Ca2+ and phospholipid-dependent protein kinase (protein kinase C) activity is not necessarily required for secretion by human neutrophils

Ca2+-dependent and phospholipid-dependent protein kinase (PKC) is a receptor for and is activated by phorbol esters. This enzyme is reportedly involved in the mechanism of superoxide anion (O2-) production and the release of intracellular granule contents from human neutrophils. As previously reported by others, we found that greater than 75% of the total cellular PKC activity existed in a soluble form in untreated neutrophils and that this activity was enhanced in a dose- dependent manner by phorbol 12-myristate 13-acetate (PMA) and by phorbol 12,13-dibutyrate (PDBu). Furthermore, mezerein, an analogue of PMA that is thought to be a competitive inhibitor, did not activate PKC, and on the contrary, inhibited PMA-stimulated activity in a dose- dependent manner. Pretreatment of intact neutrophils with PMA or PDBu caused the "translocation" of PKC activity to the insoluble cell fraction; PKC translocation was not detected after mezerein stimulation at any of the tested concentrations. Neither did mezerein cause an increase in intracellular Ca2+, as monitored by Quin 2 fluorescence. Both phorbol esters and mezerein stimulated intact neutrophils to generate O2- and release lysosomal enzymes into the extracellular medium. Finally sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis demonstrated key differences in the patterns of endogenous phosphoproteins of neutrophils stimulated with phorbol as compared with mezerein. We therefore suggest that PKC activation may not be the only pathway required to elicit neutrophil responses.     

Comparison of coronary stenting versus conventional balloon angioplasty on five-year mortality in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention

Little is known about the influence of stenting versus balloon angioplasty on long-term outcomes (particularly mortality) after primary percutaneous coronary intervention (PCI). We evaluated 2,087 patients with ST-elevation myocardial infarction enrolled in various Primary Angioplasty in Myocardial Infarction (PAMI) trials in the United States, who underwent primary PCI. The main outcome was all-cause mortality at 5 years, obtained through the National Death Index. Of the 2,087 patients, stenting was performed in 692 (33%). The absolute difference in the hospital (2.2% vs 3.3%), 1-year (3.3% vs 5.2%), and 5-year (10% vs 13%) mortality rates favored patients receiving a stent versus conventional balloon therapy, with the difference increasing with time. A multivariate Cox model identified stent use (vs balloon alone) as an independent correlate of lower 5-year mortality (hazard ratio 0.60, 95% confidence interval 0.42 to 0.85). The absolute reduction in mortality was greatest in the highest risk group. In conclusion, compared with balloon angioplasty, stenting during primary PCI not only resulted in better angiographic and short-term outcomes, but also in a sustained beneficial effect on mortality at 5 years. These data support the routine use of coronary stenting in most patients undergoing primary PCI, when feasible.     

A Hodgkin cell-specific antigen is expressed on a subset of auto- and alloactivated T (helper) lymphoblasts

A Hodgkin cell-specific antigen detected by the monoclonal antibody Ki- 1 was found on T helper lymphocytes after activation by autologous and allogeneic stimulator cells. About 50% of lymphoblasts generated by auto- and alloactivation reacted with the antibody. In contrast, only less than 6% of lymphoblasts stimulated with Con-A, phytohemagglutinin (PHA), or protein A, and none of lymphoblasts activated by oxidative mitogenesis, expressed this antigen. Among several permanent cell lines tested, the K562, MOLT-4, HL-60, and EBV transformed B lymphoblastoid cells reacted with the Ki-1 antibody. The results may indicate possible relationships between the autoreactive subset of T lymphocytes and the pathogenesis of Hodgkin's disease.     

Comparison of outcomes of diabetic and nondiabetic patients undergoing primary angioplasty for acute myocardial infarction

