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)

357 IDMs and 20 healthy newborns of non-diabetic mothers were examined at term for body measurements, red blood cell count, serum bilirubin, cord blood insulin and blood glucose during the first postnatal week. The stage of maternal diabetes did not influence the course of neonatal bilirubin levels, but the IDMs had prolonged and higher bilirubinaemia compared with the controls. Hyperbilirubinaemia was found to be most prominent in newborns with an increased birthweight/length ratio and was not simply related to macrosomia (LGA). These infants had significantly lower blood glucose concentrations immediately after birth, whereas cord blood insulin was found to be identical between the IDM sub-groups. Bilirubinaemia in heavy for length infants was slightly correlated to haematocrit. For the pathogenesis of hyperbilirubinaemia in IDMs induction of heme oxygenase (due to a lack of energy provision following a phosphorylation disorder) is discussed. Nutritional support (early feeding, glucose infusions) does not affect the course of bilirubinaemia.
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PMID:Neonatal jaundice in infants of diabetic mothers. 270 15

The effect of cyclosporin A (CyA) on regenerating liver was investigated in subtotal hepatectomized rats treated with CyA in terms of mitochondrial phosphorylative activity, hepatic energy charge, and serum bilirubin levels. In the CyA-treated hepatectomized group, the energy charge decreased from normal control value of 0.857 to 0.782 at 6 h after hepatectomy. The decreased energy charge, however, gradually increased and returned to 0.842 at 48 h after hepatectomy with no significant changes being observed between CyA-treated and untreated hepatectomized groups. Phosphorylation rate in the CyA-untreated group increased to 142% of the normal control at 24 h and then decreased to 114% at 48 h after hepatectomy. By contrast, phosphorylation rate in the CyA-treated group increased to 144% of the normal control at 24 h, but remained at the high value of 132% (P less than 0.01; compared to the CyA-untreated group) even at 48 h after hepatectomy. Serum total bilirubin levels in the CyA-treated group were significantly higher than those in the CyA-untreated group during all experimental periods. We conclude that CyA does not exert a direct detrimental effect on mitochondrial function and that, despite the marked hyperbilirubinemia induced by CyA, the mitochondrial phosphorylative activity increases adaptively to provide sufficient energy for enhanced ATP-utilizing reactions in an early process of liver regeneration.
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PMID:Effect of cyclosporine on oxidative phosphorylation and adenylate energy charge of regenerating rat liver. 281 67

A phase I trial of intramuscularly administered recombinant human tumor necrosis factor (rTNF) was conducted in 19 adult patients with advanced solid tumors. The agent was administered daily for up to five consecutive days every other week for two to four courses. Doses of rTNF ranged from 5 to 200 micrograms/m2/d. Dose-limiting toxicities were encountered at doses greater than 100 micrograms/m2/d. Toxicities included tenderness, erythema and induration at the site of injection, fatigue, fever, chills, headache, anorexia, nausea, vomiting, and diarrhea. Moderate to marked reductions in WBC and platelet counts were observed regularly at the highest dose levels, but none were clinically significant. Hepatic enzyme elevation was seen frequently, and two patients developed hyperbilirubinemia. Only one of seven patients treated with doses greater than 100 micrograms/m2/d completed the planned course of therapy. Even at the highest dose levels, serum concentrations of rTNF could only rarely be detected in the serum. No therapeutic responses were observed. The maximal tolerated dose (MTD) of rTNF in this trial was 150 micrograms/m2/d, administered for two courses.
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PMID:Phase I trial of intramuscularly administered tumor necrosis factor in patients with advanced cancer. 291 29

