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Query: UMLS:C0015672 (fatigue)
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There is now some evidence that chronic fatigue syndrome is accompanied by an activation of the inflammatory response system and by increased oxidative and nitrosative stress. Nuclear factor kappa beta (NFkappabeta) is the major upstream, intracellular mechanism which regulates inflammatory and oxidative stress mediators. In order to examine the role of NFkappabeta in the pathophysiology of CFS, this study examines the production of NFkappabeta p50 in unstimulated, 10 ng/mL TNF-alpha (tumor necrosis factor alpha) and 50 ng/mL PMA (phorbolmyristate acetate) stimulated peripheral blood lymphocytes of 18 unmedicated patients with CFS and 18 age-sex matched controls. The unstimulated (F=19.4, df=1/34, p=0.0002), TNF-alpha-(F=14.0, df=1/34, p=0.0009) and PMA-(F=7.9, df=1/34, p=0.008) stimulated production of NFkappabeta were significantly higher in CFS patients than in controls. There were significant and positive correlations between the production of NFkappabeta and the severity of illness as measured with the FibroFatigue scale and with symptoms, such as aches and pain, muscular tension, fatigue, irritability, sadness, and the subjective feeling of infection. The results show that an intracellular inflammatory response in the white blood cells plays an important role in the pathophysiology of CFS and that previous findings on increased oxidative stress and inflammation in CFS may be attributed to an increased production of NFkappabeta. The results suggest that the symptoms of CFS, such as fatigue, muscular tension, depressive symptoms and the feeling of infection reflect a genuine inflammatory response in those patients. It is suggested that CFS patients should be treated with antioxidants, which inhibit the production of NFkappabeta, such as curcumin, N-Acetyl-Cysteine, quercitin, silimarin, lipoic acid and omega-3 fatty acids.
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PMID:Not in the mind of neurasthenic lazybones but in the cell nucleus: patients with chronic fatigue syndrome have increased production of nuclear factor kappa beta. 1769 79

Chronic fatigue syndrome is a heterogeneous disorder with unknown pathogenesis and etiology, characterized by disabling fatigue, difficulty in concentration and memory, and concomitant skeletal and muscular pain. Several mechanisms have been suggested to play a role in CFS, such as excessive oxidative stress following exertion, immune imbalance characterized by decreased natural killer cell and macrophage activity, immunoglobulin G subclass deficiencies (IgG1, IgG3) and decreased serum concentrations of complement component. Autoantibodies were also suggested as a possible factor in the pathogenesis of CFS. Recent studies indicate that anti-serotonin, anti-microtubule-associated protein 2 and anti-muscarinic cholinergic receptor 1 may play a role in the pathogenesis of CFS. It has been demonstrated that impairment in vasoactive neuropeptide metabolism may explain the symptoms of CFS.
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PMID:Chronic fatigue syndrome: characteristics and possible causes for its pathogenesis. 1830 May 82

Individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have little stamina and endurance, and pose a challenge for nursing professionals. The Energy Envelope Theory, which posits that maintaining expended energy levels consistent with available energy levels may reduce the frequency and severity of symptoms, is particularly useful when working with clients with ME/CFS. Anecdotal support from the client community for this theory supports its use as a management tool for ME/CFS, but little formal research has been done in this area. In this study, a daily energy quotient was established by dividing the expended energy level by the perceived energy level and multiplying by 100. It was predicted that those participants who expended energy beyond their level of perceived energy would have more severe fatigue and symptoms and lower levels of physical and mental functioning. Findings are congruent with the Energy Envelope Theory as they indicated that the daily energy quotient was related to several indices of functioning including depression, anxiety, fatigue, pain, quality of life, and disability. The overall results provide support for a strategy health care professionals can use when working with clients with ME/CFS.
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PMID:The Energy Envelope Theory and myalgic encephalomyelitis/chronic fatigue syndrome. 1857 85

