Medicine and Health Sciences Commons^™

Loss-Of-Function Variants In Endothelial Lipase Are A Cause Of Elevated Hdl Cholesterol In Humans, Andrew Edmondson, Robert Brown, Sekar Kathiresan, L. Cupples, Serkalem Demissie, Alisa Manning, Majken Jensen, Eric Rimm, Jian Wang, Amrith Rodrigues, Vaneeta Bamba, Sumeet Khetarpal, Megan Wolfe, Stephanie Derohannessian, Mingyao Li, Muredach Reilly, Jens Aberle, David Evans, Robert Hegele, Daniel Rader

Dr Robert Brown

Elevated plasma concentrations of HDL cholesterol (HDL-C) are associated with protection from atherosclerotic cardiovascular disease. Animal models indicate that decreased expression of endothelial lipase (LIPG) is inversely associated with HDL-C levels, and genome-wide association studies have identified LIPG variants as being associated with HDL-C levels in humans. We hypothesized that loss-of-function mutations in LIPG may result in elevated HDL-C and therefore performed deep resequencing of LIPG exons in cases with elevated HDL-C levels and controls with decreased HDL-C levels. We identified a significant excess of nonsynonymous LIPG variants unique to cases with elevated HDL-C. In vitro lipase activity assays demonstrated …

Prediction Of Radiation Pneumonitis By Dose-Volume Histogram Parameters In Lung Cancer--A Systematic Review, George Rodrigues, Michael Lock, David D'Souza, Edward Yu, Jake Van Dyk

Michael Lock

BACKGROUND AND PURPOSE: To perform a systematic review of the predictive ability of various dose-volume histogram (DVH) parameters (V(dose), mean lung dose (MLD), and normal tissue complication probability (NTCP)) in the incidence of radiation pneumonitis (RP) caused by external-beam radiation therapy.

METHODS AND MATERIALS: Studies assessing the relationship between CT-based DVH reduction parameters and RP rate in radically treated lung cancer were eligible for the review. Synonyms for RP, lung cancer, DVH and its associated parameters (NTCP, V(20), V(30), MLD) were combined in a search strategy involving electronic databases, secondary reference searching, and consultation with experts. Individual or group data …

Mitochondrial Antiviral Signaling Protein Defect Links Impaired Antiviral Response And Liver Injury In Steatohepatitis In Mice, Timea Csak, Angela Dolganiuc, Karen Kodys, Bharath Nath, Jan Petrasek, Shashi Bala, Dora Lippai, Gyongyi Szabo

Gyongyi Szabo

Mitochondrial dysfunction is a pathogenic feature of nonalcoholic steatohepatitis (NASH). NASH complicates hepatotropic viral disease. The mitochondrial antiviral signaling protein (MAVS) is the adapter of helicase receptors involved in sensing double-stranded RNA (dsRNA). We hypothesized that impaired MAVS function may contribute to insufficient antiviral response and liver damage in steatohepatitis. We identified reduced MAVS protein levels and increased MAVS association with the proteasome subunit alpha type 7 (PSMA7) in livers from mice given a methionine-choline-deficient (MCD) diet. Decreased association of MAVS with mitochondria and increased cytosolic cytochrome c indicated mitochondrial damage in steatohepatitis. In vivo administration of the synthetic dsRNA …

An Essential Role For Monocyte Chemoattractant Protein-1 In Alcoholic Liver Injury: Regulation Of Proinflammatory Cytokines And Hepatic Steatosis In Mice, Pranoti Mandrekar, Aditya Ambade, Arlene Lim, Gyongyi Szabo, Donna Catalano

Gyongyi Szabo

The importance of chemokines in alcoholic liver injury has been implicated. The role of the chemokine, monocyte chemoattractant protein-1 (MCP-1), elevated in patients with alcoholic liver disease is not yet understood. Here, we evaluated the pathophysiological significance of MCP-1 and its receptor, chemokine (C-C motif) receptor 2 (CCR2), in alcoholic liver injury. The Leiber-DeCarli diet containing alcohol or isocaloric control diets were fed to wild-type (WT) and MCP-1-deficient knockout (KO) mice for 6 weeks. In vivo and in vitro assays were performed to study the role of MCP-1 in alcoholic liver injury. MCP-1 was increased in Kupffer cells (KCs) as …

