SOCIAL PROCESSES AND SOMATIZATION--THE COURSE OF CFS
Grant Number: 5R29AI35359-05
PI Name: WARE, NORMA C.
PI Title:
Project Title: SOCIAL PROCESSES AND SOMATIZATION--THE COURSE OF CFS

Abstract: This longitudinal study uses concepts and methods from medical anthropology to contribute to basic research on the course of disorders characterized by medically unexplained somatic symptoms. "Course" is construed as a variable, continuous process involving the mutual interaction of social factors and somatic distress. Chronic fatigue syndrome serves as the case study example. A dichotomized random sample of 80 CFS subjects -- 40 with histories of major depression before the onset of their current illness and 40 with no prior psychiatric histories -- will be drawn from patients meeting criteria for the CDC case definition of chronic fatigue syndrome. Forty subjects who currently meet DSMIII-R criteria for major depression will be identified as a comparison group. Qualitative and quantitative approaches to data collection and analysis are combined in the study design. Greater emphasis is placed, however, upon the qualitative component of the work. Following an initial intake interview, three waves of data will be collected over three years for each subject. Each wave consists of: (a) an ethnographic interview, (b) a semi- structured, open-ended telephone interview, and (c) completion of three questionnaires (twice per wave). An analytical plan is presented to answer each of 4 specific questions that organize the research. (1) What social factors and coping mechanisms are associated with chronic fatigue syndrome? (2) What is the subjective experience and meaning of depressive symptoms and how do symptoms of depression change in relation to somatic symptoms over time? (3) What are the sequential, mutual relations between events and processes in the social world and changes in somatic symptoms? (4) Can specific social processes be identified that serve as "critical transition points" mediating symptomatic change? A number of "qualitative hypotheses" will be examined in the course of the analyses. A typology of the course of disorder that takes social processes into account, and a series of quantitative hypotheses that can be tested in future research will be among the products of the project.

Thesaurus Terms:
chronic fatigue syndrome, major depression, pathologic process, social behavior, coping, longitudinal human study, behavioral / social science research tag, human subject, interview, questionnaire

Institution: HARVARD UNIVERSITY (MEDICALSCHOOL)
MEDICAL SCHOOL CAMPUS
BOSTON, MA 02115
Fiscal Year: 1997
Department: MEDICINE
Project Start: 01-SEP-93
Project End: 31-AUG-99
ICD: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
IRG: SSS

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BASIC STUDIES OF MYCOPLASMAS
Grant Number: 1Z01AI00027-31
PI Name: TULLY, J G.
PI Title:
Project Title: BASIC STUDIES OF MYCOPLASMAS
Abstract:
Current efforts emphasize the biology and pathogenicity of Mycoplasma species of humans and, where important, how mycoplasmas (or other mollicutes) from animals and other hosts play a role in human or other host infections. Further observations have been made on the role of mycoplasmal infections in immunocompromised patients, usually involving individuals with genetic immune deficiencies, or those patients who are receiving various immunosuppressive drugs because of organ/tissue transplants or treatment of malignant disease.

We have now additional evidence of the important role that mycoplasmas of animal origin can play in such infections. Mycoplasma maculosum, an organism commonly found in the canine respiratory and genital tracts, was identified as the causative agent of meningitis in a child with hypogammaglobulinemia. Chemotherapeutic efforts, in the absence of the patient?s ability to mount some type of an immune response, have been generally unsuccessful, until a newer experimental antibiotic was used in prolonged therapy. These findings, and our previous identification of other feline or canine mycoplasma infections in immunocompromised patients, emphasize why all patients with such immune deficiencies should avoid close animal contact.

Some recent studies using molecular probles suggest a role of mycoplasmas (especially Mycoplasma fermentans) in chronic fatigue syndrome (CFS). In a collaborative study, Mycoplasma genitalium has been isolated from the blood of a patient with this syndrome and the immunologic response of the patient and his wife indicate evidence of recent infection with the organism. Further work on the in vitro cytopathogenicity of the agent isolated is being investigated.

