Life Sciences Commons^™

Integrin (Alpha 6 Beta 4) Regulation Of Eif-4e Activity And Vegf Translation: A Survival Mechanism For Carcinoma Cells, Jun Chung, Robin E. Bachelder, Elizabeth A. Lipscomb, Leslie M. Shaw, Arthur M. Mercurio

Arthur M. Mercurio

We define a novel mechanism by which integrins regulate growth factor expression and the survival of carcinoma cells. Specifically, we demonstrate that the alpha 6 beta 4 integrin enhances vascular endothelial growth factor (VEGF) translation in breast carcinoma cells. The mechanism involves the ability of this integrin to stimulate the phosphorylation and inactivation of 4E-binding protein (4E-BP1), a translational repressor that inhibits the function of eukaryotic translation initiation factor 4E (eIF-4E). The regulation of 4E-BP1 phosphorylation by alpha 6 beta 4 derives from the ability of this integrin to activate the PI-3K-Akt pathway and, consequently, the rapamycin-sensitive kinase mTOR that …

The Integrin Alpha6beta4 Functions In Carcinoma Cell Migration On Laminin-1 By Mediating The Formation And Stabilization Of Actin-Containing Motility Structures, Isaac Rabinovitz, Arthur M. Mercurio

Arthur M. Mercurio

Functional studies on the alpha6beta4 integrin have focused primarily on its role in the organization of hemidesmosomes, stable adhesive structures that associate with the intermediate filament cytoskeleton. In this study, we examined the function of the alpha6beta4 integrin in clone A cells, a colon carcinoma cell line that expresses alpha6beta4 but no alpha6beta1 integrin and exhibits dynamic adhesion and motility on laminin-1. Time-lapse videomicroscopy of clone A cells on laminin-1 revealed that their migration is characterized by filopodial extension and stabilization followed by lamellae that extend in the direction of stabilized filopodia. A function-blocking mAb specific for the alpha6beta4 integrin …

Integrin Alpha 6 Beta 4 Mediates Dynamic Interactions With Laminin, Aydin Tozeren, Hynda K. Kleinman, Stephen Wu, Arthur M. Mercurio, Stephen W. Byers

Arthur M. Mercurio

We present here a novel form of dynamic adhesion in which both the integrin receptor and the ligand supporting dynamic adhesion have been identified. Laminar flow assays showed that laminin supported attachment of alpha 6 beta 4-positive cells in the presence of fluid shear stress (tau < or = 2 dyn/cm2), indicating that these cells adhered to laminin within a fraction of a second. Further increases in flow rate (3.5 dyn/cm2 < or = tau < or = 100 dyn/cm2) initiated rolling of attached cells in the direction of flow, suggesting that rapidly formed adhesion is reversible and repeatable. Laminin fragment E8, which …

Role Of E-Cadherin In The Response Of Tumor Cell Aggregates To Lymphatic, Venous And Arterial Flow: Measurement Of Cell-Cell Adhesion Strength, Stephen W. Byers, Connie L. Sommers, Becky Hoxter, Arthur M. Mercurio, Aydin Tozeren

Arthur M. Mercurio

Defects in the expression or function of the calcium dependent cell-cell adhesion molecule E-cadherin are common in invasive, metastatic carcinomas. In the present study the response of aggregates of breast epithelial cells and breast and colon carcinoma cells to forces imposed by laminar flow in a parallel plate flow channel was examined. Although E-cadherin negative tumor cells formed cell aggregates in the presence of calcium, these were significantly more likely than E-cadherin positive cell aggregates to disaggregate in response to low shear forces, such as those found in a lymphatic vessel or venule (< 3.5 dyn/cm2). E-cadherin positive normal breast epithelial cells and E-cadherin positive breast tumor cell aggregates could not be disaggregated when exposed to shear forces in excess of those found in arteries (> 100 dyn/cm2). E-cadherin negative cancer cells …

Human Colon Carcinoma Cells Use Multiple Receptors To Adhere To Laminin: Involvement Of Alpha 6 Beta 4 And Alpha 2 Beta 1 Integrins, Margaret M. Lotz, Cynthia A. Korzelius, Arthur M. Mercurio

