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Objective: To compare the diagnostic performance of computed tomography (CT) and the Alvarado score and to determine whether patient age and sex influence the use of CT and the Alvarado score for diagnosing acute appendicitis., Materials and Methods: We retrospectively reviewed the CT scans and medical records of 372 patients who presented with right lower quadrant pain and underwent CT to rule out acute appendicitis.The population was classified by age and sex to determine its influence on the use of the Alvarado score and CT. Receiver operating characteristic analysis was used to calculate and compare the diagnostic performance of both modalities., Results: The overall area under the receiver operating characteristic curves for CT and the Alvarado score was 0.965 (highly accurate) and 0.732 (moderately accurate), respectively. There was little effect of patient age and sex on diagnostic performance of CT. However, the diagnostic performance of the Alvarado score was variable according to the patient age and sex (lowest in older women). Furthermore, the overall sensitivity of the Alvarado score was too low (72.8%) for determining immediate surgical intervention., Conclusion: Clinical assessment using the Alvarado score should be supplemented with CT examination for accurate diagnosis of acute appendicitis in all patients who are suspected of acute appendicitis.

Conclusion: Inflammatory diseases, such as non-specific sinusitis, fungal sinusitis and mucocele, commonly involve the sphenoid sinus. Endoscopic surgery provides an easy and successful access to isolated sphenoid sinus diseases (ISSDs) with rare complications., Objectives: The incidence of ISSDs has decreased since a wide use of antibiotics. ISSDs can cause severe complications due to the deep location in the skull base. Endoscopic surgery for the sphenoid sinus has recently become popular, with several advantages. The aim of this study was to analyse ISSDs in terms of the clinical symptoms, histological diagnosis and treatment outcomes with our 22 years' experience., Patients and Methods: Seventy-six patients with ISSDs, who were treated at Seoul National University Hospital between 1985 and 2007, were analysed. Patients with lesions confined to the sphenoid sinus were included. A retrospective chart review was performed with respect to the symptoms, pathology and treatment outcomes., Results: Fifty-seven of 76 cases were inflammatory lesions, 9 neoplastic lesions and 10 fibrous dysplasia. Headache was the most common symptom (65.8%), followed by nasal obstruction (22.4%) and postnasal drip (21.0%). Ophthalmologic symptoms were observed in 15 cases (19.7%). Endoscopic sphenoidotomy was performed in 51 of the 57 ISSDs. Symptoms completely improved in 92.2% of the patients.

Neurospheres are potentially good tools to study olfactory neurogenesis. For this purpose, it is necessary to characterize neurospheres derived from the olfactory system. This study is aimed at identifying the regional difference of cellular composition within neurospheres derived from the adult mouse olfactory bulb, and studying whether these characteristics are maintained throughout the long-term culture. Neural cells were obtained from the olfactory bulbs of 8-week-old Balb/c mice and the dissociated cells were cultured in serum-free media containing epidermal growth factor and basic fibroblast growth factor to form neurospheres. These neurospheres were subjected to characterization by confocal microscopy after immunofluorescence staining with nestin, proliferating cell nuclear antigen (PCNA), neuronal cell adhesion molecule (NCAM), glial fibrillary acidic protein (GFAP), O4, and olfactory marker protein (OMP). Confocal microscopy showed that nestin-reactive cells, which are stem cell-like cells, were present at the periphery of neurospheres and PCNA-reactive cells undergoing proliferation were found throughout the neurospheres. Neuronal cell markers, NCAM-reactive cells, were observed at the center of neurospheres while glial cell markers, GFAP- or O4-reactive cells, were present at the periphery of neurospheres. No cells were found to be reactive for OMP, a differentiated olfactory neuron marker. This regional distribution of cells in neurospheres was maintained through 17 passages for a year. The neural lineage of cells showed different distribution within neurospheres and this localization was preserved throughout the culture period. These findings in the neurosphere culture system of the olfactory bulb may help to study olfactory neurogenesis.

Objective/hypothesis: Ciliary wave disorder (CWD) is essential for effective mucociliary transport. The purpose of this study was to investigate morphologic and functional restoration in recovered sinus mucosa after 12 weeks of experimentally induced rhinosinusitis and regenerated sinus mucosa after mechanical injury., Study Design: Prospective study with animal models., Methods: Ten New Zealand white rabbits weighing between 2.5 and 3 kg were used for this experiment. In the recovered mucosa group (n = 5), the natural ostium of the maxillary sinus was closed with a synthetic sponge and removed 2 weeks later. In the regenerated sinus mucosa group (n = 5), maxillary sinus mucosa was stripped off through the anterior wall. Left sinus mucosae were used as controls. Twelve weeks postoperatively, ciliary beat frequency (CBF) and CWD were measured using an image analysis system. Morphologic changes in cilia were also observed using a scanning electron microscope (SEM)., Results: The average CBFs in control, recovered, and regenerated mucosa were 13.21 +/- 3.66 Hz, 13.20 +/- 3.53 Hz, and 14.16 +/- 3.87 Hz, respectively. The average CWDs in these groups were 8.46 +/- 4.4, 21.04 +/- 14.73, and 24.43 +/- 19.2, respectively. SEM showed that loss of cilia and irregularities of ciliary arrangements were prominent in regenerated sinus mucosa., Conclusion: Although 12 weeks is enough for morphologic regeneration of the ciliated epithelium after experimental sinusitis in rabbit maxillary sinuses, it does not appear long enough for full functional recovery. Restoration of CBFs does not equate to concurrent CWD restoration.

Objective: The aim of this study was to investigate the histoimmunological features of non-eosinophilic nasal polyps (NPs)., Methods: Thirty patients with chronic rhinosinusitis and NPs were included in this study. NPs were grouped into eosinophilic and non-eosinophilic types according to the amount of eosinophils in the NPs. The amount of serum total IgE and peripheral blood eosinophils were measured. Basement membrane (BM) thickness was measured, along with the expression of chemokine receptor 5 (CCR5) and chemokine receptor 3 (CCR3) in NP lymphocytes., Results: Non-eosinophilic NPs comprised 66.7% of the total NPs included in this study. The amount of eosinophils in NPs was related to eosinophilia of the peripheral blood, but not to elevated serum IgE. BM was significantly thinner in non-eosinophilic than in eosinophilic NPs. Lymphocytes expressing CCR5 or CCR3 were less frequently found in non-eosinophilic than in eosinophilic NPs., Conclusion: Histoimmunological characteristics of non-eosinophilic NPs differ from those of eosinophilic NPs; non-eosinophilic NPs may be featured by thinner BM and fewer CCR5- and CCR3-positive lymphocytes.

Conclusion: We observed for the first time the expression of Uteroglobin (UGB) in the nasal mucosa of mice. The results of our study suggest that UGB may play an important role in the regulation of inflammation in allergic rhinitis (AR) as well as in the lower airway allergic inflammations., Objectives: Uteroglobin is a protein secreted by epithelial lining of organs communicating with the external environment. Reports of its immunomodulatory effects in allergic disease have been made, but the true physiological role still remains to be elucidated. In this study we tried to observe the expression of UGB in the nasal mucosa of mice and determine its role in AR., Materials and Methods: Thirty BALB-c mice at 3 weeks of age (10 mice/group) were sensitized systemically by intraperitoneal ovalbumin injection and locally by ovalbumin inhalation. Control group were sensitized with PBS. Treatment group had intraperitoneal dexamethasone injection 1 hour before the initial sensitization while control and AR group were injected with PBS. Symptom scores, eosinophil counts, immunohistochemical staining as well as UGB mRNA expression in the nasal mucosa and lung tissue were analyzed., Results: The symptom scores and eosinophil counts between control and treatment group was significantly different from the AR group (P<0.01). On immunohistochemical staining, UGB was localized in the epithelium and submucosal gland of the nasal mucosa as well as in the epithelium of respiratory bronchioles. UGB mRNA expression of the nasal mucosa and lung tissue was decreased in the AR group compared to the control group (P=0.022). In the treatment group UGB expression was increased compared to the AR group (P=0.016). The results of IHC and mRNA expression in the lung tissue correlated with the results in the nasal mucosa.

