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TITLE: Assessing Alcohol, Drug Abuse and Mental Health Service Needs Among Juvenile Detainees
INSTITUTE: NIMH
P.I.: Linda Tepin, PhD
INSTITUTION: Northwestern University Medical School, Evanston, IL
GRANT NO.: 5 R01 MH59463-02
KEYWORDS: Juvenile, alcohol, drug abuse, mental health services, delinquency
STUDY POP: Adolescent girls, released detainees, aged 10-13/14-17 years
TYPE STUDY: Clinical
AMOUNT: $200,000
This longitudinal study will examine released detainees to determine their on-going Alcohol, Drug Abuse and Mental (ADM) disorders, the patterns and sequencing of symptoms; ADM comorbidity; functional impairments over time; barriers, pathways and patterns of ADM service use; drug use, violence, and HIV/AIDS risk. The rate of delinquency among females is increasing faster than the rate for males. Females are increasingly arrested for violent crimes (16% in 1989 and 29% in 1993) and those females who are arrested have more psychiatric morbidity and worse outcomes than males. The sampling for this study is stratified by gender, race (Caucasian, African American, Latino), age (10-13/14-17) and legal status (processed as juvenile or adult). Of the total sample, 600 are girls, 75% of whom are minority.
TITLE: Sexual Identity and Drinking: Risk and Protect Factors
INSTITUTE: NIAAA
P.I.: Tonda L. Hughes, PhD
INSTITUTION: University of Illinois at Chicago, IL
GRANT NO.: 1 K01 AA00266-01
KEYWORDS: Alcohol, lesbians
STUDY POP: Women, aged 18 years and older
TYPE STUDY: Clinical
AMOUNT: $92,002
This study will use an existing survey instrument to examine and compare risk and protective factors for heavy drinking and alcohol-related problems in lesbians and heterosexual women. The study will include data from 600 women who are 18 years of age or older.
TITLE: Alcohol, HIV Risk Behaviors, and Sexual Victimization
INSTITUTE: NIAAA
P.I.: Maria Testa, PhD
INSTITUTION: Research Institute on Addictions, Buffalo, NY
GRANT NO.: 1 R01 AA12013-01A1
KEYWORDS: Risk behaviors, HIV, sexual victimization
STUDY POP: Women, unmarried aged 18-30 years
TYPE STUDY: Clinical
AMOUNT: $100,000
This application suggests that childhood sexual abuse and risk-prone personality (high sensation-seeking, high negative affect, low assertiveness) lead women to engage in risky behaviors (heavy alcohol and drug use, high levels of sexual activity and exposure to risky settings such as bars) which in turn increase the likelihood of experiencing both sexual victimization and HIV/STD infections. There will be a three wave cross-legged panel design using a representative sample of 1,000 unmarried women, ages 18-30, recruited from random digit dialing.
TITLE: Preventing Alcohol Use in Pregnant Women Utilizing WIC
INSTITUTE: NIAAA
RFA: Preventing Fetal Alcohol Syndrome
P.I.: Mary O'Connor, PhD
INSTITUTION: University of California Los Angeles, CA
GRANT NO.: 1 R01 AA12480-01
KEYWORDS: Pregnant women, alcohol, birth outcomes
STUDY POP: Women, pregnant
TYPE STUDY: Clinical
AMOUNT: $100,000
The study is a controlled intervention designed to decrease alcohol use by low-income ethnically diverse pregnant women enrolled in the WIC (Women, Infants and Children) program. The aims are to 1) increase the detection of alcohol use during pregnancy in the WIC population; 2) evaluate the impact of brief intervention on reduction of maternal drinking during pregnancy; 3) identify maternal characteristics that influence the effectiveness of brief intervention; 4) identify characteristics of the intervention that contribute to a reduction in maternal alcohol consumption; and evaluate the impact of the intervention on infant birth outcomes.
TITLE: Women with Schizophrenia & Co-Occurring Substance Use Disorders
INSTITUTE: NIDA
P.I.: Dr. Jean Gearon
INSTITUTION: University of Maryland, MD
GRANT NO.: 1 R29 DA11199-01A1
KEYWORDS: Schizophrenia, substance abuse, co-occurring substance use, HIV, risk factors
STUDY POP: Women
TYPE STUDY: Clinical
AMOUNT: $20,000
The primary goals of this project are: 1) to determine if women with schizophrenia and co-occurring substance use disorders are more vulnerable to HIV (e.g., engage in more high risk behaviors) and violent victimization than either women with major depression and co-occurring substance use disorders or women with substance use disorders only and no history of serious and persistent mental illness; 2) to determine if women with schizophrenia who abuse substances experience more violent victimization than women with major depression and co-occurring substance use disorders, or women with substance abuse disorders alone and no history of serious and persistent mental illness, and 3) to examine the causal sequencing between cognitive functioning, social competency, negative symptoms and HIV risk and victimization.
TITLE: Reducing Disease Risk in Low-Income, Postpartum Women
INSTITUTE: NICHD
RFA: Innovative Approaches to Disease Prevention Through Behavior Change (OD-98-002)
P.I.: Karen Peterson, RD, ScD
INSTITUTION: Harvard School of Public Health, Boston, MA
GRANT NO.: 1 RO1 HD37368-01
KEYWORDS: Postpartum, education, health promotion, disease prevention
STUDY POP: Women
TYPE STUDY: Clinical
AMOUNT: Total RFA $150,000
The postpartum period is a window of opportunity to promote behaviors to reduce risk of chronic disease and benefit reproductive health, through interventions that address multiple levels of influence in the social context of low-income women recruited from the Women, Infants and Children Program (WIC). This study will test the efficacy of an education model aimed at improving dietary and activity patterns among low income, multi-ethnic women over a twelve month postpartum period, followed by a six month maintenance period.
TITLE: The Experience of Lung Cancer Survivorship
INSTITUTE: NCI
P.I.: Linda Sarna, DNSc, RN
INSTITUTION: University of California at Los Angeles, CA
GRANT NO.: 1 RO1 CA78997 01
KEYWORDS: Lung cancer, non-small cell lung cancer, quality of life assessment, smoking, tobacco, gender differences
STUDY POP: Women and men who are lung cancer survivors
TYPE STUDY: Clinical
AMOUNT: $99,951
Little is known about gender differences after lung cancer. The purposes of this pilot study are to develop the most effective methods for recruitment of disease-free, lung cancer survivors, and to begin assessment of quality of life (QOL) outcomes of lung cancer. The physical, psychological, social, and existential dimensions of QOL will be assessed in 50 adults who are at least five years since diagnosis of non-small cell lung cancer. The variables of interest include gender, tobacco use, and pulmonary function.
TITLE: Clinical Trials of Two Human Papillomavirus (HPV) -like Particle Vaccines
INSTITUTE: NCI
P.I.: Douglas Lowy
INSTITUTION: NCI, Bethesda, MD
GRANT NO.: 1 Z01 BC09052-09
KEYWORDS: Human papillomavirus, cancer, cervical, vaccine
STUDY POP: Women, young women
TYPE STUDY: Clinical
AMOUNT: $412,500
This project will perform the early phase clinical trials of two HPV16-based papillomavirus vaccines. L1 is a major structural papilloma viral protein that can self-assemble into virus-like particles (VLPs). It is thought that L1 VLP will only protect by preventing primary infection. To add another level of protection, a chimeric VLP was developed by adding the L2 minor capsid protein to the L1. After preclinical vaccine results, an early phase human trial of L1 HPV16 VLP vaccine is being tested. There are four groups of 12 normal volunteers 18-29 years old. In each group, ten volunteers received the vaccine and two received a placebo in a double-blind fashion.
TITLE: Treatment of Bulimia Nervosa in a Primary Care Setting
INSTITUTE: NIDDK
P.I.: Dr. Bernard Walsh
INSTITUTION: New York State Psychiatric Institute, New York, NY
GRANT NO.: 5 RO1 DK53635-03
KEYWORDS: Eating disorders, bulimia nervosa, fluoxetine, guided self-help, primary care setting, antidepressant
STUDY POP: Women
TYPE STUDY: Clinical
AMOUNT: $100,000
The aim of this proposal is to examine whether the two treatments of an antidepressant medication (fluoxetine) or a form of cognitive behavioral therapy (guided self-help) can be usefully transferred to general health care settings. Over four years, 200 women with bulimia nervosa will be treated in a suburban primary care setting and randomized to receive: 1) fluoxetine or placebo and, 2) guided self-help combined with medical management or medical management alone. Changes in eating behavior and in psychological state will be assessed at the end of active treatment (4 months) and four and eight months after the end of treatment.
TITLE: Longitudinal Study of Anorexia and Bulimia Nervosa
INSTITUTE: NIMH
P.I.: David Herzog, MD
INSTITUTION: Massachusetts General Hospital, Boston, MA
GRANT NO.: 2 R01 MH38333-10
KEYWORDS: Anorexia, bulimia, long term study, pregnancy
STUDY POP: Young women, previous cohort of 246
TYPE STUDY: Clinical
AMOUNT: $102,600 (bridge funding)
Anorexia nervosa (AN) and bulimia nervosa (BN) are prevalent disorders in adolescent and young women. This study represents the only prospective long-term study of a large cohort of ANs and BNs who are contacted at frequent intervals. The investigator would like to extend this study of 246 women for five more years to: 1) describe the course of each disorder; 2) assess the impact of eating disorders on pregnancy and the impact of pregnancy on eating disorders; 3) determine definitions for recovery, relapse, remission and recurrence; and 4) contribute data on the nosology of eating disorders.
TITLE: Serum Lipids Measurements as an Outcome Measure
INSTITUTE: NIDDK
P.I.: Steering Committee for DPP
INSTITUTION: Multi centers
GRANT NO.: N/A
KEYWORDS: Diabetes, non-insulin-dependent diabetes mellitus, diabetes prevention, serum lipids, cardiovascular risk
STUDY POP: Women and men
TYPE STUDY: Clinical
AMOUNT: $200,000
The Diabetes Prevention Program (DPP) is a multi-center, randomized, controlled clinical trial and with the specific objective of comparing, in high risk individuals, the efficacy of two intervention methods (intensive behavior modification and metformin) in preventing or delaying conversion of impaired glucose tolerance (IGT) to non-insulin dependent diabetes mellitus (NIDDM). Serum lipids are expected to be abnormal in 50-60% of DPP enrollees. Repeated lipid determinations are used to assess cardiovascular risk and the effect of DPP interventions on that risk.
TITLE: Study Commitment Inventory
INSTITUTE: NIDDK
P.I.: N/A
INSTITUTION: N/A
GRANT NO.: R01 DK51975
KEYWORDS: Evaluation in teens, compliance, adherence, diabetes
STUDY POP: Women and girls
TYPE STUDY: Clinical
AMOUNT: $30,000
This is a new instrument to evaluate adherence to research protocols. This ancillary study evaluates this instrument and provides information on factors that affect compliance of girls and women with research protocols.
TITLE: Synergy between SSRIs and Ovarian Hormones
INSTITUTE: NIMH
P.I.: Louis Van De Kar, PhD
INSTITUTION: Loyola University of Chicago, IL
GRANT NO.: 1 R01 MH58448-01A2
KEYWORDS: Fluoxetine, SSRIs, estrogen
STUDY POP: Animal model (rats)
TYPE STUDY: Basic
AMOUNT: $200,000
The hypothesis is that estrogen will act synergistically with fluoxetine (a selective serotonin reuptake inhibitor, SSRI) via complementary mechanisms to desensitize hypothalamic (5-HT) receptor systems. It is predicted that estrogen or estrogen plus progesterone will shorten the delay in the effects of SSRIs. The proposed studies in rats will have the following aims: 1) to determine the doses of estrogen and progesterone that reduce 5-HT receptor function in ovariectomized rats; 2) to identify the estrogen receptor subtype(s) which mediate the effect of estrogen on 5-HT receptor systems in the hypothalamus; 3) to determine if estrogen shortens the delay in fluoxetine's effects on 5-HT receptor signaling; 4) to determine if progesterone increases estrogen's effectiveness in shortening the delay in fluoxetine-induced 5HT receptor sub-sensitivity. The proposed studies will provide a basis for the development of improved therapeutic regimens and faster clinical improvement in women suffering from premenstrual syndrome, depression, bulimia and anxiety disorders.
