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)

The goal of this phase I study was to develop a novel schedule using oral etoposide and infusional topotecan as a continually alternating schedule with potentially optimal reciprocal induction of the nontarget topoisomerase. The initial etoposide dose was 15 mg m(-2) b.i.d. days (D)1-5 weeks 1,3,5,7,9 and 11, escalated 5 mg per dose per dose level (DL). Topotecan in weeks 2,4,6,8,10 and 12 was administered by 96 h infusion at an initial dose of 0.2 mg m(-2) day(-1) with a dose escalation of 0.1, then at 0.05 mg m(-2) day(-1). Eligibility criteria required no organ dysfunction. Two dose reductions or delays were allowed. A total of 36 patients with a median age of 57 (22-78) years, received a median 8 (2-19) weeks of chemotherapy. At DL 6, dose-limiting toxicities consisted of grade 3 nausea, vomiting and intolerable fatigue. Three patients developed a line-related thrombosis or infection and one subsequently developed AML. There was no febrile neutropenia. There were six radiologically confirmed responses (18%) and 56% of patients demonstrated a response or stable disease, typically with only modest toxicity. Oral etoposide 35 mg m(-2) b.i.d. D1-5 and 1.8 mg m(-2) 96 h (total dose) infusional topotecan D8-11 can be administered on an alternating continual weekly schedule for at least 12 weeks, with promising clinical activity.
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PMID:A phase I clinical trial of continual alternating etoposide and topotecan in refractory solid tumours. 1598 34

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

In response to the evolution of the information-seeking behaviour of patients and concerns from health professionals regarding cancer patient information, the French National Federation of Comprehensive Cancer Centres (FNCLCC) introduced, in 1998, an information and education program dedicated to patients and relatives,the SOR SAVOIR PATIENT program. The methodology of this program adheres to established quality criteria regarding the elaboration of patient information. Cancer patient information, developed in this program, is based on clinical practice guidelines produced by the FNCLCC and the twenty French regional cancer centres, the National League against Cancer, The National Cancer Institute, the French Hospital Federation, the National Oncology Federation of Regional and University Hospitals,the French Oncology Federation of General Hospitals, many learned societies, as well as an active participation of patients, former patients and caregivers. The handbookSOR SAVOIR PATIENT Cancer and Fatigue is an adapted version of different publications regarding fatigue in oncology. It is meant to provide a basis for the explanationof the disease and to facilitate discussions with the healthcare team. It is available from the FNCLCC (101, rue de Tolbiac, 75013 Paris, Tel. (0033) 1, 01 76 64 78 00,www.fnclcc.fr). This document has been validated at the end of 2005 and published in January 2006. SOR SAVOIR PATIENT guides are systematically updated when new research becomes available. This article is extract from the handbook SOR SAVOIR PATIENT Cancer and Fatigue and concerns the causes and effects of fatigue and how to cope with fatigue. This information allow patients to better understand the causes and effects of fatigue, how to cope fatigue...which represent important patient information needs. This article is meant to inform patients and relatives about the disease and its treatments. It also offers health professionals a synthetic evidence-based patient information source which facilitates discussions with the patient.
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PMID:[SOR SAVOIR PATIENT Cancer and fatigue. Information dedicated to cancer patients and relatives]. 1719 50

The purpose of this investigation was to examine the influence of muscle fiber type composition on the patterns of responses for electromyographic (EMG) and mechanomyographic (MMG) amplitude and mean power frequency (MPF) during a fatiguing submaximal isometric muscle action. Five resistance-trained (mean +/- SD age = 23.2 +/- 3.7 yrs) and five aerobically-trained (mean +/- SD age = 32.6 +/- 5.2 yrs) men volunteered to perform a fatiguing, 30-sec submaximal isometric muscle action of the leg extensors at 50% of the maximum voluntary contraction (MVC). Muscle biopsies from the vastus lateralis revealed that the myosin heavy chain (MHC) composition for the resistance-trained subjects was 59.0 +/- 4.2% Type IIa, 0.1 +/- 0.1% Type IIx, and 40.9 +/- 4.3% Type I. The aerobically-trained subjects had 27.4 +/- 7.8% Type IIa, 0.0 +/- 0.0% Type IIx, and 72.6 +/- 7.8% Type I MHC. The patterns of responses and mean values for absolute and normalized EMG amplitude and MPF during the fatiguing muscle action were similar for the resistance-trained and aerobically-trained subjects. The resistance-trained subjects demonstrated relatively stable levels for absolute and normalized MMG amplitude and MPF across time, but the aerobically-trained subjects showed increases in MMG amplitude and decreases in MMG MPE The absolute MMG amplitude and MPF values for the resistance-trained subjects were also greater than those for the aerobi-cally-trained subjects. These findings suggested that unlike surface EMG, MMG may be a useful noninvasive technique for examining fatigue-related differences in muscle fiber type composition.
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PMID:The influence of muscle fiber type composition on the patterns of responses for electromyographic and mechanomyographic amplitude and mean power frequency during a fatiguing submaximal isometric muscle action. 1771 Oct 40

