Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 44-year-old woman with AML, while receiving a conditioning treatment with BU-CY for an allogeneic sibling transplant, developed septic shock with pulmonary embolism and heart failure. Conditioning was stopped at the end of the busulfan course and cyclophosphamide omitted. After antibiotics, dopamine and steroids the patient was allografted, using the donor's G-CSF-primed PBSC. She recovered her peripheral blood counts promptly and developed an acute GVHD grade II that responded to steroids. The DNA microsatellite analysis showed full donor engraftment up to a year from transplantation. This case suggests that the use of PBSC may facilitate engraftment in the absence of an effective immunosuppression during conditioning.
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PMID:Successful engraftment of allogeneic PBSC after conditioning with busulfan alone. 908 42

We treated fifteen patients with recurrent breast cancer by a combination of mitoxantrone (8 mg/m i.v., day 1), vincristine (1.2 mg/m i.v., day 1), doxifluridine (800 mg/body po, everyday) and prednisolone (30 mg/body po, day 1-7). Cycles were repeated every 3 weeks and all patients received more than 2 cycles. A response to treatment was observed in 9 of 15 evaluable patients (60.0%) with 4 complete remissions and 5 partial remissions. Eight patients were previously exposed to anthracyclines. In 5 of 7 cases with no previous chemotherapy, treatment was effective, and in 4 of 8 cases previous chemotherapy was effective. The toxicity was primarily leucopenia (86.7%), and 9 patients received G-CSF therapy. Other toxicities (alopecia, neurologic and general fatigue) were mild. Two patients with heart failure were recognized and treated with other therapy. This chemotherapy is effective for the treatment of recurrent breast cancer.
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PMID:[Efficacy of combination chemotherapy with mitoxantrone, vincristine, doxifluridine and prednisolone for recurrence of breast cancer]. 942 66

To increase the dose-intensity of two drugs in metastatic breast cancer, we tested the feasibility, in phase I studies, of two schedules of epirubicin (E) and cyclophosphamide (C) - sequential (E--> C) and alternating (E/C) - with respect to the standard combination (EC). Drugs were given at three planned-dose levels, plus either G-CSF or GM-CSF. Patients with metastatic (30), inoperable stage IIIb (2) or inflammatory (7) breast cancer were treated. The doses of EC, given every 21 days (4 cycles), were 75/1500, 82.5/2250, 90/3000 mg/m2. In the E/C schedule, epirubicin was given at cycles 1, 3 and 5, and cyclophosphamide at cycles 2, 4 and 6. In the E--> C schedule, three cycles of epirubicin then three cycles of cyclophosphamide were administered. In both experimental schedules, drugs were given every 14 days for 6 cycles at doses of 100, 110, 120 mg/m2 (E) and 2000, 3000, 4000 mg/m2 (C). The average relative dose-intensity was 1.2-fold and 2-fold greater with E/C and E--> C, respectively, than with EC. The third level dose was feasible with all schedules. Grade 4 leucopenia occurred in 77% of patients. Thrombocytopenia was absent in 6 cases and grade 4 in 12 (30.8%). Eighty-one percent of patients on experimental schedules required red blood cell support versus 44.4% of patients on EC. At the third level, platelet transfusions were more frequent among patients treated with EC (27. 8%). Non-haematological toxicity was mild: about 20% of patients experienced grade 3 vomiting, irrespective of schedule. Only 2 patients had grade 3 mucositis; no patient developed heart failure. Fever (61% of patients) and bone pain (55.5% of patients) were relevant in the GM-CSF treated groups and 12 patients shifted to G-CSF. The overall response rate was 84.6%: 5/39 (12.8%) complete response and 28/39 (71.8%) partial response. At 30/9/98, median survival was 29.5 months, with no difference between patients with metastatic and stage IIIb/inflammatory breast cancer. Median follow-up of surviving patients was 62 months (range 17-83). The 5-year estimated survival was 19% (95% confidence intervals = 7-31%). Rapidly alternating or sequential cycles of epirubicin and cyclophosphamide with CSF support is a feasible strategy that allows a higher increase of dose-intensity of the single drugs. Hospitalization and anemia were more frequent with the experimental schedules, and thrombocytopenia with the standard schedule. Overall, this intensified therapy was very active.
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PMID:The impact of schedule on acute toxicity and dose-intensity of high-dose chemotherapy with epirubicin and cyclophosphamide plus colony stimulating factors in advanced breast cancer. 1040 45

