The effects of continuous administration of diazepam on the recovery of lesion-induced nystagmus in unilaterally labyrinthectomised rats.

These findings suggested that continuous administration of diazepam accelerates the initial process of VC; however, it does not suppress the nystagmus-driving mechanisms in rats.


A Case of Downbeat Nystagmus Induced by Carbamazepine Intoxication

カルバマゼピン中毒により下眼瞼向き眼振を認めた薬剤性めまい症例


Comparison of the efficacy of the Epley maneuver and repeated Dix-Hallpike tests for eliminating positional nystagmus: A multicenter randomized study.


Risk factors of first bite syndrome after surgical resection of parapharyngeal space tumors.

The present findings suggest that concomitant surgical settings of 1) sympathetic denervation of the parotid gland with ligation of the external carotid artery or injury of the sympathetic nerve plexus around the external carotid artery during its mobilization, and 2) residual parotid gland tissue are risk factors for the development of first bite syndrome after surgical resection of parapharyngeal space tumors. J. Med. Invest. 70 : 150-153, February, 2023.

The Journal of Medical Investigation : JMI


Muscle mass, quality, and strength; physical function and activity; and metabolic status in cachectic patients with head and neck cancer.

Cancer cachexia is commonly associated with poor prognosis in patients with head and neck cancer (HNC). However, its pathophysiology and treatment are not well established. The current study aimed to assess the muscle mass/quality/strength, physical function and activity, resting energy expenditure (REE), and respiratory quotient (RQ) in cachectic patients with HNC. This prospective cross-sectional study analyzed 64 patients with HNC. Body composition was measured via direct segmental multifrequency bioelectrical impedance analysis, and muscle quality was assessed using echo intensity on ultrasonography images. Muscle strength was investigated utilizing handgrip strength and isometric knee extension force (IKEF). Physical function was evaluated using the 10-m walking speed test and the five times sit-to-stand (5-STS) test. Physical activity was examined using a wearable triaxial accelerometer. REE and RQ were measured via indirect calorimetry. These parameters were compared between the cachectic and noncachectic groups. In total, 23 (36%) patients were diagnosed with cachexia. The cachectic group had a significantly lower muscle mass than the noncachectic group. Nevertheless, there was no significant difference in terms of fat between the two groups. The cachectic group had a higher quadriceps echo intensity and a lower handgrip strength and IKEF than the noncachectic group. Moreover, they had a significantly slower normal and maximum walking speed and 5-STS speed. The number of steps, total activity time, and time of activity (<3 Mets) did not significantly differ between the two groups. The cachectic group had a shorter time of activity (≥3 Mets) than the noncachectic group. Furthermore, the cachectic group had a significantly higher REE/body weight and REE/fat free mass and a significantly lower RQ than the noncachectic group. The cachectic group had a lower muscle mass/quality/strength and physical function and activity and a higher REE than the noncachectic group. Thus, REE and physical activity should be evaluated to determine energy requirements. The RQ was lower in the cachectic group than that in the noncachectic group, indicating changes in energy substrate. Further studies must be conducted to examine effective nutritional and exercise interventions for patients with cancer cachexia.


Betuletol, a propolis component, suppresses IL-33 gene expression and effective against eosinophilia

Propolis, a resinous substance produced by honeybees, has been used in folk medicine since ancient times due to its many biological benefits such as antitumor, antioxidant, antimicrobial, anti-inflammatory, and immunomodulatory effects. Propolis contains flavonoids, terpenoids, aromatic aldehydes, and alcohols, which vary with different climate and environmental conditions. In our study, we examined the antiallergic activity of Brazilian green propolis (BGP) and isolated the active compound that can suppress an allergy-sensitive gene, IL-33, expression and eosinophilia. Ethanolic extract of BGP freeze-dried powder was fractionated with several solvent systems, and the active fractions were collected based on activity measurement. The single active compound was found by thin-layer chromatography. Using column chromatography and NMR, the active compound was isolated and identified as 3,5,7-trihydroxy-6,4'-dimethoxyflavone, also known as betuletol. Further, the antiallergic activity of that has been examined in PMA-induced up-regulation of IL-33 gene expression in Swiss 3T3 cells. Our data showed the IL-33 gene suppression both by BGP and the isolated active compound, betuletol. We also found that betuletol suppressed ERK phosphorylation, suggesting it could be effective in suppressing IL-33 mediated eosinophilic chronic inflammation and will provide new insights to develop potent therapeutics against allergic inflammations.


Clinical Statistics of Patients with Dizziness and Vertigo at Tokushima University Hospital

当科のめまい外来の臨床統計 (武田憲昭教授退任記念総説集)


Clinical Outcomes of Treatment for Tongue Cancer at Tokushima University Hospital

当科における舌癌の治療成績 (武田憲昭教授退任記念総説集)


Clinical Outcomes of Treatment for Hypopharyngeal Cancer at Tokushima University Hospital

当科における下咽頭癌の治療成績 (武田憲昭教授退任記念総説集)


Hearing Outcomes After Tympanoplasty for Cholesteatoma at Tokushima University Hospital

当科における真珠腫性中耳炎の手術成績 (武田憲昭教授退任記念総説集)


Clinical Outcomes of Treatment for Laryngeal Cancer at Tokushima University Hospital

当科における喉頭癌の治療成績 (武田憲昭教授退任記念総説集)


New method to evaluate sequelae of static facial asymmetry in patients with facial palsy using three-dimensional scanning analysis.

The present findings suggest that affected-unaffected side differences in the depth of the nasolabial fold of the measured using three-dimensional scanning analysis can be used as an index of sequelae of static facial asymmetry. It is also suggested that the index can evaluate whether interventions are effective for the treatment of sequelae.


Efficacy of dual sublingual immunotherapy with Japanese cedar pollen and house dust mite allergens in patients with allergic rhinitis sensitized to multiple allergens.


Long-term changes in serum squamous cell carcinoma antigen levels after surgery in patients with sinonasal inverted papilloma.

These findings suggest that SCCA can be a tumor marker of IP. It is also suggested that postoperative elevation of SCCA levels is a clinical marker for monitoring the recurrence of IP during the follow-up period. A SCCA cut-off value of 1.85 ng/ml postoperatively may predict the subsequent recurrence of IP with high sensitivity and specificity.


Development of receptive vocabulary and verbal intelligence in Japanese children with unilateral hearing loss.

These findings suggest that the development of receptive vocabulary and verbal intelligence was delayed in preschool-age children with UHL and that most of them caught up to exhibit normal language ability after school admission.


Effects of sublingual immunotherapy with tablets or drops containing Japanese cedar pollen antigens on nasal symptoms and sleep disturbance in patients with Japanese cedar pollinosis.

It is suggested that SLIT with JCP tablets improved both nasal symptoms and sleep disturbances at peak pollen period in patients with Japanese cedar pollinosis. SLIT with JCP tablets for one year was more effective than SLIT with JCP drops for two years and prophylactic treatment with antihistamines. J. Med. Invest. 69 : 97-100, February, 2022.

The Journal of Medical Investigation : JMI


Association of phase angle with muscle function and prognosis in patients with head and neck cancer undergoing chemoradiotherapy


A Case of Benign Fibrous Histiocytoma Arising from the Tongue in a Two-Month-Old Infant

生後2ヵ月の乳児の舌に発生した良性線維性組織球腫例

Benign fibrous histiocytoma is a soft tissue tumor of unknown etiology that arises from the subcutaneous tissue, which accounts for 15% of all soft tissue tumors. The incidence of benign fibrous histiocytoma in the head and neck region is rather low, being on the order of a few percent, and there are scarce reports of its occurrence in the oral cavity. In addition, the tumor predominantly occurs in those over 25 years old, and onset in infants is quite rare.

We report a case of a two-month-old boy with benign fibrous histiocytoma arising from the tongue. The tumor in the tongue was detected at 40 days after birth. However, the child was brought to our department at a later date, because the tumor had grown and the child had difficulty in swallowing. The tumor, 25 mm×25 mm in size, was found on the left edge of the tongue. Tumor resection under general anesthesia was performed, and histopathology of the resected tumor revealed a benign fibrous histiocytoma. There has been no recurrence of the tumor, dysarthria, or dysphagia until now, three years after the surgery. Tumors of the tongue are rare in infants, but benign fibrous histiocytoma should be included in the differential diagnosis in infants presenting with tumors of the tongue.


Aural stimulation with capsaicin prevented pneumonia in dementia patients

カプサイシン軟膏による外耳道刺激は高齢認知症患者の肺炎を予防する

Nippon Jibiinkoka Tokeibugeka Gakkai Kaiho

日本耳鼻咽喉科頭頸部外科学会会報


Development of a new method for assessing otolith function in mice using three-dimensional binocular analysis of the otolith-ocular reflex.

In the interaural direction, translational linear acceleration is loaded during lateral translational movement and gravitational acceleration is loaded during lateral tilting movement. These two types of acceleration induce eye movements via two kinds of otolith-ocular reflexes to compensate for movement and maintain clear vision: horizontal eye movement during translational movement, and torsional eye movement (torsion) during tilting movement. Although the two types of acceleration cannot be discriminated, the two otolith-ocular reflexes can distinguish them effectively. In the current study, we tested whether lateral-eyed mice exhibit both of these otolith-ocular reflexes. In addition, we propose a new index for assessing the otolith-ocular reflex in mice. During lateral translational movement, mice did not show appropriate horizontal eye movement, but exhibited unnecessary vertical torsion-like eye movement that compensated for the angle between the body axis and gravito-inertial acceleration (GIA; i.e., the sum of gravity and inertial force due to movement) by interpreting GIA as gravity. Using the new index (amplitude of vertical component of eye movement)/(angle between body axis and GIA), the mouse otolith-ocular reflex can be assessed without determining whether the otolith-ocular reflex is induced during translational movement or during tilting movement.


Dietary Supplementation with Monosodium Glutamate Suppresses Chemotherapy-Induced Downregulation of the T1R3 Taste Receptor Subunit in Head and Neck Cancer Patients.

(Background) We investigated the effect of dietary supplementation with monosodium glutamate (MSG) on chemotherapy-induced downregulation of the T1R3 taste receptor subunit expression in the tongue of patients with advanced head and neck cancer. (Methods) Patients undergoing two rounds of chemoradiotherapy were randomly allocated to a control or intervention group (dietary supplementation with MSG at 2.7 g/day during the second round of chemotherapy). The relative expression of T1R3, a subunit of both umami and sweet taste receptors, in the tongue was assessed by quantitative polymerase chain reaction analysis. Dysgeusia was assessed with a visual analog scale and daily energy intake was evaluated. (Results) T1R3 expression levels in the tongue, taste sensitivity, and daily energy intake were significantly reduced after the first round of chemotherapy compared with before treatment. Furthermore, these parameters significantly decreased after the second round of chemotherapy, but the extent of decrease was significantly attenuated in the MSG group compared with the control group. (Conclusions) MSG supplementation suppresses chemotherapy-induced dysgeusia, possibly due to the inhibition of the T1R3-containing taste receptor downregulation in the tongue, thereby increasing energy intake in patients with advanced head and neck cancer.


