Tsukasa Ito

Reliability of 80-Hz Amplitude- Modulation-Following Response Detected by Phase Coherence

The reliability and frequency specificity of the 80-Hz amplitude-modulation-following response (80-Hz AMFR) during sleep detected by phase coherence as a measure of the hearing threshold was evaluated in 169 affected ears of 125 children with hearing impairment. The 80-Hz AMFR at a carrier frequency of 1000 Hz was monitored in all 169 ears and the auditory brainstem response (ABR) elicited by 1000-Hz tone pips was evaluated in 93 ears. Both responses were examined during sleep, and the thresholds were compared with the behavioral hearing threshold, which was determined by standard pure-tone audiometry or play audiometry. In 24 ears of 22 children with various patterns of audiogram, the 80-Hz AMFR was examined at different carrier frequencies, and the threshold pattern was compared with the pure-tone audiogram to investigate the frequency specificity of 80-Hz AMFR. The mean and standard deviation of the difference between the 80-Hz AMFR at a carrier frequency of 1000 Hz and pure-tone thresholds of 1000 Hz was 3.8 and 12.9 dB, and that between the ABR and pure-tone thresholds was 6.8 and 14.1 dB, respectively. The threshold patterns of 80-Hz AMFR clearly followed the corresponding audiogram patterns in all types of hearing impairment. The measurement of 80-Hz AMFR thus appears to be accurate in hearing assessment and to have good frequency specificity in children during sleep.

Nuclear localization of diacylglycerol kinase ζ in neurons

Diacylglycerol kinase (DGK) is involved in intracellular signal transduction as a regulator of levels of diacylglycerol which leads to protein kinase C activation. Previous studies have revealed that DGK consists of a family of isozymes in mammalian species and that most if not all of them show abundant expression in the central nervous system, suggesting the importance of this enzyme in neuronal function. Among the isozymes, DGKζ (previously also known as DGK‐IV for the rat clone) has unique structural features, such as four ankyrin‐like repeats and a nuclear localization signal (NLS), and shows intense mRNA expression in neurons of the olfactory bulb, hippocampus and cerebral and cerebellar cortices (Goto, K. & Kondo, H. (1996), Proc. Natl Acad. Sci. USA, 93, 11196–11201). However, previous studies have given conflicting results about whether or not DGKζ localizes to the nucleus in these cells. In this study, we have used immunohistochemistry with specific antibodies in brain tissues and cDNA transfection into primary cultured neurons to address this question. We have shown that, while DGKζ is primarily a nuclear protein in neurons, it can also be cytoplasmic in some conditions, and the subcellular location depends not only on the cell type but also on the developmental state or growth conditions of the cell. In addition, we have used deletion mutants to show that nuclear transport of DGKζ depends on a cooperative interaction between the NLS and the C‐terminal region including ankyrin repeats in a manner which suggests that the NLS is a cryptic site whose exposure is regulated by the C‐terminal region. Together, these results support the hypothesis that the localization of DGKζ may be regulated by differential expression of these various proteins which interact with its C‐terminal region.

