Leukocyte cell population data (volume conductivity scatter) in postprandial leukocyte activation.

INTRODUCTION: Changes in leukocyte cell population data have been reported in various infectious diseases, but little is known in other inflammatory conditions such as the postprandial state. We investigated whether leukocyte cell population data change during postprandial leukocyte activation. METHODS: Healthy volunteers underwent a standardized oral fat loading test (OFLT). Flowcytometric quantitation of leukocyte activation markers CD11b, CD66b, CD35, and CD36, together with leukocyte cell population data from LH750 hematology analyzers were measured fasting and at 4 and 8 h postprandially. RESULTS: Twelve volunteers were included. Postprandial leukocyte activation was confirmed by increased expression of CD11b by monocytes (+11.7%) and neutrophils (+15.0%) and by increased expression of CD66b (+14.7%) and CD35 (+16.6%) by neutrophils at T = 4 h. The mean scatter from neutrophils, reflecting granularity, significantly decreased at T = 4 h (P < 0.05) and returned to baseline at T = 8 h (P-anova 0.048). The mean volume of monocytes increased significantly at T = 4 h (P < 0.001) and returned to baseline at T = 8 h (P-anova 0.0008). At T = 4 h, CD11b expression on neutrophils was associated with a reduction in mean scatter of neutrophils (Pearson's r: -0.677, P = 0.016). CONCLUSION: Postprandial leukocyte activation is accompanied by temporary changes in leukocyte cell population data, similar to changes observed during various infections, but to a lesser extent.

Antiplatelet therapy in therapy-resistant unstable angina. A pilot study with REO PRO (c7E3).

Patients with unstable angina, refractory to intensive medical therapy, are at high risk of developing thrombotic complications, such as myocardial infarction and coronary occlusion during coronary angioplasty. As platelet aggregation and thrombus formation play an important role in this ongoing ischaemic process, a monoclonal platelet GPIIb/IIIa receptor antibody (c7E3) has been designed to modify the clinical course and underlying coronary lesion morphology. To evaluate whether c7E3 could influence the incidence of complications, we randomized 60 patients to c7E3 or placebo after initial angiography had demonstrated a culprit lesion amenable for angioplasty. All patients exhibited dynamic ECG changes and recurrent pain attacks, despite intensive medical therapy. After study drug bolus and infusion, angiography was repeated and angioplasty performed. Recurrent ischaemia during study drug infusion occurred in nine and 16 patients from the c7E3 and placebo groups, respectively (P = 0.06). Major events defined as death, myocardial infarction or urgent intervention occurred in one and seven patients, respectively (P = 0.03). One patient from the placebo group died as a result of recurrent infarction. Resolution of clots was only observed in the c7E3 group, combined with improvement in TIMI flow grade in 20% of patients. Quantitative angiography showed an improvement in percentage diameter stenosis in the c7E3 group, which was not observed in the placebo group, although the difference between the two treatment groups was not significant. No excess bleeding was observed in the treatment group. Thus, c7E3 bolus and infusion, combined with heparin and aspirin improved the clinical course, the coronary lesion morphology and rheology in patients with unstable angina, refractory to medical treatment.

Correlation between clinical course and quantitative analysis of the ischemia related artery in patients with unstable angina pectoris, refractory to medical treatment. Results of two randomized trials. The European Cooperative Study Group.

Patients with unstable angina, refractory to intensive medical therapy, are at high risk for developing thrombotic complications, such as recurrent ischemia, myocardial infarction and coronary occlusion during coronary angioplasty. As both platelet aggregation and/or thrombus formation play an important role in this ongoing ischemic process, a monoclonal platelet GPIIb/IIIa receptor antibody (c7E3) or thrombolytic therapy (alteplase) might be able to modify the clinical course and underlying coronary lesion morphology. To evaluate whether alteplase or c7E3 could influence the incidence of complications, we randomized 36 and 60 patients, respectively to alteplase or placebo, or c7E3 or placebo. All patients exhibited dynamic ECG changes and recurrent pain attacks, despite maximal tolerated medical therapy. Patients were randomized in both studies after initial angiography had demonstrated a culprit lesion amenable for angioplasty. After study drug infusion quantitative angiography was repeated and angioplasty performed. Recurrent ischemia during study drug infusion occurred in 5, 6, 9 and 16 patients from the alteplase, placebo, c7E3 and placebo group, respectively. Major events defined as death, myocardial infarction or urgent intervention occurred in 7, 3, 1 and 7 patients, respectively. Two patients died: one in the alteplase group and one in the placebo group from the c7E3 study. The first patient due to retroperitoneal hemorrhage, the second as a result of recurrent infarction. Qualitative angiography showed resolution of clots in the c7E3 group only, while the same group of patients showed in 20% an improvement in TIMI flow grade, without deterioration in any patient from this group.(ABSTRACT TRUNCATED AT 250 WORDS)

Randomized trial of a GPIIb/IIIa platelet receptor blocker in refractory unstable angina. European Cooperative Study Group.