Effects of vocal nodules on acoustic characteristics of voice in children : an acoustic analysis of voice.

Objective : In the present study, an attempt was made to evaluate the acoustic characteristics of voice in pediatric patients with vocal nodules using acoustic analysis of voice. Methods : Thirty-five pediatric patients with vocal nodules and 32 control children without dysphonia were enrolled in this study. Their voice samples were analyzed using the Multi-Dimensional Voice Program. Acoustic parameters of voice, such as pitch period perturbation quotient (PPQ), amplitude perturbation quotient (APQ), and noise-to-harmonic ratio (NHR), were measured. Results : In phonation at a loudness of over 80 dBA, the PPQ, APQ, and NHR values of the voice significantly increased in children with vocal nodules than in the control children without dysphonia. The sensitivities and specificities of PPQ, APQ, and NHR for prediction of vocal nodules in children were 62.86% and 84.38%, 74.29% and 75.00%, and 31.43% and 93.75%, respectively. Discussion : The present findings suggest that vocal nodules affect vocal fold vibration, resulting in impaired control of pitch and loudness leading to increased noise components. NHR could be used to evaluate the efficacy of treatment, such as voice rehabilitation, in pediatric patients with vocal nodules because of its high specificity for prediction of vocal nodules in children. J. Med. Invest. 68 : 276-279, August, 2021.

The Journal of Medical Investigation : JMI


Anti-Influenza Virus-Specific Nasal Secretory IgA and Serum IgG Titers in a Japanese Adult Population and their Changes after Subcutaneous Vaccination

成人のインフルエンザウイルス特異的鼻腔分泌型 IgA 抗体価と血清 IgG 抗体価の保有状況とワクチン接種による影響

In order to clarify human mucosal and systemic immunity against influenza viral infection, the serum titers of anti-influenza virus-specific nasal secretory IgA and serum IgG and their changes after subcutaneous vaccination were measured in a Japanese healthy adult population in the present study. We recruited 155 healthy adults in 2006, with an average age of 24.1 years (range: 19-60 years). The male-female ratio was 1: 1. Nasopharyngeal lavage fluid and serum specimens were obtained prior to vaccination and a month after subcutaneous vaccination with a trivalent influenza ether split hemagglutinin vaccine of the A (H1N1), A (H3N2) subtypes and type B influenza viruses. Nasopharyngeal lavage fluid specimens were obtained by the nasal spray and aspiration method. The anti-influenza virus-specific IgA titers in the nasopharyngeal lavage fluid and IgG titers in the serum against the A (H1N1), A (H3N2) subtype and type B influenza viruses were measured by ELISA. The anti-influenza virus-specific nasal lavage fluid IgA titers were represented as a ratio to the total IgA titers. About 70% of the subjects had nasal anti-viral IgA against the A (H1N1), A (H3N2) subtype and type B influenza viruses, and almost all had serum anti-viral IgG against the A (H1N1), A (H3N2) subtype and type B viruses. The serum antiviral IgG titers, but not the nasal antiviral IgA titers, were significantly elevated at 1 month after the subcutaneous vaccination. Moreover, the serum antiviral IgG titers were significantly elevated after vaccination only in subjects with low pre-vaccination IgG titers, and not in those with high pre-vaccination IgG titers. The nasal antiviral IgA titers in the subjects of our present study were significantly higher than those in patients with influenza infection reported from our previous study. The presence of nasal anti-influenza virus-specific IgA in about 70% of Japanese adults is considered as being suggestive of a history of influenza infection. The presence of anti-influenza virus-specific IgG in the serum in almost all Japanese adults could suggest a history of influenza infection or influenza vaccination. Currently available subcutaneous influenza vaccines induce systemic immunity, with the appearance of anti-viral IgG in the serum, in adults. However, subcutaneous vaccination does not appear to be capable of inducing mucosal immunity with the induction of antiviral secretory IgA in the nasopharynx. The present findings suggest that subcutaneous influenza vaccination can suppress the progression of influenza infection by inducing the appearance of antiviral IgG in serum, but not by inducing the appearance of antiviral IgA in the nasopharynx. The findings also suggest that subjects with low antiviral secretory IgA titers in the nasopharynx are at a higher risk of influenza infection.


Vestibular and cochlear nerve enhancement on MRI and its correlation with vestibulocochlear functional deficits in patients with Ramsay Hunt syndrome.

In patients with RHS, the origin of vertigo may be superior vestibular neuritis, which is affected by reactive varicella-zoster virus from the geniculate ganglion of the facial nerve through the faciovestibular anastomosis. The results also suggested that in some RHS patients, inferior vestibular neuritis contributes to the development of vertigo and that the origin of refractory sensorineural hearing loss is cochlear neuritis.

Among RHS patients, 79%, 53%, 17% and 26% showed CP in the caloric test, abnormal responses to oVEMP and cVEMP, and refractory sensorineural hearing loss, respectively. SIinc rates of the SVN were significantly increased in RHS patients with CP in the caloric test, and with abnormal responses to oVEMP and cVEMP. SIinc rates of the SVN tended to increase in RHS patients with refractory sensorineural hearing loss (p = 0.052). SIinc rates of the IVN were significantly increased in RHS patients with abnormal responses to oVEMP and cVEMP, and refractory sensorineural hearing loss, but not in those with CP in the caloric test. SIinc rates of the CN were significantly increased in RHS patients with CP in the caloric test, abnormal response to oVEMP and refractory sensorineural hearing loss, but not in those with abnormal response to cVEMP.


A Case of Hereditary Angioedema who Underwent Endoscopic Sinus Surgery Under General Anesthesia

全身麻酔下に内視鏡下鼻内副鼻腔手術を行った遺伝性血管性浮腫例

Hereditary angioedema (HAE) is an inherited disease characterized by angioedema, that is caused by a genetic abnormality of C1-inhibitor (C1-INH). Decrease or functional abnormality of the C1-INH protein leads to excessive production of bradykinin, which causes increased vascular permeability. Patients with HAE present with edema of the face, arms and legs, as also of the larynx and gastrointestinal tract. Notably, airway stenosis caused by laryngeal edema can be fatal. Upper airway surgery under general anesthesia in patients with HAE carries the risk of airway stenosis caused by surgical site edema and by laryngeal edema due to tracheal intubation. In one guideline for the management of HAE, administration of C1-INH (Berinert®P) prior to surgery is recommended as prophylaxis against the development of angioedema.

A 68-year-old female patient with HAE (type 1) was referred to our department with the chief complaint of pain in the right maxilla. She had undergone Caldwell-Luc surgery for sinusitis as a 13-year-old. CT showed two cysts in the right maxilla, and she was diagnosed as having maxillary cysts and scheduled for surgery. As she suffered from frequent attacks of HAE, we administered C1-INH to the patient prior to surgery, according to a guideline for the management of HAE, and the patient underwent endoscopic sinus surgery (ESS) under general anesthesia without HAE attacks during the perioperative period.

ESS under general anesthesia in a patient with HAE carries the risk of angioedema developing at the surgical site and laryngeal edema developing as a result of tracheal intubation. We could safely perform ESS without angioedema developing in the perioperative period, by prophylactic administration of C1-INH according to a guideline for the management of HAE.


A Case of von Willebrand's Disease Diagnosed by Refractory Tonsillar Hemorrhage with a Family History

難治性扁桃出血を契機に診断された家族歴を有するvon Willebrand病例

The disease termed von Willebrand's disease (vWD) is an autosomal-dominant hereditary bleeding disorder caused by dysfunction or deficiency of the clotting factor called von Willebrand factor (vWF); vWF is produced by the vascular endothelial cells and bone marrow megakaryocytes, and plays a major role in platelet adhesion and aggregation in the processes of primary hemostasis.

We reported the case of 3-year-old girl with vWD, who presented us with refractory tonsillar hemorrhage. Because of the family history of refractory bleeding, the concentration and activity of vWF in the blood were measured. Accordingly, the child was diagnosed as having vWD as she met the following diagnostic criteria: 1) abnormal bleeding episode; 2) vWF antigen titer or vWF activity less than 30% or equivalent to the mean -2SD. After additional laboratory examination, we diagnosed her as having type2A vWD. Moreover, her mother, grandmother and 2 second cousins were also diagnosed having type2A vWD. Following the diagnosis, the refractory pharyngeal bleeding was controlled by intravenous factor VIII/vWF supplementation.

Because refractory epistaxis and oral mucosal bleeding are common symptoms in patients with vWD, it is important for otolaryngologists to promptly diagnose this disease by type and advise patients on the appropriate course of treatment.


Effects of Betahistine on the Development of Vestibular Compensation after Unilateral Labyrinthectomy in Rats.

These findings suggest that betahistine facilitated the late, but not the initial, process of VC in UL rats.


A new combined index of SUVmax of lymph node in PET / CT by a weighting coefficient plus its maximum minor axis in CECT to evaluate occult lymph node metastasis in clinical N0 patients with tongue cancer.

To predict occult nodal metastasis in clinical N0 patients with tongue cancer, we developed combined index (CI) : SUVmax of the largest lymph node in PET / CT by weighting coefficient plus its maximum minor axis (< 10 mm) in contrast-enhanced CT (CECT). In this retrospective study, 57 clinical N0 patients with tongue cancer, who underwent elective supraomohyoid neck dissection at cervical levels of I-III were enrolled. The cutoff value of SUVmax of 2.0 obtained using receiver operating characteristic (ROC) analysis predicted the postoperative positive cervical levels containing metastatic lymph nodes from clinical N0 cervical levels in tongue cancer patients with a sensitivity of 54.5% and a specificity of 78.2%. The cutoff value of CI with weighting coefficient of 1.5 obtained using ROC analysis was 9.8 at the maximum area under the curve of 0.750. The cutoff value of 9.8 predicted the postoperative positive cervical levels containing metastatic lymph nodes from clinical N0 cervical levels in tongue cancer patients with a sensitivity of 68.2% and a specificity of 81.5%. These findings suggest that CI of functional PET / CT and morphological CECT components might improve the diagnostic performance of occult nodal metastasis to select clinical N0 patients with tongue cancer preferable for elective neck dissection. J. Med. Invest. 68 : 154-158, February, 2021.

The Journal of Medical Investigation : JMI


Effects of sublingual immunotherapy on nasal symptoms and sleep disturbance in patients with Japanese cedar pollinosis.

These findings suggested that SLIT with JC pollen extract suppressed nasal symptoms in patients with JC pollinosis, leading to improvements in AR-related sleep disturbance and daytime troubles with daily life.


