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Biomedical subjects

Nicholas A Boon

Publications and source records attributed to Nicholas A Boon.

8 recordsLinked to original sources
PubMed2006

Vascular and fibrinolytic effects of intra-arterial tumour necrosis factor-alpha in patients with coronary heart disease.

Elevated plasma t-PA (tissue plasminogen activator) and serum CRP (C-reactive protein) concentrations are associated with an adverse cardiovascular risk. In the present study, we investigated whether acute local inflammation causes vascular dysfunction and influences t-PA release in patients with stable coronary heart disease. Serum CRP, plasma t-PA and PAI-1 (plasminogen activator inhibitor type 1) concentrations were determined in 95 patients with stable coronary heart disease. A representative subpopulation of 12 male patients received an intra-brachial infusion of TNF-alpha (tumour necrosis factor-alpha) and saline placebo using a randomized double-blind cross-over study design. Forearm blood flow and plasma fibrinolytic and inflammatory variables were measured. Serum CRP concentrations correlated with plasma t-PA concentrations (r=0.37, P<0.001) and t-PA/PAI-1 ratio (r=-0.21, P<0.05). Intra-arterial TNF-alpha caused a rise in t-PA concentrations (P<0.001) without affecting blood flow or PAI-1 concentrations. TNF-alpha pretreatment impaired acetylcholine- and sodium nitroprusside-induced vasodilatation (P<0.001 for both) whilst doubling bradykinin-induced t-PA release (P=0.006). In patients with stable coronary heart disease, plasma fibrinolytic factors correlate with a systemic inflammatory marker and local vascular inflammation directly impairs vasomotor function whilst enhancing endothelial t-PA release. We suggest that the adverse prognosis associated with elevated plasma t-PA concentrations relates to the underlying causative association with vascular inflammation and injury.

Acute Disease↗
PubMed2005

Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis.

BACKGROUND: Although the mechanisms are unknown, it has been suggested that transient exposure to traffic-derived air pollution may be a trigger for acute myocardial infarction. The study aim was to investigate the effects of diesel exhaust inhalation on vascular and endothelial function in humans. METHODS AND RESULTS: In a double-blind, randomized, cross-over study, 30 healthy men were exposed to diluted diesel exhaust (300 microg/m3 particulate concentration) or air for 1 hour during intermittent exercise. Bilateral forearm blood flow and inflammatory factors were measured before and during unilateral intrabrachial bradykinin (100 to 1000 pmol/min), acetylcholine (5 to 20 microg/min), sodium nitroprusside (2 to 8 microg/min), and verapamil (10 to 100 microg/min) infusions 2 and 6 hours after exposure. There were no differences in resting forearm blood flow or inflammatory markers after exposure to diesel exhaust or air. Although there was a dose-dependent increase in blood flow with each vasodilator (P<0.0001 for all), this response was attenuated with bradykinin (P<0.05), acetylcholine (P<0.05), and sodium nitroprusside (P<0.001) infusions 2 hours after exposure to diesel exhaust, which persisted at 6 hours. Bradykinin caused a dose-dependent increase in plasma tissue plasminogen activator (P<0.0001) that was suppressed 6 hours after exposure to diesel (P<0.001; area under the curve decreased by 34%). CONCLUSIONS: At levels encountered in an urban environment, inhalation of dilute diesel exhaust impairs 2 important and complementary aspects of vascular function in humans: the regulation of vascular tone and endogenous fibrinolysis. These important findings provide a potential mechanism that links air pollution to the pathogenesis of atherothrombosis and acute myocardial infarction.

Adult↗
PubMed2005

Do inhaled carbon nanoparticles translocate directly into the circulation in humans?

RATIONALE: Increased exposure to particulate air pollution (PM(10)) is a risk factor for death and hospitalization with cardiovascular disease. It has been suggested that the nanoparticulate component of PM(10) is capable of translocating into the circulation with the potential for direct effects on the vasculature. OBJECTIVE: The study's aim was to determine the extent to which inhaled technetium-99m ((99m)Tc)-labeled carbon nanoparticles (Technegas) were able to access the systemic circulation. METHODS AND MAIN RESULTS: Ten healthy volunteers inhaled Technegas and blood samples were taken sequentially over the following 6 h. Technegas particles were 4-20 nm in diameter and aggregated to a median particle diameter of approximately 100 nm. Radioactivity was immediately detected in blood, with levels increasing over 60 min. Thin-layer chromatography of whole blood identified a species that moved with the solvent front, corresponding to unbound (99m)Tc-pertechnetate, which was excreted in urine. There was no evidence of particle-bound (99m)Tc at the origin. gamma Camera images demonstrated high levels of Technegas retention (95.6 +/- 1.7% at 6 h) in the lungs, with no accumulation of radioactivity detected over the liver or spleen. CONCLUSIONS: The majority of (99m)Tc-labeled carbon nanoparticles remain within the lung up to 6 h after inhalation. In contrast to previous published studies, thin-layer chromatography did not support the hypothesis that inhaled Technegas carbon nanoparticles pass directly from the lungs into the systemic circulation.

