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Objective: Steroids have been widely used to treat inner-ear diseases such as sudden sensorineural hearing loss, tinnitus, and Meniere's disease. They can be given via either systemic or intratympanic (IT) injection. The purpose of the present study was to explore differences in intracochlear steroid distribution by the administration method employed (systemic vs. IT injection)., Study Design: Animal study., Methods: Twenty-three Sprague-Dawley rats were given fluorescein isothiocyanate-labeled dexamethasone (FITC-DEX) three times (on successive days) via intraperitoneal (IP) or IT injection. Cochlear uptake of FITC-DEX was evaluated via immunohistochemistry and flow cytometry at 6 hours, and 3 and 7 days after the final injection., Results: FITC-DEX uptake was evident in spiral ganglion cells (SGs), the organ of Corti (OC), and the lateral walls (LWs), the basal turns of which were stained relatively prominently in both groups. Animals receiving IP injections exhibited higher FITC-DEX uptakes by the SGs and OC, whereas IT injection triggered higher-level FITC-DEX accumulation by the OC and LWs. Flow cytometry revealed that intracochlear FITC-DEX uptake by IT-injected animals was higher and more prolonged than in animals subjected to IP injections., Conclusion: We thus describe differences in cochlear steroid distributions after systemic and IT injections. This finding could help our understanding of the pharmacokinetics of steroids in the cochlea., Level of Evidence: NA. Laryngoscope, 128:189-194, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: We compared the clinical characteristics between acute low- and high-frequency hearing loss (LF and HF, respectively) patients, and the efficacy of three different treatment protocols (systemic steroids, intratympanic steroid injection, and combination therapy)., Study Design: Prospective, randomized controlled study., Methods: A total of 111 patients diagnosed with LF or HF were treated on an outpatient basis. Each group was randomly divided into three equal subgroups based on therapy: oral steroid, intratympanic dexamethasone injection (IT), and combination therapy. Hearing gain was estimated by comparing pre- and post-treatment pure-tone averages. Recovery rate was assessed by Clinical Practice Guideline: Sudden Hearing Loss from the American Academy of Otolaryngology-Head and Neck Surgery., Results: In comparison of chief complaints, ear fullness and hearing loss were more common in the LF and HF group, respectively (P = .033 and P = .001, respectively). Hearing recovery rates were significantly different between the two groups (i.e., 74.1% [40/54] in the LF group and 45.6% [26/57] in the HF group; P < .001). Oral steroid therapy was most effective in the LF group (P = .017). In the HF group, all three modalities showed similar results, although IT tended to be the most effective (P = .390)., Conclusions: There were differences in chief complaints and treatment responses between LF and HF patients. Although they showed similar partial damage in the cochlea, the pathophysiology of LF and HF may be quite different., Level of Evidence: 1b. Laryngoscope, 127:1878-1884, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Intralabyrinthine schwannomas (ILSs) are rare benign tumors arising from the distal part of the cochleovestibular nerve confined within the labyrinth. Patients with ILSs complain of hearing loss, vertigo, tinnitus, and ear fullness. Surgical treatment of ILS is performed in special cases such as in cases of patients with nonserviceable hearing, progressive hearing loss, intractable vertigo, or tumor extension. We present an unusual case of a patient with intralabyrinthine schwannoma who underwent surgery to treat progressive hearing loss and recovered his hearing after surgery., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: The purpose of this study is to investigate the effectiveness of intratympanic dexamethasone injections (ITDI) for refractory tinnitus., Study Design: A prospective, placebo-controlled, randomized, double-blind study., Methods: Thirty patients with refractory tinnitus who were diagnosed in the Department of Otolaryngology, Ajou University Hospital, Suwon, Republic of Korea, between 2006 and 2007 were enrolled and then were assigned into two groups of ITDI (15 patients) or saline (15 patients) by permuted block randomization. Intratympanic injections were double-blind performed four times within 2 weeks. After 4 weeks, we analyzed the improvement and aggravation rates of tinnitus using the following parameters: questionnaires, tinnitus handicap index (THI), loudness matching test, frequency, and duration of tinnitus., Results: The effectiveness rates of ITDI for refractory tinnitus reported in the tinnitus questionnaires, in the THI, and in the loudness matching test were all 33.3% in the steroid group, and 26.7%, 40.0%, and 26.7% in the saline group, respectively. However, there were no statistically significant differences in both groups. To analyze the therapeutic effect of ITDI on tinnitus under 6 months of its development, the improvement rates reported in the tinnitus questionnaires, in the THI, and in the loudness matching test were all 28.5% in the steroid