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Intrinsically disordered proteins (IDPs) are widespread in eukaryotes and participate in a variety of important cellular processes. Numerous studies using state-of-the-art experimental and theoretical methods have advanced our understanding of IDPs and revealed that disordered regions engage in a large repertoire of intra- and intermolecular interactions through their conformational dynamics, thereby regulating many intracellular functions in concert with folded domains. The mechanisms by which IDPs interact with their partners are diverse, depending on their conformational propensities, and include induced fit, conformational selection, and their mixtures. In addition, IDPs are implicated in many diseases, and progress has been made in designing inhibitors of IDP-mediated interactions. Here we review these recent advances with a focus on the dynamics and interactions of IDPs., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Munehito Arai reports a relationship with PRISM BioLab Co., Ltd that includes: consulting or advisory., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Reentrant condensation (RC) is a protein behavior in which the protein solution shifts between the one- and two-phase state more than twice by increasing a single parameter. Although RC would be a candidate mechanism for the physicochemical design of food additives, no realistic model has been established under diverse contaminants like food materials. Here, we found that a mixture of cola and milk yielded RC. At pH 3.2-3.6, cola induced milk condensation at 30-40%, while lower or higher concentrations of cola did not. Furthermore, we reduced this cola/milk system to two pure components, casein in milk and polyphosphate (polyP) in cola, and investigated the characteristics of casein concentration and zeta potential. This was the first experimental demonstration of RC occurrence in a multicomponent system. The well-characterized cola/milk system would explore both the universal nature of proteins and the industrial application of RC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

The kinase-inducible domain interacting (KIX) domain is an integral part of the general transcriptional coactivator CREB-binding protein, and has been associated with leukemia, cancer, and various viral diseases. Hence, the KIX domain has attracted considerable attention in drug discovery and development. Here, we rationally designed a KIX inhibitor using a peptide fragment corresponding to the transactivation domain (TAD) of the transcriptional activator, mixed-lineage leukemia protein (MLL). We performed theoretical saturation mutagenesis using the Rosetta software to search for mutants expected to bind KIX more tightly than the wild-type MLL TAD. Mutant peptides with higher helical propensities were selected for experimental characterization. We found that the T2857W mutant of the MLL TAD peptide had the highest binding affinity for KIX compared to the other 12 peptides designed in this study. Moreover, the peptide had a high inhibitory effect on the KIX-MLL interaction with a half-maximal inhibitory concentration close to the dissociation constant for this interaction. To our knowledge, this peptide has the highest affinity for KIX among all previously reported inhibitors that target the MLL site of KIX. Thus, our approach may be useful for rationally developing helical peptides that inhibit protein-protein interactions implicated in the progression of various diseases., (© 2023. The Author(s).)

Background and Objectives: Patients with benign paroxysmal positional vertigo of the posterior canal (pc-BPPV) exhibit BPPV fatigue, where the positional nystagmus diminishes with the repeated performance of the Dix-Hallpike test (DHt). BPPV fatigue is thought to be caused by the disintegration of lumps of otoconial debris into smaller parts and can eliminate positional nystagmus within a few minutes [similar to the immediate effect of the Epley maneuver (EM)]. In this study, we aimed to show the non-inferiority of the repeated DHt to the EM for eliminating positional nystagmus after 1 week., Methods: This multicenter, randomized controlled clinical trial was designed based on the CONSORT 2010 guidelines. Patients who had pc-BPPV were recruited and randomly allocated to Group A or Group B. Patients in Group A were treated using the EM, and patients in Group B were treated using repeated DHt. For both groups, head movements were repeated until the positional nystagmus had been eliminated (a maximum of three repetitions). After 1 week, the patients were examined to determine whether the positional nystagmus was still present. The groups were compared in terms of the percentage of patients whose positional nystagmus had been eliminated, with the non-inferiority margin set at 15%., Results: Data for a total of 180 patients were analyzed (90 patients per group). Positional nystagmus had been eliminated in 50.0% of the patients in Group A compared with 47.8% in Group B. The upper limit of the 95% confidence interval for the difference was 14.5%, which was lower than the non-inferiority margin., Discussion: This study showed the non-inferiority of repeated DHt to the EM for eliminating positional nystagmus after 1 week in patients with pc-BPPV and that even the disintegration of otoconial debris alone has a therapeutic effect for pc-BPPV. Disintegrated otoconial debris disappears from the posterior canal because it can be dissolved in the endolymph or returned to the vestibule via activities of daily living., Classification of Evidence: This study provides Class II evidence of the non-inferiority of repeated DHt to the EM for eliminating positional nystagmus after 1 week., Registration Number: UMIN000016421., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Imai, Uno, Yamato, Takimoto, Sato, Matsuda, Takeda, Nishiike, Kawashima, Iga, Ueno, Ohta, Sato, Kamakura, Shingai-Higashi, Mikami, Kimura, Nakajima, Tanaka and Inohara.)

Hen eggs are rich in proteins and are an important source of protein for humans. Pasteurized frozen whole hen eggs are widely used in cooking and confectionery and can be stored for long periods. However, processed eggs differ from raw eggs in properties such as viscosity, foaming ability, and thermal aggregation. To develop pasteurized frozen whole egg products with properties similar to those of unpasteurized whole eggs, it is necessary to establish a method that can differentiate between the two egg types with respect to the structures of their proteins. In this study, size-exclusion chromatography (SEC) and SEC coupled with small-angle X-ray scattering (SEC-SAXS) were successfully used to differentiate between the proteins in unpasteurized and pasteurized frozen whole eggs. We found that proteins in the plasma fraction of egg yolk, especially apovitellenins I and II, formed large aggregates in the pasteurized eggs, indicating that their structures are sensitive to temperature changes during pasteurization, freezing, and thawing. The results suggest that SEC and SEC-SAXS can be used to differentiate between unpasteurized and pasteurized frozen whole eggs. Additionally, they may be useful in determining molecular sizes and shapes of multiple components in various complex biological systems such as whole eggs., (© 2022. The Author(s).)

Human epidermal growth factor receptors (HER/ERBB) form dimers that promote cell proliferation, migration, and differentiation, but overexpression of HER proteins results in cancer. Consequently, inhibitors of HER dimerization may function as effective antitumor drugs. An alternatively spliced variant of HER2, called herstatin, is an autoinhibitor of HER proteins, and the intron 8-encoded 79-residue domain of herstatin, called Int8, binds HER family receptors even in isolation. However, the structure of Int8 remains poorly understood. Here, we revealed by circular dichroism, NMR, small-angle X-ray scattering, and structure prediction that isolated Int8 is largely disordered but has a residual helical structure. The radius of gyration of Int8 was almost the same as that of fully unfolded states, although the conformational ensemble of Int8 was less flexible than random coils. These results demonstrate that Int8 is intrinsically disordered. Thus, Int8 is an interesting example of an intrinsically disordered region with tumor-suppressive activity encoded by an intron. Furthermore, we show that the R371I mutant of Int8, which is defective in binding to HER2, is prone to aggregation, providing a rationale for the loss of function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tashiro, Suetaka, Sato, Ooka, Kunihara, Kudo, Inatomi, Hayashi and Arai.)