Arthur M. Mercurio

In this study, we used clone A, a human colon carcinoma cell line, to characterize those integrins that mediate colon carcinoma adhesion to laminin. Monoclonal antibodies specific for the human beta 1 subunit inhibited clone A adhesion to laminin. They also precipitated a complex of surface proteins that exhibited an electrophoretic behavior characteristic of alpha 2 beta 1 and alpha 3 beta 1. A monoclonal antibody specific for alpha 2 (PIH5) blocked clone A adhesion to laminin, as well as to collagen I. An alpha 3-specific antibody (P1B5) had no effect on clone A adhesion to laminin, even though it …

Adam12 Induces Actin Cytoskeleton And Extracellular Matrix Reorganization During Early Adipocyte Differentiation By Regulating Beta1 Integrin Function, Nobuko Kawaguchi, Christina Sundberg, Marie Kveiborg, Behzad Moghadaszadeh, Meena Asmar, Nikolaj Dietrich, Charles Kumar Thodeti, Finn C. Nielsen, Peter Moller, Arthur M. Mercurio, Reidar Albrechtsen, Ulla M. Wewer

Arthur M. Mercurio

Changes in cell shape are a morphological hallmark of differentiation. In this study we report that the expression of ADAM12, a disintegrin and metalloprotease, dramatically affects cell morphology in preadipocytes, changing them from a flattened, fibroblastic appearance to a more rounded shape. We showed that the highest levels of ADAM12 mRNA were detected in preadipocytes at the critical stage when preadipocytes become permissive for adipogenic differentiation. Furthermore, as assessed by immunostaining, ADAM12 was transiently expressed at the cell surface concomitant with the reduced activity of beta1 integrin. Co-immunoprecipitation studies indicated the formation of ADAM12/beta1 integrin complexes in these preadipocytes. Overexpression …

Endothelial Cells Assemble Two Distinct Alpha6beta4-Containing Vimentin-Associated Structures: Roles For Ligand Binding And The Beta4 Cytoplasmic Tail, Suzanne M. Homan, Arthur M. Mercurio, Susan E. Laflamme

Arthur M. Mercurio

The alpha6beta4 laminin binding integrin functions in the assembly of type I hemidesmosomes, which are specialized cell-matrix adhesion sites found in stratified epithelial cells. Although endothelial cells do not express all the components of type I hemidesmosomes, endothelial cells can express the alpha6beta4 integrin. Because endothelial cells lose expression of alpha6beta4 in culture, we expressed recombinant alpha6beta4 in the dermal microvascular endothelial cell line, HMEC-1, to test whether endothelial cells can assemble adhesion structures containing alpha6beta4. Using immunofluorescence microscopy, we found that recombinant alpha6beta4 concentrates specifically in a novel fibrillar structure on the basal surface of endothelial cells in the …

Regulation Of Alpha 6 Beta 1 Integrin Laminin Receptor Function By The Cytoplasmic Domain Of The Alpha 6 Subunit, Leslie M. Shaw, Arthur M. Mercurio

Arthur M. Mercurio

The alpha 6 beta 1 integrin is expressed on the macrophage surface in an inactive state and requires cellular activation with PMA or cytokines to function as a laminin receptor (Shaw, L. M., J. M. Messier, and A. M. Mercurio. 1990. J. Cell Biol. 110:2167-2174). In the present study, the role of the alpha 6 subunit cytoplasmic domain in alpha 6 beta 1 integrin activation was examined. The use of P388D1 cells, an alpha 6-integrin deficient macrophage cell line, facilitated this analysis because expression of either the alpha 6A or alpha 6B subunit cDNAs restores their activation responsive laminin adhesion …

Transcriptional Activation Of Integrin Beta6 During The Epithelial-Mesenchymal Transition Defines A Novel Prognostic Indicator Of Aggressive Colon Carcinoma, Richard C. Bates, David I. Bellovin, Courtney Brown, Elizabeth Maynard, Bingyan Wu, Hisaaki Kawakatsu, Dean Sheppard, Peter Oettgen, Arthur M. Mercurio

