We measured IL-5, IL-8 and INF_γ concentrations in nasal polyps from 11 patients with allergic or nonallergic chronic sinusitis. Nasal polyps were homogenized in phosphate buffer and the supernatant was used for ELISA assay. IL-5 was only detected in allergic chronic sinusitis (chronic sinusitis associated with nasal allergy or bronchial asthma) patients whose nasal polyp showed increased eosinophilic infiltration. But, the concentration of IL-5 had no correlation with degree of the eosinophilic infiltration in nasal polyp or the number of neutrophils in nasal smear. IL-8 was detected in all nasal polyps, and nonallergic chronic sinusitis patients showed higher concentration IL-8 in their nasal polyps. The concentration of IL-8 was related to the number of neutrophils in nasal smear but not to neutrophilic infiltration in nasal polyps. INF_γ was detected in only a case. These results suggest that allergic and nonallergic chronic sinusitis show different activation of cytokine network in nasal polyp. This difference may lead to distinct clinical features of the two types of sinusitis.

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[in Japanese]

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Nasal epithelial cells are among the first cells to come into contact with inhaled antigens. We inves-tigated the ability of nasal epithelial cells for the mucosal immune response through the release of cytokines, IL (interleukin) -1 α, IL-1 β, and IL-8. IL -1 acts on several types of cells and promotes the release of other cytokines.
IL-8 is a potent neutrophil chemotactic and activating factor, and pro-inflammatory effect of IL-8 seems to be concerned with local immunity. Both IL -1 and IL-8 are seems to be produced by epithelial cells, with its secretion regulated by TNF-α, LPS, and some viruses. We obtained the fifteen specimens of nasal mucosa from nose operation. The speci-mens were treated overnight by protease, and single cell suspensions were obtained by gentle agitation using a small curette. After washing, nasal epithelial cells were re-suspended in medium, and cultured until confluence was reached. The cultured medium was changed for medium with or without LPS or several concentrations of OK-432, and supernatants were harvested after 24 hours for cytokine analysis. We confirmed the promoting effect of LPS on IL-1 α, IL-1 β, and IL-8 by ELISA (enzyme linked immunosolubent assay), but OK 432 reduced IL-8 secretion by nasal epithelial cells. The nasal epithelial cells may also actively participate in local immune mechanisms by producing and secreting several cyto-kines such as IL-1 and IL-8.

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Nasal polyposis and asthma are inflammatory conditions affecting the airways characterized by the presence of inflammatory cells, particularly eosinophils (Eo) and varying degree of fibrosis. IL-4 is a 20-kDa glycoprotein that is a multifunctional cytokine considered to play an important role in eosinophilic inflammation. We examined the cellular source of immunoreactive IL-4 in nasal polyps (NP) as well as in the bronchial mucosa of patients with asthma.Approximately 90% of the IL-4 positive cells in bronchial tissues was not Eo; in contrast, about 80% of the IL-4 positive cells in NP tissues was Eo. Main source of IL-4 message in NP tissues were Eo accord-ing to the results of Northern blot analysis and in situ hybridization. These data demonstrate that Eo express the message of IL-4 in vivo, and that these cells are the primary source of IL-4 in chronically inflamed upper airway tissues (NP).

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In macrolide long term therapy, it is often needed to medicate macrolides for 2-3 months. In this study, We administered roxithromycin (RXM) to guinea pigs orally, and determined the relation between the administrated term and RXM's suppressive effect on neutrophil chemotaxis. We found that the suppressive effect of RXM was administrated term dependent.
In order to estimate the acting point of RXM in neutrophil, the concentration of intracellular calcium ion was determined during the stimulation of a chemoattractant, resulting in no significant difference between medicated group and negative control group. This result suggests that the acting point is in the cascade lower than the mobilization of intracellular calcium.

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The maxillary mucosae of sinusitis patients who underwent endoscopic endonasal sinus surgery were observed by transmission and scanning electron microscopies. The epithelium was damaged due to the chronic inflammation and the area with few ciliated cells was usually observed. Evaluation of the mucociliary transport of antral mucosae was also performed. Blue-colored latex beads, 3, μm in diameter, were injected into the maxillary sinus through the widened ostium at 5' -7 days after the surgery. The trace of the beads was followed under the en-donasal fiberscope. The case of severe sinusitis tended to show a low transport of the beads.

