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)

Patients with chronic hepatitis C infection often experience fatigue. In many clinical situations, an association between fatigue and altered serum cytokine levels has been found. Altered cytokine levels in patients with hepatitis C have not shown a correlation with the degree of serum transaminase elevation or pathological change on liver biopsy. The aim of our study was to examine whether there was an association between abnormal serum cytokine levels and fatigue in patients with compensated chronic hepatitis C. Patients referred to a tertiary care hepatology clinic who were hepatitis C antibody positive and who had elevated alanine aminotransferase (ALT) levels were eligible for entry into the study. A control group was also included. Subjects in both groups who had characteristics other than hepatitis C that were known to alter cytokine values and/or cause fatigue were excluded. Patients completed a validated questionnaire to determine their fatigue severity score (FSS). Bioassays were used to measure interleukin (IL)-1, IL-6 and tumour necrosis factor-alpha (TNF-alpha) levels in early morning serum samples taken from patients and controls. Altered cytokine values were defined as those more than two standard deviations above the mean control value. Data was analysed using SPSS, version 8.01. Of the 78 patients with chronic hepatitis C who participated in the study, 19 (24%), 24 (30%) and 45 (56%) had elevated levels of IL-1, IL-6 and TNF-alpha, respectively, compared with only two (6%) of the control group who had elevation of any of the three cytokines. No correlation was found between the FSS and serum cytokine levels, when analysed singly or in combination, in patients with chronic hepatitis C. Hence, alteration in early morning serum levels of IL-1, IL-6 and TNF-alpha in patients with chronic hepatitis C infection and elevated ALT levels bear no correlation with the symptom of fatigue.
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PMID:Serum cytokine values and fatigue in chronic hepatitis C infection. 1111 49

The contribution of amino acid oxidation to total energy expenditure is negligible during short-term intense exercise and accounts for 3-6% of the total adenosine triphosphate supplied during prolonged exercise in humans. While not quantitatively important in terms of energy supply, the intermediary metabolism of several amino acids-notably glutamate, alanine, and the branched-chain amino acids-affects other metabolites, including the intermediates within the tricarboxylic acid (TCA) cycle. Glutamate appears to be a key substrate for the rapid increase in muscle TCA cycle intermediates (TCAI) that occurs at the onset of moderate to intense exercise, due to a rightward shift of the reaction catalyzed by alanine aminotransferase (glutamate + pyruvate <==> alanine + 2-oxoglutarate). The pool of muscle TCAI declines during prolonged exercise, and this has been attributed to an increase in leucine oxidation that relies on one of the TCAI. However, this mechanism does not appear to be quantitatively important due of the relatively low maximal activity of branched-chain oxoacid dehydrogenase, the key enzyme involved. It has been suggested that an increase in TCAI is necessary to attain high rates of aerobic energy production and that a decline in TCAI may be a causative factor in local muscle fatigue. These topics remain controversial, but recent evidence suggests that changes in TCAI during exercise are unrelated to oxidative energy provision in skeletal muscle.
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PMID:Regulation of skeletal muscle amino acid metabolism during exercise. 1125 39

We describe a patient who suffered from intestinal perforation after abdominal trauma. Perioperatively, he was treated with a single dose of piperacillin and 9 doses of imipenem/cilastatin over 3 days. The patient was discharged 5 days after surgery in good clinical condition and with normal liver values except for a marginal elevation of alanine aminotransferase. Two weeks after discharge, he developed fatigue, fever and pruritus, necessitating rehospitalization. He was jaundiced and had elevated alkaline phosphatase and transaminases. After exclusion of an intra-abdominal fluid collection, a vascular problem, and infectious or autoimmune liver disease, a liver biopsy was performed. The biopsy revealed centrizonal bilirubinostasis, a portal infiltrate rich in eosinophils and cholangitis. Lymphocyte transformation tests for piperacillin and imipenem/cilastatin were positive, suggesting an immunological mechanism for the observed hepatopathy. Cholestasis gradually decreased but was detectable for several weeks. The patient had a full clinical and biochemical recovery after 3 months. We conclude that short-term therapy with piperacillin, imipenem/cilastatin or the combination of these drugs can lead to the same type of hepatopathy as described for amoxycillin/clavulanic acid or antistaphylococcal penicillins. Liver biopsy and positive lymphocyte transformation are compatible with an immunological mechanism.
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PMID:Cholangiopathy after short-term administration of piperacillin and imipenem/cilastatin. 1142 85

