The effect of cochlear implants on cognitive function in older adults: A prospective, longitudinal 2-year follow-up study.

OBJECTIVES: It is shown that eliminating hearing loss in mid-life may reduce the risk for deterioration in cognitive function. Cochlear implantation (CI) is the only available therapy that can eliminate hearing loss in patients who suffer from profound sensorineural hearing loss. This suggests there may be positive effects of hearing level on cognition in older adults following CI. Therefore, the purpose of this study is to clarify whether cognitive function can be improved or maintained using cochlear implants in older adult patients with hearing impairments. METHODS: Data for patients that underwent CI surgery for profound bilateral sensorineural hearing loss were collected prospectively. Patients aged 65 years and older were recruited at our university hospital from 2013 to 2017. Twenty-one patients (age range: 65-80 years) were included in this study. The primary outcome measurement was the change in cognitive function three points assessed by Mini-Mental State Examination (MMSE): preoperatively, and at 1 and 2 years after surgery. The secondary outcome measurements were the followings; the Nijmegen Cochlear Implant Questionnaire (NCIQ), the Self-Rating Depression Scale (SDS), and hearing and speech recognition threshold assessment before CI, and 1 and 2 years after CI. Differences in MMSE scores were compared for statistical significance using the Friedman test. The Wilcoxon signed-rank test was used as a post hoc test. Possible correlations between MMSE scores and NCIQ subdomain scores 2 years after surgery were evaluated with Spearman's tests. Statistical significance was defined as a p-value <0.05. RESULTS: CI recipients showed significant improvement in MMSE scores. This improvement peaked 1 year after CI surgery. The postoperative MMSE score was correlated with the NCIQ speech production score but not with the other five NCIQ subdomains. There was no correlation between MMSE score and speech recognition. CONCLUSION: Speech production is important to improve cognitive function after CI, and this improvement peaked 1 year after CI. Although severe or profound hearing loss in older adults worsens the natural course of cognitive function decline, CI has positive impacts on cognitive function even if MMSE scores decrease 1 year after the peak (i.e., 2 years after CI). Talking with others based on hearing is crucial to improve cognitive function. We should encourage older adult patients to take many opportunities to talk with others after CI surgery.

Osteoclasts Modulate Bone Erosion in Cholesteatoma via RANKL Signaling.

Cholesteatoma starts as a retraction of the tympanic membrane and expands into the middle ear, eroding the surrounding bone and causing hearing loss and other serious complications such as brain abscess and meningitis. Currently, the only effective treatment is complete surgical removal, but the recurrence rate is relatively high. In rheumatoid arthritis (RA), osteoclasts are known to be responsible for bone erosion and undergo differentiation and activation by receptor activator of NF-κB ligand (RANKL), which is secreted by synovial fibroblasts, T cells, and B cells. On the other hand, the mechanism of bone erosion in cholesteatoma is still controversial. In this study, we found that a significantly larger number of osteoclasts were observed on the eroded bone adjacent to cholesteatomas than in unaffected areas, and that fibroblasts in the cholesteatoma perimatrix expressed RANKL. We also investigated upstream transcription factors of RANKL using RNA sequencing results obtained via Ingenuity Pathways Analysis, a tool that identifies relevant targets in molecular biology systems. The concentrations of four candidate factors, namely interleukin-1ß, interleukin-6, tumor necrosis factor α, and prostaglandin E2, were increased in cholesteatomas compared with normal skin. Furthermore, interleukin-1ß was expressed in infiltrating inflammatory cells in the cholesteatoma perimatrix. This is the first report demonstrating that a larger-than-normal number of osteoclasts are present in cholesteatoma, and that the disease involves upregulation of factors related to osteoclast activation. Our study elucidates the molecular basis underlying bone erosion in cholesteatoma.

Fibroblast growth factor 12 is expressed in spiral and vestibular ganglia and necessary for auditory and equilibrium function.

