Calorie restriction and cancer prevention: a mechanistic perspective.

Calorie restriction (CR) is one of the most potent broadly acting dietary interventions for inducing weight loss and for inhibiting cancer in experimental models. Translation of the mechanistic lessons learned from research on CR to cancer prevention strategies in human beings is important given the high prevalence of excess energy intake, obesity, and metabolic syndrome in many parts of the world and the established links between obesity-associated metabolic perturbations and increased risk or progression of many types of cancer. This review synthesizes findings on the biological mechanisms underlying many of the anticancer effects of CR, with emphasis on the impact of CR on growth factor signaling pathways, inflammation, cellular and systemic energy homeostasis pathways, vascular perturbations, and the tumor microenvironment.

Growth signals, inflammation, and vascular perturbations: mechanistic links between obesity, metabolic syndrome, and cancer.

Nearly 35% of adults and 20% of children in the United States are obese, defined as a body mass index ≥ 30 kg/m(2). Obesity, which is accompanied by metabolic dysregulation often manifesting in the metabolic syndrome, is an established risk factor for many cancers. Within the growth-promoting, proinflammatory environment of the obese state, cross talk between macrophages, adipocytes, and epithelial cells occurs via obesity-associated hormones, cytokines, and other mediators that may enhance cancer risk and progression.

Etiology and assessment of hypercoagulability with lessons from heparin-induced thrombocytopenia.

Hypercoagulability, or thrombophilia, is a condition associated with an abnormally increased tendency toward blood clotting. Affected individuals are prone to developing venous or arterial thrombosis and often require thromboprophylaxis. Hypercoagulability can be generally classified as either an inherited or acquired condition.

Platelet factor 4/heparin antibodies in blood bank donors.

Platelet factor 4 (PF4)/heparin antibody, typically associated with heparin therapy, is reported in some heparin-naive people. Seroprevalence in the general population, however, remains unclear. We prospectively evaluated PF4/heparin antibody in approximately 4,000 blood bank donors using a commercial enzyme-linked immunosorbent assay for initial and then repeated (confirmatory) testing.

Emergency department awareness of heparin-induced thrombocytopenia: how frequently is risk assessment documented in patients with thrombosis?

Evidence-based guidelines recommend that heparin-induced thrombocytopenia (HIT) should be suspected whenever a patient develops thrombosis or thrombocytopenia 5 to 14 days after heparin initiation. The authors determined how frequently emergency department (ED) physicians document HIT risk assessment in patients presenting with thrombosis. Relevant data were extracted from the ED charts of 134 patients with venous or arterial thrombosis.

Heparin-platelet factor 4 antibodies in intensive care patients: an observational seroprevalence study.

Heparin-platelet factor 4 (PF4) antibodies mediate heparin-induced thrombocytopenia (HIT) and, irrespective of thrombocytopenia, are associated with poorer outcomes in some patients. The prevalence of heparin-PF4 antibodies, including platelet-activating ones, in patients in the medical, neurotrauma, or shock-trauma intensive care unit (ICU) remains unclear. In this single-center, observational study, heparin-PF4 antibodies (IgG/A/M) were measured by ELISA in 185 adults (median APACHE II score, 16) admitted to the medical (n = 27), neurotrauma (n = 96), or shock-trauma (n = 62) ICU and after 7 +/- 2 days.

Impact of renal function on argatroban therapy during percutaneous coronary intervention.

Argatroban, a hepatically metabolized direct thrombin inhibitor, is approved for anticoagulation in patients with or at risk of heparin-induced thrombocytopenia (HIT) undergoing percutaneous coronary intervention (PCI). We investigated the effect of renal function on argatroban therapy during PCI. From previous argatroban studies in PCI, we evaluated relationships between estimated creatinine clearance (CrCl) and activated clotting times (ACTs), dosage, and outcomes in 219 patients with or at risk of HIT (HIT group, n = 67) or administered glycoprotein IIb/IIIa inhibition (non-HIT group, n = 152).

Reducing harm associated with anticoagulation: practical considerations of argatroban therapy in heparin-induced thrombocytopenia.