TITLE: Regulation of Estrogen-Responsive Genes
INSTITUTE: NICHD
P.I.: Dr. Marilyn Evans
INSTITUTION: West Virginia University School of Medicine, WV
GRANT NO.: 2 RO1 HD26339
KEYWORDS: Estrogen, estrogen-responsive genes, transcription, vitellogenin, apolipoproteins
STUDY POP: Animal model (birds)
TYPE STUDY: Basic
AMOUNT: $30,000
The long-term objective of this research is to understand the molecular basis by which estrogen regulates the transcription of genes. The avian liver provides a model system in which estrogen-responsive genes direct the synthesis of egg yolk pre- cursor proteins. The specific aims of this proposal are to 1) define the estrogen-dependent chromatin alterations and tran- scription response of the vitellogenin (VT-II) gene, 2) determine the characteristics of the secondary response of apolipo- proteins (apo-II) and VT-II to estrogen, and 3) isolate and characterize mRNAs that are altered during the response to estrogen. The techniques that will be relied on are run-on transcription assays, in vivo foot printing and subtractive cloning techniques.
TITLE: Genetics of Age-Related Macular Degeneration
INSTITUTE: NEI
P.I.: Dr. Michael Klein
INSTITUTION: Oregon Health Sciences University, OR
GRANT NO.: 1 RO1 EY12203 01
KEYWORDS: Age-related macular degeneration (AMD), gender differences, genetics
STUDY POP: Women and men, AMD Families
TYPE STUDY: Clinical
AMOUNT: $100,000
The incidence of age-related macular degeneration (AMD) continues to rise as the result of the increasing percentage of elderly persons, with women at 50% greater risk than men. This application seeks to characterize genes that cause AMD. Dr. Klein has access to a number of AMD families and will map the genetic loci co-segregating with the disease in these families. To achieve this goal he plans to 1) continue to collect and ascertain families with the disease, 2) perform genome-wide screening of AMD families, 3) fine-map loci suggestive of linkage, and 4) identify specific genetic mutations in these families.
TITLE: Biofeedback for Fecal Incontinence and Constipation
INSTITUTE: NIDDK
RFA: Integrative Approaches to Study of GI Motility (DK-99-004)
P.I.: William E. Whitehead, Ph.D.
INSTITUTION: University of North Carolina, Chapel Hill, NC
GRANT NO.: 1 R01 DK57048-01
KEYWORDS: Biofeedback, fecal incontinence, constipation, pelvic floor dyssynergia
STUDY POP: Women, men, and children
TYPE STUDY: Clinical
AMOUNT: $150,000
Among constipation patients, half are reported to have pelvic floor dyssynergia, a condition marked by an inability to relax pelvis floor muscles during evacuation. Biofeedback has been recommended for the treatment of both conditions because uncontrolled studies over the past 10-25 years suggest that these treatments are as effective as medical or surgical management and involve no risk. However, placebo-controlled trials are lacking in this area. The aims of the proposed research are: 1) to compare biofeedback to alternative therapies for which patients have a similar expectation of benefit; 2) to identify which patients are most likely to benefit; and 3) to assess the impact of treatment on quality of life. Two long-term, prospective, single-blind studies will be conducted. Study I will compare biofeedback for the treatment of fecal incontinence to a standard therapy, Kegel exercises. Study II will compare biofeedback for pelvic floor dyssynergia to a skeletal muscle relaxant drug (diazepam) and to placebo medication. These studies will help to establish the efficacy of biofeedback on the treatment of defecatory disorders.
TITLE: Neurotensin's Role in Models of IBS-Related Hyperalgesia
INSTITUTE: NIDDK
RFA: Integrative Approaches to Study of GI Motility (DK-99-004)
P.I.: Robert E. Carraway, Ph.D.
INSTITUTION: University of Massachusetts, Worcester, MA
GRANT NO.: 1 R01 DK56999-01
KEYWORDS: Neurotensin, irritable bowel syndrome, stress responses, bowel hyperalgesia
STUDY POP: Animal model (mice)
TYPE STUDY: Basic
AMOUNT: $100,000
Neurotensin (NT), a gastrointestinal peptide, participates in modulating pain perception, mediating stress responses and regulating digestive motility/secretion. NT works closely with mast cells which coordinate neuro-endocrine immune activities in the gut. This project hypothesizes that NT-mast cell interactions are involved in physiological visceral perception and/or pathological visceral hyperalgesia. It is likely that multiple chemical mediators are involved in visceral hypersensitivity associated with stress-related functional bowel disorders. This proposal will address the potential role of neurotensin as a key mediator of the pathological hyperalgesia associated with irritable bowel syndrome using animal models of post-stress and post-inflammatory bowel hypersensitivity. The hypothesis will be tested using NT receptor antagonist, an NT-knockout mouse model, and a mast cell deficient mouse model.
TITLE: Effect of Menstrual Cycle and IBS on CNS Processing of Gut Stimuli
INSTITUTE: NIDDK
RFA: Integrative Approaches to Study of GI Motility (DK-99-004)
P.I.: Ann Ouyang, M.D.
INSTITUTION: Milton S. Hershey Medical Center, Hershey, PA
GRANT NO.: 1 R21 DK57053-01
KEYWORDS: Irritable bowel syndrome, menstrual cycle, anxiety, visceral sensitivity
STUDY POP: Women
AMOUNT: $100,000
Recent evidence suggest that patients with irritable bowel syndrome (IBS) have heightened sensitivity to visceral stimuli. Little is known about factors affecting visceral sensitivity, reasons for the higher female prevalence, or the central nervous system processing of visceral sensitivity stimuli, and if this process is altered in IBS. The investigators hypothesize that: 1) menstrual cycle stage affects visceral sensitivity in both control female subjects and in subjects with IBS; 2) the areas of the brain which are activated by visceral stimulation are dependent on both the degree of distension and by the perception that the stimulus is painful; and 3) the areas of the brain activated in IBS subjects when the stimulus is painful differ from areas activated in control subjects, and that this difference may be due to the effect of anxiety. Specific aims of the study are: 1) to determine the effect of menstrual cycle on the perception of rectal balloon distention and transcutaneous nerve stimulation (TNS) in subjects without bowel symptoms (controls); 2) to determine the effect of menstrual cycle on these responses in subjects with IBS; 3) to compare the responses between controls and IBS subjects; 4) to determine the regions of the brain activated in response to rectal (non-painful and painful) and non-visceral (TNS) stimulation; and 5) to determine the influence of the state of anxiety on these parameters. An understanding of cerebral processing of non-painful and painful visceral stimuli will be helpful in defining the pathway for perceiving pain in the IBS and other functional gut disorders, and for directing therapy appropriately.
TITLE: Regional Cerebral Activation with Visceral Pain in IBS Controls
INSTITUTE: NIDDK
RFA: Integrative Approaches to Study of GI Motility (DK-99-004)
P.I.: Howard R. Mertz, M.D.
INSTITUTION: Vanderbilt University, Nashville, TN
GRANT NO.: 1 R21 DK57047-01
KEYWORDS: Irritable bowel syndrome, limbic system, antidepressants
STUDY POP: Women and men
TYPE STUDY: Clinical
AMOUNT: $50,000
Recent data have demonstrated abnormal activation of limbic and paralimbic pain centers in irritable bowel syndrome (IBS) in response to rectal pain. Conversely, non-limbic pain centers including the VPL-thalamus, sensory cortex and insular systems are critical to the generation of symptoms in IBS. This project will compare the activity of the limbic system in IBS and controls in response to graded rectal distention (non-painful and painful). Activity in non-limbic pain centers and autonomic outflow centers will be compared between IBS and controls. Understanding the function of the limbic and non-limbic pain centers in healthy and disease states, and the effect of stress and medication on the pain experience may lead to improved pharmacological and behavioral therapies for visceral pain, including IBS.
TITLE: Cognitive Therapy as a Treatment for Irritable Bowel Syndrome (IBS)
INSTITUTE: NIDDK
RFA: Integrative Approaches to Study of GI Motility (DK-99-004)
P.I.: Edward Blanchard, PhD
INSTITUTION: State University of New York, Albany, NY
GRANT NO.: 1 R01 DK54211-01A1
KEYWORDS: Irritable bowel syndrome, cognitive therapy
STUDY POP: Women and men
TYPE STUDY: Clinical
AMOUNT: $100,000
Recent research suggests that cognitive therapy (CT) is highly effective (70-80% clinically improved) in the short-term (3 months) as a treatment for IBS. This application seeks to replicate and extend previous small-scale studies by conducting a controlled clinical trial of CT vs. a self-help support group as an attention placebo control and follow-up of the treated patients for at least 12 months.
TITLE: Randomized Clinical Trial of High Dose Immunoablative Cytoxan vs Monthly IV Cytoxan for Systemic Lupus Erythematosus
INSTITUTE: NIAMS
P.I.: Michelle Petri
INSTITUTION: Johns Hopkins University, Baltimore, MD
GRANT NO.: N01 AR-92243
KEYWORDS: Lupus, cytoxan, cyclophosphamide
STUDY POP: 90% women; 50% African-American, 40% Caucasian, 10% Hispanic
TYPE STUDY: Clinical
AMOUNT: $100,000
The natural history of Systemic Lupus Erythematosus (SLE) in their cohort is one of 1) relapsing remitting or 2) chronic activity, with only 17% of patients having periods of long quiescence. Over 75% of their African-American and 50% of their Caucasian patients have renal involvement. Over 50% suffer permanent damage in one or more organ systems, with over 15% having renal failure. For patients with severe SLE, especially with renal involvement, monthly IV pulse cyclophosphamide (500-1000 mg/m@ BSA) for 6 months followed by quarterly maintenance for 2 years was superior to high dose corticosteroid treatment. However, even monthly IV cyclophosphamide is not successful in all, and it has associated toxicity, especially premature ovarian failure. For this reason, this group has pioneered the use of high dose immunoablative cyclophosphamide (200 mg/kg) in 10 patients with severe SLE refractory to other treatments.
TITLE: Specialized Center of Research in Scleroderma
INSTITUTE: NIAMS
P.I.: Frank C. Arnett, MD
INSTITUTION: Univ of Texas Medical School, Houston, TX
GRANT NO.: 1 P50 AR4488-01
KEYWORDS: Scleroderma, systemic sclerosis, collagen, genetics, lung
STUDY POP: Native American, Choctaw, animal model (mice)
TYPE STUDY: Clinical and basic
AMOUNT: $414,000
The pathogenesis of systemic sclerosis (Ssc) or scleroderma is unknown. However there is evidence for both genetic and environmental influences. The interrelated projects in this specialized center offer a range of basic and clinical studies on scleroderma. 1) There is a human genome wide search for Ssc-associated genes using microsatellite mapping and beginning with candidate genes in a unique Native American population with high disease prevalence. 2)There will be an investigation of type I collagen gene regulation by transforming growth factor (TGF) beta and other factors in transgenic mice and the tight skin (TSK) murine model of fibrosis (and Ssc). 3) There will be characterization of pulmonary macrophage phenotypes and their roles in promoting fibrosis of the lung in early Ssc patients and the potential usefulness of early cytotoxic therapy in ameliorating lung damage. 4) Finally, there will be a large study of potential demographic, clinical, autoantibody and genetic predictors of disease outcomes in three ethnic groups (Caucasians, African-Americans and Mexican Americans).