Conclusion: The changes of nasal resistance and cross-sectional area (CSA) with aging could suggest that it might be attributed to the change (atrophy) of the non-erectile structural tissues including bone and soft tissues rather than the erectile tissues. Subjects older than 60 years of age had significantly slower ciliary beat frequency (CBF), which could suggest nasal function might begin to decrease at around 60 years of age., Objectives: Nasal physiology can be changed with aging, however, there has been little data that prove senile change of the nasal cavity. This study was conducted to evaluate the effect of aging on nasal resistance and ciliary movement of the nasal cavity., Methods: One hundred and fifty three healthy subjects were included in this study. Acoustic rhinometry and rhinomanometry before and after nasal decongestion, and CBF were measured., Results: The CSA at the attachment of the inferior turbinate was increased with age in both before and after decongestion. However, the difference of CSA between pre- and post-decongestion did not change significantly with age. At the nasal valve area, the CSA showed almost same values between age groups and the difference between pre-and post-decongestion was very small. The nasal resistance was markedly decreased from 2nd to 3rd decade and did not change significantly after 3rd decade. Subjects older than 60 years of age had significantly slower CBFs compared to those younger than 60 years (10.18+/-0.98 vs. 12.43+/-1.46) (P<.001).

Conclusion: In a retrospective study of 239 cases of fungal sinusitis, noninvasive paranasal sinus aspergillosis was most common and successfully treated by endoscopic sinus surgery (ESS) with postoperative sinus irrigation. For the treatment of fungal sinusitis, ESS with or without antifungal agents and control of predisposing factors for secondary cases are recommended., Objective: The aim of this study was to investigate the clinical characteristics of fungal sinusitis and evaluate the treatment outcomes of primary and secondary fungal infections of the paranasal sinuses., Materials and Methods: Two hundred thirty-nine cases of fungal infection of the paranasal sinuses seen between January 1997 and December 2006 were retrospectively analyzed by reviewing their medical records. There were 200 cases of primary fungal infection and 39 cases of secondary fungal infection., Results: The symptoms of chronic rhinosinusitis such as nasal obstruction, purulent rhinorrhea, and postnasal drip were commonly present in both primary and secondary infections, and the sphenoid sinus was commonly involved in secondary infection. The radiological findings in fungal sinusitis included haziness, calcification, and bone destruction of the involved sinuses. CT scans in 80% of the primary and 69% of the secondary cases revealed calcific densities in a paranasal soft tissue mass. Twenty-eight of 38 cases which had MR showed decreased signal intensities on T1-weighted images and markedly reduced signal intensities surrounded by bright signal on T2-weighted images. In secondary cases, the most common concomitant disease was diabetes mellitus. All patients received surgery including biopsy, ESS, and Caldwell-Luc's operation. Mucosal hypertrophy with fungus ball, which was the most common finding in both types, was found in 124 cases (62%) with primary and in 26 cases (67%) with secondary cases, and aspergillosis was most common, followed by unidentifiable colony, and mucormycosis. Eleven cases received amphotericin-B postoperatively. Two hundred thirty-eight cases showed no recurrence during the mean follow-up period of 11 months.

Background: Subjects with allergic rhinitis but no clinical evidence of asthma have greater bronchial hyperresponsiveness (BHR), and several factors have been implicated as its determinants. However, studies in young children are lacking. The aims of this study were to evaluate the prevalence of BHR in young children with allergic rhinitis and to investigate its risk factors., Methods: Methacholine bronchial challenges were performed in 4- to 6-year-old nonasthmatic children with allergic rhinitis (n = 83) and in healthy nonatopic controls (n = 32), using a modified auscultation method. The end-point was defined as the appearance of wheezing and/or oxygen desaturation. Subjects were considered to have BHR when they had end-point concentrations of methacholine

Objectives/hypothesis: This study aimed to evaluate the effect of dexamethasone on the expression of transforming growth factor (TGF)-beta in the mouse model of allergic rhinitis., Study Design: Female BALB/c mice were randomly assigned to four groups, including two control groups and two treatment groups., Methods: General sensitization and local challenge were performed with ovalbumin (OVA). In the treatment groups, dexamethasone was injected intraperitoneally 3 hours before general sensitization or local challenge. Symptom score, eosinophil infiltration, and immunostaining for TGF-beta1 and CD4 in nasal mucosa, and TGF-beta1 and OVA-specific immunoglobulin E (IgE) in sera were analyzed., Results: Dexamethasone administration before general sensitization reduced the symptom score, OVA-specific IgE, and eosinophil infiltration and increased the serum level of TGF-beta1 significantly. Dexamethasone administration before local challenge reduced only the eosinophil infiltration significantly. Immunoreactivity of TGF-beta1 and CD4 was lower in both treatment groups., Conclusion: These results suggest that dexamethasone may play an important role in the regulation of allergic reactions by at least two mechanisms; one by suppressing allergic sensitization through decrease of CD4+ T cells and increase of TGF-beta, and the other by suppressing late allergic reactions through the inhibition of proliferation and chemotaxis of inflammatory cells such as eosinophils.

Objective: To investigate the validity of the sixth edition of the American Joint Committee on Cancer (AJCC) staging system for sinonasal squamous cell carcinoma., Design: A 15-year retrospective case series review., Setting: Multicenter study from tertiary care facilities., Patients: Data from 113 patients diagnosed as having and treated for sinonasal squamous cell carcinoma from September 1988 through August 2003 were retrieved. Ninety patients followed up for at least 12 months were included in the study., Main Outcome Measures: The TNM staging system and survival rates were analyzed using the Kaplan-Meier method to determine the mean, disease-free, and 5-year survival statistics. The effect of tumor stage on overall survival was assessed with stages defined by the fifth and sixth editions of the AJCC staging systems., Results: The overall 5-year survival rate was 59.5%. According to the sixth edition, the survival rates of patients with stages III, IVA, and IVB tumors showed a significant difference (P = .002). In 32 cases, the stages were changed in accordance with the criteria in the sixth edition. The group in which the stage changed from III (fifth edition) to IVA (sixth edition) showed a worse survival rate than the group in which the stage did not change, although the difference was statistically insignificant. The 5-year disease-free survival rates of the group in which the stage did not change and of the group in which the stage changed from III (fifth edition) to IVA (sixth edition) were 64% and 34%, respectively (P = .08). Local recurrence was more frequently observed in the group in which the stage changed from III (fifth edition) to IVA (sixth edition)., Conclusion: The new AJCC staging system seems to be more accurate in predicting the survival rates for patients with advanced but surgically resectable sinonasal squamous cell carcinoma (stage IVA).

Background: Although many studies regarding airway remodeling in asthma have been reported, only a few studies have investigated airway remodeling in allergic rhinitis., Objectives: To determine whether repetitive allergen challenge could induce airway remodeling in the nose and evaluate the effect of steroids using a murine model of allergic rhinitis., Methods: To develop a mouse model of airway remodeling, ovalbumin-sensitized mice were repeatedly exposed to inhaled ovalbumin administration twice a week for 1 month and 3 months. Matched control mice were challenged with phosphate-buffered saline, and the treatment group received intraperitoneal dexamethasone injection. Trichrome, periodic acid-Schiff, hematoxylin-eosin, and immunohistochemical staining against matrix metalloproteinase 9 and tissue inhibitors of metalloproteinase 1 were performed to nasal and lung tissues, and the level of transforming growth factor beta in the nasal lavage fluid was analyzed., Results: Repetitive ovalbumin challenge for 3 months induced circumferential peribronchial fibrosis in the lung. In the nose, subepithelial fibrosis, increased matrix metalloproteinase 9 and tissue inhibitors of metalloproteinase 1 expression, goblet cell hyperplasia, and submucous gland hypertrophy were observed compared with the control group. Features of airway remodeling were more prominent in the lung tissue. Administration of dexamethasone significantly inhibited these histologic changes., Conclusion: Airway remodeling associated with long-term allergen challenge can occur in the nasal mucosa and the lung. Steroid treatment prevents airway inflammation in response to acute allergen challenge, as well as airway remodeling by long-term allergen challenge.