Fatty Acid And Endotoxin Activate Inflammasomes In Mouse Hepatocytes That Release Danger Signals To Stimulate Immune Cells, Timea Csak, Michal Ganz, Justin Pespisa, Karen Kodys, Angela Dolganiuc, Gyongyi Szabo

Gyongyi Szabo

The pathogenesis of nonalcoholic steatohepatitis (NASH) and inflammasome activation involves sequential hits. The inflammasome, which cleaves pro-interleukin-1beta (pro-IL-1beta) into secreted IL-1beta, is induced by endogenous and exogenous danger signals. Lipopolysaccharide (LPS), a toll-like receptor 4 ligand, plays a role in NASH and also activates the inflammasome. In this study, we hypothesized that the inflammasome is activated in NASH by multiple hits involving endogenous and exogenous danger signals. Using mouse models of methionine choline-deficient (MCD) diet-induced NASH and high-fat diet-induced NASH, we found up-regulation of the inflammasome [including NACHT, LRR, and PYD domains-containing protein 3 (NALP3; cryopyrin), apoptosis-associated speck-like CARD-domain containing …

Stent Placement Compared With Balloon Angioplasty For Obstructed Coronary Bypass Grafts. Saphenous Vein De Novo Trial Investigators., M P Savage, J S Douglas, D L Fischman, C J Pepine, S B King, J A Werner, S R Bailey, P A Overlie, S H Fenton, J A Brinker, M B Leon, S Goldberg

Michael P Savage M.D.

BACKGROUND: Treatment of stenosis in saphenous-vein grafts after coronary-artery bypass surgery is a difficult challenge. The purpose of this study was to compare the effects of stent placement with those of balloon angioplasty on clinical and angiographic outcomes in patients with obstructive disease of saphenous-vein grafts.

METHODS: A total of 220 patients with new lesions in aortocoronary-venous bypass grafts were randomly assigned to placement of Palmaz-Schatz stents or standard balloon angioplasty. Coronary angiography was performed during the index procedure and six months later.

RESULTS: As compared with the patients assigned to angioplasty, those assigned to stenting had a higher rate …

A Prospective Study Of The Rate Of Progression In Compensated, Histologically Advanced Chronic Hepatitis C, Jules Dienstag, Marc Ghany, Timothy Morgan, Adrian Di Bisceglie, Herbert Bonkovsky, Hae-Young Kim, Leonard Seeff, Gyongyi Szabo, Elizabeth Wright, Richard Sterling, Gregory Everson, Karen Lindsay, William Lee, Anna Lok, Chihiro Morishima, Anne Stoddard, James Everhart

Gyongyi Szabo

The incidence of liver disease progression among subjects with histologically advanced but compensated chronic hepatitis C is incomplete. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial was a randomized study of 3.5 years of maintenance peginterferon treatment on liver disease progression among patients who had not cleared virus on peginterferon and ribavirin therapy. Patients were followed subsequently off therapy. Because maintenance peginterferon treatment did not alter liver disease progression, we analyzed treated and control patients together. Among 1,050 subjects (60% advanced fibrosis, 40% cirrhosis), we determined the rate of progression to cirrhosis over 4 years and of clinical outcomes …

Long-Stay Patients In State Psychiatric Hospitals At The End Of The 20th Century, William Fisher, Paul Barreira, Jeffrey Geller, Andrew White, Alisa Lincoln, Marylou Sudders

Alisa Lincoln

OBJECTIVES: The purpose of this study was to assess the characteristics of long-stay patients in contemporary state psychiatric hospitals and to identify factors representing possible barriers to alternative placements for these patients. METHODS: All patients in inpatient units of the Massachusetts Department of Mental Health who had been hospitalized for at least three years as of April 1, 1999, were assessed by their treatment teams with a standardized data collection instrument. Domains assessed included medical problems, need for nursing care, psychiatric diagnosis, and history of problematic behaviors. RESULTS: The 330 individuals identified as long-stay patients had an array of medical …

