Effect of Glutamine Supplementation on Chemoradiotherapy-induced Mucositis in Patients with Head and Neck Cancer

頭頸部癌化学放射線療法による口内炎に対するグルタミン含有成分栄養剤の使用経験

In head and neck cancer, almost all patients treated with chemoradiotherapy suffer from oral mucositis. But, a standard treatment for chemoradiotherapy-induced oral mucositis has not been established. It is considered that the creation of reactive oxygen species (ROS) caused by radiation and anticancer drugs is related to the mechanism that causes oral mucositis. Recently, it was reported that glutamine, an antioxidant, can reduce oral mucositis induced by chemoradiotherapy. Therefore, in the present study we examined the effects of glutamine supplementation on oral mucositis in head and neck cancer patients receiving chemoradiotherapy. Of the patients with head and neck cancer who received chemoradiotherapy or radiotherapy, we compared 6 patients receiving glutamine supplementation and 7 patients not receiving it. The patients receiving glutamine supplementation showed a reduction in the grade of oral mucositis with grade 4 never being reached, and both intake and the type of food were maintained. There was a significant elevation of the C-reactive protein (CRP) score in patients not receiving glutamine supplementation compared with those who received it (2.43 vs. 0.77, <i>P</i><0.05). This result suggested that glutamine supplementation had therapeutic effects on oral mucositis induced by chemoradiotherapy.


Effects of chemotherapy on gene expression of lingual taste receptors in patients with head and neck cancer.

We aimed to test the hypothesis that chemotherapy changes the gene expression of taste receptors in the tongue to induce dysgeusia in patients with head and neck cancer. Prospective observation study. We enrolled 21 patients who received chemoradiotherapy and five patients who underwent radiotherapy for head and neck cancer. The messenger RNA (mRNA) levels of the taste receptor subunits T1R1, T1R2, T1R3, and T2R5 were measured in lingual mucosa scrapings obtained with a small spatula. The perception thresholds of umami, sweet, and bitter tastes were assessed by the whole mouth gustatory test. In four patients with severe stomatitis induced by chemoradiotherapy, the mRNA levels of T1R1, T1R2, T1R3, and T2R5 in the lingual mucosa were significantly decreased. However, in 17 patients with mild/moderate stomatitis, the mRNA levels of T1R3 were significantly and transiently decreased, whereas those of T1R1 and T1R2 remained unchanged and those of T2R5 mRNA were significantly and transiently increased after chemotherapy. There was a significant negative correlation between the perception thresholds of umami or sweet tastes and lingual mRNA levels of T1R3 in patients with mild/moderate stomatitis after chemotherapy. Although the perception threshold of bitter taste remained unchanged, lingual mRNA levels of T2R5 were significantly increased in patients who complained of phantogeusia after chemotherapy. Chemotherapy specifically changed the gene expression of T1R3 and T2R5 in head and neck cancer patients with mild/moderate stomatitis, resulting in both dysgeusia of umami and sweet tastes as well as phantogeusia. 4. Laryngoscope, 126:E103-E109, 2016.


Disruption of Heat Shock Protein 90 (Hsp90)-Protein Kinase Cδ (PKCδ) Interaction by (-)-Maackiain Suppresses Histamine H1 Receptor Gene Transcription in HeLa Cells

The histamine H1 receptor (H1R) gene is an allergic disease sensitive gene, and its expression level is strongly correlated with the severity of allergic symptoms. (-)-Maackiain was identified as a Kujin-derived anti-allergic compound that suppresses the up-regulation of the H1R gene. However, the underlying mechanism of H1R gene suppression remains unknown. Here, we sought to identify a target protein of (-)-maackiain and investigate its mechanism of action. A fluorescence quenching assay and immunoblot analysis identified heat shock protein 90 (Hsp90) as a target protein of (-)-maackiain. A pull-down assay revealed that (-)-maackiain disrupted the interaction of Hsp90 with PKCδ, resulting in the suppression of phorbol 12-myristate 13-acetate (PMA)-induced up-regulation of H1R gene expression in HeLa cells. Additional Hsp90 inhibitors, including 17-(allylamino)-17-demethoxygeldanamycin, celastrol, and novobiocin also suppressed PMA-induced H1R gene up-regulation. 17-(Allylamino)-17-demethoxygeldanamycin inhibited PKCδ translocation to the Golgi and phosphorylation of Tyr(311) on PKCδ. These data suggest that (-)-maackiain is a novel Hsp90 pathway inhibitor. The underlying mechanism of the suppression of PMA-induced up-regulation of H1R gene expression by (-)-maackiain and Hsp90 inhibitors is the inhibition of PKCδ activation through the disruption of Hsp90-PKCδ interaction. Involvement of Hsp90 in H1R gene up-regulation suggests that suppression of the Hsp90 pathway could be a novel therapeutic strategy for allergic rhinitis.


Maackiain is a novel antiallergic compound that suppresses transcriptional upregulation of the histamine H1 receptor and interleukin-4 genes.

Kujin contains antiallergic compounds that inhibit upregulation of histamine H1 receptor (H1R) and interleukin (IL)-4 gene expression. However, the underlying mechanism remains unknown. We sought to identify a Kujin-derived antiallergic compound and investigate its mechanism of action. The H1R and IL-4 mRNA levels were determined by real-time quantitative RT-PCR. To investigate the effects of maackiain in vivo, toluene-2,4-diisocyanate (TDI)-sensitized rats were used as a nasal hypersensitivity animal model. We identified (-)-maackiain as the responsible component. Synthetic maackiain showed stereoselectivity for the suppression of IL-4 gene expression but not for H1R gene expression, suggesting distinct target proteins for transcriptional signaling. (-)-Maackiain inhibited of PKCδ translocation to the Golgi and phosphorylation of Tyr(311) on PKCδ, which led to the suppression of H1R gene transcription. However, (-)-maackiain did not show any antioxidant activity or inhibition of PKCδ enzymatic activity per se. Pretreatment with maackiain alleviated nasal symptoms and suppressed TDI-induced upregulations of H1R and IL-4 gene expressions in TDI-sensitized rats. These data suggest that (-)-maackiain is a novel antiallergic compound that alleviates nasal symptoms in TDI-sensitized allergy model rats through the inhibition of H1R and IL-4 gene expression. The molecular mechanism underlying its suppressive effect for H1R gene expression is mediated by the inhibition of PKCδ activation.


Research ethics committees in Japan: A perspective from thirty years of experience at Tokushima University.

The first Japanese ethics committee for biomedical research involving human subjects was established at Tokushima University in 1982. Although this committee was not formed as a response to national directives, the government eventually developed ethical guidelines, such as the Ethical Guidelines for Clinical Studies that were established in 2003. The practical impact of such guidelines was a rapid increase in the number of protocols seeking ethics committee approval and, accordingly, an increase in the workload of ethics committees. This review describes the activity of the ethics committee at Tokushima University during the last thirty years and discusses the infrastructure that best supports the activities of this committee. In addition, we address the issues that ethics committees now face and discuss future directions. J. Med. Invest. 62: 114-118, August, 2015.

The Journal of Medical Investigation : JMI


A Case of Adenomatoid Odontogenic Tumor in the Maxillary Canine

上顎犬歯から発生した腺様歯原性腫瘍例

The adenomatoid odontogenic tumor (AOT) is a rare benign odontogenic tumor that is mostly found in jawbone. It is generally found in the incisor region of the maxilla of young females. It rarely extends into the paranasal sinuses. This article describes a case of AOT found in the maxilla and occupying the maxillary sinus and nasal cavity.<br>A 20-year-old woman was referred to our department because of swelling of the left cheek. CT examination showed a cystic lesion in the left maxillary sinus including calcified structures and an impacted tooth. A biopsy specimen of the lesion revealed an adenomatoid odontogenic tumor. We performed tumor extirpation combined with the Caldwell-Luc operation. There is no evidence of recurrence 3 years after the operation.


Endoscopic Approach to Organized Hematoma of Maxillary Sinus Using the Swinging Technique of Nasolacrimal Duct and Inferior Turbinate

鼻涙管下鼻甲介スイング法にて内視鏡下に摘出した上顎洞血瘤腫例

We report a 63-year-old woman with recurrent nasal bleeding diagnosed with organized hematoma in the maxillary sinus. Computed tomography showed an expanding lesion with thinning and defect of the adjacent bone and magnetic resonance imaging showed heterogeneous signal intensity with thickening of the maxillary sinus mucosa and marked patchy enhancement. After selective embolization of the feeding artery, we conducted endoscopic sinus surgery and applied the swinging technique of the nasolacrimal duct and inferior turbinate for resection of the organized hematoma. It provides a wide surgical field for the maxillary sinus, resulting in en bloc resection with a straight endoscope and instruments. The postoperative course was uneventful and no recurrence was observed in the 1.5-year follow-up. The swinging technique allows wide and direct access to the maxillary sinus through anterior space of the nasolacrimal duct without damaging the nasolacrimal duct or inferior turbinate mucosal function. This technique is a safe and effective method to remove benign maxillary sinus diseases endoscopically by good accessibility to and visualization of the maxillary sinus.

鼻涙管下鼻甲介スイング法を用いて内視鏡下に摘出した上顎洞血瘤腫例を経験したので報告する．症例は63歳女性で主訴は右鼻出血．CTでは右上顎洞内に膨張性の発育を示す軟部組織陰影が充満し，上顎洞自然口付近から腫瘤中心部にかけて不均一な造影効果を認めた．MRIではT1強調画像で等信号域，T2強調画像で辺縁が低信号域，内部が低信号域と高信号域が混在した腫瘤を認めた．画像所見から血瘤腫を疑い血管造影で栄養血管を確認し，手術前日に塞栓術を施行した．内視鏡下副鼻腔手術により，腫瘤を一塊に切除する目的で鼻涙管下鼻甲介スイング法を用いて摘出術を行った．まず粘膜下下鼻甲介骨切除術を行った後，下鼻道側壁粘膜を剥離し，鼻涙管と下鼻甲介粘膜を一塊として温存した．次に鼻涙管と下鼻甲介を内側・外側へスウィングさせながら上顎洞内側壁を広く切除し，上顎洞を大きく開放した．鼻涙管と下鼻甲介を内側へスウィングさせることで，鼻涙管の前方を経由して上顎洞へアプローチし，上顎洞内の大部分を直視鏡下に弯曲の少ない手術器具を用いて処理でき，血瘤腫を一塊に上顎洞粘膜から切除した．鼻涙管下鼻甲介スイング法は，鼻涙管や下鼻甲介粘膜機能を温存して上顎洞内の処理を広い術野で直視鏡下に行うことが可能であり，血瘤腫などの上顎洞を主座とする腫瘤性病変に広く有用であると考えられた．


Efficacy of percutaneous endoscopic gastrostomy on unplanned treatment interruption and nutritional status in patients undergoing chemoradiotherapy for advanced head and neck cancer.

It is suggested that therapeutic PEG placement is useful for preventing unplanned interruption of CRT in patients with advanced head and neck cancer. After severe mucositis and inadequate oral intake have developed during CRT, PEG placement should be considered before the radiation therapy dose of 30 Gy.


Light cupula: the pathophysiological basis of persistent geotropic positional nystagmus.

Geotropic or apogeotropic positional nystagmus was recorded by video-oculography and analysed three-dimensionally.

Since its TC was >35 s, it is suggested that PGN is induced by cupula deviation in response to gravity at each head position. It is also suggested that the direction of cupula deviation in patients with PGN is opposite to that of patients with AN across the neutral head positional range with no nystagmus where the long axis of cupula is in alignment with the axis of gravity. Since the pathophysiological basis of AN is considered a heavy cupula, it is suggested that PGN is conversely induced by a light cupula.


A Case of Sinonasal-type Hemangiopericytoma Resected with Endoscopic Sinus Surgery

We report herein on a 75-year-old woman with sinonasal-type hemangiopericytoma (HPC). She complained of nasal bleeding and a nasal tumor originated from the left nasal septum was found. It was successfully resected using endoscopic sinus surgery without preoperative embolization, because we were uncertain of its feeding artery. Its pathological examination gave a diagnosis of sinonasal-type of HPC. The sinonasal-type HPC is a rare benign sinonasal tumor, but WHO has classified it as a borderline malignancy, because it may have multiple relapses. Our patient remained free of relapse 36 months after the treatment.


