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Objectives: This study was designed to analyze the outcomes of low-frequency hearing preservation (HP) 1 year after cochlear implantation (CI) and to identify the prognostic variables associated with residual low-frequency HP. Material and Methods : Among the patients who underwent CI at the Ajou University Hospital, 36 patients with preoperative pure tone average ≤ 85dB HL on 125, 250, and 500Hz were included. There were 14 males and 22 females with a mean age of 37.0 years (range: 5.1-84.8). Preoperative pure tone average was 65.3 ± 15.4 dB HL. The straight type electrode was inserted via round window approach in all patients. Sixteen patients received Cochlear devices and 20 patients received MEDEL devices. The change of pure tone average was categorized after CI (1, 6, 12 month): 'completely preserved (≤10dB)', 'partially preserved (between 10dB and 30dB)', and 'failure (> 30dB)'. The preservation of residual hearing was defined in cases of 'completely preserved' or 'partially preserved'. Results: Of the thirty six patients, the HP was observed in 25 patients (69%) 1 month after CI ('Completely preserved', N=11; 'partially preserved', N=14), 24 patients (67%) 6 months after CI ('Completely preserved', N=11; 'partially preserved', N=13), and 23 patients (64%) 1 year after CI ('Completely preserved', N=13; 'partially preserved', N=10). In multivariate regression, age was the only significant prognostic factor for better HP (p<.05) at short term (1 month and 6 months) and long term follow-ups. Conclusion: HP can be achieved until 1 year after CI and the age is associated with better HP outcomes. Further follow- up for more than 1 year could be needed to investigate the gradual deterioration of HP with time by the natural progression of hearing loss. [ABSTRACT FROM AUTHOR]

Myoclinic tinnitus consists of tinnitus due to middle ear myoclonus, middle ear myoclonic tinnitus (MEMT) and palatal myoclonic tinnitus (PMT). It is rare but can be curable which needs to be known well to many otologists. We reviewed our own clinical experiences of MEMT and PMT in large case series. Clinical characteristics, diagnostic and therapeutic modalities of myoclonic tinnitus will be introduced based on our data. Therapeutic response to surgical intervention and botox injection will be discussed. One hundred and fifty patients diagnosed as MEMT and 48 patients diagnosed as PM tinnitus in a tinnitus clinic of tertiary referral center from Jan 2003 to Dec 2015 were included in this study. Their medical records were retrospectively reviewed to evaluate the clinical and audiological characteristics and the therapeutic responses to conservative management, botox injection and surgery. Patients with MEMT and PMT were relatively young and had a tendency of female predominance. In children, MEMT associated with forceful eyelid closure were more frequently observed than in adults. Over 50% of PMT accompanied with MEMT. Impedance audiogram and otoendoscopic examinations of the tympanic membrane were helpful tools for diagnosing MEMT. Voluntary or involuntary myoclonic motion of the soft palate was observed in all of the PMT patients. With medical therapy and counseling, more than 70% of patients exhibited complete or partial remission of their tinnitus. Patients with intractable MEMT who underwent sectioning of the middle ear tendons (n=27) had very good surgical outcomes with no remarkable complications. Botox injection of the soft palate in patients with intractable PMT(n=9) showed complete remission of symptoms with acceptable short term complications of hypernasal voice and velopharyngeal insufficiency. Deep understanding of the clinical characteristics and therapeutic responses of myoclonic tinnitus will help to diagnose and to treat the patients with these rare types of tinnitus. Surgical resection of middle ear tendons and botox injection seem to be viable and safe treatment option for intractable MEMT and PMT. [ABSTRACT FROM AUTHOR]

Steroids have been widely used to treat inner-ear diseases including 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). 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 h, and 3 and 7 days after the final injection. 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 those subjected to IP injections. The preservation of residual hearing, especially in the low frequencies, became one of the main interests in cochlear implantation, because it is known to be important for speech in noise perception, sound localization, and music perception. Combined therapy using both IP and IT steroid injections may be optimal to ensure full cochlear coverage in some cases. In that sense, targeted therapies using steroid could be a future direction for the treatment of hearing loss in the clinical field. 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. [ABSTRACT FROM AUTHOR]