We sought to determine whether diabetes mellitus independently conferred poor prognosis in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI). In 3,742 patients enrolled in the Primary Angioplasty in Myocardial Infarction (PAMI) studies with the intention of undergoing primary PCI, we compared in-hospital mortality, 6-month mortality, and 6-month major adverse cardiovascular events (MACEs), i.e., composite of death, reinfarction, or ischemic target vessel revascularization (TVR), between diabetics (n = 626, 17%) and nondiabetics (n = 3,116, 83%). We evaluated the independent impact of diabetes on outcomes after adjustment for baseline clinical and angiographic differences. Diabetics had worse baseline clinical characteristics, longer pain onset-to-hospital arrival time, and longer door-to-balloon time. They had more multivessel coronary disease and lower left ventricular ejection fractions, but better baseline Thrombolysis In Myocardial Infarction (TIMI) flow. Diabetics underwent primary PCI less often (88% vs 91%, p = 0.01). During the index hospitalization, diabetics were more likely to die (4.6% vs 2.6%, p = 0.005). During 6-month follow-up, diabetics had higher incidences of death (8.1% vs 4.2%, p <0.0001) and MACEs (18% vs 14%, p = 0.036). In multivariate analysis, diabetes was independently associated with 6-month mortality (hazard ratio 1.53, 95% confidence interval 1.03 to 2.26, p = 0.03), but not with in-hospital mortality or 6-month MACEs. We conclude that diabetics with AMI have less favorable baseline characteristics and are less likely to undergo primary PCI than nondiabetics. Despite excellent angiographic results, diabetics had significantly worse 6-month mortality.     

Ischemia-driven target vessel revascularization after-primary percutaneous coronary intervention: patients at risk and their outcomes

Clinical and angiographic correlates of ischemia-driven target vessel revascularization (ITVR) in patients undergoing primary percutaneous coronary interventions (PCI) are currently less well known. Accordingly, we examined 2,981 patients enrolled in different Primary Angioplasty in Myocardial Infarction trials, who underwent primary PCI to evaluate risk factors and outcomes of individuals requiring subsequent ITVR. At 6 months, ITVR was required in 321 patients (11%). Compared to the cohort without ITVR, patients requiring ITVR were younger (P=0.036), females (P=0.018), and more likely to have systolic blood pressure >100 mmHg on presentation (P=0.022), family history of premature coronary artery disease (P=0.035), and postprocedure dissection (P=0.001). In contrast, Killip Class >I on presentation (P=0.05), left circumflex as infarct-related artery (P=0.022), and the use of ticlopidine (P=0.044) and stents (p=0.057) were less frequent among ITVR patients. Multivariate analysis identified younger age (for each 10-year decrease, odds ratio [OR], 1.18; 95% confidence interval [CI], 1.06-1.32), female gender (OR: 1.41, 95% CI: 1.05-1.89), and final dissection (OR: 1.69, 95% CI: 1.23-2.33) as independent risk factors for ITVR. In-hospital reinfarction (P < 0.001) was increased and at 6 months remained higher in ITVR patients; in-hospital and 6-month mortality did not differ between the two groups. Our study identifies the incidence, risk factors, and outcomes of patients requiring ITVR after primary PCI. Importantly, our data suggest that no increase in mortality occur, if ITVR is promptly performed to treat recurrent ischemia after primary PCI.     

Usefulness of the presence of peripheral vascular disease in predicting mortality in acute myocardial infarction patients treated with primary angioplasty (from the Primary Angioplasty in Myocardial Infarction Database)

Patients with acute myocardial infarction (AMI) often have multiple co-morbidities that influence outcome. We sought to evaluate the impact of peripheral vascular disease (PVD) on the outcome of patients with AMI treated with primary angioplasty. We evaluated 3,716 patients with AMI who underwent emergency catheterization with planned primary angioplasty in the Primary Angioplasty in Myocardial Infarction trials. Patients with a history of PVD (claudication, stroke, or transient ischemic attack) were compared with patients without PVD. Of the 3,716 patients, 394 (10.6%) had PVD and were older, more often women, and more frequently had a history of diabetes mellitus, hypertension, smoking, congestive heart failure, angina, myocardial infarction, and coronary revascularization. They presented more often with a heart rate >100 beats/min, Killip class >1, lower ejection fraction, and multivessel disease. No difference was found in stent use, final percentage of stenosis, or Thrombolysis In Myocardial Infarction 3 flow. Patients with PVD had a twofold increased in-hospital mortality (5.3% vs 2.6%, p = 0.0021). The difference remained significant at 1 month, 6 months, and 1 year (12.6% vs 6%, p < 0.0001). In multivariate logistic regression analysis, a history of PVD was an independent predictor of in-hospital mortality and death at 1 year (odds ratio 1.64, 95% confidence interval 1.04 to 2.57, p = 0.032). In conclusion, patients with AMI with PVD have increased co-morbidities and higher mortality despite treatment with primary angioplasty. The presence of PVD is an independent predictor of in-hospital mortality and death at 1 year.