The temperature of aural air stimulation equivalent to aural stimulation with water at 20<SUP>°</SUP>C in the caloric test.

少量注水法に対応するエアーカロリック検査の刺激条件の検討

In the present study, we examined the temperature of aural air stimulation that was equivalent to aural stimulation with water at 20°C in the caloric test. In 10 ears of 5 healthy volunteers, the maximum slow phase eye velocities (MSPEVs) of nystagmus induced by aural stimulation with air at 22°C, 46°C and 16°C were the same as those with water at 30°C, 44°C and 20°C, respectively. These findings suggest that caloric stimulation with air at 16°C is equivalent to that with water at 20°C that is commonly used in the caloric test in Japan. The MSPEVs of nystagmus induced by aural stimulation with air at 16°C were over 20°/sec in all ears except one, in which the MSPEV was 19.7°/sec. The criteria of canal paresis where the MSPEV of caloric nystagmus induced by aural stimulation with water at 20°C is less than 20°/sec can be used in the caloric test with aural air stimulation at 16°C.


難治性中耳炎症状を呈するANCA陽性症例の疫学調査と診断基準の問題点に関する検討


発症した病的共同運動に対するボツリヌス毒素・ミラーバイオフィードバック併用療法の治療開始時期による効果の検討


小児集団リハビリテーションにおける病的共同運動治療の長期経過観察症例の検討

小児集団リハビリテーションにおける病的共同運動治療の長期経過観察症例の検討


Effects of aural stimulation with capsaicin ointment on swallowing function in elderly patients with non-obstructive dysphagia.

In the present study, an attempt was made to examine the effects of aural stimulation with ointment containing capsaicin on swallowing function in order to develop a novel and safe treatment for non-obstructive dysphagia in elderly patients. A prospective pilot, non-blinded, non-controlled study with case series evaluating a new treatment. Secondary hospitals. The present study included 26 elderly patients with non-obstructive dysphagia. Ointment containing 0.025% capsaicin (0.5 g) was applied to the external auditory canal with a cotton swab under otoscope only once or once a day for 7 days before swallowing of a bolus of colored water (3 mL), which was recorded by transnasal videoendoscopy and evaluated according to the endoscopic swallowing score. After a single application of 0.025% capsaicin ointment to the right external auditory canal, the endoscopic swallowing score was significantly decreased, and this effect lasted for 60 minutes. After repeated applications of the ointment to each external auditory canal alternatively once a day for 7 days, the endoscopic swallowing score decreased significantly in patients with more severe non-obstructive dysphagia. Of the eight tube-fed patients of this group, three began direct swallowing exercises using jelly, which subsequently restored their oral food intake. These findings suggest that stimulation of the external auditory canal with ointment containing capsaicin improves swallowing function in elderly patients with non-obstructive dysphagia. By the same mechanism used by angiotensin-converting enzyme inhibitors to induce cough reflex, which has been shown to prevent aspiration pneumonia, aural stimulation with capsaicin may reduce the incidence of aspiration pneumonia in dysphagia patients via Arnold's ear-cough reflex stimulation.


Time Course of Changes in Gustatory Function Test Results and Subjective Symptoms,and Predictive Factors for Response in Patients with Taste Disorder Receiving 24-week Zinc Replacement Treatment

味覚障害患者に対する24週間の亜鉛内服治療における味覚機能検査と自覚症状の経時的推移および効果予測因子

In a taste disorder, an agreement between patients complaints and gustatory function test results is not necessarily found both at the initial hospital visit and during the course of treatment; therefore, it is difficult to assess treatment responses and review treatment strategies based on the assessed treatment responses. The present study investigated the time course of changes in disc gustometry results and subjective symptom scores measured at 4-week intervals in 44 patients with a taste disorder who were considered eligible for zinc replacement treatment and who received polaprezinc at a dose of 150mg/day (equivalent to a 34mg/day dose of zinc) for up to 24 weeks. The study also examined the potential differences in treatment outcomes according to the predictive factors for response such as patient background and assessed disc gustometry results during the course of treatment. Results indicated that disc gustometry results and subjective symptom scores showed different time courses of changes. The response rate as measured by disc gustometry was 47.7% at week 12 of treatment, and showed a subsequent slow increase to 56.8% at week 24. On the other hand, subjective symptom scores showed a time-proportional improvement up to week 24. Among the patients included in the present study, a clear difference was found according to the presence or absence of an improving trend as determined by disc gustometry at week 12 of treatment, although there were no differences in ultimate treatment responses, including categories of taste disorder, according to patient background. Patients showing a trend toward improvement had significantly better treatment responses in terms of both ultimate response rates and subjective symptom scores, whereas patients showing no trend toward improvement were less likely to respond to the subsequent 12-week continued treatment.

味覚障害は, 初診時のみならず治療経過においても味覚機能検査の結果と患者の訴えとが必ずしも一致せず, 治療効果の評価やそれに応じた治療方針の見直しが難しい疾患である. 本研究では, 亜鉛内服治療の適応と診断された味覚障害患者44例に対してポラプレジンク150mg/日 (亜鉛量34mg/日) を最長で24週間投与し, 濾紙ディスク味覚検査法および自覚症状スコアを4週間ごとに評価し, 経時的推移を検討した. また, 効果予測因子として, 患者背景因子または濾紙ディスク味覚検査法による治療途中での評価結果に応じた治療転帰の違いについて検討した. 濾紙ディスク味覚検査法と自覚症状スコアでは異なる経時的推移を認めた. 濾紙ディスク味覚検査法の有効率は投与12週時で47.7%に達し, その後の上昇は緩やかで, 24週時では56.8%であった. 一方, 自覚症状スコアは24週時まで時間に比例した改善を認めた. 患者背景因子では, 本研究で対象とした患者においては, 味覚障害の分類を含めて最終的な効果に違いを認めなかったが, 投与12週時の濾紙ディスク味覚検査法での改善傾向の有無により明らかな差を認めた. 改善傾向にある症例は, 最終的な有効率, 自覚症状スコアともに有意に高い効果が示されるのに対して, 改善傾向を認めない症例は, その後の12週間の治療継続によっても効果が得られることは少なかった.


Long-term prognosis of hearing loss in patients with unilateral Ménière's disease.

Abstract Conclusion: The finding of deteriorated hearing loss at the initial visit at middle to high frequencies is a factor of poor hearing prognosis in Ménière's disease. Early intervention with instructions for lifestyle changes may lead to good outcomes in hearing. Objective: An attempt was made to examine long-term changes in hearing loss in unilateral Ménière's disease and factors associated with prognosis of hearing loss retrospectively. Methods: Based on their last hearing level of the affected ear, 36 patients were subdivided into two groups: the poor prognosis of hearing (PPH) group and the good prognosis of hearing (GPH) group. Results: In the PPH group, the hearing levels at the initial visit at middle and high frequencies were significantly worse than those in the GPH group. Moreover, the hearing loss progressed during the first 2 years of the disease, and stayed flat to approximately 50 dB at the later stage. Conversely, the hearing loss at the onset in the GPH group showed no further progression over the first 2 years, and remained constant to approximately 35 dB at the later stage. In addition, the mean intervals from the onset to the initial visit in the PPH group were significantly longer than those in the GPH group.


A Case of Langerhans Cell Histiocytosis of the Temporal Bone

側頭骨に発生したランゲルハンス細胞組織球症例

We report herein on a 19-year-old female with Langerhans cell histiocytosis (LCH) of the temporal bone. She complained of right ear fullness and showed conductive hearing loss of the right ear. CT imaging showed a tumor in the temporal bone and multiple nodules in the lung, and LCH was diagnosed by biopsy of the temporal bone tumor. After a series of remission-induction therapy of B1, but not A and maintenance therapy of B2 and C on the basis of the JLSG-02 protocol of the Japan LCH Study Group, LCH lesions in both organs disappeared and the defect of the temporal bone was replaced with new bone formation.


The Molecular Mechanism of Up-regulation of Histamine H1 Receptor mRNA in the Nasal Mucosa of Patients with Allergic Rhinitis and the Effect of Antihistamine on Histamine H1 Receptor Expression

アレルギー性鼻炎におけるヒスタミンH1受容体遺伝子発現亢進の分子機構とその制御

We are focusing on the histamine H1 receptor (H1R) as an allergic disease-sensitive gene. H1R is a rate-limiting molecule of the H1R signal because the signal is increased with elevated receptor expression levels. We discovered that the direct stimulation of H1R induced the up-regulation of H1R gene expression through PKCδ activation. The mechanism of H1R gene expression was revealed to play a key role in the receptor expression level in studies using cultured HeLa cells and allergic rhinitis model rats. Antihistamines have three effects: the blocking effect on histamine signaling of H1 receptors; the suppressive effect on histamine-induced up-regulation of H1R mRNA that is the transcriptional activation of H1R; and the suppressive effect on H1R mRNA in the absence of histamine that is the basal transcription of H1R. The third effect may be another side of the inverse agonist action of antihistamine. We demonstrated that repeated pretreatment with antihistamines in the allergic rhinitis model rats resulted not only in the improvement of symptoms but also in the suppression of the up-regulation of H1R mRNA in the nasal mucosa. We next investigated the effect of preseasonal prophylactic treatment with antihistamines on nasal symptoms and the expression of H1R mRNA of the nasal mucosa in patients with cedar pollen pollinosis. During the peak pollen period, the expression of H1R mRNA in the nasal mucosa and the scores of sneezing and watery rhinorrhea in patients receiving preseasonal prophylactic treatment with antihistamines were significantly suppressed in comparison with those in the patients without treatment. These results suggest that H1R is an allergic disease-sensitive gene and H1R plays an important role in allergic rhinitis through the regulation of histamine signaling.


A Case of Descending Necrotizing Mediastinitis Treated with Continuous Saline Irrigation with a Pleated Drain

外科的ドレナージとプリーツドレーンによる持続洗浄が有効であった降下性壊死性縦隔炎例

Descending necrotizing mediastinitis (DNM) requires an early and aggressive surgical approach. We report herein on a case of DNM in which continuous saline irrigation with a pleated drain was found to be useful. A 71-year-old man presented with a sore throat and a peritonsillar abscess, CT imaging showed that an abscess with gas had spread widely over the mediastinum. The pus culture showed Streptococcus milleri group, and anaerobic bacteria were not identified in this case, The CT imaging findings on the other hand revealed suspected anaerobic infection and so the conditions in this case had caused serious mixed infection. We performed aggressive therapies such as cervicomediastinal and transthoracic drainage combined with broad-spectrum antimicrobial therapy, but the abscess was not cleared. We therefore added transcervical continuous saline irrigation with a pleated drain. The patient responded well to this treatment and was discharged on the 62nd postoperative day. We found that continuous saline irrigation with a pleated drain was useful in this case.


Effects of repeated optic flow stimulation on gait termination in humans.

Repeated optic flow caused no significant change of body deviation or the time course of the gait termination process in comparison with that in the control. The walking velocity at the start of the termination process showed short-term flexibility that denoted a gradual increase over the trial for within-set and long-term flexibility that denoted a gradual decrease for between-set.


A Case of Pyoderma Gangrenosum in the Nasal Root Associated with Ulcerative Colitis

潰瘍性大腸炎に伴う鼻根部壊疽性膿皮症例

We report herein on a case with pyoderma gangrenosum in the nasal root associated with ulcerative colitis. Pyoderma gangrenosum is characterized by progressive skin necrosis and is often associated with chronic bowel inflammatory diseases such as ulcerative colitis and Crohn's disease. Although it bears a clinical resemblance to self-destructive abscesses or bacterial infection of the soft tissues, no bacteria and non-effects of antimicrobial agents were observed and the drainage of the abscess and debridement of necrotic tissue is contraindicated in patients with pyoderma gangrenosum. The treatment of the underlying disease is also effective for the treatment of pyoderma gangrenosum. In the present case, a steroid and mesalazine were effective for both the pyoderma gangrenosum and ulcerative colitis.