TITLE: Immunologic Mechanisms in Lupus Nephritis
INSTITUTE: NIDDK
P.I.: Dr. Michael Madaio
INSTITUTION: University of Pennsylvania, Philadelphia, PA
GRANT NO.: 2 RO1 DK33694-15A1
KEYWORDS: Lupus nephritis, autoantibodies, glomerular
STUDY POP: Women and men and animals models (mice)
TYPE STUDY: Clinical and basic
AMOUNT: $50,000
A goal of this project is to identify the glomerular cell surface antigens for three nephritogenic lupus autoantibodies. The results should identify disease-relevant glomerular antigens for pathogenic lupus autoantibodies and provide insights into the overall pathogenic relevance of autoantibody-glomerular cell surface antigen interactions in lupus nephritis.
TITLE: Penn Autoimmunity Center of Excellence
INSTITUTE: NIAID
RFA: Autoimmunity Centers of Excellence (AI-98-010)
P.I.: A. M. Rostami, M.D., Ph.D.
INSTITUTION: University of Pennsylvania, Philadelphia, PA
GRANT NO.: 1 U19 AI46358-01
KEYWORDS: Multiple sclerosis, systemic lupus erythematosis, Interleukin-12, anti-CD20
STUDY POP: Children and adults
TYPE STUDY: Clinical and basic
AMOUNT: $75,000
This Center will have four projects (three clinical and one basic) There will be three clinical trials: 1) a Phase I/II trial on the use of antibody to Interleukin-12 for the treatment of multiple sclerosis; 2) a Phase I/II trial on the use of antibody Interleukin-12 in the treatment of inflammatory bowel disease; and 3) the use of anti-CD20 antibody for the treatment of systemic lupus erythematosus. The basic science component is focused on the elucidation of the mechanisms of autoimmunity and immuno-modulation related to the clinical trials.
TITLE: Denver Autoimmunity Center of Excellence
INSTITUTE: NIAID
RFA: Autoimmunity Centers of Excellence (AI-98-010)
P.I.: Brian L Kotzin, M.D.
INSTITUTION: University of Colorado Health Sciences Center, Denver, CO
GRANT NO.: 1 U19 AI46374-01
KEYWORDS: Type 1 diabetes, lupus nephritis, rheumatoid arthritis, autoimmune pdyendocrine syndrome II
STUDY POP: Children and adults
TYPE STUDY: Clinical and basic
AMOUNT: $75,000
Under this initiative, two clinical trials will be conducted. Clinical Project 1 will evaluate subcutaneous insulin vaccination to prevent the appearance anti-islet autoantibodies in infants at high risk for the development of autoantibodies and disease. Clinical Project 2 will test humanized anti-C5 mAbs in patients with active lupus nephritis. Three basic components will be studied: 1) to define the T-cell specificities and distribution of insulin-and islet antigen-reactive T-cells in murine models and patients with type 1 diabetes; 2) to determine the effects of inhibition of IL-18 and complement on cytokine production and disease in collagen-induced arthritis and rheumatoid synovium; and 3) to define the non-MHC genetic contributions to different clinical subtypes of autoimmune polyendocrine syndrome II.
TITLE: Autoimmunity: Treatment by Co-stimulatory Signal Blockade
INSTITUTE: NIAID
RFA: Autoimmunity Centers of Excellence (AI-98-010)
P.I.: Samia J. Khoury, MD
INSTITUTION: Brigham and Women's Hospital, Boston, MA
GRANT NO.: 1 U19 AI46130-01
KEYWORDS: Multiple sclerosis, inflammatory bowel disease, psoriasis, CD 40L
STUDY POP: Women and men; Animal model
TYPE STUDY: Clinical and basic
AMOUNT: $75,000
Projects supported under this initiative will focus on the study of therapy of autoimmune diseases by blocking co-stimulatory signals, focused on the CD40-CD40L pathway. The human diseases of major focus are multiple sclerosis, inflammatory bowel disease, and psoriasis. All are organ specific diseases where T-cells appear to be essential in initiating the immune response and lead to the particular disease pathology. Four projects are supported. The overall goals of two projects are to study the efficacy and safety of anti-CD40L therapy in multiple sclerosis and in inflammatory bowel disease. The immunologic changes associated with anti-CD40L therapy will be studied in patients with multiple sclerosis and inflammatory bowel disease. Another project will study the immune mechanisms of psoriasis. Immunologic investigations will help to identify surrogate markers for disease activity.
TITLE: Autoimmunity Centers of Excellence at Columbia University
INSTITUTE: NIAID
RFA: Autoimmunity Centers of Excellence (AI-98-010)
P.I.: Leonard Chess, MD
INSTITUTION: Columbia University College of Physicians & Surgeons, New York, NY
GRANT NO.: 1 U19 AI46132-01
KEYWORDS: Multiple sclerosis, type 1 diabetes, scleroderma, systemic lupus erytheamotosus, rheumatoid arthritis
STUDY POP: Children and adults
TYPE STUDY: Clinical
AMOUNT: $75,00
The investigators hypothesize that there are four principal events involved in the immunopathogenesis of rheumatoid arthritis, systemic lupus erytheamotosus, multiple sclerosis, type 1 diabetes, and scleroderma: 1) predisposing genes establish a T-cell repertoire capable of recognizing self peptides; 2) previously tolerant autoreactive CD4+ T-cell clones become activated and expand to change the T-cell repertoire to reflect autoreactive effector T-cells; 3) regulatory mechanisms, including the activation of TH1 and TH2 CD4+ T-cell subsets as well as those involving CD8 T-cell fail, through processes such as clonal deletion or changes in the cytokine milieu; and 4) pathogenic autoantibodies develop through cognitive T-cell B-cell interactions which effect tissue injury. In these diseases one would predict that reducing the clonal expansion of relevant autoreactive T-cell by blockade of T-cell receptor signaling or interruption of the CD40 ligand-dependent pathway could down modulate disease activity.
TITLE: Mechanism of Copaxone Therapy in MS
INSTITUTE: NIAID
RFA: Hyperaccelerated Award/Mechanisms in Immune Disease Trials (AI-98-006)
P.I.: Michael Racke
INSTITUTION: UT Southwestern Medical Center at Dallas, TX
GRANT NO.: 1 R01 A147133-01
KEYWORDS: Multiple sclerosis, MS, Copaxone
STUDY POP: Women
TYPE STUDY: Clinical
AMOUNT: $200,000
Multiple Sclerosis (MS) patients are categorized on the basis of whether they have clearly defined relapses, relapsing-remitting MS (RRMS), or whether they are progressing. Progressing patients are further divided on the basis of whether they initially experienced relapses (secondary progressive MS), or whether they deteriorate slowly without evidence of relapses or remissions (primary progressive MS). One question is whether the patients with primary progressive MS (PPMS) differ from the patients with secondary progressive MS or whether they represent different aspects of a clinical pathologic spectrum. This group has shown that patients with RRMS have myelin-reactive T cells that are less dependent upon costimulation than myelin-reactive T cells from normal controls. The goal is to test the hypothesis that myelin-reactive T cells in patients with PPMS can be distinguished from naive myelin-reactive T cells by a lack of dependence upon costimulation for activation and that costimulatory requirements for these myelin-reactive T cells change during the course of disease. Glatiramer acetate (Cop-1, Copaxone) has previously been shown to reduce the number of relapses in RRMS and is now being tested for efficacy in patients with PPMS. It is unclear how Copaxone exerts its therapeutic effect. This study will determine whether Glatiramer alters cytokine secretions of myelin-reactive T cells and the T cell repertoire in PPMS.
TITLE: Immune Mechanisms of Anti-CD40L Trial in Systemic Lupus Erythematosis
INSTITUTE: NIAMS
RFA: Hyperaccelerated Award/Mechanisms in Immune Disease Trials (AI-98-006)
P.I.: Syamal Datta, MD
INSTITUTION: Northwestern University, Evanston, IL
GRANT NO.: 1 R01 AR46309
KEYWORDS: Lupus, anti-CD40L
STUDY POP: Women and men
TYPE STUDY: Clinical
AMOUNT: $50,000
CD40L is hyper-expressed by lupus B cells for abnormally prolonged periods, thus sustaining the production of pathogenic autoantibodies. A brief therapy of three injections of anti-CD40L in one week into lupus mice prevents the development of nephritis for more than a year. This clinical trial provides an opportunity to study the effects of anti-CD40L on the human immune system in vivo, particularly on the cells participating in the chronic ongoing autoimmune response in lupus patients. This study will examine the status of autoimmune T and B cells that are involved in the production of pathogenic anti-nuclear autoantibodies, before, during, and after therapy .
TITLE: T-Cell Reconstitution After Stem Cell Autografting
INSTITUTE: NIAID
RFA: Hyperaccelerated Award/Mechanisms in Immune Disease Trials (AI-98-006)
P.I.: Jan Storek, MD, PhD
INSTITUTION: Fred Hutchinson Cancer Research Center, Seattle, WA
GRANT NO.: R01 A146108-01
KEYWORDS: T cells
STUDY POP: Women and men: Severe lymphocytopenic patients with autoimmune disease who have received high dose treatments
TYPE STUDY: Clinical
AMOUNT: $60,000
The goal is to evaluate how the T cell repertoire is reestablished in patients with autoimmune diseases who have undergone lymphocytopenia from high dose chemotherapy/radiation plus anti-thymocyte globulin followed by reconstitution with autologous transplantation of hemopoietic (CD34+) precursors. The hypothesis is that in young individuals, a substantial number of regenerating T cells originate from hemopoietic progenitors whereas in older individuals, the vast majority of T cells originate from the expansion of preexisting T cells. The techniques used will be spectratyping, sequencing of the T cell receptor genes withing a single spectratyping band and quantifying T cells that contain T cell receptor-rearrangement circles.
TITLE: Molecular Mimicry Between Yersinia enterocolitica and TSHR
INSTITUTE: NIEHS
RFA: Environment/Infection/Gene Interactions in Autoimmune Diseases (ES-99-003)
P.I.: Bellur Prabhakar, PhD
INSTITUTION: University of Illinois at Chicago, IL
GRANT NO.: R21 ES 10302-01
KEY WORDS: Thyrotropin receptor, mimicry, Yersinia entercolitica, Graves disease
STUDY POP: Animal model (mice)
TYPE STUDY: Basic
AMOUNT: $50,000
Studies from this lab have shown that there is molecular mimicry between a chromosomally encoded low molecular weight lipoprotein (LP) of Yersinia enterocoliticia and the thyrotropin receptor. This group has developed a highly reproducible animal model for Graves Disease (GD) using BALB/c mice. The first aim is to clone, express, purify and characterize the LP from Y. enterocolitica. Aim two is to induce immune responses to TSHR in strains of mice that are susceptible and resistant to experimental TSHR mediated autoimmune disease.
TITLE: Mechanisms of Lupus Induction in L-Canavanine
INSTITUTE: NIEHS
RFA: Environment/Infection/Gene Interactions in Autoimmune Diseases (ES-99-003)
P.I.: Patricia Fraser
INSTITUTION: Center for Blood Research, Boston, MA
GRANT NO.: 1 R21 ES10295-01
KEYWORDS: Systemic Lupus Erythematosus (SLE), estrogen receptors, androgen receptor, organochlorines
STUDY POP: Women, SLE case/control study
TYPE STUDY: Clinical
AMOUNT: $50,000
The sex difference in estrogen exposure may explain the sex imbalance in Systemic Lupus Erythematosus (SLE) risk. The specific aims of this proposal are to: 1) Determine androgen receptor (AR), estrogen receptor (ER), and cytochrome P450 genotypes in SLE subjects and controls by polymerase chain reaction based methodologies in a large SLE case/control study; and 2) Determine the relative importance of genetic markers in aim one with endogenous and exogenous estrogens and with exposure to organochlorines in predicting risk of SLE.
