Lower serum zinc in Chronic Fatigue Syndrome (CFS): relationships to immune dysfunctions and relevance for the oxidative stress status in CFS

The present study examines serum zinc concentrations in patients with chronic fatigue syndrome (CFS) versus normal volunteers. Serum zinc levels were determined by means of an atomic absorption method. We found that serum zinc was significantly lower in the CFS patients than in the normal controls. There was a trend toward a significant negative correlation between serum zinc and the severity of CFS and there was a significant and negative correlation between serum zinc and the subjective experience of infection. We found that serum zinc was significantly and negatively correlated to the increase in the alpha2 protein fraction and positively correlated to decreases in the expression of mitogen-induced CD69+ (a T cell activation marker) on CD3+ as well as CD3+CD8+ T cells. These results show that CFS is accompanied by a low serum zinc status and that the latter is related to signs of inflammation and defects in early T cell activation pathways. Since zinc is a strong anti-oxidant, the present results further support the findings that CFS is accompanied by increased oxidative stress. The results of these reports suggest that some patients with CFS should be treated with specific antioxidants, including zinc supplements.     

Chronic Fatigue Syndrome

Chronic fatigue syndrome (CFS) has emerged as a public health concern over the past decade. A working case definition was created in 1988 and revised in 1994, and this has been used to establish prevalence estimates using physician-based surveillance and an a random digit dial telephone survey. Although CFS has some characteristics of an infectious disease, so far no infectious agent has been associated with the illness. Studies of immune function in CFS patients failed to detect differences between cases and healthy controls. However, when cases were subgrouped according to whether they had a sudden or gradual onset, differences in immunologic markers were detected between cases and their matched controls.     

Integration of gene expression,clinical, and epidemiologic data to characterize Chronic Fatigue Syndrome

Background  

Chronic fatigue syndrome (CFS) has no diagnostic clinical signs or diagnostic laboratory abnormalities and it is unclear if it represents a single illness. The CFS research case definition recommends stratifying subjects by co-morbid conditions, fatigue level and duration, or functional impairment. But to date, this analysis approach has not yielded any further insight into CFS pathogenesis. This study used the integration of peripheral blood gene expression results with epidemiologic and clinical data to determine whether CFS is a single or heterogeneous illness.     

Human Herpesviruses in Chronic Fatigue Syndrome

We have conducted a double-blind study to assess the possible involvement of the human herpesviruses (HHVs) HHV6, HHV7, Epstein-Barr virus (EBV), and cytomegalovirus in chronic fatigue syndrome (CFS) patients compared to age-, race-, and gender-matched controls. The CFS patient population was composed of rigorously screened civilian and Persian Gulf War veterans meeting the Centers for Disease Control and Prevention’s CFS case definition criteria. Healthy control civilian and veteran populations had no evidence of CFS or any other exclusionary medical or psychiatric condition. Patient peripheral blood mononuclear cells were analyzed by PCR for the presence of these HHVs. Using two-tailed Fisher’s exact test analyses, we were unable to ascertain any statistically significant differences between the CFS patient and control populations in terms of the detection of one or more of these viruses. This observation was upheld when the CFS populations were further stratified with regard to the presence or absence of major axis I psychopathology and patient self-reported gradual versus acute onset of disease. In tandem, we performed serological analyses of serum anti-EBV and anti-HHV6 antibody titers and found no significant differences between the CFS and control patients.     

慢性疲劳综合征的中医研究

通过对近年来有关慢性疲劳综合征文献的回顾,对慢性疲劳综合征的中医病名、病因病机等方面进行了综述。同时笔者主要从中医整体观念、辨证论治角度出发阐述慢性疲劳综合征近十年病因病机及中医药治疗进展,提出中医药治疗优势,综述中医药治疗慢性疲劳综合征的新路,以期为临床治疗慢性疲劳综合征提供思路。     

慢性疲劳综合征综合性治疗临床疗效观察

慢性疲劳综合征(chronic fatigue syndrome,CFS)是指一组症状群,包括疲惫感、头痛、睡眠障碍、注意力集中困难,肌肉疼痛等.主要在20-40岁的人群中,女性的患病率至少是男性的两部.目前还没有一个统一的被认可的CFS诊断标准和治疗方法.一般采用英国的牛津(Oxford)标准和美国的疾病预防及控制中心(CDC)1998年和1994年的标准.本文初步观察抗抑郁药舍曲林对慢性疲劳综合征患者的疗效.     

