Effects of cholesterol alterations are mediated via G-protein-related pathways in outer hair cells.

Cholesterol is an essential component of cell membranes, and determines their rigidity and fluidity. Alterations in membrane cholesterol by MßCD or water-soluble cholesterol affect the stiffness, capacitance, motility, and cell length of outer hair cells (OHCs). This suggests that reconstruction of the cytoskeleton may be induced by cholesterol alterations. In this study, we investigated intracellular signaling pathways involving G proteins to determine whether they modulate the changes in voltage-dependent capacitance caused by cholesterol alterations. Membrane capacitance of isolated guinea pig OHCs were assessed using a two-sine voltage stimulus protocol superimposed onto a voltage ramp (200 ms duration) from -150 to +140 mV. One group of OHCs was treated with 100 µM guanosine 5'-O-(3-thiotriphosphate) tetralithium salt (GTPγS), the GTP analog, administrated into individual cells via patch pipettes. Another group of OHCs was internally perfused with 600 µM guanosine 5'-(ß-thio) diphosphate trilithium salt (GDPßS), the GDP analog. A third group was perfused with internal solution only as a control. Application of 1 mM MßCD shifted non-linear capacitance curves to the depolarized direction of the control group with reduction of the peak capacitance (C mpeak). After the 10-min application of MßCD, shifts of voltage at C mpeak (V cmpeak) and reduction of C mpeak were 73.32 ± 11.09 mV and 9.09 ± 2.10 pF, respectively (n = 4). On the other hand, in the GTPγS-treated group, the shift of V cmpeak and reduction of C mpeak were attenuated remarkably. The shift of V cmpeak and reduction of C mpeak in the 10-min application of MßCD were 9.73 ± 10.92 mV and 3.08 ± 1.91 pF, respectively (n = 7). MßCD decreased the cell length by 16.53 ± 4.27 % in the control group and by 6.45 ± 6.22 % in the GTPγS group. In addition, we investigated the effects of GDPßS on cholesterol-treated OHCs. One millimolar cholesterol was externally applied after the 4-min application of 1 mM MßCD because the shift of V-C m function caused by cholesterol alone was small. Application of cholesterol shifted V-C m curves of the control group to the hyperpolarized direction with increase of the C mpeak. After the 10-min application of cholesterol, changes of V cmpeak and C mpeak were -9.19 ± 6.68 mV and 2.14 ± 0.44 pF, respectively (n = 4). On the other hand, in the GDPßS-treated OHCs, the shift of V cmpeak and increase of C mpeak were attenuated markedly. The shift of V cmpeak and increase of C mpeak after 10 min were 5.13 ± 10.46 mV and -0.55 ± 1.39 pF, respectively (n = 6). This study demonstrated that internally perfused GTPγS inhibited the MßCD effects and GDPßS inhibited the cholesterol effects, raising the possibility that G proteins may be involved in outer hair cell homeostasis as well as the possibility that cholesterol response may be G protein mediated. More study is required to clarify the detailed role of G proteins in the relation between cholesterol and the OHC cytoskeleton.

Daily short-term intratympanic dexamethasone treatment alone as an initial or salvage treatment for idiopathic sudden sensorineural hearing loss.

