Characterisation of N-glycans in the epithelial-like tissue of the rat cochlea.

Membrane proteins (such as ion channels, transporters, and receptors) and secreted proteins are essential for cellular activities. N-linked glycosylation is involved in stability and function of these proteins and occurs at Asn residues. In several organs, profiles of N-glycans have been determined by comprehensive analyses. Nevertheless, the cochlea of the mammalian inner ear, a tiny organ mediating hearing, has yet to be examined. Here, we focused on the stria vascularis, an epithelial-like tissue in the cochlea, and characterised N-glycans by liquid chromatography with mass spectrometry. This hypervascular tissue not only expresses several ion transporters and channels to control the electrochemical balance in the cochlea but also harbours different transporters and receptors that maintain structure and activity of the organ. Seventy-nine N-linked glycans were identified in the rat stria vascularis. Among these, in 55 glycans, the complete structures were determined; in the other 24 species, partial glycosidic linkage patterns and full profiles of the monosaccharide composition were identified. In the process of characterisation, several sialylated glycans were subjected sequentially to two different alkylamidation reactions; this derivatisation helped to distinguish α2,3-linkage and α2,6-linkage sialyl isomers with mass spectrometry. These data should accelerate elucidation of the molecular architecture of the cochlea.

Molecular diversity of clustered protocadherin-α required for sensory integration and short-term memory in mice.

Clustered protocadherins (Pcdhs) are neuronal cell adhesion molecules characterized by homophilic adhesion between the tetramers of 58 distinct isoforms in mice. The diversity of Pcdhs and resulting highly-specific neuronal adhesion may be required for the formation of neural circuits for executing higher brain functions. However, this hypothesis remains to be tested, because knockout of Pcdh genes produces abnormalities that may interfere with higher brain functions indirectly. In Pcdh-α1,12 mice, only α1, α12 and two constitutive isoforms are expressed out of 14 isoforms. The appearance and behavior of Pcdh-α1,12 mice are similar to those of wild-type mice, and most abnormalities reported in Pcdh-α knockout mice are not present in Pcdh-α1,12 mice. We examined Pcdh-α1,12 mice in detail, and found that cortical depression induced by sensory mismatches between vision and whisker sensation in the visual cortex was impaired. Since Pcdh-α is densely distributed over the cerebral cortex, various types of higher function are likely impaired in Pcdh-α1,12 mice. As expected, visual short-term memory of space/shape was impaired in behavioral experiments using space/shape cues. Furthermore, behavioral learning based on audio-visual associative memory was also impaired. These results indicate that the molecular diversity of Pcdh-α plays essential roles for sensory integration and short-term memory.

Risk Factors of Recurrence in Pediatric Congenital Cholesteatoma.

OBJECTIVE: To examine the risk factors of recurrence in pediatric congenital cholesteatoma. STUDY DESIGN: Retrospective chart review. SETTING: University hospital. PATIENTS: Sixty-seven patients having tympanic type of congenital cholesteatoma under 15-years old at surgery. INTERVENTIONS: Canal wall-up tympanomastoidectomy (n = 30) or transcanal atticotomy/tympanoplasty (n = 37) was performed depending on cholesteatoma extension, 16 of which were followed by second-look surgery. Preoperative computed tomography (CT) before second-look surgery or follow-up CT was performed to detect residual recurrence 1 year after the surgery. Cholesteatoma found at the second surgery was also included in the recurrence. All patients had no recurrent cholesteatoma at the last follow-up (median, 61 mo after surgery). MAIN OUTCOME MEASURES: Possible predictive factors were compared between the groups. RESULTS: Residual cholesteatoma and retraction cholesteatoma occurred in 21 and 6%, respectively. There was no significant difference in age, sex, and type of cholesteatoma (open or closed) between the groups; however, Potsic stage and status of stapes involvement were more advanced in the residual cholesteatoma group. All residual lesions could be detected by follow-up CT or by second-look surgery. All of four retraction cholesteatoma patients were male, young at the surgery and in stage IV. CONCLUSION: Recurrence mostly occurred as residual cholesteatoma, suggesting that CT is recommended as a follow-up tool for congenital cholesteatoma. Advanced lesions had the risk of residual cholesteatoma, suggesting that complete removal of epithelium is important. Although rare, young advanced-stage patients had risk of retraction cholesteatoma and therefore normal mucosa should be preserved as much as possible for these patients.

Creating an Optimal 3D Printed Model for Temporal Bone Dissection Training.

