Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

We report the rare case of a 55-year-old female with massive eosinophilic myocarditis and severe, however reversible, impairment of left ventricular function. The patient presented with reduced physical condition, progressive dyspnea on exertion and peripheral edema. The white blood count revealed a leukocytosis and markedly elevated peripheral blood eosinophilics (48.8%). An endomyocardial biopsy demonstrated massive myocardial infiltration with eosinophilic granulocytes and necrosis. The symptoms and laboratory parameters indicate the presence of a hypereosinophilic syndrome. The differential diagnosis of a Churg-Strauss syndrome is discussed. Medical heart failure treatment according to international guidelines and an immunosuppressive treatment with prednisolone (Decortin H) 1.5 mg/kgBW) were initiated. This therapy led to a dramatic reduction of the eosinophilic granulocyte count and normalization of the peripheral blood count, which correlated with a significant improvement of clinical symptoms. Consistently, an increase of left-ventricular function was observed. Upon successive dose reduction to a maintenance dosage of 10 mg prednisolone, the patient's clinical status and peripheral blood count remained stable.
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PMID:Hypereosinophilic syndrome associated with acute necrotizing myocarditis and cardiomyopathy. 1625 79

The objective of this study was to determine a safe and effective dose of granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells in patients with advanced heart failure and to determine its effects on the cytokine profile. Patients with advanced heart failure (n = 6) and implantable defibrillators in situ were administered G-CSF after baseline echocardiographic and laboratory evaluation, using an escalating dose schedule designed to ensure safety. The peripheral CD34+ hematopoietic stem cell count increased from 3.6 +/- 0.5/microl to 38.7 +/- 13/microl (p= 0.022) after 5 days of 5 microg/kg/day G-CSF therapy. The baseline or peak white blood cell count did not predict the stem cell response. G-CSF increased plasma levels of interleukin-10. Left ventricular ejection fraction increased significantly in the 4 patients with ischemic cardiomyopathy 9 months after treatment. No major adverse effects attributable to the drug occurred during administration or 9 months of follow-up. Our results have shown that low-dose G-CSF significantly mobilized hematopoietic stem cells in advanced heart failure and improved left ventricular function in the ischemic subset of patients. G-CSF significantly increased plasma levels of the anti-inflammatory cytokine interleukin-10, without changing pro-inflammatory cytokine levels. In conclusion, these results indicate a novel mechanism of action for the potential therapeutic benefit of G-CSF in advanced ischemic cardiomyopathy.
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PMID:Safety and effectiveness of granulocyte-colony stimulating factor in mobilizing stem cells and improving cytokine profile in advanced chronic heart failure. 1649 Apr 37

Left ventricular (LV) remodeling leads to congestive heart failure and is a main determinant of morbidity and mortality following myocardial infarction. Therapeutic options to prevent LV remodeling are limited, which necessitates the exploration of alternative therapeutic targets. Toll-like receptors (TLRs) serve as pattern recognition receptors within the innate immune system. Activation of TLR4 results in an inflammatory response and is involved in extracellular matrix degradation, both key processes of LV remodeling following myocardial infarction. To establish the role of TLR4 in postinfarct LV remodeling, myocardial infarction was induced in wild-type BALB/c mice and TLR4-defective C3H-Tlr4(LPS-d) mice. Without affecting infarct size, TLR4 defectiveness reduced the extent of LV remodeling (end-diastolic volume: 103.7+/-6.8 microL versus 128.5+/-5.7 microL; P<0.01) and preserved systolic function (ejection fraction: 28.2+/-3.1% versus 16.6+/-1.3%; P<0.01), as assessed by MRI. In the noninfarcted area, interstitial fibrosis, and myocardial hypertrophy were reduced in C3H-Tlr4(LPS-d) mice. In the infarcted area, however, collagen density was increased, which was accompanied by fewer macrophages, reduced inflammation regulating cytokine expression levels (interleukin [IL]-1alpha, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, tumor necrosis factor-alpha, interferon-gamma, granulocyte/macrophage colony-stimulating factor), and reduced matrix metalloproteinase-2 (4684+/-515 versus 7573+/-611; P=0.002) and matrix metalloproteinase-9 activity (76.0+/-14.3 versus 168.0+/-36.2; P=0.027). These data provide direct evidence for a causal role of TLR4 in postinfarct maladaptive LV remodeling, probably via inflammatory cytokine production and matrix degradation. TLR4 may therefore constitute a novel target in the treatment of ischemic heart failure.
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PMID:Toll-like receptor 4 mediates maladaptive left ventricular remodeling and impairs cardiac function after myocardial infarction. 1823 39

