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Objectives Baloxavir marboxil (formerly S-033188) is a first-in-class, orally available, cap-dependent endonuclease inhibitor licensed in Japan and the USA for the treatment of influenza virus infection. We evaluated the efficacy of delayed oral treatment with baloxavir marboxil in combination with a neuraminidase inhibitor in a mouse model of lethal influenza virus infection. Methods The inhibitory potency of baloxavir acid (the active form of baloxavir marboxil) in combination with neuraminidase inhibitors was tested in vitro. The therapeutic effects of baloxavir marboxil and oseltamivir phosphate, or combinations thereof, were evaluated in mice lethally infected with influenza virus A/PR/8/34; treatments started 96 h post-infection. Results Combinations of baloxavir acid and neuraminidase inhibitor exhibited synergistic potency against viral replication by means of inhibition of cytopathic effects in vitro. In mice, baloxavir marboxil monotherapy (15 or 50 mg/kg twice daily) significantly and dose-dependently reduced virus titre 24 h after administration and completely prevented mortality, whereas oseltamivir phosphate treatments were not as effective. In this model, a suboptimal dose of baloxavir marboxil (0.5 mg/kg twice daily) in combination with oseltamivir phosphate provided additional efficacy compared with monotherapy in terms of virus-induced mortality, elevation of cytokine/chemokine levels and pathological changes in the lung. Conclusions Baloxavir marboxil monotherapy with 96 h-delayed oral dosing achieved drastic reductions in virus titre, inflammatory response and mortality in a mouse model. Combination treatment with baloxavir acid and oseltamivir acid in vitro and baloxavir marboxil and oseltamivir phosphate in mice produced synergistic responses against influenza virus infections, suggesting that treating humans with the combination may be beneficial.

ObjectivesWe aimed to elucidate the prognostic factors of the patients with taste disorders who were treated with popular and common medication in Japan.Materials and methodsA retrospective study on the medical charts of a total of 255 patients with taste disorders who were treated primarily with oral medication including a zinc agent.ResultsThe factors below were significantly linked with poor prognosis: 1) male gender, 2) taste disorders that began 3 months before starting treatment and 3) a severe taste disorder grade at the initial visit.ConclusionsWe have concluded that the prognosis for the patients with taste disorders who were treated by popular and standard medication therapy in Japan recently was significantly linked to gender, the period of 3 months before starting the treatment and the severity of the disorder at the time of diagnosis. In addition, we recognized some limitations we should resolve in further research including a method of measuring "umami" and so on.Clinical relevanceBetter awareness of these factors should be clinically useful when we manage patients with taste disorders. Earlier treatment should be started to cure the symptoms.

Mutations in SLC26A4 cause a broad phenotypic spectrum, from typical Pendred syndrome to nonsyndromic hearing loss associated with enlarged vestibular aqueduct. Identification of these mutations is important for accurate diagnosis, proper medical management and appropriate genetic counseling and requires updated information regarding spectrum, clinical characteristics and genotype-phenotype correlations, based on a large cohort. In 100 patients with bilateral enlarged vestibular aqueduct among 1511 Japanese hearing loss probands registered in our gene bank, goiter data were available for 79, of whom 15 had Pendred syndrome and 64 had nonsyndromic hearing loss. We clarified the mutation spectrum for the SLC26A4 mutations and also summarized hearing levels, progression, fluctuation and existence of genotype-phenotype correlation. SLC26A4 mutations were identified in 82 of the 100 patients (82.0%). Of the Pendred syndrome patients, 93% (14/15) were carriers, as were 77% (49/64) of the nonsyndromic hearing loss patients. Clinical characteristics of patients with SLC26A4 mutations were congenital, fluctuating and progressive hearing loss usually associated with vertigo and/or goiter. We found no genotype-phenotype correlations, indicating that, unlike in the case of GJB2 mutations, the phenotype cannot be predicted from the genotype. Our mutation analysis confirmed the importance of mutations in the SLC26A4 gene among hearing loss patients with enlarged vestibular aqueduct and revealed the mutation spectrum, essential information when performing genetic testing.

The milkfish, Chanos chanos, is an important aquaculture resource in Southeast Asia. Using NGS data, 72 microsatellite markers were developed. PCR product confirmation using agarose gel electrophoresis allowed the identification of 24 utilizable markers. Milkfish samples (n = 48) from a hatchery stock in Palawan, Philippines were analyzed for genetic variability at the aforementioned 24 loci. Consequently, nine of these microsatellite loci were noted to have high success rate in amplification, exhibited polymorphism with 19 maximum number of alleles and no null alleles. These are the first microsatellite markers to be developed and characterized for C. chanos that will efficiently enable genetic stock delineation and monitoring as well as marker-aided genetic improvement research.

While fibromyalgia is frequently associated with ear-related symptoms such as feeling of ear fullness, earache, and tinnitus, the pathogenesis of these ear-related symptoms in fibromyalgia patients is unknown. Here, we focused on clarifying the pathogenesis of ear fullness, a particularly common symptom observed in fibromyalgia patients. Twenty patients diagnosed with fibromyalgia on outpatient psychosomatic treatment complaining of ear-related symptoms answered our questionnaire and underwent neurotological examination, including pure tone audiometry and Eustachian tube function testing. While ear-related symptoms were significantly exacerbated after onset of fibromyalgia, we noted no correlation between the presence or absence of feeling of ear fullness and abnormal findings on neurotological examination. Given our findings, we suspect that onset of ear fullness may be associated not with abnormal findings in the middle and inner ear function tests but with other causes, such as central desensitization.

