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Biomedical subjects

Andrew M Wilson

Publications and source records attributed to Andrew M Wilson.

At least 19 recordsLinked to original sources
PubMed2006

Recurrent spontaneous coronary artery dissection with transient left ventricular systolic dysfunction.

Spontaneous coronary artery dissection (SCAD) is a potentially life-threatening entity with a variety of clinical presentations. We report a patient who presented with chest pain and angiographic evidence of coronary dissection. Due to the rapid resolution of symptoms and benign-appearing nature of the dissection, no intervention was pursued and the patient was maintained on medical therapy. She represented 2 days later with substernal chest pain, dynamic EKG changes, positive cardiac biomarkers and a transient depression of her left ventricular function.

Aortic Dissection↗
PubMed2006

A nonfeminizing estrogen analog protects against ethanol withdrawal toxicity in immortalized hippocampal cells.

We have shown that 17beta-estradiol protects against ethanol withdrawal toxicity in rats. Here, we investigated whether a cellular model of ethanol withdrawal could be developed in a cultured hippocampal cell line (HT22) and whether an adamantyl-containing nonfeminizing estrogen analog, ZYC26 [(3-hydroxy-2-adamantyl(1)-4-methyl-estra-1,3,5(10)-17-one], protects against ethanol withdrawal toxicity. HT22 cells were exposed to ethanol (0-500 mM) for 24 h in the presence or absence of ZYC26 or 17beta-estradiol. The ethanol solution was then removed from the cells for 4 h to create ethanol withdrawal. Samples were collected at the end of a 24-h ethanol exposure or at 4 h of ethanol withdrawal to assess cell viability using a calcein assay, lipid peroxidation by measuring malondialdehyde, and protein oxidation by measuring carbonyl contents. When tested, ethanol concentrations were constantly maintained during a 24-h ethanol exposure and eliminated at 4 h of ethanol withdrawal. Ethanol withdrawal decreased cell viability and increased the levels of malondialdehyde and carbonyls more than ethanol exposure. ZYC26 reduced the cell death and malondialdehyde levels at a lower dose (1 microM) than 17beta-estradiol (10 microM). The increased carbonyl contents were reduced only by ZYC26 treatment. These data suggest that ethanol withdrawal can be created in HT22 cells in a manner that is more toxic than ethanol exposure and that ZYC26 is a more potent cytoprotectant than 17beta-estradiol against cell death and oxidative damage induced by ethanol withdrawal. Therefore, ZYC26 can be a potential alternative estrogen therapy for a cellular and oxidative imbalance associated with ethanol withdrawal.

Adamantane↗
PubMed2006

The novel role of C-reactive protein in cardiovascular disease: risk marker or pathogen.

C-reactive protein (CRP) is a non-specific biomarker of inflammation. Recent research has shown that inflammation is an important step in the genesis of atherosclerosis, and is involved in the development of unstable plaques. Measurement of serum levels of CRP using a high sensitivity assay (hsCRP) can demonstrate subclinical inflammatory states, which may reflect vascular inflammation. Clinical studies have shown that elevated hsCRP levels in healthy populations predict vascular events such as myocardial infarction (MI) and stroke as well as the development of diabetes. In patients with acute coronary syndromes, higher hsCRP levels are associated with adverse outcomes and subsequent vascular events. There is data to suggest that aspirin, angiotensin converting enzyme (ACE) inhibitors and HMG Co-A reductase inhibitors (statins), which all reduce vascular event rates, also reduce serum levels of hsCRP and therefore hsCRP levels may potentially guide therapy. As well as having a critical role in risk prediction, recent evidence has emerged implicating CRP directly in atherogenesis. CRP has been found in human atherosclerotic plaque and CRP has been shown to cause endothelial cell dysfunction, oxidant stress and intimal hypertrophy in experimental models. We review the postulated roles of CRP in atherogenesis and prediction of vascular events, as well as discussing current recommendations for CRP testing in patients.

