Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
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Clinical, biochemical, haematological and erythrokinetic studies were performed on 63 adult males with prolonged lead exposure. Their most common symptoms and findings were abdominal pain (62%), gingival lead lines (48%), headache and/or dizziness (33%), muscle cramps (32%), anaemia (19%), and fatigue (18%). Colicky abdominal pain (27%) and gingival lead lines correlated with urinary lead excretion. Anaemia was mild, but more frequent in the subjects with the greatest urinary lead excretion. Other associated findings were: higher reticulocyte counts and more basophilic stippling of the RBCs, more sideroblasts and greater erythroid hyperplasia of the bone marrow, more reduction in 51Cr-tagged RBC survival time, smaller RBC mass, a more rapid plasma iron clearance, a greater plasma iron turnover and greater utilization of 59Fe in subjects with urinary lead excretion of greater than 100 microng/day in comparison with the remainder and normal controls. These findings suggest that minimal chronic exposure to lead causes an increased haemolysis with resulting increased production of erythrocytes.
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PMID:Chronic industrial exposure to lead in 63 subjects. I. Clinical and erythrokinetic findings. 103 Aug 53

Relapse continues to be a problem after bone marrow transplantation (BMT) for hematologic malignancies, particularly in recipients of autologous or T-cell-depleted allogeneic grafts and in patients with advanced disease. Interferon (IFN) has shown antiproliferative activity in several malignant hematologic diseases and potentially may be of benefit when administered early after BMT when the number of residual cells is minimal. We tested in a phase I study the maximum tolerated daily dose of recombinant IFN alpha-2b in patients who had received a transplant for a disease at high risk for relapse (acute myeloid leukemia or non-Hodgkin's lymphoma beyond first remission, advanced myelodysplastic syndrome, acute lymphoblastic leukemia at any stage, chronic myeloid leukemia in accelerated or blast phase. Recombinant IFN alpha-2b was started at a dose of 0.5 x 10(6) IU/m2 and escalated by 0.5 x 10(6) IU/m2 in groups of three or four patients. The intention was to administer IFN as soon as stable engraftment after BMT was achieved (defined as an absolute neutrophil count of greater than 2.0 x 10(9)/L and platelet count greater than 100 x 10(9)/L for 5 consecutive days) and continued for 2 months. A total of 14 patients were enrolled after autologous (n = 3) or allogeneic (n = 11) BMT. Dose-limiting toxicity was myelosuppression. Significant (grade 2 to 4) neutropenia and thrombocytopenia led to discontinuation or dose reduction in five of eight patients receiving 1.5 x 10(6) or 2 x 10(6) IU/m2 IFN. Mild to moderate (grade 1 or 2) anorexia, weight loss, and fatigue occurred in the majority of patients independent of the IFN dose. De novo acute GVHD responsive to steroid treatment developed in 3 of 11 allograft recipients. Natural killer (NK) cell function was low before IFN treatment and was not improved with the cytokine. Conversely, interleukin-2-activated NK cells showed normal function even before starting IFN and no change was seen during IFN treatment. Clonogenic hematopoietic progenitor studies showed depression of all progenitor lines (colony-forming unit [CFU]-granulocyte, erythroid, monocyte, megakaryocyte, CFU granulocyte-macrophage, burst-forming unit-erythroid) by IFN at all dose levels except at 0.5 x 10(6) IU/m2. Considering this result and the incidence and severity of marrow depression seen at doses greater than 1.0 x 10(6) IU/m2, we would consider this the maximum dose safely tolerated if IFN alpha-2b is administered in this setting for a prolonged course on a daily basis.
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PMID:Treatment with recombinant interferon (alpha-2b) early after bone marrow transplantation in patients at high risk for relapse [corrected]. 174 91

We report an autopsy case of acute erythremia which terminated in generalized infiltration of immature blasts similar to proerythroblasts. A 61-year-old man was admitted because of general fatigue and fever in June, 1990. Mild anemia and severe thrombocytopenia were noted. The bone marrow was hypocellular with 25.5% blasts similar to proerythroblasts and 36.5% erythroblasts, many of which were polynuclear and megaloblastoid. The blasts were cytochemically negative for POX, but positive for PAS staining. Therefore he was diagnosed as having acute erythremia. Partial remission was achieved by BHAC-EV therapy. But three months later, his marrow was replaced by 52.7% blasts as seen in admission. Those blasts were negative for lymphoid, myelocytic, megakaryocytic markers and antiglycophorin A, but positive for OKT 9. Electron microscopy revealed that some of blasts had characteristics of immature erythroblasts. In spite of low dose Ara-C therapy, he died of sudden gastrointestinal bleeding in December, 1990. The autopsy disclosed widespread infiltration of blasts, involving liver, spleen, lung, kidney and stomach. It was interesting that dysplasia had been confined to erythroid lineage throughout his clinical course. He seemed to be a rare case of blastic form of acute erythremia which should be distinguished from erythroleukemia.
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PMID:[Blastic form of acute erythremia: report of an autopsy case]. 175 58