OBJECTIVE: Intratympanic (IT) steroid therapy has been proposed as an alternative treatment option for patients with idiopathic sudden sensorineural hearing loss (ISSNHL). However, the number and frequency of IT treatments and drug delivery methods remain to be determined. The purpose of this study was to evaluate the efficacy of daily short-term IT dexamethasone (DEX) treatment alone in ISSNHL patients using laser-assisted myringotomy (LAM) for the drug delivery route as an initial and/or salvage treatment. STUDY DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: Seventy-six ISSNHL patients receiving IT DEX. Patients with low-tone hearing loss, unilateral or bilateral fluctuating hearing loss or contralateral hearing loss were excluded. INTERVENTION: DEX (4 mg/ml) was injected through a perforation made by LAM. IT DEX administration was performed on 8 sequential days. MAIN OUTCOME MEASURES: Pre- and postprocedure hearing levels. The average hearing level was determined by 5 frequencies (250, 500, 1000, 2000 and 4000 Hz). RESULTS: Nineteen out of 76 patients fit the criteria for initial treatment in the study (group I), while 24 patients, who had failed systemic therapy, received salvage treatment (group S). The mean age of the patients in groups I and S was 56.2 years with a range from 31 to 73 years of age and 46.0 years with a range from 11 to 76 years of age, respectively. The mean number of days from onset of symptoms to IT therapy in groups I and S was 4.8 days with a range of 1-23 days and 15.3 days with a range of 6-28 days, respectively. In group I, 18 of the 19 patients (95%) showed improvement of more than 10 dB in the pure-tone audiogram, with a mean improvement of 40 dB. Twelve patients (63%) recovered completely and 16 patients (84%) demonstrated successful results with an improvement of more than 30 dB. In group S, 14 of the 24 patients (58%) showed improvement of more than 10 dB with a mean improvement of 16 dB. Two (8%) of the 7 patients (29%) with successful results recovered completely. CONCLUSIONS: Daily short-term IT DEX administration using LAM for ISSNHL patients without concurrent therapy showed a high response rate and high cure rate and proved to be an alternative therapeutic option to high-dose systemic steroids as a first- and/or second-line treatment.

Hearing impairment and cognitive function among a community-dwelling population in Japan.

BACKGROUND: Hearing impairment is a prevalent and chronic condition in older people. This study investigated the relationship between cognitive function and hearing impairment in a Japanese population. METHODS: A pure-tone average (0.5-2.0 kHz) was used to evaluate hearing impairment in 846 participants of the Iwaki Health Promotion Project who were aged at least 50 years old (310 men and 536 women). We also administered the Mini-Mental State Examination (MMSE), the Center for Epidemiologic Studies for Depression (CES-D) scale, Starkstein's apathy scale (AS) and the Short Form Health Survey Version 2 (SF-36v2). A multiple linear regression analysis assessed the association between hearing impairment and mental correlates. RESULTS: The overall prevalence of hearing impairment in this study population was 37.7%. The participants with hearing impairment were older and less educated compared to those with no hearing problems. We observed significant differences in the MMSE and AS scores between the mild/moderate to severe groups versus the non-impaired group. After adjusting for age, gender and amount of education, hearing impairment was significantly associated with MMSE and AS scores, but not with CES-D scores. Hearing impairment was significantly related to the social functioning (SF) and role emotional (RE) scores of the SF-36v2. CONCLUSIONS: Hearing impairment is common among older people and is associated with cognitive impairment, apathy and a poor health-related quality of life. Screening for and correcting hearing impairments might improve the quality of life and functional status of older patients.

Differential expression of topoisomerase IIalpha protein in salivary gland carcinomas: histogenetic and prognostic implications.

BACKGROUND: Salivary gland carcinomas are relatively uncommon heterogeneous malignancies characterized by locoregional invasion and distant metastasis. Topoisomerase IIalpha (topoIIalpha), located at chromosome 17q21-22, is considered a major mediator of cell proliferation and DNA replication. The purpose of this study was to evaluate the expression of topoIIalpha in various types of salivary gland tumors and its biological significance. METHODS: The protein expression of topoIIalpha was evaluated immunohistochemically in formalin-fixed, paraffin-embedded tissue from 54 salivary gland carcinomas and 20 benign tumors (10 pleomorphic adenomas and 10 Warthin's tumors). The primary salivary gland carcinoma specimens consisted of 17 adenoid cystic carcinomas, 7 adenocarcinomas not otherwise specified, 7 mucoepidermoid carcinomas, 6 salivary duct carcinomas, 3 acinic cell carcinomas, 3 carcinomas ex pleomorphic adenomas, 3 epithelial-myoepithelial carcinomas, 2 carcinosarcomas, 2 lymphoepithelial carcinomas, 2 myoepithelial carcinomas, 1 oncocytic carcinoma, and 1 squamous cell carcinoma. The associations between clinicopathological factors and outcome were analyzed. RESULTS: Of the 54 primary salivary gland carcinomas, 38 (70%) showed positive expression (> or = 10%) of topoIIalpha protein, and 16 carcinomas (30%) and all benign tumors were negative (p < 0.001). Expression of topoIIalpha was more frequently observed in salivary duct carcinoma, carcinoma ex pleomorphic adenoma, adenocarcinoma, and adenoid cystic carcinoma, solid type, and it was associated with advanced stage and shortened survival. CONCLUSION: The results of the present study suggest that topoIIalpha expression is associated with histologically aggressive subtypes and shortened survival. Furthermore, it may provide useful prognostic information and suggests the potential efficacy of topoIIalpha-targeting therapy in patients with salivary gland carcinoma.