Superselective intra-arterial chemotherapy, which can provide local control and laryngeal preservation, is safe and useful for preserving pharyngeal and laryngeal functions.To evaluate superselective intra-arterial chemotherapy in terms of the contribution to survival and laryngeal preservation in squamous cell carcinoma (SCC) of the anterior oropharyngeal wall.A total of 51 patients with SCC of the anterior oropharyngeal wall received intra-arterial administration of docetaxel at 60 mg/m(2) and cisplatin at 60 mg/m(2) anterogradely, followed by intravenous continuous infusion of 5-fluorouracil at 750 mg/m(2)/day over 120 h starting on day 2. Neck lymph node metastases were treated by neck dissection.The 5- and 10-year survival rates of the 51 patients were 72.8% and 66.4%, respectively. The 5-year survival rates of patients with T2, T3, T4a, and T4b cancer were 100%, 88.7%, 41.9%, and 33.3%, respectively. The 5- and 10-year laryngeal preservation rates of the 51 patients were 63.4% and 30.0%, respectively. The 5-year laryngeal preservation rates of patients with T2, T3, T4a, and T4b cancer were 100%, 75.2%, 23.6%, and 33.3%, respectively. No irreversible side effects, complications, or sequelae were reported.

Background: Allergic rhinitis is the most common allergic disease, displaying the typical nasal symptom of congestion. Prostaglandin D2 (PGD2), a chemical mediator released in large amounts by mast cells upon allergic stimulation in humans, is known to be involved in nasal congestion. However, the mechanism by which this congestion occurs remains unclear. Methods: The effect of PGD2 on the nasal airflow in guinea pigs was measured using a noninvasive approach that avoided any anesthetic effect. Isometric tension of isolated nasal mucosa and the nasal vascular corrosion resin cast technique were used to clarify the area of nasal mucosal vessels affected by PGD2, and to examine the mechanism of PGD2-induced nasal congestion. Moreover, the involvement of second messengers in PGD2-induced mucosal relaxation was investigated. Results: PGD2 induced an increase in intranasal pressure in a guinea pig model of rhinitis. Additionally, sinusoidal microvessel dilatation appeared around the septum using the vascular corrosion resin cast technique in the nasal mucosa. Moreover, relaxation of the nasal mucosa following stimulation of the prostanoid DP-1 receptor was associated with cAMP levels in the tissue. Conclusions: PGD2-induced nasal congestion is caused by direct dilatation of the sinusoid vessels through the increase of cAMP levels in the nasal mucosa, demonstrating that the mechanism of PGD2-induced nasal congestion is different from other chemical mediators. Consequently, antagonists for the prostanoid DP-1 receptor would be an alternative approach for the relief of nasal congestion. Alternatively, the combined administration with antagonists for other mediators involved in nasal congestion may also be a valuable therapy for allergic rhinitis.

Patients who received concurrent chemoradiation therapy or radiation therapy alone were followed over a long term. The complete response (CR), 10-year survival, and 10-year larynx preservation rates were 87.5%, 95.3%, and 75.1%, respectively. Statistically, concurrent chemoradiation therapy contributes to laryngeal preservation but not to the survival rate.To determine the additive and synergistic effects of anticancer chemotherapy combined with chemoradiation therapy for squamous cell carcinoma (SCC) of the glottic larynx.Eighty-nine patients with untreated T2N0M0 SCC of the glottic larynx were included. Thirty-two patients received treatment cycles consisting of intravenous cisplatin (CDDP) on day 1 (80 mg/m(2)) and intravenous 5-fluorouracil (5-FU) over 120 h on days 2-6 (600 mg/m(2)/day) every 4 weeks. Radiotherapy was delivered by a 4 MV linac X-ray machine at a dose of 66 Gy. Fifty-seven patients received radiotherapy alone.After chemoradiation therapy, the overall response, CR, 10-year survival, and 10-year larynx preservation rates were 100%, 87.5%, 95.3%, and 75.1%, respectively. Side effects included leukopenia, neutropenia, mucositis, and dermatitis. Seven patients (21.9%) required salvage surgery. Pathological findings confirmed that the treatment regimen caused marked cancer tissue degeneration. Histologic examination of surgical specimens suggested that the safety margin for partial laryngectomy was 4 mm from the gross tumor.

Concurrent chemoradiation therapy with docetaxel (DOC) at a dose of 10 mg/m(2) twice a week contributed to laryngeal preservation.To determine laryngeal preservation following concurrent chemoradiation therapy with DOC.A total of 141 patients with untreated T2N0M0 squamous cell carcinoma of the glottic larynx were included in the study. The treatments were either radiation therapy alone or DOC intravenously administered at a dose of 10 mg/m(2) once or twice a week during radiotherapy with 4 MV linac X-ray (total of 66 Gy for 33 days).The response and CR rates were 100% and 90.5% in the once-weekly combination group, and 100% and 97.6% in the twice-weekly combination group, respectively. The 5-year survival rates were 76.8% in the once-weekly combination group and 96.8% in the twice-weekly combination group. The 5-year laryngeal preservation rates were 83.8% in the once-weekly combination group and 97.6% in the twice-weekly combination group. The most common side effects were mucositis, dermatitis, and alopecia. The patients who received DOC twice a week showed more severe cancer tissue degeneration, and pathological examination of serial sections indicated that the safety margin for partial laryngectomy was considered to be 3 mm from the gross tumor with good glottal closure.

