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1.
CNS Drugs ; 2024 May 29.
Article in English | MEDLINE | ID: mdl-38809343

ABSTRACT

BACKGROUND: Migraine and dizziness often coexist, with vestibular migraine (VM) presenting with vestibular symptoms and headaches. Calcitonin gene-related peptide (CGRP) may be involved in motion-induced symptoms; however, studies on the use of anti-CGRP monoclonal antibodies (mAbs) for the treatment of VM have yielded conflicting results. This study aimed to clarify the effectiveness of anti-CGRP mAbs in VM treatment. METHODS: This retrospective observational cohort study, conducted between 1 January 2021 and 31 March 2023, assessed 12 Japanese patients with VM who were treated with anti-CGRP mAbs (CGRP group) for 6 months and 11 Japanese patients who received standard of care for VM and served as controls. Clinical questionnaires and equilibrium tests were administered, with primary outcomes including changes in Dizziness Handicap Inventory (DHI) scores compared with baseline values. Objective variables included the DHI score and explanatory variables included demographic data, balance test results, head-up tilt (HUT) test results, vestibular test results and questionnaire survey results. Analysis of variance was used to assess the treatment effects of anti-CGRP mAbs, and multivariate regression analysis was performed to identify mAb responders. RESULTS: After 6 months, the CGRP group showed significant improvements in DHI scores [0 versus 6 months, odds ratio (95% confidence interval): 22.01 (0.13-43.88)] and number of vertigo/dizziness attacks per month [0 versus 6 months: 10.28 (2.80-17.76)]. No significant difference was observed in the control group [DHI scores, 0 versus 6 months: 0.65 (-26.84 to 28.14); number of vertigo/dizziness attacks per month, 0 versus 6 months: - 8.07 (- 23.77 to 7.62)]. Multivariate regression analysis showed that autonomic function at baseline was associated with mAb response in patients [ß estimates (95% confidence interval): 3.63 (0.21-7.06)]. CONCLUSIONS: Treatment with anti-CGRP mAbs was more effective than conventional treatment in preventing migraine in patients with VM. While the identified factors associated with treatment responsiveness offer valuable insights into personalised treatment approaches, further prospective studies are warranted to validate the findings due to our study's retrospective design and limited sample size.

2.
Auris Nasus Larynx ; 51(2): 343-346, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37838569

ABSTRACT

OBJECTIVE: To assess the annual incidence of vestibular neuritis (VN) in the Japanese population. METHODS: We conducted a mail-based survey targeting otolaryngologic clinics and hospitals across Japan to estimate the annual number of patients who were newly-diagnosed with VN during the one-year period of 2021. Using a stratified sampling method, we selected 1,107 departments and asked them to report the number of new patients with VN and their demographics. The total number of VN patients was estimated by multiplying the reported numbers by the reciprocal of the sampling rate and response rate. RESULTS: The overall survey response rate was 40.5 % (448 departments). The estimated number of newly-diagnosed VN patients in 2021 was 8,861 (95 % confidential interval [CI], 2,290-15,432) The annual incidence of VN was 7.05 per 100,000 population in Japan. The male-to-female ratio of VN patients was 0.96, and the mean age was 60.3 ± 16.1 years (range 11-94 years). CONCLUSIONS: The annual incidence of VN in Japan in 2021 had almost doubled and the mean age had become older compared to the previous study in 1993 (annual incidence; 3.5 per 100,000 per year; mean age: 45 years).