Objectives: In this study, we aimed to investigate the release and response of interleukin (IL)-18 to steroid treatment in a mouse model of allergic rhinitis., Methods: BALB/c mice were sensitized systemically by intraperitoneal injection of ovalbumin and locally by ovalbumin inhalation. Dexamethasone sodium phosphate was given by intraperitoneal injection in the steroid treatment group. Symptom scores, eosinophil counts, and IL-18 concentrations in the nasal and lung lavage fluids were analyzed., Results: The symptom scores and eosinophil counts of the negative control and steroid treatment groups were significantly lower than those of the positive control group (p < .01). The mean IL-18 concentrations in the nasal lavage fluid were not significantly different among the three groups (56.68 +/- 9.57,63.39 +/- 8.93, and 64.47 +/- 6.83 pg/mL, respectively). The IL-18 concentrations in the lung lavage fluid were significantly different between the positive control group and the steroid treatment group (430.75 +/- 154.54 and 69.94 +/- 14.26 pg/mL, respectively, p = .028)., Conclusions: The IL-18 concentration was found to be increased in the lung lavage fluid, but not in the nasal lavage fluid, in a mouse model of allergic rhinitis. Increased IL-18 concentrations returned toward the previous concentrations after steroid treatment. These results suggest that the roles of IL-18 may be different in the pathogenesis of allergic rhinitis and the pathogenesis of asthma.

Background: Histamine is an important inflammatory mediator and associated with early phase allergic response. However, the involvement of histamine in mucin gene expression or production has not been elucidated., Objective: The aim of this study is to investigate whether histamine induces MUC5AC production in NCI-H292 cells, and to evaluate which pathway is involved in this mucin production., Methods: MUC5AC production in NCI-H292 cells was analyzed by RT-PCR, immunoassay and immunocytochemical analysis. The effect of histamine on MUC5AC production in these cells at different time courses and concentrations was assessed, and the relationship between hCLCA1 expression and histamine concentration was also evaluated. In addition, cells were pretreated with antihistamine or an hCLCA1 blocker (niflumic acid, NFA) to evaluate the mechanism underlying histamine-induced MUC5AC production., Results: Histamine upregulated MUC5AC gene expression and mucin protein production in a dose-dependent and time-related fashion. Histamine also dose-dependently increased hCLCA1 mRNA expression. Moreover, pretreatment of cells with chlorpheniramine or NFA reduced histamine-induced MUC5AC mRNA expression and protein production in these cells. The histamine-treated cells showed increased cytoplasmic staining for MUC5AC compared to cells treated with media alone, and cells pretreated with chlorpheniramine or NFA before histamine treatment., Conclusion: Our results suggest that histamine-induced MUC5AC production occurs via the upregulation of hCLCA1. It is assumed that antihistamines or hCLCA1 channel blockers can partially suppress histamine-induced MUC5AC production in allergic diseases, e.g. allergic rhinitis., ((c) 2007 S. Karger AG, Basel.)

Conclusion: The results of our study suggest that Staphylococcus aureus enterotoxin A (SEA) may play an important role in the pathogenesis of rhinosinusitis by ciliostatic effects at high concentrations, and by a different mechanism at low concentrations., Objectives: To investigate the in vitro effects of SEA on ciliary activity and its in vivo effects on histology of the sinus mucosa., Materials and Methods: The in vitro effects of SEA on ciliary activity at different concentrations and exposure time were investigated using maxillary sinus mucosa harvested from experimental rabbits. After in vivo instillation of different concentrations (high and low dose) of SEA into the maxillary sinus, ciliary beat frequency (CBF) and histologic findings of the maxillary sinus mucosa were examined., Results: After exposure to low doses of SEA (0.03 and 0.3 ng/ml), CBF did not decrease, but after exposure to high doses of SEA (1.5, 3, and 30 ng/ml), CBF decreased significantly as a function of time. At 24 h after instillation of high-dose SEA (30 ng/ml) into the sinus, CBF decreased significantly and rhinosinusitis was induced after 7 days. Although no alteration was observed in the CBF of the sinus mucosa after instillation of low-dose SEA (0.3 ng/ml), histological findings of rhinosinusitis including subepithelial edema and inflammatory cell infiltration were observed.

Objectives: Malignancies arising from the sinonasal tract, which includes the nose, paranasal sinuses, and nasopharynx, are uncommon. Although adenoid cystic carcinoma (ACC) is the second most common cancer occurring in the sinonasal tract, only few studies have been reported. This retrospective review was performed to identify the clinical features and treatment outcomes of sinonasal ACC., Methods: Thirty-five patients diagnosed and treated for ACC of the sinonasal tract were included in this study. Medical records, radiographs, and pathologic slides were retrospectively reviewed., Results: In two thirds of the patients, the maxillary sinus was the site of origin and cribriform was the most common histologic subtype (61%). Seventy-one percent of the patients had advanced disease (T3, T4) at the time of diagnosis. Five-year overall survival rate was 86% and treatment failure occurred in 18 patients (51%). Five-year local recurrence rate and distant metastasis rate were 30% and 25%, respectively. Adjunctive radiotherapy appeared to reduce local recurrence. Presence of distant metastasis correlated with decreased 5-year survival (P = .001). Five-year survival rate after development of distant metastasis or local recurrence were 17% and 58%, respectively., Conclusions: Based on our findings, we suggest that sinonasal ACC be treated by a combined modality of radical surgery followed by postoperative radiation. The prognosis of sinonasal ACC seems to be determined by the presence of distant metastasis.

Conclusion: We have developed a simple, reliable method for the simultaneous determination of the ciliary wave disorder (CWD) and ciliary beat frequency (CBF) of actively beating cilia., Objective: The CBF and the directions of beating cilia are two important components of mucociliary transport. Although lots of studies have been performed on the measurement of the CBF, there have been few studies on the direction of cilia, with the exception of those using electron microscopy (EM). EM takes too long to determine the directions of cilia, and it cannot determine the direction of actively beating cilia. The aim of this study was to develop an image analysis (IA) system to conveniently determine the wave directions of multiple actively beating cilia as well as the CBF., Material and Methods: Sphenoid sinus mucosae obtained from 10 patients undergoing pituitary tumor removal via a trans-septal trans-sphenoidal approach were divided into two 4 x 4 mm2-sized pieces. One piece was studied using IA, the other with EM. Using IA, ciliary wave directions were determined from 5 20 x 20 microm2 regions of interest and the mean of 5 consecutive values was regarded as the CWD of each sample. The CBF was also measured. CWD was also measured using EM., Results: The average number of cilia analyzed by EM was 102.50 (range 48-136). The mean CWDs determined using IA and EM were 28.25+/-4.84 degrees and 23.59+/-8.16 degrees, respectively. There was a significant correlation between the CWDs determined using these two methods (Spearman's correlation coefficient =0.648; p =0.043). The mean CBF of sphenoid mucosa was 10.50+/-2.20 Hz.

