Low molecular weight heparin (reviparin) in percutaneous transluminal coronary angioplasty. Results of a randomized, double-blind, unfractionated heparin and placebo-controlled, multicenter trial (REDUCE trial)

Objectives. The specific objective of the REDUCE trial was to evaluate the effect of low molecular weight heparin on the incidence and occurrence of restenosis in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Background. Unfractionated heparin and its low molecular weight fragments possess antiproliferative effects and have been shown to reduce neointimal smooth muscle cell migration and proliferation in response to vascular injury in experimental studies. Methods. The REDUCE trial is an international prospective, randomized, double-blind, multicenter study. Twenty-six centers in Europe and Canada enrolled 625 patients with single-lesion coronary artery obstructions suitable for PTCA. Three hundred six patients received reviparin as a 7,000-U bolus before PTCA, followed by 10,500 U as an infusion over 24 h and then twice-daily 3,500-U subcutaneous application for 28 days. The 306 patients in the control group received a bolus of 10,000 U o

Prolonged survival of patients with angioimmunoblastic T-cell lymphoma after high-dose chemotherapy and autologous stem cell transplantation: the GELTAMO experience

Abstract OBJECTIVES: Angioimmunoblastic T-cell lymphoma (AIL) is a rare lymphoma with a poor prognosis and no standard treatment. Here, we report our experiences with 19 patients treated with high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) within the GELTAMO co-operative group between 1992 and 2004. METHODS: The median age at transplantation was 46 yr. Fifteen patients underwent the procedure as front-line therapy and four patients as salvage therapy. Most patients received peripheral stem cells (90%) coupled with BEAM or BEAC as conditioning regimen (79%). RESULTS: A 79% of patients achieved complete response, 5% partial response and 16% failed the procedure. After a median follow-up of 25 months, eight patients died (seven of progressive disease and secondary neoplasia), while actuarial overall survival and progression-free survival at 3 yr was 60% and 55%. Prognostic factors associated with a poor outcome included bone marrow involvement, transplantation in refractory disease state, attributing more than one factor of the age-adjusted-International Prognostic Index, Pretransplant peripheral T-cell lymphoma (PTCL) Score or Prognostic Index for PTCL. CONCLUSIONS: More than half of the patients with AIL that display unfavourable prognostic factors at diagnosis or relapse would be expected to be alive and disease-free after 3 yr when treated with HDC/ASCT. Patients who are transplanted in a refractory disease state do not benefit from this procedure

Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice

Chromosomal translocations involving the MALT1 gene are hallmarks of mucosa-associated lymphoid tissue (MALT) lymphoma. To date, targeting these translocations to mouse B cells has failed to reproduce human disease. Here, we induced MALT1 expression in mouse Sca1(+)Lin(-) hematopoietic stem/progenitor cells, which showed NF-κB activation and early lymphoid priming, being selectively skewed toward B-cell differentiation. These cells accumulated in extranodal tissues and gave rise to clonal tumors recapitulating the principal clinical, biological, and molecular genetic features of MALT lymphoma. Deletion of p53 gene accelerated tumor onset and induced transformation of MALT lymphoma to activated B-cell diffuse large-cell lymphoma (ABC-DLBCL). Treatment of MALT1-induced lymphomas with a specific inhibitor of MALT1 proteolytic activity decreased cell viability, indicating that endogenous Malt1 signaling was required for tumor cell survival. Our study shows that human-like lymphomas can be modeled in mice by targeting MALT1 expression to hematopoietic stem/progenitor cells, demonstrating the oncogenic role of MALT1 in lymphomagenesis. Furthermore, this work establishes a molecular link between MALT lymphoma and ABC-DLBCL, and provides mouse models to test MALT1 inhibitors. Finally, our results suggest that hematopoietic stem/progenitor cells may be involved in the pathogenesis of human mature B-cell lymphomas

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Contraction-mediated pinocytosis of RGD-peptide by dermal fibroblasts: inhibition of matrix attachment blocks contraction and disrupts microfilament organisation

Force generation in collagen and matrix contraction are basic functions of fibroblasts and important elements of tissue repair. Cell-matrix attachment is critical to this contraction, involving RGD-binding integrins. We have investigated how this process operates, in terms of force generation (in the Culture Force Monitor) and cytoskeletal structure, using a synthetic RGD-decapeptide. The RGD-peptide blocked force generation over the first 6 h, followed by near complete recovery by 20 h. However, dose response was complex indicating multiple processes were operating. Analysis of cytoskeletal structure after treatment with RGD-peptide indicated major disruption with condensed aggregates of actin and microtubular fragmentation. Fluorescent labeling and tracking of the RGD-peptide demonstrated intracellular uptake into discrete cytoplasmic aggregates. Critically, these RGD-peptide pools co-localised with the condensed actin microfilament aggregates. It is concluded that RGD-peptide uptake was by a form of contraction-mediated pinocytosis, resulting from mechanical tension applied to the untethered RGD-peptide-integrin, as contractile microfilament were assembled. These findings emphasize the importance of sound mechanical attachment of ligand-occupied integrins (e.g., to extracellular matrix) for normal cytoskeletal function. Conversely, this aspect of unrestrained cytoskeletal contraction may have important pathogenic and therapeutic applications

Impact of baseline platelet count in patients undergoing primary percutaneous coronary intervention in acute myocardial infarction (from the CADILLAC trial).