Argatroban is a hepatically metabolized, direct thrombin inhibitor used for prophylaxis or treatment of thrombosis in heparin-induced thrombocytopenia (HIT) and for patients with or at risk of HIT undergoing percutaneous coronary intervention (PCI). The objective of this review is to summarize practical considerations of argatroban therapy in HIT. The US FDA-recommended argatroban dose in HIT is 2 microg/kg/min (reduced in patients with hepatic impairment and in paediatric patients), adjusted to achieve activated partial thromboplastin times (aPTTs) 1.

Risk factors for major bleeding in patients with heparin-induced thrombocytopenia treated with argatroban: a retrospective study.

We retrospectively characterized major bleeding events and their risk factors among 269 patients with clinically diagnosed heparin-induced thrombocytopenia (HIT) treated using argatroban (2 microg x kg(-1) x min(-1) initially, adjusted to achieve activated partial thromboplastin times (aPTTs) 1.5-3 times the baseline) in a prospective multicenter study. Patients received a median (range) dose of 1.

Dosing patterns and outcomes in African American, Asian, and Hispanic patients with heparin-induced thrombocytopenia treated with argatroban.

We retrospectively evaluated dosing patterns and 37-day outcomes in argatroban-treated African American (n = 52), Asian (n = 13), and Hispanic (n = 14) patients with heparin-induced thrombocytopenia (HIT). The Asians required a lesser median dose (1.0 microg/kg/min) than the other groups (1.

Argatroban anticoagulation in intensive care patients: effects of heart failure and multiple organ system failure.

We retrospectively evaluated argatroban dosing patterns, clinical outcomes, and the effects of heart failure and multiple organ system failure on dosing requirements in 65 adult, intensive care patients administered argatroban anticoagulation for clinically suspected heparin-induced thrombocytopenia (n=56) or history of heparin-induced thrombocytopenia (n=9). Argatroban was initiated then titrated to achieve target activated partial thromboplastin times 1.5 to 3 times normal control (ie, 42-84 seconds).

Predictors of clinical outcome in patients with heparin-induced thrombocytopenia treated with direct thrombin inhibition.

We aimed to identify predictors of poor outcome in patients with heparin-induced thrombocytopenia, a serious immune-mediated reaction to heparin. All patients were treated with direct thrombin inhibition therapy, as part of two prospective studies. We performed a risk factor analysis of adverse outcomes (defined as death, amputation, new thrombosis, or their composite within a 37-day study period) in 809 patients from two reported prospective studies of the direct thrombin inhibitor argatroban in clinically diagnosed heparin-induced thrombocytopenia.

Argatroban anticoagulation in renal dysfunction: a literature analysis.

Background/aims: Argatroban, a hepatically metabolized direct thrombin inhibitor, is approved for use in heparin-induced thrombocytopenia (HIT; several countries) and in antithrombin-deficient patients undergoing hemodialysis (Japan). This literature analysis aimed to determine the effects of renal function on argatroban pharmacokinetics, pharmacodynamics, and its therapeutic dose in HIT and to evaluate argatroban dosing and safety during renal replacement therapy (RRT) and in adults with renal dysfunction undergoing surgical or invasive procedures.

Methods: A literature search identified 34 publications (12 prospective studies, 4 retrospective studies, 18 anecdotal reports) that together described 644 argatroban-treated patients (446 with HIT, 82 with antithrombin deficiency) with varying degrees of renal function.

Argatroban therapy in heparin-induced thrombocytopenia.

Argatroban is a direct thrombin inhibitor approved for anticoagulation in heparin-induced thrombocytopenia (HIT; in several countries) and in patients with or at risk of HIT undergoing percutaneous coronary intervention (PCI; in the USA). HIT is a relatively common extreme prothrombotic condition. When HIT is reasonably suspected, an alternative anticoagulant should be promptly initiated.

Platelet factor 4/heparin antibody (IgG/M/A) in healthy subjects: a literature analysis of commercial immunoassay results.

Purpose: We determined the seroprevalence of platelet factor 4 (PF4)/heparin antibodies in healthy subjects.

Methods: A literature search identified studies in which healthy subjects were evaluated using commercial immunoassays for PF4/heparin antibody (IgG/M/A). Proportions of test-positive subjects were calculated, by assay.

