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

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

[Evaluation of the Effectiveness and Safety in a Multi-center Clinical Trial of VIBRANT SOUNDBRIDGE in Japan].

Middle ear implants (MEIs) such as the Vibrant Soundbridge (VSB) are attractive and alternative treatments for patients with conductive, sensorineural, and mixed hearing loss who do not benefit from, or who choose not to wear, conventional hearing aids (HAs). Recent studies suggest that MEIs can provide better improvements in functional gain, speech perception, and quality of life than HAs, although there are certain risks associated with the surgery which should be taken into consideration, including facial nerve or chorda tympanic nerve damage, dysfunctions of the middle and inner ears, and future device failure/explantation. In Japan, a multi-center clinical trial of VSB was conducted between 2011-2014. A round window vibroplasty via the transmastoid approach was adopted in the protocol. The bony lip overhanging the round window membrane (RWM) was extensively but very carefully drilled to introduce the Floating Mass Transducer (FMT). Perichondrium sheets were used to stabilize the FMT onto the RWM. According to the audiological criteria, the upper limit of bone conduction should be 45 dB, 50 dB, and 65 dB from 500 Hz to 4, 000 Hz. Twenty-five patients underwent the surgery so far at 13 different medical centers. The age at the surgery was between 26-79 years old, and there were 15 males and 10 females. The cause of conductive or mixed hearing loss was middle ear diseases in 23 cases and congenital aural atresia in two cases. The data concerning on the effectiveness and safety of VSB was collected before the surgery and 20 weeks after the surgery. Significant improvements of free-field Pure Tone Audiogram (PTA) from 250 Hz to 8, 000 Hz were confirmed (p < 0.001). Hearing gain up to 40 dB was achieved in the 1, 000 Hz to 4, 000 Hz range. No deterioration in either air conduction or bone conduction at PTA was noted at 20 weeks after the surgery. Monosyllable speech perception in both quiet and noisy conditions improved significantly (p < 0.001). The speech discrimination score in both quiet and noisy conditions improved significantly too (p < 0.001). In the future, it is likely that there will be an increasing population even in Japan that will meet the criteria for MEIs such as VSB. However, the long-term efficacy and safety of these devices should be established.

[Multicenter Clinical Study of Vibrant Soundbridge in Japan: Analysis of Subjective Questionnaires].

The Vibrant Soundbridge (VSB) is an active middle ear implant with the Floating Mass Transducer (FMT). We performed a multicenter study to study the efficacy of the VSB by means of "the 10 Questionnaire on Hearing 2002" and "the APHAB questionnaire" at 13 hospitals between 2011 and 2013. In all, 23 patients with mixed or conductive hearing loss received VSB implantation by the round window placement technique. These individuals were generally unable to use, or gained little from conventional hearing aids or bone conduction hearing aids. Two questionnaires were administrated before the surgery and 20 weeks after the VSB implantation. Scores on every item of "the 10 Questionnaire on Hearing 2002" showed significant improvement under noise after VSB implantation. On the APHAB, the scores for Ease of Communication, Reverberation, and Background subscales improved significantly after the VSB implantation, while the score for the Aversiveness subscale alone failed to show a positive improvement from the inexperience to the new sound. Analysis of the responses to these subjective questionnaires revealed better results after VSB implantation as compared to the preoperative data. In conclusion, RW vibroplasty with the use of VSB provided subjective benefit in patients with conductive and mixed hearing loss.

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

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

[A retrospective study on parotid carcinoma].

We retrospectively analyzed the clinicopathological factors affecting survival in patients with previously untreated parotid carcinoma. The subjects were 50 patients treated in our department from 1987 through 2011. The T stage was T1, T2, T3, and T4 in 4 patients, 11 patients, 9 patients, and 26 patients, respectively. The N stage was N0, N1, and N2 in 36 patients, 3 patients, and 11 patients, respectively. The clinical stage was I, II, III, and IV in 4 patients, 10 patients, 7 patients, and 29 patients, respectively. Histopathologically, eleven tumor types were observed; mucoepidermoid carcinoma was the most common. The overall 5-year survival rate was 72.1%, and the disease-specific 5-year survival rate was 74.0% in 42 patients who received radical surgery. Twelve patients relapsed; the site of relapse was the primary site alone in 2, in the neck alone in 3 patients, in the neck with distant metastases in 2 patients, and in distant metastatic site (s) alone in 5 patients. Univariate analysis showed that significant prognostic factors for overall survival rates were the T stage, cervical lymph node metastasis, clinical stage, grade, facial nerve palsy, and tumor size. We concluded that patients at high risk of recurrence should receive adjuvant therapy to improve the therapeutic outcomes.