Subject(s)
Vestibular Neuronitis , Humans , Male , Female , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Vestibular Neuronitis/epidemiology , Vestibular Neuronitis/diagnosis , Japan/epidemiology , Incidence , Caloric Tests , Surveys and Questionnaires
3.
Microorganisms ; 11(12)2023 Dec 10.
Article in English | MEDLINE | ID: mdl-38138101

ABSTRACT

The incidence of oral cancer has recently been increasing worldwide, particularly among young individuals and women. The primary risk factors for head and neck cancers, including oral and pharyngeal cancers, are smoking, alcohol consumption, poor oral hygiene, and repeated exposure to mechanical stimuli. However, approximately one-third of the patients with oral and pharyngeal cancers are neither smokers nor drinkers, which points to the existence of other mechanisms. Recently, human microbes have been linked to various diseases, including cancer. Oral pathogens, especially periodontal pathobionts, are reported to play a role in the development of colon and other types of cancer. In this study, we employed a series of bioinformatics analyses to pinpoint Fusobacterium nucleatum as the predominant oral bacterial species in oral and pharyngeal cancer tissue samples. We successfully isolated Fn. polymorphum from the saliva of patients with oral cancer and demonstrated that Fn. polymorphum indeed promoted oral squamous cell carcinoma development by activating YAP in a mouse tongue cancer model. Our research offers scientific evidence for the role of the oral microbiome in oral cancer progression and provides insights that would help in devising preventative strategies against oral cancer, potentially by altering oral bacterial profiles.

4.
Inflamm Regen ; 43(1): 55, 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-37964391

ABSTRACT

BACKGROUND: Although vaccination is recommended for protection against invasive pneumococcal disease, the frequency of pneumococcal pneumonia is still high worldwide. In fact, no vaccines are effective for all pneumococcal serotypes. Fusion pneumococcal surface protein A (PspA) has been shown to induce a broad range of cross-reactivity with clinical isolates and afford cross-protection against pneumococcal challenge in mice. Furthermore, we developed prime-boost-type mucosal vaccines that induce both antigen-specific IgG in serum and antigen-specific IgA in targeted mucosal organs in previous studies. We investigated whether our prime-boost-type immunization with a fusion PspA was effective against pneumococcal infection in mice and cynomolgus macaques. METHODS: C57BL/6 mice were intramuscularly injected with fusion PspA combined with CpG oligodeoxynucleotides and/or curdlan. Six weeks later, PspA was administered intranasally. Blood and bronchoalveolar lavage fluid were collected and antigen-specific IgG and IgA titers were measured. Some mice were given intranasal Streptococcus pneumoniae and the severity of infection was analyzed. Macaques were intramuscularly injected with fusion PspA combined with CpG oligodeoxynucleotides and/or curdlan at week 0 and week 4. Then, 13 or 41 weeks later, PspA was administered intratracheally. Blood and bronchoalveolar lavage fluid were collected and antigen-specific IgG and IgA titers were measured. Some macaques were intranasally administered S. pneumoniae and analyzed for the severity of pneumonia. RESULTS: Serum samples from mice and macaques injected with antigens in combination with CpG oligodeoxynucleotides and/or curdlan contained antigen-specific IgG. Bronchial samples contained antigen-specific IgA after the fusion PspA boosting. This immunization regimen effectively prevented S. pneumoniae infection. CONCLUSIONS: Prime-boost-type immunization with a fusion PspA prevented S. pneumoniae infection in mice and macaques.

5.
Cureus ; 15(6): e40945, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37366477

ABSTRACT

Congenital cholesteatoma is typically an expanding cystic mass of keratinizing squamous epithelium located medial to the intact tympanic membrane in patients with no prior history of perforation, otorrhea and ear. It is generally thought to be a progressive disease and is usually surgically removed upon detection as the first-choice treatment. As such, it is rare to be observed for a long term without progression. Here we report a rare case of congenital cholesteatoma that remained in an undetectable size and did not deteriorate mild hearing loss for 12 years. A seven years old boy was referred to us with right hearing impairment. Pure-tone audiometry found conductive hearing loss with an air-bone gap of 25 dB and a high-resolution computed tomography (CT) scan found the eroded long process of incus but did not detect any soft tissue density indicating congenital cholesteatoma. He initially did not wish to undergo surgery. His hearing level and image finding remained virtually unchanged during the next 12 years of the follow-up period. Twelve years later, endoscopic ear surgery was performed, which revealed a very small cholesteatoma mass, an eroded long process of the incus and ossicular chain discontinuities. We suspect that the cholesteatoma was originally larger, partially eroded the incus, then regressed to a very small size, and remained small for at least 12 years under our observation.

