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Biomedical subjects

Jonathan Leor

Publications and source records attributed to Jonathan Leor.

At least 19 recordsLinked to original sources
PubMed2007

Trends in management, hospital and long-term outcomes of elderly patients with acute myocardial infarction.

PURPOSE: The number of elderly patients with acute myocardial infarction (AMI) is growing rapidly, and their early and postdischarge mortality is high. Several studies have reported a decline in mortality after myocardial infarction; however, the magnitude of the decline among the elderly has not been fully investigated. METHODS: We assessed trends in management, in-hospital, and long-term outcomes of 1475 elderly patients (aged > or =75 years, 42% women) hospitalized with AMI in all 25 operating coronary care units in Israel between 1992 and 2002, from our prospective nationwide biennial surveys. RESULTS: Between 1992 and 2002, a significant increase was observed in the use of acute reperfusion therapy (27%-48%), coronary angiography (6%-47%), percutaneous coronary intervention (3%-33%), coronary bypass (2%-8%), aspirin (53%-88%), beta-blockers (18%-65%), angiotensin-converting enzyme inhibitors (26%-63%), and lipid-lowering drugs (0%-43%). These changes were associated with a 42% reduction in 30-day mortality (27.6%-16.1%; adjusted odds ratio 0.57; 95% confidence interval [CI], 0.36-0.93). One-year cumulative mortality declined by 20% (37%-29%; adjusted odds ratio 0.74; 95% CI, 0.49-1.13). CONCLUSIONS: The management of elderly patients with AMI changed substantially during the last decade. This change was associated with a significant reduction in early mortality, whereas cumulative 1-year mortality improved only slightly. Better adherence to in-hospital management guidelines and better implementation of postdischarge health policy may further decrease mortality and morbidity in the elderly after AMI.

Aged↗
PubMed2006

Coronary intervention for persistent occlusion after myocardial infarction.

BACKGROUND: It is unclear whether stable, high-risk patients with persistent total occlusion of the infarct-related coronary artery identified after the currently accepted period for myocardial salvage has passed should undergo percutaneous coronary intervention (PCI) in addition to receiving optimal medical therapy to reduce the risk of subsequent events. METHODS: We conducted a randomized study involving 2166 stable patients who had total occlusion of the infarct-related artery 3 to 28 days after myocardial infarction and who met a high-risk criterion (an ejection fraction of <50% or proximal occlusion). Of these patients, 1082 were assigned to routine PCI and stenting with optimal medical therapy, and 1084 were assigned to optimal medical therapy alone. The primary end point was a composite of death, myocardial reinfarction, or New York Heart Association (NYHA) class IV heart failure. RESULTS: The 4-year cumulative primary event rate was 17.2% in the PCI group and 15.6% in the medical therapy group (hazard ratio for death, reinfarction, or heart failure in the PCI group as compared with the medical therapy group, 1.16; 95% confidence interval [CI], 0.92 to 1.45; P=0.20). Rates of myocardial reinfarction (fatal and nonfatal) were 7.0% and 5.3% in the two groups, respectively (hazard ratio, 1.36; 95% CI, 0.92 to 2.00; P=0.13). Rates of nonfatal reinfarction were 6.9% and 5.0%, respectively (hazard ratio, 1.44; 95% CI, 0.96 to 2.16; P=0.08); only six reinfarctions (0.6%) were related to assigned PCI procedures. Rates of NYHA class IV heart failure (4.4% vs. 4.5%) and death (9.1% vs. 9.4%) were similar. There was no interaction between treatment effect and any subgroup variable (age, sex, race or ethnic group, infarct-related artery, ejection fraction, diabetes, Killip class, and the time from myocardial infarction to randomization). CONCLUSIONS: PCI did not reduce the occurrence of death, reinfarction, or heart failure, and there was a trend toward excess reinfarction during 4 years of follow-up in stable patients with occlusion of the infarct-related artery 3 to 28 days after myocardial infarction. (ClinicalTrials.gov number, NCT00004562 [ClinicalTrials.gov].).

Aged↗
PubMed2006

Underuse of standard care and outcome of patients with acute myocardial infarction and chronic renal insufficiency.