The transcription factor c-Myb promotes the proliferation of hematopoietic cells by interacting with the KIX domain of CREB-binding protein; however, its aberrant expression causes leukemia. Therefore, inhibitors of the c-Myb-KIX interaction are potentially useful as antitumor drugs. Since the intrinsically disordered transactivation domain (TAD) of c-Myb binds KIX via a conformational selection mechanism where helix formation precedes binding, stabilizing the helical structure of c-Myb TAD is expected to increase the KIX-binding affinity. Here, to develop an inhibitor of the c-Myb-KIX interaction, we designed mutants of the c-Myb TAD peptide fragment where the helical structure is stabilized, based on theoretical predictions using AGADIR. Three of the four initially designed peptides each had a different Lys-to-Arg substitution on the helix surface opposite the KIX-binding interface. Furthermore, the triple mutant with three Lys-to-Arg substitutions, named RRR, showed a high helical propensity and achieved three-fold higher affinity to KIX than the wild-type TAD with a dissociation constant of 80 nM. Moreover, the RRR inhibitor efficiently competed out the c-Myb-KIX interaction. These results suggest that stabilizing the helical structure based on theoretical predictions, especially by conservative Lys-to-Arg substitutions, is a simple and useful strategy for designing helical peptide inhibitors of protein-protein interactions., (© 2022. The Author(s).)

Objective: In benign paroxysmal positional vertigo (BPPV), positional nystagmus becomes generally weaker when the Dix-Hallpike test is repeated. This phenomenon is termed BPPV fatigue. We previously reported that the effect of BPPV fatigue deteriorates over time (i.e., the positional nystagmus is observed again after maintaining a sitting head position). The aim of this study was to investigate whether the effect of BPPV fatigue attenuates after maintaining a supine position with the head turned to the affected side. Methods: Twenty patients with posterior-canal-type BPPV were assigned to two groups. Group A received Dix-Hallpike test, were returned to the sitting position (reverse Dix-Hallpike test) with a sitting head position for 10 min, and then received a second Dix-Hallpike test. Group B received Dix-Hallpike test, were kept in the supine position with the head turned to the affected side for 10 min, and then received reverse Dix-Hallpike test followed by the second Dix-Hallpike test. The maximum slow phase eye velocity (MSPEV) of positional nystagmus induced by the first, reverse, and second Dix-Hallpike test were analyzed. Results: The ratio of MSPEV of the positional nystagmus induced by the second Dix-Hallpike test relative to the first Dix-Hallpike test was significantly smaller in group B than that in group A. There was no difference in the MSPEV of the positional nystagmus induced by the reverse Dix-Hallpike test between group A and B. Conclusions: The effect of BPPV fatigue is continued by maintaining a supine position with the head turned to the affected side, while the effect is weakened by maintaining a sitting head position. On the basis of the most widely accepted theory of the pathophysiology of BPPV fatigue, in which the particles become dispersed along the canal during head movement in the Dix-Hallpike test, we found an inconsistency whereby the dispersed otoconial debris return to a mass during the sitting position but do not return to a mass in the supine position with the head turned to the affected side. Future studies are required to determine the exact pathophysiology of BPPV fatigue. Classification of Evidence: 2b., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Imai, Nishiike, Okumura, Takeda, Sato, Ohta, Kamakura and Inohara.)

The formation of symptomatic intradural mucocele associated with a paranasal osteoma is rare, and no standard treatment has been established. Here, we present a case of intradural mucocele in a 27-year-old man complaining of headache and generalized convulsion. Cranial CT and brain MRI showed a left frontoethmoidal osteoma extending into the left anterior cranial fossa and orbit along with a mass in the left frontal lobe. He underwent resection of both intracranial osteomas and the mass through left frontal craniotomy. Histological findings were consistent with a mucocele, and the diagnosis of an intradural mucocele associated with a frontoethmoidal osteoma was confirmed. The postoperative course was uneventful. Although both osteoma and mucocele are benign, they may cause life-threatening symptoms by expanding intracranially. A tailored treatment considering the invasiveness and postoperative long-term follow-up of the patient is essential for this uncommon condition.

Background: Pseudoaneurysm of the internal carotid artery (ICA) is a very rare but potentially fatal complication of deep neck space infection., Methods: This paper describes a very rare case of an ICA pseudoaneurysm rupture in the sphenoid sinus caused by a deep neck abscess., Results: A 62-year-old male with a deep neck space infection underwent surgical drainage. On the postoperative 21st day, however, he suddenly had massive epistaxis. A transnasal endoscopic examination found massive bleeding out of the sphenoid sinus. Immediate intra-arterial angiography revealed two pseudoaneurysms of the left ICA at the cavernous segment (C4) and the clinoid segment (C5), which were embolized with coils. The patient made an uneventful recovery after the embolization., Conclusion: We found no reports in the literature that pseudoaneurysms associated with a deep neck infection rupture in the sphenoid sinus. Prompt treatment along with accurate diagnosis is essential for successful management of such cases. J. Med. Invest. 66 : 188-189, February, 2019.

Purpose: In benign paroxysmal positional vertigo (BPPV), positional nystagmus is generally weaker when the Dix-Hallpike test is repeated. This phenomenon is known as BPPV fatigue. The positional nystagmus induced by the Dix-Hallpike test can be observed again when time has passed. There has been no study regarding the length of time required to recover the positional nystagmus. The purpose of this study was to examine whether positional nystagmus recovers within 30 min after the disappearance of the nystagmus by BPPV fatigue., Methods: This was a prospective observational study. Twenty patients with posterior canal type of BPPV (canalolithiasis of the posterior canal) were included. Dix-Hallpike tests were performed three times for each patient. A second Dix-Hallpike test was performed immediately after the first Dix-Hallpike test. A third Dix-Hallpike test was performed 30 min after the second Dix-Hallpike test. We recorded positional nystagmus induced by the Dix-Hallpike tests and analyzed maximum slow-phase eye velocity (SPEV) of the positional nystagmus., Results: The average maximum SPEV of positional nystagmus induced by the second Dix-Hallpike test (4.8°/s) was statistically lower than that induced by the first Dix-Hallpike test (48.0°/s); this decrease was caused by BPPV fatigue. There was no statistical difference between average maximum SPEV of positional nystagmus induced by the first Dix-Hallpike test and that induced by the third Dix-Hallpike test (41.6°/s); this indicates that the effect of BPPV fatigue disappeared. The effect of BPPV fatigue disappears within 30 min., Conclusions: A second Dix-Hallpike test should be performed at least 30 min after the first.

