CSF lactate for accurate diagnosis of community-acquired bacterial meningitis.

CSF lactate measurement is recommended when nosocomial meningitis is suspected, but its value in community-acquired bacterial meningitis is controversial. We evaluated the diagnostic performance of lactate and other CSF parameters in a prospective cohort of adult patients with acute meningitis. Diagnostic accuracy of lactate and other CSF parameters in patients with microbiologically documented episodes was assessed by receiver operating characteristic (ROC) curves. The cut-offs with the best diagnostic performance were determined. Forty-five of 61 patients (74%) had a documented bacterial (n = 18; S. pneumoniae, 11; N. meningitidis, 5; other, 2) or viral (n = 27 enterovirus, 21; VZV, 3; other, 3) etiology. CSF parameters were significantly different in bacterial vs. viral meningitis, respectively (p < 0.001 for all comparisons): white cell count (median 1333 vs. 143/mm(3)), proteins (median 4115 vs. 829 mg/l), CSF/blood glucose ratio (median 0.1 vs. 0.52), lactate (median 13 vs. 2.3 mmol/l). ROC curve analysis showed that CSF lactate had the highest accuracy for discriminating bacterial from viral meningitis, with a cutoff set at 3.5 mmol/l providing 100% sensitivity, specificity, PPV, NPV, and efficiency. CSF lactate had the best accuracy for discriminating bacterial from viral meningitis and should be included in the initial diagnostic workup of this condition.

Granulocyte and granulocyte-macrophage colony-stimulating factors, their receptors and interleukin-3 levels in newborns.

Serum levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF) and interleukin-3 (IL-3) as well as neutrophil counts were studied on the first, second and fifth days after birth, in order to elucidate the relations between neutrophil kinetics and these hematopoietic factors. The G-CSF and GM-CSF receptors on neutrophils were also investigated in 16 healthy newborns. G-CSF and GM-CSF receptor-positive neutrophil percentages were not different from those in the peripheral blood of adult controls. The receptor densities, assessed by mean fluorescence channel number, were also similar in newborn and adult neutrophils. The mean serum concentrations of G-CSF were high (191 pg/ml) on the first day of life and gradually decreased on the second (128 pg/ml) and fifth (112 pg/ml) days. A statistically significant correlation (p < 0.05) was found between G-CSF levels and absolute neutrophil counts (ANC). Furthermore, the percentage of decrease in G-CSF levels correlated significantly with the percentage of decrease in ANC (p < 0.001). GM-CSF levels were also high, though less striking, on the first day of life (9.5 pg/ml), remained at high levels on the second (10 pg/ml), and gradually decreased on the fifth (8.8 pg/ml) day. IL-3 levels were high (110 pg/ml) on the first day of life and remained at high levels on the second (138 pg/ml) and fifth (138 pg/ml) days. We found that the IL-3, GM-CSF and G-CSF levels were elevated during the first week of postnatal life. Our findings suggest that significant changes in the levels of the growth factors are likely to be the cause of significant leukocyte blood picture changes during the first week of life. We found normal GM-CSF and G-CSF receptors in uninfected newborns.

Differential expression of receptors for hemopoietic growth factors on subsets of CD34+ hemopoietic cells.

The production of peripheral blood cells is regulated by hemopoietic growth factors (HGF) which promote the survival of stem cells and stimulate the proliferation and maturation of progenitors as well as effector functions of mature blood cell subsets. The actions of HGF's are determined by the cellular distribution of receptors for these HGF's within the hemopoietic tissues and by the functional program that receptor-expressing cells can execute after growth factor stimulation. Identification of stem cells and their progeny and delineation of the growth factor receptor phenotype of these cells will establish target cell range and functions of individual growth factors in hemopoiesis. Cells with specific HGF receptors can be detected and isolated by flow cytometric methods, e.g., by staining with biotinylated ligand and fluorescently-tagged streptavidin. Receptor-expressing cells can be classified on the basis of expression of the CD34 antigen and other markers that distinguish immature progenitors from more differentiated cells. Using this approach distinct expression patterns have been shown for the receptors for interleukin-3 (IL-3), IL-6, granulocyte/macrophage colony-stimulating factor (GM-CSF) and Steel Factor (SF) on subsets of CD34+ and CD34- cells in bone marrow. Expression of the IL-3 receptor (R), IL-6R and GM-CSFR appears to be very low on the most immature subsets of CD34+ cells, but increases progressively during successive stages, of in particular myelomonocytic differentiation. In contrast, the receptor for SF, i.e., Kit, is highly expressed on very immature CD34-bright/HLA-DR-dull cells, which include stem cells. Kit levels decline during myelomonocytic and B-lymphoid differentiation whereas they increase to maximal levels during early stages of erythropoiesis. The heterogeneity in receptor expression, together with other immunophenotypic characteristics, allows for the identification of distinct progenitor cell subsets and differentiation stages within the CD34+ cell compartment. By selecting appropriate phenotypic criteria it will be possible to further dissect the stem cell compartment and eventually establish the, possibly heterogeneous, HGF receptor phenotype of pluripotent stem cells.