 73.3% in PS1, and 38.8% in PS2 (p < 0.0001).

    DOI: 10.1016/j.oraloncology.2023.106491

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  • Glomangiopericytoma with CTNNB1 mutation. International journal

    Shinji Iwata, Riko Kitazawa, Sohei Kitazawa, Naohito Hato

    BMJ case reports   16 ( 9 )   2023.9

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    Glomangiopericytoma (GPC) is a rare tumour, accounting <0.5% of all nasal cavity tumours. It is classified as borderline malignant to indolent and is associated with perivascular myeloid cells. We report a case of GPC in a woman in her 80s who presented with nasal obstruction. The tumour originated from the nasal septum and was resected via endoscopic sinus surgery. Histopathological examination revealed dense spindle-shaped to oval-shaped mesenchymal cells forming tumour nodules with staghorn-like vessel formation. Immunohistochemical analysis revealed that the tumour cells were positive for α-smooth muscle actin, CD34, β-catenin and cyclin D1, whereas they were negative for STAT6. The percentage of Ki-67-positive cells was approximately 2%. Recent studies have demonstrated a high frequency of β-catenin (CTNNB1) mutations in GPC. We report a case of GPC where identifying CTNNB1 mutations (c.94G>C, p.D32H) was crucial for establishing a definitive diagnosis.

    DOI: 10.1136/bcr-2023-256787

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  • The dynamics of deglutition during head rotation using dynamic 320‐row area detector computed tomography International journal

    Kazutaka Kochi, Hirofumi Sei, Yuki Tanabe, Kazunori Yasuda, Teruhito Kido, Hiroyuki Yamada, Aki Taguchi, Naohito Hato

    Laryngoscope Investigative Otolaryngology   8 ( 3 )   746 - 753   2023.5

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    OBJECTIVE: We aimed to elucidate the dynamics of deglutition during head rotation by acquiring 320-row area detector computed tomography (320-ADCT) images and analyzing deglutition during head rotation. METHODS: This study included 11 patients experiencing globus pharyngeus. A 320-ADCT was used to acquire images in two types of viscosity (thin and thick), with the head rotated to the left. We measured the movement time of deglutition-related organs (soft palate, epiglottis, upper esophageal sphincter [UES], and true vocal cords) and pharyngeal volume (bolus ratio at the start of UES opening [Bolus ratio], pharyngeal volume contraction ratio [PVCR], and pharyngeal volume before swallowing [PVBS]). A two-way analysis of variance was performed for statistical analysis, and all items were compared for significant differences in terms of head rotation and viscosity. EZR was used for all statistical analyses (p-value <.05). RESULTS: Head rotation significantly accelerated the onset of epiglottis inversion and UES opening compared with no head rotation. The duration of epiglottis inversion with the thin viscosity fluid was significantly longer. The bolus ratio increased significantly with thick viscosity. There was no significant difference in viscosity and head rotation in terms of PVCR. PVBS increased significantly with head rotation. CONCLUSION: The significantly earlier start of epiglottis inversion and UES opening due to head rotation could be caused by: (1) swallowing center; (2) pharyngeal volume; and (3) pharyngeal contraction force. Thus, we plan to further analyze swallowing with head rotation by combining swallowing CT with manometry and examine its relationship with pharyngeal contraction force. LEVEL OF EVIDENCE: 3b.

    DOI: 10.1002/lio2.1082

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  • Physical therapy for peripheral facial palsy: A systematic review and meta-analysis. International journal

    Haruki Nakano, Takashi Fujiwara, Yasushi Tsujimoto, Naohito Morishima, Takashi Kasahara, Misato Ameya, Keita Tachibana, Shota Sanada, Saori Toufukuji, Naohito Hato

    Auris, nasus, larynx   51 ( 1 )   154 - 160   2023.5

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    OBJECTIVE: This study aimed to reveal the efficacy of physical therapy for patients with peripheral facial palsy. METHODS: A literature search was conducted using PubMed, Ichushi-Web, and Cochrane Central Register of Controlled Trials. Published randomized controlled trials comparing the physical therapy versus placebo/non-treatment for peripheral facial palsy such as Bell's palsy, Ramsay Hunt syndrome, and traumatic facial palsy were included for meta-analysis. The primary outcome was non-recovery at the end of the follow-up. Non-recovery was defined according to the authors' definition. The secondary outcomes were the composite score of the Sunnybrook facial grading system and sequelae (presence of synkinesis or hemifacial spasm) at the end of the follow-up. Data was analyzed using Review Manager software and pooled risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) were calculated. RESULTS: Seven randomized controlled trials met the eligible criteria. The data on non-recovery from four studies was obtained and included 418 participants in the meta-analysis. Physical therapy might reduce non-recovery (RR = 0.51 [95% CI = 0.31-0.83], low quality). Pooling the data of composite score of the Sunnybrook facial grading system from three studies (166 participants) revealed that physical therapy might increase the composite scores (MD = 12.1 [95% CI = 3.11-21.0], low quality). Moreover, we obtained data on sequelae from two articles (179 participants). The evidence was very uncertain about the effect of physical therapy on reduction of sequelae (RR = 0.64 [95% CI = 0.07-5.95], very low quality). CONCLUSION: The evidence suggested that physical therapy reduces non-recovery in patients with peripheral facial palsy and improves the composite score of the Sunnybrook facial grading system, whereas the efficacy of physical therapy in reducing sequelae remained uncertain. The included studies had high risk of bias, imprecision, or inconsistency; therefore, the certainty of evidence was low or very low. Further well-designed randomized controlled trials are needed to confirm its efficacy.

    DOI: 10.1016/j.anl.2023.04.007

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  • 320列CTを用いた頸部回旋時の嚥下動態の解明

    河内 和誉, 勢井 洋史, 山田 啓之, 田口 亜紀, 羽藤 直人

    日本耳鼻咽喉科頭頸部外科学会会報   126 ( 4 )   614 - 614   2023.4

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  • Development of a proficiency-based training curriculum for beginners in endoscopic endonasal surgery. International journal

    Taro Takagi, Sohei Mitani, Kunihide Aoishi, Naoya Nishida, Naohito Hato

    Auris, nasus, larynx   50 ( 6 )   887 - 894   2023.3

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    OBJECTIVE: Precise endoscopic skills are critical for endoscopic endonasal surgery (EES) to ensure patient safety, as well as to succeed as a surgeon. Among these skills, basic skills such as hand-eye coordination and bimanual dexterity are the most important skills for novice surgeons. However, there is no proficiency-based training for the basic skills in EES. In this study, we aimed to develop a proficiency-based training curriculum for beginners in EES using tractable tasks and to assess the curriculum's validity and educational benefits. METHODS: Training tasks for basic surgical skills of EES were created by experts, using a low-cost and simple simulator. Subsequently, a proficiency-based training curriculum was developed through a preliminary study. The face and content validity of the curriculum was evaluated by expert surgeons. The construct validity was confirmed by comparing the scores of the medical students with those of the experts. In addition, the educational benefits of the curriculum were assessed by comparing the scores of the medical students before and after the implementation of the curriculum. RESULTS: A proficiency-based training curriculum using six tractable tasks was developed in the preliminary study. Replication of real surgical situation, camera navigation, and instrument operability under endoscopy were all highly appreciated (4.6, 4.6, and 4.8 out of 5 points, respectively), which indicates face validity. The content validity of the curriculum was demonstrated by the results of the questionnaire (4.4 out of 5 points). The curriculum was implemented by 12 medical students. The initial student scores were significantly lower than the expert scores (mean score: 61.9 vs. 100.0, p < 0.001), and each coefficient of variation of the student scores was higher than that of the expert scores (p < 0.01), supporting the construct validity of the curriculum. The mean student composite scores were statistically improved after the training (61.9 vs. 93.3, p < 0.0001). In addition, improvement of five other medical students' EES skills through this training curriculum was confirmed in cadaver dissection (1.7 vs. 3.7, p < 0.0001). CONCLUSION: The validity of the proficiency-based training curriculum developed through the preliminary study was established based on the questionnaire of experts and the difference between student and expert scores. In addition, the educational benefits were demonstrated by the students' learning curves. The low-cost and simple simulator seems appropriate as an entry model for beginners in EES, and this curriculum can provide rapid intervention and objective assessment of basic skills in EES.

    DOI: 10.1016/j.anl.2023.03.002

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  • Intermittent environmental exposure to hydrogen prevents skin photoaging through reduction of oxidative stress.

    Takeshi Kiyoi, Shuang Liu, Erika Takemasa, Naohito Hato, Masaki Mogi

    Geriatrics & gerontology international   23 ( 4 )   304 - 312   2023.2

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    AIM: Molecular hydrogen is not only expected to be used as an energy-generating resource, but also to have preventive effects on a variety of clinical manifestations related to oxidative stress through scavenging radicals or regulating gene expression. In the current study, we investigated the influence of intermittent environmental exposure to hydrogen gas at a safe concentration (1.3%) on photoaging using an ultraviolet A (UVA)-irradiated murine model. METHODS: To mimic the expected human daily activity cycle, UVA exposure in the daytime and hydrogen exposure in the night-time, an original design, UVA-transmission, hydrogen-exposure system was established. Mice were bred under experimental conditions of UVA irradiation and normal air for 8 h (outdoor time 09.00-17.00 hours), and UVA non-irradiation and inhalation of hydrogen gas for 16 h (indoor time 17.00-09.00 hours), and the daily cycle was continued for up to 6 weeks. The progression of photoaging, including morphological changes, collagen degradation and UVA-related DNA damage, was evaluated. RESULTS: Intermittent administration of hydrogen gas by our system prevented UVA-induced epidermal signs, such as hyperplasia, melanogenesis and appearance of senescence cells, and UVA-induced dermal signs, such as collagen degradation. In addition, we detected attenuation of DNA damage in the hydrogen exposure group as indirect evidence that intermittent exposure to hydrogen gas reduced oxidative stress. CONCLUSIONS: Our findings support the notion that long-term, intermittent environmental exposure to hydrogen gas in daily life has a beneficial effect on UVA-induced photoaging. Geriatr Gerontol Int 2023; ••: ••-••.

    DOI: 10.1111/ggi.14562

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  • [ANL Secondary Publication] 中耳真珠腫手術症例の全国調査 中耳真珠腫進展度分類2015を用いた結果報告

    小森 学, 森田 由香, 東野 哲也, 松田 圭二, 山本 裕, 阪上 雅史, 羽藤 直人, 小島 博己, 高橋 晴雄

    日本耳鼻咽喉科頭頸部外科学会会報   126 ( 2 )   169 - 171   2023.2

  • Cricotracheostomy for patients with severe COVID-19: A case control study International journal

    Naoki Mukai, Masahiro Okada, Saki Konishi, Mitsuo Okita, Siro Ogawa, Kosuke Nishikawa, Suguru Annen, Muneaki Ohshita, Hironori Matsumoto, Satoru Murata, Yutaka Harima, Satoshi Kikuchi, Shiori Aibara, Hirofumi Sei, Kunihide Aoishi, Rie Asayama, Eriko Sato, Taro Takagi, Kaori Tanaka-Nishikubo, Masato Teraoka, Naohito Hato, Jun Takeba, Norio Sato

    Frontiers in Surgery   10   1082699 - 1082699   2023.1

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    Background

    Tracheostomy is an important procedure for the treatment of severe coronavirus disease-2019 (COVID-19). Older age and obesity have been reported to be associated with the risk of severe COVID-19 and prolonged intubation, and anticoagulants are often administered in patients with severe COVID-19; these factors are also related to a higher risk of tracheostomy. Cricotracheostomy, a modified procedure for opening the airway through intentional partial cricoid cartilage resection, was recently reported to be useful in cases with low-lying larynx, obesity, stiff neck, and bleeding tendency. Here, we investigated the usefulness and safety of cricotracheostomy for severe COVID-19 patients.

    Materials and methods

    Fifteen patients with severe COVID-19 who underwent cricotracheostomy between January 2021 and April 2022 with a follow-up period of ≥ 14 days were included in this study. Forty patients with respiratory failure not related to COVID-19 who underwent traditional tracheostomy between January 2015 and April 2022 comprised the control group. Data were collected from medical records and comprised age, sex, body mass index, interval from intubation to tracheostomy, use of anticoagulants, complications of tracheostomy, and decannulation.

    Results

    Age, sex, and days from intubation to tracheostomy were not significantly different between the COVID-19/cricotracheostomy and control/traditional tracheostomy groups. Body mass index was significantly higher in the COVID-19 group than that in the control group (P = 0.02). The rate of use of anticoagulants was significantly higher in the COVID-19 group compared with the control group (P &amp;lt; 0.01). Peri-operative bleeding, subcutaneous emphysema, and stomal infection rates were not different between the groups, while stomal granulation was significantly less in the COVID-19 group (P = 0.04).

    Conclusions

    These results suggest that cricotracheostomy is a safe procedure in patients with severe COVID-19.

    DOI: 10.3389/fsurg.2023.1082699

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  • Effect of hormonal therapy on the otoconial changes caused by estrogen deficiency International journal

    Takahiro Nakata, Masahiro Okada, Eriko Nishihara, Aoi Ikedo, Sawa Asoh, Taro Takagi, Naohito Tokunaga, Naohito Hato, Yuuki Imai

    Scientific Reports   12 ( 1 )   22596 - 22596   2022.12

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    Abstract

    Benign paroxysmal positional vertigo (BPPV) is associated with menopause and/or osteopenia. Morphological changes in the otoconial layer have been reported after ovariectomy (OVX). Moreover, hormone replacement therapy decreases BPPV risk. However, knowledge concerning the effect of hormonal therapy on the otoconial changes caused by estrogen deficiency is limited. We aimed to examine the effect of hormonal therapy on otoconial changes caused by estrogen deficiency. We hypothesized that hormonal therapy could reduce otoconial changes caused by OVX. Eight-week-old C57BL/6 mice were divided into four groups: sham operation with implantation of vehicle (sham + v), OVX with implantation of vehicle (OVX + v), OVX with implantation of estradiol (E2) (OVX + E2), and OVX with implantation of raloxifene (RAL) (OVX + RAL) groups. Otoconial layer volume was measured by micro-CT at 4 weeks after OVX or the sham operation. The otic bullae were removed; immunohistochemistry was performed for estrogen receptor alpha and 4-hydroxynonenal. Otoconial layer volume was significantly higher in the OVX + v than in the sham + v group. E2 and RAL significantly reduced these changes in the endometrial layer. The staining of estrogen receptor alpha and 4-hydroxynonenal were stronger in the OVX + v than in the sham + v group but equal in the sham + v, OVX + E2, and OVX + RAL groups. These results indicate that E2 and RAL are effective against morphological changes of the otoconial layer caused by estrogen deficiency via oxidative stress reduction.

    DOI: 10.1038/s41598-022-27240-5

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  • 喉頭摘出後代用音声の進歩 音声合成スマートフォンアプリを用いた新しい代用音声

    飴矢 美里, 勢井 洋史, 三谷 壮平, 西尾 直樹, 羽藤 直人

    喉頭   34 ( 2 )   51 - 57   2022.12

  • 喉頭摘出後代用音声の進歩 音声合成スマートフォンアプリを用いた新しい代用音声

    飴矢 美里, 勢井 洋史, 三谷 壮平, 西尾 直樹, 羽藤 直人

    喉頭   34 ( 2 )   51 - 57   2022.12

  • Message to researchers: the characteristic absence of a posterior communicating artery is easily lost in the gerbil Reviewed

    Yasunori Abe, Kensuke Toyama, Akio Shinohara, Goro A. Nagura-Kato, Yuki Ikai, Chihiro Koshimoto, Joshua M. Spin, Naohito Hato

    Anatomical Science International   98 ( 3 )   426 - 433   2022.12

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    The Mongolian gerbil has historically been useful for brain ischemia experiments, owing to the gerbil's uniquely underdeveloped circle of Willis (CoW). This led to a gerbil model of cochlear ischemia being generated in our unit. However, we have found that the usual severe hearing loss seen in this model was not being induced consistently in recent experiments using the MON/Jms/GbsSlc gerbil (the sole commercially available gerbil in Japan). We set out to evaluate the posterior communicating artery (PcomA) in MON/Jms/GbsSlc, to re-establish whether this strain is appropriate for ischemia models. Having found that this unique feature is often lost, we then attempted to breed for the characteristic absent PcomA. India-ink perfusion revealed that the percentage of intact bilateral PcomA ("communicating type") in the MON/Jms/GbsSlc gerbil was 57%; unilateral only ("unilateral communicating type") was 39%; and completely absent PcomA ("non-communicating type") was 4%. We were able to obtain few examples of the indigenous old aged Japanese UNG/Mz gerbil strain (at University of Miyazaki). Unfortunately, the pure UNG/Mz female was too elderly for mating. Therefore, selective breeding crosses between MON/Jms/GbsSlc and male UNG/Mz were carried out. After five generations of selective breeding, the percentage of non-communicating type gerbils was significantly higher in the newly generated strain, MON/Jms/SlcMz (F6 generation; 63%) than in the MON/Jms/GbsSlc gerbil. Bilateral common carotid artery occlusion surgery demonstrated that the cerebral blood flow was significantly reduced in MON/Jms/SlcMz compared with MON/Jms/GbsSlc (p < 0.0001) and induced more hippocampal injuries in MON/Jms/SlcMz than in MON/Jms/GbsSlc (p < 0.01). In conclusion, the commercially available MON/Jms/GbsSlc gerbil can easily regain PcomA, and we established a new gerbil strain (MON/Jms/SlcMz) displaying non-PcomA.

    DOI: 10.1007/s12565-022-00698-z

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  • A double-blinded, randomized controlled clinical trial of hydrogen inhalation therapy for idiopathic sudden sensorineural hearing loss International journal

    Masahiro Okada, Hideo Ogawa, Taro Takagi, Eriko Nishihara, Tadashi Yoshida, Jun Hyodo, Yusuke Shinomori, Nobumitsu Honda, Takashi Fujiwara, Masato Teraoka, Hiroyuki Yamada, Shin-ichi Hirano, Naohito Hato

    Frontiers in Neuroscience   16   1024634 - 1024634   2022.11

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    Background

    Hydrogen (H<sub>2</sub>) has been reported to be effective in reducing hearing loss due to several causes in animal studies. However, no study has examined the effectiveness of H<sub>2</sub> in treating hearing loss in humans. Thus, we investigated whether H<sub>2</sub> is effective for the treatment of idiopathic sudden sensorineural hearing loss (ISSNHL).

    Materials and methods

    We conducted a double-blind randomized controlled trial at six hospitals between June 2019 and March 2022. The study protocol and trial registration have been published in the Japan Registry of Clinical Trials (jRCT, No. jRCTs06119004). We randomly assigned patients with ISSNHL to receive either H<sub>2</sub> (H<sub>2</sub> group) or air as a placebo (control group) through inhalation combined with the administration of systemic glucocorticoids and prostaglandin E1. The primary outcome was the hearing threshold and changes in hearing threshold 3 months after therapy. In contrast, the secondary outcomes included the proportion of patients with a good prognosis (complete recovery or marked improvement).

    Results

    Sixty-five patients with ISSNHL (31 and 34 in the H<sub>2</sub> and control groups, respectively) were included in this study. The hearing threshold 3 months after treatment was not significantly different between the groups; 39.0 decibels (dB) (95% confidence interval [CI]: 28.7–49.3) and 49.5 dB (95% CI: 40.3–58.7) in the H<sub>2</sub> and control groups, respectively. In contrast, the changes in hearing threshold 3 months after treatment was 32.7 dB (95% CI: 24.2–41.3) and 24.2 dB (95% CI: 18.1–30.3) in the H<sub>2</sub> and control groups, respectively. Consequently, the changes in hearing threshold were significantly better in the H<sub>2</sub> group than in the control group (P = 0.048). However, no adverse effects due to the inhalation of H<sub>2</sub> gas have been reported.

    Conclusion

    This is the first study to investigate the efficacy of H<sub>2</sub> for the treatment of ISSNHL in humans. The results suggest that H<sub>2</sub> therapy may be effective for ISSNHL treatment.

    Clinical trial registration

    [https://jrct.niph.go.jp/re/reports/detail/10442], identifier [jRCTs06119004].

    DOI: 10.3389/fnins.2022.1024634

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  • Generation of DNA-aptamers targeting galectin-7 for the identification of cholesteatoma residue. Reviewed

    Shuang Liu, Erika Takemasa, Yasuyuki Suzuki, Amarsanaa Javkhlant, Taro Takagi, Hiroyuki Yamada, Yasunori Abe, Naohito Hato, Masaki Mogi

    Journal of pharmacological sciences   150 ( 3 )   146 - 153   2022.11

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    PURPOSE: Aiming at complete excision of cholesteatoma during trympanomastoidectomy and therefore reducing the risk of recurrence, intraoperative imaging techniques are required to assist the visualization of cholesteatoma residue. Galectin-7 has been demonstrated to be a biomarker for cholesteatoma matrix and used for intraoperatively identifying the excision margins. METHODS: A galectin-7-targeted DNA-aptamer library was generated for labeling the cholesteatoma matrix using cell-systematic evolution of ligands by an exponential enrichment technique. The binding characteristics of the identified aptamers were analyzed, and structure optimization of the identified aptamers was carried out both in silico and in vitro. FINDINGS: A fluorophore-labeled structure-optimized DNA fragment was commercially synthesized as a non-invasive aptamer-based probe for intraoperative lesion detection. Using galectin-7-aptamer-guided molecular imaging, the excision margins of cholesteatoma matrix and surrounding normal tissue were successfully achieved within 15-20 min. CONCLUSIONS: Galectin-7-targeted aptamers could benefit molecular imaging-guided surgical treatment, which would enable clinicians to not only intraoperatively detect the locations of cholesteatoma matrix in the middle ear, but also assess the postoperative response of the expression profile to therapy. It is highly expected that further efforts for rational design and development should be directed towards the development of clinically translatable aptamer-based imaging agents.

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  • Laryngeal complications after endotracheal intubation and prone positioning in patients with coronavirus disease 2019 International journal

    Shiori Aibara, Masahiro Okada, Kaori Tanaka‐Nishikubo, Rie Asayama, Eriko Sato, Hirofumi Sei, Kunihide Aoishi, Taro Takagi, Masato Teraoka, Naoki Mukai, Saki Konishi, Mitsuo Okita, Siro Ogawa, Suguru Annen, Muneaki Ohshita, Hironori Matsumoto, Satoru Murata, Yutaka Harima, Satoshi Kikuchi, Jun Takeba, Norio Sato, Naohito Hato

    Laryngoscope Investigative Otolaryngology   7 ( 6 )   1909 - 1914   2022.10

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    OBJECTIVES: Laryngeal complications have been reported after endotracheal intubation and prone positioning in patients with critical coronavirus disease 2019 (COVID-19), but their association is unclear. In this study, we investigated the rate of laryngeal complications in patients with COVID-19 compared to an alternative condition (control group). METHODS: We retrospectively analyzed the data of 40 patients who underwent endotracheal intubation for either COVID-19 or an alternative condition (control group). Data on age, sex, body mass index (BMI), cardiovascular disease (CVD) risk factors, use of prone therapy, duration of endotracheal intubation, and duration from extubation/tracheostomy to laryngeal evaluation were collected from medical records. RESULTS: There were no significant differences in BMI, frequency of CVD risk factors, duration of endotracheal intubation, or duration from extubation/tracheostomy to laryngeal evaluation between the two groups. In the COVID-19 group, all patients adopted the prone position. In comparison, only one patient in the control group adopted the prone position. Significant differences were observed between the two groups regarding the incidence of vocal fold immobility and laryngeal granuloma. CONCLUSION: Laryngeal complications were more common in the COVID-19 group than in the control group. Prone positioning may be a risk factor for these complications. LEVEL OF EVIDENCE: 4.

    DOI: 10.1002/lio2.874

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  • Relationship between hearing loss and prevalence of depressive symptoms in Japan: Baseline data from the Aidai Cohort study in Yawatahama and Uchiko

    Junichiro Nobori, Yoshihiro Miyake, Keiko Tanaka, Hidenori Senba, Masahiro Okada, Daiki Takagi, Masato Teraoka, Hiroyuki Yamada, Bunzo Matsuura, Naohito Hato

    Archives of Gerontology and Geriatrics   102   104735 - 104735   2022.9

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    DOI: 10.1016/j.archger.2022.104735

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  • 肥厚性硬膜炎を合併した多発血管炎肉芽腫症により嚥下障害と音声障害を来した1例

    飴矢 美里, 田中 加緒里, 勢井 洋史, 岡田 昌浩, 羽藤 直人

    耳鼻と臨床   68 ( 4 )   291 - 298   2022.7

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    肥厚性硬膜炎を合併した多発血管炎性肉芽腫症(GPA)により嚥下障害と音声障害を来した症例を経験した。本症例の嚥下障害は、代償法の習得にて経口摂取を再獲得できた。しかし音声障害は、迷走神経麻痺による声帯の副正中位固定と弓状弛緩から高度な声門閉鎖不全を来し、代償的な過緊張性発声から粗そう性、気息性、努力性嗄声となっていた。音声機能改善術と音声治療を行うことで、声門閉鎖不全の改善や過緊張性発声の軽減が得られ、本人の自覚的印象においても改善を認めた。GPAは難治性疾患であるが、原疾患のコントロールが可能であれば、音声外科的治療と音声治療を組み合せて多角的に介入することで患者QOL向上につながると考える。(著者抄録)

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  • IL12B rs6887695 polymorphism and interaction with alcohol intake in the risk of ulcerative colitis in Japan. International journal

    Yoshihiro Miyake, Keiko Tanaka, Chisato Nagata, Shinya Furukawa, Akira Andoh, Tetsuji Yokoyama, Naoki Yoshimura, Kenichiro Mori, Tomoyuki Ninomiya, Yasunori Yamamoto, Eiji Takeshita, Yoshio Ikeda, Mitsuru Saito, Katsuhisa Ohashi, Hirotsugu Imaeda, Kazuki Kakimoto, Kazuhide Higuchi, Hiroaki Nunoi, Yuji Mizukami, Seiyuu Suzuki, Sakiko Hiraoka, Hiroyuki Okada, Keitarou Kawasaki, Masaaki Higashiyama, Ryota Hokari, Hiromasa Miura, Teruki Miyake, Teru Kumagi, Hiromasa Kato, Naohito Hato, Koji Sayama, Yoichi Hiasa

    Cytokine   155   155901 - 155901   2022.7

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    BACKGROUND: The interleukin (IL)-23/Th17 pathway plays a critical role in ulcerative colitis (UC). The IL-12p40 subunit, which is shared by IL-23 and IL-12, is encoded by the IL12B gene. The current case-control study investigated the association between IL12B SNP rs6887695 and the UC risk. METHODS: There were 384 cases within 4 years of UC diagnosis and 661 controls who were enrolled. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, and body mass index. RESULTS: Subjects with the GG IL12B SNP rs6887695 genotype had a significantly increased risk of UC compared with those with the CC genotype (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.08-2.36). This positive association was also significant using the additive and recessive models (AOR, 1.25; 95% CI, 1.03-1.52; AOR, 1.50; 95% CI, 1.08-2.09, respectively). An independent inverse relationship was observed between ever alcohol consumption and the UC risk in those with the CC genotype while no significant association was found in those with at least one G allele (P for interaction = 0.0008). CONCLUSIONS: IL12B SNP rs6887695 was significantly associated with UC. The influence of alcohol consumption might rely on rs6887695.

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  • 頭頸部外科領域における内視鏡手術 咽頭癌と甲状腺腫瘍に対して

    三谷 壮平, 木谷 卓史, 坂本 佳代, 相原 栞, 細川 裕貴, 佐藤 恵里子, 勢井 洋史, 羽藤 直人

    愛媛医学   41 ( 2 )   66 - 70   2022.6

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  • 当科における全身麻酔下に摘出した咽頭異物症例の検討

    高瀬 慎也, 勢井 洋史, 木谷 卓史, 寺岡 正人, 羽藤 直人

    耳鼻咽喉科臨床 補冊   ( 補冊159 )   149 - 149   2022.6

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  • 予防的ステントを留置しレンバチニブを導入した鎖骨下動脈浸潤を伴う甲状腺未分化癌の1例

    村川 誠太郎, 勢井 洋史, 眞田 朋昌, 羽藤 直人

    耳鼻咽喉科・頭頸部外科   94 ( 6 )   483 - 486   2022.5

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    症例は76歳男性で、甲状腺左葉に腫瘍性病変を認め、甲状腺全摘術と左D2a郭清を施行されたが左鎖骨上窩・上縦隔リンパ節転移再発と肺転移が出現、さらに全身倦怠感と左胸水貯留を認めたため、当科に緊急入院となった。入院7日目の胸水細胞診で甲状腺乳頭癌の未分化転化と診断された。全身状態が落ち着いた段階で造影CTによる再評価を行い、レンバチニブ導入を行う方針とした。入院20日目に左鎖骨下動脈ステント留置術を施行、5Fr Launcherを左椎骨動脈に挿入後、椎骨動脈起始部にAmplatzerバスキュラープラグを留置して左椎骨動脈をコイル塞栓した。その後、左鎖骨下動脈へ9Frシースよりステントを留置した。25日目にレンバチニブ内服による治療を開始し、有害事象はなく治療開始14日目のCTでは病変の縮小を認めた。

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    Other Link: https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J02122&link_issn=&doc_id=20220428050020&doc_link_id=10.11477%2Fmf.1411203052&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1411203052&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

  • 当科における上顎全摘症例の検討

    木谷 卓史, 三谷 壮平, 勢井 洋史, 佐藤 恵里子, 脇坂 浩之, 羽藤 直人

    頭頸部癌   48 ( 2 )   201 - 201   2022.5

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  • 当科における高齢者顔面神経麻痺症例の検討

    山田 啓之, 大下 美由紀, 寺岡 正人, 佐藤 恵里子, 高木 太郎, 三谷 壮平, 岡田 昌浩, 羽藤 直人

    日本耳鼻咽喉科頭頸部外科学会会報   125 ( 4 )   768 - 768   2022.4

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  • Development of a simple evaluation instrument for liquid thickness measurement

    Hirofumi Sei, Kazunori Yasuda, Rie Asayama, Kaori Tanaka, Shiori Oba, Mutsumi Shidahara, Naohito Hato

    Journal of Texture Studies   2022.1

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    Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    DOI: 10.1111/jtxs.12660

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    Other Link: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/jtxs.12660

  • Comparison of the Signal Intensity of Vestibular Schwannoma Between Growing and Nongrowing Tumors. International journal

    Hiroyuki Yamada, Naruhiko Kai, Yoshiyasu Hiratsuka, Sohei Mitani, Satoshi Suehiro, Yasuhiro Shiraishi, Takuya Kimura, Taro Takagi, Shinji Iwata, Masato Teraoka, Hiroyuki Wakisaka, Naohito Hato

    The Laryngoscope   132 ( 1 )   198 - 203   2022.1

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    OBJECTIVES/HYPOTHESIS: To determine the relationship between signal intensity on gadolinium (Gd)-enhanced magnetic resonance images and growth of vestibular schwannomas (VSs). STUDY DESIGN: Cross-sectional study. METHODS: In this cross-sectional study, we retrospectively reviewed the data of 31 patients with VSs who underwent magnetic resonance imaging (MRI). The mean signal intensities within the regions of interest in the tumor, pons, and temporal muscles were measured on Gd-enhanced T1-weighted MRI. Relative intensity ratios were calculated as follows: T/N pons ratio (T/Np) is the tumor signal intensity/pons signal intensity and T/N muscle ratio (T/Nm) is the tumor signal intensity/temporal muscle signal intensity. Volume measurements were used to assess the tumor size. Growth rate was determined by assessing previous imaging studies. Growing VS was defined as a tumor with a growth rate >100 mm3 /year. RESULTS: The mean (standard deviation) T/Np and T/Nm were 1.47 (0.27) and 1.50 (0.24), respectively, in nongrowing tumors and 1.78 (0.17) and 1.90 (0.12), respectively, in growing tumors. The T/Np and T/Nm differed significantly between the two groups (T/Np, P < .001; T/Nm, P < .001). Receiver operating characteristic curve analysis showed that cutoffs of 1.56 and 1.76 for T/Np (93.33% sensitivity, 75.00% specificity) and T/Nm (100.00% sensitivity, 93.75% specificity), respectively, could be used to diagnose a growth rate of >100 mm3 /year. The area under the curve was 0.85 (95% confidence interval, 0.70-1.00) for T/Np and 0.94 (0.82-1.00) for T/Nm. CONCLUSION: Growing VSs show higher signal intensities on Gd-enhanced MRI. Thus, measuring the signal intensity of VS on Gd-enhanced MRI may aid in predicting VS growth. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:198-203, 2022.

    DOI: 10.1002/lary.29834

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  • Imaging characteristics of hypertrophic pachymeningitis due to ANCA-associated vasculitis

    Taro Takagi, Masahiro Okada, Masashi Nakamura, Takahiro Hanari, Takahiro Nakata, Masato Teraoka, Naohito Hato

    Auris Nasus Larynx   2022.1

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    DOI: 10.1016/j.anl.2022.01.009

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  • Five Cases of Unresectable Differentiated Thyroid Cancer Treated with Weekends-Off Lenvatinib

    Hirofumi Sei, Eriko Sato, Sohei Mitani, Takashi Kitani, Tomoyoshi Sanada, Naohito Hato

    Practica Oto-Rhino-Laryngologica   115 ( 11 )   1005 - 1009   2022

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    Publishing type:Research paper (scientific journal)   Publisher:The Society of Practical Otolaryngology  

    DOI: 10.5631/jibirin.115.1005

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  • An Exploratory Investigation of a New Substitute Voice Using a Smartphone Application

    Ameya Misato, Sei Hirofumi, Mitani Sohei, Nishio Naoki, Hato Naohito

    Koutou (THE LARYNX JAPAN)   33 ( 02 )   230 - 234   2021.12

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    Patients with head and neck cancer who undergo total laryngectomy often suffer from significant communication disorders due to permanent aphonia. While various substitutes for voice loss, including an electronic artificial larynx, tracheoesophageal shunt, esophageal speech, and written communication, have been currently employed to communicate against aphonia, few methods have used the voice of a preoperative patient. “Coestation<sup>®</sup>” is a smartphone application that synthesizes patients’ voice and is now clinically applied to patients with amyotrophic lateral sclerosis (ALS). To verify whether this application has the potential to become a new substitute voice, we launched a clinical investigation for patients with head and neck cancer who were scheduled to undergo total laryngectomy. We preoperatively performed a voice synthesis using the smartphone application in two patients and postoperatively requested them to use an electronic artificial larynx and the synthesized voice. The patients stated that the synthesized voice was more similar to their original voice than the artificial larynx and were very satisfied about its voice quality. Based on these preliminary results, we plan to enroll more patients to assess the general usefulness of the synthesized voice as a new substitute voice.

    DOI: 10.5426/larynx.33.230

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  • Active and passive smoking and risk of ulcerative colitis: A case-control study in Japan. International journal

    Atsushi Nishikawa, Keiko Tanaka, Yoshihiro Miyake, Chisato Nagata, Shinya Furukawa, Akira Andoh, Tetsuji Yokoyama, Naoki Yoshimura, Kenichiro Mori, Tomoyuki Ninomiya, Yasunori Yamamoto, Eiji Takeshita, Yoshio Ikeda, Mitsuru Saito, Katsuhisa Ohashi, Hirotsugu Imaeda, Kazuki Kakimoto, Kazuhide Higuchi, Hiroaki Nunoi, Yuji Mizukami, Seiyuu Suzuki, Sakiko Hiraoka, Hiroyuki Okada, Keitarou Kawasaki, Masaaki Higashiyama, Ryota Hokari, Hiromasa Miura, Teruki Miyake, Teru Kumagi, Hiromasa Kato, Naohito Hato, Koji Sayama, Yoichi Hiasa

    Journal of gastroenterology and hepatology   2021.11

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    BACKGROUND AND AIM: Although an inverse relationship between current smoking and the development of ulcerative colitis (UC) has been shown in North America and Europe, evidence is limited in Asian countries, where the incidence of UC is rapidly increasing. This Japanese case-control study examined the association between active and passive smoking and risk of UC. METHODS: A self-administered questionnaire was used to obtain information on smoking and potential confounding factors in 384 cases with a diagnosis of UC within the past 4 years and 665 controls. RESULTS: Compared with having never smoked, having ever smoked was associated with an increased risk of UC (adjusted odds ratio [OR] = 1.70, 95% confidence interval [CI]: 1.23-2.37). No association was observed between current smoking and risk of UC, but former smokers had a significant elevation in risk (adjusted OR = 2.40, 95% CI: 1.67-3.45). There was a positive dose-response relationship with pack-years smoked (P for trend = 0.006). Among never smokers, passive smoking exposure at home was significantly associated with an increased risk of UC (adjusted OR = 1.90, 95% CI: 1.30-2.79). A significant dose-response gradient was also observed between pack-years of passive smoking at home and risk of UC (P for trend = 0.0003). CONCLUSIONS: We confirmed that former smoking elevated the risk of UC, whereas an inverse association between current smoking and the risk of UC did not reach a statistically significant level. Passive smoking may be associated with an increased risk of UC.

    DOI: 10.1111/jgh.15745

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  • Dietary intake of vegetables, fruit, and antioxidants and risk of ulcerative colitis: A case-control study in Japan International journal

    Yoshihiro Miyake, Keiko Tanaka, Chisato Nagata, Shinya Furukawa, Akira Andoh, Tetsuji Yokoyama, Naoki Yoshimura, Kenichiro Mori, Tomoyuki Ninomiya, Yasunori Yamamoto, Eiji Takeshita, Yoshio Ikeda, Mitsuru Saito, Katsuhisa Ohashi, Hirotsugu Imaeda, Kazuki Kakimoto, Kazuhide Higuchi, Hiroaki Nunoi, Yuji Mizukami, Seiyuu Suzuki, Sakiko Hiraoka, Hiroyuki Okada, Keitarou Kawasaki, Masaaki Higashiyama, Ryota Hokari, Hiromasa Miura, Teruki Miyake, Teru Kumagi, Hiromasa Kato, Naohito Hato, Koji Sayama, Yoichi Hiasa

    Nutrition   91-92   111378 - 111378   2021.11

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    OBJECTIVES: Oxidative stress is considered one of the etiologic factors involved in ulcerative colitis (UC), yet there is limited epidemiologic information regarding the relationship between antioxidant intake and the risk of UC. The aim of the present case-control study in Japan was to examine the association between intake of green and yellow vegetables, other vegetables, fruit, vitamin C, vitamin E, retinol, alpha-carotene, beta-carotene, and cryptoxanthin and UC risk. METHODS: A total of 384 cases within 4 y of diagnosis with UC and 665 controls were included in the study. Data on dietary intake and confounders were obtained using a self-reported questionnaire. Information on dietary factors was collected using a 169-item semiquantitative food-frequency questionnaire. Adjustment was made for sex, age, pack-y of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, and body mass index. RESULTS: Higher intake levels of other vegetables, vitamin C, and retinol were independently associated with a reduced risk of UC. The adjusted odds ratio between extreme quartiles was 0.51 (95% confidence interval [CI], 0.34-0.76; P for trend ≤ 0.001) for other vegetables, 0.45 (95% CI, 0.30-0.69, P for trend ≤ 0.001) for vitamin C, and 0.64 (95% CI, 0.43-0.95, P for trend = 0.04) for retinol. There were no associations between intake of green and yellow vegetables, fruit, vitamin E, alpha-carotene, beta-carotene, or cryptoxanthin and UC risk (P for trend = 0.29, 0.56, 0.89, 0.20, 0.69, and 0.22, respectively). CONCLUSIONS: Intake of other vegetables, vitamin C, and retinol was inversely associated with UC risk.

    DOI: 10.1016/j.nut.2021.111378

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  • Higher number of teeth is associated with decreased prevalence of hearing impairment in Japan

    Keiko Tanaka, Masahiro Okada, Hiromasa Kato, Hisanori Utsunomiya, Hidenori Senba, Daiki Takagi, Masato Teraoka, Hiroyuki Yamada, Bunzo Matsuura, Naohito Hato, Yoshihiro Miyake

    Archives of Gerontology and Geriatrics   97   104502 - 104502   2021.11

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    DOI: 10.1016/j.archger.2021.104502

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  • Intratympanic Insulin-like Growth Factor-1 Administration Via the Otic Bulla in a Severe Facial Paralysis Model

    Takuya Kimura, Hiroyuki Yamada, Masato Teraoka, Tomonori Joko, Shinji Iwata, Yasuhiro Tabata, Hiroyuki Wakisaka, Naohito Hato

    Otology &amp; neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology   42 ( 9 )   e1376 - e1381   2021.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:NLM (Medline)  

    HYPOTHESIS: We investigated the treatment effect of intratympanic insulin-like growth factor-1 (IGF-1) on severe facial paralysis in guinea pigs. BACKGROUND: The use of regenerative medicine involving growth factors has been reported in the treatment of peripheral nerve diseases. IGF-1 plays a crucial role in nerve regeneration. METHODS: We performed the following procedures on guinea pigs. In the normal group (n = 7), no procedure was performed. In the saline (n = 7) and IGF-1 (n = 7) groups, facial paralysis was induced by freezing of the facial canal. Subsequently, in the saline and IGF-1 groups, a gelatin hydrogel impregnated with 100 μL saline and 400 μg/100 μL IGF-1, respectively, was placed in the facial canal. Facial nerve functions were evaluated using three test batteries: facial movement observation, electrophysiological testing, and histological assessment. RESULTS: At 10 weeks postoperatively, the facial movement scores for the IGF-1 group were improved compared to those in the saline group. The conductive velocity was significantly faster in the IGF-1 group than in the saline group. There was a significant between-group difference in the nerve fiber number and myelin thickness. CONCLUSION: Intratympanic IGF-1 administration improved facial nerve regeneration. This novel method could provide prompt ambulatory regenerative treatment and reduce the incidence of poor recovery in patients with severe facial paralysis.

