Search

Objective Transglutaminase (TGM)2 and peroxisome proliferator-activated receptor (PPAR)γ are thought to participate in the pathogenesis of nasal polyp formation in cystic fibrosis (CF). We herein investigated expressions of cystic fibrosis transmembrane conductance regulator (CFTR), TGM2, PPARγ and isopeptide bonds, a reaction product of TGM, in non-CF nasal polyps. Methods Nasal polyps and inferior turbinates were collected from chronic rhinosinusitis patients without CF during transnasal endoscopic sinonasal surgery. Expressions of CFTR, TGM2, isopeptide bonds and PPARγ were examined by fluorescence immunohistochemistry and quantitative RT-PCR. Expression of CFTR was also analyzed by Western blot. Results Immunohistochemical fluorescence of the nasal polyp was significantly lower for CFTR and PPARγ, and significantly higher for TGM2 and isopeptide bonds than that of the turbinate mucosa. Lower expression of CFTR in the nasal polyp than in the turbinate mucosa was also observed in Western blot. Expression of PPARG mRNA was significantly lower in the nasal polyp than in the turbinate mucosa, whereas expressions of CFTR mRNA or TGM2 mRNA did not differ between the two tissues. Immunohistochemical fluorescence for CFTR showed significant negative correlation with that for TGM2 and isopeptide bonds, and significant positive correlation with that for PPARγ. The fluorescence for TGM2 was positively correlated with that for isopeptide bonds and negatively correlated with that for PPARγ. The fluorescence for isopeptide bonds tended to be negatively correlated with that for PPARγ. Conclusions These results suggest a possible role of the CFTR-TGM2-PPARγ cascade in the pathogenesis of nasal polyp formation in non-CF patients as in CF patients.

Background Mucociliary transport function in the airway mucosa is essential for maintaining a clean mucosal surface. This function is impaired in upper and lower airway diseases. Nasal polyps are a typical pathological feature of prolonged rhinosinusitis. Like the ordinary nasal mucosa, nasal polyps have a ciliated pseudostratified epithelium with vigorous ciliary beating. We herein measured ex vivo mucociliary transport velocity (MCTV) and ciliary beat frequency (CBF) and explored the expressions of planar cell polarity (PCP) proteins in nasal polyps in comparison with turbinate mucosae. Methods Inferior turbinates and nasal polyps were collected from patients with chronic rhinosinusitis during endoscopic sinonasal surgery. Ex vivo MCTV and CBF were measured using a high-speed digital imaging system. Expressions of PCP proteins were explored by fluorescence immunohistochemistry and quantitative RT-PCR. Results The MCTV of nasal polyps was significantly lower than that of the turbinates (7.43±2.01 vs. 14.56±2.09μm/s; P=0.0361), whereas CBF did not differ between the two tissues. The MCTV vector was pointed to the posteroinferior direction in all turbinates with an average inclination angle of 41.0 degrees. Immunohistochemical expressions of Dishevelled-1, Dishevelled-3, Frizzled3, Frizzled6, Prickle2 and Vangl2 were lower in the nasal polyps than in the turbinates. The expression levels of mRNAs for Dishevelled-1, Dishevelled-3 and Frizzled3 in the nasal polyps were also decreased in comparison with the turbinates. Conclusions These results indicate that ciliary transport in nasal polyps is impaired although vigorous ciliary beating is maintained, and that the impairment may be caused by a decrease in Dishevelled/Frizzled proteins and resultant PCP disarrangement.

Background: Nasal breathing is important for maintaining physiological respiration. However, airflow in the nasal cavity has an inherent cooling effect and may suppress ciliary beating, an essential frontline defense in the airway. Nasal airflow is thought to be perceived by transient receptor potential (TRP) M8, a thermoreceptor for cool temperatures. We herein investigated the effect of the activation of thermosensitive TRPs for cool/cold temperatures on ciliary beating and searched for a compensatory mechanism that maintains ciliary beating against the fall of temperature in the human nasal mucosa. Methods and Results: Inferior turbinates were collected from patients with chronic hypertrophic rhinitis, and ex vivo ciliary beat frequency (CBF) was immediately measured using a high-speed digital video camera attached to a phase-contrast light microscope. The samples were also subjected to fluorescence immunohistochemistry and real-time RT-PCR for TRPA1/TRPM8. CBF was significantly increased by adding either cinnamaldehyde (TRPA1 agonist) or l-menthol (TRPM8 agonist), and this increase was inhibited by pannexin-1 blockers, carbenoxolone and probenecid. Immunohistochemistry detected TRPA1 and TRPM8 on the epithelial surface and in the submucosal nasal glands. Expressions of mRNAs for these receptors were confirmed by real-time RT-PCR. Conclusions: These results indicate the stimulatory effect of the activation of TRPA1/TRPM8 on ciliary beating in the nasal mucosa, which would be advantageous to maintain airway mucosal defense under normal nasal breathing. This stimulatory effect is likely to be mediated by pannexin-1. Understanding the regulatory mechanism of airway ciliary beating should aid in the development of new, effective treatments for intractable airway diseases. BackgroundNasal breathing is important for maintaining physiological respiration. However, airflow in the nasal cavity has an inherent cooling effect and may suppress ciliary beating, an essential frontline defense in the airway. Nasal airflow is thought to be perceived by transient receptor potential (TRP) M8, a thermoreceptor for cool temperatures. We herein investigated the effect of the activation of thermosensitive TRPs for cool/cold temperatures on ciliary beating and searched for a compensatory mechanism that maintains ciliary beating against the fall of temperature in the human nasal mucosa.