Feasibility and Advantages of Transcanal Endoscopic Myringoplasty

Objective When performing transcanal myringoplasty under a microscope, the total circumference of the perforation can be difficult to confirm in patients where the external ear canal is narrow and/or protruded. In such patients, a retroauricular incision approach is usually used. However, we have developed a transcanal endoscopic myringoplasty procedure, and the microscopic and endoscopic views are compared herein for the first time. The feasibility and advantages of transcanal endoscopic myringoplasty were examined. Study Design A prospective case series. Setting Tertiary referral center. Patients Transcanal endoscopic myringoplasty was performed on 25 ears in 21 patients with chronic otitis media between September 2011 and December 2012. Intervention Microscopic and endoscopic views were compared for each patient. The 2 fields of views were both recorded and evaluated to determine the advantages and disadvantages of microscopes and endoscopes. Myringoplasty was performed using an endoscopic technique while comparing views as necessary. Results Endoscopic views revealed the entire tympanic membrane in a single field with clear visualization of the perforation edges even when the ear canal was curved. This clear visualization facilitated reliable refreshing of the perforation edges and grafting. The anterior edge of the perforation was not visible under microscopy in 5 of 25 ears. Under an endoscopic wide view, the tympanic cavity was observable through the perforation, and the orifice of the tube, ossicular chain, and tympanic isthmus were visible especially with large perforations. Transcanal endoscopic myringoplasty was successfully performed with a simple underlay technique or with an intracanal incision in cases of marginal perforation. Conclusion Comparison of microscopic and endoscopic views revealed superior visualization and operability of the endoscopic approach as opposed to transcanal simple underlay myringoplasty. Transcanal endoscopic myringoplasty does not require surgical exposure such as a retroauricular skin incision to get an anterior view. Our results demonstrated that transcanal endoscopic myringoplasty can be performed, regardless of the perforation size and the narrowness and/or protrusion of external ear canal.

Bone Conduction Thresholds and Skull Vibration Measured on the Teeth during Stimulation at Different Sites on the Human Head

Vibratory auditory stimulation or bone conduction (BC) reaches the inner ear through both osseous and non-osseous structures of the head, but the contribution of the different pathways of BC is still unclear. In this study, BC thresholds in response to stimulation at several different locations including the eye were assessed, while the magnitudes of skull bone vibrations were measured on the front teeth in human subjects with either normal hearing on both sides or unilateral deafness with normal hearing on the other side. The BC thresholds with stimulation at the ipsilateral mastoid and ipsilateral temporal region were lower than the BC thresholds with stimulation at the other sites, as reported by previous works. The lower thresholds with stimulation at the ipsilateral mastoid and ipsilateral temporal region matched higher amplitudes of skull bone vibrations measured on the teeth, but only at frequencies below 1 kHz. With stimulation at the eye, the thresholds were significantly higher than those with stimulation at the bony sites in the frequency range of 0.25–4 kHz. While skull bone vibrations as measured on the teeth during stimulation at the eye were low for low frequencies, significant bone vibrations were measured at 3 and 4 kHz, indicating different pathways for BC for either the soft tissue or bony site stimulation. This finding contradicts a straightforward relationship between vibrations of the skull bones and BC hearing thresholds.

Effects and mechanism of OK-432 therapy in various neck cystic lesions

Abstract Conclusion: Our results confirmed that OK-432 therapy is simple, easy, safe, and effective and can be used as a substitute for surgery in the treatment of benign neck cysts. In OK-432 therapy, inflammatory cytokines may play important roles in shrinkage of the cystic spaces. Objective: The aim of this study was to evaluate the outcome and mechanism of action of OK-432 therapy in benign neck cysts. Methods: We tried OK-432 therapy in 83 patients with benign neck cysts between April 1997 and August 2009. We aspirated as much of the fluid content of each cystic lesion as possible, and then replaced the volume of aspirated fluid with about half the volume of OK-432 solution. We evaluated the mechanism of action of OK-432 in 43 of the patients. The intracystic fluid in the cysts was aspirated before and after OK-432 therapy, and cytokine production in each aspirate was analyzed by ELISA. Results: Disappearance of the lesion was observed in 63 of 83 patients (76%). Marked reduction was observed in 13 of the 83 patients (16%). Partial reduction was observed in two patients (2%) and no response was seen in five (6%). Local discomfort at the injection site and low-grade fever were side effects observed in half of the patients, but such problems resolved within a few days. No local scarring or deformity of the injected sites occurred in any patient. We performed OK-432 therapy on an outpatient basis without hospitalization. Levels of various cytokines, including tumor necrosis factor, interleukin-8, interleukin-6, interferon gamma, and vascular endothelial growth factor, were significantly elevated in each aspirate after OK-42 therapy.

Extension of indications for transcanal endoscopic ear surgery using an ultrasonic bone curette for cholesteatomas.