[Purpose] The purpose of this study was to examine the relationship between lower extremity muscle mass, leg extension strength and muscle power of hemiplegic stroke patients and to examine the differences in walking independence levels (dependent and independent groups) between each variable. [Subjects] The subjects were 21 hemiplegic patients at the first onset. [Methods] The affected and unaffected thigh muscle mass (TM), lower leg muscle mass, and lower extremity muscle mass (LEM) were measured by segmental bioelectrical impedance analysis. The leg extension peak torque (LEPT) and mean power (MP) were measured using a recumbent ergometer. Values obtained by dividing the affected and unaffected LEPTs by each LEM (LEPT/LEM) and the MP by total LEM (TLEM) of the affected and unaffected lower extremities (MP/TLEM) were calculated. [Results] The affected TM was significant lower than the unaffected side. The affected and unaffected TM was significantly correlated with the LEPT of each side. The affected TM, affected and unaffected LEPT, LEPT/LEM, MP and MP/TLEM of the dependent group were significantly lower than their respective values in the independent group. [Conclusion] These results suggest that a decrease in muscle mass in hemiplegic patients decreases anaerobic exercise capacity through weaker leg extension strength or muscle power.

Vascular tumors are divided histologically into vascular lesions on the surface of the body, i.e. hemangiomas, and vascular malformations which have normal endothelial cells but manifest structurally abnormal vascular proliferation. Vascular malformations are often encountered in the head and neck region. We studied patients who underwent laryngoscopic surgery in our department for vascular malformations of the larynx.Direct laryngoscopic surgery was performed under general anesthesia. The mucosa surrounding the vascular malformation was stripped and resected. The vasa vasorum were treated with an Ho:YAG laser. We reviewed five patients who had received laryngoscopic treatment in the larynx region during the past two years.Histopathologic examination of the removed tumor tissues revealed venous malformation in four cases and lymphatic malformation in one case. The postoperative course was uneventful with neither hemorrhaging nor other complications, and none of the cases showed any recurrent disease up to the present.Our experience suggests that the laryngoscopic surgery provides minimal surgical intervention and can be applied to a wide range of age.

Objective:Only a few benign tumours of the middle ear have been reported to lead to the development of facial palsy. Here, we describe a patient with middle-ear cavernous lymphangioma and facial palsy.Study design:Single case study.Patient:A 61-year-old man presented with left-sided hearing impairment and incomplete left facial palsy. A tumour was confirmed to be occupying the epi- to mesotympanum and to be joined to the facial nerve. The tumour was removed along with facial nerve tissue, which was resected at its horizontal portion, and the remaining facial nerve was fixed by end-to-end anastomosis. Complete facial paralysis occurred after the operation, but the patient's House–Brackmann grade gradually improved to grade III. Post-operative histopathological examination revealed infiltration of the lymphangioma into the facial nerve tissue, together with mild neural atrophy of the facial nerve.Conclusion:These findings suggested that tumour invasion was the cause of facial palsy in this patient.

Growth of several genetically improved Nile tilapia (GIFT or Genetically Improved Farmed Tilapia, FaST or Freshwater Aquaculture Center Selected Tilapia, SEAFDEC-selected) and domesticated red tilapia (BFS or Binangonan Freshwater Station, NIFI-red or National Inland Fisheries Institute red, HL or Hacienda Luisita) stocks were compared in controlled (tank) and uncontrolled farm conditions (lake-based cages) with unselected NIFI or Chitralada Nile tilapia as control. Specific growth rate differed significantly (P = 0.009) in tank-reared Nile tilapia stocks where GIFT grew best at 1.358%/day followed by FaST (1.307%/day), control stock NIFI (1.257%/day) and SEAFDEC-selected (1.202%/day). Genetic effect explained 84.4% of the variance in growth of Nile tilapia in tanks. Although Nile tilapia growth in cages followed the same trend where GIFT grew best at 1.570%/day, no significant stock differences (P = 0.479) were noted. Meanwhile, red tilapia reared in either tanks or cages showed no significant stock differences in terms of growth. However, survival of the red tilapia stocks in cages differed significantly with HL having the highest percentage survival at 93.3%. The different growth responses of the Nile tilapia stocks especially under controlled (tank) farm conditions were largely due to genetic factors (stock differences).Under uncontrolled farm conditions, environmental factors were generally observed to have also affected the survival and to some extent, the growth of Asian Nile and red tilapia stocks.

Facial nerve paralysis associated with middle ear cholesteatoma, although well known, is only occasionally encountered and its clinical features and management have been evaluated in only a few studies. We studied its clinical features associated with facial paralysis. Subjects numbered 20 [15 males and 5 females] from 3-82 years old (mean: 42.6 years) with facial nerve paralysis due to middle ear cholesteatoma undergoing surgery between 1990 and 2008. After cholesteatoma lesion resection, a limited area of the fallopian canal in which facial nerve edema or redness was evident was opened, although the epineural sheath was not incised for nerve decompression. Initial paralysis was incomplete in 13 (65%). Paralysis onset was sudden in 16 (80%). The facial paralysis outcome was favorable in 14 (70%). Facial paralysis outcome was largely favorably, although poor outcomes were observed in cases with petrosal cholesteatoma and in those undergoing surgery ≥2 months after paralysis onset.

We report a rare pediatric case of congenital cholesteatoma initially manifesting as facial paralysis. A 3-year-old boy seen for acute facial palsy had developed left facial paralysis on January 4, 2008, undergoing predonisolone therapy by a local pediatrician from January 10. Upon referred on March 5, facial palsy was a severe Grade V in House-Brackman classification. Middle-ear computed tomography showed soft tissue filling the mastoid antrum through the epitympanic recess to the tympanic cavity. Endoscopic examination identified swelling of the tympanic membrane and a yellowish-white tumor of the tympanic cavity. Based on a diagnosis of congenital cholesteatoma, he underwent surgery under general anesthesia on June 27. The cholesteatoma lesion occupied the tympanic cavity, extending to the aperture of the mastoid antrum. In staged surgery, the exposed facial nerve in the tympanic cavity appeared hyperemic and adjacent to the cholesteatoma lesion. Postoperatively, facial paralysis improved incompletely remaining in Grade III in House-Brackmann classification.

