Diagnostic utility of cytology in a patient with Epstein-Barr virus-positive mucocutaneous ulcer in palatine tonsils: A case report.

Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a newly established immunodeficiency-related disease. Herein, we report a case of EBVMCU and focus on its cytological usefulness for diagnosis. An 82-year-old man manifested pharyngalgia, dysphagia, and oral pain. His medical history included rheumatoid arthritis that had been treated with methotrexate. Clinically, peritonsillar abscess was suspected, but since neoplastic lesions, including malignant lymphoma (ML), could not be excluded, a series of cytohistological examination was attempted. Despite some alarming findings (e.g., frequent mitoses), fine-needle aspiration and touch imprint cytology consistently revealed a heterogeneous population of lymphoid and plasmacytoid cells with mild nuclear atypia. The final diagnosis of EBVMCU was established based on the permanent histologic specimen; however, retrospectively, cytology was more representative of the benign nature of the lesion than histology, helping a great deal to differentiate it from ML. Cytology can be a useful tool for the correct diagnosis of EBVMCU.

Predictors of adherence to sublingual immunotherapy for Japanese cedar pollinosis: a prospective analysis.

BACKGROUND: Sublingual immunotherapy (SLIT) often has low adherence rates. OBJECTIVE: To provide effective support for SLIT continuation, we investigated potential predictors of SLIT adherence through a prospective analysis of patient characteristics. We excluded evaluation of treatment effect and symptoms during treatment, aiming instead to identify predictors of later dropout or insufficient adherence due to indolence or forgetfulness using only information obtained at initial examination. METHODS: We provided patients with a questionnaire and monitored self-reported adherence once every 6 months. Cases of dropout for clear reasons were excluded, but cases of dropout or insufficient adherence to SLIT for indolence or forgetfulness were included. RESULTS: Fifty-three patients receiving SLIT were assessed. Nine patients dropped out after providing a clear reason. Thirty-four patients maintained good adherence. Seven patients continued SLIT but with insufficient adherence, while three patients discontinued SLIT for unclear reasons (indolence or forgetfulness) and these ten individuals were classified as the poor-adherence group. Univariate analysis and multivariate logistic regression analysis of the good-adherence and poor-adherence groups showed age to be a significant predictor of SLIT adherence. Based on analysis of a receiver operating characteristic curve, age < 40.5 years was selected as the optimal cutoff value for predicting poor adherence to SLIT. CONCLUSIONS: To prevent treatment SLIT discontinuation on account of indolence or forgetfulness, the necessity of longterm treatment continuity should be communicated clearly prior to commencing treatment, especially for patients under 40 years of age.

Congenital Membranous Stapes Footplate Producing Episodic Pressure-Induced Perilymphatic Fistula Symptoms.

Introduction: Recent third window syndrome studies have revealed that the intact bony labyrinth and differences in the stiffness of the oval and round windows are essential for proper cochlear and vestibular function. Herein we report a patient with a congenital dehiscence of the right stapes footplate. This dehiscence caused long-standing episodic pressure-induced vertigo (Hennebert sign). At the time of presentation, her increased thoracic pressure changes induced the rupture of the membranous stapes footplate. Perilymph leakage was confirmed by imaging and a biochemical test [perilymph-specific protein Cochlin-tomoprotein (CTP) detection test]. Case Report: A 32-year-old woman presented with a sudden onset of right-sided hearing loss and severe true rotational vertigo, which occurred immediately after nose-blowing. CT scan showed a vestibule pneumolabyrinth. Perilymphatic fistula (PLF) repair surgery was performed. During the operation, a bony defect of 0.5 mm at the center of the right stapes footplate, which was covered by a membranous tissue, and a tear was found in this anomalous membrane. A perilymph-specific protein CTP detection test was positive. The fistula in the footplate was sealed. Postoperatively, the vestibular symptoms resolved, and her hearing improved. A more detailed history revealed that, for 15 years, she experienced true rotational vertigo when she would blow her nose. After she stopped blowing her nose, she would again feel normal. Discussion: There is a spectrum of anomalies that can occur in the middle ear, including the ossicles. The present case had a dehiscence of the stapes, with a small membranous layer of tissue covering a bony defect in the center of the footplate. Before her acute presentation to the hospital, this abnormal footplate with dehiscence induced pathological pressure-evoked fluid-mechanical waves in the inner ear, which resulted in Hennebert sign. When patients have susceptibility (e.g., weak structure) to rupture, such as that identified in this case, PLF can be caused by seemingly insignificant events such as nose-blowing, coughing, or straining. Conclusion: This case demonstrates that PLF is a real clinical entity. Appropriate recognition and treatment of PLF can improve a patient's condition and, hence, the quality of life.