A 62-year-old man presented with fatigue, pallor and mild weight loss. Laboratory studies showed Hb 7.6 g/dl, Hct 21.8%, WBC 108x10(9)/1, PLT 143x10(9)/1. At morphological examination, circulating cells appeared as 60% blasts and 40% lymphocytes, with smudge cells. A bone marrow aspirate showed infiltration by blasts (50%) and lymphocytes (40%); alpha-naphtyl-acetate esterase was positive in 90% of blasts, while myeloperoxidase was positive in 10%. The immunologic phenotype of blasts was characterized by the co-expression of CD13, CD33, CD14, CD4, CD15, CD64, CD117, HLA-DR, CD11b. Lymphocytes were characterized by a B-CLL immunophenotype: CD19+, CD5+, CD23+, CD20+(dim), FMC7+(dim), K light chain+(dim). Karyotype was normal and PCR assays for AML-ETO, CBFbeta-MYH11, PML-RARalpha, BCR-ABL and bcl-1/JH translocation were negative. Coexistence of CLL and AML with monoblastic features was diagnosed. Simultaneous appearance of CLL and AML has rarely been described and represents a peculiar biological phenomenon.
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PMID:Association of B-chronic lymphocytic leukemia and acute myeloid leukemia. 1798 6

Although an activating mutation of Ras is commonly observed in myelodysplastic syndrome (MDS), the role of Ras in the natural history of MDS remains largely unknown. We prospectively studied efficiency and tolerance of lonafarnib, a compound able to inhibit Ras signalling pathway through an inhibition of farnesyl transferase, in patients with MDS or secondary acute myeloid leukaemia (sAML). Lonafarnib was administered orally at a dose of 200 mg twice daily for three courses of 4 weeks (separated by 1 to 4 weeks without treatment). Sixteen patients were included: FAB/RAEB (n = 10), RAEB-T (n = 2), sAML (n = 2) and chronic myelomonocytic leukaemia (CMML; n = 2); WHO/RAEB-1 (n = 4), RAEB-2 (n = 5), AML (n = 5), CMML (n = 2). Median age was 70 (53-77) years. The karyotype was complex or intermediate in 11 patients, and the International Prognostic Scoring Systems (IPSS) risk groups were low in two patients, INT-1 in one patient, INT-2 in four patients and high in six patients (unknown or not applicable in three patients). Among the 14 patients tested, five had Ras mutations in codons 12, 13 or 61 of N-Ras, K-Ras or H-Ras. One patient was excluded of the analysis for protocol violation, and 15 patients were assessable for tolerance. Gastrointestinal toxicities (diarrhoea, nausea and anorexia) and myelosuppression were the major side effects. Other toxicities included infections, fatigue, increase of liver enzymes, arrhythmia and skin rash. One patient died of infection, and the treatment was stopped in one other who developed atrial fibrillation. Doses were reduced in all but one patient treated with more than one course of farnesyl transferase inhibitor. Responses were assessable in 12 patients. A partial response in one sAML patient and a very transient decrease of blast cell count with normalisation of karyotype in one MDS patient were observed. No relation between improvement of marrow parameters and detected Ras mutations was observed. Lonafarnib alone, administered following our schedule, has shown limited activity in patients with MDS or secondary AML. Gastrointestinal and haematological toxicities appear the limiting toxicity in this population of patients.
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PMID:Farnesyl transferase inhibitor (lonafarnib) in patients with myelodysplastic syndrome or secondary acute myeloid leukaemia: a phase II study. 1864 85

We describe a 79-year-old patient who presented with fatigue, weight loss, pancytopenia and a papular exanthem. Previous attempts to taking bone-marrow biopsies had resulted in a 'dry tap', with no material collected, suggesting idiopathic myelofibrosis. Histological examination of skin biopsies showed dermal infiltration of monocytoid cells, resulting in a diagnosis of acute myeloid leukaemia (French-American-British M5 morphology) with leukaemia cutis (LC). Numerous abnormalities of chromosome 8 (trisomy or tetrasomy) have been identified in association with LC. We performed fluorescent in situ analysis on cutaneous tissue using directly labelled probes for various gene loci often involved in patients with AML; these tests showed deletion of p53 and excluded trisomy 8. However, application of probes for AML/ETO, MYC and telomere 8q revealed a gain at 8q22/8q24/8q telomere in a significant number of infiltrating cells. We hypothesize that a partial gain at 8q rather than trisomy of the whole chromosome 8 exhibits an association with LC in AML.
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PMID:Papular exanthem discloses acute myeloid leukaemia: interphase fluorescence in situ hybridization revealed deletion of p53 and gain at 8q22/8q24/Tel8q without trisomy 8. 1943 43