Ten patients with refractory (n = 8) or early relapsing (n = 2) aggressive non-Hodgkin's lymphoma were enrolled in a pilot study evaluating a high-dose sequential chemotherapy regimen with peripheral blood stem cell (PBSC) support. Five treatment phases were scheduled: phase I (cyclophosphamide + etoposide followed by lenograstim (G-CSF), and a PBSC harvest); phase II (cisplatinum + cytarabine + etoposide followed by lenograstim); phases III and IV (cyclophosphamide + cytarabine + etoposide followed by autologous PBSC infusion and lenograstim); and phase V (carmustine + cytarabine + etoposide + melphalan followed by autologous PBSC infusion and lenograstim). Ten, nine, eight, six and four of the 10 patients received one, two, three, four and five of the five scheduled phases of treatment, respectively. Four patients were withdrawn from the study due to progressive disease and two due to thrombotic microangiopathy (TM). Moreover, in the four patients who completed all treatment phases, an additional case of TM was seen. In all three patients with TM, laboratory studies showed evidence of Coombs negative hemolytic anemia, thrombocytopenia, renal dysfunction and in addition cardiac failure in two patients. TM may be a new dose-limiting toxicity of high-dose sequential chemotherapy followed by repeated PBSC transplantation.
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PMID:Thrombotic microangiopathy: a new dose-limiting toxicity of high-dose sequential chemotherapy. 1131 88

Twenty-two multi-transfused patients with a long duration of severe aplastic anemia (SAA) received a transplant from an HLA-matched donor after cyclophosphamide (CY) plus antithymocyte globulin plus procarbazine using CD34(+) enriched blood stem cells + fresh marrow. Peripheral blood stem cells (PBSC) were collected on days 5 and 6 of G-CSF (10 microg/kg/day), and T cells were depleted using an immunoadsorption column (n = 15) or magnetic cell sorting (n = 7). Marrow harvesting was performed 48 hr after the last leukapheresis. Two patients (9.1%) that developed graft failure had a successful engraftment again using unpurged PBSC. Median time to neutrophils > or = 0.5 x 10(9)/l and platelets > or = 20 x 10(9)/l without platelet transfusions were 12 days and 17 days, respectively. Acute graft-versus-host disease (GVHD) grade II occurred in four of 22 patients. No patient developed grade III or IV acute GVHD. Four of the evaluable 21 patients had chronic GVHD. One patient developed extensive disease. Three patients (13.6%) died from CY-induced heart failure, extensive-type chronic GVHD, and sepsis of unknown cause. The Kaplan-Meier estimate of survival was 83.9% (95% CI, 70.1-95.2%) with a median follow-up duration of 33.5 (6-44) months. CD34(+)-enriched PBSC in combination with unmanipulated marrow seem to play a role in overcoming the sensitization to histocompatibility antigens without an apparent increase in GVHD. The stem cell component therapy may be feasible for the high-risk SAA adult patients.
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PMID:Supplemental peripheral blood stem cells to decrease marrow rejection in adult patients with severe aplastic anemia. 1183 25

The evolving challenge of managing patients with congestive heart failure is the need to develop new therapeutic strategies. The cellular, molecular, and genetic approaches investigated aim to reinforce the weak, failing heart muscle while restoring its functional potential. This approach is principally cellular therapy (i.e. cellular cardiomyoplasty), the preferred therapeutic choice because of its clinical applicability and regenerative capacity. Different stem cells: bone marrow cells, skeletal and smooth muscle cells, vascular endothelial cells, mesothelial cells, adipose tissue stroma cells, dental stem cells, and embryonic and fetal cells, have been proposed for regenerative medicine and biology. Stem cell mobilization with G-CSF cytokine was also proposed as a single therapy for myocardial infarction. We investigated the association of cell therapy with electrostimulation (dynamic cellular cardiomyoplasty), the use of autologous human serum for cell cultures, and a new catheter for simultaneous infarct detection and cell delivery. Our team conducted cell-based myogenic and angiogenic clinical trials for chronic ischemic heart disease. Cellular cardiomyoplasty constitutes a new approach for myocardial regeneration; the ultimate goal is to avoid the progression of ventricular remodeling and heart failure for patients presenting with ischemic and non-ischemic cardiomyopathies.
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PMID:Cellular cardiomyoplasty for myocardial regeneration. 1611 8