Background: The ciliary beat of the airway epithelium, including the sinonasal epithelium, has a significant role in frontline defense and is thought to be controlled by the level of intracellular Ca2+. Involvement of calmodulin and adenylate/guanylate cyclases in the regulation of ciliary beats has been reported, and here we investigated the interrelation between these components of the ciliary beat regulatory pathway. Methods: The inferior turbinates were collected from 29 patients with chronic hypertrophic rhinitis/rhinosinusitis during endoscopic sinonasal surgery. The turbinate mucosa was cut into thin strips, and mucociliary movement was observed under a phase-contrast light microscope equipped with a high-speed digital video camera. Results: The ciliary beat frequency (CBF) was significantly increased by stimulation with 100 μM CALP3 (calmodulin agonist), which was completely suppressed by adding 100 µM SQ22536 (adenylate cyclase inhibitor) and 10 µM ODQ (guanylate cyclase inhibitor) together and by adding 1 µM KT5720 (protein kinase A inhibitor) and 1 µM KT5823 (protein kinase G inhibitor) together. The CBF was significantly increased by stimulation with 10 µM forskolin (adenylate cyclase activator) and 10 µM BAY41-2272 (guanylate cyclase activator) and by stimulation with 100 µM 8-bromo-cAMP (cAMP analog) and 100 µM 8-bromo-cGMP (cGMP analog), which was not changed by adding 1 µM calmidazolium (calmodulin antagonist). Conclusions: These results confirmed that the regulatory pathway of ciliary beats in the human nasal mucosa involves calmodulin, adenylate/guanylate cyclases, and protein kinases A/G and indicate that adenylate/guanylate cyclases and protein kinases A/G act downstream of calmodulin, but not vice versa, and that these cyclases relay calmodulin signaling.

Pompe disease is an autosomal recessive disorder caused by deficiency of the acid α-glucosidase (GAA) enzyme. GAA deficiency induces progressive glycogen accumulation which leads to weakness of the respiratory muscle including the diaphragm. Pompe disease is one of the few myopathies, for which an established therapy is available. Thus, earlier detection of potential late-onset Pompe disease (LOPD) and earlier intervention would have a significant clinical impact. Our hypothesis is that sleep problems including sleep disordered breathing (SDB) and clinical symptoms may indicate an early stage of LOPD since decreased respiratory muscle activity generally first presents during sleep. Thus, the aims of this prospective, multicenter observational cohort study in Japan (PSSAP-J) are to demonstrate a higher prevalence of LOPD in a sleep lab–based population (primary outcome), and to identify predictive factors for LOPD from findings in diagnostic polysomnography (PSG) and clinical symptoms (secondary outcomes). The study design is a prospective multicenter observational cohort study. Consecutive patients who present to sleep labs due to suspected SDB for an overnight PSG will be enrolled. All patients will be measured for creatine kinase, GAA activity, and if necessary, genetic analysis of GAA. Furthermore, chest X-ray, pulmonary function test, and arterial blood gas analysis will be collected. Then, prevalence and specific findings of LOPD will be assessed. Congenital myopathy shows a shift from slow-deep to rapid-shallow breathing during transition from wakefulness to sleep accompanying a symptom of waking with gasping (actual further results are pending). The distribution in respiratory physiology between during wakefulness and sleep specific to LOPD may provide insights into early-stage detection. UMIN000039191, UMIN Clinical Trials Registry ( http://www.umin.ac.jp/ctr ).

Background: Hearing recovery would be different in each sound frequency in patients with idiopathic sudden sensorineural hearing loss (ISSNHL).Aims/objectives: To analyze frequency-specific efficac...

Nasal polyp formation is a common sequela of prolonged chronic rhinosinusitis, but the mechanism underlying this disease state is still controversial. We compared the expressions of Cl− channels/transporters in nasal polyps with those in inferior turbinates to explore whether a deficiency in Cl− transport may participate in the pathophysiology of nasal polyp formation as in patients with cystic fibrosis. Nasal polyps and inferior turbinates were collected from 12 chronic rhinosinusitis patients with hypertrophic rhinitis and/or nasal polyps. Expressions of cystic fibrosis transmembrane conductance regulator (CFTR), pendrin, Na+–K+–2Cl− cotransporter 1 (NKCC1), SLC26A3, TMEM16A and anion exchanger 2 (AE2) were examined by fluorescence immunohistochemistry using Alexa Fluor 488. CFTR was weakly expressed on the epithelial surface of the turbinate mucosa whereas the nasal polyps showed almost no fluorescence. Pendrin was mainly expressed on the epithelial surface in both tissues. The fluorescence was moderate in the nasal polyps and strong in the turbinate mucosa. For NKCC1, moderate fluorescence was observed throughout the entire epithelial layer of the nasal polyps, but the turbinate mucosa exhibited almost no fluorescence. On the other hand, no fluorescence for SLC26A3, TMEM16A or AE2 was seen in either tissue. These results suggest that CFTR, pendrin and NKCC1 may participate in the pathogenesis of nasal mucosal edema and play roles in the mechanism of nasal polyp formation.

The hearing outcome of idiopathic sudden sensorineural hearing loss (ISSNHL) is hard to predict. We herein constructed a multiple regression model for hearing outcomes in each frequency separately in an attempt to achieve practical prediction in ISSNHL.We enrolled 235 consecutive in-patients with ISSNHL who were treated in our department from 2015 to 2020 (average hearing level at 250-4000 Hz ≥ 40 dB; time from onset to treatment ≤ 14 days; 126 males/109 females; age range 17-87 years (average 61.0 years)). All patients received systemic prednisolone administration combined with intratympanic dexamethasone injection. The pure-tone hearing threshold of 125-8000 Hz was measured at every octave before (HLThe multiple correlation coefficient increased as the frequency increased. Strong correlations were seen in high frequencies, with multiple correlation coefficients of 0.784/0.830 for 4000/8000 Hz. The width of the 70% prediction interval was narrower for 4000/8000 Hz (± 18.2/16.3 dB) than for low to mid-frequencies. Among the five explanatory variables, HLThe present model would be of practical use for predicting hearing outcomes in high frequencies in patients with ISSNHL.