OBJECTIVES: To investigate characteristics, management and outcome of patients with acute myocardial infarction (AMI) and chronic renal insufficiency (CRI). BACKGROUND: Patients with AMI and CRI are considered to be at high risk of complications and death. Physicians may be reluctant to prescribe life-saving medications to patients with concomitant CRI. METHODS: We compared clinical characteristics, management and outcome of 1,683 consecutive AMI patients in three categories of renal function: (1) normal renal function (<1.5 mg/dl) (n = 1,559), (2) mild to moderate CRI (1.5-3.5 mg/dl) (n = 77), and (3) severe CRI (>3.5 mg/dl) (n = 47). RESULTS: CRI patients were older and were more likely to have other co-morbidities such as hypertension, diabetes mellitus, prior AMI, stroke, angina and heart failure. Compared with patients with normal renal function, standard therapy for AMI including thrombolysis, aspirin, angiotensin-converting-enzyme inhibitors, beta-blockers and lipid lowering agents was underutilized in CRI patients and these patients were more likely to have in-hospital complications such as heart failure, atrial or ventricular fibrillation, cardiogenic shock, sepsis, worsening of renal function and death within 30 days [odds ratio (OR) = 3.3; 95% confidence interval (CI) = 2.0-4.8]. After adjustment for age and co-morbidities, the association between mild to moderate CRI and 30-days mortality declined, whereas severe CRI remained an independent determinant of mortality (OR = 4.8; 95% CI = 2.0-11.4). Adjustment for aspirin, angiotensin-converting-enzyme inhibitors and beta-blocker therapy weakened the association between CRI and death within 30 days after AMI. CONCLUSIONS: CRI patients are more likely to experience serious complications and death early after AMI. Underutilization of standard care, particularly beta-blocker therapy, contributes to increased mortality risk in these patients.

Adrenergic beta-Antagonists↗
PubMed2006

Ex vivo activated human macrophages improve healing, remodeling, and function of the infarcted heart.

BACKGROUND: Activated macrophages have a significant role in wound healing and damaged tissue repair. We sought to explore the ability of ex vivo activated macrophages to promote healing and repair of the infarcted myocardium. METHODS AND RESULTS: Human activated macrophage suspension (AMS) was prepared from a whole blood unit obtained from young donors in a closed sterile system and was activated by a novel method of hypo-osmotic shock. The AMS (approximately 4 x 10(5) cells) included up to 43% CD14-positive cells and was injected into the ischemic myocardium of rats (n=8) immediately after coronary artery ligation. The control group (n=9) was treated with saline injection. The human cells existed in the infarcted heart 4 to 7 days after injection, as indicated by histology, human growth hormone-specific polymerase chain reaction, and magnetic resonance imaging (MRI) tracking of iron oxide-nanoparticle-labeled cells. After 5 weeks, scar vessel density (+/-SE) (25+/-4 versus 10+/-1 per mm2; P<0.05), myofibroblast accumulation, and recruitment of resident monocytes and macrophages were greater in AMS-treated hearts compared with controls. Serial echocardiography studies, before and 5 weeks after injection, showed that AMS improved scar thickening (0.15+/-0.01 versus 0.11+/-0.01 cm; P<0.05), reduced left ventricular (LV) diastolic dilatation (0.87+/-0.02 versus 0.99+/-0.04 cm; P<0.05), and improved LV fractional shortening (31+/-2 versus 20+/-4%; P<0.05), compared with controls. CONCLUSIONS: Early after myocardial infarction, injection of AMS accelerates vascularization, tissue repair, and improves cardiac remodeling and function. Our work suggests a novel clinically relevant option to promote the repair of ischemic tissue.

Adolescent↗
PubMed2006

Influence of the new definition of acute myocardial infarction on coronary care unit admission, discharge diagnosis, management and outcome in patients with non-ST elevation acute coronary syndromes: a national survey.