A 20-year-old man was admitted because of general fatigue. Peripheral blood examination revealed pancytopenia (WBC 1,700/microliters, RBC 210 x 10(4)/microliters, Plt 3.2 x 10(4)/microliters) with remarkable erythroblastosis. Bone marrow examination revealed erythroid hyperplasia and an increase of abnormal myeloblasts with Auer bodies (37% of non erythroid cells). A diagnosis of erythroleukemia (AML M6) was made. He received two courses of combination chemotherapy (BHAC-DMP and VAMA (VP-16, Ara-C, 6-MP, and doxorubicin (ADR)) but complete remission (CR) could not be achieved. Consequently, he was treated with LDAC. After two courses of LDAC. CR was obtained. Subsequently, he received two courses of HDAC as consolidation, and therapy has been off thereafter. He remains in CR state for more than 12 months.
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PMID:[Complete remission in erythroleukemia: induced with low dose Ara-C, consolidated with high dose Ara-C]. 207 31

A 56-year-old male was admitted to the Nihon University Hospital because of general fatigue and anemia on September 21st, 1985. He had mild hepato-splenomegaly. Hematological findings showed RBC 286 x 10(4)/microliters, Hb 6.0/dl, reticulocyte count 2.5%, platelet count 9.3 x 10(4)/microliters and WBC 2,400/microliters. An erythroblast per 100 leukocytes counted in a blood film was found. Bone marrow was erythroid hyperplasia with megaloblasts. The erythroblasts were PAS positive but not ringed sideroblasts. Other laboratory data including hemolysis were all negative. This case seemed to be diagnosed as refractory anemia (RA) according to the FAB classification. Chromosomal analysis of marrow cells, however, all revealed 46, XY, 20q- at diagnosis and 46, XY, 7q- 20q- after 22 months. Furthermore, Hb electrophoresis ahd family study indicated the presence of acquired HbH disease. Neither erythroid bursts (BFU-e) nor late erythroid progenitors (CFU-e) were detected. He has had progressive anemia without proliferation of blasts for over 2 years. From these findings, we postulate that the entity of erythremia should be distinguished from RA including many heterogeneous diseases.
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PMID:[An erythremia with acquired HbH disease and chromosomal abnormality]. 221 93

We report a case of malignant histiocytosis which began with the skin lesions of panniculitis. A 32-year-old woman presented with recurrent erythematous plaques, subcutaneous nodules, and ulcers on the trunk and the extremities and intermittent fever for 7 months. The cutaneous lesions consisted of erythematous and brownish irregular-shaped patches and tender cutaneous nodules 0.5-1.0 cm in diameter. Central necrosis and shallow ulcers were seen in the lesions. The patient also suffered from general fatigue, arthralgia, and weight loss. She was anemic and thrombocytopenic and had progressive impairment of liver function with coagulation defect. Histopathological study of skin lesions showed lobular panniculitis without vasculitis in the subcutaneous fat tissue. In the panniculitis lesion, moderate mixed cell infiltration consisting of lymphocytes and histiocytes was observed. Bone marrow aspiration revealed an increase in the number of histiocytes, mostly immature with active phagocytosis of erythroid cells, myeloid cells, and platelets. She was diagnosed as having malignant histiocytosis and treated with cyclophosphamide, vincristine, and prednisolone which she responded well; her fever subsided and the lesions healed with hyperpigmentation. In this patient, benign histiocytes with hemophagocytosis without immature forms were found in the skin lesions. According to our knowledge, this is the first Thai report of malignant histiocytosis with clinical features of panniculitis.
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PMID:Malignant histiocytosis with panniculitis--a case report. 222 45

A 40-year-old man who was resected ascending colon and terminal ileum (10 cm) in Aug. 1978, with the diagnosis of Crohn's disease, was admitted to our hospital with general fatigue, paresthesia and tremor in May. 1984. A peripheral blood examination on admission revealed Hb 10.1 g/dl, RBC 234 X 10(4)/mm3, MCV 131.4 fl, MCH 43.2 pg. A bone marrow specimen showed marked erythroid hyperplasia (W/E 1.44) with megaloblastic change. While serum folate level was normal, serum vitamin B12 value was low and Schilling test showed vitamin B12 malabsorption. Roentgenologic and endoscopic examinations revealed diffuse cobblestone appearances in small intestine (from anastomosis part to duodenal bulb). These examinations suggested vitamin B12 malabsorption with diffuse Crohn's disease caused megaloblastic anemia. The patient had been treated with vitamin B12 1,000 micrograms/day injection and, in Sep. 1984, he recovered from megaloblastic anemia (Hb 13.4 g/dl, RBC 440 X 10(4)/mm3, MCV 90.7 fl, MCH 30.4 pg).
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PMID:[Megaloblastic anemia associated with diffuse intestinal Crohn's disease]. 271 98

