Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum erythropoietin (S-EPO) levels were measured in 50 patients with anaemia of chronic disorders (ACD), classified into three groups according to their aetiology: inflammatory (n = 20), infectious (n = 15) and neoplastic (n = 15). The inflammatory group showed a higher mean S-EPO level (mean value +/- SEM, 69 +/- 11 mU ml-1) than the neoplastic (43 +/- 5 mU ml-1; P less than 0.05) and infectious groups (27 +/- 4 mU ml-1; P less than 0.01). The S-EPO level in the inflammatory group also differed from that of 32 healthy controls (36 +/- 3 mU ml-1; P less than 0.05). Fourteen patients with added iron deficiency (12 subjects from the inflammatory group) showed the highest S-EPO concentration (72 +/- 17 mU ml-1). Conversely, S-EPO levels were lower in febrile subjects (12 patients with infection and five with malignancy) than in non-febrile patients (28 +/- 4 mU ml-1 vs. 55 +/- 7 mU ml-1; P less than 0.01). In the infectious group, the logarithm of S-EPO correlated directly with the haemoglobin and haematocrit values. We conclude that differences in S-EPO concentration in ACD may be further related to the patient's iron stores and temperature. A decrease in EPO production may contribute to the pathogenesis of ACD secondary to infection.
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PMID:Serum erythropoietin levels in the anaemia of chronic disorders. 199 63

Recombinant human erythropoietin was administered subcutaneously to 10 patients with myelodysplasia (MDS) who had haemoglobin concentrations less than 10 g/dl, in an attempt to relieve their anaemia. Doses of 60 units/kg/d rising to 90 units/kg/d were given over a maximum period of 16 weeks. Two out of 10 patients showed a steady rise in haemoglobin concentration during treatment. One patient with refractory anaemia had a sustained rise from 9.9 g/dl to 11.3 g/dl, and one patient with refractory anaemia with excess blasts (RAEB) had a rise from 9.5 g/dl to 11.4 g/dl but then relapsed with the development of an iron deficient state. Serum concentrations of immunoreactive EPO varied considerably between patients, but both responders had relatively low baseline levels. Both responders were also new diagnoses and had received no red cell transfusions. The criteria for response to recombinant human erythropoietin therapy, as well as the indications for therapy remain to be clarified.
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PMID:The treatment of anaemia in the myelodysplastic syndromes with recombinant human erythropoietin. 201 69

Epoetin (recombinant human erythropoietin, EPO) is of proven benefit in the treatment of renal anaemia, and preliminary reports suggest that it may have a role in the management of other anaemic conditions. Pharmacokinetic and therapeutic studies have examined the use of epoetin administered intravenously, intraperitoneally and subcutaneously, and there is accumulating evidence that the last route has several advantages. After intravenous administration, epoetin is distributed in a volume comparable to the plasma volume, and plasma concentrations decay monoexponentially with a half-life of between 4 and 12 hours. Administration of epoetin in peritoneal dialysis fluid results in detectable concentrations in the bloodstream after 1 to 2 hours, and peak concentrations of the order of 2 to 4% of those obtained with the same intravenous dose are found after approximately 12 hours. The bioavailability of epoetin administered intraperitoneally in dialysis fluid is about 3 to 8%, but this may be increased by injecting the drug into a dry peritoneal cavity. Subcutaneous administration results in peak concentrations at about 18 hours which are 5 to 10% of those found after the same intravenous dose. The bioavailability of subcutaneous epoetin is about 20 to 30% and detectable serum concentrations are still present 4 days after administration, in contrast to intravenous administration after which concentrations have returned to baseline within 2 to 3 days. Remarkably little is known about the metabolic fate of either erythropoietin or epoetin. In addition, there is much controversy surrounding the relative roles of the kidney and liver in the catabolism of epoetin. About 3 to 10% of epoetin is excreted unchanged in the urine. In common with other glycoproteins, the carbohydrate residues which constitute 40% of its molecular size are essential for maintaining the stability of epoetin in circulation. Desialated epoetin, although biologically active in vitro, is cleared very rapidly from plasma with resultant loss of activity. Further work is required, however, in identifying the pathways of metabolism and elimination of this glycoprotein hormone.
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PMID:Clinical pharmacokinetics of epoetin (recombinant human erythropoietin). 202 9

