CLINICAL STUDIES OF ABNORMAL HOST DEFENSE

这个项目的目的是研究宿主异常的患者。 防守。在94财年，研究集中在吞噬细胞异常的患者 功能。这些患者包括慢性肉芽肿性疾病患者。 儿童期(CGD)，高免疫球蛋白E-反复感染综合征 (工作的)，特殊颗粒缺乏，白细胞黏附缺乏和 其他反复感染的患者，他们没有陷入 明确定义的疾病类别。目前我们跟踪了77名患者 应用CGD治疗18例高免疫球蛋白-E反复感染 其他吞噬细胞功能障碍综合征18例。 此外，对12例患者进行了播散多药的随访。 耐药非典型分枝杆菌感染，其中一些似乎有 吞噬细胞异常。第四阶段的效果研究 国立卫生研究院继续使用干扰素-伽玛素预防慢性阻塞性肺疾病的感染 应美国食品和药物管理局的具体要求。没有出现意想不到的毒性 用干扰素-伽马治疗。在中国观察到的感染的减少 初步研究一直在进行，值得注意的是， 接受干扰素-γ治疗的CGD患者的真菌感染是这个数字的一半 对于那些没有接受药物治疗的患者。鉴于发病率很高， 对于CGD患者的真菌感染，我们还启动了一项研究 旨在评估伊曲康唑治疗慢性阻塞性肺疾病的疗效。几个长的 完成了与CGD具体管理问题有关的学期研究 病人。其中包括对骨骼参与的全面审查。 在CGD中，CGD的特殊麻醉考虑，独特的泌尿外科 肺部感染的外科治疗--CGD的表现 CGD和CGD肺的外科病理改变。这其中的每一个 临床研究只能在NIH汇编，在那里有大量的 CGD患者可长期随访。几个独特的 在CGD中描述了感染及其成功的管理。这些 包括成功治疗肉孢子菌素墨水的报道， 和变色拟青霉(Paecilmyces Varoti)。鼓舞人心的 CGD患者的发现促使人们考虑使用干扰素- 作为我们长期目标的一部分， 评估干扰素-γ在结核病中的作用，我们启动了对其研究 在播散性非典型肺炎患者中的应用 分枝杆菌感染对常规治疗耐药。十二 到目前为止，已经对患者进行了研究。极大的临床益处 在接受治疗的患者中，感染被根除。

The purpose of this project is to study patients with abnormal host defense. In FY '94 studies focussed on patients with abnormal phagocyte function. These include patients with chronic granulomatous disease of childhood (CGD), Hyperimmunoglobulin E-recurrent infection sydrome (Job's), specific granule deficiency, leukocyte adhesion deficiency and other patients with recurrent infections who do not fall into a specifically defined disease category. Currently we follow 77 patients with CGD, 18 patients with the hyperimmunoglobulin-E recurrent infection syndrome, and 18 patients with other phagocyte dysfunction syndromes. In addition, 12 patients are followed with disseminated multiple drug resistant-atypical mycobacteria infections, some of whom appear to have abnormalities of phagocytic cells. A phase IV study of the effect of interferon-gamma for infection prophylaxis in CGD has continued at NIH at the specific request of the FDA. No unexpected toxicities have been seen with interferon-gamma. The reduction in infections observed in the initial study has been sustained and of note is that the incidence of fungal infections in CGD patients receiving interferon-gamma is half that for those patients not receiving the drug. In view of the high incidence of fungal infections in CGD patients, we have also initiated a study designed to assess the efficacy of itraconazole in CGD. Several long term studies were completed related to specific management issues of CGD patients. These included comprehensive reviews of skeletal involvement in CGD, special anesthetic considerations in CGD, unique urologic manifestations in CGD, the surgical management of pulmonary infections in CGD, and the surgical pathology of the lung in CGD. Each of these clinical studies could only be compiled at NIH where a large cohort of CGD patients could be followed for a long time. Several unique infections and their successful management were described in CGD. These include reports of the successful treatment of Sarcinosporon inkin, Exophiala dermatitidis, and Paecilomyces varioti. The encouraging findings in CGD patients prompted consideration of the use of interferon- gamma in other infectious diseases.As part of our long term objective of evaluating interferon-gamma in tuberculosis, we initiated studies of its use in an unusual patient population with disseminated atypical mycobacteria infection resistant to conventional therapy. Twelve patients have been studied to date. Dramatic clinical benefit with eradication of the infection was seen in the patients treated.