Noise-induced hearing loss (NIHL) is one of the most common forms of sensorineural hearing loss and a well-known contributor to presbycusis. Based on the generation of reactive oxygen species (ROS) in the pathogenesis of NIHL, augmentation of the antioxidative defense system is a major target for pharmacological prevention. In this study, we assessed whether administration of pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, which is a rate-limiting enzyme of cholesterol synthesis, before noise exposure protects against cochlear injury in BALB/c mice. Noise exposure produced both compound threshold shift (CTS) and permanent threshold shift (PTS) over 40 dB at 16 and 32 kHz. Pretreatment with pravastatin (25 mg/kg) for 5 days significantly decreased both CTS and PTS. Pravastatin also reduced hair cell death after noise exposure in the cochlea, which was identified by surface preparation and scanning electron microscopy (SEM). It also reduced the formation of noise-induced 4-hydroxynonenal (4-HNE), a byproduct of lipid peroxidation. Activation of Rac1, one of the subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex, which is a major superoxide generator in the cell membrane, was inhibited by the administration of pravastatin. These findings suggest that pravastatin can protect against cochlear acoustic injury by lowering ROS generation via inhibition of the formation of the NADPH oxidase complex. This study will be helpful for the development of new therapeutic strategies for NIHL and other hearing loss-related diseases caused by ROS overproduction., (Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.)

Objectives/hypothesis: Efferent nerves under the outer hair cells (OHCs) play a role in the protection of these cells from loud stimuli. Previously, we showed that cochlear α-synuclein expression is localized to efferent auditory synapses at the base of the OHCs. To prove our hypothesis that α-synuclein deficiency and efferent auditory deficit might be a cause of hearing loss, we compared the morphology of efferent nerve endings and α-synuclein expression within the cochleae of two mouse models of presbycusis., Study Design: Comparative animal study of presbycusis., Methods: The C57BL/6J(C57) mouse strain, a well-known model of early-onset hearing loss, and the CBA mouse strain, a model of relatively late-onset hearing loss, were examined. Auditory brainstem responses and distortion product otoacoustic emissions were recorded, and cochlear morphology with efferent nerve ending was compared. Western blotting was used to examine α-synuclein expression in the cochlea., Results: Compared with CBA mice, C57 mice showed earlier onset high-frequency hearing loss and decreased function in OHCs, especially within high-frequency regions. C57 mice demonstrated more severe pathologic changes within the cochlea, particularly within the basal turn, than CBA mice of the same age. Weaker α-synuclein and synaptophysin expression in the efferent nerve endings and cochlear homogenates in C57 mice was observed., Conclusions: Our results support the hypothesis that efferent nerve degeneration, possibly due to differential α-synuclein expression, is a potential cause of early-onset presbycusis. Further studies at the cellular level are necessary to verify our results., (Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Cisplatin, a widely used chemotherapeutic drug, causes ototoxicity in a large percentage of patients. The purpose of this study was to determine the efficacy of epicatechin (EC) as an otoprotective agent to prevent cisplatin toxicity and to investigate the molecular mechanism of EC. The effects of EC on cisplatin-induced ototoxicity were investigated in a cochlear organ of Corti-derived cell line, HEI-OC1 and in a rat model. In addition, signaling mechanisms were investigated, specifically those involving MAP kinase. Cisplatin induced apoptosis and demonstrated, conjugation of annexin V/PI in FACS, and an increase of subG1 in HEI-OC1. EC protected HEI-OC1 against cisplatin and showed inhibition of cisplatin-induced apoptosis of the HEI-OC1 by transmission electron microscopy. Intratympanic administration of EC protected against cisplatin-induced ototoxicity in the rat model, as determined by auditory brainstem responses. EC inhibited activation of JNK, ERK, cytochrome-c and caspase-3 by cisplatin. An ERK Inhibitor, cisplatin-induced ototoxicity in a dose dependent manner but a JNK inhibitor did not. The results of this study suggest that EC may provide a mechanism by which ototoxicity caused by the administration of cisplatin can be reduced through the inhibition of ERK. EC may have clinical use as a chemopreventive agent that prevents cisplatin ototoxicity., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Adenovirus vectors (AdVs) are efficient tools for gene therapy in many tissues. Several studies have demonstrated successful transgene transduction with AdVs in the inner ear of rodents [Kawamoto K, Ishimoto SI, Minoda R, Brough DE, Raphael Y (2003) J Neurosci 23:4395-4400]. However, toxicity of AdVs [Morral N, O'Neal WK, Rice K, Leland MM, Piedra PA, Aguilar-Cordova E, Carey KD, Beaudet AL, Langston C (2002) Hum Gene Ther 13:143-154.] or lack of tropism to important cell types such as hair cells [Shou J, Zheng JL, Gao WQ (2003) Mol Cell Neurosci 23:169-179] appears to limit their experimental and potential clinical utility. Histone deacetylase inhibitors (HDIs) are known to enhance AdV-mediated transgene expression in various organs [Dion LD, Goldsmith KT, Tang DC, Engler JA, Yoshida M, Garver RI Jr (1997) Virology 231:201-209], but their effects in the inner ear have not been documented. We investigated the ability of one HDI, trichostatin A (TSA), to enhance AdV-mediated transgene expression in inner ear tissue. We cultured neonatal rat macular and cochlear explants, and transduced them with an AdV encoding green fluorescent protein (Ad-GFP) under the control of a constitutive promoter for 24 h. In the absence of TSA, GFP expression was limited, and very few hair cells were transduced. TSA did not enhance transduction when applied at the onset of Ad-GFP transduction. However, administration of TSA during or just after Ad-GFP application increased GFP expression in supporting cells approximately fourfold. Moreover, vestibular hair cell transduction was enhanced approximately sixfold, and that of inner hair cells by more than 17-fold. These results suggest that TSA increases AdV-mediated transgene expression in the inner ear, including the successful transduction of hair cells. HDIs, some of which are currently under clinical trials (Sandor et al., 2002), could be useful tools in overcoming current limitations of gene therapy in the inner ear using Ad-GFP., (Published by Elsevier Ltd.)

