Tag: 2005

Brain 5-HT1A receptor binding in chronic fatigue syndrome measured using positron emission tomography and [11C]WAY-100635

Abstract:

BACKGROUND: Research from neuroendocrine challenge and other indirect studies has suggested increased central 5-HT function in chronic fatigue syndrome (CFS) and increased 5-HT1A receptor sensitivity. We assessed brain 5-HT1A receptor binding potential directly using the specific radioligand [11C]WAY-100635 and positron emission tomography (PET).

METHODS: We selected 10 patients from a tertiary referral clinic who fulfilled the CDC consensus criteria for CFS. To assemble a homogenous group and avoid confounding effects, we enrolled only subjects who were completely medication-free and did not have current comorbid psychiatric illness. We also scanned 10 healthy control subjects.

RESULTS: There was a widespread reduction in 5-HT1A receptor binding potential in CFS relative to control subjects. This was particularly marked in the hippocampus bilaterally, where a 23% reduction was observed.

CONCLUSIONS: There is evidence of decreased 5-HT1A receptor number or affinity in CFS. This may be a primary feature of CFS, related to the underlying pathophysiology, or a finding secondary to other processes, such as previous depression, other biological changes or the behavioral consequences of CFS.

 

Source: Cleare AJ, Messa C, Rabiner EA, Grasby PM. Brain 5-HT1A receptor binding in chronic fatigue syndrome measured using positron emission tomography and [11C]WAY-100635. Biol Psychiatry. 2005 Feb 1;57(3):239-46. http://www.ncbi.nlm.nih.gov/pubmed/15691524

 

Family health and characteristics in chronic fatigue syndrome, juvenile rheumatoid arthritis, and emotional disorders of childhood

Abstract:

OBJECTIVE: To compare family health and characteristics in children with chronic fatigue syndrome (CFS), in juvenile rheumatoid arthritis (JRA), and emotional disorders.

METHOD: Parents of 28 children and adolescents aged 11 to 18 years with CFS, 30 with JRA, and 27 with emotional disorders (i.e., anxiety and/or depressive disorders) were recruited from specialty clinical settings and completed interviews and questionnaires assessing family health problems, parental mental distress, illness attitudes, and family burden of illness.

RESULTS: Parents of children with CFS were significantly more likely than those of children with JRA to report a history of CFS-like illness, high levels of mental distress, and a tendency to experience functional impairment in response to physical symptoms. Families of children with CFS were characterized by significantly greater emotional involvement and reported greater family burden related to the child’s illness in comparison with families of children with JRA.

CONCLUSIONS: CFS in childhood and adolescence is associated with higher levels of parental CFS-like illness, mental distress, emotional involvement, and family illness burden than those observed in association with JRA, a chronic pediatric physical illness.

 

Source: Rangel L, Garralda ME, Jeffs J, Rose G. Family health and characteristics in chronic fatigue syndrome, juvenile rheumatoid arthritis, and emotional disorders of childhood. J Am Acad Child Adolesc Psychiatry. 2005 Feb;44(2):150-8. http://www.ncbi.nlm.nih.gov/pubmed/15689728

 

Development of a functional ability scale for children and young people with myalgic encephalopathy (ME)/chronic fatigue syndrome (CFS)

Abstract:

The numerous symptoms and unpredictable pattern of myalgic encephalopathy (ME) make it difficult to describe, especially for children. It was left to carers to guess what the child could achieve each day, often leading to over/underestimates. A functional ability scale was needed, which measured from 0 to 100 percent able and that children and young people themselves designed.

A new scale was developed from the Moss Ability Scale using the critique of 251 children and young people from the Association of Young People with ME (AYME). Responding to the shift in emphasis towards patients taking an active role in their own care, it was felt these young people would know whether the scale measured what it had set out to measure, and were asked questions on the face and content validity of the scale. There was a 99 percent agreement between the young people that the final scale was ‘workable’ or better.

