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)

Iron, iron-binding capacity, lactoferrin and total protein were determined in the plasma and pleural fluid of 30 patients with cardiac failure (n = 10), infectious/inflammatory disease (n = 9) and metastatic carcinoma (n = 11). In 16 patients pleural transferrin and ferritin was also measured. Plasma iron and total iron-binding capacity were reduced in inflammatory and neoplastic disease, whereas hyposideremia with normal iron-binding capacity was seen in patients with heart failure. Plasma lactoferrin was reduced in metastatic carcinoma. Exudates (protein greater than or equal to 30 g/l; infectious/inflammatory: 9/9, carcinomatous: 10/11) had significantly higher iron, lactoferrin, transferrin and ferritin concentrations than transudates (protein less than 30 g/l; heart failure: 10/10, carcinomatous: 1/11). Statistically, infectious/inflammatory exudates could be distinguished from neoplastic exudates by a higher median iron concentration (non-parametric Wilcoxon-Mann-Whitney test). Overlap of the respective ranges, however, did not allow a clear-cut differential diagnosis in individual cases. Pleural lactoferrin concentrations, on the other hand, correlated with the pleural granulocyte count and nonspecifically reflect the degree of granulocytic inflammation. Positive pleural/plasma correlations of protein and of iron concentrations were found in exudates only. Within exudates and transudates, on the other hand, total protein correlated with transferrin but not with iron concentrations. Therefore, and because of the substantially higher pleural/plasma ratio for iron than for transferrin concentrations, a quantitatively important, non-transferrin bound iron pool in pleural fluids, most probably ferritin, must be assumed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Iron and iron-binding proteins in the differential diagnosis of pleural effusion]. 276 88

The in vitro function of granulocytes collected by filtration leukapheresis after premedication of donors with dexamethasone was found to be normal. In vivo studies were performed in a 21-year-old woman who was transplanted with allogeneic bone marrow for severe aplastic anaemia. The patient received granulocyte transfusions for treatment of septicaemia during the transplantation period. On 11 consecutive days an average dose of 7.2 X 10(10) granulocytes/transplantation, the patient died from cardiac failure. Transfused granulocytes were found ante mortem in a pericardial effusion and post mortem in lungs, kidneys, liver and spleen. The data indicate that filter collected granulocytes function normally in the recipient and are clinically effective.
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PMID:In vitro and in vivo studies on filter collected granulocytes. 700 83

In two patients, a 50-year-old woman (case 1) and a 2-year-old girl (case 2) acute shortness of breath requiring artificial ventilation developed 3-5 hours after infusion of two erythrocyte concentrates in case 1 and unfiltered platelet-enriched plasma (20 ml/kg) in case 2. The chest radiograph showed diffuse infiltrations in the lungs of both patients. After administration of catecholamines and respirator therapy, extubation was possible in the first patient after two days, in the second after five days. In neither case had there been any evidence of hypervolaemia, heart failure or infection to explain the lung findings. However, the serum of case 1 and the serum of the platelet donor had antibodies against granulocytes. The granulocyte-compatibility test (between patient serum and donor granulocytes) was positive. This confirmed the clinical suspicion of transfusion-related acute lung injury (TRALI). However, demonstration of antibodies was not only important for the diagnosis, but made it possible to recognize a blood donor whose serum contained antibodies against granulocytes which can provoke TRALI.
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PMID:[Transfusion associated acute pulmonary insufficiency. Diagnostic confirmation by the demonstration of granulocytic antibodies]. 828 78

