Tag: 2006

An empirical delineation of the heterogeneity of chronic unexplained fatigue in women

Abstract:

OBJECTIVES: To test the hypothesis that medically unexplained chronic fatigue and chronic fatigue syndrome (CFS) are heterogeneous conditions, and to define the different conditions using both symptom and laboratory data.

METHODS: We studied 159 women from KS, USA. A total of 51 of these suffered from fatigue consistent with established criteria for CFS, 55 had chronic fatigue of insufficient symptoms/severity for a CFS diagnosis and 53 were healthy controls matched by age and body mass index (BMI) against those with CFS. We used principal components analyses to define factors that best described the variable space and to reduce the number of variables. The 38 most explanatory variables were then used in latent class analyses to define discrete subject groups.

RESULTS: Principal components analyses defined six discrete factors that explained 40% of the variance. Latent class analyses provided several interpretable solutions with four, five and six classes. The four-class solution was statistically most convincing, but the six-class solution was more interpretable. Class 1 defined 41 (26%) subjects with obesity and relative sleep hypnoea. Class 2 were 38 (24%) healthy subjects. Class 3 captured 24 (15%) obese relatively hypnoeic subjects, but with low heart rate variability and cortisol. Class 4 were 23 (14%) sleep-disturbed and myalgic subjects without obesity or significant depression. The two remaining classes with 22 (14%) and 11 (7%) subjects consisted of the most symptomatic and depressed, but without obesity or hypnoea. Class 5 had normal sleep indices. Class 6 was characterized by disturbed sleep, with low sleep heart rate variability, cortisol, and sex hormones.

CONCLUSION: Chronic medically unexplained fatigue is heterogeneous. The putative syndromes were differentiated by obesity, sleep hypnoea, depression, physiological stress response, sleep disturbance, interoception and menopausal status. If these syndromes are externally validated and replicated, they may prove useful in determining the causes, pathophysiology and treatments of CFS.

 

Source: Vollmer-Conna U, Aslakson E, White PD. An empirical delineation of the heterogeneity of chronic unexplained fatigue in women. Pharmacogenomics. 2006 Apr;7(3):355-64. https://www.ncbi.nlm.nih.gov/pubmed/16610946

 

The challenge of integrating disparate high-content data: epidemiological, clinical and laboratory data collected during an in-hospital study of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a debilitating illness characterized by multiple unexplained symptoms including fatigue, cognitive impairment and pain. People with CFS have no characteristic physical signs or diagnostic laboratory abnormalities, and the etiology and pathophysiology remain unknown. CFS represents a complex illness that includes alterations in homeostatic systems, involves multiple body systems and results from the combined action of many genes, environmental factors and risk-conferring behavior. In order to achieve understanding of complex illnesses, such as CFS, studies must collect relevant epidemiological, clinical and laboratory data and then integrate, analyze and interpret the information so as to obtain meaningful clinical and biological insight. This issue of Pharmacogenomics represents such an approach to CFS.

Data was collected during a 2-day in-hospital study of persons with CFS, other medically and psychiatrically unexplained fatiguing illnesses and nonfatigued controls identified from the general population of Wichita, KS, USA. While in the hospital, the participants’ psychiatric status, sleep characteristics and cognitive functioning was evaluated, and biological samples were collected to measure neuroendocrine status, autonomic nervous system function, systemic cytokines and peripheral blood gene expression. The data generated from these assessments was made available to a multidisciplinary group of 20 investigators from around the world who were challenged with revealing new insight and algorithms for integration of this complex, high-content data and, if possible, identifying molecular markers and elucidating pathophysiology of chronic fatigue. The group was divided into four teams with representation from the disciplines of medicine, mathematics, biology, engineering and computer science. The papers in this issue are the culmination of this 6-month challenge, and demonstrate that data integration and multidisciplinary collaboration can indeed yield novel approaches for handling large, complex datasets, and reveal new insight and relevance to a complex illness such as CFS.