Clinical outcomes of tracheoesophageal diversion and laryngotracheal separation in neurologically impaired children

Outcomes of tracheoesophageal diversion and laryngotracheal separation were evaluated in 15 neurologically impaired children treated for intractable aspiration. A retrospective analysis of the hospital records was carried out in 15 consecutive pediatric patients who underwent either tracheoesophageal diversion or laryngotracheal separation with trumpet-shaped tracheotomy from 1999 to 2006 in Kagawa Children's Hospital. The number of hospital admissions for aspiration pneumonia after surgery was significantly decreased in 6 patients who were cared for at home. The parent-reported number of secretion suctioning was decreased after surgery especially in patients with pre-operative tracheotomy or intubation. Four patients fed through naso-gastric tube progressed with oral diet post-operatively, whereas 3 patients who had pre-operative tracheotomy developed temporary post-operative tracheocutaneous fistula that was managed by local wound care. It is suggested that tracheoesophageal diversion and laryngotracheal separation decrease the morbidity of pediatric patients and improve their quality of life and that of their parents. It is suggested that the risk of developing post-operative fistula is higher in pediatric patients with than without pre-operative tracheotomy.


Risk factors for poor outcome of a single Epley maneuver and residual positional vertigo in patients with benign paroxysmal positional vertigo.

The findings suggest that in patients with posterior semicircular canal (PSCC) benign paroxysmal positional vertigo (P-BPPV), head trauma and prolonged bedrest, but not inner ear disease, are risk factors for poor outcome of a single Epley maneuver and persistent residual positional vertigo. We first examined the efficacy of a single Epley maneuver and then assessed the time course in remission of residual positional vertigo in patients with idiopathic P-BPPV and secondary P-BPPV. A total of 157 patients with idiopathic P-BPPV and 40 patients with secondary P-BPPV (secondary to head trauma in 8 patients, to prolonged bedrest in 14 patients, and to inner ear disease in 18 patients) were treated with a single Epley maneuver. The negative rates of the Dix-Hallpike test on day 7 after a single Epley maneuver in both patients with P-BPPV secondary to head trauma (25%) and those with prolonged bedrest (36%) were significantly lower than that (73%) in patients with idiopathic P-BPPV. Additionally, the remission of residual positional vertigo in the former groups of patients was significantly delayed in comparison with that of the latter group. However, there were no significant differences in the efficacy of a single Epley maneuver and persistent residual positional vertigo between idiopathic P-BPPV and P-BPPV secondary to inner ear disease.


An Intractable Case of MPO-ANCA-associated Middle Ear Disease

難治性MPO-ANCA関連中耳疾患例

We report herein on an intractable case of MPO-ANCA-associated middle ear disease with sensorineural hearing loss and facial palsy. A 73-year-old female complained of otitis media-like symptoms, but the treatment for otitis media with effusion was ineffective. She then showed bilateral progressive sensorineural hearing loss and facial palsy. PR3-ANCA was negative, but MPO-ANCA was positive in the serum. CT imaging revealed that the lesion was limited to the middle ear cavity without lesions in the lung and kidney. Non-specific findings were obtained in the histopathological examination of granular tissue of the mastoid cavity. She was diagnosed as having MPO-ANCA-associated middle ear disease with sensorineural hearing loss and facial palsy on the basis of the clinical findings and we administered cyclophosphamide in addition to a steroid. Discontinuance of the immunosuppressive therapy was, however, forced because of bacterial infection. Thereafter, steroid therapy alone failed to improve the left deafness, right moderate sensorineural hearing loss and right facial palsy.


In the patient with true anterior canalolithiasis, the direction of positional nystagmus during reverse Epley maneuver was constant and its axis was perpendicular to the plane of the right ASCC three-dimensionally. In contrast, in the patient with pseudo-anterior canalolithiasis, the first positional nystagmus of which the axis was perpendicular to the plane of the left ASCC became a second positional nystagmus of which the axis was perpendicular to the plane of the right PSCC during the reverse Epley maneuver.


Air-bone gap estimated with multiple auditory steady-state response in young children with otitis media with effusion.

These findings suggest that bone-conduction ASSR can assess the normal or near normal cochlear sensitivity in young children with conductive hearing loss. It is also suggested that ASSR-estimated ABG can be used clinically to predict their accurate ABG.


A Case of a Laryngocele with Recurrent Infection

We report herein on a case of laryngocele with recurrent infection. A 48-year-old male complained of hoarseness and swelling of the left side of his neck. The endoscopic and CT scan examinations demonstrated the combined type of laryngocele that had expanded through the thyrohyoid membrane and had swollen up both medially and laterally in a dumbbell-like shape. To avoid the risk of laryngeal stenosis with the enlarged laryngocele infected by bacteria, in addition to intravenous infusion of an anti-bacterial drug, purulent discharge was drained from the infected laryngocele with a puncture needle. Because infection of the laryngocele was recurrent, it was surgically removed via an external neck approach under general anesthesia without any prophylactic tracheotomy. The laryngocele may be translated from a saccular cyst that had developed after the obstruction of communication between the laryngeal ventricle and the laryngeal saccule.


Therapeutic effects of diphenidol and betahistine on acute vertigo as determined by the self-assessment of handicap in daily life due to vertigo

急性期のめまいに対するジフェニドールとベタヒスチンの治療効果 患者による日常生活の障害の改善から評価した治療効果の比較

Diphenidol and betahistine are anti-vertigo medications used for the treatment of vertiginous disorders. In the present study, we compared the therapeutic effects of diphenidol and betahistine on the handicap in daily life due to vertigo in patients with acute vertigo. The administration of diphenidol for four weeks significantly decreased the scores for factor 1: handicap in social activities, factor 2: handicap in head movements, factor 3: handicap in body movements, factor 4: handicap in emotion, factor 5: handicap in human interactions and factor 6: handicap due to discomfort. Because diphenidol has both anti-vertigo and anti-emetic actions, these findings suggested that its administration for four weeks recovered the functional handicap associated with factors 2 and 3 and the discomfort handicap of factor 6, resulting in recovery of the social handicap in factors 1 and 5 and emotional handicap (factor 4) in patients with vertigo. On the other hand, the administration of betahistine for four weeks only significantly decreased the scores of factors 1 and 5. This finding suggested that long-term administration of betahistine may be necessary to recover the other factors associated with handicap in patients with vertigo, because betahistine is reported to gradually accelerate the process of vestibular compensation after the development of vestibular asymmetry.

今回，われわれはめまいによりもたらされる日常生活の障害の程度を客観的に評価できるアンケートを用い，ジフェニドールとベタヒスチンの治療効果を比較検討した．ジフェニドールは 4 週間投与で，めまいによる社会活動性の障害，めまいを増悪させる身体の動き(頭位，視覚)，めまいによる身体行動の制限(全般的，体動)，めまいによる感情障害，めまいによる対人関係の障害，めまいによる不快感のすべての因子を有意に改善させた．ジフェニドールは抗めまい作用に加えて制吐作用を持つことから，めまいによる機能障害およびめまいに伴う不快感を改善させ，その結果，めまいによる社会的障害およびめまいによる感情障害を改善させたものと考えられた．ベタヒスチンは 4 週間投与で，めまいによる社会活動性の障害，めまいによる対人関係の障害を有意に改善させたが，その他の因子には有意な改善を認めなかった．薬理作用の点から，ベタヒスチンは 2 カ月以上の長期投与を推奨している報告もあり，めまいにより引き起こされる日常生活の障害に対するベタヒスチンによる効果を明らかにするためには，さらに長期間の投与による検討が必要であると考えられた．


Combination of leukotoriene receptor antagonist with antihistamine has an additive suppressive effect on the up-regulation of H1-receptor mRNA in the nasal mucosa of toluene 2,4-diisocyanate-sensitized rat.

An attempt was made to clarify the additive suppressive effects of pranlukast, a cysteinyl leukotriene-receptor (LTR) antagonist, in combination with chlorpheniramine, an antihistamine, on the up-regulation of histamine H1-receptor (H1R) mRNA in toluene 2,4-diisocyanate (TDI)-sensitized rats. Although pre-treatment with pranlukast partially, but significantly, suppressed TDI-induced up-regulation of H1R mRNA and nasal symptoms, pre-treatment with the combination of pranlukast and chlorpheniramine significantly suppressed them in a manner greater than either drug alone. These findings suggest that the additive therapeutic effect of the combination of LTR antagonist and antihistamine is due to their additive suppression of H1R up-regulation.


Vestibular and cochlear neuritis in patients with Ramsay Hunt syndrome: a Gd-enhanced MRI study

It is suggested that vertigo in patients with Ramsay Hunt syndrome is mostly induced by superior vestibular neuritis consecutive to the reactivation of varicella-zoster virus (VZV) infection from the geniculate ganglion through the faciovestibular anastomosis. Refractory hearing loss in patients with Ramsay Hunt syndrome may be due to cochlear neuritis following the spread of VZV. An attempt was made to selectively identify vestibulocochlear nerves in the internal auditory canal (IAC) on gadolinium (Gd)-enhanced MRI in patients with Ramsay Hunt syndrome. Fourteen patients with Ramsay Hunt syndrome presenting with facial palsy, herpes zoster oticus, vertigo, and/or sensorineural hearing loss were scanned on 1.5 T MRI enhanced with Gd. Perpendicular section images of the IAC were reconstructed to identify the facial, superior, and inferior vestibular nerves and the cochlear nerves separately. All except one of the patients with Ramsay Hunt syndrome with vertigo showed both canal paresis on the caloric test and Gd enhancement of the superior vestibular nerve in the IAC on MRI. Among 10 patients with hearing loss, 3 patients with severe to moderate sensorineural hearing loss showed Gd enhancement of the cochlear nerve in the IAC on MRI.


めまいを伴うHunt症候群における上前庭神経障害

めまいを伴うHunt症候群における上前庭神経障害

耳鼻咽喉科ニューロサイエンス

耳鼻咽喉科ニューロサイエンス


Three Cases of Tetanus Presenting with Dysphagia

嚥下困難を主訴とした破傷風3例

We report three patients with tetanus who complained of dysphagia. All cases showed trismus, however, physical, serological and endoscopic examinations revealed not abnormalities. Under the diagnosis of tetanus, intravenous penicillin was administered to all three cases, which resulted in the disappearance of trismus, although one case showed a brief episode of generalized convulsion. The diagnosis of tetanus should be suspected in patients complaining of dysphagia who are found to have trismus, but no accompanying endoscopic findings.


Quercetin inhibits transcriptional up-regulation of histamine H1 receptor via suppressing protein kinase C-/extracellular signal-regulated kinase/poly(ADP-ribose) polymerase-1 signaling pathway in HeLa cells.

It has been reported that the histamine H1 receptor (H1R) gene is up-regulated in patients with allergic rhinitis and H1R expression level strongly correlates with the severity of allergy symptoms. Accordingly compounds that suppress the H1R gene expression are promising as useful anti-allergic medications. Recently, we demonstrated that histamine or phorbol-12-myristate-13-acetate (PMA) stimulation induced the up-regulation of H1R gene expression through the protein kinase C (PKC)/extracellular signal-regulated kinase/poly(ADP-ribose) polymerase-1 signaling pathway in HeLa cells expressing H1R endogenously. Quercetin is one of the well-characterized flavonoids and it possesses many biological activities including anti-allergic activity. However, effect of quercetin on H1R signaling is remained unknown. In the present study, we examined the effect of quercetin on histamine- and PMA-induced up-regulation of H1R gene expression in HeLa cells. We also investigated its in vivo effects on the toluene-2,4-diisocyanate (TDI)-sensitized allergy model rats. Quercetin suppressed histamine- and PMA-induced up-regulation of H1R gene expression. Quercetin also inhibited histamine- or PMA-induced phosphorylation of Tyr(311) of PKC and translocation of PKC to the Golgi. Pre-treatment with quercetin for 3weeks suppressed TDI-induced nasal allergy-like symptoms and elevation of H1R mRNA in the nasal mucosa of TDI-sensitized rats. These data suggest that quercetin suppresses H1R gene expression by the suppression of PKC activation through the inhibition of its translocation to the Golgi.