The diagnostic performance of a novel ELISA for human CTP (Cochlin-tomoprotein) to detect perilymph leakage.

Perilymphatic fistula is defined as an abnormal communication between the perilymph-filled space and the middle ear, or cranial spaces. The manifestations include a broad spectrum of neuro-otological symptoms such as hearing loss, vertigo/dizziness, disequilibrium, aural fullness, tinnitus, and cognitive dysfunction. By sealing the fistula, perilymphatic fistula is a surgically correctable disease. Also, appropriate recognition and treatment of perilymphatic fistula can improve a patient's condition and hence the quality of life. However, the difficulty in making a definitive diagnosis due to the lack of an appropriate biomarker to detect perilymph leakage has caused a long-standing debate regarding its management. We have reported a clinical test for the diagnosis of perilymphatic fistula by detecting a perilymph specific protein, Cochlin-tomoprotein, as a diagnostic marker using a western blot. The aim of this study is to establish an ELISA-based human Cochlin-tomoprotein detection test and to evaluate its diagnostic accuracy in clinical subjects. The results of ELISA showed good dilution reproducibility. The mean concentration was 49.7±9.4 of 10 perilymph samples. The ROC curve in differentiating the perilymph leakage condition from the normal middle ear was significant (P < 0.001) with an area under the curve (AUC) of 0.918 (95% CI 0.824-0.100). We defined the diagnostic criteria as follows: CTP<0.4 negative; 0.4≦CTP<0.8 intermediate; 0.8≦CTP(ng/ml) positive in the clinical usage of the hCTP ELISA, and sensitivity and specificity were 86.4% and 100%, respectively. We further tested the expression specificity of the Cochlin-tomoprotein by testing blood and CSF samples. The concentration was below the detection limit (0.2 ng/ml) in 38 of the 40 blood, and 14 of the 19 CSF samples. We report the accuracy of this test for the diagnosis of perilymphatic fistula. Using ELISA, we can improve the throughput of the test. Furthermore, it is useful for a large-scale study to characterize the clinical picture and delineate the management of this medical condition.

[ANALYSIS OF BACKGROUNDS AND LEVEL OF UNDERSTANDING OF TREATMENT OF POOR ADHERENCE AND DROPOUT CASES ON SUBLINGUAL IMMUNOTHERAPY FOR JAPANESE CEDAR POLLINOSIS IN THE FIRST FOLLOW-UP YEAR].

BACKGROUND: We considered the factors of poor adherence to and dropout from sublingual immunotherapy (SLIT) by verifying patient backgrounds 1 year after start of treatment. METHODS: We recruited 38 patients who began SLIT between November 2014 and September 2015. We analyzed their attributes and level of understanding of the treatment, and conducted a self-reported survey on factors behind dropout cases and poor adherence cases. RESULTS: Four patients dropped out 1 year after start of treatment. Three left for reasons related to anxiety about side effects. There were five cases of poor adherence. There was no significant difference between good adherence, poor adherence, and dropout regarding level of understanding of the treatment (p=0.59). In the comparison between good and poor adherence groups, except four dropout patients, the adherence tended to be poor in patients with short duration of disease, smoking patients, and young patients. Continuous rate of SLIT achieved about 90%, suggesting relatively high level of adherence. CONCLUSION: It appears possible that anxiety related to side effects could be a factor affecting dropout from SLIT. There was no significant difference regarding level of understanding of the treatment. The adherence tended to be poor in patients with short duration of disease, smoking patients, and young patients.

A nationwide multicenter study of the Cochlin tomo-protein detection test: clinical characteristics of perilymphatic fistula cases.