Comment in: The postgenomic era and complex disease. [Pharmacogenomics. 2006]

 

Source: Vernon SD, Reeves WC. The challenge of integrating disparate high-content data: epidemiological, clinical and laboratory data collected during an in-hospital study of chronic fatigue syndrome. Pharmacogenomics. 2006 Apr;7(3):345-54. https://www.ncbi.nlm.nih.gov/pubmed/16610945

 

Postulated vasoactive neuropeptide autoimmunity in fatigue-related conditions: a brief review and hypothesis

Abstract:

Disorders such as chronic fatigue syndrome (CFS) and gulf war syndrome (GWS) are characterised by prolonged fatigue and a range of debilitating symptoms of pain, intellectual and emotional impairment, chemical sensitivities and immunological dysfunction. Sudden infant death syndrome (SIDS) surprisingly may have certain features in common with these conditions. Post-infection sequelae may be possible contributing factors although ongoing infection is unproven. Immunological aberration may prove to be associated with certain vasoactive neuropeptides (VN) in the context of molecular mimicry, inappropriate immunological memory and autoimmunity.

Adenylate cyclase-activating VNs including pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) act as hormones, neurotransmitters, neuroregulators, immune modulators and neurotrophic substances. They and their receptors are potentially immunogenic.

VNs are widely distributed in the body particularly in the central and peripheral nervous systems and have been identified in the gut, adrenal gland, blood cells, reproductive system, lung, heart and other tissues. They have a vital role in maintaining cardio-respiratory function, thermoregulation, memory, concentration and executive functions such as emotional responses including social cues and appropriate behaviour. They are co-transmitters for a number of neurotransmitters including acetylcholine and gaseous transmitters, are potent immune regulators with primarily anti-inflammatory activity, and have a significant role in protection of the nervous system against toxic assault as well as being important in the maintenance of homeostasis.

This paper describes a biologically plausible mechanism for the development of certain fatigue-related syndromes based on loss of immunological tolerance to these VNs or their receptors following infection, other events or de novo resulting in significant pathophysiology possibly mediated via CpG fragments and heat shock (stress) proteins. These conditions extend the public health context of autoimmunity and VN dysregulation and have implications for military medicine where radiological, biological and chemical agents may have a role in pathogenesis. Possible treatment and prevention options are considered.

 

Source: Staines DR. Postulated vasoactive neuropeptide autoimmunity in fatigue-related conditions: a brief review and hypothesis. Clin Dev Immunol. 2006 Mar;13(1):25-39. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2270748/ (Full article)

 

Fatigue Intervention by Nurses Evaluation–the FINE Trial. A randomised controlled trial of nurse led self-help treatment for patients in primary care with chronic fatigue syndrome: study protocol.[ISRCTN74156610]

Abstract:

BACKGROUND: Chronic fatigue syndrome, also known as ME (CFS/ME), is a condition characterised primarily by severe, disabling fatigue, of unknown origin, which has a poor prognosis and serious personal and economic consequences. Evidence for the effectiveness of any treatment for CFS/ME in primary care, where most patients are seen, is sparse. Recently, a brief, pragmatic treatment for CFS/ME, based on a physiological dysregulation model of the condition, was shown to be successful in improving fatigue and physical functioning in patients in secondary care. The treatment involves providing patients with a readily understandable explanation of their symptoms, from which flows the rationale for a graded rehabilitative plan, developed collaboratively with the therapist. The present trial will test the effectiveness and cost-effectiveness of pragmatic rehabilitation when delivered by specially trained general nurses in primary care. We selected a client-centred counselling intervention, called supportive listening, as a comparison treatment. Counselling has been shown to be as effective as cognitive behaviour therapy for treating fatigue in primary care, is more readily available, and controls for supportive therapist contact time. Our control condition is treatment as usual by the general practitioner (GP).

METHODS AND DESIGN: This study protocol describes the design of an ongoing, single-blind, pragmatic randomized controlled trial of a brief (18 week) self-help treatment, pragmatic rehabilitation, delivered by specially trained nurse-therapists in patients’ homes, compared with nurse-therapist delivered supportive listening and treatment as usual by the GP. An economic evaluation, taking a societal viewpoint, is being carried out alongside the clinical trial. Three adult general nurses were trained over a six month period to deliver the two interventions. Patients aged over 18 and fulfilling the Oxford criteria for CFS are assessed at baseline, after the intervention, and again one year later. Primary outcomes are self-reported physical functioning and fatigue at one year, and will be analysed on an intention-to-treat basis. A qualitative study will examine the interventions’ mechanisms of change, and also GPs’ drivers and barriers towards referral.