A Case of Frey's Syndrome after Fracture of the Mandibular Condyle

下顎骨関節突起骨折後に発症したFrey症候群

Frey's syndrome is a complication associated with parotid tumor operation. We report herein on a 70-year-old man who developed Frey's syndrome after fracturing his mandibular condyle. Although he underwent manipulative reduction, but not an operation, it is suggested that the dislocated condyle injured the auriculotemporal nerve, resulting in the development of Frey's syndrome. A careful and long-term follow-up is needed for early diagnosis of Frey's syndrome in patients with mandibular condyle fractures.


The Effect of Zinc Agent in 219 Patients with Zinc Deficiency-inductive/Idiopathic Taste Disorder: A Placebo Controlled Randomized Study

プラセボ対照無作為化試験による亜鉛欠乏性または特発性味覚障害219例に対するポラプレジンク投与の臨床的検討

Diagnosis and treatment of taste disorders are challenging because the disorder can only be determined by the awareness of the patient. Hence, these disorders still require comprehensive evidence. We conducted a randomized, placebo-controlled double-blind study to investigate the effect of polaprezinc, a zinc-containing agent, in 219 patients with either zinc deficiency-inductive or an idiopathic taste disorder. As a result, the zinc-treated arm experienced a statistically significant improvement against the placebo-treated arm in the perceptible threshold scores of the filter-paper disk method 8 weeks after the administration of the investigational drug. Moreover, the effect lasted for 4 weeks after discontinuation of the drug. However, the effective ratios based on the initial criteria were 55.6% in the treatment group and 43.2% in the placebo, where no statistical significance was recorded. Sex and degree of depression could be two of the potential factors to explain this discrepancy. Furthermore, the effect was not significant among male patients and patients with a high depression score based on the Self-rating Depression Scale (SDS) test. These results indicate that determining the symptom among such patients remains undisclosed. Whereas, in approximately 77%, or 168 patients with "normal" SDS scores and with completely impaired taste qualities, the ratio of effective cases reached 60.9% in the zinc-treated group, the ratio of the placebo-treated group reached 39.5%, resulting in a statistical significance. This may be partly because of a problem in the adaption of male subjects to the gustatory analyses, especially to the identification of saltiness and sourness. Care must also be taken regarding the depressive state of patients when diagnosing and treating taste disorders. Taste disorders caused by depression may not be cured by zinc supplementation due in part to the fact that the symptom is based on a mental issue, and due in part to the conservative responding bias generated by the depression itself, which may inhibit accurate and precise diagnosis of the disorder. In conclusion, administration of a zinc agent is effective for patients with taste disorders, provided selection of appropriate patients is performed, and that proper examination and evaluation are conducted. The present study also indicated that examining depressiveness based on the SDS scores and investigating disturbance of each taste quality using the filter-paper disk method are recommended for the diagnosis and determination of the treatment effect of a taste disorder.

味覚障害は, その評価において患者の自覚的な訴えに頼らざるを得ず, 現在もさらなるエビデンスの集積が求められている診断・治療の難しい疾患である. 今回われわれは亜鉛欠乏性または特発性に分類される味覚障害患者219例を対象に, ポラプレジンクを用いた亜鉛補充治療の効果をプラセボコントロールの無作為化二重盲検法により検討し, さらに背景データ等による詳細な検討を加えた. その結果, 亜鉛群は投与8週時から濾紙ディスク味覚検査法の認知域値でプラセボ群に対して有意に改善し, その差は投与終了の4週間後でも持続した. ただし, 事前に定めた「有効」の判定基準に従った有効率では統計学的な差が認められなかった. 性別または抑うつ性の程度により治療効果の違いを認め, 男性およびSDS (Self-rating Depression Scale) で抑うつ性が高いと評価された患者では, 症状の正確な評価に注意を要することが示唆された. 一方で, 約77%の症例が該当したSDSスコアが「正常」で, かつ4味質すべてで障害の見られた168例では, 有効率においても亜鉛群がプラセボ群を統計学的に有意に上回っていた. 本疾患の診断や治療効果判定においては, SDSスコアによる抑うつ性の評価や濾紙ディスク味覚検査法での個々の味質の障害程度を考慮した詳細な検討が必要であることが示された.


ボツリヌス投与量を減らしたボツリヌス毒素・ミラーバイオフィードバック併用療法

ボツリヌス投与量を減らしたボツリヌス毒素・ミラーバイオフィードバック併用療法


顔面神経麻痺の予後診断とリハビリテーションについて

顔面神経麻痺の予後診断とリハビリテーションについて


Correlation between Self-Voicing and Non-Self-Voicing, and Environmental Sound in Professional Voice Abusers:-Field Study Using Hearing Aid with Data Logging Function-

職業的音声酷使者の自己発話と他者発話，環境音との関係 ―補聴器のデータログを用いた検討─

In the present study, an attempt was made to investigate the correlation between self-voicing and non-self-voicing, and environmental sound in professional voice abusers. For this purpose, we used a hearing aid with data logging system. Kindergarten teachers and childcare workers showed longer self-voicing time, accounting for over one-third of their 8-hour working time, than speech-language-hearing therapists, housekeepers and office workers. The highest average sound pressure of self-voicing was 85 dB in kindergarten teachers, followed by 75 dB in childcare workers. Non-self-voicing time accounted for about half of the working time in kindergarten teachers and childcare workers, and their average sound pressures were 85 dB and 75 dB, respectively. Moreover, there was a significant positive correlation between self-voicing pressure and non-self-voicing pressure, but not between self-voicing pressure and environmental sound pressure. These findings suggest that kindergarten teachers and childcare workers are professional voice abusers because they have to use high-pressured self-voicing for a long time against high-pressured voicing from children in mutual verbal communication.

音声酷使者の発話環境を知る目的で，データログ機能つき補聴器を用い，自己発話時間と職業，自己発話音圧と他者発話音圧や環境音圧との関連について検討した．幼稚園教諭や保育士では，8時間の勤務時間の1/3以上を自己発話時間が占めており，言語聴覚士，専業主婦，事務職員と比べて長かった．幼稚園教諭の自己発話の平均音圧は85dBと最も強く，次いで保育士の75dBであった．幼稚園教諭と保育士の他者発話時間の比率は約1/2であったが，平均音圧は幼稚園教諭で85dB，保育士で75dBと他の職種より強かった．さらに，他者発話平均音圧が大きいほど自己発話平均音圧が大きい有意な相関が認められたが，自己発話音圧と環境音圧の間には有意な相関は認められなかった．幼稚園教諭や保育士は子供との会話が仕事であり，環境音ではなく他者発話音圧が強いため自己発話音圧が強くなり，音声を酷使している職業的音声酷使者と考えられた．

The Japan Journal of Logopedics and Phoniatrics


The effect of visual-vestibulosomatosensory conflict induced by virtual reality on postural stability in humans.

In this study, we examined the effects of sensory inputs of visual-vestibulosomatosensory conflict induced by virtual reality (VR) on subjective dizziness, posture stability and visual dependency on postural control in humans. Eleven healthy young volunteers were immersed in two different VR conditions. In the control condition, subjects walked voluntarily with the background images of interactive computer graphics proportionally synchronized to their walking pace. In the visual-vestibulosomatosensory conflict condition, subjects kept still, but the background images that subjects experienced in the control condition were presented. The scores of both Graybiel's and Hamilton's criteria, postural instability and Romberg ratio were measured before and after the two conditions. After immersion in the conflict condition, both subjective dizziness and objective postural instability were significantly increased, and Romberg ratio, an index of the visual dependency on postural control, was slightly decreased. These findings suggest that sensory inputs of visual-vestibulosomatosensory conflict induced by VR induced motion sickness, resulting in subjective dizziness and postural instability. They also suggest that adaptation to the conflict condition decreases the contribution of visual inputs to postural control with re-weighing of vestibulosomatosensory inputs. VR may be used as a rehabilitation tool for dizzy patients by its ability to induce sensory re-weighing of postural control.

The Journal of Medical Investigation : JMI


小児顔面神経麻痺後遺症患者における集団リハビリテーション

小児顔面神経麻痺後遺症患者における集団リハビリテーション


Role of Arteriosclerosis in Development of and Recovery from Sudden Deafness and Therapeutic Effects of Lipo-PGE1

突発性難聴における動脈硬化の関与とLipo-PGE1の効果

In order to clarify the role of arteriosclerosis in the development of and recovery from sudden deafness, we evaluated arteriosclerosis in patients with sudden deafness, using pulse wave velocity (PWV) as a marker. Arteriosclerosis was observed in 69% of the sudden deafness patients and the initial hearing level in the patients with arteriosclerosis was worse than those without arteriosclerosis. After treatment with a steroid and lipid microsphere-incorporated prostaglandin E1 (lipo-PGE1), the recovery rate of the patients with arteriosclerosis was significantly lower than those without arteriosclerosis. These findings suggest that arteriosclerosis is an exacerbating condition and a poor prognostic factor in patients with sudden deafness. On the other hand, PWV in the patients with arteriosclerosis who recovered tended to decrease after the treatment, suggesting that the circulation-improving effect of lipo-PGE1 may contribute to the recovery of the hearing loss related to arteriosclerosis.


PMA-induced dissociation of Ku86 from the promoter causes transcriptional up-regulation of histamine H1 receptor.


発症した病的共同運動に対するボツリヌス毒素・ミラーフィードバック併用療法の長期成績


Hunt症候群における内耳道造影MRIについて

Hunt症候群における内耳道造影MRIについて


Benign paroxysmal positional vertigo showing sequential translations of four types of nystagmus.

Three kind of nystagmus, namely P-BPPV, AH-BPPV and GH-BPPV can be explained by the otoconial debris hypothesis of the same ear. Finally, the recently reported geotropic nystagmus with a long time constant may be explained by a reversible lesion such as the denatured cupula or utricular imbalance of the same ear.


Anti-microbial and therapeutic effects of modified Burow's solution on refractory otorrhea.

These findings indicate that modified Burow's solution, in addition to bearing a broad antimicrobial activity, is as effective as the original Burow's solution in the treatment of chronic suppurative otitis.


A case of suspected perilymphatic oozer with CTP-positive cerebrospinal otorrhea


A Case of Tetanus Associated with Dysphagia

嚥下障害を主訴とした破傷風例

We report on a 79-year-old woman complaining of progressive dysphagia as an initial symptom of tetanus. Endoscopic and videofluoroscopic examination of her swallowing process showed dysphagea with food retention in the pyriform sinus, probably because of spasm of cricopharyngeal muscles due to tetanus. The patient was cured with tetanus antitoxin and antibiotics without any sequelae. Tetanus must be considered in the differential diagnosis of progressive dysphagia in spite of the lack of any history of injury.


Effects of sleep position on time course in remission of positional vertigo in patients with benign paroxysmal positional vertigo.

The side of the affected ear was significantly associated with the head-lying side during sleep in patients with P-BPPV and was closely but not significantly associated with it in patients with H-BPPV. However, the head-lying side during sleep did not affect the remission rate of their positional vertigo.


Induction and maintenance of anti-influenza antigen-specific nasal secretory IgA levels and serum IgG levels after influenza infection in adults.

