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)

We examined the thyroid status of 58 patients with primary biliary cirrhosis (PBC) using total serum thyroxin, thyroid hormone binding ratio, free thyroxin index, serum TSH, antithyroglobulin, and antimicrosomal antibodies. Seven patients were known to be hypothyroid prior to the diagnosis of PBC. Six additional patients were found to have biochemical evidence of hypothyroidism. The prevalence of hypothyroidism was 12% if we include only those six PBC patients with newly diagnosed hypothyroidism or 22% if we include all 13 patients. Five of the 58 patients had evidence for an elevation of thyroid hormone binding capacity. Three hypothyroid patients had normal total thyroxins with low thyroid hormone binding ratios. Two euthyroid patients had elevated total T4s with low thyroid hormone binding ratio and normal FTI. The prevalence of positive antimicrosomal antibodies was 34%, including 11 euthyroid PBC patients. The prevalence of positive antithyroglobulin antibodies was 20% including five euthyroid patients. There was no association between HLA DR3 or DR5 and the patients with hypothyroidism and/or antithyroid antibodies. Because fatigue, lethargy, and anorexia as well as hypercholesterolemia are common features of both hypothyroidism and PBC, patients with PBC should be screened for evidence of thyroid dysfunction. Thyroid disease may precede the diagnosis of PBC by several years. Therefore, the development of cholestatic liver disease in a patient with known autoimmune thyroiditis should arouse suspicion of PBC.
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PMID:Increased incidence of hypothyroidism in primary biliary cirrhosis. 662 57

Ursodeoxycholic acid (UDCA) and methotrexate (MTX) have both been proposed as treatments for patients with primary biliary cirrhosis (PBC). It has been suggested that a combination of the two drugs may offer advantages over either used separately. In this pilot study, we sought to evaluate the safety and efficacy of this combination for patients with PBC. Thirty-two patients with antimitochondrial antibody positive PBC were prospectively entered into a pilot study and received UDCA, 13 to 15 mg/kg/d, in conjunction with MTX, 0.25 mg/kg/wk, for a period of 2 years. The results of this treatment were compared with those obtained from 180 patients with PBC studied in a placebo-controlled trial of UDCA alone conducted during the same period. Patients in the pilot study and randomized study were comparable with regard to age, gender, and liver biochemistries. The UDCA/MTX-treated patients were of earlier histologic stage and had a lower mean Mayo risk score. During this period, seven patients in the UDCA/MTX group were withdrawn, four for pulmonary toxicity (two who required hospitalization), and one each with mouth ulcer, extreme fatigue, and hair loss. The use of UDCA/MTX was not associated with improvement in symptoms. In the patients receiving UDCA/MTX, biochemical changes were comparable to those of patients receiving UDCA alone but superior to those in the placebo group (P < .05). Histological changes were comparable in all groups at 2 years. Cessation of MTX while UDCA was continued led to no deterioration in liver biochemistries.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The combination of ursodeoxycholic acid and methotrexate for patients with primary biliary cirrhosis: the results of a pilot study. 755 66

One hundred fifty-one patients with primary biliary cirrhosis (PBC) grouped into four strata based on entry serum bilirubin ( < 2 mg/dL vs. 2 md/dL or greater) and liver histology (stages I, II vs. stages III, IV-Ludwig criteria) were randomized within each stratum to ursodiol or placebo given in a single dose of 10 to 12 mg/kg at bedtime for 2 years. Placebo- (n = 74) and ursodiol- treated (n = 77) patients were well matched at baseline for demographic and prognostic factors. Ursodiol induced major improvements in biochemical tests of the liver in strata 1 and 2 (entry bilirubin < 2), but had less effect on laboratory tests in patients with entry serum bilirubin of > or +2 (strata 3 and 4). Histology was favorably affected by ursodiol in patients in strata 1 and 2 but not in strata 3 and 4. Ursodiol enrichment in fasting bile obtained at the conclusion of the trail was approximately 40% and comparable in all strata. Thus, differences in ursodiol enrichment of the bile acid pool do not explain better responses of laboratory tests and histology found in patients with less advanced PBC. Patients treated will ursodiol tended to develop a treatment failure less frequently that those who received placebo, particularly in strata 1 and 2 (ursodiol 42%, placebo 60%, P = .078). Development of severe symptoms (fatigue/pruritus) and doubling of serum bilirubin were reduced significantly in ursodiol-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid in primary biliary cirrhosis. 765 80