Reactive oxygen species (ROS) have been suggested to play a major role in aminoglycoside-induced hair cell (HC) loss, but are difficult to detect. Moreover, ROS can occur normally in cells where they have roles in metabolism, cell signaling and other processes. Two new probes, aminophenyl fluorescein (APF) and hydroxyphenyl fluorescein (HPF) are dyes which selectively detect highly-reactive oxygen species (hROS), those most associated with cellular damage. We assessed the presence of hROS in the neonatal rat organ of Corti during chronic exposure to 50 microM gentamicin in vitro, to examine the relationship between cell damage and hROS across HC type and across the three cochlear turns. hROS were initially detected at 48 hours (h), with an increase at 72 h and persistence until at least 96 h. At 48 h, hROS were restricted to outer HCs and occurred prior to loss of stereocilia. At 72 h, outer HCs showed both hROS and stereocilia loss, and hROS were noted in a few inner HCs. Basal turn HCs showed more hROS than middle turn HCs. Very little hROS accumulation or stereocilia loss was observed in the apical turn, even at 72 h. First row outer HCs were most vulnerable to gentamicin-induced hROS, followed by second and then third row outer HCs. Inner HCs behaved similarly to third row outer HCs. By 96 h stereocilia damage was extensive, but surviving HCs showed persisting fluorescence. APF consistently showed more fluorescence than HPF. The results suggest that hROS accumulation is an important initial step in gentamicin-induced HC damage, and that the differential sensitivity of HCs in the organ of Corti is closely related to differences in hROS accumulation.

Purpose: This article describes a vascularized bony window for access to the maxillary sinus and reports the clinical results., Patients and Methods: A bony U-shaped window in the anterior sinus wall was pedicled on the surrounding soft tissue and periosteum. After the described sinus was cleared of disease, the window was repositioned in its original site either using resorbable sutures or not. The method was used in 47 maxillary sinus operations in 45 patients. Twenty-four patients were followed-up for more than 48 months., Results: The vascularized bony window technique showed uneventful healing in all patients and none of the 24 patients reported any problems., Conclusions: The vascularized bony window technique provides a large antrostomy, which gives good access and visibility and results in satisfactory postoperative healing.