6.
Surg Endosc ; 37(8): 6322-6332, 2023 08.
Article in English | MEDLINE | ID: mdl-37202526

ABSTRACT

BACKGROUND: Superficial pharyngeal cancer can be treated with curative intent while preserving function using minimally invasive peroral endoscopic resection techniques such as endoscopic submucosal dissection (ESD). However, severe adverse events occasionally occur, such as laryngeal edema requiring temporary tracheotomy and fistula formation. Therefore, we investigated the risk factors for adverse events associated with ESD for superficial pharyngeal cancer. METHODS: This retrospective observational study was conducted at a single institution, and 63 patients who underwent ESD were enrolled. The primary outcome was the risk factors for adverse events associated with ESD. The secondary outcomes were adverse events associated with ESD and their frequency. RESULTS: The overall adverse event rate was 15.9% (10/63). The incidence of laryngeal edema requiring prophylactic temporary tracheotomy was 11.1%, while laryngeal edema requiring emergency temporary tracheotomy, postoperative bleeding, aspiration pneumonia, fistula, abscess, and stricture formation occurred in 1.6% of patients, respectively. Logistic regression analyses showed that a history of radiotherapy for head and neck cancer was a risk factor for adverse events (odds ratio [OR], 16.67; 95% confidence interval [CI], 3.04-91.34; p = 0.001). After adjusting the model for differences in the baseline risk factors using the inverse probability of treatment weighting method, the adverse events were found to increase in association with a history of radiotherapy for head and neck cancer (OR, 39.66; 95% CI,5.85-268.72; p < 0.001). CONCLUSION: History of radiotherapy for head and neck cancer is an independent risk factor for adverse events associated with ESD for superficial pharyngeal cancer. Among adverse events, laryngeal edema requiring prophylactic temporary tracheotomy was particularly high.


Subject(s)
Endoscopic Mucosal Resection , Pharyngeal Neoplasms , Risk Factors , Retrospective Studies , Endoscopic Mucosal Resection/adverse effects , Pharyngeal Neoplasms/surgery , Endoscopy
7.
Heliyon ; 9(4): e15018, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37082629

ABSTRACT

Currently, vestibular rehabilitation approaches used to monitor body position and movement during rehabilitation training require specialized equipment or rely on clinician observation. Thus, a simpler position-sensing approach that can be used to monitor movement during vestibular rehabilitation is required. This study used wearable motion sensors with built-in accelerometers and gyrometers to assess movement in adults. We explored stepping patterns in adults using this motion-sensing system. Six healthy adults (men, age 27.3 ± 5.8 years) underwent a modified Fukuda stepping test (Foulage test [FT]) while wearing a six-axis motion sensor (accelerometer: X-axis, Y-axis, Z-axis; gyrometer: X-axis, Y-axis, Z-axis) positioned at the head, thorax, and lumbar spine. For motion sensor parameters, we calculated the root mean square (RMS), autocorrelation coefficient (AC), power spectrum (PS) of the AC, and Euler angles from the six-axis motion sensor. For the FT parameters, the FT value, step variance, and θ values were calculated. Data were analyzed, and multivariable regression analysis was performed using the FT value, step variance, and θ value as the dependent variables to investigate their influence on dynamic equilibrium. The explanatory variables included the motion sensor parameters, RMS, AC, and PS. Our results suggested that almost no head and lumbar spine movement occurred while stepping with eyes open. Contrastingly, the head and lumbar spine swayed with eyes closed. This accelerometric and gyroscopic device is easy to use, does not require specialized equipment, and can be used to analyze performance in the modified Fukuda stepping test in clinical practice. Inertial sensors have many advantages over other sensing technologies.