Background Mucociliary clearance of the airway epithelium is an essential function for mucosal defense. We recently proposed a hypothetical mechanism of ciliary beat regulation, in which the pannexin-1 (Panx1)-P2X7 unit serves as an oscillator generating a periodic increase in intracellular Ca2+ ([Ca2+ ]i ). In the present study, we examined the localization of Panx1 and P2X7 at the ultrastructural level, and investigated the regulatory pathway subsequent to [Ca2+ ]i increase. Methods The inferior turbinate mucosa was collected from patients with chronic hypertrophic rhinitis during endoscopic sinonasal surgery. The mucosa was examined by transmission immunoelectron microscopy for Panx1 and P2X7. Alternatively, the mucosa was cut into thin strips, and ciliary beat frequency (CBF) was measured under a phase-contrast light microscope with a high-speed digital video camera. Results In immunoelectron microscopy, immunoreactivities for Panx1 and P2X7 were localized along the plasma membrane of the entire length of the cilia. CBF was significantly increased by stimulation with 100 µM acetylcholine (Ach). The Ach-induced CBF increase was significantly inhibited by calmidazolium (calmodulin antagonist), SQ22536 (adenylate cyclase inhibitor), ODQ (guanylate cyclase inhibitor), KT5720 (protein kinase A inhibitor), and KT5823 (protein kinase G inhibitor). Fluorodinitrobenzene (creatine kinase inhibitor) completely inhibited the ciliary beat in a time- and dose-dependent manner. Conclusion These results indicate that Panx1 and P2X7 coexist at the cilia of the human nasal epithelial cells and that the ciliary beat is regulated by calmodulin, adenylate/guanylate cyclases and protein kinases A/G, and crucially depends on creatine kinase.

Purpose We retrospectively studied the efficacy of intratympanic steroid administration in comparison with hyperbaric oxygen (HBO) therapy for idiopathic sudden sensorineural hearing loss (ISSNHL) with negative prognostic factors. Method We enrolled 301 patients (302 ears) with ISSNHL (average hearing level at 250–4000 Hz ≥ 40 dB; time from onset to treatment ≤ 30 days). From August 2002 to March 2009, 174 patients (174 ears) received systemic steroid plus HBO therapy (HBO group), and from June 2015 to January 2018, 127 patients (128 ears) received systemic plus intratympanic steroid (IT group). Hearing outcomes were evaluated by 6 indices: cure rate, marked-recovery rate (percent of patients with hearing gain ≥ 30 dB), recovery rate (percent of patients with hearing gain ≥ 10 dB), hearing gain, hearing level after treatment, and percent hearing improvement compared to the unaffected contralateral ear. Results The recovery rate was significantly higher in the IT group than in the HBO group (80.5% vs. 68.4%, p = .019). The IT group showed a higher recovery rate than the HBO group in patients aged ≥ 60 years ( p = .010), patients with early (≤ 7 days from onset) treatment ( p = .005), patients with initial hearing levels ≥ 90 dB ( p = .037), and patients with vertigo/dizziness ( p = .040). The IT group also showed higher hearing gain and percent hearing improvement than the HBO group in patients with vertigo/dizziness ( p = .046 and p = .026, respectively). Conclusions Systemic plus intratympanic steroid is more effective for ISSNHL than systemic steroid plus HBO, particularly in patients with negative prognostic factors, such as old age, profound hearing loss, and/or presence of vertigo/dizziness.

Nasal polyp formation is a common sequela of prolonged chronic rhinosinusitis, but the mechanism underlying this disease state is still controversial. We compared the expressions of ClNasal polyps and inferior turbinates were collected from 12 chronic rhinosinusitis patients with hypertrophic rhinitis and/or nasal polyps. Expressions of cystic fibrosis transmembrane conductance regulator (CFTR), pendrin, NaCFTR was weakly expressed on the epithelial surface of the turbinate mucosa whereas the nasal polyps showed almost no fluorescence. Pendrin was mainly expressed on the epithelial surface in both tissues. The fluorescence was moderate in the nasal polyps and strong in the turbinate mucosa. For NKCC1, moderate fluorescence was observed throughout the entire epithelial layer of the nasal polyps, but the turbinate mucosa exhibited almost no fluorescence. On the other hand, no fluorescence for SLC26A3, TMEM16A or AE2 was seen in either tissue.These results suggest that CFTR, pendrin and NKCC1 may participate in the pathogenesis of nasal mucosal edema and play roles in the mechanism of nasal polyp formation.

Although many studies have investigated the clinical importance of sleep apnea on rapid eye movement (REM) and non-REM (NREM) sleep, the relationship between behavioral performance and apneic events during different sleep phases remains unclear. In the present study, we sought to investigate the effect of sleep phase fragmentation due to sleep-disordered breathing (SDB) during REM and NREM on the vigilance and sustainability of attention based on psychomotor vigilance task (PVT) performance. From a pool of subjects who underwent consecutive diagnostic polysomnography (PSG) for obstructive sleep apnea, 163 adult subjects with both REM and NREM sleep ≥ 30 min were enrolled for our study and performed a standardized 10-min PVT. The main outcome variables of the PVT were mean reaction time (RT), PVT Lapse count, and the slope of the reciprocal RT. Subjective sleepiness was measured using the Epworth Sleepiness Scale (ESS). After multivariate linear regression analysis with adjustment for age, sex, body mass index, and the apnea-hypopnea index (AHI) of the counterpart sleep phase, we found that AHI during NREM (AHINREM) compared to AHI during REM (AHIREM) was significantly associated with PVT lapses. Our results suggest that SDB during NREM has a significant impact on vigilance lapses compared to that of REM.

Conclusions The prevalence of obstructive sleep apnea (OSA) in preschool-aged children diagnosed by the International Classification of Sleep Disorders (ICSD) version 3 criteria was relatively higher than that diagnosed by ICSD-2. Although the assessment of the upper airway by lateral neck radiography was effective for detecting OSA in this age group, this assessment is not recommended for all children as a screening method because of parental concern related to radiation exposure. Objective This study investigated the prevalence of OSA and the screening capacity of lateral neck radiography in community-based preschool-aged children. Methods Parents of 211 children aged 3-6 years were requested to complete the sleep-related questionnaire. Subjects who agreed to further investigations were invited to undergo home type 3 portable monitoring and clinical examination, including radiography. We estimated the prevalence of OSA and evaluated the detection power of radiography for predicting OSA. Results One hundred and eighty-eight (89.1%) subjects completed the questionnaire and 67 (31.8%) agreed to further examinations. The weighted prevalence was 7.3% and 12.8% by ICSD-2 and 3, respectively. Area under the receiver operator curve for the adenoidal/nasopharyngeal and tonsil/pharyngeal ratios measured using radiography was slightly larger than that for tonsil size graded by visual inspection.