 

Source: Moss J. Development of a functional ability scale for children and young people with myalgic encephalopathy (ME)/chronic fatigue syndrome (CFS). J Child Health Care. 2005 Mar;9(1):20-30. http://www.ncbi.nlm.nih.gov/pubmed/15684437

 

Stress-associated changes in the steady-state expression of latent Epstein-Barr virus: implications for chronic fatigue syndrome and cancer

Abstract:

Antibodies to several Epstein-Barr virus (EBV)-encoded enzymes are observed in patients with different EBV-associated diseases. The reason for these antibody patterns and the role these proteins might play in the pathophysiology of disease, separate from their role in virus replication, is unknown.

In this series of studies, we found that purified EBV deoxyuridine triphosphate nucleotidohydrolase (dUTPase) can inhibit the replication of human peripheral blood mononuclear cells in vitro and upregulate the production of TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10. It also enhanced the ability of natural killer cells to lyse target cells. The EBV dUTPase also significantly inhibited the replication of mitogen-stimulated lymphocytes and the synthesis of IFN-gamma by cells isolated from lymph nodes and spleens obtained from mice inoculated with the protein.

It also produced sickness behaviors known to be induced by some of the cytokines that were studied in the in vitro experiments. These symptoms include an increase in body temperature, a decrease in body mass and in physical activity.

The data provide a new perspective on how an early nonstructural EBV-encoded protein can cause immune dysregulation and produce clinical symptoms observed in patients with chronic fatigue syndrome (CFS) separate from its role in virus replication and may serve as a new approach to help identify one of the etiological agents for CFS. The data also provide additional insight into the pathophysiology of EBV infection, inflammation, and cancer.

 

Source: Glaser R, Padgett DA, Litsky ML, Baiocchi RA, Yang EV, Chen M, Yeh PE, Klimas NG, Marshall GD, Whiteside T, Herberman R, Kiecolt-Glaser J, Williams MV. Stress-associated changes in the steady-state expression of latent Epstein-Barr virus: implications for chronic fatigue syndrome and cancer. Brain Behav Immun. 2005 Mar;19(2):91-103. http://www.ncbi.nlm.nih.gov/pubmed/15664781

 

Spinal fluid abnormalities in patients with chronic fatigue syndrome

Abstract:

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.

 

Source: Natelson BH, Weaver SA, Tseng CL, Ottenweller JE. Spinal fluid abnormalities in patients with chronic fatigue syndrome. Clin Diagn Lab Immunol. 2005 Jan;12(1):52-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC540195/ (Full article)

 

Ambulatory monitoring of physical activity and symptoms in fibromyalgia and chronic fatigue syndrome

Abstract:

OBJECTIVE: Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are associated with substantial physical disability. Determinants of self-reported physical disability are poorly understood. This investigation uses objective ambulatory activity monitoring to compare patients with FM and/or CFS with controls, and examines associations of ambulatory activity levels with both physical function and symptoms during activities of daily life.

METHODS: Patients with FM and/or CFS (n = 38, mean +/- SD age 41.5 +/- 8.2 years, 74% women) completed a 5-day program of ambulatory monitoring of physical activity and symptoms (pain, fatigue, and distress) and results were compared with those in age-matched controls (n = 27, mean +/- SD age 38.0 +/- 8.6 years, 44% women). Activity levels were assessed continuously, ambulatory symptoms were determined using electronically time-stamped recordings at 5 time points during each day, and physical function was measured with the 36-item Short Form health survey at the end of the 5-day monitoring period.

RESULTS: Patients had significantly lower peak activity levels than controls (mean +/- SEM 8,654 +/- 527 versus 12,913 +/- 1,462 units; P = 0.003) and spent less time in high-level activities when compared with controls (P = 0.001). In contrast, patients had similar average activity levels as those of controls (mean +/- SEM 1,525 +/- 63 versus 1,602 +/- 89; P = 0.47). Among patients, low activity levels were associated with worse self-reported physical function over the preceding month. Activity levels were inversely related to concurrent ambulatory pain (P = 0.031) and fatigue (P < 0.001). Pain and fatigue were associated with reduced subsequent ambulatory activity levels, whereas activity levels were not predictive of subsequent symptoms.

