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Biomedical subjects

M Ezekowitz

Publications and source records attributed to M Ezekowitz.

16 recordsLinked to original sources
PubMed2001

Acute statin treatment in reducing risk after acute coronary syndrome: the MIRACL (Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering) Trial.

Three-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors (statins) reduce coronary events and death in both primary and secondary prevention trials. In these trials benefit did not appear for years after randomization. It is noteworthy that these trials did not include patients with recent myocardial infarctions or unstable angina. It is well known that mortality and recurrent ischemic events rates are the highest in the early period after acute coronary syndromes. Favorable physiologic effects of statins have been described within a few weeks of exposure to the statin in a number of experimental studies. The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study was designed to bridge the gap between primary and secondary prevention trials and specifically included patients with unstable angina or non-ST elevation myocardial infarction.

Angina, Unstable↗
PubMed2000

In vitro evaluation of c7E3-Fab (ReoPro) eluting polymer-coated coronary stents.

OBJECTIVE: Stent thrombosis and in-stent restenosis remain problematic in certain patient sub-groups. c7E3-Fab (ReoPro, abciximab) inhibits the platelet glycoprotein IIb/IIIa receptor as well as the smooth muscle cell alpha(v)beta3 receptor, and thus may influence both processes, especially if high local concentrations could be achieved. We have studied the adsorption and elution characteristics of c7E3-Fab on commercially available polymer-coated stents. We have also investigated the effect of such antibody binding on platelet deposition in vitro, and on antibody deposition into ex vivo human saphenous vein wall to assess whether such stents may influence stent thrombosis and restenosis. METHODS AND RESULTS: Adsorption was measured using a radioisotope technique after immersing segments of polymer-coated stents in c7E3-Fab solutions. Uptake was dependent on antibody concentration and duration of immersion of wire in the solution. After 22 h (at 5 mg ml(-1)), 1146+/-101 ng cm(-1) wire was adsorbed. In an in vitro perfusion circuit, the antibody eluted slowly, with 53% remaining after 12 days washing. To determine the value that such stents might have in clinical practise, adsorption to balloon-mounted stents was assessed at room temperature, using commercially available c7E3-Fab (2 mg ml(-1)). Efficacy of eluting c7E3-Fab was determined by measuring deposition of 111-Indium platelets. Immersing stents in c7E3-Fab for 20 min inhibited platelet deposition by 82.3% compared to controls (P=0.018). Deployment of treated stents in ex vivo saphenous vein resulted in the deposition of c7E3-Fab in the intima and media. CONCLUSIONS: c7E3-Fab can be passively adsorbed onto polymer-coated stents. It elutes slowly and in a predictable manner, significantly inhibiting platelet deposition in vitro. These studies pave the way to developing stent-based delivery of a potent anti-platelet agent that may additionally affect smooth muscle cell activity.

Abciximab↗
PubMed1998

Combination Hemotherapy and Mortality Prevention (CHAMP) Study Rationale and Design.

It is now agreed that the majority of acute myocardial infarctions result from intracoronary thrombosis at sites of atherosclerotic plaque that have been disrupted. In 1947 Nicol and Fassett published the first clinical paper suggesting that agents interfering with blood coagulation could prevent myocardial infarction in patients at risk. Scores of subsequent clinical trials were performed to assess the efficacy of anticoagulants and antiplatelet agents in preventing death and reinfarction in survivors of acute myocardial infarction. Despite these efforts no agreement exists on whether these strategies are beneficial and, if so, which is superior. The primary obstacle to progress in this field has been the failure of nearly all trials to enroll the large numbers of subjects required to demonstrate a survival benefit. The large sample size requirement derives from two inescapable facts: mortality rates following acute infarction, though variable, are generally low and the potential benefit of these agents in preventing mortality is small. Combining oral anticoagulants with antiplatelet agents (combination hemotherapy) may significantly enhance their antithrombotic effect. Clinical trials of combination hemotherapy have demonstrated superiority over anticoagulant monotherapy in the setting of stroke prevention in patients with prosthetic heart valves. Similar benefit was not observed in trials studying stroke prevention in nonvalvular atrial fibrillation and vascular morbidity in patients surviving an acute myocardial infarction. The failure of these latter studies may relate to the particularly low intensity of warfarin administered in combination with aspirin. This trial proposes to demonstrate that the combination of oral anticoagulation, administered in a moderate dose intensity, and antiplatelet therapy is superior to aspirin monotherapy in reducing overall mortality following acute myocardial infarction.

