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Biomedical subjects

E Gurfinkel

Publications and source records attributed to E Gurfinkel.

At least 19 recordsLinked to original sources
PubMed2006

The role of infection and immunity in atherosclerosis.

Cardiovascular diseases account for 20% of deaths worldwide, rising to 50% in developed countries. Current understanding of atherosclerosis derives from a combination of research in animals and cell cultures, analysis of human lesions, clinical investigations of patients with acute coronary syndromes and epidemiological studies of coronary artery disease. By measuring serologic titers in the serum of patients after cardiovascular events, it was observed that the greater the infectious exposure of a patient, the larger the atherosclerotic lesion extension. In addition, gene targeting or pharmacological inhibition of certain cytokines aggravates atherosclerosis in animal experiments. Other animal experiments have succeeded in proving that B cells play a protective role in atherosclerosis through induced immunity against oxidized low-density lipoprotein and other epitopes. Molecular mimicry might respond to the question of how infection may trigger vulnerability in previously stable atherosclerotic lesions. The FLU Vaccination Acute Coronary Syndromes trial enhanced the debate on atherosclerosis prevention by the application of antiflu vaccine. So far, antibiotics have failed to reduce cardiovascular risk, as recent trials could not demonstrate a statistically significant risk reduction. Having assumed atherosclerosis to be an inflammatory disease, the WHO considered the possible role of secondary prevention with antiflu vaccine.

Animals↗
PubMed2000

Impact of enoxaparin low molecular weight heparin in patients with Q-wave myocardial infarction.

A subgroup meta-analysis from the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) and the Thrombolysis in Myocardial Infarction (TIMI) 11B studies has shown that enoxaparin is superior to unfractionated heparin in reducing the composite end points of death, myocardial infarction, and emergency revascularization in patients with Q-wave myocardial infarction. The beneficial treatment effect was significant at 43 days.

Aged↗
PubMed2000

[Rebuilding the concept of unstable angina].

Large clinical trials provide invaluable information. This, combined with a number of small studies about the pathophysiology of certain diseases, permits us to re-consider previously accepted pathophysiological mechanisms and suggests an updated theory about the definition and diagnosis of individual diseases. This information obtained appears to place unstable angina in a new light. The instability of unstable angina seems to be the transient moment in which the previous clinical state is abandoned to pass into another clinical condition, rather than the establishment of a new diagnosis or nosological entity. Is this then the end of unstable angina as a final diagnosis?The development of troponin has increased our ability to identify myocardial necrosis. The myocardial ischemia leading to myocardial necrosis is the most important issue in atherosclerosis. In addition, immune cell activation may also relate to the extent of necrosis. The activation of the immune/inflammatory system in patients with acute coronary syndromes is probably not exactly related with the presence of an unstable plaque per se, as is usually inferred by inflammatory markers, but with the total atherosclerotic burden in the arterial tree of these patients. After all the new evidence of studies regarding coronary syndromes, is it not the time to reconsider the definition of unstable angina?

Angina, Unstable↗
PubMed2000

Collaborative multidisciplinary workshop report: clinical antimicrobial trials for primary and secondary prevention of atherosclerotic cardiovascular disease.

The task assigned to the working group on Clinical Antimicrobial Trials for Primary and/or Secondary Prevention of Atherosclerotic Cardiovascular Disease was to evaluate the need for additional clinical antibiotic trials of a primary or secondary nature for the treatment of atherosclerotic heart disease and to suggest possible designs for future trials. In addition, the working group was to define the role of collaboration in answering research questions.

Anti-Bacterial Agents↗
PubMed2000

Inflammation, infection, or both in atherosclerosis: the ROXIS trial in perspective.

The role of infection in the instability of atherosclerotic plaques has been questioned because of discrepancies in the results of clinical trials that tested antibiotics in acute coronary syndromes. The results of the Randomized Trial of Roxithromycin in Non-Q-Wave Coronary Syndromes (ROXIS) are summarized and contrasted with two other pilot studies of antibiotic therapy of coronary artery disease. Relevant characteristics of patients enrolled and rationales for these trials are discussed and serologic results are presented.

Angina, Unstable↗
PubMed1999

Thrombotic reactant markers in non-ST segment elevation acute coronary syndromes treated with either enoxaparin (low molecular weight heparin) or unfractionated heparin.