Effects of narrow-band UVB on nasal symptom and upregulation of histamine H1 receptor mRNA in allergic rhinitis model rats

Intranasal pre-irradiation with narrow-band UVB dose-dependently inhibited sneezes and upregulation of H1R gene expression of the nasal mucosa in AR model rats, suggesting that the inhibition of nasal upregulation of H1R gene expression suppressed nasal symptom. The suppression after narrow-band UVB irradiation at a dose of 600 mJ/cm


Differential cytokine profiles in pediatric patients with PFAPA syndrome and recurrent tonsillitis.

Objective : An attempt was made to identify characteristic cytokine profiles to distinguish periodic fever with aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPAS) from recurrent tonsillitis, of which clinical manifestations are similar to those of PFAPAS in children. Methods : Serum concentrations of IL-6, IL-4 and IFN-γ were measured during febrile episodes in pediatric patients. Results : The levels of IL-6 during febrile episodes were markedly increased above the upper limit of normal ranges in patients with both PFAPAS and recurrent tonsillitis, but there were no significant differences between groups. The levels of IL-4 during febrile episodes in PFAPAS patients were significantly lower than those in recurrent tonsillitis patients. The levels of IFN-γ during febrile episodes in PFAPAS patients were significantly higher than those in recurrent tonsillitis patients. Conclusion : In pediatric patients with PFAPAS, despite an increase of IL-6, IL-4 was suppressed with a marked increase of IFN-γ during febrile episodes. On the contrary, in febrile pediatric patients with recurrent tonsillitis, both IL-6 and IL-4, but not IFN-γ were increased. The characteristic cytokine profiles of IL-6, IL-4 and IFN-γ can be used for differential diagnosis of PFAPAS from recurrent tonsillitis in children in clinical ear, nose and throat (ENT) settings. J. Med. Invest. 68 : 38-41, February, 2021.

The Journal of Medical Investigation : JMI


Transnasal Endoscopic Surgery for Juvenile Angiofibroma Involving the Pterygopalatine Fossa

経鼻内視鏡手術にて摘出した翼口蓋窩に進展した若年性血管線維腫例

Juvenile angiofibroma (JA) is an uncommon, locally invasive, highly vascular and benign tumor that occurs in adolescent males. Established external surgical procedures for resection of JA include lateral rhinotomy, midfacial degloving, and transpalatal or infratemporal approaches; however, transnasal endoscopic approaches are increasingly being used because of advances in surgical techniques and endoscopic instrumentation. We report the case of a 14-year-old male who presented with left nasal obstruction and repeated epistaxis. A smooth reddish and hemorrhagic tumor was found in the left posterior nasal cavity. Computed tomography and magnetic resonance imaging showed a markedly enhanced tumor of approximately 40 mm in diameter that had obstructed the left posterior nasal cavity and nasopharynx, with occupancy of the pterygopalatine fossa. The case was diagnosed as Radkowski stage IIB. Preoperative embolization was performed to reduce tumor vascularity and improve visualization for surgical removal. Transnasal endoscopic surgery was used to resect the tumor en bloc after clipping the left maxillary artery. Intraoperative bleeding was 80 mL. To prevent recurrence, careful attention must be paid to tumor invasion into the Vidian canal. The postoperative course of our patient was uneventful, and there has been no evidence of recurrence for over one and a half years since surgery.

若年性血管線維腫は思春期男子に好発し，頻回の鼻出血や鼻閉をきたす比較的稀な良性腫瘍である．治療の第一選択は手術であるが，非常に血流に富む腫瘍のため，従来は経上顎洞法，外側鼻切開法，経口蓋法などが行われてきた．近年は手術手技や機器の発展に伴い内視鏡下摘出術の適応が広がってきている．今回，我々は経鼻内視鏡手術で摘出した翼口蓋窩に進展した若年性血管線維腫例を経験したので報告する．症例は14歳男性で左鼻閉と反復する鼻出血を主訴に近医耳鼻科を受診し，左鼻腔内に腫瘍性病変を指摘され，当科紹介となった．初診時の鼻内所見では左鼻腔後方に表面平滑な赤色腫瘤を認めた．画像所見にて左鼻腔後方から上咽頭，そして翼口蓋窩を占拠する著明な造影効果のある腫瘤を認め，血管造影で栄養血管を確認し若年性血管線維腫のRadkowskiの分類StageIIBと診断した．術中の出血を抑制するために，手術当日に選択的血管塞栓療法を施行した．経鼻内視鏡下に腫瘍を一塊に摘出し，術中の出血を80 mlに抑制できた．若年性血管線維腫の再発部位は翼突管が最多であると報告されており，摘出術では翼突管への腫瘍の残存に注意する必要があると考えられた．


A Case of Extramedullary Relapse of APL on the Tympanic Membrane

鼓膜に髄外再発した急性前骨髄球性白血病例

Temporal bone lesions are rarely seen in patients with acute promyelocytic leukemia (APL) during the remission phase. We report a case of APL who showed extramedullary relapse on the tympanic membrane while in the complete remission phase. A 48-year-old male patient with APL in complete remission after the initial therapy presented with left ear fullness. Endoscopic examination revealed a mass on the left tympanic membrane, and temporal bone CT showed a mass localized on the left tympanic membrane. He was diagnosed as having extramedullary relapse of APL based on the histopathological findings of the lesion on the tympanic membrane. There were no APL cells in the blood or bone marrow. However, PCR analysis revealed the presence of PML-RARα in the bone marrow. Based on these findings, we diagnosed the patient as having molecular recurrence of APL, and administered chemotherapy. During the treatment, the ear lesion decreased steadily in size, and finally disappeared. Absence of PML-RARα in the bone marrow specimen after the treatment indicated that the patient had entered the second remission phase. Subsequently, hematopoietic stem-cell transplantation was performed, and the patient remains in remission. In a patient with a history of leukemia presenting with temporal bone lesions, extramedullary relapse should be considered in the differential diagnosis even if the patient is in the remission phase.


Assessment of the Progression of Vertical Semicircular Canal Dysfunction and Increased Vestibular Endolymphatic Hydrops in Patients With Early-Stage Ménière Disease.

In this study, during a 2-year period of medical treatment among patients with Ménière disease, vestibuloocular reflex gain decreased in the vertical semicircular canals but was maintained in the horizontal semicircular canals; the endolymphatic hydrops volume ratio increased, and the frequency of vertiginous episodes decreased. These findings describe the pathological progression of chronic Ménière disease and expand the understanding of its pathophysiological characteristics during the early stage of disease.

JAMA Otolaryngology-- Head & Neck Surgery


レンコンエキスパウダー摂取による鼻と眼のアレルギー症状軽減効果の検証―プラセボ対照ランダム化二重盲検並行群間比較試験―


Identification and characterization of the anti-allergic compound from lotus root.


Effects of corticosteroid on mRNA levels of histamine H1 receptor in nasal mucosa of healthy participants and HeLa cells.

The purpose of this study is to examine the effect of intranasal corticosteroid (INCS) administration on histamine H1 receptor (H1R) gene expression in the nasal mucosa of healthy participants and the effects of dexamethasone on basal and histamine-induced H1R mRNA expression, and histamine-induced phosphorylation of extracellular signal-regulated kinase (ERK) in HeLa cells. Sixteen healthy participants were given INCS once daily for a week. After pretreatment of dexamethasone, HeLa cells were treated with histamine. Levels of H1R mRNA and phosphorylation of ERK were measured using real time PCR and immunoblot analysis, respectively. Levels of H1R mRNA in the nasal mucosa of healthy participants receiving INCS was significantly decreased. Dexamethasone suppressed basal levels of H1R mRNA, and histamine-induced up-regulation of H1R mRNA and ERK phosphorylation in HeLa cells. These data suggested that corticosteroid inhibited both basal transcription and histamine-induced transcriptional activation of H1R through its suppression of ERK phosphorylation in the signaling pathway involved in H1R gene transcription. It is further suggested that pre-seasonal prophylactic administration of INCS suppresses both basal and pollen-induced upregulation of H1R gene expression in the nasal mucosa of patients with pollinosis, leading to prevention of the exacerbation of nasal symptoms during peak pollen season. J. Med. Invest. 67 : 311-314, August, 2020.

The Journal of Medical Investigation : JMI


Identification of pyrogallol from Awa-tea as an anti-allergic compound that suppresses nasal symptoms and IL-9 gene expression.

As the expression level of allergic disease sensitive genes are correlated with the severity of allergic symptoms, suppression of these gene expressions could be promising therapeutics. We demonstrated that protein kinase Cδ / heat shock protein 90-mediated H1R gene expression signaling and nuclear factor of activated T-cells (NFAT)-mediated IL-9 gene expression signaling are responsible for the pathogenesis of pollinosis. Treatment with Awa-tea combined with wild grape hot water extract suppressed these signaling and alleviated nasal symptoms in toluene-2,4-diisocyanate (TDI)-sensitized rats. However, the underlying mechanism of its anti-allergic activity is not elucidated yet. Here, we sought to identify an anti-allergic compound from Awa-tea and pyrogallol was identified as an active compound. Pyrogallol strongly suppressed ionomycin-induced up-regulation of IL-9 gene expression in RBL-2H3 cells. Treatment with pyrogallol in combination with epinastine alleviated nasal symptoms and suppressed up-regulation of IL-9 gene expression in TDI-sensitized rats. Pyrogallol itself did not inhibit calcineurin phosphatase activity. However, pyrogallol suppressed ionomycin-induced dephosphorylation and nuclear translocation of NFAT. These data suggest pyrogallol is an anti-allergic compound in Awa-tea and it suppressed NFAT-mediated IL-9 gene expression through the inhibition of dephosphorylation of NFAT. This might be the underlying mechanism of the therapeutic effects of combined therapy of pyrogallol with antihistamine. J. Med. Invest. 67 : 289-297, August, 2020.


ベタヒスチンが一側内耳破壊ラットの前庭代償過程に与える影響

ベタヒスチンが一側内耳破壊ラットの前庭代償過程に与える影響

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


A Case of Rosai-Dorfman Disease with Multiple Extranodal Lesion

多発する節外病変を認めたRosai-Dorfman病例

Rosai-Dorfman disease is a rare histiocytic disorder characterized by accumulation of histiocytes in the affected tissue. Herein we report on a case of Rosai-Dorfman disease with multiple lymphadenopathy and multiple extranodal lesions. A 22-year-old woman was referred to our hospital with bilateral submandibular swelling and a localized swelling in the root of the nose. Endoscopic examination revealed mass lesions in both nasal cavities and the subglottic area. A full-body CT revealed multiple nasal masses, cervical lymphadenopathy, and an intrathymic mass. We diagnosed her as having Rosai-Dorfman disease based on the histopathological findings of accumulation of histiocytes and emperipolesis in the nasal lesion and cervical lymph node specimens. Histopathological examination is required for the diagnosis of Rosai-Dorfman disease. After steroid treatment for 3 months, reduction in the size of the lymph nodes in the neck, nasal cavity lesions, and intrathymic mass was noted. However, the size of the subglottic mass remained almost unchanged. In this case, steroid treatment was mostly effective on the lesions. In case of airway obstruction due to increase in the size of the subglottic mass, surgical resection should be indicated.


