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)

Recombinant human erythropoietin is a major advance in the management of patients with chronic renal failure. The sustained dose-dependent rise in haematocrit which it produces effectively abolishes symptoms of anaemia, but at the cost of an increase in blood viscosity. This in turn predisposes to increased vascular resistance and the development of hypertension. Over half of all deaths of patients with end-stage renal failure are from cardiovascular disease, notably myocardial infarction, heart failure, and stroke, for which hypertension is a known risk factor. Erythropoietin-related increases in blood pressure are therefore of particular concern, and seem to be most severe in previously hypertensive patients. There is now a need to establish the optimum rate and extent of rise of haematocrit required to alleviate symptoms without incurring undue risk.
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PMID:Hypertension, blood viscosity, and cardiovascular morbidity in renal failure: implications of erythropoietin therapy. 289 90

Serum erythropoietin levels were measured by radioimmunoassay in 146 children and young adults with congenital heart disease to assess the relationship between erythropoietin and clinical factors (heart failure, anemia, cyanosis) and hemodynamic variables affecting oxygen delivery and utilization. Erythropoietin values were in the normal range (10 to 30 microU/mL) in 73% (58 of 80) of the patients with and 82% (54 of 66) of those without cyanosis. Elevated erythropoietin values in cyanotic patients were associated with lower mixed venous oxygen saturation and tension than in cyanotic patients with normal erythropoietin levels, even though the degree of polycythemia was similar. In contrast, most of the acyanotic patients who had elevated erythropoietin levels were anemic. Of the blood oxygen measurements, mixed venous oxygen saturation and tension had the closest inverse correlation with erythropoietin values. The normal erythropoietin values in most patients are in accord with other observations that show that an elevation in erythropoietin level in response to hypoxia will be transient if it results in a rise in hemoglobin concentration "appropriate" to the degree of hypoxia. Persistent elevation of erythropoietin in patients with congenital heart disease may indicate harmful impairment of hemoglobin production that is potentially correctable.
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PMID:Serum erythropoietin levels in patients with congenital heart disease. 355 1

Patients on dialysis have an age-adjusted death rate 3.5 times that of the general population. The most common cause of death in patients on dialysis is cardiovascular disease. We prospectively followed a cohort of 433 patients in three centers for a mean of 41 months. Mean hemoglobin level at the beginning of dialysis was 8.39 (+/- 1.7) g/dL, and the mean hemoglobin level during follow-up was 8.84 (+/- 1.5) g/dL. Using Cox's regression model, we found that anemia predicted mortality independently of age, diabetes mellitus, cardiac failure, hypoalbuminemia, serum creatinine, mean arterial pressure, or echocardiographic heart disease. The independent relative risk (RR) of mortality was 1.18 per 1.0 g/dL decrease in hemoglobin level. Anemia also independently predicted the de novo occurrence of congestive heart failure when the same covariates were controlled for (RR, 1.49 per 1.0 g/dL decrease). Anemia was also independently predictive of heart failure at the start of dialysis (RR, 1.14 per 1.0 g/dL decrease) and heart failure recurrence (RR, 1.25 per 1.0 g/dL decrease). Left ventricular hypertrophy is present in 75% of patients on dialysis at the start of therapy for end-stage renal disease. It independently predicts mortality. Our prospective cohort study identified increasing age, hypertension, and anemia as risk factors for its development. One controlled study and several uncontrolled studies demonstrated improvement (but not complete regression) of elevated left ventricular mass in patients on dialysis treated with recombinant human erythropoietin (epoetin).
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PMID:Cardiac function and hematocrit level. 770 71

Treatment of myelodysplastic syndromes (MDS) with recombinant human erythropoietin (Epo) is successful in only 10% to 25% of patients. We performed a pilot study in 10 anaemic patients with MDS to examine whether sequentially applied recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and Epo improves haemoglobin levels and/or reduces red blood cell transfusion requirements. Morphological diagnoses of patients were refractory anaemia (RA) in 3 cases, RA with ring sideroblasts in 3 cases and RA with excess blasts in 4 cases. GM-CSF was given subcutaneously at a dose of 150 micrograms/m2/d during the initial 10 days. From day 11, Epo was administered by subcutaneous injections for 8 weeks at a dose of 100 U/kg/d and subsequently at an escalated dose of 200 U/kg/d in 3 patients. Changes in reticulocyte counts, haemoglobin levels, RBC support and ferrokinetic parameters were compared with pretreatment values. Two out of 8 evaluable patients showed a rise in haemoglobin levels at week 8 and 10, respectively, and lost their transfusion dependency for a period of 13 and 27 weeks. In 1 patient, haemoglobin level increased only after dose escalation of Epo (200 U/kg/d). Leukocyte counts remained uneffected by treatment with Epo, while 1 patient showed a 4-fold increase in platelet numbers. Toxicity was mild. Two patients died of pneumonia and global heart failure, respectively, unrelated to growth factor therapy. Based on this pilot study, we conclude that sequential treatment with GM-CSF and Epo does not increase erythroid responses in anaemic patients with MDS. Because of the delayed increase in haemoglobin in both responders, we surmise that the beneficial effects were induced by Epo alone.
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PMID:Sequential administration of recombinant human granulocyte-macrophage colony-stimulating factor and human erythropoietin for treatment of myelodysplastic syndromes. 785 74

