Summary statement on primary central nervous system lymphomas from the Eighth International Conference on Malignant Lymphoma, Lugano, Switzerland, June 12 to 15, 2002.

Under the sponsorship of the International Extranodal Lymphoma Study Group, a Multidisciplinary Workshop on primary CNS lymphoma (PCNSL) with over 50 participants from Europe, North America, Israel, and Australia was held as part of the Eighth International Conference on Malignant Lymphoma in Lugano, Switzerland (June 12 to 15, 2002). The main purposes of the Workshop were to exchange the latest scientific information, to analyze methodologic issues in the design of clinical trials, to reach a consensus on treatment recommendations and prognostic factors, to discuss clinical and molecular targets for future studies, and to establish an international collaborative group to conduct laboratory and clinical investigations in PCNSL. This article summarizes the contents of the Workshop, analyzes the current knowledge on the most relevant biologic and clinical issues in PCNSL, and focuses on fundamental challenges to be addressed in future studies.

Poverty, process of care, and outcome in acute coronary syndromes.

Objectives: We sought to determine whether income-based disparities in care processes and outcome exist in patients with acute coronary syndromes.

Background: Using income proxies and limited clinical data, some observational studies have shown income disparities in outcome after acute myocardial infarction (MI).

Methods: Using annual household income from the economic substudy of the PURSUIT (Platelet Glycoprotein IIB/IIIA In Unstable Angina: Receptor Suppression Using Integrilin Therapy) trial, patients were grouped into low-, middle-, and high-income categories based on the U.

Early revascularization is associated with improved survival in elderly patients with acute myocardial infarction complicated by cardiogenic shock: a report from the SHOCK Trial Registry.

Aims: The SHould we emergently revascularize Occluded Coronaries in cardiogenic shocK (SHOCK) Trial showed no benefit of early revascularization in patients aged >/=75 years with acute myocardial infarction and cardiogenic shock. We examined the effect of age on treatment and outcomes of patients with cardiogenic shock in the SHOCK Trial Registry.

Methods And Results: We compared clinical and treatment factors in patients in the SHOCK Trial Registry with shock due to pump failure aged <75 years (n=588) and >/=75 years (n=277), and 30-day mortality of patients treated with early revascularization <18 hours since onset of shock and those undergoing a later or no revascularization procedure.

The determinants of activated partial thromboplastin time, relation of activated partial thromboplastin time to clinical outcomes, and optimal dosing regimens for heparin treated patients with acute coronary syndromes: a review of GUSTO-IIb.

Context: Unfractionated heparin remains widely utilized in the treatment of acute coronary syndromes (ACS). However, limited data exist on optimal dosing and range of activated partial thromboplastin time (aPTT) in this setting. A large trial of thrombolysis for acute myocardial infarction has reported an association between longer aPTTs and adverse outcomes.

Cardiogenic shock caused by right ventricular infarction: a report from the SHOCK registry.

Objectives: The purpose of this study was to determine the characteristics and outcomes of patients with acute myocardial infarction (MI) complicated by cardiogenic shock due to predominant right ventricular (RV) infarction.

Background: Although RV infarction has been shown to have favorable long-term outcomes, the influence of RV infarction on mortality in cardiogenic shock is unknown.

Methods: We evaluated 933 patients in cardiogenic shock due to predominant RV (n = 49) or left ventricular (LV) failure (n = 884) in the SHould we emergently revascularize Occluded coronaries for Cardiogenic shocK? (SHOCK) trial registry.

An automated strategy for bedside aPTT determination and unfractionated heparin infusion adjustment in acute coronary syndromes: insights from PARAGON A.

Background: Intravenous unfractionated heparin remains a cornerstone of anticoagulation therapy for patients with acute coronary syndromes, but regulation to a target aPTT is challenging. We assessed unfractionated heparin infusion regulation by bedside, whole-blood aPTT testing and computerized, algorithmic infusion adjustment, and further evaluated the relationship of achieving the target aPTT with clinical outcomes.

Methods And Results: We studied 1,275 patients randomized to unfractionated heparin in PARAGON-A, which tested lamifiban with or without unfractionated heparin versus unfractionated heparin.

Echocardiographic predictors of survival and response to early revascularization in cardiogenic shock.

Background: Although echocardiography is used in diagnosis and management of myocardial infarction, it has not been established whether specific features of cardiac structure or function early in the course of cardiogenic shock provide prognostic value. The purposes of this substudy of the SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK (SHOCK) trial were to describe the echocardiographic features of cardiogenic shock, identify findings on early echocardiograms associated with outcome, examine the interaction of such features with treatment, and determine whether these features could provide insights into the survival benefit observed with early revascularization and guide selection of patients for this strategy.

Methods And Results: One hundred seventy-five echocardiograms performed within 24 hours of randomization to the early revascularization (ERV) or initial medical stabilization (IMS) arms of the trial were submitted for quantitative assessment, and 169 were suitable for analysis.

Acyl glucuronidation and glucosidation of a new and selective endothelin ET(A) receptor antagonist in human liver microsomes.