We studied the effect of intratympanic steroid administration with different intervals on hearing outcomes in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). The subjects were 197 consecutive patients (197 ears) with ISSNHL (hearing level ≥40 dB, interval between onset and treatment ≤30 days). They received systemic administration of prednisolone (100 mg followed by tapered doses) combined with intratympanic injection of dexamethasone (4 mg/ml). Intratympanic injection was performed once a week for 4 weeks in 105 patients (long-interval group), or 4 times in 1 week in 92 patients (short-interval group). The hearing outcomes were evaluated at two points of time: 1 week from the start of treatment, and 1-2 months after the completion of treatment when the hearing level reached a plateau. There was no significant difference in the cure rate, marked-recovery rate, recovery rate, hearing gain, hearing level, or percent hearing improvement between the long- and short-interval groups at either point of time. Multiple regression analysis also showed that the final hearing level did not depend on the interval of intratympanic steroid injection. These results indicate that the hearing outcome of ISSNHL does not improve even if the interval of intratympanic injection is shortened. This implies that a lower total number of intratympanic steroid injections may be as effective as the present protocol.

Objective: We studied the effect of intratympanic steroid administration with different total injection times on hearing outcomes in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). Methods: The subjects were 191 consecutive patients (192 ears) with ISSNHL (hearing level ≥40 dB, interval between onset and treatment ≤30 days). They received systemic prednisolone (100 mg followed by tapered doses) combined with intratympanic injection of dexamethasone (4 mg/ml). Intratympanic injection was performed 4 times (days 1, 2, 4, and 7) in 92 patients (92 ears) or 2 times (days 1 and 2) in 99 patients (100 ears). The hearing outcomes were evaluated at 1 week from the start of treatment and 1 to 2 months after the completion of treatment. Results: There was no significant difference in hearing outcomes between the 4- and 2-injection groups at either time point. Multiple regression analysis also showed that the hearing level after treatment did not depend on the total number of intratympanic steroid injections. Conclusion: These results indicate that a protocol using only 2 intratympanic steroid injections exerts a sufficient effect on the hearing outcomes of ISSNHL. This simplified treatment protocol would be greatly beneficial to relieve the physical and mental stress of patients.

Purpose: We investigated the electrical impedance and expression of tight junction components of the turbinate mucosa, nasal polyp, and normal skin. Procedures: The inferior turbinate and nasal polyp of patients with chronic rhinosinusitis and the postauricular skin of patients with otitis media were examined. Electrical impedance was measured in vivo using a tissue conductance meter. Expressions of claudin-1 and tricellulin were examined by fluorescence immunohistochemistry and quantitative RT-PCR. Results: Electrical impedance was higher in the skin than in the turbinate and polyp, but did not differ between the turbinate and polyp. Immunoreactivities for claudin-1 and tricellulin were seen in the epithelial/epidermal layer. Expression of claudin-1 was higher in the skin than in the turbinate and polyp. The polyp tended to show higher expression of claudin-1 but showed lower expression of tricellulin than the turbinate. The ratio of claudin-1 to tricellulin was highest in the skin and lowest in the turbinate. The correlation between expressions of the two tight junction components was strongly positive in the skin (r = 0.964) and negative (r = -0.527) in the turbinate and polyp. Conclusions: These results suggest that the roles of claudin-1 and tricellulin in barrier function may be complementary, and may thereby maintain a constant level of permeability of the mucosal tissues.

Now the world works day and night, termed as the ‘unsleeping society’. Consequently, an increasing number of people are facing a biological cycle opposite to the natural day–night cycle by ‘working at night and sleeping in the daytime’. Compared with other countries, Japan has one of the highest incidences of short sleep duration similar to South Korea. Lack of sleep greatly affects our daily lives. It is now time for us to reconsider the importance of sleep to experience a high-quality and healthy life both physically and psychologically. Since the establishment of a funded course module on Somnology in Shiga University of Medical Science in 2004, the authors have been implementing awareness-raising activities on the significance of sleep not only for students in higher education but also on a broader social spectrum.

Objective: This study aimed to create a multiple regression model for predicting hearing outcomes of idiopathic sudden sensorineural hearing loss (ISSNHL). Methods: The participants were 205 consecutive patients (205 ears) with ISSNHL (hearing level ≥ 40 dB, interval between onset and treatment ≤ 30 days). They received systemic steroid administration combined with intratympanic steroid injection. Data were examined by simple and multiple regression analyses. Three hearing indices (percentage hearing improvement, hearing gain, and posttreatment hearing level [HLpost]) and 7 prognostic factors (age, days from onset to treatment, initial hearing level, initial hearing level at low frequencies, initial hearing level at high frequencies, presence of vertigo, and contralateral hearing level) were included in the multiple regression analysis as dependent and explanatory variables, respectively. Results: In the simple regression analysis, the percentage hearing improvement, hearing gain, and HLpost showed significant correlation with 2, 5, and 6 of the 7 prognostic factors, respectively. The multiple correlation coefficients were 0.396, 0.503, and 0.714 for the percentage hearing improvement, hearing gain, and HLpost, respectively. Predicted values of HLpost calculated by the multiple regression equation were reliable with 70% probability with a 40-dB-width prediction interval. Conclusion: Prediction of HLpost by the multiple regression model may be useful to estimate the hearing prognosis of ISSNHL.

Nasal resistance and the OSA-18 score were useful for evaluating surgical treatments. The sleep disturbance score may also be useful for predicting the severity of obstructive sleep apnea (OSA) in children.We evaluated the effect of surgery on children with OSA using polysomnography (PSG) parameters, nasal resistance, and the OSA-18 questionnaire, and also investigated the cut-off OSA-18 score to screen for pediatric OSA.This was a retrospective study in which PSG parameters and nasal resistance were measured using a rhinomanometer and the OSA-18 score was obtained from the OSA-18 questionnaire before and after surgery in 45 children with OSA.The mean age of the 45 patients was 5.7 ± 2.0 years. The mean value of the obstructive apnea hypopnea index (O-AHI) improved from 16.2 ± 14.3/h before surgery to 1.1 ± 1.7/h after surgery, the mean nasal resistance improved from 0.44 ± 0.19 to 0.32 ± 0.10 Pa/cm(3)/s, and the mean OSA-18 score improved from 61.1 ± 13.7 to 30.4 ± 5.8, and all these improvements were significant. The O-AHI value was lower than 1/h after surgery in 64.4% of patients (29/45). The O-AHI value was significantly correlated with the sleep disturbance score (r = 0.352, p = 0.018). When the cut-off OSA-18 score for screening was set at 40, sensitivity was 100%.

