Both paraoxonase-1 genotype and activity do not predict the risk of future coronary artery disease; the EPIC-Norfolk Prospective Population Study.

Background: Paraoxonase-1 (PON1) is an antioxidant enzyme, that resides on high-density lipoprotein (HDL). PON1-activity, is heavily influenced by the PON1-Q192R polymorphism. PON1 is considered to protect against atherosclerosis, but it is unclear whether this relation is independent of its carrier, HDL.

C-reactive protein elicits white blood cell activation in humans.

Objective: Consistent epidemiologic evidence suggests that acute infections increase the risk for acute cardiovascular events. We tested in humans whether activation of peripheral leukocytes in reaction to the administration of recombinant human C-reactive protein (rhCRP) may provide a mechanism for infectious diseases to promote atherosclerotic disease.

Methods And Results: By using quantitative real-time polymerase chain reaction analysis, whole-blood expression profiles were analyzed for 95 inflammatory markers before and after infusion of 1.

Effects of short-term and long-term danazol treatment on lipoproteins, coagulation, and progression of atherosclerosis: two clinical trials in healthy volunteers and patients with hereditary angioedema.

Background: Danazol is a synthetic androgen derivative frequently used as prophylaxis in patients with hereditary angioedema (HAE) due to complement-1 esterase inhibitor deficiency. However, danazol has been reported to decrease high-density lipoprotein cholesterol (HDL-C) levels and to adversely affect coagulation parameters, which are considered to be proatherothrombotic.

Objective: The short- and long-term effects of danazol were evaluated on proatherogenic intermediate end points in healthy volunteers and patients with HAE.

ApoAI-phosphatidylcholine infusion neutralizes the atherothrombotic effects of C-reactive protein in humans.

Background: High-density lipoprotein (HDL) exerts a variety of anti-atherothrombotic functions, including a potent anti-inflammatory impact. In line, the direct pro-inflammatory effects of C-reactive protein (CRP) can be attenuated by HDL in vitro.

Objective: To evaluate whether this also holds true in humans, we assessed the ability of reconstituted HDL to neutralize CRP-mediated activation of coagulation and inflammation.

Induction of IRAK-M is associated with lipopolysaccharide tolerance in a human endotoxemia model.

Recent in vitro and murine in vivo studies have identified several potential LPS tolerance factors. In this study, we describe the expression kinetics of these LPS tolerance factors in standardized human endotoxemia models using i.v.

A single bolus infusion of C-reactive protein increases gluconeogenesis and plasma glucose concentration in humans.

Recently, we reported that C-reactive protein (CRP) elicits inflammatory and procoagulant responses in humans. In addition, CRP has been associated with the development of type 2 diabetes mellitus. To further explore interactions between CRP and glucose handling, we evaluated the effects of CRP infusion on glucose metabolism in humans.

Apolipoprotein A-II is inversely associated with risk of future coronary artery disease.

Background: Although the vasculoprotective effects of apolipoprotein A-I (apoA-I), the major protein associated with high-density lipoprotein, have been universally accepted, apoA-II has been suggested to have poor antiatherogenic or even proatherogenic properties. To study this suggestion more closely, we evaluated how serum levels of apoA-II and apoA-I relate to the risk of future coronary artery disease (CAD) in a large, prospective study.

Methods And Results: We performed a nested case-control study in the prospective EPIC-Norfolk (European Prospective Investigation into Cancer and Nutrition-Norfolk) cohort.

Safety and tolerability of prolonged-release nicotinic acid in statin-treated patients.

Objective: To evaluate the safety and tolerability of prolonged-release nicotinic acid (Niaspan) added to statin therapy in patients at increased cardiovascular risk.

Methods: This was a 6-month, prospective, observational, multicentre, open-label evaluation of prolonged-release nicotinic acid (maximum dose 2000 mg/day) in statin-treated patients with cardiovascular disease and/or type 2 diabetes. The primary endpoint was the safety and tolerability of prolonged-release nicotinic acid, with special regard to treatment-related adverse drug reactions (ADRs).