We have recently identified two new, and previously unreported, Mycoplasma species from the respiratory tract of both desert and gopher tortoises in a collaborative study in Florida and California. The taxonomic characterization of these new organisms has allowed development of a variety of serologic and molecular techniques to rapidly identify the organisms and to study acquisition of infection, disease distribution, immunological responses, and other epidemiological features of a disease in an endangered species.

Since many mycoplasmas or other mollicutes are difficult to grow in primary culture from host material and identification techniques are prolonged and involved, we are participating in a pilot study to evaluate the use of 16S rDNA sequence data as a rapid means of identifying Mycoplasma species of humans and animals, and a group of helical mollicutes (genus Spiroplasma).

Full 16S rDNA sequences are now available on almost all of the 100 or more species in the genus Mycoplasma. Sequence data on 10 Spiroplasma species, available from our earlier collaborative study on the phylogeny of these organisms, have been combined with sequence analysis from another 38 currently defined Spiroplasma species to provide a comprehensive file to evaluate the practicality of this reference to provide rapid species identification. The phylogenetic relationships are closely correlated with previous classifications made on genome characteristics and serologic patterns. This activity is one part of a collaborative program to develop a multiple organism microbial identification project.

Thesaurus Terms:
Actinomycetales infection, Mycoplasma, host organism interaction, pathologic process, arthritis, autoimmune disorder, microorganism classification, opportunistic infection, species difference, clinical research, human tissue, laboratory rabbit, serology / serodiagnosis

Institution:
Fiscal Year: 1998
Department:
Project Start:
Project End:
ICD: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
IRG: LMM

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TRIAL OF FLUDROCORTISONE FOR CHRONIC FATIGUE SYNDROME

Grant Number: 5M01RR000052-400751
PI Name:
PI Title:
Project Title: TRIAL OF FLUDROCORTISONE FOR CHRONIC FATIGUE SYNDROME

Abstract: The trial is based on preliminary data showing that upright tilt table testing can provoke a drop in blood pressure consistent with neurally mediated hypotension (NMH) in a high proportion of those with chronic fatigue syndrome (CFS), and that unblinded treatment of the NMH leads to an improvement in CFS symptoms in 40-70% of CFS patients. The specific aim of this study is to determine whether patients aged 18 to 50 years with CFS and NMH will have a greater improvement in (1) self-reported general sense of well being and (2) objective orthostatic tolerance when treated with fludrocortisone than when treated with placebo. Eligible subjects are randomized to receive either fludrocortisone (escalating to 0.1 mg/day) or placebo for nine weeks. In week 8-9 of treatment, subjects undergo repeat tilt testing. The primary outcome measure is the proportion with a 15 point improvement in wellness on a 100 point wellness score, and a secondary outcome is the proportion with improvement in the number of minutes before the development of hypotension during upright tilt.

Thesaurus Terms: chronic fatigue syndrome, corticosteroid analog, drug screening /evaluation, hormone therapy, human therapy evaluation clinical trial phase II /III /IV, functional ability, outcomes research clinical research, human subject

Institution: JOHNS HOPKINS UNIVERSITY
Fiscal Year: 2001
Department:
Project Start:
Project End:
ICD: NATIONAL CENTER FOR RESEARCH RESOURCES
IRG: ZRR1

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MODEL FOR INDUCTION OF CFS

Grant Number: 5R01AI040990-03
PI Name: JONES, JAMES F.
PI Title: PROFESSOR
Project Title: MODEL FOR INDUCTION OF CFS

Abstract: DESCRIPTION: This is an amended application that was previously reviewed October/November 1996. The application was proceeded by an introduction that addressed critique from the first review. Changes and additions were bolded in this re-submitted application. Dr. Jones and colleagues at National Jewish Medical and Research Center in Denver, Colorado propose a case control study of adult patients (18-45 years) with CFS, half of whom have atopic disease compared to matched control groups. They plan to challenge with exercise and nasal allergy provocation 60 CFS patients and controls to determine if such provocation will evoke CFS symptoms as well as induce changes in inflammatory laboratory parameters. Their proposal would be used to define a model that would be usually for future pathophysiological studies and possible intervention trials for adults with CFS.