Despite advances in the therapy of chronic hepatitis C for some hepatitis C virus (HCV) genotypes interferon and ribavirin combination therapy is effective in less than 50% of patients. Abnobaviscum Quercus (AQ) is a mistletoe preparation containing defined amounts of mistletoe lectins (ML). It has shown immunomodulatory properties in vitro and in vivo. In small clinical trials AQ resulted, within an anthroposophical treatment concept, in a biochemical or virological response in up to 40% of patients with chronic hepatitis C. In order to evaluate the effect of this preparation we conducted an individually controlled cohort study. 25 patients with chronic hepatitis C (mean duration 147 +/- 80 months) and elevated alanine aminotransferase (ALT) levels were included in the study. As control they were observed for 6 months pre-treatment. This pre-treatment period was followed by 6 months of active treatment in which the mistletoe preparation was subcutaneously injected three times a week. Main outcome parameters were normalization of ALT and viral load. Hepatitis C associated signs and symptoms like tiredness, fullness in the right upper abdomen and musculoskeletal pain were assessed monthly in a standardized questionnaire. All 25 patients completed the study and most of the patients wanted to continue treatment. Mean duration of treatment was 9.1 months. None of the patients had complete or partial normalization of ALT or HCV RNA levels during pre-treatment or treatment period. Mean ALT did not change during the study. Tiredness, fullness in the right upper abdomen and musculoskeletal pain were present in 18, 8 and 4 patients respectively. They significantly improved within two months of treatment. A significant eosinophilia (p=0.0001) occurred between month 2 and 6 during treatment. 9 month treatment with a ML containing mistletoe preparation has no effect on viral load or ALT as markers of activity in patients with chronic hepatitis C. However, frequency and intensity of clinical signs and symptoms in our patients decreased significantly, similar to reports of improved quality of life in tumour patients treated with such preparations. A significant eosinophilia suggests that ML containing mistletoe preparations induce a T-helper 2 immune response.
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PMID:Effects of a mistletoe preparation with defined lectin content on chronic hepatitis C: an individually controlled cohort study. 1166 85

Two cases, mother and her son, suffering from acute poisoning with Tricholoma equestre were described. They had eaten 100-300 grams of this wild mushroom during nine consecutive meals. About 48 hours after the last meal containing the mushroom they developed fatigue, muscle weakness and myalgia, loss of appetite, mild nausea, profuse sweating. Maximal serum creatine kinase activity was 18,150 U/L in the mother and 48,136 U/L in the son. Maximal serum levels of aspartate aminotransferase and alanine aminotransferase were 802 U/L and 446 U/L, respectively, in the mother and 2002 U/L and 454 U/L, respectively, in the son. All routine biochemical tests were within normal range. No other causes of rhabdomyolysis such as parasitic, viral, immune diseases, trauma or exposure to medications were found. All the above mentioned symptoms and biochemical abnormalities disappeared within 23 days of hospitalization. Our observation confirms the results of Bedry and co-workers that Tricholoma equestre contains a toxin, which can cause rhabdomyolysis.
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PMID:Acute poisoning with Tricholoma equestre. 1218 17

When rats given D-galactosamine are then treated with the glucogenic amino acid alanine, their alanine aminotransferase (ALT) activity, total bilirubin level, and survival rate improve compared with when other amino acids are used. Here, we report a preliminary study of the clinical and pharmacological effects of alanine given to three patients with primary biliary cirrhosis (PBC). The patients were jaundiced and were in the end-stage of the disease. The treatment they had been receiving was continued while they were given 18 g of alanine per day for a planned 8 weeks. For all three patients, test results for total bilirubin, alkaline phosphatase, and ALT decreased by 25% or more from the base line at some time during treatment. The arterial ketone-body ratio increased. Two of the patients reported that their itching and fatigue lessened. Except for one patient given a second course, who reported nausea, adverse effects were not found. In end-stage PBC, alanine administration decreased the total bilirubin level and improved symptoms, so this compound may decrease jaundice in this disease. A long-term study of a larger group of patients is needed.
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PMID:Effects of alanine in patients with advanced primary biliary cirrhosis: preliminary report. 1264 33

Recombinant human interleukin 12 (IL-12) is an immunomodulatory cytokine that is active against several viruses. Treatment options in patients with chronic hepatitis C with nonresponse to interferon (IFN)-based therapy are limited. Prior dose-ranging studies have indicated drug tolerability and transient suppression of hepatitis C virus (HCV) RNA by IL-12. The aim of this study was to determine the safety and efficacy of prolonged IL-12 therapy in patients who have failed treatment with IFN-alpha +/- ribavirin. A total of 225 patients at 21 U.S. sites who had a history of nonresponse to IFN-alpha or combination IFN-alpha plus ribavirin for treatment of HCV were randomized to 500 ng/kg IL-12 or placebo subcutaneously twice weekly for 12 weeks. The groups were then unblinded; patients receiving IL-12 continued for another 36 weeks, and the placebo group received 48 weeks of treatment with IL-12 in an open-label fashion. HCV RNA, serum alanine aminotransferase (ALT) level, and a repeat liver biopsy were assessed at 24 weeks following therapy. Approximately 1% (2 of 160) of nonresponsive patients enrolled for treatment had a sustained virologic response to IL-12 therapy, but 3% (7 of 225) developed severe adverse events probably related to treatment, resulting in early termination of the trial. Common adverse effects reported by most patients included chills, fever, fatigue, headache, and arthralgia. At termination of the study, 160 patients had received at least 8 weeks of treatment with IL-12. Paired liver biopsy specimens were available for evaluation in 54 patients, but there were no significant changes in Knodell fibrosis or histologic activity index (HAI) scores. In conclusion, IL-12 as monotherapy at the doses used in this trial for chronic hepatitis C has low efficacy, was poorly tolerated, and is unlikely to provide an alternative to conventional IFN-based therapy.
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PMID:A multicenter study of recombinant human interleukin 12 for the treatment of chronic hepatitis C virus infection in patients nonresponsive to previous therapy. 1277 16