Allogeneic hematopoietic progenitor cell (HPC) transplantation is an established therapy for many hematologic disorders. HPCs may be collected from bone marrow, peripheral blood, or umbilical cord blood. In order to minimize the risk for healthy HPC donors, thorough investigation is required before donation. The donor work-up should include medical history, physical examination, ECG, chest x-ray, blood count, coagulation screening, and testing for infectious disease markers. Donors should be fully informed on the donation procedure and sign an informed consent for donation. HPCs are traditionally collected from bone marrow with the donor in general anesthesia. The procedure includes multiple bone marrow aspirates from pelvic bones and at least overnight hospital stay. Although marrow donation is generally safe and well tolerated, minor complications like pain at the collection site, fatigue and pain on walking or sitting may occur in a relatively small proportion of donors (6%-20%). Major and life-threatening complications such as anesthesia-related events, mechanical injury to the bone, sacroiliac joint and sciatic nerve following marrow donation are relatively rare, being estimated to 0.1%-0.3% of cases. In the last decade, peripheral blood progenitor cells (PBPC) have become an increasingly used altemative to bone marrow. PBPC transplantation offers faster hematopoietic recovery and lower early transplant-related morbidity and mortality. The incidence of acute graft vs. host disease (GvHD) is no greater than in bone marrow transplants. However, there is evidence for increased chronic GvHD, which is in part related to the higher number of T and NK cells that are collected with PBPC and re-infused to the patient. Recombinant human granulocyte colony-stimulating factor (G-CSF) is used to mobilize PBPCs for collection by leukapheresis. Leukapheresis is usually perfomed after 4 to 5 days of G-CSF subcutaneous administration at a dose of 10 mg/kg b.w. Vascular access for apheresis may be accomplished by use of apheresis needle in antecubital vein. Placement of a double-lumen central apheresis catheter is rarely required in healthy donors. Citrate is the most commonly used anticoagulant for apheresis. One to three leukapheresis procedures are required to collect adequate graft. There is an interindividual variation in progenitor cell mobilization among healthy donors, with a subset of donors that do not exhibit effective CD34+ cell mobilization. Donor age and G-CSF schedule are the factors that significantly affect PBPC mobilization and collection in healthy donors. Procedures for mobilization and collection of PBPC from healthy donors are generally well tolerated. Common adverse reactions of G-CSF application include bone pain, myalgia, headache and fatigue. Beside these mild side effects, moderate to life-threatening complications are sporadically observed. Spontaneous splenic rupture, acute lung injury, acute iritis, severe pyogenic infections, and anaphylactoid reactions were reported in healthy donors after G-CSF administration. Adverse effects of apheresis for PBPC collection are the same as for other apheresis procedure and include complications related to venous access and citrate toxicity. Leukapheresis typically results in a lower platelet count, an effect that is exacerbated by the use of G-CSF, which has been documented to cause mild, reversible thrombocytopenia. Fewer side effects were noted in pediatric donors compared to adult donors. PBPC collection in pediatric donors is safe and desired PBPC yields are easily achieved. Theoretical concerns exist about the potentially increasing long-term risk of leukemia after G-CSF administration in healthy donors. Recently, a report of AML developing in a 62-year-old female donor 14 months after G-CSF-primed PBPC donation has been published. Whether G-CSF therapy contributed to the development of this cancer is unknown, but future studies should carefully follow the donors and report any similar event. According to currently available evidence, the risk of major late toxicities secondary to administration of G-CSF is minimal.
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PMID:[Collection of hematopoietic progenitor cells from healthy donors]. 1982 52

A 35-year-old male with a FLT3(+) AML underwent allogeneic peripheral blood stem cell transplant using a myeloablative non-total body irradiation (TBI) conditioning regimen from his HLA-matched sibling donor. Following transplantation, he developed grade II acute graft-versus-host disease (GVHD) that resolved with increasing immunosuppression. The medications were subsequently discontinued, and he did not develop any evidence of chronic GVHD. Eighteen months after transplant, while off all immunosuppression, he developed fatigue and a blood count showed circulating blasts consistent with relapse of his disease. Among the various therapeutic questions is whether there is a role for a second allogeneic transplant to treat his disease and if so, at what time, with what conditioning, and with which type of donor.
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PMID:ASH evidence-based guidelines: is there a role for second allogeneic transplant after relapse? 2000 27

A 47-year-old man was admitted to our hospital in June 2009 because of fatigue and blast cells in peripheral blood. Bone marrow examination showed that 67% leukemic cells were positive for myeloperoxidase (MPO) and negative for esterase stain. Flow cytometric analysis (FCM) revealed the expressions of CD2, cyCD3, CD5, TdT, CD13 on the blasts. Chromosome analysis of the bone marrow cells demonstrated 46, XY in 18 of the 20 analyzed cells, 46,XY,t(1;11)(q21;p15) in 1 of the 20 analyzed cells, and 47,XY,+11 in 1 of the 20 analyzed cells. The patient was diagnosed as having mixed phenotype acute leukemia, T/myeloid, NOS, according to the WHO classification. He received induction chemotherapy for ALL, but could not achieve complete remission (CR). After initial treatment, residual leukemic cells with CD13, CD33 and MPO were detected by FCM; therefore, he received re-induction chemotherapy for AML, and achieved CR. Acute leukemia of ambiguous lineage is a relatively rare subtype in acute leukemia and standard chemotherapy has not been established. It was suggested that the selection of chemotherapy based on the results of FCM was successful in our patient.
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PMID:[Successful selection of chemotherapy based on cell surface antigens in a patient with mixed phenotype acute leukemia]. 2053 55


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