8.
Cureus ; 14(5): e24763, 2022 May.
Article in English | MEDLINE | ID: mdl-35676978

ABSTRACT

Objective In this article, we aimed to describe the Foulage test (FT) and investigate the test-retest reliability of parameters recorded during stepping execution in healthy adults. Materials and methods This was a single-center prospective cohort study conducted at an outpatient clinic. It included five healthy male participants [mean age ± standard deviation (SD): 27 ± 5.4 years]. The FT was performed first with the participants' eyes open and again with their eyes closed. If the heel height was not within 2-6 cm, the participant was asked to restart. The FT value and variance of steps were automatically calculated. To verify the influence of heel height, measurements were taken at different heel heights. We also evaluated the Romberg ratio (calculated from the parameters with eyes open and closed) and defined it as the dynamic Romberg ratio. Correlations between parameters were also assessed. Results The parameters' FT value (front-back width of the band of locus shape) and variance of steps plateaued under stable conditions within a heel height of 2-6 cm. FT values and variance of steps were strongly correlated. The dynamic Romberg ratios by FT value and by the variance of steps were also strongly correlated. Conclusions The FT is a dynamic and reproducible equilibrium function test that can quantify agitation with the eyes open or closed in general outpatient clinics, and it may be employed as a clinically useful method for the observation of clinical courses in patients with vestibular disorders.

9.
Int J Mol Sci ; 22(19)2021 Sep 29.
Article in English | MEDLINE | ID: mdl-34638866

ABSTRACT

RBM10 is an RNA-binding protein that regulates alternative splicing (AS). It localizes to the extra-nucleolar nucleoplasm and S1-1 nuclear bodies (NBs) in the nucleus. We investigated the biological significance of this localization in relation to its molecular function. Our analyses, employing deletion mutants, revealed that RBM10 possesses two S1-1 NB-targeting sequences (NBTSs), one in the KEKE motif region and another in the C2H2 Zn finger (ZnF). These NBTSs act synergistically to localize RBM10 to S1-1 NBs. The C2H2 ZnF not only acts as an NBTS, but is also essential for AS regulation by RBM10. Moreover, RBM10 does not participate in S1-1 NB formation, and without alterations of RBM10 protein levels, its NB-localization changes, increasing as cellular transcriptional activity declines, and vice versa. These results indicate that RBM10 is a transient component of S1-1 NBs and is sequestered in NBs via its NBTSs when cellular transcription decreases. We propose that the C2H2 ZnF exerts its NB-targeting activity when RBM10 is unbound by pre-mRNAs, and that NB-localization of RBM10 is a mechanism to control its AS activity in the nucleus.


Subject(s)
Alternative Splicing , Cell Nucleus/metabolism , Nuclear Localization Signals/metabolism , RNA-Binding Proteins/metabolism , Amino Acid Motifs , Cell Nucleus/genetics , HEK293 Cells , HeLa Cells , Hep G2 Cells , Humans , Nuclear Localization Signals/genetics , Protein Domains , Protein Transport , RNA-Binding Proteins/genetics
10.
Int J Mol Sci ; 22(5)2021 Mar 09.
Article in English | MEDLINE | ID: mdl-33803422

ABSTRACT

Psychological stress exacerbates mast cell (MC)-dependent inflammation, including nasal allergy, but the underlying mechanisms are not thoroughly understood. Because the key stress-mediating neurohormone, corticotropin-releasing hormone (CRH), induces human skin MC degranulation, we hypothesized that CRH may be a key player in stress-aggravated nasal allergy. In the current study, we probed this hypothesis in human nasal mucosa MCs (hM-MCs) in situ using nasal polyp organ culture and tested whether CRH is required for murine M-MC activation by perceived stress in vivo. CRH stimulation significantly increased the number of hM-MCs, stimulated both their degranulation and proliferation ex vivo, and increased stem cell factor (SCF) expression in human nasal mucosa epithelium. CRH also sensitized hM-MCs to further CRH stimulation and promoted a pro-inflammatory hM-MC phenotype. The CRH-induced increase in hM-MCs was mitigated by co-administration of CRH receptor type 1 (CRH-R1)-specific antagonist antalarmin, CRH-R1 small interfering RNA (siRNA), or SCF-neutralizing antibody. In vivo, restraint stress significantly increased the number and degranulation of murine M-MCs compared with sham-stressed mice. This effect was mitigated by intranasal antalarmin. Our data suggest that CRH is a major activator of hM-MC in nasal mucosa, in part via promoting SCF production, and that CRH-R1 antagonists such as antalarmin are promising candidate therapeutics for nasal mucosa neuroinflammation induced by perceived stress.