Atherosclerosis↗
PubMed2006

Latent plaque rupture in a patient undergoing stenting for acute coronary syndrome and diffuse coronary disease: a case report and review of literature.

Secondary prevention of plaque rupture following percutaneous coronary intervention in patients with acute coronary syndrome is not well studied. This case report describes a 53-year-old man who experienced plaque rupture between two previously successfully implanted stents in the right coronary artery, as documented during the 3rd intervention using intravascular ultrasound.

Aneurysm↗
PubMed2006

Successful removal of a paradoxical coronary embolus using an aspiration catheter.

BACKGROUND: A 28-year-old man presented at hospital with persistent pain in his chest and left arm, a paced rhythm on electrocardiography and elevated levels of cardiac enzymes. He was known to have patent foramen ovale and a dual-chamber pacemaker, which had been implanted following electrophysiological ablation to treat supraventricular tachycardia 3 years previously. The patient did not have a history of cardiovascular risk factors, recent travel, immobilization or clinical features of infection, and he was not taking any medication. INVESTIGATIONS: Electrocardiography, cardiac enzyme studies, coronary angiography and transthoracic echocardiography. DIAGNOSIS: Acute myocardial infarction, paradoxical coronary embolus and patent foramen ovale. MANAGEMENT: Coronary aspiration embolectomy and systemic anticoagulation.

Adult↗
PubMed2006

Safety of sputum induction in moderate-to-severe smoking-related chronic obstructive pulmonary disease.

BACKGROUND: Investigation of the safety of sputum induction in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) has been limited. OBJECTIVE: to evaluate this issue in 100 patients with a mean FEV1 of 1.2 (0.4) L. After 200 microg inhaled salbutamol, sputum induction was performed with inhaled saline in increasing and tailored concentrations (0.9% to 5%) until an adequate sample of sputum was obtained or the FEV1 fell by >20%. MAIN FINDINGS: Sputum induction was successful in 92% of occasions. The mean (SD) fall in FEV1 was 13.5 (8.6)%. Five patients had a fall >20% but all recovered to 10% of baseline after inhaled salbutamol. The magnitude of fall in FEV1 correlated weakly with salbutamol reversibility (r = 0.37, p < 0.001), baseline FEV1/VC (r = -0.32, p = 0.001) and baseline FEV1% predicted (r = -0.36, p = 0.003) but not with age, smoking history or post-Salbutamol FEV1. Principle CONCLUSION: Sputum induction can be performed safely using a patient-tailored approach in patients with moderate-to-severe COPD, supporting its use in research and clinical practice.

Adrenergic beta-Agonists↗
PubMed2006

The role of antihistamines in asthma management.

Histamine is an important mediator in airway inflammation. It is elevated in the airways of asthmatic patients and is responsible for many of the pathophysiological features in asthma. Antihistamines block the actions of histamine and also have effects on inflammation which is independent of histamine-H(1)-receptor antagonism. Antihistamines have been shown to have bronchodilatory effects, effects on allergen-, exercise-, and adenosine-monophosphate-challenge testing, and also to prevent allergen-induced nonspecific airways hyperresponsiveness. Clinical studies have shown mixed results, and some studies have reported beneficial effects of azelastine, cetirizine, desloratadine, and fexofenadine on asthma symptoms or physiological measures in patients with asthma. The combination of an antihistamine and a leukotriene receptor antagonist has been shown to have additive effects in certain studies. Antihistamines have also been shown to delay or prevent the development of asthma in a subgroup of atopic children. These data suggest that antihistamines may have beneficial effects in the management of asthma.

Asthma↗
PubMed2005

Systemic and vascular inflammation is elevated in early IgA and type 1 diabetic nephropathies and relates to vascular disease risk factors and renal function.