A case of advanced gastric cancer associated with metastatic carcinomatosis of the bone marrow, microangiopathic hemolytic anemia (MAHA) and disseminated intravascular coagulation (DIC) was reported. A 71-year-old woman complained of lumbago and general fatigue. At the time of admission, besides anemia, jaundice and a tendency to bleeding, the laboratory data showed, hyperbilirubinemia, elevated FDP and hemolytic anemia with fragmented red cells. The bone marrow was infiltrated by carcinoma, and an upper GI series examination showed Borrmann II type gastric cancer on the greater curvature of the antrum. After remission of both MAHA and DIC by mitomycin C, neothramycin and FOY, the patient successfully underwent subtotal gastrectomy. However, she died of cerebral hemorrhage on the 96th postoperative day.
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PMID:[Microangiopathic hemolytic anemia associated with gastric cancer]. 309 84

The results of a retrospective analysis of 59 patients with Gilbert's syndrome are presented. All the patients were selected on the basis of repeatedly documented, predominantly unconjugated hyperbilirubinemia in the absence of liver or hemolytic disease. The peak incidence of Gilbert's syndrome was in the 15-30 years age group with males predominating almost fivefold. Scleral icterus or a laboratory finding of hyperbilirubinemia represented the major reasons for workup. Presenting symptoms such as fatigue, upper abdominal pain and fat intolerance were largely nonspecific. Whereas minimal values for total serum bilirubin concentrations were, at l.57 +/- 0.56 mg/dl (mean +/- S.D.), often within the normal range (less than 1.2), maximal values were always clearly elevated (2.05 +/- 0.65). The sex difference in bilirubin levels was also maintained in the Gilbert's syndrome, since mean values in women were lower than in men. As expected, neither liver scan nor histology yielded evidence of structural abnormalities. The results of liver function studies such as galactose elimination capacity, aminopyrine breath test, or fasting and postprandial serum bile acids, were all within normal limits. In contrast, the initial plasma disappearance of bromsulphthalein (BSP-k1) was reduced in 6 patients to a mean of 8.7% per min (normal value 12.6 +/- 1.6), which suggests that these subjects belong to the Gilbert type with diminished hepatic clearance of anionic dyes. The hematological investigations, including hemoglobin electrophoresis, Coombs tests and erythrocyte enzymes, yielded normal results. However, osmotic fragility was increased in 5 cases and erythrocyte survival reduced to less than 24 days in 9 cases (of 17 investigated). In 35 patients, a nicotinic acid test was performed in which total serum bilirubin rose within 3 hours from a mean of 1.66 +/- 0.7 to 3.51 +/- 0.75 mg/dl. Between the third and fifth hour bilirubin levels plateaued, yielding retention values of 98%, 92% and 92% respectively. These retention values may be considered in indirect estimate of bilirubin clearance. Retentions exceeding 70% after 5 hours correspond to bilirubin clearances of less than 20 ml/min, representing evidence in favour of the diagnosis of Gilbert's syndrome.
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PMID:[Positive diagnosis of Gilbert syndrome. Retrospective analysis of 59 cases with special reference to the nicotinic acid test]. 713 40

A 7-year-old patient is reported who suffered from fatigue and jaundice due to chronic hepatitis. He had acquired hepatitis A virus infection in his community and communicated the disease to his German family 4 weeks later. While the other family members recovered from acute viral hepatitis A, the patient presented 10 weeks after the onset of hyperbilirubinemia (12 mg/dl) with the histology of chronic hepatitis, absence of markers for viral persistence, presence of autoantibodies against smooth muscle (1:320) and the asialoglycoprotein receptor (1:600), and marked hypergammaglobulinemia (3700 mg/dl), leading to the diagnosis of autoimmune hepatitis. The patient received immunosuppressive therapy, symptoms of liver disease disappeared, and autoantibodies cleared from circulation. The case is discussed in the context of a putative virus-induced autoimmune hepatitis in childhood. Autoimmune hepatitis may be induced by an external trigger. Hepatitis A virus infection is one of probably several triggers that may induce autoimmune hepatitis in predisposed individuals.
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PMID:Autoimmune hepatitis following hepatitis A virus infection. 749 93