    DOI: 10.1097/MAO.0000000000003263

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  • 側頭骨手術手技研修ワーキンググループ報告

    羽藤 直人, 平海 晴一, 伊藤 吏, 大石 直樹, 金井 理絵, 我那覇 章, 杉本 寿史, 高橋 邦行, 中条 恭子, 物部 寛子, 矢間 敬章, 山内 大輔, 山本 和央, 山本 典生, 国内学術委員会側頭骨手術手技研修ワーキンググループ

    日本耳科学会総会・学術講演会抄録集   31回   126 - 126   2021.10

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  • 頸部リンパ管腫に対して越婢加朮湯が有用であった小児の1例

    勢井 洋史, 羽藤 直人

    口腔・咽頭科   34 ( 3 )   320 - 320   2021.8

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  • Nationwide survey of middle ear cholesteatoma surgery cases in Japan: Results from the Japan Otological society registry using the JOS staging and classification system. International journal

    Manabu Komori, Yuka Morita, Tetsuya Tono, Keiji Matsuda, Yutaka Yamamoto, Masafumi Sakagami, Naohito Hato, Hiromi Kojima, Haruo Takahashi

    Auris, nasus, larynx   48 ( 4 )   555 - 564   2021.8

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    OBJECTIVE: This study was aimed to determine the characteristics of middle ear cholesteatoma and to investigate short-term outcomes regarding the rates of residual and recurrent cholesteatoma and the postoperative hearing results in Japan, via a nationwide survey using staging and classification criteria for middle ear cholesteatoma, as proposed by the Japan Otological Society (JOS). METHODS: The first-round survey was conducted in 2016. The target was patients with middle ear cholesteatoma who were surgically treated in Japan between January and December 2015. Medical information on the patients was anonymized. The questionnaire entries were age, sex, cholesteatoma classification and stage, preoperative hearing level, mastoid development, status of the stapes, and surgical method. There were a total of 1,787 registered patients from 74 facilities from all over Japan. The second survey was conducted in January 2018 and received 1,456 responses from 49 facilities in Japan. Of the 1,456 cases, 1,060 were conducted in the postoperative hearing survey and 1,084 in the residual recurrence survey. RESULTS: The most common cholesteatoma type was pars flaccida cholesteatoma (63.3%), followed by pars tensa cholesteatoma (13.0%), congenital cholesteatoma (12.9%), and cholesteatoma secondary to chronic tensa perforation (5.6%). Cholesteatoma of uncertain origin accounted for 5.0% (90 cases). Stage II was predominant in pars flaccida and pars tensa cholesteatoma, which frequently involves the mastoid, whereas about half of cases of cholesteatoma secondary to chronic tensa perforation and congenital cholesteatoma were classified as stage I. One hundred fifty-two of 1,084 cases (14.0%) had recurrent cholesteatoma, residual cholesteatoma, or both following first surgeries. The postoperative rates of hearing success rate was 63.3%. CONCLUSION: We were able to clarify not only the current epidemiological status of middle ear cholesteatoma but also the current trends of cholesteatoma surgery in Japan. The development of a staging system by the JOS Committee serving an epidemiological database for international or time-dependent comparison. It is possible to use this staging system with reasonable reliability.

    DOI: 10.1016/j.anl.2020.09.011

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  • Exteriorization of Petrous Bone Cholesteatoma by Endonasal Endoscopic Approach: A Case Report. International journal

    Naoya Nishida, Takuya Fujiwara, Suehiro Satoshi, Akira Inoue, Daiki Takagi, Taro Takagi, Naohito Hato

    The journal of international advanced otology   17 ( 4 )   368 - 371   2021.7

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    A 61-year-old woman presented with diplopia and headache. The patient had a longstanding history of petrous bone cholesteatoma (PBC) on the left side and had undergone multiple surgeries to address it. Computed tomography (CT) revealed a radiolucent lesion with bony destruction in the left petrous apex. Magnetic resonance imaging of the lesion revealed a hypointense area on T1-weighted images and a hyperintense area on T2-weighted and abnormal diffusion-weighted images. A diagnosis of recurrent petrous apex cholesteatoma was made. The patient was treated by exteriorization using an endoscopic endonasal approach. The patient is in remission and doing well. The ideal treatment of PBC is complete excision, though exteriorization using an endoscopic endonasal approach is considered a second option when excision is not possible.

    DOI: 10.5152/iao.2021.9153

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  • 経鼻内視鏡下経上顎洞アプローチで摘出した翼口蓋窩三叉神経鞘腫症例

    川元 日向子, 西田 直哉, 兵頭 純, 羽藤 直人

    耳鼻咽喉科・頭頸部外科   93 ( 8 )   661 - 665   2021.7

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  • Weekends-off法がレンバチニブの有害事象の制御に有用であった切除不能甲状腺癌3例

    勢井 洋史, 佐藤 恵里子, 木谷 卓史, 眞田 朋昌, 羽藤 直人

    耳鼻咽喉科臨床 補冊   ( 補冊157 )   108 - 108   2021.6

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  • 健診データを用いた長期コホート研究 血小板値と難聴の関係

    阿部 康範, 外山 研介, 葛山 雅哉, 田中 伸司, 山泉 雅光, 上野 愛実, Spin Joshua, 羽藤 直人, 茂木 正樹

    日本耳鼻咽喉科学会会報   124 ( 4 )   614 - 614   2021.4

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  • Development and validation of an iPad-based Japanese language monosyllable speech perception test (iCI2004 monosyllable). International journal

    Shin-Ya Nishio, Tetsuya Tono, Takako Iwaki, Hideaki Moteki, Kumiko Suzuki, Yui Tsushima, Akinori Kashio, Yusuke Akamatsu, Hiroaki Sato, Keiko Yaegashi, Hidehiko Takeda, Fumiai Kumagai, Takahiro Nakashima, Yusuke Matsuda, Naohito Hato, Teppei Dairoku, Masae Shiroma, Ryosuke Kawai, Shin-Ichi Usami

    Acta oto-laryngologica   141 ( 3 )   267 - 272   2021.3

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    BACKGROUND: Speech perception tests are commonly used as indices reflecting hearing ability in daily life. In Japan, the CI-2004 test, first developed in 2004, is widely used as standard, but it was not validated against a large number of normal hearing controls and hearing loss patients. AIMS/OBJECTIVES: The primary objective of the present study was to develop and validate iPad-based software for the Japanese monosyllable speech perception test, 'iCI2004'. MATERIAL AND METHODS: Seven universities and two medical centers participated in this study. The hearing threshold and Japanese monosyllable speech perception test results of 77 people with normal hearing and 459 people with hearing loss were collected. RESULTS: All participants with normal hearing achieved almost perfect perception results both in quiet and in noise. For cochlear implant users, the average monosyllable speech perception score was 55.1 ± 19.6% in quiet and 40.3 ± 19.2% in noise (SNR + 10dB). CONCLUSIONS AND SIGNIFICANCE: We developed iPad-based Japanese monosyllable speech perception test software and validated it by testing a large number of controls and hearing loss patients with cochlear implants or hearing aids. The developed monosyllable speech perception test has a sufficiently large dynamic range for assessing improvement in speech perception in Japanese cochlear implant users.

    DOI: 10.1080/00016489.2020.1853229

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  • Association of the prognosis and severity of idiopathic sudden sensorineural hearing loss with cervical ultrasonographic findings

    Takahiro Nakata, Masahiro Okada, Takahiro Hanari, Taro Takagi, Takashi Fujiwara, Naohito Hato

    Auris Nasus Larynx   2021.3

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    DOI: 10.1016/j.anl.2021.03.004

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  • ダブルルーメンチューブによる気管内挿管後の高度声門下浮腫例

    勢井 洋史, 細川 裕貴, 岡田 昌浩, 羽藤 直人

    耳鼻咽喉科臨床   114 ( 2 )   145 - 149   2021.2

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  • The association between ear involvement and clinical features and prognosis in ANCA-associated vasculitis

    Yuki Hosokawa, Masahiro Okada, Koichiro Suemori, Naohiko Hamaguchi, Ken-ichi Miyoshi, Taro Takagi, Masato Teraokaa, Hiroyuki Yamada, Jun Ishizaki, Takuya Matsumoto, Naohito Hato

    Auris Nasus Larynx   2021.2

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    DOI: 10.1016/j.anl.2021.01.023

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  • Pathological evaluation of tumor grade for salivary adenoid cystic carcinoma: A proposal of an objective grading system. Reviewed International journal

    Naruhiko Morita, Takayuki Murase, Kaori Ueda, Toshitaka Nagao, Kimihide Kusafuka, Masato Nakaguro, Makoto Urano, Ken-Ichi Taguchi, Hidetaka Yamamoto, Satoshi Kano, Yuichiro Tada, Kiyoaki Tsukahara, Kenji Okami, Tetsuro Onitsuka, Yasushi Fujimoto, Daisuke Kawakita, Kazuo Sakurai, Toru Nagao, Nobuhiro Hanai, Ryo Kawata, Naohito Hato, Naoki Otsuki, Ken-Ichi Nibu, Hiroshi Inagaki

    Cancer science   112 ( 3 )   1184 - 1195   2021.1

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    Three pathological grading systems advocated by Perzin/Szanto, Spiro, and van Weert are currently used for adenoid cystic carcinoma (AdCC). In these systems, the amount or presence of the solid tumor component in AdCC specimens is an important index. However, the "solid tumor component" has not been well defined. Salivary AdCC cases (N = 195) were collected after a central pathology review. We introduced a novel criterion for solid tumor component, minAmax (minor axis maximum). The largest solid tumor nest in each AdCC case was histologically screened, the maximum oval fitting the solid nest was estimated, and the length of the minor axis of the oval (minAmax) was measured. The prognostic cutoff for the minAmax was determined using training and validation cohorts. All cases were evaluated for the four grading systems, and their prognostic impact and interobserver variability were examined. The cutoff value for the minAmax was set at 0.20 mm. Multivariate prognostic analyses showed the minAmax and van Weert systems to be independent prognostic tools for overall, disease-free, and distant metastasis-free survival while the Perzin/Szanto and Spiro systems were selected for overall survival but not for disease-free or distant metastasis-free survival. The highest hazard ratio for overall survival (11.9) was obtained with the minAmax system. The reproducibility of the minAmax system (kappa coefficient of 0.81) was scored as very good while those of the other three systems were scored as moderate. In conclusion, the minAmax is a simple, objective, and highly reproducible grading system useful for prognostic stratification for salivary AdCC.

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  • Hybrid cadaver training with holograms by mixed reality technique

    Kayo Sakamoto, Sohei Mitani, Eriko Sato, Takashi Kitani, Tomoyoshi Sanada, Naohito Hato

    Toukeibu Gan   47 ( 4 )   366 - 370   2021

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    DOI: 10.5981/jjhnc.47.366

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  • A case of subglottic edema developed after intubation with a double-lumen endotracheal tube

    Hirofumi Sei, Masahiro Okada, Naohito Hato, Yuki Hosokawa

    Practica Oto-Rhino-Laryngologica   114 ( 2 )   145 - 149   2021

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    Herein, we report a case of subglottic stenosis caused by intubation with a double-lumen tube (DLT). An 80-year-old woman underwent video-assisted thoracoscopic surgery (VATS) for lung cancer. The patient was intubated preoperatively with a 32 Fr DLT. However, since it was difficult to pass the tube through the subglottic space, the tube size was changed to 28 Fr. One day later, the patient complained of hoarseness. Fiberoptic laryngoscopic examination revealed subglottic stenosis caused by mucosal edema. Emergency tracheostomy was performed under local anesthesia. By 18 days after the VATS, the subglottic stenosis had completely resolved. The findings in this case suggest that the subglottic stenosis was caused by mechanical damage caused during endotracheal intubation with the DLT. Case reports of subglottic stenosis after intubation with DLT are common among women of age group. Clinicians should be aware of the possibility of subglottic stenosis after extubation, especially in elderly women.

    DOI: 10.5631/jibirin.114.145

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  • A Case of Mucocele in the Greater Wing of the Sphenoid Bone Treated with an Endoscopic Endonasal Transmaxillary Approach

    Yudai Ohara, Naoya Nishida, Taro Takagi, Naohito Hato

    Nihon Bika Gakkai Kaishi (Japanese Journal of Rhinology)   60 ( 4 )   463 - 467   2021

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    DOI: 10.7248/jjrhi.60.463

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  • 当科における自発性異常味覚5例の臨床的検討

    勢井 洋史, 羽藤 直人

    耳鼻咽喉科臨床 補冊   ( 補冊155 )   182 - 182   2020.12

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  • 当院で使用しているとろみ調整食品と液体のレオロジー解析について

    小西 泰礼, 勢井 洋史, 河内 和誉, 羽藤 直人

    耳鼻咽喉科臨床 補冊   ( 補冊155 )   195 - 195   2020.12

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  • 当院で使用しているとろみ調整食品と液体のレオロジー解析について

    小西 泰礼, 勢井 洋史, 河内 和誉, 羽藤 直人

    耳鼻咽喉科臨床 補冊   ( 補冊155 )   195 - 195   2020.12

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  • Non-recovery animal model of severe facial paralysis induced by freezing the facial canal

    Tomonori Joko, Hiroyuki Yamada, Takuya Kimura, Masato Teraoka, Naohito Hato

    Auris Nasus Larynx   47 ( 5 )   778 - 784   2020.10

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    Objective: Some cases of peripheral facial paralysis are resistant to treatment, thus, a non-recovery model of facial paralysis is needed to develop new treatment strategies for this condition. The purpose of the current study was to develop an animal model of which facial palsy was severe and prolonged. Methods: Ten 8-week-old female Hartley guinea pigs weighing between 400 and 500 g were used for the animal model. The vertical segment of the facial canal was accessed via the otic bulla, without removing the bony wall of the facial canal. The canal was then frozen for 5 s using freeze spray. Facial movements, electroneurography (ENoG), histology, and changes in temperature were evaluated. Results: All animals exhibited complete facial paralysis immediately after the procedure and recovered gradually, however, not all of them had recovered completely 15 weeks after freezing. The ENoG values one week after freezing for all animals (10/10) were 0%. Histological examination one week after freezing revealed that most of the vertically placed myelinated nerve fibers which had been frozen were remarkably affected and denatured. The number of vertically placed myelinated nerve fibers increased 15 weeks after freezing, but the nerve fibers were smaller than normal nerve fibers and were distorted in shape. Conclusion: Complete facial paralysis was induced in Hartley guinea pigs by freezing the facial canal. The behavioral, ENoG, and histopathological data suggest that the facial paralysis was severe and prolonged. This model may assist in developing novel treatment for severe facial palsy and facilitate basic research on facial nerve regeneration.

    DOI: 10.1016/j.anl.2020.03.012

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  • The impact of clinicopathological factors on clinical outcomes in patients with salivary gland adenoid cystic carcinoma: a multi-institutional analysis in Japan.

    Daisuke Kawakita, Takayuki Murase, Kaori Ueda, Satoshi Kano, Yuichiro Tada, Kiyoaki Tsukahara, Kenji Okami, Tetsuro Onitsuka, Yasushi Fujimoto, Takuma Matoba, Kazuo Sakurai, Toru Nagao, Nobuhiro Hanai, Ryo Kawata, Naohito Hato, Ken-Ichi Nibu, Makoto Urano, Ken-Ichi Taguchi, Masato Nakaguro, Kimihide Kusafuka, Hidetaka Yamamoto, Toshitaka Nagao, Hiroshi Inagaki

    International journal of clinical oncology   25 ( 10 )   1774 - 1785   2020.10

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    BACKGROUND: Owing to the low incidence of adenoid cystic carcinoma (AdCC), reliable survival estimates and prognostic factors remained unclarified. METHODS: In this multi-institutional retrospective analysis, we collected 192 AdCC cases, and investigated the impact of clinicopathological factors on clinical outcomes of the patients. All AdCC cases were of salivary gland origin and were surgically treated with curative intent. Diagnoses of AdCC were validated by a central pathology review by expert pathologists. RESULTS: The 5-year overall survival (OS) and disease-free survival (DFS) rates were 92.5 and 50.0%, respectively. Treatment failure occurred in 89 patients (46%) with the distant failures in 65 (34%). Multivariate analysis indicated that pN2 and a pathologically positive surgical margin were independent prognostic factors for both OS and DFS. Histological grade III was an independent prognostic factor for OS. A primary site in the submandibular gland, pT3/4, pN1, and histological grade II were independent prognostic factors for DFS. Postoperative radiation therapy (PORT) improved the locoregional control (LRC) rate. Prophylactic neck dissection was not associated with a better OS or better LRC among patients with cN0. Facial nerve dissection did not improve clinical outcomes in parotid AdCC cases without facial nerve palsy. CONCLUSIONS: A higher TN classification, a pathologically positive surgical margin, and a higher histological grade were associated with a lower OS. PORT improved LRC rates but neck dissection failed to improve clinical outcomes in patients with cN0. As the distant metastasis was frequent, effective systemic therapy is imperative to improve the survival of AdCC patients.

    DOI: 10.1007/s10147-020-01731-9

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  • The hearing prognosis of otitis media with ANCA-associated vasculitis

    Shinji Iwata, Masahiro Okada, Koichiro Suemori, Masato Teraoka, Hiroyuki Yamada, Jun Ishizaki, Takuya Matsumoto, Naohito Hato

    Auris Nasus Larynx   2020.9

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    DOI: 10.1016/j.anl.2020.09.004

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  • 愛媛大学医学部附属病院で使用しているとろみ調整食品と液体のレオロジー解析について

    勢井 洋史, 小西 泰礼, 河内 和誉, 岩田 真治, 大六 鉄兵, 瀬知 亜有未, 三上 美里, 保田 和則, 羽藤 直人

    愛媛医学   39 ( 3 )   123 - 126   2020.9

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    目的:嚥下障害患者が液体を摂取する際、誤嚥の危険性を少なくするため増粘剤を添加することが多い。愛媛大学医学部附属病院では2013年の日本摂食嚥下リハビリテーション学会基準を参考にとろみ早見表を作成しているが、とろみ早見表を用いたとしても適切な粘性選択に難渋することが少なくなかった。今回、院内で使用するとろみ調整食品と飲料についてレオメーターを用いた粘度測定を行い、とろみ早見表の検証を行ったので文献的考察を含めて報告する。方法:とろみ調整食品はトロミナールplus(メディファイン)、飲料はお茶・牛乳・ヤクルトを使用した。とろみ調整食品を用いた3種類の濃度(0.5%、1%、2%)を各飲料でそれぞれ作成した後、3分後と10分後にレオメーター(Anton Paar社製/Physica MCR301)を用いてとろみの粘度測定を行った。測定は20℃にて直径35mm、コーンアングル1°のプレートを用い、ずり速度O.01-100S-1で粘度を測定した。結果:とろみ調整食品を添加した後、全ての飲料は非ニュートン流体へ変化した。10分後、とろみ調整食品0.5%の飲料は薄いとろみの基準を、とろみ調整食品1%の飲料は中間のとろみの基準を満たしていたが、とろみ調整食品2%の飲料は全て濃いとろみの基準外であった。結諭:濃いとろみを作成する際、嚥下調整食分類2013の基準を満たさないことがあるため注意が必要である。(著者抄録)

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  • 放射線治療による聴神経腫瘍の造影効果の変化に関する検討

    山田 啓之, 甲斐 成彦, 阿部 康範, 三谷 壮平, 岩田 真治, 上甲 智規, 木村 拓也, 西原 江里子, 岡田 昌浩, 寺岡 正人, 羽藤 直人

    日本耳鼻咽喉科学会会報   123 ( 4 )   1062 - 1062   2020.9

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  • Low‐Normal Platelets and Decreasing Platelets Are Risk Factors for Hearing Impairment Development Reviewed

    Yasunori Abe, Kensuke Toyama, Masaya Kazurayama, Shinji Tanaka, Masamitsu Yamaizumi, Megumi Ueno, Joshua M. Spin, Naohito Hato, Masaki Mogi

    The Laryngoscope   2020.8

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    DOI: 10.1002/lary.28970

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  • 味認識装置を用いたテーストディスクの検討

    勢井 洋史, 羽藤 直人

    口腔・咽頭科   33 ( 3 )   171 - 171   2020.8

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  • 内視鏡下鼻内副鼻腔手術中の大量出血にて発覚した外傷性仮性内頸動脈瘤例

    西田 直哉, 中田 貴大, 羽藤 直人

    耳鼻咽喉科臨床   113 ( 8 )   487 - 492   2020.8

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    23歳男。両漿液性鼻漏を主訴とした。頭部外傷後、断続的に血液の混じった漿液性鼻漏がみられ、鼻腔内視鏡検査では右蝶篩陥凹から流出する血性分泌物を認めた。鼻腔単純CTでは両側篩骨洞天蓋の骨折、両側の蝶形骨洞と後部篩骨洞に充満する軟部陰影を認め、髄液漏の有無と出血源の確認を目的として内視鏡下鼻内副鼻腔手術を行ったところ、明らかな鼻性髄液漏はみられなかったが、蝶形骨洞内に強い拍動を伴う血餅様腫瘤を認め、組織の一部を採取したところ大量の動脈性出血をきたした。脳血管造影検査では右内頸動脈の海綿静脈洞部に仮性動脈瘤を認め、浅側頭動脈-中大脳動脈バイパスとhigh flowバイパスを併用した仮性動脈瘤トラッピング術を行い、術後は仮性動脈瘤の再発を認めなかった。

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  • Central pathology review of salivary gland adenoid cystic carcinoma. Reviewed International journal

    Kaori Ueda, Takayuki Murase, Toshitaka Nagao, Kimihide Kusafuka, Makoto Urano, Hidetaka Yamamoto, Masato Nakaguro, Ken-Ichi Taguchi, Ayako Masaki, Hideaki Hirai, Daisuke Kawakita, Kiyoaki Tsukahara, Naohito Hato, Toru Nagao, Yasushi Fujimoto, Kazuo Sakurai, Nobuhiro Hanai, Satoshi Kano, Tetsuro Onitsuka, Kenji Okami, Ken-Ichi Nibu, Yuichiro Tada, Ryo Kawata, Hiroshi Inagaki

    Head & neck   42 ( 8 )   1721 - 1727   2020.8

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    BACKGROUND: To assess the role of a central pathology review in the diagnosis of salivary gland adenoid cystic carcinoma (AdCC). METHODS: Surgically resected salivary gland tumors diagnosed as AdCC (n = 219) in 15 reference hospitals in Japan were subjected to a retrospective pathological re-evaluation. RESULTS: After the review, the AdCC diagnosis was revised in 21/219 cases (9.6%). The six benign tumors (2.7%) comprised five basal cell adenomas and one pleomorphic adenoma, and among these six patients, three received postoperative radiotherapy. The remaining 15 malignant tumors (6.8%) comprised nine basal cell adenocarcinomas and six other carcinomas. All revised basal cell adenoma/adenocarcinoma cases were of rare cribriform variants. CONCLUSIONS: A significant proportion of AdCC pathology reports were revised after the central pathology review. It should be emphasized that the greatest attention should be paid in differentiating AdCC from cribriform variant basal cell adenoma/adenocarcinoma, which is very rare in salivary gland tumors.

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  • 術前の動脈塞栓術を要した鼻腔化膿性肉芽腫例

    高木 康平, 西田 直哉, 本岡 太心, 羽藤 直人

    耳鼻咽喉科臨床   113 ( 6 )   365 - 370   2020.6

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    29歳男性。左鼻漏と左鼻閉を主訴とした。既往歴に知的障害があった。左前鼻孔から突出する鼻茸様腫瘍を認め、CTでは左副鼻腔が軟部陰影で充満し、総鼻道に複数の異物が存在した。左鼻腔異物と左汎副鼻腔炎と診断し、左内視鏡下鼻内副鼻腔手術を施行した。手術は鼻茸様腫瘍を切除し、ブラシの一部と思われる異物を除去した。続いて鼻腔後方の腫瘍を切離すると、多量の出血をきたし、手術を中止した。術後5ヵ月に腫瘍の栄養血管に対し動脈塞栓術を行った上で再手術を施行した。手術は選択的左外頸動脈造影を行い、下行口蓋動脈と蝶口蓋動脈を栄養とする腫瘍を認めた。続いて両動脈の径に応じて球状塞栓物質とゼラチンスポンジ、コイルを使用した。最後に腫瘍を切除し、腫瘍の基部が広基性で多発していたため、切除床を電気凝固した。病理診断は化膿性肉芽腫であった。術後6日に軽快退院し、術後1年以上の現在まで再発を認めていない。

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  • 上咽頭多形性低悪性度腺癌例

    西田 直哉, 能田 淳平, 羽藤 直人

    耳鼻咽喉科臨床   113 ( 6 )   391 - 396   2020.6

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    81歳女性。右鼻閉、鼻出血及び右耳閉感を主訴とした。上咽頭に後鼻孔を占拠する赤色調の腫瘤を認め、造影MRIで上咽頭右側に長径26mm大の腫瘤を認めた。腫瘤はT2強調像で淡い高信号を呈し、比較的均一に強く造影された。悪性を疑い、確定診断と根治治療を目的に経鼻内視鏡下手術を施行した。手術は鼻中隔後方の骨性鼻中隔を削除して術野を確保した。続いて術者の一人が右鼻腔から内視鏡を挿入して視野を確保し、もう一人が吸引嘴管や鉗子で腫瘍を牽引しながら電気メスで切離し、1cm程度の安全域を付けて腫瘍を一塊に切除した。腫瘍の基部は右耳管隆起から後壁にかけて広範囲に存在していた。右耳管隆起を一部合併切除し、耳管咽頭口は温存した。創面をサージセルで被覆して手術を終了した。病理診断は多形性低悪性度腺癌で、切除断端に腫瘍細胞はみられなかった。術後10日に軽快退院し、術後2年の現在まで再発を認めていない。

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  • Association between hypertension, dyslipidemia, and diabetes and prevalence of hearing impairment in Japan Reviewed

    Kazuya Hara, Masahiro Okada, Daiki Takagi, Keiko Tanaka, Hidenori Senba, Masato Teraoka, Hiroyuki Yamada, Bunzo Matsuura, Naohito Hato, Yoshihiro Miyake

    Hypertension Research   2020.5

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    DOI: 10.1038/s41440-020-0444-y

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  • 甲状腺形質細胞腫の2例

    續木 彩加, 眞田 朋昌, 勢井 洋史, 羽藤 直人

    日本気管食道科学会会報   71 ( 2 )   s7 - s7   2020.4

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  • 当科にて施行した喉頭全摘、咽喉頭食道摘出術例における永久気管孔狭窄の検討

    真田 朋昌, 勢井 洋史, 羽藤 直人

    日本気管食道科学会会報   71 ( 2 )   s75 - s75   2020.4

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  • 声門閉鎖術時に輪状咽頭筋起始部離断術を併施した6例の臨床的検討

    勢井 洋史, 真田 朋昌, 羽藤 直人

    日本気管食道科学会会報   71 ( 2 )   s59 - s59   2020.4

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  • Evaluation of the structure of the otoconial layer using micro-computed tomography. Reviewed International journal

    Eriko Nishihara, Masahiro Okada, Takeshi Kiyoi, Masachika Shudou, Yuuki Imai, Naohito Hato

    Auris, nasus, larynx   2020.3

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    OBJECTIVE: Estrogen deficiency caused by bilateral ovariectomy (OVX) has been reported to lead to morphological changes in otoconia. Thus, we examined the morphological changes in the otoconial layer after OVX. We also investigated whether micro-computed tomography (µCT) is useful for the detection of morphological changes in the otoconial layer. METHODS: The otic capsules of C57BL/6 J mice were removed and evaluated using histological techniques and µCT at 2, 4, and 8 weeks after OVX or sham surgery. The volume of the utricle otoconial layer was measured and compared between the OVX and sham groups. The µCT scan and histological study results were also compared. RESULTS: The volume of the utricle otoconial layer was significantly increased 4 weeks after OVX compared to the sham group in both histological and µCT studies (p < 0.05). The volume of the otoconial layer measured using µCT was significantly correlated with the histological study results (p < 0.05). CONCLUSION: The volume of the utricle otoconial layer increased after OVX. These morphological changes could be detected by µCT.

    DOI: 10.1016/j.anl.2020.02.013

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  • 嚥下障害を生じた椎骨動脈蛇行による延髄圧迫の1例 Reviewed

    飴矢 美里, 田中 加緒里, 山田 啓之, 西田 直哉, 森 敏裕, 羽藤 直人

    嚥下医学   9 ( 1 )   77 - 83   2020.3

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    今回、左椎骨動脈の延髄圧迫により嚥下障害をきたした稀な症例を経験した。発症から13年と長期間の延髄圧迫による不可逆的な神経変性から嚥下動態の変化をきたし、嚥下障害の緩徐進行にて嚥下不能となったが、定期的な嚥下評価と病態に即した適切な介入を行うことで、経口摂取の自立を再獲得できた。椎骨動脈の延髄圧迫による嚥下障害は、血管減圧術にて症状が改善することが多いが、症状が増悪する場合は、嚥下機能改善手術と代償法を用いた嚥下訓練が有効であり、副神経麻痺と胸椎側彎症による斜頸を有する本症例の代償法は、頸部回旋法と顎突出嚥下法を組み合わせた頸部回旋顎突出位が随意的な食道入口部の開大に効果的であった。(著者抄録)

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  • A Case of Traumatic Internal Carotid Artery Pseudoaneurysm Diagnosed by Massive Bleeding during Endoscopic Sinus Surgery

    Naoya Nishida, Takahiro Nakata, Naohito Hato

    Practica Oto-Rhino-Laryngologica   113 ( 8 )   487 - 492   2020

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    We report the case of a patient with traumatic pseudoaneurysm, who developed massive bleeding during endoscopic sinsu surgery. A 23-year-old drunk man sustained severe injuries when he fell from the second floor of his home and was transported to the hospital emergency department. He was diagnosed as having traumatic subarachnoid hemorrhage, brain contusion, skull base fracture, pneumoencephalopathy, maxillary fracture, right distal radius fracture, and admitted to the hospital. He was transferred to our oral surgery department for maxillary fixation to treat the maxillary fractures. Cerebrospinal fluid rhinorrhea was suspected due to a skull base fracture, and the patient was referred to the otorhinolaryngology department. Since there was no obvious cerebrospinal fluid leakage, the patient was followed up. However, as the rhinorrhea persisted, endoscopic sinus surgery was performed under general anesthesia to confirm and treat cerebrospinal fluid leakage. The sphenoid sinuses of both sides were filled with clot-like masses with strong pulsations. Hematomas were suspected, but when a piece of tissue was removed from the left sphenoid sinus mass, arterial bleeding occurred. Hemostasis was accomplished by immediate compression with gauze. Emergency cerebral angiography revealed a pseudoaneurysm in the right internal carotid artery, and pseudoaneurysm trapping (internal carotid artery blockage) with STA-MCA bypass and high flow bypass (ECA-RAG-MCA) was performed. After the operation, there was no apparent paralysis, and MRI revealed no apparent infarct. Four years after the operation, there is no evidence of aneurysm recurrence. This case suggests that in cases that develop refractory epistaxis after head injury, traumatic internal carotid artery pseudoaneurysm must be considered in the differential diagnosis, and cerebral angiography must be performed immediately.

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  • Hearing Impairment and Prevalence of Mild Cognitive Impairment in Japan Reviewed

    Yoshihiro Miyake, Keiko Tanaka, Hidenori Senba, Susumu Ogawa, Hiroyuki Suzuki, Yoshinori Fujiwara, Masahiro Okada, Daiki Takagi, Masato Teraoka, Hiroyuki Yamada, Takashi Nobuhara, Bunzo Matsuura, Naohito Hato

    Ear and Hearing   41 ( 2 )   254 - 258   2020

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    DOI: 10.1097/aud.0000000000000773

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  • Constitutive hydrogen inhalation prevents vascular remodeling via reduction of oxidative stress. Reviewed International journal

    Takeshi Kiyoi, Shuang Liu, Erika Takemasa, Hirotomo Nakaoka, Naohito Hato, Masaki Mogi

    PloS one   15 ( 4 )   e0227582   2020

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    Molecular hydrogen is thought to have an inhibitory effect on oxidative stress, thereby attenuating the onset and progression of various diseases including cardiovascular disease; however, few reports have assessed the preventive effect of constitutive inhalation of hydrogen gas on of vascular remodeling. Here, we investigated the effect of constitutive inhalation of hydrogen gas on vascular neointima formation using a cuff-induced vascular injury mouse model. After constitutive inhalation of compressed hydrogen gas (O2 21%, N2 77.7%, hydrogen 1.3%) or compressed air only (O2 21%, N2 79%) by C57BL/6 mice for 2 weeks from 8 weeks of age in a closed chamber, inflammatory cuff injury was induced by polyethylene cuff placement around the femoral artery under anesthesia, and hydrogen gas administration was continued until sampling of the femoral artery. Neointima formation, accompanied by an increase in cell proliferation, was significantly attenuated in the hydrogen group compared with the control group. NADPH oxidase NOX1 downregulation in response to cuff injury was shown in the hydrogen group, but the expression levels of NADPH oxidase subunits, p40phox and p47phox, did not differ significantly between the hydrogen and control groups. Although the increase in superoxide anion production did not significantly differ between the hydrogen and control groups, DNA damage was decreased as a result of reduction of reactive oxygen species such as hydroxyl radical (⋅OH) and peroxynitrite (ONOO-) in the hydrogen group. These results demonstrate that constitutive inhalation of hydrogen gas attenuates vascular remodeling partly via reduction of oxidative stress, suggesting that constitutive inhalation of hydrogen gas at a safe concentration in the living environment could be an effective strategy for prevention of vascular diseases such as atherosclerosis.

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  • A case of pyogenic granuloma of the nasal cavity required preoperative arterial embolization

    Kohei Takagi, Naoya Nishida, Naohito Hato, Taishin Motooka

    Practica Oto-Rhino-Laryngologica   113 ( 6 )   365 - 370   2020

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    Pyogenic granuloma is classified as a benign vascular tumor, and sex hormones, infection and trauma are known to be involved in its pathogenesis. The treatment is surgical resection, but the highly vascular nature of the tumor may cause massive bleeding at the time of resection. Therefore, preoperative evaluation of the tumor vascularity and treatment planning for bleeding are required. In this article, we report a patient with pyogenic granuloma of the nasal cavity that was thought to be caused by nasal foreign bodies who required two operations. The patient was a 29-year-old male, who presented with left rhinorrhea and nasal congestion. Examination revealed a tumor lesion with a smooth surface protruding from the left anterior nostril. CT revealed soft tissue in the left nasal cavity and multiple nodular shadows with high density areas within it, suspected as foreign bodies. At the first operation, resection of the tumor caused massive bleeding. We determined that it was difficult to continue the operation and completed it after ensuring hemostasis. Subsequently, we performed contrast-enhanced CT to evaluate the lesion vascularity. The findings revealed persistence of the foreign bodies in the left nasal cavity, and a tumor showing contrast enhancement around them. The tumor was assessed as being highly vascular. In the second operation, arterial embolization was performed, which controlled intraoperative bleeding, prior to the endoscopic sinus surgery. Pyogenic granuloma can be caused by long-term persistence of foreign bodies. Because of the high vascularity of these lesions, a contrast-enhanced CT should be performed to evaluate the lesion vascularity prior to its resection. Arterial embolization performed at the appropriate time controls the bleeding during resection.

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  • A case of polymorphous low-grade adenocarcinoma of the nasopharynx

    Naoya Nishida, Naohito Hato, Junpei Nouta

    Practica Oto-Rhino-Laryngologica   113 ( 6 )   391 - 396   2020

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    Polymorphous low-grade adenocarcinoma (PLGA) is a rare tumor that typically occurs in minor oral salivary glands. Our review of the literature found only three reported cases of PLGA of the nasopharynx. We herein report a case of PLGA of the nasopharynx. An 81-year-old woman was referred to our hospital with symptoms of right nasal obstruction, epistaxis and a feeling of fullness in the right ear for one month. A nasal endoscopy examination revealed a tumor in the right nasopharynx. A magnetic resonance imaging (MRI) examination revealed a 26-mm well-enhanced mass over the right posterior nasopharynx. Endoscopic removal of the tumor was undertaken via an endonasal approach. A histological examination of the surgical specimen showed that relatively uniform cells with round nuclei and slightly acidophilic cytoplasm had infiltrated and proliferated in a tubular, papillary, and alveolar manner. Immunohistochemically, the tumor cells were positive for S-100 protein, vimentin, and bcl-2. The final diagnosis was PLGA. We did not perform any postoperative therapy because the area containing the malignancy was far from the surgical margin. Two years after the surgery, the patient is continuing to receive follow-up care and has not shown any signs of tumor recurrence. PLGA can recur even after long periods of time, and strict follow-up care is necessary.

    DOI: 10.5631/jibirin.113.391

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  • Post-transplantation laryngeal actinomycosis Reviewed

    Hirofumi Sei, Jumpei Nouta, Shota Miyaji, Naohito Hato

    Auris Nasus Larynx   46 ( 6 )   917 - 920   2019.12

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    © 2018 Elsevier B.V. A case of laryngeal actinomycosis occurred after bone marrow transplantation was reported. The patient was a 14-year-old girl who had a history of bone marrow transplantation for the treatment of acute lymphocytic leukemia 4 month before the onset of the disease. She was referred to our hospital complaining persistent sore throat since 2 weeks ago. Fiberscopic observation proved the presence of white tumor-like mass on her right arytenoid of the larynx. As CT image demonstrated that the mass was localized at the arytenoid region with central low-density area surrounded by granulation tissue, we underwent biopsy under local anesthesia. Excision of the mass proved it to be a soft granulation including sulfur granules. Oral administration of amoxicillin 750 mg per day was initiated as a postoperative medication. On day 17, histological study confirmed that the tumor-like mass was Actinomyces granuloma, and therefore amoxicillin administration continued. The medication was effective to subside the disease and the arytenoid lesion healed on day 31. Amoxicillin was further administered until day 70 to prevent recurrence. At 6 month after the biopsy, she was free from the disease.

    DOI: 10.1016/j.anl.2018.12.006

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  • 診断、治療に難渋している気管狭窄の1例 Reviewed

    田中 加緒里, 勢井 洋史, 阿部 康範, 麻生 沙和, 能田 純平, 伏見 勝哉, 兵頭 純, 高橋 宏尚, 羽藤 直人

    耳鼻と臨床   65 ( 5 )   158 - 158   2019.9

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  • Association of household income and education with prevalence of hearing impairment in Japan. Reviewed International journal

    Junpei Fukui, Chinatsu Nobutoh, Masahiro Okada, Daiki Takagi, Keiko Tanaka, Hidenori Senba, Masato Teraoka, Hiroyuki Yamada, Bunzo Matsuura, Naohito Hato, Yoshihiro Miyake

    The Laryngoscope   129 ( 9 )   2153 - 2157   2019.9

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    OBJECTIVES/HYPOTHESIS: Epidemiological information regarding the relationship between household income and education and hearing impairment (HI) is limited. The present cross-sectional study investigated this issue in Japan. STUDY DESIGN: Cross-sectional investigation. METHODS: Study subjects were 371 men and 639 women aged 36 to 84 years. A self-administered questionnaire was used. Audiological assessment was performed by pure-tone audiometry. HI was defined as present in subjects who did not respond to a pure-tone average of >25 dB HL in the better hearing ear according to the World Health Organization standard. Adjustment was made for age, smoking status, alcohol consumption, hypertension, dyslipidemia, diabetes mellitus, and body mass index. RESULTS: The prevalence of HI was 31.5% in 371 men and 20.8% in 639 women. In men, a slight inverted J-shaped association was observed between household income and HI, compared with a household income of <3 million yen per year. A household income of 3 to 5 million yen, but not of 5 million yen or more, was independently inversely associated with the prevalence of HI; the prevalence ratio for 3 to 5million yen was 0.73 (95% confidence interval: 0.54-0.999). After adjustment for confounding factors, no relationship was found between household income and the prevalence of HI in women. There were no associations between educational level and the prevalence of HI in either men or women in the multivariate model. CONCLUSIONS: Our results suggest that medium, but not high, household income may be associated with a lower prevalence of HI only in men. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:2153-2157, 2019.

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  • 挿管性喉頭肉芽腫を契機に心因性発声障害を来した1例 Reviewed

    飴矢 美里, 田中 加緒里, 勢井 洋史, 羽藤 直人

    耳鼻と臨床   65 ( 5 )   159 - 159   2019.9

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  • Comprehensive analysis of syndromic hearing loss patients in Japan. Reviewed International journal

    Michie Ideura, Shin-Ya Nishio, Hideaki Moteki, Yutaka Takumi, Maiko Miyagawa, Teruyuki Sato, Yumiko Kobayashi, Kenji Ohyama, Kiyoshi Oda, Takamichi Matsui, Tsukasa Ito, Hiroshi Suzumura, Kyoko Nagai, Shuji Izumi, Nobuhiro Nishiyama, Manabu Komori, Kozo Kumakawa, Hidehiko Takeda, Yoko Kishimoto, Satoshi Iwasaki, Sakiko Furutate, Kotaro Ishikawa, Masato Fujioka, Hiroshi Nakanishi, Jun Nakayama, Rie Horie, Yumi Ohta, Yasushi Naito, Mariko Kakudo, Hirofumi Sakaguchi, Yuko Kataoka, Kazuma Sugahara, Naohito Hato, Takashi Nakagawa, Nana Tsuchihashi, Yukihiko Kanda, Chiharu Kihara, Tetsuya Tono, Ikuyo Miyanohara, Akira Ganaha, Shin-Ichi Usami

    Scientific reports   9 ( 1 )   11976 - 11976   2019.8

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    More than 400 syndromes associated with hearing loss and other symptoms have been described, corresponding to 30% of cases of hereditary hearing loss. In this study we aimed to clarify the mutation spectrum of syndromic hearing loss patients in Japan by using next-generation sequencing analysis with a multiple syndromic targeted resequencing panel (36 target genes). We analyzed single nucleotide variants, small insertions, deletions and copy number variations in the target genes. We enrolled 140 patients with any of 14 syndromes (BOR syndrome, Waardenburg syndrome, osteogenesis imperfecta, spondyloepiphyseal dysplasia congenita, Stickler syndrome, CHARGE syndrome, Jervell and Lange-Nielsen syndrome, Pendred syndrome, Klippel-Feil syndrome, Alport syndrome, Norrie disease, Treacher-Collins syndrome, Perrault syndrome and auditory neuropathy with optic atrophy) and identified the causative variants in 56% of the patients. This analysis could identify the causative variants in syndromic hearing loss patients in a short time with a high diagnostic rate. In addition, it was useful for the analysis of the cases who only partially fulfilled the diagnostic criteria.