TITLE: Characterizing Microfibril Abnormalities in Scleroderma
INSTITUTE: NIAMS
RFA: Target Organ Damage in Autoimmune Diseases (AR-99-003)
P.I.: Dianna Milewicz
INSTITUTION: University of Texas Health Science Center
GRANT NO.: 1 R01 AR46718-01
KEYWORDS: Scleroderma, microfbril, tolerance, system sclercois
STUDY POP: Women and Men: Fibroblast cell strains from ethnically diverse individuals with Scleroderma & their relatives
TYPE STUDY: Basic clinical
AMOUNT: NA
Progressive fibrosis of the skin and internal organs is the pathologic hallmark of scleroderma or systemic sclerosis (Ssc). The etiology of Ssc is unknown but both genetic and environmental factors have been proposed. Evidence from genetic studies in affected Choctaw patients, indicates a role for fibrillin-1. Based on preliminary studies, the investigators hypothesize that patients with Ssc have a genetic defect that leads to degradation of fibrillin-1-containing microfibrils in tissues. The degradation of microfibrils causes release of transforming growth factor beta from sites of sequestration of microfibrils. In addition the release of microfibril fragments leads to an autoimmune response and the generation of antifibrillin-1 antibodies.
TITLE: Vasculopathy, Apoptosis and Autoimmunity
INSTITUTE: NIAMS
RFA: Target Organ Damage in Autoimmune Diseases (AR-99-003)
P.I.: Joseph Ahearn
INSTITUTION: University of Pittsburgh, PA
GRANT NO.: 1 R01 AR4764-01
KEYWORDS: Scleroderma, tolerance, nucleolar autoantigens, systemic sclerosis
STUDY POP: Women and Men: Cells and Fluids from ethnically diverse individuals with scleroderma and controls
TYPE STUDY: Basic clinical
AMOUNT: NA
The central hypothesis of this proposal is that chronic ischemia reperfusion injury in patients with systemic sclerosis not only generates immunocryptic epitopes within nucleolar autoantigens of cutaneous origin, but it also generates complement ligands that provide the molecular adjuvant required to break immune tolerance.
TITLE: Growth Factor Responses in Rheumatoid Synovium
INSTITUTE: NIAMS
RFA: Target Organ Damage in Autoimmune Diseases (AR-99-003)
P.I.: James Thomas
INSTITUTION: Vanderbilt University, Nashville, TN
GRANT NO.: 1 R01 AR46732-01
KEYWORDS: Rheumatoid arthritis, synovuim, signal transaction
STUDY POP: Women and Men: Synovial cells from ethnically diverse individuals with rheumatoid arthritis
TYPE STUDY: Basic clinical
AMOUNT: NA
The general goal of the proposed research is to study aberrant signal transduction mechanisms leading to growth dysregulation in rheumatoid arthritis (RA) synovial cells. This project will identify signal transduction and gene activation pathways that reprogram rheumatoid synoviocytes for a synergistic response to fibroblast growth factor and transforming growth factor B and then investigate how these events are coupled to receptor interactions and the intracellular fate of fibroblast growth factor (FGF-1). The approaches employed are designed to identify new targets for intervention in progressive joint destruction and a novel technique using cell permeable peptides. These studies are relevant not only to understanding progressive joint destruction in RA but are also of importance to a variety of disorders characterized by fibroproliferation including pulmonary fibrosis, interstitial nephritis, and chronic allograft rejection.
TITLE: Cytokine Regulation of RA Synoviocyte
INSTITUTE: NIAMS
RFA: Target Organ Damage in Autoimmune Diseases (AR-99-003)
P.I.: Lionel Ivashkiv
INSTITUTION: Hospital for Special Surgery, New York, NY
GRANT NO.: 1 R01 AR46713-01
KEYWORDS: Rheumatoid arthritis, synoviom, anti-inflammatory cytokines
STUDY POP: Women and Men: Synovial fibroblasts from ethnically diverse individuals with rheumatoid arthritis
TYPE STUDY: Basic clinical
AMOUNT: NA
One characteristic of rheumatoid arthritis (RA) synovitis is the consistently high expression of immunosuppressive and anti-inflammatory cytokines. One important issue is why abundant expression of these anti-inflammatory cytokines does not lead to resolution of inflammation in RA. The proposed research will examine how the deactivation of synovial inflammation is blocked. Greater understanding of mechanisms that block anti-inflammatory cytokine action will be helpful in designing novel therapeutic approaches to shift the balance of cytokine activity to limit inflammation and progression of disease.
TITLE: Modulation of T Cell Responses to "Shared Epitope" Peptides in Rheumatoid Arthritis
INSTITUTE: NIAMS
RFP: Pilot Trials on Innovative Therapies for Rheumatic and Skin Diseases (RFP NIH-NIAMS-BAA-99-02)
P.I.: Salvatore Albani
INSTITUTION: University of California, San Diego, CA
GRANT NO.: 1 N01 AR92241
KEYWORDS: Rheumatoid arthritis, DNAj peptides, T cell response(s)
STUDY POP: Patients with early RA
TYPE STUDY: Clinical
AMOUNT: NA
This is a Phase II trial of oral administration of a small peptide (DNAj peptide) which bears homology (shared epitope) to the class II molecules in rheumatoid arthritis (RA). Patients with early RA (5 years or less duration, not exposed to MTX or will be selected based on their immune reactivity with DNAj peptides. Primary outcome is the ACR 20, a standard measure of outcome in RA trials.
TITLE: Multi-Center Phase II Trial of Oral Type I Bovine Collagen in Scleroderma
INSTITUTE: NIAMS
RFP: Pilot Trials on Innovative Therapies for Rheumatic and Skin Diseases (RFP NIH-NIAMS-BAA-99-02)
P.I.: Arnold Postlethwaite
INSTITUTION: University of Tennessee, Memphis, TN
GRANT NO.: N01 AR92242
KEYWORDS: Systemic sclerosis, scleroderma, collagen
STUDY POP: Women and Men
TYPE STUDY: Clinical
AMOUNT: NA
The investigators propose to conduct a multi-center Phase II study to test the efficacy of oral collagen in systemic sclerosis (Ssc). The primary end point is change in the Modified Rodman Skin Score. Other outcomes include pulmonary function tests, creatinine levels, and scleroderma questionnaires. In addition, studies are proposed to explore the underlying mechanisms that mediate a potential effect of oral collagen peptides in the immune pathogenesis of SSc.
TITLE: New Imaging Technologies for Rheumatoid Arthritis
INSTITUTE: NIAMS
RFA: New Imaging Technologies for Autoimmune Diseases (AI-99-004)
P.I.: Donald Kimpel
INSTITUTION: Louisiana State University Medical Center, Shreveport, LA
GRANT NO.: 1 R01 AR 46976-01
KEYWORDS: Rheumatoid arthritis, imaging in vivo
STUDY POP: Animal model (mice)
TYPE STUDY: Basic
AMOUNT: NA
Intravital microscopy provides a technique for imaging in vivo the microvasculature at high magnifications. Fluorescene-labeled cells can be visualized traveling through the microvasculature, and the rate of movement can be assessed by offline analyses. These techniques will be applied to animal models of rheumatoid arthritis (RA) transgenic for expression of selected cell types. To bridge the gap between animal studies and human RA, they will develop a system to image in vivo human leukocyte and human synovium interactions by using the humanized SCID model system.
TITLE: Combining N-of-1 Trials to Assess Fibromyalgia Therapies
INSTITUTE: NIAMS
RFA: Basic and Clinical Research on Fibromyalgia (AR-98-006)
P.I.: Deborah Zucker
INSTITUTION: New England Medical Center, Boston, MA
GRANT NO.: 1 R01 AR45416-01A1
KEYWORDS: Fibromyalgia, amitriptyline, fluoxetine
STUDY POP: Women, fibromyalgia patients
TYPE STUDY: Clinical
AMOUNT: $147,927
Firbomyalgia is a common rheumatologic condition and treatment is a challenge. A recent study reported that combination therapy of amitriptyline and fluoxetine resulted in significantly greater improvement in patients' symptoms as compared with either drug alone. This project will use patient focused N-of-1 trials and combines these trials' results to obtain population estimates of treatment effectiveness. This will extend into community practice to enable comparison of center-based and practice-based results. This will also provide a methodological tool to obtain data from community physicians in practice-based settings.
TITLE: Mid-America Adolescent STD Cooperative Research Center
INSTITUTE: NIAID
P.I.: Dr. Donald Orr
INSTITUTION: Riley Hospital, Indianapolis, IN
GRANT NO.: 1 U19 AI43924 01
KEYWORDS: Infectious diseases, sexually transmitted diseases, STD, multi-disciplinary, prevention
STUDY POP: Adolescents
TYPE STUDY: Clinical
AMOUNT: $50,000
Sexually transmitted diseases (STD) produce very serious outcomes in women, regardless of race, and often affect their infants as well. In addressing the racial health disparities in the occurrence of STD, NIAID supports Sexually Transmitted Diseases Cooperative Research Centers (STDCRCs), which provide a multi-disciplinary approach to research in the area of STD by bringing together basic science, clinical and epidemiological research, and behavioral intervention strategies for the prevention and control of STD.
TITLE: Study of Women's Health Across Nation II: (SWAN II>
INSTITUTE: NIA
RFA: Menopause and Health in Aging women
P.I.: Dr. Sonai McKinlay, Coordinating Center, Multiple sites and investigators plus a lab
INSTITUTIONS: New England Research Institute, Watertown, MA
GRANT NO.: 2 UO1 AG12553-06
KEYWORDS: Menopause, aging, hormones, minorities, risk factors, disease
STUDY POP: Women, peri- and menopausal, older African-American, Hispanic
TYPE STUDY: Clinical
AMOUNT: $600,000 NIA and $200,000 NINR
SWAN consists of both cross sectional and longitudinal studies on the natural history of menopause and a characterization of endocrinology/physiology of premenopause. Five ethnic groups are included - Caucasian, African American, Hispanic, Chinese, and Japanese. There are 7 sites across the country - Boston, Pittsburgh, Chicago, Michigan, UCLA, UC Davis and New Jersey. For the cross-sectional study, there are approximately 16,000 women enrolled ranging in age from 40-55 years to determine the age of menopause. The longitudinal study has approximately 3150 women (450 at each site) between the ages of 42-52 to determine menopause-specific physiological changes and their predictors and the impact of menopause on subsequent disease. Measurements are being made of the major reproductive axis hormones (LH, FSH, estradiol, progesterone, and testosterone), adrenal markers of aging (DHEAs), other endocrine markers (TSH, sex hormone binding globulin [SHBG]) and new ovarian markers which have the potential to define the menopausal transition and the postmenopause.
TITLE: Botanical Dietary Supplements for Women's Health
INSTITUTE: ODS
RFA: Centers for Dietary Supplements Research: Botanicals (OD-99-007)
P.I.: Norman Farnesworth
INSTITUTION: University of Illinois at Chicago, IL
GRANT NO.: 1P50 AT00155-01
KEYWORDS: Botanicals, menopause, black cohosh, red clover
STUDY POP: Women, post-menopausal women aged 40-50 years; male and female rats
TYPE STUDY: Clinical and basic
AMOUNT: $250,000
This multi-disciplinary team of investigators will focus on the study of the safety and efficacy of botanicals used to treat women for menopause. Studies will address mechanisms of action, identification of active compounds, and characterization of metabolism, bioavailability and pharmacokinetics of active species in these botanicals. The research component will consist of the following: 1) A pharmacognosy project to carry out standardization of botanical dietary supplements and structure elucidation of active compounds; 2) Isolate active compounds for structure elucidation, and then to determine the mechanism(s) of action of botanicals; 3) Study the metabolism, absorption and toxicity of active compounds in botanicals including immunotoxicity; and 4) Carry out phase I and II clinical trials of black cohosh (Cimicifugai racemosa) and red clover (Trifolium pratense).