Objective: The aim of this study was to evaluate part of the area of the posterior wall of the external auditory canal (EAC) that is resected during transcanal endoscopic ear surgery (TEES) for cholesteatomas that extend to the mastoid cavity, and to determine whether TEES is a minimally invasive surgical procedure for cholesteatoma., Methods: This was a retrospective study involving 25 patients with cholesteatoma that extended to the mastoid cavity, and who underwent surgery between October 2014 and October 2015. The patients' cholesteatomas were removed using TEES. In this procedure, the superoposterior wall of the EAC was resected in order to access the deepest part of the cholesteatoma. We made a paper template by tracing the shape of the resected EAC and then reconstructed the resultant defect with a piece of cartilage, the size of which was based on the size of the template. We evaluated the size and greatest dimension of the resected part of the EAC by measuring the template. Preoperatively, we also evaluated the volume of each cholesteatoma on computed tomography (CT) images., Results: The median size of the resected region was 37.3 (14.7-68.4)mm 2 . The median length of the greatest dimension of the resected area was 8.7 (5.1-15.9)mm. The median cholesteatoma volume was 417 (43-1399)mm 3 . The correlation coefficient (R 2 ) obtained using a two-thirds order approximation curve for the relationship between the resected tissue area and the cholesteatoma volume (0.617) was higher than that obtained by linear approximation (0.387)., Conclusion: These results suggest that the resected area was minimal and of an appropriate size relative to the volume of the cholesteatoma., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Conclusion: A 30 s observation of geotropic positional nystagmus is sufficient to distinguish persistent geotropic positional nystagmus (PGPN) from transient geotropic positional nystagmus (TGPN) in patients with horizontal canal type of benign paroxysmal positional vertigo (H-BPPV) in ENT office., Objective: As a canalith repositioning procedure effectively treats H-BPPV with TGPN, but not PGPN, the differentiation between patients with PGPN and with TGPN is essential. The purpose of this study is to determine the observation period enough to distinguish TGPN from PGPN., Methods: This study first analyzed positional nystagmus images recorded with an infrared CCD camera three-dimensionally in 47 patients with H-BPPV. PGPN is distinguished from TGPN in patients with H-BPPV precisely by means of time constant calculated form analysis of positional nystagmus. Ten-second and 30-s movies were made of positional nystagmus of the all 47 patients. Ten independent otolaryngologists were then asked to distinguish TGPN from PGPN after a 10 s or 30 s observation of the geotropic positional nystagmus images in 47 patients with H-BPPV., Results: The sensitivity and specificity to distinguish TGPN from PGPN was 100% and 97% after 30 s observation, but 100% and 40% after 10 s observation, respectively.

Background: Phase I study of weekly administration of low-dose docetaxel/cisplatin concurrent with conventionally fractionated radiotherapy for locally advanced head and neck squamous cell carcinoma suggested the recommended dose of docetaxel at 10 mg/m 2 and cisplatin at 20 mg/m 2 . Phase II study of the concurrent chemoradiotherapy for technically resectable disease showed satisfactory results., Methods: This phase II study was designed to address efficacy and safety when patients with technically unresectable disease were treated with concurrent chemoradiotherapy, followed by two cycles of moderate-dose platinum-based adjuvant chemotherapy: docetaxel, cisplatin, and fluorouracil (modified TPF). Modified TPF was replaced with docetaxel/carboplatin when renal impairment became evident. Surgical salvage was considered when residual or recurrent locoregional disease was technically resectable and free of distant metastasis., Results: Of 33 enrolled patients, 31 were analyzable: 24 (78 %) and 18 (58 %) patients completed chemoradiotherapy and adjuvant chemotherapy, respectively; 15 (48 %) patients completed study treatment per protocol, and overall complete response rate was 45 %. Seven patients underwent surgical salvage, which was successful in 4 patients. At a median follow-up of 60.8 months for surviving patients, median progression-free survival and median overall survival were 16.2 and 39.9 months, respectively. Grade 3 or 4 toxicity included mucositis (77 %) and dysphagia (45 %) during the chemoradiotherapy period and neutropenia (100 %) and febrile neutropenia (35 %) during the adjuvant period. No patient died of toxicity., Conclusion: The tested regimen seems effective, although there is room for improvement in adjuvant chemotherapy because of the high toxicity and low compliance of modified TPF.

Conclusion: After repeated snowboard exercises in the virtual reality (VR) world with increasing time lags in trials 3-8, it is suggested that the adaptation to repeated visual-vestibulosomatosensory conflict in the VR world improved dynamic posture control and motor performance in the real world without the development of motion sickness., Objectives: The VR technology was used and the effects of repeated snowboard exercise examined in the VR world with time lags between visual scene and body rotation on the head stability and slalom run performance during exercise in healthy subjects., Methods: Forty-two healthy young subjects participated in the study. After trials 1 and 2 of snowboard exercise in the VR world without time lag, trials 3-8 were conducted with 0.1, 0.2, 0.3, 0.4, 0.5, and 0.6 s time lags of the visual scene that the computer creates behind board rotation, respectively. Finally, trial 9 was conducted without time lag. Head linear accelerations and subjective slalom run performance were evaluated., Results: The standard deviations of head linear accelerations in inter-aural direction were significantly increased in trial 8, with a time lag of 0.6 s, but significantly decreased in trial 9 without a time lag, compared with those in trial 2 without a time lag. The subjective scores of slalom run performance were significantly decreased in trial 8, with a time lag of 0.6 s, but significantly increased in trial 9 without a time lag, compared with those in trial 2 without a time lag. Motion sickness was not induced in any subjects.

Objective: The first-line treatment for inoperable recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) has long been the combination of cisplatin and fluorouracil (PF). Recently, cetuximab has been shown to provide an additional survival benefit to PF. It remains unknown whether docetaxel adds additional benefits to PF. Therefore, we sought to evaluate the efficacy and toxicity of docetaxel, cisplatin, and fluorouracil (TPF) for inoperable recurrent or metastatic HNSCC., Methods: A retrospective chart review from January 2005 to March 2013 identified patients who were treated with docetaxel 60 mg/m(2) on day 1, followed by cisplatin 60 mg/m(2) on day 1, and fluorouracil 600 mg/m(2)/day on days 1-5 (modified TPF) every 4 weeks for inoperable recurrent or metastatic HNSCC., Results: Twenty-four patients were identified; seven and five patients had locoregional disease only and distant metastasis only, respectively, while 12 patients had locoregional disease and distant metastasis simultaneously. Of the 17 patients with distant metastasis, multiple organs were affected in 9 patients, with the most frequently affected organ being the lung (n=11). Three patients had no prior treatment, whereas 21 patients underwent intensive prior treatment. In 17 of 21 patients who had received prior treatment, the treatment included chemoradiotherapy and/or chemotherapy. The median number of cycles of modified TPF was two (range, 1-5). One patient showed complete response, four patients showed partial response, two patients had stable disease, and 17 patients had progressive disease. Overall, the rate of objective response was 21%, with a 95% confidence interval (CI) of 9-40%. Median overall survival was 8.0 months (95%CI, 4.4-10.6 months). The treatment efficacy differed significantly according to extent of disease. Objective response in patients with distant metastasis alone was better than in patients with locoregional disease with or without distant metastasis (60% vs. 11%, respectively; P=0.02). Median overall survival in the former patients was longer than in the latter patients (not reached vs. 7.0 months, respectively; P=0.02). Fifteen patients (63%) had Grades 3-4 neutropenia, and seven patients (29%) developed Grade 3 febrile neutropenia. There were no toxic deaths., Conclusion: The efficacy of modified TPF in the setting of first-line treatment for recurrent or metastatic HNSCC is not very high, while the toxicity is acceptable with extensive care. The development of more efficacious chemotherapeutic regimen is required., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