BACKGROUND: Inflammation is implicated in cardiovascular disease (CVD) and mortality in end-stage renal failure (ESRF). Its importance in early renal disease is yet to be defined. METHODS: Serum levels of systemic and vascular inflammatory markers in early IgA nephropathy (IgAN) and control subjects were measured and related to renal function and vascular risk factors. A parallel study in type 1 diabetes mellitus subjects with (T1DM Nx) and without nephropathy (T1DM No Nx) was performed. RESULTS: Fifty-one IgAN patients aged 46+/-2 years (mean+/-SEM), calculated creatinine clearance (CrCl) 88+/-5 ml/min, were compared with 51 matched control subjects. Forty-six T1DM Nx patients aged 40+/-2 years, CrCl 84+/-5 ml/min, and 73 T1DM No Nx patients aged 38+/-2 years were also compared. High sensitivity C-reactive protein (hsCRP) was elevated in IgAN, T1DM Nx and T1DM No Nx patients compared with controls [4.2+/-0.6 (P < 0.001), 4.1+/-0.6 (P < 0.001), 2.6+/-0.4 (P < 0.05) vs 1.6+/-0.3 mg/l]. Levels in T1DM Nx patients were higher than in T1DM No Nx patients (P < 0.05). Inflammation and vascular dysfunction as measured by pulse pressure (PP) were related. HsCRP correlated with PP in IgAN and T1DM Nx (r = 0.47, P = 0.001; r = 0.40, P < 0.05). PP was the strongest independent predictor of hsCRP in IgAN (T = 2.45, P < 0.001), while body mass index (T = 7.83, P < 0.001) was the strongest predictor in T1DM Nx. Endothelial cell adhesion molecules were increased in T1DM Nx > IgAN > T1DM No Nx vs controls: soluble vascular adhesion molecule-1 (sVCAM-1) 760+/-30 (P < 0.001) > 663+/-34 (P = 0.001) > 601+/-21 (P < 0.05) vs 536+/-15 ng/ml; soluble intracellular adhesion molecule-1 (sICAM-1) 320+/-8 (P < 0.001) > 313+/-13 (P < 0.001) > 307+/-8 (P < 0.001) vs 244+/-6 ng/ml. sVCAM-1 levels were higher in T1DM Nx than in T1DM No Nx, P < 0.001. In IgAN and T1DM Nx, hsCRP correlated with sICAM-1 (r = 0.33, P = 0.017; r = 0.37; P = 0.017). sVCAM-1 was related to renal function in IgAN and T1DM Nx: serum cystatin C (r = 0.63, P < 0.001: r = 0.425, P = 0.002), and urine protein:creatinine ratio in IgAN (r = 0.48; P = 0.001). CONCLUSIONS: Systemic and vascular markers of inflammation are increased in early renal disease and relate to renal dysfunction and cardiovascular risk factors. Inflammation may be a common process in various renal diseases and may link and accelerate renal dysfunction and CVD.

Adult↗
PubMed2005

Effects of dual therapy with corticosteroids plus long acting beta2-agonists in asthma.

Asthma is a common condition characterised by inflammation, airway hyperresponsiveness and reversible airflow obstruction. Effective pharmacotherapy must therefore be aimed at attenuating these underlying hallmark features. Despite the use of regular low-to-moderate doses of inhaled corticosteroids, many patients remain symptomatic and require further 2nd line controller therapy. The addition of a concomitant long acting beta2-agonist provides an effective means in which to alleviate symptoms and reduce exacerbation frequency. Moreover, both agents can be combined in a single inhaler, and provide patients with a more convenient and effective way in which to deliver treatment to the endobronchial tree. This evidenced-based review article discusses the effects of such combination inhalers upon a variety of outcome parameters and their effects upon asthmatics across a range of severities.

Adrenergic beta-Agonists↗
PubMed2004

Leukotriene receptor antagonists for allergic rhinitis: a systematic review and meta-analysis.