We investigated fibroblast growth factor 12 (FGF12) as a transcript enriched in the inner ear by searching published cDNA library databases. FGF12 is a fibroblast growth factor homologous factor, a subset of the FGF superfamily. To date, its localisation and function in the inner ear have not been determined. Here, we show that FGF12 mRNA is localised in spiral ganglion neurons (SGNs) and the vestibular ganglion. We also show that FGF12 protein is localised in SGNs, the vestibular ganglion, and nerve fibres extending beneath hair cells. Moreover, we investigated FGF12 function in auditory and vestibular systems using Fgf12-knockout (FGF12-KO) mice generated with CRISPR/Cas9 technology. Our results show that the inner ear morphology of FGF12-KO mice is not significantly different compared with wild-type mice. However, FGF12-KO mice exhibited an increased hearing threshold, as measured by the auditory brainstem response, as well as deficits in rotarod and balance beam performance tests. These results suggest that FGF12 is necessary for normal auditory and equilibrium function.

Epiphycan is specifically expressed in cochlear supporting cells and is necessary for normal hearing.

The study of inner ear specific transcripts has revealed novel information about hereditary hearing loss and a mechanism of normal hearing. In this study, by analyzing a published cDNA library, we focused on Epiphycan (Epyc), a member of the small leucine-rich repeat proteoglycan family, whose transcript is enriched in the inner ear. Epyc mRNA was expressed abundantly and specifically in adult mice cochleae and was localized in supporting cells within the organ of Corti of both neonatal and adult mice. To examine the function of Epyc, we generated Epyc knockout (KO) mice using the CRISPR/Cas9 system. Epyc KO mice cochleae exhibited normal morphology. However, measurement of the auditory brain-stem response in Epyc KO mice revealed an elevated hearing threshold above 16 kHz frequency. This study suggests that Epyc is necessary for normal auditory function.

Unilateral posterior canal-plugging surgery for intractable bilateral posterior canal-type benign paroxysmal positional vertigo.

OBJECTIVE: To investigate the effectiveness of unilateral posterior semicircular canal (PSCC)-plugging surgery for patients with intractable bilateral PSCC-type benign paroxysmal positional vertigo (P-BPPV). METHODS: From July 2011 to December 2015, we diagnosed 136 patients with P-BPPV. Of these, 3 patients had bilateral P-BPPV, and in 2 of the 3, the condition had been refractory to conservative treatment for more than 1 year. We planned a staged PSCC-plugging surgery for these 2 patients; initially one side was treated, and the contralateral side was treated 6 months later. RESULTS: After the first surgery, both patients experienced improvement in symptoms of vertigo and nystagmus on the operated side and no change on the non-operated side. Patients underwent the Epley maneuver for the non-operated side. In one case, the non-operated side was cured. In the other case, although the P-BPPV was not completely resolved, the patient was satisfied with the result of unilateral surgery because he was now able to turn in bed to the operated side without vertigo. Before surgery, he had experienced vertigo when turning even slightly in bed. CONCLUSION: We propose that even unilateral PSCC-plugging surgery is effective for some patients with intractable bilateral P-BPPV.

Office-based differential diagnosis of transient and persistent geotropic positional nystagmus in patients with horizontal canal type of benign paroxysmal positional vertigo.

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.

Paroxysmal vertigo with nystagmus in children.

INTRODUCTION: A pathological nystagmus is an objective sign that a patient feels vertigo. However, there have been few opportunities to observe and record pathological nystagmus during a paroxysmal vertigo attack. Furthermore, it can be difficult to obtain cooperation in pediatric patients. We present two cases of paroxysmal vertigo in children in whom we successfully recorded and analyzed their pathological nystagmus during a vertigo attack. METHODS: Of a total sample of 4349 patients seen at our hospital for dizziness in the last decade, a retrospective analysis revealed that 68 were children (<15 years old; 1.6%). Of these 68 children, we successfully identified pathological nystagmus during paroxysmal vertigo in only two (2.9%). RESULTS: Case 1 was a 4-year-old girl. She felt vertigo the strongest when her left ear was down in the supine position. We observed and recorded her nystagmus during a vertigo attack with her mother's permission. Her positional nystagmus in the supine position was horizontal persistent apogeotropic nystagmus. Rightward nystagmus in the left-ear-down supine position was stronger than leftward nystagmus in the right-ear-down supine position. Therefore, the diagnosis was right lateral canal type of benign paroxysmal positional vertigo, of which the pathophysiology was cupulolithiasis. The other patient was an 11-year-old boy. He had a family history of migraines. His vertigo attacks occurred after onset of a severe migraine and lasted between 2 and 48 h. During an attack that we observed, he showed nystagmus, which was direction-fixed right torsional and rightward in darkness. His mother had noticed that his eyes moved abnormally and that his left eye did not shift to the left side when he looked leftward. He was old enough to clearly express his own symptoms. Other neurological examinations were normal. The diagnosis was vestibular migraine. CONCLUSIONS: We analyzed a pathological nystagmus during paroxysmal vertigo in two children. We conclude that children can be diagnosed with a combination of careful history taking and accurate examinations of a pathological nystagmus.