CONCLUSION: Patients with FM and/or CFS engaged in less high-intensity physical activities than that recorded for sedentary control subjects. This reduced peak activity was correlated with measures of poor physical function. The observed associations may be relevant to the design of behavioral activation programs, because activity levels appear to be contingent on, rather than predictive of, symptoms.

 

Source: Kop WJ, Lyden A, Berlin AA, Ambrose K, Olsen C, Gracely RH, Williams DA, Clauw DJ. Ambulatory monitoring of physical activity and symptoms in fibromyalgia and chronic fatigue syndrome. Arthritis Rheum. 2005 Jan;52(1):296-303. http://onlinelibrary.wiley.com/doi/10.1002/art.20779/full (Full article)

 

Do vasoactive neuropeptides and heat shock proteins mediate fatigue-related autoimmune disorders?

Abstract:

Autoimmune dysfunction of certain vasoactive neuropeptides may be implicated in a range of disorders associated with fatigue like states (chronic fatigue syndrome, Gulf War syndrome) and even sudden infant death syndrome. These substances have neurotrophic, neuroregulatory, and neurotransmission functions, as well as that of immune modulators and hormones. They exert significant control over carbohydrate and lipid metabolism.

The hypothesis is that because these substances have vital and indispensable roles in cellular processes, loss or compromise of these roles would lead to predictable and severe cellular and systemic effects. The important roles of certain VNs make them a vulnerable target for autoimmune dysfunction. They are known to be associated with heat shock proteins for intracellular functioning with which they may form immunostimulating complexes. While peptide-HSP complexes are a relatively new area for research, this paper asserts that attention could be focused on these substances and complexes in an effort to elucidate a number of perplexing fatigue-associated disorders.

 

Source: Staines DR. Do vasoactive neuropeptides and heat shock proteins mediate fatigue-related autoimmune disorders? Med Hypotheses. 2005;64(3):539-42. http://www.ncbi.nlm.nih.gov/pubmed/15617862

 

Urinary electrophoretic profiles from chronic fatigue syndrome and chronic fatigue syndrome/fibromyalgia patients: a pilot study for achieving their normalization

Abstract:

Aim of our study was to determine if there were distinct, disease-related patterns of urinary analytes in chronic fatigue syndrome (CFS) and chronic fatigue syndrome/fibromyalgia (CFS/FM) compared to normal controls (NC).

Urine was collected from these subjects for two consecutive 24 h periods and aliquots were submitted to micellar electrokinetic chromatography (MEKC). To compensate for the differences in peak migration times, these were normalized from the 35 min duration of run to a 100-point scale, and each peak was assigned its normalized time measure. Peak heights were also normalized by dividing the mAU by that of the internal standard (creatinine) and multiplying by 100. MEKC with normalization for peak height and migration time generated comparable results within each of the patient groups.

CFS/FM and CFS had significant differences in peaks compared to NC that may be of significance as biomarkers of illnesses.

 

Source: Casado B, Zanone C, Annovazzi L, Iadarola P, Whalen G, Baraniuk JN. Urinary electrophoretic profiles from chronic fatigue syndrome and chronic fatigue syndrome/fibromyalgia patients: a pilot study for achieving their normalization. J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Jan 5;814(1):43-51. http://www.ncbi.nlm.nih.gov/pubmed/15607706

 

The clinical course of interstitial pneumonia alias chronic fatigue syndrome under the control of megadose vitamin C infusion system with dehydroepiandrosterone-cortisol annex

Abstract:

The year 1995 marked the onset of interstitial pneumonia spread in Nagoya, Japan. For the last 9 years, we have been accumulating clinical experience with the disease control using the combination of prophylactic use of anti-biotics and regular practice of megadose vitamin C infusion with either dehydroepiandrosterone-annex or dehydroepiandrosterone-cortisol annex. The purpose of this study is to assess the usefulness of our new treatment system for the control of interstitial pneumonia alias chronic fatigue syndrome.