Heart failure is by far the most common cause of hospitalization in Western countries, with onerous economic consequences. Cell therapy holds great promise for use in tissue regeneration and is increasingly used in an effort to improve outcomes in cardiac disease. Recently it has been shown that adipose tissue, in addition to committed adipogenic, endothelial progenitor cells and pluripotent vascular progenitor cells, also contains multipotent cell types (adipose-derived stem cells, ADSCs) that, in cell culture conditions, have shown to have an impressive developmental plasticity including the ability to undergo multilineage differentiation and self-renewal. ADSCs express multiple CD marker antigens similar to those observed on MSCs and are also capable of secreting a large number of angiogenesis-related cytokines, including vascular endothelial growth factor, granulocyte/macrophage colony stimulating factor, stromal-derived factor-1alpha, and hepatocyte growth factor. Adipose tissue can be harvested in large quantities with minimal morbidity in several regions of the body and, on average, 100 ml of human adipose tissue yields about 1 x 10(6) stem cells. Studies conducted in porcine AMI models have shown a significant LV functional improvement, with no report of any potentially fatal arrhythmias. The APOLLO trial, a prospective, double blind, randomized, placebo-controlled trial currently in the recruiting phase, is a "first-in-man" study that explores the safety and feasibility of ADSC transplantation in patients with acute MI.
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PMID:Adipose-derived cells. 1829 95

We prospectively studied bone marrow stem cell (BMSC) therapy in 23 patients with non ischemic refractory heart failure(HF) in comparison with a HF control group with 17 patients. BMSC patients randomly underwent granulocyte-colony stimulating factor (G-CSF) administration (14 patients) or G-CSF associated to BMSC intracoronary infusion (eight patients). After the first month all BMSC patients received G-CSF with one-month interval between each one. CD34+ cell peaks (per mm(3)) in BMSC patients were 19+/-12 and in normal control 60+/-20 (p=0.003). In BMSC patients after the 1st G-CSF left ventricular(LV) ejection fraction (EF) increased from 21.4+/-4.7% to 23.6+/-7.7%(p=.048), peak VO(2) (ml/kg/min) from 9.9+/-2.4 to 11.6+/-3 (p=.04), functional class and quality of life improved whereas in the HF control group LVEF, RFEF and functional class were unchanged. Both BMSC subgroups presented improvement of LV function evaluated by DTI velocities. Evaluations after the first month in BMSC patients showed improvements in LVEF (p=.001), right VEF (p=0.01), DTI velocities (p=.009), peak VO(2) (p=0.04), functional class (p<0.001) and quality of life (p<0.001). In conclusion, CD34+ mobilization is impaired in HF. Stem cell therapy can improve HF. Randomized trials should be developed to confirm our results.
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PMID:Granulocyte-colony stimulating factor or granulocyte-colony stimulating factor associated to stem cell intracoronary infusion effects in non ischemic refractory heart failure. 1867 77

The field of autologous stem/progenitor cell transplantation for cardiovascular diseases has moved rapidly from basic science research to clinical trials. To date, only a handful of pilot studies have reported the use of this novel strategy for heart failure patients. Most of these studies have demonstrated encouraging safety and efficacy data. However, this will need to be validated in large, randomized trials. Here, we introduce the ongoing REGENERATE-IHD trial, which is the largest randomized, placebo-controlled trial in the UK investigating the use of granulocyte-colony stimulating factor and autologous bone marrow-derived stem/progenitor cells to improve cardiac function and symptoms in heart failure patients.
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PMID:Autologous bone marrow-derived stem cells for ischemic heart failure: REGENERATE-IHD trial. 1910 21