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It is well known that viral upper respiratory tract infection predisposes to the development of acute bacterial sinusitis. However, to the best of our knowledge, the effect of antecedent, concurrent or subsequent adenovirus infection on the course of experimental upper respiratory tract infection in-duced by nontypable Haernophilus influenzae (NTHi) in a chinchilla model has not been reported.
In this study, four cohorts of chinchillas were inoculated intranasally (IN) with adenovirus and/or NTHi either sequentially or concurrently. Group A received adenovirus followed 7 days later by NTHi ; Group B received NTHi followed 7 days later by adenovirus ; Group C received adenovirus and NTHi concurrently and Group D received NTHi alone. Adenovirus only and media control cohorts (Groups E and F respectively) were used from the part of a previous study.
The data obtained in both this as well as the earlier study, indicated that the chinchilla supported an active infection with this adenovirus isolate. Based on the parameters assessed, data indicated that adenovirus inoculation followed seven days later by IN inoculation of NTHi resulted in more significant damage to and altered function of the upper respiratory tract than either the reverse order of pathogen acquisition or the simultaneous receipt of both pathogens, particularly in the first 7^-10 days following inoculation of the bacterial strain.

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We worked out a new endonasal operation (Swinging of nasolacrimal duct and inferior turbinate) for chronic sinusitis and presented the theoretical ground and the outline of the operative procedure. In an immunohistochemical investigation, immune staininng of the mucous membrane of the inferior nasal turbinate and the mucous membrane around thenatural ostium was conducted using Monoclonal Mouse Anti-Human Mast Cell Tryptase (Daco-Mast Cell, AA 1). As a result of examination on the cases divided by the presence or absence of allergy involvement, it was found that there was no significant difference. It may be concluded from these results that this new operation is useful for chronic sinusitis irrespective of the presence or absence of allergy involvement.

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Experimental sinusitis was induced in adult white rabbits by injection of Staphylococcus aureus and Prevotella buccae into the maxillary sinuses. One week after the injection, the rabbits were sacrificed and dissected. We examined macroscopic findings and pathological changes under a light microscopeand a scanning electoron microscope. In the group which had been sensitized with a 2.5% concentration of a parified egg white albumin, we have experimen-tally induced sinusitis in rabbits by injection of Prevotella buccae. In macroscopic findings and pathological examination, the inflammation in the mucous membrane by injection of Staphylococcus aureus was severer than that of Prevotella buccae. We plan to observe a long period course in consideration of chronic sinusitis.

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The purpose of endoscopic sinus surgery is to reestablish ventilation and mucocilialy clearance of the sinuses. This final target is commonly believed to beachieved primarily by endoscopic surgery removing the lesion located in the key areas of anterior ethomoid and middle meatus. We confirm this theory by comparison between the two group of postoperative pansinusitis patients. One group (n= 10) of patients were operated on by removing only minimal lesion in OMC (ostiomeatal complex). The other group of patients (n =10) were operated by a more expansive resection including OMC, posterior ethmoid, and sphenoid sinus. Consequently relating to subjective symptoms and objective local findings, there proved to be no satistically significant difference between the two groups.
Postoperatively, almost half of all these patients revealed localized undesirable change such as meatus stenosis or adhesion, polypoid degeneration and so on. Ambulatory observation and care for local lesion shoud be as equally of great value as medication.

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The clinical efficacy of a long-term RXM therapy after endoscopic sinus surgery in patients with chronic paranasal sinusitis was investigated in comparison with the therapy without RXM after surgery. In twenty three patients, RXM was orally administrated 300 mg per day for an average of 15.7 weeks after surgery. Thirteen patients were treated without administration of RXM after surgery. Improve-ment rate of subjective symptoms was 65.2% in the group with RXM and 53.8% in the group without RXM, respectively. Objective findings were found to be improved in 92.5% and 60.0% of patients in each group. The overall improvement rate based on the changes in subjective and objective findings was 63.6% and 44.4%, respectively. Postoperative CT findings showed marked improvement in 81.8% of the group with RXM and in 58.8% of the group without RXM. Under endoscopic examination, mucosal pathology of the group with RXM was better than that of the group without RXM in anterior and posterior ethomoid sinuses. Openings of the middle nasal meatus and fontanelle were 88.6% and 95.5% in the group with RXM, and 90.0% and 95.0% in the group without RXM, respectively. These results suggest that long-term RXM therapy after endoscopic sinus surgery is more effective than the therapy without RXM after surgery in the patients with chronic paranasal sinusitis.

