Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fatigue is common and can be profound in patients with chronic liver diseases, such as primary biliary cirrhosis (PBC) and chronic hepatitis C. The pathogenesis of fatigue in such patients is unknown; it may be related to infection with the hepatitis C virus or the pathophysiology of cholestasis in PBC, to a psychological reaction to knowledge of the diagnosis, or to the presence of chronic liver disease. A major problem in evaluating a treatment for fatigue in a randomized controlled trial is the inherent subjectivity of fatigue and the lack of a satisfactory objective quantitative primary efficacy endpoint. Experimental studies in rats and male athletes have implicated the serotonin neurotransmitter system in fatigue of central origin. Administration of the 5-HT3 serotonin receptor subtype antagonist, ondansetron, has been associated with substantial sustained clinical ameliorations of profound fatigue in at least some patients with chronic liver disease.
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PMID:Fatigue complicating chronic liver disease. 1555 32

A 47-year-old woman with primary biliary cirrhosis and scleroderma was examined at our hospital for a 1-week history of non-resolving fever, arthralgia, myalgia, muscle weakness and fatigue. A diagnosis of systemic lupus erythematosus was made based on arthralgia, low leukocyte count, low lymphocyte count, low serum concentration of complements, positive anti-nuclear antibody and positive anti-double-strand-DNA antibody. She was negative for anti-U1RNP antibody, but positive for anti-Jo1 antibody, and her initial serum concentration of creatine phosphokinase was elevated. We diagnosed her as having overlap syndrome with scleroderma, systemic lupus erythematosus and possible polymyositis associated with primary biliary cirrhosis. Prednisolone rapidly improved her symptoms. Lobulated leukocytes were observed in her peripheral blood specimen. She was positive for anti-HTLV-1 antibody, but Southern blot hybridization did not confirm monoclonal integration of HTLV-I proviral DNA in her peripheral blood. This suggests the possibility of a relationship between HTLV-1 infection and various autoimmune disorders including primary biliary cirrhosis.
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PMID:A human T-cell lymphotropic virus type-1 (HTLV-1) carrier complicated with various autoimmune diseases including primary biliary cirrhosis. 1571 72

Fatigue is common in primary biliary cirrhosis (PBC). Altered central serotonergic neurotransmission may be involved in its pathogenesis. This multicenter, randomized, double-blind, placebo-controlled, crossover trial evaluated the efficacy of ondansetron, a selective 5-HT3 receptor subtype antagonist, for treating fatigue in PBC. A crossover design was chosen, allowing subjects to serve as their own controls-appropriate to evaluate fatigue, a subjective symptom. Sixty patients with clinically stable PBC, a Fatigue Severity Score (FSS) > 4, and no other identifiable cause for fatigue were enrolled. Subjects were randomized to receive ondansetron (4 mg) or placebo orally 3 times daily for 4 weeks (period 1). Subjects then crossed over, after a minimum 1-week washout period, for a further 4 weeks of ondansetron or placebo (period 2). Fatigue was measured at the beginning and end of each period by using the FSS and Fatigue Impact Scale (FIS). Six patients withdrew; the remaining 54 subjects had a mean baseline FSS of 5.55 (+/-0.1). Response to study medication in period 1 versus period 2 was not uniform; thus, it was necessary to analyze the trial periods separately. In period 1, there was no significant additional fatigue reduction on ondansetron over placebo. During period 2, FSS and FIS decreased significantly on ondansetron versus placebo (P = .001). However, period 2 results were invalidated because drug side effects unblinded subjects (constipation affected 63.0% of patients taking ondansetron, versus 13.3% on placebo). In conclusion, ondansetron administration did not confer clinically significant fatigue reduction when compared with placebo in our study population.
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PMID:A randomized, controlled crossover trial of ondansetron in patients with primary biliary cirrhosis and fatigue. 1591 60