Digital vascular reactivity was determined in 12 normotensive patients on chronic hemodialysis without a history of Raynaud's phenomenon before and after partial correction of anaemia with human recombinant erythropoietin (rHuEPO): apparent finger systolic pressures and finger skin temperatures were recorded at rest, after local cooling, and following 5 minutes rewarming time. Finger systolic pressures remained constant during the whole test, pre and post rHuEPO therapy. The decrease in finger skin temperatures after cold provocation as well as the rewarming behaviour after cooling were normal in both examinations. The present data indicate that treatment with EPO does not interfere with digital arterial reactivity in normotensive patients on haemodialysis.
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PMID:Digital vascular reactivity in patients on haemodialysis treated with human recombinant erythropoietin. 203 4

We studied platelet number and function in nine anaemic children with end-stage renal disease during a clinical trial with recombinant human erythropoietin (rHu-EPO). All the children showed a correction in both haematocrit and haemoglobin levels which was followed by a significant reduction in bleeding time. We also observed a significant increase in platelet count after both 6 and 12 weeks of therapy; at the same time mean platelet volume decreased and a normal platelet mass was maintained. The mean baseline platelet aggregation response to ADP was normal, but was decreased to collagen (P less than 0.05 vs normal control). Platelet production of thromboxane B2 in serum was also lower than normal controls. After correction of anaemia with rHu-EPO, platelet aggregation improved in patients with a decreased baseline response, and mean levels of thromboxane B2 became normal. In conclusion, the treatment with rHu-EPO improved haemostatic balance not only by correcting anaemia, but also by increasing platelet count and function.
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PMID:Effect of human recombinant erythropoietin on bleeding time, platelet number and function in children with end-stage renal disease maintained by haemodialysis. 203 40

Experimental and clinical data implicate inadequate erythropoietin production as an important reason that infants acquire this anemia and suggest that recombinant human erythropoietin (r-HuEPO) might be used to treat or prevent it. We therefore randomly assigned 20 small premature infants (birth weight less than or equal to 1250 gm) who were highly likely to require erythrocyte transfusions for anemia of prematurity to receive 6 weeks of treatment with either intravenously administered r-HuEPO (at a dose of 100 units/kg twice each week) or a placebo. Hematologic measurements, transfusion requirements, and growth were followed during therapy and for 6 months thereafter. Treated (EPO) and control babies did not differ with respect to weight, hematocrit, overall mean absolute reticulocyte count, calculated erythrocyte mass, or rate of growth. However, reticulocyte counts increased earlier in patients given r-HuEPO. Six of ten babies in the EPO group, and 8 of 10 assigned to the control group, received at least one erythrocyte transfusion during treatment. For all infants the amount of blood sampled for laboratory tests was strongly predictive of the volume of packed erythrocytes transfused (r = 0.890; p = 0.0001). Of nine infants who had less than 20 ml packed erythrocytes removed for laboratory tests, none of four given r-HuEPO received a transfusion, whereas three of five infants assigned to the placebo group received one. No toxic effects were attributable to r-HuEPO, and no significant changes in leukocyte or platelet counts occurred during treatment. Reticulocyte counts were correlated with simultaneous platelet counts and were inversely related to absolute neutrophil counts in both study groups. We conclude that r-HuEPO administration is safe and feasible at the dose studied. Additional controlled trials utilizing higher doses of r-HuEPO and larger numbers of patients are justified.
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PMID:Recombinant human erythropoietin in the anemia of prematurity: results of a placebo-controlled pilot study. 155 15

Plasma levels of follitropin (FSH), lutropin (LH) and testosterone (TE) were estimated in 5 anaemic haemodialyzed patients before and after 3 months of erythropoietin treatment (EPO group), in 5 male haemodialyzed patients with a haematocrit value of 33% (which was of the same magnitude as the post-treatment haematocrit value in the EPO group) and in 15 male healthy subjects. After EPO treatment, haematocrit values rose from 23.0 +/- 0.9 to 34.6 +/- 0.75%. EPO treatment induced a significant suppression of basal plasma FSH and LH levels, while plasma TE levels slightly increased. After EPO treatment, the response of plasma FSH and LH to luliberin administration was significantly reduced. As the endocrine profile of EPO-treated patients differed from that of haemodialyzed patients showing a similar haematocrit value, it seems that EPO-induced hormonal changes are not or not only related to improvement of anaemia. Normalization of the pituitary-gonadal feedback in EPO treatment seems to participate in the pathogenesis of improved sexual activity in these patients.
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PMID:Influence of erythropoietin treatment on follitropin and lutropin response to luliberin and plasma testosterone levels in haemodialyzed patients. 212 18

