Journal of Chronic Fatigue Syndrome: Volume 8, Issue 3-4, 2000-2001

Volume 8, Issue 3-4, 2000-2001

 * Subtypes of Chronic Fatigue Syndrome: A Review of Findings"'Summary - Most studies of Chronic Fatigue Syndrome (CFS) have been based on patients recruited from primary or tertiary care settings. Patients from such settings might not be typical of patients in the general population and may not accurately reflect the heterogeneity among individuals diagnosed with this condition. The current paper reviews four community-based studies that examined subtypes of individuals with CFS. Distinctions between subtype groups based on sociodemographics, illness onset and duration, stressful precipitating events, symptom frequency, and comorbidity characteristics are made with respect to outcome measures of fatigue and symptom severity, functional ability, and psychiatric comorbidity.'"
 * Depressive Comorbidity in the Fatiguing Illnesses"'Summary - Objective: The present study seeks to examine whether subjects with fatiguing illnesses and comorbid Major Depressive Disorder (MDD) have more symptoms than those without MDD. Methods: The data was based on the Chronic Fatigue Syndrome (CFS) Surveillance System of the Centers for Disease Control and Prevention (CDC). Each of the 565 subjects enrolled in the study had a fatiguing illness and some had CFS. Subjects were evaluated for the duration and severity of the 11 symptoms and 3 physical signs listed in the 1988 CDC case definition (symptoms). They completed the Diagnostic Interview Schedule for the DSM-III-R which provided a diagnosis of several psychiatric disorders including MDD. Symptoms were compared in subjects with and without comorbid MDD. Results: The mean number of symptoms was similar in the two groups. Three symptoms were found to be associated with MDD: neuro-biological (cognitive complaints), sleep disturbance, and headache. Conclusions: Comorbid MDD in the fatiguing illnesses is not associated with a higher mean number of symptoms. In the present study a pattern of three individual symptoms emerged that was associated with comorbid MDD. It is suggested that subjects with fatiguing illnesses who have this symptom pattern be evaluated for comorbid MDD.'"
 * Measuring Attributions About Chronic Fatigue Syndrome"'Summary - Three studies explored the effects of different diagnostic labels and different types of recommended treatments for Chronic Fatigue Syndrome upon attributions regarding its cause, nature, severity, contagion, prognosis, and treatment. Attributions for Chronic Fatigue Syndrome appear to change based upon the diagnostic label given for the syndrome and the type of treatment recommended. Results suggest that, in comparison to the Chronic Fatigue Syndrome label, the Myalgic Enceph-alopathy label prompts attributions that this syndrome is a serious condition associated with a physiologically-based etiology, a poor prognosis, and decreased potential for organ donation. Results also suggest that, compared with cognitive coping skills treatment, treatment with ampligen appears to be associated with perceptions of Chronic Fatigue Syndrome as an accurate diagnosis and as a severely disabling condition.'"
 * Health-Related Personality Variables in Chronic Fatigue Syndrome and Multiple Sclerosis "'Summary - This study investigated personality variables in patients with Chronic Fatigue Syndrome (CFS) and Multiple Sclerosis (MS), with healthy, sedentary subjects as controls. CFS and MS groups were higher on alexithymia, characterized as difficulty in describing and differentiating emotions and marked externalization. CFS and MS groups reported a more depressive attributional style than healthy participants, reflecting beliefs that causes for good events are not diffused into other areas of life while causes for bad events will always be present. The CFS group was significantly lower on doctors/others locus of control indicating lack of trust in medical professionals. Results indicate that CFS and MS are similar to each other while different from the healthy group on certain personality variables that likely reflect the demoralizing effects of coping with a chronic, disabling illness marked by uncertainty.'"
