Three Cases of Mikulicz's Disease as an IgG4-related Disease

We reported three cases of Mikuhcz's disease. Mikulicz's disease was diagnosed by the following criteria: 1) symmetrical enlargement of the lacrimal and salivary glands lasting at least 3 months', 2) the lacrimal and salivary glands were microscopically involved in the infiltration of inflammatory cells, 3) sarcoidosis and other lymphoproliferative diseases were excluded. Three patients with Mikulicz's disease were all characterized by elevated IgG4 concentration in the serum and prominent infiltration of IgG4-positive plasmacytes in the minor salivary glands. On the contrary, there were no findings indicating sicca syndrome or anti-SS-A and SS-B antibodies, which characterize Sjögren syndrome. It is suggested that Mikulicz's disease is an IgG4-related plasmacytec disease, with a pathogenesis differing from that of Sjögren syndrome.


外傷による眼窩先端症候群の1例

外傷による眼窩先端症候群の1例


Two Cases of Incomplete Type and Suspected Type of Behcet's Disease

ベーチェット病不全型例と疑い例

We report two cases of an incomplete type and a suspected type of Behçet's disease that met the diagnostic criteria. Both patients complained of acute sore throat with multiple oropharyngeal aphthous ulcers. The first case had additional diagnostic symptoms of genital ulcers, skin lesions of erythema nodosum with gastrointestinal ulcers, leading to a diagnosis of incomplete type of Behçet's disease. The second patient had additional diagnostic symptoms of genital ulcers with positive HLA-B51 and abnomal signals on brain MRI, leading to a diagnosis of suspected type of Behçet's disease.


鼻過敏症モデルおけるヒスタミンH1受容体発現上昇機構とその制御について

鼻過敏症モデルおけるヒスタミンH1受容体発現上昇機構とその制御について


We reported two cases of neurofibromatosis type 2. Case 1 was a 24-year-old woman with bilateral slight to moderate sensorineural hearing loss. MRI demonstrated a large acoustic tumor (AT) measuring 4.0cm on the right side and another small AT of 1.0cm on the left side. Surgical resection of the right AT resulted in deafness of the right ear. She decided to delay surgery on the left ear until the hearing diminished and/or the tumor grew. However, the remaining hearing of the left ear became further gradually impaired reaching deafness 5 years later without apparent growth of the left AT. Case 2 was a 36-year-old man with moderate sensorineural hearing loss of the left ear and juvenile deafness of the rightear. He showed right peripheral facial palsy and cerebellar ataxia. MRI demonstrated bilateral ATs measuring 2.0cm and 2.5cm, respectively, in addition to several meningiomas in the brain and neurofibromas in the spine. Neurosurgeons estimated that there was no indication for surgical resection or gammaknife treatment.


Combination of Bernouilli effect producing maneuver-induced pharyngeal narrowing rate with body mass index as predictive tool for obstructive sleep apnea syndrome

It is suggested that the combination of the pharyngeal narrowing rate during the Bernouilli effect producing maneuver (BEPM) with the body mass index (BMI) might be a promising predictive method for obstructive sleep apnea syndrome (OSAS). An attempt was made to clarify the possibility that the dynamic narrowing of the pharynx evaluated by nasopharyngoscopy with BEPM, a forced inspiration through the nose with the mouth closed, might be a reliable clinical daytime predictor for identifying patients at risk of developing OSAS. Subjects were 57 patients complaining of snoring and sleepiness during daytime. Endoscopic images of the retropalatal pharynx were obtained and their area was measured by NIH imaging. The pharyngeal narrowing rate during quiet nasal breathing and that during BEPM were compared to assess pharyngeal dynamics. To increase the sensitivity of this method, BMI was added to the pharyngeal narrowing rate during BEPM. The criterion of BEPM at a cut-off value of 50% with BMI at a cut-off value of 25 kg/m(2) achieved a sensitivity of 93%, while the specificity was 67% in differentiating simple snorers from OSAS patients (apnea index >5). In addition, the likelihood ratio of the method was found to be 2.81.


We report two young patients of Wallenberg syndrome who presented with acute vertigo as the initial symptom. Neither Case 1, an 8-year-old girl, nor Case 2, a 29-year-old man, showed any abnormal findings on the initial magnetic resonance imaging (MRI) on day 1. In addition to nystagmus, several neurological signs became positive during the clinical course. Finally, the diagnosis of Wallenberg syndrome was made in both cases based on the detection of a lateral medullary infarction in a follow-up MRI conducted on day 4. Stroke should be considered in the differential diagnosis of acute vertigo, even in young patients without risk factors for cerebrovascular disorders, such as hypertension, diabetes and/or hyperlipidemia. Since MRI may show no abnormalities in the very early stages of stroke, neurological examinations are useful to establish the diagnosis in cases presenting with vertigo induced by brain stem or cerebellar infarction.


False-positive FDG-PET Finding in the Contralateral Larynx of Patients with Unilateral Laryngeal Palsy

FDG-PETにて健側喉頭に偽陽性を示した一側喉頭麻痺症例

Positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) is useful for the diagnosis of head and neck cancers. We report 5 cases of abnormal FDG uptake in the contralateral larynx of patients with unilateral laryngeal palsy due to lung cancer, lung metastasis of breast cancer, lung metastasis of mesopharyngeal cancer, idiopathic cause and laryngeal cancer after complete remission. We concluded that overactivity of the laryngeal muscles that compensated for the paralyzed vocal cord caused a false-positive PET finding with abnormal uptake of FDG in the contralateral larynx of patients with unilateral laryngeal palsy.


Preoperative MRI for Surgery on Multiple Paranasal Mucoceles

多胞性副鼻腔嚢胞の術前MRIの有用性

We reported two cases of multiple paranasal mucoceles, in which MRI was useful to choose the appropriate surgical approach. The first case was a 53-year-old woman, with right visual disturbance due to spheno-ethmoid mucoceles. CT showed a large mucocele in the right spheno-ethmoid sinus, which was closely associated with the right optic nerve. However, MRI could detect a small mucocele lateral to the large one and showed that the small one, but not the large one, involved the optic nerve. The surgical treatment with an endonasal endoscopic approach and navigation-assisted endoscopic drainage of both mucoceles was performed, resulting in complete recovery of visual acuity.The second case was a 52-year-old woman with three paranasal mucoceles. CT showed two mucoceles in the right maxillary sinus. However, MRI showed that the lateral lesion was separated from the medial wall of the nasal cavity by two other medial lesions in the maxillary sinus. Surgical treatment was performed by an external approach and drainage of the three mucoceles was successful.


Differential diagnosis of true and pseudo-bilateral benign positional nystagmus

Two patients showing two rotational axes of their positional nystagmus had canalolithiasis in bilateral posterior semicircular canals (PSCCs), leading to the diagnosis of true bilateral benign paroxysmal positional nystagmus (P-BPPN). Another 18 patients had a single rotation axis of their positional nystagmus with short time constant (TC) on one side and long TC on the other. Since canalolithiasis in the uppermost PSCC may be transient cupulolithiasis, evoking positional nystagmus with long TC, the diagnosis of the latter patients should be pseudo-bilateral P-BPPN. To differentiate the true bilateral posterior canal type of P-BPPN from pseudo-bilateral P-BPPN. The rotational axis and TC of positional nystagmus were three-dimensionally analyzed in 20 patients showing geotropic torsional nystagmus on the left and right Dix-Hallpike (D-H) maneuvers. Two patients showed two rotational axes of their positional nystagmus, which were perpendicular to the plane of the PSCCs. There were no differences in TCs of their positional nystagmus between bilateral D-Hs. Another 18 patients showed a single rotational axis of their positional nystagmus, which was perpendicular to the plane of either the left or right PSCC. TCs of their positional nystagmus were short on one side and long on the other.


完全脱神経をきたした顔面神経麻痺例に対するリハビリテーション

完全脱神経をきたした顔面神経麻痺例に対するリハビリテーション


ボツリヌス治療とミラーバイオフィードバックの併用による病的共同運動の治療効果

ボツリヌス治療とミラーバイオフィードバックの併用による病的共同運動の治療効果


Changes in slow phase eye velocity and time constant of positional nystagmus at transform from cupulolithiasis to canalolithiasis

Changes in slow phase eye velocity (SPEV) and time constant (TC) of benign paroxysmal positional nystagmus in horizontal canal type were examined at transitional period from cupulolithiasis (apogeotropic nystagmus) into canalolithiasis (geotropic nystagmus) in two patients. SPEV and TC of positional nystagmus were tri-dimensionally analyzed. The first patient showed an apogeotropic nystagmus. Head rotation to the left in supine position induced a right-beating nystagmus with an initial SPEVof 15.3 degrees/s and a TC of 133 s. The nystagmus then gradually declined with a TC of 31.3 s after reaching a maximum SPEV of 28.8 degrees/s. After the nystagmus disappeared, he showed a geotropic nystagmus. The second patient showed a left-beating nystagmus with an initial SPEV of 2.5 degrees/s and a TC of 141 s when his head was rotated to the right in supine position. The nystagmus then gradually declined with a TC of 8.05 s after reaching a maximum SPEV of 16.7 degrees/s. After the nystagmus disappeared, he showed a geotropic nystagmus. The present findings suggested that in both patients, at the period of an increase of SPEV of the positional nystagmus with the shortening of its TC, cupulolithiasis transformed into canalolithiasis.


A Case Report of Extrapharyngeal Foreign Body

CTが有用であった咽頭腔外魚骨異物例

We report a sixty-four-year-old woman with an extrapharyngeal foreign body due to swallowing a fish bone. The patient complained of a sore throat after she swallowed fried cutlass fish. However, there was no foreign body detected under pharyngolaryngoscopy or on the cervical X-ray film. Although the sore throat disappeared, cervical CT was carried out, because fish bone as a foreign body was strongly suspected based on the case history. Accordingly, it was demonstrated that the fish bone had extruded from the pharyngeal lumen and penetrated the thyroid. The extrapharyngeal foreign body was successfully removed by lateral neck incision under general anesthesia.


Evaluation of Tonsillectomy with Four Different Methods

4種類の機器による扁摘の比較検討

In the present study, the efficacy of monopolar electrocautery, harmonic scalpel, coblater, and cold knife was evaluated in tonsillectomy. Fifty two adult patients with chronic tonsillitis were divided into four groups, and the operation time and postoperative pain were examined. The mean operation time of tonsillectomy was 35.0±13.2min with monopolar electrocautery, 40.0±10.0min with harmonic scalpel, 54.0±19.1min with coblater, and 101.0±24.1min with cold knife. Thus, the operation time of tonsillectomy with cold knife was significantly prolonged, in comparison with those employing the other three devices (p<0.05). On the contrary, postoperative pain evaluated by self-reporting scales was decreased in the order of cold knife, coblater, harmonic scalpel, and monopolar electrocautery. The pain level after tonsillectomy with monopolar electrocautery was significantly greater than that with cold knife on postoperative days 2-7 (p<0.01). In conclusion, the efficacies of harmonic scalpel and coblater in tonsillectomy lay midway between those with monopolar electrocautery and cold knife.


Autonomic responses during motion sickness induced by virtual reality.