Arthur M. Mercurio

We used a spheroid model of colon carcinoma to analyze integrin dynamics as a function of the epithelial-mesenchymal transition (EMT), a process that provides a paradigm for understanding how carcinoma cells acquire a more aggressive phenotype. This EMT involves transcriptional activation of the beta6 integrin subunit and a consequent induction of alphavbeta6 expression. This integrin enhances the tumorigenic properties of colon carcinoma, including activation of autocrine TGF-beta and migration on interstitial fibronectin. Importantly, this study validates the clinical relevance of the EMT. Kaplan-Meier analysis of beta6 expression in 488 colorectal carcinomas revealed a striking reduction in median survival time of …

P53 Inhibits Alpha 6 Beta 4 Integrin Survival Signaling By Promoting The Caspase 3-Dependent Cleavage Of Akt/Pkb, Robin E. Bachelder, Mark J. Ribick, Alessandra Marchetti, Rita Falcioni, Silvia Soddu, Kathryn R. Davis, Arthur M. Mercurio

Arthur M. Mercurio

Although the interaction of matrix proteins with integrins is known to initiate signaling pathways that are essential for cell survival, a role for tumor suppressors in the regulation of these pathways has not been established. We demonstrate here that p53 can inhibit the survival function of integrins by inducing the caspase-dependent cleavage and inactivation of the serine/threonine kinase AKT/PKB. Specifically, we show that the alpha6beta4 integrin promotes the survival of p53-deficient carcinoma cells by activating AKT/PKB. In contrast, this integrin does not activate AKT/PKB in carcinoma cells that express wild-type p53 and it actually stimulates their apoptosis, in agreement with …

The Integrin Alpha 6 Beta 4 Is A Laminin Receptor, Edward C. Lee, Margaret M. Lotz, Glenn D. Steele Jr., Arthur M. Mercurio

Arthur M. Mercurio

In this study, the putative laminin receptor function of the alpha 6 beta 4 integrin was assessed. For this purpose, we used a human cell line, referred to as clone A, that was derived from a highly invasive, colon adenocarcinoma. This cell line, which expresses the alpha 6 beta 4 integrin, adheres to the E8 and not to the P1 fragment of laminin. The adhesion of clone A cells to laminin is extremely rapid with half-maximal adhesion observed at 5 min after plating. Adhesion to laminin is blocked by GoH3, and alpha 6 specific antibody (60% inhibition), as well as …

Glycogen Synthase Kinase-3 Is An Endogenous Inhibitor Of Snail Transcription: Implications For The Epithelial-Mesenchymal Transition, Robin E. Bachelder, Sang-Oh Yoon, Clara Franci, Antonio Garcia De Herreros, Arthur M. Mercurio

Arthur M. Mercurio

We report that the activity of glycogen synthase kinase-3 (GSK-3) is necessary for the maintenance of the epithelial architecture. Pharmacological inhibition of its activity or reducing its expression using small interfering RNAs in normal breast and skin epithelial cells results in a reduction of E-cadherin expression and a more mesenchymal morphology, both of which are features associated with an epithelial-mesenchymal transition (EMT). Importantly, GSK-3 inhibition also stimulates the transcription of Snail, a repressor of E-cadherin and an inducer of the EMT. We identify NFkappaB as a transcription factor inhibited by GSK-3 in epithelial cells that is relevant for Snail expression. …

Release Of Camp Gating By The Alpha6beta4 Integrin Stimulates Lamellae Formation And The Chemotactic Migration Of Invasive Carcinoma Cells, Kathleen L. O'Connor, Leslie M. Shaw, Arthur M. Mercurio

