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Biomedical subjects

J J Ferguson

Publications and source records attributed to J J Ferguson.

At least 19 recordsLinked to original sources
PubMed2000

New insights in cardiac structural changes in patients with Fabry's disease.

BACKGROUND: Fabry's disease is an X-linked recessive genetic deficiency of the enzyme alpha-galactosidase leading to the pathologic intracellular deposition of neutral glycosphingolipids. Although cardiac involvement is frequent, there is controversy regarding the character of the associated left ventricular (LV) changes and the severity of valvular involvement. METHODS: Clinical evaluation (disease severity scaling, laboratory tests, and echocardiography) was performed in 13 hemizygous men (mean age 39 +/- 10 years) and 17 heterozygous women (mean age 35 +/- 19 years). RESULTS: LV hypertrophy (LVH) was frequent in subjects older than 30 years, more often in men (61%) than in women (18%, P <.001). The degree of LVH was independently associated with age and the logarithm of alpha-galactosidase activity (r(2) = 0.70, P <.001). The predominant LV geometric patterns were concentric LVH and remodeling, both present in 11 subjects (36%). Three patients had an asymmetric septal hypertrophy mimicking hypertrophic cardiomyopathy. In most subjects with LVH, the systolic function was normal and severe diastolic dysfunction (restrictive pattern) was not noted. Minor structural abnormalities of the mitral valve were found in 17 subjects (57%). The aortic valve was affected in 14 patients (47%). Valvular abnormalities were frequently accompanied by regurgitation of minor to mild degree. The presence of LVH or valvular changes was associated with increased disease severity. CONCLUSIONS: Echocardiographically detectable cardiac involvement is frequent with Fabry's disease, particularly in older subjects, and more pronounced in affected hemizygous men than in heterozygous women. LVH is frequently observed but usually not associated with significant systolic or restrictive diastolic dysfunction. Concentric LVH and remodeling appear to be the major manifestations of LV structural alteration. The frequently noted valvular abnormalities were not associated with a significant degree of regurgitation. Valvular and especially LV structural changes may serve as a useful marker of disease severity.

Adolescent↗
PubMed1999

Differences between men and women in the management of unstable angina pectoris (The GUARANTEE Registry). The GUARANTEE Investigators.

Few data are available in prospectively collected cohorts of patients with unstable angina pectoris or on the use of appropriate medications or interventions. Accordingly, we evaluated 2,948 consecutive patients with unstable angina admitted to 35 hospitals in the United States in 1996, and comparing men and women (39% of the patients were women). Differences were seen in coronary risk profiles with a higher incidence of systemic hypertension, diabetes mellitus, and a family history of coronary disease in women. Women were less likely to receive Agency for Health Care Policy Research (AHCPR) recommended pharmacologic treatment than men. Cardiac catheterization, coronary angioplasty, and bypass was performed less often in women compared with men (44% vs. 53%, p = 0.002; 12% vs. 18%, p = 0.02; 7% vs. 10%, p = 0.001, respectively). At catheterization, women were more likely to have no significant coronary artery disease (25% vs. 14%, p = 0.001). Although fewer women than men fulfilled the AHCPR criteria for cardiac catheterization (54% vs. 64%, p = 0.001), a similar rate of men and women with positive criteria underwent catheterization and angioplasty. However, fewer women with positive criteria underwent bypass surgery (36% vs. 46%, p = 0.03). More men "ruled-in" for a myocardial infarction at admission (13% vs. 8%, p = 0.001), but there was no difference in recurrent angina, in-hospital myocardial infarction, or death. Despite different epidemiologic profiles and less evidence of coronary artery disease by noninvasive and invasive tests, women and men had similar outcomes.

Adult↗
PubMed1999

Platelet-endothelial interactions in atherothrombotic disease: therapeutic implications.

The role of the platelet and the endothelium in the pathogenesis of atherosclerosis and subsequent ischemic events has been the subject of extensive investigation. Arterial sites where endothelial function is severely impaired are often the sites of atheroma development. Lesion evolution impairs endothelial function, leading to a self-perpetuating cycle of growth. During early lesion development, overt thrombotic events are rare. However, rupture of an advanced, necrotic plaque or intimal ulceration triggers arterial thrombosis, at which point the importance of platelet function may be seen clearly. The Antiplatelet Trialists' Collaboration meta-analysis demonstrated the benefit of antiplatelet therapy to patients with atherosclerotic disease. Aspirin is the most widely studied agent and is considered the standard of antiplatelet therapy. Newer agents that intervene at different stages of the platelet activation pathway have been developed. Clopidogrel, a new adenosine diphosphate receptor antagonist, is more effective than aspirin in reducing vascular events in patients with prior myocardial infarction, stroke, or established peripheral arterial disease. The glycoprotein IIb-IIIa antagonists such as abciximab have proven effective in the setting of active arterial thrombosis and percutaneous revascularization, but their value in secondary prevention remains unknown. All patients with atherosclerosis should be treated with an antiplatelet drug. Current evidence suggests that either aspirin or clopidogrel are appropriate first-line agents. There is urgent need for an analysis of the risk/benefit ratio in various populations and clinical settings to determine the most appropriate type and intensity of therapy for a given patient.