BACKGROUND: Major changes occurred recently in the definition and recommended management of non-ST segment elevation acute coronary syndromes (NSTE ACS). The impact of these changes on the coronary care unit (CCU) is incompletely characterized. METHODS: ACSIS is a national survey gathering data every other year among all ACS patients in all CCUs in Israel. We compared case load, baseline variables, management, outcome and distribution of diagnoses among NSTE ACS patients admitted before (during 2000 [N = 729]) and after (during 2002 [N = 970]) the widespread introduction of troponin and the new AMI definition. RESULTS: The number of NSTE ACS patients in 2002 increased by 33% compared to 2000, with no change in the number of beds, while the number of ST elevation ACS patients remained unchanged. The rate of AMI rose by 16% and hospital stay decreased by 1 day (p = 0.005). The availability of troponin values increased from 20% in 2000 to 60% in 2002; The proportion of patients given the diagnosis of NSTE AMI rose significantly more in centers with high utilization of troponin (p = 0.023). During 2002 significant increases occurred in the utilization of guideline-recommended medications, as in the use of coronary angiography and intervention. Mortality at 30 days decreased by 35%. CONCLUSIONS: This is the first large registry of ACS to describe the significant actual changes which occurred in the CCU following the introduction of troponin and the new AMI definition. We observed a substantial increase in the burden of NSTE ACS coupled with a shortened length of stay. These changes may impact significantly upon patient care and resource utilization.

Aged↗
PubMed2006

Evaluation of the pro-angiogenic effect of factor XIII in heterotopic mouse heart allografts and FXIII-deficient mice.

Thrombin-activated Factor XIII (FXIIIa), a plasma transglutaminase, stabilizes fibrin clots by crosslinking fibrin chains. FXIIIa was previously shown by us to exhibit proangiogenic activity associated with downregulation of thrombospondin-1, phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR-2), and upregulation of c-Jun. In the current study, we evaluated the proangiogenic effect of FXIIIa in two murine models: a neonatal heterotopic cardiac allograft model in normal mice, and a Matrigel plug model in FXIII-deficient mice. In the neonatal cardiac allograft model, the number of new vessels as well as graft viability (contractile performance) was significantly higher in FXIIIa-injected animals than in controls. A significant increase in the level of c-Jun mRNA and a significant decrease in the level of TSP-1 mRNA were observed in heart allografts treated with FXIIIa. A marked decrease in TSP-1 protein expression was observed within the endothelial cells of hearts treated with FXIIIa. In the Matrigel plug model, FXIII-deficient mice showed a significantly decreased number of new vessels compared to that of the control mice, and the number of vessels almost reached normal levels following addition of FXIIIa. The results of this study provide substantial in vivo evidence for the proangiogenic activity of FXIIIa.

Angiogenesis Inducing Agents↗
PubMed2006

Renovation of the injured heart with myocardial tissue engineering.

Tissue engineering aims to create, repair and/or replace tissues and organs by using cells, scaffolds, biologically active molecules and physiologic signals. It is an interdisciplinary field that integrates aspects of engineering, chemistry, biology and medicine. One of the most challenging goals in the field of cardiovascular tissue engineering is the creation of a heart muscle patch. This review describes the principles, achievements and challenges of achieving this ambitious goal of creating contractile heart muscle. In addition, the new strategy of in situ and injectable tissue engineering for myocardial repair and regeneration is presented.

Animals↗
PubMed2006

Myocardial regeneration by adult stem cells.

Ventricular remodeling and heart failure are the inevitable consequences of myocardial infarction. Current options to cure myocardial infarction and subsequent heart failure suffer from specific limitations. Thus, alternative, additional long-term therapeutic strategies are needed to cure this costly and deadly disease. Cardiac regeneration is a promising new therapeutic option. Through cellular and molecular therapies, the concept of in situ "growing" heart muscle, vascular tissue and manipulating the extracellular matrix environment promises to revolutionize the approach of treating heart disease. Recent studies have suggested that stem cells resident within the bone marrow or peripheral blood can be recruited to the injured heart. The regeneration of damaged heart tissue may include the mobilization of progenitor or stem cells to the damaged area or stimulation of a regenerative program within the organ. There is now evidence accumulating that the heart contains resident stem cells that can be induced to develop into cardiac muscle and vascular tissue. The present review aims to describe the potential, the current status and the future challenges of myocardial regeneration by adult stem cells.