Journal Article↗
PubMed1997

Minimally invasive coronary artery bypass grafting: initial Connecticut experience.

We report the initial Connecticut experience with minimally invasive coronary artery bypass grafting. This procedure allows bypass grafting to the left anterior descending coronary artery utilizing the internal mammary artery as the conduit. The procedure is minimally invasive because it is performed through a mini-thoracotomy incision in the fourth anterior intercostal space and it is conducted without the use of cardiopulmonary bypass. The procedure has been applied to 13 patients operated between February and October 1996. All but one patient selected were poor candidates for conventional coronary artery bypass surgery because of advanced age (6), chronic renal failure/dialysis/kidney transplant (4), redo status with vulnerable grafts (1), severe peripheral vascular disease (6), severe chronic obstructive pulmonary disease (4). All patients survived operation and were discharged in good condition. Mean postoperative intubation time was seven hours and mean hospital stay was 4.5 days despite the very high pre-existing comorbidity of these patients. All patients are alive at the current follow-up time. Two patients required a conventional bypass procedure for occlusion of the minimally invasive graft, the first because of diffuse disease in the target artery and the second attributable to the technical limitations of minimally invasive coronary artery bypass grafting; both tolerated the subsequent procedure well. All patients are now angina-free. All four grafts studied by routine postoperative angiography were widely patent. Routine post-operative exercise nuclear imaging was normal in an additional patient. This procedure of minimally invasive coronary artery bypass grafting offers significant advantages compared to the conventional bypass procedure (short hospital stay, quick recovery, and, especially, avoidance of cerebrovascular accidents caused by the heart-lung machine). This minimally invasive procedure is expected to apply to a growing percentage of patients. The procedure, especially vis-à-vis angioplasty, may well offer the superior long-term patency of the mammary conduit achieved with a modest initial "investment" in hospital stay, costs of medical care, and discomfort and disability. A prospective, randomized trial comparing angioplasty and minimally invasive coronary artery bypass grafting is warranted.

Aged↗
PubMed1994

Double-blind efficacy and safety study of a novel anti-ischemic agent, ranolazine, versus placebo in patients with chronic stable angina pectoris. Ranolazine Study Group.

BACKGROUND: Ranolazine modulates the metabolism of ischemic myocardial cells and improves the efficiency of oxygen use. This study was conducted to evaluate the antianginal and anti-ischemic effects and safety of different doses of ranolazine administered three times daily (tid) compared with placebo in patients with stable angina pectoris. METHODS AND RESULTS: Patients with stable angina pectoris took part in the study. Previous antianginal drugs were discontinued under medical supervision. Three hundred nineteen patients received single-blind placebo for up to 18 days, and 318 stopped exercise because of angina of moderate severity, had evidence of myocardial ischemia (> or = 1-mm ST segment depression), and were randomized to one of four study groups in a double-blind manner: ranolazine 30 mg tid (n = 81), ranolazine 60 mg tid (n = 81), ranolazine 120 mg tid (n = 78), and placebo tid (n = 79). After the 4-week double-blind phase, symptom-limited exercise tests were repeated at 1 hour (peak test) and 8 hours (trough test) after the study medication was administered. In addition, patients kept an angina diary throughout the study and wore a Holter monitor for 48 hours. Total exercise duration at baseline (+/- SEM) was 5.9 +/- 0.2 minutes for the placebo group and 6.4 +/- 0.3, 5.9 +/- 0.3, and 6.6 +/- 0.2 minutes for the ranolazine 30-, 60-, and 120-mg groups, respectively (P = NS). After 4 weeks of double-blind therapy, compared with baseline values, at 1 hour after the study medication was administered (peak effect), total exercise duration (+/- SEM) increased by 0.45 +/- 0.2 minutes in the placebo group and by 0.3 +/- 0.2, 0.6 +/- 0.2, and 0.5 +/- 0.2 minutes in the ranolazine 30-, 60-, and 120-mg groups, respectively (placebo versus ranolazine, P = NS). Times to 1-mm ST segment depression at baseline were similar in the four groups and, after 4 weeks of therapy in each group, increased significantly by similar magnitudes at 1 hour after the administration of the medications. Similar changes were seen for the time to onset of angina. Eight hours after administration (trough effect), no differences in total exercise time or any other exercise variables were observed between the placebo and the ranolazine groups. Compared with the baseline values, the number of anginal attacks per week and the number and duration of ischemic episodes per 48 hours during Holter monitoring decreased significantly by similar magnitudes in the placebo and ranolazine groups. CONCLUSIONS: Therapy with ranolazine 30, 60, and 120 mg tid was not superior to placebo. Our study does not support the published beneficial effects of similar doses of ranolazine on either myocardial ischemia or exercise performance or on anginal attacks during daily life in patients with angina pectoris.