Despite the well-recognized role of platelets in the pathogenesis of acute myocardial infarction (AMI) and in the vascular responses to angioplasty, the relation between platelet count and outcomes after primary percutaneous coronary intervention (PCI) in AMI is unknown. We therefore determined the effect of baseline platelet count on clinical and angiographic outcomes of patients with AMI undergoing primary PCI. In the prospective, randomized CADILLAC trial, platelet count on admission was available in 2,021 of 2,082 patients (97.0%). Angiographic results and outcomes at 30 days and 1 year were stratified by quartiles of platelet count. Median platelet count was 231 x 10(9)/L (range 38 to 709). Primary PCI angiographic success rates were independent of platelet count. The 30-day incidence of target vessel thrombosis or reocclusion increased steadily across the higher quartiles of baseline platelet count (0.2%, 0.6%, 1.0%, and 2.0%, p = 0.027). At 1 year, patients with a baseline platelet count \u3eor=234 versus10(9)/L had higher rates of death or reinfarction (8.9% vs 4.5%,

Relation between late patency of the infarct-related artery, left ventricular function, and clinical outcomes after primary percutaneous intervention for acute myocardial infarction (CADILLAC trial).

The importance of sustained patency of the infarct-related artery after primary percutaneous coronary intervention for acute myocardial infarction is controversial. We examined serial measures of left ventricular function and clinical outcomes in 280 patients with an initially occluded infarct artery in whom Thrombolysis In Myocardial Infarction trial grade 3 flow was achieved and routine follow-up angiography was performed 7 months after percutaneous coronary intervention. Reocclusion of the infarct artery was associated with decreased event-free survival, and the degree of restenosis was an independent predictor of the lack in improvement in left ventricular ejection fraction over time

Impact of ST-segment resolution after primary angioplasty on outcomes after myocardial infarction in elderly patients: an analysis from the CADILLAC trial.

BACKGROUND: Age is a strong independent predictor of outcomes after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). Whether lower rates of reperfusion success contribute to the poor prognosis in elderly patients is unknown. METHODS: A formal ST-segment analysis substudy was performed in 695 patients undergoing primary PCI for AMI in the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial. Reperfusion success (determined by the magnitude of ST-segment elevation resolution [STR] after PCI) was evaluated in 4 age groups:(n = 163), \u3eor=50 to(n = 187), \u3eor=60 to(n = 194), and \u3eor=70 years (n = 151). RESULTS: There were no differences in the age groups for angiographic procedural success (\u3e91% in all, P =.6), postprocedural Thrombolysis in Myocardial Infarction grade 3 flow (\u3e94%, P =.8), and the proportions of patients with complete, partial, or absent STR (P \u3e.8). However, rates of 30-day mortality (0.6%, 1.1%, 3.6%, 6.0%, respectively) and major adverse cardiac events (MACE; 2.5%, 4.8%, 6.2% 9.3%, respectively) increased with age. Rates of mortality and MACE were also inversely related to the magnitude of STR. Absent STR (hazard ratio, 3.00; 95% CI, 1.37-6.58; P =.006) and age (hazard ratio, 1.34; 95% CI, 1.01-1.77; P =.04) were independent predictors of 30-day MACE by using multivariable modeling. CONCLUSIONS: Lack of effective myocardial reperfusion is not a contributory mechanism responsible for the high morbidity and mortality rates observed in elderly patients. Nevertheless, advanced age and absent STR are both independent predictors of adverse outcomes after primary PCI, emphasizing the importance of successful reperfusion in the elderly population

Impact and determinants of left ventricular function in patients undergoing primary percutaneous coronary intervention in acute myocardial infarction.

We evaluated the prognostic effect of baseline left ventricular function and the determinants of its recovery after acute myocardial infarction (AMI) treated by primary angioplasty. Left ventriculography was performed during the index procedure in 1,620 of 2,082 patients (78%) who underwent primary angioplasty for AMI in the CADILLAC trial. One-year survival rate was significantly lower in patients whose baseline left ventricular ejection fraction (LVEF) wasor =40% (89.0% vs 97.2%, respectively,