[Treatment results of chemotherapy with S-1 for head and neck cancer].

A study of chemotherapy treatment with S-1 in patients with head and neck cancer was conducted in 20 patients with residual tumor after primary chemoradiotherapy, or recurrent tumors. Treatment courses consisted of oral administration of S-1 at a dose of 80 to 120 mg/day depending on the body surface area for 14 consecutive day followed by a 7- day rest period. The response rate in patients with residual tumors after primary chemoradiotherapy was 55.6%(5/9). In patients with recurrent tumors, the response rate was 0%(0/11), however, median survival time was 534.5 days. Therefore, S-1 seemed to be useful for the treatment of patients with head and neck cancer from the point of QOL.

Effects of small interfering RNA targeting thymidylate synthase on survival of ACC3 cells from salivary adenoid cystic carcinoma.

BACKGROUND: Thymidylate synthase (TS) is an important target for chemotherapeutic treatment of cancer and high expression of TS has been associated with poor prognosis or refractory disease in several cancers including colorectal and head and neck cancer. Although TS is known to regulate cell cycles and transcription factors, its potency as a therapeutic target has not been fully explored in adenoid cystic carcinoma (ACC). METHODS: An ACC cell line (ACC3) was transfected with siRNA targeting the TS gene and inhibition of cell growth and induction of apoptosis-associated molecules were evaluated in vitro. In addition, the in vivo effect of TS siRNA on tumor progression was assessed using a xenograft model. RESULTS: Our results demonstrated that ACC3 cells showed significantly higher TS expression than non-cancer cell lines and the induction of TS siRNA led to inhibition of cell proliferation. The effect was associated with an increase in p53, p21, and active caspase-3 and S-phase accumulation. We also found up-regulation of spermidine/spermine N1-acetyltransferase (SSAT), a polyamine metabolic enzyme. Furthermore, treatment with TS siRNA delivered by atelocollagen showed a significant cytostatic effect through the induction of apoptosis in a xenograft model. CONCLUSION: TS may be an important therapeutic target and siRNA targeting TS may be of potential therapeutic value in ACC.

Localization of dopamine receptor subtypes in the rat spiral ganglion.

Although dopaminergic neurons are thought to exist in the lateral olivocochlear efferent system and modulate the afferent nerve activity, the distribution of dopamine (DA) receptor subtypes is still obscure. In the present study, we investigated the localization of five subtypes of DA receptor (D1-5) by immunocytochemical analysis and the gene expression of D1-5 using RT-PCR procedure in the rat cochlea. Most, but not all, spiral ganglion neurons were immunolabeled with all the anti-DA receptor subunit antibodies and faint punctuate immunoreactivities were observed in inner hair cell regions. Gene expression for all receptors was detected. These results suggest that all DA receptor subtypes are present in spiral ganglion cells, and potentially regulate afferent neurotransmission.

Endoscopic transtympanic tympanoplasty in the treatment of conductive hearing loss: early results.

OBJECTIVE: We describe our initial experience with endoscopic transtympanic tympanoplasty and evaluate whether this approach is adequate and minimally invasive in the treatment of conductive hearing loss. STUDY DESIGN: Prospective trial. SETTING: University hospital. PATIENTS: Nine patients underwent endoscopic transtympanic tympanoplasty, with an average follow-up period of 17 months. Presurgical diagnosis was made by transtympanic endoscopy through a perforation made by OtoScan laser-assisted myringotomy in the outpatient clinic. METHODS: With clean endoscopic visualization, ossiculoplasty was performed by inserting a trimmed tragal cartilage through the myringotomy perforation made by laser-assisted myringotomy. Two types of ossiculoplasty were performed: columella reconstruction and interposition. The tympanic membrane was covered with a chitin membrane or sealed with a small piece of perichondrium from the tragal cartilage. MAIN OUTCOME MEASURES: Perioperative and postoperative complications and preoperative and postoperative hearing. RESULTS: Endoscopic transtympanic tympanoplasty with columella and endoscopic transtympanic tympanoplasty with interposition were performed in seven and two patients, respectively. Insertion of the cartilage was performed without conversion to a conventional otomicroscopic technique. The average hearing level before the operation was 59 dB. After the endoscopic transtympanic tympanoplasty, the average improved to the level of 27 dB, with an average air-bone gap of 11 dB. The myringotomy perforation was closed within 2 to 3 weeks. CONCLUSION: As opposed to conventional methods, this procedure does not require surgical exposure such as otosclerosis drilling and skin incision, and avoids the substantial risk of unnecessary injury to the chorda tympani. Endoscopic transtympanic tympanoplasty for a disrupted ossicular chain is an adequate and minimally invasive procedure and should prove to be a useful surgical procedure in future endoscopic tympanoplasty.