Age-related changes in rat intrinsic laryngeal muscles: analysis of muscle fibers, muscle fiber proteins, and subneural apparatuses.

We compared age-related changes in the intrinsic laryngeal muscles of aged and young adult rats by determining the number and diameter of muscle fibers, contractile muscle protein (myosin heavy chain isoforms, MHC) composition, and the morphology of the subneural apparatuses. In aged rats, both the numbers and the diameters of muscle fibers decreased in the cricothyroid (CT) muscle. The number of fibers, but not diameter, decreased in the thyroarytenoid (TA) muscle. In the posterior cricoarytenoid (PCA) muscle, neither the number nor the diameter of fibers changed significantly. Aging was associated with a decrease in type IIB and an increase in type IIA MHC isoform levels in CT muscle, but no such changes were observed in the TA or PCA muscles. Morphological examination of primary synaptic clefts of the subneural apparatus revealed that aging resulted in decreased labyrinthine and increased depression types in only the CT muscle. In the aged group, morphologically immature subneural apparatuses were found infrequently in the CT muscle, indicating continued tissue remodeling. We suggest, therefore, that age-related changes in the intrinsic laryngeal muscles primarily involve the CT muscle, whereas the structures of the TA and PCA muscles may better resist aging processes and therefore are less vulnerable to functional impairment. This may reflect differences in their roles; the CT muscle controls the tone of the vocal folds, while the TA and PCA muscles play an essential role in vital activities such as respiration and swallowing.

Analysis of risk factors for post-tonsillectomy hemorrhage in adults.

OBJECTIVES: To identify the risk factors for post-tonsillectomy hemorrhage (PTH) in adult patients (>19 years). METHODS: 275 adult patients who underwent tonsillectomy between 2009 and 2019 were retrospectively analyzed. Possible risk factors associated with PTH were investigated by univariate and multivariate logistic regression analyses. RESULTS: PTH occurred in 39 of 275 patients (14.2%). Regarding underlying diseases, PTH occurred more frequently in focal infection of IgA nephropathy. Furthermore, bipolar electrocautery was the other risk factor for PTH on multivariate analysis. CONCLUSION: Focal infection of IgA nephropathy and bipolar electrocautery were identified as the risk factors for PTH.

Liposome-encapsulated hemoglobin alleviates hearing loss after transient cochlear ischemia and reperfusion in the gerbil.

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.

Facial nerve decompression surgery in patients with temporal bone trauma: analysis of 66 cases.

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.

[Multicenter clinical study of bone-anchored hearing aids in Japan--application for congenital auricular atresia].

The effectiveness of bone anchored hearing aid (BAHA) for the patients with congenital aural atresia was evaluated by multicenter clinical study in Japan. Twenty patients (17 bilateral and 3 hemilateral) of congenital auricular atresia were registered for this study and finally, 18 of them (15 bilateral and 3 unilateral) were subjected to further evaluation. Primary endpoint of this study was free sound-field pure-tone audiometory and speech threshold hearing test in quiet and noisy circumstances. Secondary endpoint of this study was patient's satisfaction based upon APHAB (Abbreviated Profile of Hearing Aid Benefit) questionnaire survey. These results were compared between before and 12 weeks after BAHA surgery. Both hearing level of pure tone and speech threshold significantly improved after BAHA surgery. APHAB scores also suggested the improvement of the QOL after BAHA usage, except for the scores that concerned with unpleasantness of noisy sound. BAHA is one of the useful options for the treatment of congenital auricular atresia.

Delayed neuronal cell death in brainstem after transient brainstem ischemia in gerbils.

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.

A swallowing evaluation with simultaneous videoendoscopy, ultrasonography and videofluorography in healthy controls.

PURPOSE: A new bedside method for the evaluation of swallowing function was pursued. PROCEDURES: To compare our technique combining videoendoscopy (VE) and ultrasonography (US) with videofluorography (VF) in healthy controls, these images were displayed simultaneously. RESULTS: The beginning of laryngeal elevation was identified by VF and US. Thereafter, the pharynx became invisible with VE. Then the bolus head passed through the tongue base and reached the vallecula and the piriform sinus. Laryngeal elevation was at maximum height for VF and US. The timing of elevation assessed by VF and US was almost equivalent. The distances and durations of the maximum laryngeal elevation, measured by US and VF, were almost equal and significantly positively correlated (p < 0.0001). CONCLUSIONS: This study suggested that our technique could demonstrate swallowing function as efficiently as VF.

