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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fatigue is a highly distressing symptom of cancer associated with significant psychological morbidity and reduced quality of life. Cancer-related fatigue (CRF) has been underreported, underdiagnosed, and undertreated. Fatigue and depression may coexist in patients with cancer, and considerable overlap of symptoms often occurs. This has led researchers to examine the role of psychotropic medications to treat fatigue. Psychostimulants, wakefulness-promoting agents, antidepressants, and cholinesterase inhibitors have been studied for CRF treatment. Methylphenidate has been studied most and is effective and well tolerated despite common side effects. Some preliminary data support using modafinil for patients with CRF. Antidepressant studies have shown mixed results. Paroxetine shows benefit for fatigue, primarily when it is a symptom of clinical depression. Bupropion sustained release may have psychostimulant-like effects and, therefore, may be beneficial in treating fatigue. Donepezil, a cholinesterase inhibitor, has shown benefit only in open-label trials. Randomized, placebo-controlled trials with specific agents are needed to further assess the efficacy and tolerability of psychotropic medications in CRF treatment.
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PMID:Pharmacologic treatment options for cancer-related fatigue: current state of clinical research. 1884 22

Myasthenia gravis (MG) is an autoimmune disorder usually caused by antibodies against either the acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK) at the neuromuscular junction. Neuromuscular transmission failure results in muscle fatigue and weakness that can be treated symptomatically with acetylcholinesterase inhibitors (AChEIs). Long-term treatment with nonselective AChEIs may have considerable drawbacks; thus, this medication is ideally tapered when strength improves. Patients with AChR antibodies respond beneficially to treatment, whereas patients with MuSK antibodies generally do not. Recently, the selective AChEI EN101, which specifically targets the isoform of "read-through" AChE (AChE-R), has been developed and may be of importance for symptomatic relief in AChR-antibody seropositive MG. This article is a review of the mechanisms, therapeutic effects, and drawbacks, with both old and new AChEIs in MG.
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PMID:Acetylcholinesterase inhibitors in MG: to be or not to be? 1926 48

The ability of galantamine hydrobromide (GAL HBr) treatment to antagonize O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothiolate (VX)-induced lethality, impairment of muscle tension, and electroencephalographic (EEG) changes was assessed in guinea pigs. Guinea pigs were challenged with 16.8 microg/kg VX (2LD50). One min after challenge, animals were administered 0.5 mg/kg atropine sulfate (ATR) and 25 mg/kg pyridine-2-aldoxime methochloride (2-PAM). In addition, guinea pigs were given 0, 1, 2, 4, 8 or 10 mg/kg GAL as a post-exposure treatment immediately prior to ATR and 2-PAM. Animals were either monitored for 24-h survival, scheduled for electroencephalography (EEG) recording, or euthanized 60 min later for measurement of indirectly-elicited muscle tension in the hemidiaphragm. Post-exposure GAL therapy produced a dose-dependent increase in survival from lethal VX challenge. Optimal clinical benefits were observed in the presence of 10 mg/kg GAL, which led to 100% survival of VX-challenged guinea pigs. Based on muscle physiology studies, GAL post-exposure treatment protected the guinea pig diaphragm, the major effector muscle of respiration, from fatigue, tetanic fade, and muscular paralysis. Protection against the paralyzing effects of VX was dose-dependent. In EEG studies, GAL did not alter seizure onset for all doses tested. At the highest dose tested (10 mg/kg), GAL decreased seizure duration when administered as a post-exposure treatment 1 min after VX. GAL also reduced the high correlation associated between seizure activity and lethality after 2LD50 VX challenge. GAL may have additional benefits both centrally and peripherally that are unrelated to its established mechanism as a reversible acetylcholinesterase inhibitor (AChEI).
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PMID:Galantamine is a novel post-exposure therapeutic against lethal VX challenge. 1964 7

Acetylcholinesterase is the enzyme that terminates neurotransmission by hydrolyzing the acetylcholine released by the motoneurons at the neuromuscular junctions. Although acetylcholinesterase has been studied for almost a century, the underlying relationship between exercise-induced fatigue and acetylcholinesterase activity at the synaptic cleft is not clear. The purpose of this study was to assess the effects of exercise-induced fatigue on the expression and activity of acetylcholinesterase at the neuromuscular junctions. The expression and activity of acetylcholinesterase at the gastrocnemius neuromuscular junctions was decreased transiently by exercise-induced fatigue and then gradually increased over 24 hr. The expression of acetylcholinesterase in the 24 hr recovery group returned to the level of the control (non-exercised) group, but the activity of acetylcholinesterase remained significantly lower. These data suggest that the decrease of acetylcholinesterase expression and activity may be involved in the production and/or maintenance of exercise-induced fatigue.
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PMID:The effects of exercise-induced fatigue on acetylcholinesterase expression and activity at rat neuromuscular junctions. 1991 22