Bone marrow-derived stem cells may contribute to the regeneration of non-haematopoietic organs. In order to test whether an increase in circulating stem cell numbers improves impaired myocardial function we treated 16 male patients with chronic heart failure due to dilated (DCM; n = 7) or ischaemic cardiomyopathy (ICM; n = 9) with the stem cell mobilising cytokine granulocyte colony-stimulating factor (G-CSF; four 10-day treatment periods interrupted by treatment-free intervals of equal length). Safety and efficacy analyses were performed at regular intervals. Peak CD34+ cell counts remained constant from cycle to cycle. Cardiac side effects in ICM patients included occasional episodes of dyspnea or angina and one episode of fatal ventricular fibrillation. Nine (4 DCM, 5 ICM) of 12 patients receiving four full G-CSF cycles experienced an improvement by one New York Heart Association (NYHA) class and a statistically significant increase in six-minute walking distance. By contrast, none of 8 ICM historical controls had a change in NYHA class during a similar time period. Statistically significant changes in echocardiographic parameters were not recorded. Sequential administration of G-CSF is feasible and possibly effective in improving physical performance in patients with chronic heart failure. Patients with ICM may be at risk of increased angina and arrhythmias.
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PMID:Granulocyte colony-stimulating factor-induced blood stem cell mobilisation in patients with chronic heart failure--Feasibility, safety and effects on exercise tolerance and cardiac function. 1623 6

In the past few years, the dogma that the heart is a terminally differentiated organ has been challenged. Evidence from preclinical investigations emerged that there are cells, even in the heart itself, that may be able to restore impaired cardiac function after myocardial infarction. Although the exact mechanisms by which the infarcted heart can be repaired by stem cells are not yet fully defined, there is a new optimism among cardiologists that this treatment will prove successful in addressing the cause of heart failure after myocardial infarction-myocyte loss. Despite the promising preliminary data of human myocardial stem cell trials, scientists have also focused on the possibility of enhancing the underlying mechanisms of stem cell repair to gain healthier myocardial tissue. Attempts to induce neo-angiogenesis by transfecting stem cells with signaling factors (such as VEGF), to raise the number of endothelial progenitor cells with medical treatments (such as statins), to transfect stem cells with heat shock protein 70 (as a cardioprotective agent against ischemia) and to enhance the healing process after myocardial infarction with the use of various forms of stimulating factors (G-CSF, SCF, GM-CSF) have been made with notable results. In this article, we summarize the evidence from preclinical and clinical myocardial stem cell studies that have addressed the possibility of enhancing the regenerative capacity of cells used after myocardial infarction.
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PMID:Drugs, gene transfer, signaling factors: a bench to bedside approach to myocardial stem cell therapy. 1766 19

The beta-thalassemias are genetic disorders that are caused by the absent or insufficient production of the beta-chain of hemoglobin. This deficiency causes ineffective erythropoiesis and hemolytic anemia. Without treatment, the severe form of the disease is lethal within the first decade of life. The only curative therapeutic option to date is allogeneic bone marrow transplantation from a matched, related donor, which carries a low risk of morbidity and mortality. Most patients, however, lack a matched donor and are thus managed with palliative therapy, consisting of lifelong transfusion therapy combined with pharmacological chelation to curb iron accumulation. Despite a major improvement in the chelation therapy and supportive care, the major cause of death in these patients is cardiac failure due to secondary hemochromatosis. The goal of globin gene therapy is to offer a potentially curative treatment to patients lacking a matched, related donor, based on the transfer of a regulated beta-globin gene in autologous CD34+ hematopoietic cells collected following G-CSF mobilization. Our clinical trial at Memorial Sloan-Kettering Cancer Center builds on a 20-year long investigation to develop an erythroid-specific vector to regulate beta-globin transgene expression in the progeny of transduced hematopoietic stem cells. To minimize the risks to the patient, the genetically modified cells will be infused after extensive biosafety testing of the transduced cells and following the administration of a reduced intensity (non-myeloablative) conditioning regimen. The protocol will be offered to patients with transfusion-dependent ss-thalassemia who are 15 years or older and lack a matched, related donor.
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PMID:Gene therapy for homozygous beta-thalassemia. Is it a reality? 2000 25

In animal models of clinical entities causative of severe right and left ventricular (LV) pressure overload hypertrophy, increased density of the cellular microtubule network, through viscous loading of active myofilaments, causes contractile dysfunction that is normalized by microtubule depolymerization. In this study, 86 male mice were divided into seven groups. The transverse ascending aorta constriction (TAC) in six groups were performed in order to make heart failure model. Mice in each group were injected with G-CSF or/and telmisartan subcutaneously at different time respectively. Results showed that reduction in left ventricular volume and improved function persisted at 2 week, but recurrent dilatation at 4 weeks was associated with a loss of functional improvement. Compared with PBS group, the expression of VEGF protein and HIF-1 mRNA were significantly higher in mice injected with G-CSF or/and telmisartan (P<0.05). The expression of p53 mRNA, myocardial fibrosis and mortality were significantly lower in mice injected with G-CSF or/and telmisartan (P<0.05). It could be concluded that G-CSF can delay the progression of pressure overload induced ventricular reconstruction and heart failure in mice.
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PMID:The therapeutic potential of G-CSF in pressure overload induced ventricular reconstruction and heart failure in mice. 2143 59


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