Sleep apnea is sometimes associated with hypothyroidism, but the significance of thyroid function screening in sleep apnea patients has been controversial. In the present study, we investigated the relationship between thyroid function and sleep apnea in subjects who were suspected to have sleep apnea. We enrolled 156 consecutive subjects suspected of having sleep apnea. Subjects included 117 men and 39 women aged 21 to 84 years. They underwent nocturnal multichannel polysomnography during a one-night hospitalization. The examined indices of sleep apnea were apnea–hypopnea index (AHI), lowest oxygen saturation, oxygen desaturation index, longest apnea duration, mean apnea duration, and the percent of apnea time to sleep time. Serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were concomitantly measured by electrochemiluminescence immunoassays. Three subjects (1.9 %) were diagnosed with primary hypothyroidism (high TSH and low FT4), and one subject (0.6 %) with subclinical hypothyroidism (high TSH and normal FT4). No significant difference in the level of TSH, FT3, or FT4 was seen among subjects with different severity of sleep apnea. The mean apnea duration significantly correlated with TSH in both simple and multiple regression analyses. Subjects with lower FT3 (≤3.75 pg/ml) showed longer mean apnea time compared to those with higher FT3 (>3.75 pg/ml) (24.9 ± 0.8 vs. 20.2 ± 1.2 s; P = 0.009). The other indices of sleep apnea did not show significant correlation with thyroid function. These results suggest that the mean apnea duration and TSH/FT3 may be helpful in understanding reciprocity between the two disease states, and for evaluating the validity of thyroid function tests in patients with sleep apnea.

Myringoplasty is one of the basic procedures in otologic surgery, and is important to achieve good hearing outcome. The temporal fascia is most widely used and considered to be a stable graft in this procedure, although 10-20% of patients develop reperforation after surgery, which is often hard to repair, even by revision surgery. We herein conducted revision myringoplasty using a cartilage graft to repair postoperative reperforation in 7 patients (8 ears) with chronic otitis media. The patients were 3 males and 4 females, aged 13-80 years with an average of 53.9 years. A cartilage graft was harvested from the tragus, sliced in 0.3 mm thickness with perichondrium attached on one side, and trimmed into an appropriate shape and size. The graft was then underlaid beneath the perforation and fixed with fibrin glue. The operation was Wullstein type I tympanoplasty in 5 ears and myringoplasty in 3 ears, using the temporal fascia in 7 ears and subcutaneous tissue in 1 ear. The postoperative follow-up period ranged from 16 to 44 months with an average of 30.0 months. Perforation of the tympanic membrane was successfully closed in 7 ears (87.5%). Hearing outcome was judged successful in 5 ears (62.5%) according to the criteria of the Otological Society of Japan (postoperative hearing level30 dB, hearing gain15 dB, or postoperative air-bone gap15 dB). These results indicate that cartilage is a stable and reliable graft material for revision myringoplasty to repair postoperative reperforation in patients with chronic otitis media.

Osteoclasts are unlikely to be involved in bone resorption in middle ear cholesteatoma.The authors searched for osteoclasts in undecalcified bone sections in patients with middle ear cholesteatoma to determine whether and to what extent these cells are involved in this disease.Twelve patients, eight men and four women, aged 30-87 years, who underwent tympanomastoidectomy were enrolled. Six patients had primary acquired middle ear cholesteatoma (cholesteatoma group) and the other six patients had other otologic diseases including otosclerosis, non-cholesteatomatous chronic otitis media, adhesive otitis media, perilymphatic fistula and ossicular malformation (control group). The scutum bone was collected during surgery, fixed with ethanol, stained with Villanueva bone stain, and embedded in methyl methacrylate. Five-micrometer-thick sections were prepared and examined under a polarizing microscope. Images were analyzed using a semiautomatic graphics system.No osteoclasts were seen in any of the samples in either group. To avoid the risk of under-estimating the presence of osteoclasts, the number of osteoclasts was considered to be1 in each sample, and the osteoclast density was calculated. The osteoclast densities in both the cholesteatoma and control groups were significantly lower than the sex- and age-matched standard value of the normal iliac cortical bone (p = .028).

Objective Isopeptide bonds form cross-links between constituent proteins in the horny layer of the epidermis. Corneodesmosin (CDSN) is a major component of corneodesmosomes, which bind corneocytes together. Both play important roles in maintaining epidermal barrier functions. In the present study, we investigated the expressions of isopeptide bonds, CDSN, and related enzymes in middle ear cholesteatoma in comparison with the skin. Design Prospective case series of patients with middle ear cholesteatoma. Setting Tertiary medical institute. Participants Cholesteatoma and normal postauricular skin were collected from patients with acquired middle ear cholesteatoma during tympanomastoidectomy. Main outcome measures Expression of e-(g-glutamyl)lysine isopeptide bonds was examined by immunohistochemistry; Expressions of transglutaminase (TGase)1, TGase2, TGase3, and TGase5 by immunohistochemistry and quantitative RT-PCR (qRT-PCR); expression of CDSN by immunohistochemistry, qRT-PCR, and Western blot; and expressions of tissue kallikrein-related peptidase (KLK)5, KLK7, KLK14, and serine peptidase inhibitor Kazal type 5 (SPINK5) by qRT-PCR. Results TGase2 was higher (P=0.0046) and TGase5 was lower (P=0.0008) in cholesteatoma than in the postauricular skin. Immunoreactivity for isopeptide bonds was localized in the granular and horny layers, and was not different between the two tissues. Immunoreactivity for CDSN was localized in the granular layer, and was lower in cholesteatoma than in the skin (P=0.0090). Western blot and qRT-PCR confirmed that the expression of CDSN was lower in cholesteatoma than in the skin. Expressions of KLK5, KLK7, KLK14, or SPINK5 were not different between the two tissues. Conclusions These results indicate that the production of CDSN is likely to be suppressed in cholesteatoma, which would account, at least in part, for the mechanical fragility and increased permeability of the cholesteatoma epithelium.

