Tag: potassium

Identifying illness parameters in fatiguing syndromes using classical projection methods

Abstract:

OBJECTIVES: To examine the potential of multivariate projection methods in identifying common patterns of change in clinical and gene expression data that capture the illness state of subjects with unexplained fatigue and nonfatigued control participants.

METHODS: Data for 111 female subjects was examined. A total of 59 indicators, including multidimensional fatigue inventory (MFI), medical outcome Short Form 36 (SF-36), Centers for Disease Control and Prevention (CDC) symptom inventory and cognitive response described illness. Partial least squares (PLS) was used to construct two feature spaces: one describing the symptom space from gene expression in peripheral blood mononuclear cells (PBMC) and one based on 117 clinical variables. Multiplicative scatter correction followed by quantile normalization was applied for trend removal and range adjustment of microarray data. Microarray quality was assessed using mean Pearson correlation between samples. Benjamini-Hochberg multiple testing criteria served to identify significantly expressed probes.

RESULTS: A single common trend in 59 symptom constructs isolates of nonfatigued subjects from the overall group. This segregation is supported by two co-regulation patterns representing 10% of the overall microarray variation. Of the 39 principal contributors, the 17 probes annotated related to basic cellular processes involved in cell signaling, ion transport and immune system function. The single most influential gene was sestrin 1 (SESN1), supporting recent evidence of oxidative stress involvement in chronic fatigue syndrome (CFS). Dominant variables in the clinical feature space described heart rate variability (HRV) during sleep. Potassium and free thyroxine (T4) also figure prominently.

CONCLUSION: Combining multiple symptom, gene or clinical variables into composite features provides better discrimination of the illness state than even the most influential variable used alone. Although the exact mechanism is unclear, results suggest a common link between oxidative stress, immune system dysfunction and potassium imbalance in CFS patients leading to impaired sympatho-vagal balance strongly reflected in abnormal HRV.

 

Source: Broderick G, Craddock RC, Whistler T, Taylor R, Klimas N, Unger ER. Identifying illness parameters in fatiguing syndromes using classical projection methods. Pharmacogenomics. 2006 Apr;7(3):407-19. https://www.ncbi.nlm.nih.gov/pubmed/16610951

 

Biochemical and muscle studies in patients with acute onset post-viral fatigue syndrome

Abstract:

AIMS: To investigate in detail various biochemical and pathophysiological indices of muscle pathology in acute onset post-viral fatigue syndrome (PVFS).

METHODS: Twenty three patients with PVFS (of mean duration 4.6 years) were subjected to needle biopsy for histomorphometry and total RNA contents. Plasma analysis included serology and creatine kinase activities. Indices of whole body mass were also measured–namely, whole body potassium content and plasma carnosinase activities.

RESULTS: About 80% of the patients had serology indicative of persistent enteroviral infection as determined by VP1 antigen assay. Only about 10% of that same group of patients had serological indications of current enterovirus infection by IgM assay; a separate subset of 10% showed antibody changes suggestive of reactivation of Epstein-Barr virus. Quantitative morphometric analysis of skeletal muscle fibres indicated that the quadriceps muscle was normal or displayed only minor abnormalities in 22 patients. The Quetelet’s Index (body mass index) and whole-body potassium values (index of lean body mass) were not affected in PVFS. The mean plasma carnosinase and creatinine kinase activities were also generally normal in these patients. The mean muscle RNA composition–mg RNA/mg DNA: was significantly reduced in acute onset PVFS by about 15%. The protein:DNA ratio was not significantly affected.

CONCLUSIONS: Patients with acute onset PVFS, therefore, lose muscle protein synthetic potential, but not muscle bulk. Histopathology is consistent with these observations. These perturbations may contribute to the apparent feature of perceived muscle weakness associated with the persistent viral infection in the muscle themselves.

 

Source: Preedy VR, Smith DG, Salisbury JR, Peters TJ. Biochemical and muscle studies in patients with acute onset post-viral fatigue syndrome. J Clin Pathol. 1993 Aug;46(8):722-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC501456/