OBJECTIVE: To investigate the positive rate for the Cochlin tomo-protein (CTP: an inner ear-specific protein) detection test among patients with inner ear-related clinical manifestations and evaluate the clinical characteristics of definite perilymphatic fistula (PLF). METHODS: We have performed an ELISA-based CTP detection test using middle ear lavage (MEL) samples from 497 cases of suspected PLF enrolled from 70 clinical centers nationwide between 2014 and 2015. In addition to the CTP-positive rate, audio-vestibular symptoms were compared between CTP-positive and -negative cases. RESULTS: 8-50% of patients in category 1 (trauma, middle and inner ear disease cases), and about 20% of those in categories 2, 3 and 4 (external origin antecedent events, internal origin antecedent events, and without antecedent event, respectively) were positive for CTP. In category 1 cases, the earlier tested samples showed a higher CTP-positive rate, whereas no differences were observed in categories 2, 3 or 4. The characteristic clinical features in the earlier tested cases were nystagmus and fistula sign in CTP test-positive cases in category 1, and streaming water-like tinnitus in those in categories 2, 3 and 4. CONCLUSION: The present study clarified that CTP detection test-positive patients exist at considerable rates among patients with inner ear-related manifestations.

Unidirectional abnormal eye movement without gaze nystagmus - Report of a case.

We report here a case with unidirectional abnormalities of smooth eye movements without gaze nystagmus. Abnormalities of eye movements were confined to unidirectional (leftward) horizontal pursuit and slow phase of OKN; however, horizontal VOR (slow phase of caloric nystagmus) and saccade were normal, and vertical eye movements were also normal. No lesions were detected in the central nervous system, and any history of drug intake was denied. Although the cause of the unidirectional abnormality in eye movement of this case is still not clear, a congenital origin seems to be the most probable.

[Postural and Conditional Variations of Nasal Patency in Patients under General Anesthesia Approximating Sleep as Assessed with Acoustic Rhinometry].

Nasal obstruction is a known risk factor associated with obstructive sleep apnea (OSA). Multiple methods of measuring nasal abnormalities including anterior and posterior rhinomanometry and acoustic rhinometry (AR) have been used to better quantify the relationship. These measurements are usually used in the sitting and awakening situation, which differ from the situations in the supine position and while asleep. The goal of this study was to evaluate the nasal patency in patients under general anesthesia approximating sleep as assessed with AR. The nasal minimal cross-sectional area (MCSA) and nasal volume in 50 patients who underwent general anesthesia were compared with subjects in the sitting, supine, and supine position under general anesthesia using AR to measure the nasal dimensions and patency. MCSA and nasal volume decreased more significantly in the supine than in the sitting subjects and these decrements were shown more in the supine position under general anesthesia than in the supine position without anesthesia. Furthermore, regarding nasal volume, the difference between in the sitting and in the supine was larger than the difference between in the supine position with and without general anesthesia. These results suggested that the decrements regarding nasal volume under positional change were greater than those under conditional change. The positional variation can affect the airway patency hydrodynamically and these alterations indicate the relationship of the pathophysiology in patients with OSA.

[Effect of posterior nasal neurectomy combined with the inferior turbinate surgery for Japanese cedar pollinosis].

INTRODUCTION: Up to 30% of the Japanese population suffers from Japanese cedar pollinosis, and some of these patients also have severe perennial allergies or other pollen allergies. Posterior nasal neurectomy has recently been reported as effective treatment for severe perennial allergic and intrinsic rhinitis. However, the efficacy of this surgery for seasonal allergic rhinitis has not been shown. In this study, the effectiveness of posterior nasal neurectomy combined with inferior turbinate surgery for patients with Japanese cedar pollinosis with concomitant intractable perennial allergies was evaluated with a questionnaire. SUBJECTS AND METHODS: Nine patients with Japanese cedar pollinosis, who also had perennial allergies, and undergone posterior nasal neurectomy combined with inferior turbinate surgery from April in 2005 to July in 2008, were enrolled. A numeric rating scale (NMR) was used to evaluate clinical symptoms in the pre- and post-surgery periods. The frequency of medication (oral administration and nasal spray) during the cedar pollinosis season was also evaluated. RESULTS: The NMR scores for all nasal and eye symptoms during cedar pollinosis season were significantly reduced after the surgery. The frequency of medication during the season was dramatically decreased after surgery. CONCLUSION: The present study demonstrates that posterior nasal neurectomy combined with inferior turbinate surgery is a highly effective treatment for Japanese cedar pollinosis. Since the Japanese cedar pollinosis season is limited to 2 to 3 months, such surgery is indicated for patients who suffer from severe perennial allergies and are also sensitized to some allergens such as Japanese cedar and ragweed pollen.

Five adult laryngeal venous malformation cases treated effectively with sclerotherapy.