Objective The present study aimed at investigating ATP release in response to acetylcholine (Ach) and pharmacologically elucidating the intracellular signal transduction pathway of this reaction in an ex vivo experiment. Methods The inferior turbinate mucosa was collected from 21 patients with chronic hypertrophic rhinitis who underwent endoscopic turbinectomy. The mucosa was shaped into a filmy round piece, and incubated with chemical(s) in Hank's balanced salt solution for 10 min. After incubation, the ATP concentration was measured by a luciferin-luciferase assay. Results The baseline release of ATP without stimulus was 57.2 ± 10.3 fM. The ATP release was significantly increased by stimulation with 100 μM Ach. The Ach-induced ATP release was completely inhibited by removing extracellular Ca 2+ . Significant inhibition of the Ach-induced ATP release was also observed by the addition of 1 μM atropine, 40 μM 2-APB, 10 μM CBX, and 100 μM PPADS, whereas 30 nM bafilomycin A1 did not affect the ATP release. Conclusion These results indicate that the Ach-induced ATP release from the human nasal mucosa is dependent on the pannexin-1 channel and purinergic P2X7 receptor, suggesting that these two molecules constitute a local autocrine/paracrine signaling system in the human nasal epithelium.

Purpose: To investigate the expression of erbBs in the nasal mucosa of patients with chronic hypertrophic rhinitis. Procedures: Inferior turbinates were collected from 12 turbinectomized patients with allergic and nonallergic chronic hypertrophic rhinitis. Differential cell counts in the peripheral blood and allergy tests were conducted before surgery. The expressions of erbB1, 2, 3 and 4 were examined by fluorescence immunohistochemistry and by quantitative real-time transcription polymerase chain reaction (qRT-PCR). Immunohistochemical fluorescence was quantitatively measured using image-analyzing software. Eosinophils infiltrated into the mucosa were counted in sections stained with Hansel solution. Results: Each of the erbB types 1-4 was expressed in both epithelial cells and nasal gland cells. Immunoreactivity for erbB1 was strong and that for erbB2 and 3 was moderate, while that for erbB4 was faint. These findings were consistent with the results of qRT-PCR. The percentage of peripheral blood eosinophils was significantly correlated with the eosinophil count in the nasal mucosa and with immunoreactivity for erbB1 in the nasal gland. Conclusions: These results suggest a possible role of eosinophils in regulating erbB1 and thus in regulating mucosal hypertrophy in chronic hypertrophic rhinitis.

Tonsillectomy is one of the prevailing treatments for IgA nephropathy. This retrospective study aimed to elucidate prognostic factors for the postoperative kidney function of tonsillectomized patients with IgA nephropathy. Forty consecutive patients with IgA nephropathy who underwent tonsillectomy in our department between 1999 and 2008 were enrolled. They were 21 men and 19 women with ages ranging 14-52 years with an average age of 25.5 years. The patients were classified into remission and non-remission groups based on their kidney function assessed 1 year after surgery according to the clinical guidelines for IgA nephropathy of the Japanese Society of Nephrology. Patients' profiles and preoperative physical findings/laboratory data in the remission group were then compared with those in the non-remission group. The remission and non-remission groups included 13 and 27 patients, respectively. The remission group showed a significantly shorter interval between onset to surgery (2.3 +/- 2.1 vs. 5.0 +/- 6.7 years; p = 0.032), a lower diastolic blood pressure (66 +/- 13 vs. 75 +/- 17 mmHg; p = 0.040), a higher level of serum total protein (7.6 +/- 0.5 vs. 7.0 +/- 0.7 mg/dl; p = 0.015), and a higher degree of tonsillar hypertrophy (I degrees: II degrees: III degrees = 5 : 8: 0 vs. 21 : 6 : 0; p = 0.033) in comparison with the non-remission group. Multiple logistic regression analysis also revealed that patients with a higher level of serum total protein and those with a higher degree of tonsillar hypertrophy were more likely to recover. We should carefully consider these prognostic factors when indicating tonsillectomy for the treatment of IgA nephropathy.

We analyzed 19 consecutive cases of paranasal sinus mucoceles manifesting visual disturbance requiring surgery. Subjects were 12 men and 7 women aged 37 to 82 years (average; 57.4 years). Six negative prognostic factors examined were: (i) patients' age 70 years, (ii) time from onset to surgery 8 days, (iii) sphenoid sinus involvement, (iv) abnormal ocular fundus findings, (v) optic canal bone defect, and (vi) preoperative visual acuity ≤0.1. A prediction equation obtained by multivariate analysis provided highly accurate in predicting visual prognosis. We also found that factors ii), v), and vi) were mainly responsible for visual prognosis, whereas the impact of factors iii) and iv) was minor. We explored predicting more simply and feasibly visual prognosis with sufficient accuracy using the number of positive items from among the above 6 factors, using the number of those of i), ii), iv), v), and vi), or using the number of those of i), ii), v), and vi). Sensitivity/specificity was 80/93%, 80/100%, and 100/93%. We would like to stress that accurate prediction by these methods is helpful in managing paranasal sinus mucocele associated with visual disturbance.

Chondrosarcoma is rare, accounting for 0.2% of all malignant head and neck tumors. We report a case of chondrosarcoma arising from the nasal septum. A 63-year-old woman seen for 15-month of nasal obstruction and headache was found in rhinoscope, to have a bilaterally bulging posterior nasal septum. Computed tomography (CT) confirmed a tumorous mass extending to the sphenoid sinus and partially to the right posterior ethmoid sinus. T1- and T2-weighted magnetic resonance imaging (MRI) showed low and high intensity in spotty gadolinium enhancement. Transnasal endoscopic biopsy under general anesthesia yielded a histopathological diagnosis of chondrosarcoma. The woman refused proposed wide tumor resection for religious reasons but alternatively underwent carbon ion radiotherapy of 70.4 Gy, markedly reducing the tumor without severe complications. She has been remaining fairly well without recurrence in the 13 months since irradiation.

