CLINICAL TRIALS WITH TRANSPLANT ASPIRATION CYTOLOGY

移植抽吸细胞学临床试验

• 批准号: 3152332
• 负责人: PEKKA J HAYRY
• 金额: $ 8.53万
• 依托单位: UNIVERSITY OF HELSINKI
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-08-01 至 1986-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3152332
• 关键词: antiinflammatory agents; biopsy; combination chemotherapy; cyclosporines; drug administration rate /duration; glucocorticoids; human subject; human therapy evaluation; immune adherence reaction; immunosuppressive; kidney transplantation; longitudinal human study; monoclonal antibody; radiation therapy; radioimmunoassay

We have developed a new assay for daily monitoring of intragraft events after renal transplantation in man. Fine needle aspiration biopsies of approximately 10-20 Mu1 in volume are drawn from renal transplants without risk to the transplant or the transplant recipient. From transplant aspiration cytology we can (a) evaluate the condition of the graft parenchymal component; (b) quantitate the expression of the major locus (and other) antigens on the graft parenchymal (and inflammatory) cells, and (c) quantitate the onset, size, type and duration of the in situ inflammatory response of rejection. We will utilize this technology in prerandomized clinical trials to evaluate the in situ mode(s) of action of different immunosuppressive and anti-inflammatory drugs in renal allograft rejection. The immunosuppressive effects will be evaluated in prophylactic trials: Prerandomized patient groups will receive for immunosuppression (i) azathioprine (AZA) plus low dose methyl-prednisolone (MP), (ii) AZA plus high dose MP, (iii) cyclosporin A (CyA), (iv) CyA plus MP, or (v) AZA, low dose MP and (monoclonal) anti-T cell serum (ATS). The impact of the treatment on the graft, on the display of graft MHC antigens and on the onset, size and type of the (first) in situ inflammatory episode(s) of rejection are monitored by transplant aspiration cytology. The anti-inflammatory effects are examined in therapeutic trials: Patients treated with a single immunosuppressive regime (probably AZA plus high initial MP) are randomized at the onset of the first in situ episode of inflammation (i.e., rejection) for the following treatment groups: (i) oral low dose MP, (ii) intravenous high dose MP, (iii) (monoclonal) ATS, (iv) CyA, (v) local irradiation or (vi) nothing at all. The impact of the treatment on the size, type and duration of the in situ inflammatory response of rejection will be quantitated. We believe that our approach will help to define the site(s) of action of these drugs on the intragraft immune and inflammatory effects, provide a basis for logical and more discriminate use of these drugs, lead to steroid-sparing or steroid-free immunosuppressive programs and hopefully to less complications and better impact on patient therapy.

我们开发了一种新的检测方法，用于每日监测移植物内事件 肾移植后的细针穿刺活检 从肾移植物中抽取大约10-20 μ l体积， 对移植物或移植受体的风险。 从移植 抽吸细胞学我们可以（a）评估移植物的状况 （B）定量主要基因座的表达 (and其他）移植物实质（和炎性）细胞上的抗原，和 (c)定量原位损伤的发生、大小、类型和持续时间 排斥反应的炎症反应。 我们将利用这项技术， 评价的原位作用方式的预随机临床试验 不同免疫抑制和抗炎药物在肾移植中的应用 排斥反应 将在预防性治疗中评价免疫抑制作用。 试验：预随机化患者组将接受免疫抑制治疗 (i)硫唑嘌呤（AZA）加低剂量甲基强的松龙（MP），（ii）AZA 加高剂量MP，（iii）环孢菌素A（CyA），（iv）CyA加MP，或（v）AZA， 低剂量MP和（单克隆）抗T细胞血清（ATS）。 的影响 对移植物、对移植物MHC抗原的展示和对移植物的免疫应答进行治疗。 （首次）原位炎症发作的发作、大小和类型 通过移植抽吸细胞学监测排斥。 的 在治疗试验中检查抗炎作用：患者 用单一免疫抑制方案治疗（可能是AZA加高 初始MP）在首次原位发作时随机分组， 炎症（即，拒绝），用于以下治疗组：（i） 口服低剂量MP，（ii）静脉内高剂量MP，（iii）（单克隆）ATS， (iv)CyA，（v）局部照射或（vi）完全不照射。 的影响 原位炎症的大小、类型和持续时间 将对排斥反应进行定量。 我们相信我们的方法 将有助于确定这些药物在移植物内的作用部位 免疫和炎症作用，提供了逻辑和更多的基础 歧视使用这些药物，导致类固醇节省或类固醇免费 免疫抑制方案，并希望减少并发症， 影响患者治疗。

项目成果

Prophylactic oral acyclovir after renal transplantation.

肾移植后预防性口服阿昔洛韦。

• DOI: 10.1097/00007890-198503000-00014
• 发表时间: 1985
• 期刊: Transplantation
• 影响因子: 6.2
• 作者: Pettersson,E;Hovi,T;Ahonen,J;Fiddian,AP;Salmela,K;Höckerstedt,K;Eklund,B;vonWillebrand,E;Häyry,P
• 通讯作者: Häyry,P

Antagonistic effects of gamma interferon and steroids on tissue antigenicity.

γ干扰素和类固醇对组织抗原性的拮抗作用。

• DOI: 10.1084/jem.164.5.1470
• 发表时间: 1986
• 期刊: The Journal of experimental medicine
• 作者: Leszczynski,D;Ferry,B;Schellekens,H;vanderMeide,PH;Häyry,P
• 通讯作者: Häyry,P