This paper describes an endoscopic transseptal approach to identify and access the frontal sinus and reviews the clinical cases. Between May 2004 and July 2010, endoscopic modified Lothrop procedure (EMLP) with transseptal approach was performed on sixteen patients. The indications for EMLP were complicated frontal sinusitis or cyst, revision surgery for failed frontal sinusotomy or Lynch procedure, or trauma cases. The first step of this procedure was to open a window in the bilateral anterior portion of the middle turbinates and nasal septum. The nasal septum, which could be observed through the window, should be the landmark of the midline during the surgery. A drill bur was raised up just behind the nasal bone along the midline of the nose. After the bilateral frontal sinuses and their posterior walls were confirmed, the interfrontal septum was removed superiorly. We reviewed the clinical records of patients who underwent the EMLP with transseptal approach. We have managed sixteen patients in this fashion. Neither intracranial nor orbital complications were encountered during or after surgery. Endoscopic transseptal frontal sinus surgery is simple to perform, and does not cause severe complications.

Objective: To clarify the pathophysiological basis of persistent geotropic positional nystagmus (PGN) in patients with the horizontal canal type of benign paroxysmal positional vertigo (H-BPPV), the time constant (TC) of nystagmus and the relationship between its slow phase eye velocity (SPV) and the angle of head rotation in supine were defined., Methods: Geotropic or apogeotropic positional nystagmus was recorded by video-oculography and analysed three-dimensionally., Results: Geotropic positional nystagmuses in patients with H-BPPV were classified as transient geotropic positional nystagmus with a TC of ≤35 s or PGN with a TC of >35 s. Alternatively, the TC of persistent apogeotropic positional nystagmus (AN) in patients with H-BPPV was >35 s. The direction of the SPV of patients with PGN was opposite to that of patients with AN at each head position across the range of neutral head positions. The relationship between the SPV of patients with PGN and the angle of head rotation was linearly symmetrical against that of patients with AN with respect to a line drawn on the neutral head position., Conclusions: Since its TC was >35 s, it is suggested that PGN is induced by cupula deviation in response to gravity at each head position. It is also suggested that the direction of cupula deviation in patients with PGN is opposite to that of patients with AN across the neutral head positional range with no nystagmus where the long axis of cupula is in alignment with the axis of gravity. Since the pathophysiological basis of AN is considered a heavy cupula, it is suggested that PGN is conversely induced by a light cupula., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Thyroid-stimulating hormone-secreting ectopic pituitary adenoma of the nasopharynx is highly unusual, with only three reported cases in the world literature. We describe the clinical presentation and radiologic findings in one patient with such rare lesions. A 46-year-old male with typical symptoms of Grave's disease was found to have a mass on magnetic resonance imaging. An otolaryngologic examination revealed a nasopharyngeal mass lesion, which was endoscopically resected. The results of immunohistochemical staining for thyroid-stimulating hormone were positive. After the resection, the patient's TSH was within normal limits. The clinical significance of the case and a brief literature review are presented., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Conclusion: The finding of deteriorated hearing loss at the initial visit at middle to high frequencies is a factor of poor hearing prognosis in Ménière's disease. Early intervention with instructions for lifestyle changes may lead to good outcomes in hearing., Objective: An attempt was made to examine long-term changes in hearing loss in unilateral Ménière's disease and factors associated with prognosis of hearing loss retrospectively., Methods: Based on their last hearing level of the affected ear, 36 patients were subdivided into two groups: the poor prognosis of hearing (PPH) group and the good prognosis of hearing (GPH) group., Results: In the PPH group, the hearing levels at the initial visit at middle and high frequencies were significantly worse than those in the GPH group. Moreover, the hearing loss progressed during the first 2 years of the disease, and stayed flat to approximately 50 dB at the later stage. Conversely, the hearing loss at the onset in the GPH group showed no further progression over the first 2 years, and remained constant to approximately 35 dB at the later stage. In addition, the mean intervals from the onset to the initial visit in the PPH group were significantly longer than those in the GPH group.

The olfactory neuroblastoma, first described in 1924, is a rare tumor arising from the olfactory epithelium. Because of its rarity, it is difficult to accrue a large individual series. To elucidate the characteristics of olfactory neuroblastomas in Japan, we report herein on our institutional experience of 14 cases and reviewed 104 cases reported from Japan. In our cases, one out of nine surgically treated patients died during treatment and the remaining 8 patients are alive without disease. Among the five non-surgically treated patients, four patients experienced local treatment failure and the other one patient died of metastasis. In the 104 Japanese cases, 54 patients were treated with multimodality treatment including surgery and radiation. The 3-year overall survival rates for surgically treated patients and non-surgically treated patients were 85% and 73%, respectively. The prognostic factors for survival were modified Kadish stage, Hyams' grade and surgical treatment. Further investigation is required for the validation of endoscopic resection.

The 5-hydroxytryptamine type 3 (5-HT3) receptor is a ligand-gated ion channel and a member of the Cys-loop family of receptors. Previous studies have shown 5-HT3 receptor expression in various neural cells of the central and peripheral nervous systems. Although the function and distribution of the 5-HT3 receptor has been well established, its role in the inner ear is still poorly understood. Moreover, no study has yet determined its localization and function in the peripheral vestibular nervous system. In the present study, we reveal mRNA expression of both 5-HT3A and 5-HT3B receptor subunits in the mouse vestibular ganglion (VG) by RT-PCR and in situ hybridization (ISH). We also show by ISH that 5-HT3 receptor mRNA is only expressed in the VG (superior and inferior division) in the peripheral vestibular nervous system. Moreover, we performed Ca(2+) imaging to determine whether functional 5-HT3 receptors are present in the mouse VG, using a selective 5-HT3 receptor agonist, SR57227A. In wild mice, 32% of VG neurons responded to the agonist, whereas there was no response in 5-HT3A receptor knockout mice. These results indicate that VG cells express functional 5-HT3 receptor channels and might play a modulatory role in the peripheral vestibular nervous system., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Conclusions: To establish a system of differential diagnosis for vertigo/dizziness at the Emergency Department (ED), careful history-taking of complications and examinations of nystagmus should be helpful and therefore prepared by ED staff., Objectives: Vertigo/dizziness could come from various kinds of organs for equilibrium, sometimes resulting in an emergency due to the central origin. In the present study, we checked patients' background data at the ED in advance of a definitive diagnosis at the Department of Otolaryngology and examined the significance of the correlation between the data and the diagnosis., Methods: We studied a series of 120 patients with vertigo/dizziness, who visited the Departments of Emergency and Otolaryngology between April 2011 and March 2012. At the ED, we first checked patients' backgrounds and carried out neurologic and neuro-otologic examinations. At the Department of Otolaryngology, we finally diagnosed all the patients according to the criteria and classified the origins of vertigo/dizziness into central and non-central diseases., Results: The ratio of patients with disease of central origin was 12.5% and that for non-central origin was 87.5%. The risk factors for cerebrovascular disease such as hypertension, heart disease, and diabetes were also the risk factors for central vertigo/dizziness by the chi-squared test. To predict a central origin for vertigo/dizziness, only gaze nystagmus was the significant factor by multivariate regression analysis.