Although colchicine induced myopathy has been described in patients with chronic renal failure, colchicine induced myopathy with myotonia has been reported very rarely. A 49-year-old man with chronic renal failure was hospitalised for investigation of fatigue, malaise and severe pain in all extremities. He was on colchicine therapy for 5 months. Neurological examination showed mildly decreased sensation in a distal symmetric pattern in lower extremities, moderate proximal limb weakness, hyporeflexia and severe myalgia on palpation. No clinical evidence of myotonia was present. Laboratory studies showed elevated creatine phosphokinase (CK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Electromyographic (EMG) findings were compatible with myopathy and abundant, widespread myotonic discharges were determined. Muscle biopsy was consistent with vacuolar myopathy. After withdrawal of colchicine, CK, LDH, AST and ALT levels were normalised and the symptoms were disappeared gradually. In conclusion, the detection of myopathic motor unit potentials with myotonic discharges on EMG in patients on colchicine therapy is an important finding and it is possible to suggest that this clue may lead to the invasive procedure of muscle biopsy unnecessary.
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PMID:Colchicine-induced myopathy with myotonia in a patient with chronic renal failure. 1295 45

The risk of transmission of hepatitis C virus (HCV) infection is an important problem for the health care worker. HCV transmission by blood splashing into eyes is very rare. In a hemodialyses department, a 23-year-old female nurse splashed blood from a patient who was anti-HCV positive into her eyes. She washed her eyes with water immediately and reported to the infection control department. She had never used intravenous drugs nor received transfusions. At the time of exposure, there was no abnormality in her laboratory tests. Her anti-HCV and HCV-RNA tests produced negative results. She was followed up for anti-HCV and alanine aminotransferase activity. After 6 months, she presented with sore throat, nausea, vomiting, fatigue, and weight loss. She had icterus and hepatomegalia. In laboratory tests, alanine aminotransferase level was 504 U/L, aspartate aminotransferase level was 388 U/L, and anti-HCV and HCV-RNA tests produced positive findings. She was treated with interferon alfa-2a for a 1-year period. After treatment, an HCV-RNA test produced negative results and transaminase levels were normal. In conclusion, splashing blood from patients who are HCV positive into the face or eyes is a risk for health care workers. They should be educated to prevent a nosocomial acquisition of bloodborne infection and they should observe protective precautions.
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PMID:Transmission of hepatitis C by blood splash into conjunctiva in a nurse. 1545 4

We report a case of primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome with concurrent idiopathic thrombocytopenic purpura (ITP) and Hashimoto's disease with positivity for anticentromere antibody. The patient was a 64-year-old woman with symptoms of jaundice and general fatigue. About 30 years earlier, she had been diagnosed as having ITP and had undergone splenectomy. As part of her present history, she had exhibited liver dysfunction in 1995, during the follow-up of Hashimoto's disease, and a liver biopsy led to the diagnosis of PBC. In March 2000, she was admitted to hospital because of general fatigue and jaundice. Blood tests revealed: total protein (TP), 6.6 g/dl; gamma-globulin (glb), 35.9%; total bilirubin (T-bil), 9.41 mg/dl; direct bilirubin (D-bil), 7.52 mg/dl; aspartate aminotransferase (AST), 957 U/l; alanine aminotransferase (ALT), 651 U/l; alkaline phosphatase (ALP), 595 U/l; gamma-guanosine triphosphate (GTP), 129 U/l; IgG, 2620 mg/dl; IgM, 223 mg/dl; hepatitis B surface antigen (HBsAg), negative; anti-hepatitis C virus (HCV), negative; antinuclear antibody, positive; antimitchondrial antibody (AMA), negative (by the immunofluorescence [IF] method); and anti-pyruvate dehydrogenase complex (PDC)-E2 antibody, positive (by Western blotting). Anticentromere antibody (ACA), which is an alternative diagnostic marker for PBC, was detected in this patient. Prednisolone was administered after admission and liver function test results improved markedly. The liver biopsy in 1995 had revealed infiltration of lymphocytes and plasma cells in the portal areas with fibrous expansion and periportal necrosis. Destructive cholangitis was observed, as well as scattered epitheloid cell granulomas in some portal areas. Liver biopsy after the steroid treatment revealed alleviated necrotic inflammatory responses of hepatocytes, while the destructive cholangitis persisted. This is a very rare case of PBC-AIH overlap syndrome accompanied by ITP and Hashimoto's disease which provides a possible insight into the mechanisms and interplay of autoimmune diseases.
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PMID:PBC-AIH overlap syndrome with concomitant ITP and Hashimoto's disease with positivity for anti-centromere antibody. 1517 50


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