CLINICAL STUDIES OF ABNORMAL HOST DEFENSE

本项目的目的是研究宿主异常的患者 防御 在1994财政年度，研究重点是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， 儿童（CGD），高免疫球蛋白E-复发性感染综合征 (Job s）、特异性颗粒缺陷、白细胞粘附缺陷和 其他患有复发性感染的患者， 明确定义的疾病类别。目前，我们跟踪了77名患者， CGD组18例高免疫球蛋白-E复发感染 综合征，其他吞噬细胞功能障碍综合征18例。 此外，12例患者接受了播散性多种药物 耐药非典型分枝杆菌感染，其中一些人似乎有 吞噬细胞异常。 第四阶段研究的影响， NIH继续在CGD中使用干扰素-γ预防感染 根据FDA的要求。未发生意外毒性 用干扰素-γ观察。 观察到的感染减少， 初步研究已经持续，值得注意的是， 接受干扰素-γ治疗的CGD患者的真菌感染率是接受干扰素-γ治疗的CGD患者的一半， 对于那些没有接受药物治疗的患者。 鉴于高发病率 CGD患者的真菌感染，我们还启动了一项研究 旨在评估伊曲康唑在CGD中的疗效。 几个长 完成了与CGD具体管理问题有关的学期研究 患者 其中包括对骨骼受累的全面审查 在CGD中，CGD中的特殊麻醉考虑，独特的泌尿外科 CGD的临床表现，肺部感染的外科治疗 以及CGD中肺的外科病理学。 这一切成功都 临床研究只能在NIH进行汇编， CGD患者可长期随访。 几个独特 感染及其成功管理在CGD中进行了描述。 这些 包括成功治疗Sarcinosporoninkin的报道， 皮肤外瓶霉（Exophialadermativae）和多变拟青霉（Paecilomycesvarioti）。 的令人鼓舞 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， 为了评估γ-干扰素在结核病中的作用， 在具有播散性非典型性的罕见患者人群中使用 对常规治疗有抵抗力的分枝杆菌感染。 十二 患者至今仍在研究中。 显著的临床获益， 在接受治疗的患者中观察到感染的根除。

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.