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


Identification and analysis of the promoter region of the type II transmembrane serine protease polyserase-1 and its transcript variants

Polyserase-1/TMPRSS9 and its alternative transcripts, serase-1B and serase-2B, are novel type II transmembrane serine proteases that may regulate physiological and pathological phenomena on the cell surface. To understand the mechanisms of gene expression and regulation of these transcripts, we cloned and characterized the 5' promoter region of the mouse polyserase-1 (mpolyserase-1) gene. Using 5'-rapid amplification of cDNA ends, we located the transcription initiation site 272 nucleotides upstream of the translation initiation site. Luciferase reporter gene analysis revealed that the region from +186 to +272 bp in the 5'-untranslated region (UTR), containing the GATA motif (AGATAA), glucocorticoid responsible element (TGTTCT), and E-box sequence (CAGGTG), is required for maximal promoter activity. Mutations introduced into the E-box sequence but not elsewhere in the promoter region caused a selective decrease in transcriptional activity. Furthermore, a DNA probe (+229 to +255 bp) containing the E-box sequence formed a single nuclear protein complex in a sequence-specific manner. These data suggest that the expression of mpolyserase-1 and its transcript variants is positively regulated by the E-box in its 5'-UTR, which might be responsible for the binding of basic helix-loop-helix transcription factors involved in the development of various organelles.


Follow-up Survey of Patulous Eustachian Tube Syndrome

In the present study, the natural course of patulous eustachian tube syndrome (PETS) was examined. Fifteen patients (3 males, 12 females, 21 to 79 years old; mean age, 61.1 years) were given the diagnosis of PETS, meeting the criteria of both aural symptoms and hyperpatent eustachian tube findings by sonotubometry and tubo-tympano-aerodynamic graphy. Their aural symptoms were assessed by questionnaire at a mean of 16.7 months after the initial diagnosis in the absence of continuous medical treatment. Based on their answers, 7 patients were subjectively cured or in remission, but the other 8 patients showed intractable aural symptoms. The function of the eustachian tube was then re-examined in 7 of the 15 patients after the questionnaire. Six patients with intractable aural symptoms still showed open tubal function, while the tubal function was improved in another patient with relief from aural symptoms.


Two cases of invasive aspergillus sinusitis and mastoiditis successfully treated with voriconazole

ボリコナゾールが著効した副鼻腔と中耳の侵襲性アスペルギルス症例

We report two cases of invasive aspergillosis of the head and neck regions. One patient was a 56-year-old male with invasive aspergillus sinusitis. The other patient was a 14-year-old boy with aspergillus mastoiditis after bone-marrow transplantation. Both cases were inoperable because of vascular invasion by aspergillus, and treatment with antifungal agents was discontinued due to severe side effects. A novel triazole voriconazole (VRCZ) was then used for salvage therapy and successfully treated invasive aspergillosis in both cases. VRCZ is an effective and well tolerated agent to treat invasive aspergillosis of the head and neck regions.


Stimulation of histamine H1 receptor up-regulates histamine H1 receptor itself through activation of receptor gene transcription.

Histamine is a major mediator in allergy acting mainly through the histamine H(1) receptor (H1R). Although H1R up-regulation has been suggested as an important step for induction of allergic symptoms, little is known about the regulation of H1R level. Here we report that the activation of H1R up-regulates H1R through augmentation of H1R mRNA expression in HeLa cells. Histamine stimulation significantly increased both H1R promoter activity and mRNA level without alteration in mRNA stability. H1R protein was also up-regulated by histamine. An H1R antagonist but not histamine H(2) receptor antagonist blocked histamine-induced up-regulation of both promoter activity and mRNA expression. A protein kinase C (PKC) activator, phorbol-12-myristate-13-acetate, increased H1R mRNA expression, whereas an activator of PKA or PKG (8-Br-cAMP or 8-Br-cGMP, respectively) did not. Furthermore, histamine-induced up-regulation of both promoter activity and mRNA level were completely suppressed by the PKC inhibitor Ro-31-8220. H1R antagonists have long been thought to block H1R and inhibit immediate allergy symptoms. In addition to this short-term effect, our data propose their long-term inhibitory effect against allergic diseases by suppressing PKC-mediated H1R gene transcription. This finding provides new insights into the therapeutic target of H1R antagonist in allergic diseases.


他施設におけるメニエール病行動特性調査

他施設におけるメニエール病行動特性調査

厚生労働省科学研究費補助金 特定疾患対策研究事業 前庭機能異常に関する調査研究 平成18年度報告書


平成18年度内リンパ水腫疾患疫学臨床調査

平成18年度内リンパ水腫疾患疫学臨床調査


眼振の3次元主軸解析による両側性後半規管BPPVの病態解明

眼振の3次元主軸解析による両側性後半規管BPPVの病態解明


前庭型メニエール病の臨床的検討

前庭型メニエール病の臨床的検討


当科における真珠腫性中耳炎の術式と術後聴力成績

当科における真珠腫性中耳炎の術式と術後聴力成績


A Case of Dissociated Taste Impairment after Injury of the Major Petrosus Nerve

頭部外傷後の大錐体神経障害による乖離性味覚障害例

We report the case of a 16-year-old female patient with taste impairment of the soft palate. After receiving a skull fracture due to a traffic accident, she experienced the taste of bitter chocolate. CT showed the fracture around the right temporal bone. Electrogustometry showed that the decreased sensation of taste was restricted to the right soft palate. Shirmer test showed that lacrimal secretion of the right eye was decreased. These findings indicated that the selective injury of the major petrosus nerve on the right side due to the fracture caused taste impairment of the soft palate. It has been reported that the sensation of a sweet taste is more sensitive in the soft palate of young women. Therefore, it is suggested that the taste impairment of the soft palate caused the dissociated impairment of a sweet taste, resulting in the taste of bitter chocolate in the present case.


A Case of Tracheobronchial Foreign Body Diagnosed by Multi-detector Row CT

Multi-detector Row CT(多列検出器型CT)が診断に有用であった気道異物例

We report the case of a 6-month-old baby with a radiolucent tracheobronchial foreign body. Multidetector row CT (MDCT) imaging was obtained without anesthesia and multi-planar reconstruction (MPR) imaging, three-dimensional CT (3D-CT) imaging, and virtual bronchoscopy (VB) imaging were reconstructed. MPR, 3D-CT, and VB imaging were useful not only for diagnosis of the radiolucent bronchial foreign body, but also for the pre-operative evaluation of its size and location. A piece of cellophane packaging was then safely removed from the bronchus using flexible bronchoscopy under general anesthesia. The present case suggests that MDCT imaging is necessary as a routine procedure in the diagnosis and pre-operative evaluation of tracheobronchial foreign body.


Natural history of benign paroxysmal positional vertigo and efficacy of Epley and Lemtert maneuvers

We assessed the efficacy of Epley maneuver in patients with posterior canal benign paroxysmal positional vertigo (P-BPPV) and Lempert maneuver in patients with horizontal canal BPPV (H-BPPV). In patients with P-BPPV, positional vertigo in patients treated by Epley maneuver was significantly resolved more quickly than that in untreated patients. But in patients with H-BPPV, there were no significant differences of time course in remission of positional vertigo between untreated patients and patients treated by Lempert maneuver. Among the untreated patients, the positional vertigo in patients with H-BPPV was significantly resolved more quickly than that in patients with P-BPPV. Epley maneuver was effective for the treatment of patients with P-BPPV, whereas the efficacy of Lempert maneuver for the treatment of patients with H-BPPV was limited. The natural courses in remission of positional vertigo in untreated patients with H-BPPV showed significantly faster resolution than that in patients with P-BPPV.


The Usefulness of FDG-PET in Diagnosing Head and Neck Cancer : Report of Four Cases

頭頸部癌の診断にFDG-PETが有用であった4例

FDG-PET (2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography) is clinically useful in detecting head and neck cancer providing accurate estimate of primary cancer and metastasis lymph node especially in cancers that are equivocal on conventional imaging. FDG-PET scan shows unknown primary cancer and metastatic lymph nodes that appear normal CT scan/or MRI. Furthmore, whole body FDG-PET makes it possible to simultaneously detect distant metastasis.We reported 4 cases of head and neck cancer and showed the efficacy of 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in the diagnosis of head and neck cancer. FDG-PET is highly useful for detecting previously unrecognized primary cancer with lymph node metastasis to the neck. FDG-PET also has a high potential for detecting neck lymph node metastasis, staging head and neck cancer and assessing its response to irradiation and chemotherapy. Finally, FDG-PET is useful for diagnosing recurrent or residual head and neck cancer and its distant metastasis.


First Bite Syndrome after Dissection of Parapharyngeal Tumor

Two cases of first bite syndrome (FBS) were reported as a complication after surgery for parapharyngeal tumor. FBS is the development of pain in the parotid area associated with the first bite of food, especially the first meal of the day. In one case, pleomorphic adenoma of the left parotid gland extended into the parapharyngeal space. During resection, dissection around the external carotid artery was performed to mobilize the parotid tail and part of the parotid gland tissue was preserved. In the other case, acinic cell carcinoma of the left parapahryngeal space was resected. During resection, the external carotid artery was cut and most of the parotid gland was preserved. In both cases, sympathetic innervation of the parotid gland through the sympathetic plexus around the external carotid artery was lost without Homer's syndrome. It is possible that sympathectomy of the residual parotid gland is responsible for the development of FBS.


Endoscopic evaluation of dynamic narrowing of the pharynx by the Bernouilli effect producing maneuver in patients with obstructive sleep apnea syndrome

To evaluate the dynamic narrowing of the retropalatal pharynx by the Bernouilli effect producing maneuver (BEPM) in patients with obstructive sleep apnea syndrome (OSAS) with computer-assisted analysis of nasopharyngoscopic images. Endoscopic images of the retropalatal pharynx were obtained and their area was measured by NIH imaging. Because changes in distance between the CCD camera of the nasopharyngoscope and the site of pharyngeal narrowing decreased the measurement reliability, the area of the retropalatal pharynx was divided by the square of the uvula's lateral side length for normalization. We calculated both normalized areas: the pharyngeal narrowing during quiet nasal breathing and that during BEPM, which is a forced inspiration through the nose with the mouth closed. The narrowing rate was then calculated as an index of the pharyngeal dynamics. Nasopharyngoscopy combined with BEPM showed a medial motion of the lateral walls of the pharynx due to the Bernoulli effect, which is an increase in speed and a reduction in pressure of a moving gas passing through a tube constriction. There was a significant correlation between the narrowing rate of the retropalatal pharynx and the apnea index. The decrease in intraluminal pressure at the narrowing combined with the higher atmospheric pressure exercised on the lateral pharyngeal walls would induce the pharyngeal collapse. There was also a significant correlation between the normalized retropalatal are and the apnea index. Nasopharyngoscopy with BEPM suggest that in addition to the static narrowing, the dynamic narrowing of the retropalatal pharynx contributes to the pathophysiology of OSAS. The correlation between the apnea index and both the normalized retropalatal area and the narrowing rate of the retropalatal pharynx due to the Bernoulli effect constitute a quantitative and predictive alternative to the evaluation and understanding of the upper airways changes in OSAS.