We report a case of hemorrhage from brainstem cavernous angioma that caused various symptoms including neurootological, gustatory and facial sensory disturbances. A man experienced nausea and numbness of his right ear. It was confirmed that the symptom were derived not from a peripheral lesion but from retrocochlear and brainstem impairment based upon the findings of the DPOAE, ABR, VEMP, caloric test, optokinetic nystagmus etc. We detected an area of retrocochlear lesion that was responsible for both the auditory and vestibular disturbances based upon detailed neurootological examination in addition to MRI findings, and showed that the impairment was improved one year later without specific treatment.

Multiple sclerosis patients sometimes complain of vertigo as one of their symptoms. We experienced a case in which vertigo was seen as the chief complaint. MRI and neurootological examinations led to the diagnosis that the vertigo was caused by recurrent multiple sclerosis lesions of the posterior cranial fossa. We then considered five earlier multiple sclerosis patients who had vertigo. Their pure tone audiogram and caloric tests were almost normal. However, neurootological examinations ETT, OKP and gravicorder showed abnormalities. Therefore, in addition to MRI T2 and T2 FLAIR image examinations, neurootological examinations are valuable for diagnosis, especially in order to detect posterior cranial fossa lesions.

Intractable oropharyngeal mucosa disease is common and its diagnosis may be delayed if the mucosal lesion is simply a symptom of systemic disease. We report two cases of pemphigus vulgaris localized in the oropharyngeal mucosa. Case 1: A 50-year-old man showed multiple oropharyngeal erosiones and was biopsied at his first visit. The histopathological diagnosis was pemphigus vulgaris and antidesmogleinauto antibody 3 based on a blood examination positive. Case 2: A 66-year-old woman originally diagnosed histopathologically with inflamed mucosa was reconsiderd for pemphigus vulgaris and checked for antidesmogleinauto antibodies 1 and 3, both found to be positive. Based on the additional immunopathological findings of the earlier rechecked specimen, the definitive diagnosis was pemphigus vulgaris. Both cases were treated by steroids. The numerical value of antidesmogleinauto antibody gradually decreased based on the recovery from symptoms. We found antidesmogleinauto antibody blood testing to be valuable for diagnosis and for evaluating therapeutic effect and symptom progress. It is also important to check for antidesmogleinauto antibody early with such intractable oropharyngeal mucosal disease patients.

We systematically investigated the role of the top interface for TaC x and HfC x /HfO 2 gate stacks on the effective work function (Φ m,eff ) shift by inserting a SiN layer at the gate/HfO 2 top interface or HfO 2 /SiO 2 bottom interface. We found that Φ m,eff of the TaN gate electrode on HfO 2 was larger than that on SiO 2 because of the HfO 2 /SiO 2 -bottom-interface dipole. On the other hand, we found that Φ m,eff values of the TaC x and HfC x gate electrodes on HfO 2 agree with Φ m,eff on SiO 2 . This is because the potential offset of the opposite direction with respect to the bottom interface dipole appears at the metal carbide/HfO 2 interface. It is thus concluded that the top interface in the metal carbide/HfO 2 gate stacks causes the negative Φ m,eff shift.

The deterioration in the circumstances of the economy and human resources for hospitals and medical industry is now broadly recognized. We succeeded in reducing the assessed loss of the Otolaryngology Department Outpatient Clinic, which resulted in a gain of over 75% profit through the cooperation of the doctors and office staff. It was assumed that the communication and knowledge management between doctors and office staff was important. While this project was planned by a doctor, it was found that creative suggestions and ideas from office staff as professionals also had a desirable effect. It appears that the resolution of problems by establishing procedures of good communication and knowledge management leads to better quality of medical treatment and would ultimately raise awareness, resulting in a better hospital and more desirable workplace.

We report a case of Hunt syndrome with the primary complaint of lower cranial nerve paralysis. The patient experienced not only lower cranial nerve paralysis, but also, finally, paralysis of the facial nerve. The patient was a 68-year-old woman. She came to the hospital complaining of herpetic vesicles around the right ear and pain, vertigo, and hoarseness, but there was no facial palsy. Hydrocortisore sodium succinate and acyclovir were administered intravenously.Twelve days after, she developed right facial palsy. Prednisolone and Valaciclovir hydrochloride were orally administered. Fifty Four days after disease onset, the function of all cranial nerves recovered completely.A review of the Japanese literature revealed 44 cases of Hunt syndrome with multiple cranial nerve palarisis from 1954-2005. In our case, the development of right facial palsy occurred later than all other symptoms. The late-onset facial palsy was only 5 cases and rare.

A 3 M NaCl solution does not stimulate the trigeminal nerve in the human tongue. Objectives. In rats, the trigeminal nerve has been reported to respond when the tongue is stimulated by a solution with an NaCl concentration of 0.4 M or greater. We have attempted to clarify whether or not relatively high concentrations of NaCl stimulate the trigeminal nerves of the human tongue.We examined four patients whose bilateral chorda tympani nerves were resected during middle ear surgeries. We performed subjective tactile and taste tests. Next, we conducted objective examinations of the subjects' tactile and gustatory functions by magnetoencephalography (MEG).The subjective examination confirmed that all four subjects maintained normal tactile sensory functions in their tongues and that the gustatory sensation at their lingual apexes was totally abolished. Furthermore, the objective examination of the tactile function using MEG indicated that their brain responses to trigeminal nerve stimulations were normal. Further examination using MEG failed to produce brain responses to a 3 M NaCl solution in spite of their normally functioning trigeminal nerves. Therefore, we concluded that a 3 M NaCl solution does not stimulate the trigeminal nerve at the tip of the human tongue.