To determine the induction and changes in anti-influenza virus secretory IgA (s-IgA) levels in nasal washes and serum IgG levels in patients with influenza. The study recruited 16 patients with influenza aged 35.6 ± 9.6 years in 2007/2008 and 2008/2009 seasons. Nasal washes and serum were obtained throughout the first year. Anti-viral s-IgA levels and neutralization activities in nasal washes, and serum anti-viral IgG levels and hemagglutination inhibition (HI) titers were measured. Anti-viral(H1N1) s-IgA to total IgA ratio and neutralizing antibody titer were low in nasal washes of all patients, whereas serum levels of anti-viral IgG and HI titers varied widely at day 1.4 ± 1.0 postinfection. Both nasal s-IgA and serum IgG levels later increased significantly, reaching peak levels at day 9.6 ± 3.3 postinfection. The induced nasal s-IgA then returned toward the initial levels within 300 days, although the levels at day 143 ± 70 were 3.03-fold of the initial. Individual serum IgG levels also returned toward the initial levels within 300 days, although the mean levels remained high probably because of re-infection in a subgroup of patients. Although influenza A (H3N2) was a minor epidemic subtype in both flu seasons, a significant rise in nasal anti-viral (H3N2) s-IgA levels and a slightly increase in serum IgG levels were noted. Low levels of nasal anti-viral s-IgA and neutralizing antibody were noted compared with a wide range of serum anti-viral IgG and HI titers at the onset of infection. Elevated s-IgA and IgG returned toward the initial levels within 300 days of infection with minor exceptions.


Effects of Oral Administration of Prostaglandin I2 as a Salvage Treatment in Patients with Sudden Deafness

突発性難聴難治例に対するプロスタグランディンI2製剤を用いた二次治療の検討

We examined the effect of oral administration of beraprost sodium, a derivative of prostaglandin I2 (PGI2) in patients with sudden deafness as a salvage treatment after failure of initial systemic steroid therapy with prostaglandin E1. We then compared them with those of mecobalamin, a derivative of vitamin B12. A significant improvement in the average hearing level was obtained in patients who received beraprost sodium for 12 weeks, but not in patients who received mecobalamin. The hearing levels at 125 Hz, 250 Hz, 500 Hz and 8000 Hz significantly improved after the salvage treatment of beraprost sodium over those of mecobalamin. These findings suggested that oral administration of the PGI2 derivative could be utilized as a salvage treatment for refractory sudden deafness after failure of initial steroid therapy.


Preseasonal prophylactic treatment with antihistamines suppresses IL-5 but not IL-33 mRNA expression in the nasal mucosa of patients with seasonal allergic rhinitis caused by Japanese cedar pollen.

These findings suggest that the down-regulation of interleukin (IL)-5 gene expression in collaboration with the suppression of histamine H(1) receptor (H1R) gene expression in the nasal mucosa provides the basis for better therapeutic effects of preseasonal prophylactic treatment with antihistamines in patients with seasonal allergic rhinitis caused by Japanese cedar pollen. The effects of prophylactic administration of antihistamines on the expression of IL-5 and IL-33 mRNA in the nasal mucosa of the patients with pollinosis were investigated. Eight patients had already visited the hospital before the peak pollen period and started preseasonal prophylactic treatment with antihistamines. Seventeen patients who first visited the hospital during the peak pollen period were designated as the no treatment group. After local anesthesia, nasal mucosa was obtained by scraping the inferior concha with a small spatula during the peak pollen period. During the peak pollen period, the expression of IL-5 mRNA, but not that of IL-33 mRNA, in the nasal mucosa of patients receiving preseasonal prophylactic treatment with antihistamines was significantly lower in comparison with that of patients without treatment. Moreover, there was a significant correlation between the expression of IL-5 mRNA and the nasal symptoms or the expression of H1R mRNA.


3D analysis of spontaneous upbeat nystagmus in a patient with astrocytoma in cerebellum.

Since the cerebellar vermis is known to plays an inhibitory role on the central vertical vestibule-ocular reflex (VOR), the present results suggest that the spontaneous UBN in darkness observed in this patient was induced by an imbalance of central vertical VOR tone.


Implication of substance P neuronal system in the amygdala as a possible mechanism for hypergravity-induced motion sickness

We previously reported that motion sickness was prevented in rats with amygdala lesion and that provocative motion stimuli increased the number of Fos-positive neurons in the amygdala, suggesting that the amygdala is one of the neural substrates involved in the development of motion sickness. NK-1 receptors in the brain stem and amygdala are thought to play an important role in emesis and affective disorders, respectively. In the present study, to elucidate a role of substance P neuronal system and NK-1 receptors in the brain stem and amygdala in the development of motion sickness, we measured changes in gene expression of NK-1 receptors and preprotachykinin, a precursor of substance P, using quantitative real-time PCR methods in solitary tract nucleus and amygdala in rats after provocative motion stimuli induced by 2G hypergravity load. Effects of systemic administration of CP-99,994, an antagonist for NK-1 receptors, on hypergravity-induced motion sickness were also examined using pica behavior, eating non-nutritive substances such as kaolin, as an index of motion sickness in rats. Hypergravity-induced motion sickness was inhibited by CP-99,994 with a dose-dependent and enantioselective manner. Preprotachykinin mRNA expression was increased in basolateral nucleus of amygdala and solitary tract nucleus after hypergravity load for 3h, whereas NK-1 receptor mRNA expression was not changed by hypergravity in amygdala and solitary tract nucleus. Present results suggest that 2G hypergravity load activated the substance P neuronal system in amygdala as well as in the brain stem and this activation would be related to the development of motion sickness.


Effects of dietary zinc deprivation on zinc concentration and ratio of apo/holo-activities of angiotensin converting enzyme in serum of mice.

These findings suggest that ACE ratio is as sensitive as serum zinc concentration for the evaluation of zinc deficiency and can be used for the biochemical diagnosis of zinc nutritional status in patients with zinc deficiency-induced taste impairment.


顔面神経麻痺患者に対する集団リハビリテーション

顔面神経麻痺患者に対する集団リハビリテーション


MPO-ANCA陽性の難治性中耳炎と顔面神経障害

MPO-ANCA陽性の難治性中耳炎と顔面神経障害


We report a case of infantile middle-ear teratoma. A 6-month-old girl was first seen and reported to have a history of refractory left-ear otitis media. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a tumor occupying the tympanic cavity and eustachian tube. The tumor, was biopsied twice transaural, under general anesthesia, contained squamous epithelium, striated muscle, and adipose tissue, suggesting middle-ear teratoma. The tumor was resected completely in canal wall tympanoplasty with mastoidectomy under general anesthesia. Histologically, the heterogeneous tumor consisted of tissues including squamous epithelium, sebaceous gland and hair follicle, skin appendages, adipose tissue, striated muscle, cartilage, minor salivary-gland-like tissue, and bone. Mature middle-ear teratoma was diagnosed due to the absence of immaturity and malignancy. The girl remains recurrence-free in the 3 years since surgery.


Dietary zinc intake and its effects on zinc nutrition in healthy Japanese living in the central area of Japan.

In the present study, we first examined the dietary zinc intake from food groups in 109 healthy Japanese (24-82 years old, 45 male and 64 female) by means of the 72-h recall method. We then used the ratio of apo/holo-activities of angiotensin converting enzyme (ACE ratio) that is a more sensitive index of zinc nutrition than zinc concentration in the serum and examined the correlation between their zinc intake and ACE ratio. Dietary zinc intake in healthy Japanese was maximal from rice and rice products. There were significant inverse correlations between the ACE ratio and dietary zinc intake from rice and rice products and shellfish, and a significant positive correlation between ACE ratio and dietary zinc intake from other beans and bean processed foods. On the other hand, there were no significant correlations between serum zinc concentrations and dietary zinc intake from any food group except processed fish. These findings suggested that rice is a major source of dietary zinc intake in healthy Japanese. It is also suggested that shellfish also has a major impact on zinc nutrition, although dietary zinc intake from this source is minimal. Since beans contain phytic acid, which inhibits the absorption of dietary zinc, it is suggested that intake of beans causes impairment of zinc nutrition.

The Journal of Medical Investigation : JMI


Albizia lebbeck suppresses histamine signaling by the inhibition of histamine H1 receptor and histidine decarboxylase gene transcriptions.

Histamine plays major roles in allergic diseases and its action is mediated mainly by histamine H(1) receptor (H1R). We have demonstrated that histamine signaling-related H1R and histidine decarboxylase (HDC) genes are allergic diseases sensitive genes and their expression level affects severity of the allergic symptoms. Therefore, compounds that suppress histamine signaling should be promising candidates as anti-allergic drugs. Here, we investigated the effect of the extract from the bark of Albizia lebbeck (AL), one of the ingredients of Ayruvedic medicines, on H1R and HDC gene expression using toluene-2,4-diisocyanate (TDI) sensitized allergy model rats and HeLa cells expressing endogenous H1R. Administration of the AL extract significantly decreased the numbers of sneezing and nasal rubbing. Pretreatment with the AL extract suppressed TDI-induced H1R and HDC mRNA elevations as well as [(3)H]mepyramine binding, HDC activity, and histamine content in the nasal mucosa. AL extract also suppressed TDI-induced up-regulation of IL-4, IL-5, and IL-13 mRNA. In HeLa cells, AL extract suppressed phorbol-12-myristate-13-acetate- or histamine-induced up-regulation of H1R mRNA. Our data suggest that AL alleviated nasal symptoms by inhibiting histamine signaling in TDI-sensitized rats through suppression of H1R and HDC gene transcriptions. Suppression of Th2-cytokine signaling by AL also suggests that it could affect the histamine-cytokine network.


Involvement of protein kinase Cdelta/extracellular signal-regulated kinase/poly(ADP-ribose) polymerase-1 (PARP-1) signaling pathway in histamine-induced up-regulation of histamine H1 receptor gene expression in HeLa cells.

The histamine H(1) receptor (H1R) gene is up-regulated in patients with allergic rhinitis. However, the mechanism and reason underlying this up-regulation are still unknown. Recently, we reported that the H1R expression level is strongly correlated with the severity of allergic symptoms. Therefore, understanding the mechanism of this up-regulation will help to develop new anti-allergic drugs targeted for H1R gene expression. Here we studied the molecular mechanism of H1R up-regulation in HeLa cells that express H1R endogenously in response to histamine and phorbol 12-myristate 13-acetate (PMA). In HeLa cells, histamine stimulation caused up-regulation of H1R gene expression. Rottlerin, a PKC-selective inhibitor, inhibited up-regulation of H1R gene expression, but Go6976, an inhibitor of Ca(2+)-dependent PKCs, did not. Histamine or PMA stimulation resulted in PKC phosphorylation at Tyr(311) and Thr(505). Activation of PKC by H(2)O(2) resulted in H1R mRNA up-regulation. Overexpression of PKC enhanced up-regulation of H1R gene expression, and knockdown of the PKC gene suppressed this up-regulation. Histamine or PMA caused translocation PKC from the cytosol to the Golgi. U0126, an MEK inhibitor, and DPQ, a poly(ADP-ribose) polymerase-1 inhibitor, suppressed PMA-induced up-regulation of H1R gene expression. These results were confirmed by a luciferase assay using the H1R promoter. Phosphorylation of ERK and Raf-1 in response to PMA was also observed. However, real-time PCR analysis showed no inhibition of H1R mRNA up-regulation by a Raf-1 inhibitor. These results suggest the involvement of the PKC/ERK/poly(ADP-ribose) polymerase-1 signaling pathway in histamine- or PMA-induced up-regulation of H1R gene expression in HeLa cells.


Periodic Fever with Aphthous Stomatitis, Pharyngitis and Cervical Adenitis (PFAPA) Syndrome, an Autoinflammatory Disease Treated with Tonsillectomy

扁摘が有効であった自己炎症疾患PFAPA症候群例

We report a case of PFAPA (Periodic fever with aphthous stomatitis, pharyngitis and cervical adenitis). A 5-year-old boy admitted for idiopathic fever 12 times within 8-months. Fever of >38°C occurred for 5 days at 10-to-20-days intervals. Antibiotics failed to decrease the fever. PFAPA was diagnosed when the boy was found to be febrile with aphthous stomatitis. Steroid administration decreased the fever, but not its recurrence. Following tonsillectomy, however, the boy had fever only once 2 weeks after surgery in the 12 months since. PFAPA etiology is unknown, but recent reports suggest irregular pro-inflammatory cytokine production. Serum IL-6, TNF- and IFN- concentration increased during febrile attack in our case.