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Recently one of the common therapy for chronic sinusitis is a long-term macrolides therapy and the other is endoscopic sinus surgery (ESS). In our department, ESS was performed on 180 patients who did not respond to macrolides therapy from January 1995 to May 1996. Among them 52 cases were mild disease and we investigated the clinical character of them.
Most patients had obstructive lesion of the ostiomeatal complex (OMC) which is the key to normal sinus function. All the patients' symptoms persisted after at least 1 month's macrolides therapy. The average of the term from the development of the symptoms to operation was 11.5 months. Thirty-five patients continued treatment in our department after surgery. 74.3% of them were cured and the average duration of the post-operative treatment was 3.8 months. Two cases required re-operation for relapse of obstruction of the OMC.
We suggest that chronic sinusitis with obstructive lesion of the OMC, even if it is mild sinusitis, under-goes endoscopic sinus surgery for it is resistant for macrolides therapy. After all surgery causes rapid cure and benefit for social life of patient.
Our hospital encourage corporation with clinics on the treatment of sinusitis ; a clinic take charge of pre-and post-operative conservative therapy and a hos-pital performs operation. For the treatment after surgery is important to keep patency of OMC and to prompt normalization of sinus mucosae, we expect ideal management of chronic sinusitis on this corpora-tion.

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This study was designed to evaluate the effectiveness of a long-term and low dose administration of Clarithromycin (CAM) in chronic sinusitis (CS). The subjects of this study were 75 patients with CS aged more than 16 years old. Fifty-eight patients were administered 200 mg of CAM per day for 3 or 6 months. Seventeen patients received 600 mg of Erythromycin (EM) per day for 3 months. The overall clinical efficacy determined by subjective symptoms and rhinoscopic observations was classified into excellent, good, fair, poor and worse categories. The general effectiveness that includes both excellent and good categories was tending to increase up to the 3 months of the administration period of CAM. The similar observation was exist in the EM administration. On the 3 months of administration period, the general effectiveness of CAM and EM was 44.5% and 25.0% respectively, and this difference was not statistically significant. The general effectiveness of CAM was discussed in relation to that of other therapeutic methods for CS.

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The effect of a long-term and low-dose macrolide administration on chronic sinusitis patients was quantitatively evaluated by measuring the improvement of paranasal sinus aeration in computed tomography (CT) images.
Ten patients with non-allergic chronic sinusitiswere orally given 150 mg roxithromycin per day without other treatments for 4 to 11 months. They underwent CT scan of the paranasal sinuses before and after the treatment. Then, the proportion of aerated areas within the sinus (% aeration) was calculated using public domain NIH image program. Percent aeration significantly increased in the maxillary sinus, ethmoid sinus, sphenoid sinus and frontal sinus after the treatment by 29.4, 34.5, 37.6 and 45.4%, respectively.
This result objectively and quantitatively demonstrates the clinical effectiveness of long-term and low-dose macrolide therapy on chronic sinusitis patients. In addition, percent aeration is thought to be an objective and useful parameter, which surpasses nasal symptom/objective finding scores or paranasal sinus X-rays in the evaluation of the severity of sinusitis.

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Low-dose and long-term administration of Erythromycin (RXM ; Roxithromycin) has been reported to be an effective therapy for patients with chronic paranasal sinusitis. However the way of the adequate administration has not been decided. We investigated the clinical effects of RXM with changing of the dose of RXM. Fifty-nine adults were treated with RXM, 300 mg/day for a period of 4 weeks. Then the 59 patients were devided into Group A and B. Group A received 150 mg daily while Group Breceived 150 mg every other day for 20 weeks. Furthermore, follow-up study was carried out one year later. Results were as follows;
1) In Group A, the improvement rate of subjective and objective symptoms were 54.3 and 34.3%. In Group B, the improvement rate of subjective and objective symptoms were 65.4 and 42.3% 24 weeks later.
2) From follow-up study in one year later, Group A showed an improvement rate in 73%, Group B in 47%. These findings suggested that RXM therapy was more effective in chronic paranasal sinusitis by the every day administration compared to every other day administration.
3) Only one case in Group B had adverse reaction with eczema.

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Bacterial isolation was performed both in effusionof the paranasal sinuses (PNS) obtained by a YAMIK sinus catheter and in the nasal cavity on the same side in cases with chronic sinusitis. These cases had not been treated by antibiotics at least for one week. The incidence of isolated bacteria was not remarkably different between in the effusion of PNS and in the middle nasal meatus. In 32.1% cases, the bacterial flora of the effusion of PNS coincided with that in the middle nasal meatus. The 54.5% of aerobic pathogenic bacteria detected in the effusion of PNS coincided with that detected in the middle nasal meatus.
We classified these cases into 2 groups dependingon the result of this bacteriological examination ; in Group 1 apparent pathogenic bacteria were isolated, in Group 2 nonpathogenic bacteria were isolated or no bacteria grew. While improved-case ratio in Group 1 was only about 54.5%, that in Group 2 was about 70.6%. It suggested that another recovery system exsist in upper air way disorder except for the effect by antibiotics. Drainage of effusion of PNS was shown to be one of the most important factors in the treatment of sinusitis in this study.