ヒスタミンH1受容体とIL-33遺伝子発現亢進に対する小青竜湯の抑制効果

ヒスタミンH1受容体とIL-33遺伝子発現亢進に対する小青竜湯の抑制効果


顔面神経麻痺程度の客観的評価 ―ハイスピードカメラを用いた自発性瞬目速度の測定―


上眼瞼向き自発眼振，方向交代性背地性頭位眼振と低音障害型感音難聴を呈した第四脳室毛様細胞性星細胞腫例


Daily auricular stimulation with capsaicin ointment improved cough reflex sensitivity in elderly patients with dysphagia: a pilot study.

Daily auricular stimulation with capsaicin ointment would be a safe and effective intervention to prevent pneumonia in elderly with a risk of aspiration.


Effects of FM system fitted into the normal hearing ear orcartilage conduction hearing aid fitted into the affected ear on speech-in-noise recognition in Japanese children with unilateral congenital aural atresia.

The effects of FM system fitted into the normal hearing ear (NHE) or a cartilage conduction hearing aid (CCHA) fitted into the affected ear (AE) on the speech recognition ability in noise were examined in children with unilateral congenital aural atresia (UCAA). In children with bilateral normal hearing (BNH), speech recognition score (SRS) was significantly decreased in the noisy environment of -5 dB signal-to-noise ratio (SNR), compared with those in quiet. In children with UCAA, SRS was significantly decreased in noisy environments of 0 and -5 dB SNR, compared with those in quiet. In noisy environments of 0 and -5 dB SNR, SRS in children with UCAA was significantly decreased, compared those in children with BNH. In the noisy environment of -5 dB SNR, SRS in UCAA children aided by FM system fitted into NHE was significantly better than those in unaided children in the same group. In the noisy environment of 0 dB SNR, SRS in UCAA children aided by CCHA into AE tended to be higher than those in unaided children in the same group. FM system and CCHA can be recommended as an audiological management for the improvement of speech recognition in children with UCHL in classrooms. J. Med. Invest. 67 : 134-138, February, 2020.

The Journal of Medical Investigation : JMI


Electroneurography cannot predict when facial synkinesis develops in patients with facial palsy.

The objective of this study is to clarify when facial palsy patients with lower value of Electroneurography (ENoG) should begin the rehabilitation to prevent the development of facial synkinesis. For this purpose, we examined the relationship between the value of ENoG measured 10-14 days after facial palsy onset and the onset day of the development of oral-ocular synkinesis. Sixteen patients with facial palsy including 11 with Bell's palsy and 5 with Ramsay Hunt syndrome (7 men and 9 women ; 15-73 years old ; mean age, 41.6 years) were enrolled in this study. There was no correlation between ENoG value and the onset day of the development of oral-ocular synkinesis (ρ = .09, p = .73). Oral-ocular synkinesis began to develop in 4.0 ± 0.7 months (mean ± SD ; range : 3.1-5.0 months) after facial palsy onset regardless of ENoG value. In conclusion, ENoG value cannot predict when facial synkinesis develops in patients with facial palsy. We recommend that facial palsy patients with a high risk for the development of synkinesis begin the biofeedback rehabilitation with mirror to prevent the development of facial synkinesis 3 months after facial palsy onset. J. Med. Invest. 67 : 87-89, February, 2020.


Postural stability against full-field dynamic visual disturbance in archery players.

Objectives : The effects of full-field dynamic visual disturbance on body sway were examined in archery players (n = 24), ball game players (n = 35), and untrained subjects (n = 34). Methods : Participants were asked to stand on a platform surrounded a box, the inside of which was randomly dotted. After the box suddenly began to swing and continued to swing back and forth at a frequency of 0.42 Hz for 60 seconds in a damped sinusoidal waveform, the body center sway was recorded using a stabilometer. Results : Standard deviation (SD) of body center sway in the anterior-posterior direction suddenly increased just after the box began to swing, and gradually decreased as the box swung in a damped sinusoidal waveform. After a sudden initial increase in SD of body center sway, it significantly decreased in archery players, compared with that of ball game players 20 seconds or untrained subjects 15 and 20 seconds after the onset of the box motion. Conclusion : Archery players showed higher stability against visual disturbance, compared with ball game players and untrained subjects, suggesting that they rely on proprioceptive inputs to maintain balance, and that their training re-weights sensorimotor dominance from vision to proprioception for posture regulation to increase shooting accuracy. J. Med. Invest. 67 : 67-69, February, 2020.


Aural stimulation with capsaicin prevented pneumonia in dementia patients.

These findings suggest that daily long-term aural stimulation with capsaicin ointment enhanced the cough reflex via Arnold's ear-cough reflex as a glottis protective measure, resulting in the reduction of incidence of pneumonia in elderly dementia patients at high risk of aspiration. The daily aural stimulation with capsaicin ointment may be a safe and promising intervention to prevent aspiration pneumonia in elderly people, especially those who cannot undergo swallowing exercise.


Annual change in articulatory acquisition of /k/ and / / in three-year-old children

3歳児健診受診児における構音発達の経年変化 ─/K//g/を中心とした検討─

In the present study, we investigated the articulatory acquisition in three-year-old children who received municipal medical check-up from 2011 to 2016. The percentage of three-year-old children with articulatory errors gradually increased from 59.5% in 2011 to 84.1% in 2016. Although articulation of /k/ and / / is believed to be acquired around the age of 3-year-6-month, 52.3% an 23.9% of three-year-old children enrolled in 2016 could not properly pronounce /k/ and / /, respectively. Because 24.3% and 5.4% of three-year-old children enrolled in 2011 had articulatory errors of /k/ and / /, respectively, it is suggested that the articulatory acquisition was delayed in Japanese children recently. The delayed articulatory acquisition may be related to insufficient exercise and poor communication with the adults around one in the childhood.

平成23年度から平成28年度のA市の3歳児健診を受診した幼児の構音の誤りと誤り方の経年変化を調査した．構音に誤りのある幼児の割合は平成23年度の59.5%から平成28年度の84.1%に増加していた．3歳6か月前後に完成するとされている/k/と/ɡ/の構音に誤りのある幼児の割合は，平成23年度の24.3%と5.4%から平成28年度の52.3%と23.9%に増加していた．このことから，最近の日本の幼児の構音の獲得が遅れていることが示唆された．/k/と/ɡ/の構音の誤り方に置換や未熟構音に伴う歪みが多く認められ，6年間で増加傾向を示したことに，最近の幼児の口腔習癖に伴う不正咬合，咀嚼能力，手指の協調運動，バランス能力の低下，言語発達の遅れが関与している可能性が考えられた．/k/の側音化構音に伴う歪みが増加していたことに，口呼吸，異常な嚥下癖，口腔習癖の増加，健診に参画する言語聴覚士の構音の誤りの検出精度の向上が関与している可能性が考えられた．


Vestibular Compensation after Vestibular Dysfunction Induced by Arsanilic Acid in Mice.

-arsanilic acid sodium salt solution in the tympanic cavity for 5 min. From behavioral observations, vestibular functions were worst at 2 days and recovered by 7 days after surgery. Spontaneous nystagmus appeared at 1 day after surgery with arsanilic acid and disappeared by 2 days. Histological studies revealed specific damage to the vestibular endorgans. In the ipsilateral spinal vestibular nucleus, the medial vestibular nucleus, and the contralateral prepositus hypoglossal nucleus, a substantial number of c-Fos-immunoreactive cells appeared by 1 day after surgery with arsanilic acid, with a maximum increase in number by 2 days and complete disappearance by 7 days. Taken together, these findings indicate that chemical labyrinthectomy with arsanilic acid and the subsequent observation of vestibular compensation is a useful strategy for elucidation of the molecular mechanisms underlying vestibular pathophysiologies.


Clinical trials of Cry j 1 and Cry j 2 T-cell epitope peptide-expressing rice in patients with Japanese cedar pollinosis.

Tolerability and safety of 7Crp-expressing rice was accepted. Daily intake of up to 20 g transgenic rice did not provide beneficial effects on Japanese cedar pollinosis within 24 weeks, however, continuous intake of 5 g rice might reduce allergen specific T cell response.

Asian Pacific Journal of Allergy and Immunology


Vertical head impulse and caloric are complementary but react opposite to Meniere's disease hydrops.

Abnormal vHIT results in MD patients were found most frequently in the posterior (44.4%) SCs, followed by the horizontal (13.3%) and anterior (10%) SCs. Canal paresis (CP) was assessed using the vHIT and the caloric test, and results were not significant when vHIT responses were assessed as CP only using the horizontal SC. The difference in the vestibular EH between the presence and absence of CP was not significant if assessed using the vHIT (P = .5591), but it was statistically different if assessed using the caloric test (P = .0467).


Stability of Endolymphatic Hydrops in Ménière Disease Shown by 3-Tesla Magnetic Resonance Imaging During and After Vertigo Attacks.

JAMA Otolaryngology-- Head & Neck Surgery


Comparative study of anti-vertiginous and anti-anxious drugs for the treatment of chronic vestibular patients with secondary anxiety.

Targeting for comorbid anxiety was beneficial for subjective symptoms of chronic dizziness with secondary anxiety.

Forty-three patients who had chronic dizziness lasting more than three months due to organic vestibular diseases with secondary anxiety. Anxiety was evaluated by the State-Trait Anxiety Inventory (STAI). Subjective handicaps due to dizziness were assessed by the validated questionnaire consisted of 14 questions that were categorized into two physical and three emotional factors. During the initial six months of the study, 21 patients were treated by anti-anxious benzodiazepines (loflazepate, 2 mg/day) for four weeks, whereas anti-vertiginous cholinergic antagonist (diphenidol, 75 mg/day) was used for four weeks for other 22 patients during the later six months-period. Subjective handicaps and STAI were compared between pre- and post-treatment.


動物モデルを用いた免疫組織化学的手法により前庭代償の新しい評価法

動物モデルを用いた免疫組織化学的手法により前庭代償の新しい評価法

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


A new immunohistochemical method to evaluate the development of vestibular compensation after unilateral labyrinthectomy in rats.

These findings suggested that the number of MK801-induced Fos-LIR neurons in contra-MVe was decreased in concordance with the restoration of ipsi-MVe-activity during the late process of VC after UL and that thioperamide accelerated the late, but not the initial process of VC.


Effects of Interval Time of the Epley Maneuver on Immediate Reduction of Positional Nystagmus: A Randomized, Controlled, Non-blinded Clinical Trial.


Three-Dimensional Magnetic Resonance Imaging Reveals the Relationship Between the Control of Vertigo and Decreases in Endolymphatic Hydrops After Endolymphatic Sac Drainage With Steroids for Meniere's Disease.