Conclusion: Endolymphatic hydrops could be a reversible inner ear pathological condition. After sac surgery, hydrops was reduced and symptoms went into remission in some cases, although vertigo suppression was not always a result of the reduced hydrops., Objective: To examine the changes in endolymphatic hydrops detected by gadolinium (Gd) contrast-enhanced magnetic resonance imaging (MRI) before and 6 months after endolymphatic sac surgery in patients with unilateral Ménière's disease., Methods: Fluid-attenuated inversion recovery MRI was obtained 4 h after intravenous administration or 24 h after intratympanic administration of Gd contrast medium. An enlarged negative stain corresponding to the cochlear duct and endolymphatic space of the vestibule was assessed as hydrops., Results: Of seven patients with hydrops confirmed by MRI before surgery, both cochlear and vestibular hydrops became negative in two, cochlear hydrops became negative in one, both hydrops were present, but reduced, in one, and there was no change in three patients. The number of vertigo spells was reduced in all cases at 6-12 months after surgery. As for the three cases of negative hydrops, vertigo was completely suppressed. In two cases in which hearing level improved, hydrops became negative after surgery.

Objective: Gadolinium (Gd) contrast-enhanced MRI has recently been introduced to clinical practice to detect endolymphatic hydrops. However, since the image depends on the hardware, pulse sequence or the way of Gd administration, the protocol and the evaluating criteria for hydrops on MRI have not yet been standardized. In this study, we assessed the usefulness of the hydrops detection by MRI following the intratympanic or intravenous Gd administration methods, and compared these findings with the electrocochleography and glycerol test., Methods: MRI was taken in 27 patients with Meniere's disease or delayed endolymphatic hydrops. All patients had frequent episodes of vertigo attacks which were clinically considered as of unilateral ear origin. Two types of Gd administration were used; injection into the tympanic cavity in 17 patients or intravenous injection in 10 patients. Axial 2D-FLAIR images were obtained with a 3.0T MRI unit, 24 and 4 h after intratympanic or intravenous administration, respectively. The endolymphatic space was detected as a low signal intensity area, while the surrounding perilymphatic space showed high intensity with Gd contrast. Those cases in which low signal areas corresponding to the cochlear duct could be clearly noticed, were classified as cochlear hydrops. When the greater part of the vestibule was occupied by a low signal area in more than half of the images, it was classified as vestibular hydrops., Results: Endolymphatic hydrops was detected in 88% (15/17 cases) by the intratympanic Gd administration method, and 90% (9/10) by the intravenous method. In the contralateral ears, 20% (2/10) showed hydrops, detected by the intravenous method. ECochG and the glycerol test were difficult when the hearing of the patient was severely impaired. Positive results of EcochG and the glycerol test were obtained only in 15 and 6 cases, respectively. However, as far as the waves could be obtained, ECochG showed a high detection rate of 88% (15/17) in the affected ear. In those cases in which both MRI and EcochG could be obtained, including both ears, the results were matched in 78% (21/27ears)., Conclusion: For the qualitative detection of hydrops, intratympanic and intravenous Gd administration methods were equivalent. Inner ear Gd contrast-enhanced MRI had higher efficacy in the detection of hydrops than the conventional tests.

Conclusion: Because nystagmus induced by ampullopetal inhibition of the posterior semicircular canal (PSCC) rotates around the axis perpendicular to the plane of the anterior semicircular canal (ASCC) of the other side, when free-floating debris is initially located at the distal portion of the PSCC, a patient showing positional nystagmus appears to have the ASCC type of benign paroxysmal positional nystagmus. We name this 'pseudo-anterior canalolithiasis'., Objective: We report on pseudo-anterior canalolithiasis originating in the PSCC and discuss the differential findings between pseudo-anterior and true anterior canalolithiasis by means of three-dimensional (3D) analysis of the positional nystagmus., Methods: We performed 3D analysis of the positional nystagmus in a patient with true anterior canalolithiasis and in another patient with pseudo-anterior canalolithiasis., Results: In the patient with true anterior canalolithiasis, the direction of positional nystagmus during reverse Epley maneuver was constant and its axis was perpendicular to the plane of the right ASCC three-dimensionally. In contrast, in the patient with pseudo-anterior canalolithiasis, the first positional nystagmus of which the axis was perpendicular to the plane of the left ASCC became a second positional nystagmus of which the axis was perpendicular to the plane of the right PSCC during the reverse Epley maneuver.

Conclusions: Because the basic strategies to stop walking are stored as motor programs, visual stimulation may have little influence on body deviation during gait termination and its time course. Walking velocity, however, demonstrated dynamic flexible changes, which may subserve the stable process of gait termination under variable circumstantial changes such as optic flow., Objective: The aim of this study was to examine the effect of repeated optic flow on body deviation and walking velocity during gait termination, which may be more complicated than continuous standing or walking., Methods: Twenty-three healthy subjects were instructed to start walking upon an acoustic cue and to stop walking when the scenery changed in a virtual reality environment. Subjects underwent eight control trials without optic flow and three sets of optic flow conditions including four trials each of optic horizontal and rotational movement randomly., Results: Repeated optic flow caused no significant change of body deviation or the time course of the gait termination process in comparison with that in the control. The walking velocity at the start of the termination process showed short-term flexibility that denoted a gradual increase over the trial for within-set and long-term flexibility that denoted a gradual decrease for between-set.

In this study, we examined the effects of sensory inputs of visual-vestibulosomatosensory conflict induced by virtual reality (VR) on subjective dizziness, posture stability and visual dependency on postural control in humans. Eleven healthy young volunteers were immersed in two different VR conditions. In the control condition, subjects walked voluntarily with the background images of interactive computer graphics proportionally synchronized to their walking pace. In the visual-vestibulosomatosensory conflict condition, subjects kept still, but the background images that subjects experienced in the control condition were presented. The scores of both Graybiel's and Hamilton's criteria, postural instability and Romberg ratio were measured before and after the two conditions. After immersion in the conflict condition, both subjective dizziness and objective postural instability were significantly increased, and Romberg ratio, an index of the visual dependency on postural control, was slightly decreased. These findings suggest that sensory inputs of visual-vestibulosomatosensory conflict induced by VR induced motion sickness, resulting in subjective dizziness and postural instability. They also suggest that adaptation to the conflict condition decreases the contribution of visual inputs to postural control with re-weighing of vestibulosomatosensory inputs. VR may be used as a rehabilitation tool for dizzy patients by its ability to induce sensory re-weighing of postural control.

We operated on three patients with juvenile nasopharyngeal angiofibroma in the past 3 years. The endoscopic transnasal approach was utilized in all the cases, and in one case it was accompanied with a Caldwell-Luc procedure. All the tumors were located around the sphenopalatine foramen, but also had involved and enlarged the pterygoid canal. All the cases underwent preoperative selective embolization, but it was difficult to embolize the branch of the internal carotid artery. A partial resection of the middle turbinate facilitated the manipulation of the sphenopalatine foramen and the pterygoid canal. Endoscopic management of juvenile nasopharyngeal angiofibroma should be considered as a first-choice option for tumors at the early stage.