TITLE: Continuous Low-Dose Hormone Replacement Therapy Combined
INSTITUTE: NIAMS
with Alendronate in Postmenopausal Women
P.I.: Robert Recker, MD
INSTITUTION: Creighton University, Omaha, NE
GRANT NO.: N01 AR-92237
KEYWORDS: Hormone replacement therapy, alendronate, postmenopausal women, bone mineral density
STUDY POP: Women aged 60 years and older and estrogen deprived for at least 6 months
TYPE STUDY: Clinical
AMOUNT: $100,000
The specific aim is to conduct a 3½ year, randomized, double-blind, controlled trial of low-dose 0.625 mg/d, continuous hormone replacement therapy (HRT) combined with alendronate, 10 mg/d (ALN) in three groups (72/group) of estrogen-deprived postmenopausal women over age 60. Group 1 will receive low-dose HRT, Group 2 will receive ALN, and Group 3 will receive both low-dose HRT and ALN. Calcium and vitamin D supplements will be given to persons in all three groups. The primary outcome measures will be spine bone mineral density and total hip bone mineral density measured by dual energy X-ray absorptiometry. Secondary outcome measures will be total body bone mineral content and forearm bone mineral content.
MENTAL HEALTH
TITLE: Genes, Environment, and Maternal Adjustment
INSTITUTE: NIMH
P.I.: Dr. David Reiss
INSTITUTION: George Washington University Medical Center, Washington, DC
GRANT NO.: R01 MH54610
KEYWORDS: Genes, maternal adjustment, mental health
STUDY POP: Women, men and children, (Swedish Twin Registry)
TYPE STUDY: Clinical
AMOUNT: $20,000
This study of 300 twin pairs, identified through the Swedish Twin Registry, their mothers, spouses and adolescent children, tests models of the interaction of direct and indirect and genetic and environmental influences on well-being. Genetic and social data are available for this cohort. Outcomes include personality, family relationships, characteristics of the husband. In cooperation with an international team, the study examines how a combination of family relationships and genetic factors affect positive and negative measures of mental health.
TITLE: A Prospective Study of the Mental Health of Black Women
INSTITUTE: NIMH
P.I.: Dr. Margaret Ensminger
INSTITUTION: Johns Hopkins School of Hygiene and Public Health, Baltimore, MD
GRANT NO.: 1 R01 MH 52336 01
KEYWORDS: Mental health, African American, behavior
STUDY POP: Women, African American
TYPE STUDY: Clinical
AMOUNT: $35,000
This project re-interviews a cohort of older African American women who were originally interviewed in 1966-67. At that time, each had a child in the first grade. Now the women range in age from 49-79. The study uses a framework both to model the continuity and change in these women's roles and their psychological and physical health since 1967.
TITLE: Women's Mental Health (Brain Abnormalities)
INSTITUTE: NIMH
P.I.: Dr. Jill Goldstein
INSTITUTION: Harvard, Boston, MA
GRANT NO.: 1 RO1 MH56956 02
KEYWORDS: Mental health, schizophrenia, brain, sexual dimorphism, gender differences, risk factors
STUDY POP: Women and men, their families with schizophrenia
TYPE STUDY: Clinical
AMOUNT: $36,080
Although sex differences in the expression of schizophrenia have been reported, no study has attempted to explain these differences as a function of sexual dimorphism of the brain. This study will test the hypothesis that sex is a risk factor for brain abnormalities in schizophrenia by examining families with multiple ill members with magnetic resonance imaging (MRI). Images will be analyzed using a system that parcels the entire brain into defined areas.
TITLE: Sex Differences in Self-Evaluation: Social Factors
INSTITUTE: NIMH
P.I.: Eva Pomerantz, PhD
INSTITUTION: University of Illinois, Champaign, IL
GRANT NO.: R29 MH57505-01A2
KEYWORDS: Gender socialization, self-evaluation, depression
STUDY POP: Girls and boys
TYPE STUDY: Clinical
AMOUNT: $26,777
Girls are more likely than boys to possess self-evaluative mechanisms that may heighten vulnerability to depressive and anxiety symptoms. It is hypothesized that culturally held gender stereotypes may cause parents to be more controlling in certain behavioral domains with girls than with boys. This pattern of gender socialization is expected to lead girls to be more likely than boys to possess self-evaluative mechanisms that heighten vulnerability to depressive and anxiety symptoms.
TITLE: Black Rural and Urban Caregivers Mental Health Functioning
INSTITUTE: NIA
P.I.: Lethia Chadia
INSTITUTION: Washington University, St Louis, MO
GRANT NO.: 1 R01 AG15962-01A1
KEYWORDS: Mental health, caregivers, African American, rural, urban
STUDY POP: Women, African American
TYPE STUDY: Clinical
AMOUNT: $150,000
This study will assess the mental health and social functioning of rural and urban African-American women who provide unpaid care to an elder (65 years and older) by using a cross-sectional research design and random sample of elders. This study will identify the type and quality of caregivers' formal and informal service use. Data will be obtained through personal interviews.
TITLE: Effects on Children of Treating Maternal Depression
INSTITUTE: NIMH
P.I.: Dr. Anne Riley
INSTITUTION: Johns Hopkins University, Baltimore, MD
GRANT NO.: 5 R01 MH58384-02
KEYWORDS: Mental health, maternal depression, depression, children, environment
STUDY POP: Women and children - African-American, Caucasian, Hispanic
TYPE STUDY: Clinical
AMOUNT: $50,000
Maternal depression has devastating effects on the mental and physical health of children. This project will study the influence of treating maternal depression on children ages 5-11. This project will study 150 elementary-school aged children whose mothers are depressed (50 Hispanic, 50 African American and 50 Caucasian) and 50 comparable children whose mothers are not depressed. Their mental health and functioning will be assessed by natural raters in their environments over a two-year time period that will link child functioning, symptomatology, and psychiatric disorders to mothers' symptomatology, parenting behavior, and family environment.
TITLE: Doxycycline Effect on Osteoarthritis Progression
INSTITUTE: NIAMS
P.I.: Kenneth Brandt, MD
INSTITUTION: Indiana University School of Medicine, Indianapolis, IN
GRANT NO.: 5 R01 AR43348-03
KEYWORDS: Osteoarthritis, doxycycline
STUDY POP: Women
TYPE STUDY: Clinical
AMOUNT: $200,000
Osteoarthritis (OA) of the knee is the most common cause of chronic disability in this country. This group has shown that prophylactic oral administraiton of doxycycline (doxy) markedly reduces the severity of cartilage damage in a canine model of OA; even when therapy was initiated after cartilage lesions were established, a protective effect was apparent. Similar results have been noted in guinea pig and rabbit models of OA. The effect is associated with reduction in the levels of collagenase and gelatinase in the OA cartilage. Based on the encouraging data in animal modesl of OA, a randomized-placebo-controlled 30-month clinical trial will examine the effect of this drug and its ability to prevent the progression of early knee osteoarthritis in women.
TITLE: Glucocorticoids Alter the Birth and Death of Osteoblasts
INSTITUTE: NIAMS
P.I.: Robert Weinstein
INSTITUTION: University of Arkansas for Medical Sciences, Little Rock, AR
GRANT NO.: RO1 AR 46191 01
KEYWORDS: Glucocorticoids, osteoblasts, alendronate, parathyroid hormone
STUDY POP: Women and men, animal model (mice)
TYPE STUDY: Clinical and basic
AMOUNT: $100,000
This study will characterize the effects of chronic glucocorticoid excess on several aspects of bone physiology. Patients with glucocorticoid-induced bone loss will be included. The effect of alendronate (Fosamax) and parathyroid hormone will be tested in mice for efficacy in ameliorating the effect of glucocorticoids.
TITLE: Perimenopausal Mobilization of Lead from Bone
INSTITUTE: NIEHS
P.I.: Susan Muldoon, PhD, MPH
INSTITUTION: University of Florida, Gainesville, FL
GRANT NO.: 5 R29 ES07052-05
KEYWORDS: Bone loss, blood lead levels, menopause
STUDY POP: Women, entering menopause
TYPE STUDY: Clinical
AMOUNT: $43,878
Cross-sectional epidemiologic data from the second National Health and Nutrition Examination Survey (NHANESII) have shown significantly higher blood lead levels in postmenopausal women than in premenopausal women, suggesting that bone lead may be mobilized via osteoporosis bone loss in older women. The investigators will test the hypothesis that menopausal bone loss is associated with increased blood lead levels in women participating in the healthy Women's Lifestyle Project (WHLP), a randomized clinical trial of weight and cholesterol reduction in 500 women. This study will make measurements of blood lead levels and bone mineral density on an annual basis as this cohort enters menopause. An epidemiologic analysis of data from this unique cohort will help answer important questions about bone lead release in older women.
TITLE: Estrogen Induced Hippocampal Seizure Susceptibility
INSTITUTE: NINDS
P.I.: Catherine Woolley
INSTITUTION: Northwestern University, Evanston, IL
GRANT NO.: 5 R29 MS37324-02
KEYWORDS: Epilepsy, hippocampus, estradiol
STUDY POP: Animal model (rats)
TYPE STUDY: Basic
AMOUNT: $70,000
A significant proportion of women with epilepsy experience increased seizure frequency during phases of the menstrual cycle in which estradiol levels are elevated. This is termed catemenial epilepsy. Animal models of epilepsy also demonstrate that estradiol increases seizure susceptibility. Previous work in the adult female rat has shown that estradiol induces new dendritic spines and axospinous synapses on CA1 pyramidal cells in the hippocampus, a key brain structure in the generation and propagation of seizure activity. Furthermore, estradiol-induced dendritic spines and synapses are correlated with increased excitability of hippocampal neurons and decreased hippocampal seizure threshold. This correlation suggests that estradiol-induced seizure susceptibility in women with catamenial epilepsy may be due, at least in part, to hormone-mediated alterations in hippocampal synaptic connectivity. The studies in this proposal will use the adult female rat to test the hypothesis that estradiol facilitates seizure activity through alteration of hippocampal synaptic structure and physiology.
TITLE: Clinical and Experimental Study of Human Obesity
INSTITUTE: NIDDK
P.I.: Dr. Albert Stunkard
INSTITUTION: University of Pennsylvania, Philadelphia, PA
GRANT NO.: 2 RO1 DK56251-03
KEYWORDS: Eating disorders, obesity, body size, fat percentage, risk factors, mothers
STUDY POP: Children
TYPE STUDY: Clinical
AMOUNT: $100,000
This project is a longitudinal study of 78 children, from 3-5 years of age, from either obese or non-obese mothers. The goal is to examine a group of variables related to food intake and energy expenditure along with measures of body size or composition, utilizing not only weight and length but measures of skinfold thickness and percent fat by dual energy x-ray absorptiometry and body water, and isotope dilution measures. The study has already found that the two independent measures of energy intake at three months of age predict body size and composition at one year of age and discounted the belief that a low total energy expenditure and maternal obesity predict body size and composition at one year of age. This study will continue to search for risk factors for obesity in the early childhood years.
TITLE: A Mentor-Based Approach to Long Term Weight Loss
INSTITUTE: NIDDK
RFA: Innovative Approaches to Prevention of Obesity (DK-99-010)
P.I.: John M Jakicic, PhD
INSTITUTION: The University of Kansas Center for Research, Lawrence, KS
GRANT NO.: 1 R01 DK57384-01
KEYWORDS: Obesity, mentor, long-term weight loss
STUDY POP: Women, overweight adult
TYPE STUDY: Clinical
AMOUNT: $60,000
The primary goal of this study is to examine the effect of a mentor-based intervention on long-term weight loss in overweight adult women. The primary analysis will focus on the effect of this intervention on long-term weight loss in women receiving a mentor-based intervention, with additional analysis focusing on the effect of this intervention on long-term weight loss in women functioning as mentors in this study. The investigators hypothesize that a mentor-based intervention will improve long-term weight loss in both mentors and mentor-recipients compared to individuals receiving a standard non-mentored-based weight loss intervention. It is believed that a mentor-based intervention will lead to improvements in the long-term treatment of obesity.
