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The Japanese Three Academic Societies Joint Antimicrobial Susceptibility Surveillance Committee conducted a nationwide surveillance on six otorhinolaryngological diseases and investigated the antimicrobial susceptibility patterns and isolation rates of the causative pathogens. The surveillance program was conducted in the otorhinolaryngological departments of 12 universities, and 36 affiliated hospitals and clinics. Patients with acute otitis media (children under six years old), chronic otitis media, acute nasal sinusitis, chronic nasal sinusitis, acute tonsillitis, and peritonsillar abscess (over 20 years old) between December 2015 and June 2017 were investigated. The collected swab or incision samples were cultivated for microbial identification, and the antimicrobial susceptibility of the detected bacteria was measured at the Kitasato University Research Center for Infections and Antimicrobials. The surveillance focused on three gram-positive bacteria (Streptococcus pneumoniae , Streptococcus pyogenes , and Staphylococcus aureus), three gram-negative bacteria (Haemophilus influenzae , Moraxella catarrhalis , and Pseudomonas aeruginosa), and three anaerobic bacteria (anaerobic gram-positive cocci, Prevotella spp., Porphyromonas spp., and Fusobacterium spp.). Bacterial susceptibility to 40 antimicrobial agents was investigated. We were unable to completely mitigate the rise in the occurrence of resistant bacteria, such as methicillin-resistant S. aureus , penicillin-resistant S. pneumoniae , penicillin-intermediate resistant S. pneumoniae , beta-lactamase non-producing ampicillin-resistant H. influenzae , and beta-lactamase producing ampicillin-resistant H. influenzae. We suggest promoting the proper usage of antimicrobial agents to prevent the spread of these bacteria. We also suggested that immunization with pneumococcal vaccines is useful for decreasing the occurrence of otorhinolaryngological infectious diseases caused by pneumococci. [ABSTRACT FROM AUTHOR]

Objective: One in 1000-3000 carriers of human T-cell leukemia virus type 1 (HTLV-1) develops adult T-cell leukemia/lymphoma (ATLL) per year; however, the pathogenic mechanism is not completely clear. We have observed that some patients with squamous cell carcinoma (SCC) develop ATLL during treatment at our hospital. The aim of this study was to examine treatment factors associated with onset of ATLL through an evaluation of the therapeutic background of these patients.Methods: The impact of radiotherapy, chemotherapy and surgery on occurrence of ATLL was evaluated in 146 patients with head and neck SCC who were treated at our hospital between April 2010 and December 2013.Results: Of 146 patients, 17 were HTLV-1 positive and 6 developed ATLL. There was a significant relationship between ATLL development and administration of S-1 chemotherapy (p=0.0003), but not with use of radiotherapy, surgery or other drugs.Conclusion: The involvement of S-1 chemotherapy in ATLL development suggests that a test for HTLV-1 antibody should be performed before treatment and that S-1 should not be administered in HTLV-1 positive patients with head and neck carcinoma. [ABSTRACT FROM AUTHOR]

Objective Transcutaneous immunization (TCI) is a novel route of vaccination through application of a topical vaccine antigen on the skin. Phosphorylcholine (PC) is a structural component of a variety of pathogens and anti-PC immune responses protect mice against invasive bacterial diseases. The purpose of the study was to examine the effect of TCI using PC in BALB/c mice. Methods TCI was performed in BALB/c mice using PC–keyhole limpet hemocyanin (KLH) plus cholera toxin (CT). Immunogenicity was evaluated by measuring PC-specific IgG and specific IgG1, IgG2a, IgM, IgA, and secretory IgA antibodies by ELISA. The concentrations of IL-4, IL-5, IL-10, IL-12, IL-13 and IFN-γ were also measured using ELISA for mouse. Results Six months after immunization, IgG after TCI using PC plus CT was significantly higher than in controls, but this was not found for IgA. In saliva, secretory IgA antibodies decreased with a peak level at 2–3 months. IgG1 was significantly higher than IgG2 after TCI. Production of IL-4 from CD4 + cells was significantly higher after TCI than in controls, whereas production of IFN-γ, IL-5, IL-12 and IL-13 was not detected in either group. Conclusion These results suggest that TCI using PC plus CT with BALB/c mice is a simple approach for induction of systemic and mucosal immune responses that are shifted in the Th-2 direction. [ABSTRACT FROM AUTHOR]

The Japanese Three Academic Societies Joint Antimicrobial Susceptibility Surveillance Committee has conducted a nationwide surveillance on antimicrobial susceptibility patterns and rates of isolation in 6 otolaryngological diseases. The surveillance program was conducted in the otorhinolaryngological departments of 29 universities, and their 26 affiliated hospitals. Patients suffering from acute otitis media, chronic otitis media, acute nasal sinusitis, chronic nasal sinusitis, acute tonsillitis, and peritonsillar abscess between January 2011 and June 2012 were investigated. The collected swab or incision samples were cultivated for microbial identification, and the drug susceptibility of detected bacteria was measured at the Kitasato University Research Center for Infections and Antimicrobials. The surveillance focused on three gram-positive bacteria ( Streptococcus pneumoniae , Streptococcus pyogenes , and Staphylococcus aureus ), three gram-negative bacteria ( Haemophilus influenzae , Moraxella Catarrhalis , and Pseudomonas aeruginosa ), and three anaerobic bacteria ( Peptostreptococcus spp., Prevotella spp., and Fusobacterium spp.). Bacterial susceptibility to 39 antimicrobial drugs was investigated. We compared bacterial isolation ratio of each disease in this surveillance from those of past 4 times surveillance which we performed formerly, and we also compared percentage of main drug resistant strains from those of past 4 times surveillance. The age composition between this time and former surveillances was not statistically significant by student-t test. We were unable to completely resolve the rise in resistant bacteria, such as methicillin-resistant S. aureus , penicillin-resistant S. pneumoniae , penicillin-intermediate resistant S. pneumoniae , beta-lactamase non-producing ampicillin-resistant H. influenzae , beta-lactamase producing ampicillin-resistant H. influenzae , and beta-lactamase producing amoxicillin clavulanic acid-resistant H. influenzae . We suggest promoting the proper usage of antimicrobial drugs in order to avoid the spread of these bacteria. [ABSTRACT FROM AUTHOR]

