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)

From 1970 to 1986, 3 males and 6 females, ranging in age from 13 to 69 years (median 45 years), underwent heart surgery for a primary cardiac tumor. Six patients had a left atrial myxoma; a lipofibroma, a lymphosarcoma and a rhabdomyosarcoma were found each in 1 patient. The following complaints were present: congestive heart failure in 8, fatigue in 7, cardiac arrhythmia in 3, palpitations in 3, fever in 2 and finally weight loss, nocturnal perspiration and clubbing were each in one patient. The duration of symptoms ranged from 6 weeks to more than 2 years (median 10.8 months). All patients were operated with the aid of extracorporeal circulation as soon as they were diagnosed. One patient with extensive tumor growth died at the end of the procedure. During the follow-up period all patients with a primary malignant tumor died within 3 months. Those with myxoma or fibroma are still alive with a follow-up period extending to 13 years (median 7 years). All surviving patients are asymptomatic and well. Malignant cardiac tumors do have a very poor prognosis, they are only amenable for palliative resection and even then prognosis remains poor. When an endocardial biopsy confirms the diagnosis of a cardiac malignancy, the indication for operation is questionable, although there is an absolute indication in case of obstruction. Cardiac myxoma should be resected after diagnosis because the potential embolic complications may be debilitating or lethal. The operative risk is small, and the long term results are excellent.
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PMID:Primary cardiac tumors. 329 13

A 20-year-old white male was initially suspected clinically and pathologically of having an acute lymphoblastic leukemic process because of fatigue, severe anemia, thrombocytopenia, a leuko-erythroblastic peripheral blood picture, and a diffusely infiltrated bone marrow. Subsequent review of the bone marrow material indicated cytologic features consistent with either an embryonal, undifferentiated small cell mesenchymal malignancy or reticulo-endothelial malignancy. Ultimately, the electron microscopic (EM) study of the tumor proved to be diagnostic of rhabdomyosarcoma. An extensive search for a primary site of rhabdomyosarcoma did not show any lesion, although the genitourinary region was clinically suspected. The clinical course was a rapidly downhill one with extensive bone and CNS involvement. The patient died 5 months later. An autopsy permit was not obtained. This case emphasizes the occasional tendency of rhabdomyosarcoma to masquerade as a hematopoietic malignancy at the time of presentation and the usefulness of EM study in confirming a diagnosis.
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PMID:Systemic rhabdomyosarcoma presenting as leukemia: case report with ultrastructural study and reviews. 330 41

Neutropenic pediatric patients with solid tumors and malignant lymphomas were treated with recombinant granulocyte-macrophage colony stimulating factor (rh-GM-CSF). Eleven patients, including seven lympho-reticular malignancies, two Ewing's sarcoma and one patient in each group with the diagnosis of nasopharyngeal rhabdomyosarcoma, malignant mesenchymal tumor, entered the study. Six were females and five were males, the mean age was 10.4 yr, the range was 4 to 21 years. rh-GM-CSF was given at the dose of 5 micrograms/kg s.c. daily, starting either on the day following the last day of cytotoxic chemotherapy or when ANC < 1000/ml was determined. All patients received rh-GM-CSF for a total of seven days. Hematopoietic recovery occurred in all children except one. The response to rh-GM-CSF was achieved in a mean time of 7.4 days. Tolerance to rh-GM-CSF treatment was good. Adverse events were documented as fever, nausea, vomiting, fatigue, chills and itching. Sagittal sinus thrombosis developed in one patient 5 days following the completion of chemotherapy and rh-GM-CSF cycle. In conclusion, rh-GM-CSF can be applied during the intensive chemotherapy schedules of pediatric cancer patients.
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PMID:Granulocyte-macrophage colony stimulating factor (rh-GM-CSF) in the treatment of chemotherapy-induced neutropenia. 859 35