In most cases, pendular tonsils are benign. We report a 75-year-old man who presented with a pendular tonsil which was finally diagnosed as a squamous cell carcinoma of the tonsil. The patient was seen with the chief complaint of a foreign body in his throat. On his first visit, a smooth-surfaced pedunculated mass protruding from the lower pole of the right palatine tonsil was observed. Biopsy of the pendular lesion revealed a squamous cell carcinoma. Extended right tonsillectomy was performed. Pathological examination of the lesion revealed squamous cell carcinomas in the pendular tonsil as well as in the palatine tonsil. At present, no recurrence has been observed and his clinical course is favorable. It is necessary to perform a histological examination for every case of pendular tonsil.

Two-dimensional faceted crystal growth of silicon from undercooled melt of Si-20 mass%Ni alloy was experimentally investigated, in which a droplet sample from 10 to 100 mg was undercooled on a single-crystal sapphire and growing crystals were observed in situ. Observed crystals were classified according to the shapes of square, wedge and irregular shapes. The growth velocity was measured for different undercooling conditions. The growth velocity of square shaped crystals was about half times smaller than that of wedge shaped crystals. The growth of square shaped crystals is regarded to be two-dimensional and it is compared with the results of two-dimensional phase-field simulations. Growth velocity in both is in good agreement and the linear kinetic coefficient is estimated to be 0.002 m/sK.

The feelings of dizziness and unsteadiness of the patients with fibromyalgia supposed specifically amplified by the hypersensitivity mechanism of CSS (central sensitivity syndrome) of them. The severity of subjective pain and physical distress according to the questionnaires were not correlated with the objective body sway on the stabilometer.Fibromyalgia manifests primarily as chronic pain of the entire body, but is also often associated with a variety of physical symptoms including dizziness and unsteadiness. This study assessed whether objective measures of body sway and unsteadiness of them are associated with their subjective dizziness findings.Subjects were 24 patients diagnosed with fibromyalgia, but one patient who had the past history of sudden deafness was excluded. The 23 patients were assessed by a stabilometer as the objective measures of body sway, and JFIQ (Japanese version of the fibromyalgia impact questionnaire), DHI (dizziness handicap inventory) and ABC (activities-specific balance confidence) as the subjective questionnaires.The significant correlations were shown between the scores of JFIQ and DHI, JFIQ and ABC, and DHI and ABC. Then, the body sway index of stabilometer environmental area was significantly correlated with DHI score. However, the stabilometer index was not correlated neither with JFIQ or ABC.

Background Impaired epithelial barrier function renders the airway vulnerable to environmental triggers associated with the pathogenesis of bronchial asthma. We investigated the influence of protocadherin-1 (PCDH1), a susceptibility gene for bronchial hyperresponsiveness, on airway epithelial barrier function. Methods We applied transepithelial electric resistance and dextran permeability testing to evaluate the barrier function of cultured airway epithelial cells. We studied PCDH1 function by siRNA-mediated knockdown and analyzed nasal or bronchial tissues from 16 patients with chronic rhinosinusitis (CRS) and nine patients with bronchial asthma for PCDH1 expression. Results PCDH1 was upregulated with the development of epithelial barrier function in cultured airway epithelial cells. Immunocytochemical analysis revealed that PCDH localized to cell-cell contact sites and colocalized with E-cadherin at the apical site of airway epithelial cells. PCDH1 gene knockdown disrupted both tight and adhesion junctions. Immunohistochemical analysis revealed strong PCDH1 expression in nasal and bronchial epithelial cells; however, expression decreased in inflamed tissues sampled from patients with CRS or bronchial asthma. Dexamethasone (Dex) increased the barrier function of airway epithelial cells and increased PCDH1 expression. PCDH1 gene knockdown eradicated the effect of Dex on barrier function. Conclusion These results suggest that PCDH1 is important for airway function as a physical barrier, and its dysfunction is involved in the pathogenesis of allergic airway inflammation. We also suggest that glucocorticoids promotes epithelial barrier integrity by inducing PCDH1.

HfOxN p-channel metal–oxide–semiconductor field-effect transistors (MOSFETs) with a low threshold voltage (|Vth|) were successfully fabricated using a partially silicided (PASI) platinum gate electrode for scaled complementary MOS (CMOS). The PASI platinum (PASI-PtSi) gate electrode is composed of a monoclinic-Pt3Si phase in the vicinity of a HfOxN dielectric. The reduced silicon content of the PASI gate electrodes is effective in suppressing the Fermi-level pinning on the Hf-based gate dielectrics which induces a significant |Vth| shift in p-channel MOSFETs. It is shown that the |Vth| of HfOxN p-channel MOSFETs with the PASI-PtSi gate electrode is sufficiently low and applicable to low-standby-power devices. The mobility of the holes at 0.8 MV/cm is as high as about 90% of the universal mobility. It is concluded that the PASI technology in which the gate electrode has a reduced silicon content is useful for scaled CMOSs.

The clinical and surgical findings of this study indicated advanced cholesteatoma in many patients with facial paralysis. The outcome of facial paralysis was good. Poor outcomes were observed in cases with petrosal cholesteatoma and in those who underwent surgeryor = 2 months after the onset of paralysis.To investigate clinical features of cholesteatoma associated with facial paralysis.Sixteen patients with facial paralysis due to middle ear cholesteatoma were reviewed. After removal of the cholesteatoma lesion, a limited area of the fallopian canal, that in which facial nerve edema or redness was evident, was opened. Incision of the epineural sheath for nerve decompression was not performed.Initial paralysis was incomplete in 11 patients (69%). The onset of paralysis was sudden in 12 patients (75%). Labyrinthine fistulae (n = 9; 56%) and bone destruction in the cranial fossa (n = 10; 63%) were frequently observed. Six patients (38%) were totally deaf due to labyrinthitis. The outcome of facial paralysis was good in 13 patients (81%). Patients who underwent surgeryor = 2 months after the onset of paralysis frequently had a poor outcome. Paralysis was not improved in two cases with petrosal cholesteatoma.

