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)

Yoshida ascites hepatoma cells growing in vivo are characterized by a large number of monosomes and dimers which further increase when the cells are incubated anaerobically in vitro in the absence of glucose: under the latter condition most of the ribosomes are present as inactive particles. These monosomes can be incorporated into polyribosomes if the elongation step of protein synthesis is inhibited by cycloheximide. The degradation of polysomes in the absence of glucose under anaerobic conditions can be reversed promptly on addition of glucose to the medium and less promptly by oxygenation. These data suggest that the large monosome-dimer pool of hepatoma cells depends on a relative inefficiency of the initiation step of protein synthesis, which is magnified by the lack of energy caused by anaerobic incubation in the absence of glucose, and counteracted by interference with further steps of protein synthesis or conditions which favor glycolysis or, less efficiently, respiration of the tumor cells.
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PMID:Effect of energy deprivation on the polyribosomes of Yoshida ascites hepatoma cells. 661 29

A Phase II trial of combination therapy with recombinant leukocyte interferon (alpha IFN) and doxorubicin was performed in patients with unresectable hepatocellular carcinoma. alpha IFN was administered at a starting dose of 20 x 10(6) U/m2 intramuscularly or subcutaneously with doxorubicin 20 mg/m2 intravenously weekly x 3 weeks followed by a 2-week period rest. There were 22 patients entered into the study. Among the 21 patients, there were 2 partial responses (10%), one minor response, and one patient had stable disease. Toxicity was generally tolerable, with fever, fatigue, and myelosuppression being the most common side effects. This combination of weekly recombinant leukocytic interferon and doxorubicin has modest and limited activity in hepatocellular carcinoma.
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PMID:A phase II trial of recombinant leukocyte interferon plus doxorubicin in patients with hepatocellular carcinoma. 809 9

The Cooperative Study Group conducted a study to assess the therapeutic effects of chemoembolization in patients with advanced hepatocellular carcinoma (HCC) using either epirubicin hydrochloride (FARM) or doxorubicin hydrochloride (ADR). A total of 77 patients were enrolled in this study and randomized into 2 groups: 39 patients were treated with a FARM solution as the material for Lipiodol-transcatheter arterial embolization (TAE; FARM group), and 38 patients were treated with an ADR solution as the material for L-TAE (ADR group). For the FARM group, the 1-year survival rate was 69.9% and the 2-year survival rate was 44.5%. For the ADR group, the corresponding survival rates were 74.7% and 44.0%. The differences among the above figures were not statistically significant. As side effects, fever, nausea, and generalized fatigue occurred at almost the same frequencies in the two groups. Changes detected in the liver function and the peripheral blood cell count in both groups were not severe. There was no significant difference between the toxic effects observed in the two groups. In conclusion, there was no significant difference in therapeutic efficacy between the FARM and ADR groups.
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PMID:Prospective and randomized controlled study of chemoembolization therapy in patients with advanced hepatocellular carcinoma. Cooperative Study Group for Liver Cancer Treatment in Shikoku area. 813 92

A 59-year-old male with liver cirrhosis was admitted to our hospital for further examination of general fatigue. A huge tumor was found in the right lobe of his liver with abdominal ultrasonography and computed tomography (CT). The titers of serum AFP (14,055 ng/ml) and PIVKA-II (more than 50.0 AU/ml) were extremely high. A tumor embolus was observed in the portal vein with abdominal angiography. According to these findings, he was diagnosed as having advanced hepatocellular carcinoma (HCC). He was treated by oral administration of UFT (600 mg/day) as an unresectable case of HCC. Three months later, the clinical symptoms were greatly improved and HCC was almost diminished with abdominal ultrasonography and CT, although a small tumor embolus was found by angiography. The titers of AFP and PIVKA-II were reduced to the normal range. This case suggests the clinical effectiveness of UFT for the treatment of HCC.
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PMID:[A case of advanced hepatocellular carcinoma, in which the tumor almost disappeared by orally administered UFT]. 823 87