Abstract: Many countries throughout the world have experienced an increase in the prevalence of allergic rhinitis (AR), which has come to be a major cause of morbidity in developed countries. The pathology underlying AR is regarded as IgE-mediated type I allergy characterized by mucosal inflammation that occurs in response to allergen exposure. In Japan, AR caused by Japanese cedar pollen, the most common allergic disease, has become a salient public health challenge. Almost all primary care physicians and otorhinolaryngologists have been consulted by AR patients between February and April. Although most such patients have received treatment, numerous patients with AR have not received proper examinations for AR. Clinical guidelines are systematically developed statements that are designed to help practitioners make decisions about appropriate and effective health care. Guidelines in many countries including Japan have been published for AR. Unfortunately, those guidelines have remained untested. Moreover, they might be difficult for non-specialists to use. In this review, we specifically examine the present standard examination for diagnosis of AR and optimal classification for AR in Japan. We hope that this review would be used not only for the support of daily practice but also for selection of AR patients for clinical trials. [Copyright &y& Elsevier]

Abstract: Objective: In Japan, fourteen-membered ring macrolides, antibacterial agents, and S-carboxymethylcysteine (SCMC; carbocisteine), a mucolytic, are commonly used to treat chronic rhinosinusitis (CRS), and they are also used in combination. However, no large-scale randomized study has examined the effects of these pharmacotherapies. The aim of this study is to evaluate the effect of combined administration of clarithromycin (CAM), a fourteen-membered ring macrolide, and SCMC, compared with CAM single therapy. Methods: Patients with CRS were centrally registered and randomly assigned to treatment with CAM (200mg/day) alone (monotherapy group) or CAM (200mg/day) in combination with SCMC (1500mg/day; combination group) for 12 weeks. We assessed the clinical efficacy of the treatments using measures of subjective symptoms and objective findings, health-related quality of life (HRQOL) determined by the 20-Item Sino-Nasal Outcome Test (SNOT-20) score and computed tomography (CT) score. Results: Four hundred twenty-five subjects were enrolled (combination group, 213; monotherapy group, 212). At week 12 of treatment, the rate of effectiveness was significantly higher in the combination group (64.2%) compared with the monotherapy group (45.6%; P =0.001). In addition, objective findings, including characteristics of nasal discharge (P =0.008) and post-nasal discharge (P =0.002) were significantly improved in the combination group. In both groups, SNOT-20 and CT scores were significantly improved from week 0 (P <0.001), and were not significantly different between groups. Conclusion: The results indicated that long-term combination therapy with SCMC at a dose of 1500mg/day and CAM at a dose of 200mg/day is effective for improving subjective symptoms and objective findings in adult patients with CRS. [Copyright &y& Elsevier]

Abstract: Objective: The objective of this study was to assess the reliability and validity of a Japanese version of the 20-Item Sino-Nasal Outcome Test SNOT-20, which is one of the quality-of-life (QOL) evaluation sheets for chronic rhinosinusitis (CRS), and assess its reliability and validity. Methods: The SNOT-20 was conducted in patients with CRS and in healthy volunteers. The response rate was evaluated as the feasibility of this test, and reliability and internal consistency were assessed as reliability. In addition, concurrent validity and discriminant validity were assessed as validity. Results: Regarding the feasibility of this test, the response rate for each question item in the SNOT-20 was nearly 100% for all 20 items. For reliability, test–retest reliability was r =0.890 and the internal consistency was α =0.903. For validity, the concurrent validity was r =0.162 when compared with objective findings in the nasal cavity, and was r =0.431 when compared with the score for general physical condition, which evaluate the patient''s general condition. Discriminant validity was significantly higher in patients with CRS than in healthy volunteers (p <0.001). Moreover, when the discriminant validity was assessed using an ROC (receiver operating characteristic) curve, it was found that ROC-AUC (the area under the curve)=0.775. Conclusion: The reliability and validity of a Japanese version of the SNOT-20 were assessed in this study. It is thought that the SNOT-20 serves as a useful QOL evaluation sheet for CRS. [Copyright &y& Elsevier]

Objective: To better understand the causes of the exacerbation of rhinitis medicamentosa (RM) induced by oxymetazoline (OMZ) or benzalkonium chloride (BKC), we examined the impact of pretreatment with OMZ or BKC on cultured human nasal epithelial cells. We also examined the effect of mometasone furoate (MF) on the cultured human nasal epithelial cells treated with OMZ or BKC.Methods: Cells of the human nasal epithelial cell line HNEpC were treated with OMZ or BKC, and the OMZ- and BKC-induced expression of histamine H1 receptor (H1R) mRNA was assayed using real-time polymerase chain reaction. In some experiments, 1.0×10(-5)M MF was added to the HNEpC cells for 24h before treatment with OMZ or BKC.Results: Treatment with OMZ slightly increased the expression level of H1R mRNA in HNEpC cells. This enhanced expression was not significantly reduced by pretreatment with MF. In contrast, treatment with BKC remarkably increased the expression level of H1R mRNA in HNEpC cells. In addition, this enhanced expression was significantly reduced by pretreatment with MF.Conclusion: These results suggest that the increased expression of H1R mRNA due to treatment with OMZ or BKC might be one of the factors underlying the exacerbation of symptoms in patients with RM and those complicated with allergic rhinitis. The concomitant use of a nasal steroid might reduce the exacerbation of symptoms caused by BKC, although there remains a risk of developing histamine hypersensitivity from the long-term use of a topical steroid-containing BKC. [ABSTRACT FROM AUTHOR]