Meniere's disease is a common disease, that presents with recurrent vertigo and cochlear symptoms. The pathology of Meniere's disease was first reported to involve endolymphatic hydrops in 1938. The endolymphatic sac is thought to have a role to keep the hydrostatic pressure and endolymph homeostasis for the inner ear. As a surgery for intractable Meniere's disease, endolymphatic sac drainage with intraendolymphatic sac application of large doses of steroids is performed to control the endolymphatic hydrops and preserve or improve inner ear function. In the present study, to observe the effect of this surgery, we calculated the endolymphatic space size using 3-Tesla magnetic resonance imaging (MRI) 4 h after intravenous injection of gadolinium enhancement at two time points: just before surgery and 2 years after. To reveal the condition of the endolymphatic space, we constructed three-dimensional MR images semi-automatically and fused the three-dimensional images of the total fluid space of inner ear and the endolymphatic space. After fusing the images, we calculated the volume of the total fluid space and endolymphatic space. Two years after surgery, 16 of 20 patients (80.0%) showed relief from vertigo/dizziness and reductions in the ratio of the volume of the endolymphatic size to the total fluid space of inner ear. Endolymphatic sac drainage with intraendolymphatic sac application of large doses of steroids could control vertigo/dizziness and decrease the endolymphatic hydrops. These results indicate that endolymphatic sac drainage is a good treatment option for patients with intractable Meniere's disease. In addition, volumetric measurement of inner ear volume could be useful for confirming the effect of treatments on Meniere's disease.


A Case of Kimura Disease with a Bulky Preauricular Mass

耳前部に巨大な腫瘤を形成した木村病例

Kimura disease, or eosinophilic granuloma of the soft tissue, is a chronic inflammatory granuloma arising from the subcutaneous soft tissues or lymph nodes of the head and neck. We report the case of a 51-year-old male patient with Kimura disease who presented with a bulky left preauricular mass. The peripheral blood eosinophil count and serum levels of IgE and antibodies against candida antigens were elevated. Contrast-enhanced MRI revealed involvement of the parotid gland, and the patient was treated by resection of the bulky mass and of the superficial lobe of the parotid gland. Histopathological examination of the resected specimen showed proliferation of the lymphoid follicles with marked eosinophilic infiltration in the lesion, and we made the diagnosis of Kimura disease. After the surgery, the peripheral blood eosinophil count as well as the serum levels of IgE and antibodies against candida antigens decreased, with no evidence of relapse for at least three years after the surgery. Our findings suggest that type I allergy to Candida albicans plays an important role in the development of Kimura disease.


Effect of Surgical Training Using a Virtual Reality Temporal Bone Simulator in Medical Education

医学教育におけるバーチャルリアリティーを用いた側頭骨手術シミュレーション実習の効果

 To estimate the effects of a virtual reality temporal bone simulator in medical education.

 Two hundred and thirty-five medical students undergoing bedside learning were recruited in this study for two years. The same instructor provided the training during the first year, while several instructors provided the training, based on a guidance manual, during the second year. We examined the students' knowledge of anatomy of the temporal bone and administered a questionnaire to determine their comprehension of surgical procedures involving the temporal bone after the training as compared to the level of understanding before the training.

 The percentage of correct answers in the examination of anatomical knowledge about the temporal bone after the simulation in the first and second year improved from 51.8% to 83.9% and 49.4% to 80.0%, respectively. The percentages of medical students who responded with "well understood" or "I think I understood" to questions in the questionnaire on comprehension of surgical procedures involving the temporal bone in the first and second year were 84.3% and 76.4% for mastoidectomy, 74.8% and 66.4% for tympanotomy and 67.8% and 52.3% for cochleostomy, respectively. The anatomical and surgical comprehension levels, except for the case of cochleostomy, did not differ between students who received instructions from several instructors and those who received from the same instructor in this study. The training using a virtual reality temporal bone simulator was useful to improve the students' anatomical knowledge about the temporal bone and their comprehension of surgical procedures involving the temporal bone, and to unify the training content, regardless of the instructor because of standardization and customization of the surgical procedure. Thus, the training using a virtual reality temporal bone simulator is one of the most effective tools of medical education for both medical students and instructors.


Short-term pre-operative systemic administration with low-dose of steroid does not make a false-negative diagnosis of definite eosinophilic chronic rhinosinusitis after endoscopic sinus surgery.

According to JESREC criteria, definite eosinophilic chronic rhinosinusitis (ECRS) is postoperatively diagnosed based on over 70 eosinophils in high power magnification fields of the resected nasal polyps in patients with probable ECRS. Preoperative systemic administration with steroid is a standard practice, because it reduced intraoperative bleeding during endoscopic sinus surgery (ESS) in patients with ECRS. However, it was recently reported that systemic administration with steroid decreased the number of eosinophils in the nasal polyps, leading to a false negative diagnosis of definite ECRS. To overcome the risk, we have adopted short-term pre-operative systemic administration with low-dose of steroid and examined if our steroid administration makes a false-negative diagnosis. We performed a retrospective chart review of 42 patients with probable ECRS. Eleven patients were administered with 0.5 mg of bethametasone for 7 days before ESS, and other 31 patients were not administered. The average number of eosinophils in nasal polyps in patients who were administered with steroid was 188 ± 167, which was not different from 199 ± 149 in the patients who were not administered. These findings suggest that short-term preoperative administration with low-dose of steroid has few risk of a false-negative diagnosis of definite ECRS. J. Med. Invest. 66 : 233-236, August, 2019.

The Journal of Medical Investigation : JMI


Recovery of positional nystagmus after benign paroxysmal positional vertigo fatigue.

A second Dix-Hallpike test should be performed at least 30 min after the first.

European Archives of Oto-Rhino-Laryngology


Effects of irradiation with narrowband-ultraviolet B on up-regulation of histamine H1 receptor mRNA and induction of apoptosis in HeLa cells and nasal mucosa of rats.

once a day for three days suppressed TDI-induced sneezes and up-regulation of H1R mRNA in nasal mucosa without induction of apoptosis. These findings suggest that repeated intranasal irradiation with low dose of NB-UVB could be clinically used as phototherapy of AR.

, irradiation with 310 nm NB-UVB induced apoptosis. Western blot analysis showed that the suppressive effect of NB-UVB irradiation on H1R gene expression was through the inhibition of ERK phosphorylation. In TDI-sensitized rat, intranasal irradiation with 310 nm NB-UVB at an estimated dose of 100 mJ/cm


Dysgeusia during cancer treatment and dietary intervention

第38回徳島医学会賞受賞論文 がん治療中の味覚変化と食事介入の取り組み

For patients with cancer, malnutrition is one of the most serious problems. Cancer treatments, such as chemotherapy and radiotherapy, are effective for metastasis and tumor reduction as adjuvant therapy at the perioperative stage, in addition to prolonging the life of a patient and providing a radical cure. On the other hand, loss of appetite that is induced by the above treatment sometimes worsens the nutritional health of a patient. Therefore, it confers prolonged hospitalization and a delay in additional chemotherapy or surgery. Moreover, other side effects besides the loss of appetite due to chemoradiotherapy(hair loss, nausea, vomiting, and diarrhea, among others)can lead to worse nutritional health. Among these side effects, taste disorder is a major factor of decreasing meal intake and is a severe problem occurring frequently during treatment. However, its fundamental reasons, remedial measures, and treatments have not been established yet. In this article, we will report the previous basic research and clinical problems of dysgeusia that occurs during cancer treatment, and introduce a nutritional approach to preventing or improving dysgeusia.


Electroneurography in the acute stage of facial palsy as a predictive factor for the development of facial synkinesis sequela.

The value of ENoG 10-14days after the onset of facial palsy is a predictive factor for the development of facial synkinesis 12 months later. Since facial palsy patients with a ENoG value inferior to 46.5% have a high risk of developing synkinesis, they should receive the facial biofeedback rehabilitation with a mirror as a preventive therapy.


Effects of FM system fitted into normal hearing ear on speech-in-noise recognition in Japanese school-aged children with unilateral severe-to-profound hearing loss

We examined speech recognition ability of elementary school-aged Japanese children with unilateral hearing loss under noisy environments and then examined the effects of the FM system fitted into their normal hearing ear on their speech recognition ability. Twelve children with severe-to-profound sensorineural hearing loss and ten age-matched children with bilateral normal hearing received speech recognition test in quiet and noisy environments. Other nine children with severe-to-profound sensorineural hearing loss received speech recognition test with or without the FM receiver fitted to the normal hearing ear in quiet and noisy environments. Signal-to-noise ratio (SNR) in Japanese elementary school classrooms was estimated to be -6.9 dB at a preferential seat. In noisy environment of -5 dB SNR similar to working classrooms, the correct rates of speech recognition test in children with unilateral hearing loss were significantly lower, compared with those in children with bilateral normal hearing. In the noisy environment, the correct rates in children aided by the FM system with unilateral hearing loss were significantly better, compared with unaided ones. The results suggested that the FM system is recommended as an audiological management for improvement of speech recognition of children with unilateral hearing loss in noisy classrooms. J. Med. Invest. 65:216-220, August, 2018.


Visual Target Strategies in Infantile Nystagmus Patients With Horizontal Jerk Waveform.

The aim of this study was to propose a new pathophysiological hypothesis for involuntary eye oscillation in infantile nystagmus (IN): patients with IN exhibit impaired gaze fixation, horizontal smooth pursuit and optokinetic nystagmus (OKN) and use saccadic eye movements for these underlying impairments. In order to induce saccades, they make enough angle between gaze and target by precedent exponential slow eye movements. IN consists of the alternate appearance of the saccade and the slow eye movements. Unlike most previous theories, IN is therefore considered a necessary strategy allowing for better vision and not an obstacle to clear vision. In five patients with IN, eye movements were analyzed during the smooth pursuit test, saccadic eye movement test, OKN test and vestibulo-ocular reflex (VOR) test. Their gaze fixation, horizontal smooth pursuit, OKN and the last half of the slow phase of VOR were impaired. The lines obtained by connection of the end eye positions of fast phase of nystagmus coincided with the trajectories of targets. The findings indicate that patients followed the target by the fast but not the slow phase of nystagmus, which supports our hypothesis. By setting the direction of slow phase of nystagmus opposite to the direction of the OKN stimulation, enough angle can be effectively made between the gaze and target for the induction of saccade. This is the mechanism of reversed OKN response. In darkness and when eyes are closed, IN weakens because there is no visual target and neither the saccade for catching up the target or slow phase for induction of the saccade is needed.


Ramsay Hunt Syndrome during Anti-Retroviral Therapy in an HIV-Seropositive Patient

治療中にハント症候群を発症したHIV感染症例

We report the case of an HIV-seropositive patient with Ramsay Hunt syndrome. A 55-year-old bisexual man diagnosed as being HIV-seropositive was started on anti-retroviral therapy (ART), because his CD4+T cell count had decreased to under 200/μL over a period of 2 months. A week after the start of ART, he was diagnosed as having Ramsay Hunt syndrome, based on the presence of herpes zoster oticus and a positive serological test for VZV antibody. We speculate that the facial palsy was associated with the immune reconstitution inflammatory syndrome (IRIS), as follows. The decrease of the CD4+T cell count induced reactivation of VZV in the geniculate ganglion, but facial palsy did not develop. With the reconstitution of the immune system associated with increase of the CD4+T cell count by the ART, the reactivated VZV in the geniculate ganglion elicited an inflammatory response; the associated release of cytokines caused injury to the facial nerve.