感音難聴と顔面神経麻痺を示すMPO-ANCA関連中耳疾患の1例 診断基準案の提案


The Importance of Language Disorder Screening in School Medical Examinations

学校健診における言語障害検診の重要性

Two hundred thirty-one preschool children received language disorder screening in school medical examinations. Pre-screening by speech-language-hearing-therapists found 47 children were suspected to have language disorders, and medical examination by an otolaryngologist led to a diagnosis of language disorder in 31 children. Among children not suspected of having a language disorder during pre-screening, no language disorder was diagnosed. This finding suggests that screening by a speech-language-hearing-therapist before a medical examination is helpful for otolaryngologists to determine language-impaired preschool children. Fourteen language-impaired preschool children found during language disorder screening received a detailed examination, and all except one required language training. This finding suggests that language disorder screening performed properly gives unidentified language-impaired children the opportunity to receive language training.

就学時健診の231児に対して, 耳鼻咽喉科医による「学校保健での音声言語障害の検診法」を用いた言語障害の検診, 言語聴覚士による事前の言語スクリーニングおよび言語障害と診断された児の言語の精密検査を実施した. 医師による言語障害の検診にて言語異常の所見ありと診断されたのは, 31児であった. 一方, 言語聴覚士による事前の言語スクリーニングにて言語異常の所見ありと評価された児は47名であり, 異常の所見なしと評価された児のなかで, 医師が検診で言語障害と診断した児はなかった. 精密検査を実施した14児のうち, 異常なしと診断されたのは1児のみであり, 他の13児は言語訓練が必要であった. 健診で医師が「学校保健での音声言語障害の検診法」を活用するためには, 言語聴覚士による事前の言語スクリーニングが有用であり, 言語障害の検診を適切に実施すれば, それまでに診断されていなかった言語障害児を発見して言語訓練の機会を与えることができると考えられた.

The Japan Journal of Logopedics and Phoniatrics


Chemosurgery with Mohs' Paste Improves Terminal Recurrent Maxillary Cancer QOL

Mohs 軟膏を用いた chemosurgery で緩和ケアを行った上顎洞癌末期例

Chemosurgery with Mohs' paste created by Frederic E. Mohs, is microscopically controlled to treat common skin cancer. This was repeated for a 68-year-old woman with recurrent malignant spindle cell carcinoma of the maxillary sinus, who suffered from repeated bleeding and malodorous discharge from outgrowth tumor. After treatment with Mohs' paste without apparent side-effects, the tumor coagulated, relieving her distress. Chemosurgery with Mohs' paste is thus useful to improve the quality of life (QOL) in such terminal cases.


ヒスタミンH1受容体遺伝子発現機構のアレルギー疾患における病理学的意義

ヒスタミンH1受容体遺伝子発現機構のアレルギー疾患における病理学的意義

Therapeutics targeting disease-sensitive genes are required for the therapy of multifactorial diseases. There is no clinical report on therapeutics for allergic disease-sensitive genes. We are focusing on the histamine H1 receptor (H1R) as a sensitive gene. H1R mediates allergy histamine signals. H1R is a rate-limiting molecule of the H1R signal because the signal is increased with elevated receptor expression level. We discovered that the stimulation of H1R induced H1R gene expression through PKCδ activation, resulting in receptor upregulation. The mechanism of H1R gene expression was revealed to play a key role in the receptor expression level in studies using cultured HeLa cells and allergic rhinitis model rats. Preseasonal prophylactic treatment with antihistamines is recommended for the therapy of pollinosis. However, the mechanism of the therapy remains to be elucidated. We demonstrated that repeated pretreatment treatment with antihistamines in the allergic rhinitis model rats resulted not only in improvement of symptoms but also in suppressed elevation of H1R mRNA levels in the nasal mucosa. A clinical trial was then initiated. When symptoms and H1R mRNA levels in the nasal mucosa of pollinosis patients with or without preseasonal prophylactic treatment with antihistamines were examined, both symptoms and high levels of H1R mRNA were significantly improved in treated compared with untreated patients. These results strongly suggest that H1R is an allergic disease-sensitive gene.

Journal of the Pharmaceutical Society of Japan


Natural course of positional vertigo in patients with apogeotropic variant of horizontal canal benign paroxysmal positional vertigo.

OBJECTIVE: The purpose of this study was to assess the natural course of positional vertigo in patients with the apogeotropic variant of horizontal canal type of benign paroxysmal positional vertigo (AH-BPPV), which is reported to be more refractory to physiotherapy than the geotropic variant of horizontal canal type of BPPV (GH-BPPV). METHODS: 14 patients with AH-BPPV treated without physiotherapy were asked to visit the hospital every 2 weeks. At every follow-up visit, they were interviewed and positional nystagmus was assessed. After the disappearance of positional nystagmus, patients were asked about the time of cessation of the positional vertigo. Thus, the primary outcomes were evaluated by the self-reported onset and remission of positional vertigo. The time course of remission of positional vertigo was then calculated. RESULTS: The average and median period from the onset to natural remission of positional vertigo in patients with AH-BPPV was 13 and 7 days, respectively. CONCLUSION: We have already reported that the average and median period from the onset to natural remission of positional vertigo in patients with GH-BPPV was 16 and 7 days, respectively (Imai et al., 2005 [8]). Thus, the natural course of AH-BPPV is not as refractory as that of GH-BPPV.


徳島県における過去26年間のヒノキ科花粉の飛散状況

徳島県における過去26年間のヒノキ科花粉の飛散状況

徳島県におけるヒノキ科花粉の飛散状況を1981年から2007年までの26年間測定した．1)ヒノキ科花粉の総飛散数はスギ花粉の総飛散数の3割以下であった．両者の花粉の飛散総数の変化はほぼ一致したが，両者の比率は年によって異なっており，ヒノキ科花粉の独自の飛散予報も必要と考えられた．2)スギ花粉の飛散総数は前年7月の最高気温，平均気温，日照時間との間に有意な正の相関がみられ，湿度との間に有意な負の相関が認められたが，降水量との間に相関は確認されなかった．一方，ヒノキ科花粉の飛散総数は前年7月の最高気温，平均気温との間にのみ相関が認められた．3)ヒノキ科花粉の飛散総数に影響する，スギ花粉とは異なる気象因子の解明が必要であると考えられた．すなわちヒノキ科花粉の飛散期間は3月下旬から4月下旬でスギ花粉飛散期間よりも約1ヵ月遅かった．尚，両花粉は共通抗原性を持つため，ヒノキ科花粉がスギ花粉症患者の症状遷延化や増悪の一因となっていると考えられた．


Innervation of histamine neurons in the caudal part of the arcuate nucleus of hypothalamus and their activation in response to food deprivation under scheduled feeding.

It has been well established that histaminergic neurons innervate densely the anterior hypothalamus and regulate several functions through the histamine H receptor (H1R). However, the physiological function of the histaminergic neurons in other regions including the posterior hypothalamus has not been fully investigated. Recently, we have found a selective c-Fos expression in the caudal part of the arcuate nucleus of the hypothalamus (cARC) by food deprivation under scheduled feeding in rats. In this study, we histochemically examined the correlation of this c-Fos expression with the activation of histaminergic neurons in this region using an anti-H1R antibody. Strong H1R immunoreactivity was observed in the perikarya of the c-Fos positive cells. Abundant histamine-containing fibers were also found in the cARC and in the area between the cARC and the tuberomammillary nucleus (TM), where the histaminergic neuronal cell bodies are exclusively distributed. Our morphological observations suggest that c-Fos expression in the cARC by food deprivation under scheduled feeding is caused by the activation of histaminergic neurons projected from the TM.

Methods and Findings in Experimental and Clinical Pharmacology


上前庭神経障害によるめまいと考えられた不完全Hunt症候群症例

上前庭神経障害によるめまいと考えられた不完全Hunt症候群症例


Hunt症候群における聴力障害の検討

Hunt症候群における聴力障害の検討


完全脱神経を来たしたHumt症候群に対するリハビリテーション

完全脱神経を来たしたHumt症候群に対するリハビリテーション


Preseasonal prophylactic treatment with antihistamines suppresses nasal symptoms and expression of histamine H1 receptor mRNA in the nasal mucosa of patients with pollinosis.

Administration of antihistamines 2-4 weeks before the pollen season showed a greater inhibitory effect on nasal allergy symptoms in patients with seasonal allergic rhinitis. However, the mechanism of slow-onset effects of preseasonal treatment with antihistamines remains unclear. Here, we investigated the effect of preseasonal prophylactic treatment with antihistamines on nasal symptoms and the expression of histamine H₁ receptor (H1R) mRNA of the nasal mucosa in patients with cedar pollen pollinosis. During the peak pollen period, the expression of H1R mRNA in the nasal mucosa and the scores of sneezing and watery rhinorrhea in patients receiving preseasonal prophylactic treatment with antihistamines were significantly suppressed in comparison with those in the patients without treatment. Moreover, there was a significant correlation between the nasal symptoms and the expression of H1R mRNA in both patients with or without preseasonal prophylactic treatment. These findings suggest that preseasonal prophylactic treatment with antihistamines is more effective than on-seasonal administration to patients with pollinosis in reducing nasal symptoms during the peak pollen period by suppressing H1R gene expression in the nasal mucosa.


Clinical characteristics of delayed endolymphatic hydrops in Japan: A nationwide survey by the Peripheral Vestibular Disorder Research Committee of Japan.

CONCLUSION: Similarly to almost all delayed endolymphatic hydrops (DEH) cases with both precedent sudden deafness and mumps deafness, two-thirds of DEH cases with precedent deafness of unknown cause with onset in early childhood developed DEH symptoms within 40 years after the precedent deafness. In spite of the diagnosis of precedent deafness, viral labyrinthitis may build up the late endolymphatic hydrops in most DEH cases up to four decades. OBJECTIVE: To clarify the characteristics of DEH in Japan. METHODS: Clinical information on 198 DEH cases was collected by nationwide, multicenter surveys conducted by the Peripheral Vestibular Disorders Research Committee of Japan. RESULTS: The incidence of the ipsilateral type of DEH was 47.5%, which was almost equal to that of the contralateral type. In both types of DEH, the most common diagnosis of precedent deafness was deafness of unknown cause with onset in early childhood: 43.9% in both types of DEH. Sudden deafness and mumps deafness were the subsequent diagnoses of precedent deafness. The distribution of time delay of the onset between precedent deafness of unknown cause with onset in early childhood and DEH was different from that between precedent sudden and mumps deafness and DEH.


スギ花粉症における初期療法の作用機序の検討

スギ花粉症における初期療法の作用機序の検討


A case of apogeotropic nystagmus with brainstem lesion: An implication for mechanism of central apogeotropic nystagmus.

We report a case showing apogeotropic nystagmus with the lesion of the brain stem, and discuss a possible mechanism of central apogeotropic nystagmus. The case was a 73-year-old male. We analyzed his nystagmus three-dimensionally. He showed apogeotropic nystagmus. Axis angles of slow phase eye velocity of his apogeotropic nystagmus were not in line with the axes perpendicular to the plane of horizontal semicircular canals, but with the patient's vertical axis. We then found that his nystagmus including the apogeotropic nystagmus was positioning, but not positional and that the direction of his positioning nystagmus was the same direction of postrotatory nystagmus after his head movement. His MRI scans showed an infarction around the prepositus hypoglossi nucleus of the brain. His apogeotropic nystagmus seemed to consist of a combination of prolonged postrotatory nystagmus after his head rotation to the left and right lateral position because the axis of postrotatory nystamus was in line with the axis of the head rotation. Therefore, it is suggested that a possible mechanism of central apogeotropic nystagmus is a prolonged postrotatory nystagmus after his head movement in the supine position due to the brain lesion involving the velocity storage mechanisms.


Palliative Treatment with Mohs' Paste for Unresectable Cervical Lymph Node Metastasis in Hypopharyngeal Carcinoma

Mohs軟膏によりQOLを改善しえた下咽頭癌の手術不能頸部リンパ節転移例

Mohs' paste used in skin cancer chemosurgery was used palliatively to treat unresectable cervical lymph node metastasis in hypopharyngeal carcinoma. A 54-year-old man had suffered from repeated bleeding and malodorous discharge from an ulcer from cervical metastasis. After Mohs' paste was applied, the ulcer coagulated relieving his distress. Mohs' paste is useful in such treatment in for improving the quality of life in such subjects.