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  • 涙嚢鼻腔吻合術鼻内法(E-DCR)を施行した涙嚢結石の1例 Reviewed

    羽成 敬広, 西田 直哉, 羽藤 直人

    耳鼻咽喉科・頭頸部外科   91 ( 9 )   791 - 794   2019.8

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    46歳女性。左眼脂と左流涙を主訴とした。眼科で涙嚢結石を伴う涙嚢炎と診断され、シース誘導内視鏡下穿破法、涙道内視鏡下シース誘導シリコンチューブ挿入術が施行された。術後8ヵ月に左流涙と左眼脂が再燃し、CTで涙嚢内の結石再発と鼻涙管の狭窄が認められた。結石が大きく、涙道内視鏡下での排石が困難であったため、当科紹介受診となった。精査の結果、涙嚢結石に対し涙嚢鼻腔吻合術鼻内法(E-DCR)を施行した。涙嚢壁を観音開きになる様に切開すると、涙嚢内に黄白色の結石を認めた。結石はもろく、分割して全摘出した。開窓した涙嚢壁を、露出した骨面を被覆する様に翻転し、鼻粘膜と縫合した。病理診断はアスペルギルスの菌糸を核とする結石であった。術後1年以上経過しているが、涙嚢は大きく開放され、結石の再発を認めていない。

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  • 解離性味覚障害の2例 Reviewed

    勢井 洋史, 羽藤 直人

    口腔・咽頭科   32 ( 3 )   213 - 213   2019.8

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  • 鼻涙管の開窓を併用した術後性上顎嚢胞の手術経験 Reviewed

    西田 直哉, 阿部 康範, 能田 淳平, 木谷 卓史, 羽藤 直人

    耳鼻咽喉科臨床   112 ( 6 )   371 - 375   2019.6

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    症例1(73歳女)は左術後性上顎嚢胞の再発、症例2(57歳男)は左術後性上顎嚢胞と診断され、手術目的で入院した。副鼻腔CT所見ではいずれも左上顎部前内方に位置し、内側に鼻涙管が広く接する嚢胞性病変を認め、通常の内視鏡下鼻内副鼻腔手術では治療困難と考え、全身麻酔下にEndoscopic Modified Medial Maxillectomy(EMMM)でのアプローチを行った。2例とも鼻涙管と嚢胞開窓部が重なり、術後の開窓部の狭窄が危惧されたため、鼻涙管を縦に切開し、鼻涙管内腔と嚢胞内の上皮がつながるように広げた結果、術後1年以上経過後も嚢胞開窓部は大きく開存しており、症状の再燃や鼻涙管閉塞の合併症は認めていない。上顎部前内方に位置し、骨性鼻涙管に広く接する術後性上顎嚢胞症例に対して、EMMMでのアプローチと鼻涙管開窓の併用は有用な手技と考えられた。

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  • Elevated exosomal lysyl oxidase like 2 is a potential biomarker for head and neck squamous cell carcinoma. Reviewed International journal

    Sanada T, Islam A, Kaminota T, Kirino Y, Tanimoto R, Yoshimitsu H, Yano H, Mizuno Y, Okada M, Mitani S, Ugumori T, Tanaka J, Hato N

    The Laryngoscope   130 ( 5 )   E327-E334   2019.6

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    OBJECTIVES: The secretory enzyme lysyl oxidase like 2 (LOXL2) is speculated to contribute to tumor progression through its functions in the remodeling of extracellular matrix and epithelial-mesenchymal transition. We previously identified elevated expression of LOXL2 in metastatic human head and neck squamous cell carcinoma (HNSCC) cells in a mouse lymph node metastases model. Here we performed a case series study examining LOXL2 expression levels in human serum from HNSCC patients to evaluate whether LOXL2 is worth evaluation in a large cohort study. METHODS: LOXL2 protein levels in three serum samples from HNSCC patients were assessed by immunoblotting and LOXL2 tissue expression was examined in one human tongue squamous cell carcinoma (SCC) tissue by immunohistochemistry as a representative of HNSCC tissue. Serum samples were further fractionated in exosomes and supernatants by ultracentrifugation, which were then subjected to immunoblot and in vitro LOX activity analyses. Exosomal LOXL2 levels of 36 serum samples from HNSCC patients and seven healthy volunteers were measured using polymer sedimentation exosome preparation followed by ELISA measurement and subjected to statistical analyses. RESULTS: Immunoblot analyses revealed that LOXL2 was present in serum exosomal fractions from three HNSCC patients, and we observed approximately threefold higher levels of LOXL2 in HNSCC patients compared with three healthy volunteers. Immunohistochemical LOXL2 staining was detected in HNSCC cells in addition to non-cancerous lipid tissues and some muscles in human tongue HNSCC tissue. Further measurements of exosomal LOXL2 by ELISA showed over ninefold higher mean LOXL2 levels in patients compared with controls. Statistical analysis revealed a correlation between elevated serum exosomal LOXL2 levels and low-grade, but not high-grade, HNSCC. CONCLUSIONS: Our case series study that elevated serum exosomal LOXL2 levels exhibited a correlation with low-grade HNSCCs. A follow-up large cohort clinical study will be required to determine the potential clinical utility of LOXL2 as a new biomarker and/or therapy target for HNSCCs. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:E327-E334, 2020.

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  • Nationwide survey of congenital cholesteatoma using staging and classification criteria for middle ear cholesteatoma proposed by the Japan Otological Society. Reviewed International journal

    Morita Y, Tono T, Sakagami M, Yamamoto Y, Matsuda K, Komori M, Hato N, Hashimoto S, Takahashi H, Kojima H

    Auris, nasus, larynx   46 ( 3 )   346 - 352   2019.6

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    OBJECTIVE: This study was undertaken to determine the characteristics of congenital cholesteatoma (CC) in Japan, via a nationwide survey using staging and classification criteria for middle ear cholesteatoma, as proposed by the Japan Otological Society (JOS). METHODS: A nationwide survey regarding middle ear cholesteatoma treated in 2015 was performed. There were 1787 registrations from 74 facilities, among which, CC accounted for 12.9% (231 cases) of all middle ear cholesteatoma cases. The extent of the disease was classified according to the classification and staging of cholesteatoma proposed by JOS in 2015. RESULTS: The age of the patients ranged from 1 to 55 years (mean, 8.2 years; median, 6 years; 149 ears of males; 82 ears of females). Among these cases, 105 (45.5%) were classified as stage I, 121 (52.4%) as stage II, and 5 (2.1%) as stage III, with no cases in stage IV. In the sub classification of stage I, 35 (33%), 43 (41%) and 27 (26%) ears were classified as stages I-a, I-b and I-c, respectively. Stage I-b (cholesteatoma confined to the posterior half of the tympanic cavity) was more frequent than stage I-a (the anterior half of tympanic cavity). Pre-operative hearing level of air-conduction was 20.5dB for stage I-a, 34.5dB for stage I-b, 30.5dB for stage I-c, 38.6dB for stage II, and 59.0dB for stage III. The rate of missing stapes superstructure increased as the disease progressed. In the same way, the mastoid development lowered as the stage of the disease progressed. There were significant differences in the age at operation, pre-operative hearing level, status of stapes, and major ossiculoplasty, between stage l-a and l-b. CONCLUSIONS: The current condition of CC in Japan was been evaluated; in particular, it was observed that the cases limited to the posterior part of tympanic cavity were not rare. The JOS stage classification based on the progression of the disease seemed simple and efficient.

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  • 手術加療を行った副鼻腔真菌症症例の検討 Reviewed

    麻生 沙和, 西田 直哉, 勢井 洋史, 山田 啓之, 羽藤 直人

    日本耳鼻咽喉科感染症・エアロゾル学会会誌   7 ( 2 )   75 - 78   2019.5

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    内視鏡下鼻副鼻腔手術(ESS)加療を行った慢性非浸潤性副鼻腔真菌症症例について検討を行った。ESSを施行し、慢性非浸潤性副鼻腔真菌症と診断した38症例を対象とした。年齢については50歳以上がほとんどを占め、また男女比は13:25と女性が男性の2倍近くに上っていたことから、高齢と女性は副鼻腔真菌症のリスク因子と考えられた。42.1%が自覚症状を有さず、悪性腫瘍の経過観察やめまいの精査等を目的とした画像検査で偶然発見された症例であった。罹患副鼻腔は過去の報告と同様、上顎洞が過半数を占めていた。鼻中隔彎曲は9例(23.7%)で認め、罹患側は凸側が3例、凹側が4例、両側が2例であり、罹患側と鼻中隔彎曲の関連はみられなかった。治療はESSにて罹患副鼻腔の開放・真菌塊の除去を行った。上顎洞病変に対しては全例、自然口経由で洞内の真菌塊の除去・洗浄を行い、対孔を作成した症例はなかった。蝶形骨洞病変に対しては嗅裂側から自然口を開放した症例(経自然口法)が3例、篩骨洞側から蝶形骨洞前壁篩骨部を開放した症例(経篩骨洞法)が3例、鼻中隔経由で開放した症例(経鼻中隔法)が5例であった。compromised hostの1例と90歳の超高齢者の1例で再発を認めたが、再発までの期間はそれぞれ6ヵ月と13ヵ月と、手術から時間を経て再発しており、compromised hostや超高齢者では比較的長期の経過観察が望ましいと考えられた。

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  • 顔面神経麻痺:非治癒例を減らすために(サルベージ治療) 麻痺発症2週以降に行う徐放化栄養因子を用いた顔面神経減荷術

    山田 啓之, 羽藤 直人, 藤原 崇志, 飴矢 美里, 上甲 智則, 阿部 康範, 木村 拓也

    Facial Nerve Research   38   25 - 27   2019.3

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    顔面神経減荷術の至適時期は発症後2週間以内とされているが、実際には発症2週間を超えて手術となる症例が多く、今後の課題とされてきた。当科ではこの問題を克服するために2006年から徐放化栄養因子(basic fibroblast growth factor添加ゼラチンハイドロゲル)を用いた顔面神経減荷術を行ってきた。今回その効果を検証するため、麻痺発症2週以降の患者に対して本法を行った群(40例)と、従来の顔面神経減荷術を行った群(45例)、保存的治療を行った群(80例)の成績を比較検討した。成績の評価方法は、柳原スコアが38点以上に改善したものを「著明改善」、32点以上に改善したものを「改善」とし、各々の割合を調べた。結果、本法施行群は他の2群に比べて著明改善率・改善率とも明らかに高かった。

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  • 本邦におけるcadaver surgical trainingの現況 Reviewed

    西田 直哉, 羽藤 直人

    耳鼻咽喉科臨床   112 ( 2 )   134 - 135   2019.2

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  • The treatment outcomes of rituximab for intractable otitis media with ANCA-associated vasculitis. Reviewed International journal

    Masahiro Okada, Koichiro Suemori, Daiki Takagi, Masato Teraoka, Hiroyuki Yamada, Jun Ishizaki, Takuya Matsumoto, Hitoshi Hasegawa, Naohito Hato

    Auris, nasus, larynx   46 ( 1 )   38 - 42   2019.2

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    OBJECTIVE: To investigate treatment outcomes, hearing outcomes, and adverse effects of rituximab (RTX) for intractable otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV). METHODS: Twenty-three patients who met the criteria proposed by the OMAAV study group were included. RTX was used for patients who had difficulty achieving induction of remission using glucocorticoids (GC) and intravenous cyclophosphamide (IVCY). RESULTS: Six patients were treated with RTX (RTX group), while 17 patients did not require RTX for induction of remission (non-RTX group). All six patients in the RTX group achieved remission. Age, sex, and months from onset to diagnosis did not differ significantly between the groups. The air-conduction hearing thresholds at diagnosis and remission were 71.7±6.3dB and 50.1±5.1dB in the RTX group, and 56.8±4.8dB and 35.8±4.8dB in the non-RTX group, respectively. Hearing level at remission was significantly better in the non-RTX group (p<0.05), while hearing gain did not differ significantly between the groups. Infectious complications were similar between the groups. CONCLUSIONS: Our findings suggest that RTX is effective and safe for intractable OMAAV patients who have a poor response to GC and IVCY.

    DOI: 10.1016/j.anl.2018.05.011

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  • Surgery of Postoperative Maxillary Cyst Combined with Fenestration of the Nasolacrimal Duct

    Naoya Nishida, Yasunori Abe, Junpei Nouta, Takashi Kitani, Naohito Hato

    Practica Oto-Rhino-Laryngologica   112 ( 6 )   371 - 375   2019

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    DOI: 10.5631/jibirin.112.371

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  • 「中耳真珠腫全国調査結果と中耳手術術式国際分類案」 用語委員会報告 中耳手術術式の国際分類(IOOG Categorization of Tympanomastoid Surgery)について

    東野 哲也, 山本 裕, 阪上 雅史, 羽藤 直人, 小森 学, 森田 由香, 松田 圭二, 高橋 晴雄, 小島 博己, 日本耳科学会用語委員会

    Otology Japan   28 ( 5 )   653 - 658   2018.12

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  • 造影MRI検査を用いた聴神経腫瘍の増大予測に関する検討

    山田 啓之, 阿部 康範, 上甲 智規, 岡田 昌浩, 寺岡 正人, 羽藤 直人

    Otology Japan   28 ( 4 )   383 - 383   2018.9

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  • 当科における補聴器外来5年間の老人性難聴患者の検討

    Audiology Japan   61 ( 5 )   423 - 423   2018.9

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    DOI: 10.4295/audiology.61.423

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  • Intractable Otitis Media Presenting as Falsely Positive for Proteinase 3-ANCA: A Case Report. Reviewed

    Okada M, Ogawa H, Suemori K, Takagi D, Teraoka M, Yamada H, Hato N

    The journal of international advanced otology   14 ( 2 )   337 - 340   2018.8

  • 鼻涙管の開窓を行った術後性上顎嚢胞の2例

    西田 直哉, 阿部 康範, 能田 淳平, 羽藤 直人

    耳鼻咽喉科臨床 補冊   ( 補冊153 )   68 - 68   2018.6

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  • 特発性舌下間隙血腫の一例

    阿部 康範, 三谷 壮平, 眞田 朋昌, 鵜久森 徹, 羽藤 直人

    日本気管食道科学会会報   69 ( 2 )   s25 - s25   2018.4

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  • アレルギー性鼻炎モデルマウスに対する新規低分子化合物SH-2251の治療効果

    木谷 卓史, 西田 直哉, 阿部 康範, 林 祐志, 羽藤 直人

    日本耳鼻咽喉科学会会報   121 ( 4 )   535 - 535   2018.4

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  • Prevention of ischemia-induced hearing loss by intravenous administration of hydrogen-rich saline in gerbil Reviewed

    Hideo Ogawa, Masahiro Okada, Masachika Shudou, Kiyofumi Gyo, Naohito Hato

    Neuroscience Letters   665   195 - 199   2018.2

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    Objective Hydrogen-rich water, which is a potent antioxidant agent, was investigated for its protective effects against ischemic damage of the cochlea in gerbils. Methods The animals were subjected to transient cochlear ischemia by occluding the bilateral vertebral arteries for l5 min. Five milliliters of hydrogen-rich saline was then intravenously administered immediately after the insult. Saline without hydrogen was used as a control. Effects of hydrogen were evaluated using the auditory brainstem response (ABR) and histological studies of the inner ear. Results In non-ischemia animals, ABR thresholds and histological findings of the cochlea did not change by administration of saline or hydrogen-rich saline. In contrast, transient cochlear ischemia caused a 24.2 ± 3.8 dB increase in the ABR threshold at 8 kHz, and a decrease of 14.1% ± 1.8% in the number of inner hair cells (IHCs) at the basal turn on day 7. Ischemic damage was more severe at 16 and 32 kHz. When the animals were treated with hydrogen-rich saline, cochlear damage was significantly reduced: the increase in ABR threshold was 11.7 ± 2.6 dB at 8 kHz and the IHC loss was 7.5% ± 2.1% at the basal turn on day 7. The effects of hydrogen-rich saline were more prominent at higher frequencies. Conclusions Intravenous administration of hydrogen-rich saline was effective in preventing acute hearing loss due to transient cochlear ischemia.

    DOI: 10.1016/j.neulet.2017.12.013

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  • A case of sudden sensorineural hearing loss associated with phosphodiesterase type 5 inhibitors

    Yuji Hayashi, Masahiro Okada, Hiroyuki Yamada, Naohito Hato

    Practica Otologica, Supplement   152   6 - 7   2018.1

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    © 2018 Society of Practical Otolaryngology.All Rights Reserved. The phosphodiesterase type 5 (PDE5) inhibitors -sildenafil, vardenafil and tadalafil- are used in the treatment of erectile dysfunction, pulmonary hypertension and benign prostatic hyperplasia (BPH). Recently, hearing loss associated with PDE5 inhibitor use has been reported. We report a patient who developed unilateral sudden hearing loss possibly related to the use of tadalafil. This is the first case report of sudden sensorineural hearing loss related to the use of a PDE5 inhibitor drug in Japan. A 64-year-old male was started on treatment with tadalafil for BPH. Eight days after the start of treatment, the patient developed sudden right-sided hearing loss. He was referred our hospital, as his hearing did not recover despite oral prednisolone treatment (PSL 40 mg/day for 5 days) prescribed by an ENT specialist. An audiogram revealed sensorineural hearing loss in the right ear, with normal hearing in the other ear. DP-OAE elicited no responses in the right ear. The patient had no tinnitus or disequilibrium, and no nystagmus was observed. The patient was restarted on prednisolone (60 mg/day), which was administered for three days, with the dose tapered over 9 days and discontinuation of tadalafil. An audiogram after the corticosteroid therapy showed complete recovery of the hearing on the right side. The acute sensorineural hearing loss in this patient was probably caused by the ototoxic effects of the PDE5 inhibitor drug.

    DOI: 10.5631/jibirinsuppl.152.6

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  • WITHDRAWN: Serum uric acid and prevalence of age-related hearing loss in the Japanese population: Baseline data from the Aidai Cohort Study in Yawatahama. Reviewed

    Takagi D, Furukawa S, Okada M, Tanaka K, Senba H, Teraoka M, Yamada H, Hato N, Miyake Y

    Experimental gerontology   2018.1

  • A study of cases of cervical neurinoma surgery Reviewed

    Sohei Mitani, Toru Ugumori, Hinako Kawamoto, Tomoyoshi Sanada, Junpei Nota, Hiroyuki Wakisaka, Naohito Hato

    Journal of Otolaryngology of Japan   121 ( 5 )   673 - 678   2018

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    Surgery for cervical neurinoma requires a different procedure from that for other common cervical tumors, for nerve preservation. We analyzed the data of 12 cases of cervical neurinoma who underwent surgery at our department between 2000 and 2016. There were 6 males and 6 females, and the average age was 46 years (range, 14-81 years). In regard to the nerve of origin, the vagus nerve was the most common nerve of origin of the tumor (4 cases), followed by the sympathetic nerve and brachial plexus (2 cases each), and sublingual nerve/supraclavicular nerve (1 case each)
    the nerve of origin remained unknown in 2 cases. At our department, we attempt to perform intercapsular resection to preserve the nerve that is important for maintenance of the postoperative quality of life. Cervical neurinoma is a relatively rare tumor, and it is often not possible to make a definitive diagnosis before surgery. It has been suggested that the shape and the site of the tumor in preoperatively obtained images are important findings in cases of neurinoma. Five of 9 cases (56%) in which we performed intercapsular resection developed postoperative neurological deficits (permanent paralysis in 4 cases, and temporary paralysis in 1 case). Especially, postoperative neurological deficits occurred at a high rate (80%
    4/5 cases) in cases where the tumor was located in the parapharyngeal spaces, at a level higher than the hyoid bone. It is necessary to carefully make surgical decisions taking into consideration the fact that postoperative neurological deficits are highly likely to develop in cases where the neurinoma exists at a level higher than the hyoid bone. When performing intercapsular resection aimed at nerve preservation, it is necessary to pay attention to the incision site on the epineurium.

    DOI: 10.3950/jibiinkoka.121.673

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  • Japanese translation, cross-cultural adaption and multicentre validation of the Zurich chronic middle ear inventory (ZCMEI-21-Jap) Reviewed

    David Bächinger, Daiki Takagi, Hiroyuki Yamada, Masato Teraoka, Masahiro Okada, Jun Hyodo, Christof Röösli, Alexander M. Huber, Naohito Hato

    Auris Nasus Larynx   46 ( 1 )   18 - 23   2018

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    Objective: In the assessment of chronic otitis media (COM) and its treatment, patient-reported outcomes are becoming increasingly important. The aim of the present study was to translate and validate the Zurich chronic middle ear inventory (ZCMEI-21) in Japanese in order to provide the first Japanese-language instrument for measuring health-related quality of life (HRQoL) in COM. Methods: The ZCMEI-21 was translated into Japanese according to published guidelines. In order to assess validity, the ZCMEI-21-Jap total score was compared to a question directly addressing HRQoL as well as the five-level version of the EQ-5D questionnaire, a generic measure of HRQoL. Results: Demographic data and validity were assessed in a total of 91 COM patients. The ZCMEI-21-Jap total and subscale scores were well comparable to those of the original validation study. Cronbach's α of the ZCMEI-21-Jap was 0.85, indicating an excellent internal consistency. The ZCMEI-21-Jap total score showed a strong correlation (r = 0.68, p &lt
    0.0001) to the question directly addressing HRQoL and, as expected, only a moderate correlation to the EQ-5D scores (r = 0.49, p &lt
    0.0001 for descriptive system score and r = 0.44, p &lt
    0.0001 for VAS score). Conclusion: We successfully translated the ZCMEI-21 into Japanese and were able to obtain sufficient information during the validation process for the use of the ZCMEI-21-Jap to quantify HRQoL in patients with COM. With the current study, we aim to take a step forward towards an international standardization of reporting HRQoL in COM.

    DOI: 10.1016/j.anl.2018.05.008

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  • Comparison of localized and systemic otitis media with ANCA-associated vasculitis Reviewed

    Masahiro Okada, Koichiro Suemori, Daiki Takagi, Masato Teraoka, Hiroyuki Yamada, Naohito Hato

    Otology and Neurotology   38 ( 10 )   e506 - e510   2017.12

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    Objective: To investigate differences in immune activity based on the presence of multiple organ involvement in patients with antineutrophil cytoplasmic antibody (ANCA)- associated vasculitis (AAV) and whether hearing outcomes are different between patients with AAV localized to the ear and patients with systemic AAV. Study Design: Retrospective case review. Setting: University hospital. Patients: Twenty patients with otitis media with AAV (OMAAV) who met the criteria proposed by the OMAAV study group in Japan. Main Outcome Measure(s): Serum levels of C-reactive protein, ANCA titer, soluble interleukin-2 receptor levels, and hearing outcome. Results: Thirteen patients had disease involvement of organs other than the ear (systemic OMAAV group)
    involvement was localized to the ear in seven patients (localized OMAAV group). Serum levels of C-reactive protein, ANCA titer, and soluble interleukin-2 receptor were not significantly different between the groups. Hearing levels at diagnosis and in remission were significantly worse in the localized OMAAV group compared with the systemic OMAAV group. Hearing gain was not significantly different between groups. Conclusion: It is suggested that immune activity in patients with AAV localized to the ear is equivalent to activity in patients with systemic AAV. Therefore, we may need treatment for OMAAV equal in intensity to that for systemic AAV. As the hearing level at diagnosis was worse in patients with AAV localized to the ear than in patients with systemic AAV, earlier diagnosis may be needed to improve hearing outcome.

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  • 中耳真珠腫進展度分類2015、英語版JOS staging system、EAONO/JOS合意案の整合性について

    東野 哲也, 山本 裕, 阪上 雅史, 羽藤 直人, 小森 学, 松田 圭二, 森田 由香, 高橋 晴雄, 小島 博己

    Otology Japan   27 ( 4 )   262 - 262   2017.10

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  • PDE5阻害薬による急性感音難聴例

    林 祐志, 岡田 昌浩, 山田 啓之, 羽藤 直人

    耳鼻咽喉科臨床   110 ( 8 )   505 - 509   2017.8

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    症例は64歳男性で、前立腺肥大症に対してタダラフィルを処方された。内服8日目に左難聴が出現し改善しないため、難聴発症から3日目に近医耳鼻咽喉科を受診した。左感音難聴を認めたため、タダラフィルの内服を中止し、プレドニゾロンで治療を開始されたが、聴力が改善しなかった。聴力検査で左低音域を中心とした感音難聴を認めた。歪成分耳音響放射では右耳は年齢相応に反応が誘発されたが、左耳では誘発される反応が低下していた。タダラフィルの内服は中止したまま、プレドニゾロン60mgより9日間かけて漸減投与を行った。聴力は難聴発症から17日目に改善した。泌尿器科へ依頼し、前立腺肥大症に対する治療は他剤へ変更した。患者の希望がなく頭部MRI検査は施行していないが、以後、聴力の悪化はみられていない。

    DOI: 10.5631/jibirin.110.505

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  • 涙嚢周囲に眼窩骨膜下膿瘍を認めた一例

    阿部 康範, 寺岡 正人, 羽藤 直人

    小児耳鼻咽喉科   38 ( 2 )   169 - 169   2017.5

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  • 頭頸癌診療への挑戦 唾液腺癌におけるPD-L1発現は予後不良因子である

    向川 卓志, 林 隆一, 橋本 和樹, 鵜久森 徹, 羽藤 直人, 藤井 誠志

    頭頸部癌   43 ( 2 )   140 - 140   2017.5

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  • 中耳真珠腫進展度分類2015を用いた全国真珠腫手術症例登録結果報告

    小森 学, 東野 哲也, 阪上 雅史, 小島 博己, 松田 圭二, 山本 裕, 羽藤 直人, 森田 由香, 橋本 省, 日本耳科学会用語委員会

    Otology Japan   27 ( 2 )   83 - 89   2017.5

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    日本耳科学会用語委員会では弛緩部型真珠腫、緊張部型真珠腫に新たに二次性真珠腫、先天性真珠腫を追加し、中耳真珠腫進展度分類案2015を作成した。今回、中耳真珠腫の病態・進展度の疫学調査ならびに術式選択の実態調査として大規模な全国登録調査を行った。対象は中耳真珠腫初回手術例とし、2015年1月1日から1年間を症例集積期間とした。結果、全国74施設より計1,787例が登録された。弛緩部型が1,133例(63.4%)、緊張部型が233例(13.0%)、二次性が100例(5.6%)、先天性が231例(12.9%)、分類不能が90例(5.0%)であった。術式選択では乳突非削開鼓室形成術が452例(25.3%)、外耳道後壁保存型鼓室形成術が496例(27.8%)、外耳道後壁削除・乳突非開放型鼓室形成術が656例(36.7%)、外耳道後壁削除・乳突開放型鼓室形成術が183例(10.2%)であった。(著者抄録)

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    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J02471&link_issn=&doc_id=20170616170001&doc_link_id=%2Fed7otolj%2F2017%2F002702%2F002%2F0083-0089%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fed7otolj%2F2017%2F002702%2F002%2F0083-0089%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 【臨床力UP! 耳鼻咽喉科検査マニュアル】顔面神経検査 筋電図検査(electroneurography:ENoG)

    藤原 崇志, 羽藤 直人

    耳鼻咽喉科・頭頸部外科   89 ( 5 )   186 - 190   2017.4

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  • Staging and classification criteria for middle ear cholesteatoma proposed by the Japan Otological Society Reviewed

    Tetsuya Tono, Masafumi Sakagami, Hiromi Kojima, Yutaka Yamamoto, Keiji Matsuda, Manabu Komori, Naohito Hato, Yuka Morita, Sho Hashimoto

    AURIS NASUS LARYNX   44 ( 2 )   135 - 140   2017.4

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    In order to provide a basis for meaningful exchange of information among those treating cholesteatoma, the Committee on Nomenclature of the Japan Otological Society (JOS) was appointed in 2004 to create a cholesteatoma staging system as simple as possible to use in clinical practice in Japan. Following the announcement of preliminary criteria for the staging of pars fiaccida (attic) cholesteatoma in 2008, we proposed the 2010 JOS staging system for two major types of retraction pocket cholesteatoma, pars fiaccida and pars tensa cholesteatoma. Since then, the JOS staging system has been widely used in clinical studies of cholesteatoma in Japan, allowing standardization in reporting of surgical outcomes based on the respective stages of cholesteatoma. We have recently expanded the range of cholesteatoma by adding cholesteatoma secondary to a tensa perforation and congenital cholesteatoma as the 2015 JOS staging system for middle ear cholesteatoma. Although further revisions may be required for universal acceptance of these criteria, we hope our staging system will open the way for international consensus on staging and classification of middle ear cholesteatoma in the near future. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.an1.2016.06.012

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  • 日本耳科学会中耳真珠腫進展度分類を用いた全国症例登録の結果と今後の展望

    東野 哲也, 小森 学, 山本 裕, 松田 圭二, 森田 由香, 阪上 雅史, 小島 博己, 羽藤 直人, 橋本 省, 高橋 晴雄

    日本耳鼻咽喉科学会会報   120 ( 4 )   530 - 530   2017.4

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  • 【臨床力UP! 耳鼻咽喉科検査マニュアル】顔面神経検査 Q&A (Q14)6日前に発症し,柳原法で8/40点,ENoGは10%の症例です。今後の検査の留意点と顔面神経減荷術の適応は?

    藤原 崇志, 羽藤 直人

    耳鼻咽喉科・頭頸部外科   89 ( 5 )   199 - 199   2017.4

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  • Elevated Na+/H+ exchanger-1 expression enhances the metastatic collective migration of head and neck squamous cell carcinoma cells Reviewed

    Teppei Kaminota, Hajime Yamo, Kohei Shiota, Noriko Nomura, Haruna Yaguchi, Yui Kirino, Kentaro Ohara, Issei Tetsumura, Tomoyoshi Sanada, Toru Ugumori, Junya Tanaka, Naohito Hato

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   486 ( 1 )   101 - 107   2017.4

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    Cancer cells can migrate as collectives during invasion and/or metastasis; however, the precise molecular mechanisms of this form of migration are less clear compared with single cell migration following epithelial-mesenchymal transition. Elevated Na+/H+ exchanger) (NHE1) expression has been suggested to have malignant roles in a number of cancer cell lines and in vivo tumor models. Furthermore, a metastatic human head and neck squamous cell carcinoma (HNSCC) cell line (SASL1m) that was isolated based on its increased metastatic potential also exhibited higher NHE1 expression than its parental line SAS. Time-lapse video recordings indicated that both cell lines migrate as collectives, although with different features, e.g., SASL1m was much more active and changed the direction of migration more frequently than SAS cells, whereas locomotive activities were comparable. SASL1m cells also exhibited higher invasive activity than SAS in Matrigel invasion assays. shRNA-mediated NHE1 knockdown in SASL1m led to reduced locomotive and invasive activities, suggesting a critical role for NHE1 in the collective migration of SASL1m cells. SASL1m cells also exhibited a higher metastatic rate than SAS cells in a mouse lymph node metastasis model, while NHE1 knockdown suppressed in vivo SASL1m metastasis. Finally, elevated NHE1 expression was observed in human HNSCC tissue, and Cariporide, a specific NHE1 inhibitor, reduced the invasive activity of SASL1m cells, implying NHE1 could be a target for antiinvasion/metastasis therapy. (C) 2017 Elsevier Inc. All rights reserved.

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  • Facial paralysis induced by ear inoculation of herpes simplex virus in rat Reviewed

    Takashi Fujiwara, Seiji Matsuda, Junya Tanaka, Naohito Hato

    AURIS NASUS LARYNX   44 ( 1 )   58 - 64   2017.2

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    Objective: Bell's palsy is caused by the reactivation of herpes simplex virus type 1 (HSV-1). Using Balb/c mice inoculated with the KOS strain of HSV-1, we previously developed an animal disease model that simulated mild Bell's palsy. The current study developed an animal disease model of more severe facial palsy than that seen in the mouse model.
    Methods: Three-week-old female Wister rats weighing 60-80 g were inoculated on the auricle with HSV-1 and acyclovir was administered intraperitoneally to deactivate the infected HSV-1. Instead of HSV-1, phosphate-buffered saline was used for inoculation as a negative control. Quantitative polymerase chain reaction (PCR), behavior testing (blink reflex), electroneuronography, histopathology of the peripheral nerve, and immunohistochemistry of the facial nerve nucleus were evaluated.
    Results: Facial palsy occurred 3-5 days after virus inoculation, and the severity of the facial palsy progressed for up to 7 days. Quantitative PCR showed an increase in HSV-1 DNA copies in the facial nerve from 24 to 72 h, suggesting that HSV-1 infection occurred in the nerve. Electroneuronography values were 33.0 +/- 15.3% and 110.0 +/- 18.0% in HSV-1-inoculated and control rats, respectively. The histopathology of the peripheral nerve showed demyelination and loss of the facial nerve, and the facial nerve nucleus showed degeneration.
    Conclusion: Facial palsy developed in Wister rats following inoculation of the KOS strain of HSV-1 onto the auricles. The behavioral, histopathological, and electroneuronography data suggested that the severity of facial palsy was greater in our rats than in animals in the previous mouse disease model. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

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  • 当科音声外来を受診した反回神経麻痺症例の臨床的検討 Reviewed

    池田 健二, 田中 加緒里, 飴矢 美里, 田口 亜紀, 羽藤 直人

    音声言語医学   58 ( 1 )   66 - 67   2017.1

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  • Suppressive Effect of a Thioamide-Related Compound SH-2251 on a Murine Allergic Rhinitis Model Reviewed

    Takashi Kitani, Saho Maruyama, Kunihide Aoishi, Naoya Nishida, Hideo Ogawa, Yasunori Abe, Yuji Hayashi, Masakatsu Yamashita, Naohito Hato

    Journal of Allergy & Therapy   08 ( 04 )   2017

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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 Reviewed

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

    ACTA OTO-LARYNGOLOGICA   137 ( sup565 )   S17 - S23   2017

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    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 &gt;= 25kg/m(2)).
    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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  • Epidemiological survey of acute low-tone sensorineural hearing loss Reviewed

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

    ACTA OTO-LARYNGOLOGICA   137 ( sup565 )   S34 - S37   2017

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    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, chi(2) test and logistic regression.
    Results: Female gender (p&lt; .013), younger age (p&lt; .001), low-grade hearing loss (p&lt; .001), and shorter interval between onset and initial visit (p&lt; .004) were significantly predictive of a good prognosis. The prognosis for definite ALHL was significantly better than that for probable ALHL (p&lt; .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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  • The effect of initial treatment on hearing prognosis in idiopathic sudden sensorineural hearing loss: a nationwide survey in Japan Reviewed

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

    ACTA OTO-LARYNGOLOGICA   137 ( sup565 )   S30 - S33   2017

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    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 (&gt;= 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: a retrospective, multi-institutional investigation in Japan Reviewed

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

    ACTA OTO-LARYNGOLOGICA   137 ( sup565 )   S44 - S47   2017

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    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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  • Nationwide epidemiological survey of idiopathic sudden sensorineural hearing loss in Japan Reviewed

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

    ACTA OTO-LARYNGOLOGICA   137 ( sup565 )   S8 - S16   2017

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    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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  • Idiopathic sudden sensorineural hearing loss and acute low-tone sensorineural hearing loss: a comparison of the results of a nationwide epidemiological survey in Japan Reviewed

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

    ACTA OTO-LARYNGOLOGICA   137 ( sup565 )   S38 - S43   2017

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    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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  • 高齢者の嚥下障害と最新の嚥下機能評価法 Reviewed

    田中 加緒里, 西田 直哉, 山田 啓之, 羽藤 直人

    愛媛医学   35 ( 4 )   159 - 166   2016.12

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  • Efficacy of chlorophyll c2 for seasonal allergic rhinitis: single-center double-blind randomized control trial Reviewed

    Takashi Fujiwara, Naoya Nishida, Jumpei Nota, Takashi Kitani, Kunihide Aoishi, Hirotaka Takahashi, Takuya Sugahara, Naohito Hato

    EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY   273 ( 12 )   4289 - 4294   2016.12

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    Chlorophyll c2 extracted from Sargassum horneri improved allergic symptoms in an animal model of allergic rhinitis. In the present study, we explored the efficacy of chlorophyll c2 in patients with seasonal allergic rhinitis. This was a single-center, randomized, double-blind placebo-controlled trial. Sixty-six patients aged 20-43 years, each with a 2-year history of seasonal allergic rhinitis, were randomly assigned to receive either a single daily dose (0.7 mg) of chlorophyll c2 or placebo for 12 weeks. The use of medications including H1-antihistamines and topical nasal steroids was recorded by rescue medication scores (RMSs) noted after 4, 8, and 12 weeks of treatment. Disease-specific quality of life was measured using the Japan Rhinitis Quality of Life Questionnaire (JRQLQ) both before and after 4, 8, and 12 weeks of treatment. The RMS at 8 weeks was significantly better in the chlorophyll c2 than the placebo group (mean RMS difference = -3.09; 95 % confidence interval = -5.96 to -0.22); the mean RMS at 4 weeks was only slightly better in the chlorophyll c2 group. The JRQLQ scores did not differ significantly between the two groups. Chlorophyll c2 would have a potential to be an alternative treatment for allergic rhinitis.

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  • Prognostic impact of salvage treatment on hearing recovery in patients with sudden sensorineural hearing loss refractory to systemic corticosteroids: A retrospective observational study Reviewed

    Takayuki Nakagawa, Michio Yamamoto, Kozo Kumakawa, Shin-ichi Usami, Naohito Hato, Keiji Tabuchi, Mariko Takahashi, Keizo Fujiwara, Akira Sasaki, Shizuo Komune, Norio Yamamoto, Harukazu Hiraumi, Tatsunori Sakamoto, Akira Shimizu, Juichi Ito

    AURIS NASUS LARYNX   43 ( 5 )   489 - 494   2016.10

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    Objective: To determine the prognostic factors for hearing recovery in patients with sudden sensorineural hearing loss (SSHL) refractory to systemic corticosteroids following salvage treatment.
    Methods: This is a retrospective observational study at nine tertiary referral hospitals. A total of 120 patients with sudden deafness refractory to systemic corticosteroids were enrolled. The patients were randomly assigned to receive topical application of recombinant human IGF-1 or intratympanic injection of dexamethasone as salvage treatment. Multiple regression analysis was performed to identify determinants of hearing recovery using pure tone audiometry results at 8 weeks after treatment. Clinical predictors that were evaluated included age, sex, pretreatment hearing level, presence of vertiginous symptoms, days to study entry from symptom onset and salvage treatment assignment (IGF-1 vs. dexamethasone).
    Results: The linear regression model identified age (P = 0.001), pretreatment hearing level (P &lt; 0.001), days to study entry from symptom onset (P = 0.011) and treatment assignment (P = 0.033) at 8 weeks after treatment as significant variables influencing the recovery of pure tone audiometry average thresholds. Younger age (&lt;60 years), early initiation of salvage treatment and treatment with topical IGF-1 therapy had significant effects on hearing recovery.
    Conclusion: The results indicate that early initiation and choice of treatment modalities for salvage treatment may be important for the prognosis of patients with refractory SSHL. The positive effect of topical IGF-1 therapy on hearing recovery indicates its utility as salvage treatment. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

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  • 当科における喉頭肉芽腫に対する音声治療の検討 Reviewed

    飴矢 美里, 田中 加緒里, 池田 健二, 田口 亜紀, 羽藤 直人

    言語聴覚研究   13 ( 3 )   198 - 199   2016.9

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  • Endoscopic Modified Medial Maxillectomyを施行した歯根嚢胞の3例

    能田 淳平, 西田 直哉, 阿部 康範, 羽藤 直人

    日本鼻科学会会誌   55 ( 3 )   459 - 459   2016.9

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  • 頭蓋咽頭管の遺残が反復性髄膜炎の原因と考えられた一例

    阿部 康範, 西田 直哉, 能田 淳平, 羽藤 直人

    日本鼻科学会会誌   55 ( 3 )   451 - 451   2016.9

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  • 用語委員会報告 全国真珠腫手術症例登録2015結果報告 二次性真珠腫

    山本 裕, 東野 哲也, 阪上 雅史, 小島 博己, 松田 圭二, 羽藤 直人, 小森 学, 森田 由香, 橋本 省

    Otology Japan   26 ( 4 )   387 - 387   2016.9

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  • 用語委員会報告 全国真珠腫手術症例登録2015結果報告 弛緩部型・緊張部型

    松田 圭二, 東野 哲也, 阪上 雅史, 小島 博己, 山本 裕, 羽藤 直人, 小森 学, 森田 由香, 橋本 省

    Otology Japan   26 ( 4 )   386 - 386   2016.9

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  • 用語委員会報告 全国真珠腫手術症例登録2015結果報告 調査概要

    小森 学, 東野 哲也, 阪上 雅史, 小島 博己, 松田 圭二, 山本 裕, 羽藤 直人, 森田 由香, 橋本 省

    Otology Japan   26 ( 4 )   385 - 385   2016.9

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  • 当科における副鼻腔嚢胞手術症例の検討

    西田 直哉, 能田 淳平, 阿部 康範, 羽藤 直人

    日本鼻科学会会誌   55 ( 3 )   494 - 494   2016.9

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  • 用語委員会報告 全国真珠腫手術症例登録2015結果報告 先天性真珠腫

    森田 由香, 東野 哲也, 阪上 雅史, 小島 博己, 松田 圭二, 山本 裕, 羽藤 直人, 小森 学, 橋本 省

    Otology Japan   26 ( 4 )   388 - 388   2016.9

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  • Anatomic Invasive Depth Predicts Delayed Cervical Lymph Node Metastasis of Tongue Squamous Cell Carcinoma Reviewed

    Sohei Mitani, Toshifumi Tomioka, Ryuichi Hayashi, Toru Ugumori, Naohito Hato, Satoshi Fujii

    AMERICAN JOURNAL OF SURGICAL PATHOLOGY   40 ( 7 )   934 - 942   2016.7

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    Delayed cervical lymph node metastasis (CLNM) is the most negative prognostic factor of tongue squamous cell carcinoma (SCC). This study analyzed the relationship between clinicopathologic factors, including anatomic invasive depth (AID), and CLNM. A total of 212 patients with clinically node-negative (cN0) tongue SCC who had undergone partial glossectomy through the mouth were eligible for this retrospective study. The deepest portions where tongue SCC cells invaded as determined by microscopic analyses were classified into 5 categories, including epithelial and submucosal tissue, lateral extrinsic tongue muscle (ETM), intrinsic tongue muscles (ITM), paralingual and sublingual spaces, and medial ETM according to AID. We examined the relationship between clinicopathologic factors including AID and delayed CLNM. Multivariate analysis demonstrated that AID was an independent predictive factor for delayed CLNM (P=0.0022; odds ratio=7.1). Deeper invasion than ITM, including ITM, paralingual and sublingual spaces, and medial ETM, had high sensitivity and negative predictive value for delayed CLNM (94.4% and 95.7%, respectively). Precise elucidation of AID may be useful for the preoperative decision for performing elective neck dissection. None of 11 patients in whom the deepest portion where tumor invaded to lateral ETM (according to AID) showed delayed CLNM, although tongue SCC T4a tumor is defined by the presence of invasion of cancer cells to ETM. Tumors with invasion to lateral ETM might have to be excluded from the pathologic T4a category.