OBJECTIVE: Making a 3-dimensional (3D) temporal bone model is simple using a plaster powder bed and an inkjet printer. However, it is difficult to reproduce air-containing spaces and precise middle ear structures. The objective of this study was to overcome these problems and create a temporal bone model that would be useful both as a training tool and for preoperative simulation. METHODS: Drainage holes were made to remove excess materials from air-containing spaces, ossicle ligaments were manually changed to bony structures, and small and/or soft tissue structures were colored differently while designing the 3D models. The outcomes were evaluated by 3 procedures: macroscopic and endoscopic inspection of the model, comparison of computed tomography (CT) images of the model to the original CT, and assessment of tactile sensation and reproducibility by 20 surgeons performing surgery on the model. RESULTS: Macroscopic and endoscopic inspection, CT images, and assessment by surgeons were in agreement in terms of reproducibility of model structures. Most structures could be reproduced, but the stapes, tympanic sinus, and mastoid air cells were unsatisfactory. Perioperative tactile sensation of the model was excellent. CONCLUSIONS: Although this model still does not embody perfect reproducibility, it proved sufficiently practical for use in surgical training.

Auditory cortical field coding long-lasting tonal offsets in mice.

Although temporal information processing is important in auditory perception, the mechanisms for coding tonal offsets are unknown. We investigated cortical responses elicited at the offset of tonal stimuli using flavoprotein fluorescence imaging in mice. Off-responses were clearly observed at the offset of tonal stimuli lasting for 7 s, but not after stimuli lasting for 1 s. Off-responses to the short stimuli appeared in a similar cortical region, when conditioning tonal stimuli lasting for 5-20 s preceded the stimuli. MK-801, an inhibitor of NMDA receptors, suppressed the two types of off-responses, suggesting that disinhibition produced by NMDA receptor-dependent synaptic depression might be involved in the off-responses. The peak off-responses were localized in a small region adjacent to the primary auditory cortex, and no frequency-dependent shift of the response peaks was found. Frequency matching of preceding tonal stimuli with short test stimuli was not required for inducing off-responses to short stimuli. Two-photon calcium imaging demonstrated significantly larger neuronal off-responses to stimuli lasting for 7 s in this field, compared with off-responses to stimuli lasting for 1 s. The present results indicate the presence of an auditory cortical field responding to long-lasting tonal offsets, possibly for temporal information processing.

Pediatric middle ear cholesteatoma: the comparative study of congenital cholesteatoma and acquired cholesteatoma.

This study examined the differences between congenital cholesteatoma (CC) and acquired cholesteatomas (AC) in children by comparing clinical features and treatment courses. This was a retrospective study which retrospectively evaluated 127 children with middle ear cholesteatomas using medical records from January 1999 to December 2012 in the Department of Otolaryngology, Niigata University Hospital. The study comprised 69 and 58 cases of CC and AC, respectively. The main outcome measures include patient backgrounds, the opportunities for consultations, mastoid cell development, intraoperative finding of stapes, surgical procedure and number of surgeries. The average age at operation was 6.4 and 9.8 years in CC and AC, respectively. AC was more prevalent in boys. Mastoid development was better in CC than in AC. We adopted a two-stage operation in 17 cases (25 %) of CC and in 22 cases (38 %) of AC. The repeat surgery rate was 11.6 % in CC and 27.6 % in AC. Three times as many operations were required for three cases (4.3 %) of CC and 10 cases (17.2 %) of AC. The lesions in AC were more difficult to control. In the treatment of pediatric middle ear cholesteatoma, we had to keep the outcome in mind.

A Survey of the Otorhinolaryngological Screening of Children in Niigata Prefecture: Kindergarten to High School.

We conducted the first survey of otorhinolaryngological (ORL) screening at educational institutions, from kindergarten to high school, in Niigata Prefecture. The survey results showed that ORL screening is not performed in 62.1% of kindergartens and nursery schools, and that screening was conducted by non-ENT doctors in 23.9% of them. At elementary school entry health check-ups, ORL screening was performed by otorhinolaryngologists in only 4.2% of children overall. ORL screening was conducted in students in all grades by 51.7% of all elementary schools and 31.6% of all junior high schools. Audiometry was performed in students in all grades by over 80% of elementary schools and junior high schools. With regard to high schools, ORL screening was performed in students in all grades at only three schools among 105 high school; ORL screening and audiometry were conducted primarily in the first-year students. In addition to the above results, the survey revealed that no ORL screening whatsoever was performed during a period of 9 years at an elementary school and a junior high school in a certain municipality; as a result of discussion with the relevant municipality, it was decided that screening will be conducted starting at 2016. From the viewpoint of reinforcing the structure of conducting ORL screening in infants in whom ORL findings are identified at a high frequency, we requested that Niigata City conduct ORL screening at private kindergartens in Niigata City where the ORL screening rate is low. We consider this survey to have been productive, as it identified meaningful new facts and measures that could be devised to address the relevant issues. It is our aim to become more proactively than ever involved in school health including health check-ups.