Chronic Fatigue Syndrome is a physiological state in which the patient feels high levels of fatigue without an obvious organic cause, which affects around 1 in 400 people in the developed world. A wide range of causes have been suggested, including immune or hormonal dysfunction, viral or bacterial infection, and psychological somatization. It is likely that several causes are needed to trigger the disease, and that the triggers are different from the mechanisms that maintain fatigue over months or years. Many treatments have been tested for CFS, with very limited success - a programme of combined CBT and graded exercise shows the most effect. I suggest that patients with CFS have a reduced ability to increase mitochondrial energy production when exertion requires it, with fewer mitochondria that are each more efficient, and hence nearer to their maximum energy output, than normal. A range of indirect evidence suggests that the renin-angiotensin system stimulates mitochondrial responsiveness and reduces mitochondrial efficiency: chronic under-stimulation of this system could contribute to CFS aetiology. If correct, this means that CFS can be successfully treated with RAS agonists (eg angiotensin mimetics), or adrenergic agonists. It also suggests that there will be a positive link between the use of adrenergic- and RAS-blocking drugs and CFS incidence, and a negative link between adrenergic agonist use and CFS.
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PMID:Treating Chronic Fatigue states as a disease of the regulation of energy metabolism. 1868 70

Disturbances in intestinal microbial ecology and in the immune system of the host have been implicated as a part of the pathogenesis in chronic fatigue syndrome. Probiotic lactic acid producing bacteria have been shown to prevent and alleviate gastrointestinal disturbances and to normalize the cytokine profile which might be of an advantage for patients suffering from chronic fatigue syndrome. The aim of the study was to evaluate the effect of Lactobacillus paracasei ssp. paracasei F19, Lactobacillus acidophilus NCFB 1748 and Bifidobacterium lactis Bb12 on fatigue and physical activity in CFS patients. Fifteen patients fulfilling the criteria set by international researchers in the field at the US Centre for Disease Control and Prevention in 1994 for chronic fatigue syndrome, were included in the study. The patients had high fatigue severity scores and high disability scores. During the first two weeks baseline observations without treatment were assessed, succeeded by four weeks of intake of a probiotic product and a four-week follow-up period. The fatigue, health and physical activity was assessed by the use of the Visual Analogue Scales and the SF-12 Health Survey. Faecal samples were collected and the normal microflora was analysed. Neurocognitive functions improved during the study period while there were no significant changes in fatigue and physical activity scores. No major changes occurred in the gastrointestinal microflora. At the end of the study 6 of 15 patients reported that they had improved according to the assessment described. The findings in this study that improvement of health is possible to achieve should encourage further studies with interventions with probiotics in patients with CFS.
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PMID:Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome. 1917 Oct 24

Clearly, the use of functional neuroimaging for the study of fatigue is in its infancy. Relatively few studies focusing on fatigue using functional neuroimaging techniques have been published, and the few that exist focus primarily on persons with MS and CFS. The vast majority of these studies have examined self-reported fatigue, an approach that benefits from ease of administration but suffers from significant difficulties in interpretation. For example, we know that self-reported fatigue most often correlates with the degree of psychopathology.1 We also know that with more than 100 years of inquiry, self-reported fatigue does not correlate with objective measures of fatigue. As such, when functional imaging studies show a relationship between self-reported fatigue and activities in distinct areas of the brain, one must remain cautious about the interpretation of these results. A more recent approach in the functional imaging literature is to assess fatigue behaviorally during scanning and relate such objective measures of fatigue with cerebral activation. Although this is a new and novel approach, it remains unclear if this approach of operationally defining fatigue behaviorally will be a more valid paradigm in understanding the elusive construct of fatigue. Although fatigue is extraordinarily common as a symptom in many neurologic and psychiatric diseases, little is known about its precise mechanism. Chaudhuri and Behan hypothesized that the nonmotor functions of the basal ganglia play a key role in central fatigue. Specifically, they posit that fatigue is due to "alterations in the normal flow of sequential activation within the basal ganglia system affecting the neural integrator and the cortical feedback by the associated loop of the striato-thalamo-cortical fibers is a possible mechanism of central fatigue ." (p40). Therefore, other regions interacting with the basal ganglia may also contribute to fatigue, including the frontal cortex, thalamus, and the amygdala. In general, the functional imaging studies reviewed in this article tend to generally support the suggestion that damage to cortical-subcortical circuitry might be to blame for fatigue as well. If indeed fatigue is associated with functional impairment in a cortical-subcortical circuitry, it might be that studies that have examined structural damage (eg, total lesion load throughout the brain) may simply not provide the sensitivity required to detect a relationship between fatigue and pathology. After more than 100 years of frustration, it appears that functional neuroimaging techniques promise to provide an exciting potential for significant advances in our elusive understanding of the brain mechanisms associated with fatigue in clinical populations.
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PMID:Functional neuroimaging of fatigue. 1938 14