group, and 40.0%, 40.0%, and 30.0% in the saline group, respectively. There were also no statistically significant differences in both groups., Conclusions: ITDI may not be effective for refractory tinnitus. The indication of ITDI for tinnitus needs to be limited to specific cases., (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Tumor necrosis factor-alpha (TNF-α) is released in a variety of pathological states in the inner ear. Inducible nitric oxide synthase (iNOS) can be induced by cytokines and other inflammatory factors, and is generally thought to be associated with inflammation and other pathological processes in the cochlea. The purpose of the present study was to reveal that TNF-α could induce apoptosis in the auditory cell line and to investigate the role of nitric oxide (NO) in TNF-α-induced auditory cell death., Study Design: Experimental study., Methods: UB-OC1 cells and zebrafish were exposed to TNF-α. Flow cytometry, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) assay, assay of mitochondrial membrane potential (MMP), and electron microscopy were used to show that TNF-α could induce apoptosis. Western blot was used to measure iNOS expression and mitogen-activated protein kinase pathway., Results: Flow cytometric analysis, TUNEL assay, MMP, and electron microscopy all demonstrated that TNF-α could induce apoptosis in UB-OC1 cells. TNF-α significantly increased NO generation and iNOS expression. Pretreatment with iNOS blocker NG-methyl-L-arginine (NMA) attenuated TNF-α-induced cell death and caspase-3 activation. Also, TNF-α treatment increased p-p38 and p-ERK, and pretreatment of NMA reduced this increased expression of p-p38 and p-ERK., Conclusions: TNF-α can induce apoptosis in the auditory cell line, and NO production in response to TNF-α is essential for apoptosis., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objectives: To evaluate the preventive effects of Korean red ginseng (KRG) on gentamicin (GM)-induced ototoxicity and to identify the effective components of KRG., Study Design: In vivo and in vitro studies., Methods: Thirty-five Sprague-Dawley rats were divided into four groups. The GM group (n = 15) received intraperitoneal injections (IPI) of GM (160 mg/kg) for 5 days. The KRG + GM group (n = 12) was treated with intragastric feeding of KRG (500 mg/kg) for 12 days with 5 days of IPIs of GM. KRG (n = 4) and control (n = 4) groups were treated with KRG and saline, respectively. Auditory brainstem response (16 or 32 kHz) and Rotarod treadmill tests were done before and after treatments. Cochleas were evaluated by a scanning electron microscope (SEM) and phalloidin staining. Ginsenosides Rb1, Rb2, Rg1, and Re were evaluated as the water-soluble terazolium salt assay, annexin V/propidium iodide assay, and Western blots in HEI-OC1 cells., Results: Posttreatment hearing thresholds in GM, KRG + GM, KRG, and control groups were: 27.7 ± 7.2 dB, 23.1 ± 4.1 dB, 16.9 ± 2.6 dB, and 21.3 ± 3.5 dB, respectively, for 16 kHz, 30.5 ± 6.6 dB, 25.2 ± 4.3 dB, 22.5 ± 2.7 dB, and 22.5 ± 3.8 dB, respectively for 32 kHz. The KRG + GM group had significantly better hearing than the GM group (P < .05). On SEM and phalloidin staining, the GM group showed severe loss of stereocilia in the basal outer hair cells and a few losses in the middle turns, whereas the KRG + GM group showed relatively intact hair cells. Balance impairment in treadmill tests was not definite in any group. Rb1 and Rb2 showed more effective protection than other components., Conclusions: KRG protects against GM-induced hearing loss and hair cell death in rats. Laryngoscope, 2011., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objectives/hypothesis: Horizontal semicircular canal (HSC) benign paroxysmal positional vertigo (BPPV) has been reported to have a poorer prognosis than posterior semicircular canal BPPV. Incorrect determination of the affected ear appears to be one of the causes of poorer outcome. The aim of this study was to assess the efficacy of the "bow and lean test" (BLT) for proper determination of the affected ear followed by preferable treatment outcomes of HSC-BPPV., Study Design: A prospective study., Methods: The 211 patients (225 cases) with HSC-BPPV were sequentially classified into two groups by hospital visiting time and diagnostic methods. The head roll test (HRT) group (61 cases) was treated with canalith repositioning procedure (CRP) on the basis of the results of HRT alone between 2001 and 2004. The BLT group (164 cases) was treated based on the results of both BLT and HRT from 2005 to 2008., Results: The remission rates after two sessions of CRPs in the BLT group and the HRT group were 83.1% and 67.4% (P = .041), respectively, for the canalolithiasis type and 74.7% and 61.1% (P = .250), respectively, for the cupulolithiasis type. In the BLT group, 76.8% had bowing and/or leaning nystagmus; 35.7% of them (45 of 126 cases) benefited from BLT with regard to determining the affected ears because HRT was unable to provide the definitive affected ears (17 cases) or showed different localization between two methods (28 cases)., Conclusions: BLT is a useful method to improve the remission rates of HSC-BPPV, giving more corrective information regarding affected ears than the HRT alone.