Receptor and Interleukin-9 Gene Expressions Responsible for the Pathogenesis of the Allergic Rhinitis.

phosphorylation of PKCδ in HeLa cells. In RBL-2H3 cells, RJ and BGPP also suppressed NFAT-mediated IL-9 gene expression. These results suggest that RJ and BGPP improve allergic symptoms by suppressing PKCδ and NFAT signaling pathways, two important signal pathways for the AR pathogenesis, and suggest that RJ and BGPP could be good therapeutics against AR.


Effect of wild grape on the signaling of histamine H1 receptor gene expression responsible for the pathogenesis of allergic rhinitis.

receptor (H1R) and IL-9 gene expressions, respectively, are responsible for the pathogenesis of allergic rhinitis. We explore anti-allergic compounds that suppress these signaling pathways and found that wild grape (WG) contains such compounds. Here, we investigated the effect of WG hot water extract (WGE) on the signaling pathways for PKCδ-mediated H1R and NFAT-mediated IL-9 gene expressions. WGE suppressed histamine/PMA-induced H1R gene up-regulation in HeLa cells. Toluene-2,4-diisocyanate (TDI)-induced H1R mRNA elevation in TDI-sensitized rats was also suppressed by WGE treatment. Treatment with WGE in combination with Awa-tea, suppresses NFAT signaling-mediated IL-9 gene, markedly alleviated nasal symptoms. Furthermore, WGE suppressed PMA-induced IL-33 gene up-regulation in Swiss 3T3 cells. Data suggest that combination of WGE, suppresses PKCδ signaling with Awa-tea, suppresses NFAT signaling would have distinct clinical and therapeutic advantages as a substitute for anti-allergic drugs. In addition, as the expression level of IL-33 mRNA was correlated with the blood eosinophils number in patients with pollinosis, WG could alleviate eosinophilic inflammation through the suppression of IL-33 gene expression. J. Med. Invest. 65:242-250, August, 2018.

The Journal of Medical Investigation : JMI


Longitudinal up-regulation of endolymphatic hydrops in patients with Meniere's disease during medical treatment

Meniere's disease (MD) is a common inner ear disease characterized by repeated episodic vertigo, fluctuating sensorineural hearing loss, and tinnitus. Its pathology is defined as endolymphatic hydrops (EH) in the inner ear and EH has been hypothesized to correlate with the clinical symptoms of MD. We presented the dynamics of in vivo EH in MD patients during medical treatments. Prospective, single-arm repeated measures. Eleven MD patients were enrolled. All subjects prospectively underwent gadolinium-enhanced inner ear magnetic resonance (MR) imaging and neuro-otological testing before and after medical treatment. The volume of EH was quantitatively evaluated by processing MR images. All MD patients were administered continuous medication and followed up for more than 12 months. The frequency of vertigo episodes decreased in all patients and vestibular function decreased to 13-91% of the pre-treatment level. The volume ratio of post-treatment EH-to-pre-treatment EH ranged from 1.01-3.22. The total volume of pre-treatment EH was significantly correlated with cochlear symptom disease duration and the affected ear's hearing level. EH in MD patients developed longitudinally with deterioration of inner ear function during medical treatment. The natural course of MD may progress with development of EH at least for a certain period. 2b.


Aural stimulation with capsaicin ointment improved swallowing function in elderly patients with dysphagia: a randomized, placebo-controlled, double-blind, comparative study.

The aim of this study was to assess whether aural stimulation with ointment containing capsaicin improves swallowing function in elderly patients with dysphagia. A randomized, placebo-controlled, double-blind, comparative study. Secondary hospital. Twenty elderly dysphagic patients with a history of cerebrovascular disorder or Parkinson's disease were randomly divided into two groups: 10 receiving aural stimulation with 0.025% capsaicin ointment and 10 stimulated with placebo. The ointments were applied to the external auditory canal with a cotton swab. Then, swallowing of a bolus of blue-dyed water was recorded using transnasal videoendoscopy, and the swallowing function was evaluated according to both endoscopic swallowing scoring and Sensory-Motor-Reflex-Clearance (SMRC) scale. The sum of endoscopic swallowing scores was significantly decreased 30 and 60 min after a single administration in patients treated with capsaicin, but not with placebo. Reflex score, but not Sensory, Motion and Clearance scores, of the SMRC scale was significantly increased 5, 30 and 60 min after single administration in patients treated with capsaicin, but not with placebo. No patient showed signs of adverse effects. As capsaicin is an agonist of the transient receptor potential vanilloid 1 (TRPV1), these findings suggest that improvement of the swallowing function, especially glottal closure and cough reflexes, in elderly dysphagic patients was due to TRPV1-mediated aural stimulation of vagal Arnold's nerve with capsaicin, but not with a nonspecific mechanical stimulation with a cotton swab.


Contralateral type of delayed endolymphatic hydrops may consist of two phenotypes based on a magnetic resonance imaging preliminary study

This study was performed to determine the volume distribution of EH in contralateral DEH. Five contralateral DEH patients (age range = 21-77 years) and one ipsilateral DEH patient. Visualization of in vivo EH using 3T magnetic resonance (MR) imaging was performed by intravenous administration of gadolinium. The EH volume was determined quantitatively by adding the area of EH in consecutive MR images. The total EH volume of the patients with contralateral DEH varied from 24.2 to 56.6 μL in the first ear and 20.2 to 35.7 μL in the contralateral ear. EH was dominantly developed in the first ear for Patient no. 3 and 4, and not dominantly developed in the first ear for Patient no. 1, 2, and 5. The volume distribution of endolymphatic hydrops (EH) in contralateral delayed endolymphatic hydrops (DEH) was classified into two phenotypes. This suggests that contralateral DEH may consist of two etiologies.


Hoarseness in Children and its Relation to Sports Activities:-A Cross-Sectional Study based on Speech Disorders Detected in School Health Checks of the ENT Region-

学校検診における嗄声の出現率とスポーツ活動

In the present study, we examined the relationship between prevalence of hoarseness and sports activities in 1,384 children who received health checks at their elementary or junior high schools. The prevalence of hoarseness was higher in boys (17.7%) than in girls (5.2%). At the elementary school level, boys had higher risk of hoarseness than girls. The prevalence of hoarseness in boys was high until the third grade and then turned to a decreasing trend. In girls, the prevalence of hoarseness was high until the second grade, here again followed by a decreasing trend, but at the junior high school level their rate turned high again in second and third year students. With senior elementary school boys, the prevalence of hoarseness was 21.2% with sports activities and 4.9% without sports activities, and was significantly higher than the corresponding 5.8% with sports and 0.6% without sports in senior elementary school girls. In junior elementary school boys, baseball was accompanied by a significantly high risk of hoarseness (odds ratio: 2.88), while in senior elementary school boys, playing baseball (odds ratio: 2.92) or soccer (odds ratio: 2.29) brought significant high risk of hoarseness. These results suggest that outdoor team sports associated with strong glottal closure at kicking, batting or vocalizing, such as baseball and soccer, lead to the development of hoarseness in elementary school boys. We concluded that voice hygiene education is needed for boys who play baseball or soccer to prevent the development of hoarseness.

小中学校の耳鼻咽喉科定期健康診断を受診した1384名について，嗄声の出現率とスポーツ活動との関連を検討した．嗄声の出現率は，女児(5.2%)に比べて男児(17.7%)が高く，男児は小学校3年生まで高く4年生以降に減少し，女児は小学校2年生まで高く以降減少したが中学校2，3年生では高かった．小学校の高学年ではスポーツ活動を行っていない児童(男児4.9%，女児0.6%)に比べて，スポーツ活動を行っている児童(男児21.2%，女児5.8%)は嗄声の出現率が有意に高かった．スポーツの種類と嗄声とのオッズ比は，男児の小学校低学年の野球が2.88，小学校高学年でサッカー2.29，野球2.92で高く，強い声門閉鎖を伴う屋外の団体スポーツであることが要因と考えられた．小学校の男児に野球やサッカーを行わせる場合には，声の衛生を行い嗄声の予防が必要である．中学生は，対象者を増やして再検討が必要である．

The Japan Journal of Logopedics and Phoniatrics


Three-dimensional analysis of linear vestibulo-ocular reflex in humans during eccentric rotation while facing downwards.

When participants undergo eccentric rotation (ER), i.e., they are rotated while displaced from the axis of rotation, they undergo both rotational stimulation and linear acceleration, which induces both the angular vestibulo-ocular reflex (aVOR) and linear VOR (lVOR). During ER, the lVOR induced by tangential linear acceleration enhances the eye movement induced by aVOR. In this study, we attempted to measure aVOR and lVOR separately, while participants underwent ER while facing the ground in a dark room. We analyzed three-dimensional eye movements using a video-oculography system. The participants sat on the ER chair either directly above the center of rotation, or with their head out, head in, right ear out, or left ear out against the center of rotation. Under these conditions, the rotational axis of the eye was perpendicular to the ground for rotational stimulation (aVOR), and the axis was parallel to the ground for linear stimulation (lVOR). Thus, measured eye movements could be separated into these two components. At 0.1 and 0.3 Hz rotation, we observed aVOR but not lVOR. However, when the stimulation frequency was above 0.5 Hz, we observed both aVOR and lVOR. These data indicate that lVOR is activated when the stimulation frequency is above 0.5 Hz. We conclude that it is possible to separately analyze aVOR and lVOR, and to simultaneously assess the function of aVOR and lVOR by analyzing eye movements induced when participants undergo ER above 0.5 Hz while facing the ground.


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

As a canalith repositioning procedure effectively treats H-BPPV with TGPN, but not PGPN, the differentiation between patients with PGPN and with TGPN is essential. The purpose of this study is to determine the observation period enough to distinguish TGPN from PGPN.

The sensitivity and specificity to distinguish TGPN from PGPN was 100% and 97% after 30 s observation, but 100% and 40% after 10 s observation, respectively.


Three Cases of Facial Palsy Following Herpes Zoster in the Face and Neck Region

顔面や頸部に帯状疱疹を伴った顔面神経麻痺の3例

Herein, we report three cases diagnosed as having facial palsy concomitantly with herpes zoster in the head and neck region. Case 1 presented with Ramsay Hunt syndrome, and was concomitantly diagnosed as having herpes zoster in the neck skin innervated by the ipsilateral C3 nerve. Case 2 showed facial palsy and herpes zoster in the cheek skin innervated by the ipsilateral 2nd and 3rd branches of the trigeminal nerve. Case 3 showed facial palsy and herpes zoster in the cheek skin innervated by the contralateral 2nd branch of the trigeminal nerve. We treated all three cases using methylprednisolone and aciclovir (or valaciclovir), and both the facial palsy and herpes zoster resolved within four months.