Objectives: This study aimed to investigate the cellular pathogenetic mechanism involved in olfactory tissue injury and regeneration., Study Design: Adult male mice were exposed to 40 ppm SO2 for 2 hours., Methods: The mice were sacrificed immediately, 4 hours, and 1, 3, 5, 7, 10, 14, and 21 days after exposure to SO2. Olfactory neuroepithelium and bulbs were harvested at the time of sacrifice. Western blot and immunohistochemical staining were performed., Results: Injuries of the olfactory neuroepithelium were found 24 hours after exposure to SO2. The number of total olfactory neuroepithelial cells decreased after SO2 exposure and recovered after 3 weeks. In contrast, the number of proliferating cell nuclear antigen (PCNA)-positive cells increased after SO2 injury and then decreased. In the neuroepithelium, where PCNA expression increased, olfactory marker protein (OMP)-positive cells were sparse. The expression of inducible nitric oxide synthase (iNOS) was localized in the lateral half of the turbinates. However, there was no expression of iNOS in the medial half of the turbinates, in which PCNA was strongly expressed. There was increased immunoreactivity of neuronal NOS (nNOS) in the surviving cells after SO2 exposure. Immediately after exposure to SO2, the immunoreactivity to phosphorylated fraction of extracellular signal-regulated kinases (phospho-ERK)-1/2 increased in the cytoplasm and nucleus of supporting cells. In Western blot analysis, nNOS expression increased 4 hours after SO2 exposure., Conclusions: These findings suggest that the regenerative activity of the neuroepithelium might be well demonstrated by PCNA immunoreactivity and that regeneration of the neuroepithelium can be activated several days after SO2 injury. The two NOS isoforms, iNOS and nNOS, might contribute to neuroprotection in the olfactory neuroepithelium.

Background: Adenoid cystic carcinoma (ACC) is a unique tumor characterized by frequent and delayed distant metastasis (DM) with uncommon regional lymph node metastasis., Objectives: To evaluate the factors affecting DM of ACC and survival after appearance of DM., Design: A retrospective analysis of 94 cases of ACC from 1979 through 2001., Setting: Academic tertiary referral center., Results: Distant metastasis of ACC occurred in 46 patients and developed more frequently in patients with tumors of the solid histologic subtype than in patients with tubular or cribriform subtypes. Distant metastasis occurred less frequently in the minor salivary glands of the sinonasal tract than in major salivary glands or in other minor salivary glands, and development of DM was not affected by tumor stage. Disease-specific 5- and 10-year survival rates were 88% and 72% for patients without DM, respectively, and 76% and 48% for those with DM (P =.02). Regarding the site of DM and its impact on outcomes, 30 patients had lung metastasis alone; 5 patients, bone metastasis alone; and 6 patients developed both lung and bone metastasis. Median survival times after appearance of DM among patients with isolated lung metastases and those with bone metastases with or without lung involvement were 54 and 21 months, respectively (P =.04)., Conclusions: Development of DM in ACC can be predicted by solid histologic subtype and major salivary gland or oral/pharyngeal rather than sinonasal primary site. Those patients with bone involvement with or without lung metastases had worse outcomes than those with pulmonary metastasis only.

Nitric oxide (NO), which is produced by nitric oxide synthase (NOS), has been recently identified as a multifunctional mediator. As for nasal tissue, however, the distribution and expression patterns of 3 isoforms of NOS, including neuronal NOS (nNOS, type I NOS), inducible NOS (iNOS, type II NOS), and endothelial NOS (eNOS, type III NOS), are still unclear. To evaluate the function of NO in the pathophysiology of nasal allergy, we investigated the distribution of NOSs in the nasal mucosa of C57BL/6 mice with allergic rhinitis to the house dust mite, Dermatophagoides farinae. Immunoreactivity to each isoform of NOS was immunohistochemically observed. In the allergic nasal mucosa, many eosinophils had infiltrated. Immunoreactivity to NOS types I and III was localized to the surface epithelial and vascular endothelial cells in both allergic and control groups without a statistically significant difference. In contrast, the type II NOS immunoreactivity was weak in normal mice and increased after allergic sensitization. The type II NOS expression of the surface epithelial and vascular endothelial cells was significantly elevated in the allergic group as compared with the control group. These findings suggest that a large amount of NO may be produced in the nasal mucosa of mice by type II NOS after allergic sensitization and that type II NOS may play an important role in the pathogenesis of allergic rhinitis.

Primary ciliary dyskinesia is characterized by chronic upper and lower respiratory infections which are caused by the grossly impaired ciliary transport. Since the cilia and neutrophils both utilize microtubular system for their movement, it has been speculated that neutrophil motility such as chemotaxis might be impaired in patients with primary ciliary dyskinesia. Neutrophils were purified from whole blood from 16 patients with primary ciliary dyskinesia and from 15 healthy controls. Chemotactic responses of neutrophils to leukotriene B(4) (LTB(4)), complement 5a (C5a), and formylmethionylleucylphenylalanine (fMLP) were examined using the under agarose method. The chemotactic differentials in response to LTB4, C5a, and fMLP in neutrophils from the patient group were significantly lower than the corresponding values in neutrophils from the control group (p<0.05 for all comparisons). The difference in chemotactic index between the two groups was statistically significant for LTB4 and fMLP (p<0.05 for both comparisons), but not for C5a (p=0.20). Neutrophils from patients with primary ciliary dyskinesia showed a decreased chemotactic response as compared with those from normal subjects. It is concluded that the increased frequency of respiratory tract infection in patients with primary ciliary dyskinesia is possibly due to the defective directional migration of neutrophils, as well as to the defective mucociliary clearance of the airways.

Background: Allergic rhinitis is a known predictor and correlate of asthma incidence. However, it is not clear which patients with allergic rhinitis are at greater risk of the development of asthma., Objective: The aim of this study was to investigate whether airway hypersensitivity and/or increased maximal response on the dose-response curve to methacholine would predict the development of asthma in subjects with allergic rhinitis., Methods: One hundred and forty-one children with allergic rhinitis were prospectively studied for 7 years. At the initiation of the study, bronchial provocation test with methacholine using a stepwise increasing concentration technique was performed to measure PC(20) (provocative concentration causing a 20% fall in FEV(1)) and maximal response. Each subject was evaluated at least every 6 months and details of asthmatic symptoms or signs experienced during the intervening period were taken., Results: Twenty of 122 subjects available for the follow-up developed asthma. Nine (19.6%) of 46 hypersensitive (PC(20) < 18 mg/mL) subjects developed asthma, compared with 11 (14.5%) of 76 normosensitive subjects (P = 0.462). Eight (32%) of 25 subjects without maximal response plateau developed asthma, compared with 12 (12.4%) of 97 subjects with maximal response plateau (P = 0.018). Score test for trend revealed a significant association between the level of maximal response (P = 0.007), but not the degree of methacholine PC(20) (P = 0.123), and the future development of asthma., Conclusion: An increased maximal airway response to methacholine is shown to be a better predictor for the future development of asthma in patients with allergic rhinitis, than airway hypersensitivity to methacholine.

Multicenter Study on the Prevalence of Perennial Allergic Rhinitis and Allergy-Associated Disorders This study was aimed to determine the prevalence of perennial allergic rhinitis (PAR) using the skin test, radioallergosorbent test (RAST), or multiple allergosorbent test (MAST) and to clarify the clinical aspects of the patients diagnosed as having PAR by the questionnaire survey and rhinologic examination. The 71,120 subjects who had visited the 23 otolaryngology clinics at the randomly selected tertiary referral hospitals in Korea between November 1, 1999 and April 30, 2000 were studied. PAR was diagnosed when subjects complained of two or more associated symptoms and the skin test, RAST, or MAST using perennial inhalant allergens was positive. The questionnaire survey and rhinologic examination were performed in subjects with PAR. The prevalence of PAR was 3.93%. We could find no significant difference in the prevalence of PAR between the two sexes. However, there was a significant difference in the prevalence of PAR between the child and adult groups. The chief complaints were, in order of decreasing frequency, nasal obstruction, watery rhinorrhea, and sneezing. There was a family history of PAR in 40.2% of the subjects. The 39.6% of the subjects had associated allergic diseases, being atopic dermatitis most common. In conclusion, the prevalence of PAR in tertiary referral hospitals in Korea is 3.93%. Many subjects with PAR have family history and appear to be associated with other allergic diseases.