Two-dimensional faceted dendrite growth of silicon from undercooled melt of Si–6 wt%Ni alloy was experimentally investigated, in which molten alloy film from 10 to 20 μm in thickness was undercooled up to 115 K and growing dendrites were observed in situ. Both the in situ observation of dendrite morphology and the EBSP crystallographic analysis for solidified samples showed that both a 〈2 1 1〉 twin dendrite and a 〈1 0 0〉 twin-free dendrite grew in the range of undercooling from 50 to 115 K. Dendrite growth velocity was also measured for different undercooling conditions. The growth velocity of 〈2 1 1〉 dendrites was slightly larger than that of 〈1 0 0〉 dendrites. It is concluded that the upper envelope of the data provide the correct dendrite growth velocity and it is compared with that obtained by phase-field simulations. Growth velocity in both follows power relationships to undercooling and the linear kinetic coefficient is estimated to be 0.01 m/s K.

Objective: To show the significance of various factors when predicting the outcome of facial nerve paralysis. Design: Retrospective chart review. Setting: Nihon University Itabashi Hospital in Tokyo. Subjects Four hundred sixty-seven patients with facial paralysis who visited the hospital within 14 days of disease onset. Methods: The failure rate of complete recovery was studied for each of these nine factors: sex, age, varicella-zoster virus (VZV) infection as the cause of paralysis, initial severity of paralysis, number of days from onset of paralysis to the beginning of medical treatment, nerve excitability test (NET), stapedial reflex, lacrimal secretion, and severity of facial paralysis 1 month after onset. These factors were analyzed by logistic regression. Results: Logistic regression clarified that age, VZV infection, NET response, loss of stapedial reflex, and the state of paralysis 1 month after the onset had statistical significance for the prognosis of facial paralysis. The poor recovery rate was greater than 50% in the patients who exhibited abnormal responses on NET or failed to attain recovery to grade III or better during the 1-month period after the onset of paralysis. These findings were therefore considered as high risk factors for the prognosis. The poor recovery rate was between 25% and 50% in patients who were 50 years or older or whose initial grading of paralysis was V or worse. These findings were classified as moderate risk factors. Patients with VZV-caused paralysis and loss of stapedial reflex had poor recovery rates of below 25%, and these were classified as low risk factors. Conclusion: It is possible to predict the prognosis of facial paralysis on the basis of several clinical findings. NET response, severe initial paralysis, age 50 years or older, and, as a second-stage factor, severity of facial paralysis 1 month after the onset were found to be especially important factors for predicting the prognosis of facial paralysis.

The authors would like to thank Ms. Adelaida L Arago, Messrs. Bienvenido Banaag and Federico Reyes for their technical assistance. The Japan Society for the Promotion of Science (JSPS) and SEAFDEC are gratefully acknowledged for funding this study.

A 58-year-old man presents with bilateral total ophthalmoplegia caused by malignant lymphoma in the cavernous sinuses. He reported right retrobulbar pain and diplopia; however, corticosteroid therapy was not effective. After admission, right total ophthalmoplegia progressed to bilateral involvement within a few days. From biopsy of the ethmoidal sinus and axillary lymph nodes, non-Hodgkin's lymphoma was diagnosed. Chemotherapy was started immediately, and non-Hodgkin's lymphoma was completely remitted within 3 months. Bilateral total ophthalmoplegia also improved; however, tonic pupils became prominent in both eyes. Paraneoplastic effects of non-Hodgkin's lymphoma may be responsible for the tonic pupils.

Facial palsy may cause excessive stress due to the obviousness of its manifestations. We evaluated psychological stress in patients with facial palsy.Subjects were 57 patients with Bell's palsy, 12 with Ramsay Hunt syndrome, and 11 with zoster sine herpete. Eighteen of 50 questions from the Psychological Stress Response Scale (PSRS) were selected and used to in a questionnaire completed by each patient on 2 separate occasions the first hospital visit and after recovery from facial palsy. They also completed a second bodily condition questionnaire before and after treatment.The psychological stress response score of patients with facial palsy was high on the first visit. Intermediate and high psychological stress were observed in 35% on the first visit. These psychological stress response score decreased after recovery from facial palsy. The psychological stress response of patients under 65 years of age in those over 65 years. No gender difference was seen in psychological stress response. Those with herpes zoster showed a higher psychological stress response than others and this decreased after recovery from facial palsy.Psychological stress response score of patients with facial palsy was high on the first hospital visit, suggesting that we must treat the psychological aspects of this manifestation by adequately explaining prognosis and pathology, in addition to physical therapy.

Objective: For clarification of the direct relationship between the reactivation of herpes simplex virus and the development of Bell's Palsy, a detection of the virus genome by deoxyribonucleic acid diagnostics and a quantitative analysis of its time-course change are both needed. The authors detected the HSV genome in specimens from patients with Bell's Palsy, quantified its number of copies, and examined time-course changes. Subjects and Methods: The subjects were 16 patients with Bell's Palsy. The tear fluid and saliva from the submandibular gland and the parotid gland were separately collected from the affected and unaffected sides twice or more. A total of 244 specimens were subjected to extraction of deoxyribonucleic acid, polymerase chain reaction, and microplate hybridization. Results: Herpes simplex virus-1 deoxyribonucleic acid was detected in 38 specimens (11.8%) from 5 patients (31%). The high detection (28.5%) was obtained within 2 weeks after onset. Detection at 3 weeks and later (2.8%) was significantly lower (p < 0.05). In three cases, deoxyribonucleic acid was also found on the unaffected side in the initial phase of the disease, but detection on that side (18.9%) was significantly lower than on the affected side (83.8%) (p < 0.01). The number of copies of the herpes simplex virus-1 genome was large on the affected side and early after the onset of the disease. Conclusions: The reactivation of herpes simplex virus-1 on the affected side is involved as a pathogenic factor of Bell's Palsy. A reactivation of herpes simplex virus-1 may be generated even on the unaffected side in the early phase of the disease. Herpes simplex virus deoxyribonucleic acid was not detected in any of the examined specimens collected from the remaining 11 cases. The need for constant study to clarify other causative factors of Bell's Palsy remains.

