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Conclusions. Prednisolone protects against inner ear damage, even when administered after ischemic injury in Mongolian gerbils. Objective. The effect of prednisolone on ischemia-induced cochlear damage was investigated in Mongolian gerbils. Materials and methods. The bilateral vertebral arteries were occluded for 15 min to transiently induce cochlear ischemia, followed by an intraperitoneal injection of prednisolone (1 mg/kg) or physiological saline (control). Sequential changes in hearing were evaluated by recording the auditory brainstem response (ABR) before and at 1, 4, and 7 days after treatment. In our histologic analysis, the numbers of dead and intact inner hair cells (IHCs) were counted in specimens stained with rhodamine-phalloidin. Results. In control animals, transient ischemia increased the ABR threshold (24.2±8.6 dB) within 7 days of treatment, whereas prednisolone-treated animals exhibited a threshold of 14.2±9.2 dB. Furthermore, the percent IHC loss at the basal turn of the cochlea was 26.5±11.4% in control animals compared with 5.3±3.0% in the prednisolone-treated group. [ABSTRACT FROM AUTHOR]

Abstract Background Because of the lack of reproducible brainstem ischemia models in rodents, the temporal profile of ischemic lesions in the brainstem after transient brainstem ischemia has not been evaluated intensively. Previously, we produced a reproducible brainstem ischemia model of Mongolian gerbils. Here, we showed the temporal profile of ischemic lesions after transient brainstem ischemia. Results Brainstem ischemia was produced by occlusion of the bilateral vertebral arteries just before their entry into the transverse foramina of the cervical vertebrae of Mongolian gerbils. Animals were subjected to brainstem ischemia for 15 min, and then reperfused for 0 d (just after ischemia), 1 d, 3 d and 7 d (n = 4 in each group). Sham-operated animals (n = 4) were used as control. After deep anesthesia, the gerbils were perfused with fixative for immunohistochemical investigation. Ischemic lesions were detected by immunostaining for microtubule-associated protein 2 (MAP2). Just after 15-min brainstem ischemia, ischemic lesions were detected in the lateral vestibular nucleus and the ventral part of the spinal trigeminal nucleus, and these ischemic lesions disappeared one day after reperfusion in all animals examined. However, 3 days and 7 days after reperfusion, ischemic lesions appeared again and clusters of ionized calcium-binding adapter molecule-1(IBA-1)-positive cells were detected in the same areas in all animals. Conclusion These results suggest that delayed neuronal cell death took place in the brainstem after transient brainstem ischemia in gerbils.

We describe a right external auditory canal (EAC) recurrent ceruminous pleomorphic adenoma (CPA) accompanied by itching and review the clinical features and histopathology of this disease. A female in her 70s presented with a right EAC mass accompanied by itching. We initially diagnosed the mass as a ceruminous gland adenoma (CGA) following excisional biopsy. Two years and nine months later, the tumor recurred at the same site. A preoperative computed tomography (CT) scan demonstrated no bone destruction, and magnetic resonance imaging (MRI) showed a 1 × 1 cm mass with a clearly defined margin in the right EAC. We completely excised the recurrent tumor using a transmeatal approach under general anesthesia. Histopathology demonstrated haphazard proliferation of tubule-glandular structures lined by two layers of the epithelium in the hypocellular stroma composed of a mucoid matrix. The recurring tumor was diagnosed as a CPA. Here, an EAC tumor-originally diagnosed as a CGA following excisional biopsy-recurred and was subsequently diagnosed as a CPA. CPA can be considered an unusual variant of CGA., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To obtain new insights into research questions on how executive function and social interaction would be observed to change after the introduction of hearing aids (HAs) in older people with hearing impairment., Design: Multi-institutional prospective single-arm observational study., Setting and Participants: Outpatients with complaints of hearing difficulty who visited HA clinics between October 18, 2017, and June 30, 2019, in 7 different university hospitals in Japan., Methods: The inclusion criteria of the study named Hearing-Aid Introduction for Hearing-Impaired Seniors to Realize a Productive Aging Society-A Study Focusing on Executive Function and Social Activities Study (HA-ProA study) were age ≥60 years and no history of HA use. A series of multi-institution common evaluations including audiometric measurements, the digit symbol substitution test to assess executive functions, convoy model as an index of social relations, and hearing handicap inventory for the elderly (HHIE) were performed before (pre-HA) and after 6 months of the HA introduction (post-HA)., Results: Out of 127 enrollments, 94 participants completed a 6-month follow-up, with a mean age of 76.9 years. The digit symbol substitution test score improved significantly from 44.7 at baseline to 46.1 at 6 months (P = .0106). In the convoy model, the social network size indicated by the number of persons in each and whole circles were not significantly different between pre- and post-HA; however, the total count for kin was significantly increased (P = .0344). In the analyses of HHIE, the items regarding the family and relatives showed significant improvement., Conclusions and Implications: HA use could benefit older individuals beginning to use HAs in executive function and social interaction, though the results should be interpreted cautiously given methodological limitations such as a single-arm short 6 months observation. Reduction in daily hearing impairment would have a favorable effect on relationships with the family., (Copyright © 2021 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