剣道によると思われた難聴の臨床的検討と発症機序に関する考察

剣道によると思われた難聴の臨床的検討と発症機序に関する考察


Dexamethasone suppresses histamine synthesis by repressing both transcription and activity of HDC in allergic rats.

BACKGROUND: Histamine synthesized by histidine decarboxylase (HDC) from L-histidine is a major chemical mediator in the development of nasal allergy which is characterized by nasal hypersensitivity. However the regulatory mechanism of histamine synthesis by HDC remains to be elucidated. The objectives of the present study were to examine the changes of histamine content, HDC activity and HDC mRNA expression in the nasal mucosa of allergy model rats sensitized by the exposure to toluene diisocyanate (TDI) and to investigate the effect of dexamethasone on the above mentioned allergic parameters. METHODS: Rats were sensitized and provocated by TDI and the nasal allergy-like behaviors were scored during a 10 minute period after provocation. Histamine content and HDC activity in the nasal mucosa were determined using fluorometric high performance liquid chromatography. The expression of HDC mRNA in nasal mucosa was determined using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: In TDI-sensitized rats, nasal allergy-like behaviors such as sneezing and watery rhinorrhea were induced. Histamine content, HDC activity and HDC mRNA expression in nasal mucosa were also significantly increased after TDI provocation. Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and HDC mRNA induced by TDI in TDI-sensitized rats. CONCLUSIONS: These findings indicate that increased synthesis of histamine through up-regulation of HDC gene expression and HDC activity in nasal mucosa plays an important role in the development of nasal hypersensitivity. Repression of HDC gene expression and HDC activity by dexamethasone may underlie its therapeutic effect in the treatment of allergy.


前庭型メニエール病に対するプロスタグランディンI2誘導体の治療効果

前庭型メニエール病に対するプロスタグランディンI2誘導体の治療効果

We treated 44 cases of vestibular Ménières disease with prostaglandin I2 (PGI2), a vasodialator, at a dose of 120μg per day for more than two months (mean: 8.0 months). The long-term administration of constant daily amounts of PGI2 attained good long-term results in vertigo according to the criteria of the Japan Society for Equilibrium Research. The results were as follows: the administration of PGI2 completely controlled vertigo in 65.9% (29/44) and improved it in 29.5% (13/44); however, four cases suffered from the typical type of Menieres disease thereafter (9.1%: 4/44). The objective findings of nystagmus were also reduced in 85.7% (24/28) after PGI2 treatments.
PGI2 was significantly more effective in patients with a vertigo duration within 120 min and -SP/AP negative results on electro-cochleogram (ECoG) than the others. On the contrary, patients with a vertigo duration of more than 120 min and -SP/AP positive results on ECoG experienced cochlear symptoms together with vertiginous sensations later. These patients should be treated with an oral osmotic diuretic, isosorbide. These findings suggest that cases presently diagnosed as vestibular Ménières disease could include at least two kinds of oto-pathologies; vascular disease and endolymphatic hydrops.


Autonomic Dysfunction in Patients with Vertigo


Three-dimensional analysis of benign paroxysmal positional nystagmus in a patient with anterior semicircular canal variant.

To show the positional nystagmus in a patient who had suffered from benign paroxysmal positional vertigo (BPPV) that was thought to be caused by involvement of the anterior semicircular canal (ASCC) (A-BPPV). Retrospective case report. City hospital. The present study reports a rare case of A-BPPV in a 41-year-old woman. The patient is 41-year-old woman who developed a positional vertigo after playing volleyball on March 22, 2005 and consulted our hospital the next day. When left Dix-Hallpike maneuver was performed, she showed a positional nystagmus of which fast phase direction of the torsional component was clockwise while that of the vertical component was downward. We plotted the slow phase eye velocity of the positional nystagmus during the left Dix-Hallpike maneuver on three-dimensional coordinates that showed the axis of the positional nystagmus to be perpendicular to the plane of the right ASCC. These results suggested that the patient was suffering from A-BPPV.


喉頭截開術の適応と術式について

喉頭截開術の適応と術式について

The Journal of Japan Society for Clinical Anesthesia


Three cases of herpes zoster oticus with only the 8th cranial nerve dysfunction

第8脳神経症状のみを呈した耳性帯状疱疹の3症例


Zinc nutrition in healthy subjects and patients with taste impairment from the view point of zinc ingestion, serum zinc concentration and angiotensin converting enzyme activity.

To estimate the zinc nutrition in healthy subjects and patients with taste impairment. Dietary zinc intake, zinc concentration in the serum and the ratio of apo/holo-activities of angiotensin converting enzyme (ACE), a zinc dependent enzyme in the serum (ACE ratio) were used as indices. Healthy paramedical volunteers from a local hospital and patients with taste impairment seen in the Department of Otolaryngology, Tokushima University Hospital. Dietary zinc intake was estimated with the food frequency questionnaire (FFQ). Zinc concentration in the serum was measured by means of atomic absorption spectrometry. The ACE activity in the serum was measured spectrophotometrically as the activity of holo-ACE, which contains zinc and shows full ACE activity. The activity of apo-ACE, which dose not contain zinc, was determined as the increase of its activity over that of the initial holo-ACE activity after the addition of zinc to the serum in vitro. ACE ratio was used as a more sensitive indicator of zinc nutrition than measuring zinc concentration in the serum. There were no differences in dietary intake of zinc after adjusting for energy and zinc concentration in the serum between patients and age-adjusted healthy subjects. The ACE ratio in patients with taste impairment was significantly higher than that in age-adjusted healthy subjects (P<0.05). Our date demonstrate that zinc deficiency is a predominant factor underlying taste impairment and we hypothesize that patients with taste impairment may have malabsorption of dietary zinc.


Benign paroxysmal positional vertigo due to a simultaneous involvement of both horizontal and posterior semicircular canals.

From April 2001 to November 2003, we investigated 8 patients with benign paroxysmal positional vertigo (BPPV) that was suspected to simultaneously affect both the horizontal and posterior semicircular canals (HSCC and PSCC). These cases showed typical vertical-torsional nystagmus induced by the Dix-Hallpike maneuver, followed by a horizontal nystagmus. They also showed a direction-changing geotropic or apogeotropic positional nystagmus triggered by lateral head rotations in the supine position. Using the three-dimensional analysis of the positional nystagmus, the rotation axis of the positional nystagmus had a component perpendicular to the plane of PSCC and another component perpendicular to the plane of HSCC. All these findings suggest that BPPV in these patients was a combination of posterior and horizontal canal BPPV. The observation of a vertical-torsional positional nystagmus should prompt the specialist to perform not only the canalith repositioning procedure, but also to execute lateral head turns in the supine position.


遅発性内リンパ水腫症例の臨床的検討

遅発性内リンパ水腫症例の臨床的検討

厚生労働省科学研究費補助金 特定疾患対策研究事業 前庭機能異常に関する調査研究 平成17年度報告書


メニエール病患者におけるストレス関連遺伝子発現変化のDNAマイクロアレイ解析

メニエール病患者におけるストレス関連遺伝子発現変化のDNAマイクロアレイ解析

厚生労働省科学研究補助金，特定疾患対策研究事業，前庭機能異常に関する調査研究，平成17年度報告書


遅発性内リンパ水腫症例の臨床的検討

遅発性内リンパ水腫症例の臨床的検討

厚生労働省科学研究補助金,特定疾患対策研究事業,前庭機能異常に関する調査研究,平成17年度報告書


アンギオテンシン変換酵素活性比を用いた味覚障害患者の亜鉛栄養状態の評価

アンギオテンシン変換酵素活性比を用いた味覚障害患者の亜鉛栄養状態の評価


めまいといえば，メイロンでよいのか?

めまいといえば，メイロンでよいのか?


Microarray Analysis of Stress-Related Gene Expression in Patients with Ménière's Disease

We developed an original microarray carrying 1,467 cDNAs of stress-related genes for the assessment of stress responses. In this study, we used microarray analysis to assess the stress-related gene expression profiles in peripheral leukocytes in 2 patients with definite Ménière's disease. In the attack and active phases, mRNA expression levels of 57 genes and 163 genes were either up-regulated more than twofold or down-regulated by less than half in patient 1 and patient 2, respectively. Patient 1 had sporadic episodes of vertigo attack, while patient 2 had an intractable course with frequent vertigo attacks, suggesting that the magnitude of changes in gene expression is correlated with the severity of the disorder in Ménière's disease. The expression of a total of 26 genes commonly changed in both patients in the attack and active phases and returned to the baseline levels in the remission phase, suggesting the involvement of the distinct group of stress-related genes in the development of vertigo attacks in Ménière's disease. We then examined the effects of caloric stimulation on the stress-related gene expression profiles in peripheral leukocytes in 5 healthy volunteers. Although unilateral caloric stimulation with cold water caused acute vertigo with nystagmus, the expression profiles of stress-related genes did not significantly change after this experiment. This finding indicated that the up- or down-regulated genes in the attack and active phases in patients with Ménière's disease are not secondary to vertigo or vertigo-associated anxiety. All these findings suggested that the distinct group of stress-related genes contributed to the development of vertigo attacks of Ménière's disease and that stress-related gene expression profiles in peripheral leukocytes can be a predictive and therapeutic tool for episodic vertigo attacks in patients with Ménière's disease.

ORL; Journal for Oto-Rhino-Laryngology and its Related Specialties


Regional difference in corticotropin-releasing factor immunoreactivity in mossy fiber terminals innervating calretinin-immunoreactive unipolar brush cells in vestibulocerebellum of rolling mouse Nagoya

Unipolar brush cells (UBCs), a class of interneurons in the vestibulocerebellum, play roles in amplifying excitatory inputs from vestibulocerebellar mossy fibers. This study aimed to clarify whether corticotropin-releasing factor (CRF)-positive mossy fiber innervation of calretinin (CR)-positive UBCs was altered in rolling mouse Nagoya (RMN). The distribution and the number of CR-positive UBCs in the vestibulocerebellum were not different between RMN and control mice. Double immunofluorescence revealed that some CRF-positive mossy fiber terminals were in close apposition to CR-positive UBCs. In the lobule X of vermis, such mossy fiber terminals were about 5-fold greater in number in RMN than in controls. In contrast, the number of CRF-positive mossy fiber terminals adjoining CR-positive UBCs in the flocculus was not significantly different between RMN and controls. The results suggest increased number of CRF-positive mossy fiber terminals innervating CR-positive UBCs in the lobule X but not in the flocculus of RMN. CRF may alter CR-positive UBC-mediated excitatory pathways in the lobule X of RMN and may disturb functions of the lobule X such as cerebellar adaptation for linear motion of the head.