The Case Definition of Chronic Fatigue Syndrome

The 1994 case definition of chronic fatigue syndrome is widely used not only for diagnosis but also for clinical and laboratory-based observations of this clinical entity. The criteria for the 1994 case definition are based primarily on symptoms and not on physical signs or chemical or immunological tests. This situation has resulted in conflicting clinical and laboratory observations that in all likelihood is due to different populations of patients being studied in different centers. Based on some of the recent publications, there appears to be an emerging picture of this disease entity that we propose could be used to subgroup chronic fatigue syndrome into four different subclasses. These subclasses would consist of chronic fatigue with primarily nervous system disorders such as impaired memory or concentration and headache, chronic fatigue with primarily endocrine system disorders such as unrefreshing sleep and postexertional malaise, chronic fatigue with musculoskeletal system disorders such as muscle pain and joint pain, and chronic fatigue with immune system/infectious disorders such as sore throat and tender lymph nodes. It is suggested that if clinical and laboratory-based studies on chronic fatigue syndrome were conducted on more homogeneous subgroups of patients, the data from one center to the other might not be as conflicting and more insights can be shed on the nature of this clinical condition.     

Immunological Abnormalities in Patients with Chronic Fatigue Syndrome

Between January 1991 and January 1993, 265 patients who fulfilled the CDC criteria of the working case definition of Chronic Fatigue Syndrome (CFS) have been observed at our Institution and submitted for clinical and laboratory evaluation. One hundred and sixty-three patients were females and 102 males, the median age was 35 years (range 4–55 years); all patients reported profound and prolonged fatigue, lasting for a median of 3 years (range 6 months–10 years), preceded or accompanied at appearance by fever in 185 cases, and neuropsychologic problems including inability to concentrate, difficulty in thinking, confusion, irritability, forgetfulness, and depression. The fatigue was so severe that it required 102 patients to stop their working activities for a period of time ranging from 3 months to 2 years (range 7 months). In 40 consecutive patients a comprehensive immunologic testing by single and two-colour flow cytometry was performed and results compared with a group of 35 healthy, age- and sex-matched controls. Whilst no significant differences were found in the absolute numbers of circulating total T cells (CD3⁺) and of total helper/inducer (CD4⁺) or suppressor/cytotoxic (CDS⁺) T cells, an evident reduction in CD3⁻/CD16⁺ and CD57⁺/CD56⁺ NK lymphocytes along with an expansion of the CD8⁺/CD56⁺ and CD16⁻/CD56⁺ NK subsets, were found in the CFS group. In addition, CD56⁺ NK cells from CFS subjects were found to express an increased amount of cell adhesion molecules (CD11b. CD1 1c, CD54) and activation antigens (CD38). Both the percentage and absolute numbers of CD4⁺ T cells bearing the CD45RA antigen appeared significantly reduced in CFS patients, and CD4⁺ T lymphocytes from CFS subjects displayed an increased expression of the intercellular adhesion molecule-1 (ICAM⁻ 1/CD54). Finally, the total numbers of circulating (CD19⁺) B lymphocytes, were significantly higher in CFS cases than in controls, and in 11 out of 30 CFS patients the increase in circulating B cells was sustained by the expansion of the CD5⁺/CD19⁺ subset of B lymphocytes. We conclude that CFS is a syndrome not previously described in Italy, with already known clinical characteristics and appears to be associated with several immunologic abnormalities, including those reported previously in cohort of patients from different countries. We also show for the first time that CD56⁺ NK cell subsets from CFS patients display an abnormally increased expression of cell adhesion molecules and activation markers.     