Arthur M. Mercurio

The alpha6beta4 integrin promotes carcinoma in-vasion by its activation of a phosphoinositide 3-OH (PI3-K) signaling pathway (Shaw, L.M., I. Rabinovitz, H.H.-F. Wang, A. Toker, and A.M. Mercurio. Cell. 91: 949-960). We demonstrate here using MDA-MB-435 breast carcinoma cells that alpha6beta4 stimulates chemotactic migration, a key component of invasion, but that it has no influence on haptotaxis. Stimulation of chemotaxis by alpha6beta4 expression was observed in response to either lysophosphatidic acid (LPA) or fibroblast conditioned medium. Moreover, the LPA-dependent formation of lamellae in these cells is dependent upon alpha6beta4 expression. Both lamellae formation and chemotactic migration are inhibited or "gated" by …

Protein Kinase C-Dependent Mobilization Of The Alpha6beta4 Integrin From Hemidesmosomes And Its Association With Actin-Rich Cell Protrusions Drive The Chemotactic Migration Of Carcinoma Cells, Isaac Rabinovitz, Alex Toker, Arthur M. Mercurio

Arthur M. Mercurio

We explored the hypothesis that the chemotactic migration of carcinoma cells that assemble hemidesmosomes involves the activation of a signaling pathway that releases the alpha6beta4 integrin from these stable adhesion complexes and promotes its association with F-actin in cell protrusions enabling it to function in migration. Squamous carcinoma-derived A431 cells were used because they express alpha6beta4 and migrate in response to EGF stimulation. Using function-blocking antibodies, we show that the alpha6beta4 integrin participates in EGF-stimulated chemotaxis and is required for lamellae formation on laminin-1. At concentrations of EGF that stimulate A431 chemotaxis ( approximately 1 ng/ml), the alpha6beta4 integrin is …

Distribution Of Health Care Expenditures For Hiv-Infected Patients, Ray Y. Chen, Neil A. Accortt, Andrew O. Westfall, Michael J. Mugavero, James L. Raper, Gretchen A. Cloud, Beth K. Stone, Jerome Carter, Stephanie Call, Maria Pisu, Jeroan J. Allison, Michael S. Saag

Jeroan J. Allison

BACKGROUND: Health care expenditures for persons infected with human immunodeficiency virus (HIV) in the United State determined on the basis of actual health care use have not been reported in the era of highly active antiretroviral therapy.

METHODS: Patients receiving primary care at the University of Alabama at Birmingham HIV clinic were included in the study. All encounters (except emergency room visits) that occurred within the University of Alabama at Birmingham Hospital System from 1 March 2000 to 1 March 2001 were analyzed. Medication expenditures were determined on the basis of 2001 average wholesale price. Hospitalization expenditures were determined on …

Trends In Aids-Defining And Non-Aids-Defining Malignancies Among Hiv-Infected Patients: 1989-2002, Roger Bedimo, Ray Y. Chen, Neil A. Accortt, James L. Raper, Carol Linn, Jeroan J. Allison, John Dubay, Michael S. Saag, Craig J. Hoesley

Jeroan J. Allison

In a comparison of rates of acquired immunodeficiency syndrome (AIDS)-defining malignancies (ADMs) for 1989-1996 versus 1997-2002, we found a decrease in ADMs (rate ratio, 0.31; P<.0001) and a significant increase in non-AIDS-defining malignancies (non-ADMs; rate ratio, 10.87; P<.0002). The mean CD4 cell count was lower among patients with ADMs than among those with non-ADMs. A longer duration of survival during highly active antiretroviral therapy might explain the increasing incidence of non-ADMs.

Body Mass Index, Treatment Practices, And Mortality In Patients With Acute Heart Failure, Timothy Fitzgibbons, Olga Hardy, Darleen Lessard, Joel Gore, Jorge Yarzebski, Robert Goldberg

Jorge L. Yarzebski

OBJECTIVES: Obesity is associated with an increased risk of heart failure (HF). Among patients presenting with acute HF, however, differences in clinical characteristics, treatment regimens, and short-term prognosis of varying weights are largely unknown, particularly from a broader population-based perspective. METHODS: A total of 3722 patients admitted with acute HF to 11 greater Worcester (Massachusetts, USA) hospitals during 1995 and 2000 were categorized as being lean (n = 216), normal weight (n = 1465), overweight (n = 1007), or obese (n = 1034) at the time of hospitalization. RESULTS: Obese patients with decompensated HF were significantly younger (mean age = …