OBJECTIVES/HYPOTHESIS: Laryngeal venous malformation is a comparatively rare condition in adults. It presents as a livid or bluish mass that may cause bleeding, hoarseness, stridor, and even difficulty in breathing. So far, treatment has largely consisted of laser therapy and surgical removal. Five cases of adult laryngeal venous malformations that were treated by sclerotherapy (local injection of monoethanolamine oleate solution) are reported. All lesions disappeared after one or two treatment sessions, and two of the five cases that presented recently were cured in the outpatient clinic setting with no sequelae. Sclerotherapy with monoethanolamine oleate is a safe, easy, and effective treatment for laryngeal venous malformations.

[Effect of posterior nasal neurectomy combined with the inferior turbinate surgery for the patients with perennial allergic rhinitis or vasomotor rhinitis].

INTRODUCTION: Until recently, Vidian neurectomy had been applied mainly in intractable vasomotor rhinitis and severe perennial allergic rhinitis. Although the results were excellent, the operation has not been applied recently because of the adverse events such as xerophthalmia and trigeminal neuralgia. To resolve these problems, a new surgical technique, posterior nasal neurectomy, was developed. In this report, we examined the effectiveness of posterior nasal neurectomy combined with the inferior turbinate surgery for severe perennial allergic rhinitis and intrinsic rhinitis by questionnaire. PATIENTS AND METHODS: Twenty patients who had undergone posterior nasal neurectomy combined with the inferior turbinate surgery between April in 2005 and March in 2009 were enrolled. Numeric Rating Scale was used to evaluate clinical symptoms and quality of life (QOL) of pre- and postsurgery. Frequency of medication (oral administration and nasal spray) was also evaluated. RESULTS: Questionnaires were collected from 17 patients. As for all patients but one, the surgery significantly reduced rhinorrhea, nasal obstruction, and sneezing. Furthermore, QOL for many symptoms such as sleep disorder and malaise/feebleness was also significantly improved after the surgery. Eighty-one percent of patients were satisfied with the surgery. CONCLUSION: Posterior nasal neurectomy combined with the inferior turbinate surgery is effective in alleviating clinical symptoms and improving QOL in the patients with severe perennial allergic rhinitis and intrinsic rhinitis, although a longer follow-up is needed.

[Prevalence of allergic rhinitis among asthmatic patients in two different seasons].

INTRODUCTION: Allergic rhinitis and asthma are often comorbid, and allergic rhinitis has been shown to be a risk factor for asthma in adults and children. Recently, the prevalence of allergic rhinitis among bronchial asthma (BA) patients was reported to be 67.3% in Japan. However, seasonal variation in the prevalence of rhinitis in Japan remains unclear. OBJECTIVES AND METHODS: To investigate the seasonal differences in comorbid allergic rhinitis among asthmatic patients, a survey of BA outpatients aged six years and older was conducted at the Allergy Center, Saitama Medical University. In total, 150 patients (mean age, 43.8±21.8 years old) in summer 2012 and 181 patients (mean age, 48.7±18.3 years old) in spring 2013 completed the Self Assessment of Allergic Rhinitis and Asthma (SACRA) questionnaire. RESULTS: The prevalence of allergic rhinitis in BA patients was 50% in the summer of 2012 and 85.6% in the spring of 2013, indicating a significant seasonal variation. Control of asthma was significantly poorer in both seasons in patients with rhinitis compared to those without rhinitis. Furthermore, in patients with moderate/severe-persistent rhinitis, control of asthma was significantly worse than in patients with mild-intermittent rhinitis in spring 2013, but not in summer 2012. CONCLUSION: Although the comorbidity rate of rhinitis among BA patients was greater in the spring than in the summer, rhinitis is thought to be closely related with asthma control regardless of the season.

Efficacy of combined treatment with S-carboxymethylcysteine (carbocisteine) and clarithromycin in chronic rhinosinusitis patients without nasal polyp or with small nasal polyp.

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.

[IgG4-related Mikulicz's disease: a report of 3 cases].