Taste disorders: a survey of the examination methods and treatments used in Japan

In Japan, the number of patients seeking treatment for taste disorders from otolaryngologists is approximately 240 000/year, and this number has almost doubled in the last 13 years. Taste examinations are routinely conducted in almost all university hospitals; testing is not as common in private clinics. Administration of zinc is the main treatment for taste disorders in Japan. To investigate the number of patients who visited otolaryngologists for treatment of taste disorders between 2000 and 2002. In addition to determining changes in the number of patients that had occurred in the 13 years since the last study in 1990, the survey also sought to find out what types of taste examination were used to diagnose taste disorders in Japan and what therapies were used to treat them. A questionnaire was mailed to 1559 members of the Japan Society of Stomato-pharyngology. The average number of patients with taste disorders who visited otolaryngological clinics between 2000 and 2002 was 244 858/year. This number is 1.77-fold greater than the number of patients reported by the last study in 1990 (138 575). Electrogustometry was used in 99% of university hospitals and in 20% of private clinics. The filter-paper disk method was also used in 57% of university hospitals and in 27% of private clinics. The main treatment was zinc administration. Most doctors (70%) prescribed polaprezinc, a zinc-containing drug that is used to treat peptic ulcers. Of these doctors, 78% stated that it effectively treated taste disorders and 11% that it did not.


Prognosis of Inner Ear Periphery and Central Vestibular Plasticity in Sudden Deafness With Vertigo

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

The Annals of Otology, Rhinology, and Laryngology


Analysis of in vivo role of alpha-fodrin autoantigen in primary Sjogren's syndrome

The alpha-fodrin N-terminal portion (AFN) autoantigen mediates in vivo immunoregulation of autoimmune responses in primary Sjögren's syndrome (SS). We further examined this process and found that cleavage products of AFN were frequently detected in the salivary gland duct cells of SS patients. In in vitro studies using human salivary gland HSY cells, anti-Fas-induced apoptosis resulted in specific cleavage of alpha-fodrin into the 120-kd fragment, in association of alpha-fodrin with mu-calpain, and activation of caspase 3. Significant proliferative responses against AlphaFN autoantigen were observed in the peripheral blood mononuclear cells (PBMCs) from SS patients with higher pathological score (grade 4) and with short duration from onset (within 5 years). In vivo roles of AFN peptides were investigated using PBMCs from patients with SS, systemic lupus erythematosus, and rheumatoid arthritis. Significant proliferative T-cell responses of PBMCs to AFN peptide were detected in SS but not in systemic lupus erythematosus or rheumatoid arthritis. AFN peptide induced Th1-immune responses and accelerated down-regulation of Fas-mediated T-cell apoptosis in SS. Our data further elucidate the in vivo role of AFN autoantigen on the development of SS and suggest that the AFN autoantigen is a novel participant in peripheral tolerance.


Screening of Sleep Apnea Syndrome Using Subjective Sleepiness Evaluation, ESS

自覚的眠気評価法Epworth Sleepiness Scale(ESS)の有用性 ─睡眠時無呼吸症候群のスクリーニング─

In the present study, we evaluated daytime sleepiness in 32 patients with obstructive sleep apnea syndrome (OSAS) using epworth sleepiness scale (ESS). ESS scores of patients with OSAS were significantly higher than those of patients with simple snoring and healthy subjects. ESS scores of patients with OSAS were significantly correlated with apnea-hypopnea index, the longest apnea time, but not with the lowest oxygenation. It is suggested that ESS score is a predictive index of the severity of OSAS. We then examined whether ESS in combination with body mass index (BMI) can identify patients with OSAS among patients complaining of snoring. When the cut off points were 11 in ESS and 25 in BMI, the combination of ESS and BMI correctly classified 18 of 25 patients with OSAS (sensitivity=72.0%) and 7 of 10 patients without OSAS (specificity=70.0%). We concluded that the combination of ESS and BMI was useful for screening of sleep apnea syndrome.


大学病院におけるめまい症例の統計的検討とめまい疾患の診断基準の問題点

大学病院におけるめまい症例の統計的検討とめまい疾患の診断基準の問題点

Subjects were 626 patients reporting vertigo or dizziness seen at the University Hospital Department of Otolaryngology from April 2001 to September 2003. Patients were diagnosed based on diagnostic criteria prescribed by the Japan Society for Equilibrium Research. The most common peripheral vestibular disorder was benign paroxysmal positional vertigo (32%), followed by Meniere's disease (12%). All peripheral vestibular disorders accounted for 65%. Central vestibular disorder accounted for 7%, of which space-occupying lesions in the posterior fossa accounted for 1.0% and cerebral infarction 1.9%. Dizziness due to orthostatic hypotension accounted for 4.0%. Among past reports on clinical statistics of vertigo, the incidence of vertigo and dizziness disorders differed greatly, but our research and the past 2 reports based on diagnostic criteria prescribed by the Japan Society for Equilibrium Research showed almost the same incidence, i. e., BPPV of 30-40%, Meniere's disease of 7-10%, other peripheral vestibular disorders of 15-20%, and central vestibular disorder of 6-8%. Unified diagnostic criteria are thus important in the statistical analysis of vertigo disorders.


めまい発作に伴い左右側方注視眼振が周期性に変化した特異な1症例

めまい発作に伴い左右側方注視眼振が周期性に変化した特異な1症例

We report on a case with periodic nystagmus on lateral gaze during vertigo attack. The case is a 19-year-old woman who had repeated vertigo attacks in the early stage of the disease. During remission, she had continuous nystagmus on lateral gaze with a large amplitude. During vertigo attack, she had periodic nystagmus with a small amplitude on lateral gaze with null periods of 8s. At onset, her tentative diagnosis was spinocerebellar degeneration such as dentatorubral-pallidoluysian atrophy because of brain stem tegmentum and cerebellar vermis atrophy identified on MRI, but brainstem encephalitis and cerebellitis couldnt be excluded. Periodic nystagmus during vertigo attack may be induced by the depression of higher neural control which was indicated by lesions in the cerebellar vermis shown on MRI.


Effects of immersion in virtual on postural control

In the present study, we examined the effects of the time lag between visual scene and the head movement in the virtual reality (VR) world on motion sickness and postural control in healthy volunteers. After immersion in VR with additional time lags (from 0 to 0.8 s) to the inherent delay (about 250 ms), the visual-vestibular conflict induced a slight motion sickness in experimental subjects, but no change was noticed in the body sway path with eyes open and closed. However, Romberg ratio of body sway path with eyes closed divided by that with eyes open after immersion in VR was significantly decreased in comparison with that before immersion in VR. Since Romberg ratio is an index of visual dependency on postural control, this finding indicates that the immersion in VR decreases the visual dependency on postural control. It is suggested that adaptation to visual-vestibular conflict in VR immersion increases the contribution of vestibular and somatosensory inputs to postural control by ignoring the conflicting delayed visual input in the VR world. VR may be a promising treatment for visual vertigo in vestibular patients with unsuccessful compensation by its ability to induce vestibular and somatosensory reweighing for postural control.


重複障害児に対する聴性定常反応を用いた骨導検査と音場検査の試み

重複障害児に対する聴性定常反応を用いた骨導検査と音場検査の試み


Natural course of the remission of vertigo in patients with benign paroxysmal positional vertigo

The authors assessed the natural course of benign paroxysmal positional vertigo (BPPV) in 108 patients who were not treated with canalith repositioning procedure. The average number of days from onset to remission of positional vertigo in patients with posterior canal BPPV (P-BPPV) (39 days) was longer than in those with horizontal canal BPPV (H-BPPV) (16 days). The ratio of patients with H-BPPV to those with BPPV was 33%.


Comparing the accuracy of video-oculography and the scleral search coil system in human eye movement analysis

The measurement of eye movements in three dimensions is an important tool to investigate the human vestibular and oculomotor system. The primary methods for three dimensional eye movement measurement are the scleral search coil system (SSCS) and video-oculography (VOG). In the present study, we compare the accuracy of VOG with that of SSCS using an artificial eye. We then analyzed the Y (pitch) and Z (yaw) component of human eye movements during saccades, smooth pursuit and optokinetic nystagmus, and the X (roll) component of human eye movement during the torsional vestibulo-ocular reflex induced by rotation in normal subjects, using simultaneous VOG and SSCS measures. The coefficients of the linear relationship between the angle of a simulated eyeball and the angle measured by both VOG and SSCS was almost unity with y-intercepts close to zero for torsional (X), vertical (Y) and horizontal (Z) movements, indicating that the in vitro accuracy of VOG was similar to that of SSCS. The average difference between VOG and SSCS was 0.56 degrees , 0.78 degrees and 0.18 degrees for the X, Y and Z components of human eye movements, respectively. Both the in vitro and in vivo comparisons demonstrate that VOG has accuracy comparable to SSCS, and is a reliable method for measurement of three dimensions (3D) human eye movements.


Blink Reflex R2 Recovery Curves in Patients with Facial Palsy within Ten Days after Onset

The purpose of this study was to investigate the acute changes in blink reflex responses in patients with facial palsy. We used the blink reflex R2 recovery curves as an index of the excitability of the blink reflex neural circuit and evaluated the excitability of the blink reflex within 10 days after onset. Twelve patients with peripheral facial palsy were selected on condition that the degree of facial palsy was so mild that R2 responses of the blink reflex were measurable on the affected side, and they were compared with 12 healthy volunteers. Conditioning and test electrical stimuli were delivered on the affected side of the supraorbital nerve. Ipsilateral R2 response (iR2) of the blink reflex in patients was significantly enhanced at interstimulus intervals (ISIs) between conditioning and test stimuli from 100 to 1,000 ms, in comparison with the control subjects. These findings suggested hyperexcitability of the blink reflex neural circuit in patients with facial palsy. In addition to iR2, contralateral R2 response (cR2) in the patients was also significantly increased at ISIs of 100-1,000 ms to the same extent as the enhancement of iR2. All these findings suggested that the hyperexcitable changes developed in a common pathway of iR2 and cR2, but not in the ipsilateral facial motor neurons. It is suggested that the hyperexcitability of the neural circuit of the blink reflex during an acute period of facial palsy is an adaptive response to compensate for impaired facial motor function.

ORL; Journal for Oto-Rhino-Laryngology and its Related Specialties


良性発作性頭位めまい症における眼振の性状と治癒期間

良性発作性頭位めまい症における眼振の性状と治癒期間

平成16年度厚生労働省科学研究補助金 特定疾患対策研究事業 前庭機能異常に関する調査研究報告書


メニエール病の難聴の長期予後

メニエール病の難聴の長期予後


Zinc deficiency in patients with idiopathic taste impairment with regard to angiotensin converting enzyme activity

The present study aimed at measuring the ratio of apo/holo activities of angiotensin converting enzyme (ACE) ratio in the serum of patients with taste impairment to evaluate their status of zinc nutrition. Nineteen patients complaining of taste impairment were divided into two groups: zinc-deficiency taste impairment (n=6) and idiopathic taste impairment (n=13) and compared to 30 volunteers. Zinc concentrations in the serum were measured by atomic absorption spectrometry (normal values: 64-111 microg/dl). Patients with zincemia values of <63 microg/dl with no history of other disorder or medication known to cause dysgeusia were diagnosed as zinc deficient, while those with the same condition and values >64 microg/dl were considered to belong to the idiopathic group. The activities of ACE in the serum were measured spectrophotometrically as the activity of the holo-ACE, and after addition of 80 microM of zinc to the serum in vitro, the increase of ACE activity over initial value in the serum was determined as that of the apo-ACE. Finally, the apo/holo-ACE activities ratio was used as an index of zinc nutritional status. The mean concentrations of zinc in the serum were 77.4+/-8.4 microg/dl in volunteers, 77.6+/-8.4 microg/dl in the idiopathic patients and significantly decreased at 55.7+/-5.8 microg/dl in zinc-deficiency patients. ACE activities in the serum were 14.7+/-7.6, 14.5+/-4.0 and 14.1+/-3.3 IU/l in volunteers, the idiopathic group and zinc-deficiency taste impairment group, respectively. The mean ACE ratios were 1.10+/-0.6% in volunteers and significantly increased at 9.8 +/- 4.0% in the idiopathic group and at 13.7+/-6.6% in zinc-deficiency taste impairment group. The results of the present study indicated that zinc deficiency is a predominant factor underlying hypogeusia even when zinc concentrations are within normal ranges in the serum and show that clinically, ACE ratio may be a more sensitive indicator of the zinc nutritional status than measuring zinc concentration in the serum.