Subject(s)
Cell Degranulation/drug effects , Cell Proliferation/drug effects , Corticotropin-Releasing Hormone/pharmacology , Mast Cells/metabolism , Nasal Mucosa/metabolism , Rhinitis, Allergic/metabolism , Stress, Physiological/drug effects , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Mast Cells/pathology , Middle Aged , Nasal Mucosa/pathology , Rhinitis, Allergic/pathology
11.
Inflamm Res ; 70(5): 539-541, 2021 May.
Article in English | MEDLINE | ID: mdl-33811487

ABSTRACT

OBJECTIVE: Histamine derived from mast cells and basophils plays important roles in inducing allergic symptoms. Although T cells also produce histamine, the involvement of the histamine produced from T cells has remained enigmatic. We sought to reveal the roles of T helper 2 (Th2) cell-derived histamine in nasal allergic disorders. METHODS: The histamine production from Th2 cells was measured by EIA. The mRNA expression of histidine decarboxylase (HDC) was measured by real-time PCR. To investigate the roles of Th2 cell-derived histamine in vivo, we analyzed an antigen-specific Th2 cell transfer mouse model. RESULTS: Th2 cells produced histamine by T cell receptor stimulation, and these properties were specific for Th2 cells, but not Th1 cells and naïve CD4 T cells. The histamine produced from Th2 cells was involved in the infiltrations of Th2 cells in response to antigen exposure. CONCLUSION: These results suggest that Th2 cell-derived histamine play important roles in nasal allergic disorders.


Subject(s)
Histamine/immunology , Nasal Mucosa/immunology , Rhinitis, Allergic/immunology , Th2 Cells/immunology , Allergens/immunology , Animals , Cell Movement , Histidine Decarboxylase/genetics , Mice, Inbred BALB C , Mice, Knockout , Ovalbumin/immunology , Th2 Cells/physiology , Th2 Cells/transplantation
12.
PLoS One ; 16(3): e0248158, 2021.
Article in English | MEDLINE | ID: mdl-33662037

ABSTRACT

Histamine, which is mainly produced by mast cells and basophils, participates in various allergic symptoms, and some studies have reported that macrophages also produce histamine. Moreover, recent studies have revealed that macrophages, especially alternatively activated macrophages (M2) induced by T helper 2 (Th2) cytokines, such as interleukin (IL)-4 and IL-13, participate in the pathogenesis of allergic diseases. The major source of Th2 cytokines is antigen-specific Th2 cells. To elucidate the relationship between histamine, macrophages, and Th2 cells in allergic inflammation, we established a macrophage-Th2 cell co-culture model in vitro and an antigen-specific Th2 cell transfer mouse model of rhinitis. In vitro analyses indicated that macrophages produce histamine by interacting with antigen-specific Th2 cells through the antigen. Furthermore, Th2 cells and macrophages cooperatively elicited rhinitis in the mouse model. We determined that histamine induces Th2- and macrophage-elicited sneezing responses through H1 receptor signaling, whereas it induces nasal eosinophil infiltrations through H4 receptor signaling. Collectively, these results indicate a novel histamine production mechanism by macrophages, in which Th2 cells and macrophages cooperatively induce nasal allergic inflammation through histamine signaling.


