Measurement of glomerular filtration rate in ICU patients using 99mTc-DTPA and inulin.

Improved and reliable methods for assessing glomerular filtration rate (GFR) in intensive care patients are needed in light of known deficiencies using creatinine clearance. We compared simultaneous two-hour clearances of inulin (CIn), creatinine (CCr), and 99mTc-diethylenetriaminepentaacetic acid (CDTPA) in 18 medical or surgical intensive care patients (range, 49 to 92 years old) with blood urea nitrogen (BUN) levels greater than 17.9 mmol/liter (0.5 mg/ml), serum creatinine levels greater than 150 mumol/liter (0.02 mg/ml), or estimated Cockcroft clearance less than 60 ml/min. Patients had severe renal dysfunction with average GFR of 35 ml/min (range, 2 to 69 ml/min). CDTPA and CCr correlated significantly with CIn, although CDTPA tended to provide a closer approximation. Cockcroft clearance (32 +/- 4 ml/min) was grossly similar to CDTPA and CIn and correlated significantly, especially when weight was calculated using actual as opposed to ideal body weight. In a subset of 13 patients with CIn less than 30 ml/min, only CDTPA was significantly correlated with CIn. In patients in the intensive care unit, CDTPA provides a rapid, accurate, and inexpensive clinical assessment of GFR, even at very low GFRs.

Diamine oxidase is important in assessment of polyamine effects on hemopoietic cell proliferation in vitro.

A difference was observed in the effect of difluoromethlyornithine (DFMO), a specific inhibitor of ornithine decarboxylase, on human and murine granulocyte-macrophage precursor cell (CFU-C) proliferation in vitro, in the presence of fetal bovine serum (FBS) and horse serum (HS). A dose of DFMO which almost totally abolished CFU-C colonies in cultures containing FBS had no effect or very little effect on CFU-C in cultures supplemented with HS. This effect could be reversed by aminoguanidine reacting with diamine oxidase (DAO), which is present in FBS but not in HS. The importance of DAO in the assessment of polyamine effects is also suggested by decreased colony formation in cultures containing HS and DFMO only after the addition of this enzyme. Additionally, Mo T cell line cultures containing DFMO demonstrated a substantially lower intracellular concentration of putrescine in the presence of FBS rather than HS.

Haematological cell proliferation and differentiation responses to perturbations of polyamine biosynthesis.

Combined administration of methylglyoxal-bis-guanylhydrazone (MGBG) (25 mg/kg) with difluoromethylornithine (DFMO), or MGBG alone at a higher dose (50 mg/kg), to mice resulted in a decreased white cell count (WBC) in the peripheral blood while DFMO or MGBG alone at a lower dose (25 mg/kg) had no effect. As expected, DFMO alone increased the number of colony forming units spleen (CFU-s), colony forming units diffusion chamber granulocyte (CFU-dg) and colony forming units culture (CFU-c) in the bone marrow. MGBG treatment led to an increase in CFU-dg alone. Combined treatment seemingly had no effect on marrow stem cells. Total tibial and differential counts were not affected by any of the treatments. Cell proliferation in diffusion chamber cultures, as judged by CFU-dg colony formation, was impaired by MGBG alone or in combination with DFMO, at dose levels which had no effect or increased the precursor cell number in the bone marrow. This effect was partially reversed with either putrescine or spermidine. Determination of intracellular polyamine concentrations, demonstrated decreased putrescine and spermidine levels after DFMO administration. As expected, MGBG treatment resulted in decreased spermidine and spermine levels, concomitant with an increase in putrescine. In mice which received both agents, rather than only MGBG, after 3 days higher intracellular polyamine concentrations were observed. After 11 days, however, there was no significant difference between the two groups.