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)

A 67-year-old female was admitted with fatigue. Peripheral blood examination showed severe pancytopenia. Bone marrow biopsy revealed hypoplastic marrow. She was diagnosed as having aplastic anemia. Steroid pulse therapy was not effective. After treatment with erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF), blasts which were positive for CD13, CD33, CD34 and HLA-DR and negative for myeloperoxidase appeared in the peripheral blood. At this time, bone marrow biopsy revealed myelofibrosis with increased blasts. Chromosome analysis showed 46XX, add (1) (p36), add (1) (q44), -2, -5, del (7) (q11), -12, +3mar. She died of pneumonia despite chemotherapy with etoposide. Administration of EPO and G-CSF may have led to the rapid development of leukemia and myelofibrosis.
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PMID:[Transformation of aplastic anemia to acute myeloid leukemia with myelofibrosis following treatment with granulocyte colony-stimulating factor and erythropoietin]. 877 84

Two hypotheses were examined in the combined data from 3 case-control studies of aplastic anaemia, conducted in Thailand, Europe/Israel and the US: 1. Cases exposed to drugs associated with a significantly increased risk of aplastic anaemia are more likely to present with thrombocytopenia (e.g. petechiae, easy bruising); and 2. cases exposed to these drugs are more likely to recover quickly than non-exposed cases. After excluding all cases who lacked information on timing of symptoms and those whose symptoms began > or = 180 d before hospital admission, 392 cases remained for analysis. A total of 51 (13%) had been exposed to one of the significantly associated drugs; the remaining 341 (87%) had not. Among the former, 31% reported thrombocytopenia either before or at the same time as non-bleeding symptoms (e.g. pallor, fatigue); the corresponding proportion among the non-exposed was 53%. Data on time to recovery (return of the 3 blood cell lines to normal levels) were not available for the Thai cases; among the others, the median time to recovery for the non-fatal cases was 7 and 6 months in the 29 exposed and the 83 non-exposed cases, respectively. The data do not support either hypothesis: the two groups of aplastic anaemia cases appeared to be similar in both the presenting symptoms and the recovery time.
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PMID:An epidemiological study of aplastic anaemia: relationship of drug exposures to clinical features and outcome. 898 41

Between 1971 and 1989 we have treated 19 patients with hepatitis-associated aplastic anemia by marrow transplantation from their HLA-identical siblings following conditioning with 200 mg/kg cyclophosphamide (Cy) administered over a period of 4 days. One patient failed to engraft by day 34 and was given a second transplantation. He died from infection 15 days after the second transplantation. Eighteen patients had sustained engraftment. Six patients developed acute graft-vs.-host disease (GVHD) and two of these patients died 2.8 and 3.3 months after transplantation. Fifteen patients are surviving 4 to 24 (median 13) years after transplantation, while one patient died in a car accident 17 years after successful transplantation. Six of the surviving patients developed chronic GVHD. Two of the patients with chronic GVHD had preceding acute GVHD and four did not. Five of the six patients with chronic GVHD received donor buffy coat cells in addition to the marrow inoculum to prevent graft rejection. Twelve of the 15 surviving patients have Karnofsky performance scores of 100%. One patient, living more than 4 years after transplantation, has a Karnofsky score of 40% because of persistent cognitive deficits following non-A, non-B hepatitis with hepatic coma. Two patients developed hepatitis C infection 12 and 18 years after transplantation, respectively. Except for mild fatigue and mildly elevated liver function tests, these patients are doing well with Karnofsky performance scores between 95 and 100%. One patient developed severe coronary artery disease 10 years after transplantation, decreasing his Karnofsky performance score to 80%. Serum samples before and after transplantation from 13 patients were tested for hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA by polymerase chain reaction (PCR). Only one patient tested positive for HCV RNA before transplantation. Seven of 15 sera were hepatitis C RNA-positive posttransplantation, but only one of these patients has developed active hepatitis C. All 13 patients were were negative for hepatitis B surface antigen and HBV DNA. Only one patient had IgM antibodies against hepatitis A virus (HAV) before transplantation, which suggested HAV infection. Hepatitis-associated aplastic anemia apparently was caused in most patients by a non-A, non-B, non-C agent. HLA-identical marrow transplantation for hepatitis-associated aplastic anemia with Cy as conditioning regimen is well-tolerated and has a long-term event-free survival in excess of 80%, not different from results of marrow transplantations for aplastic anemia of other etiologies.
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PMID:Marrow transplantation for hepatitis-associated aplastic anemia: a follow-up of long-term survivors. 911 4