Subject(s)
Histamine/immunology , Inflammation/immunology , Macrophages/immunology , Rhinitis, Allergic/immunology , Th2 Cells/immunology , Animals , Cells, Cultured , Humans , Inflammation/pathology , Macrophages/pathology , Mice , Mice, Inbred BALB C , Rhinitis, Allergic/pathology , Signal Transduction , Th2 Cells/pathology
13.
Immun Inflamm Dis ; 7(3): 191-200, 2019 09.
Article in English | MEDLINE | ID: mdl-31210032

ABSTRACT

BACKGROUND: In the clinical setting, chronic rhinosinusitis with nasal polyps (CRSwNP) is usually divided into eosinophilic-CRS (ECRS) and non-ECRS (NECRS) in Japan. Patients with the former are believed to be at risk for postoperative recurrence of CRS. However, some patients have been missed according to these phenotypic classifications due to the low number of infiltrating eosinophils in polyp tissues. OBJECTIVE: In the present study, we attempted to identify cellular or molecular candidate markers to predict nasal polyp recurrence. METHODS: Nasal polyps were collected from 32 patients with CRSwNP who had undergone an endoscopic sinus surgery. These patients were divided into ECRS and NECRS groups in accordance with the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) scoring system and the number of eosinophils in polyp tissues. Unclassifiable patients were referred to as the unknown group. RESULTS: Eosinophil infiltration in resected nasal polyps was most evident in the ECRS group. However, the number of mast cells and tryptase-positive cells in nasal polyps were significantly lower in ECRS and unknown groups compared with the NECRS group. A significant positive correlation was detected between the JESREC score and number of eosinophils. The numbers of mast cells and tryptase-positive cells were negatively correlated with the JESREC score in all included samples. Significant positive correlations were detected between the number of transforming growth factor ß1-positive cells and the number of mast cells, tryptase-positive cells, and chymase-positive cells mast cells. CONCLUSIONS AND CLINICAL RELEVANCE: These findings indicated that the enumeration of mast cells in resected polyps may be another approach to predict postoperative polyp recurrence in CRSwNP patients.


Subject(s)
Mast Cells/pathology , Nasal Polyps/pathology , Rhinitis/diagnosis , Sinusitis/diagnosis , Chronic Disease , Chymases/metabolism , Female , Humans , Japan , Leukocyte Count , Male , Mast Cells/enzymology , Middle Aged , Nasal Polyps/surgery , Postoperative Period , Prognosis , Recurrence , Rhinitis/metabolism , Sinusitis/metabolism , Transforming Growth Factor beta1/metabolism , Tryptases/metabolism
15.
Brain Res ; 1537: 164-73, 2013 Nov 06.
Article in English | MEDLINE | ID: mdl-24055105

ABSTRACT

In daily communication, we can usually still hear the spoken words as if they had not been masked and can comprehend the speech when spoken words are masked by background noise. This phenomenon is known as phonemic restoration. Since little is known about the neural mechanisms underlying phonemic restoration for speech comprehension, we aimed to identify the neural mechanisms using magnetoencephalography (MEG). Twelve healthy male volunteers with normal hearing participated in the study. Participants were requested to carefully listen to and understand recorded spoken Japanese stories, which were either played forward (forward condition) or in reverse (reverse condition), with their eyes closed. Several syllables of spoken words were replaced by 300-ms white-noise stimuli with an inter-stimulus interval of 1.6-20.3s. We compared MEG responses to white-noise stimuli during the forward condition with those during the reverse condition using time-frequency analyses. Increased 3-5 Hz band power in the forward condition compared with the reverse condition was continuously observed in the left inferior frontal gyrus [Brodmann's areas (BAs) 45, 46, and 47] and decreased 18-22 Hz band powers caused by white-noise stimuli were seen in the left transverse temporal gyrus (BA 42) and superior temporal gyrus (BA 22). These results suggest that the left inferior frontal gyrus and left transverse and superior temporal gyri are involved in phonemic restoration for speech comprehension. Our findings may help clarify the neural mechanisms of phonemic restoration as well as develop innovative treatment methods for individuals suffering from impaired speech comprehension, particularly in noisy environments.