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  • Programmed Death Ligand-1 Expression Is Associated With Poor Disease Free Survival in Salivary Gland Carcinomas Reviewed

    Takashi Mukaigawa, Ryuichi Hayashi, Kazuki Hashimoto, Toru Ugumori, Naohito Hato, Satoshi Fujii

    JOURNAL OF SURGICAL ONCOLOGY   114 ( 1 )   36 - 43   2016.7

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    Background and Objectives: The immune checkpoint ligand programmed death ligand-1 (PD-L1) is expressed in various carcinomas and allows carcinoma cells to elude the immune system. PD-L1 expression is associated with the response to anti-programmed death 1 (PD-1)/PD-L1 drugs. This study aimed to clarify the relationship between PD-L1 expression and clinicopathological factors of salivary gland carcinomas (SGCs) and identify its clinical significance.
    Methods: PD-L1 expression was examined by immunohistochemical analysis using a tissue microarray comprised of 219 surgically resected SGC specimens. Detailed clinicopathological factors, including patient outcome, were available for all cases.
    Results: A case showing complete membranous expression of PD-L1 in more than 1% of whole carcinoma cells was considered positive by ROC analysis. A total of 50 (22.8%) patients showed PD-L1 expression in SGC cells. Positive PD-L1 expression was significantly associated with poor disease free survival (P &lt; 0.001) and overall survival (P &lt; 0.001). Multivariate analysis revealed that positive PD-L1 expression was one of the independent predictors for poor disease free survival (hazard ratio = 2.287, 95% confidence interval = 1.24-4.15; P = 0.008).
    Conclusions: Positive PD-L1 expression was significantly associated with poor disease free survival of SGCs, suggesting that antibody therapies targeting PD-1/PD-L1 may have potential application in SGCs. (C) 2016 Wiley Periodicals, Inc.

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  • 舌扁平上皮癌の解剖学的深達度は後発リンパ節転移に関係する

    三谷 壮平, 富岡 利文, 林 隆一, 篠崎 剛, 丸尾 貴志, 鵜久森 徹, 羽藤 直人, 藤井 誠志

    頭頸部癌   42 ( 2 )   196 - 196   2016.5

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  • 良性発作性頭位めまい症例における骨代謝マーカー

    岡田 昌浩, 中田 貴大, 西原 江里子, 山田 啓之, 羽藤 直人

    日本耳鼻咽喉科学会会報   119 ( 4 )   626 - 626   2016.4

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  • Treatment of allergic rhinitis with intranasal infusion of botulinum toxin type A in mice Reviewed

    Kunihide Aoishi, Hirotaka Takahashi, Naohito Hato, Kiyofumi Gyo, Makoto Yokota, Shinya Ozaki, Motohiko Suzuki

    LIFE SCIENCES   147   132 - 136   2016.2

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    Aims: To determine whether intranasal infusion of botulinum toxin type A (BTX-A) relieves symptoms of ovalbumin (OVA)-induced allergic rhinitis (AR) and reduces nasal inflammation in mice.
    Main methods: AR was induced via intraperitoneal injection of OVA followed by daily intranasal challenge with OVA. Five weeks after the initiation of OVA sensitization, nasal cavities were exposed to a single intranasal infusion of BTX-A. The behavior of mice was observed before and 1, 3, 5, 7, 14, 21, and 28 days after infusion. Mice were sacrificed after 28 days and late histological findings were examined. PBS was administered to control mice.
    Results: On Day 3, the frequency of typical AR symptoms, including sneezing and nose scratching, significantly decreased in the BTX-A-treated group (n = 6) compared to the control group (n = 6). Although the AR-inhibiting effects of BTX-A persisted until Day 21, AR symptoms re-appeared in response to daily OVA stimulation. Histological findings of the nasal mucosa also improved following BTX-A administration. Although capillary dilatation and eosinophil infiltration decreased by Day 3, these effects disappeared by Day 28. In contrast, the number and size of the secretary glands in the nasal mucosa did not change following BTX-A administration. PBS had no effect on nasal symptoms or histology.
    Conclusions: Topical treatment with BTX-A efficiently and temporarily ameliorates AR symptoms. Intranasal infusion does not cause pain or bleeding, and the effects of a single infusion of BTX-A last for at least three weeks. This treatment might be a promising therapeutic strategy for the treatment of AR. (C) 2015 Published by Elsevier Inc.

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  • A case of childhood parotid cancer suspected as second malignant neoplasm Reviewed

    Takahiro Nakata, Tadashi Yoshida, Hiroyuki Yamada, Toru Ugumori, Naohito Hato

    Japanese Journal of Head and Neck Cancer   42 ( 4 )   414 - 417   2016

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    The prognosis for childhood cancer has improved drastically recently due to advances in anti-tumor therapy. The current 5-year survival rate is over 70%
    hence, childhood cancer is curable. However, secondary malignant neoplasms are a late effect of primary cancer therapy. The patient was an 8-year-old girl. When she was 2 years old, she suffered from neuroblastoma (stage IV). Chemotherapy, hematopoietic stem cell transplantation, surgery, and radiotherapy brought about complete remission. However, 6 years later a right parotid gland tumor appeared. A tumorectomy was then conducted, and intraoperative consultation revealed inflammation of the parotid gland. The final pathological diagnosis was low-grade mucoepidermoid carcinoma of the parotid gland, so we performed an additional operation. This cancer seemed to be secondary malignant neoplasm induced later following childhood cancer therapy. Eighteen months have passed since her final operation, and there is no recurrence of cancer.

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  • 小児人工内耳手術例における補聴器装用開始時期に関する検討

    寺岡 正人, 羽藤 直人

    AUDIOLOGY JAPAN   59 ( 5 )   407 - 408   2016

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    DOI: 10.4295/audiology.59.407

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  • 中耳真珠腫進展度分類2015改訂案

    東野 哲也, 橋本 省, 阪上 雅史, 小島 博己, 羽藤 直人, 山本 裕, 小森 学, 松田 圭二, 日本耳科学会用語委員会

    Otology Japan   25 ( 5 )   845 - 850   2015.12

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  • A case of hypertrophic cranial pachymeningitis associated with invasive Aspergillus mastoiditis Reviewed

    Masahiro Okada, Naohito Hato, Yoko Okada, Eriko Sato, Hiroyuki Yamada, Nobuhiro Hakuba, Kiyofumi Gyo

    AURIS NASUS LARYNX   42 ( 6 )   488 - 491   2015.12

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    We report a rare case of hypertrophic cranial pachymeningitis (HCP) associated with invasive Aspergillus mastoiditis. A 63-year-old man with diabetes mellitus underwent mastoidectomy because of chronic discharge from his left ear. The mastoidectomy was unsuccessful in resolving purulent otorrhea; moreover, 7 months later, the patient developed left abducens nerve palsy. Magnetic resonance imaging revealed HCP at the left middle cranial fossa. Although the pathogen could not be identified, an Aspergillus infection was considered based on elevated serum beta-D-glucan and a positive Aspergillus antigen test result. Voriconazole treatment resolved diplopia and left otorrhea and dramatically improved HCP. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

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  • 人工内耳埋込術を施行したCHARGE症候群の2症例

    阿部 康範, 羽藤 直人, 山田 啓之

    Otology Japan   25 ( 4 )   437 - 437   2015.9

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  • Preventive effects of bortezomib on denervation-induced atrophy of the intrinsic laryngeal muscles: an experimental study in the rat Reviewed

    Hirofumi Sei, Aki Taguchi, Naoya Nishida, Naohito Hato, Kiyofumi Gyo

    ACTA OTO-LARYNGOLOGICA   135 ( 7 )   713 - 717   2015.7

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    Conclusion: Bortezomib was effective in attenuating atrophy of the posterior cricoarytenoid (PCA) muscle, but not the thyroarytenoid (TA) muscle. This was probably due to differences in the fiber composition of the two muscles. The PCA muscle is composed of a combination of fast- and slow-twitch fibers, and therefore is more resistant to atrophy than the TA muscle, which is composed solely of fast-twitch fibers. Objectives: To investigate the preventive effects of bortezomib on denervation-induced atrophy of the TA and PCA muscles in the rat. Methods: Following transection of the left recurrent laryngeal nerve, bortezomib (100 mu g/kg) was administered subcutaneously on post-denervation days 1 and 4, followed by a 10-day rest period every 14 days; each 2-week period constituted a single treatment cycle. In controls, saline was administered instead. Animals were killed for histological examination at 4 (n = 6), 8 (n = 7), and 12 (n = 7) weeks post-denervation. Muscle atrophy was assessed using three indices: wet muscle weight, muscle fiber cross-sectional area, and the number of muscle fibers/mm2. The effects of bortezomib were evaluated by comparing the left (L) and right (R) muscles, with sequential changes in the L/R ratio assessed. Results: In saline-administered animals, atrophy of the left-sided TA and PCA muscles progressed rapidly during the first 4 weeks post-denervation, following which progression slowed. Atrophy was greater in the TA compared with the PCA muscle, although this difference was not statistically significant. In bortezomib-administered animals, atrophy of the PCA muscle was attenuated significantly at post-denervation weeks 8 and 12; no such reduction in atrophy was observed for the TA muscle.

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  • ゼラチンハイドロゲルを用いたIGF-1局所投与による突発性難聴治療 聴力予後関連因子に関する多変量解析

    中川 隆之, 熊川 孝三, 宇佐美 真一, 羽藤 直人, 田渕 経司, 高橋 真理子, 藤原 敬三, 佐々木 亮, 小宗 静男, 平海 晴一, 坂本 達則, 山本 典生, 伊藤 壽一

    日本耳鼻咽喉科学会会報   118 ( 4 )   602 - 602   2015.4

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  • Use of ambulatory anesthesia with manually assisted ventilation for tympanic membrane regeneration therapy in children Reviewed

    Nobuhiro Hakuba, Keizo Ikemune, Masahiro Okada, Naohito Hato

    AMERICAN JOURNAL OF OTOLARYNGOLOGY   36 ( 2 )   153 - 157   2015.3

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    Purpose: To present the utility of ambulatory anesthesia using manually assisted ventilation via a facemask for tympanic membrane (TM) regeneration therapy in children.
    Material and methods: The study included 10 children (age 4-11 years) in whom the duration of perforation before treatment exceeded 6 months and who were followed for at least 1 year after treatment between December 2009 and December 2012. Under ambulatory anesthesia using manually assisted ventilation via a facemask, TM regenerative therapy with atelocollagen combined with basic fibroblast growth factor was performed in children who could not tolerate the procedure under local anesthesia alone.
    Results: All of the children completed the TM regenerative therapy under ambulatory anesthesia in less than 5 min. Complete closure was achieved in nine (81.8%) ears after 1 year of postoperative follow-up.
    Conclusion: TM regenerative therapy can be performed under local anesthesia in less than 5 min without a skin incision. However, local anesthesia is often insufficient in small children undergoing this procedure. Therefore, ambulatory anesthesia using manually assisted ventilation via a facemask is appropriate to complete this procedure safely in small children. (C) 2015 Elsevier Inc. All rights reserved.

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  • 心不全で増悪したオスラー病例

    勢井 洋史, 高木 太郎, 岡田 昌浩, 高橋 宏尚, 羽藤 直人

    耳鼻咽喉科臨床   108 ( 2 )   115 - 119   2015.2

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    45歳女性。たびたび繰り返す鼻出血を遺伝性出血性毛細血管拡張症と診断され、ホルモン療法により概ね抑制されていた。だが、その後、10日に1回程度の頻度で大量の鼻出血を繰り返すようになったため、反復性鼻出血コントロール目的で著者らの施設へ受診となった。所見では口腔ならびに舌表面に丘疹状の血管拡張ほか、鼻入口部に孤立性点状血管拡張をスポット状に多数認められた。対処として初診2ヵ月後に局所麻酔下で両下鼻甲介と鼻中核、鼻腔底粘膜のアルゴンプラズマ凝固装置による焼灼術を施行することで鼻出血の頻度は低下したが、初診6ヵ月後から発熱が持続、更に2週間後には鼻出血の頻度が日に1回と増加した。以後、入院となり、輸血によって改善したが、1週間経過で再び頻回の鼻出血と肝機能異常を認め再入院となった。血液検査を行なったところ、高度炎症所見から細菌感染による敗血症が示唆され、血液培養にて表皮ブドウ球菌が検出された。既往として13年前に大動脈弁置換術を受けたことがあることから同部位の細菌感染が強く疑われた。そこで、再入院1ヵ月後に感染症内科に転科させ、広域抗菌薬の投与を行なった結果、敗血症は軽快傾向となったものの呼吸状況と心不全の悪化を認め、心エコーで大動脈弁の弁輪破壊を確認、大動脈弁再置換術+心室中隔欠損閉鎖術を施行することで、患者の鼻出血は著明に減少した。尚、目下、3年経過で治療を要するような鼻出血は認められていない。

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  • Infusion reactions induced by cetuximab Reviewed

    Tadashi Yoshida, Toru Ugumori, Sohei Mitani, Yuichi Tomidokoro, Hiroyuki Yamada, Naohito Hato

    Japanese Journal of Head and Neck Cancer   40 ( 4 )   485 - 489   2015.1

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    Cetuximab, a human–mouse chimeric IgG1 monoclonal antibody used against the epidermal growth factor receptor, is approved for the treatment of squamous cell carcinoma of the head and neck. Currently, cases of hypersensitivity to cetuximab are attributed to the production of an IgE antibody specific for galactose-alpha-1,3-galactose (α-Gal) positioned on the Fab portion of the cetuximab heavy chain. Because such IgE antibodies bind to various mammalian proteins, red meat allergy is also related to α-Gal. In addition, tick bites also induce the production of this IgE antibody against α-Gal. Therefore, we retrospectively investigated 17 patients diagnosed with head and neck cancer for the incidence of infusion reactions, following cetuximab chemotherapy from January to December 2013 at the Department of Otolaryngology-Head and Neck Surgery, Ehime University Hospital. We conducted serological analysis for specific IgE reactions to beef, pork, chicken, α-Gal and interviewed the patients to see whether or not they had tick bites. Infusion reactions were observed in 4 patients (23.5%) and IgE antibodies specific for pork, chicken, or α-Gal were detected in 3 of these 4 patients. These data suggest that the infusion reactions resulted from allergic reactions induced by cetuximab-containing α-Gal.

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  • Expression of atrophy-related transcription factors in the process of intrinsic laryngeal muscle atrophy after denervation Reviewed

    Hirofumi Sei, Aki Taguchi, Naoya Nishida, Naohito Hato, Kiyofumi Gyo

    EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY   272 ( 1 )   137 - 141   2015.1

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    We examined changes in the expressions of three atrophy-related transcription factors (FOXO3a, P-FOXO3a, and PGC-1 alpha) in the process of intrinsic laryngeal muscle atrophy after denervation. In total, 51 Wistar rats were used. After transection of the unilateral recurrent laryngeal nerve, the thyroarytenoid (TA) muscle and the posterior cricoarytenoid (PCA) muscle were excised and subjected to histological and Western blot studies. Relationships between the expressions of transcription factors during atrophy of the intrinsic laryngeal muscles were investigated by comparing the results of the treated side (T) with those of the untreated side (U), and sequential changes in the T/U ratio after denervation were assessed. Loss of wet muscle weight, together with a decrease in muscle fiber cross-sectional area and increase in the number of muscle fibers/mm(2), occurred more quickly in TA muscle than in PCA muscle. Muscle atrophy progressed rapidly between 7 and 28 days after denervation, while expression of FOXO3a was maximal on day 7, in both TA and PCA muscles. By contrast, P-FOXO3a expression decreased gradually after denervation. Expression of PGC-1 alpha increased slowly until day 7, and then it declined. Denervation-induced atrophy of the intrinsic laryngeal muscles was closely linked with the expression of FOXO3a and PGC-1 alpha, suggesting that atrophy of these muscles may involve the actions of these transcription factors. In addition, muscle atrophy progressed faster in TA muscle than in PCA muscle, due mainly to differences in muscle fiber composition.

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  • Preoperative Factors Affecting Tympanic Membrane Regeneration Therapy Using an Atelocollagen and Basic Fibroblast Growth Factor Reviewed

    Nobuhiro Hakuba, Naohito Hato, Masahiro Okada, Kazuyo Mise, Kiyofumi Gyo

    JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY   141 ( 1 )   60 - 66   2015.1

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    IMPORTANCE The use of growth factors to achieve closure of perforated tympanic membranes (TMs) has recently become popular. However, preoperative factors affecting treatment outcomes have seldom been discussed.
    OBJECTIVE To evaluate preoperative factors contributing to the success or failure of healing of perforated TMs.
    DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of 153 patients (48 males and 105 females) in whom the duration of perforation was longer than 6 months prior to treatment and who were observed for at least 1 year after treatment between July 2009 and June 2012. Eight factors considered likely to affect the outcome of perforation closure were statistically evaluated using multivariate logistic regression analysis.
    INTERVENTIONS Each perforated TM was filled with a synthetic graft material (atelocollagen sponge and silicone membrane) containing human basic fibroblast growth factor to promote wound healing after TM perforation closure.
    MAIN OUTCOMES AND MEASURES Complete closure vs residual perforation.
    RESULTS After 1 year of follow-up, 101 patients (66.0%) achieved complete closure, 30 patients (19.6%) had residual pinhole perforations (&lt;1mm diameter), and 22 patients (14.4%) had larger residual perforations. Multivariate logistic regression analysis adjusted for each explanatory variable identified a TM without calcification (odds ratio [OR], 2.68 [95% CI, 1.17-6.15]; P = .03) and a perforation not involving the tympanic annulus (odds ratio, 2.75 [95% CI, 1.09-6.94]; P = .04) as significant. Insignificant factors included perforation margin identified on microscopy (OR, 0.24 [95% CI, 0.99-6.27]; P &lt; .001), perforation margin without epithelial migration (OR, 7.27 [95% CI, 0.66-80.49]; P = .11), absence of preoperative otorrhea (P = .38), no previous ear operations (P = .82), perforation size (P = .14), and patient age (P = .26).
    CONCLUSIONS AND RELEVANCE Tympanic membrane regeneration therapy can be applied to all patients, except those with cholesteatoma or malignant neoplasm. However, patients with severe calcification of the TM and those with marginal perforations close to the fibrous annulus should be treated more prudently to achieve perforation closure.

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  • A case of spindle cell carcinoma of the hypopharynx Reviewed

    Teppei Kaminota, Hiroyuki Yamada, Naohito Hato

    Practica Oto-Rhino-Laryngologica   108 ( 11 )   839 - 843   2015

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    Spindle cell carcinoma is a rare tumor that contains both a conventional epithelial squamous component and a sarcomatous spindle cell component. Here, we report a rare case of spindle cell carcinoma of the hypopharynx. The patient was a 49-year-old woman who visited our hospital complaining of discomfort in the throat. A pedunculated tumor originating from the left piriform sinus was observed. Contrast-enhanced CT and T1-weighted MR images showed a well-demarcated mass with heterogeneous enhancement and a pedunculated mass adjacent to the left piriform sinus. A biopsy led to the diagnosis of an undifferentiated pleomorphic sarcoma. A partial pharyngectomy and left neck dissection were performed. The pathologic diagnosis was consistent with spindle cell carcinoma. Pathologically, the surgical margins were negative, and cervical lymph node metastasis was not observed. No signs of recurrence were observed at a 26-month follow-up examination.

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  • 愛媛県下における突発性難聴の疫学調査

    藤原 崇志, 岡田 昌浩, 吉田 正, 白馬 伸洋, 羽藤 直人, 暁 清文

    愛媛医学   33 ( 4 )   182 - 186   2014.12

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    愛媛県下の大学病院1施設、病院15施設、診療所66施設にアンケート用紙を送付し、2012年4月〜2013年3月に耳鼻咽喉科外来を受診した突発性難聴患者の疫学調査を行った。参加率は大学病院1施設(100%)、病院13施設(86.7%)、診療所55施設(83.3%)であり、期間中841名(男324名、女517名、平均年齢56.1歳)が受診した。再診も含め最終的に病院・大学病院には259名が受診し、男女比は1:1.33、平均年齢59.3歳、重症度はGrade1が14.7%、Grade2が22.8%、Grade3が44.4%、Grade4が18.1%であったのに対し、診療所には582名が受診し、男女比は1:1.73、平均年齢54.7歳、重症度はGrade1が50.3%、Grade2が33.0%、Grade3が14.1%、Grade4が2.6%であった。病院・大学病院と診療所では患者の背景・重症度に差異があることから、突発性難聴の研究は病院だけでなく診療所も含めた調査を行う必要があると思われた。

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  • 40点法(柳原法)による麻痺スコアの採点法

    羽藤 直人, 藤原 崇志, 山田 啓之, 飴矢 美里

    Facial Nerve Research   34   67 - 68   2014.12

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    1977年12月~2011年12月のBell麻痺患者654例(15歳以上)を対象に、発症1週以内の柳原スコアと麻痺転帰を比較した。発症1週以内の最悪時スコアが22点以上を軽症、20~12点を中等症、10点以下を重症として3群に分類すると、軽症例は151例(23.1%)・中等症例は286例(43.7%)・重症例は217例(33.2%)であった。発症後6ヵ月以内に治癒に至ったのは軽症例の99.3%・中等症例の95.1%・重症例の80.2%、発症3ヵ月以内の早期治癒症例の比率は、軽症例96.0%・中等症例83.6%・重症例57.6%と、いずれも3群間の治癒率にすべて有意差が認められた。また、治癒群596例と非治癒群58例の2群における発症1週間以内の40点スコアの比較では、治癒群の平均は15.7点、非治癒群は8.4点と両群間で有意差が認められた。

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  • Idiopathic sudden sensorineural hearing loss in Japan Reviewed

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

    ACTA OTO-LARYNGOLOGICA   134 ( 11 )   1158 - 1163   2014.11

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    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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  • A randomized controlled clinical trial of topical insulin-like growth factor-1 therapy for sudden deafness refractory to systemic corticosteroid treatment Reviewed

    Takayuki Nakagawa, Kozo Kumakawa, Shin-ichi Usami, Naohito Hato, Keiji Tabuchi, Mariko Takahashi, Keizo Fujiwara, Akira Sasaki, Shizuo Komune, Tatsunori Sakamoto, Harukazu Hiraumi, Norio Yamamoto, Shiro Tanaka, Harue Tada, Michio Yamamoto, Atsushi Yonezawa, Toshiko Ito-Ihara, Takafumi Ikeda, Akira Shimizu, Yasuhiko Tabata, Juichi Ito

    BMC MEDICINE   12   219   2014.11

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    Background: To date, no therapeutic option has been established for sudden deafness refractory to systemic corticosteroids. This study aimed to examine the efficacy and safety of topical insulin-like growth factor-1 (IGF-1) therapy in comparison to intratympanic corticosteroid therapy.
    Methods: We randomly assigned patients with sudden deafness refractory to systemic corticosteroids to receive either gelatin hydrogels impregnated with IGF-1 in the middle ear (62 patients) or four intratympanic injections with dexamethasone (Dex; 58 patients). The primary outcome was the proportion of patients showing hearing improvement (10 decibels or greater in pure-tone average hearing thresholds) 8 weeks after treatment. The secondary outcomes included the change in pure-tone average hearing thresholds over time and the incidence of adverse events.
    Results: In the IGF-1 group, 66.7% (95% confidence interval [CI], 52.9-78.6%) of the patients showed hearing improvement compared to 53.6% (95% CI, 39.7-67.0%) of the patients in the Dex group (P = 0.109). The difference in changes in pure-tone average hearing thresholds over time between the two treatments was statistically significant (P = 0.003). No serious adverse events were observed in either treatment group. Tympanic membrane perforation did not persist in any patient in the IGF-1 group, but did persist in 15.5% (95% CI, 7.3-27.4%) of the patients in the Dex group (P = 0.001).
    Conclusions: The positive effect of topical IGF-1 application on hearing levels and its favorable safety profile suggest utility for topical IGF-1 therapy in patients with sudden deafness.

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  • Yanagihara Facial Nerve Grading System as a Prognostic Tool in Bell's Palsy Reviewed

    Naohito Hato, Takashi Fujiwara, Kiyofumi Gyo, Naoaki Yanagihara

    OTOLOGY & NEUROTOLOGY   35 ( 9 )   1669 - 1672   2014.10

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    Objective: The aim of this study was to evaluate the accuracy of the Yanagihara facial nerve grading system in assessing the course of recovery and in determining the probability of a complete recovery of Bell's palsy within 1 week after onset.
    Study Design: Retrospective study of patients at a single trial center.
    Setting: Tertiary referral center.
    Patients: Six hundred sixty-four patients with Bell's palsy were assigned to three groups by degree of facial palsy using the Yanagihara 40-point system.
    Main Outcome Measure: The rate of recovered patients was assessed until 6 months after onset.
    Results: Ultimately, 151 (23.1%) patients were assessed with mild palsy, 286 (43.7%) with moderate palsy, and 217 (33.2%) with severe palsy. The average Yanagihara score in the recovered patients was 15.7, whereas the score in the nonrecovered patients was 8.4. The rate of recovered patients in the mild group was 99.3%, that in the moderate group was 95.1%, and that in the severe group was 80.2%. These differences among the groups were significant (p &lt; 0.05).
    Conclusion: The Yanagihara system was able to distinguish the probability of a complete recovery of the facial palsy within 1 week after the onset of palsy. We believe that the key point in improving the prognosis of Bell's palsy is to diagnose the severity, using the Yanagihara system, and to treat it promptly to prevent progressive nerve degeneration.

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  • [Evidence for the treatment of facial paralysis with antiviral drugs]. Reviewed

    Hato N

    Nihon Jibiinkoka Gakkai kaiho   117 ( 10 )   1292 - 1293   2014.10

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  • 突発性難聴に対するゼラチンハイドロゲルを用いたIGF-1局所投与の有効性

    中川 隆之, 熊川 孝三, 宇佐美 真一, 羽藤 直人, 田渕 経司, 高橋 真理子, 藤原 敬三, 佐々木 亮, 小宗 静男, 坂本 達則, 平海 晴一, 山本 典生, 伊藤 壽一

    Otology Japan   24 ( 4 )   638 - 638   2014.9

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  • Intravenous administration of bone marrow mononuclear cells alleviates hearing loss after transient cochlear ischemia through paracrine effects Reviewed

    Taro Takagi, Tadashi Yoshida, Masahiro Okada, Ryuji Hata, Naohito Hato, Kiyofumi Gyo, Nobuhiro Hakuba

    NEUROREPORT   25 ( 11 )   807 - 813   2014.8

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    Bone marrow mononuclear cells (BMMCs) are known to enhance recovery from ischemic insults by secreting angiogenic factors and inducing the expression of angiogenic factors from host tissues. Therefore, the transplantation of BMMCs is considered a potential approach to promoting the repair of ischemic damaged organs. Here, we investigated the influence of BMMCs on progressive hair cell degeneration after transient cochlear ischemia in gerbils. Transient cochlear ischemia was produced by extracranial occlusion of the bilateral vertebral arteries immediately before their entry into the transverse foramen of the cervical vertebra. An intravenous injection of BMMCs prevented ischemia-induced hair cell degeneration and ameliorated hearing impairment. A tracking study showed that BMMCs injected into the femoral vein were limited in the spiral artery of the cochlea, suggesting that, although transplanted BMMCs were retained within the spiral ganglion area of the cochlea, they were neither transdifferentiated into cochlear cells nor fused with the injured hair cells and supporting cells in the organ of Corti to restore their functions. We also showed that the protein level of neurotrophin-3 and glial cell line-derived neurotrophic factor in the organ of Corti was upregulated after treatment with BMMCs. These results suggested that BMMCs have therapeutic potential possibly through paracrine effects. Thus, we propose the use of BMMCs as a potential new therapeutic strategy for hearing loss. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

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  • Prognostic factors of Bell's palsy: prospective patient collected observational study Reviewed

    Takashi Fujiwara, Naohito Hato, Kiyofumi Gyo, Naoaki Yanagihara

    EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY   271 ( 7 )   1891 - 1895   2014.7

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    The purpose of this study was to evaluate various parameters potentially influencing poor prognosis in Bell's palsy and to assess the predictive value for Bell's palsy. A single-center prospective patient collected observation and validation study was conducted. To evaluate the correlation between patient characteristics and poor prognosis, we performed univariate and multivariate analyzes of age, gender, side of palsy, diabetes mellitus, hypertension, and facial grading score 1 week after onset. To evaluate the accuracy of the facial grading score, we prepared a receiver operating characteristic (ROC) curve and calculated the area under the ROC curve (AUROC). We also calculated sensitivity, specificity, positive/negative likelihood ratio, and positive/negative predictive value. We included Bell's palsy patients who attended Ehime University Hospital within 1 week after onset between 1977 and 2011. We excluded patients who were less than 15 years old and lost-to-follow-up within 6 months. The main outcome was defined as non-recovery at 6 months after onset. In total, 679 adults with Bell's palsy were included. The facial grading score at 1 week showed a correlation with non-recovery in the multivariate analysis, although age, gender, side of palsy, diabetes mellitus, and hypertension did not. The AUROC of the facial grading score was 0.793. The Y-system score at 1 week moderate accurately predicted non-recovery at 6 months in Bell's palsy.

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  • Clinical features, presenting symptoms, and surgical results of congenital cholesteatoma based on Potsic's staging system Reviewed

    Taro Takagi, Kiyofumi Gyo, Nobuhiro Hakuba, Jun Hyodo, Naohito Hato

    ACTA OTO-LARYNGOLOGICA   134 ( 5 )   462 - 467   2014.5

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    Conclusions: Potsic's staging system is a clinically useful procedure for evaluating the extent of congenital cholesteatoma (CC). Objectives: We investigated the clinical features, presenting symptoms, and surgical results of CC according to Potsic's staging system. Methods: A total of 71 patients who had undergone surgery at our hospital were retrospectively analyzed for presenting symptoms, the location of cholesteatoma, and surgical results according to Potsic's staging system. Results: Of the 71 patients, 21 were classified as Potsic stage I, 9 as stage II, 31 as stage III, and 10 as stage IV. More than half of the patients with early-stage CC (stages I and II) were diagnosed asymptomatically by a chance visit to a clinic or on ear screening. Others were diagnosed following a complaint of hearing loss, acute otitis media, or otitis media with effusion. The location of CC varied somewhat by stage. In stage I CC, the most frequent location was behind the anterior-superior quadrant of the tympanic membrane; however, in stage III CC, it was behind the posterior-superior quadrant. All patients were treated surgically. Recurrence was detected in 2 of the 71 patients (2.8%); both had stage II CC. Recurrent lesions were removed during revision surgery.

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  • Air-bone gap in ears with a well-repaired tympanic membrane after Type III and Type IV tympanoplasty Reviewed

    Masahiro Okada, Kiyofumi Gyo, Taro Takagi, Takashi Fujiwara, Hirotaka Takahashi, Nobuhiro Hakuba, Naohito Hato

    AURIS NASUS LARYNX   41 ( 2 )   153 - 159   2014.4

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    Objective: To investigate the air-bone conduction hearing gap (A-B gap) after Type III and Type IV stapes columella tympanoplasty in ears with mobile stapes and a well repaired tympanic membrane (TM).
    Methods: Those patients who underwent tympanoplasty in our hospital between 2003 and 2009 and satisfied the following criteria were eligible: (1) good stapes mobility, confirmed intraoperatively; (2) postoperative TM and/or computed tomography (CT) findings that showed a well-aerated tympanic cavity without TM perforation, otorrhea, or middle ear effusion; and (3) measurable air and bone conduction hearing thresholds 1 year postoperatively at all test frequencies (250 Hz, 500 Hz, 1 kHz, 2 kHz, and 4 kHz).
    Results: Hearing results were better after Type III tympanoplasty than after Type IV tympanoplasty. After Type III (n = 70) and Type IV (n = 24) tympanoplasty, the respective mean A-B gaps were 16.4 +/- 7.2 dB and 20.1 +/- 5.6 dB, respectively. The mean A-B gap was significantly smaller after Type III tympanoplasty than after Type IV tympanoplasty (p &lt; 0.05). Regardless of the type of tympanoplasty, the postoperative A-B gap was greatest at 4 kHz.
    Conclusion: The mean A-B gap was smaller after Type III tympanoplasty than after Type IV tympanoplasty. The magnitude of the A-B gap was greatest at 4 kHz in both procedures. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

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  • Gelatin Hydrogel With Basic Fibroblast Growth Factor for Tympanic Membrane Regeneration Reviewed

    Nobuhiro Hakuba, Yasuhiko Tabata, Naohito Hato, Takashi Fujiwara, Kiyofumi Gyo

    OTOLOGY & NEUROTOLOGY   35 ( 3 )   540 - 544   2014.3

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    Hypothesis In this developmental research study that aimed to develop tympanic membrane regeneration therapy, we devised a method of sustained bFGF formulation release using gelatin hydrogel in a guinea pig eardrum perforation model.
    Background Basic fibroblast growth factor (bFGF) can promote perforation closure. In addition, several studies of bFGF formulations have used gelatin hydrogel-bFGF coupled electrostatically to a gelatin polymer. BFGF is released gradually as a result of degradation of the gelatin polymer, and studies have shown that the long-term pharmacologic effects of bFGF can be maintained.
    Methods Using a CO2 laser, total tympanic membrane perforations were created in 24 guinea pig ears and divided into 3 groups: the bFGF-gelatin hydrogel group(n = 8), the saline-gelatin hydrogel group (n = 8), and the control group (n = 8). Either a bFGF formulation or saline was impregnated into gelatin hydrogen and implanted into the perforated tympanic membrane.
    Results All ear drums of the control group showed large perforations at even the 30th postoperative day. The perforation persisted in 3 of 8 ears in the saline-gelatin hydrogel group, and the tympanic membranes that had achieved closure were thinned, whereas all ears in the bFGF-gelatin hydrogel group achieved closure of the perforation. In the ears in which a normal tympanic membrane had regenerated, histologic observation with hematoxylin and eosin staining revealed that, although mucosal and epithelial layer regeneration had occurred in the saline-gelatin hydrogel group, the bFGF-gelatin hydrogel group showed regeneration of the fibrous layer in addition to the other 2 layers.
    Conclusion These data suggest that hydrogel impregnated with bFGF induces regeneration of the tympanic membrane and can conservatively treat tympanic membrane perforation.

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  • Infantile inflammatory pseudotumor of the facial nerve as a complication of epidermal nevus syndrome with cholesteatoma Reviewed

    Naohito Hato, Mika Tsujimura, Taro Takagi, Masahiro Okada, Kiyofumi Gyo, Mikiko Tohyama, Hisamichi Tauchi

    AURIS NASUS LARYNX   40 ( 6 )   569 - 572   2013.12

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    The first reported case of facial paralysis due to an inflammatory pseudotumor (IPT) of the facial nerve as a complication of epidermal nevus syndrome (ENS) is herein presented. A 10-month-old female patient was diagnosed with ENS at 3 months of age. She was referred to us because of moderate left facial paralysis. Epidermal nevi of her left auricle extended deep into the external ear canal. Otoscopy revealed polypous nevi and cholesteatoma debris filling the left ear. Computed tomography showed a soft mass filling the ear canal, including the middle ear, and an enormously enlarged facial nerve. Surgical exploration revealed numerous polypous nevi, external ear cholesteatoma, and tumorous swelling of the facial nerve. The middle ear ossicles were completely lost. The facial paralysis was improved after decompression surgery, but recurred 5 months later. A second operation was conducted 10 months after the first. During this operation, facial nerve decompression was completed from the geniculate ganglion to near the stylomastoid foramen. Histological diagnosis of the facial nerve tumor was IPT probably caused by chronic external ear inflammation induced by epidermal nevi. The facial paralysis gradually improved to House-Blackmann grade III 5 years after the second operation. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

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  • Role of Nitric Oxide in the Onset of Facial Nerve Palsy by HSV-1 Infection Reviewed

    Naohito Hato, Hisashi Kohno, Hiroyuki Yamada, Hirotaka Takahashi, Kiyofumi Gyo

    JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY   139 ( 12 )   1339 - 1342   2013.12

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    IMPORTANCE Although herpes simplex virus type 1 (HSV-1) is a causative agent of Bell palsy, the precise mechanism of the paralysis remains unknown. It is necessary to investigate the pathogenesis and treatment of Bell palsy due to HSV-1 infection.
    OBJECTIVE This study elucidated the role of nitric oxide (NO) in the incidence of facial nerve paralysis caused by HSV-1 in mice and to evaluate the possible role of edaravone, a free radical scavenger, in preventing the paralysis.
    DESIGN, SETTING, PARTICIPANTS Sixty-two mice served as animal models of Bell palsy in this laboratory study conducted at an academic institution.
    INTERVENTIONS Levels of NO in the facial nerve were measured using high-performance liquid chromatography and absorption photometry. The incidence of facial palsy was assessed following administration of edaravone immediately after HSV-1 inoculation and daily for 11 days thereafter.
    MAIN OUTCOMES AND MEASURES The ratio of NO (inoculated side to control side) and incidence of facial palsy.
    RESULTS Before the onset of facial palsy, no substantial difference in the NO level was noted between the HSV-1-inoculated side and the control side. When facial palsy occurred, usually at 7 days after inoculation, the NO level was significantly higher on the inoculated side than on the control side. Following recovery from the palsy, the high NO level of the inoculated side decreased. No increase in the NO level was observed in animals without transient facial palsy. When edaravone was administered, the incidence of facial palsy decreased significantly.
    CONCLUSIONS AND RELEVANCE These findings suggest that NO produced by inducible NO synthase in the facial nerve plays an important role in the onset of facial palsy caused by HSV-1 infection, which is considered a causative virus of Bell palsy. Hato and colleagues elucidate the role of nitric oxide in HSV-1-related facial nerve paralysis in mice and evaluate the role of edaravone, a free radical scavenger, in preventing the paralysis.

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  • Liposome-encapsulated hemoglobin alleviates hearing loss after transient cochlear ischemia: An experimental study in the gerbil Reviewed

    Masahiro Okada, Akira T. Kawaguchi, Nobuhiro Hakuba, Jun Hyodo, Naohito Hato, Kiyofumi Gyo

    Neuroscience Letters   553   176 - 180   2013.10

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    The effects of liposome-encapsulated hemoglobin (LEH), an artificial oxygen carrier, were experimentally investigated in gerbils in the context of alleviation of hearing loss after transient cochlear ischemia. Animals were randomly assigned to receive 2mL/kg of either LEH (P50O2=15mmHg) or saline 1h after the experimental induction of 15min of ischemia. Sequential recordings of auditory brainstem response (ABR) showed that administration of LEH prevented hearing loss due to cochlear ischemia. The mean ABR threshold at 32kHz on day 1 was 21±7dB in the LEH group (n=6) and 45±6dB in the saline group (n=6). Thereafter, hearing impairment gradually improved up to day 7 in both groups. The animals were then subjected to histological study, which revealed that there was more substantial loss of the inner hair cells, but not the outer hair cells, in the saline group as compared to the LEH group. These results suggest that LEH is an efficient agent with regard to protection against hearing loss and underlying hair cell damager due to ischemic insult. © 2013 Elsevier Ireland Ltd.

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  • Prosaposin-derived peptide alleviates ischaemia-induced hearing loss Reviewed

    Takehiro Terashita, Shouichiro Saito, Hiroaki Nabeka, Naohito Hato, Hiroyuki Wakisaka, Tetsuya Shimokawa, Naoto Kobayashi, Kiyofumi Gyo, Seiji Matsuda

    ACTA OTO-LARYNGOLOGICA   133 ( 5 )   462 - 468   2013.5

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    Conclusion: An 18-mer peptide derived from the neurotrophic region of prosaposin (PS-pep) prevents hearing loss and cochlear damage due to transient cochlear ischaemia by activating an anti-apoptotic pathway. PS-pep is a potent candidate molecule for alleviating ischaemia-induced hearing loss. Objective: PS-pep was investigated for its protective effects against ischaemia-induced hearing loss and cochlear damage. Methods: Ischaemia was induced in both cochleae in Mongolian gerbils by pulling the ligatures around both vertebral arteries in an anterior direction using 5 g weights for 15 min. PS-pep was synthesized artificially and administered subcutaneously four times after the induction of transient cochlear ischaemia. Results: An increase in the auditory brainstem response threshold was alleviated in animals treated with 2.0 mg/kg PS-pep. Histological examinations conducted on day 7 showed that the loss of inner hair cells (IHCs) was more prominent than that of outer hair cells. Higher doses of PS-pep significantly alleviated IHC loss. An increase in the anti-apoptotic factor bcl-2 was also noted in the IHCs treated with PS-pep.