The etiology of the anemia of chronic disorders is complex. Factors which clearly contribute to the suppression of erythropoiesis are (a) reduced iron availability and (b) stimulation of the synthesis of immunomodulatory peptides such as IL-1, TNF-alpha and IFN-gamma, which inhibit the proliferation of erythrocytic progenitors in the bone marrow. The question as to whether lack of EPO is of general importance in the pathogenesis of the anemia of chronic inflammatory and malignant diseases is still a subject of controversy. The present in vitro studies show that IL-1 and TNF-alpha, but not IFN-gamma significantly lower the pO2-dependent formation of EPO in HepG2 cultures. In addition, clinical examples are given of anomalously low or high EPO levels in association with diseases involving the immune system. It is proposed that monokines and related immunomodulatory peptides could play a role in the control of the production of EPO.
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PMID:Modulation of the production of erythropoietin by cytokines: in vitro studies and their clinical implications. 212 66

Lymphocyte subpopulations were studied by immunofluorescence staining with monoclonal antibodies and laser flow cytometry in the blood of 23 hemodialysis patients before and after 3 months of treatment with recombinant human erythropoietin (rhEPO). Correction of anemia was accompanied by an increase in natural killer cells and a decrease in B lymphocytes. In the 11 patients (Group 1) with a baseline helper/suppressor (T4/T8) ratio greater than or equal to 2, the latter significantly decreased from 3.0 +/- 0.3 to 2.1 +/- 0.3 through both an increase in T8 cells and a decrease in T4 cells (p less than 0.005). Among the 12 patients with a pre-EPO T4/T8 ratio less than 2 (Group 2), no difference in T cell subsets was observed. The decrease in ferritin levels observed over the study period was not significant. In addition, the mean increase in hemoglobin levels during the first month of rhEPO therapy was greater in Group 2 than in Group 1 (1.1 +/- 0.3 vs. 0.6 +/- 0.3 g/dl, p less than 0.025). No change in any parameter was observed in eight control patients not receiving rhEPO. These results suggest that rhEPO can induce changes in lymphocyte subpopulations of hemodialysis patients through mechanism(s) yet to be clarified; conversely, the T4/T8 ratio might be a predictive factor for the erythropoietic response to rhEPO.
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PMID:Effects of recombinant human erythropoietin on T lymphocyte subsets in hemodialysis patients. 214 56

Sequential changes in serum erythropoietin (sEPO) levels were measured by radioimmunoassay in six patients receiving autologous rescue (AR) and 11 patients receiving an allogeneic bone marrow transplant (BMT) for malignant disease. Longitudinal studies showed an inverse relationship between sEPO and haemoglobin levels in the autologous rescue and allogeneic transplant patients throughout the 130 d post-transplant study period. Early post-conditioning EPO responses were normal for the haemoglobin level in both groups, but after day 14 post-transplant, erythropoietin production in response to anaemia became impaired in one autologous rescue patient and eight of the 11 allogeneic transplant patients. There was no clear association between late impairment of sEPO production and conditioning therapy, infection, graft-versus-host disease, immunosuppressive therapy or serum creatinine. Blood transfusion requirements were similar for both groups in the first month after transplantation, but from days 31 to 90 post-transplant, BMT patients required an average of 5.5 units per patient compared with 1 unit per patient for the autologous group. Marrow transplant procedures do not affect early EPO responses but may diminish late responses. The potential value of exogenous rHuEPO in hastening engraftment and decreasing transfusion requirements, particularly for those patients who appear to have impaired EPO responses, remains to be shown by clinical trials.
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PMID:Serum erythropoietin changes in autologous and allogeneic bone marrow transplant patients. 222 32


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