Vertical Canal Function in Normal Subjects and Patients with Benign Paroxysmal Positional Vertigo

To assess the dynamics of the vertical semicircular canal (VSCC)-ocular reflex in normal subjects and then to compare their gain in VSCC-ocular reflex with that of patients with benign paroxysmal positional vertigo (BPPV). Subjects were sinusoidally rotated around the earth-vertical axis with their head tilted 60 degrees backward and turned 45 degrees to the right or left side from the sagittal plane at frequencies of 0.1, 0.3, 0.5, 0.7 and 1.0 Hz with a maximum angular velocity of 50 degrees/s. Head rotation to the right side on the right anterior semicircular canal (SCC)-left posterior SCC plane or to the left side on the left anterior SCC-right posterior SCC plane stimulated the pair of VSCCs. Eye movements were recorded on a video imaging system with an infrared charge-coupled device camera, using our new technique for analyzing the rotation vector of eye movements in three dimensions. The mean gains in left posterior SCC-ocular reflex in normal subjects ranged from 0.44 at 0.1 Hz to 0.79 at 1.0 Hz, while the mean gains in right anterior SCC-ocular reflex ranged from 0.45 at 0.1 Hz to 0.73 at 1.0 Hz. The mean gains in right posterior SCC-ocular reflex in normal subjects ranged from 0.53 at 0.1 Hz to 0.89 at 1.0 Hz, while the mean gains in left anterior SCC-ocular reflex ranged from 0.53 at 0.1 Hz to 0.88 at 1.0 Hz. Thus, the gains in VSCC-ocular reflex did not differ among the four VSCCs in normal subjects. Similarly, vestibulo-ocular reflex (VOR) gains of the four VSCCs in patients with right- or left-sided BPPV were almost the same at all frequencies compared to those of normal subjects. In patients with BPPV, gains in VOR in the four VSCCs were not changed in comparison with those of normal subjects. It is suggested that the mass of free-floating otoconial debris associated with canalolithiasis was too small compared to that of the endolymph to change the canal dynamics.


Differential activity of drugs to induce emesis and pica behavior in Suncus murinus (house musk shrew) and rats

We have previously reported that emetic stimuli induce kaolin ingestion behavior (pica behavior) in rats and mice (i.e., species that do not have the emetic reflex) and that the behavior may be analogous to gastrointestinal discomfort, such as nausea and emesis. We hypothesized that pica behavior may also occur in species capable of vomiting and that it may serve as an additional index of discomfort relevant to antiemetic drug development. The present experiments were conduced using Suncus murinus and rats and kaolin consumption was measured at 24 h after the administration of nicotine (1.25-5 mg/kg, s.c.), copper sulfate (10-120 mg/kg, p.o.), lithium chloride (50-200 mg/kg, i.p.) and cisplatin (1-30 mg/kg, i.p.). In S. murinus, all treatments, excepting lithium chloride, were emetic but none induce kaolin consumption. Conversely, all treatments induced kaolin consumption in rats without inducing emesis. The results indicate that pica behavior is not likely to be useful to assess gastrointestinal discomfort in S. murinus.


A Case Report of Localized Wegener's Granulomatosis Presenting as Otitis Media

耳症状初発の限局型Wegener肉芽腫症例

Wegener's granulomatosis is a distinct clinicopathologic entity characterized by granulomatosis vasculitis of the respiratory tract accompanied by glomerulonephritis. We report a case of a 56-year-old female with localized Wegener's granulomatosis presenting as otitis media. The patient complained of right ear pain. Antibiotic treatment was ineffectual and right sensorineural deafness and right facial palsy became apparent. Perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) was positive, but cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) was negative. The histopathologic appearance of granulation tissue in her tympanic and nasal cavity indicated inflammatory granulation involving multinucleated giant cells and epithelioid cells. The disease did not involve her lung or kidney, so it was diagnosed as localized Wegener's granulomatosis. Glucocorticoid treatment with cyclophosphamide improved the right hearing loss and facial palsy. CRP and p-ANCA became negative.Early diagnosis of Wegener's granulomatosis is difficult because of atypical manifestations of the disease, but ANCA measurements may be effective in the diagnosis. The present case suggests that inner ear blood flow impairment due to p-ANCA-associated small vessel vasculitis induces hearing loss.


Paroxetine, a Selective Serotonin Reuptake Inhibitor, Reduces Depressive Symptoms and Subjective Handicaps in Patients with Dizziness

When treating dizzy patients, the psychiatric aspect should be carefully addressed regardless of whether a well-defined organic disease is present. In this prospective study, we aimed to elucidate the role of paroxetine, a selective serotonin reuptake inhibitor, in the treatment of dizziness. Forty-seven patients who complained of dizziness were treated with 20 mg of paroxetine per day. The depressive state of the patient was evaluated by the Zung Self-Rating Depression Scale (SDS). Treatment outcomes were measured with self-assessment of subjective handicaps in daily life using a dizziness and unsteadiness questionnaire. The questionnaire consisted of five factors related to emotional or bodily dysfunction that could be affected by dizziness. Changes in Self-Rating Depression Scale scores and subjective handicaps were assessed at 4 and 8 weeks after the start of paroxetine. In patients having well-defined organic diseases with high Self-Rating Depression Scale scores, paroxetine improved all five subjective handicap factors as well as Self-Rating Depression Scale scores. The decline in Self-Rating Depression Scale scores showed a significant correlation with improvement of subjective handicaps, which was related to emotional problems but not factors related to bodily dysfunction. Paroxetine was also effective for an improvement of factors related to emotional problems and Self-Rating Depression Scale scores in patients not having organic diseases but with high Self-Rating Depression Scale scores. In patients either with or without organic diseases with low Self-Rating Depression Scale scores, paroxetine had no effect on any subjective handicap factors and Self-Rating Depression Scale scores. In the treatment of dizzy patients, paroxetine was effective at relieving subjective handicaps caused by dizziness, specifically, in patients with high Self-Rating Depression Scale scores.


メニエール病に対する浸透圧利尿薬の長期連続投与の治療効果と蝸電図におよぼす影響

メニエール病に対する浸透圧利尿薬の長期連続投与の治療効果と蝸電図におよぼす影響

We treated 7 cases of Meniere's disease with an oral osmotic diuretic, isosorbide, at a dose of 90 ml per day for more than one year (mean: 31.7 months). One case suffered from bilateral Meniere's disease. The long-term administration of constant daily amounts of isosorbide attained good long-term results in vertigo but poor in hearing according to the criteria of the Japan Society for Equilibrium Research for Meniere's disease. The results were as follows: the administration of isosorbide completely controlled vertigo in 29% and improved it in 42%, however, hearing was unchanged in 71% and worsened in 29%. To see if long-term follow-up of Meniere's patients using electro-cochleogram (ECoG) is useful for determination of therapeutic effects of isosorbide and establishment of its effective medication protocol, we examined relation-ships between long-term results of oral medication of isosorbide and the medication-induced changes in dominant -SP of ECoG. All eight affected ears of seven cases showed dominant -SP at their first visit and half of them didn't show it anymore after the long-term medication. There was no significant relationship between normalization of ECoG findings and improvement of vertigo. These findings indicate that normalization of ECoG findings cannot be a good marker for determination of therapeutic effects of isosorbide or establishment of its effective medication protocol.


Dynamics of the vestibulo-ocular reflex in patients with the horizontal semicircular canal variant of benign paroxysmal positional vertigo

Two types of direction-changing positional nystagmus, the geotropic and apogeotropic variants, are observed in patients with the horizontal semicircular canal (HSCC) type of benign paroxysmal positional vertigo (H-BPPV). In this study, we assessed the dynamics of the vestibulo-ocular reflex (VOR) of the HSCC in patients with H-BPPV. Patients were rotated about the earth-vertical axis at frequencies of 0.1, 0.3, 0.5, 0.7 and 1.0 Hz with a maximum angular velocity of 50 degrees/s. Eye movements were recorded on a video imaging system using an infrared charge-coupled device (CCD) camera, and our new technique for analyzing the rotation vector of eye movements in three dimensions was used. In the patients with geotropic positional nystagmus, there were no differences in VOR gain between rotation to the affected and unaffected sides at frequencies of 0.1-1.0 Hz. Although no differences in VOR gain at frequencies of 0.3-1.0 Hz were noticed in patients with apogeotropic positional nystagmus, the VOR gain at 0.1 Hz was significantly smaller on rotation to the affected compared to the unaffected side. The results indicate that cupulolithiasis in the HSCC affected the dynamics of the HSCC-ocular reflex at 0.1 Hz, but not at higher frequencies, and that canalolithiasis in the HSCC does not change the VOR gain of the HSCC at any frequency. It is suggested that cupulolithiasis causes transient impairment of HSCC function by means of its mechanical restriction of movements of the cupula.


Abnormal expression of tyrosine hydroxylase not accompanied by phosphorylation at serine 40 in cerebellar Purkinje cells of ataxic mutant mice, rolling mouse Nagoya and dilute-lethal


Effect of glucocorticoid on upregulation of histamine H1 receptor mRNA in nasal mucosa of rats sensitized by exposure to toluene diisocyanate.

OBJECTIVE: Histamine is a major chemical mediator in the development of nasal allergy, which is characterized by nasal hypersensitivity. In this study, we used rats sensitized by exposure to toluene diisocyanate (TDI) as an animal model of nasal hypersensitivity and examined changes in expression of histamine H1 receptor (H1R) in the nasal mucosa. The effect of glucocorticoid on upregulation of H1R in nasal mucosa induced by TDI was also examined. MATERIAL AND METHODS: In rats sensitized by exposure to TDI, nasal allergy-like behavior was scored during a 10-min period after TDI provocation. The expression of H1R in the nasal mucosa was determined by means of a real-time quantitative reverse transcriptase polymerase chain reaction and a [3H]mepyramine binding assay. RESULTS: In TDI-sensitized rats, nasal allergy-like behavior, such as sneezing and watery rhinorrhea, was induced after intranasal application of TDI and nasal hypersensitivity to histamine was significantly increased. The level of H1R mRNA expression and the specific binding of [3H]mepyramine in the nasal mucosa were significantly increased after intranasal application of TDI in TDI-sensitized rats. Pretreatment with dexamethasone significantly reduced both nasal allergy-like behavior and the upregulation of H1R induced by TDI in the rats. CONCLUSION: As shown in TDI-sensitized rats, our findings suggest that the upregulation of H1R in the nasal mucosa is one of the mechanisms responsible for nasal hypersensitivity behavior and nasal hypersensitivity to histamine and that the therapeutic effects of dexamethasone are, in part, due to its inhibitory action on the upregulation of H1R.