To examine the effects of recombinant human erythropoietin (rHuEPO) on hospital utilization, hospital costs, and Medicare reimbursements for hospital care, a longitudinal, matched cohort study was conducted using Medicare claims data of 23,806 Medicare-eligible, dialysis patients who received rHuEPO, did not have a transplant, and were alive for 18 mo or longer and 22,720 controls matched on age, sex, race, cause of ESRD, and dialysis modality. The relative odds (rHuEPO versus control) of admission for all causes and for specific causes over 9 mo, adjusted for admission in the prior 9 mo and the per patient change in total admissions, inpatient days, hospital costs, and Medicare hospital payments between the prior 9-mo period and the subsequent 9-mo period was examined. The adjusted relative odds (95% confidence interval) of admission (rHuEPO versus control) was: higher and statistically significant for all causes, 1.08 (1.03 to 1.14); seizure, 1.52 (1.28 to 1.75); vascular access revision, 1.11 (1.06 to 1.17), and heart failure, 1.17 (1.09 to 1.26); higher but not statistically significant for angina, 1.09 (0.99 to 1.20) and stroke, 1.08 (0.86 to 1.31); and lower but not statistically significant for myocardial infarction, 0.91 (0.72 to 1.10); peripheral vascular disease, 0.81 (0.60 to 1.02); anemia, 0.86 (0.56 to 1.17); and depression, 0.89 (0.37 to 1.40). The mean change per 1,000 patients in admissions was less by 38 (P = 0.03) because of fewer readmissions, and in days was 1,309 less (P < 0.001), for patients treated with rHuEPO versus controls. The mean change per patient in hospital costs was $371 less and was statistically significant (P = 0.03) and in Medicare hospital payments was $132 less but was not statistically significant (P = 0.43) for patients treated with rHuEPO versus controls. rHuEPO was associated with an increase in the probability of hospital admission (particularly admissions potentially related to adverse effects) but a decrease in readmissions, overall admissions, hospital days, and cost to hospitals in this cohort of patients surviving for 18 mo. Although not realized short term, Medicare savings from potential rHuEPO-related reductions in hospital care may be long term through future adjustments in diagnosis-related group-based hospital payment.
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PMID:Effect of recombinant erythropoietin on hospital admissions, readmissions, length of stay, and costs of dialysis patients. 816 27

Aiming to know the factors that influenced the use of erythropoietin (EPO) in chronic hemodialysis patients, we retrospectively studied 82 patients (41 male), of whom 15 received EPO. No differences, between patients receiving or not receiving EPO, were found in age (46.9 +/- 25 and 57 +/- 13 years respectively), male/female ratio (9/6 and 32/35 respectively), time on dialysis (36.4 +/- 25.6 and 36.8 +/- 31.8 months respectively), dialysis hours (3.19 +/- 0.6 and 3.33 +/- 0.39 h respectively) and proportion of diabetics (6.6 and 20.8% respectively). Prior to EPO use and compared to untreated patients, treated patients were transfused with a higher frequency (60 vs 22%) and with more units/patients/years (0.12 vs 0.08). Hemoglobin levels at the start of the treatment was similar in treated and untreated patients (8.4 +/- 1.46 vs 8.78 +/- 1.97 g/dl). EPO was indicated in 11 patients due to general symptomatology associated to anemia and in 4 due to cardiac failure or angina. We conclude that EPO treatment is indicated in approximately 18% of patients in dialysis. An adequate dialytic treatment may achieve optimal hemoglobin levels with minimal transfusion requirements and without need of EPO, thus reducing costs.
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PMID:[Erythropoietin and transfusions in patients with anemia of chronic renal failure origin : an update view]. 852 89

