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

A 60-year-old man complained of severe general fatigue on October 11, 1992. Pertinent laboratory findings were: aspantate aminotransferase (AST) 1920 IU, alanine aminotransferase (ALT) 2050 IU, and total bilirubin (T. Bil) 124 micromol/l (normal range, 0-17 micromol/l). Virological assay revealed that hepatitis B surface antigen (HBsAg), anti-hepatitis B e (HBe), anti-HBc, and immunoglobulin M (IgM) anti-HBc were positive, and anti-HBs, HBeAg, and anti-delta antibody were negative. A diagnosis of acute hepatitis due to hepatitis B virus was made. Despite a decrease in transaminase, jaundice worsened and prothrombin time was prolonged. On the 60th day of hospitalization, massive ascites developed, but the patient's consciousness was not impaired. Although, albumin and diuretics were given, the ascites further increased. Paracentesis of 2000 ml of ascitic fluid was performed twice a week. On the 120th day of hospitalization, the patient passed black stools and he exhibited renal failure 3 weeks later. Although severe jaundice persisted, he was still alert. On the 150th day of hospitalization, massive gastrointestinal bleeding occurred, due to hemorrhagic gastritis. Despite receiving intensive care, the patient died. Determination of the HBV DNA sequence revealed two point mutations in the pre-core region; these have not been reported elsewhere.
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PMID:Late onset hepatic failure due to hepatitis B virus with mutations in the pre-core region. 857 43

We studied 13 patients with lipoamide dehydrogenase (LAD) deficiency, originating from seven Ashkenazi Jewish families. Their disease was characterized by recurrent attacks of vomiting, abdominal pain, and encephalopathy accompanied by elevated liver transaminases, prolonged prothrombin time, and occasionally associated with lactic and ketoacidemia or with myoglobinuria. Two patients who presented neonatally suffered from residual neurological damage with attention deficit hyperactive disorder, mild ataxia, motor incoordination, muscle hypotonia, and weakness. Nine patients who presented in early childhood or later suffered from exertional fatigue between decompensation episodes but were otherwise asymptomatic. Two patients died because of intractable metabolic acidosis and multi-organ failure. In all patients LAD activity was reduced to 8 to 21% of the control in muscle or lymphocytes. In four patients LAD protein in muscle was reduced to 20 to 60% of the control. Direct sequencing of the cDNA of the LAD gene showed that 12 of the 14 mutated alleles carried the G229C mutation and two carried an insertion mutation 105insA (Y35X). The patients who presented neonatally and had more severe sequelae were compound heterozygotes for the two mutations; patients who presented in early childhood or later were homozygous for the G229C mutation. Using an allele-specific oligonucleotide hybridization technique, nine heterozygotes for the G229C mutation were identified among 845 anonymous individuals of Ashkenazi Jewish origin disclosing a carrier rate of 1:94. Because of the significant morbidity associated with the disease, screening for the G229C mutation among Ashkenazi Jewish couples should be considered.
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PMID:Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews. 993 85

The present study was designed to determine the maximum tolerated dose (MTD), toxicity profile, pharmacokinetics (PKs), and antitumor activity of the protein kinase C-alpha antisense oligonucleotide ISIS 3521 (ISIS Pharmaceuticals, Inc., Carlsbad, CA) when administered in combination with 5-fluorouracil (5-FU) and leucovorin (LV). Patients with refractory solid tumors received ISIS 3521 as a 21-day continuous infusion administered simultaneously with 5-FU and LV given daily for 5 days repeated every 4-5 weeks (one cycle). 5-FU and ISIS 3521 PK analysis were performed on samples taken during the first cycle in all patients. Fifteen patients received ISIS 3521 at one of three dose levels: (a) 1.0 (n = 3 patients); (b) 1.5 (n = 3 patients); and (c) 2.0 (n = 9 patients) mg/kg/day. All patients simultaneously received 5-FU (425 mg/m(2)/day) and LV (20 mg/m(2)/day) for 5 consecutive days. Grade 1-2 toxicities included alopecia, fatigue, mucositis, diarrhea, anorexia, nausea/vomiting, and tumor pain. One patient had grade 3 chest pain considered to be related to 5-FU therapy, another patient had dose-limiting grade 3 mucositis resolving in <7 days, and one patient with a history of gastritis had an acute upper gastrointestinal bleed thought to be 5-FU-induced toxicity. Five patients developed cycle 1 grade 4 neutropenia, which resolved without colony-stimulating factors before the next treatment cycle. There were no effects on prothrombin time and activated partial thromboplastin time. A clinically defined MTD was not reached. The character and severity of these toxicities do not seem to be dose related, and, as such, there was no classical dose-limiting toxicity defining the MTD. ISIS 3521 PKs in the presence of 5-FU was consistent with those reported previously. 5-FU PK parameters were also similar in the presence or absence of ISIS 3521. Six of 14 patients ( approximately 43%) across all dose cohorts had an improvement in measurable tumor response ranging from minor reduction in tumor size (4 patients) to objective partial response (>50% reduction in tumor size, 2 patients). ISIS 3521 is tolerable at its recommended single-agent dose when given with 5-FU and LV. There is no apparent PK interaction between ISIS 3521 and 5-FU and LV. Antitumor activity was observed with the combination; however, it is uncertain whether clinical activity is a result of enhanced drug interaction. Our study warrants further exploration of efficacy in a Phase II and/or Phase III clinical trial setting.
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PMID:Phase I clinical and pharmacokinetic study of protein kinase C-alpha antisense oligonucleotide ISIS 3521 administered in combination with 5-fluorouracil and leucovorin in patients with advanced cancer. 1194 11