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 β-d-glucan and a positive Aspergillus antigen test result. Voriconazole treatment resolved diplopia and left otorrhea and dramatically improved HCP., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

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 4-11years) in whom the duration of perforation before treatment exceeded 6months and who were followed for at least 1year 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 5min. Complete closure was achieved in nine (81.8%) ears after 1year of postoperative follow-up., Conclusion: TM regenerative therapy can be performed under local anesthesia in less than 5min 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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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 (<1 mm 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 < .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.

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.

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.

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<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., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

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 CO(2) 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.

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 2 mL/kg of either LEH (P₅₀O₂=15 mmHg) or saline 1h after the experimental induction of 15 min 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 32 kHz on day 1 was 21 ± 7 dB in the LEH group (n=6) and 45 ± 6 dB 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., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

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.

Our surgical treatment for middle ear cholesteatoma is based on the following 2 concepts: (1) Preservation of the physiological morphology and function of the middle ear, that is, maximal preservation of the posterior wall of the external auditory meatus and the middle ear mucosa and (2) Careful resection of the matrix membrane of the cholesteatoma through the continuity of the matrix membrane. In case the cholesteatoma matrix membrane is ruptured, a staged operation should be performed to prevent the development of residual cholesteatoma from the residual matrix. In this study, we classified a total of 238 cases of the pars flaccida cholesteatoma primary operated on Osaka Red Cross Hospital between January 2006 and March 2008 according to the Classification and Staging of Cholesteatoma proposed in 2010. The age of the patients ranged from 4 to 79 years (average: 49.8 years) and there were 123 males and 115 females. Follow up ranged from 1 year to 5 years with a mean follow-up period of 47.8 months. Regarding the stage, 38 (16.0%) ears had stage I cholesteatoma, 155 (65.1%) ears had stage II, and 45 (18.9%) ears had stage III. The successful outcome rate was 97.4% for stage I, 78.7% for stage II and 60.0% for stage III. The rate of the residue and the postoperative recurrence was 2.5% and 4.2%.

Conclusion: Severity of ipsilateral facial palsy (UFP) can be assessed objectively by use of OKAO Vision®. 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®, 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 × 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 < 0.05) and was inversely related to the House-Brackmann grade (r = -0.90, p < 0.05).

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 mRNA was 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.

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, P₅₀0₂ = 40 mm Hg), high-affinity LEH (h-LEH, P₅₀0₂ = 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 < 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., (© 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

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 < 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.

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 2h 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 48h, 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<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., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Because of the lack of reproducible brainstem ischemia models in rodents, the temporal profile of ischemic lesions in the brainstem after transient brainstem ischemia has not been evaluated intensively. Previously, we produced a reproducible brainstem ischemia model of Mongolian gerbils. Here, we showed the temporal profile of ischemic lesions after transient brainstem ischemia., Results: Brainstem ischemia was produced by occlusion of the bilateral vertebral arteries just before their entry into the transverse foramina of the cervical vertebrae of Mongolian gerbils. Animals were subjected to brainstem ischemia for 15 min, and then reperfused for 0 d (just after ischemia), 1 d, 3 d and 7 d (n = 4 in each group). Sham-operated animals (n = 4) were used as control. After deep anesthesia, the gerbils were perfused with fixative for immunohistochemical investigation. Ischemic lesions were detected by immunostaining for microtubule-associated protein 2 (MAP2). Just after 15-min brainstem ischemia, ischemic lesions were detected in the lateral vestibular nucleus and the ventral part of the spinal trigeminal nucleus, and these ischemic lesions disappeared one day after reperfusion in all animals examined. However, 3 days and 7 days after reperfusion, ischemic lesions appeared again and clusters of ionized calcium-binding adapter molecule-1(IBA-1)-positive cells were detected in the same areas in all animals., Conclusion: These results suggest that delayed neuronal cell death took place in the brainstem after transient brainstem ischemia in gerbils.