Insurance Status And Length Of Stay For Involuntarily Hospitalized Patients, William Fisher, Paul Barreira, Alisa Lincoln, Lorna Simon, Andrew White, Kristen Roy-Bujnowski, Marylou Sudders

Alisa Lincoln

General and private psychiatric hospitals are becoming increasingly common as sites for involuntary hospitalization. Unlike the public facilities that these settings are supplanting, these hospitals must pay strict attention to issues associated with reimbursement, insurance status, and managed care. This article examines the effects of insurance status on length of stay for involuntarily hospitalized patients in general and private hospitals in Massachusetts. Using a two-stage sampling procedure, data on episodes of involuntary hospitalization were gathered and assessed using multiple regression. The primary effect was found between patients with Medicare, who had the longest stays, and individuals who were uninsured, who …

Mothers With Severe Mental Illness Caring For Children, Carla White, Joanne Nicholson, William Fisher, Jeffrey Geller

Joanne Nicholson

This research identifies and describes the Massachusetts population of Department of Mental Health (DMH) case-managed women with severe mental illness who are caretakers of their minor children (N = 314), and compares their demographic and clinical characteristics and service utilization with those of a matched, randomly selected group of DMH case-managed noncaretaking women (N = 328) using the Client Tracking System database. Caretakers were significantly younger, had less formal education, and had higher rates of marriage than did noncaretakers. They are diagnosed more often with major affective disorders and less often with psychotic disorders. Caretakers demonstrate higher levels of functioning …

Why Not Support(Ed) Parenting, Joanne Nicholson, William Deveney

Joanne Nicholson

No abstract provided.

Outcomes Of Father Involvement In Pregnancy And Birth, Joanne Nicholson, Nancy Gist, Robert Klein, Kay Standley

Joanne Nicholson

No abstract provided.

Privatized Medicaid Managed Care In Massachusetts: Disposition In Child And Adolescent Mental Health Emergencies, Joanne Nicholson, Stephen Young, Lorna Simon, William Fisher, Anne Bateman

Joanne Nicholson

Data from child and adolescent emergency mental health screening episodes prior and subsequent to privatized Medicaid managed care in Massachusetts are used to investigate the relationship between payer source and disposition and to compare the match between clinical need and disposition level of care. Having Medicaid as the payer in the post-Medicaid managed care period decreased the odds of hospitalization by nearly 60%. None of the clinical need variables that contributed to hospitalization for Medicaid episodes in the pre-Medicaid managed care period were significant in the post-Medicaid managed care period. Multiple forces shaping professional standards, decision making, and quality of …

Fathers With Severe Mental Illness: Characteristics And Comparisons, Joanne Nicholson, Margaret Nason, Anne Calabresi, Regina Yando

Joanne Nicholson

Among patients with severe mental illness attending a large, urban, outpatient mental health clinic, fathers are described and compared with nonfathers and with mothers on demographic, clinical, and child-related characteristics, and on resources and service needs. While fathers and nonfathers with mental illness differed significantly on most variables, fathers and mothers with mental illness were remarkably similar except on child-related characteristics. Issues regarding fathers' experiences and service needs are discussed.

A Qualitative Study Of Programs For Parents With Serious Mental Illness And Their Children: Building Practice-Based Evidence, Joanne Nicholson, Beth Hinden, Kathleen Biebel, Alexis Henry, Judith Katz-Leavy

Joanne Nicholson

The rationale for the development of effective programs for parents with serious mental illness and their children is compelling. Using qualitative methods and a grounded theory approach with data obtained in site visits, seven existing programs for parents with mental illness and their children in the United States are described and compared across core components: target population, theory and assumptions, funding, community and agency contexts, essential services and intervention strategies, moderators, and outcomes. The diversity across programs is strongly complemented by shared characteristics, the identification of which provides the foundation for future testing and the development of an evidence base. …