54歳男．約2年前より左頸部リンパ節腫脹が出現しその3ヵ月後に受診し，下咽頭梨状陥凹癌，頸部リンパ節転移(T1N3M0)と診断され，放射線治療，ドセタキセルの化学療法を行った．原発巣は消失したが左頸部リンパ節転移は残存し，頸部リンパ節転移は内頸動脈に浸潤し，右ルビエールリンパ節にも転移を認めたため手術不能であった．アルコール性肝障害に汎血球減少も認め，化学療法の継続も困難で，肝障害の悪化，食欲不振，疼痛に対する補液，栄養管理，癌性疼痛緩和で入院を繰り返した．左頸部リンパ節転移が皮膚に浸潤して突出，自潰し，滲出液，悪臭が出現したため，ガーゼによる被覆も難しく，QOLも大きく低下したためMohs軟膏治療を開始した．造影CTで頸部動脈が腫瘍から離れていることを確認し，Mohs軟膏を自潰部に約1mmの厚さで塗布し，2時間後に軟膏を除去して翌日に固定された部分をメスで切除する治療を計7回毎日繰り返した．自潰した腫瘍はほぼ平坦になり，自潰部は凝固されて出血や滲出液は停止し悪臭も消失した．QOLは改善したが約1ヵ月後に原因不明の呼吸不全で死亡した．剖検よりMohs軟膏による治療部位に好塩基性物質を伴った凝固壊死組織を認め，最も深いところで表面から17mmまで及んでいた．


Zinc deficiency in patients with idiopathic taste impairment from the view point of ratio of apo/holo-activities of angiotensin converting enzyme as an index.

【亜鉛酵素・トランスポーター研究の最前線】 亜鉛酵素「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


Effects of zinc supplementation on serum zinc concentration and ratio of apo/holo-activities of angiotensin converting enzyme in patients with taste impairment.

OBJECTIVE: The aim of the present study was to evaluate the effects of zinc supplementation on hypogeusia, serum zinc concentration and the ratio of apo/holo-activities of angiotensin converting enzyme (ACE ratio) in patients with taste impairment. ACE ratio was used as an index of zinc nutritional status. METHODS: Forty patients complaining of taste impairment were divided into two groups: zinc deficiency taste impairment (n=12) and idiopathic taste impairment (n=28). Patients with zincemia values of less than 63 microg/dl with no history of other disorder or medication known to cause dysgeusia were diagnosed as zinc deficiency group, while those with the same condition and values more than 64 microg/dl were considered to belong to the idiopathic group. Patients orally received 150 mg of polaprezinc containing 33 mg of zinc every day. Subjective symptom was scored according to visual analogue scale (VAS). RESULTS: Zinc supplementation improved hypogeusia in both idiopathic and zinc deficiency groups. The mean improvements of VAS were 3.02+/-3.03 in the idiopathic group and 3.13+/-2.53 in the zinc deficiency group. Thus, there were no significant differences in idiopathic and zinc deficiency groups. Significant correlations were found between the improvement of VAS score and the ACE ratio after zinc supplementation in both idiopathic and zinc deficiency groups. On the contrary, significant correlations were not found between the improvement of VAS score and the zinc concentration in the serum after zinc supplementation in both groups. CONCLUSION: The results of the present study indicated that zinc deficiency is a predominant factor underlying taste impairment and ACE ratio may be a predictor of the prognosis for taste impairment after zinc supplementation, in addition to a more sensitive indicator of zinc nutrition than zinc concentration in the serum.


吃音児への早期介入の効果

吃音児への早期介入の効果

3ヵ月以上の言語指導期間のある18歳未満の吃音児57名を対象に,介入時期と吃音の改善効果について検討した．紹介元では,他機関の専門職からの紹介が59


急性期のめまいに対するジフェニドールとベタヒスチンの効果:日常生活障害度の改善の評価

厚生労働省 難治性疾患克服研究事業 前庭機能異常に関する調査研究班 平成21年度報告書


アルコール性頭位眼振の3次元主軸解析

アルコール性頭位眼振の3次元主軸解析

厚生労働省 難治性疾患克服事業 前庭機能異常に関する調査研究班 平成21年度報告書


【めまいのup date】 めまい疾患の診断と治療 メニエール病

【めまいのup date】 めまい疾患の診断と治療 メニエール病


A case of Costen's syndrome with chewing-induced vertigo

咀嚼によりめまいが誘発されたCosten症候群症例

症例は31歳女性で，歯科で下顎の左第1第2大臼歯の治療を受け，治療5日後，朝より咀嚼時の発作性回転性めまいが出現した．めまいは2~3分持続し，頭痛を伴い，その後，浮動感が持続した．夜になっても症状が持続するため救急外来を受診した．当初，注視眼振検査およびフレンツェル眼鏡を用いた座位の頭位眼振検査，頭振後眼振検査で眼振を認めなかった．また標準純音聴力検査も正常であった．冷温交互法による温度刺激検査は左右差なく，視標追跡検査および視運動性眼振検査も異常を認めなかった．めまいを誘発するためにガムを咀嚼させると回転性のめまい発作を誘発できた．赤外線CCDカメラで記録したところ，ガムの咀嚼時に右向きの眼振が出現し，次第に眼振の方向が左向きへと変化する水平性の眼振を認めた．Costen症候群と診断し，開発した三次元主軸解析法により眼振を解析した．原因を歯科治療に伴う咬合不全である可能性を考え，口腔外科を紹介したが，2週間後には症状が軽快したため無治療で経過観察したが，症状の再発は認めなかった．


Sho-seiryu-to suppresses histamine signaling at the transcriptional level in TDI-sensitized nasal allergy model rats.

BACKGROUND: The therapeutic use of Kampo medicine, Sho-seiryu-to (SST) in allergic disorders is well known. As histamine plays a central role in allergic diseases, it is possible that SST affects the allergy-related histamine signaling. In this study, we investigated the effect of SST on allergy-related histamine signaling in the nasal mucosa of toluene 2, 4-diisocyanate (TDI)-sensitized nasal allergy model rats. METHODS: Six-week-old male, Brown Norway rats were sensitized for 2 weeks with 10 microl of 10% TDI, and after a 1 week interval, provocation was initiated with the same amount of TDI. SST (0.6g/rat) was given orally 1 hour before TDI treatment began for a period of 3 weeks. Nasal symptoms were scored for 10 minutes immediately after TDI-provocation. The genes expression in nasal mucosa was determined using real-time quantitative RT-PCR. RESULTS: SST significantly suppressed TDI-induced nasal allergy-like symptoms. TDI provocation showed a significant up-regulation of histamine H(1) receptor (H1R) and histidine decarboxylase (HDC) gene expressions. Prolonged pre-treatment of SST significantly suppressed the mRNA levels of H1R and HDC that was up-regulated by TDI. SST also suppressed TDI-induced interleukin (IL)-4 and IL-5 mRNA elevation. However, SST showed no significant effect for TDI-induced mRNA elevation of IL-13. CONCLUSIONS: These results demonstrate that SST alleviates nasal symptoms by the inhibition of histamine signaling through suppression of TDI-induced H1R and HDC gene up-regulation. SST also suppresses cytokine signaling through suppression of IL-4 and IL-5 gene expression. Suppression of histamine signaling may be a novel mechanism of SST in preventing allergic diseases.


A new video laryngo-pharyngoscope with shape-holding coiled tube and surgical forceps: a preliminary study

We developed a new video laryngo-pharyngoscope with a shape-holding coiled tube and examined its effectiveness in some patients. The video laryngo-pharyngoscope is designed to inspect the pharynx and larynx transorally and to perform surgical manipulations. The scope consists of a coiled tube, a grip with trigger connected to the forceps and a CCD Camera with a battery. The stainless coiled tube of the scope is flexible but shape-holding, so that its shape can be changed by hand with the characteristic that the new orientation remains invariable during both inspection and operation in the pharynx and larynx. After a local anesthesia, the operator holds the scope in one hand and pulls the patient's tongue by the other hand. The operator then inserted the scope transorally while monitoring video images that were wirelessly transferred to the display to ensure that the forceps has reached the area of interest and treated lesions successfully. Using the scope, we successfully examined the upper airway lesions and removed foreign bodies from the pharynx and performed both resection of a benign tumor and taking a biopsy of a malignant tumor from the pharynx and larynx. But, we could hardly remove vocal fold polyps because of the structural limitation of the scope. We demonstrated that the new video laryngo-pharyngoscope can be used safely and successfully in the inspection and removal of lesions in the oropharynx and supraglottic area of the larynx and will be a useful tool for minimally invasive office-based surgery.


A zinc-containing compound, Polaprezinc, is effective for patients with taste disorders: randomized, double-blind, placebo-controlled, multi-center study.

Conclusions. The effect of a zinc-containing compound, Polaprezinc, was shown to clinically improve the disease conditions of idiopathic taste disorders with no serious side effects in a well controlled double-blinded clinical study. Objectives. The purpose of the present study was to evaluate the efficacy and safety of a zinc-containing compound in the treatment of patients with idiopathic taste disorders, including patients with low serum zinc, by a Good Clinical Practice (GCP)-compliant, randomized, placebo-controlled, double-blind, multi-center clinical study. Subjects and methods. A group of 109 patients suffering from taste disorders was assigned into placebo and three treatment groups. Each group of patients was given either placebo (n=28), or 17 mg (n=27), 34 mg (n=26) or 68 mg (n=28) of oral zinc, Polaprezinc preparations, daily for 12 weeks. Results. The group of patients given 68 mg zinc showed a significant improvement in their gustatory sensitivity compared with the placebo group. The most common side effects observed were increase in serum triglyceride and serum alkaline phosphatase, decrease in serum iron, and some gastrointestinal incidents, although they were not serious.


3D analysis of benign positional nystagmus due to cupulolithiasis in posterior semicircular canal

The characteristic of both the vertical-torsional positional nystagmus with long time constant and its disappearance at the neutral head position could diagnose cupulolithiasis in posterior semicircular canal (PSCC) in the eight patients with the PSCC type of benign paroxysmal positional vertigo (P-BPPV). The aim of the study was to diagnose cupulolithiasis in patients with P-BPPV. We used three-dimensional rotation axis analysis of nystagmus of the vertical-torsional positional nystagmus in 111 patients with P-BPPV and evaluated its time constant. We then examined whether the vertical-torsional positional nystagmus with long time constant disappeared at the neutral head position where the axis of the heavy cupula of the affected PSCC is aligned with gravity. The first parameter showed a wide variation that could be divided into two groups: one lasting more than 40 s in 8 patients and another below 20 s in 103 patients. Since the time constant of the positional nystagmus induced by cupulolithiasis was much longer than that induced by canalolithiasis, this finding suggests that cupulolithiasis in the PSCC induced the vertical-torsional positional nystagmus with a long time constant in the group of eight patients. The vertical-torsional positional nystagmus disappeared in these patients at the neutral head position, where the axis of the cupula of affected PSCC aligned with gravity.


A Case of Solitary Plasmacytoma of Bone in the Clivus

頭蓋底骨斜台部に発生した骨の孤発性形質細胞腫例

Most patients with plasmacytoma demonstrate a generalized disease at diagnosis such as multiple myeloma (MM). However, 3-5 percents of patients with plasmacytoma present with either a single bone lesion, or less commonly, a soft tissue mass, of monoclonal plasma cells: solitary plasmacytoma of bone (SPB) or extramedullary plasmacytoma (EMP). Moreover, SPB has a high risk of progression to MM. We report a 65-year-old female with SPB that only involved the skull base bone. She complained of discomfort of the throat for one month and endoscopic examinations showed a submucosal tumor of the nasopharynx. The tumor was biopsied by an endoscopic transnasal approach with the navigation system under general anesthesia. Resected tumor tissue showed monoclonal proliferation of CD138-positive plasma cells with lambda light chain expression in the cytoplasm. Although a small M protein was present in serum, CT, MRI and FDG-PET demonstrated that the osteolytic lesion arising from the clivus of the skull base bone gave rise to a submucosal tumor of the nasopharynx without skeletal lesions and other related organ or tissue impairment. Bone marrow did not contain monoclonal plasma cells, which is not consistent with MM. Finally, we diagnosed the patient as having SPB, but not EMP, without complication of MM.