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  • Prosaposin-derived peptide alleviates ischaemia-induced hearing loss. Reviewed

    Terashita Takehiro, Saito Shouichiro, Nabeka Hiroaki, Hato Naohito, Wakisaka Hiroyuki, Shimokawa Tetsuya, Kobayashi Naoto, Gyo Kiyofumi, Matsuda Seiji

    Acta oto-laryngologica   133 ( 5 )   462 - 468   2013.5

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    An 18-merpeptide derived from the neurotrophic region of prosaposin (PS-pep) prevents hearing loss and cochlear damage due to transient cochlear ischaemia by activating an anti-apoptotic pathway. PS-pep is a potent candidate molecule for alleviating ischaemia-induced hearing loss.PS-pep was investigated for its protective effects against ischaemia-induced hearing loss and cochlear damage.Ischaemia was induced in both cochleae in Mongolian gerbils by pulling the ligatures around both vertebral arteries in an anterior direction using 5 g weights for 15 min. PS-pep was synthesized artificially and administered subcutaneously four times after the induction of transient cochlear ischaemia.An increase in the auditory brainstem response threshold was alleviated in animals treated with 2.0 mg/kg PS-pep. Histological examinations conducted on day 7 showed that the loss of inner hair cells (IHCs) was more prominent than that of outer hair cells. Higher doses of PS-pep significantly alleviated IHC loss. An increase in the anti-apoptotic factor bcl-2 was also noted in the IHCs treated with PS-pep.

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  • Treatment of Neural Anosmia by Topical Application of Basic Fibroblast Growth Factor-Gelatin Hydrogel in the Nasal Cavity An Experimental Study in Mice Reviewed

    Jumpei Nota, Hirotaka Takahashi, Nobuhiro Hakuba, Naohito Hato, Kiyofumi Gyo

    JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY   139 ( 4 )   396 - 400   2013.4

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    Importance: A new treatment of neural anosmia.
    Objective: To investigate the effects of basic fibroblast growth factor (bFGF)-gelatin hydrogel on recovery of neural anosmia in mice.
    Design: Anosmia was induced by intraperitoneal injection of 3-methylindole, 200 mg/kg. One week later, the animals underwent 1 of the following 3 procedures bilaterally: (1) group A: single-shot intranasal drip infusion of phosphate-buffered saline, (2) group B: single-shot intranasal drip infusion of bFGF, and (3) group C: placement of bFGF-gelatin hydrogel in the nasal cavity. The olfactory function of the animal was evaluated by the odor-detection test (ODT) 2 and 4 weeks later. Following the testing, the animal was killed, the thickness of the olfactory epithelium was measured, and the number of olfactory marker protein (OMP)-positive cells was counted.
    Setting: Research installation.
    Participants: Mice.
    Intervention: The placement of bFGF-gelatin hydrogel in the nasal cavity.
    Main Outcomes and Measures: An ODT, thickness of olfactory epithelium, the number of OMP-positive cells
    Results: The ODT proved that neural anosmia recovered in group C but not in groups A and B. Histologically, olfactory epithelium became thicker and the number of OMP-positive cells increased in group C, while such functional and histologic recovery was poor in groups A and B. These findings suggested that placement of bFGF-gelatin hydrogel in the nasal cavity was an efficient way to facilitate recovery of neural anosmia.
    Conclusions and Relevance: As a gelatin hydrogel degrades slowly in the body, bFGF is gradually released around the site of the lesion; thus, it constantly exerts its effects on neural regeneration.

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  • Re-implantation of the Rion E-type semi-implantable hearing aid: Status of long-term use and hearing outcomes in eight patients Reviewed

    Masahiro Komori, Naoaki Yanagihara, Yasuyuki Hinohira, Naohito Hato, Kiyofumi Gyo

    AURIS NASUS LARYNX   39 ( 6 )   572 - 576   2012.12

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    Objectives: The Rion Ehime (E)-type implantable hearing aid (IHA) is the first middle ear implant. We implanted 39 IHAs into 39 patients, and found that the IHA functioned well for &gt;15 years. So far, 28 IHAs have been removed because they stopped functioning. An IHA was re-implanted in 8 of the 28 cases. This study assessed the status of long-term use and hearing outcomes in the eight patients to confirm the safety and advantages of repeated implant operation.
    Methods: Current status and operational findings of the eight re-implantees and hearing outcomes were investigated by reviewing the patients' records.
    Results: Four of the eight cases still use their devices; all four originally suffered from cholesteatoma. In the remaining four cases, the devices stopped functioning 2.4-9.4 years after re-implantation; they suffered from chronic otitis media. Preoperative air and bone conduction hearing and IHA hearing 3 months after the first implantation were 61.1 +/- 13.1 dB, 40.6 +/- 11.3 dB, and 26.9 +/- 10.5 dB, respectively (n = 8). At the time of removal, they were 59.4 +/- 12.4 dB, 40.2 +/- 14.2 dB, and 42.9 +/- 14.9 dB, respectively. Three months after re-implantation, they were 60.4 +/- 14.6 dB, 37.3 +/- 14.7 dB, and 29.4 +/- 13.4 dB, respectively.
    Conclusions: Re-implantation of an IHA is beneficial and safe for patients. As the absence of active inflammation has a crucial effect on the period of use, re-implantation should be judged carefully after deterioration of the initial implant. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

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  • One-step nucleic acid amplification for detecting lymph node metastasis of head and neck squamous cell carcinoma Reviewed

    Hiroyuki Goda, Koh-ichi Nakashiro, Ryota Oka, Hiroshi Tanaka, Hiroyuki Wakisaka, Naohito Hato, Masamitsu Hyodo, Hiroyuki Hamakawa

    ORAL ONCOLOGY   48 ( 10 )   958 - 963   2012.10

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    Objectives: Lymph node stage is an important prognostic factor in head and neck squamous cell carcinoma (HNSCC). We previously reported the clinical usefulness of sentinel lymph node biopsy diagnosed by genetic analysis using quantitative RT-PCR. However, this method takes about 3 h. In this study, we attempted to develop a more efficient method for the intraoperative genetic detection of lymph node metastasis in HNSCC.
    Materials and methods: A total of 312 lymph nodes (65 patients) were diagnosed by the one-step nucleic acid amplification (OSNA) method using GD-100. OSNA consists of a short homogenization step followed by amplification of cytokeratin 19 (CK19) mRNA directly from the lysate. Each lymph node was divided into two to diagnose metastasis. One half was used for the OSNA assay, and the other was subjected to semi-serial sectioning, sliced at 200-mu m intervals and examined by H&E and cytokeratin AE1/AE3 immunohistochemical staining. The accuracy of OSNA assay was evaluated based on histopathological diagnosis.
    Results: Sixty-one of 312 lymph nodes were pathologically metastasis-positive. The overall concordance rate between the OSNA assay using breast cancer criteria and histopathology was 94.2%. The optimal cutoff for the copy number of CK19 mRNA in assessing lymph node metastasis of HNSCC was 300 copies/mu l, which had the highest diagnostic accuracy (95.2%). The OSNA assay can be completed within 30 min.
    Conclusion: The OSNA assay, which shows high sensitivity and specificity, suggests the possibility to be used as a novel tool for the genetic detection of lymph node metastasis in HNSCC patients. (C) 2012 Elsevier Ltd. All rights reserved.

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  • Objective assessment of the severity of unilateral facial palsy using OKAO Vision (R) facial image analysis software Reviewed

    Naoki Sawai, Naohito Hato, Nobuhiro Hakuba, Hirotaka Takahashi, Masahiro Okada, Kiyofumi Gyo

    ACTA OTO-LARYNGOLOGICA   132 ( 9 )   1013 - 1017   2012.9

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    Conclusion: Severity of ipsilateral facial palsy (UFP) can be assessed objectively by use of OKAO Vision (R). Facial symmetry percentage (FSP) values were well correlated with the results by two conventional grading systems. Objectives: To introduce the basic principle of facial motion analysis using OKAO Vision (R), to represent the data measured in patients with UFP, and to show the correlation between the severity of facial palsy assessed by this method and conventional systems. Methods: Two independent facial motions, closing the eyes and grinning, were recorded with a video camera. By comparing the movement distances between right and left sides, the eye symmetry ratio (ESR) and grin symmetry ratio (GSR) were obtained. The degree of UFP was assessed by FSP, which was calculated by the formula: FSP = (ESR + GSR)/2 x 100 (%). FSP was measured in 12 normal volunteers and in 30 patients with UFP. Results: In patients with UFP, varying degrees of FSP were noted corresponding to the grade of facial palsy. The severity of facial palsy assessed by FSP was closely correlated with the Yanagihara score (r = 0.88, p &lt; 0.05) and was inversely related to the House-Brackmann grade (r = -0.90, p &lt; 0.05).

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  • Myogenin expression in facial muscle following damage to the facial nerve Reviewed

    Masato Teraoka, Naohito Hato, Hirotaka Takahashi, Hayato Komobuchi, Naoki Sawai, Masahiro Okada, Nobuhiro Hakuba

    ACTA OTO-LARYNGOLOGICA   132 ( 7 )   783 - 787   2012.7

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    Conclusion: Gene analysis of facial muscle may be a promising way to detect denervation of facial muscle, helping to determine the prognosis of a facial palsy early in its progression. Objectives: In the treatment of intratemporal facial palsy, early diagnosis of neural damage is important in deciding about therapeutic modalities. In this study, we investigated the relationship between the severity of facial palsy and the level of myogenin expressed in the facial muscle. Methods: The animals were divided into two groups, depending on whether the facial nerve was resected or compressed. Expression of myogenin mRNAwas examined using real-time PCR and in situ hybridization of the facial muscle following the nerve damage. Results: Increased expression of myogenin was observed in the nerve resection group, while no such increase was seen in the nerve compression group. In situ hybridization indicated that myogenin was expressed exclusively in satellite cells around the denervated muscle fibers.

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  • 中耳内に限局した髄膜腫の一例

    竹田 将一郎, 羽藤 直人, 岡田 昌浩, 暁 清文

    Otology Japan   22 ( 3 )   238 - 243   2012.7

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    髄膜腫は原発性脳腫瘍の中では最も頻度の高い組織型であるが、頭蓋内病変を伴わず、頭蓋外に孤立して見つかることは稀である。今回我々は、中耳内に限局する髄膜腫の1例を経験したので、報告する。症例は50歳女性。主訴は左耳閉感。近医耳鼻咽喉科にて加療されるも改善なく、近くの総合病院耳鼻咽喉科を受診。MRIにて中耳腫瘍疑われ平成21年11月27日愛媛大学耳鼻咽喉科を受診。左鼓膜後象限に白色塊が透見されたが、陥凹や穿孔認めなかった。標準純音聴力検査では、聴力に左右差なく正常範囲内であった。MRIにて左上鼓室〜乳突洞口にT2強調像でやや高信号、造影効果のあるMassを認めた。また、CTでも同部位に軟部組織陰影を認めるも、頭蓋内には髄膜腫を疑う所見はなかった。平成22年2月16日経乳突洞的に腫瘍生検を施行。Meningioma;WHO grade Iと診断された。平成22年4月16日、左中耳腫瘍摘出術を施行した。明らかな硬膜や神経との連続性は認めず全摘出しえた。特記すべき後遺症や再発はなく、現在愛媛大学耳鼻咽喉科外来にて経過観察中である。(著者抄録)

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  • 腫瘍性病変が疑われた特発性眼窩内血腫の一例

    能田 淳平, 高橋 宏尚, 岡田 昌浩, 羽藤 直人, 暁 清文

    日本鼻科学会会誌   51 ( 2 )   115 - 118   2012.7

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    72歳女。左眼球突出、左眼痛を主訴とした。近眼科医を受診し、画像所見で左眼窩腫瘍が指摘されて紹介となった。特記すべき既往歴、明らかな外傷歴はなかった。CTでは、左眼窩内側壁に腫瘍と、近接した部位に骨欠損が疑われたが、MRIでは造影効果は認めなかった。シンチでの異常集積も認めず、腫瘍マーカーは全て陰性であった。経過観察を行ったが軽快せず、悪性腫瘍も否定できないため、確定診断を目的に、左内視鏡下鼻内副鼻腔手術(ESS)による生検を施行した。眼窩骨膜を切開して腫瘍に到達したが、腫瘍内部は血腫を思わせる貯留液であった。内容物を可及的に吸引し、手術を終了した。病理所見では検体内に上皮成分はなく、赤血球、フィブリンとわずかな慢性炎症細胞を認めるのみで、特発性眼窩内血腫と診断した。術後、視力障害等の合併症はなく、眼球突出は軽快した。術後約2年の時点で再発は認めず、経過良好である。

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  • Facial Nerve Decompression Surgery Using bFGF-Impregnated Biodegradable Gelatin Hydrogel in Patients with Bell Palsy Reviewed

    Naohito Hato, Jumpei Nota, Hayato Komobuchi, Masato Teraoka, Hiroyuki Yamada, Kiyofumi Gyo, Naoaki Yanagihara, Yasuhiko Tabata

    OTOLARYNGOLOGY-HEAD AND NECK SURGERY   146 ( 4 )   641 - 646   2012.4

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    Objective. Basic fibroblast growth factor (bFGF) promotes the regeneration of denervated nerves. The aim of this study was to evaluate the regeneration-facilitating effects of novel facial nerve decompression surgery using bFGF in a gelatin hydrogel in patients with severe Bell palsy.
    Study Design. Prospective clinical study.
    Setting. Tertiary referral center.
    Subjects and Methods. Twenty patients with Bell palsy after more than 2 weeks following the onset of severe paralysis were treated with the new procedure. The facial nerve was decompressed between tympanic and mastoid segments via the mastoid. A bFGF-impregnated biodegradable gelatin hydrogel was placed around the exposed nerve. Regeneration of the facial nerve was evaluated by the House-Brackmann (H-B) grading system. The outcomes were compared with the authors' previous study, which reported outcomes of the patients who underwent conventional decompression surgery (n = 58) or conservative treatment (n = 43).
    Results. The complete recovery (H-B grade 1) rate of the novel surgery (75.0%) was significantly better than the rate of conventional surgery (44.8%) and conservative treatment (23.3%). Every patient in the novel decompression surgery group improved to H-B grade 2 or better even when undergone between 31 and 99 days after onset.
    Conclusion. Advantages of this decompression surgery are low risk of complications and long effective period after onset of the paralysis. To the authors' knowledge, this is the first clinical report of the efficacy of bFGF using a new drug delivery system in patients with severe Bell palsy.

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  • Galectin-7 as a Marker of Cholesteatoma Residue and Its Detection During Surgery by an Immunofluorescent Method-A Preliminary Study Reviewed

    Daiki Takagi, Naohito Hato, Masahiro Okada, Nobuhiro Hakuba, Kiyofumi Gyo, Kazuhiro Shigemoto, Toshifusa Toda, Masahito Ogasawara, Kenji Kameda

    OTOLOGY & NEUROTOLOGY   33 ( 3 )   396 - 399   2012.4

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    Objectives: To visualize the distribution of galectin-7 in middle ear cholesteatomas using an immunofluorescent method and to establish whether galectin-7 can be used as a marker of cholesteatoma residue at the time of operation.
    Methods: Middle ear cholesteatomas were obtained at surgery from 30 patients. Samples were frozen and preserved in a freezer until histological study. After serial sectioning with a cryostat, 2 of the specimens were processed with primary antibody and Zenon rabbit immunoglobulin G labeling kits. After sufficient reaction time, the samples were observed using a confocal laser microscope. In the remaining 28 specimens, the cholesteatoma was treated as 1 block and stained with the same solution. It was then observed using a fluorescent stereomicroscope.
    Results: Confocal microscopic analyses showed that galectin-7 was distributed in the cholesteatoma matrix. Because this area strongly stained green, it was easily recognized using a confocal laser microscope. In the stereomicroscopic study using the 1-block specimen in which the cholesteatoma was processed together with the surrounding granulation and mucosal tissue, only the matrix and overlying debris was yellow-green in response to excitation by light; the surrounding granulation and mucosal tissues did not respond in 7 specimens. In the remaining 21 specimens, the whole sample was composed of cholesteatoma and responded well to excitation by light. These findings suggest that galectin-7 might be a useful marker of cholesteatoma residue that can be visualized using this immunofluorescent method.
    Conclusion: Because residual cholesteatoma matrix is considered to be one of the main causes of cholesteatoma recurrence, staining with galectin-7 at the time of operation would be a promising way to facilitate complete removal of the residue.

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  • Liposome-Encapsulated Hemoglobin Alleviates Hearing Loss After Transient Cochlear Ischemia and Reperfusion in the Gerbil Reviewed

    Masahiro Okada, Akira T. Kawaguchi, Nobuhiro Hakuba, Shoichiro Takeda, Jun Hyodo, Kiyohiro Imai, Naohito Hato, Kiyofumi Gyo

    ARTIFICIAL ORGANS   36 ( 2 )   178 - 184   2012.2

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    To test liposome-encapsulated hemoglobin (LEH) in transient cochlear ischemia/reperfusion as a model of sudden deafness, Mongolian gerbils were randomly assigned to receive 2 mL/kg of either low-affinity LEH (l-LEH, P50O2 = 40 mm Hg), high-affinity LEH (h-LEH, P50O2 = 10 mm Hg), homologous red blood cells (RBCs), or saline (each group n = 6) 30 min before 15-min occlusion of the bilateral vertebral arteries and reperfusion. Sequential changes in hearing were assessed by auditory brain response 1, 4, and 7 days after ischemia/reperfusion, when the animals were sacrificed for pathological studies. h-LEH was significantly more protective than l-LEH in suppressing hearing loss, in contrast to RBC or saline treatment, at 8, 16, and 32 kHz, where hearing loss was most severe (P &lt; 0.05 between any two groups) on the first day after cochlear ischemia/reperfusion. Thereafter, hearing loss improved gradually in all groups, with a significant difference among groups up to 7 days, when morphological studies revealed that the inner hair cells but not the outer hair cells, were significantly lost in the groups in the same order. The results suggest that pretreatment with h-LEH is significantly more protective than l-LEH in mitigating hearing loss and underlying pathological damage, in contrast to transfusion or saline infusion 7 days after transient cochlear ischemia/reperfusion.

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  • Protection Against Ischemic Cochlear Damage by Intratympanic Administration of AM-111 Reviewed

    Yoshinori Omotehara, Nobuhiro Hakuba, Naohito Hato, Masahiro Okada, Kiyofumi Gyo

    OTOLOGY & NEUROTOLOGY   32 ( 9 )   1422 - 1427   2011.12

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    Objective: AM-111, a cell-permeable peptide inhibitor of c-Jun N-terminal kinase, was investigated for its protective effects against ischemic damage of the cochlea in gerbils.
    Methods: Transient cochlear ischemia was introduced in animals by occluding the bilateral vertebral arteries for 15 minutes. Then, 10 mu l of AM-111 at a concentration of 1, 10, or 100 mu M in hyaluronic acid gel formulation was applied onto the round window 30 minutes after the insult. Gel without active substance was used in a control group. Treatment effects were evaluated by auditory brainstem response (ABR) and histology of the inner ear.
    Results: In controls, transient cochlear ischemia caused a 25.0 +/- 5.0 dB increase in the ABR threshold at 8 kHz and a decrease of 13.3 +/- 2.3% in inner hair cells at the basal turn on Day 7. Ischemic damage was mild at 2 and 4 kHz. When the animals were treated with AM-111 at 100 mu M, cochlear damage was significantly reduced: the increase in ABR threshold was 3.3 +/- 2.4 dB at 8 kHz, and the inner hair cell loss was 3.1 +/- 0.6% at the basal turn on Day 7. The effects of AM-111 were concentration dependent: 100 mu M was more effective than 1 or 10 mu M.
    Conclusion: Direct application of AM-111 in gel formulation on the round window was effective in preventing acute hearing loss because of transient cochlear ischemia.

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  • Facial Nerve Decompression Surgery in Patients With Temporal Bone Trauma: Analysis of 66 Cases Reviewed

    Naohito Hato, Junpei Nota, Nobumitsu Hakuba, Kiyofumi Gyo, Naoaki Yanagihara

    JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE   71 ( 6 )   1789 - 1792   2011.12

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    Background: In the treatment of facial nerve paralysis after temporal bone trauma, it is important to appropriately determine whether nerve decompression surgery is indicated. The aim of this study was to examine the efficacy of facial nerve decompression surgery according to fracture location and the ideal time for surgery after trauma by analyzing the therapeutic outcome of traumatic facial nerve paralysis.
    Methods: In total, 66 patients with facial nerve paralysis after temporal bone trauma who were treated at our institution between 1979 and 2009 were studied retrospectively. The patients were divided into five subgroups, according to the fracture location and the period of time between trauma and surgery.
    Results: The number of patients who achieved complete recovery of House-Brackmann (H-B) grade 1 was 31 of 66 (47.0%). There was no difference in therapeutic outcomes among the subgroups classified by fracture location. The rate of good recovery to H-B grade 1 or 2 in patients undergoing decompression surgery within 2 weeks after trauma reached 92.9%, resulting in a significantly better outcome than that of patients undergoing later decompression surgery (p &lt; 0.01).
    Conclusions: The results of this study demonstrated that the ideal time for decompression surgery for facial nerve paralysis after temporal bone fracture was the first 2 weeks after trauma in patients with severe, immediate-onset paralysis. Our study also showed that surgery should be performed within 2 months at the latest. These findings provide useful information for patients and help to determine the priority of treatment when concomitant disease exists.

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  • Clinical features and outcomes of four patients with invasive fungal sinusitis Reviewed

    Hirotaka Takahashi, Yasuyuki Hinohira, Naohito Hato, Hiroyuki Wakisaka, Jun Hyodo, Toru Ugumori, Kiyofumi Gyo

    AURIS NASUS LARYNX   38 ( 2 )   289 - 294   2011.4

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    Objective: The frequency of invasive fungal sinusitis (IFS) has increased in recent years with the use of steroids, onset of diabetes mellitus, and the administration of antibacterial agents. We report on the clinical features and outcomes of four patients with IFS involving the cavernous sinus and orbit. Prognostic factors facilitating an early diagnosis are described, and the usefulness of combination therapy involving systemic administration of antifungal agents and surgical intervention is discussed.
    Methods: We treated four patients with IFS between March 2003 and November 2007 at Ehime University Hospital. Patients were two males and two females, aged from 61 to 74 years (mean 67.8 years).
    Results: With regard to clinical symptoms, headache was observed in all patients, and cranial nerve paralysis (visual disturbance, blindness, cheek paresthesia) was seen in 3 patients. beta-D-Glucan levels in four patients were high compared with normal values. Aspergillus was histopathologically identified from biopsy specimens in all patients. One patient was complicated with Candida in addition to the Aspergillus infection. Orbital exenteration and ESS were performed in 2 patients as surgical debridement. In all patients, systemic administration of antifungal agents was initiated after surgery.
    Conclusions: All patients received strategic treatment with surgery and systemic administration of anti-fungal agents. The single fatality was due to train infarction caused by the spread of Aspergillus, and the remaining three patients are still alive. Our observations in these patients suggest that early diagnosis and strategic treatment may improve the prognosis of IFS. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

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  • Local hypothermia in the treatment of idiopathic sudden sensorineural hearing loss Reviewed

    Naohito Hato, Jun Hyodo, Shoichiro Takeda, Daiki Takagi, Masahiro Okada, Nobuhiro Hakuba, Kiyofumi Gyo

    AURIS NASUS LARYNX   37 ( 5 )   626 - 630   2010.10

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    Objective: The additive effects of local hypothermia and restricted activity in the treatment of idiopathic sudden sensorineural hearing loss (ISSHL) were investigated by case-matched study as a multicenter (13 hospitals) pilot trial.
    Patients and methods: In a preliminary experiment, we evaluated the effects of cooled water pillow (15 degrees C). Cooling the neck and mastoid with the pillow decreased the tympanic membrane temperature for 1.4 degrees C in 2 h without causing uncomfortable sensation or frostbite. In this study, 86 patients with ISSHL were enrolled in the hypothermic group, which received hypothermic treatment with restricted activity in addition to medication, and 86 ISSHL patients constituted the control group, which received the same medication but without cooling and rest. Control patients were selected retrospectively from case records by matching the experimental patients with respect to age, gender, days until the start of treatment, hearing loss, shape of the audiogram, and accompanying vertigo. The patients in the hypothermic group were admitted and treated with a cooled water pillow for 48 h, in addition to conventional drug treatment (e.g., 60 mg of prednisone) for 7 days. The water pillow was cooled to 15 degrees C and was changed 4-5 times per day. The patients used the water pillow for the first 48 h after admission, with restricted activity. The control patients received only the medications.
    Results: Hearing results were evaluated using criteria proposed by the Sudden Sensorineural Hearing Loss Research Group of the Japanese Ministry of Health and Welfare. The recovery rates were judged 6 months after onset. The recovery rate in the hypothermic group was significantly (p &lt; 0.05) better than that in the control group. When the comparison was limited to younger patients, the use of the cooled water pillow was effective in facilitating the recovery of hearing.
    Conclusions: Hearing restoration in ISSHL may be improved by adding mild hypothermia and restricted activity to the conventional treatment. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

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  • Long-term results with the Rion E-type semi-implantable hearing aid Reviewed

    Masahiro Komori, Naoaki Yanagihara, Yasuyuki Hinohira, Naohito Hato, Kiyofumi Gyo

    OTOLARYNGOLOGY-HEAD AND NECK SURGERY   143 ( 3 )   422 - 428   2010.9

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    OBJECTIVE: The Rion implantable hearing aid (IHA) Ehime (E)-type was developed for ears with middle ear diseases. This study focused on the current status of the patients, device problems, postoperative difficulties, and preventive measures against them.
    STUDY DESIGN: Case series with chart review.
    SETTING: Tertiary referral hospital.
    SUBJECTS AND METHODS: Subjects were 30 patients who were implanted with the IHA E-type between 1984 and 1997 and followed up for more than 10 years. Current status of IHA implantees, incidents of device problems, and postoperative troubles and hearing outcomes were reviewed.
    RESULTS: Eleven patients (36.7%) still use the original device. The average period of use was 16.6 +/- 3.3 years (21 years at most). The incidence of problems was lower with the second version of the device compared to the first version. Frequencies of the troubles were related to the types of original ear diseases: even of 17 cases with chronic otitis media (41.2%), two of seven cases with cholesteatoma (28.6%), and two of six cases with tympanosclerosis (33.3%). No cholesteatoma occurred after surgical procedures (i.e., external ear canal closure and tympanic membrane lateralized) (P = 0.06). The device was exposed through a retroauricular skin fistula where the internal coil had been implanted. Significantly fewer infections were observed when the two-stage operation was used (P &lt; 0.01).
    CONCLUSION: For long-term success in implantation of the IHA, careful control of middle ear inflammation and measures against eustachian tube dysfunction are required in addition to technological advancements. (C) 2010 American Academy of Otolaryngology Head and Neck Surgery Foundation. All rights reserved.

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  • One-and-a-half症候群ならびに顔面神経麻痺で発症した多発性硬化症例

    岡田 昌浩, 澤井 尚樹, 兵頭 純, 羽藤 直人, 暁 清文

    耳鼻咽喉科臨床   103 ( 6 )   517 - 521   2010.6

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    35歳男。複視、ふらつき、および左顔面神経麻痺で末梢性顔面神経麻痺と診断され、ステロイドと抗ウイルス薬を処方され紹介受診となった。鼓膜所見に異常はなく自発眼振は左方注視時の両眼の注視麻痺、右方注視時の左眼内障害および右眼の右向き水平性眼振を認めた。水直注視、輻輳は正常で典型的なOHA症候群所見を認めた。さらに左末梢性顔面神経麻痺を認め、麻痺スコアは高いが他の脳神経症状、四肢の運動障害や感覚障害、失調も認めなかった。MRIでは橋背側にT2強調画像、FLAIRで高信号を呈する病変を認め、Gd造影では淡く造影された側脳室周囲にも高信号領域が多発していた。以上より、8年前にも顔面神経麻痺を罹患していることから、多発性硬化症と診断した。ステロイド投与で顔面神経麻痺、ふらつきは軽快し、眼球運動の左右注視は可能となったが、左方注視麻痺が残存したため、ステロイドパルス療法を行った。眼球運動障害は徐々に改善し左外転麻痺も消失し再発は認めていない。

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  • Facial Synkinesis After Experimental Compression of the Facial Nerve Comparing Intratemporal and Extratemporal Lesions Reviewed

    Hiroyuki Yamada, Naohito Hato, Shingo Murakami, Nobumitsu Honda, Hiroyuki Wakisaka, Hirotaka Takahashi, Kiyofumi Gyo

    LARYNGOSCOPE   120 ( 5 )   1022 - 1027   2010.5

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    Objectives/Hypothesis: The anatomical configuration of the facial nerve differs greatly between the intratemporal and extratemporal portions. The purpose of this study was to investigate the incidence of facial synkinesis and misdirection on clamping the facial nerve at the intratemporal or extratemporal portion of the facial nerve in guinea pigs.
    Study Design: Experimental study.
    Methods: In 16 guinea pigs, the facial nerve was clamped with microsurgical needle forceps at either the extratemporal (group A) or intratemporal (group B) segment. Facial nerve function was evaluated 1 week postoperatively using electroneurography (ENoG), and the incidence of facial synkinesis was evaluated 15 weeks postoperatively using an evoked blink reflex test. Fifteen weeks postoperatively, two retrograde fluorescent tracers (Dil [1-1'-dioctodecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate] and True Blue) were injected into the facial muscles to observe reorganization of the facial nucleus.
    Results: No significant difference in the ENoG threshold was observed between groups A and B. In group A, none of the animals developed facial synkinesis and the somatotopic organization of the facial nucleus was not disturbed. In contrast, synkinesis occurred and the somatotopic organization was disturbed in group B.
    Conclusions: A lack of funicular structure within the intratemporal facial nerve increases the possibility of misdirected regenerating axons and synkinesis.

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  • Basic fibroblast growth factor combined with biodegradable hydrogel promotes healing of facial nerve after compression injury: An experimental study Reviewed

    Hayato Komobuchi, Naohito Hato, Masato Teraoka, Hiroyuki Wakisaka, Hirotaka Takahashi, Kiyofumi Gyo, Yasuhiko Tabata, Masaya Yamamoto

    ACTA OTO-LARYNGOLOGICA   130 ( 1 )   173 - 178   2010.1

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    Conclusion. Topical application of basic fibroblast growth factor (bFGF) hydrogel facilitates faster healing from traumatic facial paralysis due to continuous release of bFGF. Objectives. bFGF is considered a potent agent to facilitate recovery from neuronal damage, however, exogenously applied bFGF does not work well because of its short acting time. To enhance the effects in vivo, we developed a new drug delivery system by embedding bFGF in a gelatin hydrogel that degrades slowly. In this study, the effects of bFGF-hydrogel on traumatic facial nerve paralysis were investigated in guinea pigs. Methods. The intratemporal facial nerve was exposed and clamped at the vertical portion using micro needle forceps. The animals were then subjected to one of the following three procedures: group A, no further treatment; group B, one-shot application of bFGF to the nerve; and group C, application of bFGF-hydrogel instead. Six weeks later, facial nerve functions were evaluated by three test batteries: observation of facial movements, electrophysiological testing, and histological study. Results. The results for groups A and B were similar in the three tests, indicating that one-shot application of bFGF did not benefit facial nerve recovery. In contrast, group C achieved better results in all tests.

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  • G0200-1-2 Development of implantable hearing aid using giant magnetostrictive material : Investigation of the frequency response of a vibrator installed in human cadavers

    HARASHIMA Tatsunari, KOIKE Takuji, HOMMA Kyoji, AOKI Michihito, HATO Naoto, KANZAKI Syo

    The proceedings of the JSME annual meeting   2010   3 - 4   2010

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    In this study, a new subcutaneously implanted bone-conduction hearing aid with an external unit and an internal unit is proposed. A prototype transducer was made and installed in a cadaver head, and the performance of the transducer was investigated when the method of installation (number of fixed point) of the transducer was changed. The frequency response of the amplitude of the cadaver generated by the transducer depended on the number of the fixed point. The ear-canal sound pressure generated by the transducer with single point fixation was higher than that with two point fixation. These results suggest that single point fixation method is suitable for installing the transducer to the cadaver.

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  • Assessment of an implanted bone-conduction hearing aid performance by experiments using human cadavers

    Harashima Tatsunari, Fujii Makiko, Koike Takuji, Aoki Michihito, Homma Kyoji, Hato Naohito, Kanzaki Sho

    17 - 23   2010

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    &lt;p&gt;In this study, a new subcutaneously implanted bone-conduction hearing aid is proposed. A vibrator unit of the hearing aid consists of two coils and an element made of giant magnetostrictive material (GMM). For the first stage in the development of the new boneconduction hearing aid, fundamental properties of the GMM vibrator were examined. In addition, a prototype transducer was made and installed in cadaver heads, and the performance of the prototype transducer was investigated. The output of the prototype transducer was linearly increased with increasing the input current. The frequency response varied depends on the cadavers. These results suggest that the gain of our hearing aid can be controlled by changing the input current, but individual differences of patients should be considered.&lt;/p&gt;

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  • Ischemic tolerance in the cochlea Reviewed

    Shoichiro Takeda, Ryuji Hata, Fang Cao, Tadashi Yoshida, Nobuhiro Hakuba, Naohito Hato, Kiyofumi Gyo

    NEUROSCIENCE LETTERS   462 ( 3 )   263 - 266   2009.9

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    Ischemic tolerance in the cochlea was investigated in a gerbil model of cochlear ischemia. Transient cochlear ischemia was produced by extracranial occlusion of the bilateral vertebral arteries. The gerbils were divided into two groups; single ischemia group and double ischemia group. In the single ischemia group, animals were subjected to lethal cochlear ischemia for 15 min. In the double ischemia group, animals were subjected to sublethal cochlear ischemia for 2 min at 2 days before lethal ischemia for 15 min. Consequently, sublethal ischemia prevented lethal ischemia-induced hair cell degeneration and ameliorated hearing impairment, suggesting ischemic tolerance in the cochlea. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

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  • Glutamate agonist causes irreversible degeneration of inner hair cells Reviewed

    Jun Hyodo, Nobuhiro Hakuba, Naohito Hato, Shoichirou Takeda, Masahiro Okada, Yoshinori Omotehara, Kiyofumi Gyo

    NEUROREPORT   20 ( 14 )   1255 - 1259   2009.9

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    Glutamate neurotoxicity in cochlear hair cells was investigated by administering the glutamate agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) into the scala tympani of Mongolian gerbils. AMPA administration caused the formation of large number of vacuoles in the inner hair cells (IHCs) and dendritic terminals. The number of degenerated hair cells was counted using rhodamine-phalloidin and Hoechst 33342 staining. The administration of 50 mu M AMPA caused reversible elevation of the auditory brainstem response threshold without loss of IHCs. In contrast, 200 mu M AMPA induced a substantial elevation of the auditory brainstem response threshold with the characteristic disappearance of IHCs. As cochlear ischemia involves excessive glutamate release, these results suggest that an elevated glutamate level in the cochlea is responsible for the progressive IHC death related to ischemic injury. NeuroReport 20:1255-1259 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

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  • Pharyngolaryngeal Stenosis Caused by Cicatricial Pemphigoid

    NISHIKUBO K., Hyodo Masamitsu, Okada Masahiro, Hato Naohito

    Pract.Otol. (Kyoto)   102 ( 2 )   88 - 89   2009.2

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  • J0204-2-4 Evaluation of the vibration force generated by a bone-conduction implantable hearing aid using giant magnetostrictive material

    KOIKE Takuji, YAMAMOTO Kensei, HARASHIMA Tatsunari, AOKI Michito, HOMMA Kyoji, HATO Naoto, KANZAKI Sho

    The proceedings of the JSME annual meeting   2009   217 - 218   2009

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    In this study, a new subcutaneously implanted bone-conduction hearing aid with an external unit and an internal unit is proposed. The internal unit consists of a receiving coil, a driving coil, and a vibrator made of giant magnetostrictive material (GMM). AM signals were applied to the internal unit through mutual induction between a transmitting coil and the receiving coil, and the force generated by the GMM vibrator was measured with a piezoelectric force sensor. The high-frequency carrier signal was efficiently transmitted from the transmitting coil to the receiving coil, and the force with a component of audible frequency corresponding to the modulating frequency was generated with high intensity. This result suggests that the GMM vibrator had a function of self-demodulation, and a simple structured implanted bone-conduction hearing aid can be developed using GMM.

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  • Congenital cholesteatoma: a clinical study in 59 patients Reviewed

    J. Hyodo, H. Sato, N. Hato, K. Gyo

    OTITIS MEDIA 2009: 6TH EXTRAORDINARY INTERNATIONAL SYMPOSIUM ON RECENT ADVANCES IN OTITIS MEDIA   143 - 147   2009

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    We analyzed the clinical features of congenital cholesteatoma (CC) in 59 patients of our clinic. We examined the opportunity of diagnosis, location, surgical procedure and incidence of recurrence. CC was identified by various opportunities; during examination of hearing loss in 3, during treatment of acute otitis media in 29, during regular infant health examination in 10, and during examination of diseases other than ear disorder in 17. Locations of CC were anterior-superior quadrant (ASQ) in 19, posterior-superior quadrant (PSQ) in 20, expanding to the attic or mastoid antrum (invasive type) in 18, and multiple in 2. Surgical procedures were transcanal approach in 32 and Canal wall up tympanoplasty in 27. Recurrence occurred in 11 of 55. Recurrent rate was high in PSQ, invasive and multiple type. These results suggest that regular health check-up including otoscopic examination would be essential for early detection. Postoperative follow-up is important in the treatment of CC because of high incidence of recurrence.

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  • Bilateral and recurrent facial palsy Reviewed

    Naoki Sawai, Naohito Hato, Masato Teraoka, Hayato Komobuchi, Hirotaka Takahashi, Kiyofumi Gyo

    Practica Oto-Rhino-Laryngologica   102 ( 3 )   191 - 195   2009

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    Some facial palsy patients develop bilateral and/or recurrent facial palsy. To clarify the characteristic of bilateral and recurrent facial palsy, we retrospectively investigated 193 patients with bilateral and recurrent facial palsy in the 3385 patients who were treated for facial palsy during the past 3 decades. Among the 193 cases, 62 patients had ipsilateral recurrent palsy, 25 patients had bilateral simultaneous palsy, 88 patients had bilateral alternative palsy, and 18 patients had bilateral recurrent palsy. The major cause of palsy was Bell's palsy, and it accounted for 84. 5 % (163/193). Traumatic palsy, Guillain-Barré syndrome and facial schwannoma were rare, with rates below 3%. Therefore, the 163 patients with Bell's palsy were further investigated, and the following characteristic were found. (1) Patients with bilateral alternative palsy were more frequently associated with diabetes mellitus and hypertension, and patients with bilateral recurrent palsy were more frequently associated with diabetes mellitus than patients who had a single ipsilateral palsy. (2) The age at the first episode in patients with bilateral recurrent palsy and ipsilateral recurrent palsy was significantly younger than that in those without recurrent palsy.

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  • Hyperbaric oxygen therapy for chronic otitis media caused by mrsa: A case report Reviewed

    Daiki Takagi, Naohito Hato, Jun Hyodo, Kiyofumi Gyo

    Practica Oto-Rhino-Laryngologica   102 ( 11 )   911 - 915   2009

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    A 34-year-old man seem for bilateral hearing loss and headache due to intractable chronic otitis media (OMC) caused by methicillin-resistant Staphylococcus aureus (MRSA). He had a OMC recurrence despite microsurgery, irrigation, and antibiotics. After conventional treatment, we attempted hyperbaric oxygen therapy (HBO), which succeeded in symptoms after 8 attempts. His hearing recovered completely. This case is, to our knowledge, the first to demonstrate HBO efficacy in treating intractable OMC. We assume that HBO encouraged antibacterial oxidation and new capillary formation in wound healing.

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  • Insulin-like growth factor I treatment via hydrogels rescues cochlear hair cells from ischemic injury Reviewed

    Takashi Fujiwara, Naohito Hato, Takayuki Nakagawa, Yasuhiko Tabata, Tadashi Yoshida, Hayato Komobuchi, Shoichiro Takeda, Jun Hyodo, Nobuhiro Hakuba, Kiyofumi Gyo

    NEUROREPORT   19 ( 16 )   1585 - 1588   2008.10

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    This study was designed to investigate the protective effects of recombinant human insulin-like growth factor I (rhIGFI), applied locally via a hydrogel, against ischemic damage of the cochleae in gerbils. A hydrogel was immersed in rhIGFI or saline and was applied on the round window membrane 30 min after the ischemia. Local rhIGFI treatment significantly reduced the elevation of auditory brain responses thresholds at a frequency of 8kHz on days 1, 4, and 7 after ischemia. A histological analysis revealed increased survival of inner hair cells in the animals treated with rhIGFI via the hydrogel 7 days after ischemia. These findings showed that local rhIGFI application using a hydrogel has the potential to protect the cochleae from ischemic injury. NeuroReport 19:1585-1588 (C) 2008 Wolters Kluwer Health Lippincott Williams & Wilkins.