This retrospective study examined the etiology and treatment results for traumatic, conductive hearing loss in 22 patients who underwent surgery between 1998 and 2008 at Osaka Red Cross Hospital. All patients underwent computed tomography (CT) of the temporal bone preoperatively. The ear surgery comprised closure of the ruptured tympanic membranes and restoration of the sound-transmitting function of the ossicular chain. Their mean age was 30.3 years, and the average delay from injury until treatment was 6.0 years. Of the injuries due to foreign-body insertion, the most common cause was ear-pick injury. Incudostapedial disarticulation was the most common finding, which was diagnosed preoperatively using CT in seven cases and identified at surgery in 15 cases. Closure of the air-bone gap to within 10 and 20 dB was observed in 50.0 and 68.2% of the patients, respectively. The hearing threshold improved by 10 dB or more in 16 (72.7%) patients. If no improvement in hearing loss follows the absorption of hemotympanium or closure of an eardrum perforation, dislocation of the ossicular bones should be suspected. Ossicular reconstruction following trauma produces more stable and better hearing results, even after delayed treatment.

The effects on distortion product otoacoustic emissions (DPOAEs) during the late phase of ischemia/reperfusion injury in the cochlea were studied. Ischemia/reperfusion injury was induced in a gerbil model by occluding both vertebral arteries for 15min. Hearing was assessed by recording compound action potentials (CAPs) before, during, and 7 days after ischemia. The histological changes in the hair cells were evaluated in specimens stained with rhodamine-phalloidin and Hoechst 33342. The average increase in CAP threshold 7 days after ischemia was 16.3+/-8.0dB at 8kHz. In contrast, interruption of the blood supply to the cochlea decreased the DPOAE amplitudes to the noise floor; this usually recovered to the same level as that seen under pre-ischemic conditions 7 days after ischemia. Histologically, the mean respective losses of inner and outer hair cells (IHCs and OHCs, respectively) of the inner ear were 26.5% and 3.3% in the basal turn, respectively. These results indicate that in gerbils OHCs are tolerant to ischemia/reperfusion injury pathologically and physiologically because DPOAE is closely related to the active process of OHCs and is a useful test to examine OHC function.

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.

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 microM AMPA caused reversible elevation of the auditory brainstem response threshold without loss of IHCs. In contrast, 200 microM 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.

This study was designed to investigate the protective effects of recombinant human insulin-like growth factor 1 (rhIGF1), applied locally via a hydrogel, against ischemic damage of the cochleae in gerbils. A hydrogel was immersed in rhIGF1 or saline and was applied on the round window membrane 30 min after the ischemia. Local rhIGF1 treatment significantly reduced the elevation of auditory brain responses thresholds at a frequency of 8 kHz on days 1, 4, and 7 after ischemia. A histological analysis revealed increased survival of inner hair cells in the animals treated with rhIGF1 via the hydrogel 7 days after ischemia. These findings showed that local rhIGF1 application using a hydrogel has the potential to protect the cochleae from ischemic injury.

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, 3-6, 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.

The effects of transient cochlear ischemia on spiral ganglion cells (SGCs) were studied in Mongolian gerbils. Ischemic insult was induced by occluding the bilateral vertebral arteries of gerbils for 15min. Seven days after ischemia, the percentage of SGCs decreased to 67.5% from the preischemic baseline in the basal turn. Evaluation with immunohistochemical staining showed TUNEL-positive reactions in the SGCs with fragmented nuclei. In addition, we investigated the protective effects of ginsenoside Rb1 (gRb1) against ischemic injury to SGCs. Seven days after ischemia, the auditory brainstem response threshold shift was significantly reduced and the percentage of SGCs decreased to 90.2% from the preischemic baseline in the basal turn in the gRb1-treated group. These findings suggest that gRb1 prevented hearing loss caused by ischemic injury to SGCs in Mongolian gerbils.