The effects in clinical studies of UDCA on the endpoints "death" or "pre-transplantation survival" can only be shown when UDCA therapy is started in an early disease phase, preferably in stage I but no later than stage II, and is then continued into stages III/IV, or preferably stage IV. The reasons for this lie in the observation that, in stages I/II, no patient suffers from progressive disease that irrevocably leads to death or transplantation, while a measurable effect of UDCA, as is true for other drugs and other hepatic diseases, continues to dwindle and finally disappears as patients progress through the fibrotic and cirrhotic stages III and IV. Hence, administration of UDCA must begin in the phase of progressive inflammation (stages I and II) and the outcome documented after many years of long-term therapy. This requires very large, probably unattainable, patient collectives. Whether it is justified to administer placebo to one-half of these patients over such an extended period of time represents a profound ethical dilemma. Because these arguments were not considered in the two meta-analyses cited above or in any other study, they do not allow a definitive statement on the life expectancy of patients on UDCA therapy. On the other hand, it is possible using generally accepted, independent prognostic variables and mathematical models, whose limitations are well-known and must be considered, to predict with a high degree of accuracy the disease course of treated and untreated patients and calculate their life expectancy and/or pre-transplantation survival. Because UDCA exerts a significant positive effect on the most important prognostic markers for PBC, such as serum bilirubin, piecemeal necroses, histological disease progression, ascites and edema, and apparently the scores for pruritus and fatigue, this permits us to demonstrate not only a decrease in the incidence of transplantation but also to calculate a prolongation in life expectancy.
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PMID:Ursodeoxycholic acid in the therapy for primary biliary cirrhosis: effects on progression and prognosis. 1614 14

We describe two patients with primary biliary cirrhosis (PBC) who presented with specific symptoms mimicking an undifferentiated connective tissue disease (arthromyalgia, fatigue, cutaneous lesions either morbillous-like or urticarial, the latter with an eosinophil infiltrate of upper dermis). Subsequent detection firstly of eosinophilia in the blood and secondarily of antimitochondrial antibodies with results of liver biopsy allowed a diagnosis of asymptomatic PBC. In our cases, a peculiar sign of early stage of PBC was represented also by the eosinophilia in the liver.
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PMID:Cutaneous lesions as presenting symptoms of primary biliary cirrhosis: an undifferentiated connective tissue disease-like onset. 1626 99

Profound fatigue is a clinically significant complication of chronic liver disease. A mechanism of fatigue in experimental animals and male athletes appears to be increased serotoninergic neurotransmission in the brain. Recently, attempts have been made to assess the efficacy of a serotonin antagonist, specifically the 5-HT3 receptor subtype antagonist, ondansetron, in ameliorating fatigue in patients with chronic liver disease. However, the results of a randomized controlled trial of ondansetron for fatigue in patients with primary biliary cirrhosis did not indicate that ondansetron was either effective or ineffective. The reasons for the uncertain outcome of the randomized controlled trial are not clear. One contributing factor may have been the use of subjective indices of fatigue as primary efficacy endpoints. There is a need to develop objective quantitative primary efficacy endpoints for use in trials of therapy for fatigue. Another contributing factor may relate to the conduct of a randomized controlled trial not invariably being the optimal approach to resolve a specific clinical issue, particularly when the application of statistical methods yields equivocal findings. When the results of a randomized controlled trial are indecisive, findings based on clinical judgement, medicine's most important asset, should be carefully evaluated.
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PMID:Personal view: a potential novel treatment for fatigue complicating chronic liver disease--how should its efficacy be evaluated? 1661 Dec 71

A significant proportion of patients with primary biliary cirrhosis (PBC) suffer from severe fatigue. The aim of this study was to characterize patterns of daytime sleep in patients with PBC (using both objective and subjective assessment approaches) and to study the association between sleep abnormality and fatigue severity. Fatigue severity was assessed in 48 female subjects with PBC (using a disease-specific quality of life instrument (the PBC-40) and a generic fatigue measure (Fatigue Impact Scale [FIS]) as well as 48 case-matched normal controls. All participants also completed the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS, which assesses daytime hypersomnolence). Objective sleep assessment was performed using accelerometry over 7 days. Global sleep quality assessed by the PSQI was significantly lower in the PBC group compared to controls (P < .0001). ESS scores were significantly higher in patients with PBC than controls (P = .0001), suggesting significantly greater daytime somnolence in the patients with PBC. Objective sleep assessment confirmed that subjects with PBC were sleeping on average almost twice as long as controls during the daytime. Both degree of daytime somnolence (ESS) and actual daytime sleep activity (accelerometry) correlated strongly with fatigue severity in the patient group (r2 = 0.5, P < .0001 and r2 = 0.2, P < .01, respectively). In conclusion, Sleep abnormality, in the form of excessive daytime somnolence, is present in a significant proportion of patients with PBC, with the degree of daytime somnolence correlating strongly with the degree of fatigue. Existing agents effective at reducing daytime somnolence (such as modafinil) hold potential for the treatment of fatigue in PBC.
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PMID:Fatigue in primary biliary cirrhosis is associated with excessive daytime somnolence. 1680 7