Myasthenia gravis is a rare autoimmune neuromuscular junction disorder mainly caused by antibodies being targeted against the muscle acetylcholine receptors (AChRs). The loss of AChRs leads to a defect in neuromuscular transmission resulting in muscle weakness and fatigue. Although once an often fatal illness, Myasthenia gravis can now be well managed with relatively safe and effective treatments. However, the severe myasthenic cases associated with thymus tumors remain often fatal exception in the management of the disease. The early treatment includes the use of acetylcholinesterase inhibitors (AChEI) which enhance neuromuscular transmission. To ensure a peripheral effect, charged molecules are used, particularly quaternary ammonium salts. The structure of AChEIs has been continuously modified to obtain the optimal ratio between AChE inhibition and potential side-effects. This review summarizes progress in the use of quaternary compounds as AChE inhibitors in vitro with respect to their structure and inhibitory ability. Namely, carbamic acid esters, piperidinium and pyridinium salts, bisquaternary pyridinium salts and heterogeneous quaternary inhibitors are all discussed. Among data found in the literature, many compounds have shown promising inhibition of AChE when compared to commercial standards (pyridostigmine, neostigmine). Besides a promising inhibitory ability, selectivity for AChE versus butyrylcholinesterase (BChE) for the most potent compounds (sub-nanomolar IC(50)) was also identified.
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PMID:Structure-activity relationship of quaternary acetylcholinesterase inhibitors - outlook for early myasthenia gravis treatment. 2034 42

A 72-year-old woman was admitted to a local hospital with general fatigue, ptosis and dysarthria. Her anti-AchR antibody titer was high, so myasthenia gravis was diagnosed. She was given a cholinesterase inhibitor, but her symptoms did not improve. CT and MRI scans revealed a mass in the anterior mediastinum infiltrating the superior vena cava (SVC) and the right atrium (RA) . The diagnosis was an invasive thymoma extending into the SVC and the RA. Moreover, there was a mass in the right middle lobe of her lung, which was suspected to be the result of metastasis of the thymoma. She was transferred to our hospital for medication and surgery for the invasive thymoma. Urgent surgery was performed without preoperative therapy, because the tumor was nearly obstructing her tricuspid valve. An expanded thymomectomy and a right middle lobectomy were performed. As the tumor had infiltrated into the SVC, the SVC was replaced with an artificial graft. The clinicopathological diagnosis of thymoma (Masaoka Stage IVb) was given. The patient had a myasthenic crisis for several weeks after surgery, so her breathing was controlled by an artificial respirator. Her symptoms improved after treatment with steroids, tacrolimus and a cholinesterase inhibitor. Although major surgery was required to prevent tumor embolism, the patient survived. Careful observation is necessary to detect signs of relapse of invasive thymoma.
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PMID:[A case of myasthenia gravis with an invasive thymoma infiltrating the superior vena cava and right atrium and causing lung metastasis]. 2047 80

The common shallow-water sea urchin Lytechinus variegatus is capable of surviving inorganic phosphate exposures as high as 3.2 mg L(-1) and organic phosphate exposures of 1000 mg L(-1) . Nonetheless, chronic exposure to low, medium, and high-sublethal concentrations of organic phosphate inhibits the muscle enzyme acetyl cholinesterase (AChE), responsible for the break down of the neurotransmitter acetylcholine, as well as inhibiting contractions in the muscles associated with the Aristotle's lantern. AChE activity, measured in both a static enzyme assay and by vesicular staining, displayed concentration-dependent declines of activity in individuals maintained in organic phosphate for 4 weeks. The activity of AChE was not adversely affected by exposure to inorganic phosphate or seawater controls over the same time period. Maximum force of muscle contraction and rates of muscle contraction and relaxation also decreased with chronic exposure to increasing concentrations of organic phosphate. Chronic exposure to inorganic phosphates elicited no response except at the highest concentration, where the maximum force of muscular contraction increased compared to controls. These findings indicate that shallow-water populations of Lytechinus variegatus subjected to organic phosphate pollutants may display impaired muscular activity that is potentially related to the inhibition of the muscle relaxant enzyme AChE, and subsequently muscular overstimulation, and fatigue.
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PMID:Acetyl cholinesterase activity and muscle contraction in the sea urchin Lytechinus variegatus (Lamarck) following chronic phosphate exposure. 2060 21