This study aimed to determine the characteristics of ciliogenesis and the ciliary beat frequency (CBF) of cultured human nasal epithelial cells by means of an in vitro air-liquid interface (ALI) culture system. On the 14th, 21st, and 27th days of ALI culture, CBFs of cultured cells were measured with a video computerized analysis system, and the epithelial cell-collagen matrix complex was examined by scanning and transmission electron microscopy. Using a CBF distribution map, we calculated the proportion of ciliary beating area (CBA) on the cultured cells. On the 14th day, ciliated cells could be easily distinguished from other cells on scanning electron microscopy by their elongated cilia. Between the 14th and 27th days, the number of mature cilia increased, and after 27 days of air exposure, the cilia of each cell pointed to one direction. From the beginning of air-exposure culture until the 7th day, the number of secretory cells increased; however, from the 7th day to the 27th day, it decreased, and the number of ciliated cells increased. Total CBAs increased from the 7th day to the 21st day. The proportions of actively beating cells and the mean CBFs of beating cells among cultured epithelial cells increased with culture time. On the 21st day, the mean CBF of the cultured cells was similar to that of nasal ciliated cells in biopsy specimens (10.9 +/- 0.5 Hz versus 11.4 +/- 1.3 Hz), but until the 27th day, the CBF of cultured cells increased significantly (13.9 +/- 0.8 Hz). It is suggested that there may be some difference in CBF between nasal epithelial cells submitted to biopsy and nasal epithelial cells cultured by the ALI culture system.

Objectives: To introduce a new surgical technique for endoscopic removal of the antral portion of antrochoanal polyp (ACP) by powered instrumentation and to determine its efficacy by measures of relevant patient outcome., Study Design: Prospective study in 28 patients undergoing endoscopic sinus surgery for ACP by our surgical technique., Methods: Improvements of clinical symptoms and endoscopic and computed tomographic findings were evaluated postoperatively with a follow-up period ranging from 12 to 52 months. All symptom scores on a 100-mm visual analogue scale before operation were compared with those at the last visit after operation. Postoperative endoscopic and computed tomographic findings were graded using a three-point scale ranging from 0 to 2. In surgical technique, the antral portion of ACP was identified through the enlarged ostium under intranasal endoscopy and removed by a blade of powered instrumentation that was inserted through the canine fossa., Results: Symptom scores were all significantly reduced postoperatively. All but one patient showed improvement in clinical symptoms and endoscopic and computed tomographic findings during the follow-up period. There were no major complications specific to this technique., Conclusion: Our technique provides an attractive alternative to other methods for removing the antral portion of an ACP and is associated with excellent outcomes and minimal morbidities.

Various saline solution formulae are frequently used in patients with rhinosinusitis. Osmolarity affects ciliary beat frequency (CBF); however, little is known about the effects of saline solutions on ciliary activity of nasal epithelial cells. The aim of this study was to assess whether CBF of normal turbinate mucosa is affected by hypertonic, isotonic, or hypotonic saline solution in vitro and whether histologic changes are associated with the alteration of ciliary movement. We assessed variations of CBF after exposure to 0.06%, 0.12%, 0.9%, 3.0%, or 7.0% saline solutions and histologic changes were examined by transmission electron microscopy. Isotonic and hypotonic solutions produced no ciliary slowing; however, ciliostasis was observed within a few minutes in 3.0% or 7.0% solution. The histologic changes demonstrated that the ciliary slowing might be attributed to epithelial damage by fluid transport toward the surrounding medium. In conclusion, hypertonic saline solutions decrease CBF and disrupt nasal epithelial cells in vitro.

Objectives: This study was performed to investigate the changes in ciliary beat frequency (CBF) after treatment with Larginine in the human sinus mucosa and to determine the distribution of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in the healthy sinus mucosa., Study Design/methods: CBF was measured in the sphenoid sinus mucosa of 12 patients who underwent trans-septal trans-sphenoidal hypophysectomy for the treatment of pituitary gland tumor. CBF was measured over 24 hours in Dulbecco's modified Eagle's medium (DMEM) after treatment with L-arginine, its inactive spatial isomer D-arginine, or an NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME). DMEM without treatment with these materials was used as a control. Other pieces of the mucosa were exposed to L-NAME and its inactive spatial isomer D-NAME after preincubation with L-arginine. The specimens were immunohistochemically stained for iNOS and eNOS., Results: CBF increased 24 hours after treatment with L-arginine as compared with control groups. CBF increased in proportion to the increasing concentrations of L-arginine. There was no significant change after treatment with D-arginine or L-NAME. CBF increased after treatment with L-arginine at 30 minutes and maintained for 24 hours. L-NAME inhibited the increase in CBF by L-arginine, but D-NAME showed no such effect. Immunoreactivity to both iNOS and eNOS was frequently observed in the ciliated epithelial cells and was stronger to eNOS than to iNOS., Conclusions: From the results of this study it is suggested that nitric oxide (NO) produced by iNOS and eNOS using L-arginine may increase CBF in the healthy sinus mucosa and that NO may have a regulatory function in ciliary motility in the human sinus mucosa.

Objectives: Temperature-controlled and temperature-monitored radiofrequency tissue volume reduction (RFTVR) for the turbinate is a new treatment modality for nasal obstruction secondary to turbinate hypertrophy. We compared the nasal functions after the treatment ofRFTVR and laser vaporizing turbinoplasty (LVT) using subjective symptom scores and objective tests., Study Design: Prospective, randomized clinical trial., Methods: Twenty-four patients with nasal obstruction secondary to inferior turbinate hypertrophy were prospectively evaluated from March 1999 to October 1999 at Seoul National University Hospital (Seoul, Korea). Sixteen patients were treated with RFTVR, and eight patients with LVT. The preoperative and postoperative nasal functions were investigated by visual analogue scale of symptoms, butanol threshold test, saccharine test, acoustic rhinometry, rhinomanometry, and ciliary beat frequency., Results: At 8 weeks postoperatively, the severity and the frequency of nasal obstruction improved subjectively in 81.3% and 93.8% of RFTVR group and in 87.5% and 87.5% of LVT group, respectively. Significant improvement of nasal symptoms began from 2 to 3 days after the operation in the RFTVR group, whereas there was significant improvement of nasal symptoms at 8 weeks after operation in the LVT group. However, objective nasal functions including nasal volume and total nasal resistance were significantly improved at 8 weeks after surgery in both groups. Among patients reporting symptoms of hyposmia, 55.6% of RFTVR group and 63.6% of LVT group showed improved olfaction. Saccharin transit time and ciliary beat frequency were preserved after RFTVR CONCLUSION: RFTVR for the turbinate may be useful as an alternative approach for the treatment of chronic turbinate hypertrophy.