Objective: Nebulizer therapy is an effective and safe topical treatment for rhinosinusitis and is frequently used by otolaryngologists in Japan. However, treatment methods used vary among regions and according to doctors' preferences. In this study, we aimed to investigate the use of nebulizer therapy for rhinosinusitis. Administration of nebulizer therapy has been affected by the coronavirus disease 2019 (COVID-19) pandemic. Thus, we also investigated the difference in the prevalence of nebulizer use before and during the pandemic.Methods: Between February and September 2016 and in January 2021, we administered questionnaire surveys on nebulizer treatment for rhinosinusitis to otorhinolaryngologists, who were members of the Oto-Rhino-Laryngological Society of Japan, in Aomori, Saitama, Mie, Fukui, Shiga, Okayama, and Kagoshima prefectures.Results: More than 90% of the otorhinolaryngologists performed nebulizer treatment for rhinosinusitis in 2016. In April 2020 (the first wave of the COVID-19 pandemic), the use rate decreased to 20%, but in January 2021, the use rate increased to 60%. Jet nebulizers were the most frequently used type. One-third of the otolaryngologists enlarged the natural opening of the paranasal sinuses in more than half of their patients by using vasoconstrictors. Cefmenoxime and betamethasone were the most commonly used antibiotics and steroids, respectively.Conclusion: Because it is important to perform nasal pretreatment and strict disinfection of nebulizer equipment, it is clear that education of otorhinolaryngologists as well as paramedical personnel is required to ensure safe and effective use of nebulizer therapy in Japan. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of the study was to evaluate upper gastrointestinal endoscopy with movable over tube (i.e., the movable over tube method) for observing the hypopharynx to cervical esophagus, for use in treatment, and to determine its safety. Methods: The study population consisted of 28 patients (23 men, 5 women; a mean age of 66.6 years old; age range of 50–80 years old). The patients consisted of nine cases of globus sensation, eight cases of hypopharyngeal cancer (post-chemoradiotherapy), three cases of hypopharyngeal cancer (untreated), two cases of hoarseness, two cases of unknown primary carcinoma, two cases of foreign body, one case of esophageal cancer, and one case of dysphagia. We used upper gastrointestinal endoscopy with movable over tube to examine the hypopharynx to the cervical esophagus in subjects. Results: With the movable over tube method, which was performed under pharyngeal surface anesthesia and an infusion of diazepam (5–10mg/kg body weight), one could observe from the hypopharynx to cervical esophagus without any blind spots. There were no complications after the examination. Conclusions: The results suggest that the movable over tube method is an easy, useful, and safe method to observe the region from the hypopharynx to the cervical esophagus. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of the study was to clarify the relationship between a globus sensation and esophageal diseases using upper gastrointestinal endoscopy. Methods: The study population consisted of 52 consecutive patients (33 men, 19 women, age 46–94 years old) with a globus sensation without laryngeal and hypopharyngeal findings who were referred to the Department of Otolaryngology at Ooshima Prefecture Hospital. The subjects were examined by upper gastrointestinal endoscopy. Results: Nineteen patients (36.5%) had esophageal disorder, including 10 cases of reflux esophagitis, 5 of esophageal candidiasis, 3 of esophageal cancer. and 1 of herpes and reflux esophagitis. Neither age nor duration of symptoms differed significantly between patients without an esophageal disorder and those with reflux esophagitis or esophageal candidiasis. Conclusions: The results suggest that examination for esophageal diseases is important in patients with a globus sensation without laryngeal and hypopharyngeal findings. [Copyright &y& Elsevier]

Abstract: Polymyositis is characterized by non-specific inflammatory disease associated with an autoimmune disorder involving muscles of the limbs and neck. We report a case of an 80-year-old man who was referred to our clinic with a chief complaint of dysphagia and muscle weakness in all four limbs. The patient was diagnosed with polymyositis based on pathological findings, muscle weakness, electromyogram findings, and an elevated creatine phosphokinase level. The patient was also positive for HLA-DR3. Intravenous predonine administration was initiated, but dysphagia was not improved. We considered a cricopharyngeal myotomy, but this could not be performed because of heart failure. Endoscopic balloon dilation was performed and dysphagia improved on the same day. Therefore, we suggest that this method is a safe and effective approach for polymyositis with dysphagia. [Copyright &y& Elsevier]

Abstract: Malignant fibrous histiocytoma (MFH) is the most common soft-tissue sarcoma, but is relatively uncommon in head and neck area. Histologically, it is difficult to distinguish this tumor from other sarcomas and carcinomas. Surgery is the most reliable treatment for MFH, but the 5-year survival rate for cases of this tumor in the head and neck is low in comparison with MFH of the extremities and trunk. In the case reported here, the patient was a 61-year-old man who presented with swelling and pain of the left bucca. A CT scan demonstrated a 2.5cm×5.0cm inhomogeneous lesion. In MRI, the tumor displayed an inhomogeneous isointense signal on T1-weighted images and a high-intensity signal on T2-weighted images. Fine-needle aspiration (FNA) was performed twice but we were unable to reach a definitive diagnosis histologically. MFH was subsequently diagnosed by open biopsy, and external radiotherapy with 38Gy of radiation was performed. However, the tumor enlarged after this therapy, and therefore CyberKnife therapy was performed twice, after which the tumor gradually reduced in size. The patient is alive after a follow-up period of 22 months, and therefore we suggest that CyberKnife treatment may be useful for head and neck MFH. [Copyright &y& Elsevier]

CD3−CD4+CD45+ cells are thought to be an inducer cell population for Peyer''s patch (PP) and lymph node development. Nasopharyngeal-associated lymphoid tissue (NALT) is an organized lymphoid structure found on both sides of the nasopharyngeal duct dorsal to the cartilaginous soft palate. Although NALT is considered to be functionally analogous to PP in the intestinal tract, the association of CD3−CD4+CD45+ cells with the initiation of NALT development has not yet been clarified. To examine this issue further, we isolated CD3−CD4+CD45+ cells from the fetal intestines of wild-type mice. Id2−/− mice genetically deficient in NALT were adoptively transferred with purified CD3−CD4+CD45+ cells or fetal liver cells. After the adoptive transfer, we employed immunohistochemical analysis to examine the expression of PNAd, an important addressin for the recruitment of lymphocytes, in the nasal tissue of Id2−/− mice transferred with fetal liver cells. Though NALT-like structures were indeed induced in Id2−/− mice adoptively transferred with CD3−CD4+CD45+ cells or fetal liver cells, those structures were not observed to express PNAd. These findings indicate that CD3−CD4+CD45+ cells and Id2 genes are key to the initiation of NALT. However, they also suggest that an additional element is required for the induction of PNAd. [Copyright &y& Elsevier]