Intercellular Communication between Keratinocytes and Fibroblasts Induces Local Osteoclast Differentiation: a Mechanism Underlying Cholesteatoma-Induced Bone Destruction.

Bone homeostasis is maintained by a balance in activity between bone-resorbing osteoclasts and bone-forming osteoblasts. Shifting the balance toward bone resorption causes osteolytic bone diseases such as rheumatoid arthritis and periodontitis. Osteoclast differentiation is regulated by receptor activator of nuclear factor κB ligand (RANKL), which, under some pathological conditions, is produced by T and B lymphocytes and synoviocytes. However, the mechanism underlying bone destruction in other diseases is little understood. Bone destruction caused by cholesteatoma, an epidermal cyst in the middle ear resulting from hyperproliferation of keratinizing squamous epithelium, can lead to lethal complications. In this study, we succeeded in generating a model for cholesteatoma, epidermal cyst-like tissue, which has the potential for inducing osteoclastogenesis in mice. Furthermore, an in vitro coculture system composed of keratinocytes, fibroblasts, and osteoclast precursors was used to demonstrate that keratinocytes stimulate osteoclast differentiation through the induction of RANKL in fibroblasts. Thus, this study demonstrates that intercellular communication between keratinocytes and fibroblasts is involved in the differentiation and function of osteoclasts, which may provide the molecular basis of a new therapeutic strategy for cholesteatoma-induced bone destruction.

Gadolinium contrast-enhanced MRI reveals cystic lateral semicircular canal contents.

CONCLUSION: Contrast-enhanced magnetic resonance imaging (MRI) reveals variations in the endolymphatic morphology of the cystic lateral semicircular canal (CLSC) that correlate with inner ear function. This report is the first to suggest a relationship between the morphology and function of this common inner ear malformation in clinical cases. OBJECTIVES: This study investigated the radiological and functional findings of a common inner ear malformation using computed tomography (CT), gadolinium contrast-enhanced magnetic resonance imaging (MRI), caloric testing, and cervical and ocular vestibular evoked myogenic potential (VEMP) testing. METHOD: Four ears in three patients who were radiologically diagnosed with a CLSC and a normal cochlea on high-resolution CT and contrast-enhanced MRI were included. Semicircular canal and vestibular functions were analyzed using the caloric test and cervical and ocular VEMP testing. RESULTS: Unilateral and bilateral cystic canals were found in two and one patients, respectively. In the first patient, the malformed vestibule and cystic space were separate on imaging, and perilymph filled the cystic space. The functional test results were normal. In the second patient, endolymph filled both cystic spaces, and the functional responses were poor. In the third patient, endolymph filled the cystic space, and the ear did not respond during functional testing.

Effects of endolymphatic sac decompression surgery on vertigo and hearing in patients with bilateral Ménière's disease.