TITLE: Weight Control in Peri- and Early Postmenopausal Women
INSTITUTE: NIDDK
RFA: Innovative Approaches to Prevention of Obesity (DK-99-010)
P.I.: Susan Racette, PhD
INSTITUTION: Washington University, St. Louis, MO
GRANT NO.: 1 R01 DK5746-01
KEYWORDS: Obesity, perimenopausal, postmenopausal
STUDY POP: Women; perimenopausal and early postmenopausal at risk for obesity
TYPE STUDY: Clinical
AMOUNT: $60,000
The primary aim of this study is to assess the effectiveness of a modest lifestyle intervention program on preventing gains in body weight, whole body fat mass, and abdominal adipose tissue during a 2-year period in perimenopausal and early postmenopausal women who are at risk for obesity. The second aim is to determine the effects of the intervention on daily physical activity, which will be calculated from total daily energy expenditure and resting metabolic rate, as determined by the doubly labeled water method and indirect calorimetry, respectively. A randomized, controlled trial will be used to evaluate the intervention in female employees of a large Midwestern medical center.
TITLE: Weight Gain in Pregnancy: Staying the Range
INSTITUTE: NIDDK
RFA: Innovative Approaches to Prevention of Obesity (DK-99-010)
P.I.: Christine Olson, PhD
INSTITUTION: Cornell University, Ithaca, NY
GRANT NO.: 1 R01 DK57439-01
KEYWORDS: Pregnancy, weight gain
STUDY POP: Women, pregnant patients
TYPE STUDY: Clinical
AMOUNT: $60,000
The proposed project focuses on primary prevention of obesity in women by slowing the accumulation of weight in the childbearing years. The long-term goal of the proposed study is to decrease the amount of weight retained in the postpartum period by lower income, rural white women who enter pregnancy with normal or high body mass indices. This goal will be addressed by encouraging women to gain an amount of weight during pregnancy that is within the appropriate ranges recommended by the Institute of Medicine (IOM). The project specifically aims to decrease by 50% the proportion of women who gain above the upper limit of the appropriate IOM range. The project will be implemented in a primary health care setting. The study has a prospective cohort design with an historical control group.
TITLE: Internet-Aided Prevention of Pregnancy-Induced Obesity
INSTITUTE: NIDDK
RFA: Innovative Approaches to Prevention of Obesity (DK-99-010)
P.I.: Jennifer Lovejoy, PhD
INSTITUTION: Pennington Biomedical Research Center, Baton Rouge, LA
GRANT NO.: 1 R01 DK57446-01
KEYWORDS: Pregnancy, obesity, African American
STUDY POP: Women, 56 African American previously non-obese postpartum with at least 25 pounds of excess weight after pregnancy
TYPE STUDY: Clinical
AMOUNT: $60,000
This application targets the prevention of pregnancy-associated obesity in African-American women. The overall goal of this proposal is to evaluate the effectiveness of traditional vs. Internet-aided behavior modification for weight management in postpartum African-American women. The Internet-based intervention will be used in face-to-face group sessions to allow for more extensive behavioral feedback. The research will address the primary hypothesis that the use of the Internet-aided behavioral intervention will be more effective than traditional behavioral intervention programs in preventing excess postpartum weight retention.
TITLE: Primary Care Office Management of Obesity
INSTITUTE: NIDDK
RFA: Innovative Approaches to Prevention of Obesity (DK-99-010)
P.I.: Pamela Davis Martin, PhD
INSTITUTION: Pennington Biomedical Research Center, Baton Rouge, LA
GRANT NO.: 1 R01 DK57476-01
KEYWORDS: Obesity, African-American, patient-centered intervention, weight loss
STUDY POP: Women, low income African-American
TYPE STUDY: Clinical
AMOUNT: $60,000
This randomized, two-arm treatment study will use culturally sensitive educational materials by trained primary care physicians. It will compare physician-directed education (standard care group) to another group who receive customized education plus patient-centered messages by primary care physicians. It will attempt to determine whether a physician-delivered patient-centered intervention is more effective than standard care in regard to prevention of weight gain and achievement of weight loss at six months. It will also examine whether the groups differ in regard to weight maintenance at 12 and 18 months follow-ups. It is hypothesized that patients in the patient-centered group will demonstrate less weight gain, more weight loss at six months, greater maintenance of weight loss at 12 and 18 months as well as dietary and physical activity improvement throughout the observation period than patients receiving standard care.
RFA: Study of Health Outcomes of Weight-Loss [SHOW] (DK 98-019)
INSTITUTE: NIDDK
P.I.: N/A
INSTITUTION: N/A
GRANT NO.: N/A
KEYWORDS: Type 2 diabetes, weight loss, cardiovascular, cerebrovascular
STUDY POP: Obese, type 2 diabetics
TYPE STUDY: Clinical
AMOUNT: $454,343
The goal of this RFA is to select clinical centers to participate in planning and implementing a randomized, controlled, multi-center clinical trial in obese type 2 diabetic patients. This trial will examine the effects of interventions designed to produce sustained weight loss and a range of health outcomes. The primary outcome is anticipated to be differences in progression of atherosclerosis. This study will examine the effects of the interventions on cardiovascular and cerebrovascular event rates, cardiovascular and all-cause mortality, cardiovascular risk factors, glycemic control, and other outcomes. There will be three arms: 1) Community Care-The primary care physician will be given standard of care recommendations for treatment of obesity and comorbid conditions such as diabetes; 2) Intensive Lifestyle Intervention - Patients will undergo a long-term behavioral treatment program that includes dietary modification, increased physical activity, and behavioral therapies designed to enhance weight loss and weight maintenance. Obesity related comorbid conditions will be treated as in group 1; 3) Intensive Lifestyle Intervention plus Weight Loss Medication - Medication will be added to the intensive lifestyle intervention in an attempt to enhance long-term weight maintenance. Comorbid conditions will be treated as in group 1.
TITLE: Research on Low Back Pain & Common Spinal Disorders
INSTITUTE: NIAMS
P.I.: James Weinstein, DO
INSTITUTION: Dartmouth Medical School, Hanover, NH
GRANT NO.: 1 R01 AR45444-01A1
KEYWORDS: Back pain, intervertebal disc herniation, spinal stenosis, degenerative spondylolithesis
STUDY POP: Women and men
TYPE STUDY: Clinical
AMOUNT: $400,000
Low back pain is considered one of the most widely experienced health problems. Rates of spinal surgery have increased sharply over time and 15-fold geographic variation in rates of these surgeries has been documented. There is little evidence proving the effectiveness/efficacy of these surgical therapies over non-operative management. This study will use the resource of the National Spine Network to conduct multi-centered, randomized, controlled trials for three common diagnostic groups - lumbar intervertebral disc herniation (IDH), spinal stenosis (SpS) and spinal stenosis secondary to degenerative spondylolithesis (DS). The trials will compare the most commonly used standard surgical treatments to the most commonly used standard non-operative treatments. The primary endpoints will be changes in general health-related quality of life as measured by the SF-36 health status questionnaire and spine-related disability as measured by the Oswestry Low Back Pain questionnaire. Secondary endpoints will include patient satisfaction with treatment, resource utilization of estimation of cost, and utility for current health for estimation of quality adjusted life years
TITLE: Uterine Pain - Mechanisms and Modulation
INSTITUTE: NINDS
P.I.: Dr. Ursula Wesselmann
INSTITUTION: Johns Hopkins University, Baltimore MD
GRANT NO.: 1 RO1 NS6553 01A1
KEYWORDS: Pelvic pain, uterine pain, chronic pain, neurobiology,
STUDY POP: Animal model (rats)
TYPE STUDY: Basic
AMOUNT: $130,000
These studies will provide fundamental new information about the neuroanatomical and neurophysiological mechanisms of pelvic and uterine pain. An experimental model of uterine pain will be used to obtain information about the spinal pathways that process nociceptive afferent input from the uterus; assess the effects of peripheral opioid application on the spinal processing of nociceptive inputs from the uterus; and to determine the influence of the estrous cycle on spinal cord processing of noxious uterine stimulation.
TITLE: Gender & Sex Differences in Pain
INSTITUTE: NIDCR
RFA: Sex and Gender-Related Differences in Pain and Analgesic Response (DE-97-003)
P.I.: Dr. Jeffrey Mogil
INSTITUTION: University of Illinois at Urbana, IL
GRANT NO.: 1 RO1 DE12735-01
KEYWORDS: Pain, analgesia, sex differences, non-opioid, pharmacology,
STUDY POP: Animal model (mice)
TYPE STUDY: Basic
AMOUNT: $60,000
Evidence suggests that sex differences in pain and analgesia may reflect the activation of qualitatively different pain modulatory systems in each sex. The investigators have provided pharmacological and genetic evidence supporting the contention that female mice possess a sex-specific, non-opioid analgesic mechanism. This project aims to examine three sex-specific gene effects. Testing will be done on additional genetic populations, including transgenic knock-out mice.
TITLE: Sex-Related Opiate and Autonomic Mechanisms in TMD Pain
INSTITUTE: NIDCR
RFA: Sex and Gender-Related Differences in Pain and Analgesic Response (DE-97-003)
P.I.: Dr. David Bereiter
INSTITUTION: Rhode Island Hospital, Providence, RI
GRANT NO.1 RO1 DE12758-01
KEYWORDS: Pain, temporomandibular disorders (TMD), efferent nerves, temporomandibular joint (TMJ)
STUDY POP: Animal model (rats)
TYPE STUDY: Basic
AMOUNT: $50,000
Temporomandibular disorders (TMD) refer to a family of conditions that cause pain of the temporomandibular joint (TMJ) region and surrounding deep craniofacial muscles. The proposed studies use an animal model to selectively activate small diameter afferent nerves to examine the properties of second-order neurons that receive noxious sensory input from the TMJ region in anesthetized male and female rats. The specific aims will examine the effects of the well-known activators of endogenous pain control systems, morphine and vagal afferent nerve activity, to assess the properties of TMJ-responsive neurons.
TITLE: Sex Differences in Regional -Opioid Receptor Pain Processing
INSTITUTE: NIDCR
RFA: Sex and Gender-Related Differences in Pain and Analgesic Response (DE-97-003)
P.I.: Dr. Joh-Kar Zubieta
INSTITUTION: University of Michigan, Ann Arbor, MI
GRANT NO.: 1 RO1 DE12743-01
KEYWORDS: Pain, opioid system, gender-specific neurobiology, analgesia, temporomandibular pain
STUDY POP: Women and men
TYPE STUDY: Clincial
AMOUNT: $60,000
The goal of the proposed research is to describe and understand the relevant aspects gender-specific neurobiology that occurs as the human undergoes chronic pain. The current proposal focuses on the opioid system, and specifically the opioid receptors, since these sites mediate many of the actions of exogenously-administered antinociceptive drugs, as well as stress-and nociception-induced analgesia. This project will utilize position-emission tomography (PET) with a validated model of temporomandibular pain in a randomized, double blind, repeated measures, cross over design.
TITLE: Pain and Analgesic Response: Sex and Hormone Variations
INSTITUTE: NIDCR
RFA: Sex and Gender-Related Differences in Pain and Analgesic Response (DE-97-003)
P.I.: Dr. Sandra Comer
INSTITUTION: Research Foundation for Mental Hygiene
GRANT NO.: 1 RO1 DE12763-01
KEYWORDS: Pain, gender differences, menstrual cycle, opioids,
STUDY POP: Women and men
TYPE STUDY: Clinical
AMOUNT: $50,000
The purpose of the project is to investigate sex differences in response to painful stimuli, specifically focusing on 1) the influence of gonadal hormones on pain responsitivity and 2) the analgesic response to mu (morphine) and kappa (butorphanol) opioid agonists. Two pain procedures will be used: the cold pressor test, which combines sensory and emotional aspects of pain, and the mechanical pressure test, which can distinguish between sensory and emotional pain. Each study will compare normally cycling women to women on oral contraceptives and to men. Pain response will be measured at five different phases of the menstrual cycle (menstrual, follicular, evaluator, lutea, and late lutea.)