Achieving The Goal Of Evidence-Based Psychiatric Rehabilitation Practices For Mothers With Mental Illnesses, Joanne Nicholson, Alexis Henry

Joanne Nicholson

There is a growing commitment to evidence-based practices in mental health. There is no well-articulated evidence base for interventions for mothers with mental illnesses. Parenthood is common among women with mental illnesses. Women themselves report motherhood is an important role. The risks of parental mental illness to children have been demonstrated; the challenges that motherhood brings to people with mental illnesses have been described. Because outcomes for both children and adults are multiply determined, there are many intervention opportunities. Recommendations for intervention are drawn from a focus group study and from the existing literature on parent training and support, exemplary …

A Comparison Of The Health And Mental Health Status Of Homeless Mothers In Worcester, Mass: 1993 And 2003, Linda Weinreb, John Buckner, Valerie Williams, Joanne Nicholson

Joanne Nicholson

OBJECTIVES: We assessed background characteristics, health status, and prevalence rates of mental health disorders in 2 studies of homeless mothers conducted in Worcester, Mass, one in 1993 and the other in 2003.

METHODS: We compared the women taking part in the 2 studies, which involved similar methodologies, on the key variables of interest over time.

RESULTS: Homeless families taking part in the 2003 study were poorer than those taking part in the 1993 study, and female heads of household in that study reported more physical health limitations, major depressive illness, and posttraumatic stress disorder.

CONCLUSION: Data from 2003 suggest that …

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.

Creating Job Opportunities For People With Psychiatric Disabilities At A University-Based Research Center, Alexis Henry, Joanne Nicholson, Jonathan Clayfield, Susan Phillips, Lawrence Stier

Joanne Nicholson

The consumer empowerment movement has led to an increase in opportunities for people with psychiatric disabilities to take on roles in the development and delivery of mental health services. However, to date there has been less involvement of people with psychiatric disabilities in services research. In this paper, we describe our experiences creating employment opportunities for people with psychiatric disabilities in a university-based mental health services research center. Working with two local clubhouse programs we developed research assistant positions using both transitional and supported employment approaches. We describe the development of the jobs, employee characteristics, the orientation and training provided …

State Policies And Programs That Address The Needs Of Mentally Ill Mothers In The Public Sector, Joanne Nicholson, Jeffrey Geller, William Fisher, George Dion

Joanne Nicholson

OBJECTIVE: The authors sought to determine whether state departments of mental health have specific policies and programs addressing the needs of mentally ill women served in the public sector who have preschool-age children. METHODS: A questionnaire was sent to the commissioner of mental health for each state and the District of Columbia. Questions addressed whether information was routinely collected on the parenting status of women who receive public-sector psychiatric services, whether services targeting mentally ill women with young children were available, and whether the state had policies concerning hospitalized women who are pregnant or who have young children. RESULTS: Sixteen …

"Sylvia Frumkin" Has A Baby: A Case Study For Policymakers, Joanne Nicholson, Jeffrey Geller, William Fisher

Joanne Nicholson

"Sylvia Frumkin" was a pseudonym given to a 32-year-old woman with chronic mental illness described by Susan Sheehan in her books Is There No Place on Earth for Me? This paper presents the case of "Gloria Morrison," a patient similar to Ms. Frumkin, who is also a mother. Issues raised by the case in three areas are discussed. Issues for the service delivery system include developing better assessment, prediction, and reduction of the risk that a parent's mental illness may pose to a child's safety and well-being; targeting supportive and educational interventions to relatives and foster parents caring for children …

A Comparison Of Mothers With Co-Occurring Disorders And Histories Of Violence Living With Or Separated From Minor Children, Joanne Nicholson, Norma Finkelstein, Valerie Williams, Jennifer Thom, Chanson Noether, Megan Devilbiss

Joanne Nicholson

Data from the Women with Co-occurring Disorders and Histories of Violence Study are used to examine characteristics distinguishing mothers currently providing care for all their minor children (n = 558) from mothers separated from one or more minor children (n = 1396). Mothers are described and compared on background characteristics and experiences, well-being and current functioning, situational context, and services used. Analyses control for number of children, race, and years of education. Mothers separated from children have more children, less education, have more often been homeless, in juvenile detention or jail, and have lower incomes than mothers living with all …

Frontline Reports: The Clubhouse Family Legal Support Project For Parents With Mental Illness, Kate Nemens, Joanne Nicholson

Joanne Nicholson

No abstract provided.