This study was performed to determine the three-dimensional (3D) structure of the murine temporal bone and to provide a survey atlas of the temporal bone structures in mice. The temporal bones of adult BALB/c mice were examined and 3D high-resolution reconstructions of the temporal bone were obtained using a micro-CT system. Using the system described here, the bony labyrinth and membranous labyrinth could be investigated in a non-destructive manner. The turning rate of the cochlea was two (human rate: two and a half). The shapes of the superior and posterior semicircular canals were more flexed than those in humans. The malleus manubrium was directed anteriorly and was thin and fan-shaped like a Persian sword. The size of the incus relative to the malleus was smaller than that in the human ossicles. The 3D reconstruction of murine temporal bone described in this study provides anatomical information that will be useful in future studies using mouse model.

Objective: Preauricular sinuses (PAS) are common congenital malformations that usually occur at the anterior margin of the ascending limb of the helix, but the positions of PAS and directions on the fistular tracts are rarely posterior to the external auditory canal (EAC), which presents as a postauricular swelling. We named these cases as the variant type of PAS ('postauricular sinuses'), and compared their clinical manifestations with those of the classical type., Study Design: A retrospective study., Methods: We retrospectively reviewed the charts of patients who had undergone preauricular fistulectomy from 2002 to 2006. These patients were then categorized into two groups according to the position of the preauricular sinus sac. The classical group was defined as the group of patients with sacs located on the (superior) anterior to the EAC, and the variant group as those whose sacs are located on the posterior site of the EAC. We analyzed the incidence, previous histories, clinical manifestations, recurrence rates, and surgical techniques of the variant type of preauricular sinuses and compared them with those of the classical type., Results: Eleven (10.9%) of 101 patients were diagnosed with preauricular sinuses of the variant type. The male to female ratios of the classical and the variant groups were 44:46 and 7:4, respectively. The average age of the patients was approximately 11 to 13 years in both groups. All variant types of preauricular sinuses showed preauricular pits located posterior to the imaginary line that connects the tragus with the posterior margin of the ascending limb of the helix, unlike the classical type. Most (72.8%) of the fistular tracts of the variant type were directed in the posterior-middle direction from the pits. The variant types were operated with a dual approach using preauricular and retroauricular incisions, unlike the classical type, and the recurrence rate was 0% (compared with 2.2% in the classical type)., Conclusion: Frequent postauricular infected swellings may indicate the presence of the variant type of preauricular sinuses. The variant type of preauricular sinuses presenting in the postauricular area were found to have an unusual location of the fistula pit that was positioned posterior to the imaginary tragal extended line. A comprehensive physical examination of the preauricular pits should be performed to avoid incomplete excision of the variant types.

Objective: The present study prospectively investigated the frequencies and characteristics of audio-vestibular disturbance and the results of audiologic and vestibular function tests in patients with Behçet's disease., Study Design: A prospective study., Methods: Seventeen patients with Behçet's disease (mean age 41.2 [30-56] years, 5 males and 12 females), as well as age- and sex-matched healthy controls, were included in this study. All subjects satisfied the diagnostic criteria of the International Study Group for Behçet's Disease. Information on the subjects was obtained through questionnaires. Tests, including those for hearing impairment, tinnitus, ear fullness, and dizziness, pure-tone audiometry, and vestibular function, were performed., Results: Auditory symptoms were reported by 7 (41.2%) and dizziness by 14 (82.4%) of the subjects. Sensorineural hearing loss was present in four (23.5%) subjects. One was treated with a cochlear implantation because of bilateral sudden deafness. Spontaneous nystagmus was detected in two (11.8%) subjects. Abnormal findings were noted in 1 (5.9%) in saccadic movement, 5 (29.4%) in the bithermal caloric tests, and 10 (58.9%) in the rotation chair tests. In total, audiologic or vestibular disturbance were noted in 16 (94.1%) of the subjects. However, audio-vestibular abnormalities were not noted in the healthy controls., Conclusion: Audio-vestibular disturbance is not rare in Behçet's disease patients compared with healthy controls. We believe that audio-vestibular assessment and management may be helpful for the diagnosis and treatment of patients with Behçet's disease.