Objective: To investigate the incidence of acute epiglottitis (AE) and the clinical features of patients with AE complicated by peritonsillar abscess (PTA), considering that PTA, especially inferior-type PTA, is often a comorbidity of AE.Methods: We retrospectively reviewed the medical records of patients who were diagnosed as having AE by otolaryngologists and referred to our hospital between January 2009 and December 2017. All the patients underwent laryngeal endoscopy and contrast-enhanced computed tomography (CT) for examination of the severity of AE and its complications by other infections, including PTA. The clinical characteristics of patients with PTA were compared with those of patients without PTA.Results: A total of 139 patients were enrolled, of whom 21 (15%) were found to have PTA. Among the 21 patients, only one had a superior-type PTA and the others had an inferior-type PTA. The patients with complicated AE by an inferior Cap-type PTA frequently showed unilateral arytenoid swelling.Conclusion: PTA is a comorbidity of AE, and unilateral arytenoid swelling is considered to suggest the presence of inferior-type PTA. [ABSTRACT FROM AUTHOR]

Parapharyngeal abscess (PPA) may cause life-threatening complications and peritonsillar abscess (PTA) and tonsillitis frequently precede PPA. The optimal management of PPA caused by PTA has been the subject of debate with respect to the surgical approach. We present three cases of PPA concomitant with PTA in elderly patients. In two cases, the abscesses in parapharyngeal space were drained by abscess tonsillectomy followed by intraoral incision of the tonsillar bed. On the other hand, the third case did not undergo abscess tonsillectomy because of his refusal of surgery and needed extraoral drainage after the aggravation of PPA. Based on the experience of those three cases, it was suggested that abscess tonsillectomy followed by intraoral incision of the tonsillar bed might be a useful surgical approach for the drainage of PPA concomitant with PTA, especially in elderly patients. [ABSTRACT FROM AUTHOR]

Malignancies have been reported to occasionally arise in scar tissue following injury. One hypothesis involves prolonged overactivation of tissue repair systems due to chronic inflammation and irritation, although the pathogenesis of cancers occurring in scars is not fully understood. We describe here two cases with a history of maxillary fracture at the site where squamous cell carcinoma (SCC) subsequently developed. The first patient developed SCC 7 years after right maxillary fractures resulting from a traffic accident. He underwent chemoradiotherapy (70 Gy in 35 fractions) and maintained complete response (CR) for 10 months. The second patient developed SCC 3 years after sustaining right maxillary fractures in an ice hockey game. Radiotherapy and total maxillectomy were performed, but local recurrence arose and he has since been receiving chemotherapy. [ABSTRACT FROM AUTHOR]

The guidance deals with the recommended applications, procedures, and safety management of nebulizer therapy for acute rhinosinusitis. In Japan, nebulizer therapy for sinusitis has been covered by public health insurance since 1958 and has been commonly carried out nationwide. The Japan Society for Infection and Aerosol in Otorhinolaryngology and the Oto-Rhino-Laryngological Society of Japan set up a working group to draw up a consensus guidance on nebulizer therapy for acute rhinosinusitis. The device for nebulizer therapy are classified into jet, ultrasound, and mesh types. In Japan, cefmenoxime hydrochloride (CMX) was approved for use in nebulizer therapy since 1996. The widening of the obstructed lesions such as large polyps prior to nebulizer therapy were recommended. The numbers of times of nebulizer therapy is recommended for three times in a week for at least for 2 weeks (cure rate: 68%, eradication ratio: 48%). Concerns should be pay for the changes of activity of medicine due to the mixing and bacterial contamination. Pseudomonas cepacia growing in a short even in both saline and distilled water leads to contamination at high concentrations by 2 days. Nebulizer therapy is an effective treatment based on a drug delivery system (DDS) to the nasal and paranasal cavities. The therapy effectively increases the local drug concentration by promptly and uniformly delivering drugs to a targeted local site. The therapy is safe with less systemic absorption and with few adverse reactions. [ABSTRACT FROM AUTHOR]

• Effects of PCV13 vaccination and intranasal (IN) immunization were assessed in mice. • PCV13 followed by phosphorylcholine boosted immune response against S. pneumoniae. • IN can achieve protection against S. pneumoniae serotypes not contained in PCV13. This study aimed to investigate whether systemic immunization with a 13-valent pneumococcal conjugate vaccine (PCV13) followed by intranasal (IN) immunization with phosphorylcholine (PC) can boost immune response against Streptococcus pneumoniae. Two weeks after the intraperitoneal (IP) injection of PCV13, mice were divided into two groups (mice requiring another IP injection of PCV13 and mice requiring PC-keyhole limpet hemocyanin IN immunization in combination with cholera toxin as a mucosal adjuvant) to compare the magnitude of systemic and mucosal immune responses against S. pneumoniae and PC. Serum immunoglobulin (Ig) G antibody titer against the vaccine strains of S. pneumoniae was similar between the PCV13 systemic immunization group and PC IN immunization group, while the serum IgG antibody titer against PC was significantly higher in the PC IN immunization group. PC-specific IgA antibody titer in the nasal lavage and PC-specific IgA-producing cell number in the nasal mucosa were also significantly higher in the PC IN immunization group. Induction of PC-specific IgA in the PC IN immunization group enhanced the clearance of bacteria from the middle ear. Additional IN immunization with PC after PCV13 immunization, which is currently conducted under a periodic vaccination program, can produce a booster effect comparable to that achieved by additional systemic immunization as well as PC-specific mucosal immune response, thereby providing protection against S. pneumoniae serotypes not contained in PCV13. [ABSTRACT FROM AUTHOR]