Acetanilides↗
PubMed1993

An integrated software system for quality assurance-related kappa coefficient analysis of intraoperative transesophageal echocardiography interpretive skills.

This report describes the development of a quality assurance-oriented integrated software system designed for an anesthesiology-based intraoperative transesophageal echocardiography service. Entry data include patient and operation demographics, two-dimensional echocardiographic, saline-contrast, and color flow/pulsed Doppler assessments of the heart and great vessels, presented in a defined sequence. A statistical analysis component (kappa coefficient analysis) allows for comparison of intraoperative real-time interpretations with laboratory interpretations made by experienced full-time echocardiographers on a field-by-field basis. This provides a means of quantifying expertise in each individual aspect of the patient examination sequence. We believe that such self-appraisal data are essential for delineating the status and tracking the progress of service being provided.

Echocardiography, Transesophageal↗
PubMed1993

A clinical computer database entry form for an intraoperative anesthesiology-based transesophageal echocardiography monitoring service.

Transesophageal echocardiography (TEE) has been increasingly applied to supplement and, in instances, to supplant conventional intraoperative cardiac monitoring. Our body of experience (> 1600 intraoperative TEE procedures), combined with insights gleaned from an intramural quality assurance study, and clinical implications of certain recent advances in the field, led us to develop the following TEE computer database entry form. The form, completed intraoperatively, consists of a patient and surgical procedure demographics section, followed by fields based on the TEE examination. The scans encompass transverse plane basal short axis, long axis, and transgastric views of the heart and great vessels. The two-dimensional echocardiographic, saline-contrast, color flow and pulsed Doppler data represent both right and left ventricular performance, valvular function and specific lesions. This database entry form is intended to serve as a guide for performance of a nominally complete intraoperative study and facilitate maintenance of a TEE archive consistent with current advances.

Anesthesia Department, Hospital↗
PubMed1993

Quality assurance for intraoperative transesophageal echocardiography monitoring: a report of 846 procedures.

We evaluated our experience with 846 consecutive transesophageal echocardiography (TEE) intraoperative monitoring procedures performed between November 1989 and July 1991. TEE frequency was 36 +/- 11 per month (range 16-55) and represented 69.8% of cardiac valve surgery cases, 40.2% of coronary artery bypass graft cases, and 2.2% of total operative caseload. Major patient complications consisted of transient vocal cord paresis and ingestion of glutaraldehyde-disinfectant solution. Minor complications consisted of a chipped tooth (one case) and pharyngeal abrasions (three cases). The Quality Assurance (Q/A) Program evaluated both record keeping and quality of imaging, as judged by cardiologist echocardiographer reviewers. The percentage of completion for each Q/A indicator was as follows: medical record documentation, 88%; database form annotation, 94%; and provision of videotape recording, 91%. TEE database forms were analyzed further in terms of the percentage of fields completed. Completion scores were 73%. The following scoring system was utilized for videotape evaluation by the cardiologists: 1 = excellent; 2 = good; 3 = poor. The median grade for both two-dimensional echocardiography and color flow Doppler (CFD) examinations was 2. Poor quality images (grade 3) were present in 15.2% of two-dimensional echocardiography and 20.3% of color flow Doppler examinations, and disproportionately associated with 4/26 attendings. Supplemental audit of the cardiology reviewers performance demonstrated 569/846 videotapes showed no objective evidence of review. The cardiology reviewer forms of the remaining 277 videotapes were evaluated in terms of the percentage of fields completed. The completion score was 56%. These data suggest the need for formal Q/A for intraoperative TEE, both for anesthesiologists and reviewing cardiologists.