To evaluate the clinical efficacy of interferon-alpha in hepatocellular carcinoma, 71 adult Chinese patients with histologically proven inoperable hepatocellular carcinoma were randomized to receive recombinant interferon-alpha 2a (50 x 10(6) IU/m2) intramuscularly three times a week (n = 35) or no antitumor therapy (n = 36). The survival of interferon-alpha-treated patients was significantly better than that of patients who received no antitumor therapy (p = 0.0471); median lengths of survival were 14.5 and 7.5 wk, respectively. Objective tumor regression greater than 50% was observed in 31.4% (11 of 35) of patients receiving interferon-alpha. Interferon-alpha induced tumor regression greater than 50% in 11 (31.4%) patients. Compared with the group receiving no antitumor therapy, the interferon-alpha therapy group had more tumor regression (p < 0.0001) and less tumor progression (p = 0.001). This high-dose interferon-alpha therapy was relatively well tolerated; only 34.3% of patients required reduction of dosage by one third or one half because of persistent fatigue. Two patients with diabetes mellitus (one also had tabes dorsalis) exhibited mental deterioration that might have been partially attributable to interferon-alpha therapy. We conclude that interferon-alpha is useful in a proportion of Chinese patients with inoperable hepatocellular carcinoma, both in prolonging survival and in inducing tumor regression.
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PMID:Recombinant interferon-alpha in inoperable hepatocellular carcinoma: a randomized controlled trial. 838 88

Carcinosarcoma of the liver with mesenchymal differentiation are very rare in adult patients. A case is reported with an exhaustive pathologic examination and review of the literature. A 61-year old man presented with general fatigue and dull abdominal pain. Two liver masses were diagnosed and resected by a right hepatectomy. Specimen pathology revealed that the tumor and lymph node consisted of two cancerous components. One carcinomatous component corresponding to a hepatocellular carcinoma and a sarcomatous component characterized by a diffuse proliferation of spindle shaped cells with chondrosarcomatous and osteosarcomatous changes. Patient died 9 months later of a diffusion of the tumor. For the first time, to our knowledge, a mesenchymal differentiation is demonstrated in liver carcinosarcoma.
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PMID:Carcinosarcoma of the liver with mesenchymal differentiation: a case report. 868 74

We determined the course of hepatitis C infection in 125 patients with a history of injection drug use. The mean age at presentation was 43.5 years, and the mean age of initiating injection drug use was 23.1 years. Fatigue and hepatomegaly were present in as many as 60% of patients. All had antibodies to the hepatitis C recombinant protein C25, and 99% were positive for hepatitis C virus RNA. After the initial workup, 33 (26%) patients had chronic hepatitis, 46 (37%) had chronic active hepatitis, 45 (36%) had cirrhosis, and 1 (0.8%) presented hepatocellular carcinoma. During follow-up, hepatocellular carcinoma developed in 2 other patients. In 74 patients with a 1-year history of injection drug use, the mean number of years to the development of chronic hepatitis, chronic active hepatitis, cirrhosis, and hepatocellular carcinoma were 15.6, 17.6, 19.4, and 26.3 years, respectively. In this subgroup of patients, heavy alcohol abuse did not appear to influence the progression of liver disease. The 2-year case-fatality rate was 2%. Our findings indicate that hepatitis C is a progressive disease, but only a few died during the average 20.4 years after the initiation of injection drug use. Antiviral treatment to eradicate the virus and halt the progression of disease is indicated in this group of patients.
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PMID:Clinical sequelae of hepatitis C acquired from injection drug use. 876 37