Objective: To provide an evidence-based recommendation for the management of olfactory dysfunction in accordance with the consensus reached by the Subcommittee of the Japanese Clinical Practice Guideline for olfactory dysfunction in the Japanese Rhinologic Society.Methods: Seven clinical questions (CQs) regarding the management of olfactory dysfunction were formulated by the subcommittee of the Japanese Clinical Practice Guideline for olfactory dysfunction. We searched the literature published between April 1990 and September 2014 using PubMed, the Cochrane Library, and Ichushi Web databases. The main search terms were "smell disorder," "olfactory dysfunction," "olfactory loss," "olfactory disturbance," "olfactory impairments," "olfaction disorder," "smell disorder," "anosmia," "cacosmia," and "dysosmia." Based on the results of the literature review and the expert opinion of the Subcommittee, 4 levels of recommendation, from A-strongly recommended to D-not recommended, were adopted for the management of olfactory dysfunction.Results: Both oral and locally administered corticosteroids have been strongly recommended for patients with olfactory dysfunction due to chronic rhinosinusitis. Nasal steroid spray and antihistamine drugs have been moderately recommended for patients with allergic rhinitis. Although no drugs have been deemed to be truly effective for post-viral olfactory dysfunction by randomized-controlled trials (RCTs) or placebo-controlled trials, olfactory training using odorants has been reported to be effective for improving olfactory function. There is considerable evidence that olfactory testing is useful for differential diagnosis, prediction of disease progression, and early detection of cognitive decline in neurodegenerative diseases.Conclusion: The Clinical Practice Guideline has developed recommendations for the management of various aspects of olfactory dysfunction. [ABSTRACT FROM AUTHOR]

Objective: Phosphorylcholine (PC) is a structural component of Streptococcus pneumoniae (Spn) and nontypeable Haemophilus influenzae (NTHi), and is known to be associated with adherence through the platelet activating factor receptor (PAF-R). Furthermore, high PC expression is considered to be involved in Spn and NTHi virulence. In this study, we examined the influence of PC expression on the adherence of Spn and NTHi to epithelial cells in order to clarify the potential effectiveness of a vaccine targeting PC.Methods: Twenty-seven strains of Spn and twenty-two strains of NTHi were used, cultured overnight, and PC expression was evaluated by fluorescence activated cell sorting; the strains were divided into two groups: PC low expression (PC-low) and PC high expression (PC-high) groups. Bacterial adherence was then examined using Detroit 562 cells and BALB/c mice. Bacterial invasion was then examined in Detroit 562 cells.Results: The adherence of Spn and NTHi and invasion of NTHi in the PC-high group was significantly reduced by pretreatment with a monoclonal anti-PC antibody (TEPC-15), PAF-R antagonist (ABT-491), and PC-keyhole limpet hemocyanin (PC-KLH). However, such findings were not observed in the PC-low group.Conclusion: The present study suggests that PC is involved in the mucosal adhesion of Spn and NTHi, and the mucosal invasion of NTHi with PC-high strains, but not PC-low strains. These results suggest that a PC-targeting mucosal vaccine only affects PC-high Spn and NTHi strains and does not disturb commensal bacterial flora in the upper respiratory tract, which comprises nonpathogenic PC-low bacteria. [ABSTRACT FROM AUTHOR]

Objective: Transcutaneous immunization (TCI) is a novel route of vaccination through application of a topical vaccine antigen on skin. Phosphorylcholine (PC) is a structural component of a variety of pathogens, and anti-PC immune responses protect mice against invasive bacterial diseases. The purpose of the study was to examine the effect of TCI using PC in back skin or auricle skin in BALB/c mice.Methods: TCI was performed in BALB/c mice in back skin or auricle skin using PC-keyhole limpet hemocyanin (KLH) plus cholera toxin (CT). Inoculations were given once each week for six consecutive weeks. Immunogenicity was evaluated by measuring PC-specific IgG and specific IgG1, IgG2a, IgM, IgA, and secretory IgA antibodies by ELISA. IL-4, IL-5, IL-10, IL-12, IL-13 and IFN-γ levels were also measured by ELISA.Results: Serum IgG after TCI in auricle skin was significantly higher than after TCI in back skin and in controls. Secretory IgA antibodies after TCI in auricle skin were also significantly higher than after TCI in back skin and in controls in nasal, BALF, vaginal and fecal samples. PC-specific IgG1 and IgG2a were significantly higher after TCI in auricle skin compared to controls and compared to TCI in back skin. IgG1 was significantly higher than IgG2a after TCI in auricle skin. Production of IFN-γ, IL-4 and IL-10 from CD4+ cells was significantly higher after TCI in auricle skin than after TCI in back skin and in controls, whereas IL-5, IL-12 and IL-13 were not detected in any mice.Conclusion: These results suggest that TCI in auricle skin using PC plus CT in BALB/c mice is a simple approach for induction of systemic and mucosal immune responses that are shifted in the Th2 direction. [ABSTRACT FROM AUTHOR]

Objective: To clarify indications for immediate abscess tonsillectomy (IAT) for peritonsillar abscess (PTA). Methods: A retrospective study was performed on 99 patients who were diagnosed with PTA on the basis of computed tomography (CT). Based on CT findings, PTA patients were classified into two categories by abscess shape: Oval type and Cap type. Furthermore, abscess location was differentiated into superior and inferior, resulting in a final classification of 4 categories: superior Oval type; superior Cap type; inferior Oval type; and inferior Cap type. In addition, the proportion of PTA patients showing extraperitonsillar spread into parapharyngeal spaces in each category was examined. Results: Superior Oval-type PTA was the most common. Thirteen patients showed extraperitonsillar spread. When CT classifications were compared with clinical findings, patients with inferior Cap-type abscess displayed extraperitonsillar spread more frequently than the other categories of PTA. In all 13 patients, the parapharyngeal space was involved. In addition, 3 patients displayed retropharyngeal space involvement. In all 13 cases, abscess remained above the hyoid bone. Conclusions: Inferior Cap-type PTA may need more intensive and reliable treatment, such as IAT, which might be effective for PTA showing extraperitonsillar spread. [ABSTRACT FROM AUTHOR]