[A Case of the Relapsing Polychondritis Limited to the Trachea].

A 62-year-old woman, who had dysesthesia in the throat, and polyposia the previous year, was admitted in a coma because of respiratory failure. Computed tomography scans demonstrated dilatation of the esophagus and stenosis of the trachea. After emergency intubation, extubation was not possible due to a collapsed trachea, so we performed a tracheostomy. The tracheoscopy from the stoma showed an esophagus-like trachea due to disappearance of the tracheal cartilage and the straight pattern on the membranous portion, and the lumen deformed with coughing. With the continuous dyspnea episode, the patient was diagnosed as having tracheomalacia. Anti-type II collagen antibody and pathological findings of the trachea led us to the diagnosis of Relapsing Polychondritis.

[Clinical Study of Skull Base Osteomyelitis].

Typical osteomyelitis is reportedly caused by Pseudomonous aeruginosa in elderly diabetic patients after malignant external otitis. Recently, complications have arisen due to the emergence of atypical osteomyelitis. We have experiensed 5 cases of skull base osteomyelitis at our hospital. All patients were male with a mean age of 75.2 years. Four patients had diabetes. Regarding the clinical and radiographic findings, patients 1, 2, and 3 had typical osteomyelitis after malignant external otitis, whereas patients 4 and 5 had atypical osteomyelitis without temporal bone findings. Sample culturing revealed Pseudomonas aeruginosa in 4 cases and Aspergillus in one. Intravenous antibiotics were administered to all patients. Two patients responded positively and survived, while 3 died. Typical osteomyelitis is reportedly caused by P. aeruginosa in elderly diabetic patients after malignant external otitis. Recently, complications have arisen due to the emergence of atypical osteomyelitis. The prognosis of skull base osteomyelitis is still poor in Japan. Early diagnosis and long-term antibiotic administration is required to improve outcome.

A case of lateral sinus insufficiency with acute otitis media: Early surgical intervention for prevention of lateral sinus thrombosis.

OBJECTIVE: To describe a case of lateral sinus insufficiency, presumably occurring just prior to lateral sinus thrombosis (LST), and to discuss the importance of early surgical intervention and the pathophysiology of full-blown LST. CASE REPORT: A 4-year-old boy developed headaches and vomiting after exhibiting typical symptoms of acute otitis media. Contrast-enhanced CT revealed narrowing of the sigmoid sinus medially by gas and low-density material. We diagnosed the patient with suspected LST and consequently performed mastoidectomy. A large amount of bloody pus was found in the mastoid cavity and below the bony sinus plate. Sigmoid sinus blood flow was completely restored after drainage of the hemorrhagic and purulent material, and the patient recovered fully. CONCLUSION: Because of the anatomical features of the dural venous sinus, hemorrhage per diapedesis may be strongly associated with the development of LST. In the patient with suspected LST, early diagnosis and surgery prior to the development of intravenous thrombus are key for full recovery from this condition.

Therapeutic outcome after resection of pulmonary metastasis from head and neck carcinomas.

Hematogenous metastasis is the most common form of metastasis in head and neck cancer, and reports have described successful resection of pulmonary metastases of such cancers. We report treatment outcomes after surgical resection of pulmonary metastases of head and neck cancer and identify prognostic factors. This clinicopathologic study investigated the clinical records of 16 patients with pulmonary metastases of head and neck cancer (excepting cases of thyroid cancer) who had undergone metastasectomy at our center during the period 2001-2012. The mean age of the 16 patients (11 men and 5 women) was 62.1 years. The mean interval between completion of successful treatment of the primary tumor and detection of pulmonary metastasis was 21 months (range, 6-56 months). All patients underwent pulmonary resection. The overall 1-year survival rate was 79.4 %, and the 2- to 5-year survival rate was 63.2 %. These rates compare favorably to those in previous reports on resection of pulmonary metastases. When prognostic factors for survival rates were compared, the factors associated with a negative prognosis were a disease-free interval of <12 months and partial resection of pulmonary metastases. Multivariate analysis did not reveal any prognostic factors associated with negative outcomes. Surgical resection of pulmonary metastases of head and neck cancer might improve outcomes.