Objective To clarify the dynamics of the reactivation of the varicella zoster virus in Ramsay Hunt syndrome. Subjects and methods Varicella zoster virus DNA in the tear fluid, submandibular gland saliva, and parotid gland saliva of 15 patients with Ramsay Hunt syndrome was studied. The presence of varicella zoster virus DNA was detected quantitatively by the use of polymerase chain reaction and a microplate hybridization method. Results Of 102 specimens of the tear fluid and saliva collected from 15 patients, varicella zoster virus DNA was detected in 40 specimens (39%) from 12 patients (80%). The detection rate was 72% in the submandibular saliva, 57% in the parotid saliva, and 27% in the tear fluid. Varicella zoster virus DNA was detected not only in specimens from the affected side but also in specimens from the unaffected side at the same rate of detection, and at nearly the same number of DNA copies. Regarding the parotid saliva, varicella zoster virus DNA was detected in samples collected at an early stage of the disease. In the tear fluid and submandibular saliva, however, the detection rate was high in samples collected 2 weeks after the onset of disease or later. Conclusions Secretion of varicella zoster virus DNA into the tear fluid and saliva was confirmed in the patient with Ramsay Hunt syndrome. The increase and decrease in the detection rate and the number of varicella zoster virus DNA copies detected in samples collected at different times was considered to substantiate varicella zoster virus reactivation in Ramsay Hunt syndrome. Varicella zoster virus reactivation was thought to occur in the unaffected side at the same level as in the affected side, and some of the secreted varicella zoster virus DNA was suspected to be derived from the ganglion trigeminale.

In 96 patients who visited our hospital with glossodynia, we conducted gustatory tests, measured serum zinc and copper levels, examined lingual papillae using biomicroscopy, conducted psychological tests and investigated the effectiveness of treatments directed at the cause of dysgeusia. Gustatory test results showed that 43 (44.8%) of the patients had dysgeusia, which was mild in 62.8%, moderate in 30.2% and severe in 7.0%. By giving higher priority to treatment of dysgeusia than to glossodynia, pain disappeared or was relieved and gustatory sensation improved in 27 (62.8%) of these 43 patients. Overall, pain disappeared or was improved in 65 (67.7%) cases. When treating glossodynia, it is important to diagnose the cause of pain and to give higher priority to treating that cause. The clinical efficacy of treatment for glossodynia will be improved when the presence or absence of dysgeusia is diagnosed early in the course of treatment.

Changes in gustatory sense were investigated in 97 pregnant women and in 30 healthy, non-pregnant women who served as controls. All 97 pregnant women completed a questionnaire regarding taste changes and 32 of them underwent serial tests of gustatory function, including electrogustometry and testing with filter paper disks placed over the areas of the chorda tympani nerve and glossopharyngeal nerve. All gustatory testing was performed by the same person. In addition, serum levels of trace elements were measured in 72 of the pregnant women. Of the 97 pregnant women, 90 (92.8%) reported in the questionnaire that they had experienced some type of change in taste during pregnancy, usually a change in sour taste (59 women; 65.6%). Pregnant women had higher gustatory thresholds than non-pregnant women, with an especially marked decrease in gustatory function being noticed in the first trimester. Although serum zinc levels decreased in pregnant women between the second and third trimesters, zinc levels were in the normal range in the early stage of pregnancy. Thus, it is difficult to explain dysgeusia in the early stage of pregnancy as being associated with a deficiency of zinc. The decrease in gustatory function during the first trimester is considered to be due to the notable changes in secretion of hormones that occur during this stage.

The course of recovery from taste receptor disturbance was studied in 119 patients with moderate-to-severe taste receptor disturbance that was cured or improved with zinc therapy. Taste receptor disturbance was idiopathic in 45 patients, drug-induced in 38 and due to zinc deficiency in 36. Recovery of taste, evaluated by filter paper disk testing and electrogustometry, followed 1 of 3 patterns: (i) in 54 (45.4%) of the 119 cases, taste improved simultaneously in the anterior (innervated by the chorda tympani nerve) and posterior (innervated by the glossopharyngeal nerve) portions of the tongue; (ii) in 53 (44.5%) of the cases, taste improved in the posterior portion first; and (iii) in 12 (10.1%) of the cases, taste improved in the anterior portion first. Zinc therapy was more effective in patients with the "posterior" pattern of recovery, and these patients also recovered the ability to sense sweet and bitter tastes earlier than other tastes. These results indicate that recovery of taste begins on the posterior portion of the tongue, which has an abundance of taste buds. The results of electrogustometry were not helpful in assessing recovery from taste disturbance, but testing for taste using the filter paper disk method on the posterior portion of the tongue was useful for identifying the onset of recovery.