BACKGROUND: Patients with unstable angina despite intensive medical therapy, ie, refractory angina, are at high risk for developing thrombotic complications: myocardial infarction or coronary occlusion during percutaneous transluminal coronary angioplasty (PTCA). Chimeric 7E3 (c7E3) Fab is an antibody fragment that blocks the platelet glycoprotein (GP) IIb/IIIa receptor and potently inhibits platelet aggregation. METHODS AND RESULTS: To evaluate whether potent platelet inhibition could reduce these complications, 60 patients with dynamic ST-T changes and recurrent pain despite intensive medical therapy were randomized to c7E3 Fab or placebo. After initial angiography had demonstrated a culprit lesion suitable for PTCA, placebo or c7E3 Fab was administered as 0.25 mg/kg bolus injection followed by 10 micrograms/min for 18 to 24 hours until 1 hour after completion of second angiography and PTCA. During study drug infusion, ischemia occurred in 9 c7E3 Fab and 16 placebo patients (P = .06). During hospital stay, 12 major events occurred in 7 placebo patients (23%), including 1 death, 4 infarcts, and 7 urgent interventions. In the c7E3 Fab group, only 1 event (an infarct) occurred (3%, P = .03). Angiography showed improved TIMI flow in 4 placebo and 6 c7E3 Fab patients and worsening of flow in 3 placebo patients but in none of the c7E3 Fab patients. Quantitative analysis showed significant improvement of the lesion in the patients treated with c7E3 Fab, which was not observed in the placebo group, although the difference between the two treatment groups was not significant. Measurement of platelet function and bleeding time demonstrated > 90% blockade of GPIIb/IIIa receptors, > 90% reduction of ex vivo platelet aggregation to ADP, and a significantly prolonged bleeding time during c7E3 Fab infusion, without excess bleeding. CONCLUSIONS: Combined therapy with c7E3 Fab, heparin, and aspirin appears safe. These pilot study results support the concept that effective blockade of the platelet GPIIb/IIIa receptors can reduce myocardial infarction and facilitate PTCA in patients with refractory unstable angina.

Prehospital thrombolysis with alteplase (rt-PA) in acute myocardial infarction.

The improvement in survival in patients undergoing thrombolytic therapy in myocardial infarction is determined by the delay between coronary occlusion and reperfusion. The REPerfusion in Acute Infarction Rotterdam (REPAIR) study was designed to examine the feasibility and safety of prehospital thrombolysis with alteplase (rt-PA, 'Actilyse'). A small portable ECG computer system is used to confirm the presence of a large myocardial infarction (at least 1.0 mV ST-deviation) 'on the spot'. Between 22 June 1988 and 1 January 1991, 226 patients were treated by the ambulance service after the evaluation of 9052 patients complaining of chest pain. Therapy could be initiated within an average of 100 +/- 56 min (SD) after the onset of symptoms, and within 22 +/- 9 min after ambulance arrival. Three patients were defibrillated during transportation. Six patients (3%) died after arrival in the hospital. The time gained by prehospital treatment was 47 min (95% confidence limits 44-51 min) in comparison with 220 patients who did not meet the criteria for prehospital thrombolysis, but received thrombolytic therapy as soon as possible after hospital admission. The developed procedure allows rapid and safe initiation of thrombolytic therapy in selected patients, even in the absence of a physician. The observed low mortality supports the concept that prehospital thrombolytic therapy is indeed beneficial to the patient.

[Earlier treatment of acute myocardial infarction with administration of alteplase (rt-PA) before hospitalization]. / Snellere behandeling van het acute myocardinfarct door toediening van alteplase (rt-PA) vóór opname.

The gain in survival by thrombolytic therapy in patients with myocardial infarction is determined by the delay between coronary occlusion and reperfusion. The REPAIR study was designed to examine the feasibility and safety of prehospital thrombolysis with alteplase (rt-PA, Actilyse). Indications and contraindications are verified by general practitioner or ambulance nurse with a short questionnaire. A small portable ECG computer system is used to confirm the presence of a large evolving myocardial infarction 'on the spot'. Between June 1988 and May 1990, 150 patients were treated by the ambulance service. Therapy could be initiated within an average of 91 (+/- 40) minutes (sd) after the onset of symptoms, and within 23 (+/- 9) minutes after ambulance arrival. Three patients were defibrillated during transportation, in one of these therapy had to be discontinued because of cardiac massage. No other complications were observed. Five patients (3%) died after arrival in the hospital. The time gained by prehospital treatment averaged 47 (+/- 2) minutes in comparison with 220 patients who received thrombolytic therapy after hospital admission. The procedure allows rapid and safe initiation of thrombolytic therapy in selected patients, even in the absence of a physician.