High-density lipoprotein attenuates inflammation and coagulation response on endotoxin challenge in humans.

Objective: Low high-density lipoprotein (HDL) cholesterol is a strong independent cardiovascular risk factor, which has been attributed to its role in reverse cholesterol transport. Whereas HDL also has potent antiinflammatory effects, the relevance of this property remains to be established in humans. In the present study, we evaluated whether there is a relation between HDL and sensitivity toward a low-dose endotoxin challenge.

Effects of CRP infusion on endothelial function and coagulation in normocholesterolemic and hypercholesterolemic subjects.

C-reactive protein (CRP) has been suggested to exert direct adverse effects on the vasculature in experimental setups, including endothelial dysfunction and proinflammatory changes. Here, we assessed the consequences of 1.25 mg/kg highly purified recombinant human CRP, administered as an intravenous bolus, in six patients with familial hypercholesterolemia (FH) and six normocholesterolemic subjects.

[The role of the high-density lipoprotein (HDL) particle in atherogenesis and potential methods to increase HDL concentrations].

The concentration of high-density lipoprotein (HDL) cholesterol has a strong inverse relationship to the incidence of cardiovascular disease. The protective effect of HDL cholesterol is due not only to its promotion of reverse cholesterol transport from the vascular wall to the liver, but also to its anti-inflammatory, antioxidative and antithrombotic effects. Patients with low HDL cholesterol concentrations are at increased risk for cardiovascular disease and may be considered for treatment with lipid-lowering drugs, such as statins, niacin and fibrates.

Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds: a meta-analysis of randomized controlled trials.

Objectives: The aim of this research was to estimate the efficacy and safety of current high-density lipoprotein cholesterol (HDL-C)-increasing drugs.

Background: Epidemiologic evidence has shown that HDL-C is inversely related to coronary heart disease (CHD) risk. However, the evidence for reducing CHD risk by raising HDL-C is thin, predominantly due to the paucity of effective and safe HDL-increasing drugs.

Loss of heterozygosity and immunohistochemistry of adenocarcinomas of the esophagus and gastric cardia.

Purpose: Adenocarcinomas of the distal esophagus and gastric cardia are two tumors that have many features in common. They have similar prognoses, treatment modalities, and patterns of dissemination. The etiology is different, with gastroesophageal reflux disease playing a major role for esophageal adenocarcinoma, in contrast to adenocarcinoma of the gastric cardia.

Increasing HDL cholesterol with extended-release nicotinic acid: from promise to practice.

Background: The inverse relation between high-density lipoprotein cholesterol (HDL-C) and cardiovascular (CV) disease underscores the need for clinical evaluation of the effect of HDL-C increasing drugs on the prevalence of CV disease.

Methods: We review the efficacy of Niaspan on serum lipids and the occurrence of side effects either alone or in combination with statins, in randomised controlled trials (RCT) and comparative cohort trials (CCT).

Results: In four RCTs, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and lipoprotein(a) (Lp(a)) were decreased by 13, 26, and 17%, respectively, whereas HDL-C increased by 18%.

The effect of preoperative biliary drainage on postoperative complications after pancreaticoduodenectomy.

Background: The benefit of preoperative biliary drainage in jaundiced patients undergoing pancreaticoduodenectomy for a suspected malignancy of the periampullary region is still under debate. This study evaluated preoperative biliary drainage in relation to postoperative outcomes.

Study Design: At the Academic Medical Center, Amsterdam, the Netherlands, a cohort of 311 patients undergoing pancreaticoduodenectomy from June 1992 up to and including December 1999 was studied.

IL-10-deficient mice demonstrate multiple organ failure and increased mortality during Escherichia coli peritonitis despite an accelerated bacterial clearance.

To determine the role of endogenous IL-10 in local antibacterial host defense and in the development of a systemic inflammatory response syndrome during abdominal sepsis, IL-10 gene-deficient (IL-10(-/-)) and wild-type (IL-10(+/+)) mice received an i.p. injection with Escherichia coli.