BACKGROUND: This study was designed to analyze the impact of treatment with either unfractionated heparin or enoxaparin (low molecular weight heparin) on plasma markers of thrombotic and endogenous thrombolytic activity in patients with non-ST segment elevation acute coronary syndromes. METHODS: A subset of 174 patients derived from the 3,171 patients of the ESSENCE study was evaluated. Eighty-seven patients were assigned to intravenous unfractionated heparin (target aPTT: 55-85 sec) (group UH), and 87 assigned to subcutaneous enoxaparin (1 mg/kg/q12hr) (group ENOX) for a minimum of 48 hours of treatment (average duration of treatment 88+/-45 hours). The thrombin time, and plasma levels of anti-factor Xa activity, prothrombin fragment F 1+2, thrombin-antithrombin complex (TAT), and D-dimer, were assayed at baseline, and at or close to peak activity 24-36 hrs, and at 72-90 hrs for those remaining on treatment with antithrombotic therapy. Major ischemic and hemorrhagic events were assessed throughout hospitalization. The levels of the thrombotic markers measured at or close to peak activity at 36 hours are presented below, and compared to clinical outcome at 30 days. RESULTS: In UH patients, the thrombin time increased 7 fold while the mean value for anti-Xa activity was 0.27 IU/ml; in ENOX patients the thrombin time increased 2.3 fold, and the mean value for anti-Xa activity was 0.83 IU/ml. In UH pts, basal levels of F 1+2, TAT, and D-dimer declined by (deltapaired) -0.8, -3. 3, and -66, respectively. In ENOX pts, basal levels of F 1+2, TAT, and D-dimer declined by (deltapaired) -0.3, -4.7, and -23, respectively. No significant differences were observed between the paired differences in thrombotic markers (UH vs ENOX), nor in the rate of recurrent ischemic events or major hemorrhage. CONCLUSIONS: In this subset of patients enrolled in the ESSENCE study, enoxaparin 1 mg/kg ql2hr significantly increased anti-Xa activity above that seen with unfractionated heparin, and reduced thrombin production without prolonging the thrombin time. The high anti-Xa activity achieved with enoxaparin was not associated with a loss of safety.

Biomarkers↗
PubMed1999

Treatment with the antibiotic roxithromycin in patients with acute non-Q-wave coronary syndromes. The final report of the ROXIS Study.

AIMS: Mounting evidence suggests infection, specifically Chlamydia pneumoniae, plays a role in atherosclerosis. We tested whether antibiotic treatment with the macrolide roxithromycin improves clinical outcome in patients with acute non-Q-wave coronary syndromes. Preliminary reports revealed a reduction in events in the roxithromycin group at 30 days. We now report the long-term follow-up results. METHODS AND RESULTS: Sixty-four per cent of the initial 202 patients with unstable angina who were randomly assigned to receive either roxithromycin or placebo for 30 days completed the active treatment period. At day 30, the primary triple and double end-point rates were 9% and 4% in the placebo group compared to 2% and 0% in the roxithromycin group (unadjusted P = 0.032 and 0.058, respectively). The secondary triple and double end-point rates were again higher in the placebo group at day 90 (12.5% and 6.25% vs 4.37% and 0%, unadjusted P = 0.065 and 0.029, respectively), and at day 180 (14.6% and 7.29% vs 8.69% and 2.17%, unadjusted P = 0.259 and 0.17, respectively). Anti-C, pneumoniae IgG titres were unchanged in both groups while C-reactive protein levels decreased in both strategies, with a more significant decrease in the roxithromycin arm (P = 0.03). Elevated C-reactive protein levels predicted the need for revascularization. CONCLUSIONS: In this pilot trial, roxithromycin appears to extend the clinical benefit of preventing death and re-infarction for at least 6 months after initial treatment.

Aged↗
PubMed1998

Rationale for the management of coronary syndromes with low-molecular-weight heparins.

The well-documented disadvantages of unfractionated heparin in the management of coronary syndromes, such as unpredictable bioavailability and maintenance of therapeutic range, has prompted several studies into the benefits of low-molecular-weight heparins (LMWHs). The favorable pharmacologic properties of LMWHs include a binding affinity for antithrombin III, anti-factor IIa activity, excellent bioavailability, minimal protein binding, predictable anticoagulant response, and clinical tolerance by patients. LMWHs are also characterized by having a specific anti-factor Xa effect and inducing only a small prolongation in general clotting tests-i.e., activated partial thromboplastin time, prothrombin time, and antithrombin activity-when used in high doses. Several studies have recently demonstrated that LMWHs are superior to placebo and are at least equal or superior to standard heparin when added to aspirin for the treatment of unstable angina and following non-Q-wave myocardial infarction. These studies, which include Thrombolysis in Myocardial Infarction (TIMI) 11A and Efficacy and Safety of Subcutaneous Enoxaparin versus intravenous unfractionated heparin in Non-Q-wave Coronary Events (ESSENCE), will be reviewed and discussed.

Aspirin↗
PubMed1998

Chlamydia pneumoniae: inflammation and instability of the atherosclerotic plaque.