OBJECTIVE: The aim of the present study, which involved a 2-year observation period and a nonsurgical control group, was to determine whether endolymphatic sac decompression surgery (ESDS) has the potential to prevent the progression of vertigo and hearing loss in patients with intractable bilateral Ménière's disease (MD). STUDY DESIGN: Prospective case-control study. SETTING: Tertiary referral center. METHODS: Between 1996 and 2008, we subjected 67 patients with intractable bilateral MD to ESDS and local corticosteroid treatment. Another 34 patients with intractable bilateral MD who declined ESDS were treated with the best available medical therapies. All of the patients underwent regular follow-up examinations for at least 2 years. RESULTS: Vertigo was resolved in 22 of 34 patients in the non-ESDS group and 60 of 67 patients in the ESDS group (p = 0.055, Fisher's exact test). Of the 24 patients in the non-ESDS group and 55 patients in the ESDS group in whom the ipsilateral ear (the treated ear) exhibited worse hearing function than the contralateral ear, the hearing level of the former ear was preserved in 13 and 52 patients, respectively (p = 0.007, Fisher's exact test). Of the 10 patients in the nonsurgical group and 12 patients in the surgical group in whom the ipsilateral ear exhibited better hearing function than the contralateral ear, the hearing level of the former ear was preserved in 2 and 11 patients, respectively (p = 0.035, Fisher's exact test). CONCLUSION: The present findings suggest that ESDS combined with local corticosteroid treatment can control progressive hearing loss in both ears in patients with bilateral MD at least during the first 2 postoperative years.

Chronic otitis media with cholesteatoma with canal fistula and bone conduction threshold after tympanoplasty with mastoidectomy.

OBJECTIVE: To understand the third mobile window effect of chronic otitis media with cholesteatoma with inner ear fistula on the bone conduction threshold, we examined changes in the bone conduction audiogram after tympanoplasty with mastoidectomy for chronic otitis media with cholesteatoma with canal fistula. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: According to the intraoperative classification of Dornhoffer and Milewski, we focused especially on Type IIa (anatomic bony fistula with no perilymph leak). We checked the bone conduction threshold at least 3 times: just before, just after, and 6 months after surgery in 20 ears with Type IIa lateral semicircular canal fistula. INTERVENTION: Tympanoplasty with mastoidectomy. MAIN OUTCOME MEASURE: Bone conduction thresholds before and after tympanoplasty with mastoidectomy. RESULTS: Compared with the preoperative bone conduction threshold, 6 cases were better, 12 cases were unchanged, and 2 cases were worse within the first postoperative week. Finally, 1 case was better, 15 cases were unchanged, and 4 cases were worse at the sixth postoperative month. Patients with a better bone conduction threshold in the low-tone frequencies immediately after surgery had a tendency to show no preoperative fistula symptoms. Postoperative spontaneous nystagmus had a tendency to be observed in patients with a worse bone conduction threshold in the high-tone frequencies. CONCLUSION: The better bone conduction threshold at low-tone frequencies immediately after tympanoplasty with mastoidectomy and no preoperative fistula symptoms might imply the third mobile window theory. The worse bone conduction threshold in high-tone frequencies with spontaneous nystagmus after surgery might indicate inner ear damage.

Does endolymphatic sac decompression surgery prevent bilateral development of unilateral Ménière disease?

OBJECTIVES/HYPOTHESIS: The aim of the study was to elucidate whether endolymphatic sac decompression surgery (ESDS) has the potential to prevent unilateral Ménière disease (MD) from becoming bilateral. STUDY DESIGN: Prospective case-control study at tertiary referral center. METHODS: Between 1996 and 2008, we performed a glycerol test (G-test) and electrocochleography (ECoG) on 237 patients with intractable unilateral MD. We performed ESDS on 179 patients (144 with no endolymphatic hydrops and 35 with silent endolymphatic hydrops in the contralateral ear). The other 58 patients (40 without endolymphatic hydrops and 18 with silent endolymphatic hydrops in the contralateral ear) were given available medical treatments. All underwent regular follow-up for at least 5 years. RESULTS: Altogether, 22.4% (53 of 237) of patients with clinically diagnosed unilateral intractable MD had silent endolymphatic hydrops in the contralateral ear using G-test and ECoG. In the nonsurgical group, six of 40 patients with unilateral MD with no endolymphatic hydrops in the contralateral ear developed bilateral disease, whereas in the surgical group 12 of 144 patients did so (P = .231, Fisher test). In the nonsurgical group, nine of 18 patients with unilateral MD and silent endolymphatic hydrops developed the disease in the contralateral ear, whereas in the surgical group six of 35 patients developed bilateral disease (P = .022, Fisher test). CONCLUSIONS: The present findings suggest that ESDS may decrease the incidence of developing MD in silent endolymphatic hydronic contralateral ears diagnosed with G-test and ECoG within the first 5 postoperative years.