Reduced argatroban doses after coronary artery bypass graft surgery.

Background: The Food and Drug Administration-approved argatroban dose for heparin-induced thrombocytopenia (HIT) is 2 microg/kg/min (0.5 microg/kg/min in hepatic impairment), adjusted to achieve activated partial thromboplastin time (aPTT) 1.5-3 times baseline.

Argatroban therapy for heparin-induced thrombocytopenia in acutely ill patients.

Heparin-induced thrombocytopenia (HIT) is a prothrombotic, immune-mediated adverse reaction to heparin therapy. To evaluate clinical outcomes and effects of argatroban therapy in acutely ill HIT patients. Retrospective analysis.

Argatroban therapy in patients with coronary artery disease and heparin-induced thrombocytopenia.

The efficacy of the direct thrombin inhibitor argatroban was investigated in patients who developed heparin-induced thrombocytopenia following heparin therapy for coronary artery disease. The outcome of 121 patients treated with argatroban was compared with that of 26 patients in a historical control (i.e.

Reducing thrombotic complications in the perioperative setting: an update on heparin-induced thrombocytopenia.

Heparins are widely used in the perioperative setting. Immune heparin-induced thrombocytopenia (HIT) is a serious, antibody-mediated complication of heparin therapy that occurs in approximately 0.5%-5% of patients treated with heparin for at least 5 days.

Argatroban therapy in women with heparin-induced thrombocytopenia.

Objectives: Women have increased risk of developing heparin-induced thrombocytopenia (HIT), a serious, immune-mediated prothrombotic condition, and have a worse prognosis when affected. We compared gender differences for treatment and outcomes in HIT patients administered argatroban therapy.

Methods: From a multicenter retrospective registry of argatroban-treated patients, we identified females (n = 42) and males (n = 50) with clinically diagnosed HIT who were administered argatroban View Article and Find Full Text PDF

Argatroban anticoagulation for heparin-induced thrombocytopenia in elderly patients.

Background: Argatroban, a direct thrombin inhibitor that has reduced clearance in elderly versus younger volunteers, is used for thromboprophylaxis or treatment in heparin-induced thrombocytopenia (HIT).

Objective: To evaluate the effect of aging on argatroban therapy, including dosage, anticoagulant responses, clinical outcomes and factors influencing those responses, in elderly patients with HIT or a history of HIT.

Methods: This was a retrospective multicentre database analysis of 118 inpatients treated with argatroban at six medical centres between August 2001 and January 2005.

Effect of body mass index on Argatroban therapy during percutaneous coronary intervention.

Background: Obesity is common in patients undergoing percutaneous coronary intervention (PCI). Argatroban, a direct thrombin inhibitor, is used during PCI in patients with or at risk of heparin-induced thrombocytopenia (HIT) and also has been evaluated in conjunction with glycoprotein IIb/IIIa inhibition in nonHIT patients. We investigated the effect of body mass index (BMI), and specifically obesity (BMI>30 kg/m2), on argatroban therapy during PCI.

Heparin-platelet factor 4 antibodies in patients presenting to the ED with thrombosis.

Background: Patients with heparin-platelet factor 4 (PF4) antibodies, particularly platelet-activating ones, are at risk for heparin-induced thrombocytopenia if administered heparin. We determined the heparin-PF4 antibody prevalence in emergency department (ED) patients presenting with chest pain or symptoms of thrombosis.

Methods: Admission samples from 324 ED patients with chest pain or symptoms of thrombosis were tested for heparin-PF4 antibodies and, if positive, platelet-activating antibodies.

Heparin-induced thrombocytopenia, a prothrombotic disease.

Heparin-induced thrombocytopenia (HIT) is a serious, yet treatable prothrombotic disease that develops in approximately 0.5% to 5% of heparin-treated patients and dramatically increases their risk of thrombosis (odds ratio, 37). The antibodies that mediate HIT (ie, heparin-platelet factor 4 antibodies) occur more frequently than the overt disease itself, and, even in the absence of thrombocytopenia, are associated with increased thrombotic morbidity and mortality.