Life Sciences Commons^™

Bone Morphogenetic Protein Receptor Type Ia Localization Causes Increased Bmp2 Signaling In Mice Exhibiting Increased Peak Bone Mass Phenotype., Beth Bragdon, Jeremy Bonor, Kathryn L Shultz, Wesley G Beamer, Clifford J Rosen, Anja Nohe

Clifford J Shultz

Bone morphogenetic protein 2 (BMP2) is a growth factor that initiates osteoblast differentiation. Recent studies show that BMP2 signaling regulates bone mineral density (BMD). BMP2 interacts with BMP receptor type Ia (BMPRIa) and type II receptor leading to the activation of the Smad signaling pathway. BMPRIa must shuttle between distinct plasma membrane domains, enriched of Caveolin-1 alpha and Caveolin-1 beta isoforms, and receptor activation occurs in these domains. Yet it remains unknown whether the molecular mechanism that regulates BMP2 signaling is driving mineralization and BMD. Therefore, the B6.C3H-1-12 congenic mouse model with increased BMD and osteoblast mineralization was utilized in …

Novel Ubiquitin Neuropathology In Frontotemporal Dementia With Valosin-Containing Protein Gene Mutations, Mark Forman, Ian Mackenzie, Nigel Cairns, Eric Swanson, Philip Boyer, David Drachman, Bharati Jhaveri, Jason Karlawish, Alan Pestronk, Thomas Smith, Pang-Hsien Tu, Giles Watts, William Markesbery, Charles Smith, Virginia Kimonis

Jason Karlawish

Frontotemporal dementia (FTD) with inclusion body myopathy and Paget disease of bone (IBMPFD) is a rare, autosomal-dominant disorder caused by mutations in the valosin-containing protein (VCP) gene, a member of the AAA-ATPase gene superfamily. The neuropathology associated with sporadic FTD is heterogeneous and includes tauopathies and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). However, there is limited information on the neuropathology in IBMPFD. We performed a detailed, systematic analysis of the neuropathologic changes in 8 patients with VCP mutations. A novel pattern of ubiquitin pathology was identified in IBMPFD that was distinct from sporadic and familial FTLD-U without VCP gene …

Pseudohypoparathyroidism Type 1a And Insulin Resistance In A Child, Benjamin U. Nwosu, Mary M. Lee

Mary M. Lee

Background. A 5-year-old white girl with a history of hypothyroidism in infancy presented to the endocrinology clinic of a tertiary hospital. Her physical examination noted a stocky physique, broad chest, short neck and short digits. Two years later, skin examination revealed subcutaneous nodules and acanthosis nigricans. Investigations. Measurement of levels of serum phosphate, parathyroid hormone, ionized calcium and insulin; measurement of peak growth hormone by the arginine-levodopa stimulation test; calculation of homeostasis model assessment of insulin resistance; assessment of bone age; DNA analysis of the GNAS gene. Diagnosis. Pseudohypoparathyroidism type 1a in a patient with Albright hereditary osteodystrophy, characterized by …

Perinatal Administration Of Pcp Alters Adult Behaviour In Female Sprague-Dawley Rats, Teresa Du Bois, Xu-Feng Huang, Chao Deng

Xu-Feng Huang

Perinatal phencyclidine (PCP) treatment leads to neuronal damage and causes long-term behavioural alterations in rodents. This study examined the effects of perinatal PCP treatment on behaviour of adult rats in holeboard, elevated plus maze, social interaction and forced swim tests. PCP-treated rats displayed hyperactivity in the holeboard and forced swim tests. These persistent behavioural changes are relevant to the study of psychiatric disorders such as schizophrenia.

The Responsiveness Of State Mental Health Authorities To Parents With Mental Illness, Kathleen Biebel, Joanne Nicholson, Valerie Williams, Beth Hinden

Joanne Nicholson

The majority of adults with serious mental illness living in the community are parents, many of whom may be receiving services from State Mental Health Authorities (SMHA). Innovative intervention approaches are available to improve outcomes for these parents and their children. Analyses of SMHA and state-level data, as well as qualitative interviews of administrators, service providers, and consumers, underscore the importance of organizational structure and philosophy, an advocacy presence, and available funding to SMHA efforts on behalf of parents and their families.