INTRODUCTION: We report three cases of hyper-IgG4 disease with synchronous or asynchronous lymphocytic infiltration onset, IgG4 positive plasma cell infiltration, and fibril formation in multiple exocrine glands and extranodal organs. IgG4-related sialadenitis attracting recent attention has yet to be clarified as a clinical entity. CASE REPORT: Case 1, a 61-year-old man, had a submandibular gland sample showing IgG4-positive plasma cell infiltration. Case 2, a 61-year-old man, was diagnosed with IgG4-related Mikulicz's disease confirmed by a sublingual gland sample. Case 3, a 57-year-old woman, had a diagnosis of IgG4-related Mikulicz's disease confirmed based on labial and sublingual gland samples. All reported oral dryness and bilateral submandibular swelling. Cases 1 and 2 recovered following Predonine administration tapered from 30 or 20 mg. DISCUSSION: IgG4-related Mikulicz's disease must be recognized as a clinical entity, together with its diagnostic criteria and treatment. Sublingual gland biopsy should be done to confirm its diagnosis following sublingual gland swelling.

[Questionnaire for determining relationship between nasal and asthma symptoms].

BACKGROUND: The interaction between allergic rhinitis and bronchial asthma is well known. However, there is little epidemiological data on the relationship between nasal diseases and asthma, especially in Japan. METHODS: We administered a questionnaire to 126 patients to examine the frequency of associations between nasal and asthma symptoms in patients with both nasal disease and asthma. We also investigated in which type of patients the asthma symptoms were affected by changes in nasal symptoms. RESULTS: Thirty-eight patients (30%) were aware that their asthma was worsened by exacerbated nasal disease, and nasal treatment improved asthma in 28 patients (22%). The influence of changes in nasal symptoms on asthma symptoms was stronger in patients lacking good asthma control. The relationship between nasal and asthma symptoms tended to be stronger in patients with sinusitis. CONCLUSION: About 30% of patients with nasal disease and asthma reported an association between their nasal and asthma symptoms. Nasal treatment is considered to be important for asthma control, especially in patients with asthma symptoms. These results suggested the important role of comprehensive allergy care in controlling both nasal disease and asthma.

[Statistical study on the case of aural foreign bodies].

Although aural foreign bodies are very frequently seen in daily practice, few reports systematically analyze a large case population. We report 509 cases seen at our clinic during the 16 years from January 1986 to December 2001. All were clinically confirmed during the same period among a total of 68,579 new visitors and cases with aural foreign bodies accounted for 0.74%. Cases seen during routine outpatient clinic hours were 161 (31.6%), and others seen in emergencies were 348 (68.4%). Among these were 307 men (60.3%) and 202 women (39.7%). The right side involved 251 (49.3%), the left side 241 (47.3%), and bilateral 4 (0.8%). Monthly distribution showed an average of 42.4 cases a month, peaking during the months of July and August, when temperatures are highest. Age distribution showed an average of 25.4 years old, ranging from 1 month to 90 years of age. Those under 9 years numbered 182 (35.8%) and were the peak incidence by age. In classification by organic and inorganic, organic materials accounted for 206 (40.5%) and inorganic for 288 (56.6%). Organic materials appeared to be related to monthly distribution, i.e. more cases in hot months.

Caspase 3 activation in nasal capillary in patients with epistaxis.

OBJECTIVE: We investigated whether an apoptosis of nasal microvessels contributes to probable mechanism of the onset of epistaxis. STUDY DESIGN AND SETTING: Nasal septal mucosa of Little's areas taken from patients without (n = 19) and with (n = 26) epistaxis were examined. Active caspase-3 in the mucosa was detected according to the methods of immunohistochemistry and Western blotting. On Western blot analysis of the homogenates of the mucosa, we also sought probable signaling factors after caspase-3 activation. RESULTS: Marked activation of caspase-3 was detected in the capillaries and its neighboring muscle cells of Little's area from patients with epistaxis, and the activation was due to enhanced expression of procaspase-3 protein and progressive cleavage of the precursor. As a result of Western blotting of signaling factors, enhanced expressions of caspase-9 and Bax protein in the homogenates of Little's area in epistaxis group were found compared with those in control group. Increased levels of cytochrome c released into a cytosol were also detected in the capillaries in epistaxis group. CONCLUSION: In the present study, caspase-3 activation was found in the capillaries of Little's area from patients with epistaxis, suggesting that an apoptosis of capillaries may contribute to a mechanism of the onset of epistaxis. Moreover, alterations of some apoptotic factors such as caspase-9, Bax, and cytochrome c in the tissues demonstrated participation of mitochondrial disturbance in one of the apoptotic mechanisms. SIGNIFICANCE: Further explorations of the pathobiologic mechanism of capillary apoptosis can lead not only to an identification of risk factors in the onset of epistaxis but also to the development of medical therapy of epistaxis.