Subject(s)
Brain/physiology , Comprehension/physiology , Magnetoencephalography , Speech Perception/physiology , Speech/physiology , Acoustic Stimulation/methods , Adolescent , Adult , Brain Mapping/methods , Functional Laterality/physiology , Healthy Volunteers , Hearing/physiology , Humans , Magnetoencephalography/methods , Male , Noise , Young Adult
16.
Acta Otolaryngol ; 133(5): 491-8, 2013 May.
Article in English | MEDLINE | ID: mdl-23320814

ABSTRACT

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


Subject(s)
Surveys and Questionnaires , Tinnitus/complications , Tinnitus/psychology , Activities of Daily Living , Adult , Female , Humans , Japan , Male , Psychometrics , Quality of Life , Reproducibility of Results , Severity of Illness Index , Stress, Psychological/etiology , Young Adult
17.
Acta Otolaryngol ; 132(10): 1054-60, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22998558

ABSTRACT

CONCLUSION: Significant reduced visualization of the reuniting duct (ductus reuniens; RD), saccular duct (SD) and endolymphatic sinus (ES) in Meniere's disease (MD) compared with normal control ears on three-dimensional (3D) CT imaging suggests the blockage of endolymphatic flow there with radiodense substances, which may be explained by dislodged otoconia from the saccule. These structures could be involved in the pathogenesis of MD. OBJECTIVE: This study was designed to visualize and assess the RD, SD and ES in patients with MD using 3D CT. METHODS: Sixty-two patients with a definite diagnose of unilateral MD, based on criteria proposed by the Committee on Hearing and Equilibrium of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS), were compared with contralateral ears and normal controls (26 ears) using 3D CT. The RD, SD and ES were scrutinized for patency on 3D CT images. RESULTS: MD ears showed loss of continuity of the RD, SD and ES based on evaluation of 3D CT images, and differed significantly from normal healthy control ears (p < 0.01).


Subject(s)
Cochlear Duct/diagnostic imaging , Endolymph/diagnostic imaging , Imaging, Three-Dimensional , Meniere Disease/diagnostic imaging , Otolithic Membrane/diagnostic imaging , Tomography, X-Ray Computed/methods , Adult , Aged , Aged, 80 and over , Case-Control Studies , Chi-Square Distribution , Cohort Studies , Female , Humans , Male , Meniere Disease/diagnosis , Middle Aged , Reference Values , Saccule and Utricle/diagnostic imaging
18.
J Biol Chem ; 287(26): 21584-98, 2012 Jun 22.
Article in English | MEDLINE | ID: mdl-22544735

ABSTRACT

The vertebrate-restricted carcinoembryonic antigen gene family evolves extremely rapidly. Among their widely expressed members, the mammal-specific, secreted CEACAM16 is exceptionally well conserved and specifically expressed in the inner ear. To elucidate a potential auditory function, we inactivated murine Ceacam16 by homologous recombination. In young Ceacam16(-/-) mice the hearing threshold for frequencies below 10 kHz and above 22 kHz was raised. This hearing impairment progressed with age. A similar phenotype is observed in hearing-impaired members of Family 1070 with non-syndromic autosomal dominant hearing loss (DFNA4) who carry a missense mutation in CEACAM16. CEACAM16 was found in interdental and Deiters cells and was deposited in the tectorial membrane of the cochlea between postnatal days 12 and 15, when hearing starts in mice. In cochlear sections of Ceacam16(-/-) mice tectorial membranes were significantly more often stretched out as compared with wild-type mice where they were mostly contracted and detached from the outer hair cells. Homotypic cell sorting observed after ectopic cell surface expression of the carboxyl-terminal immunoglobulin variable-like N2 domain of CEACAM16 indicated that CEACAM16 can interact in trans. Furthermore, Western blot analyses of CEACAM16 under reducing and non-reducing conditions demonstrated oligomerization via unpaired cysteines. Taken together, CEACAM16 can probably form higher order structures with other tectorial membrane proteins such as α-tectorin and ß-tectorin and influences the physical properties of the tectorial membrane. Evolution of CEACAM16 might have been an important step for the specialization of the mammalian cochlea, allowing hearing over an extended frequency range.