Mothers With Mental Illness: I. The Competing Demands Of Parenting And Living With Mental Illness, Joanne Nicholson, Elaine Sweeney, Jeffrey Geller

Joanne Nicholson

OBJECTIVE: The purpose of this study is to understand the parenting experiences of women with mental illness from the perspectives of mothers and case managers employed by the state department of mental health. METHODS: Six focus groups of mothers and five focus groups of case managers met to discuss the problems facing mothers with mental illness and to recommend solutions. Focus-group transcripts were coded and items grouped by themes in qualitative analyses to explore the conflicts mothers face in meeting the dual challenges of parenting and living with mental illness. RESULTS: Mothers and case managers identified sources of conflict in …

Mothers With Mental Illness: Ii. Family Relationships And The Context Of Parenting, Joanne Nicholson, Elaine Sweeney, Jeffrey Geller

Joanne Nicholson

OBJECTIVE: This study explores the experiences of mothers with mental illness regarding their family relationships.

METHODS: Six focus groups of mothers with mental illness and five focus groups of case managers met to discuss problems facing mothers with mental illness and to recommend solutions. Focus groups were audiotaped, and transcripts were coded and analyzed qualitatively to describe ways in which husbands and partners, grandparents, and other family members contribute to the context of parenting for mothers with mental illness.

RESULTS: Mothers with mental illness and case managers described a range of relationships and attitudes of family members and provided examples …

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 …

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), …

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 …

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. …

Use Of Aspirin, Beta-Blockers, And Lipid-Lowering Medications Before Recurrent Acute Myocardial Infarction: Missed Opportunities For Prevention, Danny Mccormick, Jerry Gurwitz, Darleen Lessard, Jorge Yarzebski, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: For patients who have had a previous myocardial infarction (MI), the use of aspirin, beta-blockers, and lipid-lowering agents reduces the risk of recurrent MI and death. OBJECTIVE: To examine trends in and determinants of receipt of these 3 medications before hospitalization for recurrent acute MI (AMI). METHODS: The study population consisted of 1710 patients with a previous history of MI hospitalized with a validated recurrent AMI in all hospitals in Worcester, Mass, during 1986, 1988, 1990, 1991, 1993, and 1995. Logistic regression analyses were used to assess the effect of demographic, clinical, and temporal factors on the receipt of …

Temporal Trends And Factors Associated With Extent Of Delay To Hospital Arrival In Patients With Acute Myocardial Infarction: The Worcester Heart Attack Study, Jorge Yarzebski, Robert Goldberg, Joel Gore, Joseph Alpert

Jorge L. Yarzebski

Factors associated with delay to hospital arrival after the onset of symptoms suggestive of acute myocardial infarction (AMI) were examined in the late 1960s and 1970s, but recent data concerning these characteristics are limited. The purpose of the present study was to examine overall and temporal distributions of the extent of patients' delay from the time of onset of AMI symptoms to hospital arrival and factors associated with delay in seeking medical care from a multihospital, population-based perspective. Review of medical records was undertaken of patients hospitalized with a discharge diagnosis of AMI in 16 teaching and community hospitals in …

A Community-Wide Survey Of Physician Practices And Attitudes Toward Cholesterol Management In Patients With Recent Acute Myocardial Infarction, Jorge Yarzebski, Carmen Bujor, Robert Goldberg, Frederick Spencer, Darleen Lessard, Joel Gore

Jorge L. Yarzebski

BACKGROUND: Physicians' current attitudes and practices toward the management of high cholesterol levels in patients with recent acute myocardial infarction are not well defined. OBJECTIVE: To examine threshold levels of serum cholesterol and other factors that influence physicians' decision to prescribe lipid-lowering drugs and initiate dietary therapy in patients with recent acute myocardial infarction. METHODS: Community-wide questionnaire survey of general internists, cardiologists, and family physicians practicing in the Worcester, Mass, metropolitan area. RESULTS: Among the 257 responding physicians, lipid-lowering drug therapy was more likely to be initiated in younger patients at lower total serum and low-density lipoprotein (LDL) cholesterol levels …

Patient Delay And Receipt Of Thrombolytic Therapy Among Patients With Acute Myocardial Infarction From A Community-Wide Perspective, Robert Goldberg, Jerry Gurwitz, Jorge Yarzebski, J. Landon, Joel Gore, Joseph Alpert, P. Dalen, James Dalen

Jorge L. Yarzebski

The duration of patient delay from the time of onset of symptoms of acute myocardial infarction (AMI) to hospital presentation, and the relation of delay time and various patient characteristics to receipt of thrombolytic therapy were examined as part of a community-based study of patients hospitalized with AMI in the Worcester, Massachusetts, metropolitan area. In all, 800 patients with validated AMI hospitalized at 16 hospitals in the Worcester metropolitan area in 1986 and 1988 constituted the study sample. Patients delayed on average 4 hours between noting symptoms suggestive of AMI and presenting to area-wide emergency departments with no significant change …