Family Options For Parents With Mental Illnesses: A Developmental, Mixed Methods Pilot Study, Joanne Nicholson, Karen Albert, Bernice Gershenson, Valerie Williams, Kathleen Biebel

Joanne Nicholson

OBJECTIVE: The objective of this paper is to provide a description of Family Options, a rehabilitation intervention for parents with serious mental illnesses and their children focusing on recovery and resilience, and to report the findings from a pilot study at 6-months post-enrollment for participating mothers. METHODS: A developmental design, and mixed quantitative and qualitative methods facilitate an in-depth understanding of Family Options and its impact on parents early in the implementation process. RESULTS: Participating families faced significant challenges, including long-term mental health conditions in adults, and emotional and behavioral difficulties in children. Data from mothers (n = 22) demonstrate …

Integrating Behavioral Health Services For Homeless Mothers And Children In Primary Care, Linda Weinreb, Joanne Nicholson, Valerie Williams, Frances Anthes

Joanne Nicholson

This article describes an innovative trauma-informed care management model in which mental health, substance abuse, and support services are integrated for homeless families in primary care. The rationale for service integration in a health care setting is discussed and the conceptual underpinnings of the model are elaborated, drawing from the literature and clinical experience. Service encounter data collected by each staff member over a 1-year period (N = 7,214 encounters) allow for description of program functions and provider roles and activities, an essential step in developing the fidelity indicators necessary for future program replication and rigorous testing in additional settings. …

Psychosocial Rehabilitation Service Needs Of Women, Carol Mowbray, Joanne Nicholson, Chyrell Bellamy

Joanne Nicholson

No abstract provided.

The Invisible Children's Project: Key Ingredients Of An Intervention For Parents With Mental Illness, Beth Hinden, Kathleen Biebel, Joanne Nicholson, Liz Mehnert

Joanne Nicholson

This study used a collective case study design to identify key ingredients of the Invisible Children's Project, an intervention program for families in which a parent has a mental illness. Data were obtained from interviews with parents and service providers, and from family file records. Qualitative analyses were used to generate hypotheses regarding key ingredients and targeted outcomes, and to develop a testable intervention model. Key ingredients were defined as core processes, essential services, and mediators. Strong convergence across parents and providers suggested core processes defined by family-centered, strengths-based, emotionally supportive, and comprehensive approaches; essential services including family case management, …

Responding To Depression In Parents, Joanne Nicholson, Jonathan Clayfield

Joanne Nicholson

Pediatric professionals may naturally view themselves as gatekeepers or facilitators of access to mental health services for children, but may not see themselves as the first line of "defense" for parents with mental health issues. However, about two thirds of women who meet criteria for affective disorders, and slightly more than half of the men who do, are parents. Given that the average age of onset for affective disorders is several years after the birth of first children, parental depression may initially come to the attention of pediatric providers, the most likely professionals with whom parents have contact prior to …

Use Of Child Custody As Leverage To Improve Treatment Adherence, Joanne Nicholson

Joanne Nicholson

No abstract provided.

Commentary On "Community Mental Health Care For Women With Severe Mental Illness Who Are Parents" - The Tragedy Of Missed Opportunities: Of Missed Opportunities: What Providers Can Do, Joanne Nicholson, Kathleen Biebel

Joanne Nicholson

Women and men who meet criteria for psychiatric disorder are likely to be parents. Many go undiagnosed and untreated, putting themselves and their children at risk of poor outcomes. Adults with mental illness may fear disclosing their status as parents; providers may not ask. Practices can be modified to promote the well being of parents with mental illness and their children.