Comparison of intratympanic and intravenous dexamethasone treatment on sudden sensorineural hearing loss with diabetes.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of intratympanic administration of dexamethasone (IT-DEX) treatment on sudden sensorineural hearing loss (SSNHL) patients with diabetes by comparing the results with intravenous administration of dexamethasone (IV-DEX) treatment. STUDY DESIGN: Comparative study. SETTING: University hospital and affiliated hospital. PATIENTS: Ten sequential SSNHL patients with diabetes receiving IT-DEX and 21 sequential SSNHL patients with diabetes receiving IV-DEX. Patients with low tone hearing loss were excluded. INTERVENTION: In the IT-DEX group, two methods were applied to deliver DEX (4 mg/ml): injection through a perforation made by laser-assisted myringotomy or through a tympanostomy tube. IT-DEX administration was performed on 8 sequential days. In the IV-DEX group, DEX was administrated intravenously starting from an amount of 8 mg/d followed by taped doses for 10 days. MAIN OUTCOME MEASURES: Preprocedure and postprocedure hearing levels and complications. RESULTS: In the IT-DEX group, the average hearing level before the treatment was 79 dB. Overall, all 10 patients showed improvement of more than 10 dB in the pure-tone audiogram, with a mean improvement of 41 dB. Seven patients (70%) demonstrated successful results, and four recovered completely. In the IV-DEX group, 14 (67%) of the 21 patients showed improvement of more than 10 dB with a mean improvement of 25 dB. Thirteen patients (62%) demonstrated successful results. Free blood sugar during and after the IT-DEX treatment remained below the pretreatment levels, whereas four patients in the IV-DEX group demonstrated worsening of the hyperglycemia. CONCLUSION: IT-DEX treatment is at least as effective as IV-DEX treatment for SSNHL patients with diabetes.

Analysis of 95 cases of squamous cell carcinoma of the external and middle ear.

OBJECTIVE: To analyze the clinical characteristics, 5-year survival, and prognostic factors of squamous cell carcinoma (SCC) of the external and middle ear. METHODS: A multi institutional study. Ninety five cases of patients from 10 institutions were reviewed on their age and sex distribution, initial complaints, stages, tumor locations, treatments, and outcomes. Prognostic factors were discussed based on the Pittsburgh staging system. RESULTS: This disease seems to appear in the elderly with a peak age of 50-69 years. Males appear to be more predisposed than females with an odd ratio of 1.7. The initial complaints were not typical, while 12.6% of patients presented a history of recurrent otitis externa or chronic otitis media. Regional metastasis was recognized in 13.7% of patients, while no distant metastasis was confirmed. SCC located in the external ear could be detected in an earlier stage than that in the middle ear. The overall 5-year survival was 66.8% in total, and decreased significantly with stage. SCC in stages I and II was susceptible to each therapeutic strategy with a 5-year survival of 100%. Operation combined with radiotherapy and/or chemotherapy was the major treatment for stages III and IV SCC, while radiotherapy and chemotherapy were applied mainly for those who had been considered inappropriate for operation. The overall survival was 67.2% for stage III and 29.5% for stage IV, and operation with pathologically tumor free margin could improve the survival to 72.7% when combined with radio- and chemotherapy. Stage, completeness of operation with tumor free margin, recurrence, and metastasis have significant influence on survival. CONCLUSION: Local infiltration seems to be the main behavior of SCC in the external and middle ear. Early diagnosis and treatment were important because SCC in the earlier stage is susceptible to be cured. For tumors of advanced stage, operation should be performed with pathologically tumor free margin, and operation combined with radiotherapy and chemotherapy could improve the survival. Tumor stage adds more influence on survival than its location. Recurrence and metastasis mainly occur in advanced stages and result in a poor survival.