Anxiety symptoms are commonly described in children with chronic fatigue syndrome or myalgic encephalopathy (CFS/ME) but to date there has been little information on the type of anxiety children experience or the relationship between anxiety and school attendance, disability or fatigue. The aim of this study was to first describe the prevalence and type of anxiety symptoms in children with CFS/ME compared with a normal European population, and secondly to investigate the association of anxiety symptoms with age, gender, school attendance, fatigue, and physical function in paediatric CFS/ME. Data were prospectively collected on children and young people with CFS/ME referred to a large specialist CFS/ME service. One hundred and sixty-four children with CFS/ME had complete data for the Spence Children's Anxiety Scale. Teenage girls had the highest rates of total anxiety symptoms with 38% (95% CI 27-49) over the cut off (top 10% of normal European population) and significantly higher rates of symptoms in each subscale. Younger girls were more likely to score over the cut off in separation anxiety (37%, 19-40) and social phobia (39%, 25-47). There was no evidence of association between total anxiety symptoms and: time at school, time to assessment, pain or age. Associations with fatigue and physical function were attenuated when adjusted for other variables. Although anxiety symptoms are high in CFS/ME, particularly in teenage girls, it does not appear to be associated with school attendance or other measures of disability. Separation anxiety and social phobia were the most clearly elevated in paediatric CFS/ME.
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PMID:Anxiety in children with CFS/ME. 1945 95

The new diagnostic criteria for pediatric ME/CFS are structurally based on the Canadian Clinical Adult case definition, and have more required specific symptoms than the (Fukuda et al. Ann Intern Med 121:953-959, 1994) adult case definition. Physicians specializing in pediatric ME/CFS referred thirty-three pediatric patients with ME/CFS and 21 youth without the illness. Those who met ME/CFS criteria were separated into Severe and Moderate categories. Significant differences were found for symptoms within each of the six major categories: fatigue, post-exertional malaise, sleep, pain, neurocognitive difficulties, and autonomic/neuroendocrine/immune manifestations. In general, the results showed participants who met the Severe ME/CFS criteria reported the highest scores, the Moderate ME/CFS group show scores that were a little lower, and the control group evidenced the lowest scores. Findings indicate that the Pediatric Case Definition for ME/CFS can distinguish between those with this illness and controls, and between those with Severe versus Moderate manifestations of the illness.
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PMID:Severe versus Moderate criteria for the new pediatric case definition for ME/CFS. 1951 26

Persons with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often complain of fatigue states (eg, postexertional malaise, brain fog) that are qualitatively different than normal, daily fatigue. Given the heterogeneous nature of ME/CFS, it is likely that individuals with this illness experience these fatigue types differently in terms of severity and frequency. It is also possible that meaningful subgroups of patients exist that exhibit different patterns of the fatigue experience. The purpose of this study was to investigate whether individuals with ME/CFS can be classified in a meaningful way according to the different types of fatigue they experience. One hundred individuals with ME/CFS participated in the study. Individuals that met inclusion criteria were administered the Multiple Fatigue Types Questionnaire (MFTQ), a 5-factor instrument that distinguishes between different types of fatigue. A cluster analysis was used to classify patients into various clusters based on factor subscale scores. Using a 3-factor solution, individuals were classified according to illness severity (low, moderate, severe) across the different fatigue factors. However, a 5-cluster solution enabled participants with moderate to severe fatigue levels to fall into more differentiated clusters and demonstrate distinct fatigue state patterns. These results suggest that fatigue patterns of individuals with ME/CFS are heterogeneous, and that patients may be classified into meaningful subgroups.
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PMID:Classification of myalgic encephalomyelitis/chronic fatigue syndrome by types of fatigue. 2018 98

Fatigue is one of the most common reasons why people consult health care providers. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is one cause of clinically debilitating fatigue. The underdiagnosis of CFS/ME, along with the spectrum of symptoms that represent multiple reasons for entry into physical therapy settings, places physical therapists in a unique position to identify this health condition and direct its appropriate management. The diagnosis and clinical correlates of CFS/ME are becoming better understood, although the optimal clinical management of this condition remains controversial. The 4 aims of this perspective article are: (1) to summarize the diagnosis of CFS/ME with the goal of promoting the optimal recognition of this condition by physical therapists; (2) to discuss aerobic system and cognitive deficits that may lead to the clinical presentation of CFS/ME; (3) to review the evidence for graded exercise with the goal of addressing limitations in body structures and functions, activity, and participation in people with CFS/ME; and (4) to present a conceptual model for the clinical management of CFS/ME by physical therapists.
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PMID:Conceptual model for physical therapist management of chronic fatigue syndrome/myalgic encephalomyelitis. 2018 14


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