Objectives: To investigate the in vitro effects of staphylococcal beta-toxin on ciliary activity and the in vivo effects on sinusitis induction., Study Design: The in vitro effects of staphylococcal beta-toxin on ciliary activity were investigated at different concentrations and exposure times. Experimental sinusitis was induced in rabbits with application of beta-toxin and confirmed 7 days later., Methods: Ciliated epithelial cells were taken from the maxillary sinus mucosa of 10 rabbits. Five culture dishes from each rabbit were used for the experimental group, and one culture dish from each rabbit was used for the control group. In the experimental group, ciliary beat frequency (CBF) was measured at concentrations of 0.1, 1, 2, 5 and 10 U/mL of beta-toxin using a video-computerized analysis technique, while in the control group, culture medium containing no toxin was used. CBF was measured 1, 2, 4, 6, 8, 12, 24, and 48 hours after administration of beta-toxin. To induce experimental sinusitis, 2 U/mL of beta-toxin was percutaneously applied to the maxillary sinus of 10 rabbits without occlusion of the natural ostium, while normal saline was percutaneously applied to the right-side maxillary sinus of 4 rabbits in the control group. At 7 days, mucosal membranes were taken from the inferomedial wall of the maxillary sinus for light microscopic study., Results: CBF dropped significantly after an 8-hour incubation at 2, 5, and 10 U/mL of beta-toxin. No ciliary activity was observed after a 24-hour incubation at 2 and 5 U/mL and a 12-hour incubation at 10 U/mL of beta-toxin. Mucoid, purulent discharge was observed in the maxillary sinuses of the beta-toxin-applied group. Prominent epithelial disruption and infiltration of inflammatory cells into the epithelium and lamina propria were observed in the beta-toxin-applied group., Conclusions: Staphylococcal beta-toxin may reduce ciliary activity and induce sinusitis without occlusion of the natural ostium of the maxillary sinus in rabbits This study provides another animal model of sinusitis for understanding the pathogenesis of sinusitis induced by bacterial exotoxins.

Platelet activating factor (PAF), a potent chemical mediator in inflammation and allergic reaction, has been thought to induce mucociliary inhibition and epithelial damage in the airway mucosa. However, several recent papers have reported that PAF may not readily damage the airway epithelium. The aim of this study was to elucidate the pathogenesis of PAF-induced epithelial damage in terms of ultrastructural changes. Sixteen micrograms of PAF (1 mL of 16 microg/mL) was administered into the maxillary sinuses of rabbits. The rabbits were divided into 2 groups according to time intervals, and the antral mucosa was taken 1 and 3 days after administration of PAF. The tissue was processed for routine transmission electron microscopy. No epithelial degeneration was observed other than platelet aggregation, red blood cell stasis, and swelling of the endothelial cells 1 day after administration of PAF. Migration of inflammatory cells into the perivascular connective tissue, infiltration of eosinophils into the subepithelial and intraepithelial spaces, and vacuolar degeneration of the epithelial cells with focal loss of cilia were seen 3 days after administration of PAF. In conclusion, PAF induced infiltration of eosinophils into the epithelium, and resulted in epithelial degeneration that varied according to the time interval. Our findings suggest that PAF may cause epithelial damage through a series of secondary events, probably due to cytotoxicity of eosinophils infiltrating the epithelium.

Since the last decade, new insights into inflammatory processes have become possible by investigating the pattern of cytokines in acute and chronic sinus diseases. This review aims to update and discuss the findings of in vitro and in vivo studies concerning the role of cytokines in sinusitis and nasal polyposis. The proinflammatory cytokines interleukin-1beta, interleukin-6 and the neutrophil-chemoattractant interleukin-8 may play a major role in acute sinusitis, as shown in viral and allergic rhinitis. In chronic sinusitis interleukin-3 dominates the cytokine profiles, giving support to a variety of inflammatory cells. Interleukin-5 is a key protein in the pathogenesis of nasal polyposis. Activation and survival of eosinophils in nasal polyps are thought to be regulated by interleukin-5. Further investigation of cytokine expression patterns in inflammatory sinus diseases will lead to a better understanding of their pathogenesis and to a development of new therapeutic modality.

Macrolide antibiotics have a variety of actions along with antimicrobial action. To determine the effects of oral administration of clarithromycin (CAM) on rheological properties, we measured the spinability, dynamic viscoelasticity, and solid composition of human nasal mucus from 18 patients with chronic sinusitis before and after administration of CAM for 4 weeks. After administration of CAM, the spinability and percent solid composition of nasal mucus increased from 26.5 +/- 12.2 mm to 40.2 +/- 18.7 mm and 7.86% +/- 3.47% to 13.90% +/- 3.67% (p < .05), respectively, whereas the ratio of the viscosity to the elasticity (eta'/G') of nasal mucus after the administration of CAM decreased in all of the mucus samples. These results suggest that treatment with CAM may modulate the rheological properties of nasal mucus in patients with chronic sinusitis.

Study Objective: There is growing evidence that regular beta(2)-agonist use in patients with asthma is associated with decreased airway caliber and increased bronchial responsiveness. The aim of this study was to determine whether regular treatment with beta(2)-agonists induces changes in lung function and bronchial responsiveness in patients with primary ciliary dyskinesia., Design: A randomized, double-blind, placebo-controlled, crossover study., Patients: Nineteen children with primary ciliary dyskinesia., Interventions: Subjects received inhaled salbutamol or identical placebo (2 x 100 microg qid) for periods of 6 weeks with a wash-out period of 4 weeks., Measurements and Results: FEV(1) was measured before and 3 weeks and 6 weeks after salbutamol or placebo treatment. High-dose methacholine inhalation tests were performed before and 6 weeks after each treatment. The provocative concentration of methacholine producing a 20% fall in FEV(1) (PC(20)) and maximal airway narrowing (MDeltaFFEV(1)) was measured. No significant change in FEV(1) was observed during the salbutamol or placebo periods. No significant differences in the parameters of bronchial responsiveness (PC(20) and MDeltaFFEV(1)) were noted as the result of either salbutamol or placebo treatment., Conclusion: Our data have shown that salbutamol, inhaled regularly for 6 weeks, did not cause either a decline in lung function or an increase in bronchial responsiveness in subjects with primary ciliary dyskinesia.

Objective: The in vitro effects of staphylococcal alpha-toxin on ciliary activity were investigated at different concentrations and exposure times., Study Design: Ciliated epithelial cells of the sphenoid sinus were taken from patients operated on for pituitary tumors. Video-computerized analysis technique and transmission electron microscopy were used to analyze the effects of the toxin on ciliary activity., Methods: Ciliary beat frequency (CBF) was measured in four different concentrations of alpha-toxin including 0.1, 1, 10, and 50 microg/mL. CBF was measured at 2, 4, 6, 12, 24, and 48 hours after administration of the toxin. To observe reversibility of the reduced ciliary activity, after 24-hour incubation in the media containing 10 microg/mL of alpha-toxin, the media were replaced with alpha-toxin-free media. The tissues were also processed for transmission electron microscopy to observe ultrastructural changes of the epithelial cells., Results: CBF increased significantly at 2-hour incubation and then decreased significantly after 12-hour incubation in 10 microg/mL of alpha-toxin (P< .05, repeated-measures ANOVA). The transmission electron microscopic findings showed mitochondrial swelling and a slight protrusion of the plasma membrane of the cilia. In toxin-free media, loss of ciliary activity was not recovered., Conclusions: CBF increased at first, but with increasing incubation time ciliary movements decreased gradually and stopped eventually. This loss of CBF may be an irreversible change associated with ultrastructural changes in the mitochondria and the plasma membrane of the cilia.

Background: The melanoma antigen (MAGE) 3 gene may be a useful tumor specific marker since it is expressed in a variety of cancers., Materials & Method: The expression and intracellular location of MAGE 3 gene product were investigated in 40 squamous cell carcinomas, 2 tumor lines, 20 benign diseases, and 20 normal tissues of the head and neck. Immunohistochemical staining with anti-MAGE 3 mAb 57B was conducted from fresh frozen specimens. Correlations between MAGE 3 expression and clinicopathological parameters were also evaluated., Results: The MAGE 3 gene product was detected in squamous cell carcinomas (18/40, 45%) and in tumor cell lines (2/2, 100%), but not in benign diseases and normal tissues. No significant correlation was drawn between MAGE 3 expression and clinical parameters including clinical stages and metastasis., Conclusion: These results show MAGE 3 antigen could represent a potential target for immunotherapy in head and neck squamous cell carcinomas.