TITLE: K Opioid Systems: Sex- and Pregnancy- Linked Differences
INSTITUTE: NIDCR
RFA: Sex and Gender-Related Differences in Pain and Analgesic Response (DE-97-003)
P.I.: Dr. Carrie Drake
INSTITUTION: Cornell University Medical College, Ithaca, NY
GRANT NO.: 1 R29 DE12738-01
KEYWORDS: Pain, gender differences, pregnancy, opioids, analgesia,
STUDY POP: Animals model (rats and guinea pigs)
TYPE STUDY: Basic
AMOUNT: $50,000
Two lines of evidence from human and animal studies suggest that drugs activating kappa opioid receptors (KOR) may be uniquely analgesic in women. KOR agonists have been shown to relieve post-surgical pain better in women than in men. Second, the well-documented increase in pain threshold during late pregnancy has been shown to involve KOR and their endogenous opioid ligand, dymorphin. The studies in this application are designed to test the hypotheses that 1) KOR are located on neurons involved in the modulation of pain transmission in the central nervous system; (CNS); 2) the greater responsiveness of females to KOR agonists is correlated with higher levels of KOR in nociception-related regions of the CNS in females; and 3) increases in KOR in spinal cord occur during late pregnancy.
TITLE: Noradrenergic Dysfunction: A Model of Fibromyalgia Pain
INSTITUTE: NIAMS
RFA: Basic and Clinical Research on Fibromyalia (AR-98-006)
P.I.: Luc Jasmin, M.D.
INSTITUTION: Georgetown University, Washington, DC
GRANT NO.: 1 R2 AR46085
KEYWORDS: Fibromyalagia, pain, noradrenergic system, substance P, hyperalgesia
STUDY POP: Animal model (female rats)
TYPE STUDY: Basic
AMOUNT: $107,166
The goal of this project is to develop a model of fibromyalgia pain in the rat, which could provide the basis for future research into this complex disease. The hypothesis is that in fibromyalgia, chronically decreased noradrenergic input to the spinal cord facilitates substance P release and subsequent hyperalgesia (increased threshold for pain). This is based on clinical evidence of decreased noradrenaline and increased substance P in the spinal cord. A dysfunction of the noradrenergic system, the basis for the proposed model, presents a unifying explanation for the disparate findings in fibromyalgia through neuroendocrine and autonomic abnormalities, in addition to pain.
TITLE: Gender and Risk of Drug-Induced Cardiac Arrhythmias
INSTITUTE: NHLBI
P.I.: Ray Woosley, MD, PhD
INSTITUTION: : Georgetown University, Washington, DC
GRANT NO.: 1 R01 HL58743-01A2
KEYWORDS: QT interval, drug-induced arrhythmias, gender differences
STUDY POP: Animal model (rabbit)
TYPE STUDY: Basic
AMOUNT: $100,000
This study will test the hypothesis that gender-specific differences in cardiac ion current densities are responsible for the observed gender differences in QT interval length and the greater sensitivity of females to drugs that cause QT lengthening. They will use the rabbit model system to identify gender-related differences in cardiac electrophysiological characteristics (action potential and whole cell patch clamp recordings at baseline and after quinidine or d-sortalol) and identify the ionic basis for these differences in rabbit ventricular muscle. They will also evaluate the potential roles for sex steriod hormones in the regulation of specific ion channels that display gender differences at baseline or in response to drugs.
TITLE: LAM Patient Registry
INSTITUTE: NHLBI
P.I.: Gerald, Beck PhD
INSTITUTION: Cleveland Clinic Foundation, OH
GRANT NO.: 1 R01 HL58440
KEYWORDS: Lymphangioleiomyomatosis, rare diseases, pulmonary disease, registry
STUDY POP: Women and men with LAM identified through NIH Clinical Center
TYPE STUDY: Clinical
AMOUNT: $100,000
Lymphangioleiomyomatosis (LAM) is a rare but fatal pulmonary disease of unknown etiology that strikes women, primarily in their reproductive years. The goal of this project is to establish a registry of individuals with LAM by forming a consortium of six clinical centers and referring physicians who treat patients with LAM. The cohort of identified individuals with LAM will be used to characterize the clinical features of subjects and provide information on the natural course of the disease. The registry will include clinical data and tissue samples which will be used to study the course of the disease and assess interventions. Data and tissue samples will also be banked for future studies.
TITLE: LAM Tissue Repository
INSTITUTE: NHLBI
P.I.:
INSTITUTION: NIH Clinical Center, Bethesda MD
GRANT NO.: U01 HL58440
KEYWORDS: Lymphangioleiomyomatosis (LAM), rare diseases, pulmonary disease
STUDY POP: Women and men with LAM identified through NIH Clinical Center
TYPE STUDY: Clinical
AMOUNT: $10,147
The Lymphangioleiomyomatosis (LAM) registry tissue repository is maintained by the NIH Clinical Center with the assistance of ORWH and NHLBI. The NIH Clinical Center pathology laboratory serves as a resource for specimens of this rare condition that affects more women than men.
TITLE: Medicine or Surgery?
INSTITUTE: AHCPR
P.I.: Stephen Hulley, MD
INSTITUTION: University of California, San Francisco
GRANT NO.: 5 U01 HS09478-04
KEYWORDS: Hysterectomy
STUDY POP: Women
TYPE STUDY: Clinical
AMOUNT: $100,000
This clinical trial is comparing outcomes of medical and surgical treatment for abnormal uterine bleeding in premenopausal women with or without coexisting uterine leiomyomas (fibroids). The study will include a randomized trial to assess outcomes of supracervical vs. total abdominal hysterectomy. Researchers also will study patient preferences for hysterectomy and other options in a racially/ethnically diverse population. Findings will be used to develop a decision-assisting tool to help women of diverse backgrounds make informed choices that reflect their preferences regarding whether to undergo hysterectomy or alternative treatment.
TITLE: Aging of Brain: Effects of Prenatal Nutrition
INSTITUTE: NIA
P.I.: Jan Blusztajn, PhD
INSTITUTION: Boston University, MA
GRANT NO.: 2 PO1 AG09525 -08
KEYWORDS: Prenatal nutrition, choline, folic acid
STUDY POP: Animals model (rats)
TYPE STUDY: Basic
AMOUNT: $100,000
The goal of this study is to determine the mechanisms by which the availability of choline and folic acid during the prenatal period modifies brain structure and function in development, adulthood and old age. The proposed studies will 1) determine the molecular mechanisms involved in the brain reorganization that is governed by choline and folate availability by studying signal transduction pathways and developmental patterns of gene expression in brain; 2) measure synaptic function and plasticity in hippocampus of rats exposed to varying levels of choline or folate in utero; 3) examine age-related changes in conditioned stimulus processing (attention) as a function of the prenatal availability of choline and folate; 4) determine if supplementation with folate in early development leads to lifelong changes in spatial memory, brain anatomy and neurochemistry; 5) investigate whether choline supplementation either prenatally or across the lifespan ameliorates behavioral, anatomical, and biochemical deficits seen in mice lacking the apolipoprotiein E.
TITLE: HLA and Maternal/Placental Immune Function
INSTITUTE: NIAID
P.I.: Dr. Daniel Geraghty
RFA: Mechanisms of Embryonic/Fetal Tolerance (AI-94-023)
INSTITUTION: Fred Hutchinson Cancer Research Center
GRANT NO.: 1 RO1 AI 38508 01
KEYWORDS: Maternal/placental immune response, pregnancy, HLA-G
STUDY POP: Women, human tissue
TYPE STUDY: Clinical
AMOUNT: $29,247
This study will further investigate the expression of alternative HLA-G proteins and examine the unique roles that these proteins play in maternal-placental immune interaction. HLA-G protein expression in placental and maternal tissues and soluble G protein in maternal blood will be examined, emphasizing potential differences in abnormal pregnancies. The experimental plan will employ a combination of biochemical, molecular, and cellular approaches to examine the role of these molecules. The results of this study will enhance understanding of basic molecular mechanisms associated with the immune response during pregnancy, as it may relate to pregnancy outcomes.
TITLE: HLA-G and Equivalent and Fetal-Maternal Interaction
INSTITUTE: NIAID
RFA: Mechanisms of Embryonic/Fetal Tolerance (AI-94-023)
P.I.: Dr. Hidde L. Ploegh
INSTITUTION: Massachusetts Institute of Technology, Boston, MA
GRANT NO.: 1 R01 AI38577 05
KEYWORDS: Fetal-maternal, trophoblast, viral pathogens, HLA-G
STUDY POP: Women, human cell cultures
TYPE STUDY: Clinical
AMOUNT: $29,247
This study will examine fetal-maternal interactions in the immune system mediated by the trophoblast-specific Class I gene products, HLA-G. Expression of HLA-G in cultured human trophoblast will be examined both under normal circumstances and in cells infected with herpes simplex virus or cytomegalovirus. Each of these viruses down-modulates Class I expression in a unique manner, and has been associated with spontaneous abortion. This study will enhance understanding of the molecular basis of fetal-maternal immune interactions and the effects of viral pathogens.
TITLE: Fetal Trophoblast Maintain Maternal Tolerance
INSTITUTE: NIAID
RFA: Mechanisms of Embryonic/Fetal Tolerance (AI-94-023)
P.I.: Dr. John H. Russell
INSTITUTION: Washington University Medical School, St Louis, MO
GRANT NO.: 1 R01 AI38494
KEYWORDS: Maternal tolerance, trophoblast, pregnancy
STUDY POP: Animal model (mice)
TYPE STUDY: Basic
AMOUNT: $29,247
Maternal tolerance is critical during pregnancy, not only to prevent the initiation of an immunological response, but also to minimize the potential damage to the fetus. Maternal acceptance of the fetal allograft appears to be local, as it occurs without either general immunosuppression or specific tolerance to paternal antigens. A number of antigen-specific and antigen-independent models have been suggested to explain the tissue-specific acceptance of the fetus by the maternal immune system. This study will examine the role of the trophoblast in triggering antigen-dependent T cell death, using two mutant strains of mice (lpr and gld) deficient in this pathway. These mice are prone to autoimmune disease and have mutations in TNF proteins and receptors. The study will provide insights into basic mechanisms of maternal immunological tolerance to the fetus.
TITLE: Decidual T Lymphocyte Phenotype and Function
INSTITUTE: NICHD
RFA: Mechanisms of Embryonic/Fetal Tolerance (AI-94-023)
P.I.: Dr. Kent D. Heyborne
INSTITUTION: Swedish Medical Center
GRANT NO.: 1 R29 HD34079
KEYWORDS: Maternal-fetal immune, T lymphocytes
STUDY POP: Animal model (mice)
TYPE STUDY: Basic
AMOUNT: $21,935
Substantial evidence exists supporting a role for maternal-fetal immune interactions in mediating a wide variety of reproductive complications, including infertility, recurrent miscarriage, preeclampsia, intrauterine growth retardation, and preterm birth. This study will address the maternal-fetal immune relationship by examining phenotype and function of decidual T lymphocytes in a murine model. It will employ flow cytometry, immunohistochemistry, quantitative cDNA analysis, and hybridoma production of lymphocytes obtained from reproductive tissues at several points during gestation. The study will provide enhanced understanding of immunological mechanisms during pregnancy.
TITLE: Regulation of MHC Genes in the Trophoblast
INSTITUTE: NICHD
RFA: Mechanisms of Embryonic/Fetal Tolerance (AI-94-023)
P.I.: Dr. Douglas F. Antczak
INSTITUTION: Cornell University , NY
GRANT NO.: 1 R01 HD34086
KEYWORDS: Trophoblast, immunology, MHC
STUDY POP: Animal model (horse)
TYPE STUDY: Basic
AMOUNT: $29,247
This study will characterize the expression and regulation of MHC class I genes in the trophoblast of equids during early pregnancy. The horse was chosen as the experimental model because its trophoblast shows many morphological and endocrinological similarities to that of humans. In addition, the form and time course of placental development in equids allows a clarity of in vivo and in vitro investigations of immunological questions not found in other animal models. The study will examine different aspects of MHC gene expression and regulation using three distinct populations of equine trophoblasts.