We speculated that in cases 1 and 2, the varicella zoster virus (VZV) that was reactivated in the geniculate ganglion or the trigeminal ganglion was transmitted to other ipsilateral nerves via neural anastomosis. In case 3, we propose two possible mechanisms. The first is that VZV was reactivated in the geniculate ganglion and contralateral trigeminal ganglion simultaneously, although this patient developed neither herpes zoster in the auricle nor complained of hearing loss or vertigo. The second is that herpes simplex virus (HSV) was reactivated in the geniculate ganglion and VZV was reactivated in the contralateral trigeminal ganglion simultaneously.


Classification, diagnostic criteria and management of benign paroxysmal positional vertigo

Benign paroxysmal positional vertigo (BPPV) is the most common peripheral vertigo and the posterior and/or lateral semicircular canals are usually affected. BPPV is characterized by brief attacks of rotatory vertigo associated with positional and/or positioning nystagmus, which are elicited by specific head positions or changes in head position relative to gravity. In patients with the posterior-canal-type of BPPV, torsional nystagmus is induced by the Dix-Hallpike maneuver. In patients with the lateral-canal-type of BPPV, horizontal geotropic or apogeotropic nystagmus is induced by the supine roll test. The pathophysiology of BPPV is canalolithiasis comprising free-floating otoconial debris within the endolymph of a semicircular canal, or cupulolithiasis comprising otoconial debris adherent to the cupula. The observation of positional and/or positioning nystagmus is essential for the diagnosis of BPPV. BPPV is treated with the canalith repositioning procedure (CRP). Through a series of head position changes, the CRP moves otoconial debris from the affected semicircular canal to the utricle. In this review, we provide the classification, diagnostic criteria, and examinations for the diagnosis, and specific and non-specific treatments of BPPV in accordance with the Japanese practical guidelines on BPPV published by the Japan Society for Equilibrium Research.


Complementary and alternative medicine for allergic rhinitis in Japan.

Many patients who receive CAM report feeling that the effects of treatment provided by hospitals are insufficient and have concerns about the side effects of such treatments. Information regarding standard treatments, as described in the guidelines, should become widely known and diffused, and strong communication with patients should be considered.


Assessment of endolymphatic hydrops and otolith function in patients with Ménière's disease.

Ménière's disease is associated with hydrops of the inner ear endolymphatic space, and histopathologically, the cochlea and vestibule are usually involved. We used gadolinium-enhanced magnetic resonance imaging and measured cervical and ocular vestibular evoked myogenic potentials and the gain in the utricular induced linear vestibulo-ocular reflex to test the hypothesis that vestibular hydrops in Ménière's disease patients is associated with otolith organ dysfunction. We evaluated 21 patients diagnosed with unilateral definitive Ménière's disease using gadolinium magnetic resonance imaging to detect endolymphatic hydrops in the cochlea and vestibule. Cervical and ocular vestibular evoked myogenic potentials and the gain in utricular induced linear vestibulo-ocular reflex during eccentric rotation were measured to assess otolith organ function. For eccentric rotation, patients were rotated while displaced from the axis of rotation, while linear acceleration stimulated the utricle and induced the vestibulo-ocular reflex. Magnetic resonance imaging revealed vestibular hydrops in 14 of 20 patients (70%). Among the 14 patients, ten (71%) had abnormal cervical and three (21%) had abnormal ocular vestibular evoked myogenic potentials. Four patients (4/21, 19%) had abnormal linear vestibulo-ocular reflexes, three of whom also had abnormal ocular vestibular evoked myogenic potentials. Overall, 16 of 17 patients had normal linear vestibulo-ocular reflexes and normal ocular vestibular evoked myogenic potentials. Vestibular endolymphatic hydrops in Ménière's disease patients caused otolith organ dysfunction, mainly in the saccule. The number of Ménière's disease patients with abnormal ocular vestibular evoked myogenic potentials was low (19%), and they also had abnormal utricular induced linear vestibulo-ocular reflexes.

European Archives of Oto-Rhino-Laryngology


Efficacy of proton pump inhibitor in combination with rikkunshito in patients complaining of globus pharyngeus

Globus pharyngeus (GP) is a common symptom of laryngopharyngeal reflux disease (LPRD), and proton pump inhibitor (PPI) and rikkunshito, a traditional Japanese medicine having prokinetic effect improve LPRD symptoms. In the present study, we examined the efficacy of high-dose PPI in combination with rikkunshito in patients complaining of GP. 106 patients complaining of GP without any organic endoscopic findings were enrolled. Patients were first administrated with high-dose PPI alone for 4 to 8 weeks and the symptom was improved in 65 patients. Among 41 patients with PPI-refractory GP, 22 patients were administrated with high-dose PPI in combination with rikkunshito, and the symptom was improved in 14 of 22 patients 4 weeks later. The average value of a modified reflux symptom index of the responders was similar to that of non-responders. Only a few patients had positive values in reflux finding scores in both groups. The present findings suggest the existence of a high prevalence of LPRD in patients complaining of GP. The data also suggest that gastroesophageal dysmotility is involved in GP, in addition to excessive acid reflux. The pre-therapeutic laryngopharyngeal symptoms and endoscopic findings could not predict the efficacy of the treatment for GP. J. Med. Invest. 63: 227-229, August, 2016.

The Journal of Medical Investigation : JMI


Effects of repeated snowboard exercise in virtual reality with time lags of visual scene behind body rotation on head stability and subjective slalom run performance in healthy young subjects

After repeated snowboard exercises in the virtual reality (VR) world with increasing time lags in trials 3-8, it is suggested that the adaptation to repeated visual-vestibulosomatosensory conflict in the VR world improved dynamic posture control and motor performance in the real world without the development of motion sickness. The VR technology was used and the effects of repeated snowboard exercise examined in the VR world with time lags between visual scene and body rotation on the head stability and slalom run performance during exercise in healthy subjects. Forty-two healthy young subjects participated in the study. After trials 1 and 2 of snowboard exercise in the VR world without time lag, trials 3-8 were conducted with 0.1, 0.2, 0.3, 0.4, 0.5, and 0.6 s time lags of the visual scene that the computer creates behind board rotation, respectively. Finally, trial 9 was conducted without time lag. Head linear accelerations and subjective slalom run performance were evaluated. The standard deviations of head linear accelerations in inter-aural direction were significantly increased in trial 8, with a time lag of 0.6 s, but significantly decreased in trial 9 without a time lag, compared with those in trial 2 without a time lag. The subjective scores of slalom run performance were significantly decreased in trial 8, with a time lag of 0.6 s, but significantly increased in trial 9 without a time lag, compared with those in trial 2 without a time lag. Motion sickness was not induced in any subjects.


A Case of Subacute Pharyngo-laryngeal Swelling after Accidental Ingestion of Dimethylammonium Chloride

界面活性剤の誤飲により亜急性に生じた咽喉頭粘膜腫脹例

An 88-year-old woman put dodecyl dimethylammonium chloride (quaternary ammonium salt) in her mouth by accident. She spat it out immediately without swallowing, but thereafter, she developed severe oral pain. Twelve hours later, she also developed dyspnea and visited our hospital. At that time, laryngoscopy revealed severe pharyngo-laryngeal swelling with erosion of the oro-pharyngo-laryngeal mucosa. Emergent tracheotomy was performed. After two weeks, a repeat laryngoscopy revealed improvement of the pharyngo-laryngeal swelling. The patient eventually recovered completely without any complications. We report the progression of the pharyngo-laryngeal swelling as examined by laryngoscopy.


A Case of Foreign Body in the Ethmoid Sinus Diagnosed Nine Years after the Dental Implant Surgery

インプラント治療9年後に発覚した篩骨洞異物例

Dental implant surgery is carried out in edentulous patients to fix the denture on the foundation of a dental implant body embedded in the maxilla. This procedure has become popular over the last 20 years, and one of the complications is the intrusion of the dental implant body into the paranasal sinuses.
Herein, we report the case of a 64-year-old man in whom a dental implant body was found in the ethmoid sinus nine years after the dental implant surgery. The patient complained of discomfort in the right cheek and ipsilateral purulent rhinorrhea. CT revealed a shadow extending from the maxillary sinus to the ethmoid sinus on the right side, representing the dental implant body in the right ethmoid sinus. It is believed that the dental implant body which was fixed on the maxilla had intruded into the maxillary sinus and remained there for a long period, and then advanced into the ethmoid sinus due to chronic sinusitis. Finally, the dental implant body was removed by endoscopic sinus surgery.
It is thought that dental implant interventions will increase in the future, and ENT surgeons need to increase their awareness to prevent complications related to these interventions.


Irradiation with narrowband-ultraviolet B suppresses phorbol ester-induced up-regulation of H1 receptor mRNA in HeLa cells

Conclusion These findings suggest that low dose irradiation with 310 nm NB-UVB specifically suppressed the up-regulation of H1R gene expression without inducing apoptosis and that UVB of shorter or longer wavelength than 310 nm NB-UVB had no such effects. Objective To develop a narrowband-ultraviolet B(NB-UVB) phototherapy for allergic rhinitis, this study investigated the effects of irradiation with NB-UVB at wavelength of 310 nm on phorbol-12-myristate-13-acetate (PMA)-induced up-regulation of histamine H1 receptor (H1R) mRNA in HeLa cells. Methods The mRNA levels of H1R in HeLa cells were measured using real-time RT-PCR. Apoptosis were evaluated with DNA fragmentation assay. Results PMA induced a significant increase in H1R mRNA expression in HeLa cells. Irradiation with 305 nm UVB and 310 nm NB-UVB, but not with 315 nm UVB at doses of 200 and 300 mJ/cm(2) significantly suppressed PMA-induced up-regulation of H1R mRNA. At a dose of 200 mJ/cm(2), irradiation with 305 nm UVB, but not with 310 nm NB-UVB, induced apoptosis, although exposure of the cells to both 305 and 310 nm UVB induced apoptosis at a dose of 300 mJ/cm(2) after PMA treatment in HeLa cells. Conversely, irradiation with 315 nm UVB at doses of 200 and 300 mJ/cm(2) did not induce apoptosis.


High-Speed Video-Oculography for Measuring Three-Dimensional Rotation Vectors of Eye Movements in Mice.

To the best of our knowledge, this is the first report of this algorithm being used to calculate a 3D rotation vector of eye movement in mice using high-speed VOG. We developed a technique for analyzing the 3D rotation vector of eye movements in mice with a high-speed infrared CCD camera. We concluded that the technique is suitable for analyzing eye movements in mice. We also include a C++ source code that can calculate the 3D rotation vectors of the eye position from two-dimensional coordinates of the pupil and the iris freckle in the image to this article.