Background One-handed endoscopic procedures have, up until now, limited the indications for transcanal endoscopic ear surgery (TEES) in cholesteatoma surgery. However, the development of electrically powered instruments has opened the door to such one-handed endoscopic procedures in restricted surgical spaces. Objective We examined the feasibility of using one such powered instrument, the ultrasonic bone curette (UBC) in TEES for cholesteatoma surgery. The UBC offers several advantages, including nonrotational motion and the combination of both suction and irrigation in a single handpiece. Study Design A prospective case series. Setting Tertiary referral center. Patients TEES was performed on 43 cases of primary cholesteatoma between September 2011 and December 2012, including 14 cases extending to the antrum. Intervention Zero-, 30-, or 70-degree angled rigid endoscopes with an outer diameter of 2.7 mm (Karl Storz) were used together with a high-definition video system. A Sonopet UBC (Stryker) was used to cut bony tissue. The nonrotational motion of the UBC prevents injury to the tympanomeatal flap and other soft tissue, which may result with standard drills. Transcanal endoscopic retrograde mastoidectomy on demand was performed to access the pathologies in the attic and antrum. Results A minimum attico-antrotomy was performed using the UBC, removing only the bony tissue necessary to visualize the pathology. The cholesteatoma was completely removed from the antral mucosa under clear endoscopic visualization in 13 of 14 cases. After removal of the cholesteatoma, the canal wall was reconstructed using cartilage taken from the tragus. This procedure resulted in greater mastoid preservation. Conclusion The transcanal endoscopic approach to the antrum using the UBC proved to be less invasive and more functional. The UBC contains both a suction and irrigation system in a single handpiece, and this UBC is an appropriate cutting tool that extends the indications for TEES.

Transcanal endoscopic ear surgery for pediatric population with a narrow external auditory canal

OBJECTIVES To retrospectively determine the size of the external auditory canal (EAC) in a pediatric population and to describe our experience with transcanal endoscopic ear surgery (TEES) in this pediatric population which had been successfully treated for middle ear disease using TEES. METHODS We analyzed 31 patients ranging in age from 2 to 13 years old (median: 7.6 years) with middle ear disease who underwent TEES between November 2011 and August 2014. Sixteen of these patients had surgery for cholesteatomas; 11 for chronic otitis media; and 4 for malformation of the middle ear. A preoperative CT scan was performed to evaluate the middle ear disease. Transcanal endoscopic tympanoplasty was performed using a rigid endoscope with a 2.7mm outer diameter. Transcanal endoscopic atticoantrotomy was also performed, as necessary, on some patients to access pathologies in the antrum. The values of anterior-posterior diameters and superior-inferior diameters of the bony parts of EAC were measured retrospectively based on the preoperative CT scan data. RESULTS TEES was successfully performed in all 31 pediatric patients without resorting to a retroauricular incision. Twenty-seven patients were evaluated for postoperative hearing levels which were found to fall within an acceptable range and for postoperative air-bone gap (ABG) by pure tone audiometry with a resulting mean of 8.6dB. The smallest anterior-posterior diameters of the external ear canal ranged from 3.2 to 7.1mm (5.0±1.0mm) and the smallest superior-inferior diameters ranged from 3.4 to 10.3mm (5.9±1.3mm). CONCLUSION TEES can be used to safely and effectively treat middle ear disease even in the pediatric population in its narrow EAC.