Thesaurus Terms: allergen, chronic fatigue syndrome, exercise, hypersensitivity

Institution: NATIONAL JEWISH MEDICAL & RES CTR
Fiscal Year: 2000
Department:
Project Start: 01-FEB-1998
Project End: 31-JAN-2002
ICD: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
IRG: ZRG5

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MITOCHONDRIA IN CHRONIC FATIGUE SYNDROME PATHOPHYSIOLOGY
Grant Number: 5M01RR00046-39S21069
PI Name: CHAZOTTE, BRAD J.
PI Title:
Project Title: MITOCHONDRIA IN CHRONIC FATIGUE SYNDROME PATHOPHYSIOLOGY

Abstract:
The purpose of this study is to determine if mitochondrial bioenergetic function is impaired in the cells of Chronic Fatigue Syndrome (CFS) patients compared to normal, healthy individuals.

Thesaurus Terms:
bioenergetics, cellular pathology, chronic fatigue syndrome, mitochondria. clinical research, human subject, tissue / cell culture

Institution: UNIVERSITY OF NORTH CAROLINA CHAPEL HILL
CHAPEL HILL, NC 27514
Fiscal Year: 1999
Department: CLINICAL RESEARCH CENTER
Project Start: 01-OCT-74
Project End: 30-NOV-02
ICD: NATIONAL CENTER FOR RESEARCH RESOURCES
IRG: RIRG

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MECHANISMS OF RHINITIS IN CHRONIC FATIGUE SYNDROME
Grant Number: 5R01AI42403-03
PI Name: BARANIUK, JAMES N.
PI Title:
Project Title: MECHANISMS OF RHINITIS IN CHRONIC FATIGUE SYNDROME

Abstract:
DESCRIPTION: (Adapted From Applicant's Abstract) Rhinitis is present in 70% of CFS subjects. The investigators have intensively studied the nasal mucosa in CFS rhinitis to evaluate three hypotheses of CFS pathology:

(1) immune dysfunction with atopy;

(2) mucosal inflammation including viral infections;

They propose to prospectively analyze atopy, mucosal inflammation, and neural dysfunction in age- and sex-matched CFS and control groups by using integrated nasal analysis models. They feel strongly that their hypothesis-driven approach will precisely define specific neural pathophysiological mechanisms in CFS, allow pharmacological manipulation of these dysfunctional systems, and potentially lead to the development of simple new diagnostic tests (i.e. nasal provocation) as the means to evaluate future treatments of CFS.

Thesaurus Terms:
chronic fatigue syndrome, nasal, pathologic process, rhinitis, atopy, disease / disorder etiology, fibromyalgia, mucosa, neuropathology, neurophysiology, pain, virus infection mechanism, clinical research, human subject

Institution: GEORGETOWN UNIVERSITY
37TH AND O STS NW
WASHINGTON, DC 20057
Fiscal Year: 1999
Department: MEDICINE
Project Start: 01-JUL-97
Project End: 30-JUN-01
ICD: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
IRG: ZRG5

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CIRCULATORY CONTROL IN YOUNG PEOPLE WITH CHRONIC FATIGUE
Grant Number: 5R01HL62385-02
PI Name: SAUL, JEROME P.
PI Title:
Project Title: CIRCULATORY CONTROL IN YOUNG PEOPLE WITH CHRONIC FATIGUE

Abstract:
There is no text on file for this abstract.

Thesaurus Terms:
cardiac output, cerebral circulation, chronic fatigue syndrome, blood pressure, blood volume, adolescence (12-18), clinical research, human subject, young adult human (19-34)

Institution: MEDICAL UNIVERSITY OF SOUTH CAROLINA
171 ASHLEY AVE
CHARLESTON, SC 29403
Fiscal Year: 1999
Department: PEDIATRICS
Project Start: 15-JUL-98
Project End: 30-JUN-01
ICD: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
IRG: ZRG5

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CENTER FOR MULTIDISCIPLINARY STUDIES OF CFS PATHOGENESIS

Grant Number: 5U01AI045940-02
PI Name: KLIMAS, NANCY G.
PI Title: PROFESSOR OF MEDICINE
Project Title: CENTER FOR MULTIDISCIPLENERY STUDIES OF CFS PATHOGENESIS