Artificial liver support system (ALSS) has been used to treat hepatic failure and has significantly decreased the mortality. TECA hybrid artificial liver support system (TECA-HALSS), which combines the hollow fiber bioreactor with a plasma exchange circuit, was used to assess the efficacy, safety and feasibility in treating severe hepatitis patients. The hybrid artificial liver support system (HALSS) consists of a bioreactor containing more than 5 x10(9) porcine hepatocytes and plasma exchange device. Fifteen patients with severe hepatitis were treated with this hybrid system. All patients experienced a reduction in symptoms such as fatigue, abdominal distention or ascites. After each treatment serum total bilirubin decreased markedly while prothrombin activity increased. There were ten patients whose progress of hepatocyte necrosis was stopped after HALSS treatment, and finally they recovered completely. One patient received liver transplantation after HALSS therapy and survived. No serious adverse events were noted in the fifteen patients.
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PMID:Study of severe hepatitis treated with a hybrid artificial liver support system. 1286 56

Ecstasy is a synthetic amphetamine widely used as a "week-end" recreational drug because it produces euphoria and eliminate the sense of fatigue. It was initially considered to be a drug with few toxic effects, but later various complications and even fatal cases have been reported. Although the 23 year old woman already tried the Ecstasy in the past, but during the month before the admission she took 8 pills. She became icteric after 6 days taking the last pill and 3 days later her prothrombin level became very low. Due to the rapid deterioration we planed liver transplantation, but since there was no acceptable donor, we could only make plasmapheresis. The autopsy proved sever liver necrosis.
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PMID:[Acute liver failure caused by Ecstasy]. 1293 67

Although it is well known that the incidence of idiopathic steatorrhea is much higher in relatives of patients with this disease than it is in the general population, there has been little comment on the variability of symptoms in familial cases. Two sisters with this disease are reported. One presented with a relatively acute history of diarrhea, weight loss, fatigue and peripheral edema and was found to have a normal hemoglobin, hypocalcemia and a markedly decreased prothrombin activity. Her elder sister tended to constipation and had a 10-year history of refractory iron-deficiency anemia. The diagnosis was confirmed in both by peroral jejunal biopsy.
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PMID:IDIOPATHIC STEATORRHEA PRESENTING WITH DIFFERENT MANIFESTATIONS IN SISTERS. 1412 63

A recombinant enzyme-linked immunosorbent assay (ELISA) followed by a neutralization test (NT) and recombinant immunoblot assay (RIBA) were used for the detection of antibody to hepatitis C virus (anti-HCV) in 71 patients receiving 84 orthotopic liver grafts between 1984 and 1990. Before the liver transplantation (LTX) anti-HCV was present in six of the 71 recipients (8.5%) who were accepted for LTX because of acute or chronic liver failure. After LTX anti-HCV could not be detected in one of the patients, but it was continuously present in the others for more than 12 months. Detectable HCV antibodies were not present in the three patients who underwent LTX because of clinical evidence of fulminant NANB hepatitis. Two of 48 (4.2%) previously HCV seronegative recipients, who survived more than 3 months, seroconverted 9 and 16 months, respectively, after transplantation. The postoperative seroconversion was probably due to the transfer of virus via perioperative blood transfusions. Thus, these liver recipients may be able to respond by producing anti-HCV despite immunosuppressive therapy. None of the seven post-transplant HCV-seropositive patients developed symptoms such as icterus or fatigue, which would suggest the presence of liver insufficiency due to HCV infection. However, two of them had increased transaminase levels and histological signs of mild hepatitis. No significant difference was found in 1-year survival, prothrombin complex, albumin levels or the risk for retransplantation in post-transplant anti-HCV-seropositive patients, compared with those without detectable HCV antibodies (71% vs 69%, respectively). Thus, during the study period of 1-5 years, the clinical course of HCV infection was milder than that reported for hepatitis B infection in liver recipients.
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PMID:Seroprevalence and outcome of hepatitis C in liver transplantation. 1462 69

