Autoantibodies against granulocyte–macrophage colony stimulating factor and interleukin-3 are rare in patients with Felty's syndrome

Objectives: Antibodies against granulocyte colony stimulating factor are frequently found in patients with Felty's syndrome (FS). In this study, we examined the prevalence of antibodies against two other granulopoietic cytokines: granulocyte–macrophage colony stimulating factor (GM-CSF) and interleukin-3 (IL3). Methods: Sera of 32 patients with FS, 20 normocytic patients with rheumatoid arthritis (RA), and 72 healthy individuals were screened for the presence of antibodies against GM-CSF and IL3 by ELISA and bioassays, using the human erythroleukaemia cell line TF-1. Results: In two of the 32 patients with FS, antibodies to GM-CSF and IL3 were detectable by ELISA. Binding anti-GM-CSF antibodies were also detected in one of the 72 healthy controls, while in another healthy subject and in one of the patients with normocytic RA, anti-IL3 antibodies were present. Serum from one of the two patients with FS who tested positive for anti-IL3 and anti-GM-CSF antibodies by ELISA showed strong neutralising capacity to the biological effect of IL3, but not to GM-CSF in vitro. Patients with FS had significantly higher serum levels of GM-CSF (median; 2.82 pg/mL; interquartile range 2.64–3.19 pg/mL) compared with patients with RA (2.52 pg/mL; 2.28–2.72 pg/mL; p = 0.012) and healthy controls (2.23 pg/mL; 2.04–2.52; p<0.001). In addition, serum levels of IL3 in patients were significantly higher in FS (10.05 pg/mL; 8.94–11.98) compared with controls (4.79 pg/mL; 3.72–7.22; p<0.001), but not compared with RA patients (9.52 pg/mL; 8.32–10.42; p = 0.17). Conclusions: Antibodies to GM-CSF and IL3 are rare in patients with FS and RA and in healthy subjects. In individual patients with FS, the presence of neutralising anti-IL3 antibodies may contribute to the development of cytopenia

Impact of Iodinated Contrast Injections on Percent Diameter Coronary Arterial Stenosis and Implications for Trials of Intracoronary Pharmacotherapies in Patients With ST-Elevation Myocardial Infarction

Administration of fibrinolytic, antiplatelet, and antithrombotic agents by the intracoronary route may disaggregate clot, but the potential role of the mechanical force of the injection itself in decreasing clot burden has not been studied. Patients with ST-segment elevation myocardial infarction who were pretreated in the emergency room (ER) with unfractionated heparin and aspirin in the TITAN-TIMI 34 study were randomized to treatment with eptifibatide in the ER (n = 131) versus after diagnostic catheterization (n = 150). Quantitative coronary angiography was used to assess change in diameter stenosis from time of first contrast injection to injection before percutaneous coronary intervention (PCI) immediately preceding wire placement down the culprit artery in a matching view. Successful perfusion of the myocardium was assessed after PCI by the presence of Thrombolysis In Myocardial Infarction myocardial perfusion grade of 2 or 3. In patients treated with eptifibatide in the ER, there was a 1.3% absolute improvement in diameter stenosis from the first injection to the injection before PCI (p = 0.02), whereas there was no change in diameter stenosis in patients not treated with eptifibatide in the ER (0.0%, p = NS). Each 1% improvement in percent diameter stenosis during diagnostic injections before PCI was strongly correlated with an open muscle after PCI (adjusted odds ratio 1.09, 95% confidence interval 1.02 to 1.16, p = 0.012). In conclusion, the mechanical force of a contrast injection decreases thrombotic burden in patients with ST-segment elevation myocardial infarction pretreated with eptifibatide but not with placebo. Future trials of intracoronary pharmacotherapies should include a control arm in which saline is injected to account for the potential clot disaggregation that occurs as a result of iodinated contrast injections, particularly if the patient has been pretreated with aggressive pharmacotherapy

Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation

BACKGROUND: A substantial proportion of patients receiving fibrinolytic therapy for myocardial infarction with ST-segment elevation have inadequate reperfusion or reocclusion of the infarct-related artery, leading to an increased risk of complications and death. METHODS: We enrolled 3491 patients, 18 to 75 years of age, who presented within 12 hours after the onset of an ST-elevation myocardial infarction and randomly assigned them to receive clopidogrel (300-mg loading dose, followed by 75 mg once daily) or placebo. Patients received a fibrinolytic agent, aspirin, and when appropriate, heparin (dispensed according to body weight) and were scheduled to undergo angiography 48 to 192 hours after the start of study medication. The primary efficacy end point was a composite of an occluded infarct-related artery (defined by a Thrombolysis in Myocardial Infarction flow grade of 0 or 1) on angiography or death or recurrent myocardial infarction before angiography. RESULTS: The rates of the primary efficacy end point were 21.7 percent in the placebo group and 15.0 percent in the clopidogrel group, representing an absolute reduction of 6.7 percentage points in the rate and a 36 percent reduction in the odds of the end point with clopidogrel therapy (95 percent confidence interval, 24 to 47 percent; P<0.001). By 30 days, clopidogrel therapy reduced the odds of the composite end point of death from cardiovascular causes, recurrent myocardial infarction, or recurrent ischemia leading to the need for urgent revascularization by 20 percent (from 14.1 to 11.6 percent, P=0.03). The rates of major bleeding and intracranial hemorrhage were similar in the two groups. CONCLUSIONS: In patients 75 years of age or younger who have myocardial infarction with ST-segment elevation and who receive aspirin and a standard fibrinolytic regimen, the addition of clopidogrel improves the patency rate of the infarct-related artery and reduces ischemic complications