A Comprehensive Immunological Analysis in Chronic Fatigue Syndrome

A detailed analysis of cell-mediated and antibody-mediated immunity was performed in 20 CDC-defined patients with chronic fatigue syndrome (CFS) and 20 age- and sex-matched healthy controls. CD3+, CD4+, CD8+, and CD20+ lymphocytes were comparable in two groups. Natural killer cells as defined by CD16, CD56 and CD57 antigens were significantly reduced in CFS. A significant increase in the proportions of CD4+ ICAM 1+ T cells was observed in CFS. Monocytes from CFS displayed increased density (as determined by mean fluorescence channel numbers) of intercellular adhesion molecule 1 (ICAM-1) and lymphocyte function associated antigen 1 (LFA-1), but showed decreased enhancing response to recombinant interferon-gamma in vitro. The lymphocyte DNA synthesis in response to phytohaemoglobulin (PHA), Concanavalin A (Con A) and pokeweed mitogen (PWM) was normal but the response to soluble antigens was significantly reduced. Serum IgM, IgG, IgA, and IgG subclasses were normal. In vivo specific antibody response to pneumococcus vaccine was depressed in CFS. Forty percent of patients showed titres of anti-human herpes virus 6 (anti-HHV-6) antibody higher than that in the controls (greater than or equal to 1/80). These data suggest immunological dysfunction in patients with chronic fatigue syndrome. The significance of these observations is discussed.     

Immune and hemorheological changes in Chronic Fatigue Syndrome

Background  

Chronic Fatigue Syndrome (CFS) is a multifactorial disorder that affects various physiological systems including immune and neurological systems. The immune system has been substantially examined in CFS with equivocal results, however, little is known about the role of neutrophils and natural killer (NK) phenotypes in the pathomechanism of this disorder. Additionally the role of erythrocyte rheological characteristics in CFS has not been fully expounded. The objective of this present study was to determine deficiencies in lymphocyte function and erythrocyte rheology in CFS patients.     

A comparison of classification methods for predicting Chronic Fatigue Syndrome based on genetic data

Background  

In the studies of genomics, it is essential to select a small number of genes that are more significant than the others for the association studies of disease susceptibility. In this work, our goal was to compare computational tools with and without feature selection for predicting chronic fatigue syndrome (CFS) using genetic factors such as single nucleotide polymorphisms (SNPs).     

慢性疲劳综合征在大学生群体中患病情况的调查分析

目的 首次评价和分析大学生群体慢性疲劳综合征(CFS)患病情况.方法 对289名医学院校大学生集中进行CFS调查.结果 大学生中不同程度疲劳感的人有227人,占被调查者的78.5％;符合CFS诊断标准的占5.4％;最常见的3个症状是:“注意力难以集中”(占被调查总体的83.3％),“记忆力下降”(占65.2％),“睡眠...     

Daily Fluctuation in Chronic Fatigue Syndrome Severity and Symptoms

The present study characterized 46 chronic fatigue syndrome (CFS) patients' experiences of CFS and compared these patients with 11 healthy control participants. Chronic fatigue syndrome patients reported more symptoms of CFS, distress, and functional impairment than the controls. These heightened symptoms remained relatively stable over time within the patient group. However, within individual patients, there were daily fluctuations in symptom reporting, indicating that some days were better than others. Additionally, there was a close association between CFS symptoms and reports of perceived stress and negative affect in the patient group. These results demonstrate the usefulness of the Daily Record Form for assessing symptom severity in CFS patients.     

Sleep Quality and Psychological Adjustment in Chronic Fatigue Syndrome

Without specific etiology or effective treatment, chronic fatigue syndrome (CFS) remains a contentious diagnosis. Individuals with CFS complain of fatigue and poor sleep—symptoms that are often attributed to psychological disturbance. To assess the nature and prevalence of sleep disturbance in CFS and to investigate the widely presumed presence of psychological maladjustment we examined sleep quality, sleep disorders, physical health, daytime sleepiness, fatigue, and psychological adjustment in three samples: individuals with CFS; a healthy control group; and individuals with a definite medical diagnosis: narcolepsy. Outcome measures included physiological evaluation (polysomnography), medical diagnosis, structured interview, and self-report measures. Results indicate that the CFS sample had a very high incidence (58%) of previously undiagnosed primary sleep disorder such as sleep apnea/hypopnea syndrome and restless legs/periodic limb movement disorder. They also had very high rates of self-reported insomnia and nonrestorative sleep. Narcolepsy and CFS participants were very similar on psychological adjustment: both these groups had more psychological maladjustment than did control group participants. Our data suggest that primary sleep disorders in individuals with CFS are underdiagnosed in primary care settings and that the psychological disturbances seen in CFS may well be the result of living with a chronic illness that is poorly recognized or understood.     

Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome

Arguments exist as to the cause of chronic fatigue syndrome (CFS). Some think that it is an example of symptom amplification indicative of functional or psychogenic illness, while our group thinks that some CFS patients may have brain dysfunction. To further pursue our encephalopathy hypothesis, we did spinal taps on 31 women and 13 men fulfilling the 1994 case definition for CFS and on 8 women and 5 men serving as healthy controls. Our outcome measures were white blood cell count, protein concentration in spinal fluid, and cytokines detectable in spinal fluid. We found that significantly more CFS patients had elevations in either protein levels or number of cells than healthy controls (30 versus 0%), and 13 CFS patients had protein levels and cell numbers that were higher than laboratory norms; patients with abnormal fluid had a lower rate of having comorbid depression than those with normal fluid. In addition, of the 11 cytokines detectable in spinal fluid, (i) levels of granulocyte-macrophage colony-stimulating factor were lower in patients than controls, (ii) levels of interleukin-8 (IL-8) were higher in patients with sudden, influenza-like onset than in patients with gradual onset or in controls, and (iii) IL-10 levels were higher in the patients with abnormal spinal fluids than in those with normal fluid or controls. The results support two hypotheses: that some CFS patients have a neurological abnormality that may contribute to the clinical picture of the illness and that immune dysregulation within the central nervous system may be involved in this process.     

Naloxone-Reversible Monocyte Dysfunction in Patients with Chronic Fatigue Syndrome

We studied monocyte function in 35 consecutive patients with chronic fatigue syndrome (CFS) and 25 healthy controls. Eighty-five per cent of the patients showed monocyte dysfunction characterized by marked reduction in the number of monocytes displaying immunoreactive cytoskeletal vimentin filaments, a low phagocytosis index, and a reduced expression of HLA-DR antigens. These values increased dramatically after incubation of the patients' monocytes with the opioid antagonist naloxone. Other immunological abnormalities also noted in the patients were low lymphocyte blastogenesis and diminished numbers of monocytes displaying receptors for Fc of IgG (FcR) and C3b (CR1). These findings suggest that an increased opioid activity acting through a classical receptor mechanism is active on monocytes from a high proportion of patients with CFS and that this represents a novel example of immunomodulation by opioid peptides in human disease. We suggest that endogenous opioids are involved in the pathogenesis of the chronic fatigue syndrome.     

Self-Efficacy as a Psychological Moderator of Chronic Fatigue Syndrome

Chronic fatigue syndrome (CFS) is characterized by debilitating fatigue and a variety of somatic symptoms. Few studies have examined psychological aspects of CFS. In the present study, self-efficacy is shown to be a significant predictor of CFS symptoms beyond the variance accounted for by demographic variables and distress. Further psychological CFS research is encouraged by (1)identifying dimensions that are salient in the experience and study of CFS, (2) providing preliminary psychometric data for measures of those dimensions, and (3)identifying psychological variables that serve as moderators of the experience of CFS.     

Alpha Interferon Treatment of Patients with Chronic Fatigue Syndrome

Thirty patients who fulfilled clinical criteria defined by the CDC for Chronic Fatigue Syndrome were treated with alfa 2a interferon or placebo in a double-blind crossover study. Outcome was evaluated by Natural Kilter (NK) cell function, lymphocyte proliferation to mitogens and soluble antigens, CD4/CD8 counts and a 10 item Quality of Life (QOL) survey. Although mean NK function rose from 87.8 +/- 19.6 to 129.3 +/- 20.7 lytic untis (LU; p <.05) with 12 weeks of interferon therapy, there was no significant change in the other immunologic parameters or QOL scores. When the 26 patients who completed the study were stratified according to their baseline NK function and lymphocyte proliferation, 4 groups were identified: 3 patients had normal NK cell function and lymphocyte proliferation when compared to normal, healthy controls, 9 had isolated deficiency in lymphocyte proliferation, 7 had diminished NK function only, and 7 had abnormalities for both parameters. QOL scores were not significantly different for the four groups at baseline. After 12 weeks of interferon therapy, QOL score significantly improved in each of the seven patients with isolated NK cell dysfunction (mean score, 16.3 +/- 7.9) compared to baseline (39.7 +/- 12.1; p < .05). In these patients the mean NK function increased from 35.1 +/- 11.7 to 91.5 +/- 22.7 LU (p < .01). Significant improvement was not recorded for QOL in the other three groups. Thus, therapy with alpha interferon has a significant effect on the QOL of that subgroup of patients with CFS manifesting an isolated decrease in NK function.