Post-traumatic stress-induced disorders are still the focus of interest and most recently discussions are under way whether stress-induced cortisol excess leads to atrophy of the brain. In investigation on carcinogenesis the first reports were published on the use of antisense-oligonucleotides during inhibition of the development of tumours by a humoral mechanism and on the gene-based neuroendocrine differentiation of the lungs, perhaps associated with the basis for the development of small cell carcinoma. The oncogenic action of superoxides has also humoral mediators. Interest in nitrogen oxide is focused on two areas: inflammations and hypertension. Intraluminal NO concentrations increase in asthma 2-10x, in cystitis 30-100x, in Crohn's disease 20-200x. Humoral mechanisms in asthma offer new drugs--inhibitors of the development or action of leucotrienes. The basal NO production is reduced in "essential" hypertension but it is not known whether it is the cause or consequence. IGF-I increases the formation of NO in the vascular wall and thus perhaps reduces vascular contractility. As far as IGF is concerned, it is obvious that if recombinant preparations will be available, they will be tested in amyotrophic lateral sclerosis, myotonic dystrophy, multiple sclerosis, catabolic conditions, osteoporosis, in renal failure and to promote wound healing. STH may also prove useful in cardiac failure, in particular in cardiac cachexia. That TRH has receptors in the gut is not surprising, it acts, however, even there via TSH. Thrombopoietin is being tested in clinical trials. Neocytolysis is a new phenomenon: when erythropoietin secretion declines new erythrocytes disappear and only old ones remain in the blood stream. Alpha-adducin is a renal tubular protein, regulating the sodium balance.
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PMID:[Endocrinology 1996-1997]. 965 Mar 40

Erythropoietin is an essential growth factor that promotes survival, proliferation, and differentiation of mammalian erythroid progenitor cells. Erythropoietin(-/-) and erythropoietin receptor(-/-) mouse embryos die around embryonic day 13.5 due, in part, to failure of erythropoiesis in the fetal liver. In this study, we demonstrated a novel role of erythropoietin and erythropoietin receptor in cardiac development in vivo. We found that erythropoietin receptor is expressed in the developing murine heart in a temporal and cell type-specific manner: it is initially detected by embryonic day 10.5 and persists until day 14.5. Both erythropoietin(-/-) and erythropoietin receptor(-/-) embryos suffered from ventricular hypoplasia at day 12-13 of gestation. This defect appears to be independent from the general state of hypoxia and is likely due to a reduction in the number of proliferating cardiac myocytes in the ventricular myocardium. Cell proliferation assays revealed that erythropoietin acts as a mitogen in cells isolated from erythropoietin(-/-) mice, while it has no effect in hearts from erythropoietin receptor(-/-) animals. Erythropoietin(-/-) and erythropoietin receptor(-/-) embryos also suffered from epicardium detachment and abnormalities in the vascular network. Finally, through a series of chimeric analysis, we provided evidence that erythropoietin acts in a manner which is non-cell-autonomous. Our results elucidate a novel role of erythropoietin in cardiac morphogenesis and suggest a combination of anemia and cardiac failure as the cause of embryonic lethality in the erythropoietin(-/-) and erythropoietin receptor(-/-) animals.
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PMID:Inactivation of erythropoietin leads to defects in cardiac morphogenesis. 1040 5

In the present study, the relationship between the blood erythropoietin level and cardiac function was investigated in 15 patients on chronic hemodialysis who developed chronic heart failure. Another 45 patients without cardiac dysfunction were selected as a control group that was matched for gender, age, and the duration of dialysis. The erythropoietin level was 256.3 +/- 481.8 mU/ml in the heart failure group, which was significantly higher than that in the control group (17.0 +/- 10.0 mU/ml, P < 0.01). Eight of the 15 patients in the heart failure group maintained a hematocrit of more than 30% without receiving recombinant human erythropoietin therapy, whereas 29 of the 45 patients in the control group required erythropoietin. In the heart failure group, the erythropoietin level was significantly correlated with the levels of atrial natriuretic peptide and brain natriuretic peptide (P < 0.01). These results suggest that heart failure can increase the erythropoietin level in proportion to the severity of cardiac dysfunction, even in patients on long-term dialysis.
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PMID:Relationship between erythropoietin and chronic heart failure in patients on chronic hemodialysis. 1054 2

Cardiovascular disease is a major cause of mortality and morbidity in patients with end-stage renal disease. Anemia, a result of erythropoietin deficiency, is associated with increased all-cause and cardiovascular mortality in this population, and predisposes patients to the development of symptomatic heart disease. Anemia is also associated with the development and progression of left ventricular echocardiographic disorders, which strongly predict cardiac failure and death. Left ventricular dilatation with compensatory hypertrophy, the major pattern of echocardiographic disease progression in hemodialysis patients, is a particularly strong predictor of late mortality. Partial correction of anemia with recombinant human erythropoietin likely reduces left ventricular mass and volume. Complete correction of anemia may prevent progressive left ventricular dilatation in patients with normal left ventricular volumes. A recent trial, however, reports excess mortality and vascular access loss in patients with preexisting symptomatic heart disease when anemia was completely corrected. Consequently, hematocrit target ranges above 32% to 36% cannot be recommended in this population. In patients without symptomatic heart disease, it is not possible to conclude that potential benefits derived from a normalized hematocrit will outweigh potential risks.
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PMID:The impact of anemia correction on cardiovascular disease in end-stage renal disease. 1092 37


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