A 15-year-old man with the chief complaint of general fatigue was referred to our hospital on November 11, 1993. Bilateral percutaneous nephrostomy was performed for postrenal anuria. X-ray examinations revealed a huge intrapelvic tumor, and it was histopathologically diagnosed as rhabdomyosarcoma by transrectal needle biopsy. He was initially treated with combination chemotherapy regimen of vincristine, actinomycin-D and cyclophosphamide (VAC therapy). Pelvic exenteration was performed on December 15, 1993. Histopathological findings were alveolar rhabdomyosarcoma with degenerative change and partial necrosis. After the operation, he was given two course of VAC therapy. In May, 1994, brain metastasis occurred, so 4 courses of VAC therapy were administered. For a very short period, neurological symptoms improved, but he died of pneumonia on November 15, 1994.
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PMID:[Rhabdomyosarcoma of the bladder: a case report]. 871 32

A 14-year-old boy presented with a short history of general fatigue. Laboratory examination of the peripheral blood revealed white blood cells 11,300/microl, hemoglobin 10.4 g/dl, platelets 45,000/microl, fibrinogen < 50 mg/dl, fibrin/fibrinogen degradation products 536 microg/ml and lactate dehydrogenase 1,684 U/l. A bone marrow aspirate contained 89.6% of undifferentiated tumor cells. A hematological malignancy was suspected and the patient was treated with idarubicin and cytarabine. However, further examination revealed that tumor cells were positive for CD56 and lacked lineage markers of lymphoid or myeloid cells. They were positive for PAS, HHF35 and desmin, and negative for MPO. Reverse transcriptase polymerase chain reaction demonstrated PAX3/FKHR fusion transcripts, confirming the diagnosis of alveolar rhabdomyosarcoma. Radiological examination revealed only one enlarged lymph node being 1.5 cm in diameter at the paraaortic region in the abdomen, and failed to find a primary tumor. After three courses of chemotherapy containing etoposide, cyclophosphamide, pirarubicin, cisplatin and vincristine, tumor cells were eradicated from the bone marrow. The patient received an allogeneic bone marrow transplantation eight months after diagnosis, although he died of hepatic veno-occlusive disease on day 21. Alveolar rhabdomyosarcoma often develops in older children and younger adults, and its bone marrow infiltration may mimic acute leukemia.
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PMID:[Alveolar rhabdomyosarcoma of unknown origin mimicking acute leukemia at the initial presentation]. 1751 23

We present the case of an extremely rare tumor of the diaphragm. The patient was a middle-aged woman with a 1-month history of dyspnea, fatigue, and cough. Chest roentgenogram and computed tomography scan of the thorax revealed a mass located at the dome of the right diaphragm. Pathologic examination of the biopsy specimen revealed pleomorphic rhabdomyosarcoma.
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PMID:A rare tumor of the diaphragm: pleomorphic rhabdomyosarcoma. 1844 96

Mitogen activated protein kinases (MAPKs), such as c-Jun N-terminal kinase (JNK) and P38, have been reported to play important roles in energy homeostasis. In this study, we show that the activity of extracellular signal-regulated kinase (ERK) is increased in the livers of diet induced and genetically obese mice. Activation of ERK in the livers of lean mice by over-expressing the constitutively active MAPK kinase 1 (MEK CA) results in decreased energy expenditure, lowered expression of genes involved in fatty acid oxidation, increases fasting hyperglycemia and causes systemic insulin resistance. Interestingly, hepatic glycogen content is markedly increased and expression of G6Pase gene is decreased in mice over-expressing MEK CA compared to control mice expressing green fluorescent protein (GFP), therefore hepatic glucose output is not likely the major contributor of hyperglycemia. One potential mechanism of decreased expression of G6Pase gene by MEK CA is likely due to ERK mediated phosphorylation and cytosolic retention of FOXO1. Adipocytes isolated from MEK CA mice display increased lipolysis. Circulating levels of free fatty acids (FFAs) in these mice are also increased, which possibly contribute to systemic insulin resistance and subsequent hyperglycemia. Consistent with these results, knocking down ERK expression in the liver of diet induced obese (DIO) mice improves systemic insulin and glucose tolerance. These results indicate that increased hepatic ERK activity in DIO mice may contribute to increased liver glycogen content and decreased energy expenditure in obesity.
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PMID:Hepatic ERK activity plays a role in energy metabolism. 2373 16