The results obtained are given as follows:

i) The long-term maintenance of the above treatment system was effective not only for decreasing the risk for recurrence of active form pneumonia, but also for prevention of malignancy emergence in aged patients with interstitial pneumonia.

ii) Evidence is presented to indicate that interstitial pneumonia was associated with increased risk for depression of which the emergence is a candidate subject causally related to the long-term use of glucocorticoid.

iii) A patient with both interstitial pneumonia and depression was found to be less responsive to our treatment system. It is suggested that the use of more dehydroepiandrosterone at the sacrifice of cortisol in the infusion annex may be a choice for the control of both interstitial pneumonia and depression.

iv) The description of chronic fatigue syndrome as regards the endocrinological, epidemiological and psychiatric characteristics are in good agreement with our experience on patients having interstitial pneumonia, evidence in support of our proposal that there is no convincing reasoning to separate chronic fatigue syndrome from interstitial pneumonia.

v) The long-term practice of our treatment system for the control of interstitial pneumonia (an autoimmune disease) was found to suppress the inflammatory process but not the fibrotic process in the long run. vi) A few innovations were made in our treatment system to reduce the risk of bleeding or thrombosis–vascular complications of pneumonia.

vii) The merit of our treatment system is to create a new hormonal environment to improve the state of immunodeficiency by use of a non-steroid substance–vitamin C which encounters little resistance from the feedback mechanism of steroid metabolism in the in vivo system.

Source: Kodama M, Kodama T. The clinical course of interstitial pneumonia alias chronic fatigue syndrome under the control of megadose vitamin C infusion system with dehydroepiandrosterone-cortisol annex. Int J Mol Med. 2005 Jan;15(1):109-16. http://www.ncbi.nlm.nih.gov/pubmed/15583836

 

Stress-induced changes in LPS-induced pro-inflammatory cytokine production in chronic fatigue syndrome

Abstract:

OBJECTIVE: It has been suggested that a hypofunctional hypothalamic-pituitary-adrenal (HPA) axis in chronic fatigue syndrome could result in an exaggerated release of pro-inflammatory cytokines during stress. As pro-inflammatory cytokines are involved in the induction of sickness behavior and thus constitute a potential physiological correlate of stress-induced symptom exacerbation in chronic fatigue syndrome, we set out to evaluate the LPS-induced production of pro-inflammatory cytokines during psychosocial stress in CFS and healthy controls.

METHOD: Twenty-one CFS patients and 20 healthy controls matched for age and gender underwent a standardized psychosocial stress test (Trier social stress test, TSST). Adrenocorticotropine hormone (ACTH), salivary cortisol and plasma cortisol levels were measured before and repeatedly following exposure to the stressor. Lipopolysaccharide-stimulated production of interleukin-6 and tumor necrosis factor-alpha were assessed at baseline as well as 10 and 60 min after the stress test.

RESULTS: CFS patients showed an inverse stress-induced response pattern of LPS-stimulated cytokines responses in comparison to healthy controls, i.e. stimulated cytokine production decreased shortly after stress in CFS patients, while it increased in controls. Fatigue scores and basal LPS-induced cytokine levels were significantly associated for TNF-alpha in controls and for both cytokines in CFS patients. Stress-induced changes in stimulated cytokine production were not associated with general fatigue scores in the control group, whereas in the CFS group, fatigue scores were significantly correlated with integrated levels of LPS-induced cytokines. However, partial correlations revealed that these results were due to the high correlations with basal LPS-induced cytokine levels.

CONCLUSION: CFS patients do not show an exaggerated secretion of LPS-induced cytokines. Although cortisol responses to stress were normal, pro-inflammatory cytokine levels in CFS patients were significantly attenuated. Possible intracellular mechanisms, such as for example an enhanced sensitivity to inhibitory effects of glucocorticoids, a diminished responsivity to catecholaminergic stimulation, and a disruption of intracellular activation are discussed. Basal levels of stimulated pro-inflammatory Il-6 levels are generally related to fatigue scores. However, in CFS patients this association is of greater magnitude and can also be observed for TNF-alpha.

 

Source: Gaab J, Rohleder N, Heitz V, Engert V, Schad T, Schürmeyer TH, Ehlert U. Stress-induced changes in LPS-induced pro-inflammatory cytokine production in chronic fatigue syndrome. Psychoneuroendocrinology. 2005 Feb;30(2):188-98. http://www.ncbi.nlm.nih.gov/pubmed/15471616