Surgical management of retropharyngeal nodes metastases from papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) often metastasizes to the central and lateral neck lymph nodes, but rarely affects retropharyngeal nodes (RPN). METHODS: We retrospectively reviewed 12 patients (three men, nine women) with PTC who underwent dissection of RPN metastases between 1994 and 2012. Mean age at dissection was 65 years (range 23-77). RESULTS: Dissection was performed with the initial surgery for PTC in eight patients, while the remaining four patients underwent dissection as secondary surgery. RPN metastases arose from an ipsilateral primary in nine patients, bilateral in two, and contralateral in one, with primaries located at the superior pole of the thyroid lobe in nine patients. All patients showed simultaneous or previous lymph node metastases in the upper jugular chain. A transcervical approach was applied for RPN dissection in 11 patients, while a transcervical-transparotid approach was applied in the remaining patient. No patients needed mandibulotomy or showed severe complications. Median duration of follow-up after RPN dissection was 48 months (range 3-206). No recurrences in the retropharyngeal space were identified. Two patients died of the disease, one died from other carcinoma, and five survived with distant metastases from PTC. The remaining four patients remain free of the disease as at the time of writing. CONCLUSIONS: If lymph node metastases are identified in the upper jugular chain, the possibility of RPN metastases should be checked. Most RPN metastases from PTC can be dissected safely without mandibulotomy. In particular, low-risk patients can expect favorable outcomes.

Acquired cholesteatoma in children: clinical features and surgical outcome.

OBJECTIVE: In general, cholesteatoma tends to recur more frequently in children than in adults. This has been suggested to be due to immature Eustachian tube function, underdeveloped mastoid air cells, and subsequent repetitive otitis media in children. This study was undertaken to determine the characteristics of acquired cholesteatoma in children by comparison with that in adults. METHODS: We retrospectively evaluated 42 children with acquired cholesteatoma (males, 38; females, 4; age range, 3-15 years) using medical records from January 1999 to December 2009 at the Department of Otolaryngology, Niigata University Hospital. The extent of disease was classified according to the Classification and Staging of cholesteatoma proposed by the Japan Otological Society in 2010. RESULTS: No major differences in stage classification were observed between children and adults. In children with pars flaccida-type cholesteatoma, the epithelium tended to invade from the attic to the mastoid cavity and mesotympanum. In contrast, adult patients with invasion to the mesotympanum were fewer. The rate of disappearance of the stapes superstructure was almost the same in children and in adults. The destruction of the superstructure of the stapes was more common in pars tensa type than pars flaccida type; so it was dependent on the pathology. Postoperative hearing levels were better in children, even in those with widespread lesions. However, the recurrence rate was significantly higher in children. CONCLUSIONS: Acquired cholesteatoma in children showed a wider invasion, and the recurrence rates were higher than that in adults. For patients with a widespread lesion and severe destruction of the ossicles, a two-stage surgery is recommended.

Long-term follow-up results of canal wall down tympanoplasty with mastoid obliteration using the bone pate plate for canal wall reconstruction in cholesteatoma surgery.

BACKGROUND: The pathogenesis of recurrent cholesteatoma can be roughly divided into residual lesions and re-retraction of the epithelium. To prevent both residual and re-retraction cholesteatoma, we performed canal wall down tympanoplasty with mastoid obliteration using the bone pate plate for canal wall reconstruction as a fundamental surgical treatment for patients with acquired cholesteatoma. We attempted to achieve the complete extirpation of cholesteatoma in the wide surgical field made by the canal wall down procedure and simultaneously prevent recurrent retraction cholesteatoma and regain the physiologic canal wall, in which patients can have a "maintenance-free ear." OBJECTIVE: The surgical method used in the present study was described, and the long-term postoperative results of this method were evaluated. STUDY DESIGN: Retrospective study. PATIENTS: Participants were 118 patients with acquired cholesteatoma who underwent canal wall down tympanoplasty with mastoid obliteration and could be followed-up for more than 5 years. MAIN OUTCOME MEASURES: Postoperative changes in the reconstructed canal wall, the rate of otorrhea, and exposure of the material were examined using endoscopic images, medical charts, and CT scans. RESULTS: A total of 113 ears (95.8 %) achieved the nearly physiologic appearance of the external auditory canal, and these conditions were maintained throughout the follow-up periods. However, recurrent cholesteatoma was not observed during the follow-up periods. Postoperative otorrhea was observed in 2.5% of ears. Exposure of the bone pate was only noted in 1 patient (0.8 %). Postoperative CT scans confirmed that ossification developed in the bone pate used in the reconstructed canal wall and mastoid surface. CONCLUSION: Canal wall down tympanoplasty with mastoid obliteration using the bone pate plate for canal wall reconstruction prevents both recurrent and residual cholesteatoma and contributes to a good quality of life for the patient.