 * Chronic Fatigue Syndrome: Overcoming the Attitudinal Impasse"'Summary - Context: Patients with Chronic Fatigue Syndrome and their physicians are often in conflict about the etiology and treatment of CFS. Objectives: 1. Survey the literature regarding physician's attitudes towards CFS; 2. Examine the contributing factors to physician's attitude towards the disorder; and 3. Suggest solutions. Data Sources: The relevant medical and psychological literature (years 1988-2000) was searched using the search term “Chronic Fatigue Syndrome.” This was supplemented with papers from the bibliographies of the retrieved papers, additional related literature, and clinical experience.Data Synthesis: Forty-six to ninety percent of GPs accept CFS as a discrete clinical entity and 30-82% are willing to make the diagnosis in qualifying patients. Conclusions: CFS is a heterogeneous, multifactorial host response disorder that is inadequately described by the biomedical model. Despite substantial evidence of multisystemic physical abnormality in CFS, the lack of pathognomic tests and the female gender predominance cause some physicians to continue to treat CFS as a psychosocial disorder. This leads to conflict between patients and physicians. CFS challenges physicians to think beyond current disease models, to tolerate diagnostic and therapeutic uncertainty, and to work collaboratively with patients rather than taking the role of expert.'"
 * G-Actin Cleavage Parallels 2-5A-Dependent RNase L Cleavage in Peripheral Blood Mononuclear Cells—Relevance to a Possible Serum-Based Screening Test for Dysregulations in the 2-5A Pathway"'Summary - A dysregulation in the 2N,5N-oligoadenylate (2-5A)-dependent RNase L antiviral pathway has been detected in peripheral blood mononuclear cells (PBMC) of chronic fatigue syndrome (CFS) patients, which is characterized by an unregulated RNase L activity and the presence of a low molecular weight (LMW) 2-5A-binding protein (37-kDa 2-5A-BP). This study was undertaken to test the possibility that the 37-kDa 2-5A-BP of CFS is produced by proteolytic cleavage of the 80-kDa monomeric enzyme. Incubation of the 80-kDa human recombinant RNase L (r-hRNase L) with PBMC extracts either positive or negative for the presence of 37-kDa 2-5A-BP, respectively, demonstrates that the LMW protein is produced by the former, not the latter, and that the size of the fragment generated from the recombinant protein matches the 37-kDa size of the fragment observed in the original PBMC. Digestion of r-hRNase L with calpain generated the same 37-kDa 2-5A-BP observed in PBMC extracts, and calpain immunoprecipitation from PBMC extracts reduced their proteolytic activity, an observation that suggests that calpain may be involved in the cleavage. We further examined G-actin, a known calpain substrate, for possible cleavage in PBMC. Actin fragments were observed of which the presence correlated with the presence of 37-kDa 2-5-BP. Since G-actin is cleared by serum transport, we further screened serum samples for the presence of LMW forms. A single LMW actin fragment could be detected in serum, the presence of which correlated significantly with the presence of both G-actin and RNase L fragments in PBMC. This latter observation offers the opportunity to screen large populations of patients for dysregulations in the RNase L pathway by a serum-based assay.'"
 * Interactions Between Rnase L Ankyrin-Like Domain and ABC Transporters as a Possible Origin for Pain, Ion Transport, CNS and Immune Disorders of Chronic Fatigue Immune Dysfunction Syndrome"'Summary - Low molecular weight (LMW) ribonuclease L (RNase L) forms have been identified in peripheral blood mononuclear cells (PBMC) of patients with chronic fatigue immune dysfunction syndrome (CFIDS). Data from our laboratory indicate that these LMW RNase L proteins are produced by proteolytic cleavage of the native monomeric enzyme and we have identified calpain as one of the possible proteases involved. Using human recombinant RNase L (r-hRNase L) His-tagged at the N-terminus, we show here at the one hand that both calpain and PBMC extracts from CFIDS patients cleave the protein in fragments of identical sizes containing ankyrin-like repeat sequences. At the other hand, the activity of RNase L is modulated by its interaction with a specific inhibitor (RLI), a member of the ATP binding cassette (ABC) superfamily. RLI interacts with the ankyrin domain of RNase L, which results in a blockade of the 2N,5N-oligoadenylate (2-5A)-binding site of the enzyme. We show that RLI contains a small ankyrin-interacting peptide cluster through which it interacts with the first two β-hairpin coils of the RNase L ankyrin domain. A similarity search performed at the NCBI using RLI aminoacid sequence as the entry allowed to identify several other ABC transporter proteins sharing significant identities with RLI, including the ankyrin-interacting peptide. Taken together, these results show that upon pathological cleavage of RNase L, fragments containing the ankyrin domain are released, which could be capable of interacting with selected members of the human ABC superfamily, preventing their interaction with the normal cognate ankyrin protein and hence impairing their proper cellular function. This interaction constitutes a common physiological mechanism explaining numerous and currently unexplained symptoms experienced by patients with CFIDS, which are otherwise totally unrelated.'"