Objective: One of the problems in the management of horizontal semicircular canal benign paroxysmal positional vertigo (HSC-BPPV) is the difficulty in determining the affected ear using Ewald's second law. The purpose of this study is to develop the new "bow and lean test (BLT)" to easily determine the affected ear of HSC-BPPV and evaluate its efficiency., Methods: We compared the efficiency between the classic method and BLT in 26 patients with HSC-BPPV. The classic method is based on Ewald's second law comparing the intensity of nystagmus or symptoms in the head roll test. BLT is based on the direction of both "bowing nystagmus" and "leaning nystagmus" at the head's bowing and leaning state in a sitting position. The affected ear is the same direction of bowing nystagmus in canalolithiasis and the same direction of leaning nystagmus in cupulolithiasis., Results: In 26 patents (15 canalolithiasis, 11 cupulolithiasis), 3 (11.5%) patients did not show a prominent affected ear in the classic method, and 7 (26.9%) patients showed the different affected ear between the two methods. All 10 patients were successfully treated with just one trial of barbecue rotation based on the affected ear in BLT. Three patients did not show any bowing or leaning nystagmus. The side with canal paresis in all four patients, who showed significant canal paresis in bithermal caloric tests, was equal to the affected ear based on BLT., Conclusions: The "bow and lean test" (also called "Choung's test") is a new method that can easily determine the affected ear of HC-BPPV.

Objective: This case-control study aimed to analyze the effect of intratympanic dexamethasone injection (ITDI) as a treatment option for patients with sudden sensorineural hearing loss (SSNHL) who were refractory to classic oral steroid treatment., Methods: Sixty-six patients with SSNHL, who were refractory to a course of oral steroid therapy, were included in this study. We prospectively treated consecutive 33 patients (34 ears) with ITDI from August 2002 to January 2004. We then retrospectively collected data from age- and sex-matched previous patients who did not take any more treatments after the initial regimen between March 2000 and July 2002. ITDI was performed in the supine position on four separate occasions over the course of 2 weeks. Hearing was assessed immediately before every injection and at 1 week after therapy. Hearing improvement was defined as more than 10 dB in pure-tone average (PTA)., Results: Hearing improvement was observed in 13 (39.4%) of 33 patients who underwent ITDI and in two (6.1%) of 33 patients in the control group. Five of 13 represented hearing improvement over than 20 dB in PTA, and 11 of 20 patients, who showed no improvement in PTA by ITDI, showed improvement over 10 dB in some frequencies. There were no definite prognostic factors between the patients who responded to ITDI and those who did not., Conclusion: ITDI may be a simple and effective therapy for patients with refractory SSNHL.

Objectives/hypothesis: The gene of the gap junction protein connexin 26 (Cx26) was found to be the main causative gene of autosomal recessive nonsyndromic hearing loss (DFNB1). Although 35delG has been known as the major mutation in Western countries, 235delC was reported to be a specific form of mutation in Asian populations. The objective of the study was to identify how 235delC and E114G changes found in the Korean population affected the function of using molecular biological techniques., Methods: Genes containing 235delC and E114G were cloned into the pcDNA3 vector, and HeLa cells were transfected with the recombinant DNA samples by the liposome complex method. The expression and subcellular localization of Cx26 were determined, using antibodies against amino acid sequences in the intracellular loop (IL) and N-terminal (NT) portions of Cx26. To analyze functions of the as a gap junction channel, we examined Lucifer yellow dye transfer between cells with a scrape-loaded technique. Wild-type (WT) with normal hearing was used as a positive control, and mock transfected cells were used as a negative control., Results: Immunocytochemical analysis showed that cells transfected with E114G and WT gave characteristic punctate patterns of reaction in the cell membrane with both antibodies. However, 235delC cells were not stained with anti-IL antibody but stained slightly just around the nucleus only with anti-NT antibody. In a functional study of, transfer of Lucifer yellow into contiguous cells was detected in both WT and E114G, but no transfer activity was observed in 235delC., Conclusions: The 235delC mutation showed a loss of targeting activity to the cell membrane and severe deterioration of gap junction activity. For the E114G, we did not find any difference from WT transfected cells.