Guided Tissue Regeneration↗
PubMed2005

Human umbilical cord blood-derived CD133+ cells enhance function and repair of the infarcted myocardium.

The use of adult stem cells for myocardial tissue repair might be limited in elderly and sick people because their cells are depleted and exhausted. The present study was conducted to explore the potential of human umbilical cord blood (UCB) CD133+ progenitor cells for myocardial tissue repair in a model of extensive myocardial infarction (MI). CD133+ progenitor cells were isolated from newborn UCB. Cells (1.2-2 x 10(6)) or saline (control) was infused intravenously 7 days after permanent coronary artery ligation in athymic nude rats. Left ventricular (LV) function was assessed before and 1 month after infusion by echocardiography. Tracking of human cells was performed by fluorescent in situ hybridization for human X and Y chromosomes or by immunostaining for HLA-DR or HLA-ABC. One month after delivery, LV fractional shortening improved by 42 +/- 17% in cell-treated hearts and decreased by 39 +/- 10% in controls (p = .001). Anterior wall thickness decreased significantly in controls but not in treated hearts. Microscopic examination revealed that the UCB cells were able to migrate, colonize, and survive in the infarcted myocardium. Human cells were identified near vessel walls and LV cavity and were occasionally incorporated into endothelial cells in six of nine cell-treated animals but not in controls. Scar tissue from cell-treated animals was significantly populated with autologous myofibroblasts as indicated by colocalization of HLA-DR and alpha-smooth muscle actin staining. In conclusion, the present work suggests that, after MI, intravenous delivery of human UCB-derived CD133+ cells can produce functional recovery by preventing scar thinning and LV systolic dilatation.

AC133 Antigen↗
PubMed2005

Effect of bezafibrate on incidence of type 2 diabetes mellitus in obese patients.

AIMS: To assess the effect of fibric acid derivative bezafibrate on incidence of type 2 diabetes in obese patients over a median 6.3 years follow-up period. METHODS AND RESULTS: The study sample comprised 339 non-diabetic obese patients (body mass index > or = 30.0 kg/m2) aged 42-74. Patients received either bezafibrate retard 400 mg (178 patients) or placebo (161 patients) once daily. Development of new diabetes was recorded in 98 patients: in 56 (37.0%) from the placebo group vs. 42 (27.1%) from the bezafibrate group, (P log-rank=0.01). The median time (interquartile range) until onset of new diabetes was significantly delayed in patients on bezafibrate when compared with those on placebo: 4.0 (2.1-5.0) vs. 2.0 (0.5-3.5) years, P=0.002. Multivariable analysis identified bezafibrate treatment as an independent predictor of reduced risk of new diabetes with hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.39-0.91]. Other significant variables associated with future overt type 2 diabetes in obese patients were triglycerides (50 mg/dL increment) with HR 1.15 (95% CI 1.02-1.28) and fasting glucose (10 mg/dL increment) with HR 2.27 (95% CI 1.83-2.81). CONCLUSION: Bezafibrate, when compared with placebo, reduced the incidence and delayed the onset of type 2 diabetes in obese patients over a long-term follow-up period.

Adult↗
PubMed2005

Recommendations for the structure, organization, and operation of intensive cardiac care units.

Two major changes in patient characteristics and management occurred recently that demand distinctive alterations in the function of the intensive cardiac care unit (ICCU). These changes include the introduction of an early invasive strategy for the treatment of acute coronary syndromes, enabling early recuperation and shorter need for intensive care on the one hand, while the number of older and sicker patients requiring prolonged and more complex intensive care is steadily increasing. A task force of the European Society of Cardiology Working Group on Acute Cardiac Care was set to give a modern updated comprehensive recommendations concerning the structure, organization, and function of the modern ICCUs and intermediate cardiac units. These include the statement that specially trained cardiologists and cardiac nurses who can manage patients with acute cardiac conditions should staff the ICCUs. The optimum number of physicians, nurses, and other personal working in the unit is included. The document indicates the desired architecture and structure of the units and the intermediate cardiac unit and their relations to the other facilities in the hospital. Specific recommendations are also included for the minimal number of beds, monitoring system, respirators, pacemaker/defibrillators, and necessary additional equipment. The desired function is discussed, namely, the patients to be admitted, the length of stay, and the relocation policy. A uniformed electronic chart for ICCUs is advised, anticipating a common European database.