 * Assessment of Functional Impairment by Cardiopulmonary Exercise Testing in Patients with Chronic Fatigue Syndrome"'Summary - Functional impairment in a population of patients with chronic fatigue syndrome (CFS) was determined by exercise testing. The criteria established by Weber and Janicki (1) were employed because impairment levels are based on maximal oxygen consumption. Oxygen consumption was obtained by cardiopulmonary exercise testing and was used to classify subjects according to the severity of impairment. All the subjects in this study met the CDC case definition (2) for CFS. All patients underwent at least two maximal graded exercise tests in which expired air was collected for assessment of V02max. Data are included for eighty-seven CFS patients, the highest V02 was used for determining impairment. Although all patients met the CDC case definition for CFS, only 35 (40%) would be classified as having greater than “Mild” functional impairment. The highest V02 of any of the patients in this study was 29.5 ml/kg/min, very close to what normative data predicts to be the average maximal value for the entire group. Without a sedentary control group it is unclear if the low V02 in this population is due to the pathology of CFS or results from the inactivity that accompanies the disease. However, use of maximal V02 during exercise can clearly discriminate between levels of functional impairment and may be efficacious for diagnosis of CFS. Additionally, in cases where cardiopulmonary analysis is unavailable, exercise duration on a standardized test may also be employed.'"
 * Hypercoaguable State Associated with Active Human Herpesvirus-6 (HHV-6) Viremia in Patients with Chronic Fatigue Syndrome"'Summary - Objectives: A subset of patients with Chronic Fatigue Syndrome (CFS) have been found to be hypercoaguable in small previous studies. We wanted to analyze the incidence of a hypercoaguable state and assess hereditary hypercoaguable risk factors in a group of patients with known CFS and HHV-6 viremia. Methods: Thirty patients diagnosed with CFS that had at least one prior positive blood culture for active HHV-6 by rapid culture method were studied. A hypercoaguable panel was obtained to assess activation of coagulation. Two or more positive tests were determined to represent activation of coagulation. Hereditary thrombosis risk panels were also performed which included eight different genetic tests to assess hereditary abnormalities. Results: Twenty-four of thirty (80%) patients had a hypercoaguable state, thus activation of coagulation. Twenty-five of thirty (83%) of patients had a hereditary abnormality. Conclusions: CFS patients with active HHV-6 infection (viremia) have activation of coagulation and are hypercoaguable. Hereditary thrombosis risk factors are very prevalent in these patients. These hereditary abnormalities increase the hypercoaguable tendencies. The hypercoaguable state associated with active HHV-6 infection may be a significant contributing factor to the symptoms seen in CFS patients.'"
 * Chronic Fatigue Syndrome, Ampligen, and Quality of Life: A Phenomenological Perspective"'Summary - The purpose of this investigation was to identify significant quality-of-life issues for two women previously diagnosed with chronic fatigue syndrome (CFS), and their families. Both women were participants in a cost-recovery, clinical trial of the antiviral and immuno-modulatory drug, Ampligen. A qualitative, case study approach was adopted to access information not normally available from clinical trials. Specifically, semi-structured, in-depth interviews were conducted with the CFS patients, and their spouses, to discover if these families perceived any changes in their patterns of daily living contingent with participation in the Ampligen trial. Patient diaries were also analyzed for the purpose of triangulation. Content analysis of the interview transcripts and diary entries revealed a number of significant quality of life improvements for the women and their families, for which they perceived the drug therapy responsible. After an initial acclimation period, and with the exception of the day when the drug was administered, both women reported a reduction in pain, increased energy levels, and improved cognitive functioning. They each cited numerous cases to illustrate their improvement.'"
 * Preface by Roberto Patarca-Montero