[Prediction of the date of Japanese cedar pollen release in Aomori Prefecture].

When we treat patients with pollen allergy, we require correct information about pollen release. The total count of pollen and the date of first pollen release are strongly influenced by local weather conditions, so we wanted to predict local pollen release. Patients have degrees of sensitivity to pollen, with symptoms triggered in some cases by only small amounts. Therefore, we wanted to determine the previous dates of first pollen release (A), the first of two consecutive dates when one (count/cm2) or more grains were released (B), and the first of two consecutive dates when ten (count/cm2) or more grains were released (C). Aomori Prefecture has three different weather zones because it is surrounded by three oceans the Sea of Japan, the Pacific Ocean, and Mutsu Bay. We predicted pollen release in the major cities--Aomori, Hirosaki, and Hachinohe. Using nine years (1996-2004) of temperature data for each city from January 1 through February 1, we recorded the number of days in which the daily highest temperature was higher than each of five set temperatures (0 degree C, 1 degree C, 2 degrees C, 3 degrees C, 4 degrees C) up to the dates of A, B, and C. Multiple recordings were made for each year with the initial date of recording staggered at 10-day intervals. We then calculated the standard deviation and the efficient of variation of total days and totals of temperatures over set temperatures. For Aomori, results indicated that A was predicted as day 19 with temperatures over 4 degrees C after January 21. B was day 23 over 4 degrees C after January 21. C was the day 31 with over 4 degrees C after January 21. For Hirosaki, A was expected to be day 26 having temperatures over 0 degrees C after February 1. B was day 21 over 3 degrees C after February 1. C was day 30 over 3 degrees C after January 21. For Hachinohe, A was day 34 with temperatures over 0 degrees C after February 1. B was day 33 over 1 degree C after January 21. C was day 27 over 4 degrees C after January 21. We examined the day of pollen release in 2005.

Carcinoma ex pleomorphic adenoma of the parotid gland: a multi-institutional retrospective analysis in the Northern Japan Head and Neck Cancer Society.

CONCLUSION: The 3-year progression-free survival rate of non-invasive salivary duct carcinoma (SDC) or adenocarcinoma not otherwise specified (NOS) was significantly better than that of invasive SDC or adenocarcinoma NOS in Carcinoma ex pleomorphic adenoma (CXPA). The presence of invasion is an important prognostic factor for SDC and adenocarcinoma NOS in CXPA. OBJECTIVES: CXPA is a rare parotid gland malignant tumor for which therapy is not yet standardized. The purpose of this study was to review the characteristics of CXPA patients and to analyze their outcomes in the Northern Japan Head and Neck Cancer Society. METHOD: The medical records of 33 patients who had been provided initial treatment in 12 institutes of northern Japan from 2002-2011 were reviewed as a multi-institutional retrospective study. RESULTS: The 3-year overall and progression-free survival rate of all patients was 79.9% and 76.8%, respectively. Both the 3-year overall and progression-free survival rates were 87.5% for patients with non-invasive SDC or adenocarcinoma NOS. The 3-year overall and progression-free survival rates for patients with invasive SDC or adenocarcinoma NOS were 60.4% and 30.5%, respectively. The progression-free survival rates for patients with invasive SDC or adenocarcinoma NOS was significantly poor (p < 0.05).

Evaluation of attic retraction pockets by microendoscopy.