Coronary Care Units↗
PubMed2005

Effect of matrix metalloproteinase inhibition by doxycycline on myocardial healing and remodeling after myocardial infarction.

The aim of conducting this study was to assess the clinical relevance of matrix metalloproteinase (MMP) inhibition by doxycycline, an effective MMP inhibitor, in a rat model of extensive myocardial infarction (MI) and left ventricular (LV) dysfunction. Rats (n = 22) were subjected to extensive anterior MI. Doxycycline (25 mg SC, daily) or saline (control) injections were started for nine days thereafter. The effect of doxycycline on MMP activity in the infarcted and remote myocardium was measured by zymography, in another subgroup (n = 8), nine days after MI. Echocardiography and magnetic resonance imaging (MRI) studies were performed at one and thirty days after MI to assess LV remodeling and function. After 4 weeks, hearts were fixed, and subjected to morphometric and histological analysis. Compared with control, doxycycline treatment attenuated MMP-9 and -2 activity in both infarcted and remote myocardium. Serial echocardiography studies showed that doxycycline failed to attenuate scar thinning, LV dilatation and dysfunction. MRI study showed that doxycycline impaired LV compensatory hypertrophy. Furthermore, compared with control, doxycycline reduced vessel density (/mm(2) +/- SEM) in the infarcted myocardium (84 +/- 16 vs. 46 +/- 9/mm(2), respectively; p < 0.05). Our work suggest that effective MMPs' inhibition in the infarcted and remote myocardium by doxycycline does not prevent LV remodeling and dysfunction but impairs angiogenesis and compensatory LV hypertrophy. Our findings caution against aggressive, non-selective inhibition of MMPs in the early healing phase after MI.

Animals↗
PubMed2005

Cancer cells ablation with irreversible electroporation.

In this study we perform in vitro irreversible electroporation (IRE) experiments with human hepatocarcinoma cells (HepG2) to investigate IRE as a new technique for undesirable tissue ablation. Irreversible electroporation (IRE) is the irreversible permeabilization of the cell membrane through the application of microsecond through millisecond electrical pulses. Until now IRE was studied only as an undesirable condition during the use of reversible electroporation in gene therapy and electrochemotherapy. There was a possibility that the IRE ablation domain is mostly superimposed on the electrical pulses induced Joule heating thermal ablation domain. This study demonstrates that there is a real and substantial domain of electrical parameters for IRE ablation of cancer that is distinct from the thermal domain and which results in complete cancer cell ablation. Experiments show that the application of 1500 V/cm in three sets of ten pulses of 300 microseconds each can produce complete cancer cell ablation. We also find that the use of multiple pulses appears to be more effective for cancer cell ablation than the application of the same energy in one single pulse.

Carcinoma, Hepatocellular↗
PubMed2005

Protocols for myocardial infarction repair using fetal cardiac myocytes.

We review an experimental protocol for investigating concepts and methods for myocardial repair using fetal cardiomyocyte transplantation. We describe methods of cell isolation, culture, labeling, and assessment of the influence of the engrafted cells on left ventricular remodeling and function.

Animals↗
PubMed2004

Cells, scaffolds, and molecules for myocardial tissue engineering.

Unlike heart valves or blood vessels, heart muscle has no replacement alternatives. The most challenging goal in the field of cardiovascular tissue engineering is the creation/ regeneration of an engineered heart muscle. Recent advances in methods of stem cell isolation, culture in bioreactors, and the synthesis of bioactive materials promise to create engineered cardiac tissue ex vivo. At the same time, new approaches are conceived that explore ways to induce tissue regeneration after injury. The purpose of our review is to describe the principles, status, and challenges of myocardial tissue engineering with emphasize on the concept of in situ cardiac tissue engineering and regeneration.

Biocompatible Materials↗
PubMed2004

Peroxisome proliferator-activated receptor ligand bezafibrate for prevention of type 2 diabetes mellitus in patients with coronary artery disease.