PURPOSE: To compare the clinical efficacy of leukotriene receptor antagonists with that of placebo, antihistamines, and nasal corticosteroids in patients with allergic rhinitis or nasal polyposis. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials of the effectiveness of leukotriene receptor antagonists in patients with rhinitis. Composite daily rhinitis symptom scores (as a percentage of the maximum score) and rhinitis-specific quality of life (unit scores ranging from 0 to 6) were pooled after assessing heterogeneity among studies. The pooled estimates were expressed as weighted mean differences between treatments in a random-effects model. We considered a difference of 10% in nasal score and 0.6 units in quality-of-life score to be clinically relevant. RESULTS: Of the 196 citations, 11 studies on seasonal allergic rhinitis were used in the analysis: eight evaluating leukotriene receptor antagonists alone or in combination with other treatments versus placebo or other treatments (n = 3924) and three evaluating leukotriene receptor antagonists plus an antihistamine (n = 80). Leukotriene receptor antagonists reduced mean daily rhinitis symptom scores (in absolute terms) 5% (95% confidence interval [CI]: 3% to 7%) more than did placebo. However, antihistamines improved the nasal symptoms score 2% (95% CI: 0% to 4%) more than did leukotriene receptor antagonists, and nasal corticosteroids improved the score 12% (95% CI: 5% to 18%) more than did leukotriene antagonists. Leukotriene receptor antagonists significantly improved rhinoconjunctivitis quality of life by 0.3 units (95% CI: 0.24 to 0.36 units) when compared with placebo. There were no randomized controlled trials evaluating the effect of leukotriene receptor antagonists on perennial allergic rhinitis or polyposis. CONCLUSION: Leukotriene receptor antagonists are modestly better than placebo, as effective as antihistamines, but less effective than nasal corticosteroids in improving symptoms and quality of life in patients with seasonal allergic rhinitis.

Drug Therapy, Combination↗
PubMed2004

Comparison of arterial assessments in low and high vascular disease risk groups.

BACKGROUND: An increasing number of arterial function assessments are available, including small and large arterial elasticity (SAE/C2, LAE/C1), endothelial function as measured by flow mediated dilation (FMD), carotid intima-medial thickness (IMT), ankle brachial index (ABI), pulse pressure (PP), and pulse wave velocity (PWV). We have consecutively performed these measures in subjects with low and high vascular disease risks to assess the interrelationships. METHODS AND RESULTS: Twenty healthy subjects (HS) and 20 older subjects with type 2 diabetes mellitus (DM) were studied with all techniques at a single sitting by a single operator. In HS, C2 correlated with FMD (R = 0.577, P = .008), PWV (R = 0.522, P = .046), and ABI (R = 0.463, P = .04). There was no significant correlation of C1 and FMD or blood pressure (BP) measurements. In DM, C2 correlated with FMD (R = 0.443, P = .05), systolic BP (R = -0.553, P = .01), PP (R = -0.601, P = .005), and systemic vascular resistance (R = -0.577, P = .008). There was no significant correlation between anthropometric measures and arterial function measures in either group. The IMT was not correlated with any measure of arterial function in either group. CONCLUSIONS: C2 assessed by pulse wave analysis correlated with endothelial function measured by FMD in young apparently healthy subjects and older subjects with type 2 diabetes. Systolic BP and PP correlated with C2 and FMD in older diabetic subjects but not healthy subjects. The interrelationships between arterial function measures are different in high and low risk populations. This variability needs to be considered when applying these techniques to individuals in different populations.

Adult↗
PubMed2004

Application of data mining techniques in pharmacovigilance.

