title: Bone marrow transplantation: effects of conditioning and cyclosporin prophylaxis on microvascular permeability to a small solute (technetium 99m diethylene triamine penta-acetic acid).
abstract: Microvascular permeability to small diffusible solutes has rarely been measured at a clinical level. We have developed a simple non-invasive technique for measuring the permeability surface area (PS) product, which is suitable for clinical use. We illustrate its potential value in six subjects who underwent bone marrow transplantation for chronic myeloid leukaemia. These patients received high-dose cyclosporin A (CyA) for prevention of graft versus host disease (GVHD) and sustained an easily measurable increase in microvascular permeability to technetium 99m diethyltriamine penta-acetic acid (99mTc-DTPA). This was measured as the PS product, which increased from 1.1 (SD 0.3) to 2.2 (0.4) ml/min per 100 ml tissue between baseline and treatment with CyA for prevention of GVHD (P less than 0.01). The increase broadly correlated with nephrotoxicity which was measured, from the plasma DTPA clearance, as global glomerular filtration rate (GFR). This decreased from 106 (11.1) to 49 (6.7) ml/min (P less than 0.001). These abnormalities, both in PS product and GFR, were sustained for several months, after which they tended to return towards baseline levels. We conclude firstly that this technique has a potential clinical role and secondly that endothelial abnormalities due to CyA deserve further study.
authors.affiliation: Department of Diagnostic Radiology, Royal Postgraduate Medical School, London, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Peters
authors.forename: D S
authors.initials: DS
authors.lastname: Vassilarou
authors.forename: J M
authors.initials: JM
authors.lastname: Hows
authors.forename: F W
authors.initials: FW
authors.lastname: Ballardie
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology; D003524:Cyclosporins / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000000981:diagnostic imaging / Q000628:therapy*; D008297:Male; D011877:Radionuclide Imaging; D016284:Technetium Tc 99m Pentetate
chemical_list: D003524:Cyclosporins; D016284:Technetium Tc 99m Pentetate