Piroxantrone, a synthetic intercalating agent, was studied in patients with advanced, measurable gastric adenocarcinoma who had not received prior chemotherapy. The starting piroxantrone dose was 150 mg/m2 given intravenously over 1 hour on day 1 and repeated every 21 days. Response and toxicity could be evaluated in 15 patients. No complete, partial, or minor responses were observed. Toxic effects included granulocytopenia, anemia, vomiting, nausea, anorexia, fatigue, stomatitis, alopecia, hyperbilirubinemia, and increased alkaline phosphatase levels. At the stated dose and schedule, piroxantrone does not possess significant activity against advanced gastric cancer.
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PMID:Phase II trial of piroxantrone in metastatic gastric adenocarcinoma. 789 47

A phase I and pharmacokinetics study of oral uracil, ftorafur, and leucovorin was performed in patients with advanced cancer. Uracil plus ftorafur (UFT) was given in a 4:1 molar ratio in three divided doses for 28 consecutive days. Patient cohorts were treated at 200, 250, 300, and 350 mg/m2 of UFT daily. For all patients, 150 mg of leucovorin was given daily in three oral doses. A 1-week rest period followed each 28-day treatment course. Gastrointestinal toxicity, characterized by diarrhea, nausea, and vomiting, was dose-limiting at 350 mg/m2 UFT in patients who had received prior chemotherapy. Mild fatigue and transient hyperbilirubinemia were also common. In previously untreated patients, UFT at 350 mg/m2 was well-tolerated, suggesting this as an acceptable phase II dose in this schedule with leucovorin. Two of eight previously untreated patients with advanced colorectal cancer had partial responses with UFT (350 mg/m2) plus leucovorin. Pharmacokinetic parameters [ftorafur, uracil, 5-fluorouracil (5-FU), 5-methyltetrahydrofolate] showed wide interpatient variations. Plasma levels of 5-FU (Cmax 1.4 +/- 1.9 microM) were comparable to those achieved with protracted venous infusions, and folate levels (Cmax 6.1 +/- 3.6 microM) were sufficient for biochemical modulation. Ongoing study will determine if this convenient oral regimen will compare favorably in terms of efficacy, toxicity, and cost with intravenous fluoropyrimidine programs.
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PMID:A phase I and pharmacokinetic study of oral uracil, ftorafur, and leucovorin in patients with advanced cancer. 861 13

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

The goal of our study was to determine the epidemiological and clinical features of imported malaria seen at our military hospital in Hawaii. We reviewed the records of malaria cases seen from January 1, 1979, to December 31, 1995, and compared our results with published reviews from civilian hospitals in North America. Seventy-nine patients were diagnosed with malaria by blood smears. All acquired malaria abroad, mostly in southeast Asia. Sixty-seven percent of cases were vivax malaria, 22% were falciparum malaria, and 11% were caused by undetermined species. Common symptoms were fever (100%), alternate day fever (41%), rigors (91%), headache (59%), nausea (41%), fatigue (39%), dark urine (32%), and vomiting (31%). Ninety-one percent had fever during hospitalization, but 39% were afebrile on admission. Splenomegaly was detected in 49% of cases. The white blood cell count was normal in 65%, low in 31%, and elevated in 4% of cases. Other laboratory findings were anemia (58%), thrombocytopenia (74%), and mild hyperbilirubinemia (64%). Military physicians initially considered the diagnosis of malaria in only 54% of patients. The epidemiological features of our patients differ from those described in the civilian hospitals. Most of our patients were nonimmune, U.S.-born, military personnel infected in southeast Asia, whereas patients described in reviews from U.S. civilian hospitals were usually foreign-born civilians who were infected in Africa or India. The clinical features of malaria, and the problems of initial misdiagnosis in our patients, were similar to those reported from civilian hospitals. Military physicians, like their civilian colleagues, need more training and experience in malaria.
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PMID:A review of 79 patients with malaria seen at a military hospital in Hawaii from 1979 to 1995. 950 98


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