Objective: To evaluate whether the incus of the cholesteatomatous ear preserved in the mastoid bowl during the first stage of planned two-stage tympanoplasty can tolerate long-term implantation and be used in ossicular reconstruction during the second stage., Methods: The study group included 24 ears of 23 patients who underwent staged tympanoplasty for the treatment of middle ear cholesteatoma. At the first stage, after removing the incus to eradicate the middle ear disease, it was returned to the mastoid bowl and stored there until use at the second stage. The average interval between the two stages was 8.3 months (range 6-12 months)., Results: The incus was identified in all cases at the second stage: 10 incudes were found to be covered with a thin mucosa layer, 12 were buried in fibrous or granulation tissue, and 2 were joined to the surrounding bone. Residual cholesteatoma was found in six ears, either in the attic (three ears) or tympanic sinus (three ears). It never occurred in the mastoid bowl where the incus had been preserved. In 19 cases, the incus was available as a short columella for ossicular reconstruction. The remaining five cases were reconstructed using a hydroxyapatite ossicle as a long columella, since the stapes superstructure was missing at the second stage. In one case, the stored incus underwent remarkable absorption between stages., Conclusion: Preservation of the incus in the mastoid bowl is an effective option in planned two-stage tympanoplasty, when the incus is considered useful for ossicular reconstruction at the second stage.

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 malleus-incus 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.

We describe a case of small cell carcinoma arising in the nasal cavity using combined chemotherapy with irinotecan (CPT-11)/cisplatin followed by surgical salvage which successfully avoided a radical operation. In a follow-up no local recurrence was observed over 3 years after the operation. Ours is the first report of the use of combined irinotecan (CPT-11)/cisplatin chemotherapy in small cell carcinoma of the nasal cavity.

The present study was designed to elucidate the dynamic changes of nitric oxide (NO) production in the perilymph and to investigate the immunostaining for inducible nitric oxide synthase (iNOS) in the cochlea for 7 days after transient cochlear ischemia. Moreover, aminoguanidine, which is a selective iNOS inhibitor, was administrated immediately following ischemia and every 24h thereafter for 7 days to investigate whether the production of NO is dependent on the iNOS pathway. Significant increases in the oxidative NO metabolites, nitrite (NO(2)(-)) and nitrate (NO(3)(-)), were measured on day 1 using an in vivo microdialysis and on-line high performance liquid chromatography (HPLC) system. The immunostaining for iNOS was strongly expressed on days 1 and 4 and returned to normal on day 7 after the ischemia. The administration of aminoguanidine reduced the oxidative NO metabolites on day 1 and suppressed the expression of iNOS. These findings suggest that transient ischemia causes a remarkable increase in NO production in the perilymph, which might be attributable to the iNOS pathway.

Neural stem cells are multipotent progenitor cells that show self-renewal activity. In this study, we assessed the use of neural stem cells for ameliorating ischemia-reperfusion injury of the gerbil cochlea. Neural stem cells were injected into one inner ear through the round window 1 day after ischemic insult. Immunostaining for nestin showed that the distribution of neural stem cells was concentrated within the organ of Corti. Seven days after ischemia, the injury-induced auditory brainstem response threshold shift and progressive inner hair cell damage were markedly less on the neural stem cell-transplanted side. These results suggest that the transplantation of neural stem cells is therapeutically useful for preventing damage to hair cells that occurs after transient ischemia of the cochlea.

Glutamate-aspartate transporter (GLAST), a powerful glutamate uptake system, removes released glutamate from the synaptic cleft and facilitates the re-use of glutamate as a neurotransmitter recycling system. Aminoglycoside-induced hearing loss is mediated via a glutamate excitotoxic process. We investigated the effect of aminoglycoside ototoxicity in GLAST knockout mice using the recorded auditory brainstem response (ABR) and number of hair cells in the cochlea. Kanamycin (100 mg/mL) was injected directly into the posterior semicircular canal of mice. Before the kanamycin treatment, there was no difference in the ABR threshold average between the wild-type and knockout mice. Kanamycin injection aggravated the ABR threshold in the GLAST knockout mice compared with the wild-type mice, and the IHC degeneration was more severe in the GLAST knockout mice. These findings suggest that GLAST plays an important role in preventing the degeneration of inner hair cells in aminoglycoside ototoxicity.