Abstract: Recent advances in our understanding of neuroendocrine mediators in CFS have raised more questions than answers. Certainly two areas of research stand out and are intertwined: the biology of orthostatic hypotension and the biology of reactivity. Several novel observations are made in this Center application and the four projects will complement each other in a way that, like pieces of a puzzle, bring the overall picture and understanding of CFS into clearer focus. Project I examines autonomic mechanisms that would lead to the low RBC mass as well as the potential for CFS associated cytokines to inhibition erythropoietin production. This leads to a study of RBC mass expansion vs. volume expansion vs. placebo to further delineate our understanding of renal hemodynamics. Project 3 uses the blood volume manipulation to study mechanisms of autonomic and cardiovascular interactions in CFS, and pools data with Project I for a complete picture of this shared study population. Project 2 also manipulates the biology of CFS by modifying the stress response through a cognitive behavioral stress management paradigm, and evaluating its impact on potential mediators of the illness, such as immune function and inflammatory cytokine production. Project 4 capitalizes on the availability of pre intervention post intervention samples to look at mechanisms of natural killer cell dysfunction in CFS, including the role of stress hormones (catecholamines, cortisol) and inflammatory cytokines (TNF-(x) on NK cell function at the molecular level. These projects will each be supported by administrative, health, psychosocial, and laboratory assessment core units.

Thesaurus Terms: chronic fatigue syndrome, cooperative study, pathologic process

Institution: UNIVERSITY OF MIAMI
Fiscal Year: 2000
Department: MEDICINE
Project Start: 30-SEP-1999
Project End: 31-JUL-2003
ICD: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
IRG: ZAI1

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MOTOR LEARNING IN CFS--NEURAL DYSFUNCTION IMPLICATION

Grant Number: 5R01NS038337-03
PI Name: SERVATIUS, RICHARD J.
PI Title:
Project Title: MOTOR LEARNING IN CFS--NEURAL DYSFUNCTION IMPLICATION

Abstract: Chronic Fatigue Syndrome (CFS) patients have registered cognitive complaints such as impaired concentration, memory lapses, and confusion. These complaints are cited as the most debilitating aspect of their disorder. Our pilot study, funded through the New Jersey Chronic Fatigue Research Center, showed that acquisition of a new motor response is impaired in CFS patients. Failure to acquire the classically conditioned eyeblink response was associated with white matter abnormalities in the prefrontal cortex, which are more prevalent in CFS patients without a concurrent psychiatric diagnosis. The present proposal seeks to determine the nature and diagnostic specificity of the learning deficit, as well as advance our understanding of the pathophysiology of some of the cognitive complaints in CFS. We will compare acquisition of the classically conditioned eyeblink response in CFS patients without a concurrent diagnosis of depression to CFS patients with concurrent depression, depressed patients, and healthy sedentary controls. A two-tone discrimination procedure, wherein one tone (CS+) predicts the onset of the unconditioned stimulus (US) and one which does not (CS-), will be used. In this study, we will address two hypotheses derived from neuropsychological research, namely, that CFS patients without depression have slower information processing and they are also impaired in their ability to processes complex auditory information. To address the former, we will manipulate the time between CS+ onset and US onset, the interstimulus interval. To address the latter, we will reverse the contingencies between the CS+ and CS- with respect to the US. Learning of the eyeblink response will be related to performance on neuropsychological tests. We will also obtain MRI scans to quantify brain abnormalities. In this manner, we will relate the prevalence of brain abnormalities in CFS patients to learning and memory impairments. In the absence of a medical marker of the disorder, the diagnosis of CFS relies on concordance with the current case definition. The lack of a medical marker also hinders efforts toward an identification of the pathophysiology of CFS. Our strategy will be to employ a learning and memory paradigm about which a great deal is known concerning the underlying neuroanatomy, neurophysiology and neuropharmacology. We will then be in a position to relate learning abnormalities to brain pathology as measured in MRI scans and characterized by neuropsychological deficits.

Thesaurus Terms: chronic fatigue syndrome, learning disorder, neuropsychology, psychomotor function, psychophysiology

Institution: UNIV OF MED/DENT NJ NEWARK
Fiscal Year: 2001
Department: NEUROSCIENCES
Project Start: 02-AUG-1999
Project End: 31-MAY-2003
ICD: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
IRG: ZRG1

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