OBJECTIVE: We administered a questionnaire survey to a working population in an attempt to clarify the relationships between self-reported nasal obstruction, observed apnea during sleep, and daytime sleepiness. STUDY DESIGN: A total of 7980 daytime workers were asked to complete questionnaires about nasal obstruction, apnea during sleep, and daytime sleepiness. Of the 7702 responses, the data from 4818 subjects were analyzed. Nasal obstruction and observed apnea were graded into 3 categories. Daytime sleepiness was assessed by the Epworth Sleepiness Scale. RESULTS: Subjects with chronic nasal obstruction had 5.22 and 2.17 times higher odds for having habitual observed apnea and excessive daytime sleepiness (EDS), respectively, compared with those without nasal obstruction (P < 0.001). After adjusting for 3 potential confounding factors (age, sex, and body mass index) and the presence of habitual observed apnea, odds ratios for having EDS decreased, but still remained significant. CONCLUSION: Nasal obstruction is likely to cause daytime sleepiness, at least in part, by causing sleep-disordered breathing including apnea during sleep.

18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a powerful tool for the detection of malignant tumors. We herein reported a case of cervical metastasis from unknown primary. Primary tumor was successfully diagnosed by FDG-PET. A 70-year-old man presented with a right-sided cervical lymph node swelling. Fine needle aspiration cytology in the previous hospital showed class III atypia, however, the primary tumor was not found by physical examination, fiberscopy, computed tomography (CT), or magnetic resonance imaging. Open biopsy of the neck demonstrated that the lesion was metastatic squamous cell carcinoma, and he subsequently underwent neck dissection on the affected side. FDG-PET and PET/CT after surgery revealed demonstrated uptake in the right piriform recess of the hypopharynx. The patient was eventually referred to our department, and underwent biopsy of the piriform recess via direct endoscopy. Histopathological diagnosis was the poorly-differentiated squamous cell carcinoma, and then he received radical radiotherapy of 72Gy to the whole neck. There was no evidence of recurrence on FDG-PET performed four months after radiation. The literature on the clinical usefulness of FDG-PET for the diagnosis of head and neck cancers were reviewed.

The risk factors for methicillin-resistant Staphylococcus aureus (MRSA) detection in head and neck cancer patients are the duration of hospitalization, intravenous hyperalimentation, prior antibiotic use, and the coexistence of other pathogens.To shed light on the clinical characteristics of MRSA-positive inpatients with head and neck cancers. The secondary goal was to evaluate risk factors for MRSA detection in comparison with methicillin-sensitive S. aureus (MSSA).Sixty-one consecutive inpatients with head and neck cancers with S. aureus detection were analyzed based on their medical records. The antimicrobial susceptibility of isolated S. aureus was tested by the broth microdilution method.MRSA and MSSA were detected in 46 (75.4%) and 15 (24.6%) of the 61 patients, respectively. There was no significant difference in the male/female ratio, age, primary site, comorbidity, cancer stage, cancer treatment, or 5-year survival rate between the MRSA and MSSA groups. Compared with the MSSA group, the MRSA group had significantly longer hospitalization periods and intervals between admission and MRSA detection, as well as significantly greater likelihood of intravenous hyperalimentation, prior antibiotic use, and co-isolation of other pathogens. Isolated strains of MRSA were thoroughly sensitive to vancomycin and arbekacin and moderately sensitive to minocycline.

Objectives: There has been growing awareness that nasal obstruction may impair various daily and social activities. We performed a questionnaire survey on a working population to clarify the relationships among nasal obstruction, daytime sleepiness, and quality of life (QOL). Methods: Seven thousand nine hundred eighty daytime workers were asked to complete questionnaires, and the data from 7,180 subjects without any missing answers were finally analyzed (90.0% of the total participants). The severity ofnasal obstruction was graded into the following three categories: never/rarely, sometimes, and always/often. Daytime sleepiness and QOL were assessed by the Epworth Sleepiness Scale and the Medical Outcomes Study 36-Item Short-Form Health Survey, respectively. Results: Younger subjects reported a higher degree of nasal obstruction. Subjects who reported a higher degree of nasal obstruction had higher daytime sleepiness and lower quality of life. Subjects with higher daytime sleepiness had lower quality of life. The degree of nasal obstruction was not associated with body mass index. Conclusions: Taking into account the impact of nasal airway resistance on sleep-disordered breathing, the present results suggest that chronic nasal obstruction impairs QOL, at least partially, through excessive daytime sleepiness possibly caused by sleep-disordered breathing. We stress that sufficient and appropriate rhinologic treatment may improve the quality of daily and social activities of individuals with sinonasal diseases.

Hyalinizing clear cell carcinoma is a low-grade indolent and rare salivary gland tumor originally described by Milchgrub et al. in 1994. We herein report a case of this tumor of the base of the tongue. A 66-year-old Japanese woman presented with a large painless mass in the throat. Computed tomography and magnetic resonance imaging revealed a 40x30-mm well-defined ovoid tumor arising from the base of the tongue. She underwent tracheostomy followed by a resection of the tumor via the transmandibular approach combined with a right-sided supra-omohyoid neck dissection. Because the tumor invasion of the surrounding tissue was limited, the surgical defect at the base of the tongue was relatively small, and no reconstructive procedure needed to be performed. The tumor was histopathologically diagnosed as hyalinizing clear cell carcinoma of the minor salivary gland. Her postoperative clinical course was uneventful. No aspiration or difficulty upon deglutition was recognized when she started transoral ingestion on the eighth postoperative day. The patient is currently free from disease 21 months after surgery. The pathology, clinical characteristics, and treatment of hyalinizing clear cell carcinoma are bibliographically reviewed.

We report a rare case of schwannoma arising from the pharyngeal branch of the vagus nerve. An 18-year-old woman presented with an egg-sized nontender upper cervical swelling. Computed tomography and magnetic resonance imaging (MRI) revealed a well-defined tumor measuring 50mm in its major axis in the left carotid space. The tumor was moderately enhanced, and showed hypointensity and isointensity on T1- and T2-weighted MRI, respectively. Otorhinolaryngological findings were otherwise normal. A schwannoma was most likely suspected, and she underwent transcervical resection of the tumor. A cordlike strand connected to the cephalad end of the tumor was severed, while both the vagus and hypoglossal nerves were identified and preserved. The histopathological diagnose is schwannoma. After surgery, the patient manifested a curtain sign toward the unaffected side without showing vocal cord palsy or Homer's syndrome, indicating that the tumor had arisen from the pharyngeal branch of the vagus nerve. Clinical characteristics of schwannomas in the carotid space were reviewed.