Prognosis Of Acute Myocardial Infarction Complicated By Complete Heart Block (The Worcester Heart Attack Study), Robert Goldberg, Juan Zevallos, Jorge Yarzebski, Joseph Alpert, Joel Gore, Z. Chen, James Dalen

Jorge L. Yarzebski

As part of a community-based study of patients hospitalized with acute myocardial infarction (AMI) in the Worcester, Massachusetts, metropolitan area, changes over time in the incidence rates of complete heart block (CHB) complicating AMI, and the prognostic impact of CHB on the in-hospital and long-term survival of these patients were examined. In all, 4,762 patients with validated AMI hospitalized at 16 hospitals in the Worcester metropolitan area during 1975, 1978, 1981, 1984, 1986 and 1988 constituted the study sample. The incidence rates of CHB complicating AMI remained relatively stable at 5.8% over the 13-year (1975 to 1988) period studied. The …

Thirty-Year Trends (1975 To 2005) In The Magnitude Of, Management Of, And Hospital Death Rates Associated With Cardiogenic Shock In Patients With Acute Myocardial Infarction: A Population-Based Perspective, Robert Goldberg, Frederick Spencer, Joel Gore, Darleen Lessard, Jorge Yarzebski

Jorge L. Yarzebski

BACKGROUND: Limited information is available about potentially changing and contemporary trends in the incidence and hospital death rates of cardiogenic shock complicating acute myocardial infarction. The objectives of our study were to examine 3-decade-long trends (1975 to 2005) in the incidence rates of cardiogenic shock complicating acute myocardial infarction, patient characteristics and treatment practices associated with this clinical complication, and hospital death rates in residents of a large central New England community hospitalized with acute myocardial infarction at all area medical centers.

METHODS AND RESULTS: The study population consisted of 13 663 residents of the Worcester (Mass) metropolitan area hospitalized …

Narrowing Gender Differences In Procedure Use For Acute Myocardial Infarction: Insights From The Worcester Heart Attack Study, Leslie Harrold, Julian Esteban, Darleen Lessard, Jorge Yarzebski, Jerry Gurwitz, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

OBJECTIVE: To examine age-specific gender differences and trends over time in the management of patients with acute myocardial infarction (AMI). DESIGN: Cross-sectional study of patients admitted with AMI from a community-wide perspective over a 10-year period (1990-1999). SETTING: All hospitals in the Worcester (Mass) metropolitan area (1990 census = 437000). PATIENTS/PARTICIPANTS: We identified 2037 women and 2645 men who were hospitalized in the Worcester metropolitan area with confirmed AMI during six 1-year periods between 1990 and 1999. Four age groups (<55, 55 to 64, 65 to 74 and >or=75 years) of men and women were studied. MEASUREMENTS AND MAIN RESULTS: Use of echocardiography, exercise treadmill testing (ETT), …

Changes Over Time In The Use Of Aspirin In Patients Hospitalized With Acute Myocardial Infarction (1975 To 1997): A Population-Based Perspective, Elizabeth Jackson, Ramya Sivasubramian, Frederick Spencer, Jorge Yarzebski, Darleen Lessard, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

OBJECTIVE: The purpose of this study was to examine 2 decade-long trends in the use of aspirin and associated outcomes in patients hospitalized with acute myocardial infarction. BACKGROUND: Aspirin has been shown to be beneficial in the secondary prevention of AMI. However, little is known about changes over time in the use of aspirin in patients hospitalized with AMI and associated outcomes, particularly from a more generalizable population-based perspective. METHODS: We examined trends in aspirin use and hospital and long-term outcomes in 9336 metropolitan Worcester, Mass, residents hospitalized with validated AMI in all area hospitals between 1975 and 1997. RESULTS: …