A case of erythroleukemia coexistent with pulmonary emphysema is reported. A 67-year-old male was admitted to our hospital in May 1981, with a few year history of cough, sputum and fatigue. He had already been diagnosed as having pulmonary emphysema and moderate anemia. On physical examination, except for pallor, no other findings were remarkable. The initial hematological examination showed hemoglobin, 9.6 g/dl, red cell count, 251 x 10(4)/microliters, platelet count, 7.3 x 10(4)/microliters, white cell count, 2600/microliters with neither myeloblasts nor erythroblasts. A sternal marrow aspiration revealed 21% myeloblasts and 40% erythroblasts including 7.5% megaloblastoids. Periodic Acid Schiff staining was strongly positive for a part of erythroblasts. A chest X-P finding was typical for pulmonary emphysema. Pulmonary function was moderately damaged. He was started on chemotherapy with AAAP (ACNU 50 mg/d i.v. drip over 4 hr x 4d, adriamycin 20 mg/d i.v. push x 4d, Methotrexate 20 mg i.v. push x 4d). The first course of AAAP brought him a complete remission with both disappearance of myeloblasts and erythroid precursors with megaloblastoid nuclei in the marrow and the normalization of white cell count and platelet count in the blood. He was discharged in September 1981 after completion of a consolidation chemotherapy with AAAP. Since then, he received two courses of AAAP as an intensification chemotherapy and has been in complete remission for more than 13 months. His pulmonary function has not been affected and no myocardial damage has been seen throughout AAAP therapy. Thus, AAAP therapy seems to be an excellent chemotherapy even for an aged patient with erythroleukemia.
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PMID:[A case report of an aged patient with erythroleukemia coexistent with pulmonary emphysema, responding well to AAAP therapy]. 696 34

Astronauts have a reduction in their red cell mass when exposed to microgravity. This is probably mainly due to a physiological response to decreased energy requirements. Further studies of erythropoiesis were carried out in microgravity on rats flown on Soviet Biosatellite 2044 and in hypergravity by centrifugation at 2G. Studies included: bone marrow cell differential counts, clonal studies of RBC colony formation, and plasma erythropoietin determinations. In the bone marrow of Cosmos flight animals there was a slight increase in granulocytic cells and in centrifuged animals, a slight decrease in the percentage of erythroid cells which led to an increased M:E ratio. The bone marrow cells of flight and centrifuged rats responded to erythropoietin. Cosmos flight animals' cells formed fewer CFU-E than the controls but this was reversed in the centrifuge studies. There were no essential differences in the erythropoietin levels of test groups as compared to control groups.
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PMID:Effects of microgravity and increased gravity on bone marrow of rats. 798 Mar 33

A 32-year-old man visited Kanto Teishin Hospital complaining of general fatigue in May, 1992. He had been diagnosed as having paroxysmal nocturnal hemoglobinuria since 1980, because of brownish urine in the morning. He received blood transfusion in 1980. In 1983, he was treated with medication. There was no remarkable improvement, however, and he stopped coming to the hospital. When he was admitted to our hospital, hemolytic anemia and hemosiderinuria were noticed. Sucrose hemolysis test and acidified-serum lysis test (Ham test) were both positive. Positive rates of decay accelerating factor and CD59 were 38.8% (control 100%) and 45.4% (control 100%), respectively. His diagnosis was thus confirmed. Bone marrow was slightly hypocellular, and erythroid cells were relatively hyperplastic (M/E ratio 0.68). The oral administration of iron and oxymetholone was not effective for anemia. He was treated with daily subcutaneous administration of recombinant human erythropoietin (EPO, 3,000U/body/day). His hemoglobin level increased from 7.5g/dl to 12.0g/dl in 4 weeks, and general fatigue disappeared. Since he had concurrent chronic hepatitis C, alpha-interferon was also administered and his hemoglobin level is now controlled between 10 and 11g/dl. This case suggests that EPO can be useful for treating hemolytic anemia, even though erythroid cells in the bone marrow are hyperplastic.
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PMID:[Improvement of anemia by recombinant human erythropoietin in paroxysmal nocturnal hemoglobinuria]. 823 Jul 45


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