BACKGROUND: Recent studies have shown that type 2 diabetes is preventable by both lifestyle interventions and medications that influence primary glucose metabolism. Whether pharmacological interventions that influence primary lipid metabolism can also delay development of type 2 diabetes is unknown. The goal of this study was to evaluate the effect of the peroxisome proliferator-activated receptor ligand bezafibrate on the progression of impaired fasting glucose phase to type 2 diabetes in patients with coronary artery disease over a 6.2-year follow-up period. METHODS AND RESULTS: The study sample comprised 303 nondiabetic patients 42 to 74 years of age with a fasting blood glucose level of 110 to 125 mg/dL (6.1 to 6.9 mmol/L). The patients received either 400 mg bezafibrate retard (156 patients) or placebo (147 patients) once a day. No patients were using statins, and use of ACE inhibitors, which also reduce diabetes incidence, was relatively low. During follow-up, development of new-onset diabetes was recorded in 146 patients: in 80 (54.4%) from the placebo group and 66 (42.3%) from the bezafibrate group (P=0.04). The mean time until onset of new diabetes was significantly delayed in patients on bezafibrate compared with patients on placebo: 4.6+/-2.3 versus 3.8+/-2.6 years (P=0.004). Multivariate analysis identified bezafibrate treatment as an independent predictor of reduced risk of new diabetes development (hazard ratio, 0.70; 95% CI, 0.49 to 0.99). Other significant variables associated with future overt type 2 diabetes in patients with impaired fasting glucose were total cholesterol level (hazard ratio, 1.22; 95% CI 1.0 to 1.51) and body mass index (hazard ratio, 1.10; 95% CI, 1.05 to 1.16). CONCLUSIONS: Bezafibrate reduces the incidence and delays the onset of type 2 diabetes in patients with impaired fasting glucose. Whether the combination of bezafibrate with other recommended drugs for secondary prevention (statins and ACE inhibitors) would be as efficacious as suggested by our results remains to be determined.

Aged↗
PubMed2004

Prolonged 24-hour subzero preservation of heterotopically transplanted rat hearts using antifreeze proteins derived from arctic fish.

BACKGROUND: Arctic fish survive subzero temperatures by producing a family of antifreeze proteins (AFPs) that noncolligatively lower the freezing temperature of their body fluids. We report 24-hour storage of mammalian hearts for transplantation at subzero temperatures using AFPs derived from arctic fish. METHODS: Forty-two heterotopic transplantations were performed in isoimmune Sprague-Dawley rats. Harvested hearts were retrogradely infused with cold 4 degrees C University of Wisconsin (UW) solution and were preserved in a specialized cooling bath at two target temperatures, 4 degrees C and -1.3 degrees C for 12,18, and 24 hours (6 experiments/group). Preservation solutions were UW alone for the 4 degrees C group, and UW with 15 mg/mL AFP III for the -1.3 degrees C group. After hypothermic storage the hearts were heterotopically transplanted into isoimmune rats. Viability was assessed and graded on a scale of 0 to 6 (0 = no contractions to 6 = excellent contractions). Transplanted hearts were then fixed in vivo and were subject to electron microscopy and histopathologic examination. RESULTS: None of the hearts preserved at -1.3 degrees C in UW/AFP III solution froze. All control hearts preserved at -1.3 degrees C without AFP protection froze and died at reperfusion. Viability of hearts preserved at -1.3 degrees C in UW/AFP III solution was significantly better after 18 hours of preservation, 30 and 60 minutes after reperfusion (median, 5 versus 3 and 6 versus 3, respectively; p < 0.05) and after 24 hours of preservation 30 and 60 minutes after reperfusion (median, 4.5 versus 1.5 and 5 versus 2, respectively; p < 0.05). Histologic and electron microscopy studies demonstrated better myocyte structure and mitochondrial integrity preservation with UW/AFP III solution. CONCLUSIONS: Antifreeze proteins prevent freezing in subzero cryopreservation of mammalian hearts for transplantation. Subzero preservation prolongs ischemic times and improves posttransplant viability.

Adenosine↗