スギ花粉症患者に対する塩酸セチリジン初期投与の有用性(第4報) --- 多段層別分析による検討


The effect of centirizine prophylactic treatment on the quality of life in patients with Japanese cedar pollinosis. The 3rd report --- SF-36によるPCS/MCSの検討

スギ花粉症患者に対する塩酸セチリジン初期投与の有用性(第3報) --- SF-36によるPCS/MCSの検討


Between 1993 and 1995, 178 patients complaining of fullness of the ear visited our clinic. Of these, 24 were found to have low-tone sensorineural hearing loss. Glycerol test revealed positive/ pseudopositive results in 20 of these 24 cases. Of these, 15 cases were followed up more than 3 years. Average hearing level at low-tone (125 Hz, 250 Hz and 500 Hz) in the 24 hearing-impaired patients were 34.0 dB. Clinical symptoms and low-tone sensorineural hearing loss of all patients were improved by isosorbide or betamethasone. The subjects who had temporary hearing impairment at 4, 000 Hz or 8, 000 Hz had significantly higher risk of recurrence. One findings suggested that low-tone deafness with a chief complaint of ear fullness is caused by endolymphatic hydrops. Prognosis may be dependent on the extent rather than the degree of the impairment in the inner ear. Prompt treatment and follow-up is important for patients who complain ear fullness, because some of them may progress to Meniere disease in the future.


Fos induction in the amygdala by vestibular information during hypergravity stimulation

Altered gravity environments including both hypo- and hypergravity can elicit motion sickness. Vestibular information is known to be essential for motion sickness, but its other neural substrates are poorly understood. We previously showed that bilateral lesions of the amygdala suppressed hypergravity-induced motion sickness in rats, using pica behavior as an emetic index. We show in the present study that during hypergravity stimulation, vestibular information activated the central nucleus of the amygdala (CeA), as determined by the induction of Fos expression, in comparison between normal and bilaterally labyrinthectomized rats. The finding that Fos expression was confined to the CeA and almost completely absent in other subnuclei of the amygdala contrasted with many previous studies that used other stressful stimuli such as foot shock, restraint and forced swimming, suggesting a specific vestibular effects on the amygdala. Prolongation of hypergravity resulted in reduction of Fos expression in the CeA, suggesting a process of habituation. Such decreases appeared earlier than in the vestibular nucleus, suggesting that adaptive changes in the CeA to hypergravity were independent of changes in the vestibular input. Our results suggest the amygdala is a neural substrate involved in the development of and habituation to motion sickness.


Two Cases of Laryngeal Palsy Caused by Varicella-Zoster Virus

水痘帯状疱疹ウイルスによる喉頭麻痺の2例


A new rotational test for vertical semicircular canal function


A Case of Calcific Retropharyngeal Tendinitis with a Differential Diagnosis of Retropharyngeal Abscess

咽後膿瘍と鑑別を要した切開沈着性長頸筋炎例


Long-term Prognosis of Vertigo and Hearing Loss in Ramsay Hunt Syndrome

ハント症候群におけるめまいと難聴の長期予後


Visual-vestibular conflict induced by virtual reality in humans

Conflicting inputs from visual and vestibular afferents produce motion sickness and postural instability. However, the relationship of visual and vestibular inputs to each other remains obscure. In this study, we examined the development of subjective sickness- and balance-related symptoms and objective equilibrium ataxia induced by visual-vestibular conflict (VVC) stimulation using virtual reality. The subjective symptoms evaluated by Graybiel's and Hamilton's criteria got gradually worse during the VVC. The objective postural instability was not observed during the VVC, but it occurred immediately after the VVC. There was a time lag between the subjective symptoms and objective ataxia induced by VVC. Our study suggests that the VVC inputs are processed in different pathways causing subjective autonomic symptoms and postural instability in humans.


Steroid effects on vestibular compensation in human

Vestibular neuritis (VN) rapidly damages unilateral vestibular periphery, inducing severe balance disorders. In most cases, such vestibular imbalance is gradually restored to within the normal level after clinical therapies. This successive clinical recovery occurs due to regeneration of vestibular periphery and/or accomplishment of central vestibular compensation. We experienced 36 patients with VN treated at our hospital, including cases in our previous preliminary report. To elucidate effects of steroid therapy both on the recovery of peripheral function and on the adaptation of central vestibular compensation, we examined caloric test and several questionnaires with two randomly divided groups, 18 steroid-treated and 18 nonsteroid-treated patients, over two years after the onset. These examinations revealed that steroid-treated patients had a tendency of better canal improvements (13/18, 72%) than nonsteroid-treated ones (10/18, 55.6%). However, there was no significant difference between these two groups. In cases with persistent canal paresis, steroid-treated patients (n = 5) reduced handicaps in their everyday life due to the dizziness induced by head and/or body movements and the disturbance of their mood, more effectively than those with nonsteroid therapy (n = 8). These findings suggest that steroid therapy with VN could be effective on not only vestibular periphery but central vestibular system, to restore the balance.


Biofeedback rehabilitation for prevention of synkinesis after facial palsy

We developed a new training method of biofeedback rehabilitation for the prevention of synkinesis after facial palsy and evaluated the efficacy of the training. Twenty-seven patients with complete facial palsy were divided randomly into 2 groups. Twelve of the patients were treated with the training method, and the other 15 patients served as controls. Patients were instructed to keep their eyes open symmetrically during mouth movements using a mirror. Thirty minutes of daily training was continued for a period of 10 months. The degree of synkinesis was evaluated by computing the percent asymmetry of eye opening width. The percent asymmetry of eye opening width was significantly greater in the training group than in the control group (P < 0.05). The results indicate that the degree of synkinesis is much less in the training group than in the control group. Our new training method is very effective for preventing the development of synkinesis after facial palsy.


Radiation Therapy for Middle Ear Carcinoma;A Report of Three Cases

放射線治療を行った中耳癌の3症例

Three cases of middle ear carcinoma treated at our hospital are reported. All cases had histories of chronic otitis media or middle ear surgery. According to Stell's classification, staging was T3N0M0, T2N0M0 and T3N0M0, respectively. Because of advanced age or tumor extension around the carotid artery or the dura mater, irradiation, but not surgery, was indicated in all cases. Two of three cases also received Stereotactic Radiosurgery (SRS) to residual tumors. To date, both patients treated with SRS have survived for two years without recurrence. Another patient with a residual tumor with a volume beyond SRS indication died of disease one year after irradiation. We suggest that adding SRS therapy to irradiation is effective in the treatment of middle ear carcinoma.


ローリングマウス小脳におけるカルレチニン陽性unipolar brush cellとCRF陽性苔状線


ムンプス不顕感染によりめまい，難聴をきたした3歳児の症例

ムンプス不顕感染によりめまい，難聴をきたした3歳児の症例


スギ花粉症患者における塩酸セチリジン初期投与の有用性(第2報) --- QOLに対する効果


Differential action of ondansetron and dexamethasone to modify cisplatin-induced acute and delayed kaolin consumption in rats


Three-Dimensional Eye Rotation Axis Analysis of Benign Paroxysmal Positioning Nystagmus

We have developed a new technique for analyzing the rotation vector of eye movement with an infrared CCD camera [Imai et al.: Acta Otolaryngol 1999;119:24-28]. We used this technique to analyze the eye rotation axis of benign paroxysmal positioning nystagmus (BPPN) that was induced by the Dix-Hallpike maneuver in 14 patients with benign paroxysmal positioning vertigo (BPPV). Eye rotation axes of BPPN in 8 patients were closely perpendicular to the posterior canal of the undermost ear in the provocative head position. Under the hypothesis that BPPN is due to a mechanical stimulation of the posterior canal by canalolithiasis, this finding suggested that the posterior canal of the undermost ear is the lesion. On the other hand, eye rotation axes of BPPN in the other 6 patients were closely aligned with the naso-occipital axis. It is suggested that canalolithiasis induces endolymphatic flow in both posterior and anterior canals via the common crus and the summation of the eye movements induced by stimulation of both the posterior and anterior canals rotates the eye along the naso-occipital axis.

ORL; Journal for Oto-Rhino-Laryngology and its Related Specialties


Magnetic cortical responses evoked by visual linear forward acceleration

Cortical site processing the information of whole body linear acceleration has not yet been identified. In this study, neuromagnetic responses to visually induced linear forward acceleration were recorded in six healthy-right-handed adult subjects using a 122-channel whole cortex neuromagnetometer. Significant activation was estimated in the cortex around the posterior insula, which belongs to the vestibular cortex. Hence, it is suggested that the vestibular cortex not only receives vestibular input from the peripheral vestibular apparatus, but also processes the vestibular sensation from multi-modal information.


Changes in Fos Expression in the Rat Brainstem after Bilateral Labyrinthectomy

In order to elucidate the role of the vestibulocerebellar neural circuits during two-stage bilateral labyrinthectomy (BL) we examined Fos-like immunoreactive (-LIR) neurons as a marker of neural activation in the rat brainstem after BL and the projections of these neurons into the vestibulocerebellum using retrograde tracing and immunohistochemical techniques. Simultaneous BL did not show any Fos expression in the medial vestibular nucleus (MVe). However, with an interval of > 6 h between the two stages of BL, Fos-LIR neurons were induced in the ipsilateral (ipsi-) MVe of the side operated on second, partially projecting into the ipsi-vestibulocerebellum. A previous study demonstrated that some of the unilateral labyrinthectomy-induced Fos-LIR neurons in the ipsi-MVe projected into the ipsi-vestibulocerebellum and inhibited the contra-MVe neurons, resulting in the restoration of the right-left balance. Taken together with our present data, it is suggested that some of the labyrinthectomy-induced Fos expression in the ipsi-MVe is representative of a switch-on signal for the vestibulo-cerebello-vestibular inhibitory neural circuits, which remain turned off after symmetrical lesions such as simultaneous BL but are turned on after severe asymmetrical lesions in order to restore the balance.


Establishiment of an Animal Model for Radiation-induced Vomiting in Rats Using Pica

We investigated whether radiation-induced pica, a behavior characterized by the eating of a non-food substance, such as kaolin, can be used as an index of radiation-induced vomiting in rats. Since there was an individual difference in the susceptibility to pica, we selected rats that actually ate kaolin following X-ray irradiation, and used them for the experiment. The total-body irradiation (TBI) increased kaolin consumption in a dose-dependent manner (sham, 0.05 +/- 0.03 (SEM) g; 2 Gy, 0.38 +/- 0.11 g; 4 Gy, 1.54 +/- 0.28 g; 8 Gy, 3.55 +/- 0.67 g), and the increased kaolin consumption after 4 Gy of TBI was inhibited by a pretreatment with the serotonin 5-HT3 receptor antagonist ondansetron (2 mg/kg, i.p.) (saline, 1.49 +/- 0.33 g; ondansetron, 0.75 +/- 0.11 g). Furthermore, 4 Gy of abdominal irradiation was more effective to induce pica than that of head irradiation (abdomen: 0.37 +/- 0.05 g, head: 0.06 +/- 0.01 g). These findings suggested that peripheral serotonergic pathway is predominantly involved in the development of radiation-induced pica in rats and that the radiation-induced pica could be useful as a behavioral index for the severity of radiation-induced vomiting in rats.