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[in Japanese]

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In the analysis of the patients with chronic sinusitis who underwent endoscopic sinus surgery, the differences of postoperative courses between the groups classified by the differences of pathological status of the sinuses were discussed. All of the patients with hemilateral sinusitis had a good postoperative course. Chronic sinusitis where asthma, where polyps had numerous eosinophil infiltration, often fail to be cured. In chronic sinusitis with allergic rhinitis, which seems to be caused not only by type I allergy but by various factors, endoscopic sinus surgery was effective. Some of the groups classified by the endoscopic observation of the maxillary sinuses during operation, including the-group with both polyps and pus in their maxillary sinuses, had worse postoperative courses compared to the other groups. However a clear classification which can explain the variety of pathological findings of sinusitis have notbeen established in this study.

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YAMIK sinus catheter, which was developed in Russia, was applied for the treatment of sinusitis after endonasal sinus surgery (ESS). YAMIK catheter was performed once a week for three consecutive weeks, started at 10-12 days after surgery. Physiological saline solution and/or 2% polyvidone iodine (Isodine Solution) was used for irrigation of sinuses by a YAMIK catheter. An evaluation of subjective symptoms and objective findings by the endoscope showed good results after surgery, although the evaluation dates were earlier. The long-term evaluation is needed in a future study. CT findings also showed improvement of cloudiness of sinuses. It is concluded that YAMIK sinus catheter is useful for postoperative sinus cleaning.

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Macrolide therapy has been reported to be effective for the treatment of chronic sinusitis in adults. However, whether it is effective for the treatment of chronic sinusitis in children is still controversial. Here we report the results of a clinical study on the effectiveness for the treatment in chronic sinusitis in children, as compared with adults. In this study, we included 30 children and 30 adults with chronic sinusitis who underwent macrolide therapy. The children were given 100 mg of clarithromycin and the adults 200 mg of clarithromycin or 150 mg of roxithromycin per day orally for three months. Rhinorrhea were improved at the end of the three months in 87% of the children and 67% of the adults, but the difference of the efficacy was not statistically significant. However, sinus X-rays revealed significant improvement in the shadow of the sinuses in the children after the macrolide therapy. In bacteriological examinations the pathogens were frequently isolated from the middle nasal meatus at the entry of the study, but rarely at the end of the three months in the case of the children. From these results, we concluded that macrolide therapy can be extremely effective for the treatment of chronic sinusitis in children, since bacterial inflammation may play a greater role than allergic inflammation in the pathogenesis of chronic sinusitis in children.

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Low-dose and long-term treatment with macrolides antibiotics, including roxithromycin (RXM), is widely accepted, particulary in Japan, to favorably modify the clinical status of certain patients with chronic sinusitis. Although investigation of the mechanisms of its efficacy has suggested that it is not due to the antimicrobiological effects of the drugs, theprecise mechanisms are not well understood. The present study was designed to investigate the possible mechanisms of a low-dose and long-term RXM administration treatment.
Specific pathogen-free 5-week-old male BALB/c mice were divided into three groups, nontreated normal control, RXM-treated and RXM-nontreated group. Each group consisted with 20 mice, and they were maintained bacteria-, fungi-and parasite-free conditions throughout the experiments. The mice, which were treated with RXM at a single dose of 2.5 mg/kg once a day for various periods via stomach tube, were intratracheally instillated with 1.0 μg/ml LPS (0.1 ml), and aqueous lung extracts (ALE) were prepared 24 hrs after LPS instillation. The cytokine activities in ALE was measured by enzyme-linked immunosorbent assay in duplicate.
The results showed that long-term administration of RXM for a period of 7 and 12 weeks significantly (P <0.01) inhibited IL-1 β and TNF-α appearance in ALE induced by LPS instillation in comparison with those appearance in ALE from RXM-nontreated mice, whereas administration of RXM for 1 and 5 weeks scarcely affected IL-1 β and TNF-α appearance in ALE.
These results strongly suggested that the favorable effects of low-dose and long-term RXM administration treatment on chronic sinusitis might be explained partially by its inhibitory effects on inflammatory cytokine production.

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