Echocardiography↗
PubMed1992

Transesophageal color flow Doppler imaging for aortic insufficiency in patients having cardiac operations.

Transesophageal color flow Doppler findings were studied in 30 patients with aortic insufficiency who had cardiac operations. Measurements were expressed as ratios of corresponding left ventricular outflow tract dimensions. Regurgitant jet proximal width ratio was significantly related to jet area ratio (r = 0.92) and correlated poorly with the degree of jet penetration into the left ventricular cavity (r = 0.32). The vectors of the regurgitant jets were variable. Nine patients had undergone aortography. Regurgitant jet proximal width and area ratios were significantly related to angiographic grade (r = 0.88 and 0.87, respectively) in these patients. We concluded that the esophagus offers a satisfactory transducer orientation for color flow Doppler assessment of aortic insufficiency.

Adult↗
PubMed1991

Molecular cloning, characterization and expression of cDNA for rabbit brain tissue factor.

Tissue factor (TF) is a membrane anchored glycoprotein that initiates blood coagulation by forming a complex with circulating factor VII or VIIa. TF has been identified in atherosclerotic plaques and may possibly trigger thrombosis after spontaneous plaque rupture as seen in acute myocardial infarction or angioplasty. We have previously developed an atherosclerotic rabbit model for study of the acute and chronic outcomes following angioplasty. As a first step in developing inhibitors of TF, we have isolated and characterized a rabbit cDNA coding for the mature TF. The sequence comparison of rabbit TF cDNA with those of human and mouse TFs show considerable similarity at both the nucleotide and amino acid levels. The TF cDNA when expressed in E. coli demonstrates a procoagulant activity comparable to that of native rabbit brain TF. The TF activity can be blocked by a polyclonal antibody against rabbit TF.

Animals↗
PubMed1985

Intracardiac thrombi and systemic thromboembolism: detection, incidence, and treatment.

The detection of thrombus in the left atrium is discussed in this chapter, along with the problem of arterial thromboembolism in patients with valvular heart disease and prosthetic heart valves. The detection and occurrence of thrombus within the left ventricle are considered, as is the frequency of thromboembolism in acute myocardial infarction, left ventricular aneurysm, and cardiomyopathy. Treatment recommendations are given for each of these medical problems.

Anticoagulants↗
PubMedDate not supplied

Extended storage of platelets in a new plastic container. II. In vivo response to infusion of platelets stored for 5 days.

A new blood container material (PL 1240 plastic) made of polyvinyl chloride containing a tri(2-ethylhexyl) trimellitate plasticizer was evaluated in three laboratories. When platelet concentrates (50-60 ml) were stored on a variety of agitators for 7 days at 22 +/- 2 degrees C, poststorage pH (mean +/- SD) ranged from 7.29 +/- 0.05 (6 rpm elliptical rotator) to 6.87 +/- 0.8 (70 cycles per minute flatbed agitator). The platelet counts ranged from 1.51 +/- 0.12 to 0.95 +/- 0.36 X 10(6) per microliter. Morphology scores and hypotonic shock response values of platelets stored 7 days in PL 1240 plastic containers were better than those noted following 3-day storage of control platelets in PL 146 plastic containers. The percent discharge of lactic dehydrogenase from platelets stored 7 days in PL 1240 plastic containers for 3 days (p less than 0.05). Mean platelet recoveries of 44 +/- 15 percent (n = 11; 111Indium) and 39 +/- 8 percent (n = 29; 51Chromium) were seen when autologous platelets were infused following 5-day storage in PL 1240 plastic bags. Platelet half-lives of 3.6 +/- 0.4 (n = 9) 4.1 +/- 0.4 (n = 20) days were reported in the two laboratories which used 51Cr labeling, while survival values of 7.0 +/- 1.0, 2.8 +/- 0.8, and 5.4 +/- 1.9 days were seen when data from the 111Indium studies (n = 11) were analyzed using linear, exponential, and multiple hit programs, respectively. Platelets stored for 5 days also were administered to 13 thrombocytopenic oncology patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