Cervical spine osteomyelitis and epidural abscess after chemoradiotherapy for hypopharyngeal carcinoma: a case report.

Osteomyelitis of mandible as a delayed adverse event following radiation therapy has been widely reported; however, osteomyelitis of the cervical spine has rarely been reported. In this study, we reported our experience with a case of cervical spine osteomyelitis and epidural abscess after concurrent chemoradiotherapy (CCRT) for hypopharyngeal carcinoma. The case involved a 68-year old man who underwent radical CCRT after a diagnosis of stage IVb, T4bN2cM0 posterior hypopharyngeal wall carcinoma. At 7 months after completing the initial therapy, the patient complained of severe pain in the neck and both shoulders and reduced muscular strength in the extremities. A large defect was found on the mucosa of posterior hypopharyngeal wall. On cervical magnetic resonance imaging, cervical spine osteomyelitis and an epidural abscess were observed. Because antimicrobial therapy was not effective, hyperbaric oxygen therapy was administered. Abscess reduction and improvement of the mucosal defect were observed. Because cervical spine complications after CCRT can be fatal upon worsening, adequate attention must be given.

Primary paraganglioma in the facial nerve canal.

OBJECTIVE: To describe primary paraganglioma in the facial nerve canal and discuss the characteristics of facial nerve paraganglioma in contrast with other tumors. CASE REPORT: A 23-year-old man developed gradually progressive right facial palsy as the initial symptom. One year later, he exhibited hearing loss without tinnitus in his right ear. CT demonstrated an enlarged facial nerve canal with irregular bony erosion of the circumference. MRI showed a well-enhanced heterogeneous mass with hypo-intensity spots inside it. During surgery, a blood-rich tumor was observed along the facial nerve: however, extensive bleeding interfered with tumor removal. The surgical specimen demonstrated paraganglioma. The tumor was completely removed in the second surgery in combination with arterial embolization. Facial nerve function was reconstructed with a free muscle flap more than one year following resection. CONCLUSION: Because paraganglioma is a blood-rich tumor, it is important to perform angiography and embolization. If preoperative facial nerve palsy is demonstrated, careful management of facial nerve function is needed. Paraganglioma must be considered in the differential diagnosis of a facial nerve tumor.

Can the pathogenesis of auditory ossicular malformations be explained by the branchial-based theory?--Evaluation by the consecutive distribution of embryologic foci in 87 cases.

BACKGROUND: Development of the auditory ossicles is initiated by induction of the cartilage primordium of each ossicle between the fifth and seventh fetal week. It is well known that primordium of the upper part of the ossicular chain is derived from the first branchial arch and that of the lower part develops from the second branchial arch. Previous studies have suggested that auditory ossicular malformations are caused by deficiencies in the early period of induction of the cartilage primordium. However, auditory ossicular malformations can occur at any developing stage, and their clinical features are very complicated. OBJECTIVE: The precise embryologic foci of auditory ossicular malformations were estimated by evaluating the consecutive distribution of these anomalies, and the pathogenesis of these malformations was discussed using new aspects. STUDY DESIGN: Retrospective study. PATIENTS: Eighty-seven ears of 78 patients that underwent surgical treatment after the diagnosis of an auditory ossicular malformation in Niigata University Hospital between 1998 and 2012. MAIN OUTCOME MEASURES: The types of malformations were roughly divided into 4 groups based on intraoperative findings: Type A--ankylosis of the malleus head or short process of the incus; type B--defect in the connection between the incus and stapes; type C--fixation of the footplate; and type D--a complex lesion combining types B and C. Additionally, the consecutive points of the malformation were precisely evaluated, and a distribution map of the malformation was made. Foci of the malformations of each type were then estimated. RESULTS: Type A malformations were observed in 8 ears, type B in 33 ears, type C in 32 ears, type D in 6 ears, and unclassified anomalies in 8 ears. A deformity was observed in the malleus handle, which is located in the lower part of the ossicle, in 5 of 7 ears with type A malformations, which suggests that the pathogenesis of ankylosis of the malleus head or short process of the incus could not simply be explained by the branchial-based theory. The focus of the type B malformation was located on the long process of the incus and not onthe I-S joint. We suggest that pathogenesis of the defect inthe connection between the incus and stapes could not be explained by a conjugation deficiency in the cartilage primordium but could be explained by an ossification deficiency after the conjugation period. The focus of the location of the defect was shifted more medially in type D malformations than in type B malformations, and this was significantly different, which suggests that this type of malformation is not caused by 2 independent anomalies but is inducted by a monogenic abnormality. CONCLUSION: The foci of auditory ossicular malformations were highly variable, which suggests that the pathogenesis of these malformations could not be simply explained by a branchial-based theory. Auditory ossicular malformations occur at various developmental stages of the auditory ossicles.