We treated five patients with Hunter's glossitis following total gastrectomy. The major complaints of the patients were taste disorder and abnormal glossal sensation. In all five cases, the patient's tongue was red and smooth, and laboratory testing showed the presence of macrocytic anemia and decreased serum concentration of vitamin B12 (cyanocobalamin). Gustometry was carried out in four cases and the results documented the presence of taste disorder. All five patients were treated by administration of vitamin B12, which led to improvements in the appearance of the tongue, the patients' subjective complaints and the results of taste testing. When patients present with a red, smooth tongue, Hunter's glossitis (which can easily be improved by administration of vitamin B12) should be considered in the differential diagnosis.

Objectives: Most tracheobronchial foreign bodies in children are radiolucent, and accurate diagnosis of such foreign bodies is not always easy. This can result in delay of diagnosis or misdiagnosis of foreign body aspiration. We report the usefulness and pitfalls of use of digital subtraction fluoroscopy (DSF) to diagnose radiolucent aspirated foreign bodies in infants. Methods: From 1991 through 1999, DSF was conducted for a total of 19 patients (ranged from 11 months to 4 years and 7 months in age (mean 1.8±0.9 years)) who were suspected to have radiolucent aspirated foreign bodies. Since DSF revealed abnormal findings in a trachea or main bronchus in 18 cases, inspection was performed for foreign body bronchofiberscopically. In the one remaining case, no abnormality was recognized on DSF, but since the symptoms at the time of onset strongly suggested aspirated foreign body, bronchofiberscopy was also performed. Results: Foreign body was verified bronchoscopically in 13 of 19 cases, and all 13 (100%) had abnormal findings on DSF, including obstruction of the trachea in two, obstruction of the bronchial lumen in nine, and indistinct visualization of the bronchial lumen in two. Bronchial stenosis was verified bronchoscopically in five of the remaining six cases, including mucus plug in three, granuloma in one and mucosal edema in one case. All five patients (100%) had abnormal findings on DSF, including obstruction of the bronchial lumen in four and indistinct visualization of the bronchial lumen in one. In the one remaining patient with normal findings of DSF, no foreign body or pathological bronchial changes were noted. Conclusions: DSF was very sensitive in the diagnosis of foreign body aspiration and stenotic changes in the bronchial lumen. However, its diagnostic specificity for aspirated foreign body itself was not high (17%). Therefore, when abnormalities are found on DSF, we recommend to perform flexible bronchofiberscopy initially under general anesthesia via a tracheal tube. When a foreign body is verified, rigid ventilation bronchoscopy is successively performed to retrieve the foreign body.

We studied the postoperative stability of canal wall down tympanoplasty with canal reconstruction for middle ear cholesteatoma with preoperative otorrhea.155 ears with middle ear cholesteatoma treated with canal wall down tympanoplasty with canal reconstruction were evaluated retrospectively. A comparison was made between the group of 80 ears which showed otorrhea, preoperatively, and the group of 75 without preoperative otorrhea. Problems observed in the tympanic membrane or reconstructed external auditory canal were evaluated both at the postoperative initial stage and more than 1 year after surgery. Postoperative hearing prognosis was also studied.1) In the postoperative initial stage, local infection and necrosis of materials for canal reconstruction were significantly more likely to be observed in ears with preoperative otorrhea. 2) In ears with postoperative local infection, necrosis of materials for canal reconstruction occurred more frequently, and the period until drying of the reconstructed external auditory canal was significantly extended. 3) No significant difference was seen in postoperative status of the tympanic membrane and reconstructed ear canal at least 1 year after surgery. 4) The presence of preoperative otorrhea had no influence on hearing prognosis.When canal wall down tympanoplasty with canal reconstruction is used for ears with preoperative otorrhea, careful attention should be paid to local treatment at the postoperative initial stage. However, no significant problem occurred in the outcome of preoperative ear draining at least 1 year after surgery.

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The Yanagihara method and the House-Brackmann (H-B) method are widely used in Japan to evaluate facial paralysis. The present study focuses on the relationship between the evaluation of facial paralysis using these methods and self-evaluation by patients. One-hundred and thirty-one patients with facial paralysis were included in the study, consisting of 68 males and 63 females between the ages of 17 and 84 years (mean age: 41 +/- 18 years). In addition to the Yanagihara and H-B methods, two methods of self-evaluation were used by the patients. In the first self-evaluation method, the patient was asked to rate the degree of paralysis as a grade of one to six. In the second method, the patient was asked to rate the severity of the paralysis on a scale of 0-100. The paralysis scores and grades determined using the Yanagihara and H-B methods were correlated with the self-evaluations. However, the strength of the correlation varied among the patients, indicating that the evaluation of subjective symptoms differed among individuals. Even patients who were evaluated as either "completely paralyzed" or "cured" according to the Yanagihara and H-B methods did not always rate their subjective symptoms as being consistent with these scores. In particular, 20 to 30% of patients who were evaluated as "cured" complained of minor dyskinesia.

Fifty five cases with middle ear cholesteatoma which were performed second look and revision surgery were studied. In those cases, at the first operation, the posterior wall of the external auditory canal was reconstructed after canal down mastoidectomy. At the second operation, in 27 cases, the reconstructed posterior wall was totally removed, again, for investigation of residual cholesteatoma. In 26 cases, partial removal near to the epitympanum and the tympanic cavity was enough for inspection of the residual cholesteatoma. As the part was reconstructed with small cartilage, it was not complicated to remove it. At the second surgery, reconstruction of the mastoid cavity and the posterior wall was performed in 37 cases, and in 16 cases, the mastoid cavity was obliterated because of its severe pathological changes. After the second surgery, small bony absorption of the reconstructed posterior wall was observed in two cases, and abnormal findings of the eardrum were recognized in 10 cases. However, no cases were needed for frequent management or additional surgery. Improvement of hearing was succeeded in 100% of the cases with type I, 60% with type III and 30% with type IV tympanoplasty.