Objective: We report a case of benign paroxysmal positional vertigo (BPPV) showing sequential translation of four types of nystagmus and discuss its pathophysiology., Methods: The case was 65-year-old female. We analyzed her nystagmus three-dimensionally., Results: At the first visit, she showed vertical-torsio nystagmus of the posterior canal type of BPPV (P-BPPV) and subsequently showed recently reported geotropic nystagmus with a long time constant. Two weeks later, she showed apogeotropic nystagmus of the horizontal canal type of BPPV (AH-BPPV) and subsequently a geotropic nystagmus with a short time constant of the horizontal canal type of BPPV (GH-BPPV)., Conclusions: Three kind of nystagmus, namely P-BPPV, AH-BPPV and GH-BPPV can be explained by the otoconial debris hypothesis of the same ear. Finally, the recently reported geotropic nystagmus with a long time constant may be explained by a reversible lesion such as the denatured cupula or utricular imbalance of the same ear., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Aims: We report the case of a 58-year-old female patient who consulted our Department complaining of positional vertigo and showing spontaneous upbeat nystagmus (UBN) in darkness., Method: We analyzed her UBN three-dimensionally. The MRI scan revealed the astrocytoma in the left cerebellum involving the cerebellar vermis., Result: Three-dimensional analysis showed a spontaneous UBN rotating around the intra-aural axis in the pitch plane., Conclusion: Since the cerebellar vermis is known to plays an inhibitory role on the central vertical vestibule-ocular reflex (VOR), the present results suggest that the spontaneous UBN in darkness observed in this patient was induced by an imbalance of central vertical VOR tone., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

We previously reported that motion sickness was prevented in rats with amygdala lesion and that provocative motion stimuli increased the number of Fos-positive neurons in the amygdala, suggesting that the amygdala is one of the neural substrates involved in the development of motion sickness. NK-1 receptors in the brain stem and amygdala are thought to play an important role in emesis and affective disorders, respectively. In the present study, to elucidate a role of substance P neuronal system and NK-1 receptors in the brain stem and amygdala in the development of motion sickness, we measured changes in gene expression of NK-1 receptors and preprotachykinin, a precursor of substance P, using quantitative real-time PCR methods in solitary tract nucleus and amygdala in rats after provocative motion stimuli induced by 2G hypergravity load. Effects of systemic administration of CP-99,994, an antagonist for NK-1 receptors, on hypergravity-induced motion sickness were also examined using pica behavior, eating non-nutritive substances such as kaolin, as an index of motion sickness in rats. Hypergravity-induced motion sickness was inhibited by CP-99,994 with a dose-dependent and enantioselective manner. Preprotachykinin mRNA expression was increased in basolateral nucleus of amygdala and solitary tract nucleus after hypergravity load for 3h, whereas NK-1 receptor mRNA expression was not changed by hypergravity in amygdala and solitary tract nucleus. Present results suggest that 2G hypergravity load activated the substance P neuronal system in amygdala as well as in the brain stem and this activation would be related to the development of motion sickness., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Conclusion: The prediction of subtype and the affected ear of benign paroxysmal positional vertigo (BPPV) derived from the answers to our questionnaire can support the definitive diagnosis of BPPV., Objectives: We examined to what extent the diagnosis of subtype and the affected ear of BPPV judged from answers to a questionnaire agreed with the diagnosis decided by the results of the positional nystagmus test., Methods: We asked the following questions: 'What kind of head movements induce vertigo?' and 'How long does the vertigo continue?'. As for the affected ear, we asked which ear was lower during stronger vertigo when induced in a supine position or during sleep., Results: The percentages of correct diagnosis speculated by the combined answers were 69% in posterior canal-type BPPV, 48% in BPPV with geotropic nystagmus, and 39% in BPPV with apogeotropic nystagmus. The percentage of correct diagnoses of the affected ear was more than 80%.

Renal cell carcinoma (RCC) tends to metastasize hematogenously, although metastasis to the head and neck is rare. We report 3 cases of RCC head and neck metastasis within the last 6 years. CASE 1: A 74-yearold woman presented with cervical metastasis from RCC 4 years after right total nephrectomy, involving modified neck dissection. She later had additional surgery and radiation for further distant metastases, survived almost 5 years after the first neck metastasis. CASE 2: A 60-year-old man showed metastatic RCC in the right parotid gland 3 years after right total nephrectomy, involving superficial parotidectomy. CASE 3: A 54-year-old man presented with a metastasis lesion from RCC to the right maxillary sinus 7 years after left total nephrectomy, involving total maxillectomy. Distant metastasis reportedly often occurs long after initial primary RCC treatment. Physicians considering metastatic RCC in differential head and neck diagnosis and resection could conceivably promote better prognosis.

Conclusion: Bipolar scissors tonsillectomy followed by cooling down the pharyngeal mucosa has advantages in terms of postoperative pain and intraoperative blood loss compared with cold dissection., Objectives: The purpose of this study was to compare the postoperative pain between bipolar scissors tonsillectomy followed by cooling the pharyngeal mucosa and a traditional cold dissection., Methods: A total of 189 patients aged more than 16 years were operated due to habitual tonsillitis, obstructive sleep apnea syndrome, and IgA nephropathy. Of these, 79 patients were operated using bipolar scissors followed by cooling the pharyngeal mucosa with 4°C saline for 10 min just after the removal of tonsils. The other 110 patients underwent cold dissection tonsillectomy. Outcome measures were intraoperative blood loss, operative time, postoperative pain evaluated on a visual analog scale, and postoperative secondary hemorrhage., Results: Significantly lower levels of intraoperative blood loss and less postoperative pain were obtained in bipolar scissors tonsillectomy followed by cooling the pharyngeal mucosa compared with cold dissection. Postoperative hemorrhage needing hemostatic surgery occurred in 2 of 79 patients who underwent bipolar scissors tonsillectomy with cooling, while it occurred in 1 of 110 patients after cold dissection. However, the difference was not statistically significant.

Conclusion: The detection rate of endolymphatic hydrops was significantly higher in patients with Meniere's disease compared with those with sudden deafness, indicating that 3 T magnetic resonance imaging (MRI) with intratympanic gadolinium injection was effective in diagnosing endolymphatic hydrops., Objectives: To compare the detection rate of endolymphatic hydrops between patients with Meniere's disease and sudden deafness as controls by 3 T MRI after intratympanic gadolinium injection with conventional pulse sequence such as two-dimensional fluid-attenuated inversion recovery., Methods: Ten patients with unilateral Meniere's disease and eight with sudden deafness underwent inner ear MRI 24 h after intratympanic gadolinium injection., Results: The endolymphatic space was detected as a low signal intensity area, while the perilymphatic space showed high intensity by gadolinium enhancement. Due to faint enhancement, images could not be evaluated in 1 of 10 patients with Meniere's disease. However, the other nine patients together with two of the eight with sudden deafness were diagnosed as having hydrops. The difference in detection rates between the two diseases was statistically significant. Two hydrops-positive cases with sudden deafness were considered to be of the secondary type of hydrops, because images were taken after partial recovery from hearing loss several months after the onset of the disease.