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  • Myasthenia gravis experimentally induced with muscle-specific kinase Reviewed

    Kazuhiro Shigemoto, Sachiho Kubo, Chen Jie, Naohito Hato, Yasuhito Abe, Norifumi Ueda, Naoto Kobayashi, Kenji Kameda, Katsumi Mominoki, Atsuo Miyazawa, Akihito Ishigami, Seiji Matsuda, Naoki Maruyama

    MYASTHENIA GRAVIS AND RELATED DISORDERS: 11TH INTERNATIONAL CONFERENCE   1132   93 - 98   2008

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    Here we present the first evidence that muscle-specific kinase (MUSK) antigen can cause myasthenia in animals. MUSK is expressed at the postsynaptic membranes of neuromuscular junctions (NMJ) and forms complexes with acetylcholine receptors (AChR) and rapsyn. MUSK is activated by agrin, which is released from motoneurons, and induces AChR clustering and subsequent formation of NMJ in embryos. Notably, autoantibodies against MUSK were found in a proportion of patients with generalized myasthenia gravis (MG) but without the characteristic AChR autoantibodies. However, MUSK autoantibodies had no known pathogenic potential, and animals immunized with purified MUSK proteins did not develop MG in former studies. In contrast, we have now injected rabbits with MUSK ectodomain protein in vivo and evoked a MG-like muscle weakness with a reduction of AChR clustering at the NMJ. Our results showed that MUSK is required for maintenance of synapses and that interference with that function by MUSK antibodies causes myasthenic weakness. In vitro, AChR clustering in myotubes is induced by agrin and agrin-independent inducers, which do not activate MUSK. Neither the receptor nor the activation mechanisms of AChR clustering induced by agrin-independent inducers has been identified with certainty, but MUSK autoantibodies in myasthenic animals inhibited both agrin and agrin-independent AChR clustering. MUSK plays multiple roles in pre-patterning of the postsynaptic membrane before innervation and formation of NMJ in embryos. Some of these mechanisms may also participate in the maintenance of mature NMJ. This model system would provide new knowledge about the molecular pathogenesis of MG and MUSK functions in mature NMJ.

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  • 虚血関連遺伝子SNP(一塩基多型)と突発性難聴

    寺岡 正人, 羽藤 直人, 暁 清文

    Audiology Japan   50 ( 5 )   421 - 422   2007.9

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  • Repair of a malleus-handle fracture using calcium phosphate bone cement Reviewed

    Naohito Hato, Masahiro Okada, Nobuhiro Hakuba, Masamitsu. Hyodo, Kiyofumi Gyo

    LARYNGOSCOPE   117 ( 2 )   361 - 363   2007.2

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    We report a case of a 60-year-old woman who reported a popping sound in her left ear, induced by changes in pressure, since she pulled her index finger out of her ear canal after accidentally inserting it while washing her hair. Otoscopic examination revealed a wrinkled tympanic membrane and irregular malleus handle. An isolated malleus-handle fracture resulting from barotrauma was suspected. The fracture was repaired surgically using calcium phosphate bone cement. Postoperatively, the problem disappeared and her hearing recovered. This case is the first to demonstrate the efficacy of calcium phosphate bone cement for repairing a malleus-handle fracture.

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  • A new tool for testing ossicular mobility during middle ear surgery: Preliminary report of four cases Reviewed

    Naohito Hato, Hisashi Kohno, Masahiro Okada, Nobuhiro Hakuba, Kiyofumi Gyo, Takashi Iwakura, Makoto Tateno

    OTOLOGY & NEUROTOLOGY   27 ( 5 )   592 - 595   2006.8

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    Objective: We developed an ossicular vibration tester for the objective and quantitative assessment of ossicular mobility, which is one of the most critical factors affecting postoperative hearing after tympanoplasty.
    Methods: Our device consists of three components: a probe shaft with a curved tip to be attached to the target ossicle, a vibration exciter to activate the probe, and a piezoelectric sensor to detect vibrations of the probe. These components are encased in a stainless steel holder, allowing easy hand manipulation during ear surgery. The probe is activated with an electric signal at around 1,600 Hz. The system is controlled with a laptop computer, and the results are presented as the ratio of the ossicular resistance (ROR) to a reference value as a percentage. One measurement takes 10 ms. The device was applied in four selected patients during ear surgery.
    Results: Several measurements in two of the cochlear implantees showed a greater difference in the RORs of the stapes (15-20% in Case 1 and 35-45% in Case 2), whereas the RORs of the malleus and incus were within the same range. This was thought to correspond to the partial cochlear calcification noted in Case 2. In Case 3, who underwent surgery because of otosclerosis, the ROR of the stapes was high, ranging from 70 to 80%. When measured for the malleusincus fixation anomaly (Case 4), the ROR of the malleus and incus was in the range of 60 to 70%. Owing to the limited surgical view, the ROR of the stapes could not be measured. No problems related to the measurements with this device were noted.
    Conclusion: The design, principles, measuring procedures, and preliminary results of our new tool for testing ossicular mobility are reported. Measuring the ossicular mobility during surgery may provide important information for deciding the surgical procedures.

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  • Induction of myasthenia by immunization against muscle-specific kinase Reviewed

    K Shigemoto, S Kubo, N Maruyama, N Hato, H Yamada, C Jie, N Kobayashi, K Mominoki, Y Abe, N Ueda, S Matsuda

    JOURNAL OF CLINICAL INVESTIGATION   116 ( 4 )   1016 - 1024   2006.4

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    Muscle-specific kinase (MuSK) is critical for the synaptic clustering of nicotinic acetylcholine receptors (AChRs) and plays multiple roles in the organization and maintenance of neuromuscular junctions (NMJs). MuSK is activated by agrin, which is released from motoneurons, and induces AChR clustering at the postsynaptic membrane. Although autoantibodies against the ectodomain of MuSK have been found in a proportion of patients with generalized myasthenia gravis (MG), it is unclear whether MuSK autoantibodies are the causative agent of generalized MG. In the present study, rabbits immunized with MuSK ectodomain protein manifested MG-like muscle weakness with a reduction of AChR clustering at the NMJs. The autoantibodies activated MuSK and blocked AChR clustering induced by agrin or by mediators that do not activate MuSK. Thus MuSK autoantibodies rigorously inhibit AChR clustering mediated by multiple pathways, an outcome that broadens our general comprehension of the pathogenesis of MG.

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  • Role of T-lymphocyte subsets in facial nerve paralysis owing to the reactivation of herpes simplex virus type 1 Reviewed

    H Kisaki, N Hato, M Mizobuchi, N Honda, H Takahashi, H Wakisaka, Y Hitsumoto, N Yanagihara, K Gyo

    ACTA OTO-LARYNGOLOGICA   125 ( 3 )   316 - 321   2005.3

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    Conclusion. Although both T-cell subsets are essential for inhibiting HSV-1 reactivation in the GG, CD4+ T cells play a more important role in host defense against virus replication. Objective. To elucidate the host immunological factors that participate in herpes simplex virus type 1 (HSV-1) reactivation in the geniculate ganglia ( GG) and lead to facial paralysis, we developed a mouse model of facial paralysis that involved the reactivation of HSV-1 following general immune suppression. Material and methods. Eight weeks after recovery from primary facial paralysis caused by inoculating the auricle with HSV-1 the auricle was scratched and mice (n = 69) were given an i.p. injection of either anti-CD4 (n = 46) or anti-CD8 (n = 23) monoclonal antibody to deplete specific T-lymphocyte subsets. Following this reactivation procedure, the rate of recurrent facial paralysis was compared between the two models. The GG were examined histopathologically and using polymerase chain reaction to detect HSV-1 DNA. Results. Facial paralysis developed in 42% of mice in the anti-CD4 model and in 13% in the anti-CD8 model. HSV-1 DNA was detected in 50% of the mice in both models. Histopathologically, neurons were destroyed in parts of the GG and numerous virus particles were seen in the surviving neurons.

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  • Experimental study of an adjustable-length titanium ossicular prosthesis in a temporal bone model Reviewed

    SQ Zhao, N Hato, RL Goode

    ACTA OTO-LARYNGOLOGICA   125 ( 1 )   33 - 37   2005.1

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    Conclusions. This prosthesis has the advantage of rapid adjustment at the time of insertion in order to achieve optimal tension and, as a result, optimal sound transmission. Objective. To test the acoustic performance of a new, adjustable incus replacement prosthesis in a human temporal bone model. Material and methods. Experiments were performed in seven human temporal bones, before and after removal of the incus and insertion of the prosthesis. The input comprised 406 pure tones ranging in frequency between 0.1 and 10 kHz at an intensity of 80 dB SPL at the tympanic membrane. The output measurement was stapes footplate displacement, determined by means of a laser Doppler vibrometer. Three lengths of the prosthesis were investigated: optimal, optimal +0.2 mm and optimal +0.4 mm. Results. The optimal-length prosthesis produced similar results to those of an intact middle ear. The slightly longer prostheses decreased middle ear sound transmission at all test frequencies, except those near 1.5 kHz.

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  • Fluid volume displacement at the oval and round windows with air and bone conduction stimulation Reviewed

    S Stenfelt, N Hato, RL Goode

    JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA   115 ( 2 )   797 - 812   2004.2

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    The fluids in the cochlea are normally considered incompressible, and the fluid volume displacement of the oval window (OW) and the round window (RW) should be equal and of opposite phase. However, other channels, such as the cochlear and vestibular aqueducts, may affect the fluid flow. To test if the OW and RW fluid flows are equal and of opposite phase, the volume displacement was assessed by multiple point measurement at the windows with a laser Doppler vibrometer. This was done during air conduction (AC) stimulation in seven fresh human temporal bones, and with bone conduction (BC) stimulation in-eight temporal bones and one human cadaver head. With AC stimulation, the average volume displacement of the two windows is within 3 dB, and the phase difference is close to 180degrees for the frequency range 0.1 to 10 kHz. With BC stimulation, the average volume displacement difference between the two windows is greater: below 2 kHz, the volume displacement at the RW is 5 to 15 dB greater than at the OW and above 2 kHz more fluid is displaced at the OW. With BC stimulation, lesions at the OW caused only minor changes of the fluid flow at the RW. (C) 2004 Acoustical Society of America.

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  • Bilateral spontaneous cerebrospinal fluid otorrhea Reviewed

    N Hondo, Y Okouchi, H Sato, T Sanuki, N Hato, N Yanagihara, S Murakami, K Gyo

    AMERICAN JOURNAL OF OTOLARYNGOLOGY   25 ( 1 )   68 - 72   2004.1

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    We present a rare case of bilateral cerebrospinal fluid (CSF) otorrhea via multiple bony defects in the left tegmen and a single defect with the herniated brain tissue on the right side. Initially, the patient complained of left hearing loss and fullness and was diagnosed with serous otitis media. After myringotomy, the pulsating watery discharge suggested CSF otorrhea. Five months after surgical repair of the left side, right-side CSF leakage occurred. The right side was repaired surgically, and the patient recovered without incident. From our findings and a review of the literature, we postulate that bilateral CSF otorrhea resulted mainly from the thinness of the tegmen because of well-pneumatized mastoid air cells and the weakness of the dura after chronic inflammatory changes. In case of spontaneous CSF otorrhea, the roof of tegmen should be assessed bilaterally with care using radiologic examinations so as not to overlook a subclinical condition on the contralateral side. (C) 2004 Elsevier Inc. All rights reserved.

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  • Cochlear implantation in patients with defect of the posterior canal wall Reviewed

    Yusuke Shinomori, Naohito Hato, Hidemitsu Sato, Kiyofumi Gyo

    Cochlear Implants International   5 ( 1 )   82 - 83   2004

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  • Development of a handheld ossicular vibration tester for surgery Reviewed

    T Iwakura, H Fujioka, M Tateno, H Kohno, N Hato, H Sato, K Gyo

    PROCEEDINGS OF THE 3RD SYMPOSIUM ON MIDDLE EAR MECHANICS IN RESEARCH AND OTOLOGY   324 - 327   2004

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    It has been desired for checking of the stapes footplate mobility in tympanoplasty and surgery of middle ear implant by surgeons. In this study, an ossicular vibration tester to detect small mechanical impedance such as a stapes footplate is presented. The probe of this tester is constituted by a vibrator and a force sensor built in the vibrator. The vibrator force into vibrating at the resonance frequency, thus the mechanical output impedance of the vibrator is reduced to an extremely small value. Therefore, if the vibrator tip touches a stapes, the motion of the vibrator will be significantly affected. This change of the vibration may be detected from the output of the force sensor. Actually, evaluating the stapes footplate mobility by using the tester in the surgery for both patients having a normal stapes footplate and having a otosclerosis, the tester has found to be useful.

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  • A handheld ossicular vibration tester and its application during surgery Reviewed

    K Gyo, H Kohno, N Hato, T Iwakura, H Fujioka, M Tateno

    PROCEEDINGS OF THE 3RD SYMPOSIUM ON MIDDLE EAR MECHANICS IN RESEARCH AND OTOLOGY   328 - 332   2004

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    We developed an ossicular vibration tester for evaluation of the ossicular mobility. The device consists of three components: a probe to be attached to the ossicle, a vibrator to activate the probe shaft, and a sensor to detect vibration of the probe. The vibrator is activated with an electric signal at around 2000 Hz, which is supposed to be a resonant frequency of human ossicular chain. These components are encased in a hand-holder for easy manipulation during surgery and are controlled by a computer. Using this device, we measured the ossicular mobility during ear surgery. The results were evaluated by calculating the percentage of resistance in comparison with that of reference. This paper reports the design, principles and measuring procedures of our device, and shows preliminary results of 4 patients.

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  • Efficacy of early treatment of Bell&apos;s palsy with oral acyclovir and prednisolone Reviewed

    N Hato, S Matsumoto, H Kisaki, H Takahashi, H Wakisaka, N Honda, K Gyo, T Murakami, N Yanagihara

    OTOLOGY & NEUROTOLOGY   24 ( 6 )   948 - 951   2003.11

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    Objective: To investigate the therapeutic effects of acyclovir and prednisolone in relation to the timing of treatment in Bell&apos;s palsy.
    Study Design: This was a retrospective study of 480 Bell&apos;s palsy patients who were treated with oral acyclovir and prednisolone (94 cases) or prednisolone alone (386 cases).
    Patients: Patients met the after criteria: (I) severe or complete Bell&apos;s palsy with a score lower than 20 on the 40-point Yanagihara facial score and (2) treatment started within 7 days after onset. The patients were treated with oral prednisolone (60-40 mg/day) with or without oral acyclovir (2,000 mg/day).
    Main Outcome Measure: Rate of recovery, which was defined as a facial score of 36 or more, and the absence of contracture with synkinesis.
    Results: The overall recovery rate of patients treated with acyclovir and prednisolone was 95.7 percent, which was better than that of patients treated with prednisolone alone (88.6%). The recovery rate in patients who began the combined therapy within 3 days of the onset of palsy was 100 percent and early treatment resulted in early remission. In contrast, the recovery rate in patients who started the combined therapy more than 4 days after onset was 86.2 percent.
    Conclusion: These results suggest that early diagnosis and treatment within 3 days of the onset of paralysis are necessary for maximal efficacy of combined acyclovir and prednisolone therapy for Bell&apos;s palsy.

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  • Basilar membrane and osseous spiral lamina motion in human cadavers with air and bone conduction stimuli Reviewed

    S Stenfelt, S Puria, N Hato, RL Goode

    HEARING RESEARCH   181 ( 1-2 )   131 - 143   2003.7

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    It is generally accepted that bone conduction (BC) stimuli yield a traveling wave on the basilar membrane (BM) and hence stimulate the cochlea by the same mechanisms as normal air conduction (AC). The basis for this is the ability to cancel or mask a BC tone with an AC tone and the ability to generate two tone distortion products with a BC tone and an AC tone. The hypothesis is proposed that BC stimulates the BM not only through the hydrodynamics of the scala vestibuli and scala tympani, but also through osseous spiral lamina (OSL) vibrations. To test this hypothesis the BM and OSL response with AC as well as BC stimulation was measured with a laser Doppler vibrometer. Human temporal bones mounted on a shaker were used to record the velocities of the bone per se, the BM and the OSL. The measurements were then converted to relative BM and OSL velocities. The results from the basal turn of the cochlea show similar behavior with AC and BC stimulation. The motion of the OSL at the edge where it connects to the BM is in phase and is typically 6 dB lower than the BM motion. With BC stimulation, there is less phase accumulation in the OSL after the cochlea is drained; the OSL moves due to inertial forces and resonates at approximately 7 kHz. Inertial vibration of the OSL may partially contribute to the total response of BC sound, especially at the high frequencies, although current models of the cochlea assume a rigid OSL. The measurements reported here can be used to include a flexible OSL in cochlear models. (C) 2003 Elsevier Science B.V. All rights reserved.

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  • Three-dimensional stapes footplate motion in human temporal bones Reviewed

    N Hato, S Stenfelt, RL Goode

    AUDIOLOGY AND NEURO-OTOLOGY   8 ( 3 )   140 - 152   2003.5

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    The literature provides Conflicting information on whether the motion of the stapes footplate is piston-like or some other type of motion, such as rotational or rocking. Examination of the three-dimensional (3D) motion of the stapes footplate appears to be an excellent way to understand this complicated motion. Five microsphere reflective targets were placed on the stapes footplate in ten fresh human cadaver temporal bone preparations, and their vibration measured through an extended facial recess approach using a laser Doppler vibrometer. The five target sites on the stapes footplate were center, anterior, posterior, superior and inferior. The stimulus was a sound input of 80-120 dB SPL at the tympanic membrane over a frequency range of 0.1 to 10 kHz. The 3D motion of the stapes footplate was calculated using the Velocity amplitude and phase obtained for each target. For frequencies up to 1.0 kHz the vibration of the stapes footplate was primarily piston-like; this motion became complex at higher frequencies, with rotary motion along both the long and short axis of the footplate. When the cochlea was drained, stapes footplate motion became essentially piston-like for all frequencies. Copyright (C) 2003 S. Karger AG, Basel.

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  • Lateralization of the tympanic membrane as a complication of canal wall down tympanoplasty: A report of four cases Reviewed

    K Gyo, N Hato, Y Shinomori, N Hakuba

    OTOLOGY & NEUROTOLOGY   24 ( 2 )   145 - 148   2003.3

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    Objective: To describe the pathophysiology and treatment of the lateralized tympanic membrane that occurs after canal wall down tympanoplasty.
    Study Design: Retrospective case review.
    Setting: Tertiary referral hospital.
    Patients: Four patients in whom lateralization of the tympanic membrane developed as a complication of canal wall down tympanoplasty.
    Results: The patients had undergone middle ear surgery 20 to 34 years before their first visit to the authors. A Bondy operation with soft-wall reconstruction of the ear canal had been performed in three patients and a modified radical mastoidectomy in one patient. They all had severe conductive hearing loss. Common findings were anterior canal sulcus blunting, good tubal function, normal middle ear mucosa, and mobile stapes. At revision surgery, the lateralized tympanic membrane was removed, and the temporalis fascia was grafted medial to the malleus manubrium. The exposed bony surface in the ear canal was covered with a split-thickness skin graft, and the ear canal and the mastoid cavity were tightly packed to secure the graft. All the patients regained good hearing after the revision. Although deterioration of the anterior tympanic ring was presumed to be the primary cause of the graft lateralization, the lack of a posterior bony ear canal might have facilitated this condition.
    Conclusion: Lateralization of the tympanic membrane can occur even in an ear with a radicalized mastoid cavity, especially when the anterior tympanic ring is tom and the posterior ear canal is reconstructed with soft tissue.

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  • Effects of acyclovir on facial nerve paralysis induced by herpes simplex virus type 1 in mice Reviewed

    H Takahashi, N Hato, N Honda, H Kisaki, H Wakisaka, S Matsumoto, K Gyo

    AURIS NASUS LARYNX   30 ( 1 )   1 - 5   2003.2

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    Objectives: Bell's palsy has recently been claimed to be caused by herpes simplex virus type 1 (HSV-1) infection. The anti-viral agent acyclovir is a specific inhibitor of herpesvirus replication, and the most effective agent for the treatment herpesvirus infection. The purpose of this experiment was to assess the effect of acyclovir on the facial nerve paralysis included by HSV-1 infection. Methods: We succeeded in producing an animal model of acute and transient facial nerve paralysis induced with HSV-1 neuritis simulating human Bell's palsy. In this study, acyclovir administration was performed before and after facial nerve paralysis. and continued for 5 days. Controls were given phosphate-buffer saline (PBS) instead of acyclovir, and the incidence and duration of facial nerve paralysis was compared in the acyclovir groups and controls. Results: The incidence of facial nerve paralysis was significantly lower in the group given acyclovir before the paralysis than in the controls, and the duration of facial nerve paralysis was shorter. Conclusions., Administration of acyclovir before the paralysis reduced the incidence and duration of facial nerve paralysis. Administration of acyclovir after the paralysis improved the duration of facial nerve paralysis. (C) 2002 Published by Elsevier Science Ireland Ltd.

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  • Factors contributing to bone conduction: The outer ear Reviewed

    S Stenfelt, T Wild, N Hato, RL Goode

    JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA   113 ( 2 )   902 - 913   2003.2

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    The ear canal sound pressure and the malleus umbo velocity with bone conduction (BC) stimulation were measured in nine ears from five cadaver heads in the frequency range 0.1 to 10 kHz. The measurements were conducted with both open and occluded ear canals, before and after resection of the lower jaw, in a canal with the cartilage and soft tissues removed, and with the tympanic membrane (TM) removed. The sound pressure was about 10 dB greater in an intact ear canal than when the cartilage part of the canal had been removed. The occlusion effect was close to 20 dB for the low frequencies in an intact ear canal; this effect diminished with sectioning of the canal. At higher frequencies, the resonance properties of the ear canal determined the effect of occluding the ear canal. Sectioning of the lower jaw did not significantly alter the sound pressure in the ear canal. The sound radiated from the TM into the ear canal was investigated in four temporal bone specimens; this sound is significantly lower than the sound pressure in an intact ear canal with BC stimulation. The malleus umbo velocity with air conduction stimulation was investigated in nine temporal bone specimens and compared with the umbo velocity obtained with BC stimulation in the cadaver heads. The results show that for a normal open ear canal, the sound pressure in the ear canal with BC stimulation is not significant for BC hearing. At threshold levels and for frequencies below 2 kHz, the sound in the ear canal caused by BC stimulation is about 10 dB lower than air conduction hearing thresholds; this difference increases at higher frequencies. However, with the ear canal occluded, BC hearing is dominated by the sound pressure in the outer ear canal for frequencies between 0.4 and 1.2 kHz. (C) 2003 Acoustical Society of America.

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  • Assessment of facial nerve function following acoustic neuroma surgery: Facial nerve grading systems Reviewed

    N Yanagihara, N Hato

    ACOUSTIC NEUROMA   10   91 - 98   2003

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    A number of grading systems for assessment of facial nerve function using gross or regional scales have been proposed internationally. At the Consensus Meeting of Acoustic Neuroma, the discussants agreed that the House-Brackmann scale was used most widely throughout the world, the Yanagihara system was always used in Japan and in some other countries, and other systems were used only by small groups. In view of the current situation, this chapter reviews the House-Brackmann scale and the Yanagihara system and describes the advantages and disadvantages of each system. The House-Brackmann grading scale is a representative gross scale that is useful for clinical purposes in general. However, all of the discussants agreed that the House-Brackmann scale needed to be modified to make it more relevant and reliable for assessing facial nerve function after acoustic neuroma surgery. The modification and its rationale are described. The Yanagihara system developed in Japan is a representative regional scale. The chart for obtaining the paralysis score is presented. The score provides accurate information on the grade of facial dysfunction to assess the course of recovery and to predict the outcome of the palsy. Conversion between the House-Brackmann scale and the Yanagihara paralysis score is described.

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  • Sinonasal malignant melanoma; clinical analysis of 14 cases Reviewed

    Masamitsu Hyodo, Hidemitsu Sato, Takahiko Yamagata, Naohito Hato, Hiroshi Aritomo

    Practica Oto-Rhino-Laryngologica   96 ( 2 )   121 - 126   2003

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    Malignant melanoma arising from the mucosa of the nasal cavity and paranasal sinuses is a rare disease with a generally poor prognosis. Clinical data on 14 patients were analyzed in a retrospective manner. They consisted of 4 males and 10 females, and their mean age was 63.6 years (range 46-74). All patients complained of recurrent epistaxis. Primary tumor sites were the nasal cavity in 12 patients and paranasal sinuses in 2. Immunohistochemical staining for HMB-45, S-100 protein and vimentin was considered necessary for differential diagnosis, especially in amelanotic melanoma. In 12 patients, treatment involved radical surgery with or without adjuvant chemotherapy. However, all 12 patients developed local recurrence. The disease-specific survival was 38.5% at 2 years, 20.5% at 5 years, and 10.2% at 10 years. Eight patients died of distant metastasis and 4 died of local failure, suggesting distant metastasis as the limiting factor for long-term survival. Patients who underwent craniofacial surgery for local disease had significantly better survival than those who did not. Repetitive chemotherapy tended to improve the prognosis, however, the difference was not significant. This study shows that wide local resection appears to have the best efficacy in managing sinonasal melanoma, and adjuvant chemotherapy and radiotherapy may have benefit for increasing disease control.

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  • Labyrinthine fistula as a late complication of middle ear surgery using the canal wall down technique Reviewed

    N Hakuba, N Hato, Y Shinomori, H Sato, K Gyo

    OTOLOGY & NEUROTOLOGY   23 ( 6 )   832 - 835   2002.11

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    Objectives: To evaluate the clinical features of labyrinthine fistulae occurring as a late complication of middle ear surgery using the canal wall down technique.
    Study Design: This,was a retrospective study of the past 23 years, conducted at a single tertiary care center. The authors evaluated the backgrounds, clinical features, and surgical findings in 25 patients with labyrinthine fistulae, who had a history of ear surgery using the canal down technique and who underwent a second operation at their hospital.
    Interventions: All the patients underwent revision surgery because of persistent or recurrent vertigo caused by labyrinthine fistulae, circumscribed labyrinthitis, or suppurative labyrinthitis.
    Main Outcome Measures: The clinical features of this disease entity were assessed by history, surgical findings, and the results of audiovestibular testing.
    Results : The patients had a long history of repetitive postoperative aural discharge before experiencing vertigo, which initially occurred 4 to 64 years (average, 20.2 years) after the previous operation. At the first visit to the authors' clinic, the results of a fistula test conducted with a Politzer's bulb were positive in 14 patients and negative in 5 patients. In the remaining 6 ears, pressure loading of the ear canal induced the sensation of vertigo without accompanying nystagmus. Surgical intervention showed that the fistulae were located at the lateral semicircular canal in 19 ears, at the footplate of the stapes in 4 ears, and at the promontory in 2 ears. Labyrinthine fistulae were closed with conchal cartilage, bone paste (bone dust mixed with fibrin glue), and/or temporalis fascia. In some patients, the fistulae were further covered with pedicled temporalis muscle. In 2 cases complicated by acute suppurative labyrinthitis, the mastoid cavity was obliterated after completion of the labyrinthectomy. The postoperative courses in all patients were uneventful.
    Conclusions: A labyrinthine fistula may be created by repeated and insidious infection of a mastoid cavity that has been exposed to the outside during canal wall down surgery. Intensive care of the opened mastoid cavity is essential to avoid this late complication.

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  • Demyelination associated with HSV-1-induced facial paralysis Reviewed

    H Wakisaka, N Hato, N Honda, H Takahashi, H Kisaki, S Murakami, K Gyo, K Mominoki, N Kobayashi, S Matsuda

    EXPERIMENTAL NEUROLOGY   178 ( 1 )   68 - 79   2002.11

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    In 1995, we developed an animal model of transient homolateral facial nerve paralysis by inoculating Herpes simplex virus type 1 (HSV-1) into the auricle of mice. This study examined the mechanism of facial nerve paralysis in this model histopathologically. Using the immunofluorescence technique with anti-HSV-1 antibody, the time course of viral spread and the site of viral replication were investigated over the entire course of the facial nerve. Furthermore, viral replication and nerve degeneration at the site of viral replication were observed by electron microscopy. On the 7th day after inoculation, facial paralysis was observed in more than 60% of mice. Immunofluorescence study revealed HSV-1 in the geniculate ganglion, the descending root, and the facial nucleus at this stage. On the 9th day, the descending root in the sections stained with osmium. looked pale, because prominent demyelination had occurred in this region; electron micrographs showed many degenerated oligodendrocytes and large naked axons. In contrast, the facial nucleus neurons showed no remarkable degeneration, despite HSV-1 particles in their cytoplasm. From these findings, we concluded that facial nerve paralysis in this model is caused mainly by facial nerve demyelination in the descending root. (C) 2002 Elsevier Science (USA).

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  • Pathophysiology of facial nerve paralysis induced by herpes simplex virus type 1 infection Reviewed

    N Honda, N Hato, H Takahashi, H Wakisaka, H Kisaki, S Murakami, K Gyo

    ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY   111 ( 7 )   616 - 622   2002.7

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    Herpes simplex virus type 1 (HSV-1) has been proven to be a cause of Bell's palsy however, the underlying pathophysiology of the facial nerve paralysis is not fully understood. We established a mouse model with facial nerve paralysis induced by HSV-1 infection simulating Bell's palsy and investigated the pathophysiology of the facial nerve paralysis. The time course of the R1 latency in the blink reflex tests paralleled the recovery of the facial nerve paralysis well, whereas electroneurographic recovery tended to be delayed, compared to that of the paralysis these responses are usually seen in Bell's palsy. On histopathologic analysis, intact, demyelinated. and degenerated nerves were intermingled in the facial nerve in the model. The similarity of the time course of facial nerve paralysis and the electrophysiological results in Bell's palsy and the model strongly suggest that the pathophysiological basis of Bell's palsy is a mixed lesion of various nerve injuries.

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  • Swelling of the intratemporal facial nerve in Ramsay Hunt syndrome Reviewed

    N Honda, N Yanagihara, N Hato, H Kisaki, S Murakami, K Gyo

    ACTA OTO-LARYNGOLOGICA   122 ( 3 )   348 - 352   2002.4

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    Although Ramsay Hunt syndrome is one of the most important diseases causing peripheral facial palsy, the detailed pathology of the disease in the intratemporal facial nerve remains unclear. The purpose of this study was to increase knowledge of the pathogenesis of the syndrome by means of surgical findings. Between April 1976 and March 1997 we performed subtotal decompression of the facial nerve in 74 patients with severe Ramsay Hunt syndrome. The grade Of nerve swelling was assessed using a microscope and recorded in a standardized form. The relationships between nerve swelling the timing of surgery and the swelling of each segment were analyzed. Pronounced neural swelling. involving the geniculate ganglion and the horizontal segment, as consistent finding in the acute phase. Although the incidence of pronounced swelling of the horizontal segment gradually declined with time after onset, in most cases nerve swelling persisted even beyond the 16th week after onset. These data suggest that diffuse viral neuritis Occurs throughout the intratemporal facial nerve. We assume that the viral inflammatory swelling involving the geniculate ganglion and horizontal segment is mostly responsible for the acute facial palsy in the acute phase.

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  • Factors contributing to bone conduction: The middle ear Reviewed

    S Stenfelt, N Hato, RL Goode

    JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA   111 ( 2 )   947 - 959   2002.2

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    Measurement of the motion of the malleus umbo and stapes footplate during bone conduction (BC) stimulation was conducted in vitro in 26 temporal bones using a laser Doppler vibrometer over the frequency range 0.1 to 10 kHz. For lower frequencies, both ossicular sites followed the motion of the temporal bone. The differential motion between the malleus and the surrounding bone was a greater than the differential motion of the stapes footplate; both resonated near 1.5 kHz. Different lesions were shown to affect the response: (1) a mass attached to the umbo lowered the resonance frequency of the ossicular vibration; (2) fixation of either the malleus or stapes increased the stiffness and shifted the resonance frequency upward; and (3) dislocation of the incudo-stapedial joint did not significantly affect the ossicular vibration. The sound radiated from the tympanic membrane was approximately 85 dB SPL at an umbo differential velocity of 1 mm/s for low frequencies in an open ear canal and about 10 dB higher for an occluded one; at higher frequencies (above 2 kHz) resonances of the canal determine the response. It was also found that the motion between the footplate and promontory was within 5 dB when the specimen was stimulated orthogonal to the vibration direction of the ossicles than in line with the same. Measurement of the differential motion of the umbo in one live human skull gave similar response as the average result from the temporal bone specimens. (C) 2002 Acoustical Society of America.

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  • Herpes simplex virus in the vestibular ganglion and the geniculate ganglion-role of loose myelin. Reviewed

    Wakisaka H, Kobayashi N, Mominoki K, Saito S, Honda N, Hato N, Gyo K, Matsuda S

    Journal of neurocytology   30 ( 8 )   685 - 693   2001.8

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    This study presents the first direct evidence for herpes simplex virus type 1 (HSV-1) infection in the neurons of the vestibular ganglion. Although many investigators have reported electron microscopic evidence of HSV-1 infection in sensory ganglia, HSV-1 infection in the vestibular ganglion has not been described. Vestibular ganglion neurons have a unique structure, with a loose myelin sheath instead of the satellite cell sheath that is seen in other ganglia. This loose myelin is slightly different from compact myelin which is known as too tight for HSV-1 to penetrate. The role of loose myelin in terms of HSV-1 infection is completely unknown. Therefore, in an attempt to evaluate the role of loose myelin in HSV-1 infection, we looked for HSV-1 particles, or any effects mediated by HSV-1, in the vestibular ganglion as compared with the geniculate ganglion. At the light microscopic level, some neurons with vacuolar changes were observed, mainly in the distalportion of the vestibular ganglion where the communicating branch from the geniculate ganglion enters. At the electron microscopic level, vacuoles, dilated rough endoplasmic reticulumand Golgi vesicles occupied by virus were obse

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  • Mouse model of Bell's palsy induced by reactivation of herpes simplex virus type 1 Reviewed

    H Takahashi, Y Hitsumoto, N Honda, N Hato, M Mizobuchi, S Murakami, H Kisaki, H Wakisaka, K Gyo

    JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY   60 ( 6 )   621 - 627   2001.6

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    In order to investigate the mechanism of Bell's palsy. we developed an animal model of facial nerve paralysis induced by the reactivation of herpes simplex virus type 1 (HSV-1). Eight weeks after recovery from facial nerve paralysis caused by inoculation with HSV-1, the mice were treated with auricular skin scratch at the site of the previous inoculation. or with intraperitoneal injection of anti-CD3 monoclonal antibody (mAb), or combination of both procedures. No mice developed facial nerve paralysis when they were treated with either auricular scratch or mAb injection alone. In contrast, 20% of mice developed facial nerve paralysis with the combined treatment. With one exception, no mouse treated with either auricular scratch or mAb injection showed HSV-1 DNA in their facial nerve tissue, whereas 4 out of 6 mice receiving both treatments showed HSV-I DNA on day 10 after treatment. Histopathological findings showed neuronal degeneration in the geniculate ganglion and demyelination of the facial motor nerve in paralyzed mice. These findings suggest that a combination of stimuli, local skin irritation, and general immunosuppression is essential for successfully inducing facial nerve paralysis in mice with latent HSV-1 infection.

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  • Transmastoid decompression as a treatment of Bell palsy Reviewed

    N Yanagihara, N Hato, S Murakami, N Honda

    OTOLARYNGOLOGY-HEAD AND NECK SURGERY   124 ( 3 )   282 - 286   2001.3

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    OBJECTIVE: We sought to assess the efficacy of transmastoid decompression after steroid treatment.
    STUDY DESIGN: One hundred one adults with Bell palsy having denervation exceeding 95% after steroid treatment were divided into 2 groups. in 58 patients decompression from the labyrinthine segment to the stylomastoid foramen was performed, and the remaining 43 patients were only followed up. Using the Yanagihara score and House Brackmann grading system, the recovery from the palsy was assessed.
    RESULTS: There was a statistically significant difference in the final facial score of the 2 groups. Within 60 days after the onset, the chance of better recovery from the palsy was higher in the patients with decompression.
    CONCLUSION: In the era of steroid treatment, we cannot discard the transmastoid decompression of the facial nerve in the treatment of severe Eel palsy with profound denervation, although further effort is needed to obtain definitive evidence to show the benefit of the operation.

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  • Acoustic role of the buttress and posterior incudal ligament in human temporal bones Reviewed

    N Hato, JT Welsh, RL Goode, S Stenfelt

    OTOLARYNGOLOGY-HEAD AND NECK SURGERY   124 ( 3 )   274 - 278   2001.3

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    OBJECTIVES: In middle ear surgery using intact ear canal wail techniques, the buttress, which is the bony bridge at the medial end of the posterior-superior bony ear canal, is commonly retained during posterior tympanotomy, In some cases, the surgical exposure may be improved by resectioning the buttress, and this requires sectioning the posterior incudal ligament, To date, the acoustic effects of removing the buttress with sectioning of the attached ligament have not been studied,
    METHOD: Using a laser Doppler vibrometer system, 15 human cadaver temporal bones were measured with 80 dB sound pressure level at the tympanic membrane over the 0.1 to 10 kHz frequency range.
    RESULT: The resection of the buttress and sectioning the posterior incudal ligament had no effect on stapes footplate velocity.
    CONCLUSION: These results suggest that the posterior incudal ligament does not play a significant role in the acoustic function of the ossicles.

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  • Edematous swelling of the facial nerve in Bell's palsy Reviewed

    N Yanagihara, N Honda, N Hato, S Murakami

    ACTA OTO-LARYNGOLOGICA   120 ( 5 )   667 - 671   2000.8

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    Surgical decompression of the intratemporal facial nerve from the geniculate ganglion to the stylomastoid foramen was carried out in 91 patients with Bell's palsy. All of the patients had denervation exceeding 95% and a suprastapedial lesion. Edematous swelling of the nerve was assessed using the following three grades: + +,nerve swells beyond the bony facial canal; +,nerve swells beyond the nerve sheath, but within the bony canal, and -, no notable swelling observed. Varying degrees of swelling of the nerve were noted in all of the patients From onset to the end of the ninth week. The incidence of + + swelling was highest within 3 weeks of onset and then declined. + + swelling was most often noted in the vicinity of the geniculate ganglion, and was thought to be a manifestation of inflammation due to herpes simplex virus infection. There was a altar time dependency of the swelling in the horizontal and pyramidal segments, but not in the mastoid segment. After the ninth week, the incidence of swelling decreased sharply and no swelling of the nerve was observed in about one-third of the patients. Considering the etiology and the analysis of edematous swelling, we propose that the course of Brill's palsy be differentiated into an acute phase (the first 3 weeks after onset), a subacute phase (from the fourth to ninth weeks) and a chronic phase (after the tenth week).

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  • Treatment of Bell's palsy with acyclovir and prednisolone Reviewed

    N. Hato, N. Honda, K. Gyo, H. Aono, S. Murakami, N. Yanagihara

    Journal of Otolaryngology of Japan   103 ( 2 )   133 - 138   2000

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    Many current studies have suggested that herpes simplex virus is a probable cause of Bell's palsy, and that treatment with antiviral agents such as acyclovir might benefit the patients. In the present study, 69 patients with Bell's palsy were treated with oral administration of acyclovir (2000mg/day) and prednisolone (60~40mg/day) at Ehime University Hospital between Oct. 1995 and Dec. 1998. Patients enrolled in this study met the following criteria: 1) severe or complete paralysis with a score lower than 20 by the 40-point Japanese grading system, and 2) treatment started within 7 days of onset. The overall recovery rate was 95.7% (66/69). The rate in patients who started this treatment within 3 days after disease onset was 100%, and this early treatment was highly efficacious in the prevention of nerve degeneration and resulted in a significantly better recovery. By comparison, the recovery rate in patients whose treatment was started 4 days or more after onset was only 84.2%. All patients who were given a diagnosis of zoster sine herpete and treated with acyclovir-prednisolone had a good outcome. These results suggest that early treatment, within 3 days after palsy onset, is necessary for effective acyclovir-prednisolone therapy of Bell's palsy.

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  • Recovery of lacrimation, taste and facial palsy after removal of acoustic neuroma by the middle cranial fossa approach Reviewed

    H Wakisaka, S Murakami, N Honda, N Hato, H Sato, K Gyo, N Yanagihara

    THIRD INTERNATIONAL CONFERENCE ON ACOUSTIC NEURINOMA AND OTHER CPA TUMORS   897 - 900   1999

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  • Rapid diagnosis of varicella zoster virus infection in acute facial palsy Reviewed

    S Murakami, N Honda, M Mizobuchi, Y Nakashiro, N Hato, K Gyo

    NEUROLOGY   51 ( 4 )   1202 - 1205   1998.10

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    Patients with zoster sine herpete and Ramsay Hunt syndrome without pathognomonic vesicles at the initial visit are often misdiagnosed with Bell's palsy and treated without antiviral agents. With PCR, we found that varicella zoster virus genomes were frequently detectable in auricular skin exudate from patients with tester sine herpete or Ramsay Hunt syndrome before the appearance of vesicles.

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  • Varicella-zoster virus distribution in Ramsay Hunt syndrome revealed by polymerase chain reaction Reviewed

    S Murakami, Y Nakashiro, M Mizobuchi, N Hato, N Honda, K Gyo

    ACTA OTO-LARYNGOLOGICA   118 ( 2 )   145 - 149   1998.3

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    The pathogenesis of facial nerve paralysis and vestibulo-cochlear dysfunction of Ramsay Hunt syndrome remains unclear as varicella-zoster virus (VZV) has not been demonstrated in the lesions. Using the polymerase chain reaction, we detected VZV genomes not only in the vesicles on the auricles or oral cavity but also in the facial nerve sheath, middle ear mucosa and cerebrospinal fluid from patients with Ramsay Hunt syndrome. The VZV genome was undetectable in the same kinds of clinical samples obtained from control patients with facial nerve paralysis of other etiologies. The results indicated that VZV spreads widely in the neural components, mucocutaneous tissue and cerebrospinal fluid. The present study will facilitate better understanding of the pathogenesis of facial nerve paralysis, vertigo, hearing impairment and other cranial nerve dysfunction of Ramsay Hunt syndrome.

