Yoichiro Ichikawa

Erythromycin Reduces Neutrophils and Neutrophil-Derived Elastolytic-Like Activity in the Lower Respiratory Tract of Bronchiolitis Patients

Diffuse panbronchiolitis (DPB) is a disease of adults characterized by chronic inflammation of the respiratory bronchioles and the infiltration of chronic inflammatory cells. The clinical efficacy of erythromycin therapy has been demonstrated in DPB patients, but the mechanism of action of this drug is unknown. We investigated the localization of neutrophils in lung biopsy specimens, as well as the cell population and elastolytic-like and chemotactic activity of bronchoalveolar lavage (BAL) fluid, before and after treatment with erythromycin or ampicillin in 11 DPB patients (six biopsy-proven and five clinically diagnosed) and one follicular bronchiolitis patient. These bronchiolitis patients had a high percentage of neutrophil and a high neutrophil-derived elastolytic-like activity in BAL fluid compared with chronic bronchitis patients and normal control subjects. The number of neutrophils and the neutrophil-derived elastolytic-like activity in BAL fluid decreased significantly after treatment with erythromycin along with a significant improvement in pulmonary function studies, although there was no significant change in the chemotactic activity of BAL fluid. No significant reduction in BAL fluid neutrophilia was found in the ampicillin-treated patients. These results suggest an important role for the neutrophil in the pathogenesis or development of bronchiolitis, and also suggest that erythromycin may be useful for the treatment of bronchiolitis through its direct action upon host phagocytic cells.

Spontaneous production of various cytokines except IL-4 from CD4+ T cells in the affected organs of sarcoidosis patients

We investigated surface antigens and spontaneous cytokine production of T cells from broncho‐alveolar lavage fluid (BALF) and aqueous humor (AH) from pulmonary sarcoidosis patients for a better understanding of the role of T cells in granuloma formation. The levels of CD3, CD11b, and CD28 antigen expression on freshly isolated T cells in the BALF of patients were significantly lower than those in peripheral blood lymphocytes (PBL) of either sarcoidosis patients or healthy donors (HD). In contrast, the levels of CD80 (B7/B7‐1) and CD86 (B70/B7‐2) antigen expression were significantly higher on these T cells and alveolar macrophages in the BALF of patients. Fifty‐three T cell clones (TCC) established from the BALF and AH of the three sarcoidosis patients displayed primarily either CD4+ CD11b+ CD28+ or CD4+ CD11b‐ CD28‐ phenotypes. Most (61–90%) of these TCC spontaneously produced greater amounts of IL‐1a, IL‐10, tumour necrosis factor (TNF), and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) than did TCC from the PBL from sarcoidosis patients or HD (P < 0·05). Interferon‐gamma (IFN‐γ), IL‐6, and IL‐2, but not IL‐4, were also produced by 40–48% of these TCC. These results suggest that CD4+ T cells of the affected organs of sarcoidosis patients are activated and involved in the immunopathogenesis of sarcoidosis through production of various cytokines.

The benefit of cisplatin-based polychemotherapy for adenocarcinoma of the lung

SummaryWe studied the efficacy of cisplatin-based polychemotherapy for adenocarcinoma of the lung. A total of 136 patients were randomized for treatment with either cyclophosphamide, Adriamycin, cisplatin and mitomycin C (CAPM) or mitomycin C, cytosine arabinoside and tegafur (MCT). Radiation was given to the chests of patients at stage III. The differences in the response rate (35% in the CAPM arm and 13% in the MCT arm) were statistically significant (P <0.01). However, the significant difference was observed in stage-IV patients (CAPM, 33%; MCT, 4%;P <0.001) and not in stage-III patients (CAPM, 40%; MCT, 40%). The median period of survival was 9.5 months for the CAPM arm and 5.5 months for the MCT arm (P <0.035, Wilcoxon-Gehan test;P <0.1, log-rank test). Improved median survival for the CAPM regimen was demonstrated only by stage-IV patients (CAPM, 10 months; MCT, 5.5 months;P <0.025, Wilcoxon-Gehan test;P <0.05, log-rank test). The duration of the response, including PRs and NCs, was significantly different depending on the treatment, showing 5 months for the CAPM arm and 3 months for the MCT arm (P <0.05). The significant difference was also only observed in stage-IV patients. Myelosuppression was more severe with CAPM than with the MCT regimen. Nausea and vomiting were significantly increased in patients receiving the CAPM regimen. However, all toxicities were acceptable and there were no treatment-related deaths. We concluded that cisplatin-based chemotherapy, CAPM therapy, was of more benefit to patients with adenocarcinoma of the lung than MCT therapy.

[A case of Shy-Drager syndrome with respiratory failure due to bilateral vocal cord paresis].

両側声帯麻痺に基づく呼吸不全を来した, Shy-Drager症候群(以下, SDSと略す)の1例を経験した.症例は, 64才,男性で,昭和52年から,陰萎,尿失禁,昭和55年には,音声減弱,いびきおよび立ちくらみが出現し,昭和58年12月,重篤な呼吸不全を来し,昭和59年6月,当科に入院となつた.起立性低血圧,陰萎,屎尿失禁などの自律神経症状と,錐体路症状,小脳症状を認めたことから,臨床的に, SDSと診断した.呼吸不全の原因は,気管支ファイバースコープを用いて行なつた喉頭の観察で,両側声帯麻痺であることが判明した. SDSでみられる声帯麻痺の機序および,呼吸不全に対して,気管切開が有効であることを述べた.