Pazopanib, an oral tyrosine kinase inhibitor, is the first molecular-targeted agent approved for the treatment of advanced soft tissue sarcoma(STS). Rhabdomyosarcoma in adults is rare, accounting for less than 3%of all adult STS cases. A 57-year old woman presented with cervical lymphadenopathy. Computed tomography revealed a heterogeneous mass in the retroperitoneum, replacing the entire right kidney. On the basis of the above findings, the patient was diagnosed with alveolar rhabdomyosarcoma. She was first treated with 4 courses of vincristine, actinomycin D, and cyclophosphamide(VAC), which resulted in a partial response. Dose reduction and delay occurred owing to hematological toxicity and febrile neutropenia. As second-line chemotherapy, the patient was administered a single daily dose of 800 mg of pazopanib. Because of an episode of hand-foot syndrome and hepatic impairment, the 800-mg daily dose of pazopanib was reduced to a daily dose of 600 mg, which had to be further reduced to a daily dose of 400 mg owing to fatigue and anorexia. The patient maintained a partial response for a total of 4.3 months when treated with pazopanib. Therefore, this drug may be a new treatment option for patients showing metastatic STS after previous chemotherapy.
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PMID:[Effective treatment of metastatic rhabdomyosarcoma with pazopanib]. 2513 42

A 52-year-old woman presented with fatigue and thrombocytopenia. Imaging studies were unremarkable with the exception of a positron emission tomography scan, which demonstrated intense F-18 fluorodeoxyglucose uptake fusing to the marrow. A bone marrow aspirate was notable for large discohesive cells with basophilic cytoplasm, and flow cytometric analysis identified a population of phenotypically unusual cells that coexpressed CD56 and CD71. Immunohistochemical findings in the marrow biopsy demonstrated that the neoplasm was alveolar rhabdomyosarcoma, further supported by the presence of a t(2;13). This unusual case demonstrates that leukemic presentations of rhabdomyosarcoma can occur in older adults in the absence of an identifiable primary tumor.
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PMID:A leukemic presentation of alveolar rhabdomyosarcoma in a 52-year-old woman without an identifiable primary tumor. 2530 20

Mutations in the FHL1 gene, and FHL1 protein deletion, are associated with rare hereditary myopathies and cardiomyopathies. FHL1-null mice develop age-dependent myopathy and increased autophagic activity. However, the molecular pathway involved in contractile function and increased autophagic activity in the FHL1-null mouse has not yet been fully elucidated. In this study, FHL1 protein was knocked out in mice using Transcription Activator-like Effector Nucleases (TALENs) and the IRS1-FOXO1/mTOR signaling pathway was investigated in skeletal muscles and heart. TALEN constructs caused targeted mutations in 30% of newborn mice; these mutations caused a deletion of 1-13 base pairs which blocked synthesis of the full-length FHL1 protein. Furthermore, 2.5-month old FHL1-null male mice were not prone to global muscular fatigue when compared with WT littermates, but histological analysis and ultrastructural analysis by transmission electron microscopy confirmed the presence of myofibrillar disorganization and the accumulation of autophagosome or autolysosome-like structures in FHL1-null mice. Moreover, autophagy and mitophagy were both activated in FHL1 KO mice and the degradation of autophagic lysosomes was impeded. Enhanced autophagic activity in FHL1 KO mice was induced by FOXO1 up-regulation and protein synthesis was increased via mTOR. The cytoskeletal proteins, MYBPC2 and LDB3, were involved in the formation of pathological changes in FHL1 KO mice. Markers of early differentiation (MEF2C and MYOD1) and terminal differentiation (total MYH) were both up-regulated in tibialis anterior (TA) muscles in FHL1 KO mice. The number of type I and type II fibers increased in FHL1-null TA muscles, but the number of type| | b, and type | | d fibers were both reduced in FHL1-null TA muscles. The results obtained from the heart were consistent with those from the skeletal muscle and indicated autophagic activation by FOXO1 and an increase in protein synthesis via mTOR also occurred in the heart tissue of FHL1 knockout mice. In conclusion, aberrant protein turn-over associated with myofibrillar disorganization in FHL1 knockout mice. the up-regulation of FOXO1 was associated with enhanced autophagic activity and pathological changes in the muscle fibers of FHL1 KO mice. These results indicated that autophagy activated by FOXO1 is a promising therapeutic target for hereditary myopathies and cardiomyopathies induced by FHL1.
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PMID:Aberrant Protein Turn-Over Associated With Myofibrillar Disorganization in FHL1 Knockout Mice. 3008 83


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