A 78-year-old female was admitted with complaints of malaise and fatigue in the legs. The patient was diagnosed as severe aplastic anemia and treatment was started with metenolone and steroid pulse therapy. Administration of antibiotics and granulocyte-colony stimulating factor which led to a resolution of the high fever. About four months after admission, the patient developed vomiting and abdominal pain with a spiking fever. The next day after suddenly losing consciousness, she died. B. cereus was isolated from blood cultures. Autopsy specimens of the liver, cardiac muscle and lung showed changes due to B. cereus. This pathogen is widely distributed in nature. We should not overlook B. cereus as a contamination, but rather should consider it a potential pathogen in immunocompromised hosts, when it is isolated from blood cultures.
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PMID:[Bacillus cereus septicemia in a patient with severe aplastic anemia]. 991 22

Human parvovirus B19 is considered an etiologic agent of aplastic anemia in immunosuppressed patients. Microscopic vasculitis, with or without renal involvement, has recently been attributed to this viral infection in immunocompetent patients. This study describes four cases of thrombotic renal graft microangiopathy presumably secondary to B19 infection. Twelve to 50 days after transplantation, four patients presented a renal graft dysfunction with creatinine rising to 360 to 1088 micromol/L and requiring hemodialysis in three cases. Renal involvement appeared after a systemic illness characterized by fever, fatigue and arthralgia, aplastic anemia (hemoglobin ranged from 5.3 to 7.8 g/dl), and thrombocytopenia. A thrombotic microangiopathy was observed in the renal biopsies, and the parvovirus B19 genome was isolated by PCR from the specimens. All four patients also became IgM-positive for parvovirus. Three of the four renal biopsies taken at the time of transplantation (T0) from the same patients were found positive for the B19 genome. Graft function recovered, with resolution of the aplastic anemia, within 22 to 110 d. Twenty biopsies performed as routine controls or for suspected acute rejection and nine T0 biopsies of patients with no signs of B19 infection were used. The B19 genome was found in two of 20 posttransplant biopsies and in one of nine T0 biopsies. The temporal association between aplastic anemia and the onset of thrombotic graft microangiopathy, isolation of the viral genome in renal specimens, seroconversion, and endothelial tropism of the virus suggests that B19 could be the etiologic agent of thrombotic microangiopathy in these cases. The development of the disease after infection could depend on other detrimental cofactors, which make the patient more susceptible to microthrombi formation in the renal microvasculature. The renal graft could represent the route of B19 transmission.
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PMID:Thrombotic microangiopathy associated with parvovirus B 19 infection after renal transplantation. 1082 Jan 78

The use of hematopoietic growth factors has increased rapidly during the last decade. Among the growth factors available, erythropoietin (EPO) was the first growth factor to be used clinically. To date, EPO has shown activity in the treatment of the tumor-associated anemia and for correction of tumor hypoxia, however, when compared with transfusion of erythrocytes EPO treatment did not significantly prolong survival in cancer patients in any published study so far. Recently, novel extramedullary EPO receptors have been identified leading to a better understanding of the molecular mechanisms of action of EPO. Results from these experiments and from several clinical studies suggest that EPO treatment may be beneficial for patients with (chronic) infections (HIV, inflammatory bowel disease, septic episodes) and for treatment of the fatigue syndrome following cancer chemotherapy. In addition, EPO may also improve stem cell engraftment following high-dose chemotherapy and can increase survival rates of patients with aplastic anemia and myelodysplastic syndrome. Currently, new EPO derivatives, synthetic fusion proteins and gene therapeutic studies are under clinical investigation suggesting that the EPO-induced effects may be increased significantly by these agents in the future.
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PMID:[Possible new indications for erythropoietin therapy]. 1156 47