Abstract: Von Willebrand disease (vWD) is a common hereditary bleeding disorder resulting from a quantitative and/or qualitative deficiency of von Willebrand factor (vWF). We report two cases of peritonsillar abscess complicated by vWD. A 46-year-old Japanese man was intravenously administered factor VIII clotting antigen (500U×3 days)and platelet transfusion (10U), when before puncture was performed. After puncture, his symptoms promptly improved with the administration of the antibiotic doripenem (DRPM, 1.5g/day). He left our facility one week later and had no recurrence of symptoms. A 24-year-old Japanese woman was intravenously administered factor VIII clotting antigen (4500U×3 days) and desmopressin (DDAVP) before undergoing a puncture. Her symptoms promptly improved with DRPM treatment (1.5g/day). The patient left our facility one week later. However, the peritonsillar abscess recurred in three weeks. Afterwards, tonsillectomy was enforced three months later. Intravenous factor VIII clotting antigen (4500U×2 days) and platelet transfusion (10U×1 day) had been used before tonsillectomy. We therefore suggest that a peritonsillar abscess in patients with vWD can be safely treated by factor VIII clotting antigen and DDAVP at the appropriate disease stage and by performing paracentesis for the acute phase or tonsillectomy for the chronic phase. [Copyright &y& Elsevier]

Abstract: Objective: Self-care with Ten-Cha is the most common complementary alternative medicine for allergic rhinitis in Japan, but evidence for an actual therapeutic effect is lacking. The purpose of the study was to investigate the effect of Ten-Cha (Rubus suavissimus) on house dust mite allergic rhinitis. Methods: The study was performed in the otolaryngology departments of 5 facilities (Chiba University, Kagoshima University, Fukui University, Okayama University, and Nippon Medical School) from July to December 2009. A randomized double-blind study was performed with central enrollment and allocation. The subjects ingested 400mg of Ten-Cha extract or placebo (3 capsules/day) daily for 4 weeks as a food intervention. The number of subjects was chosen with anticipation of an effect equivalent to that of mast cell-stabilizing drugs. A nasal allergy diary-based symptom score and a QOL score were used for evaluation. Results: The Ten-Cha and placebo groups included 47 and 42 subjects, respectively. The improvement rates for sneeze, nasal discharge, nasal obstruction, and symptom scores were greater in the Ten-Cha group than in the placebo group throughout the intervention period, and the effect tended to increase with time in the Ten-Cha group. However, the differences between the groups were not significant. QOL was not significantly improved in either group. Conclusion: Ingestion of Ten-Cha had an effect on allergic rhinitis, but the effect of Ten-Cha was limited and did not differ significantly from placebo. These results suggest that Ten-Cha does not exhibit an effect equivalent to mast cell-stabilizing drugs at the dose used in this study. [Copyright &y& Elsevier]

Abstract: Objectives: Vascular endothelial growth factor (VEGF) is a potent and critical inducer of angiogenesis and vascular permeability, and has been shown to play an important role in inflammatory events, together with hypoxia and inflammatory cytokines. VEGF messenger ribonucleic acid (mRNA) is expressed in the middle ear in an experimental animal model of otitis media with effusion (OME) and in patients with OME. However, the protein levels of VEGF in middle ear effusions (MEEs) are unknown and the role of VEGF in the pathogenesis of OME is unclear. The goals of this study were to determine the VEGF levels in MEEs and to investigate the role of VEGF in production of MEEs by comparing these levels with those of interleukin-8 (IL-8), endotoxin, and albumin. Methods: Forty-six MEEs obtained from 33 children (24 boys, 9 girls) were used in the study. The mean age of the subjects was 6.3 years old (range, 1–12 years old). The patients underwent myringotomy and/or insertion of a ventilation tube for treatment of OME. After myringotomy, MEEs were collected with a Juhn Tym-Tap. The samples were divided into serous and mucoid types based on observation by the naked eye. After measuring the weight of the MEE, the sample was diluted with phosphate-buffered saline and frozen until use. The concentrations of VEGF and IL-8 in the MEEs were determined by enzyme-linked immunosorbent assays, endotoxin concentrations were measured by the Limulus Amebocyte Lysate test, and albumin levels were determined using an immunoturbidimetric assay. Results: VEGF, endotoxin, IL-8, and albumin were detected in 100%, 89%, 98%, and 100% of the 46 MEEs, respectively. The concentrations of VEGF, endotoxin, and IL-8 were significantly higher in mucoid MEEs than in serous MEEs (p <0.01), whereas there was no significant difference in the albumin concentration between mucoid and serous MEEs. The VEGF levels were positively correlated with those of endotoxin (R 2 =0.17, p <0.05) and albumin (R 2 =0.65, p <0.01) in mucoid MEEs, but not in serous MEEs. Conclusions: Our results suggest that VEGF is produced in response to bacterial components such as endotoxin in the middle ear cavity and is associated with production of mucoid MEEs by increasing serum exudation and mucosal secretion. [Copyright &y& Elsevier]

Abstract: Malignant tumors in the paranasal sinuses and nasal cavity are mostly squamous cell carcinomas, with comparatively few adenocarcinomas. Adenocarcinoma developing in paranasal sinuses and nasal cavity generally has a low response to radiotherapy and low chemotherapeutic sensitivity, making surgery the most reliable treatment. However, advanced adenocarcinoma is often difficult to treat due to anatomical complexity, and the outcome may not be satisfactory. We report the case of a 62-year-old man who presented with nasal congestion and epistaxis. We were unable to observe an oncogenic lesion in the nasal cavity directly, but the tumor gave inhomogeneous low intensity signals on T1-weighted images and an isointense signal on T2-weighted images in MRI. Adenocarcinoma was diagnosed by open biopsy. Six courses of chemotherapy by super-selective intra-arterial infusion of cisplatin with concurrent intensity-modulated radiation therapy of 70Gy were performed at another hospital. However, the tumor enlarged and developed distant metastasis to the lung after this therapy. Therefore, TPF chemotherapy (docetaxel, cisplatin and 5-fluorouracil) was performed 5 times, after which the tumor gradually reduced in size. The patient is alive after a follow-up period of 43 months, indicating that TPF chemotherapy may be useful for adenocarcinoma of the paranasal sinuses and nasal cavity. [Copyright &y& Elsevier]