[Endolymphatic hydrops detected with inner ear gd contrast-enhanced MRI; comparison between administration routes or with ECochG or glycerol test].

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.

Psychological condition in patients with intractable Meniere's disease.

CONCLUSIONS: Physicians should consider additional treatment strategies for Meniere's disease patients with a long history of disease and hearing loss in the secondary affected ear and also provide psychological support regarding future progressive bilateral hearing loss. OBJECTIVES: To treat intractable Meniere's disease patients effectively, we need to understand the psychological condition of each patient. We examined the state of neurosis and depression in patients and correlated this with demographic and background information. METHODS: Between 1998 and 2009, we enrolled 207 patients with intractable Meniere's disease in this prospective study. We used the Cornell Medical Index and the Self-rating Depression Scale to evaluate their psychological condition. We also obtained demographic and background information relating to sex, age, duration of disease, vertigo frequency, hearing level in bilateral sides, and plasma vasopressin level. RESULTS: Neurosis and depression was diagnosed in 40.1% and 60.4%, respectively, of patients with intractable Meniere's disease. Our results showed that surgical treatment significantly improved vertigo and hearing ability in patients with no psychological symptoms compared with those exhibiting psychological symptoms. Patients with a longer duration and worse hearing level in the secondary affected ear had a significantly higher incidence of mental illness than those with a shorter duration and better level of hearing.

Pseudo-anterior canalolithiasis.

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.

Long-term results of endolymphatic sac drainage with local steroids for intractable Meniere's disease.

OBJECTIVES: Meniere's disease is a common inner ear disease characterized by vertigo, hearing loss and tinnitus. Since Meniere's disease is thought to be triggered by an immune insult to inner ear hydrops, we examined endolymphatic sac drainage with intra-endolymphatic sac application of large doses of steroids for intractable Meniere's patients and observed long-term results from 2 years to over a decade until 13 years. METHODS: Between 1998 and 2009, we enrolled and assigned 286 intractable Meniere's patients to two groups: group-I (G-I) included patients who underwent endolymphatic sac drainage with steroid instillation and group-II (G-II) included those who declined endolymphatic sac drainage. Definitive spells and hearing improvement in these two groups were determined for 2-13 years after treatment. RESULTS: According to the established criteria, vertigo was completely controlled in 88% of patients in G-I in the 2nd year, in 73% in the 12th year and in 70% in the 13th year. These results in G-I were significantly better than those in G-II for 13 years after treatment. Hearing was improved in 49% of patients in G-I in the 2nd year, in 27% in the 12th year and in 25% in the 13th year. These results in G-I were significantly better than those in G-II for 12 years after treatment, but this was not significant in the 13th year. CONCLUSIONS: Endolymphatic sac drainage with intra-endolymphatic sac application of large doses of steroids could improve long-term follow-up results of hearing as well as vertigo control. This means that the drainage with local steroids could also improve patients' long-term quality in the prime of life.

An inhibitory role for Sema4A in antigen-specific allergic asthma.