 

Source: Wearden AJ, Riste L, Dowrick C, Chew-Graham C, Bentall RP, Morriss RK, Peters S, Dunn G, Richardson G, Lovell K, Powell P. Fatigue Intervention by Nurses Evaluation–the FINE Trial. A randomised controlled trial of nurse led self-help treatment for patients in primary care with chronic fatigue syndrome: study protocol. [ISRCTN74156610]. BMC Med. 2006 Apr 7;4:9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1456982/ (Full article)

 

Efficacy of neurotropin in chronic fatigue syndrome: a case report

Abstract:

Chronic fatigue syndrome (CFS) is a disorder that causes general fatigue and chronic widespread pain. A 28-year-old male visited an outpatient department due to general fatigue and pain involving the entire body. He did not suffer from fibromyalgia, but he was diagnosed with CFS. At the initial visit, he complained of lack of concentration, memory decline, frequent urination, insomnia and occasional difficulty of emotional control, as well as general fatigue and pain involving the entire body. Four tablets of Neurotropin per day alone were administered.

General fatigue and pain were gradually alleviated one week later. His sleep condition, concentration power, and memory also improved two weeks later. Medication was discontinued from 11 weeks based on the patient’s judgment as he felt little general fatigue and pain involving the entire body. Treatment was completed 3 months later. The symptoms disappeared and did not recur five months after the discontinuation of Neurotropin. He was looking for a job without fatigue and pain 8 months later (5 months after the cessation of treatment). The functional mechanisms of Neurotropin in CFS are unknown.

 

Source: Toda K, Kimura H. Efficacy of neurotropin in chronic fatigue syndrome: a case report. Hiroshima J Med Sci. 2006 Mar;55(1):35-7. https://www.ncbi.nlm.nih.gov/pubmed/16594551

 

Psychiatric comorbidity and chronic fatigue syndrome

Prins et al (2005) assessed psychiatric comorbidity in chronic fatigue syndrome (CFS) using the Structured Clinical Interview for DSM–III–R. Comorbidity was remarkably low compared with similar investigations, and in particular the apparent absence of current post-traumatic stress disorder (PTSD) was striking. The authors speculated that the low comorbidity rates might result mainly from a lack of ‘psychiatric bias’ of the examiners. They also found that psychiatric comorbidity did not predict the outcome of cognitive–behavioural therapy.

You can read the rest of this comment here: http://bjp.rcpsych.org/content/188/4/395.2.long

 

Source: Van Houdenhove B. Psychiatric comorbidity and chronic fatigue syndrome. Br J Psychiatry. 2006 Apr;188:395; author reply 396. http://bjp.rcpsych.org/content/188/4/395.2.long (Full article)

 

 

Beneficial effect of brewers’ yeast extract on daily activity in a murine model of chronic fatigue syndrome

Abstract:

The aim of this study was to assess the effect of Brewers’ yeast extract (BYE) on daily activity in a mouse model of chronic fatigue syndrome (CFS). CFS was induced by repeated injection of Brucella abortus (BA) antigen every 2 weeks. BYE was orally administered to mice in a dose of 2 g per kg per day for 2 weeks before injecting BA and for 4 weeks thereafter. We evaluated daily running activity in mice receiving BYE as compared with that in untreated mice.

Weekly variation of body weight (BW) and survival in both groups was monitored during the observation period. Spleen weight (SW), SW/BW ratio, percent splenic follicular area and expression levels of interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) mRNA in spleen were determined in both groups at the time of sacrifice. The daily activity during 2 weeks after the second BA injection was significantly higher in the treated group than in the control. There was no difference in BW between both groups through the experimental course. Two mice in the control died 2 and 7 days after the second injection, whereas no mice in the treated group died. Significantly decreased SW and SW/BW ratio were observed in the treated mice together with elevation of splenic follicular area.

There were suppressed IFN-gamma and IL-10 mRNA levels in spleens from the treated mice. Our results suggest that BYE might have a protective effect on the marked reduction in activity following repeated BA injection via normalization of host immune responses.