A 14-year-old girl was admitted because of general fatigue and cervical lymphadenopathy. She showed bilateral struma (IInd degree) and enlargement of her left cervical lymph nodes. Laboratory data revealed neutropenia (219/microliter) and thrombocytopenia (Plt 5.1 x 10(4)/microliter) with mild anemia (Hb 11.1 g/dl), and the bone marrow aspirate and biopsy specimens showed hypocellularity. In addition, auto-antibodies against thyroid peroxidase (TPO) and thyroglobulin (TG) were highly elevated. Computed tomography of the neck showed a nodule in the left thyroid lobe with marked lymphadenopathy, and fine needle aspiration biopsy demonstrated papillary thyroid carcinoma with Hashimoto's thyroiditis and metastasis to the lymph nodes. One month after left thyroid lobectomy and cervical lymphadenectomy, the patient's condition progressed to very severe aplastic anemia, and she received immunosuppressive therapy consisting of cyclosporin A and anti-thymocyte globulin. Hematologically, partial and complete responses were obtained three and six months later, respectively. Of interest, anti-TPO and TG antibody titers remarkably decreased after immunosuppressive therapy. The patient had HLA-DR 2(DRB 1*1501) and DR 8(DRB 1*0802). The former is frequently found in patients with cyclosporin A-dependent aplastic anemia, and the latter is frequently found in Asian patients with Hashimoto's thyroiditis, suggesting an underlying autoimmune background for the simultaneous outbreak of aplastic anemia and Hashimoto's thyroiditis complicated by thyroid carcinoma.
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PMID:[Development of severe aplastic anemia in a girl with Hashimoto's thyroiditis and papillary thyroid carcinoma]. 1282 8

Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by intravascular haemolysis, nocturnal haemoglobinuria, thrombotic events, serious infections and bone marrow failure. This acquired disease, caused by a deficiency of glycosylphosphatidylinositol (GPI) anchored proteins on the haematopoietic cells, is rare in children. We describe 11 Dutch paediatric PNH patients (median age: 12 years, range 9-17 years) diagnosed since 1983, seven cases associated with aplastic anaemia (AA), four with myelodysplastic syndrome (MDS). Presenting symptoms were haemorrhagic diathesis (n = 10), palor/tiredness (n = 8), dark urine (n = 1), fever (n = 1) and serious weight loss (n = 1). Treatment consisted of prednisolone (n = 7), anti-thymocyte globulin (n = 3) and/or androgens (n = 5). Eventually, five patients received a bone marrow transplantation (BMT) (three matched unrelated donors/two matched family donors), of whom four are still alive. PNH, diagnosed by immunophenotypic GPI-linked anchor protein analysis, should be considered in all children with AA or MDS. BMT should be considered as a therapeutic option in every paediatric PNH patient with BM failure.
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PMID:Childhood paroxysmal nocturnal haemoglobinuria (PNH), a report of 11 cases in the Netherlands. 1568 69

A 10-year-old boy was admitted with complaints of fever, pallor, fatigue and skin bleeds of 10 days duration and diagnosed as very severe aplastic anemia. He was given intensive immunosuppressive therapy but showed no response to therapy. He later evolved into acute myeloid leukemia. The occurrence of AML is reviewed and possible pathogenesis is discussed.
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PMID:Acute myeloid leukemia after intensive immunosuppressive therapy in aplastic anemia. 1620 56

Imatinib (STI571, Gleevec/Glivec) and other small-molecule tyrosine kinase inhibitors are highly effective in the treatment of chronic myeloid leukemia (CML), gastrointestinal stromal tumors and, for example, eosinophilia-associated chronic myeloproliferative disorders. This molecularly targeted approach disrupts abnormal tyrosine kinase dependent signalling pathways, thus providing a preferred treatment option for selected neoplastic disorders with activating mutations of Abelson-, Abl-related-, Kit-, and platelet-derived growth factor receptor A and B genes. Loss of response to imatinib may be due to an acquired resistance of emerging mutant tumor cell clones. Therapy is generally well tolerated. However, toxicities including edema, skin rashes, fatigue, nausea and myelosuppression have been reported. Philadelphia/Bcr-Abl-negative clonal chromosomal abnormalities may develop. Bone marrow trephines obtained from CML patients in complete remission with prolonged pancytopenia secondary to imatinib generally show marrow hypoplasia. Morphological features may be in keeping with either aplastic anemia or myelodysplasia developing in Philadelphia-negative hematopoiesis. Single or multilineage myelodysplasia may be accompanied by an excess of blasts and rarely evolves into acute leukemia in CML patients. Severe adverse hematological effects of imatinib are extremely rare. Current questions involve the molecular mechanisms of hematological side effects of tyrosine kinase inhibitors with special regard to the emergence of distinct aberrant clones.
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PMID:[Hematological side effects of tyrosine kinase inhibition using imatinib]. 1642 5


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