内リンパ嚢高濃度ステロイド挿入術と血中内耳関連ホルモン動態

内リンパ嚢高濃度ステロイド挿入術と血中内耳関連ホルモン動態


Pica in mice as a new model for the study of emesis

In general, rats and mice have not been used in research on emesis because they do not vomit. However, emetogenic stimuli such as anticancer drugs, apomorphine, copper sulfate and rotation induced pica, a behavior characterized by eating nonfood substances such as kaolin, in rats. We also found that cisplatin induced pica in mice, but it was rather difficult to determine the exact kaolin consumption in this species. In this study, we prepared kaolin pellets mixed with carmine, a dye not absorbed in the gastrointestinal tract, and estimated kaolin consumption by determination of carmine excreted in feces. Cisplatin (5 mg/kg) caused a significant increase in kaolin consumption (saline: 0.15 +/- 0.08 g vs. cisplatin: 0.45 +/- 0.16 g) and pretreatment with the 5-HT3 receptor antagonist, ondansetron (2 mg/kg), suppressed the increased consumption (vehicle: 0.33 +/- 0.05 g vs. ondansetron: 0.13 +/- 0.04 g). These findings suggested that the exact kaolin consumption could be quantified by the determination of carmine in feces and that mice could be useful for studying emesis.

Methods and Findings in Experimental and Clinical Pharmacology


The effect of cetirizine prophylactic treatment for patients with Japanese cedar pollinosis --- 花粉症症状に対する効果

スギ花粉症患者における塩酸セチリジン初期投与の有用性(第1報) --- 花粉症症状に対する効果


An increased expression of Ca2+ channel alpha1A subunit immunoreactivity in deep cerebellar neurons of rolling mouse Nagoya.

Rolling mouse Nagoya (RMN) is an ataxic mutant and carries a mutation in the gene coding for the alpha(1A) subunit of the P/Q-type Ca(2+) channel. We examined the immunohistochemical expression of the alpha(1A) subunit in deep cerebellar nuclei of RMN. The antibody used recognized residues 865-883 of the mouse alpha(1A) subunit not overlapping the altered sequences in RMN. In RMN, many neurons exhibited definite alpha(1A) subunit-staining in the medial nucleus, interposed nucleus, and lateral nucleus of deep cerebellar nuclei. The number of positive neurons in these nuclei was significantly higher in RMN than in controls. Increased expression of the alpha(1A) subunit in deep cerebellar neurons might compensate for the altered function of the P/Q-type Ca(2+) channel of RMN.


Effect of AF64A, a cholinergic neurotoxin, on footshock stimulation-induced locus coeruleus excitation in rats

We studied the effect of ethylcholine mustard aziridinium ion (AF64A), a cholinergic neurotoxin, on the footshock stimulation (FS)-induced excitation of the locus coeruleus (LC) neurons in rats. The FS-evoked LC excitation was significantly reduced in AF64A-treated rats, in comparison with normal rats. In particular, the early component of LC excitation was less pronounced. The number of choline acetyltransferase immunoreactive neurons in the septal complex was significantly lower than those in normal rats, except for in the ventral subgroup. These findings suggest that the cholinergic neuron system is involved in the early component of LC excitation in rats.


Effects of Exposing the Opened Endolymphatic Sac to Large Doses of Steroids to Treat Intractable Meniere's Disease

To enhance the effect of treatment for intractable Meniere's disease, we exposed the opened endolymphatic sac to high concentrations of steroids. This technique--endolymphatic sac drainage and steroid instillation surgery--involves the application of a mass of prednisolone followed by absorbable gelatin sponges soaked in a high concentration of dexamethasone into a sac lumen opened and expanded with a bundle of absorbable gelatin film. These sponges are also placed around the sac and coated with biochemical adhesive so that the medicine is slowly delivered into the sac over a prolonged period of time by means of a natural sustained-release vehicle. The short-term results (6 to 14 months) in 12 patients with Meniere's disease, including those in stage IV, treated by the above techniques showed that definitive spells were completely controlled in all cases. Hearing was improved, and annoyance due to tinnitus was decreased in all cases except one.

The Annals of Otology, Rhinology, and Laryngology


Role of cholinergic mossy fibers in medial vestibular and prepositus hypoglossal nuclei in vestibular compensation

Several lines of evidence have suggested that acetylcholine is a possible neurotransmitter/neuromodulator involved in vestibular compensation. Further, the central vestibular system, oculo- and spino-motor neurons and peripheral vestibular efferents contain abundant cholinergic neurons. However, details of cholinergic effective sites during vestibular compensation remain to be clarified. In the present study, we selectively damaged rat vestibulo-floccular and vestibulo-uvulonodular cholinergic mossy fibers using ethylcholine mustard aziridinium ions. In these treated animals, unilateral labyrinthectomy caused more severe vestibulo-ocular deficits especially during the initial stage. From these findings we suggest that vestibulo-floccular and vestibulo-uvulonodular cholinergic mossy fibers contribute to the restoration of a balance between intervestibular nuclear activities for the induction of vestibular compensation during the initial stage.


末梢性顔面神経麻痺の発症早期における瞬目反射の興奮性の検討

末梢性顔面神経麻痺の発症早期における瞬目反射の興奮性の検討


前庭神経炎にたいするステロイド治療の効果に関する検討

前庭神経炎にたいするステロイド治療の効果に関する検討


メニエール病に対する内リンパ嚢局所ステロイド暴露による長期治療成績

メニエール病に対する内リンパ嚢局所ステロイド暴露による長期治療成績


[Vestibular symptoms and ENG findings during periods of convalescence after endolymphatic sac drainage and steroid-instillation surgery (EDSS)].

内リンパ嚢高濃度ステロイド挿入術の手術侵襲に伴うめまい経過

Understanding the appearance of vestibular symptoms during periods of convalescence after surgery for the treatment of Meniere's disease is important for determining when a patient can return to work as well as the long-term results of the operation. We have treated 20 cases of intractable Meniere's disease with endolymphatic sac drainage & steroid-instillation surgery (EDSS) [Kitahara T, et al., Ann Otol Rhlnol Laryngol in press, 2000] and observed the subjective symptoms and objective vestibular findings using electronystagmogram (ENG) during the subsequent period of convalescence. The average postoperative durations of subjective static and evoked vestibular symptoms were 1.7 and 6.7 days, respectively. Those of spontaneous, positional and positioning nystagmus observed using ENG were 1.2, 2.0 and 7.9 days, respectively. In cases with a long history of Meniere's disease, postoperative static vestibular sensation and positional nystagmus lasted significantly longer than in cases with short histories. In cases with poorly developed temporal bony pneumatization in the area behind the posterior semicircular canal, postoperative evoked vestibular sensations and positioning nystagmus lasted significantly longer than in cases with well developed temporal bony pneumatization. Vestibular symptoms resulting from direct invasion during EDSS were considered to be slighter than those resulting from vestibular neurectomy or gentamicin treatment and almost the same as those resulting from endolymphatic sac surgery.


Effects of Pre-flocculectomy on Fos Expression and NMDA Receptor-mediated Neural Circuits in the Central Vestibular System after Unilateral Labyrinthectomy

In this study in order to elucidate the role of the flocculus in the whole process of vestibular compensation from the very early stage to the chronic stage, we first examined unilateral labyrinthectomy (UL)-induced spontaneous nystagmus (SN), a behavioral marker of vestibular compensation, and Fos expression, a marker of neural activity, in the vestibular brainstem in pre-unilateral flocculectomized (pre-UF) rats. UL in pre-UF rats caused more severe vestibulo-ocular deficits at the very early stage than it did in floccular-intact rats. Fos expression occurred in the medial vestibular nucleus contralateral to the UL side (contra-MVe) and the prepositus hypoglossal nucleus ipsilateral to the UL side (ipsi-PrH), whereas Fos expression was never seen after UL in floccular-intact rats. Therefore, these findings suggest the UL in pre-UF rats activates the contra-MVe and ipsi-PrH neurons and causes great imbalance between intervestibular nuclear activities, inducing more severe vestibular symptoms at the very early stage than those in floccular-intact rats. Next, we observed MK801 (a specific antagonist on the NMDA receptor)-induced SN in pre-UF rats at the chronic stage after UL. MK801 administration to pre-UL rats caused reappearance of SN even 14 days after UL, while administration to floccular-intact rats at a post-UL interval of 14 days never induced decompensation. Therefore, these findings suggest that the flocculus takes part in NMDA receptor-mediated neural circuits involved in vestibular compensation and modifies the neural interactions at the chronic stage after UL. Taken together, those results suggest that the flocculus plays important roles in the restoration of a balance between intervestibular nuclear activities, to reduce vestibular symptoms during the very early stage, and thereafter in the modification of NMDA receptor-mediated neural interactions in the central vestibular system at the chronic stage.


Effects of Amygdala or Hippocampus Lesion on Hypergravity-induced Motion Sickness in Rats

We examined the effects of amygdala lesion (AL) or hippocampal lesion (HL) on hypergravity-induced motion sickness in rats. Rats do not vomit, but the behavior known as pica, the eating of non-nutritive substances such as kaolin, can be used as an index of motion sickness. In the present study, hypergravity-induced kaolin intake and apomorphine-induced kaolin intake were measured before and after brain lesions. After AL, hypergravity-induced kaolin intake and the ratio of the hypergravity- to apomorphine-induced kaolin intakes were decreased. These results indicate that AL suppressed motion sickness more than pica behavior itself, suggesting that the amygdala plays an important role in the development of motion sickness in rats. Conversely, after HL, hypergravity-induced kaolin intake was increased, as was the ratio of the hypergravity- to apomorphine-induced kaolin intakes. These results indicate that HL aggravates motion sickness induced by hypergravity in rats, suggesting that the hippocampus counteracts motion sickness.


Postoperative results for cholesteatoma in children

to review the postoperative results for cholesteatoma in children. 32 ears with acquired cholesteatoma in children operated on by a single surgeon between 1987 and 1995 and followed up more than 2 years. The mean follow-up period was 5.4 years. a one-stage operation was performed in seven ears (21.9%) and preplanned stage operation in 25 ears (78.1%). In the first operation, closed tympanoplasty was performed in 31 ears (96.9%) and open tymapanoplasty in one ear (3.1%). During the second stage operation, residual cholesteatoma was found in 16 ears (64.0%). Recurrent cholesteatoma was detected in 19.4% of ears treated with closed tympanoplasty. The mean postoperative air conduction hearing level was within 20 dB in 12.5%, 30 dB in 40.6% and 40 dB in 78.1%. The hearing results of type III tympanoplasty was better than those of type IV tympanoplasty. preplanned stage tympanoplasty is safer because of the high risk of recurrent and residual cholesteatoma. Surgical methods should be selected flexibly in individual cases depending upon cavity size, eustachian tube function and hearing level. Cholesteatoma in children should be operated on while stapes is present.