Thalidomide has been reported to be effective in treating graft-versus-host disease, a condition with many clinical and pathological similarities to primary biliary cirrhosis. We performed a double-blind, placebo-controlled pilot study to assess the efficacy of thalidomide in 18 patients with biopsy-proven primary biliary cirrhosis (10 thalidomide, 8 placebo). Each patient was treated for 6 months and had a liver biopsy before and after treatment. Side effects, particularly sedation and fatigue, were more common on thalidomide and two patients were withdrawn from this group. There were no improvements in liver function tests or in liver histology, assessed morphometrically. A number of patients treated with thalidomide reported an improvement in pruritus. This study suggests that thalidomide is unlikely to be effective in altering the natural history of primary biliary cirrhosis.
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PMID:Thalidomide as therapy for primary biliary cirrhosis: a double-blind placebo controlled pilot study. 781 94

The beneficial effects of ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis led to therapeutic trials with this bile acid for the treatment of PSC. In two prospective placebo-controlled trials, UDCA led to a significant improvement of AP, GGT, ALT, AST, and, in one study, also of serum bilirubin. In both studies liver histology improved significantly, mainly due to a decrease of cellular infiltrates in portal triads. Pruritus and fatigue improved in approximately one-third of the patients, but, compared to placebo, this effect was not significant. In a follow-up study after on average 3.1 years of UDCA treatment, 7/43 of the patients with stages I-IV disease developed a stenosis of the common bile duct which was effectively treated by endoscopic dilatations. Of 57 patients with PSC included since 1987 in the study, 14 dropped out and of these in 10 information on the outcome is available. In patients treated by UDCA and, whenever necessary, by endoscopic dilatations, the frequency of transplantations was significantly reduced in comparison to patients who dropped out of the study. Bile duct carcinoma developed in 5% of our patients. The data indicate that treatment of patients with PSC with UDCA and by endoscopic dilatations of common duct stenoses is promising. In patients with endstage disease, the only effective therapy is liver transplantation. Therefore, the early diagnosis of the disease seems very important.
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PMID:Ursodeoxycholic acid therapy in treatment of primary sclerosing cholangitis. 782 79

Methotrexate (2.5 mg/day) was used in addition to ursodeoxycholic acid (10-15 mg/kg per day) in 8 female patients with primary biliary cirrhosis. All patients had undergone ursodeoxycholic acid treatment for more than 6 months preceding this study and their serum alkaline phosphatase remained constant at more than 300 U/l for more than 2 months. One patient showed histologic stage I, three stage II, two stage III and two stage IV disease. Within 6 months, fatigue and itching disappeared in all symptomatic patients. Serum alkaline phosphatase activities improved dramatically (621 +/- 299 to 378 +/- 258, mean +/- S.D.) in all but one patient and normalized in four. Serum gamma-glutamyltransferase activities (180 +/- 99 U/l vs. 150 +/- 125 U/l) and immunoglobulin M concentrations (616 +/- 424 vs. 362 +/- 195 mg/dl) also improved. Adverse effects of methotrexate therapy were only regularly observed within the first 2-6 weeks, such as fatigue and transient enhancement of transaminases and serum bile acid concentrations. We conclude that methotrexate may be a highly effective drug for the treatment of primary biliary cirrhosis in patients whose symptoms and/or laboratory liver function tests are not improved enough by ursodeoxycholic acid alone. However, its influence on histology and the natural history of the disease needs to be established.
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PMID:Positive responses to methotrexate and ursodeoxycholic acid in patients with primary biliary cirrhosis responding insufficiently to ursodeoxycholic acid alone. 810 53

Twenty-six days after liver transplantation for primary biliary cirrhosis, a 52 year-old patient was rehospitalized for viral infection. The clinical features were fatigue, anorexia and vomiting. On physical examination, vesicular skin lesions involving the left 8 th intercostal space were suggestive of herpes-zoster infection. The following day the patient was extremely tired and dyspnoeic. The abdomen was distended with moderate abdominal epigastric pain. The clinical picture worsened rapidly and the patient died a few hours later. Autopsy revealed acute haemorrhagic necrosis of the pancreas due to herpes-zoster virus.
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PMID:[Acute pancreatitis caused by varicella-zoster virus after liver transplantation]. 820 3