Virus-associated hemophagocytic syndrome (VAHS) is associated with a systemic viral infection and is mainly observed in immunosuppressed adult patients. This rare disease is characterized by symptoms which include a high fever, pancytopenia, and splenomegaly and sometimes results in a fatal outcome. However, thus far, little has been reported on VAHS in general surgical patients. We herein report this rare complication which occurred in a patient with hepatocellular carcinoma, as well as chronic hepatitis C, after a hepatic resection. A 66-year-old man with chronic hepatitis C and recurrent hepatocellular carcinoma underwent a repeat hepatic resection without any blood transfusions. In the early postoperative period, he recovered uneventfully. However, he suddenly began to suffer from a high fever (38.4 degrees C) and severe pancytopenia 8 days after surgery. Activated macrophages, which phagocytosed erythrocytes, were identified by a cytological study of the bone marrow. The patient was therefore treated with methylprednisolone pulse therapy 13 days after surgery. On the day following the initial administration of methylprednisolone, his clinical condition drastically improved. Fortunately, with methylprednisolone therapy, our patient recovered from acute, severe pancytopenia. In general surgery, it is often difficult for surgeons to use steroids due to their negative side effects. However, when symptoms such as fever, general fatigue and pancytopenia are observed, even in posthepatectomy patients with hepatocellular carcinoma and hepatitis, a bone marrow aspiration should be performed as soon as possible, and when VAHS is suspected, steroid pulse therapy should be the first treatment of choice. This rare but sometimes fatal complication should thus be taken into consideration in the postoperative management of hepatectomized patients with chronic hepatitis C.
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PMID:Virus-associated hemophagocytic syndrome after hepatic resection: a case report. 949 16

A 73-year-old man complaining of general fatigue and abdominal fullness was hospitalized in April 1994. Hepatocellular carcinoma (HCC) measuring 25 x 11 cm was detected in the right liver lobe. The patient received transcatheter artery embolization, and AFP and PIVKA-II levels were decreased thereafter. However, after three months, AFP levels were increased gradually. Therefore, 300 mg of UFT was administered daily. AFP and PIVKA-II levels decreased and the tumor decreased in size. The patient remained in a good state of health for about two years and six months. Our case suggests that UFT is effective for the treatment of HCC.
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PMID:[A case of giant hepatocellular carcinoma effectively treated with UFT]. 967 85

GI147211 is a novel, totally synthetic camptothecin with promising preclinical and early clinical activity. This study was designed to determine the maximum tolerated dose of Gl147211 as a 72-h infusion and to describe its pharmacokinetics and pharmacodynamics on this schedule. In a single-arm, rising-dose study in patients with advanced cancer, eight cohorts of three or more patients received 72-h infusions of Gl147211 at doses ranging from 0.25 to 2.5 mg m(-2) day(-1). Forty-four patients received a total of 124 cycles. All patients had refractory tumours and 40 had received prior chemotherapy and/or radiotherapy. Whole-blood Gl147211 lactone, total blood and total concentrations were measured during and over the 12 h following the infusion. Myelosuppression was observed at all dose levels. Neutropenia was dose limiting at 2.0 mg m(-2) day(-1) in minimally pretreated patients, while both neutropenia and thrombocytopenia were limiting at 1.5 mg m(-2) day(-1) in those more heavily pretreated. Phlebitis occurred with infusions through peripheral veins early in this study, necessitating the use of central venous access. Other toxicities included mild nausea and vomiting, fatigue, headache, central venous catheter infections and alopecia. Three partial and two minor responses lasting 8-34+ weeks were noted in patients with ovarian, colon and breast carcinomas and hepatoma. Mean steady-state concentrations of Gl147211 increased with dose over a range of 0.25-1.24 ng ml(-1). The mean terminal elimination half-life was 7.5 h, and the clearance averaged 1074 ml min(-1) m(-2) over the doses studied. The mean fractional excretion of unchanged drug in urine was 0.114. Gl147211 lactone exposure correlated with haematological toxicity. The recommended phase II doses for this regimen are 1.75 mg m(-2) day(-1) and 1.2 mg m(-2) day(-1) for minimally pretreated and heavily pretreated patients respectively. At these doses, steady-state Gl147211 concentrations within the range of those effective in vitro were achieved. Extensive phase II evaluation of this compound and further phase I trials evaluating more prolonged infusions are ongoing.
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PMID:A phase I clinical and pharmacokinetic study of the new topoisomerase inhibitor GI147211 given as a 72-h continuous infusion. 982 74


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