We report a case of fatal liver failure due to reactivation of lamivudine-resistant HBV. A 53-year-old man was followed since 1998 for HBV-related chronic hepatitis. Serum HBV-DNA was 150 MEq/mL (branched DNA signal amplification assay) and ALT levels fluctuated between 50-200 IU/L with no clinical signs of liver cirrhosis. Lamivudine (100 mg/d) was started in May 2001 and serum HBV-DNA subsequently decreased below undetectable levels. In May 2002, serum HBV-DNA had increased to 410 MEq/mL, along with ALT flare (226 IU/L). The YMDD motif in the DNA polymerase gene had been replaced by YIDD. Lamivudine was continued and ALT spontaneously decreased to the former levels. On Oct 3 the patient presenting with general fatigue, nausea and jaundice was admitted to our hospital. The laboratory data revealed HBV reactivation and liver failure (ALT: 1828 IU/L, total bilirubin: 10 mg/dL, and prothrombin INR: 3.24). For religious reasons, the patient and his family refused blood transfusion, plasma exchange and liver transplantation. The patient died 10 d after admission. The autopsy revealed remarkable liver atrophy.
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PMID:Fatal liver failure due to reactivation of lamivudine-resistant HBV mutant. 1516 53

Reactions after bee or wasp sting are similar to anaphylaxis. Symptoms such as weakness, fatigue, vomiting, diarrhea, urticaria, and hypotension may occur. Serious toxic reactions usually occur after numerous stings. Massive bee envenomations can result in immediate onset of shock, hemolysis, rhabdomyolysis, disseminated intravascular coagulation (DIC), coma, and renal failure. In milder cases, patients may only have isolated prolonged activated partial thromboplastin time (aPTT) and normal prothrombin time (PT), clinically without a tendency to bleed. As a rule, they recover spontaneously without any complication. We report three cases of wasp stings; they all manifested prolongation of aPTT and finally recovered completely. Isolated prolongation of aPTT in cases of wasp stings may be related to an extract from the venom inhibiting the coagulation pathway.
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PMID:Isolated prolongation of activated partial thromboplastin time following wasp sting. 1623 65

The chronic and immediate post-exercise responses in the hemostatic and fibrinolytic systems have been shown to be variable and reflect differing adaptations with ageing and responses to exercise protocols. This study investigated the effects of acute and exhaustive exercise on the amplitude and duration of hemostatic and fibrinolytic responses in young adolescent males. The sample comprised 10 sedentary boys (13.2+/-0.5 years, 55.8+/-11.3kg, 165.7+/-7.4cm), who had not exercised or received any medication for at least 2 weeks before the experiments. The subjects performed exhaustive stepping exercise, consisting of 1s up and down cycles to fatigue. When the subjects were unable to maintain the required stepping rhythm, they were given a 30s recovery period. Following each 30s recovery participants recommenced the stepping cadence until fatigue prevented them continuing. Venous blood samples were drawn before and immediately, 1 and 24h after exercise to assess the following coagulation and fibrinolytic parameters: Platelet counts, activated partial thromboplastin time (aPTT), prothrombin time (PT), coagulation factor VIII (FVIII:C), von Willebrand factor (vWF), fibrinogen concentration, thrombin-antithrombin complex (TAT), D-dimer, plasminogen activator inhibitor (PAI-1), and tissue-type plasminogen activator (t-PA). Immediately following exercise, platelet counts, aPTT, FVIII, vWF and t-PA were significantly elevated in contrast to PAI-1, which decreased significantly until 1h after exercise. FVIII and platelet counts were elevated at 1 and 24h after exercise, respectively. Only the parameters FVIII and PAI-1 did not return to baseline values during the first hour after physical exercise. When compared to adults the results revealed different rates and ranges of coagulation and fibrinolysis parameters being activated by exhaustive exercise in this group of adolescents.
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PMID:Hemostatic response to acute physical exercise in healthy adolescents. 1684 9


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