ABSTRACT
INTRODUCTION: Treating recipient mice with palifermin (recombinant human keratinocyte growth factor) prevents the development of acute, lethal, graft-versus-host disease (GVHD). This is due, at least in part, to the ability of palifermin to protect epithelial cells from injury. Using the C57BL/6-->(C57BL/6 x DBA/2)F(1)-hybrid model, we previously showed that the protective effect of palifermin was also associated with redirection of the cytokine profile from Th1 to Th2. DISCUSSION: To study this immunoregulatory effect more directly, we induced acute GVH reactions in which we treated the donors rather than the recipients with palifermin. The recipient mice were protected from GVHD-associated morbidity, and their cytokine profile was predominantly Th2. The palifermin-treated donor mice alone showed a similar Th2 cytokine profile, and we observed elevated levels of thymic stromal lymphopoietin mRNA in the thymus. We further demonstrated that treating the donor mice with palifermin protects against GVHD-associated morbidity, even if the donors are deficient in Valpha14i natural killer T cells. Our findings clearly show that palifermin mediates immunoregulatory effects in addition to its cytoprotective effects and that both are likely to be involved in the mechanism through which palifermin provides protection from acute murine GVHD.
Subject(s)
Fibroblast Growth Factor 7/administration & dosage , Graft vs Host Disease/prevention & control , Recombinant Proteins/administration & dosage , Th1 Cells/metabolism , Th2 Cells/metabolism , Acute Disease , Animals , Cell Line, Transformed , Cytokines/metabolism , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Epithelial Cells/pathology , Graft vs Host Disease/immunology , Hematopoietic Stem Cell Transplantation , Injections, Subcutaneous , Killer Cells, Natural/immunology , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Mice, Knockout , Receptor, Fibroblast Growth Factor, Type 2/agonists , Th1 Cells/immunology , Th1 Cells/pathology , Th2 Cells/immunology , Th2 Cells/pathologyABSTRACT
OBJECTIVES: Total testosterone (TT) is frequently prescribed with an SHBG and/or free or bioavailable testosterone measurement. Our objective was to identify a TT range for which subsequent SHBG measurement/calculation adds no additional clinical information. DESIGN AND METHODS: Study data were composed of 3955 sets of TT, SHBG and calculated bioavailable testosterone (cBAT) results from unscreened ambulatory male subjects, aged 18-99. RESULTS: 90% of mismatches between TT and cBAT were observed with TT levels between 6.5 and 13.0 nmol/L, with only slight age variation and no important change with albumin level. SHBG measurement restricted to male patients with TT between 6.5 and 13.0 nmol/L should enable reagent cost savings of over 55%. CONCLUSION: We suggest that a TT level below 6.5 nmol/L or above 13.0 nmol/L provides sufficient useful information for ruling out hypogonadism in ambulatory adult males. This strategy of BAT testing should lead to significant time and cost savings.
Subject(s)
Diagnostic Tests, Routine/methods , Hypogonadism/diagnosis , Hypogonadism/metabolism , Testosterone/metabolism , Adolescent , Adult , Aged , Albumins , Biological Availability , Diagnostic Tests, Routine/economics , Diagnostic Tests, Routine/standards , Humans , Male , Middle Aged , Sex Hormone-Binding Globulin/metabolism , Testosterone/analysisABSTRACT
BACKGROUND: B-type natriuretic peptide (BNP) is a cardiac hormone that regulates hemodynamic equilibrium and alleviates ventricular stress. In patients with chronic heart failure, BNP levels increase in proportion to the severity of clinical symptoms and degree of decreased left ventricular ejection fraction. BNP has clinical utility in the evaluation, management, and prognosis of patients with heart failure. METHODS: We evaluated the analytical performance characteristics of the BNP immunochemiluminometric assay in the ACS:180 instrument at three hospital laboratory sites. The analytical performance characteristics evaluated included imprecision, sensitivity (minimum detectable concentration, MDC), analytical measurement range (AMR), dilution linearity/recovery, lot-to-lot reagent variation, high-dose hook effect, and comparison against ADVIA Centaur BNP results on patients' EDTA-plasma samples. RESULTS: Total imprecision was <10% coefficient of variation at BNP concentrations of 43-1830 pg/ml; MDC was 6.9 pg/ml; AMR was 6.9-5000 pg/ml; overall recovery of BNP in samples diluted up to 1:10 was 98%; there was no lot-to-lot reagent variation in BNP results and no high-dose hook effect at BNP concentrations up to 100,000 pg/ml; and, ACS:180 results were highly correlated (r=0.996) with Centaur BNP results. CONCLUSIONS: The ACS:180 BNP assay demonstrated excellent analytical performance characteristics and agreement with BNP results obtained using the Centaur instrument.