This study aimed to investigate expression of various cytokine mRNAs, including IL-6, IL-8, TGF-beta, IL-4, IL-5, and IFN-gamma in maxillary sinus mucosa of patients with chronic sinusitis. Maxillary sinus mucosae of six patients with chronic sinusitis and turbinate mucosae of six healthy subjects were obtained. We performed RT-PCR and Southern blot to examine gene expression of the cytokines IL-6, IL-8, TGF-beta, IL-4, IL-5, and IFN-gamma in maxillary sinus mucosa and compared the results with cytokine gene expressions in normal turbinate mucosa. IL-6, IL-8, TGF-beta, IL-4, IL-5, and IFN-gamma mRNAs were expressed more frequently in maxillary sinus mucosa from patients with chronic sinusitis than in normal turbinate mucosa. All the maxillary sinus mucosa specimens revealed relatively higher mean density ratio for each cytokine investigated than did normal turbinate mucosa. IL-6, IL-8, TGF-beta, IL-4, IL-5, and IFN-gamma mRNAs were expressed simultaneously in maxillary sinus mucosa of chronic sinusitis. These cytokines may be responsible for recruitment of inflammatory cells and for mucosal thickening in chronic sinusitis, and thus chronicity of the disease.

Eosinophil-chemoattracting cytokines are thought to be important in the pathogenesis of allergic inflammation. However, little is known about the presence and significance of RANTES in nasal allergy and nasal polyps, two well-known rhinologic disorders characterized by eosinophil infiltration in the tissue. In order to evaluate the role of RANTES in eosinophil infiltration in vivo, the tissue distributions of RANTES and interleukin-5 (IL-5) and their correlation with eosinophil infiltration were investigated. Nasal mucosa specimens were obtained from 9 allergic and 12 control subjects, and nasal polyps from 6 allergic and 9 nonallergic subjects. All the subjects were divided into 4 groups: normal mucosa, allergic mucosa, nonallergic polyps, and allergic polyps. To identify the cellular localizations of RANTES and IL-5, we used specific immunohistochemical staining. We also investigated the differences in cytokine expression among the 4 groups, and the correlation between cytokine expression and eosinophil infiltration in the tissue. RANTES was expressed in the epithelium, endothelium, and some submucosal cells, while IL-5 was confined to the cells in the submucosa. Expression of both RANTES and IL-5 significantly increased in allergic mucosa and nasal polyps compared to normal mucosa; however, there was no significant difference in their expression between allergic and nonallergic polyps. Both cytokines had a significant correlation between their expression and either total or activated eosinophil numbers. The results of this study suggest that RANTES, as well as IL-5, plays a role in eosinophil recruitment in allergic nasal mucosa and nasal polyps in vivo.

Objective: There have been few reports on the effects of free oxygen radicals on ciliary mobility of nasal respiratory epithelial cells. The aim of this study was to determine the effects of free radicals and antioxidants on human nasal epithelial cells (HNECs) using video-computerized analysis., Methods: Human nasal epithelial cells were obtained from the nasal cavity of normal volunteers. Ciliary beat frequency (CBF) was calculated as the mean value of ten randomly selected cells. The proportion of the area with normal CBF (above 8 Hz) was calculated from 10 randomly selected sites per specimen. Free radicals were produced by xanthine-xanthine oxidase enzymatic system. The generation of free radicals was confirmed by chemoilluminometer. CBF and the proportion of the area with normal CBF were measured at every 5 min for 30 min after the addition of enzyme. For the evaluation of the antioxidant effects on free radical-mediated ciliary slowing in HNECs, cells were incubated in superoxide dismutase solution (300 unit/ml) for 30 min and 3-aminobenzamide (5 mM)., Results: Superoxide produced by 0.4 mM xanthine and 400 miliunit/ml xanthine oxidase decreased CBF (7.71 +/- 1.91 Hz). A total of 2 min later, ciliary slowing was evident (3.87 +/- 1.10 Hz). Regarding the changes in proportion of epithelial area that showed normal CBF experimental group showed a significant decrease in percentage of epithelial area with normal CBF over time. Superoxide dismutase prevented ciliary slowing (8.76 +/- 0.99 Hz). Moreover, 3-aminobenzamide, an inhibitor of the DNA repair enzyme poly-ADP ribose polymerase, prevented inhibition of CBF (8.32 +/- 0.61 Hz)., Conclusions: These results suggest that oxygen-mediated damage to DNA may be the mechanism of the deterioration effects of oxygen radicals on the ciliated respiratory nasal epithelium.

Objective: To investigate the effects of mucokinetic drugs on the rheological properties of human nasal mucus in patients with chronic sinusitis., Design: We reconstituted human nasal mucus obtained from 74 patients with chronic sinusitis and determined the effects of 4 mucokinetic drugs, including acetylcysteine, deoxynuclease I, 2% sodium bicarbonate, and a combination product containing tyloxapol (Alevaire), on rheological properties of reconstituted human nasal mucus (RHNM). We used 5% RHNM dissolved in phosphate-buffered solution as the optimal buffer and concentration of RHNM for the study because it showed a viscoelastic response similar to that of freshly collected nasal mucus from patients with chronic sinusitis., Methods: Four experiments were performed to determine the influence of each drug on dynamic viscosity and elasticity of 5% RHNM. Distilled water was used as a control., Results: Acetylcysteine and deoxynuclease I significantly decreased both dynamic viscosity and elastic modulus, while distilled water had no effect on rheological properties of 5% RHNM in vitro. Alevaire significantly reduced both dynamic viscosity and elastic modulus. Sodium bicarbonate significantly reduced elastic modulus but not dynamic viscosity. Reduction of elastic modulus by Alevaire was significantly greater than that by sodium bicarbonate, while there was no difference in reduction of dynamic viscosity between them., Conclusion: Our results indicate that RHNM may be useful for studying the topical effects of various drugs on nasal mucus from patients with chronic sinusitis.

Previous reports suggested that several cytokines may influence the ciliary beat of the airway ciliated epithelial cells. The aim of this study is to determine the effects of cytokines including IL-1 beta, TNF-alpha, and TGF-beta on ciliary beat frequency (CBF) of human nasal ciliated epithelial cells. CBF of cultured human nasal ciliated epithelial cells was measured 24 hours after incubating with concentrations of 0.01 ng/mL, 0.1 ng/mL, 1 ng/mL, 10 ng/mL, and 100 ng/mL of each recombinant human (rh) cytokine including rhIL-1 beta, rhTNF-alpha, and rhTGF-beta. CBF was measured with time at concentrations of 1 ng/mL of rhIL-1 beta, 10 ng/mL of TNF-alpha, and 1 ng/mL of TGF-beta solutions. CBF of the human nasal ciliated epithelial cells increased after addition of rhIL-1 beta and rhTNF-alpha. Maximum CBF was observed at 1 ng/mL of rhIL-1 beta and at 10 ng/mL of rhTNF-alpha. CBF increased progressively to 4 hours after addition of rhIL-1 beta and rhTNF-alpha. Increased CBF sustained for 24 hours and decreased by 2 days. However, no variation of CBF was observed after addition of rhTGF-beta, regardless of concentrations and time. The results of this study suggest that during acute inflammation, IL-1 beta and TNF-alpha may have a potential role in defense mechanism of human nasal epithelium by regulating CBF of the nasal ciliated epithelial cells.