Temporal Trends (1986-1997) In Cholesterol Level Assessment And Management Practices In Patients With Acute Myocardial Infarction: A Population-Based Perspective, Jorge Yarzebski, Frederick Spencer, Robert Goldberg, Darleen Lessard, Joel Gore

Jorge L. Yarzebski

BACKGROUND: Elevated serum cholesterol levels are associated with increased risk for acute myocardial infarction (AMI) and adverse patient outcomes. It is unclear what proportion of patients have their serum cholesterol levels measured during hospitalization for AMI and are given hypolipidemic therapy. OBJECTIVE: To examine decade-long trends in measurement of serum cholesterol levels during hospitalization for AMI and use of hypolipidemic therapy. METHODS: Observational study of 5204 residents of the Worcester, Mass, metropolitan area hospitalized with validated AMI in all greater Worcester hospitals in seven 1-year periods from 1986 through 1997. RESULTS: Increases in the measurement of serum cholesterol levels during …

Temporal Trends And Factors Associated With Pulmonary Artery Catheterization In Patients With Acute Myocardial Infarction, Jorge Yarzebski, Robert Goldberg, Joel Gore, Joseph Alpert

Jorge L. Yarzebski

STUDY OBJECTIVE: To examine changes over time in the utilization of and factors associated with pulmonary artery (PA) catheterization in patients hospitalized with acute myocardial infarction (AMI). DESIGN: Nonconcurrent prospective study carried out in 16 teaching and community hospitals in Worcester, Mass, in seven time periods between 1975 and 1990. A total of 5,480 patients hospitalized with validated AMI comprised the study sample. RESULTS: Use of PA catheterization increased from 1975 to 1984 with a consistent decline thereafter in all patients with AMI studied. Among the 2,441 patients with complicated AMI, use of PA catheterization increased from 1975 through 1988 …

A Community-Wide Perspective Into Changing Trends In The Utilization Of Diagnostic And Interventional Procedures In Patients Hospitalized With Acute Myocardial Infarction, Jessica Hahn, Darleen Lessard, Jorge Yarzebski, Jordan Goldberg, Sean Pruell, Frederick Spencer, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: Limited data are available describing contemporary trends in the utilization of diagnostic and interventional procedures in patients hospitalized with acute myocardial infarction (AMI). The objectives of our population-based investigation were to examine long-term trends (1986-2003) in the utilization of cardiac catheterization, percutaneous coronary interventions (PCI), and coronary artery bypass graft surgery (CABG) in a community sample of patients hospitalized with AMI. We examined the demographic and clinical characteristics of patients who received these diagnostic and interventional procedures and determined whether the profile of patients undergoing these procedures had changed over time. METHODS: The study sample consisted of 9422 greater …

Declining Length Of Hospital Stay For Acute Myocardial Infarction And Postdischarge Outcomes: A Community-Wide Perspective, Frederick Spencer, Darleen Lessard, Joel Gore, Jorge Yarzebski, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: The objectives of this population-based study were to describe trends of more than a decade (1986-1999) in duration of hospitalization after acute myocardial infarction (AMI), patient characteristics associated with varying lengths of stay, and the impact of declining length of stay on postdischarge mortality. METHODS: The study sample consisted of 4551 patients discharged after AMI from all greater Worcester, Mass, hospitals in 8 annual periods during the study period. Regression models were used to examine the influence of demographic, clinical, and treatment variables on length of stay and the association between declining length of hospital stay and postdischarge mortality. …

Polymorphonuclear Functions In Patients With Mixed Connective Tissue Disease, E. Bodolay, Katalin Lukacs, G. Frendl, Gyongyi Szabo, G. Arato, Gyula Szegedi

Gyongyi Szabo

Polymorphonuclear leukocytes (PMNs) from 29 patients with mixed connective tissue disease (MCTD) were studied "in vitro" for their phagocytic and chemotactic function as well as for granulocyte alkaline phosphatase (GAP) activity. Fc-receptor expression detected by EA-rosette formation was comparable to the control. Yeast-phagocytosis, C3b-receptor mediated phagocytosis and chemotaxis of PMNs, however, significantly decreased in MCTD. At the same time, photometric measure of alkaline phosphatase activity indicated a nearly two fold increase in PMNs from patients with MCTD. Although no correlation was found between PMN functions and the activity of the disease, PMN disorders may play a role in pathogenesis of …