Ken-ichiro Fujita

Effects of macrolides on interleukin-8 secretion from human nasal epithelial cells

Abstract Low-dose, long-term macrolide treatment has recently been reported to be very effective in patients with chronic airway diseases. We examined the in vivo and in vitro effects of 14-membered macrolide antibiotics erythromycin (EM) and clarithromycin (CAM) on interleukin (IL)-8 secretion from human nasal epithelial cells. Fifteen patients with chronic sinusitis received macrolide treatment (CAM 400 mg/day) for 1 to 3 months. The number of infiltrated neutrophils and IL-8 concentrations in the nasal discharges of these patients decreased significantly at 1 to 2 months after the treatment. In vitro effects of EM and CAM on IL-8 secretion were examined in nasal epithelial cells cultured at the air-liquid interface. After 14-day culture in the air-liquid interface, macrolide antibiotics were added in medium for 24 h. EM and CAM at concentrations of 10–4 M did not affect spontaneous secretions or IL-1β-induced secretions of IL-8 either apically or basolaterally. When cells were preincubated with 10–4 M CAM for 7 days, the IL-1β-induced secretion of IL-8 decreased significantly. However, no difference was observed between the effects of 10–4 M CAM and 10–4 M josamycin, a 16-membered macrolide. These results suggest that macrolide treatment inhibits neutrophil infiltration and IL-8 secretion in nasal epithelium in vivo and that these clinical effects depend on a mechanism other than the direct action of macrolide on nasal epithelial cells.

Secretory cell differentiation and mucus secretion in cultures of human nasal epithelial cells : Use of a monoclonal antibody to study human nasal mucin

We have developed an air-liquid interface culture system for human nasal epithelial cells that differentiate into mucociliary phenotypes in a defined serum-free medium. Dissociated cells obtained from nasal polyps were cultured on a collagen gel substrate. At confluence, the cells lost characteristics of differentiated cells, and secretory cell and ciliated cell differentiation appeared after 7 days in an air-liquid interface. After 21 days, about half of the epithelial cells were stained with Alcian blue—periodic acid—Schiff stain or monoclonal antibody HCS18, which was directed against human nasal mucin specific for epithelial secretory (goblet) cells. The quantitative examination using the antibody HCS 18 revealed that the antibody-reactive nasal mucin was secreted only on the apical side of the cultures, and interleukin-1 β and tumor necrosis factor α stimulated these mucus secretions. The culture system with an antimucin monoclonal antibody developed in this study should be useful for studying polarized mucus secretion from human nasal epithelial cells.

Nine cases of piriform sinus fistula with acute suppurative thyroiditis

OBJECTIVE Acute suppurative thyroiditis is a disease of an infection originated from the piriform sinus via congenital fistula. The purposes of this study are the establishment of accurate and necessary examinations for the diagnosis and necessary treatment for complete remission of this disease. METHODS We reported nine cases with acute suppurative thyroiditis who were treated by operation. Preoperative examinations and operative procedures for nine cases were investigated. RESULTS A congenital fistula was detected in seven of nine patients preoperatively, and in all seven patients, the fistula was detected during the operation. Serum thyroglobulin was elevated in four of five patients who were examined the serum level. Ultrasonogram was performed in eight cases, and localized swelling of the thyroid lobe was observed in all cases. No inflammatory recurrence was observed in eight cases, and recurrence was observed in one case where complete fistelectomy was not performed. CONCLUSION Measurements of serum thyroglobulin, ultrasonography, and pharyngoesophagography were useful in the diagnosis of acute suppurative thyroiditis. Complete removal of the fistula with or without affected thyroid lobe is necessary to prevent recurrent suppuration.

Monoclonal antibody-detectable carbohydrate epitopes of human nasal secretions are differentially expressed in tissue and diseases.

To study the differential carbohydrate expression of airway secretions, we have produced a series of monoclonal antibodies that recognize human nasal secretory cell products. Mice were immunized with purified nasal secretion from patients with chronic sinusitis (CS) and hybridomas were selected by ELISA and immunohistochemical staining of the maxillary sinus mucosa from patients with CS. Eighteen antibodies were obtained. Antibody HCS 18 reacted with epithelial goblet cells, antibody HCS 4, 5, 6, and 16 stained submucosal gland cells, and antibody HCS 13 and 15 reacted with epithelial goblet cells, submucosal gland cells, and endothelial cells of vessels. The other eleven antibodies recognized epithelial goblet cells and submucosal gland cells. Cross-reactivity of these antibodies with secretory cells in other organs and in other species was determined and the different staining pattern was observed between upper and lower airway tissue, suggesting that secretory products from upper and lower airways may be different. Reactivity of the antibodies with nasal secretory cells was also examined in patients with perennial allergic rhinitis (AR) and normal subjects. Antibody HCS 18 weakly reacted with nasal glands in the tissue from CS and AR patients, but minimally reacted with gland cells in normal tissue. Antibody HCS 1 and 7 partially lost their reactivity with nasal epithelium of inferior turbinate from normal subjects and AR patients. These antibodies may be useful to study nasal secretions.