Objectives: We detected chronic low-tone air-bone gaps (LTABGs) in some patients with Meniere's disease after endolymphatic sac surgery. The aim of the present study was to elucidate the mechanism of LTABGs after endolymphatic sac surgery., Methods: We investigated 50 patients with Meniere's disease, who underwent surgery more than two years prior. LTABGs were defined as the three-tone-average=20dB formulated by (a+b+c)/3, where a, b, and c are ABGs at 0.25, 0.5, and 1kHz, respectively (ABG ±). The intra-operative finding was focused on identifying operculum (OPC ±)., Results: The ratio of post-operative ABG(+) was 50.0% (25/50). The ratio of intra-operative OPC(+) was 72.0% (36/50). The surgery results were as follows: the ratio of complete vertigo suppression (VS(+)) was 84.0% (42/50), air-conduction hearing gain (aHG(+)) was 40% (20/50), bone-conduction hearing gain (bHG(+)) was 64% (32/50), and speech discrimination gain (SDG(+)) was 28% (14/50). The post-operative ABG(+) was commonly observed in patients with intra-operative OPC(+) (chi-square test, p=0.013). aHG(+) and SDG(+) results were related to the post-operative ABG(+) (chi-square test, p=0.021 and p=0.0018, respectively)., Conclusions: These data suggest that intra-operative OPC(+) may be causative for post-operative ABG(+), resulting in post-operative aHG(+) and SDG(+). Thus, as enlarged vestibular aqueduct syndrome and superior semicircular canal deficiency syndrome exhibit LTABGs due to the third mobile inner ear window, endolymphatic sac surgery with adequate endolymphatic sac decompression and exposure to high doses of steroids, might induce LTABGs and the beneficial results of endolymphatic sac surgery., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The Notch signaling pathway has a crucial role in the differentiation of hair cells and supporting cells by mediating "lateral inhibition" via the ligands Delta-like1 (Dll1) and Jagged2 (Jag2) and the effectors Hes1 and Hes5 during mammalian inner ear development. Recently, another Notch ligand, Jagged1 (Jag1)-dependent Notch activation, has been revealed to be important for the determination of the prosensory region in the earlier stage before cell differentiation. However, little is known about the effectors of the Notch pathway in this context. P27(Kip1), a cyclin-dependent kinase inhibitor, is also known to demarcate the prosensory region in the cochlear primordium, which consists of the sensory progenitors that have completed their terminal mitoses. Hes1 reportedly promotes precursor cell proliferation through the transcriptional down-regulation of p27(Kip1) in the thymus, liver, and brain. In this study, we observed Hes1 as a mediator between the Notch signaling pathway and the regulation of proliferation of sensory precursor cells by p27(Kip1) in the developing cochlea. We showed that Hes1, but not Hes5, was weakly expressed at the time of onset of p27(Kip1). The expression pattern of Hes1 prior to cell differentiation was similar to that of activated Notch1. P27(Kip1) was up-regulated and BrdU-positive S-phase cells were reduced in the developing cochlear epithelium of Hes1 null mice. These results suggest that the Notch-Hes1 pathway may contribute to the adequate proliferation of sensory precursor cells via the potential transcriptional down-regulation of p27(Kip1) expression and play a pivotal role in the correct prosensory determination., (Copyright 2009 Wiley-Liss, Inc.)

Aim: Our aim was to determine the roles of the ubiquitin (Ub)-proteasome system (UPS) in valvular diseases by immunohistochemically identifying Ub-positive cells in aortic and mitral valves and determining if Ub+cells were associated with the severity of valvular diseases., Methods: We evaluated surgically removed aortic and mitral valves from 60 patients (mean age, 64.5 years) for thickening, fibrosis, foam cell infiltration, thrombus, and atheromatous plaques by using grading scores. U+cells were detected immunohistochemically., Results: We found Ub+cells in 16 (26.7%) of the 60 patients. Eleven (28.2%) of the 39 aortic valves and 5 (23.8%) of the 21 mitral valves were Ub-positive. Ub was found with granular depositions in the cytoplasm of monocyte-derived foam cells that were CD68+. The aortic valvular thickness of the Ub+group was significantly greater than that of the Ub- group (3.9+/-1.6mm vs. 3.2+/-1.6mm, p<0.05). Foam cells and fibrosis were greater in the Ub+group (p<0.05), and calcifications were prominent in aortic valves. There was no difference in the number of apoptotic cells in Ub+ and Ub- groups. Ub+cells were present in the affected valves and ubiquitinated proteins were accumulated in macrophage-derived foam cells., Conclusions: Ub+ foam cells are present in valves that are vulnerable to valvular disease, and UPS may contribute to the development of atherosclerosis through the inflammatory process.

Conclusions: Exposure to a virtual environment for 20 min was sufficient to cause adaptive changes in locomotion in healthy subjects, suggesting that virtual environments might improve locomotor deviation in patients with unilateral labyrinthine defects., Objective: Postural and locomotor control in patients with unilateral labyrinthine defects deviates towards the lesion side. The aim of this study was to examine whether active locomotion within a virtual environment can increase the functionality of rehabilitation., Subjects and Methods: We examined the effects of optokinetic stimulation produced by a virtual reality environment on ocular movement and locomotor tracks in 10 healthy subjects., Results: During the 20 min experiment, the mean locomotor deviation and the mean frequency and mean amplitude of optokinetic nystagmus during the last period of the experiment were significantly higher than those during the initial period.

Conclusions: Routine embolization of the ipsilateral facial artery (FA) is effective because of the high success rate. The use of different embolic materials for the internal maxillary artery (IMA) and the FA was considered safe because of the absence of major complications., Objective: To evaluate outcomes of routine embolization of the FA as well as the IMA ipsilateral to the bleeding site for intractable epistaxis, and outcomes using different embolic materials for the FA and the IMA., Patients and Methods: Twenty-two patients with intractable epistaxis who underwent superselective embolization were retrospectively analyzed with a mean follow-up of 7 months. The FA and the IMA ipsilateral to the bleeding site were embolized. Two embolic materials, gelatin sponge and microcoils, were used for the IMA and the FA, respectively., Results: The short-term success rate within the first 7 days was 77.3% (17/22). The long-term success rate was 95.5% (21/22). There were no major complications in 22 cases. Minor complications occurred in 13 cases (59%). These minor complications usually did not last more than a week and most resolved within a day.