Abstract: We explore cellular and molecular mechanisms of nasal adjuvant of a combination of a plasmid encoding the Flt3 ligand cDNA (pFL) and CpG oligodeoxynucleotides (CpG ODN). The double DNA adjuvant given with OVA maintained prolonged OVA-specific secretory IgA (S-IgA) Ab responses in external secretions for more than 25 weeks after the final immunization. Further, both Th1- and Th2-type cytokine responses were induced by this combined adjuvant regimen. The frequencies of plasmacytoid DCs (pDCs) and CD8+ DCs were significantly increased in nasopharyngeal-associated lymphoreticular tissue (NALT) of mice given the combined adjuvant. Importantly, when we examined adjuvanticity of pFL plus CpG ODN in 2-year-old mice, significant levels of mucosal IgA Ab responses were also induced. These results demonstrate that nasal delivery of a combined DNA adjuvant offers an attractive possibility for the development of an effective mucosal vaccine for the elderly. [Copyright &y& Elsevier]

Abstract: Objective: Microvascular free-tissue transfer is essential for functional reconstruction in head and neck cancer surgery. The risk of free flap failure depends on venous thrombosis rather than arterial thrombosis, and any type of failure caused by venous thrombosis is often diagnosed late. In this study, we studied the flap survival rate achieved by this technique depending on the recipient vein. Further, the risk factor was analyzed for venous thrombosis with regard to preservation of recipient vein during neck dissection. Methods: This study is a retrospective review of 102 consecutive free flaps performed by a single head and neck surgical team from 2000 to 2006 at the Department of Otolaryngology, Head and Neck Surgery at Kagoshima University Hospital. The recipient vessels such as the external jugular (EJ) vein and internal jugular (IJ) system were carefully preserved during neck dissection. All patients received 80μg of prostaglandin E1 (Alprostadil) for 5 days after surgery. Results: The overall success rate was 94.1%. All the six cases of unsuccessful free flap transfer were caused by venous thrombosis. Microvascular free flaps anastomosed to the EJ vein failed at a significantly higher rate (13.3%) than those anastomosed to the IJ system (2.8%) (p <0.05). On studying the failed cases after IJ system anastomosis, we found that all complications were caused by internal jugular vein thrombosis (IJVT) and not by microvascular anastomotic thrombosis. In all the three cases of flap failure with IJVT, the dissected IJ vein was patently ballooning because of the remaining connective tissue, including the adventitia around the IJ vein in the supraclavicular lesion. Conclusions: Although the IJ system is the ideal recipient vessel when compared with EJ vein, there is another risk of flap failure due to IJVT. To improve the survival rate, IJVT should be prevented by a careful manipulation of IJ system during neck dissection to avoid ballooning of the IJ vein in head and neck cancer surgery. [Copyright &y& Elsevier]

Objective: Lung and synovial fibroblasts produce VCAM-1 in response to TNF-alpha. However, the massive infiltration of eosinophils, the effects of the increased amount of TNF-alpha and the production of VCAM-1 in human nasal polyp fibroblasts are not yet fully understood. The present study examines the role of VCAM-1 and the molecular mechanism of its expression in nasal fibroblasts.Methods: Nasal fibroblasts were isolated from human nasal polyps and after four passages, the cells were stimulated with TNF-alpha and VCAM-1 expression was examined by ELISA, flow cytometry, and RT-PCR. The activation of NF-kappaB induced by TNF-alpha was determined by electrophoretic mobility shift assays and the influence on the expression of VCAM-1 was investigated.Results: VCAM-1 protein and mRNA were expressed in unstimulated controls and remarkably increased by TNF-alpha stimulation. NF-kappaB activity was enhanced by TNF-alpha stimulation and remarkably suppressed by NF-kappaB proteasome inhibitor.Conclusions: The present study discovered that nasal fibroblasts produce VCAM-1 protein and mRNA and that production is increased by TNF-alpha stimulation. Furthermore, VCAM-1 expression in nasal fibroblasts is induced through an NF-kappaB-dependent pathway. These findings might provide a rationale for using NF-kappaB inhibitors as a treatment for nasal inflammatory diseases such as polyps. [ABSTRACT FROM AUTHOR]

Abstract: Phosphorylcholine (PC) is a structural component of a wide variety of pathogens including Streptococcus pneumoniae and Haemophilus influenzae, and anti-PC immune responses are known to protect mice against invasive bacterial diseases. The present study tested the capability of PC as an intranasal plurispecific vaccine against upper airway infections. BALB/c mice immunized with intranasal PC-keyhole limpet hemocyanin (KLH) plus cholera toxin (CT) as a mucosal adjuvant showed increased PC-specific IgM in serum, IgA in nasal wash and saliva, and numbers of PC-specific nasal and splenic antibody producing cells. Enhanced production of IL-4 and IFN-γ by CD4+ T cells indicated the participation of Th2- and Th1-type cells. Salivary IgA antibodies produced by intranasal immunization with PC-KLH plus CT reacted to most strains of S. pneumoniae and H. influenzae. Further we demonstrated that the clearance of S. pneumoniae and H. influenzae from the nasal tract was significantly enhanced by nasal immunization with PC-KLH and CT. Thus, intranasal vaccination to induce PC-specific immune responses might help to prevent upper airway infections caused by S. pneumoniae and H. influenzae. [Copyright &y& Elsevier]

Abstract: Objective:: Vascular endothelial growth factor (VEGF) promotes angiogenesis and is associated with the invasion and metastasis of malignant tumors. It enhances vascular permeability and is expressed in inflammatory nasal as well as middle-ear mucosa. As the mechanism of VEGF induction during chronic inflammation, such as chronic paranasal sinusitis (CPS) remains to be clarified, we studied the factors regulating the production of VEGF in cultured human nasal fibroblasts and discussed the role of VEGF in the pathogenesis of CPS. Methods:: We used ELISA to quantify VEGF levels in paranasal sinus effusions, nasal secretions, and serum from patients with CPS. In addition, we cultured human nasal fibroblasts isolated from nasal polyps of CPS patients and studied the effects of hypoxia, TNF-α, and endotoxin on their production of VEGF using ELISA and PCR. Results:: The VEGF concentration was significantly higher in paranasal sinus effusions than in nasal secretions and serum. Nasal fibroblasts produced high levels of VEGF, when cultured under hypoxic condition and this production was remarkably enhanced in the presence of TNF-α or endotoxin. Conclusion:: VEGF is locally produced in paranasal sinuses as well as nasal mucosa and its production is increased in patients with CPS. Hypoxia is associated with the production of VEGF by nasal fibroblasts and TNF-α and endotoxin may act synergistically to enhance VEGF production in paranasal sinuses under hypoxic condition. [Copyright &y& Elsevier]

