No abstract

The authors question whether the d-dimer assay and pulmonary computed tomography angiography (CTA) are being used appropriately to evaluate suspected acute pulmonary embolism (PE) at their hospital. To answer this question, a retrospective review was performed on all emergency department (ED) patients who underwent d-dimer assay and/or CTA from August 15, 2008, to August 14, 2009. The authors' algorithm for diagnosing PE requires that patients with low or intermediate probability of acute PE undergo a d-dimer assay, followed by CTA if the d-dimer is positive. Patients with high probability of PE should have CTA performed without a d-dimer assay. This result suggests that d-dimer assay and CTA are used inappropriately to evaluate patients with suspected acute PE in our ED. The low threshold for initiating an evaluation for PE decreases the prevalence of PE in this population.

Infusion of the oxidant lipid peroxide tert-butyl hydroperoxide (t-bu-OOH) causes pulmonary vasoconstriction and increases vascular permeability in isolated perfused rabbit lungs. We have previously shown that t-bu-OOH stimulates arachidonic acid metabolism, increasing the synthesis of the cyclooxygenase products. The current experiments were designed to determine the role that cyclooxygenase- and lipoxygenase-derived mediators play in the lung injury caused by t-bu-OOH. In the present experiments, we found that t-bu-OOH not only increased the synthesis of the cyclooxygenase-derived products thromboxane and prostacyclin but also increased the synthesis of the lipoxygenase-derived products leukotrienes B4, C4, D4, and E4. To determine the role that these arachidonic acid metabolites play in the increase in pressure and vascular permeability caused by t-bu-OOH, we studied the effect that inhibitors of arachidonic acid metabolism or a leukotriene receptor blocker had on the pulmonary edema. We compared an uninjured control group with 4 groups of lungs given t-bu-OOH: a t-bu-OOH control group; a group pretreated with the cyclooxygenase inhibitor indomethacin (14 microM); a group pretreated with an analogue of arachidonic acid, 5-, 8-, 11-, 14-eicosatetraynoic acid (ETYA) (100 microM), that inhibits both the cyclooxygenase and lipoxygenase pathways; and a group pretreated with the leukotriene receptor antagonist FPL 55712 (38 microM). To produce lung injury, t-bu-OOH (300 microM) was infused throughout the first minute of 4 successive 10-min periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Leukotriene B4 (LTB4) is a potent stimulus for neutrophil chemotaxis, aggregation, and activation. Although this mediator has been postulated as a possible stimulus for the neutrophil accumulation seen after mast cell triggering in vivo, the ability of human mast cells to produce this leukotriene has never been described. The purpose of this study was to investigate the ability of purified human lung mast cells and mast cells in lung fragments to generate leukotriene B4 after immunologic (anti-IgE) and nonimmunologic (calcium ionophore, A23187) activation. Release of LTB4 was quantitated by 2 specific radioimmunoassays with biochemical characterization by high performance liquid chromatography. In a first series of experiments using radioimmunoassay 1, purified human lung mast cells (n = 10) released LTB4 in response to both an immunologic and nonimmunologic stimulus in a time- and dose-dependent manner. In response to an optimum concentration of anti-IgE (3 micrograms/ml), mast cells of 4.5 to 98% purity, generated 6.2 +/- 1.7 ng immunoreactive LTB4 (iLTB4)/10(6) mast cells. HPLC characterization revealed that 30 +/- 0.3% of the iLTB4 coeluted with standard synthetic LTB4 in these studies. In a second series of experiments using radioimmunoassay 2, mast cell activation resulted in the release of 0.5 to 1 ng iLTB4/10(6) mast cells with greater than 75% coeluting with synthetic LTB4. Thus, we estimate that human lung mast cells can generate approximately 1 to 2 ng of LTB4 per million mast cells.(ABSTRACT TRUNCATED AT 250 WORDS)