AIMS: To discuss the potential use of data mining and knowledge discovery in databases for detection of adverse drug events (ADE) in pharmacovigilance. METHODS: A literature search was conducted to identify articles, which contained details of data mining, signal generation or knowledge discovery in relation to adverse drug reactions or pharmacovigilance in medical databases. RESULTS: ADEs are common and result in significant mortality, and despite existing systems drugs have been withdrawn due to ADEs many years after licensing. Knowledge discovery in databases (KDD) is a technique which may be used to detect potential ADEs more efficiently. KDD involves the selection of data variables and databases, data preprocessing, data mining and data interpretation and utilization. Data mining encompasses a number of statistical techniques including cluster analysis, link analysis, deviation detection and disproportionality assessment which can be utilized to determine the presence of and to assess the strength of ADE signals. Currently the only data mining methods to be used in pharmacovigilance are those of disproportionality, such as the Proportional Reporting Ratio and Information Component, which have been used to analyse the UK Yellow Card Scheme spontaneous reporting database and the WHO Uppsala Monitoring Centre database. The association of pericarditis with practolol but not with other beta-blockers, the association of captopril and other angiotensin-converting enzymes with cough, and the association of terfenadine with heart rate and rhythm disorders could be identified by mining the WHO database. CONCLUSION: In view of the importance of ADEs and the development of massive data storage systems and powerful computer systems, the use of data mining techniques in knowledge discovery in medical databases is likely to be of increasing importance in the process of pharmacovigilance as they are likely to be able to detect signals earlier than using current methods.

Data Collection↗
PubMed2004

Single and short-term dosing effects of levocetirizine on adenosine monophosphate bronchoprovocation in atopic asthma.

AIMS: Adenosine monophosphate (AMP) acts indirectly via primed airway mast cells to induce bronchial hyper-responsiveness, which in turn correlates with eosinophilic asthmatic inflammation and atopic disease expression. We evaluated single and short-term dosing effects of a modern histamine H1-receptor antagonist, levocetirizine, given at the usual clinically recommended dose, on the primary outcome of AMP bronchoprovocation. METHODS: Fifteen atopic asthmatics were randomized in double-blind, cross-over fashion to receive for 1 week either levocetirizine 5 mg or placebo. There was a 1-week washout period prior to each randomized treatment. The provocative concentration of AMP producing a 20% fall in FEV1 (PC20) was measured after each washout at baseline and at 4-6 h following the first and last doses of each randomized treatment. RESULTS: Baseline mean +/- SEM values after washout prior to each randomized treatment comparing levocetirizine vs placebo were not significantly different for prechallenge FEV1 (% predicted) 83 +/- 4 vs 82 +/- 4, or AMP PC20 (mg ml(-1)) 45 +/- 24 vs 45 +/- 22, respectively. Airway calibre as prechallenge FEV1 for levocetirizine vs placebo was not significantly different following the first dose 86 +/- 4 vs 82 +/- 4, or the last dose 85 +/- 4 vs 83 +/- 4, respectively. There were significant improvements (P < 0.05) in AMP PC20 comparing levocetirizine vs placebo following the first dose 123 +/- 73 vs 48 +/- 24, a 1.4 doubling dilution difference (95% CI 0.8, 1.9), and the last dose 127 +/- 74 vs 53 +/- 29, a 1.2 doubling dilution difference (95% CI 0.5, 2.0). AMP PC20 was also improved (P < 0.05) by the first and last doses of levocetirizine but not placebo, vs respective baseline values, with there being no difference in the degree of protection between first and last doses. CONCLUSIONS: Single and short-term dosing with levocetirizine conferred similar improvements in bronchial hyper-responsiveness to AMP challenge, which was unrelated to prechallenge airway calibre. Further studies are indicated to evaluate the longer-term effects of levocetirizine on asthma exacerbations.

Adenosine Monophosphate↗
PubMed2003

Estimation of primary and secondary particulate matter intake fractions for power plants in Georgia.