 

Source: Takahashi T, Yu F, Zhu SJ, Moriya J, Sumino H, Morimoto S, Yamaguchi N, Kanda T. Beneficial effect of brewers’ yeast extract on daily activity in a murine model of chronic fatigue syndrome. Evid Based Complement Alternat Med. 2006 Mar;3(1):109-15. Epub 2006 Jan 23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1375235/ (Full article)

 

The association between experimental and clinical pain measures among persons with fibromyalgia and chronic fatigue syndrome

Abstract:

Evoked or experimental pain is often used as a model for the study of clinical pain, yet there are little data regarding the relationship between the two. In addition, there are few data regarding the types of stimuli and stimulus intensities that are most closely related to clinical pain. In this study, 36 subjects with fibromyalgia (FM), chronic fatigue syndrome (CFS), or both syndromes were administered measures of clinical pain and underwent a dolorimetry evaluation. Subjects also underwent experimental pain testing utilizing heat and pressure stimulation.

Stimulation levels evoking low, moderate and high sensory intensity, and comparable levels of unpleasantness, were determined for both types of stimuli using random staircase methods. Clinical pain was assessed using visual analogue ratings and the short form of the McGill Pain Questionnaire (MPQ). Ratings of heat pain sensation were not significantly associated with clinical pain ratings, with the exception of unpleasantness ratings at high stimulus intensities. Pain threshold and tolerance as assessed by dolorimetry were significantly associated with average measures of clinical pain.

Both intensity and unpleasantness ratings of pressure delivered using random staircase methods were significantly associated with clinical pain at low, moderate and high levels, and the strength of the association was greater at increasingly noxious stimulus intensities. These findings suggest that random pressure stimulation as an experimental pain model in these populations more closely reflects the clinical pain for these conditions. These findings merit consideration when designing experimental studies of clinical pain associated with FM and CFS.

 

Source: Geisser ME, Gracely RH, Giesecke T, Petzke FW, Williams DA, Clauw DJ. The association between experimental and clinical pain measures among persons with fibromyalgia and chronic fatigue syndrome. Eur J Pain. 2007 Feb;11(2):202-7. Epub 2006 Mar 20. https://www.ncbi.nlm.nih.gov/pubmed/16546424

 

On the important role of Siguan points in treatment of chronic fatigue syndrome

Abstract:

OBJECTIVE: To probe into the role of Siguan points in treatment of chronic fatigue syndrome.

METHODS: Based on diagnosis, pathogenesis and etiology of chronic fatigue syndrome in TCM, the role of Siguan points in treatment of chronic fatigue syndrome were induced by means of relative literatures of Siguan points in recent 10 years from 3 aspects.

CONCLUSION: Acupuncture at Siguan as main points has a better therapeutic effect on chronic fatigue syndrome.

 

Source: Wang JJ, Meng H, Cui CB, Song YJ, Wang XH, Wu ZC. On the important role of Siguan points in treatment of chronic fatigue syndrome. Zhongguo Zhen Jiu. 2006 Feb;26(2):116-9. [Article in Chinese] https://www.ncbi.nlm.nih.gov/pubmed/16541862

 

The Spanish version of the FibroFatigue Scale: validation of a questionnaire for the observer’s assessment of fibromyalgia and chronic fatigue syndrome

Abstract:

OBJECTIVE: To examine some of the psychometric properties of the Spanish version of the FibroFatigue Scale (FFS).

METHODS: FFS was administered to 120 patients diagnosed with fibromyalgia and chronic fatigue syndrome. Internal consistency was evaluated by using Cronbach’s alpha, test-retest reliability with weighted kappa and construct validity by correlations among FFS, the Fibromyalgia Impact Questionnaire (FIQ), the EuroQol 5D (EQ-5D) and the Hospital Anxiety and Depression Scale (HADS). The interrater reliability was tested using analysis of variance with patients and raters as independent factors.

RESULTS: Internal consistency (alpha) was .88, test-retest reliability was .91, and interrater reliability was .93. Significant correlations were obtained between overall FFS and the FIQ (.55, P<.01), the EQ-5D (-.48, P<.01) and the HADS depression subscale (.25, P<.01), but not with the HADS anxiety subscale.

CONCLUSION: These results support the reliability and validity of the data obtained with the Spanish version of the FSS.

 

Source: García-Campayo J, Pascual A, Alda M, Marzo J, Magallon R, Fortes S. The Spanish version of the FibroFatigue Scale: validation of a questionnaire for the observer’s assessment of fibromyalgia and chronic fatigue syndrome. Gen Hosp Psychiatry. 2006 Mar-Apr;28(2):154-60. https://www.ncbi.nlm.nih.gov/pubmed/16516066