The effect of ursodiol on the clinical and biochemical features, serum, urinary, and biliary bile acids was investigated over a 2-yr treatment period in 14 patients with primary biliary cirrhosis (stages II-IV). Pruritus and fatigue improved, and alkaline phosphatase and liver transferases declined significantly in all patients during therapy. In four patients, less inflammation was noted by liver biopsy after 2 yr, but histology of disease did not change. Serum and urinary bile acids were increased several-fold before treatment, with cholic acid predominating. Ursodiol accounted for 30% of biliary bile acids after administration (gallstone subjects approximately 50%), and was conjugated with glycine and taurine in a ratio of 7.3:1. However, in the endogenous bile acids, the ratio increased from 1.2:1 to only 2.1:1. About 6% unconjugated bile acids were secreted into the bile (healthy controls < 1%). Thus, in patients with primary biliary cirrhosis, a larger fraction of free bile acids and a higher proportion of taurine-conjugated bile acids are secreted into the bile, compared with healthy controls. Ursodiol improves symptoms and histology with lower biliary enrichment with this bile acid.
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PMID:Effect of long-term treatment with ursodiol on clinical and biochemical features and biliary bile acid metabolism in patients with primary biliary cirrhosis. 848 Jul 34

The aminoterminal propeptide of type III procollagen (PIIINP) and hyaluronan have previously been studied in different liver diseases. The results of these studies are controversial. The aim of the present study was to examine the relationship between PIIINP and hyaluronan levels and the clinical, biochemical and histological features of primary biliary cirrhosis (PBC) and its prognosis. Fifty-five PBC patients were studied at the time of diagnosis of PBC and were followed up for a mean of 58 months. During the follow-up period 21 patients died. In addition, 30 healthy subjects were examined in the present study. Hyaluronan and PIIINP were measured by radioimmunoassay and the levels of both PIIINP and hyaluronan were higher in PBC patients than in healthy volunteers (P < 1.8 x 10(-6) and 1.6 x 10(-9), respectively). Hyaluronan and PIIINP levels were above normal values in 82 and 84% of PBC patients, respectively. There were correlations between PIIINP and hyaluronan and the histological stage of PBC (r = 0.44, P < 0.004 and r = 0.56, P < 0.00001, respectively). The correlation between PIIINP and hyaluronan was 0.46 (P < 0.0035). In symptomatic patients, both PIIINP and hyaluronan values were higher than in controls (P < 0.002 and P < 0.006, respectively). The levels of PIIINP correlated significantly with bilirubin (r = 0.43, P < 0.006), while hyaluronan was correlated with age (r = 0.33, P < 0.015), pruritus (r = 0.32, P < 0.02), fatigue (r = 0.41, P < 0.003), hepatomegaly (r = -0.46, P < 0.0008), the presence of oesophageal varices (r = 0.34, P < 0.002), weight loss (r = 0.29, P < 0.05), bilirubin (r = 0.54, P < 0.0001), albumin (r = -0.30, P < 0.04), extent of fat excretion (r = 0.53, P < 0.009) and length of symptomatic period before diagnosis of PBC (r = 0.43, P < 0.002). Using Cox's logistic regression analysis, survival was found to be influenced by bilirubin concentration but not by hyaluronan, PIIINP, age, albumin or histological stage. Therefore, hyaluronan is a more sensitive marker for predicting advanced PBC than is PIIINP. However, neither hyaluronan nor PIIINP gave any indication of prognostic outcome.
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PMID:Aminoterminal propeptide of type III procollagen and hyaluronan in patients with primary biliary cirrhosis: markers of fibrosis in primary biliary cirrhosis. 898 19

Primary biliary cirrhosis (PBC) is likely an autoimmune disease that destroys the interlobular bile ducts. Although the term PBC implies cirrhosis, this is not always present. The condition may be entirely silent clinically, save for the hallmark mitochondrial antibodies in serum. The clinical spectrum of PBC ranges from asymptomatic anicteric cholestasis with or without extrahepatic manifestations to severe cholestasis with decompensated cirrhosis. It is uncertain whether or not the course of this disease is universally fatal. Currently, no specific features have been identified which predict progression from asymptomatic to symptomatic disease, although once hyperbilirubinemia is present, a rising level indicates a poor prognosis. The liver-specific complications include pruritus, abdominal pain, xantholasma, and portal hypertension. The latter is often an early feature, as the portal hypertension is presinusoidal in nature and, when present, does not always reflect the presence of cirrhosis. There are many extrahepatic features of PBC, the most common being metabolic, chiefly hypothyroidism and metabolic bone disease. Other common associations are rheumatologic, renal, pulmonary, neuromuscular, and dermatologic. The non-specific yet distressing symptom of fatigue affects up to two-thirds of PBC subjects, but its etiology remains obscure.
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PMID:The clinical expression of primary biliary cirrhosis. 908 8


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