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Biomedical subjects

Jan Brozek

Publications and source records attributed to Jan Brozek.

7 recordsLinked to original sources
PubMed2006

Plasma homocysteine affects fibrin clot permeability and resistance to lysis in human subjects.

OBJECTIVE: Homocysteine (Hcy) is a risk factor for thrombosis. We investigated a hypothesis that the clot permeability and its resistance to fibrinolysis is associated with plasma total Hcy (tHcy) in human subjects. METHODS AND RESULTS: We studied healthy men not taking any medication (n=76), male patients with advanced coronary artery disease (CAD) taking low-dose aspirin (n=33), men with diabetes mellitus diagnosed recently (median hemoglobin A(1c) 7.65%; n=16), and patients with isolated hypercholesterolemia (>7.0 mmol/L; n=15). We assessed clot permeability and turbidimetric lysis time as the determinants of fibrin clot structure. In a regression model, including age and fibrinogen, plasma tHcy was an independent predictor of clot permeation and fibrinolysis time in healthy subjects (R2=0.88, P<0.0001 and R2=0.54, P<0.0001, respectively). In CAD patients, tHcy and fibrinogen were stronger predictors of the permeation coefficient (R2=0.84; P<0.0001) than was fibrinogen alone (R2=0.66; P<0.0001), whereas tHcy was the only predictor of lysis time (R2=0.69; P<0.0001). Elevated tHcy levels observed after methionine load were not associated with any of the fibrin clot properties. In patients with diabetes or hypercholesterolemia, the influence of Hcy on permeation and, to a lesser extent, on the lysis time was obscured by dominant effects of glucose and cholesterol. In 20 asymptomatic men with hyperhomocysteinemia treated with folic acid, reduction in tHcy levels resulted in increased clot permeability (P=0.0002) and shorter lysis time (P<0.0001). CONCLUSIONS: Our results indicate that plasma tHcy predicts clot permeation and susceptibility to fibrinolysis in healthy men and CAD patients. Our data are consistent with a mechanism of thrombosis in hyperhomocysteinemia, which involves modification of fibrinogen by Hcy-thiolactone.

Acute Disease↗
PubMed2005

Homocysteine and thrombosis: from basic science to clinical evidence.

Homocysteine is a sulfhydryl-containing amino acid formed during the metabolism of methionine. Rapidly accumulating evidence links elevated homocysteine levels to thrombosis via several mechanisms such as increased tissue factor expression, attenuated anticoagulant processes, enhanced platelet reactivity, increased thrombin generation, augmented factor V activity, impaired fibrinolytic potential, and vascular injury, including endothelial dysfunction. Molecular mechanisms underlying prothrombotic actions of homocysteine are incompletely understood and involve oxidative stress, DNA hypomethylation, and proinflammatory effects. Current evidence from retrospective and prospective studies supports the concept that higher total plasma homocysteine concentration is associated with increased risk of coronary artery disease, stroke, and venous thromboembolism. Hyperhomocysteinemia is currently considered a relatively weak prothrombotic factor. It is still unclear whether administration of vitamins, that reduce homocysteine levels acting as cofactors of the enzymes involved in the methionine metabolism, may decrease the risk of arterial and/or venous thromboembolic events. Ongoing clinical trials might help clarify this issue.

Homocysteine↗
PubMed2004

Glycemic control in the ICU: a multicenter survey.

BACKGROUND: Intensive insulin therapy has recently been shown to decrease morbidity and mortality in the critically ill population in a large randomized clinical trial. OBJECTIVE: To determine the beliefs and attitudes of ICU clinicians about glycemic control. DESIGN: Self-administered survey. PARTICIPANTS: ICU nurses and physicians in five university-affiliated multidisciplinary ICUs. RESULTS: A total of 317 questionnaires were returned from 233 ICU nurses and 84 physicians. The reported clinically important threshold for hypoglycemia was 4 mmol/l (median, IQR 3-4 mmol/l). In non-diabetic patients, the clinically important threshold for hyperglycemia was 10 mmol/l (IQR 9-12 mmol/l); however, nurses had a significantly higher threshold than physicians (difference of 0.52 mmol/l (95% CI 0.09-0.94 mmol/l, P=0.018). In diabetic patients, the clinically important threshold for hyperglycemia was also 10 mmol/l (IQR 10-12 mmol/l), and again nurses had a significantly higher threshold than physicians (0.81 mmol/l, 95% CI 0.29-1.32 mmol/l, P=0.0023). Avoidance of hyperglycemia was judged most important for diabetic patients (87.7%, 95% CI 84.1-91.3%), patients with acute brain injury (84.5%, 95% CI 80.5-88.5%), patients with a recent seizure (74.4%, 95% CI 69.6-79.3%), patients with advanced liver disease (64.0%, 95% CI 58.7-69.3%), and for patients with acute myocardial infarction (64.0%, 95% CI 58.7-69.3%). Physicians expressed more concern than nurses about avoiding hyperglycemia in patients with acute myocardial infarction ( P=0.0004). ICU clinicians raised concerns about the accuracy of glucometer measurements in critically ill patients (46.1%, 95% CI 40.5-51.6%). CONCLUSIONS: Attention to these beliefs and attitudes could enhance the success of future clinical, educational and research efforts to modify clinician behavior and achieve better glycemic control in the ICU setting.

Attitude of Health Personnel↗
PubMed2002

Anti-inflammatory and antithrombotic effects of statins in the management of coronary artery disease.

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins), a potent class of cholesterol-lowering drugs, exert a number of pleiotropic effects, including anti-inflammatory and antithrombotic properties. Evidence is now accumulating that these effects are not related to the reduction in lipid levels. In vitro studies, supported recently by in vivo data, indicate that treatment with statins results in a significant decrease in the levels of inflammation markers, such as C-reactive protein, interleukin 6, and tumor necrosis factor alpha, which appear to be predictors of acute coronary events and help stratify cardiovascular risk. Up to now, only high-sensitive C-reactive protein testing has the potential to become an adjunctive method to assess the risk of coronary events in low- and high-risk individuals. Statins can also inhibit tissue factor expression, leading to impaired activation of the blood coagulation cascade, as evidenced by a decrease in thrombin generation in vivo. Interrelated inhibition of inflammation and thrombosis induced by statins is believed to largely contribute to clinical benefits from statin therapy, regardless of cholesterol levels. Further studies will answer the question whether markers of inflammation, other than C-reactive protein and possibly indices of thrombin formation, might improve cardiovascular risk stratification.

Anti-Inflammatory Agents, Non-Steroidal↗