The cytokine modulating effects of inotropic agents on human umbilical vein endothelial cells (HUVEC) were investigated. Confluent HUVEC in 24-well plates were treated with inotropic agents and then stimulated with 10 ng/ml of human interleukin (IL)-1 beta. After 24 h of incubation, the cytokine levels in the culture supernatants were determined by specific enzyme-linked immunosorbent assay (ELISA) kits. Vesnarinone [OPC-8212; 3,4-dihydro-6-(4-(3,4-dimethoxybenzoil)-1-piperazinyl)-2(1H)- quinolinone] at 26 mumol/l significantly suppressed the production of IL-6, granulocyte macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF) induced by IL-1 beta. Although 8 bromoadenosine 3'5' cyclic monophosphate (8Br-cAMP) at 100 mumol/l also inhibited the production of these cytokines, the inhibitory effect was less marked than that of vesnarinone. Amrinone at 26 mumol/l and NKH477 at 10 nmol/l also had a less marked inhibitory effect against the production of IL-6. Next, the inhibitory effect of inotropic agents against the expression of the adhesion molecules of HUVEC was measured by a cell ELISA method. Vesnarinone at 26 mumol/l and NKH477 at 10 mumol/l, a water soluble forskolin derivative used as a positive control, both significantly inhibited the expression of E-selectin induced by 10 ng/ml of human tumor necrosis factor (TNF)-alpha. Amrinone at 26 mumol/l did not inhibit the expression of E-selectin. The level of HUVEC cAMP induced by vesnarinone at 26 mumol/l was much lower than that induced by NKH477 at 10 mumol/l. Moreover, according to a 3-(4,5-dimethyl-thiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) cell viability assay, vesnarinone did not affect the viability of HUVEC. The immunosuppressive effects of vesnarinone described above are not derived from either a cAMP elevating effect or a cytotoxic effect against HUVEC. Although the cytokine network in heart failure has not yet been elucidated, patients with congestive heart failure might benefit from the immunomodulating effects of inotropic agents.
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PMID:Inotropic agent vesnarinone inhibits cytokine production and E-selectin expression in human umbilical vein endothelial cells. 857 41

Vesnarinone (OPC-8212) is a new positive inotropic agent that augments myocardial contractility. A recent multi-center randomized trial in the United States demonstrated that 60 mg/day of vesnarinone significantly reduced morbidity and mortality and improved quality of life in patients with symptomatic chronic heart failure. Vesnarinone, however, is also known for its propensity to cause granulocytopenia. In search of effective safety measures against this side effect, data have been collected in Japan as part of the post-marketing surveillance of this drug. This article reviews the results of this post-marketing surveillance and other works available to date, including an illustrative case report, and presents measures that should be taken with regard to safety during treatment with vesnarinone. Vesnarinone-induced granulocytopenia has appeared in relatively early stages of vesnarinone therapy, and characteristically results in a rapid decrease in granulocyte count. Hematologic monitoring should be performed at least once a week during the initial 16 weeks of vesnarinone therapy. Granulocyte colony-stimulating factor may contribute to recovery from severe granulocytopenia, although it should be used carefully because of its potential to cause adult respiratory distress syndrome.
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PMID:Vesnarinone-induced granulocytopenia: incidence in Japan and recommendations for safety. 873 27

The direct toxic effect of alcohol and its metabolite acetaldehyde has been demonstrated both in laboratory animals and in humans. Alterations in the mitochondrial ultrastructure and the dilatation of the sarcoplasmatic reticulum have been shown after an acute infusion of alcohol in the heart. These changes correlate with decreased mitochondrial function, defects in protein synthesis and the occurrence of arrhythmias. The risk of developing alcoholic cardiomyopathy is related to both the mean daily alcohol intake and the duration of drinking, but there is much individual susceptibility to the toxic effect of alcohol. Most patients, in whom alcoholic cardiomyopathy develops, have been drinking over 80 g/d for more than 5 years. The clinical diagnosis of alcoholic cardiomyopathy reflects the coexistence of global myocardial dysfunction in a heavy drinker in whom no other cause for myocardial disease was found. In studies focussing on alcoholic cardiomyopathy the surprising histologic findings in endomyocardial biopsy in about 30% of all cases was myocarditis with a lymphocytic infiltrate in association with myocyte degeneration or focal necrosis. In myocarditis, the network of microtubules and intermediate filaments is also disrupted by the inflammatory reaction which involves resident cells (myocytes, fibroblasts, endothel cells) and systemic cells (granulocytes, macrophages, monocytes, lymphocytes). Changes in the cardiac cytoskeleton and the extracellular matrix may affect contractile function, since the cytoskeleton organizes the intra- and intercellular architecture. After all, in patients with alcohol abuse and myocarditis the immune functioning appears to be compromised. Several studies suggest that heavy drinking alters both lymphocyte and granulocyte production and function. Alcohol consumption per se might harm the immune system. Furthermore, the myocardial damage due to alcohol consumption could initiate autoreactive mechanisms comparable to those in viral or idiopathic myocarditis. Patients with alcohol abuse and myocarditis have a poor prognosis: signs of biventricular failure including tachycardia, hepatomegaly, and peripheral and lung edema are observed. These symptoms are as nonspecific as are various echocardiographic and electrocardiographic changes such as atrial and ventricular arrhythmias which may be associated both with myocarditis, alcoholic cardiomyopathy and acute effects of drinking without hemodynamic alterations. For the management of patients with alcohol abuse the prevention of further alcohol intake is mandatory to reverse the myocardial damage and the unfavorable predisposition for infection. Specific treatment of myocarditis is the second important option, and treatment of heart failure by reducing the size of the dilated heart and alleviating the signs and symptoms of heart failure is a logical third step.
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PMID:[Alcohol and myocarditis]. 880 5