Thirty-Year Trends (1975-2005) In The Magnitude, Patient Characteristics, And Hospital Outcomes Of Patients With Acute Myocardial Infarction Complicated By Ventricular Fibrillation, Robert Goldberg, Jorge Yarzebski, Frederick Spencer, Juan Zevallos, Darleen Lessard, Joel Gore

Jorge L. Yarzebski

Limited contemporary data are available describing the incidence rates, hospital prognosis, and factors associated with the occurrence of ventricular fibrillation (VF) in patients hospitalized with acute myocardial infarction (AMI). The objectives of our study were to examine 3-decade-long trends (1975 to 2005) in the magnitude, predictors, and hospital case-fatality rates associated with VF in residents of a large New England metropolitan area hospitalized at all area medical centers with an uncomplicated AMI. The study population consisted of 7,472 residents of the Worcester (Massachusetts) metropolitan area hospitalized with an uncomplicated AMI in 15 annual periods from 1975 to 2005. The overall …

Temporal Trends (1975 Through 1990) In The Incidence And Case-Fatality Rates Of Primary Ventricular Fibrillation Complicating Acute Myocardial Infarction. A Communitywide Perspective, David Chiriboga, Jorge Yarzebski, Robert Goldberg, Joel Gore, Joseph Alpert

Jorge L. Yarzebski

BACKGROUND: As part of a population-based study of acute myocardial infarction, we examined changes over time in the incidence and in-hospital case-fatality rates of primary ventricular fibrillation complicating acute myocardial infarction. METHODS AND RESULTS: Patients with validated acute myocardial infarction hospitalized at 16 hospitals in the Worcester, Mass, metropolitan area between 1975 and 1990 comprised the study sample. During the 15-year study period, 5.1% of patients developed primary ventricular fibrillation in the setting of uncomplicated acute myocardial infarction, with this rate remaining relatively constant over time. Both age- and multivariable-adjusted analyses showed no significant trend in the incidence rates of …

Long-Term Trends (1986-2003) In The Use Of Coronary Reperfusion Strategies In Patients Hospitalized With Acute Myocardial Infarction In Central Massachusetts, Robert J. Goldberg, Frederick A. Spencer, Joseph Okolo, Darleen M. Lessard, Jorge L. Yarzebski, Joel M. Gore

Jorge L. Yarzebski

BACKGROUND: The objectives of our study were to examine long-term (1986-2003) trends in the use of percutaneous coronary interventions (PCI) and thrombolytic therapy in the management of patients hospitalized at all Central Massachusetts medical centers with acute myocardial infarction (AMI). Our secondary study goal was to examine factors associated with use of these coronary reperfusion strategies. Limited contemporary data are available about changing trends in the use of coronary reperfusion strategies, particularly from a population-based perspective. METHODS: The sample consisted of 9422 greater Worcester (MA) residents hospitalized with AMI at all metropolitan Worcester medical centers in 10 annual periods between …

A Community-Wide Perspective Of Gender Differences And Temporal Trends In The Use Of Diagnostic And Revascularization Procedures For Acute Myocardial Infarction, David Chiriboga, Jorge Yarzebski, Robert Goldberg, Z. Chen, Jerry Gurwitz, Joel Gore, Joseph Alpert, James Dalen

Jorge L. Yarzebski

This study compares the overall use, as well as temporal trends, of various diagnostic and revascularization procedures for acute myocardial infarction (AMI) in men and women. The study sample comprised a total of 2,924 men and 1,838 women with validated AMI admitted to any of the 16 teaching and community hospitals in the Worcester, Massachusetts, metropolitan area during 1975, 1978, 1981, 1984, 1986 and 1988. During the period under study there was a significant increase in use of each of the examined procedures during hospitalization for AMI in both men and women. Increasing use of multiple procedures was also seen …

Temporal Trends And Associated Factors Of Inpatient Cardiac Rehabilitation In Patients With Acute Myocardial Infarction: A Community-Wide Perspective, Frederick Spencer, Bobak Salami, Jorge Yarzebski, Darleen Lessard, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