Basaloid squamous cell carcinoma is a rare and high-grade variant of squamous cell carcinoma. Here we report two cases of this tumor of the head and neck. The first case was a 71-year-old man who presented with an 8-month history of foreign body sensation in the throat. Physical examination and computed tomography demonstrated a tumor measuring 17mm in diameter on the right lateral pharyngeal wall. He underwent tumor resection via lateral pharyngotomy followed by reconstruction with a sternocleidomastoid myocutaneous flap. The histopathological diagnosis was basaloid squamous cell carcinoma. Because he manifested recurrent aspiration pneumonia postoperatively, total laryngectomy was eventually performed. The second case was a 41-year-old man who complained of persistent oral pain. An ulcerated lesion measuring 10×5mm was seen on the left buccal mucosa, and squamous cell carcinoma was suspected through biopsy. He underwent transoral resection, and the lesion was histopathologically diagnosed as basaloid squamous cell carcinoma. Both patients are currently free from disease about one and a half years after surgery. The pathology, clinical characteristics, and treatment of basaloid squamous cell carcinoma are bibliographically reviewed.

A case of papillary carcinoma arising from a thyroglossal duct cyst is reported. A 43-year-old man was referred to our clinic with an anterior cervical mass. CT scan and MRI imaging revealed a ring-enhanced cystic mass in his anterior neck, while ultrasonography showed an irregular echo in the mass. He was preoperatively diagnosed with thyroglossal duct cyst, and underwent resection of the mass by Sistrunk's procedure. Histopathological examination of the surgical specimen showed papillary carcinoma in the thyroglossal duct cyst. Because the histological findings indicated that the tumor had been completely resected, no additional treatment was given. His postoperative course was uneventful, and the patient is currently free from disease 3 years after surgery.It is known that carcinoma, mostly papillary carcinoma, occurs more frequently in thyroglossal duct cysts than in the ordinary thyroid gland. Ultrasonography is a sensitive and useful method for detecting calcified lesions for the diagnosis of this disease. The epidemiology and clinical characteristics of papillary carcinoma associated with thyroglossal duct cyst were reviewed in the literature.

Sleep apnea syndrome (SAS) is a risk factor in lifestyle-related disease known to be closely associated with traffic and occupational accidents. Because of its high morbidity in middle-aged men, early diagnosis and management by industrial physicians are important. We clarified the degree of knowledge and concern about SAS among industrial physicians. We e-mailed questionnaires to 199 industrial physicians belonging to the Industrial Medical Promotion Society, and Most answered that industrial received responses from 51 (40 contracted and 11 part-time industrial physicians). physicians should participate in the management of SAS to prevent doze accidents, to control lifestyle-related diseases, to judge vocational fitness, and to lower economical expense. Fewer than 30% of physicians had conducted educational activities, and even fewer had practiced interviews and screening for SAS. Financial difficulty, lack of specialized hospitals for SAS, lack of labor, and a lack of concern among executives are major obstacles to SAS screening for employees. We concluded that, despite the concern industrial physicians, SAS is practically disregarded in their work. Cost-and time-effective screening and guidelines for employees with SAS should be established to facilitate the management of SAS by industrial physicians.

Objective We investigated the electrical impedance of and the expressions of tight junction molecules in the cholesteatoma epithelium to provide supporting evidence for the acid lysis theory of bone resorption in middle ear cholesteatoma. Methods Study subjects were patients with primary acquired middle ear cholesteatoma and those with non-cholesteatomatous chronic otitis media who underwent tympanomastoidectomy. The electrical impedance of the cholesteatoma epithelium was measured during tympanomastoidectomy by loading alternating currents of 320 Hz and 30.7 kHz. The expressions of tricellulin (MARVELD2), claudin-1 (CLDN1) and claudin-3 (CLDN3) were examined by fluorescence immunohistochemistry and quantitative reverse transcription-polymerase chain reaction. Results The electrical impedance of the cholesteatoma epithelium was significantly lower than that of the post-auricular skin and external auditory canal skin at both 320 Hz and 30.7 kHz. Immunoreactivity for MARVELD2, CLDN1 and CLDN3 was localised mainly in the granular layer, and to lesser degree, in the horny and spinous layers in both the cholesteatoma tissue and post-auricular skin. Fluorescence intensity was moderate for MARVELD2, weak for CLDN1 and strong for CLDN3. The expressions of MARVELD2, CLDN1 and CLDN3 mRNA were significantly lower in the cholesteatoma tissue than in the post-auricular skin. Conclusions These results indicate the increased permeability of the cholesteatoma epithelium and suggest that this change is, at least partially, dependent on the decrease in the expressions of the tight junction molecules. This evidence supports the acid lysis hypothesis of bone resorption in cholesteatoma.

Changing the sleep position from supine to non-supine is a simple but effective treatment for some patients with sleep apnea syndrome. In the present study, we compared the clinical data for good responders (GRs), those who responded well to the sleep position change, with those for poor responders (PRs), and also evaluated the effect of surgical treatment on the positional improvement of ventilation in the PR group. Forty-one adult patients with sleep apnea syndrome (mean age: 47.1 years, mean obesity index: 125.8%) were divided into two groups based on their polysomnographic responses to sleep position change. Thirty-two patients were classified as the GR group, whose apnea-hypopnea index (AHI) in the non-supine position declined to less than half of their AHI in the supine position, and nine whose non-supine AHI remained greater than half of their supine AHI were classified as the PR group. The AHI and the desaturation index (DI) for the PR group were significantly higher than those for the GR group, and the obesity index was also higher in the PR group. For the eight PRs who had surgical therapy, their polysomnographic data improved much more in the non-supine position than in the supine position. Of six patients whose total AHI was still 10 or more after surgery, four changed into GRs. The combination of surgery and sleep position change seemed to be an effective treatment even for patients with a little improvement before surgery.