Extramedullary hematopoiesis occurring in the myocardium has previously only been reported in a single case of a neonate with cyanotic congenital heart disease. Herein we report the incidental discovery of extramedullary hematopoiesis or pure erythropoiesis in four failing adult hearts with myocardial infarction. In two cases, extramedullary hematopoiesis or erythropoiesis was identified in cardiectomy specimens removed at orthotopic heart transplantation; in two other cases, erythropoiesis was found in left ventricular tissue removed at the time of implantation of left ventricular assist devices. Myocardial hematopoiesis/erythropoiesis was identified based on characteristic light-microscopic findings in routinely processed tissue and was confirmed by immunhistochemistry using monoclonal antibodies to the erythroid cell marker glycophorin A (positive in all cases), the megakaryocyte marker CD61, and the granulocyte marker neutrophil elastase (the latter two markers positive in one case only). None of the four patients had a myeloproliferative disorder or evidence of a myelophthisic process. No hematopoietic elements were identified in 109 cardiectomy specimens without acute or recent infarcts. Myocardial hematopoiesis or erythropoiesis could represent heretofore-unrecognized manifestations of altered cytokine expression in patients with heart failure due to myocardial infarction.
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PMID:Hematopoiesis/erythropoiesis in myocardial infarcts. 1140 61

The present trial was designed to determine the efficacy of the combination of gemcitabine/doxorubicin/paclitaxel (GAT) delivered every other week as first-line therapy in patients with metastatic breast cancer. From February 1998 to September 1999, 41 patients were included in this trial. Doses delivered were doxorubicin 30 mg/m2 on day 1 and paclitaxel 135 mg/m2 plus gemcitabine 2500 mg/m2 both given on day 2, every 14 days. Doses were selected from a previous phase I trial conducted at our institution. Eligibility criteria for the phase II trial included histologically confirmed metastatic breast cancer with bidimensionally measurable lesions; no prior therapy for metastatic disease; adjuvant or neoadjuvant chemotherapy was allowed if given more than 1 year before and cumulative doses of doxorubicin or epirubicin were less than 200 mg/m2 or 360 mg/m2, respectively; Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less; and adequate hematological, hepatic, and renal function. Prophylactic use of granulocyte colony-simulating factor (G-CSF) was allowed if patients were not fully recovered (absolute neutrophil count greater than 1500/microL) from chemotherapy administration before the next dose. Left ventricular ejection fraction was determined initially, at the end of the study, and every 6 months thereafter. The patients' median age was 55 years (range, 33-68 years), and their median ECOG performance status was 0 (range, 0-1). Twenty-eight patients had received adjuvant therapy, 17 with epirubicin (none with doxorubicin). Metastases were present in the bone (19 patients), lung (19 patients), liver (11 patients), and soft tissues (18 patients). Twenty patients had one metastatic site and 21 had two or more sites. Efficacy was assessed on an intent-to-treat basis. A total of 216 cycles of GAT were given. Twenty-two percent of the courses were delayed or given at reduced doses mostly due to neutropenia or thrombocytopenia. G-CSF was required in 58% of the cycles. Grade 3/4 neutropenia was the main toxicity and appeared in 17 patients, one of whom had an episode of febrile neutropenia. Nonhematological toxicities consisted mainly of neurotoxicity and myalgias. A drop of 10%-20% in the left ventricular ejection fraction was detected in two patients and another patient had a decrease greater than 20%, although none developed symptoms of heart failure. Overall response rate was 80.4% (95% confidence interval: 68.3-92.5), with 15 patients (36.6%) achieving a complete response. Median survival time was 27 months and median time to progression was 15 months. The GAT combination is feasible and very active in patients with metastatic breast cancer, with an encouraging response rate including a high rate of complete responses. No congestive heart failure was documented and other toxicities were mild, with the exception of neutropenia.
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PMID:Phase II trial of gemcitabine/doxorubicin/paclitaxel administered every other week in patients with metastatic breast cancer. 1189 47