Subject(s)
Cell Adhesion Molecules/biosynthesis , Cell Adhesion Molecules/genetics , Hearing Loss/genetics , Hearing Loss/metabolism , Animals , Cochlea/metabolism , Extracellular Matrix Proteins/metabolism , Female , GPI-Linked Proteins/metabolism , Hair Cells, Auditory/metabolism , Hearing , Humans , Male , Membrane Proteins/metabolism , Mice , Mice, Transgenic , Mutation , Myosin Heavy Chains/genetics , Myosin Type II/genetics , Recombination, Genetic , Tectorial Membrane/metabolism
19.
Acta Otolaryngol ; 131(5): 469-73, 2011 May.
Article in English | MEDLINE | ID: mdl-21366506

ABSTRACT

CONCLUSION: The saccular duct and endolymphatic sinus run in the bony groove, before reaching the orifice of the vestibular aqueduct. We first clinically visualized this sulciform groove using three-dimensional (3D) cone beam CT images. This strategy can be useful to assess the condition of the saccular duct and endolymphatic sinus concerning the longitudinal flow system of endolymph. OBJECTIVE: To assess the saccular duct and endolymphatic sinus in the endolymphatic system in order to advance clinical studies on inner ear dysfunction. METHODS: The sulciform groove of the saccular duct and endolymphatic sinus of human subjects was analyzed by cone beam CT and compared with that of a cadaver. RESULTS: We could obtain reconstructed 3D CT images of the sulciform groove of the saccular duct and endolymphatic sinus using several CT window levels.


Subject(s)
Endolymphatic Duct/diagnostic imaging , Saccule and Utricle/diagnostic imaging , Adult , Aged , Cone-Beam Computed Tomography , Female , Humans , Male , Middle Aged
20.
Acta Otolaryngol ; 130(2): 233-9, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19585278

ABSTRACT

CONCLUSION: The bony saccular orifice to the bony groove of the ductus reuniens (reuniting duct) could not be visualized in the Meniere's ear with significantly greater frequency compared with normal subjects, which suggests that the reuniting duct is affected by radio-opaque substances in CT findings. OBJECTIVE: This study investigated a more specific, objective, and simpler strategy to diagnose Meniere's disease by assessing the reuniting duct. SUBJECTS AND METHODS: We examined the ears of 12 patients with definitely diagnosed unilateral Meniere's disease in stage 3 based on Meniere's disease criteria proposed by the Committee on Hearing and Equilibrium of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS), and the ears of 12 normal control subjects using three-dimensional (3D) cone beam CT. RESULTS: The bony groove of the reuniting duct between the saccule and cochlea was visualized in all control subjects. However, the bony saccular orifice to the bony groove could not be visualized in the lesional ear of Meniere's patients with significantly greater frequency compared with those of the contralateral non-lesional ears and control ears (p < 0.01). This orifice was not patent in 66.7% (8 of 12 ears) on the lesional side but all contralateral non-lesional ears of the patients and normal control ears were patent.


Subject(s)
Cochlea/physiopathology , Cochlear Duct/physiopathology , Meniere Disease/physiopathology , Saccule and Utricle/physiopathology , Adult , Aged , Aged, 80 and over , Audiometry, Pure-Tone , Cochlea/diagnostic imaging , Cochlear Duct/diagnostic imaging , Endolymphatic Hydrops/diagnosis , Endolymphatic Hydrops/physiopathology , Female , Humans , Male , Meniere Disease/diagnosis , Middle Aged , Otolithic Membrane/diagnostic imaging , Otolithic Membrane/physiopathology , Saccule and Utricle/diagnostic imaging , Tomography, X-Ray Computed
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