PURPOSE: Cardiac rehabilitation (CR) has been shown to be an important therapeutic intervention after the development of acute myocardial infarction (AMI), but historically has been underused. Inpatient CR often represents cardiac patients' first exposure to risk factor modification education and acts as a gateway to outpatient programs. METHODS: The authors performed a longitudinal study of the use of inpatient CR in 5204 Worcester residents hospitalized with validated AMI in seven 1-year periods between 1986 and 1997. RESULTS: The overall rate of referral to inpatient CR was 68%, with a slight decline in use to less than 60% in the authors' …

Communitywide Trends In The Use And Outcomes Associated With Beta-Blockers In Patients With Acute Myocardial Infarction: The Worcester Heart Attack Study, Helme Silvet, Frederick Spencer, Jorge Yarzebski, Darleen Lessard, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: Despite the benefits associated with beta-blocker therapy in patients with acute myocardial infarction (AMI), limited recent data are available describing the extent of use of this therapy and the associated hospital and long-term outcomes, particularly from the perspective of a population-based study. Data are also limited about the characteristics of patients with AMI who do not receive beta-blockers. This study examines more than 2 decades of trends in the use of beta-blockers in hospitalized patients with AMI. METHODS: Communitywide study of 10,374 patients hospitalized with confirmed AMI in all metropolitan Worcester hospitals during 12 annual periods between 1975 and …

The Impact Of The Stent Era On The Management Strategy For Acute Myocardial Infarction: A Population-Based Perspective, Harold Dauerman, Robert Goldberg, Jorge Yarzebski, Darleen Lessard, Joel Gore

Jorge L. Yarzebski

We determined trends in the use of invasive diagnostic and revascularization strategies from a multihospital community-wide perspective for patients suffering acute myocardial infarction (AMI). Comparing 3,824 patients treated in the prestent era (1986-1993) to 1,915 patients hospitalized during the stent era (1995-1997), there was a significant increase in the use of invasive procedures and revascularization techniques across a broad spectrum of AMI patients during their index hospitalization. This resulted in a higher-risk profile of patients referred for invasive management of AMI in the stent era. Cathet. Cardiovasc. Intervent. 51:255-258, 2000.

Decade-Long Trends And Factors Associated With Time To Hospital Presentation In Patients With Acute Myocardial Infarction: The Worcester Heart Attack Study, Robert Goldberg, Jorge Yarzebski, Darleen Lessard, Joel Gore

Jorge L. Yarzebski

BACKGROUND: Duration of prehospital delay in patients with acute myocardial infarction (AMI) is receiving increasing attention given the time-dependent benefits associated with prompt use of coronary reperfusion strategies. OBJECTIVE: To examine trends (1986-1997) in time to hospital presentation and factors associated with prolonged delay in a community-wide study of patients with AMI. METHODS: Longitudinal study of 3837 residents of the Worcester, Mass, metropolitan area hospitalized with AMI in 7 one-year periods between 1986 and 1997 in whom information about prehospital delay was available. RESULTS: The mean, median, and distribution of delay times exhibited either inconsistent or no changes over time. …

Multidecade-Long Trends (1986-2005) In The Utilization Of Coronary Reperfusion And Revascularization Treatment Strategies In Patients Hospitalized With Acute Myocardial Infarction: A Community-Wide Perspective, Jared Wasser, Robert Goldberg, Frederick Spencer, Jorge Yarzebski, Joel Gore

Jorge L. Yarzebski

OBJECTIVES: The objectives of our community-wide investigation were to describe multidecade-long trends (1986-2005) in the utilization of thrombolytic therapy, percutaneous coronary interventions, and coronary artery bypass graft surgery in patients hospitalized with acute myocardial infarction (AMI). METHODS: The study sample consisted of 9422 greater Worcester (MA) residents hospitalized with confirmed AMI at all metropolitan Worcester medical centers in 11 annual periods between 1986 and 2005. RESULTS: Increases in the utilization of percutaneous coronary interventions were observed between 1986 (2.0%) and 2005 (50.7%) with the most rapid increases beginning in the late 1990s. Utilization of coronary artery bypass graft surgery during …