Stem cell-based cell therapy has emerged as a potentially therapeutic option for patients with acute myocardial infarction (AMI) and heart failure. With the completion of a number of trials using bone marrow (BM)-derived adult stem cells, critical examination of the overall clinical benefits, limitations and potential side effects of this revolutionary treatment will pave the way for future clinical research. At present, clinical trials have been conducted almost exclusively using BM stem cells. The primary endpoints of these trials are mainly safety and feasibility, with secondary endpoints in the efficacy of post-myocardial infarction (MI) cardiac repair. Intervention with BM-derived cells was mainly carried out by endogenously-mobilised BM cells with granulocyte-colony stimulating factor, and more frequently, by intracoronary infusion or direct intramyocardial injection of autologous BM cells. While these studies have been proven safe and feasible without notable side effects, mixed outcomes in terms of clinical benefits have been reported. The major clinical benefits observed are improved cardiac contractile function and suppressed left ventricular negative remodelling, including reduced infarct size and improved cardiac perfusion of infarct zone. Moderate and transient clinical benefits have been mostly observed in studies with intracoronary infusion or direct intramyocardial injection of BM cells. These effects are widely considered to be indirect effects of implanted cells in association with paracrine factors, cell fusion, passive ventricular remodelling, or the responses of endogenous cardiac stem cells. In contrast, evidence of cardiac regeneration characterised by differentiation of implanted stem cells into cardiomyocytes and other cardiac cell lineages, is weak or lacking. To elucidate a clear risk-benefit of this exciting therapy, future studies on the mechanisms of cardiac cell therapy will need to focus on confirming the ideal cell types in relation to dosage and timing for post-MI cardiac repair, developing more effective cell delivery techniques, and devising innovative cell tracking modalities that could unveil the fates of implanted cells such as survival, engraftment and functionality.
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PMID:Human bone marrow-derived adult stem cells for post-myocardial infarction cardiac repair: current status and future directions. 1990 81

BACKGROUND: Left ventricular remodeling after myocardial infarction (MI) results in ventricular dilation, fibroplasia, and decline in cardiac function. There is significant morbidity and mortality associated with this process, often leading to heart failure despite medical management. New therapies aimed at altering ventricular remodeling after MI are needed, and cytotherapy utilizing progenitor cells is a current area of investigation. THE PROBLEM: Many variables need to be considered to maximize the therapeutic benefit of cytotherapy, including the cell type, the method of delivery, the timing, and patient selection. Investigation into progenitor cell biology will continue to identify novel treatment strategies that then must be tested clinically to demonstrate safety, feasibility, and ultimately therapeutic benefit. BASIC/CLINICAL SCIENCE ADVANCES: Although progenitor cells have the potential to affect ventricular remodeling through multiple mechanisms, their major effect is likely due to actions of secreted factors. Hepatocyte growth factor, stromal-derived growth factor-1 alpha, and stem cell factor affect the mobilization of progenitor cells, which makes it possible to develop treatment strategies based on recruitment of endogenous progenitor cells. CLINICAL CARE RELEVANCE: There have been a number of randomized controlled trials demonstrating modest improvements in cardiac function using progenitor cell therapies after MI. In addition, clinical trials have used granulocyte-colony-stimulating factor as a treatment aimed at increasing progenitor cell mobilization. CONCLUSION: Progenitor cell therapy after MI has been shown to be safe and feasible with some improvements in cardiac function and clinical outcomes. Further investigation is needed to better understand the biology of progenitor cells and the effects of progenitor cell-based therapies.
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PMID:Progenitor Cells for the Treatment of Acute Myocardial Infarction. 2202 3