OBJECTIVE: Attic retraction pockets (RPs) are one of the important sequelae of otitis media with effusion and are classified on the basis of the findings of otoscopy or otomicroscopy. It is unclear when and how RPs turn into cholesteatomas. We compared the findings of RPs obtained with the use of a microendoscope with those from an otomicroscope to determine the extension of RPs. STUDY DESIGN: Comparative study. PATIENTS: Twenty-seven attic RPs (Tos type III or IV) and 10 precholesteatomas previously classified under an otomicroscope were reexamined. MAIN OUTCOME MEASURES: A high-resolution, fine, rigid microendoscope with an outer diameter of 1.0 mm was used to observe the extension of a retraction. In addition, to confirm the extent of the RP, computed tomography (CT) scans using water as the contrast media were performed in representative cases. RESULTS: Endoscopy with the microendoscope revealed that in 59%, the RP was deeper than indicated by the initial otomicroscopic estimation, suggesting that the extension of the RP was underestimated. The findings of water-enhanced CT scans were comparable with the endoscopic findings. The bottom was observable with the microendoscope and the otomicroscope in 20 (74%) and 11 (41%) of 27 RPs, respectively. Seven ears had a deeper RP, which extended beyond the incudomallear joint. Of the 10 precholesteatoma cases, in which the bottoms were not visible with an otomicroscope or conventional endoscopes, the microendoscope revealed the bottom in 5 (50%). CONCLUSION: On the basis of the observations of our study, we suggest that reexamination of cases of RP classified as Tos type III or IV, preferably with a microendoscope, if available, and assessment of the depth of the RP using water-enhanced CT, would be useful and that careful follow-up is necessary for deep RPs because of a potential risk of development into cholesteatoma.

Inflammatory pseudotumour (plasma cell granuloma) arising in the maxillary sinus.

CONCLUSIONS: Inflammatory pseudotumours in the maxillary sinus may present as malignant tumours and manifest locally aggressive features characteristic of such tumours. Despite their locally destructive features, they pursue a benign course after local excision. OBJECTIVE: Inflammatory pseudotumour (plasma cell granuloma) is an uncommon non-neoplastic lesion comprising a proliferation of spindle myofibroblasts and chronic inflammatory cells. Despite its benign histopathological nature, it may exhibit aggressive behaviour that is yet to be characterized in the head and neck area. MATERIAL AND METHODS: We present the cases of two adult patients with inflammatory pseudotumour arising from the maxillary sinus. Immunohistochemistry and polymerase chain reaction for immunoglobulin from tissue sections were performed to confirm the polyclonality of the infiltrating plasma cells. RESULTS: CT and MRI disclosed expansive soft masses eroding surrounding soft and bony tissues. Histopathologically, the lesions were unencapsulated and composed of numerous plasma cells, histiocytes and spindle cells with minimal nuclear pleomorphism.

Office-based endoscopic procedure for diagnosis in conductive hearing loss cases using OtoScan Laser-Assisted Myringotomy.

OBJECTIVES/HYPOTHESIS: In conductive hearing loss (HL), even though preoperative examinations including audiometry, tympanometry, and computed tomography (CT) scan are applied, exploratory tympanotomy is necessary to make an exact diagnosis of ossicular interruption and stapes fixation. Precise preoperative diagnosis would be useful for patient counseling, surgical indications, and planning. The advantages of office-based OtoScan laser-assisted myringotomy (LAM), which makes a circular and non-hemorrhagic perforation, prompted us to investigate other uses of LAM in addition to ventilation and drainage of the tympanic cavity. To make presurgical diagnosis in conductive HL, endoscopes with an outer diameter of 1.7 or 1.9 mm were used to inspect the middle ear pathology through perforations with a diameter of 2 mm made by LAM. METHODS: In the outpatient clinic, a circular perforation with a diameter of 2 mm was made in the tympanic membrane with LAM. An endoscopic view of the ossicular chain through a 70degrees angled tip endoscope held immediately to the outer side of the perforation was obtained to diagnose conduction disturbance loci in conductive HL cases. RESULTS: Ossicular chain abnormalities were easily and safely detected by clean endoscopic views obtained through a nonhemorrhagic circular perforation. When necessary, insertion of the tip of the endoscope into the tympanic cavity provided additional views of epitympanum. CONCLUSION: We suggest that transtympanic endoscopy through the perforation made by LAM is an effective and safe office-based procedure for diagnosis in conductive HL cases and could be an alternative procedure to replace exploratory tympanotomy.

Localization of gamma-aminobutyric acid A receptor subunits in the rat spiral ganglion and organ of Corti.