A Case of Laryngeal Chondroma in the Bilateral Laminae of the Thyroid Cartilage

甲状軟骨両翼に生じた喉頭軟骨腫例

An 80-year-old male patient with multiple laryngeal chondromas is reported. Bilateral thyroid cartilage masses were identified incidentally on CT. The masses remained constant in size over a two-year follow-up period, however, pharyngolaryngeal endoscopy at the end of two years showed submucosal swelling of the false folds of the larynx. A mass lesion measuring 15 mm in diameter in the right lamina of the thyroid cartilage was surgically resected by the cervical approach under local anesthesia. Histopathological examination showed mild proliferation of chondrocytes without nuclear atypia in a hyaline cartilage matrix, based on which the diagnosis of laryngeal chondroma was made. Another mass measuring 7 mm in diameter found in the left lamina of the thyroid cartilage was left unresected and will be followed up.


Antihistamines suppress upregulation of histidine decarboxylase gene expression with potencies different from their binding affinities for histamine H1 receptor in toluene 2,4-diisocyanate-sensitized rats.

Antihistamines inhibit histamine signaling by blocking histamine H1 receptor (H1R) or suppressing H1R signaling as inverse agonists. The H1R gene is upregulated in patients with pollinosis, and its expression level is correlated with the severity of nasal symptoms. Here, we show that antihistamine suppressed upregulation of histidine decarboxylase (HDC) mRNA expression in patients with pollinosis, and its expression level was correlated with that of H1R mRNA. Certain antihistamines, including mepyramine and diphenhydramine, suppress toluene-2,4-diisocyanate (TDI)-induced upregulation of HDC gene expression and increase HDC activity in TDI-sensitized rats. However, d-chlorpheniramine did not demonstrate any effect. The potencies of antihistamine suppressive effects on HDC mRNA elevation were different from their H1R receptor binding affinities. In TDI-sensitized rats, the potencies of antihistamine inhibitory effects on sneezing in the early phase were related to H1R binding. In contrast, the potencies of their inhibitory effects on sneezing in the late phase were correlated with those of suppressive effects on HDC mRNA elevation. Data suggest that in addition to the antihistaminic and inverse agonistic activities, certain antihistamines possess additional properties unrelated to receptor binding and alleviate nasal symptoms in the late phase by inhibiting synthesis and release of histamine by suppressing HDC gene transcription.


Suplatast tosilate alleviates nasal symptoms through the suppression of nuclear factor of activated T-cells-mediated IL-9 gene expression in toluene-2,4-diisocyanate-sensitized rats.

Histamine H1 receptor (H1R) gene is upregulated in patients with pollinosis; its expression level is highly correlated with the nasal symptom severity. Antihistamines are widely used as allergy treatments because they inhibit histamine signaling by blocking H1R or suppressing H1R signaling as inverse agonists. However, long-term treatment with antihistamines does not completely resolve toluene-2,4-diisocyanate (TDI)-induced nasal symptoms, although it can decrease H1R gene expression to the basal level, suggesting additional signaling is responsible for the pathogenesis of the allergic symptoms. Here, we show that treatment with suplatast tosilate in combination with antihistamines markedly alleviates nasal symptoms in TDI-sensitized rats. Suplatast suppressed TDI-induced upregulation of IL-9 gene expression. Suplatast also suppressed ionomycin/phorbol-12-myristate-13-acetate-induced upregulation of IL-2 gene expression in Jurkat cells, in which calcineurin (CN)/nuclear factor of activated T-cells (NFAT) signaling is known to be involved. Immunoblot analysis demonstrated that suplatast inhibited binding of NFAT to DNA. Furthermore, suplatast suppressed ionomycin-induced IL-9 mRNA upregulation in RBL-2H3 cells, in which CN/NFAT signaling is also involved. These data suggest that suplatast suppressed NFAT-mediated IL-9 gene expression in TDI-sensitized rats and this might be the underlying mechanism of the therapeutic effects of combined therapy of suplatast with antihistamine.


A novel benzofuran, 4-methoxybenzofuran-5-carboxamide, from Tephrosia purpurea suppressed histamine H1 receptor gene expression through a protein kinase C--dependent signaling pathway.

Histamine H1 receptor (H1R) gene is upregulated in patients with allergic rhinitis (AR), and its expression level is strongly correlated with the severity of allergic symptoms. We previously reported isolation of the putative anti-allergic compound, 4-methoxybenzofuran-5-carboxamide (MBCA) from Tephrosia purpurea and its chemical synthesis (Shill et al., Bioorg Med Chem 2015;23:6869-6874). However, the mechanism underlying its anti-allergic activity remains to be elucidated. Here, we report the mechanism of MBCA on phorbol 12-myristate-13-acetate (PMA)- or histamine-induced upregulation of H1R gene expression in HeLa cells, and in vivo effects of MBCA were also determined in toluene-2,4-diisocyanate (TDI)-sensitized rats. MBCA suppressed PMA- and histamine-induced upregulation of H1R expression at both mRNA and protein levels and inhibited PMA-induced phosphorylation of PKCδ at Tyr(311) and subsequent translocation to the Golgi. Furthermore, MBCA ameliorated allergic symptoms and suppressed the elevation of H1R and helper T cell type 2 (Th2) cytokine mRNAs in TDI-sensitized rats. Data suggest that MBCA alleviates nasal symptoms in TDI-sensitized rats through the inhibition of H1R and Th2 cytokine gene expression. The mechanism of its H1R gene suppression underlies the inhibition of PKCδ activation.


[Aural Stimulation with Capsaicin Ointment Improved the Swallowing Function in Patients with Dysphagia: Evaluation by the SMRC Scale].

外耳道へのカプサイシン軟膏刺激による嚥下障害患者の嚥下機能の改善 SMRCスケールを用いた評価

Cough and swallowing reflexes are important airway-protective mechanisms against aspiration. Angiotensin-converting enzyme (ACE) inhibitors, one of the side effects of which is cough, have been reported to reduce the incidence of aspiration pneumonia in hypertensive patients with stroke. ACE inhibitors have also been reported to improve the swallowing function in post-stroke patients. On the other hand, stimulation of the Arnold nerve, the auricular branch of the vagus, triggers the cough reflex (Arnold's ear-cough reflex). Capsaicin, an agonist of Transient Receptor Potential Vanilloid 1 (TRPV1), has been shown to activate the peripheral sensory C-fibers. Stimulation of the sensory branches of the vagus in the laryngotracheal mucosa with capsaicin induces the cough reflex and has been reported to improve the swallowing function in patients with dysphagia. In our previous study, we showed that aural stimulation of the Arnold nerve with 0.025% capsaicin ointment improved the swallowing function, as evaluated by the endoscopic swallowing score, in 26 patients with dysphagia. In the present study, the video images of swallowing recorded in the previous study were re-evaluated using the SMRC scale by an independent otolaryngologist who was blinded to the information about the patients and the endoscopic swallowing score. The SMRC scale is used to evaluate four aspects of the swallowing function: 1) Sensory: the initiation of the swallowing reflex as assessed by the white-out timing; 2) Motion: the ability to hold blue-dyed water in the oral cavity and induce laryngeal elevation; 3) Reflex: glottal closure and the cough reflex induced by touching the epiglottis or arytenoid with the endoscope; 4) Clearance: pharyngeal clearance of the blue-dyed water after swallowing. Accordingly, we demonstrated that a single application of capsaicin ointment to the external auditory canal of patients with dysphagia significantly improved the R, but not the S, M or C scores, and this effect lasted for 60 min. After repeated aural stimulation with the ointment for 7 days, the R score improved significantly in patients with severe dysphagia. The present findings suggest that stimulation of the Arnold's branch of the vagus in the external auditory canal with capsaicin improves the glottal closure and cough reflex in patients with dysphagia. Thus, aural stimulation with capsaicin represents a novel treatment for dysphagia. It is also suggested that repeated alternative aural stimulation with capsaicin for a week, rather than a single application, is needed to improve the swallowing function in patients with severe dysphagia. By the same mechanism as that underlying the effect of ACE inhibitors, aural stimulation with capsaicin may reduce the incidence of aspiration pneumonia in patients with dysphagia.

ACE (angiotensin converting enzyme) 阻害薬は, 副作用である咳反射の亢進により誤嚥を防止して嚥下性肺炎の罹患率を減少させ, 嚥下障害患者の嚥下機能を改善させる. 一方, 外耳道の刺激は迷走神経反射を介して咳を誘発する. また, カプサイシンは TRPV1 (transient receptor potential vanilloid 1) を活性化して知覚神経を刺激する. われわれは以前の研究で, 嚥下障害患者の外耳道へのカプサイシン軟膏刺激が, 嚥下内視鏡検査のスコア評価法により評価した嚥下機能を改善させることを報告した. 本研究では, 以前の研究の嚥下内視鏡検査ビデオ動画を, 患者情報およびスコア評価法の結果を知らない耳鼻咽喉科専門医が独立して SMRC スケールにより評価した. SMRC スケールは嚥下内視鏡検査の評価法であり, 嚥下の4つの機能である咽頭知覚 (Sensory), 嚥下運動 (Motion), 声門閉鎖反射・咳反射 (Reflex), 咽頭クリアランス (Clearance) を別々に評価する. その結果, 外耳道への0.025%カプサイシン軟膏塗布により, 26名の嚥下障害患者の嚥下機能のうち声門閉鎖反射・咳反射が有意に改善し, この効果は塗布後60分後まで持続した. 嚥下機能がより低下している患者の声門閉鎖反射・咳反射は, 外耳道へのカプサイシン軟膏の単回塗布では変化しなかったが, 1週間連日塗布により有意に改善した. この結果から, カプサイシン軟膏による外耳道刺激は, 新しい嚥下障害の治療法として用いられる可能性があり, ACE 阻害薬のように嚥下性肺炎を予防できる可能性も考えられた.


Effects of antihistamine on up-regulation of histamine H1 receptor mRNA in the nasal mucosa of patients with pollinosis induced by controlled cedar pollen challenge in an environmental exposure unit.

In the present study, we examined the effects of antihistamine on the up-regulation of H1R mRNA in the nasal mucosa of patients with pollinosis induced by controlled exposure to pollen using an environmental exposure unit. Out of 20 patients, we designated 14 responders, whose levels of H1R mRNA in the nasal mucosa were increased after the first pollen exposure and excluded 6 non-responders. Accordingly, the first exposure to pollen without treatment significantly induced both nasal symptoms and the up-regulation of H1R mRNA in the nasal mucosa of the responders. Subsequently, prophylactic administration of antihistamine prior to the second pollen exposure significantly inhibited both of the above effects in the responders. Moreover, the nasal expression of H1R mRNA before the second pollen exposure in the responders pretreated with antihistamine was significantly decreased, as compared with that before the first pollen exposure without treatment. These findings suggest that antihistamines suppressed histamine-induced transcriptional activation of H1R gene in the nasal mucosa, in addition to their blocking effect against histamine on H1R, resulting in a decrease of nasal symptoms. These findings further suggest that by their inverse agonistic activity, antihistamines suppress the basal transcription of nasal H1R in the absence of histamine in responders.


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.