Background: Nonasthmatic subjects with allergic rhinitis often have bronchial hyperresponsiveness (BHR). The mechanisms responsible for BHR in asthma include genetic predisposition and airway inflammation, but the causes of BHR in allergic rhinitis are poorly understood., Objective: The aim of this study was to investigate whether there is a familial predisposition in allergic rhinitis-associated BHR., Methods: One hundred fifteen children with allergic rhinitis (probands) and their family members underwent methacholine bronchial challenge and skin prick tests with airborne allergens. The probands were divided into 2 groups: BHR(+) (methacholine PC20 <18 mg/mL determined by the dosimeter method; n = 42) and BHR(-) (n = 73)., Results: The overall prevalence of BHR was higher in family members of BHR(+) probands than in those of BHR(-) probands (23.3% [27 of 116] vs 10.5% [21 of 200], P <.01). In mothers, this difference was marked (21.4% vs 8.2%, P <.05); a similar trend was observed in fathers (16.7% vs 6.8%) and siblings (34.4% vs 18.5%), although the differences did not reach significance (.05 < P <.1). The bronchial responsiveness index (BR index), a continuous variable derived from the results of methacholine challenge, was significantly higher among family members of the BHR(+) group than those of the BHR(-) group. Furthermore, even when only family members without BHR were considered, the BR index was significantly higher among those (n = 89) of the BHR(+) group than those (n = 179) of the BHR(-) group. There was no difference in atopic status as assessed by the prevalence of atopy (or atopy index) between family members of the BHR(+) group and the BHR(-) group., Conclusion: Our results indicated that there is a significant familial predisposition for BHR among patients with allergic rhinitis. Further studies are needed to elucidate whether genetic factors play a role in allergic rhinitis-associated BHR.

Nasal polyps are the most common mass lesion of the nasal cavity. Various pathogenetic mechanisms have been proposed. However, the cause is still largely unknown, and treatment methods have not been changed for several hundred years. In order to investigate the role of cytokines in the pathogenesis of nasal polyps, expression of cytokine messenger RNAs (mRNAs) in nasal polyps was investigated. We performed reverse transcriptase-polymerase chain reaction and Southern blot to examine gene expression of the cytokines interleukin (IL)-1 beta, IL-6, IL-8, transforming growth factor (TGF)-beta, IL-4, IL-5, and interferon (IFN)-gamma and compared the results with the gene expressions of these cytokines in normal nasal mucosa. Nasal polyp tissues were obtained from 14 patients undergoing polypectomy for nasal obstruction. Among them, 4 patients suffered from associated perennial allergic rhinitis. The mRNAs of IL-4 and IL-5 (Th2 cytokines) as well as IFN-gamma (Th1 cytokine) were expressed in all of the nasal polyps obtained from the 14 patients, irrespective of the presence or absence of allergy, while 2, 0, and 4 of 6 normal turbinate mucosae expressed IL-4, IL-5, and IFN-gamma mRNAs, respectively. The mRNAs of IL-1 beta, IL-6, IL-8, and TGF-beta were expressed in 6, 1, 2, and 3 of 6 normal turbinate mucosae, respectively, while the mRNAs of these cytokines were expressed in all of the 14 polyp tissues except IL-6 mRNA, which was expressed in 13 nasal polyp tissues. There were no differences in the mean density ratios of each cytokine band on Southern blot between polyp tissues with allergy and those without allergy. These results suggest that many cytokines are produced in nasal polyps, that they may play important roles in the pathogenesis of nasal polyps, and that allergy per se may not play a fundamental role in the pathogenesis of nasal polyps.

Previous reports suggest that cytokines may be involved in proliferation of the epithelium. The aim of this study was to determine the effects of cytokines, IL-1 beta, TNF-alpha, and TGF-beta on proliferation of human nasal epithelial cells (HNECs) in vitro. Primary cells were cultured from HNECs on collagen gel matrix. Subcultured HNECs were incubated in a medium with recombinant human (rh) cytokines, rhIL-1 beta, rhTNF-alpha, and rhTGF-beta at different concentrations of 0.01 ng/mL, 0.1 ng/mL, 1 ng/mL, 10 ng/mL, and 100 ng/mL. After 2-day incubation with these cytokines, daily cell proliferation was measured by MTT assay for 6 days. While rhIL-1 beta inhibited proliferation of HNECs in concentration-dependent and time-dependent manners, rhTNF-a stimulated HNEC growth at concentrations ranging from 0.01 ng/mL to 10 ng/mL in concentration-dependent and time-dependent manner. In contrast, rhTGF-b inhibited HNEC growth irrespective of concentration and incubation time. This study suggests that IL-1 beta, TNF-alpha, and TGF-beta may have an important role in the repair of the nasal mucosa by regulating proliferation of the nasal epithelium.

The in vitro effects of phenylephrine solution on ciliary beat frequency (CBF) in terms of different concentrations and exposure times were investigated using a video-computerized analysis technique. Nasal epithelial cells were taken from inferior turbinate of 10 volunteers by scraping the nasal mucosa with a cytology brush. CBF was measured in five different concentrations including 0.125%, 0.25%, 0.5%, 1%, and 2.5%. Each specimen was incubated in different solution for 6 days and CBF was measured at 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 days, and 6 days. CBF decreased significantly after 12-hour incubation in 0.125% phenylephrine solution and after 8-hour incubation in 0.25% phenylephrine solution, both clinically used concentrations. There were significant decreases in CBF after incubation in 0.5% phenylephrine for 2 hours, in 1% for 1 hour, and in 2.5% for 30 minutes (P < 0.05, repeated measure analysis of variance [ANOVA]). CBF of the nasal respiratory ciliated cells significantly decreased with increasing concentrations of phenylephrine solution and with increasing incubation times at the same concentration (P < 0.05, repeated measure ANOVA). The results of this study suggest that phenylephrine may inhibit ciliary beat in vitro by its pharmacological effect at lower concentrations than clinically used ones.

Acoustic rhinometry and rhinomanometry have been used to assess nasal airway patency objectively. We compared nasal obstruction symptoms before and after decongestion with several parameters of these objective tests. The patients assessed their nasal obstruction using a visual analogue scale (VAS). Cross-sectional areas and nasal resistance were measured by acoustic rhinometry and rhinomanometry before and after topical application of 1% phenylephrine solution in 32 patients with nasal obstruction symptoms. There was no significant correlation between the difference in the VAS and the difference in nasal resistance. There was also no significant correlation between the difference in the VAS and minimal cross-sectional area and cross-sectional areas at 3.3 cm (CA3.3), CA4.0 and CA6.4 from the nosepiece both in the wide and narrow sides and in both nasal cavities before and after nasal decongestion. It is concluded that rhinomanometry and acoustic rhinometry may have no diagnostic value in estimating the severity of nasal obstruction symptoms.

Through their rapid periodic actions, the cilia of the human respiratory tract play an important role in clearing inhaled noxious particles. An automated method is developed, based on an image-processing technique, to measure and analyse objectively and quantitatively, ciliary beat frequency (CBF). Microscopic ciliary images are transformed into digitised grey images through an image grabber inside a PC, and signals are extracted from these, based on an image-subtraction algorithm, and are processed through power spectrum analysis using a fast Fourier transform (FFT). By means of the FFT power spectrum, maximum peak frequencies are detected as CBFs in each partitioned block for the entire digitised field. Using these CBFs, distribution maps are composed in various resolutions, showing visually the spatial distribution of CBFs through cells and in a single cell. To measure CBF variations quantitatively, phenylephrine hydrochloride is used, and the changes in CBF influenced by its concentration and duration are observed.

We evaluated the distribution of nitric oxide (NO) in the rat nasal mucosa using nicotineamide adenosine dinucleotide phosphate (NADPH)-diaphorase histochemistry. The NADPH-diaphorase positive nerve fibers in the nasal mucosa were observed around blood vessels and submucosal glands and in sphenopalatine ganglions. Strong positive reactions for NADPH-diaphorase were observed in ganglions as compared with the other tissues. In septal and turbinate mucosa, positive reactions for NADPH-diaphorase were mainly seen in the anterior portion, and a few positive reactions were observed in the posterior portion. No positive reactions for NADPH-diaphorase were demonstrated in the sinus mucosa. These results suggest that NO may be related to regulation of blood flow, glandular secretion and neurotransmission, and also that NO may play an important role in the defense mechanism of the upper airway system against external environments.