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  • Clinical features and prognosis of facial palsy and hearing loss in patients with Ramsay hunt syndrome Reviewed

    Shingo Murakami, Naohito Hato, Joji Horiuchi, Yoshito Miyamoto, Hisashi Aono, Nobumitsu Honda, Naoaki Yanagihara

    Journal of Otolaryngology of Japan   99 ( 12 )   1772 - 1779   1996

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    Clinical studies were performed on 325 patients with Ramsay Hunt syndrome who were treated in the Facial Nerve Clinic at Ehime University Hospital between 1976 and 1995. The clinical manifestations of Ramsay Hunt syndrome were various. Three major symptoms, auricular vesicles, facial paralysis and vestibulo-cochlear dysfunction, were found in 57.6% of the patients although these symptoms did not always appear simultaneously. Auricular vesicles appeared before (19.3%), during (46.5%), or after (34.2%) the onset of facial paralysis. Hearing loss was observed subjectively in only 20% but objectively in 48.2% of the patients. Hearing loss appeared before (34.3%), during (34.3%), or after (31.3%) the onset of facial paralysis. Complete recovery from facial paralysis was achieved in 52.4% of the patients. Good recovery of the facial nerve function was achieved in patients who had zoster vesicles or vestibulo-cochlear dysfunction preceding the development of facial paralysis. Complete recovery of hearing was also achieved in 45.4% of the patients, and the recovery was better in patients having light hearing loss, less than 35dB. The patients younger than 16 years old showed better recovery from both facial paralysis and hearing loss than the patients older than 60 years. Glossopharyngeal nerve or vagal nerve paralysis concomitant with facial paralysis was found in 8 (2.5%) patients. The outcome of glossopharyngeal nerve paralysis was good but that of the vagal nerve was poor.

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  • Immunological determinants and the spread of viral infection in facial nerve paralysis induced by herpes simplex virus in mice Reviewed

    Naohito Hato

    Journal of Otolaryngology of Japan   99 ( 4 )   544 - 551   1996

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  • Bilateral Gradenigo's Syndrome; a Case Report Reviewed

    Naohito Hato, Seiji Kawakita, Naoaki Yanagihara, Hiroshi Aritomo, Shoko Inaki

    Practica Otologica   87 ( 11 )   1473 - 1479   1994

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    Gradenigo's syndrome was diagnosed in a 5-year-old male with bilateral acute otitis media, paralysis of both abducens nerves and bilateral irritation of the trigeminal nerves. After myringotomy and administration of antibiotics, his tympanic membrance became normal, and the bilateral trigeminal nerve irritation disappeared, but residual mastoiditis was revealed by X-ray examination. Right extended mastoidectomy was performed including removal of the bony sinus plate on Mar. 2, 1990. Although bilateral abducens palsy improved immediately, serological findings and double vision deteriorated again 10 days after the operation. Reexploration was done on Mar. 16, 1990. Residual inflammatory changes in the petrous apex were eradicated, especially around the lateral sinus and anterior to the superior semicircular canal through the petrous apex. An extradural abscess was found at the petrous apex. The left trigeminal nerve irritation and the left abducens paralysis was attributed to the right petrositis because bilateral abducens nerve function recovered completely after the second operation on the right temporal bone. Since extradural abscess at the petrous apex is difficult to diagnose preoperatively and has been reported in many patients with Gradenigo's syndrome, it must be kept in mind in the diagnosis and the treatment of Gradenigo's syndrome. Twelve cases of Gradenigo's syndrome reported in Japan from 1960 to 1992 were reviewed. Acute otitis media was the cause in five, all children. In three of them abducens paralysis appeared within one week after onset of the acute otitis media. Mortality of Gradenigo's syndrome is still 10%, similar to that of brain abscess associated with otitis media. © 1994, The Society of Practical Otolaryngology. All rights reserved.

    DOI: 10.5631/jibirin.87.1473

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  • Congenital and Acquired Atresia of Cartilaginous External Auditory Canal; A Report of Two Cases Reviewed

    Naohito Hato, Hiroshi Aritomo, Shoko Inaki, Seiji Kawakita, Naoaki Yanagihara

    Practica Otologica   86 ( 5 )   675 - 680   1993

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    Two cases of atresia of the cartilaginous external auditory canal are presented to emphasize importance of 1) preoperative assessment of the obstructive portion and 2) prevention of recurrence. Case 1: A 12-year-old girl consulted us with complaints of right otorrhea and otalgia. She had right congenital external auditory canal atresia with a fistula draining pus from the bony external canal. CT showed the atresia limited to the cartilaginous portion. Case 2: A 26-year-old female consulted us with a complaint of left hearing loss. She had left traumatic external auditory canal atresia. CT showed the ear canal totally obstructed with connective tissue, and MRI showed that the atresia was limited to the cartilaginous portion with effusion in the bony external canal. A canalplasty was done successfully in both cases. In case 1, the canalplasty was combined with tympanoplasty to control the complicated severe chronic otitis media with adhesive ear drum and defect of the lenticular process. The bony external canal was filled with cholesteatoma mass. Early surgical treatment is needed to avoid such complications. A stent must be placed for a long time to prevent the recurrence of stenosis. We recommend the placement of a silastic tube for that purpose. © 1993, The Society of Practical Otolaryngology. All rights reserved.

    DOI: 10.5631/jibirin.86.675

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Books

  • Middle Ear Mechanics in Research and Otology

    World Scientific  2004 

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  • Middle Ear Mechanics in Research and Otology

    World Scientific  2004 

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  • 骨粗鬆症モデルマウスにおける骨粗鬆症治療薬の耳石形態変化への影響

    中田貴大, 岡田昌浩, 羽藤直人

    耳鼻咽喉科ニューロサイエンス   35   2022

  • 頭頸部癌患者における化学放射線療法前後の体組成分析の意義について

    志田原 睦, 勢井 洋史, 佐藤 恵里子, 木谷 卓史, 眞田 朋昌, 羽藤 直人

    耳鼻咽喉科臨床 補冊   ( 補冊157 )   119 - 119   2021.6

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  • 耳鼻咽喉科医のための結紮縫合カリキュラムの開発

    三谷 壮平, 佐藤 恵里子, 西尾 直樹, 木谷 卓史, 眞田 朋昌, 鵜久森 徹, 羽藤 直人

    日本耳鼻咽喉科学会会報   123 ( 4 )   1073 - 1073   2020.9

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  • The treatment outcomes of rituximab for intractable otitis media with ANCA-associated vasculitis

    Masahiro Okada, Koichiro Suemori, Daiki Takagi, Masato Teraoka, Hiroyuki Yamada, Jun Ishizaki, Takuya Matsumoto, Hitoshi Hasegawa, Naohito Hato

    Journal of Otolaryngology of Japan   123 ( 2 )   38 - 39   2020

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    Language:Japanese   Publishing type:Rapid communication, short report, research note, etc. (scientific journal)   Publisher:Oto-Rhino-Laryngological Society of Japan Inc.  

    DOI: 10.3950/jibiinkoka.123.177

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  • A case of a dacryocystolite treated with endonasal dacryocystrhinostomy (E-DCR)

    Takahiro Hanari, Naoya Nishida, Naohito Hato

    Otolaryngology - Head and Neck Surgery (Japan)   91 ( 9 )   791 - 794   2019.8

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    Language:Japanese   Publishing type:Book review, literature introduction, etc.   Publisher:Igaku-Shoin Ltd  

    Dacryolithiasis causes the lacrimal duct obstruction and can be found in any part of the canaliculus, common canaliculus, lacrimal sac and nasolacrimal duct. Although its formation mechanism is still unknown, it is often in women under the age of 50 and smokers. Fungus infection cause dacryolithiasis in the lacrimal sac and nasolacrimal duct. We reported a case of E-DCR performed on recurrent cases of cystic lamella with some literature review.

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  • 当科にて経験した経口摂取経験のない長期挿管乳幼児症例の嚥下機能についての臨床学的検討

    田中加緒里, 勢井洋史, 羽藤直人

    小児耳鼻咽喉科   40 ( 2 )   102   2019.5

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  • 当科における嗅覚障害に合併する味覚障害30例の検討

    勢井洋史, 木谷卓史, 能田淳平, 羽藤直人

    日本耳鼻咽喉科学会会報   122 ( 4 )   693   2019.4

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  • 顔面神経麻痺:非治癒例を減らすために(サルベージ治療) 麻痺発症2週以降に行う徐放化栄養因子を用いた顔面神経減荷術

    山田 啓之, 羽藤 直人, 藤原 崇志, 飴矢 美里, 上甲 智則, 阿部 康範, 木村 拓也

    Facial Nerve Research   38   25 - 27   2019.3

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    顔面神経減荷術の至適時期は発症後2週間以内とされているが、実際には発症2週間を超えて手術となる症例が多く、今後の課題とされてきた。当科ではこの問題を克服するために2006年から徐放化栄養因子(basic fibroblast growth factor添加ゼラチンハイドロゲル)を用いた顔面神経減荷術を行ってきた。今回その効果を検証するため、麻痺発症2週以降の患者に対して本法を行った群(40例)と、従来の顔面神経減荷術を行った群(45例)、保存的治療を行った群(80例)の成績を比較検討した。成績の評価方法は、柳原スコアが38点以上に改善したものを「著明改善」、32点以上に改善したものを「改善」とし、各々の割合を調べた。結果、本法施行群は他の2群に比べて著明改善率・改善率とも明らかに高かった。

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  • Deep Learning型人工知能を用いた顔面神経麻痺の診断

    秋山 昌毅, 岡本 伸吾, 李 在勲, 羽藤 直人, 山田 啓之, 寺岡 正人, 飴矢 美里

    Facial Nerve Research   38   75 - 77   2019.3

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    顔面神経麻痺の診断には現在、柳原法やHouse-Brackmann法などが用いられているが、これらの方法は、評価を行う医師の視覚と経験によって判断されているため、同じ所見でも医師によって評価結果に違いが生じてしまう。近年、人工知能の分野で人の脳神経回路を模したNeural Networkを発展させたConvolution Neural Network(CNN)を用いるDeep Learning(DL)が注目されている。著者等はCNNを用いたDLを利用することで医師の視覚や経験に依存しない診断方法を開発することを目的に研究を行った。当科で顔面神経麻痺と診断された患者のうち治療前後に顔表情の動画を撮影できた患者を対象とし、柳原法の点数が8点以下(高度麻痺)、10〜18点(中等度麻痺)、20点以上(軽度麻痺)の3段階に分類した症例の画像をDLに学習させて最適な重みパラメータを求めた。検証のために各段階から1症例を検証用データとして学習から除き、学習によって求められた重みパラメータを用いて、検証用データをDLに診断させ、DLの精度を評価した。その結果、DL型人工知能を用いれば麻痺の重症度評価がある程度可能なことが明らかになった。

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  • 当科で手術加療を行った副鼻腔真菌症症例の検討

    麻生沙和, 勢井洋史, 羽藤直人

    日本耳鼻咽喉科感染症・エアロゾル学会会誌   6 ( 3 )   66   2018.9

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  • 小児の喉頭放線菌症の1例

    勢井洋史, 麻生沙和, 羽藤直人

    日本耳鼻咽喉科感染症・エアロゾル学会会誌   6 ( 3 )   51   2018.9

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  • 愛媛県におけるRamsay Hunt症候群の疫学的検討 全耳鼻咽喉科施設を対象にしたアンケート調査

    寺岡 正人, 羽藤 直人, 山田 啓之

    Otology Japan   28 ( 4 )   604 - 604   2018.9

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  • 滲出性中耳炎を伴う小児に対するCE-chirp音を用いたASSR検査

    寺岡 正人, 羽藤 直人, 大六 鉄兵

    Audiology Japan   61 ( 5 )   363 - 363   2018.9

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  • 顔面神経検査 顔面神経麻痺スコア

    藤原 崇志, 羽藤 直人

    JOHNS耳鼻咽喉科・頭頸部外科   34 ( 7 )   891 - 894   2018.7

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  • 吸気時喘鳴を主訴に当科を受診した乳幼児の臨床的検討

    田中 加緒里, 西田 直哉, 山田 啓之, 羽藤 直人

    日本気管食道科学会会報   69 ( 3 )   189 - 196   2018.6

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    当科における乳幼児吸気時喘鳴症例について検討を行った。原因は、従来の報告同様喉頭軟弱症が最も多く、そのうち21.4%では声帯運動障害や舌根嚢胞等、他の気道狭窄所見(secondary airway lesions:SALs)を合併していた。SALsは喘鳴の重症度や予後にも影響するため、重症例やSALsを疑う症例では、外来での喉頭内視鏡検査に加え、全身麻酔下喉頭直達鏡検査等を追加して正確な診断を行う必要がある。また背景疾患、挿管歴、低出生体重はrisk factorであった。問診では、これらの既往に加えて喘鳴タイプ(吸気性/呼気性/二相性、急性/慢性)や発症時期、喘鳴を生じる場面や程度、嚥下障害の有無等を十分に把握することが適切な診断および治療法選択には不可欠である。乳幼児は解剖学的・生理学的に気道狭窄をきたしやすく、短期間で重篤になりやすい特徴があることを認識し、迅速な診断かつ対応を行う必要がある。(著者抄録)

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  • High‐resolution impedance manometryによる食道入口部機能評価

    田中加緒里, 勢井洋史, 羽藤直人

    日本気管食道科学会総会ならびに学術講演会プログラム・予稿集   70th   114   2018

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  • 人工内耳手術が有効であったCHARGE症候群の2例

    阿部 康範, 山田 啓之, 羽藤 直人

    Otology Japan   27 ( 5 )   725 - 732   2017.12

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    CHARGE症候群は胎生期の器官形成異常により多発奇形を合併する症候群である。視覚・聴覚といった感覚器官の障害は、その発達遅滞に大きく関与すると言われており、先天性難聴がある場合には人工内耳手術が行われる。しかし、その多彩な症候のために難聴に対する診断、治療は後手に回ることが多い。また多種多様な耳領域の奇形により、極めて手術難易度が高い。今回我々はCHARGE症候群の2例に対して人工内耳手術を施行した。安全に人工内耳手術を施行するためには、術前の詳細な解剖学的指標の評価と手術のプランニングが重要であると考えられた。(著者抄録)

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    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J02471&link_issn=&doc_id=20180118300010&doc_link_id=%2Fed7otolj%2F2017%2F002705%2F011%2F0725-0732%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fed7otolj%2F2017%2F002705%2F011%2F0725-0732%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 当科で手術を行った外傷性耳小骨離断症例の検討

    寺岡 正人, 岡田 昌浩, 山田 啓之, 羽藤 直人

    Otology Japan   27 ( 4 )   530 - 530   2017.10

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  • 小児人工内耳手術の変遷と展望 低年齢、両側、内耳奇形、発達障害への対応

    羽藤 直人, 寺岡 正人, 岡田 昌浩, 山田 啓之

    Otology Japan   27 ( 4 )   283 - 283   2017.10

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  • 突発性難聴の治療に関するシステマティックレビュー

    神崎 晶, 西尾 信哉, 武田 英彦, 岡田 昌浩, 藤岡 正人, 寺西 正明, 伊藤 吏, 菅原 一真, 内田 育恵, 狩野 章太郎, 小川 洋, 鬼頭 良輔, 曾根 三千彦, 羽藤 直人, 小川 郁, 宇佐美 真一

    Otology Japan   27 ( 4 )   441 - 441   2017.10

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  • 突発性難聴の治療に関するシステマティックレビュー

    神崎 晶, 西尾 信哉, 武田 英彦, 岡田 昌浩, 藤岡 正人, 寺西 正明, 伊藤 吏, 菅原 一真, 内田 育恵, 狩野 章太郎, 小川 洋, 鬼頭 良輔, 曾根 三千彦, 羽藤 直人, 小川 郁, 宇佐美 真一

    Otology Japan   27 ( 4 )   441 - 441   2017.10

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  • 突発性難聴の初期治療と予後に関する検討

    寺岡 正人, 岡田 昌浩, 羽藤 直人

    Audiology Japan   60 ( 5 )   357 - 357   2017.9

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  • 就学後に対側手術を行った両側人工内耳装用児の検討

    大六 鉄兵, 寺岡 正人, 羽藤 直人, 高橋 信雄

    Audiology Japan   60 ( 5 )   300 - 300   2017.9

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  • 経蝶形骨洞手術後に遅発性髄液鼻漏を生じた2例

    西田 直哉, 高橋 宏尚, 高木 大樹, 能田 淳平, 羽藤 直人

    日本鼻科学会会誌   56 ( 2 )   119 - 124   2017.7

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    髄液鼻漏は経蝶形骨洞手術(transsphenoidal surgery,TSS)の重要な合併症の一つで,その頻度は1.5-40%と報告されている。通常,髄液鼻漏は術後数日以内に発生し,遅発性に髄液鼻漏が発生した報告は少ない。今回我々はTSS後,遅発性に髄液鼻漏を生じ,鼻中隔粘膜弁を用いて閉鎖術を行った2例を経験したので報告する。症例1は59歳,女性で,頭蓋内・海綿静脈洞に浸潤する下垂体腺腫に対してTSSによる摘出術を行い,残存腫瘍に対して放射線治療を計50Gy行った。術後15ヵ月後に髄液鼻漏発症し,脂肪と筋膜による閉鎖術施行されたが,その4ヵ月後髄液鼻漏再発し,鼻中隔粘膜弁を用いた多重閉鎖法を行い,その後再発は認めていない。症例2は61歳女性で,他院での頭部MRIにてトルコ鞍部腫瘍を指摘され,TSSによる生検を施行したところ,肺腺癌の下垂体転移と診断された。化学療法を行うも腫瘍増大傾向を認めたため,同部位にガンマナイフ治療施行され,その後化学療法継続していた。TSS後17ヵ月目に意識消失発作あり,近医に救急搬送され,頭部CTにて気脳症を認め当院へ転院となった。全身麻酔下に鼻中隔粘膜弁を用いた多重閉鎖法による髄液鼻漏閉鎖術を行った。その後髄液鼻漏の再発はなかったが,病状の進行により,術後1年11ヵ月後永眠された。今回の症例のように,TSS術後遅発性に髄液鼻漏が生じた例では,放射線治療の既往など,閉鎖材料が生着しにくい要因があるため,鼻中隔粘膜弁を用いた閉鎖方法が非常に有用であると考えられた。(著者抄録)

    DOI: 10.7248/jjrhi.56.119

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  • 愛媛県における軽・中等度難聴児補聴器購入助成制度の現況

    寺岡 正人, 高木 大樹, 羽藤 直人

    小児耳鼻咽喉科   38 ( 2 )   226 - 226   2017.5

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  • 鼻アレルギーモデルマウスに対する新規低分子化合物SH-2251の有効性

    木谷 卓史, 山下 政克, 丸山 砂穂, 西田 直哉, 羽藤 直人

    耳鼻咽喉科ニューロサイエンス   31   43 - 45   2017.5

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    OVAにより感作させたアレルギー性鼻炎モデルマウスに新規低分子化合物SH-2251を投与し、有効性を検討した。SH-2251の投与は10mg/kgの濃度で1日1回経口投与を行った。対照群はSH-2251の調整に用いたVehicle(DMSO+Tween80水溶液)の経口投与を行った。OVA点鼻開始と同時に薬剤の経口投与を開始し、3週間経口投与を行った時点で効果を判定した。行動学的評価として点鼻後10分間のくしゃみ・鼻掻きの回数を検討したところ、SH-2251群ではVehicle群に比べ有意に減少し、即時相反応の改善を認めた。また、組織学的評価として最終OVA点鼻24時間後の好酸球浸潤や粘膜の厚みを検討したところ、SH-2251群ではVehicle群に比べ改善傾向を認め、遅発相反応も軽減していると考えられた。最終点鼻1時間後の鼻粘膜よりRNAを抽出しmRNA発現量を比較したところ、H-2251群ではVehicle群に比べ有意にIL-5、IL-13の発現が抑制されていた。以上、SH-2251はIL-5産生抑制・好酸球浸潤抑制を介した鼻アレルギー・好酸球性炎症に対し有用である可能性が示唆された。

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  • Prognostic impact of salvage treatment on hearing recovery in patients with sudden sensorineural hearing loss refractory to systemic corticosteroids : A retrospective observational study

    Takayuki Nakagawa, Michio Yamamoto, Kozo Kumakawa, Shin-Ichi Usami, Naohito Hato, Keiji Tabuchi, Mariko Takahashi, Keizo Fujiwara, Akira Sasaki, Shizuo Komune, Norio Yamamoto, Harukazu Hiraumi, Tatsunori Sakamoto, Akira Shimizu, Juichi Ito

    Journal of Otolaryngology of Japan   120 ( 3 )   274 - 275   2017

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    DOI: 10.3950/jibiinkoka.120.274

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  • 愛媛県における小児難聴の発見と療育の現状

    小川 日出夫, 高木 大樹, 寺岡 正人, 羽藤 直人

    愛媛医学   35 ( 4 )   182 - 187   2016.12

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    目的:乳幼児の聴覚障害は、言語発達、学習、心理面、コミュニケーションなどに大きな影響を及ぼすとされ、早期発見および早期対応が重要とされている。今回、愛媛県における難聴児の早期発見、療育介入の現況を調査したので報告する。方法:2005年4月から2015年3月の10年間に、難聴精査のために愛媛県身体障害者福祉センターを受診した7歳未満の未就学児512例を対象とした。これらの512例に対して、他覚的聴力検査(ABR、ASSR)を中心に精密聴力検査を行い、聴力を推定した。さらに、補聴器による療育開始年齢、新生児聴覚スクリーニング検査陽性児の精密聴力検査結果、愛媛県内の療育機関の状況について後ろ向きに検討した。結果:未就学児512例に対して精密聴力検査を行った結果、両側難聴は174例(34%)、一側性難聴は41例(8%)、健常聴力は281例(55%)、その他16例(3%)であった。補聴器による療育介入に関しては、10年間の集計期間において補聴器装用開始が早くなっており、早期発見、早期対応の傾向がみられた。新生児聴覚スクリーニング検査で要精査となり、受診した児の10年間の年平均は7.4人、受診者全体に対する聴覚スクリーニング陽性児の割合は平均14.2%であった。両者は徐々に増加傾向がみられた。新生児聴覚スクリーニング検査要精査児51例の精密聴力検査結果は重度難聴13例(25.5%)、高度難聴10例(20.0%)、中等度難聴10例(20.0%)、軽度難聴6例(11.8%)、一側性難聴5例(9.8%)、健常聴力7例(13.7%)であった。結論:愛媛県では小児難聴の診療に関して、診断、治療、療育と一連のプロセスが確立している点が評価できた。今後も早期発見、早期対応や充実した支援体制を目指し、新生児聴覚スクリーニング検査のさらなる普及、公的補助の改善が必要と思われた。(著者抄録)

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  • 【私はこうしている-耳科手術編】 顔面神経手術 顔面神経鞘腫の手術

    寺岡 正人, 羽藤 直人

    JOHNS   32 ( 9 )   1367 - 1370   2016.9

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  • 当科における小児人工内耳手術症例の検討

    寺岡 正人, 羽藤 直人, 山田 啓之, 岡田 昌浩

    Otology Japan   26 ( 4 )   400 - 400   2016.9

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  • Volume rendering imageを用いた内視鏡下副鼻腔手術トレーニングの有効性

    高木 大樹, 西田 直哉, 羽藤 直人

    日本鼻科学会会誌   55 ( 2 )   129 - 133   2016.7

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    内視鏡下副鼻腔手術(Endoscopic sinus surgery,ESS)の基本的なコンセプトを学ぶための新たな手法として,Volume rendering imageを用いたトレーニング法を考案した。この手法はCone Beam CTの閲覧用ソフトであるモリタ社のi-viewを用いて行った。i-viewには削開モードが搭載されており,任意の点を中心とした球状の空間を,マウスクリックによって削除することができる。限界領域に色付けを行うことで危険領域を認識するなど,i-viewの特性を生かした学習法が可能である。正常粘膜と病変部位の境界が識別困難であるため,現時点では副鼻腔炎などの手術シミュレーションに用いることはできないが,基本的な手術の手順や解剖の理解に有用であると考える。当科で勤務して2年以内の若手耳鼻科医5名を対象に,本トレーニングを行ったところ,操作時間の短縮だけでなく,初期にみられた不十分な蜂巣の開放や危険領域の認識などが大幅に改善するなどの成果を得られた。一方で実際の手術と比較して,内視鏡と鉗子の干渉が再現困難などの課題も見られた。本トレーニング法の有効性と今後の検討課題について,文献的考察を含め報告する。(著者抄録)

    DOI: 10.7248/jjrhi.55.129

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  • 頸部縦隔ガス壊疽後嚥下障害に対し嚥下機能改善術を行った一例

    西窪加緒里, 池田健二, 三瀬和代, 飴矢美里, 勢井洋史, 西田直哉, 清水清貴, 羽藤直人

    嚥下医学   4 ( 2 )   297   2015.9

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  • Treatment of neural anosmia by topical application of bFGF-gelatin hydrogel in the nasal cavity: an experimental study in mice

    Jumpei Nota, Hirotaka Takahashi, Nobuhiro Hakuba, Naohito Hato, Kiyofumi Gyo, Yasuhiko Tabata

    CHEMICAL SENSES   40 ( 7 )   627 - 628   2015.9

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  • ラット内喉頭筋における脱神経後のタンパク転写因子に関する研究

    勢井洋史, 西田直哉, 羽藤直人

    耳鼻咽喉科ニューロサイエンス   29   62 - 63   2015.6

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  • ラット内喉頭筋における脱神経後のタンパク転写因子に関する研究

    勢井洋史, 田口亜紀, 西田直哉, 羽藤直人

    日本耳鼻咽喉科学会会報   118 ( 4 )   552   2015.4

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  • 声門に病変を生じたRosai-Dorfman病の1例

    真田 朋昌, 羽藤 直人, 鵜久森 徹, 山田 啓之, 西田 直哉, 勢井 洋史

    日本気管食道科学会会報   66 ( 2 )   s103 - s103   2015.4

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  • 長時間の胃内視鏡手術後に生じた一側性声帯麻痺に対する音声治療の経験

    田口 亜紀, 三瀬 和代, 勢井 洋史, 西田 直哉, 平松 宏之, 羽藤 直人

    日本気管食道科学会会報   66 ( 2 )   s9 - s9   2015.4

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  • 当院における誤嚥性肺炎症例の検討

    池田 健二, 三瀬 和代, 飴矢 美里, 山田 啓之, 西田 直哉, 羽藤 直人

    愛媛医学   34 ( 1 )   66 - 67   2015.3

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  • 甲状腺内に悪性リンパ腫と乳頭癌が重複した一例

    勢井洋史, 吉田正, 鵜久森徹, 羽藤直人

    日本頭頚部外科学会総会・学術講演会プログラム・予稿集   25th   134   2015

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  • Facial nerve decompression surgery for bell's palsy

    Naohito Hato

    Practica Oto-Rhino-Laryngologica   108 ( 4 )   257 - 263   2015

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    Bell's palsy is one of the most common causes of facial nerve paralysis, usually on one side of the face, that has no known underlying cause. The natural course of this disease is generally favorable, and approximately 70% of patients recover completely without treatment. The pathogenesis of Bell's palsy involves herpes simplex virus infection, inflammatory changes, secondary edema, and entrapment neuropathy in the narrow fallopian canal. Steroids and adjunctive antiviral agents are the treatment of choice. However, approximately 10% of patients do not respond to conservative treatment and experience profound denervation leading to severe sequelae. The treatment strategy for severe paralysis is acceleration of recovery by preventing further worsening of nerve degeneration in the early phase of the incident. Facial nerve decompression surgery is indicated in cases of Bell's palsy suspected to have a poor prognosis, usually within 2 weeks of onset. Since Ballance and Duel first reported decompression of the facial nerve at the distal mastoid segment in 1932, several treatment procedures have been proposed
    however, there only very low quality evidence exists, based on which an informed decision could not be made as to whether an operation would be helpful or harmful for patients with Bell's palsy. Currently, most patients are treated medically, and decompression surgery is rarely undertaken. Decompression more than weeks after the onset of paralysis is particularly rare because the surgical procedure is unlikely to facilitate nerve regeneration. However, the history of, the evidence for, and the procedure of facial nerve decompression surgery are still interesting for neuro-otologists who have to treat patients with severe Bell's palsy, therefore those must be described in detail.

    DOI: 10.5631/jibirin.108.257

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  • 突発性難聴に対するIGF1局所投与有効性に関するランダム化対照試験

    中川隆之, 坂本達則, 平海晴一, 山本典生, 熊川孝三, 宇佐美真一, 羽藤直人, 田渕経司, 村上信五, 内藤泰, 佐々木亮, 小宗静男, 伊藤壽一

    日本耳鼻咽喉科学会会報   117 ( 4 )   469   2014.4

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  • Epithelial pearl formation following tympanic membrane regeneration therapy using an atelocollagen/silicone membrane and basic fibroblast growth factor: Our experience from a retrospective study of one hundred sixteen patients

    N. Hakuba, N. Hato, Y. Omotehara, M. Okada, K. Gyo

    CLINICAL OTOLARYNGOLOGY   38 ( 5 )   394 - 397   2013.10

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    DOI: 10.1111/coa.12164

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  • 検査結果をどう読むか?顔面神経領域の検査 NET,ENoG

    藤原 崇志, 羽藤 直人

    JOHNS耳鼻咽喉科・頭頸部外科   29 ( 9 )   1566 - 1568   2013.9

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  • 副鼻腔炎に対する塩酸モキシフロキサシンの有効性

    高橋 宏尚, 青石 邦秀, 西田 直哉, 羽藤 直人, 暁 清文

    日本耳鼻咽喉科感染症研究会会誌   31 ( 1 )   91 - 93   2013.5

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    2008年1月〜2009年12月の2年間に著者らの施設で加療した副鼻腔炎64症例(急性副鼻腔炎44例、慢性副鼻腔炎18例、副鼻腔炎の術後感染2例)に対するモキシフロキサシン塩酸塩(MFLX)の臨床効果について検討した。MFLXの投与方法は400mgを1日1回、5〜7日間内服とし、自覚症状、他覚所見および画像所見をスコア化して投薬前後で評価した。その結果、自覚症状では鼻漏、後鼻漏、鼻閉および頭痛・顔面痛の全てで投与前に比べ投与後有意に改善していた。一方、他覚所見では鼻粘膜発赤、鼻粘膜浮腫・腫脹および後鼻漏量の全てにおいて投与後は有意な改善がみられた。また、CTおよびX線像でも上顎洞・篩骨洞ともに投与後の所見が有意に改善していた。以上より、MFLXは急性副鼻腔炎、慢性副鼻腔炎の急性増悪期に対して早期に臨床症状を改善できる薬剤と考えられた。

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  • Bell麻痺に対する再生促進顔面神経減荷手術

    羽藤 直人, 能田 淳平, 菰渕 勇人, 澤井 尚樹, 寺岡 正人, 暁 清文

    Facial Nerve Research   32   128 - 130   2012.11

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    高度に変性にした顔面神経麻痺では、通常の治療を行っても十分な神経再生が得られず後遺障害を生じる場合が多い。このような症例の予後改善には、神経障害部位の軸索伸長および再髄鞘化を促すことが重要であり、再生医療のターゲットとなり得る。著者等は、顔面神経に徐放化栄養因子を投与する再生促進治療を行っており、良好な成績が得られているので報告した。この新しい顔面神経減荷手術は、1)神経再生を促進、2)発症2週以降でも適応、3)低侵襲な手術手技、4)合併症の軽減、をコンセプトとしており、普遍的な治療となる可能性を持っている。これまでに高度Bell麻痺20例に施行し、治療成績は、House-Brackmann法におけるグレード1または2への回復率が95%(19例)であり、従来の治療法施行例に比べて有意に高かった。

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  • EFFECT OF LIPOSOME-ENCAPSULATED HEMOGLOBIN AFTER TRANSIENT COCHLEAR ISCHEMIA AND REPERFUSION IN THE GERBIL

    M. Okada, A. T. Kawaguchi, N. Hakuba, S. Takeda, J. Hyodo, N. Hato, K. Gyo

    INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS   34 ( 8 )   647 - 647   2011.8

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  • Roll of Antibiotics to Reducing Post-Tonsillectomy Hemorrhage in Adult Patients

    Masahiro Okada, Hirotaka Takahashi, Naohito Hato, Kiyofumi Gyo, Taisuke Kobayashi, Koshiro Nakamura

    RECENT ADVANCES IN TONSILS AND MUCOSAL BARRIERS OF THE UPPER AIRWAYS   72   218 - 219   2011

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  • Bell麻痺における健側電気味覚検査の検討

    能田 淳平, 羽藤 直人, 寺岡 正人, 澤井 尚樹, 飴矢 美里, 暁 清文

    Facial Nerve Research   30   43 - 45   2010.12

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    最近Bell麻痺の病態として単純ヘルペスウイルス1型(HSV-1)の関与が明らかにされた。ウイルス同定が左右個々に施行可能な耳介や涙液などの検体からはHSV-1が健側からも検出されており、Bell麻痺患者では両側性にHSV-1の再活性化が生じている可能性が指摘されている。そこで今回、その可能性について、健側電気味覚閾値の観点から検討した。対象は、過去35年間に当科受診したBell麻痺患者のうち初診時に電気味覚検査を施行された595例とし、健常コントロール群として中里らの「健康人の電気味覚検査」のデータを使用した。検討の結果、健常コントロール群と比較してBell麻痺群では患側のみならず健側の味覚閾値も有意に上昇しており、両側性HSV-1再活性化が示唆された。このことから、Bell麻痺患者の電気味覚検査においては従来の左右差に基づく診断基準を見直す必要があると考えられた。

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  • Development of an implanted bone-conduction hearing aid using giant magnetostrictive material

    Takuji Koike, Kensei Yamamoto, Michihito Aoki, Kyoji Homma, Naohito Hato, Sho Kanzaki

    HEARING RESEARCH   263 ( 1-2 )   240 - 240   2010.5

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    DOI: 10.1016/j.heares.2010.03.034

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  • The new tool of ossicular mobility tester using an electromagnetic driver and a piezoelectric sensor

    Daiki Takagi, Kiyofumi Gyo, Naohito Hato, Takeshi Iwakura

    HEARING RESEARCH   263 ( 1-2 )   246 - 246   2010.5

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    DOI: 10.1016/j.heares.2010.03.055

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  • Hearing improvement with laser contraction myringoplasty far tympanic membrane atelectasis

    Naohito Hato, Daiki Takagi, Kiyofumi Gyo

    HEARING RESEARCH   263 ( 1-2 )   247 - 248   2010.5

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    DOI: 10.1016/j.heares.2010.03.059

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  • Long-term follow up study of Rion implantable hearing aid

    Kiyofumi Gyo, Naohito Hato, Masahiro Komori, Naoaki Yanagihara

    HEARING RESEARCH   263 ( 1-2 )   241 - 241   2010.5

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    DOI: 10.1016/j.heares.2010.03.036

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  • Evaluation Of Electrogustometry for Patients with Peripheral Facial Nerve Palsy

    TERAOKA Masato, SAWAI Naoki, HATO Naohito, GYO Kiyofumi

    29   148 - 150   2010.1

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  • Clinical Trial of Facial Nerve Decompression Surgery using a Basic Fibroblast Growth Factor Combined with Biodegradable Hydrogel

    HATO Naohito, SAWAI Naoki, TERAOKA Masato, GYO Kiyofumi

    29   54 - 55   2010.1

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  • New Objective Evaluation of Facial Paralysis using Face Sensing Technology "OKAO^【○!R】 Vision"

    SAWAI Naoki, HATO Naohito, TERAOKA Masato, TAKAHASHI Hirotaka, WAKISAKA Hiroyuki, AMEYA Misato, GYO Kiyofumi

    Facial N Res Jpn   29   68 - 70   2010.1

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  • 患者アンケートを用いた顔面神経麻痺後遺症に対するリハビリテーションの効果検討

    飴矢 美里, 羽藤 直人, 澤井 尚樹, 寺岡 正人, 暁 清文

    Facial Nerve Research   29   124 - 126   2010.1

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    麻痺発症から4ヵ月以上後にリハビリテーションを開始した高度顔面神経麻痺患者5名(平均53.8歳)を対象として、リハビリテーション前後のQOLの変化をFacial Clinimetric Evaluation Scale(FaCE Scale)を用いて評価した。原因疾患はBell麻痺3例、Hunt症候群1例、外傷性1例であり、FaCE Scaleのアンケート項目を各分野別に分けて調査した結果、リハビリテーション後は社会活動や食事摂取の分野で変化がみられ、顔面神経麻痺患者の日常生活動作や心理的側面が改善されていることが示唆された。また、FaCE ScaleでのQOL改善とともに柳原法での機能的回復も認められた。FaCE Scaleは患者の心理的側面を含め多面的に評価でき、簡便なアンケートで後遺症程度を定量的に判定可能であった。

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  • One-step nucleic acid amplification for detecting lymph node metastasis of head and neck cancer

    H. Goda, K. Nakashiro, T. Yoshimura, T. Sumida, H. Wakisaka, N. Hato, M. Hyodo, H. Hamakawa

    JOURNAL OF CLINICAL ONCOLOGY   27 ( 15 )   2009.5

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  • BILATERAL AND RECURRENT FACIAL PALSY

    SAWAI Naoki, HATO Naohito, TERAOKA Masato, WAKISAKA Hiroyuki, TAKAHASHI Hironao, GYO Kiyohumi

    Facial N. Res. Jpn.   28   54 - 57   2009.2

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  • Treatment for Bell&apos;s palsy - Reply

    Naohito Hato, Shingo Murakami, Kiyofumi Gyo

    LANCET   372 ( 9645 )   1220 - 1221   2008.10

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  • Valacyclovir for the treatment of Bell's palsy

    Naohito Hato, Naoki Sawai, Masato Teraoka, Hiroyuki Wakisaka

    EXPERT OPINION ON PHARMACOTHERAPY   9 ( 14 )   2531 - 2536   2008.10

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    Despite recent evidence suggesting that Bell's palsy is associated with reactivation of alfa-herpes viruses, the disease has been treated empirically, and the use of valacyclovir has not been definitively established. In 2007, two prospective, randomised, placebo-controlled trials evaluating valacyclovir were reported in patients with Bell's palsy. One demonstrated that valacyclovir/prednisolone therapy was statistically more effective than placebo/prednisolone therapy in improving the recovery of patients with Bell's palsy, excluding zoster sine herpete. However, considering the cost-benefit ratio of this treatment and the limitations of virological diagnoses, we recommend that valacyclovir should be used in cases of severe palsy within 3 days after the onset of Bell's palsy.

    DOI: 10.1517/14656560802365447

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  • Postischemic mild hypothermia alleviates hearing loss because of transient ischemia

    Shoichiro Takeda, Nobuhiro Hakuba, Tadashi Yoshida, Kensuke Fujita, Naohito Hato, Ryuji Hata, Jun Hyodo, Kiyofumi Gyo

    NEUROREPORT   19 ( 13 )   1325 - 1328   2008.8

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    The effect of postischemic mild hypothermia on the inner ear has not been clarified. In this study, we investigated whether hypothermia after transient ischemia could prevent cochlear damage and its therapeutic time window. Mongolian gerbils were divided into six groups: a sham-operation group, a normothermia group, and four hypothermia groups in which hypothermia was induced 1-7, 1-4, 36, and 6-9 h after reperfusion. Animals subjected to postischemic mild hypothermia within 3 h after reperfusion had attenuated hearing loss and inner hair cell loss. The protective effect was greater when hypothermia was induced earlier and had a longer duration. This implies that mild hypothermia after ischemia could have therapeutic effects for inner ear ischemic damage. NeuroReport 19:1325-1328 (c) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

    DOI: 10.1097/WNR.0b013e32830b5f73

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  • Sentinel lymph node molecular staging in head and neck squamous cell carcinoma

    H. Goda, K. Nakashiro, T. Yoshimura, H. Nishikawa, T. Sumida, H. Wakisaka, N. Hato, M. Hyodo, H. Hamakawa

    JOURNAL OF CLINICAL ONCOLOGY   26 ( 15 )   2008.5

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  • Steroid and antiviral treatment for Bell&apos;s palsy

    Naohito Hato, Shingo Murakami, Kiyofumi Gyo

    LANCET   371 ( 9627 )   1818 - 1820   2008.5

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    DOI: 10.1016/S0140-6736(08)60776-X

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  • IDENTIFICATION OF DIFFERENTIALLY EXPRESSED GENES IN DENERVATED FACIAL MUSCLE

    TERAOKA Masato, KOMOBUCHI Hayato, HATO Naohito, GYO Kiyofumi

    27   120 - 122   2008.1

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  • FACIAL NERVE REGENERATION FOLLOWING DECOMPRESSION SURGERY WITH A BACIC FIBROBLAST GROWTH FACTOR-IMPREGNATED BIODEGRADABLE HYDROGEL

    HATO Naohito, KOMOBUCHI Hayato, TERAOKA Masato, GYO Kiyofumi

    27   218 - 220   2008.1

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  • THE CHANGE IN THE INCIDENCE OF DIABETES MELLITUS AND THE PROGNOSIS IN PATIENTS WITH BELL'S PALSY

    KISAKI Hisanobu, HATO Naohito, GYO Kiyofumi

    Facial N Res Jpn   27   55 - 58   2008.1

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  • FACIAL NERVE REGENERATION WITH A BIODEGRADABLE NERVE GUIDE

    KOMOBUCHI Hayato, HATO Naohito, TERAOKA Masato, GYO Kiyofumi

    27   210 - 213   2008.1

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  • b-FGF の徐放投与による再生促進を目的とした顔面神経減荷手術 Reviewed

    羽藤直人, 菰渕勇人, 寺岡正人, 田畑泰彦

    第7回再生医療学会(2008.3.14.名古屋)   2008

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  • 当科における小児顔面神経麻痺の臨床統計

    寺岡 正人, 辻村 美佳, 羽藤 直人, 暁 清文

    小児耳鼻咽喉科   28 ( 2 )   45 - 45   2007.6

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  • Valacyclovir and prednisolone treatment for Bell&apos;s palsy: A multicenter, randomized, placebo-controlled study

    Naohito Hato, Hiroyuki Yamada, Hisashi Kohno, Shuichi Matsumoto, Nobumitsu Honda, Kiyofumi Gyo, Satoshi Fukuda, Yasushi Furuta, Fumio Ohtani, Hiroshi Aizawa, Masaru Aoyagi, Hiroo Inamura, Tsutomu Nakashima, Seiichi Nakata, Shingo Murakami, Jun Kiguchi, Koji Yamano, Taizo Takeda, Masashi Hamada, Kazuhiro Yamakawa

    OTOLOGY & NEUROTOLOGY   28 ( 3 )   408 - 413   2007.4

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    Objective: To investigate the effects of valacyclovir and prednisolone in comparison with those of placebo and prednisolone for the treatment of Bell&apos;s palsy, excluding zoster sine herpete.
    Study Design: Prospective, multicenter, randomized placebo-controlled study.
    Setting: Six academic tertiary referral centers.
    Patients: Ultimately, 221 patients with Bell&apos;s palsy who were treated within 7 days of the onset. Serological and polymerase chain reaction examinations were performed to distinguish Bell&apos;s palsy from zoster sine herpete.
    Intervention: The patients were treated with either valacyclovir (dosage, 1,000 mg/d for 5 days) plus prednisolone (VP [n = 114]) or placebo plus prednisolone (PP [n = 107]) administered orally.
    Main Outcome Measure: Recovery from the palsy was defined as a score higher than 36 using Yanagihara 40-point scoring system without facial contracture or synkinesis. The patients were followed up until complete recovery occurred or for more than 6 months in cases with a poor prognosis.
    Results: The overall rate of patient recovery among those treated with VP (96.5%) was significantly better (p &lt; 0.05) than the rate among those treated with PP (89.7%). The rate of patient recovery was also analyzed by classifying the initial severity of facial palsy. In cases of complete or severe palsy, the rates of patients treated with VP and PP who recovered were 95.7% (n = 92) and 86.6% (n = 82), respectively; the recovery rate for treatment with VP was significantly better than that with PP (p &lt; 0.05).
    Conclusion: The valacyclovir and prednisolone therapy was more effective in treating Bell&apos;s palsy, excluding zoster sine herpete, than the conventional prednisolone therapy. To our knowledge, this is the first controlled study of an antiviral agent in the treatment of a sufficient number of Bell&apos;s palsy cases based on an etiologic background.