Age-related deterioration of cortical responses to slow FM sounds in the auditory belt region of adult C57BL/6 mice.

To compare age-related deterioration of neural responses in each subfield of the auditory cortex in C57BL/6 mice, we evaluated amplitudes of tonal responses in young (5-11 weeks old) and adult (16-23 weeks old) groups using transcranial flavoprotein fluorescence imaging. Cortical responses to 20-kHz amplitude-modulated (AM) sounds, which were mainly found in the anterior auditory field (AAF) and the primary auditory cortex (AI) of the core region, were not markedly different between the two groups. In contrast, cortical responses to direction reversal of slow frequency-modulated (FM) sounds, which were mainly found in the ultrasonic field (UF), were significantly disrupted in the adult group compared with those in the young group. To investigate the mechanisms underlying such age-related deterioration, biotinylated dextran amine (BDA) was injected into UF. The number of retrograde labeled neurons in the dorsal division of the medial geniculate body (MGd) was markedly reduced in the adult group compared with that in the young group. These results strongly suggest that cortical responses to FM direction reversal in UF of adult C57BL/6 mice are mainly deteriorated by loss of non-lemniscal thalamic inputs from MGd to UF due to aging.

Auditory cortical areas activated by slow frequency-modulated sounds in mice.

Species-specific vocalizations in mice have frequency-modulated (FM) components slower than the lower limit of FM direction selectivity in the core region of the mouse auditory cortex. To identify cortical areas selective to slow frequency modulation, we investigated tonal responses in the mouse auditory cortex using transcranial flavoprotein fluorescence imaging. For differentiating responses to frequency modulation from those to stimuli at constant frequencies, we focused on transient fluorescence changes after direction reversal of temporally repeated and superimposed FM sweeps. We found that the ultrasonic field (UF) in the belt cortical region selectively responded to the direction reversal. The dorsoposterior field (DP) also responded weakly to the reversal. Regarding the responses in UF, no apparent tonotopic map was found, and the right UF responses were significantly larger in amplitude than the left UF responses. The half-max latency in responses to FM sweeps was shorter in UF compared with that in the primary auditory cortex (A1) or anterior auditory field (AAF). Tracer injection experiments in the functionally identified UF and DP confirmed that these two areas receive afferent inputs from the dorsal part of the medial geniculate nucleus (MG). Calcium imaging of UF neurons stained with fura-2 were performed using a two-photon microscope, and the presence of UF neurons that were selective to both direction and direction reversal of slow frequency modulation was demonstrated. These results strongly suggest a role for UF, and possibly DP, as cortical areas specialized for processing slow frequency modulation in mice.

Clinical behavior and pathogenesis of secondary acquired cholesteatoma with a tympanic membrane perforation.

CONCLUSION: The pathogenesis of secondary acquired cholesteatoma with a tympanic membrane (TM) perforation is very different from that of other types of cholesteatoma. This disease should be clearly categorized as a different type of cholesteatoma. OBJECTIVE: Primary cholesteatoma generally arises from retraction of the squamous epithelium of the TM. However, in rare cases, epithelial invasion occurs from the edge of the TM perforation and migrates to the medial surface of the TM and middle ear cavity. The aim of this study was to evaluate the clinical features of secondary acquired cholesteatoma with a TM perforation. METHODS: We investigated 13 ears that underwent surgical treatment after the diagnosis of secondary acquired cholesteatoma with a TM perforation. Patient backgrounds, the preoperative appearances of TM, intraoperative findings, and histopathological findings were investigated. RESULTS: The average age was much higher than that of patients with other types of cholesteatoma, suggesting that it must require long periods of time to establish the disease. The common area of the epithelial invasion was on the superior part of the TM perforation around the tip of the malleus handle. The tendon of the tensor tympani muscle plays an important role as an extension route for this disease.