Animals↗
PubMed1999

Trials of glycoprotein IIb-IIIa inhibitors in non-ST-segment elevation acute coronary syndromes: applicability to the practice of medicine in the United States.

Platelet-mediated thrombosis has been recognized as the primary pathophysiologic mechanism of acute coronary syndromes (ACS) and acute complications of percutaneous coronary intervention (PCI). Despite the clinical efficacy of the two most widely used antithrombotic agents, aspirin and heparin, each of them has significant therapeutic limitations. As a result, thrombosis and clinical events may occur despite the use of aspirin and heparin. The discovery that the platelet glycoprotein (GP) IIb-IIIa represents the final common pathway to platelet aggregation and the growing recognition of the key role of platelets in the progression of thrombosis prompted the development of several GP IIb-IIIa inhibitors as a potentially more effective form of antithrombotic therapy. Numerous trials of various GP IIb-IIIa inhibitors as adjuncts to PCI have strongly supported this hypothesis. The subject of this supplement is the review of more recent evaluations of GP IIb-IIIa inhibitors in the context of various treatment strategies for the management of patients with unstable angina or non-ST-segment elevation myocardial infarction, collectively known as non-ST-segment elevation ACS. Appropriate translation of these trials into clinical practice requires not only the knowledge of the trials' results but also the understanding of the design of individual studies, most notably the entry criteria and patient management strategies.

Acute Disease↗
PubMed1999

Racial differences in the management of unstable angina: results from the multicenter GUARANTEE registry.

BACKGROUND: Prior studies, usually conducted with the use of insurance databases, have shown differences in the use of cardiac procedures between black patients and white patients hospitalized with various types of coronary artery disease. However, few data are available in prospectively collected cohorts of patients with unstable angina or on the use of appropriate medications or interventions. METHODS AND RESULTS: We evaluated 2948 consecutive patients with unstable angina admitted to 35 hospitals across the United States in 1996, comparing nonwhite and white patients. Seventy-seven percent of patients were white, 14% were black, 4% were Hispanic, 1% were Asian, and 3% were other or unknown race. Differences were seen in coronary risk profile, with a higher incidence of hypertension and diabetes mellitus in nonwhites. Cardiac catheterization was performed less often in nonwhites compared with whites (36% vs 53%, P =.001). Even in patients meeting the criteria for appropriate catheterization in the Agency for Health Care Policy Research unstable angina guidelines, fewer nonwhites underwent catheterization (44% vs 61%, P =.001), but among these, fewer nonwhites had significant coronary stenosis (72% vs 90%, P =.001). However, among patients catheterized who had indications for revascularization, angioplasty and coronary artery bypass grafting were performed equally often in nonwhites and whites. CONCLUSIONS: Current guidelines would recommend more aggressive use of cardiac catheterization for nonwhite patients. However, our findings suggest that racial differences may need to be included in the diagnostic and interventional algorithms.

Aged↗
PubMed1999

IIb/IIIa receptor blockade in acute myocardial infarction.

To appreciate the clinical potential of antiplatelet therapy in the treatment of patients with acute myocardial infarction (MI), it is important to understand the mechanism and pathophysiology of acute MI and to understand the role that platelets play in the process of acute thrombus formation. Recognition of the limitations of current therapy has sparked intense interest in the development of more potent platelet inhibitors such as antagonists of the platelet glycoprotein (GP) IIb/IIIa receptor. Because this receptor represents the final common pathway of platelet aggregation, it emerges as a very attractive therapeutic target for phamacologic interventions. The purpose of this review is to summarize the results of recent large-scale clinical trials that use GP IIb/IIIa antagonist therapy in patients with acute MI both as an adjunct to percutaneous coronary interventions and as an adjunct to exogenously administered fibrinolytic therapy. As an adjunct to percutaneous coronary interventions, GP IIb/IIIa antagonists have shown significant benefit in the prevention of composite end points of death, MI, and emergency revascularization. As an adjunct to fibrinolytic agents, GP IIb/IIIa antagonists enhance the speed and degree of reperfusion achievable pharmacologically. Although the potential risk of bleeding remains a concern (particularly with higher doses of streptokinase), recent phase II trials such as TIMI 14 and SPEED suggest considerable potential for these potent antiplatelet agents in the medical treatment of patients with acute MI.