    DOI: 10.1097/01.mao.0000265190.29969.12

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  • Valacyclovir and prednisolone treatment for Bell&apos;s palsy: A multicenter, randomized, placebo-controlled study

    Naohito Hato, Hiroyuki Yamada, Hisashi Kohno, Shuichi Matsumoto, Nobumitsu Honda, Kiyofumi Gyo, Satoshi Fukuda, Yasushi Furuta, Fumio Ohtani, Hiroshi Aizawa, Masaru Aoyagi, Hiroo Inamura, Tsutomu Nakashima, Seiichi Nakata, Shingo Murakami, Jun Kiguchi, Koji Yamano, Taizo Takeda, Masashi Hamada, Kazuhiro Yamakawa

    OTOLOGY & NEUROTOLOGY   28 ( 3 )   408 - 413   2007.4

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    Objective: To investigate the effects of valacyclovir and prednisolone in comparison with those of placebo and prednisolone for the treatment of Bell&apos;s palsy, excluding zoster sine herpete.
    Study Design: Prospective, multicenter, randomized placebo-controlled study.
    Setting: Six academic tertiary referral centers.
    Patients: Ultimately, 221 patients with Bell&apos;s palsy who were treated within 7 days of the onset. Serological and polymerase chain reaction examinations were performed to distinguish Bell&apos;s palsy from zoster sine herpete.
    Intervention: The patients were treated with either valacyclovir (dosage, 1,000 mg/d for 5 days) plus prednisolone (VP [n = 114]) or placebo plus prednisolone (PP [n = 107]) administered orally.
    Main Outcome Measure: Recovery from the palsy was defined as a score higher than 36 using Yanagihara 40-point scoring system without facial contracture or synkinesis. The patients were followed up until complete recovery occurred or for more than 6 months in cases with a poor prognosis.
    Results: The overall rate of patient recovery among those treated with VP (96.5%) was significantly better (p &lt; 0.05) than the rate among those treated with PP (89.7%). The rate of patient recovery was also analyzed by classifying the initial severity of facial palsy. In cases of complete or severe palsy, the rates of patients treated with VP and PP who recovered were 95.7% (n = 92) and 86.6% (n = 82), respectively; the recovery rate for treatment with VP was significantly better than that with PP (p &lt; 0.05).
    Conclusion: The valacyclovir and prednisolone therapy was more effective in treating Bell&apos;s palsy, excluding zoster sine herpete, than the conventional prednisolone therapy. To our knowledge, this is the first controlled study of an antiviral agent in the treatment of a sufficient number of Bell&apos;s palsy cases based on an etiologic background.

    DOI: 10.1097/01.mao.0000265190.29969.12

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  • GLOBAL ANALYSIS OF GENE EXPRESSION IN DENERVATED FACIAL MUSCLE

    TERAOKA Masato, HATO Naohito, KOMOBUCHI Hayato, WAKISAKA Hiroyuki, TAKAHASHI Hirotaka, GYO Kiyofumi

    26   38 - 40   2006.3

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  • DDS を用いたbFGF の顔面神経再生促進効果 Reviewed

    寺岡正人, 羽藤直人, 菰渕勇人, 暁清文, 田畑泰彦

    第9 回日本組織工学会(2006.9.7-8. 京都)   2006

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  • Round window membrane motion with air conduction and bone conduction stimulation

    S Stenfelt, N Hato, RL Goode

    HEARING RESEARCH   198 ( 1-2 )   10 - 24   2004.12

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    The vibration patterns of the round window (RW) membrane in human cadaver temporal bone specimens were assessed by measurements of the velocity of reflective targets placed on the RW membrane with an approximate spacing of 0.2 mm. The velocity was measured in the frequency range 0.1-10 kHz by a laser Doppler vibrometer in four specimens with air conduction (AC) stimulation and in four specimens with bone conduction (BC) stimulation. The response pattern was investigated by analyzing the velocity response of all targets on the RW membrane, by making iso-amplitude and iso-phase contour plots of the membrane surface, and by creating animations of the surface vibration at several frequencies. Similar response pattern was found with AC and BC stimulations. At frequencies below 1.5 kHz, the RW membrane vibrates nearly as a whole in an in-and-out motion and above 1.5 kHz, the membrane moves primarily in two sections that vibrate with approximately 180degrees difference. Indication of some traveling wave motion of the RW membrane at those frequencies was also found. At higher frequencies, above 3 kHz, the membrane motion is complex with a mixture of modal and traveling wave motion. An increase of the stimulation level did not alter the vibration pattern; it only gave an increase of the RW membrane vibration amplitude corresponding to the increase in stimulation. When the mode of stimulation at the oval window was altered, by the insertion of a 0.6 mm piston, the vibration pattern of the RW membrane changed. (C) 2004 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.heares.2004.07.008

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  • 人工神経と神経再生

    Facial Nerve Research   24   16 - 18   2004

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  • Fluid volume displacement at the oval and round windows with air and bone conduction stimulation

    J Acoust Soc Am.   25 ( 1 )   68 - 72   2004

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  • Fluid volume displacement at the oval and round windows with air and bone conduction stimulation

    J Acoust Soc Am.   25 ( 1 )   68 - 72   2004

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  • Ramsay Hunt syndrome in children

    N Hato, H Kisaki, N Honda, K Gyo, S Murakami, N Yanagihara

    ANNALS OF NEUROLOGY   48 ( 2 )   254 - 256   2000.8

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    In a retrospective study, 52 children were diagnosed with Ramsay Hunt syndrome. The facial palsy was milder and complete recovery of the function was achieved in 78.6% of patients. Associated cranial neuropathies were less common in children than in adults. The timing of vesicle appearance tended to be delayed in children. In preschool children, Ramsay Hunt syndrome was rare, although the frequency has recently increased. The syndrome is relatively common in older children. This study suggested that vaccination can prevent or reduce the occurrence of Ramsay Hunt syndrome.

    DOI: 10.1002/1531-8249(200008)48:2<254::AID-ANA17>3.0.CO;2-V

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  • Immunologic aspects of facial nerve paralysis induced by herpes simplex virus infection in mice

    N Hato, Y Hitsumoto, S Murakami, N Honda, N Yanagihara

    ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY   107 ( 8 )   633 - 637   1998.8

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    The immunologic aspects of facial nerve paralysis due to herpes simplex virus type 1 (HSV-1) infection were investigated in a mouse model system. Half of the 4- to 5 week-old mice developed facial nerve paralysis, whereas none of the 6-week-old mice died or developed facial nerve paralysis on inoculation with HSV-1. Six-week-old mice showed significantly higher titers of anti-HSV-1 neutralizing antibody than did 4-week-old animals. Passive transfer of either anti-HSV-1 antibody or HSV-1-immunized splenic T cells into 4-week-old mice 3 hours after HSV-1 inoculation prevented development of facial nerve paralysis and death, whereas such transfers 48 or 96 hours after HSV-1 inoculation did not prevent or exacerbate facial nerve paralysis. These results demonstrate that the age and the immunologic potency of mice are closely related to the pathogenesis of facial nerve paralysis. That facial nerve paralysis developed even in 6-week-old mice whose T-cell function was suppressed with anti-CD3 antibody suggests that virus-induced cellular demyelination is unlikely as a cause of facial nerve paralysis in this animal model.

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  • Treatment of ramsay hunt syndrome with acyclovir prednisone: Significance of early diagnosis and treatment

    S Murakami, N Hato, J Horiuchi, N Honda, K Gyo, N Yanagihara

    ANNALS OF NEUROLOGY   41 ( 3 )   353 - 357   1997.3

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    Although the antiviral agent acyclovir is currently used for the treatment of Ramsay Hunt syndrome, its effects on facial nerve and hearing recovery remain controversial. We retrospectively analyzed the effects of acyclovir-prednisone treatment in 80 Ramsay Hunt patients. Of 28 patients for whom treatment was begun within 3 days of the onset of facial paralysis, the recovery from paralysis was complete in 21 (75%). By comparison, of 23 patients for whom treatment was begun more than 7 days after onset, recovery from facial paralysis was complete in only 7 (30%). A significant difference in facial nerve recovery was found between these groups. Early administration of acyclovir-prednisone was proved to reduce nerve degeneration by nerve excitability testing. Hearing recovery also tended to be better in patients with early treatment. There was no significant difference in facial nerve outcome between intravenous and oral acyclovir treatment.

    DOI: 10.1002/ana.410410310

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  • Role of herpes simplex virus infection in the pathogenesis of facial paralysis in mice

    S Murakami, N Hato, M Mizobuchi, T Doi, N Yanagihara

    ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY   105 ( 1 )   49 - 53   1996.1

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    To clarify the role and site of herpes simplex virus (HSV) infection in the pathogenesis of facial paralysis, we examined the viral genome by the polymerase chain reaction and the neutralization antibody titer using microplates in an animal model. Following inoculation with HSV type 1 of the KOS strain into mouse auricles, HSV DNA appeared in the ipsilateral facial nerve on the 3rd day, and in bilateral facial nerves and the brain stem on the 10th day only in animals with facial paralysis. In animals without facial paralysis, no HSV DNA was detected in these tissues. The neutralization antibody titer was elevated between 4 and 20 days in all animals, with or without facial paralysis. Facial paralysis developed only on the inoculated side, even though HSV DNA was also present in the contralateral facial nerve. We conclude that HSV infection in the facial nerve and brain stem is prerequisite for facial paralysis, and suggest that an immunologic reaction following viral infection plays a key role in the pathogenesis.

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  • Bell palsy and herpes simplex virus: Identification of viral DNA in endoneurial fluid and muscle

    S Murakami, M Mizobuchi, Y Nakashiro, T Doi, N Hato, N Yanagihara

    ANNALS OF INTERNAL MEDICINE   124 ( 1 )   27 - 30   1996.1

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    Objective: To determine whether herpes simplex virus type 1 (HSV-1) causes Bell palsy.
    Design: Prospective study.
    Setting: University inpatient service.
    Patients: 14 patients with Bell palsy, 9 patients with the Ramsay-Hunt syndrome, and 12 other controls.
    Measurements: Viral genomes of HSV-1, varicella-zoster virus, and Epstein-Barr virus were analyzed in clinical samples of facial nerve endoneurial fluid and posterior auricular muscle using polymerase chain reaction (PCR) followed by hybridization with Southern blot analysis.
    Results: Herpes simplex virus type 1 genomes were detected in 11 of 14 patients (79%) with Bell palsy but not in patients with the Ramsay-Hunt syndrome or in other controls. The nucleotide sequences of the PCR fragments were identical to those of the HSV-1 genome.
    Conclusions: Herpes simplex virus type 1 is the major etiologic agent in Bell palsy.

    DOI: 10.7326/0003-4819-124-1_Part_1-199601010-00005

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Industrial property rights

  • 埋込み型骨導補聴器

    小池 卓二, 羽藤 直人, 山本 顕生

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    Applicant:国立大学法人電気通信大学, 国立大学法人愛媛大学

    Application no:特願2008-246342  Date applied:2008.9

    Announcement no:特開2010-075394  Date announced:2010.4

    J-GLOBAL

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  • 埋込み型骨導補聴器

    小池 卓二, 羽藤 直人, 山本 顕生

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    Applicant:国立大学法人電気通信大学, 国立大学法人愛媛大学

    Application no:特願2008-246342  Date applied:2008.9

    Announcement no:特開2010-075394  Date announced:2010.4

    Patent/Registration no:特許第5219037号  Date issued:2013.3

    J-GLOBAL

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Awards

  • 日本耳科学会奨励賞

    2008  

    羽藤 直人

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  • 愛媛県医学会賞

    2006  

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Research Projects

  • Molecular pathological analysis of salivary gland carcinomas promoting personalized medicine: A large-scale multicenter study

    2021.4 - 2024.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Grant amount:\17550000 ( Direct Cost: \13500000 、 Indirect Cost:\4050000 )

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  • Development of a novel treatment for severe facial nerve palsy by intratympanic administration of sustained-release neurotrophic factor

    2020.4 - 2023.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

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  • Molecular pathological analysis of salivary gland carcinomas focusing on personalized medicine: A large-scale multicenter study

    2018.4 - 2021.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Inagaki Hiroshi

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    Grant amount:\17420000 ( Direct Cost: \13400000 、 Indirect Cost:\4020000 )

    Salivary gland carcinomas are rare tumors, and a large number of these carcinoma cases were collected through multicenter joint research and clinical pathological analysis was performed. We clarified that certain types of benign tumors are difficult to distinguish from adenoid cystic carcinoma, and proposed a novel grading system of adenoid cystic carcinoma. We reported that the prognosis of patients with specific fusion-positive mucoepidermoid carcinoma is extremely good, and that in these patients, postoperative radiotherapy can be omitted. It is hoped that these studies will promote molecular pathology of salivary gland carcinomas and that it will be directly and indirectly applied to the stratified and individualized treatment for patients with salivary gland carcinomas.

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  • Development of a new treatment for sequelae of facial nerve palsy

    2016.4 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Hato Naohito, Joko Tomonori, Kimura Takuya

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    Grant amount:\4810000 ( Direct Cost: \3700000 、 Indirect Cost:\1110000 )

    Peripheral facial palsy is a poor prognosis when neuropathy is severe, and sequelae is inevitable. It is necessary to promote regeneration of the nerve for cases of severe paralysis but it has not been universalized. Therefore, we sought to develop a treatment that could be easily treated with otolaryngology outpatients, with few complications, and with a high therapeutic effect, and conceived of an intratympanic administration of a controlled release nutritional factor. We succeeded in creating a reproducible high facial nerve paralysis model by local cooling, and observed the facial nerve paralysis regeneration by slow release administration of bFGF. Histologically and electrophysiologically, the nerve regeneration was evaluated, and compared with the control, bFGF sustained-release administration rapidly improved the facial nerve palsy and caused less aftereffects.

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  • Expression of Galectin-7 in cholesteatoma matrix and its clinical significance

    2014.4 - 2016.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    HATO NAOHITO, Takagi Daiki

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    Grant amount:\3510000 ( Direct Cost: \2700000 、 Indirect Cost:\810000 )

    Galectin-7, a member of lectin family, contributes to different events associated with the differentiation and development of pluristratified epithelia. By proteomic analysis of middle ear cholesteatoma obtained at operation, we found galectin-7 as a specific protein constituting cholesteatoma. As galectin 7 could be detected in cholesteatoma matrix but not in middle ear mucosa, it might be a good marker of the residue in surgery of middle ear cholesteatoma. Residue of the matrix is considered a main cause of cholesteatoma recurrence. Therefore, detection of galectin-7 by immunofluorescent staining method would be an useful procedure in detecting presence of residual cholestetoma.

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  • 超磁歪素子を用いた次世代埋め込み型骨導補聴器の開発とその臨床評価

    2012.4 - 2014.3

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    暁 清文, 羽藤 直人, 白馬 伸洋, 岡田 昌浩

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    Grant amount:\12350000 ( Direct Cost: \9500000 、 Indirect Cost:\2850000 )

    超磁歪素子を用いた埋込み式骨導補聴器(me-BAHA:Magnetostrictive Element Bone Anchored Hearing Aid)の開発を目的に、試作したme-BAHA用骨導振動子をBAHA埋め込み患者のチタン製接合子に連結させ、検査音を聞かせた時の聴覚閾値や語音明瞭度、騒音下語音明瞭度を求め、BAHAとの聞こえの違いを比較した。本研究はヒトを対象とした実験であるため、研究内容について愛媛大学医学部附属病院倫理委員会の審査・承認を得た上で実施した。
    この検査は当院外来の聴力検査室内で行い、語音聴力検査には57-S語表の単音節語表を用いた。まず正常者の耳後部に経皮的にme-BAHA用振動子をあてて骨導刺激し、その時の聴覚的な印象を求めた。その結果、皮膚を介するため10dB程度の音の減衰が生じたが、会話音声は明瞭でよく聞こえ、特に高音域での聴覚は良好であった。ついでBAHAの埋め込み患者で行った検査では、me-BAHA使用時の聴力レベルはBAHA使用時とほぼ同程度であり、高音域ではむしろme-BAHA使用時の方が10dB~40dB、優れていた。語音明瞭度検査の比較でも、me-BAHA はBAHAとほぼ同等の成績であり、これは10dB~15dBのホワイトノイズを負荷した騒音下語音明瞭度検査でも同じであった。以上の結果より、me-BAHA による骨導聴覚はBAHAとほぼ同程度であり、さらに8kHzなどの高音域ではさらに良好な骨伝導が得られ、十分に臨床応用可能な成績であった。このことからme-BAHAは両側外耳道閉鎖症や難治性中耳炎患者にとって有力な聴力改善手段になることが期待できる。

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  • RNA expression in facial muscle following damage to the facial nerve -As a tool of early prognostic diagnosis-

    2010 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    HATO Naohito, WAKISAKA Hiroyuki

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    Grant amount:\4420000 ( Direct Cost: \3400000 、 Indirect Cost:\1020000 )

    This study investigated and identified differentially expressed facial muscle genes in rats with facial nerve damage. Two types of adult Wistar rats: 1) the main trunk of the facial nerve was transected(Group A) and 2) the main trunk was compressed for ten minutes (Group B) wereused for the analysis. Global gene expressions of facial muscles were analyzed using a micro-array system. A total of 26,835 RNA molecules were examined. Myogenin mRNA expression increased to the highest level at 7 days after denervation, thereafter it gradually decreased in Group A. Vesicle-associated membrane protein 2 and insulin-like growth factor binding protein 6 expression increased at 7 and 14 days in Group A. The gene expression was different depending on the degree of the facial nerve damage. Therefore, we concluded that analysis of the facial muscle profile gene expression could be a possible diagnostic tool for use in asthe prognosis after facial nerve injury.

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  • Liposome-encapsulated hemoglobin alleviates inner eardamage after transient cochlear ischemia in the gerbil

    2010 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    GYO Kiyofumi, HATO Naohito, HAKUBA Nobuhiro, KAWAGUCHI Akira

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    Grant amount:\2700000 ( Direct Cost: \2400000 、 Indirect Cost:\300000 )

    To test liposome-encapsulated hemoglobin (LEH) in transient cochlear ischemia/reperfusion as a model of sudden deafness, Mongolian gerbils were randomly assigned to receive 2 mL/kg of either low-affinity LEH (l-LEH, P50O2 = 40 mm Hg), high-affinity LEH (h-LEH, P50O2 = 10 mm Hg), homologous red blood cells (RBCs), or saline (each group n = 6) 30 min before 15-min occlusion of the bilateral vertebral arteries and reperfusion. As a result, h-LEH was significantly more protective than l-LEH in suppressing hearing loss, in contrast to RBC or saline treatment. The results suggested that pretreatment with h-LEH is significantly more protective than l-LEH in mitigating hearing loss and underlying pathological damage, in contrast to transfusion or saline infusion.

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  • Dynamic change of Myogenin in denervated rat mimetic muscle: Does the neural repair repress its expression ?

    2010 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    YAMAMOTO Yuhei, SEKIDOU Mitsuru, HATOU Naoto, FURUKAWA Hiroshi, OYAMA Akihiro

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    Grant amount:\18980000 ( Direct Cost: \14600000 、 Indirect Cost:\4380000 )

    Myogenin expression in facial mimetic muscles would be accumulated by denervation rapidly, and repressed by nerve repair. Myog expression level of mimetic muscle, just after nerve repair, will help surgeon to predict thepost-operative prognosis for facial palsy.

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  • Proteomic analysis of ischemic cochlear damage as a diagnostic tool of sudden sensorineural hearing loss

    2008 - 2010

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    GYO Kiyofumi, HATA Ryuji, HATO Naohito, HAKUBA Nobuhiro

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    Grant amount:\18330000 ( Direct Cost: \14100000 、 Indirect Cost:\4230000 )

    Pathology of transient cochlear ischemia as a cause of sudden deafness was investigated in gerbils. 1) Proteomic analysis showed that two genes, encoding GPCRs Class A and Peptide GPCRs, were dominantly expressed, suggesting needs for clinical study. 2) Cochlear damage was ameliorated by applying minor ischemia 2 days before major ischemia 3) Administration of AM-111, an apoptosis inhibitor, on the round window membrane was proved effective in decreasing damage of the cochlea.

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  • Treatment of facial nerve synkinesis by basic fibroblast growth factor impregnated in a biodegradable hydrogel

    2007 - 2008

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    HATO Naohito, TAKAHASHI Hirotaka, WAKISAKA Hiroyuki, KOMOBUCHI Hayato

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    Grant amount:\4420000 ( Direct Cost: \3400000 、 Indirect Cost:\1020000 )

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  • Treatment modality of ischemic hearing loss based on therapeutic time window

    2006 - 2007

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    GYO Kiyofiuni, HATA Ryuji, HATO Naohito, HYODO Jun, TAKEDA Shoichiro

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    Grant amount:\14250000 ( Direct Cost: \13500000 、 Indirect Cost:\750000 )

    Cochlear ischemia is supposed to be one of the major causes of idiopathic sudden sensorineural hearing loss (ISSH). The present study was conducted to reveal the mechanisms of cochlear damage in an animal model of transient cochlear ischemia using Mongolian gerbils. We further evaluated various therapeutic agents to develop a new treatment modality based on the therapeutic time window. Loading of transient cochlear ischemia for I5-min demonstrated that the cochlea was damaged not only by energy failure but also by a large amount of free radicals induced in the inner ear. Excessive release of glutamate from the synaptic clefts exclusively devastated the inner hair cells and the spiral ganglion neurons. Post-ischemic processes differed by the sites of the cochlea. Damage of the stria vascularis was severe immediate after the ischemia, which recovered gradually within a week. In the organ of Corti, the hair cells underwent apoptotic cell death that went on for 3 days. Degeneration of the spiral ganglion neurons progressed slowly, which lasted for more than a week. They were supposed to be due to secondary degeneration following death of the inner hair cells.
    In the treatment of ischemic cochlear damage, recovery of the blood supply is essential. Application of glutamate antagonist is effective only when applied immediate after the insult. This seems clinically impractical. In contrast, application of free radical scavenger (edaravon) or predonisone was effective to prevent damages of the cochlea. Furthermore, AM-111, a blocker of apoptotic process, protected death of the inner hair cells. All these findings suggested that treatment of ISSH should be individualized base on the therapeutic time window, since degenerative processes of the cochlea sequentially change after the onset of ischemia.

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  • 再生軟骨を利用した外耳道造成術の開発とその臨床応用上の問題点の研究

    2005 - 2006

    日本学術振興会  科学研究費助成事業  萌芽研究

    暁 清文, 羽藤 直人, 篠森 裕介, 兵頭 純

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    Grant amount:\2000000 ( Direct Cost: \2000000 )

    鼓室形成術の発展に伴い中耳疾患に対する手術成績は著しく向上したが、技術的に比較的単純と思われる外耳道閉鎖症の手術成績は今なお概して不良である。せっかく外耳道を造成しても、骨削開面からの肉芽増生や鼓膜の浅在化、移植皮膚弁感染などのため、やがて外耳道の再閉鎖が始まり、一旦改善した聴力は次第に悪化することが多い。このような現状を背景に、本研究では「手術で削開した外耳道骨面を軟骨で被覆することにより外耳道造成術後に高頻度でみられる肉芽性再閉鎖を防止する」という新しい発想による治療法開発をめざした。軟骨は柔軟性があり移植しても生着が容易なことから移植材料として最適であり、形態と強度が確保できれば、狭窄の起こらない安定した外耳道が造成できる。耳介形成術では肋軟骨でフレームを作成するため、残った軟骨片で外耳道を形成すれば余計な手術侵襲を加える必要がない。これまでの基礎的研究において、この術式の有効性を確認するとともに、先天性外耳道閉鎖症の3例にこの術式を適応した。手術は耳介形成術の初回手術(形成外科医による軟骨フレームワークの埋め込み)時に行い、上述の術式による外耳道造成術と鼓室形成術を同時に施行した。今回の研究により、以下のような問題点が明らかとなった。1)軟骨を遊離皮弁で覆うため、皮弁が壊死に陥りやすい。2)軟骨部外耳道には狭窄を防ぐ組織がないため、入口部狭窄が起こりやすい、3)骨部外耳道は比較的狭いので(健側とほぼ同じサイズ)、耳内が乾燥しにくい、などである。一方、形成された骨部外耳道の形態は安定しており、手術回数が削減できるメリットもあり、改良を加えれば本法は優れた術式に発展しうると結論した。

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  • Role of nitric oxide in facial nerve paralysis in mice induced by herpes simplex type 1 infection

    2005 - 2006

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    HATO Naohito

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    Grant amount:\3500000 ( Direct Cost: \3500000 )

    The present study was under gone to elucidate a role of nitric oxide (NO) on induction of facial palsy by inoculation of herpes simplex type 1 (HSV-1), and to evaluate the effects of edarabone to prevent occurrence of facial palsy of the viral origin. NO levels of in the facial nerve were measured by use of a high performance liquid chromatography and absorption photometry. Before the incidence of facial palsy, no substantial difference in NO levels was noted between HSV-1 inoculated sides (right) and the control (left) sides. When the facial nerve palsy occurred, NO levels of the paralyzed side were higher than of the other side. Following recovery of the palsy, NO of both sides were at the same level. In the mice that facial nerve paralysis did not occur in spite of inoculation of HSV-1, NO of both sides were at the same level. According to immunohistological study using the confocal laser microscope, inducible nitric oxide synthase (iNOS) was observed in the inflammatory cells at the geniculate ganglion in animals with facial palsy presents. It was recognized only at the involved paralyzed side not at the contralateral side. Edarabone, a free radical scavenger, was administed to the animals immediately after inoculation of HSV-1 for as long as 11 days. The results indicated that 10mg/kg of edarabone was effective in reducing the incidence of facial palsy. In conclusion, NO, which is supposed to be produced at the geniculate ganglion via iNOS, plays an important role in induction of facial palsy by HSV-1, and, such damages may be prevented by use of edarabone.

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  • New strategy for the treatment of sudden-onset hearing loss based on ischemic cell damage theory

    2004 - 2005

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    GYO Kiyofumi, HATO Naohito, SHINOMORI Yusuke

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    Grant amount:\14300000 ( Direct Cost: \14300000 )

    Underlining mechanisms of an ischemic cochlear damage were investigated using Mongolian gerbils. The animals were subjected to ischemic insult by occluding the vertebral arteries bilaterally for 15 min. The ischemia caused severer damage at the basal turn than at the apical turn. At the spiral ganglion, the number of neurons decreased gradually by ischemic insult ; to be 71% of preischemic level at day 7. Bax, an apoptosis-related protein, was noted prominently at day 1, which gradually disappeared thereafter. At the stria vascularis, positive immunostaining for connexin 26 decreased on day 1, but recovered to some extent at day 4 and completely healed at day 7. At the organ of Corti, the auditory hair cells were sporadically damaged due to apoptotic process, more prominently in the inner hair cells. From a study with glutamate transporter knock-out mice, glutamate was proved to be a key substance in aggravating the ischemic cochlear damage.
    Three treatment modalities were assessed in this study. 1.Ginsenoside Rb1, which belongs to Kanpo medicine, was proved effective in prevention of ischemic cochlear damage. 2.Prosaposin, which is know to have neurotrophic effects, was also effective in protecting the ischemic cochlear damage. Stem cells derived from bone marrow prevented ischemic damage of the hair cells and the spiral ganglion cells, probably via release of neurotrophic factors. However, they were not effective in facilitating regeneration of the hair cells.

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  • 神経再生

    2004

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    Grant type:Competitive

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  • 埋め込み型骨導補聴器の開発

    2004

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    Grant type:Competitive

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  • 軟骨を利用した新しい外耳道作成術の研究

    2003 - 2004

    日本学術振興会  科学研究費助成事業  萌芽研究

    暁 清文, 羽藤 直人, 白馬 伸洋, 篠森 裕介

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    Grant amount:\3200000 ( Direct Cost: \3200000 )

    鼓室形成術の発展に伴い中耳疾患に対する手術成績は著しく向上したが、技術的に単純と思われる外耳道閉鎖症の手術成績は今なお概して不良である。せっかく外耳道を造設しても、骨削開面からの肉芽増生や形成鼓膜の浅在化、移植皮膚の感染などのため、やがて外耳道の再閉鎖が始まり、一旦改善した聴力は次第に悪化することが多い。一方、軟骨は栄養状態が悪い環境下でも生着し、感染にも強いことから移植材料として最適の素材と考えられる。そこで我々は外耳道を軟骨で補強することにより、術後の肉芽増殖や鼓膜浅在化が防止できるのではないかと着想し以下の研究を行った。
    基礎研究にはモルモットを用いて実験を行った。耳後部に切開を加えて耳胞を開放、外部から中耳骨胞に至る「穴」を形成した。その後、A群では反体側の耳介から軟骨を軟骨膜とともに採取してリング状とし、上記の造設した穴に縫合して外耳道を形成した。B群では軟骨の代わりに筋膜を、C群では表皮を、それぞれ造設した穴に縫合して外耳道を形成した。術後は定期的に観察し、4週後に組織を採取、外耳道の形態と外耳道周囲の組織学的変化を検討した。その結果、外耳道を軟骨で形成することにより肉芽の増殖が阻止できることを明らかにした。一方、B群やC群では高頻度で肉芽の増殖が生じ、外耳道は狭窄傾向を示した。
    この結果を活用し、実際の症例において軟骨を用いた外耳道造設術を施行した。症例は11歳の男児で、左側小耳症と外耳道閉鎖症の合併例である。外耳道造設術は耳介形成術と同時に行なった。軟骨カッターを用いて肋軟骨を厚さ0.2-0.3mmの板状に切断し、これをトリミングして外耳道の骨削開面に貼り付けたところ、術後、肉芽増殖はおこらず外耳道の形態は安定していた。本法は外耳道閉鎖症の新しい術式として有望であると結論した。

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  • ベル麻痺の神経障害機構とウイルスゲノム解析

    2002 - 2003

    日本学術振興会  科学研究費助成事業  若手研究(B)

    羽藤 直人

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    Grant amount:\3900000 ( Direct Cost: \3900000 )

    申請者はこれまでの研究で、単純ヘルペス1型(HSV-1)潜伏感染マウスに対し、免疫抑制剤や局所刺激の再活性化刺激を加え、再活性化による顔面神経麻痺を発症するマウスモデルの作製に成功している。本モデルはHSV-1の再活性化により一過性の一側性麻痺を生じ、ベル麻痺に類似したモデルと考えられた。この麻痺モデルに対し分子生物学的検討を行った結果、HSV-1の再活性化は必ずしも顔面神経麻痺には至らず、顔面神経麻痺を生じるためには再活性化したHSV-1が増殖し、相当数の運動神経を障害する必要があると考えられた。また、real time PCR法を用いウイルスゲノムの動態解析も行った。膝神経節を含む側頭骨内顔面神経と、神経終末組織として顎下腺、角膜、耳介皮膚を採取し、real time PCR法にてHSV-1 DNAの出現部位を経時的に検討した。結果、膝神経節からHSV-1の再活性化が認められたマウスの多くでは、刺激側の顎下腺または耳介皮膚からもHSV-1 DNAの検出が可能であった。また、これらの結果からベル麻痺患者においても、早期病因診断部位として耳介皮膚が有用と考えられたため、同部位を検体としてHSV-1 DNAの検出を試みた。結果、患者耳介皮膚より80% (8/10)と高率にウイルスが検出され、新たな病因診断法として意義深いと考える。また、再活性化モデルの病理組織学的、免疫組織学的検討の結果、実際に側頭骨内顔面神経を病理組織学的に検討し、膝神経節の神経細胞内にHSV-1の増殖と運動神経の髄鞘脱落を確認した。このことは再活性化したHSV-1により側頭骨内顔面神経が障害され麻痺が発症していることの強い裏づけになると考えられ、ベル麻痺の病態としても同様の機序が推測された。

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  • Development of treatment modalities for ischemic cochlear damage

    2002 - 2003

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    GYO Kiyofumi, SNINOMORI Yusuke, HAKUBA Nobuhiro, HATO Naohito

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    Grant amount:\14100000 ( Direct Cost: \14100000 )

    Prevention of cochlear damage due to inner ear ischemia was investigated based on the underlying apoptotic mechanism. We used Mongolian gerbils as experimental animals, which lack the posterior cerebral communicating arteries and have labyrinthine arteries nourished solely by the vertebral arteries. The animals were subjected to ischemic insult by occluding both vertebral arteries for 15 min. The ischemia caused 20 dB of increase in CAP threshold. Histologically the hair cells and spiral ganglion cells underwent sporadic degeneration, while the damage to the stria vascularis was reversible. The degeneration was proved to be due to apoptosis, which was most prominent at 12 hours of ischemia and was no longer seen later than 3 days.
    A variety of treatment modalities were assessed if and how they can prevent ischemia-reperfusion injury of the cochlea. 1.Edarabon (MCI-186) which belongs to a free radical scavenger was proved effective in preventing increase in CAP threshold and degradation of the hair cells, when it was administration intravenously 1 hour after ischemic insult. 2.Lowering of the body temperature to 32 degree (hypothermia) completely blocked degradation of the inner ear, mainly by preventing release of glutamate in the perilymph, reducing production of superoxide and decreasing metabolic rate in the inner ear. 3.Ginsenoside Rb1, which belongs to Kanpo medicine, was also proved effective in prevention of ischemic cochlear damage. 4.AMPA/kainate type of glutamate antagonist such as DNQX was efficient in prevention of cochlear damage, while NMDA type such as D-AP5 had limited value. 5. GDNF which was incorporated in a denatured adenovirus dramatically decreased the cochlear damage due to ischemia, when administered directly into the inner ear.

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  • 人工神経開発

    2002

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    Grant type:Competitive

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  • 単純ヘルペスウイルス再活性化による顔面神経麻痺モデルに関する基礎研究

    1998 - 1999

    日本学術振興会  科学研究費助成事業  奨励研究(A)

    羽藤 直人

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    Grant amount:\1900000 ( Direct Cost: \1900000 )

    近年諸家の報告により、ベル麻痺(特発性顔面神経麻痺)の病因として顔面神経節に潜伏感染した単純ヘルペスウイルス1型(以下HSV-1)の再活性化が強く関与していることが有力視されている。申請者らは既にHSV-1初感染顔面神経麻痺モデルの作製に成功しており、同モデルにて再活性化の必要条件である潜伏感染も共生培養法にて証明している。今回、よりベル麻痺発症に類似したHSV-1再活性化による顔面神経麻痺モデルの作製を試みた。
    実験方法はBalb/cマウスの一側耳介にHSV-1を接種し、初感染による一側性一過性顔面神経麻痺を発症させた。麻痺治癒後、潜伏感染の成立した2から4カ月経過したマウスに対して、抗T細胞抗体(抗TCR抗体、抗CD3ε抗体)を用いた選択的細胞性免疫抑制と神経終末である耳介擦過による局所刺激を併用しHSV-1再活性化を誘発した。以後、連日マウスの全身状態と髭・鼻翼の動き、また瞬目反射にて顔面神経機能を詳細に観察した。
    免疫抑制後翌日から全てのマウスに立毛と活動性に低下が出現した。免疫抑制後7から14日目に約28%のマウスに顔面神経麻痺が出現し、麻痺は約14日間持続した。初感染麻痺モデルと比較すると麻痺程度は軽度であった。免疫蛍光法にて麻痺側脳幹顔面神経下行脚と運動核にHSV-1抗原を同定し、病理組織学的には脳幹顔面神経下行脚から膝部に炎症細胞の浸潤を、また脳幹運動核にHSV-1の炎症に特異的とされる核内封入体を認めた。これらのことからHSV-1再活性化による麻痺と考えられた。

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  • Etiopathology and eary diagnosis of Bell's palsy

    1997 - 1998

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    MURAKAMI Shingo, HATO Naohito, MATSUDA Jhoji, MIZOBUCHI Mutsuhiko

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    Grant amount:\3100000 ( Direct Cost: \3100000 )

    The immunological aspects to facial nerve paralysis due to herpes simplex virus type I (HSV-1) infection were investigated in a mouse model system. Passive transfer of either anti-HSV- I antibody or HSV- 1 immunized splenic T cells into 4-week-old mice 3 hr after HSV- 1 inoculation prevented development of facial nerve paralysis and death, whereas such transfers 48 hr or 96 hr after HSV- I inoculation did not prevent or exacerbate facial nerve paralysis. These results demonstrated that the immunological potency of mice are closely related to the pathogenesis of facial nerve paralysis. Facial nerve paralysis developed even in 6-week-old mice whose T-cell function was suppressed with anti-CD3 antibody, suggesting virus induced cellular demyelination is unlikely as a cause of facial nerve paralysis in this animal model.
    Ramsay Hunt syndrome is usually diagnosed by facial palsy, auricular vesicles and/or vestibulocochlear dysfunction. However, patients with zoster sine herpete and Ramsay Hunt syndrome without pathognomonic vesicles at the initial visit are misdiagnosed with Bell's palsy. By use of polymerase chain reaction, we found that VZV genomes were frequently detectable in auricular skin exudate from patients with zoster sine herpete or those with Ramsay Hunt syndrome before the appearance of vesicles. VZV genomes were also detected not only in the vesicles on the auricles or oral cavity but also in the facial nerve sheath, middle ear mucosa and cerebrospinal fluid (CSF) from patients with Ramsay Hunt syndrome. The results indicated that VZV spreads widely in the neural components, mucocutaneous tissue and CSF.

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  • ベル麻痺の原因と病態に関する基礎的研究

    1996

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    柳原 尚明, 羽藤 直人, 村上 信吾, 湯本 英二, 暁 清文

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    Grant amount:\4900000 ( Direct Cost: \4900000 )

    1.<臨床的研究>ベル麻痺、Ramasay Hunt症候群、及びzoster sine herpete (ZSH)の患者の涙、リンパ球、耳介の組織液からpolymerase chain reaction (PCR)を用い、帯状疱疹ウイルス(VZV)、ヒト単純ヘルペスウイルス1型(HSV-1)のDNAの有無を検討した。ベル麻痺患者およびコントロールの涙からはVZVは検出されず、Hunt症候群、ZSHの患者の涙、耳介組織液からは高率にVZVが検出された。HSV-1の検出はそれぞれにあまり差が認められなかった。この結果、早期にはベル麻痺と診断されていた急性末梢性顔面神経麻痺の中にVZV感染によるものが存在することを明らかにし、これらの症例の早期診断の可能性を示唆した。
    2.<基礎的研究>我々はBalb/cマウスを用いて、耳介にHSV-1を接触することにより一側性一過性の顔面神経麻痺を発症させ、ベル麻痺のモデル動物として報告してきた。本年度はこのモデル動物に対し、麻痺発症への免疫の関与、麻痺発症の病態を知るために組織学的および電気生理学的に検討した。組織学的検討から麻痺の発症したマウスにおいて脳幹部を含む顔面神経に高度の脱髄病変が認められた。また、電気生理学的検討からは三又神経-顔面神経反射では麻痺側の反射波に潜時の遅れが認められたが、誘発筋電図ではconduction blockの状態であった。以上のことよりHSV-1による顔面神経麻痺は脱髄により発症していることが明らかとなった。免疫移入実験の結果、この脱髄は自己破壊的な免疫応答ではなく、HSV-1による顔面神経の直接障害により生じていることが示唆された。

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  • ウィルス性顔面神経麻痺

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    Grant type:Competitive

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  • Facial Nerre Parolysis induced by Uiral Infection

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    Grant type:Competitive

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