Recent studies have suggested that cytokines such as macrophage colony-stimulating factor (M-CSF) might be involved in the pathogenesis of ischaemic heart disease. Macrophage colony-stimulating factor, granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage-colony stimulating factor (GM-CSF), stem cell factor (SCF), interleukin-3 (IL-3) and interleukin-7 (IL-7) are potent cytokines belonging to the same structual class that may affect function, growth and apoptosis both in the heart and other organs. The aims of the present study were to characterize a post-infarction model in the mouse and to examine mRNA expression of M-CSF, GM-CSF, SCF, IL-3 and IL-7 during the development of heart failure. Myocardial infarction (MI) was induced in mice by ligation of the left coronary artery. Average infarct size was 40% and the mice developed myocardial hypertrophy and pulmonary oedema. Ribonuclease (RNAase) protection assays showed abundant cardiac expression of M-CSF and SCF. After MI, we measured down-regulation of cytokine mRNA expression in the heart (M-CSF, SCF), lung (M-CSF), liver (M-CSF) and spleen (M-CSF) compared with sham. Cardiac G-CSF, GM-CSF and IL-7 mRNAs were not detected. In conclusion, abundant cardiac gene expression of M-CSF and SCF was found. In our mouse model of MI, M-CSF and SCF were down-regulated in the heart and several other organs suggesting specific roles for these cytokines during development of ischaemic heart failure.
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PMID:Gene expression of colony-stimulating factors and stem cell factor after myocardial infarction in the mouse. 1210 Mar 56

Mobilization of bone marrow stem cells by granulocyte-colony-stimulating factor (G-CSF) is considered to be an alternative to invasive transplantation of autologous myoblasts or stem cells directly into injured cardiac tissue. We have started a 24 week randomized open study in order to elucidate effects of G-CSF (filgrastim) on clinical, hemodynamic and neurohumoral status of patients with NYHA class II-IV chronic heart failure due to ischemic heart disease with zones of nonviable myocardium and left ventricular ejection fraction <40% as well as to assess safety of addition of G-CSF to standard therapy with ACE inhibitors and beta-blockers. It is planned to include 20 patients into each filgrastim (5 mg/kg/day) and control (0.9% NaCl) groups. Methods to be used: dobutamine stress echocardiography for detection of myocardial viability, magnetic resonance tomography, 6-minute walk test, quality of life questionnaire. By the present time 5 patients were included (4 in filgrastim and 1 in control group) and passed 3-6 months points. A control patient died suddenly on 11th week. All patients in filgrastim group are alive (1 experienced obvious improvement, 2 remained stable, and 1 deteriorated and required urgent hospitalization). None of the patients had signs of appearance of 'regenerated' myocardial zones. The patient with positive clinical dynamics was characterized by young age (48 years), moderately severe heart failure (NYHA class II) and pronounced leukocyte reaction to filgrastim (12 fold increase in white blood cell count with appearance of myelocytes and myeloblasts ). In contrast patients without improvement were older than 60 years, had NYHA class III heart failure and experienced just 6-8 fold increases in leukocyte count. These factors are suggested to be predictors of clinical efficacy of G-CSF in patients with heart failure.
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PMID:[Mobilization of bone marrow stem cells in the management of patients with heart failure. Protocol and first results of ROT FRONT trial]. 1289 Dec 52


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