Clinical and Pathological Characteristics of Organized Hematoma

Objective. To study the clinical and pathological characteristics of patients with organized hematoma with malignant features in maxillary sinuses. Subjects and Methods. This was a retrospective study of five patients who were treated surgically for organized hematoma. The preoperative CT and MRI findings were studied clinically. The expressions of CD31, CD34, and periostin in surgical samples were investigated by immunohistochemistry. Results. The clinical features of organized hematoma, such as a mass expanding from the maxillary sinus with bone destruction, resembled those of maxillary carcinoma. However, CT and MRI provided sufficient and useful information to differentiate this condition from malignancy. Surgical resection was the first-line treatment because of the presence of a firm capsule. Characteristic histopathological findings were a mixture of dilated vessels, hemorrhage, fibrin exudation, fibrosis, hyalinization, and neovascularization. The expressions of periostin, CD31, and CD34 were observed in organized hematoma of the maxillary sinus. Conclusion. The expressions of periostin, CD31, and CD34 were observed in organized hematoma of the maxillary sinus. Organized hematoma is characterized pathologically by a mixture of bleeding, dilated vessels, hemorrhage, fibrin exudation, fibrosis, hyalinization, and neovascularization. CT and MRI show heterogeneous findings reflecting a mixture of these pathological entities.

Gene expression and localization of diacylglycerol kinase isozymes in the rat spinal cord and dorsal root ganglia

The dorsal root ganglion (DRG) and dorsal horn of the spinal cord are areas through which primary afferent information passes enroute to the brain. Previous studies have reported that, during normal neuronal activity, the regional distribution of a second messenger, diacylglycerol (DG), which is derived from phosphoinositide turnover, is diverse in these areas. However, the way that DG is regulated in these organs remains unknown. The present study was performed to investigate mRNA expression and protein localization of DG kinase (DGK) isozymes, which play a central role in DG metabolism. Gene expression for DGK isozymes was detected with variable regional distributions and intensities in the spinal cord. Among the isozymes, most intense signals were found for DGKζ and DGKι in the DRG. By immunohistochemical analysis, DGKζ immunoreactivity was detected heterogeneously in the nucleus and cytoplasm of small DRG neurons with variable levels of distribution, whereas it was detected exclusively in the cytoplasm of large neurons. On the other hand, DGKι immunoreactivity was distributed solely in the cytoplasm of most of the DRG neurons. Double-immunofluorescent imaging of these isozymes showed that they coexisted in a large population of DRG neurons at distinct subcellular sites, i.e., DGKζ in the nucleus and DGKι in the cytoplasm. Thus, DGK isozymes may have different functional roles at distinct subcellular sites. Furthermore, the heterogeneous subcellular localization of DGKζ between the nucleus and cytoplasm implies the possible translocation of this isozyme in small DRG neurons under various conditions.

Safety of ultrasonic bone curette in ear surgery by measuring skull bone vibrations.

Hypothesis Mastoidectomy using an ultrasonic bone curette (UBC) is as safe for the inner ear as a mastoidectomy using a high-speed drill. Background Transcanal endoscopic ear surgery (TEES) is a minimally invasive, secure, and functional technique, which has been performed using high-speed drills. We have started to use a UBC instead of the high-speed drill because a UBC allows for simultaneous bone cutting, irrigation, and aspiration. These features of the UBC make it an excellent candidate for use in one-handed TEES, but the safety of the UBC still needs to be confirmed. We thus measured skull vibrations caused by the UBC to estimate the effects of UBC on the inner ear. Methods Eight patients with cholesteatoma underwent mastoidectomy using a Sonopet UST-2001 UBC (Stryker, MI, USA) and 2 high-speed drills (drills A and B). Skull vibrations were measured using polyvinylidene difluoride film taped to the forehead as a piezoelectric vibration sensor. The recorded data were transformed to the power spectrum in the frequency domain by fast Fourier transform. The mean and peak values of vibrations were analyzed in four frequency bands: 200 to 500 Hz, 500 to 2,000 Hz, 2,000 to 8,000 Hz, and 8,000 Hz to 20 kHz. Results Both the mean values and the peak values of skull vibrations caused by the UBC were significantly smaller than those values obtained for drill B between 500 and 8,000 Hz, (p < 0.05). No significant differences were found among the 3 instruments below 500 Hz or above 8,000 Hz. Conclusion Skull vibration levels generated by the UBC were found to be comparable or even lower than those levels associated with conventional high-speed drills. These findings indicated that the UBC can be safely applied to TEES without the risk of harmful effects on the inner ear.