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

OBJECTIVE: Hydrogen-rich water, which is a potent antioxidant agent, was investigated for its protective effects against ischemic damage of the cochlea in gerbils. METHODS: The animals were subjected to transient cochlear ischemia by occluding the bilateral vertebral arteries for l5min. Five milliliters of hydrogen-rich saline was then intravenously administered immediately after the insult. Saline without hydrogen was used as a control. Effects of hydrogen were evaluated using the auditory brainstem response (ABR) and histological studies of the inner ear. RESULTS: In non-ischemia animals, ABR thresholds and histological findings of the cochlea did not change by administration of saline or hydrogen-rich saline. In contrast, transient cochlear ischemia caused a 24.2±3.8dB increase in the ABR threshold at 8kHz, and a decrease of 14.1%±1.8% in the number of inner hair cells (IHCs) at the basal turn on day 7. Ischemic damage was more severe at 16 and 32kHz. When the animals were treated with hydrogen-rich saline, cochlear damage was significantly reduced: the increase in ABR threshold was 11.7±2.6dB at 8kHz and the IHC loss was 7.5%±2.1% at the basal turn on day 7. The effects of hydrogen-rich saline were more prominent at higher frequencies. CONCLUSIONS: Intravenous administration of hydrogen-rich saline was effective in preventing acute hearing loss due to transient cochlear ischemia.

Localization of prosaposin in rat cochlea.

Prosaposin, the precursor of the sphingolipid hydrolase activator proteins called saposins A, B, C, and D, is abundant in the nervous system and muscles. Besides its role as the precursor of saposins, prosaposin is reported to function as a neurotrophic factor, initiating neural differentiation and preventing neuronal cell death in vivo and in vitro. In this study, we examined the localization and synthesis of prosaposin in the rat cochlea. Intense prosaposin immunoreactivity was observed in the organ of Corti, stria vascularis, and spiral ganglion. In an immuno-electron microscopic study, prosaposin immunoreactivity was found mainly in lysosomal granules of the cells in these regions. In the lysosome, prosaposin does not always colocalize with cathepsin D, but was localized mainly in the dark area of the lysosome. Prosaposin mRNA was observed in these same regions. Our results suggest that prosaposin plays a role in homeostasis in the peripheral auditory system.

Ginsenoside Rb1 protects against damage to the spiral ganglion cells after cochlear ischemia.

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.

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

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

Improvements to staged canal wall up tympanoplasty for middle ear cholesteatoma.

OBJECTIVE: To describe our improvements to staged canal wall up tympanoplasty with mastoidectomy (SCUT) for middle ear cholesteatoma, and to show more successful outcomes of the surgery compared with our data previously reported. STUDY DESIGN: Retrospective study in a tertiary referral hospital. SETTING: 78 ears of 76 patients with extensive cholesteatoma were operated on using the improved SCUT between July 1998 and December 2006. Improved SCUT included new techniques such as scutum plasty and mastoid cortex plasty performed in a staged manner. RESULTS: Only 2 ears showed retraction pocket formation (7.7%) without recurrence in 26 ears followed for more than 5 years. In 48 followed for more than 3 years, frequency of postoperative retraction pocket formation (5/48; 10.4%) was significantly lower compared to our previous results (41/134; 30.6%, P < 0.01). CONCLUSION: Our improvements to SCUT contributed to the decreasing of frequency of postoperative retraction pocket that may lead to cholesteatoma recurrence, although a longer follow-up study is required.

Valacyclovir and prednisolone treatment for Bell's palsy: a multicenter, randomized, placebo-controlled study.

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

Storage of the incus in the mastoid bowl for use as a columella in staged tympanoplasty.

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.

Polyglycolic acid sheet attached with fibrin glue can facilitate faster epithelialization of the mastoid cavity after canal wall-down tympanoplasty.

OBJECTIVE: This study retrospectively investigated whether polyglycolic acid (PGA) sheet attached to the bone surface using fibrin glue facilitate faster epithelialization of the mastoid bowl after canal wall-down (CWD) tympanoplasty compared to a simple dressing using poly-N-acetyl-glucosamine (Kichin) sheet. MATERIALS AND METHODS: After completion of the CWD tympanoplasty, PGA sheet (n=16, PGA group) with fibrin glue or Kichin sheet (n=38, Kichin group) were placed on the bone surface of the mastoid bowl. RESULTS: Postoperative epithelialization of the mastoid cavity was significantly (p<0.05) faster in the PGA group than in the Kichin group (mean 135 versus 244 days, respectively). Use of the Kaplan-Meier method showed that only the short-term epithelialization rate (up to 100 days after operation) was significantly higher. No major adverse effects related to either procedure were seen. CONCLUSION: Epithelialization of the mastoid bowl after CWD tympanoplasty was faster in the postoperative short term when it was dressed with PGA sheet using fibrin glue compared with Kichin sheet.