1歳6ヵ月児および3歳児健康診査における聴覚スクリーニングの現状と問題点の検討

1歳6ヵ月児および3歳児健康診査における聴覚スクリーニングの現状と問題点の検討


Suplatast tosilate inhibits histamine signaling by direct and indirect down-regulation of histamine H1 receptor gene expression through suppression of histidine decarboxylase and IL-4 gene transcriptions.

Allergic rhinitis (AR) is an inflammatory disorder typified by symptoms such as sneezing, congestion, and rhinorrhea. Histamine plays important roles in eliciting AR symptoms. Up-regulation of the histamine H(1) receptor (H1R) and histidine decarboxylase (HDC) mRNAs was observed in AR patients. Th2 cytokines are also involved in the pathogenesis of AR. We examined the effect of suplatast tosilate on nasal symptoms, and H1R, HDC, and IL-4 gene expression using toluene-2,4-diisocyanate (TDI)-sensitized rats and HeLa cells expressing endogenous H1R. Provocation with TDI increased nasal symptoms, HDC activity, the histamine content of nasal lavage fluid, and the expression of H1R, HDC, and IL-4 mRNAs in TDI-sensitized rats. Pretreatment with suplatast for 2 wk significantly suppressed TDI-induced nasal symptoms and elevation of H1R, HDC, and IL-4 mRNAs. Suplatast also suppressed HDC activity in the nasal mucosa and the histamine content of the nasal lavage fluid. Bilateral injection of IL-4 into the nasal cavity of normal rats up-regulated H1R mRNA, while intranasal application of histamine up-regulated IL-4 mRNA. Suplatast suppressed IL-4-induced up-regulation of H1R mRNA in HeLa cells. However, it did not inhibit histamine-induced H1R mRNA elevation. These results suggest that suplatast alleviates nasal symptoms by inhibiting histamine signaling in TDI-sensitized rats through the suppression of histamine- and IL-4-induced H1R gene expression by the inhibitions of HDC and IL-4 gene transcriptions, respectively.


Endoscopic Re-operation on a Patient with Sphenoidal Sinus Cyst through Contralateral Sphenoidal Sinus under X-ray Imaging

術中X線透視を用い対側よりアプローチした蝶形骨洞嚢胞再手術例

We performed endoscopic re-operation on a patient with a relapsed cyst of the right sphenoidal sinus under X-ray imaging. The case was a 59-year-old man complaining of double vision due to a right sphenoidal cyst, and cysts of the bilateral sphenoidal sinus had been operated on at 52 years old. Because of postoperative stenosis of the right nasal cavity, we endoscopically opened the right sphenoidal cyst through the left sphenoidal sinus. In order to avoid skull base injury, endoscopic opening of the cyst wall was performed securely under X-ray imaging. X-ray imaging is a useful tool supporting endoscopic sinus surgery, as an alternative to the navigation system.


Eye Analysis of Ocular Counter Rolling: Is There an Effect of Somatosensory?

Ocular counter rolling (OCR) is the approximately conjugate rotational movement of the eyes about their visual axes, rotating opposite to the direction of head tilt. OCR may be induced by either angular acceleration acting on the semicircular canals, or by linear acceleration influencing otolith receptors. In the latter instance, the utricles are the main receptors. However, it has been suggested that an extralabyrinthine stimulus i.e., somatosensory input, can evoke OCR. We recorded OCR in six young, healthy volunteers and used eye analysis. We also recorded OCR when the subject sat down on a hard chair with and without a cushion in order to know if there was any effect of somatosensory input to the OCR. We used the Mann-Whitney U-test for the statistical analysis and P<0.05 was considered significant. There was no significant difference between the two groups. We considered there was not enough stimulation to the somatosensory input to affect the otolith-ocular reflex.


病的共同運動に対するボツリヌス治療とミラーバイオフィードバック併用療法におけるQOLの評価


病的共同運動に対するボツリヌス治療とミラーバイオフィードバックの併用療法の治療効果


神経障害の程度に応じたミラーバイオフィードバック

神経障害の程度に応じたミラーバイオフィードバック


第8脳神経症状のみを呈する耳性帯状疱疹(Haymann IV型)の検討

第8脳神経症状のみを呈する耳性帯状疱疹(Haymann IV型)の検討


Changes in the characteristics of definite Meniere's disease over time in Japan: a long-term survey by the Peripheral Vestibular Disorder Research Committee of Japan, formerly the Meniere's Disease Research Committee of Japan

The incidence of new cases of Meniere's disease (MD) in elderly patients aged 60 years or more was found to have increased over time after correction for age distribution in the overall population. Job- and care-related fatigue may be involved in the recent increase in elderly-onset cases because physical and mental fatigue can induce onset of the disease. Changes over time in the epidemiologic characteristics of MD in Japan were analyzed. Between 1975 and 2006, four nationwide, multi-center surveys of MD were conducted by the Meniere's Disease Research Committee of Japan (1975-1976) and the Peripheral Vestibular Disorders Research Committee of Japan (1982-1984, 1990, and 2001-2006). Information was collected by the committee members on a total of 1368 de novo cases of definite MD, 520 reported in the first survey, 290 in the second survey, 148 in the third survey, and 410 in the fourth survey. Clear changes were seen over time in the population-adjusted sex distribution of the disease and population-adjusted age at onset. The number of definite MD cases in females increased over time relative to the number of cases in males. The proportion of cases in which onset occurred at 60 years of age or more increased over time when the number of cases in each age group was adjusted for changes in age distribution of the population over time. From the time of the third survey, there was a slight increase in the proportion of cases with bilateral involvement.


Effects of hypergravity on histamine H1 receptor mRNA expression in hypothalamus and brainstem of rats: implications for development of motion sickness

The study findings suggest that histamine was released from the axon terminals in the hypothalamus and brainstem and the released histamine activated post-synaptic H1 receptors there, resulting in the development of motion sickness. We first examined which subtype of post-synaptic histaminergic receptor was responsible for the development of motion sickness. We then examined whether H1 receptors were up-regulated in various areas of the rat brain after 2 G hypergravity load, because the stimulation of H1 receptor was reported to up-regulate the level of H1 receptor protein expression through augmentation of H1 receptor mRNA expression. For this purpose, we used an animal model of motion sickness, using pica (eating non-nutritive substances such as kaolin), as a behavioral index in rats. After 2 G hypergravity load, rats ate a significant amount of kaolin, indicating that they suffered from motion sickness. The hypergravity-induced kaolin intake was suppressed by mepyramine, but not by terfinadine or zolantizine. This finding indicates that cerebral post-synaptic H1 but not H2 or peripheral H1 receptors play an important role in the development of motion sickness. The expression of H1 receptor mRNA was up-regulated in the hypothalamus and brainstem, but not in the cerebral cortex after 2 G hypergravity load in rats.


Evaluation of nasal IgA secretion in normal subjects by nasal spray and aspiration.

Nasal washing (NW) is a popular method for collecting human nasal lavage fluid. However, for NW the subject must be trained, and the method is unsuitable for field studies on untrained subjects. To overcome this problem, we have developed an easy and painless method, a nasal spray and aspiration (NSA) method. This method is different from NW in that the nasal cavity is misted over with saline, and the nasal lavage fluid is aspirated from the nostrils through a silicon tube. First, nasal lavage fluid was obtained twice by NSA with an interval of a week between lavages to evaluate intraindividual variability, and the IgA and protein levels in the nasal lavage fluid were measured by enzyme-linked immunosorbent assay and bicinchoninic acid assay, respectively. Next, the IgA value determined by NSA was compared with that by NW in another 12 normal subjects 2 days after NSA. In 10 normal subjects, mean volume of saline sprayed into the nose was 0.46+/-0.15 ml (mean+/-S.D.). Mean volume of aspirated nasal lavage fluid containing both sprayed saline and nasal secretion was 0.44+/-0.37 ml. The mean IgA level/mg protein in the nasal lavage fluid determined by NSA was 112+/-18 microg/mg protein at the first and 99+/-20 at the second times of measurement, being highly reproducible. The mean value by NSA was 114+/-19 microg/mg protein, being almost the same as that by NW of 99+/-27. These findings suggest that the IgA level/mg protein in nasal lavage fluid determined by NSA instead of NW might be useful for assessing the variability of nasal IgA secretion.


Repeated pre-treatment with antihistamines suppresses [corrected] transcriptional up-regulations of histamine H(1) receptor and interleukin-4 genes in toluene-2,4-diisocyanate-sensitized rats.

Antihistamines are effective for treatment of seasonal nasal allergy. Recently, prophylactic treatment with antihistamines in patients with pollinosis was reported to be more effective when started before the pollen season. The administration with antihistamines from 2 to 6 weeks before onset of the pollen season is recommended for management of allergic rhinitis in Japan. To determine the reason for the effectiveness of prophylactic treatment with antihistamines, the effects of repeated pre-treatment with antihistamines before provocation with toluene 2,4-diisocyanate (TDI) on their nasal allergy-like behavior and up-regulations of histamine H(1) receptors (H1R) and interleukin (IL)-4 mRNAs in their nasal mucosa were examined. Provocation with TDI induced sneezing and up-regulations of H1R and IL-4 mRNAs in the nasal mucosa of TDI-sensitized rats. Repeated pre-treatments with antihistamines including epinastine, olopatadine, or d-chlorpheniramine for 1 to 5 weeks before provocation with TDI suppressed TDI-induced sneezing and the up-regulations of H1R and IL-4 mRNAs in the nasal mucosa more than their administrations once or for 3 days before TDI provocation. Our data indicate that repeated pre-treatment with antihistamines before provocation with TDI is more effective than their single treatment in reducing nasal allergy-like behavior by causing additional suppression of up-regulations of H1R and IL-4 mRNAs in the nasal mucosa.


Effects of optokinetic stimulation induced by virtual reality on locomotion: a preliminary study

Exposure to a virtual environment for 20 min was sufficient to cause adaptive changes in locomotion in healthy subjects, suggesting that virtual environments might improve locomotor deviation in patients with unilateral labyrinthine defects. Postural and locomotor control in patients with unilateral labyrinthine defects deviates towards the lesion side. The aim of this study was to examine whether active locomotion within a virtual environment can increase the functionality of rehabilitation. We examined the effects of optokinetic stimulation produced by a virtual reality environment on ocular movement and locomotor tracks in 10 healthy subjects. During the 20 min experiment, the mean locomotor deviation and the mean frequency and mean amplitude of optokinetic nystagmus during the last period of the experiment were significantly higher than those during the initial period.


We report a case of Bow hunters stroke with the complaint of cervical vertigo. A 48-year-old man complained of cervical vertigo following head rotation to the left. He showed positional nystagmus when his head was rotated to the left in the supine position and, if the head rotation was maintained, he felt a gradual drop into unconsciousness. The positional nystagmus and fainting were not, however, induced in the patient in the left lateral decubitus position without head rotation. Three-dimensional analysis of his positional nystagmus showed its inconsistent rotational axis, which is different from the single rotational axis in patients with peripheral positional nystagmus. These findings suggested the central cervical positional vertigo/nystagmus in the patients. MRI showed an old infarction of the left cerebellum and MRA showed severe hypoplasia of the left vertebral artery. Vertebral angiography showed severe stenosis of the left vertebral artery and the mechanical occlusion of the right vertebral artery by the atlas-axis joint at C1-C2 when the patients head was rotated to the left. Therefore, it is demonstrated that his positional vertigo/nystagmus with fainting caused by head rotation to the left was induced by the vertebrobasilar insufficiency due to mechanical occlusion of the vertebral artery associated with head rotation, resulting in the diagnosis of Bow hunters stroke in this patient.