Study Objective: To investigate the analgesic efficacy of preoperative flurbiprofen on postoperative pain after tonsillectomy., Design: Prospective, randomized, nonblinded, non-placebo-controlled study., Setting: Municipal hospital., Patients: Twenty-five ASA physical status I patients older than 20 years of age, who were scheduled for tonsillectomy., Interventions: Patients were randomly allocated to two groups to receive preoperative intravenous (IV) 50 mg flurbiprofen (group F) or not (group C). Anesthesia was induced with IV propofol two mg/kg and maintained with nitrous oxide and sevoflurane., Measurements: Pain scores at rest and at swallowing, intraoperative bleeding, vital signs during the postanesthetic period, interval until diclofenac sodium suppository rescue, and the total dose required for 12 hours postoperatively were all recorded., Main Results: Pain scores at rest as well as those recorded after swallowing 30 minutes after tonsillectomy were significantly lower in group F than in group C. During the first postoperative 1.5 hours, significantly fewer patients in group F required rescue diclofenac suppository than did group C patients. However, total dose of required rescue during the postoperative 12 hours in group F did not significantly differ from that of group C. There were no significant differences in intraoperative bleeding or in any vital signs during the postanesthetic period either., Conclusion: Preoperative flurbiprofen suppressed immediate postoperative pain after tonsillectomy. The analgesic effect, however, disappeared in a few hours and was insufficient for overnight pain relief.

Objective: To examine the development of subjective symptoms and heart rate variability (HRV) during motion sickness induced by virtual reality (VR)., Methods: Subjects were 10 healthy young volunteers. During VR immersion, subjects were immersed in a visual-vestibular conflict produced by VR. The levels of the subjective symptoms were assessed by Graybiel's and Hamilton's criteria. HRV was determined by measuring microvascular blood flow or electrocardiogram., Results: Subjective symptoms evaluated by Graybiel's and Hamilton's criteria were gradually worsened during VR. Power spectrum analysis of HRV demonstrated a gradual increase in the low frequency but no change in the high frequency during VR. In this study, individual subjective symptoms were not correlated with the individual result of power spectrum analysis., Conclusion: These findings indicate that there was an increase in sympathetic nervous activity, but no change in parasympathetic nervous activity during motion sickness induced by VR. Given the large inter-individual variability and the reliability of subjective measures, it is not surprising that there is scarcely a relation between the subjective symptoms and the results of power spectrum analysis.

Objective: To look for factors relating to the vertigo control and hearing changes after intratympanic injections of gentamicin (GM)., Study Design: Prospective., Setting: Tertiary referral medical center., Patients: Twenty-eight patients with intractable Ménière's disease., Interventions: Three intratympanic injections of GM (once per day for three consecutive days)., Main Outcome Measures: Although five patients needed further GM injections or vestibular neurectomy because of poor control (Group I), 23 patients had their vertigo controlled for more than two years without further treatment (Group II). The number of vertigo spells per month, pure-tone audiometry, electrocochleography, caloric response, post-head shake nystagmus, and plasma vasopressin as a stress marker were examined., Results: Before GM injections, there was no difference in the number of vertigo spells per month between Groups I and II. However, the hearing thresholds were higher in Group I. Hearing improvement, increase in percentage of canal paresis and induction of post-head shake nystagmus were observed after GM injections only in Group II. Even in the 11 patients who showed an improvement in hearing of more than 10 dB (hearing improvement group), percentage of canal paresis was increased after GM. More, premedication plasma vasopressin levels were lower in the hearing improvement group as compared with the hearing loss/no changes group. Four of eight patients became negative for dominant negative summating potential in electrocochleography after GM injections in the hearing improvement group., Conclusion: Our data indicate that the frequency of vertigo is not a key factor in the vertigo control after GM injections, that induction of vestibular damage in the injected ear is essential for the control of vertigo and this effect is mostly pronounced in patients with milder hearing loss, and that hearing improvement is not only a consequence of good vertigo control but also affected by the stress level before treatment.

Laryngeal tuberculosis is a rare entity and the disease related to laryngeal cancer is extremely rare. We describe a case of laryngeal tuberculosis in a 74-year-old man with a history of radiotherapy for laryngeal carcinoma four months earlier. Laryngoscopy demonstrated a white mass on the right vocal fold at the site carcinoma had previously occupied. Recurrence of the cancer was suspected, but the biopsy result showed histological features of tuberculosis. We discuss the derangement of the host's mucosal barrier by the malignancy as a contributing factor in secondary tuberculous infection. Tubercular bacilli may be reactivated due to the immunosuppression associated with the therapy.

Objectives: We sought to elucidate the clinical problems and otopathology of patients with sudden deafness with vertigo (SDV)., Methods: In 24 patients with SDV who had significant canal paresis (CP) at their first visit to our hospital between 1997 and 2001, we examined pure tone audiograms, caloric tests, and several questionnaires twice, at the first visit within 5 days after the onset and around 2 years after steroid therapy., Results: These examinations revealed that improvements of auditory and vestibular function in patients with SDV tended to be correlated with one another. Sixteen of the 24 patients (66.7%) still had CP. This rate in SDV was significantly worse than that reported previously for vestibular neuritis (VN). On the other hand, patients with SDV with long-lasting CP had a faster reduction of head-shaking afternystagmus and of handicaps in their everyday life due to dizziness than did patients with VN and CP., Conclusions: These findings suggest that SDV may deteriorate the inner ear function more severely but accelerate the central vestibular compensation more effectively than VN after the lesion. It is well known that vestibular neurectomy causes much more severe motion-induced dizziness after surgery than does labyrinthectomy. Taken together, these findings suggest different regions of damage in SDV (mainly the labyrinth, as in labyrinthectomy) and VN (mainly the ganglion, as in vestibular neurectomy).

Objective: To evaluate the endoscopic transantral insertion of antral bone grafts into the orbit for repair of orbital floor defects., Design: A retrospective analysis with a mean follow-up of 5.3 months., Patients: Eleven patients who underwent surgical repair of orbital floor fractures., Setting: Municipal hospital., Main Outcome Measures: Preoperative and postoperative Hess screen tests and the presence of diplopia, enophthalmos, donor site complications, cosmetic deformity, infection, and graft extrusion., Results: Subjectively, 3 patients with diplopia had complete resolution of their symptoms after surgery, and 8 patients had improvement of their symptoms. Objectively, 11 patients had significant improvement in the postoperative Hess area ratio compared with the preoperative Hess area ratio. In 1 patient with a floor defect measuring 2.5 cm, enophthalmos existed after surgery, but reoperation was not performed in this case because diplopia was improved. There were no donor site complications, cosmetic deformity, infection, or graft extrusion., Conclusions: The endoscopic transantral insertion of antral bone grafts through the floor defect into the orbit is an effective technique that prevents injury to the lower eyelid, carries minimal donor site morbidity, and provides an optimal support function for the globe. It merits consideration in cases of orbital defects less than 2 cm in diameter.

Otorrhea of leaked cerebrospinal fluid and meningitis in a 33-year-old male originated from an encephalic herniation into the middle ear following traumatic temporal bone fracture. CT demonstrated a mixed-type fracture consisting of a longitudinal fracture and a posterior oblique fracture of the left temporal bone. The left tegmen tympani was broken into a bellows-like shape and a bone splinter from it had stuck in the epitympanum at the level of the incus body. Surgery via a middle cranial fossa approach confirmed penetration of the brain tissue between the incus and lateral semicircular canal. The diagnosis and management of this condition are discussed in the context of a literature review.