PURPOSE: The class IV semaphorin Sema4A is critical for efficient Th1 differentiation and Sema4a (-/-) mice exhibit impaired Th1 immune responses. However, the role of Sema4A in Th2 cell-mediated allergic diseases has not been fully studied. The aim of this study was to clarify the regulatory role possessed by Sema4A in mouse models of allergic diseases, particularly allergic asthma. METHODS: Sema4a (-/-) mice on a BALB/c background were examined for the development of allergic diseases. To induce experimental asthma, mice were sensitized with ovalbumin (OVA) followed by intranasal challenges with OVA. After challenge, airway hyperreactivity (AHR) and airway inflammation were evaluated. The role of Sema4A in asthma was examined using Sema4a (-/-) mice and Sema4A-Fc fusion proteins. The direct effects of Sema4A-Fc on antigen-specific effector CD4(+) T cells were also examined. RESULTS: A fraction of Sema4a (-/-) BALB/c mice spontaneously developed skin lesions that resembled atopic dermatitis (AD) in humans. Furthermore, AHR, airway inflammation, and Th2-type immune responses were enhanced in Sema4a (-/-) mice compared to wild type (WT) mice when immunized and challenged with OVA. In vivo systemic administration of Sema4A-Fc during the challenge period ameliorated AHR and lung inflammation and reduced the production of Th2-type cytokines in WT mice. The inhibitory effects of Sema4A on airway inflammation were also observed in mice deficient in Tim-2, a Sema4A receptor. Finally, we showed that Sema4A-Fc directly inhibited IL-4-producing OVA-specific CD4(+) T cells. CONCLUSION: These results demonstrate that Sema4A plays an inhibitory role in Th2-type allergic diseases, such as allergic asthma.

[Staging-based surgical results in chronic otitis media with cholesteatoma].

Discussions of surgical results in chronic otitis media involving cholesteatoma usually include hearing improvement, side effects, and cholesteatoma recurrence, although such talks could easily involve the influence on surgical results of the intraoperative extension of the cholesteatoma-affected area around the tympanomastoid cavity. Based on intraoperative chronic otitis media staging involving cholesteatoma proposed by the Japan Otological Society in 2010, we studied our tympanoplasty results between April 1997 and March 2010. Hearing improvement in all subjects with pars flaccida cholesteatoma was 79.0% (n= 100) and that with pars tensa 73.3% (n = 30)--results not significantly influenced by intraoperative staging grade but significantly dependent on stapes presence (tympanoplasty type I and III) or absence (type IV). Nine cases of recurrence were seen in pars flaccida and four in pars tensa. Intraoperative side effects and postoperative recurrence often occurred in advanced cases. These findings suggest that intraoperative chronic otitis media staging involving cholesteatoma may make it important to be aware of the need for more careful procedures during surgery and in follow-up.

Changes in caloric responses after temporal bone surgery with posterior tympanotomy.

OBJECTIVE: To elucidate the role of facial recess bony plate in the thermal transmission route from external auditory canal to lateral semicircular canal during caloric stimulation test, we performed the test on patients before and after removal of the plate, i.e. posterior tympanotomy. In the present study, we adopted facial nerve decompression (FND) as posterior tympanotomy without surgery-induced inner ear damages and cochlear implantation (CI) as posterior tympanotomy with surgery-induced inner ear damages. METHODS: Between 1999 and 2003, we performed FND on 19 patients with unilateral facial nerve paresis due to Bell's palsy (n=7), Ramsay-Hunt syndrome (n=7) or facial nerve trauma (n=5) at Osaka Rosai Hospital. We also performed CI on 34 patients with bilateral deafness at Osaka University Hospital. To examine effects of FND or CI on caloric responses in vestibular periphery, caloric stimulation (30 degrees C cold water and 44 degrees C hot water) with ENG was performed twice, just before and 6 months after surgery in each subject. The caloric-induced nystagmus was recorded by using ENG under dark and open-eyes situation to calculate the maximum slow phase eye velocity. RESULTS: In cases of FND (n=19), there were significant decreases between pre- and post-operative 30 degrees C responses (t-test: p=0.049<0.05). There were no significant differences between pre- and post-operative 44 degrees C responses (t-test: p=0.467>0.05). In cases of CI (n=34), there were significant changes between pre and post-operative responses in both temperatures (t-test: p<0.0001 in 30 degrees C; p=0.011<0.05 in 44 degrees C). CONCLUSION: The insertion of electrodes during CI did some damages to vestibular peripheral function and reduced both hot and cold caloric responses according to the results of CI. However, the procedure during posterior tympanotomy could also decrease caloric responses especially in cold stimulation according to the results of FND. Therefore, we should consider the effect of structural change in temporal bone on the thermal transmission in case of evaluation of vestibular peripheral function by using caloric stimulation test.