A Long-term Prognosis of Sudden Deafness with Vertigo ; A Retrospective

めまいを伴う突発性難聴の平衡障害長期予後


Effects of Vestibular Cerebellum Lesion on Motion Sickness in Rats

The importance of the vestibular apparatus in the development of motion sickness is widely accepted, although the role of the vestibular cerebellum remains controversial. We examined the effects of vestibular cerebellum lesion on the development of motion sickness in rats. Rats do not vomit, but the behaviour known as "pica", the eating of non-nutritive substances, such as kaolin, can be used as an index of motion sickness. A 2 h load of hypergravity induced pica in rats, indicating that they suffered from motion sickness. Pica was induced by hypergravity load even after surgical lesion to the bilateral cerebellar flocculus or to the cerebellar vermis. We concluded that the vestibular cerebellum was not essential in the development of motion sickness in rats.


Cholinergic Influence on Vestibular Stimulation-Induced Locus Coeruleus Inhibition in Rats

In our previous study, caloric stimulation (CS) of the vestibular apparatus inhibited noradrenergic neuronal activity in the locus coeruleus (LC) in urethane-anaesthetized rats. Therefore, the inhibition of LC noradrenergic neurons is involved in vestibulo-autonomic responses. Since motion sickness can be cured by scopolamine, cholinergic neuron system may also be involved in vestibulo-autonomic responses. The present study examined the effects of intracerebroventricular injection of ethylcholine mustard aziridinium ion (AF64A), a presynaptic cholinergic neurotoxin, on CS-induced LC inhibition. In AF64A-treated rats, the CS-induced LC inhibition was less pronounced than in normal rats. In a subsequent series of experiments, the intravenous injection of scopolamine blocked the CS-induced LC inhibition. These findings suggest that central cholinergic neurons are associated with noradrenergic neuronal inhibition during the vestibulo-autonomic reflex.


VR技術を用いたシミュレータの体験時間の検討

VR技術を用いたシミュレータの体験時間の検討

Transactions of the Virtual Reality Society of Japan

日本バーチャルリアリティ学会論文誌


Rotation Vector Analysis of Eye Movement in Three Dimensions with an Infrared CCD Camera

We have developed a new technique for analyzing the rotation vector of eye movement in three dimensions with an infrared CCD camera based on the following four assumptions; i) the eye rotates on a point; ii) the pupil edge is a circle; iii) the distance from the center of eye rotation to pupil circle remains unchanged despite the rotation; iv) the image of the eye by the CCD camera is projected onto a plane which is perpendicular to the camera axis. After taking digital images of voluntary circular eye movements, we first constructed a three-dimensional frame of reference fixed on the orbita of the subject wearing a goggle equipped with an infrared CCD camera, and determined the space coordinates of the center of eye rotation, the center of the pupil, and an iris freckle. We then took digital images of the eye movements during a saccade or vestibulo-ocular reflex (VOR) and analyzed the axis and angle of the eye movements by the trajectories of the center of the pupil and the iris freckle. Finally, Listing's plane of saccade and the gain and the phase of VOR were obtained. The suitability of this technique is examined.


Developmental localization of semaphorin H messenger RNA acting as a collapsing factor on sensory axons in the mouse brain

Semaphorins/collapsins, a family of genes with a semaphorin domain conserved from insects through to mammals, are believed to be involved in axon guidance during neuronal development. We report the expression patterns of mouse semaphorin messenger RNAs. Among secreted semaphorins, mouse semaphorin H is structurally most similar to semaphorin III/D, the first semaphorin identified as a collapsing factor for sensory axons. However, its expression patterns apparently differ from those of semaphorin III/D. The messenger RNAs are distributed in the brain widely but unevenly during development, in particular, in the main olfactory bulb, hippocampus and pontine nucleus. In the trunk, the expression level is high in mesodermal tissues surrounding the dorsal root ganglia, while it is low in the spinal cord. Moreover, we examined whether this molecule has activity to collapse growth cones of sensory neurons, as well as semaphorin III/D. Mouse semaphorin H collapsed growth cones of sensory neurons of the dorsal root ganglion in a dose-dependent manner, and anti-neuropilin antibodies inhibited this activity. Taken together, these results suggest that mouse semaphorin H can function as a chemorepellent to guide sensory peripheral nerves, most likely via neuropilin as a receptor.


Mouse semaphorin H inhibits neurite outgrowth from sensory neurons

Mouse semaphorin H (M-semaH) was structurally similar to semaphorin III/D, a mammalian homologue of collapsin 1 which was identified as a collapsing factor for sensory nerves. In this study we investigated the expression patterns of M-semaH mRNA and the protein binding sites in the trunk of mouse embryos. M-semaH mRNA was expressed in the mesenchymal tissues surrounding each dorsal root ganglia. These tissues include the caudal sclerotome and perinotochordal mesenchyme, which were thought to express factors repulsive to axons. M-semaH binding was detected on the spinal nerves. We further investigated, using in vitro co-culture assay, whether M-semaH acted as a chemorepulsive molecule on sensory axons. The results suggested that M-semaH was a candidate for a chemorepellent expressed in the mesenchyme surrounding the sensory ganglia, which is involved in the axonal guidance mechanism of sensory nerves in the trunk.


Expression of mouse semaphorin H mRNA in the inner ear of mouse fetuses

Semaphorins constitute a large family of secreted and cell-surfaced proteins that appear to function as chemorepellents to guide axons. We examined the expression pattern of M-semaH mRNA in the inner ear of mouse fetuses by in situ hybridization histochemistry. M-semaH mRNA expression was high in the endolymphatic sac involved in endolymph homeostasis. It was also high in the semicircular ducts except for the crista ampullaris, whereas no expression was detected in the epithelium of cochlear ducts.


Nitric oxide in the flocculus works the inhibitory neural circuits after unilateral labyrinthectomy

We previously reported that nitric oxide (NO) production in the unipolar brush (UB) cells is involved in vestibular compensation [T. Kitahara, N. Takeda, P.C. Emson, T. Kubo, H. Kiyama, Changes in nitric oxide synthase-like immunoreactivities in unipolar brush cells in the rat cerebellar flocculus after unilateral labyrinthectomy, Brain Res. 765 (1997) 1-6]. To further elucidate the role of NO-mediated signaling in flocculus after unilateral labyrinthectomy (UL), we examined UL-induced Fos expression, a marker of neural activity, in vestibular brainstem with continuous floccular infusions of Nomega-nitro-l-arginine methyl ester (l-NAME), an inhibitor of NO synthase (NOS). After UL with floccular l-NAME infusions, Fos expression appeared in bilateral medial vestibular (MVe) and prepositus hypoglossal (PrH) nuclei. After UL with floccular saline infusions, however, Fos expression was observed only in the ipsi-MVe and contra-PrH. Furthermore, it has been revealed that UL with l-NAME infusions caused more severe vestibulo-ocular disturbances than UL with saline infusions at the initial stage [Kitahara et al. Brain Res. 765 (1997) 1-6]. Therefore, it is suggested that UL with floccular l-NAME infusions activates the contra-MVe and ipsi-PrH neurons and causes more severe imbalance between intervestibular nuclear activities at the initial stage. NO-mediated signaling in flocculus could be a possible driving force of the flocculus-mediated inhibition on the contra-MVe and ipsi-PrH at the initial stage of vestibular compensation.


内リンパ嚢開放高濃度ステロイド挿入術

内リンパ嚢開放高濃度ステロイド挿入術


Unilateral labyrinthectomy downregulates glutamate receptor δ-2 expression in the rat vestibulocerebellum

The differential display method was applied to identify genes expression of which is altered in the flocculus after unilateral labyrinthectomy (UL). Total RNA from sham operated and labyrinthectomized rat flocculi was isolated, amplified by PCR using an arbitrary primer set and separated by electrophoresis on a polyacrylamide gel. PCR products the amounts of which were significantly lower in samples from labyrinthectomized animals than those from controls, were cut out of the gel and sequenced. One of the cDNA fragments showed 100% nucleotide sequence identity to the rat glutamate receptor (GluR) delta-2 subunit mRNA. In situ hybridization autoradiography showed that GluR delta-2 mRNA expression was intensely located to the floccular Purkinje cell layers. Furthermore, northern blot analysis showed that the delta-2 mRNA expression was decreased for at least two days after UL in accordance with diminishing UL-induced behavioral deficits. Therefore, it is suggested that the downregulation of delta-2 mRNA is involved in vestibular compensation. UL-induced spontaneous nystagmus (SN) was then examined in GluR delta-2 mutant mice. The frequency of SN in mutant mice was significantly more than that in wild mice until 12 h after UL. GluR delta-2-associated synaptic efficacy may be changed for the induction of vestibular compensation at the initial stage.

Brain Research. Molecular Brain Research


An Implication of Protein Phosphatase 2A-ß in the Rat Flocculus for Lesion-induced Vestibular Plasticity

The differential display method was applied to identify genes, the expression of which is up-regulated in the cerebellar flocculus after unilateral labyrinthectomy (UL). Total RNA from sham-operated and labyrinthectomized rat flocculi was isolated, amplified by polymerase chain reaction (PCR) using a single arbitrary primer and separated by electrophoresis on a polyacrylamide gel. PCR products in amounts significantly higher in samples from labyrinthectomized animals than in those from controls were cut out of the gel and sequenced. One of the cDNA fragments showed 100% nucleotide sequence identity to the rat protein phosphatase 2A (PP2A)-beta catalytic subunit mRNA. In situ hybridization histochemistry and Northern blot analysis showed that PP2A-beta mRNA expression was intensely localized to the floccular Purkinje cell layer and up-regulated with a maximum increase within 2 days after UL. In labyrinthectomized rats, UL-induced nystagmus gradually disappeared within 3 days after UL. However, in animals with continuous floccular infusion of okadaic acid, a potent inhibitor of PP2A, UL-induced nystagmus lasted significantly longer. All these findings suggest that up-regulation of PP2A-beta mRNA in floccular Purkinje cells after UL is involved in lesion-induced vestibular plasticity. So far, various kinds of neural plasticity-associated molecules have been investigated mainly by slice in vitro studies. This paper indicates that differential display is the feasible molecular biological in vivo method for an investigation about the mechanism of neural plasticity.


Auditory evoked off-response: its source distribution is different from that of on-response


分子生物学的手法による前庭代償分子機構の解明 --- Differential Display 法を用いて


遅発性内リンパ水腫症例の臨床的検討

遅発性内リンパ水腫症例の臨床的検討


めまいに対するブロマゼパムの治療効果

めまいに対するブロマゼパムの治療効果


垂直半規管の回転検査 --- 頭位別の眼球運動解析

垂直半規管の回転検査 --- 頭位別の眼球運動解析


上眼瞼向き眼振を認めた Werniche 脳症例

上眼瞼向き眼振を認めた Werniche 脳症例


Changes in nitric oxide synthase-like immunoreactivities in unipolar brush cells in the rat cerebellar flocculus after unilateral labyrinthectomy


Histamine Release From the Hypothalamus Induced by Gravity Change in Rats and Space Motion Sickness


Neurons in rostral ventrolateral medulla mediate vestibular inhibition of locus coeruleus in rats