Coronary heart disease remains the most common cause of death in industrialized countries. Although atherosclerosis is generally asymptomatic in the early stages, progressive plaque development leads to arterial stenosis which is characterized by angina and may eventually lead to unstable angina, myocardial infarction and cardiac death. Evidence that the coagulation cascade is activated during acute coronary events has justified the use of antithrombotic agents such as aspirin, heparin and low molecular weight heparin (LMWH) in the standard management of acute coronary syndromes. The inflammatory process is also known to play a significant role in the pathogenesis of atherosclerosis, resulting in a cycle of continued inflammatory cell activation and ongoing cell recruitment. As the human leukocyte-associated antigen (HLA) system plays a key role in the regulation of the inflammatory process, the expression of HLA antigens in patients with symptomatic coronary heart disease has been investigated. These studies have demonstrated a relationship between the major histocompatibility complex (MHC) class II expression and the most severe pattern of angina refractory to conventional therapy, within the framework of a chronic infectious disease. A number of studies have documented an association between coronary heart disease and the presence of high titres of antibodies to Chlamydia pneumoniae, and this organism has been implicated in plaque instability. Such findings have stimulated interest in the role of C. pneumoniae in the pathogenesis of coronary heart disease, with a view to developing novel and effective treatment approaches. The ROXIS study showed a lower incidence of acute ischaemic events in patients with unstable angina treated with an antichlamydial antibiotic, roxithromycin.

Angina, Unstable↗
PubMed1997

Randomised trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS Pilot Study. ROXIS Study Group.

BACKGROUND: There is serological evidence for an association between Chlamydia pneumoniae and coronary heart disease. We investigated the hypothesis that an antichlamydial macrolide antibiotic, roxithromycin, can prevent or reduce recurrent major ischaemic events in patients with unstable angina. METHODS: The effect of roxithromycin was assessed in a double-blind, randomised, prospective, multicentre, parallel-group, placebo-controlled pilot study of 202 patients with unstable angina or non-Q-wave myocardial infarction. Patients were randomly assigned either roxithromycin 150 mg orally twice a day (n = 102) or placebo orally twice a day (n = 100). The treatment was for 30 days. Patients were followed up for 6 months. We report the primary clinical endpoints (cardiac ischaemic death, myocardial infarction, and severe recurrent ischaemia), assessed at day 31, in 202 patients on an intention-to-treat basis. FINDINGS: A statistically significant reduction in the primary composite triple endpoint rates was observed in the roxithromycin group: p = 0.032. The rate of severe recurrent ischaemia, myocardial infarction, and ischaemic death was 5.4%, 2.2%, and 2.2% in the placebo group and 1.1%, 0%, and 0%, in the roxithromycin group, respectively. No major drug-related adverse effects were observed. INTERPRETATION: Antichlamydial antibiotics may be useful in therapeutic intervention in addition to standard medication in patients with coronary-artery disease. Large-scale trials are needed to confirm these preliminary observations.

Adult↗
PubMed1996

Comparison of high-dose with low-dose aspirin in patients with mechanical heart valve replacement treated with oral anticoagulant.

BACKGROUND: There are no reported studies on the safety and efficacy of low-dose aspirin with low-intensity oral anticoagulation in patients with heart valve replacement. In this study, we compared the use of 100 mg/d aspirin with 650 mg/d aspirin in the prevention of systemic embolism and vascular death in patients with heart valve replacement who were being treated with oral anticoagulants with a target international normalized ratio (INR) of 2.0 to 3.0. METHODS AND RESULTS: Four hundred nine of 416 consecutive patients who had cardiac valve replacement were randomized in open allocation into one of two groups; both groups were treated with oral anticoagulant therapy with a target INR of 2.0 to 3.0. Two hundred seven patients who received 100 mg/d aspirin for an average of 24.1 months were compared with 202 patients who received 650 mg/d aspirin for an average of 21.7 months in a randomized-treatment, open-allocation study. There were no significant differences in systemic embolism, vascular death, or total death rates between the low- and high-dose aspirin treatment groups (0.5 and 1.1, 1.2 and 0.5, and 4.6 and 2.5 per 100 patients/y, respectively). The total number of hemorrhagic events was 13.4 per 100 patients/y in the high-dose aspirin group and 7.9 per 100 patients/y in the low-dose aspirin group (P = .035), but the rate of bleeding was influenced by dipyridamole in the 650-mg aspirin group. CONCLUSIONS: In patients with mechanical heart valve replacements, low-dose aspirin (100 mg/d) in conjunction with oral anticoagulants at an INR of 2.0 to 3.0 is as effective as the use of high-dose aspirin (650 mg/d) in the prevention of systemic embolism.

Administration, Oral↗