A 66-year-old man visited our clinic suffering from swelling of right pharyngeal space. He was not aware of other symptoms. The contrast CT showed patchy enhancement with calcification. The enhanced MRI revealed a non-homogeneous signal pattern and patchy central enhancement. During surgery, egg-shaped hard elastic tumor was observed in parapharyngeal space without any sign indicating an invasion into surrounding nerves or feeding vessels. Then the tumor was removed without significant hemorrhage or damage to the cranial nerve. Histological examination of the tumor revealed a nodular lesion with blood clot and hematoma encapsulated with fibrous tissue having vascular spaces of irregular shape and size. From those findings, the tumor was diagnosed as papillary endothelial hyperplasia (PEH). However, since the location of the tumor differed from that of PEH commonly observed in the intravascular space, the tumor was classified as extravascular PEH. [ABSTRACT FROM AUTHOR]

Pustulosis palmaris et plantaris (PPP) is a skin disease considered to be caused by a focal infection of the palatine tonsils. We studied patients with PPP, recurrent tonsillitis and tonsillar hypertrophy, from whom tonsillar mononuclear cells (TNMC) and peripheral blood mononuclear cells (PBMC) were isolated; PBMC were collected again 6 months after surgery. The number of keratin-specific antibody-forming cells (AFC) in TNMC was found to be greater than those in PBMC as determined by ELISPOT assays, and were increased in patients with PPP when compared with patients with recurrent tonsillitis or tonsillar hypertrophy. In patients showing a remarkable improvement of PPP, the number of keratin-specific IgA AFC in TNMC was higher than in those who showed no improvement in their skin lesions. Further, the numbers of keratin-specific IgG AFC in PBMC were significantly decreased after surgery in patients with a good prognosis. The present results demonstrated the presence of keratin-specific immune responses in palatine tonsils. Further, keratin-specific IgA and IgG immune response in tonsils and peripheral blood were significantly correlated with the prognosis of PPP. Together, these findings suggest that keratin-specific immune responses in palatine tonsils might be associated with the pathogenesis of PPP. [Copyright &y& Elsevier]

In most peritonsillar abscess, the lesion is usually found in the superior pole of the palatine tonsil and typical symptoms such as trismus and resting of uvula are observed. On the other hand, inferior pole peritonsillar abscesses (IPPA) are rare and the symptoms are different from that of superior pole peritonsillar abscesses (SPPA). In the present study, the clinical aspects of patients with IPPA were compared with that of SPPA in order to clarify the characteristics of this disease. One hundred and six patients with peritonsillar abscess who were treated in our clinic between 1990 and 2002 were retrospectively investigated. The diagnosis of SPPA and IPPA was obtained by the findings of CT and during surgery. Among all patients, SPPA was found in 87% and IPPA, 13%. IPPA was more frequently observed in senior patients when compared with SPPA. Tonsil displacement and trismus were observed only in 25% and 17% of IPPA, respectively. The incidence of those symptoms was remarkably lower than that in SPPA. There was no significant difference in laboratory examinations between SPPA and IPPA. Bacteriological findings were quite different between IPPA and SPPA. Those results suggest that the pathogenesis of IPPA might be different from that of SPPA. [Copyright &y& Elsevier]

Background: Although various bacterial antigens are frequently found in upper respiratory tract mucosal secretions, fatal responses, such as endotoxin shock, are rare, suggesting the presence of some regulatory system in mucosal as well as systemic tissues. In the present study, we examined the immune responses of tonsillar mononuclear cells against bacterial antigens. Materials and methods: Mononuclear cells were isolated from the palatine tonsils and peripheral blood (tonsil mononuclear cells [TNMC] and peripheral blood mononuclear cells [PBMC]) of patients who underwent palatine tonsillectomy. TNMC and PBMC were stimulated using lipopolysaccharide (LPS) or lipoteichoic acid (LTA) for 24 h, and cytokine production were determined by ELISA. Furthermore, the expression of Toll-like receptor (TLR) 4 and TLR2 on CD14+ and CD11c+ cells were examined by FACS. Results: The production of TNFα, IL-1β, IL-6 and IL-8 from TNMC after stimulation with LPS or LTA were significantly lower than those from PBMC. Although CD11c+ cells were observed in both TNMC and PBMC, the incidence of TLR4 or TLR2 expressing cells was lower in TNMC than in PBMC. Conclusions: Results suggest that the decreased expression of TLR4 and TLR2 in TNMC might be associated with the hyporesponses of palatine tonsils against LPS and LTA. [Copyright &y& Elsevier]

Juvenile nasopharyngeal angiofibroma (JNA) tumors can be locally destructive when they spread submucosally. The purpose of this study was to present an image-guided, robotic radiotherapy (Cyberknife) to successfully treat a 12-year-old boy with Juvenile nasopharyngeal angiofibroma (JNA). He complained of progressive right nasal obstruction, intermittent epistaxis. Computed tomography (CT), and magnetic resonance imaging (MRI) revealed the presence of a tumor in the right nasal cavity and nasopharynx with significant hypervascularization from the right maxillary artery. Pathological findings confirmed the diagnosis of JNA. Surgical treatment was recommended but refused by religious reasons. We initially treated the patient with external-beam radiation therapy (total treatments, 12; total dose, 2400 cGy), which, after 7 months, failed to reduce the size of the tumor or relieve the patient''s symptoms. We subsequently treated the patient with Cyberknife therapy (total treatments, 3; total dose, 4512 cGy) and observed almost complete disappearance of the tumor after 7 months. After 2 years of observation, there has been no tumor recurrence. Cyberknife therapy is compared with other therapeutic options for JNA, and its benefits are discussed in the context of the findings in the literature. [Copyright &y& Elsevier]