Angioplasty, Balloon, Coronary↗
PubMed1999

Platelet glycoprotein IIb/IIIa receptor antagonists: current concepts and future directions.

Platelets play a key role in the development of thrombosis. Glycoprotein (GP) IIb/IIIa antagonists are a new class of potent drugs that profoundly inhibit platelet function by blocking the key receptor involved in platelet aggregation. Several antiplatelet agents with varying characteristics have emerged in the past few years and have been evaluated in a variety of potential clinical settings. Clinical trials have established the effectiveness of these drugs in conditions where thrombosis plays a major contributing role such as unstable angina pectoris, myocardial infarction, and high-risk coronary intervention. Despite their potent antiplatelet effects, GP IIb/IIIa antagonists appear to be remarkably well tolerated, provided that the concomitant use of other anticoagulants such as heparin is managed carefully. Ongoing and future studies will further refine the role of GP IIb/IIIa antagonists, explore new applications, and further test their safety and cost effectiveness in the short and long term.

Animals↗
PubMed1999

Influence of different stent materials on endothelialization in vitro.

The objective of our study was to investigate the influence of different stent materials on endothelialization in vitro. Using the non-destructive Alamar Blue assay and scanning electron microscopy, we compared long-term growth and morphology of vascular cells on disks of three prospective stent materials, i.e., 316 L stainless steel, 18 K, and 24 K gold. Our results demonstrate superior human EC proliferative capacity on gold surfaces compared to that on 316 L stainless steel. Thus, both the hyperplasia and thrombotic complications which often follow stenting might be minimized by employing gold stents, which have a greater capacity than steel in supporting a functional neo-endothelium.

Cell Division↗
PubMed1998

Pharmacodynamic efficacy, clinical safety, and outcomes after prolonged platelet Glycoprotein IIb/IIIa receptor blockade with oral xemilofiban: results of a multicenter, placebo-controlled, randomized trial.

BACKGROUND: Parenteral administration of platelet glycoprotein IIb/IIIa (GP IIb/IIIa) receptor blockers can reduce ischemic complications of coronary angioplasty. Orally active GP IIb/IIIa blockers may allow more sustained receptor antagonism with the potential for long-term secondary prevention. The pharmacodynamic efficacy, clinical safety, and outcomes after prolonged receptor blockade with an orally active GP IIb/IIIa antagonist are not known. The Oral Glycoprotein IIb/IIIa Receptor Blockade to Inhibit Thrombosis (ORBIT) Trial is a multicenter, placebo-controlled, randomized trial of xemilofiban, an oral platelet GP IIb/IIIa blocking agent, administered to patients after percutaneous coronary intervention. METHODS AND RESULTS: After successful elective percutaneous coronary intervention, 549 patients were randomized to receive either placebo or xemilofiban in a dose of 15 or 20 mg. Stented patients randomized to placebo also received ticlopidine 250 mg orally BID for 4 weeks. Patients who received abciximab during the coronary intervention and who were randomized to receive xemilofiban were administered a reduced dosage (10 mg TID for 2 weeks) followed by the randomized maintenance dose of 15 or 20 mg BID for 2 more weeks. All patients received 325 mg aspirin PO QD. Ex vivo platelet aggregation in response to 20 micromol/L ADP and 4 microg/mL collagen was measured over time after the initial dose of study drug and at days 14 and 28 of long-term therapy in 230 patients. All patients were followed clinically for 90 days. Xemilofiban inhibited platelet aggregation to both ADP and collagen with peak levels of inhibition that were similar at 14 and 28 days of long-term oral therapy. Plasma levels of xemilofiban correlated with the degree of platelet inhibition. Peak platelet inhibition on day 1 correlated with the subsequent occurrence of insignificant or mild bleeding events. Although this study was not powered to evaluate differences in clinical outcomes, a trend (P=0.04) was observed for reduction of cardiovascular events at 3 months in patients not treated with abciximab who received the highest dose (20 mg) of xemilofiban studied. CONCLUSIONS: Xemilofiban inhibited platelet aggregation and was well tolerated during 28 days of long-term oral therapy. The observed trend in reduction of cardiovascular events in follow-up awaits confirmation in the larger-scale phase III study (EXCITE trial) currently in progress.

Administration, Oral↗
PubMed1998

Complications associated with combined use of abciximab and an intracoronary thrombolytic agent (urokinase or tissue-type plasminogen activator).

A potent platelet inhibitor combined with an intracoronary thrombolytic agent is aggressive therapy that may be used for high-risk, complex, refractory thrombotic coronary lesions. A retrospective review of the records of 56 patients who received abciximab plus an intracoronary thrombolytic agent during a coronary interventional procedure did not reveal a prohibitive incidence of major bleeding with this combination therapy.

Abciximab↗