Adult↗
PubMed2005

A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis.

BACKGROUND: Calcific aortic stenosis has many characteristics in common with atherosclerosis, including hypercholesterolemia. We hypothesized that intensive lipid-lowering therapy would halt the progression of calcific aortic stenosis or induce its regression. METHODS: In this double-blind, placebo-controlled trial, patients with calcific aortic stenosis were randomly assigned to receive either 80 mg of atorvastatin daily or a matched placebo. Aortic-valve stenosis and calcification were assessed with the use of Doppler echocardiography and helical computed tomography, respectively. The primary end points were change in aortic-jet velocity and aortic-valve calcium score. RESULTS: Seventy-seven patients were assigned to atorvastatin and 78 to placebo, with a median follow-up of 25 months (range, 7 to 36). Serum low-density lipoprotein cholesterol concentrations remained at 130+/-30 mg per deciliter in the placebo group and fell to 63+/-23 mg per deciliter in the atorvastatin group (P<0.001). Increases in aortic-jet velocity were 0.199+/-0.210 m per second per year in the atorvastatin group and 0.203+/-0.208 m per second per year in the placebo group (P=0.95; adjusted mean difference, 0.002; 95 percent confidence interval, -0.066 to 0.070 m per second per year). Progression in valvular calcification was 22.3+/-21.0 percent per year in the atorvastatin group, and 21.7+/-19.8 percent per year in the placebo group (P=0.93; ratio of post-treatment aortic-valve calcium score, 0.998; 95 percent confidence interval, 0.947 to 1.050). CONCLUSIONS: Intensive lipid-lowering therapy does not halt the progression of calcific aortic stenosis or induce its regression. This study cannot exclude a small reduction in the rate of disease progression or a significant reduction in major clinical end points. Long-term, large-scale, randomized, controlled trials are needed to establish the role of statin therapy in patients with calcific aortic stenosis.

Anticholesteremic Agents↗
PubMed2004

Calcific aortic stenosis: same old story?

Calcific aortic stenosis is the commonest adult valvular heart condition seen in the western world. Its prevalence is continuing to rise, with predominance in older patients who are frequently undergoing successful aortic valve replacement. This review discusses the natural history of calcific aortic stenosis, highlights recent insights into its pathogenesis, and outlines current medical and surgical management. The potential role of novel therapeutic interventional strategies is discussed.

Age Factors↗
PubMed2004

Contrast agent increases Doppler velocities and improves reproducibility of aortic valve area measurements in patients with aortic stenosis.

Observer variability may limit assessment of aortic stenosis by Doppler echocardiography. This study aimed to assess whether echocardiographic contrast agent improves reproducibility of aortic valve area (AVA) measurements for patients with aortic stenosis. In all, 20 patients with aortic stenosis (67 +/- 10 years old) underwent noncontrast and contrast Doppler echocardiography on 2 occasions, 3 weeks apart. Intraobserver and interobserver coefficients of reproducibility were 0.36 and 0.20 cm for left ventricular outflow tract (LVOT) diameter, and 0.38 and 0.24 cm(2) for AVA, respectively. Although intraobserver reproducibility was unaffected, contrast improved interobserver reproducibility for LVOT diameter (mean of differences -0.02 +/- 0.07 cm vs 0.01 +/- 0.10 cm, P <.05) and AVA (mean of differences 0.02 +/- 0.10 cm(2) vs 0.07 +/- 0.12 cm(2), P <.05). Prevalve and postvalve velocities were increased with contrast compared with noncontrast imaging (prevalve, 1.07 +/- 0.20 vs 0.94 +/- 0.19 m/s, P <.01; postvalve, 3.76 +/- 0.87 vs 3.47 +/- 0.78 m/s, P <.01). We conclude that contrast significantly increases Doppler velocities and produces modest improvements in reproducibility of LVOT diameter and AVA. We suggest that, when assessing patients with aortic stenosis, contrast agents should be considered in patients who are difficult to image with poor baseline LVOT images or Doppler studies, or where there is poor interobserver reproducibility.

Aged↗
PubMed2003

Immunopathogenesis of HIV-related heart muscle disease: current perspectives.

As more effective antiretroviral therapies improve survival times, growing numbers of HIV-positive patients are at risk of developing end-organ damage or neoplasia. Heart muscle disease is the most important cardiovascular manifestation of HIV infection and seems set to become increasingly prevalent. This may take the form of either a dilated cardiomyopathy or isolated left or right ventricular dysfunction, is associated with a poor prognosis, and results in symptomatic heart failure in up to 5% of HIV patients. The precise cause of HIV-associated cardiomyopathy remains unclear but is undoubtedly complex, and most probably multifactorial. This report examines our current understanding of the immunopathogenesis of HIV-associated cardiomyopathy.

AIDS-Related Opportunistic Infections↗