Primary biliary cirrhosis (PBC) is a chronic cholestatic autoimmune liver disease that predominantly affects middle-aged women. It is characterized by slowly progressive destruction of the small intrahepatic bile ducts together with portal inflammation, and this initially leads to fibrosis and later to cirrhosis. It is currently accepted that the pathogenesis of PBC is multifactorial with genetic and environmental factors interplaying to determine the disease onset and progression. In addition to antimitochondrial antibody (AMA), which is the hallmark of PBC and is detected in at least 90% of the patients, other autoantibodies (antinuclear antibody, anti-smooth muscle antibody and rheumatoid factor, etc.) may also be found in the patients. There is no correlation between the titer of AMAs and the disease severity. Most patients are diagnosed either during the asymptomatic phase of PBC or after presenting with non-specific symptoms. Pruritus and fatigue are the most common symptoms of PBC. The prognosis of PBC has improved significantly during the last few decades. Patients are now diagnosed earlier in its clinical course, they are more likely to be asymptomatic at diagnosis and they are more likely to receive medical treatment. A wide variety of drugs have been assessed for the treatment of this condition: such immunosuppressive agents as corticosteroids, cyclosporine and azathioprine have a weak effect on the disease's natural history. Ursodeoxycholic acid (UDCA) is the only currently approved medical treatment. For PBC patients with end-stage liver disease or an unacceptable quality of life, liver transplantation is the only accepted therapeutic option. Early diagnosis and treatment of PBC are important because effective treatment with UDCA has been shown to delay disease progression and improve rate survival in the early stage.
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PMID:[Primary biliary cirrhosis]. 1699 88

Recent advances in cholestatic liver disease have occurred in several areas. Molecular cloning of hepatobiliary transport systems has resulted in the identification of the molecular basis of hereditary and acquired cholestatic syndromes. Apoptosis has been identified as an important mechanism of cholestatic liver injury and bile duct loss. New insights into the pathogenesis of pruritus and fatigue have resulted in new treatment strategies for these debilitating symptoms. Important new studies have been published about pathogenesis, clinical features, and treatment of primary biliary cirrhosis, primary sclerosing cholangitis, cholestasis of pregnancy, and drug-induced cholestasis.
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PMID:Cholestatic syndromes. 1702 48

Fatigue is a common symptom in primary biliary cirrhosis (PBC). In animal models of cholestasis, abnormalities in serotonin neurotransmission are observed with fatigue. The role of selective serotonin reuptake inhibitors in fatigue-related PBC, however, is unknown. A double-blind, placebo-controlled study design was conducted to determine the safety and efficacy of fluoxetine for the treatment of fatigue in PBC. Patients were randomized to fluoxetine, 20 mg daily, or matched placebo for 8 weeks' duration. Fatigue was assessed by the Fisk Fatigue Impact Scale (FFIS). The primary study endpoint was a > or =50% reduction in overall FFIS score at the end of treatment. Health-related quality of life (HRQL) was assessed as a secondary endpoint. Among 220 consecutively screened patients, only 18 (9%) eligible individuals were randomized to fluoxetine (n=10) or placebo (n=8) for 8 weeks. Baseline variables including median FFIS scores (52 vs 42; P=0.21) were similar between treatment arms (P > 0.05). After 8 weeks of therapy, no statistically significant change in median FFIS score was observed in the fluoxetine group. Median FFIS score in the placebo group was reduced (42 to 28), but not statistically significant. No difference in HRQL was observed between treatment arms after 8 weeks. Fourteen (78%) patients completed therapy, while four (22%) individuals withdrew from the trial. Three of the four patients had drug-related adverse events with fluoxetine. In this study, fluoxetine did not improve fatigue in PBC and was associated with adverse events.
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PMID:Fluoxetine for the treatment of fatigue in primary biliary cirrhosis: a randomized, double-blind controlled trial. 1705 55


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