Cell based therapy for ischemic heart disease has the potential to reduce post infarct heart failure and chronic ischemia. Treatment with granulocyte-colony stimulating factor (G-CSF) mobilizes cells from the bone marrow to the peripheral blood. Some of these cells are putative stem or progenitor cells. G-CSF is injected subcutaneously. This therapy is intuitively attractive compared to other cell based techniques since repeated catheterizations and ex vivo cell purification and expansion are avoided. Previous preclinical and early clinical trials have indicated that treatment with G-CSF leads to improved myocardial perfusion and function in acute or chronic ischemic heart disease. The hypothesis of this thesis is that patient with ischemic heart disease will benefit from G-CSF therapy. We examined this hypothesis in two clinical trials with G-CSF treatment to patients with either acute myocardial infarction or severe chronic ischemic heart disease. In addition, we assed a number of factors that could potentially affect the effect of cell based therapy. Finally, we intended to develop a method for in vivo cell tracking in the heart. Our research showed that subcutaneous G-CSF along with gene therapy do not improve myocardial function in patients with chronic ischemia despite a large increase in circulation bone marrow-derived cells. Also, neither angina pectoris nor exercise capacity was improved compared to placebo treatment. We could not identify differences in angiogenic factors or bone marrow-derived cells in the blood that could explain the neutral effect of G-CSF. Next, we examined G-CSF as adjunctive therapy following ST segment elevation myocardial infarction. We did not find any effect of G-CSF neither on the primary endpoint--regional myocardial function--nor on left ventricular ejection fraction (secondary endpoint) compared to placebo treatment. In subsequent analyses, we found significant differences in the types of cells mobilized from the bone marrow by G-CSF. This could explain why intracoronary injections of unfractionated bone marrow-derived cells have more effect that mobilization with G-CSF. A number of other factors could explain the neutral effect of G-CSF in our trial compared to previous studies. These factors include timing of the treatment, G-CSF dose, and study population. It is however, remarkable that the changes in our G-CSF group are comparable to the results of previous non-blinded studies, whereas the major differences are in the control/placebo groups. We found that ejection fraction, wall motion, edema, perfusion, and infarct size all improve significantly in the first month following ST-segment myocardial infarction with standard guideline treatment (including acute mechanical revascularization), but without cell therapy. This is an important factor to take into account when assessing the results of non-controlled trials. Finally, we found that ex vivo labeling of cells with indium-111 for in vivo cell tracking after intramyocardial injection is problematic. In our hand, a significant amount of indium-111 remained in the myocardium despite cell death. It is difficult to determine viability of the cells after injection in human trials, and it is thus complicated to determine if the activity in the myocardium tracks viable cells. Cell based therapy is still in the explorative phase, but based on the intense research within this field it is our hope that the clinical relevance of the therapy can be determined in the foreseeable future. Ultimately, this will require large randomized, double-blind and placebo-controlled trials with "hard" clinical endpoints like mortality and morbidity.
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PMID:Granulocyte-colony stimulating factor therapy to induce neovascularization in ischemic heart disease. 2238 Oct 94

Administration of granulocyte CSF preparation to patients with chronic heart failure produced a hemostimulating effect and increased the content of leukocytes and neutrophils in the peripheral blood. Granulocyte CSF induced mobilization of bone marrow progenitor cells into the peripheral blood. The content of hemopoietic CD34(+)progenitor cells, which attained 0.42% (0.25-0.64) by the end of mobilization, inversely correlated with the number of myocardial infarctions. Administration of granulocyte CSF not only led to mobilization of bone marrow hemopoietic cells, but also increased the pool of endothelial progenitor cells in the peripheral blood: the content of CD34(+)/CD133(+)and CD34(+)/KDR(+)attained 0.02% (0.013-0.075) and 0.1% (0.05-0.20), respectively. Peripheral blood is an available source of progenitor cells, while mononuclear cells after administration of granulocyte CSF can produce a reparative effect on ischemic myocardium.
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PMID:Phenotype of peripheral blood cells mobilized by granulocyte colony-stimulating factor in patients with chronic heart failure. 2280 10


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