A Clinical Study of Nasopharyngeal Carcinoma.

Forty previously untreated patients with nasopharyngeal carcinoma treated for 18 years from 1981 through 1998 at the Mie University Hospital are reviewed. The male to female ratio was 2.3:1. The most frequent chief complain was cervical mass. More than half of the patients were classified into stages IIB or III. Until 1988, patients were treated mainly with radiotherapy, but the results were unsatisfactory. Since 1992, to decrease the occurrence of locoregional relapse and/or distant metastasis, we have used pirarubicin, cisplatin and peplomycin alternating with radiation, two cycle of chemotherapy alternating with two courses of radiation (30 Gy each after the first and second chemotherapy cycle). The chemotherapy consisted of pirarubicin, 30mg/m2/day on day 1, cisplatin, 50mg/m2/day on day 2 and peplomycin 5 mg/day on day 3-6, all given intravenously. The 5 years survival rate of 13 patients who recieved this new trearment was 61.5%. We conclude that alternative chemoradiotherapy is necessary for a better prognosis of nasopharyngeal carcinoma.

Operative Indication of Chronic Thyroiditis for Avoidance the Unnecessary Operation

Twenty patients of chronic thyroiditis without neoplasm were operated in our department from September 1986 to August 2000. Of these patients, 15 were suspected the involvement of malignant tumors preoperatively, and 6 were observed class IlI by fine needle aspiration cytology (FNA). Hemithyroidectomy and partial resection were conducted in 17 patients, and subtotal and/or total thyroidectomy were conducted in 3 patients. Two patients underwent total thyroidectomy had dyspnea or swallowing disorder. Class i by FNA is sometimes observed in the patients with chronic thyroiditis, then the carefull interpretation for class III is proposed. Thyroid associated autoimmune antibodies (at least anti thyrogurobulin antibody) is necessary for the diagnosis of chronic thyroiditis. The operation for the chronic thyroiditis without malignancy is proposed to avoid by the accurate diagnosis of chronic thyroiditis.

Mesurement of Basedow's Disease as Head and Neck Surgeons

Thirty two patients with Basedows disease were operated in Yamada Red Cross Hospital for recent 14 years and 6 months. Total thyroidectomy were performed in 7 patients, and Subtotal thyroidectomy were in residual 25 patients. In 25 patients who were performed subtotal thyroidectomy, normalization of the thyroid function were observed in 11, and hypothyroid were in 6, but recurrence of hyperthyroidism were observed in 1 case. None of the 32 patients who were operated were observed postoperative recurrent nerve paresis and hypoparathyroidism. Thirteen patients were determined as surgical operation for poor controled thyroid function, and 5 patients were determined afraid of combined thyroid malignancy. Recently Medical measurement was adopted in our department, in short, slow reduction of methymazole and block and replacement. Furthermore, surgical indication is determined by our department. Thirty two patients who were operated in our department were reconsidered about the surgical indication, and 19 patients were determined that surgery were not hurried. It is important that head and neck surgeons aggressively perticipate for the measurement of Basedows disease, and it is necessary that head and neck surgeons the take the initiative for the determination of surgical indication.

Studies of Endoscopic Diurnal Sleep Study and Laser-Assisted Uvulopalatoplasty(LAUP) for Snoring Patients.

We present a prospective analysis of an endoscopic diurnal sleep study using diazepam and the clinical efficacy of laser-assisted uvulopalatoplasty (LAUP) for patients with snoring problems. Between February 1998 and August 1999, 91 patients visited our hospital for treatment of snoring problems. Among them, 69 patients were examined by the present sleep study, and 87.0% involved snoring caused by airway obstruction in the soft palate. Fifty-eight patients who were diagnosed as having snoring arising from the soft palate underwent LAUP, and 38 patients completed postoperative questionnaires. The mean of snoring scores significantly decreased from 10 to 4.1±0.8 at 1 month after LAUP. Other subjective symptoms also showed significant improvements, including onset of sleep apnea, wakening at night, daytime somnolence, and frequent daytime fatigue. These desirable improvements persisted for 18 months. It is concluded that our sleep study was useful for examination of patients with snoring problems, and that LAUP is an effective method, especically for snoring arising from the soft palate.