TITLE: Prenatal Exposure to Organochlorine and Fecundability
INSTITUTE: NIEHS
P.I.: Barbara Cohn
INSTITUTION: Public Health Institute, Berkeley, CA
GRANT NO.: 5 R01 ES08345-02
KEYWORDS: Fertility, environmental toxicology, generation difference, environmental contamination
STUDY POP: Women and children, 312 mother-daughter pairs
TYPE STUDY: Epidemiological
AMOUNT: $95,116
This epidemiological study will investigate the inter-generational effects of exposure to DDT/DDE and the PCBs in a subset of a unique study population, the Child Health and Development Studies (CHDS), consisting of 312 mother-daughter pairs followed for more than 30 years since mothers' pregnancies in 1960-1963, a period of high exposure to DDE and PCBs. The following markers of endocrine disruption will be studied: 1) Fecundability in women exposed prenatally, and 2) Endocrine status (estrogens) in the early follicular phase of the menstrual cycle among women exposed prenatally. Significantly, fecundability is a sensitive and efficient indicator of reproductive toxicity. This study will investigate the following primary hypothesis: Prenatal DDE and PCB exposure are associated with decreased fecundability in women. This study will also complete a pilot study to evaluate the hypothesis that prenatal DDE and PCB exposures at background levels are associated with levels of estrogen in menstruating women. In summary, the proposed study will provide the first inter-generational investigation of the relation of organochlorine exposure at background levels to reproductive performance and endocrine function.
TITLE: Recurrent Spontaneous Abortion
INSTITUTE: NICHD
P.I.: Michael Steinkampf
INSTITUTION: Reproductive Medicine Network - Two sites: Brigham and Women's Hospital and University of Alabama at Birmingham
GRANT NO.: U10 HD33172 -05
KEYWORDS: Abortion, immunomodulating therapy
STUDY POP: Women, aged 21-40 who have had a minimum of three prior pregnancy losses before 20 weeks gestation, total of 45
TYPE STUDY: Clinical
AMOUNT: $35,000
This pilot study is designed to gather preliminary data regarding the efficacy of immunomodulating therapy (IVIG and/or progesterone vaginal suppositories) in the treatment of unexplained recurrent spontaneous abortion (RSA). Traditionally defined as the occurrence of three or more clinically detectable pregnancy losses prior to the 20th week of gestation, RSA occurs in approximately 1 in 300 pregnant women. Studies to date on the efficacy of IVIG for recurrent pregnancy loss have reported conflicting results. However, these studies have lacked sufficient power to allow a definitive conclusion due to their sample size. This study will conduct a pilot study to test feasibility and logistics of recruitment and data collection, and to acquire pilot pregnancy data for power calculations needed to conduct a future large, multi-center randomized double-blind placebo-controlled clinical trial.
TITLE: Do Women with Prolapse have Levator Ani Impairment?
INSTITUTE: NICHD
RFA: Basic Science Research on Female Pelvic Floor Disorders (99-HD-003)
P.I.: John O. DeLancey
INSTITUTION: University of Michigan Medical Center, Ann Arbor, MI
GRANT NO.: 1 R01 HD38665-01
KEYWORDS: Pelvic organ prolapse, levator ani muscle
STUDY POP: Women
TYPE STUDY: Clinical
AMOUNT: Total RFA $250,000
This grant proposes a case controlled study to gain insight into the functional and anatomic defects occurring in women with pelvic organ prolapse. Levator ani muscular structure and function will be evaluated in women with pelvic organ prolapse and asymptomatic controls. The proposed work employs high-resolution magnetic resonance imaging (MRI) technology to quantify structural abnormalities in levator ani muscle anatomy. The investigators have developed and tested an instrumental vaginal speculum that measures pelvic muscle strength and will use it to assess structural abnormalities.
TITLE: Macaque Model for Pelvic Floor Disorders
INSTITUTE: NICHD
RFA: Basic Science Research on Female Pelvic Floor Disorders (99-HD-003)
P.I.: Amanda L. Clark
INSTITUTION: Oregon Health Sciences University, OR
GRANT NO.: 1 R01 HD38673-01
KEYWORDS: Pelvic organ prolapse, hormones, collagen, elastin
STUDY POP: Animal model (primates)
TYPE STUDY: Basic
AMOUNT: Total RFA $250,000
This application proposes to examine the role of extracellular matrix components and metalloproteinases in a macaque model of pelvic organ prolapse. The research addresses the underlying role of steroid hormones, aging and parity in the rhesus macaque, an animal model that is valid and clinically relevant to this human disorder. The intent is to measure changes in collagen and elastin content to perform a first approximation and analysis of the changes in the vaginal and paravaginal connective tissue of this primate model.The major feature of this study is that important information on connective tissue changes in the vaginal wall of an animal model may be useful in evaluating the role of the hormonal milieu on the integrity of the pelvic floor in human studies.
TITLE: Anorectal Manifestations of Female Pelvic Floor Disorder
INSTITUTE: NICHD
RFA: Basic Science Research on Female Pelvic Floor Disorders (99-HD-003)
P.I.: Adil E. Bharucha
INSTITUTION: Mayo Foundation Rochester, St. Paul, MN
GRANT NO.: 1 R01 HD38666-01
KEYWORDS: Pelvic floor dysfunction, fecal incontinence, obstructed defecation
STUDY POP: Women, 60 female patients with fecal incontinence and 25 age-matched controls
TYPE STUDY: Clinical
AMOUNT: Total RFA $250,000
This project endeavors to study two poorly understood aspects of pelvic floor dysfunction: fecal incontinence and obstructed defecation. The authors suggest that pelvic magnetic resonance imaging can directly visualize pelvic floor processes during normal and abnormal defecation. The project will integrate clinical assessments, a validated questionnaire, reproducible measurements of rectal compliance, and translational applications of magnetic resonance imaging in patients with reduced rectal compliance. The proposal may ultimately yield significant information on two pervasive clinical problems that could provide a basis for novel diagnostic methods and therapeutic approaches that are standardized and reproducible.
TITLE: Molecular and Biochemical Study of Collagen in Prolapse
INSTITUTE: NICHD
RFA: Basic Science Research on Female Pelvic Floor Disorders (99-HD-003)
P.I.: Anthony C. Visco
INSTITUTION: Duke University Medical Center, Durham, NC
GRANT NO.: 1 R01 HD38680-01
KEYWORDS: Pelvic floor prolapse, collagen
STUDY POP: Women with advanced-stage pelvic organ prolapse
TYPE STUDY: Clinical
AMOUNT: Total RFA $250,000
This proposal will compare collagen content, deposition, and extent of cross-linking in a cohort of women with normal pelvic support and with advanced pelvic organ prolapse. The long-term objective is to gain insight into the mechanisms of pelvic floor dysfunction through the study of collagen at the molecular and biochemical levels. This proposal may deliver important insights into the underlying mechanism of pelvic floor disorders by applying current basic science technologies.
TITLE: Childbirth Related Pelvic Floor Injurya
INSTITUTE: NICHD
RFA: Basic Science Research on Female Pelvic Floor Disorders (99-HD-003)
P.I.: Kenneth J. Leveno
INSTITUTION: University of Texas Southwestern Medical Center, TX
GRANT NO.: 1 R01 HD38663-01
KEYWORDS: Pelvic floor injury, childbirth, pelvic floor dysfunction
STUDY POP: 11,000 primiparous women
TYPE STUDY: Clinical
AMOUNT: Total RFA $250,000
This application will examine the direct role of childbirth in the causation of pelvic floor dysfunction and evaluate an intervention to prevent pelvic floor disorders. Two research components are presented: (1) a prospective analysis of the relationship between precise obstetrical events and subsequent pelvic floor dysfunction in 11,000 primiparous women, and (2) a randomized trial of the effects of coached versus uncoached maternal pushing during the second stage of labor on postpartum pelvic floor function. The investigators will identify factors that influence delivery practice and subsequent development of pelvic floor disorders that may challenge routine clinical management of intrapartum birth injury.
TITLE: Neurotrophins, Hormones and Postparous Incontinence
INSTITUTE: NICHD
RFA: Basic Science Research on Female Pelvic Floor Disorders (99-HD-003)
P.I.: Peter G. Smith
INSTITUTION: University of Kansas Medical Center, KS
GRANT NO.: 1 R01 HD38670-01
KEYWORDS: Neurotrophins, vaginal delivery, hormones, postparous incontinence, pelvic nerves
STUDY POP: Animal model (rats)
TYPE STUDY: Basic
AMOUNT: Total RFA $250,000
This proposal will concentrate on the hormonal influences on smooth muscle sympathetic reinnervation following axonal damage during vaginal delivery. The investigators will address factors influencing recovery from denervation injury, and examine the interplay between estrogen and neurotrophin production in the rat model. Damage to the pelvic nerves and failure to achieve complete reinnervation may be a primary focus and account for much of pelvic floor dysfunction. Factors that moderate regrowth of damaged axons may also influence functional recovery. Much of the proposal centers on the denervation injury model at parturition as the cause of incontinence. The conceptual framework is that neural injury following pregnancy and vaginal delivery may not recover due to estrogen levels and variations in smooth muscle hormonal responsiveness. Results from this study may provide a better explanation for the conflicting information regarding the role of estrogen in maintaining continence.
TITLE: Mechanisms of Incontinence Following Vaginal Distension
INSTITUTE: NICHD
RFA: Basic Science Research on Female Pelvic Floor Disorders (99-HD-003)
P.I.: Margot S. Damaser
INSTITUTION: Loyola University Medical School
GRANT NO.: 1 R01 HD38679-01
KEYWORDS: Urinary incontinence, vaginal distension, hormones, pelvic floor disorders
STUDY POP: Animal model (rats)
TYPE STUDY: Basic
AMOUNT: Total RFA $250,000
This project proposes to develop a rat model to test the clinical observation that vaginal distention during childbirth causes urinary incontinence, to determine the specific pattern of associated neural damage and recovery, and to evaluate if sex steroids can reduce the severity of urinary incontinence and/or accelerate the rate of recovery from nerve injury. The investigators will use this animal model to test the hypothesis that gonadal steroids may be effective in reducing the long term effects of peripheral nerve damage, and thus reduce the risk of developing pelvic floor disorders. Other study components will introduce hormonal interventions that may accelerate recovery of nerve damage immediately following injury. This study may result in data that could further our understanding of the role of sex steroids in pelvic floor disorders and serve to validate an animal model of nerve injury and recovery, allowing investigators to test a variety of hormonal agents to reduce the long term impact of pelvic floor injuries.
TITLE: Neuromuscular Injury and Recovery after Vaginal Delivery
INSTITUTE: NICHD
RFA: Basic Science Research on Female Pelvic Floor Disorders (99-HD-003)
P.I.: Alison C. Weidner
INSTITUTION: Duke University Medical Center, Durham, NC
GRANT NO.: 1 R01 HD38661-01
KEYWORDS: Vaginal delivery, neuromuscular injury
STUDY POP: Nulliparous women - African-American, Hispanic and Caucasian
TYPE STUDY: Clinical
AMOUNT: Total RFA $250,000
This application proposes to document the specific labor events associated with neuromuscular maternal injury and to determine the differences of these injury mechanisms among women of color. The first phase will extend research on Caucasian women that targeted neuromuscular function and radiographic anatomy by including minority women, particularly of African American and Hispanic backgrounds. The second phase of the project includes recruiting women in the third trimester of pregnancy for a longitudinal observational study that evaluates their symptoms of prolapse and incontinence, as well as their pelvic neuromuscular function over time. By including antepartum, intrapartum, and postpartum time frames, the principal investigator has designed a study potentially capable of delivering a definitive answer with regard to the neuropathic role that delivery plays in the development of pelvic floor disorders.
Content revised: 11/16/99
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