The present investigation envisages the toxic effects of aluminium on the cholinergic system of male albino rat brain. Aluminium toxicity (LD(50)/24 h) evaluated as per Probit method was found to be 700 mg/kg body weight. One-fifth of lethal dose was taken as the sublethal dose. For acute dose studies, rats were given a single lethal dose of aluminium acetate orally for one day only and for chronic dose studies, the rats were administered with sublethal dose of aluminium acetate once in a day for 25 days continuously. The two constituents of the cholinergic system viz. acetylcholine and acetylcholinesterase were determined in selected regions of rat brain such as cerebral cortex, hippocampus, hypothalamus, cerebellum, and pons-medulla at selected time intervals/days under acute and chronic treatment with aluminium. The results revealed that while acetylcholinesterase activity was inhibited, acetylcholine level was elevated differentially in all the above mentioned areas of brain under aluminium toxicity, exhibiting area-specific response. All these changes in the cholinergic system were subsequently manifested in the behavior of rat exhibiting the symptoms such as adipsia, aphagia, hypokinesia, fatigue, seizures, etc. Restoration of the cholinergic system and overt behavior of rat to the near normal levels under chronic treatment indicated the onset of either detoxification mechanisms or development of tolerance to aluminium toxicity in the animal which was not probably so efficient under acute treatment.
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PMID:Cholinergic system under aluminium toxicity in rat brain. 2117 Feb 57

To assess health risks in agricultural workers associated with environmental exposure to pollutants released from a petroleum refinery and from traffic, we performed a cross-sectional study that included 119 randomly selected subjects divided in two groups. Group 1 included 60 agricultural workers living in a rural community near the petroleum refinery and a motorway overpass, whereas Group 2 consisted of 59 agricultural workers performing similar activities and living in a rural community with no exposure to industrial and traffic pollutants. Risk assessment included a questionnaire, blood pressure measurement, spirometry, laboratory tests, and toxicological analysis. The groups showed a similar prevalence of health problems, with exception of muscle pain in the extremities, headache, and fatigue, which were significantly more common in Group 1. Diastolic blood pressure was higher in Group 1, but not significantly (p=0.057). The same is true for blood carbon monoxide. Significantly higher in Group 1 were blood haemoglobin (p=0.001) and blood lead (p<0.001). Serum cholinesterase activity was similar in both groups. Our findings indicate the need of regular medical exams, ambient monitoring and environmental impact assessment in agricultural population in order to detect individuals at risk and to institute adequate preventive measures.
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PMID:Environmental and occupational health risks among agricultural workers living in a rural community near petroleum refinery and motorway in Skopje region. 2118 33

Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous group of inherited disorders of the neuromuscular junction. A difficult to diagnose subgroup of CMS is characterised by proximal muscle weakness and fatigue while ocular and facial involvement is only minimal. DOK7 mutations have been identified as causing the disorder in about half of the cases. More recently, using classical positional cloning, we have identified mutations in a previously unrecognised CMS gene, GFPT1, in a series of DOK7-negative cases. However, detailed description of clinical features of GFPT1 patients has not been reported yet. Here we describe the clinical picture of 24 limb-girdle CMS (LG-CMS) patients and pathological findings of 18 of them, all carrying GFPT1 mutations. Additional patients with CMS, but without tubular aggregates, and patients with non-fatigable weakness with tubular aggregates were also screened. In most patients with GFPT1 mutations, onset of the disease occurs in the first decade of life with characteristic limb-girdle weakness and fatigue. A common feature was beneficial and sustained response to acetylcholinesterase inhibitor treatment. Most of the patients who had a muscle biopsy showed tubular aggregates in myofibers. Analysis of endplate morphology in one of the patients revealed unspecific abnormalities. Our study delineates the phenotype of CMS associated with GFPT1 mutations and expands the understanding of neuromuscular junction disorders. As tubular aggregates in context of a neuromuscular transmission defect appear to be highly indicative, we suggest calling this condition congenital myasthenic syndrome with tubular aggregates (CMS-TA).
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PMID:Congenital myasthenic syndrome with tubular aggregates caused by GFPT1 mutations. 2197 7


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