Compound A [(+)-(5S,6R,7R)-2-isopropylamino-7-[4-methoxy-2-((2R)-3-methoxy-2-methylpropyl)-5-(3,4-methylenedioxyphenyl) cyclopenteno [1,2-b] pyridine 6-carboxylic acid] is a new and selective endothelin ET(A) receptor antagonist. It underwent significant acyl glucuronidation and acyl glucosidation in human liver microsomes supplemented with UDP-glucuronic acid (UDPGA) and UDP-glucose (UDPG). These two conjugations were observed in a panel of human liver microsomal samples (n = 16) that gave rise to varying activities but with no significant correlation with each other in the native and activator-treated microsomal preparations (r(2) View Article and Find Full Text PDF

Topical treatment of Bowen's disease with 5-Fluorouracil.

Background: Bowen's disease is a common skin cancer. There are many different therapeutic approaches to treatment. Topical 5-Fluorouracil (5-FU) cream has been used for many years and there are many published papers attesting to its effectiveness.

Mortality at 1 year with combination platelet glycoprotein IIb/IIIa inhibition and reduced-dose fibrinolytic therapy vs conventional fibrinolytic therapy for acute myocardial infarction: GUSTO V randomized trial.

Context: Among patients with acute myocardial infarction, combination reperfusion therapy with a platelet glycoprotein IIb/IIIa receptor inhibitor (abciximab) and a half dose of a plasminogen activator (reteplase) did not significantly reduce mortality at 30 days compared with a full dose of reteplase. Rates of nonfatal ischemic complications were significantly diminished.

Objective: To determine if the beneficial effects of abciximab and reteplase (combination therapy) on early nonfatal complications would translate into a reduction in the risk of death by 1 year.

Is glycoprotein IIb/IIIa antagonism as effective in women as in men following percutaneous coronary intervention?. Lessons from the ESPRIT study.

Objective: The study was done to determine whether eptifibatide, a platelet glycoprotein (GP) IIb/IIIa antagonist, prevents ischemic complications following percutaneous coronary interventions (PCIs) in women as well as in men.

Background: Eptifibatide reduces ischemic complications after nonurgent coronary stent interventions.

Methods: We compared outcomes in women (n = 562) and men (n = 1,502) enrolled in the Enhanced Suppression of the Platelet GP IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial of double-bolus eptifibatide during PCI.

Evaluation of drug interactions with P-glycoprotein in drug discovery: in vitro assessment of the potential for drug-drug interactions with P-glycoprotein.

The pharmacological effects of a drug are highly dependent on the absorption, metabolism, elimination, and distribution of the drug. In the past few years it has become apparent that transport proteins play a major role in regulating the distribution, elimination and metabolism of some drugs. As a consequence of our new understanding of the influence of transport proteins on the pharmacokinetic and pharmacodynamic behavior of drugs, increasing attention has been focused on the potential for drug-drug interactions arising from interactions with drug transport proteins.

First experience with direct factor Xa inhibition in patients with stable coronary disease: a pharmacokinetic and pharmacodynamic evaluation.

Background: Thrombin generation is critical to the formation of an arterial thrombus after rupture of an atherosclerotic plaque. In patients with stable coronary disease receiving standard medical therapy, we evaluated the pharmacokinetics, pharmacodynamics, and safety profile of DX-9065a, a novel small-molecule anticoagulant that directly, selectively, and reversibly inhibits factor Xa.

Methods And Results: In a double-blind trial, 73 patients (median age, 63 years; 29% women) were randomly assigned to receive a fixed-dose intravenous bolus, followed by a 72-hour infusion of placebo or 1 of 4 weight-adjusted regimens of DX-9065a.

Differences in the absorption, metabolism and biliary excretion of a diastereomeric pair of alphavbeta3-antagonists in rat: limited role of P-glycoprotein.

1. The study investigated mechanisms underlying the pharmacokinetic differences of two zwitterionic diastereomers ((3S)-3-[(3R or 3S)-2-oxo-3-[3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl]pyrrolidin-1-yl]-3-quinolin-3-ylpropanoic acid) with different lipophilicities using a combination of in vivo and in vitro approaches. 2.

Autoimmune hemolytic anemia associated with Crohn's disease.

Autoimmune hemolytic anemia (AHA) is a well-recognized entity associated with ulcerative colitis. Only a single case of AHA previously has been reported in association with Crohn's disease. We describe the first case of this association in a child with perinuclear antineutrophil cytoplasmic antibody-positive Crohn's disease.

Absence of gender differences in clinical outcomes in patients with cardiogenic shock complicating acute myocardial infarction. A report from the SHOCK Trial Registry.

Objectives: The aim of this study was to assess the impact of gender on clinical course and in-hospital mortality in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI).

Background: Previous studies have demonstrated higher mortality for women compared with men with ST elevation myocardial infarctions and higher rates of CS after AMI. The influence of gender and its interaction with various treatment strategies on clinical outcomes once CS develops is unclear.

The late open artery hypothesis--a decade later.

Background: Early reperfusion after myocardial infarction has been proved to preserve left ventricular function and reduce mortality. However, a significant number of patients have persistent occlusion of the infarct-related artery late (days to weeks) after myocardial infarction because of ineligibility for thrombolytic therapy, failure of reperfusion, or reocclusion.

Methods: In this report we review the data on the potential mechanisms and benefits of late reperfusion and present prospective data on the incidence of and current practice patterns for the management of persistently occluded infarct-related arteries late after myocardial infarction.

Entry routes of malignant lymphoma into the brain and eyes in a mouse model.

We have recently developed a novel mouse model for studying the infiltration of malignant lymphoma to the eye and brain. After i.p.