Gamma-aminobutyric acid (GABA) is thought to be the major inhibitory neurotransmitter in the central nervous system. Although it is distributed in the olivo-cochlear bundles, which constitute the mammalian cochlear efferent system, its function in the cochlea is still obscure. In this study, we investigated the localization of GABAa receptor subunits (alpha1-6, beta1-3, gamma) in the rat cochlea in order to determine the role of GABA in the cochlea. Most spiral ganglion cells were intensely immunolabeled with all the anti-GABAa receptor subunit antibodies. In the organ of Corti, punctate immunoreactivities were observed in inner hair cell regions corresponding to the distribution of GABA. These data suggest that GABAa receptor was present in afferent nerve terminals in inner hair cell regions, and that GABA regulated afferent nerve transmission contacting efferent nerve endings by means of the axo-dendritic synapse function.

[Prediction of Japanese cedar pollen emission in a snowy area--surveillance in Hirosaki City].

Japanese cedar is the most common pollinosis allergen in Japan. Predictions of total pollen counts and the first 2 or more days of the Japanese cedar pollen season are beneficial to patients. We developed predictive methods for those 2 factors in Hirosaki. We conducted an atmospheric Japanese cedar pollen survey from 1996 to 2002 in Hirosaki and compared yearly data with the male flowering index counted in 50 cedar trees in the preceding autumn. The male flowering index correlated highly positively with total cedar pollen counts in regression analysis, indicating its usefulness in predicting total pollen counts. Although the number of days from January 1 to the first day of continuous pollen emission showed no correlation with the cumulative maximum temperature during these days, the number of days from the day of first detection of pollen emission (minimum of 1 particle per sq. cm) to the first day of continuous pollen emission correlated highly with the cumulative maximum temperature and cumulative amount of snowfall on these days, suggesting that it is possible to predict the first day of continuous pollen emission by the cumulated daily maximum temperature after the day of first detection of pollen emission.

[A case of enlarged vestibular aqueduct syndrome with PDS gene mutations].

Enlarged vestibular aqueduct (EVA) is an inner ear anomaly occasionally associated with sensorineural hearing loss (SNHL) and/or dizziness. Recent genetic studies indicate that mutations in the PDS gene may cause EVA. A 10-year-old EVA patient who had undergone annual hearing tests for 7 years had an aunt and cousin who also had hearing loss and EVA, so genetic examinations were conducted for a possible genetic link. Two new PDS gene mutations, S610X and S657N, were found in all 3, including the proband. We discuss the importance of genetic analysis, which offers new insight into SNHL diagnosis and treatment in children.

B-cell malignant lymphoma presenting as otitis media and mastoiditis associated with sinus thrombosis.

Cerebral venous thrombosis as a manifestation of paraneoplastic angitis and otitis media, revealing non-Hodgkin B-cell lymphoma (NHBL), is extremely rare. A 57-year-old woman presented with headache, auditory disturbance and recalcitrant otitis media. Magnetic resonance imaging showed brain edema in the temporal lobe and transverse sinus thrombosis. External drainage under antibiotic treatment was repeated based on a diagnosis of invasive otitis media and mastoiditis associated with infectious sinus thrombosis, but the condition deteriorated progressively. Open surgery for otitis media was performed 6 years after the initial symptoms and after a tumorous lesion had been detected in the middle ear. Pathological findings revealed NHBL. We report a rare case of NHBL presenting as otitis media and mastoiditis associated with sinus thrombosis, and a literature review.

Immunoelectron microscopic analysis of neurotoxic effect of glutamate in the vestibular end organs during ischemia.

CONCLUSION: The excessive glutamate released from the type I and type II hair cells and the supporting cells injure the bouton-type endings and the nerve chalices in 30 min ischemia, and neuronal damage of glutamate was slight in 10 min ischemia. OBJECTIVE: In the present study, we investigated by means of post-embedding immunoelectron microscopic analysis whether neuronal damage in the vestibular end organs is associated with the change of cellular glutamate concentration during ischemia. METHODS: Transient local anoxia (10 min, 30 min) of guinea pig inner ear was induced by pressing the left labyrinthine artery. The right sides were used as controls. The morphological changes of the vestibular end organs and the areal gold particle densities representing glutamate were compared in the ischemia side and the control side. RESULTS: The areal gold particle densities of the type I and type II hair cells and the supporting cells in the ischemic side were lower than those of the control side. There were no remarkable morphological changes compared to the control side in 10 min ischemia. In 30 min ischemia, the bouton-type endings were swollen and intercellular spaces between the type I hair cells and the nerve chalices were enlarged.