The effects of transient cochlear ischemia on the stria vascularis were studied. Fifteen minutes of ischemia decreased the endocochlear potential by up to 17.5 mV on day 1; it returned to normal on day 7. Immunostaining for Na+,K+-ATPase, a marker for the Na+/K+-pump, and for connexin 26, a marker for gap junctions, was inhibited on days 1 and 4, and returned to normal on day 7. Electron microscopy showed expansion of the intercellular space with abundant vacuolar formation in the stria vascularis. These morphological changes disappeared completely by day 7. The results indicate that transient ischemia causes a reversible functional disorder of the stria vascularis with fine structural changes, which may be owing to dysfunction of Na+/K+-pump or gap junctions.

A chondroma located in the external auditory canal is a rare finding. Here, we report the case of a 12-year-old girl who attended our clinic with complaints of a rustling sound in her left ear. Otoscopic examination revealed a tiny bone-like tumor protruding from the anterior wall of the bony external auditory canal, attached to the short process of the malleus. An audiogram revealed a conductive hearing loss in her left ear, although she did not notice it. After excision of the tumor through the ear canal, her complaints disappeared and her hearing recovered. Histologically, the tumor proved to be a chondroma.

Objective: The aim of this experimental study was to examine whether recombinant human bone morphogenetic protein-2 (rhBMP-2) could induce new bone formation in a small hole drilled through the temporal bone near the external auditory canal wall in guinea pigs., Material and Methods: A 4-mm diameter hole was made in the center of the temporal bone and a piece of collagen sheet infiltrated with rhBMP-2 was placed in the hole. New bone formation was confirmed by means of X-ray examination and the bone mineral density was quantified using dual-energy X-ray absorptiometry 1, 2 and 4 weeks after treatment., Results: The bone mineral density in the rhBMP-2-treated group was significantly increased compared to the control group., Conclusion: These results suggest that rhBMP-2 induces remarkable new bone formation in the temporal bone and will be useful in clinical ear surgery.

We investigated the protective effects of edaravone, a free radical scavenger, against ischemic damage of inner hair cells (IHCs) in gerbils. Cochlear ischemia was induced in the animals by occluding the vertebral arteries bilaterally for 15 min. Edaravone (1 mg/kg, i.v.) or saline was administered 1 h after ischemia. Hearing was assessed by auditory brain response (ABR). In animals treated with saline, the ABR threshold shift was 24.1 dB and there was a 26.5% decrease in the number of IHCs. By contrast, in animals treated with edaravone, the threshold shift was 7.5 dB and only 8.8% of IHCs was lost. These results suggest that edaravone protects against damage to the inner ear following transient ischemia.

Objective: To present a new method for closing tympanic membrane perforations using basic fibroblast growth factor (bFGF) combined with an atelocollagen/silicone bilayer membrane as a patch material., Study Design: Closure of tympanic membrane perforations was attempted using bFGF, which is thought to facilitate the growth of fibroblasts and collagen fibers at the margin of the perforation., Methods: Under an operating microscope, the margin of the perforation was trimmed, and a piece of an atelocollagen/silicone bilayer membrane infiltrated with 0.2 mL Trafermin (0.1% solution) (bFGF group) or saline (control group) was then placed in the perforation with the silicon layer facing outward. Nine patients were treated with bFGF, and five were treated with saline. Data obtained from patient records included patient age, perforation size, and duration of treatment, with a focus on hearing improvement and complete tympanic membrane closure., Results: The mean perforation size before treatment was 16.5% in the bFGF group and 9.6% in the control group. Closure of the tympanic membrane perforation was achieved in all cases in the bFGF group, whereas it was achieved in only two of five cases in the control group. With bFGF treatment, the tympanic membrane perforations closed completely within 3.7 weeks, and hearing improved by 13.3 dB in the bFGF group., Conclusion: The study demonstrated that bFGF combined with an atelocollagen/silicone bilayer membrane is effective for the conservative treatment of tympanic membrane perforation.