Air pollution benefit-cost analyses depend on dispersion models to predict population exposures to pollutants, but it is difficult to determine the reasonableness of the model estimates. This is in part because validation with field measurements is not feasible for marginal concentration changes and because few models can capture the necessary spatial and temporal domains with adequate sophistication. In this study, we use the concept of an intake fraction (the fraction of a pollutant or its precursor emitted that is eventually inhaled) to provide insight about population exposures and model performance. We apply CALPUFF, a regional-scale dispersion model common in health benefits assessments, to seven power plants in northern Georgia, considering both direct emissions of fine particulate matter (PM2.5) and secondarily formed ammonium sulfate and ammonium nitrate particles over a domain within 500 km of Atlanta. We estimate emission-weighted average intake fractions of 6 x 10(-7) for primary PM2.5, 2 x 10(-7) for ammonium sulfate from SO2, and 6 x 10(-8) for ammonium nitrate from NOx, with no effect of SO2 on ammonium nitrate. To provide insight about model strengths and limitations, we compare our findings with those from a frequently applied source-receptor (S-R) matrix. Using S-R matrix over an identical domain, the corresponding intake fractions are 5 x 10(-7), 2 x 10(-7), 3 x 10(-8), and -2 x 10(-8), respectively, with the values approximately doubling if the domain is expanded to cover the continental United States. Evaluation of model assumptions and comparison of past intake fraction estimates using these two models illustrates the importance of assumptions about the relative concentrations of ammonia, sulfate, and nitrate, which significantly influences ammonium nitrate intake fractions. These findings provide a framework for improved understanding of the factors that influence population exposures to particulate matter.

Air Pollutants↗
PubMed2003

The skin vasoconstrictor assay does not correlate significantly to airway or systemic responsiveness to inhaled budesonide in asthmatic patients.

OBJECTIVE: The responsiveness to inhaled corticosteroid varies among individual asthmatic patients. It is not known, however, whether the effects of corticosteroids on one bodily tissue reflect the response in another in a given individual. The aim was to a assess whether skin vasoconstrictor assay might predict airway and systemic tissue responsiveness to inhaled budesonide in patients with asthma. METHODS: Twenty-two patients with mild to moderate persistent asthma previously enrolled in a dose-response study assessing the effects of inhaled budesonide on airway bronchial challenge testing, exhaled nitric oxide and blood cortisol and eosinophil count were recalled for assessment of vasoconstrictor response to topical budesonide. The MacKenzie vasoconstrictor assay was performed by applying tenfold dilutions from 10(-2) g/ml to 10(-8) g/ml budesonide and visually assessing the degree of skin blanching after 18 h at each concentration. RESULTS: There was a significant overall dose-response effect for the degree of skin blanching at each concentration. There was no significant correlation between the effects on the skin and measures of anti-asthmatic efficacy or systemic effect after 3 weeks of 400 microg/day inhaled budesonide. There was a significant correlation with the overall dose-cutaneous response effect versus the overall dose-response effect with adenosine monophosphate (r=-0.53) but not methacholine bronchial challenge testing or serum cortisol. CONCLUSION: It may not be possible to use the McKenzie vasoconstrictor assay to predict which patients are most or least susceptible to inhaled corticosteroids for anti-asthmatic efficacy or systemic adverse effects.

Administration, Inhalation↗
PubMed2003

An evaluation of short-term corticosteroid response in perennial allergic rhinitis using histamine and adenosine monophosphate nasal challenge.

AIMS: To evaluate the role of AMP nasal challenge as a measure of short-term treatment response in patients receiving intranasal corticosteroids. Adenosine monophosphate (AMP) challenge has been shown to be a good inflammatory surrogate in the lower airways, but it has not been properly evaluated as a nasal challenge test. METHODS: Fourteen patients with perennial allergic rhinitis (PAR) were randomized to receive 2 weeks treatment with placebo (PL) or 200 microg intranasal mometasone furoate (MF) once daily in a randomized single-blind crossover study. AMP (25-800 mg ml-1) and histamine (0.25-8 mg ml-1) nasal challenge testing were performed after each treatment period with 30% decrease in minimal cross-sectional area (MCA). Domiciliary symptom data were collected. RESULTS: There was a significant (P < 0.05) improvement in PC30 MCA and nasal volume with AMP but not with histamine comparing MF vs PL. This amounted to a 2.8 (95% CI 1.5, 4.0) and 0.7 (95% CI -0.5, 1.9) doubling-dose change for AMP and histamine challenges, respectively. There were significant (P < 0.05) improvements in nasal symptoms and quality of life. CONCLUSIONS: AMP nasal challenge using acoustic rhinometry may be a useful test to assess short-term treatment response in patient with PAR.

Adenosine Monophosphate↗