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)

Recombinant human erythropoietin (rHu-EPO) is an effective growth factor for erythroid progenitor cells in anemia provoked by several conditions, including bone marrow tumors such as multiple myeloma (MM). We studied a group of 54 patients with MM undergoing second-induction chemotherapy. Thirty of them were randomly assigned to receive rHu-EPO at an initial dosage of 150 units/kg body weight three times a week, increased to 300 units/kg from the sixth week to the end of the 24-week study. Hemoglobin (Hb) levels increased in 77.7% of these patients by the eighth week. In addition, five transfusion-dependent patients in treatment with the VMCP protocol completed the trial without requiring blood supplement after the third month, whereas seven control patients required frequent supplements. Monthly assessment of hematologic parameters demonstrated the ability of rHu-EPO to increase reticulocyte counts, whereas five patients became resistant to the second-induction chemotherapy in apparent concurrence with their rHu-EPO therapy. The response to rHu-EPO in four of the five MM patients receiving cytotoxic protocols combined with alpha-interferon (alpha-IFN) included an increase of serum IgM after the third month. This effect was not demonstrable in any other group, including three rHu-EPO-untreated patients undergoing alpha-IFN + VMCP combined therapy, as well as rHu-EPO-treated patients not receiving alpha-IFN. Our data suggest that alpha-IFN plus rHu-EPO treatment in MM patients is effective in restoring normal B cell function. These results may reflect in vivo the modulation of normal human B cells and lymphoblasts by rHu-EPO observed in vitro.
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PMID:Long-term therapy with recombinant human erythropoietin (rHu-EPO) in progressing multiple myeloma. 763 11

Measurements of erythropoietin in fetal blood obtained by cordocentesis or in umbilical cordblood and maternal blood have shown a lack of correlation indicating an independent regulation of EPO concentration in fetal and maternal compartments. There is a good correlation between amniotic fluid EPO concentration in fetal blood levels. Fetal EPO concentration therefore might serve as an indicator of chronic fetal hypoxia with fetal EPO production being responsive to tissue hypoxia early on in pregnancy. The lack of human placental permeability for EPO was further investigated using a dual in vitro perfusion system of an isolated cotyledon in freshly delivered term placentae. With recirculation of both circuits trace amounts of EPO (0.04% of the amount added to the maternal compartment) were transferred to the fetal side during 4-5 hours of perfusion. This transfer is comparable to the rate determined in the same experiments for albumine, and the biological significance of this very slow transfer is questionable. A very low rate of diffusion across the human placenta has also been shown for dextran, horseradish peroxidase and heparin using an in vitro perfusion system. The only exception among macromolecules are immunoglobulines G, which towards the end of pregnancy are transferred by an Fc-receptor mediated transcellular mechanism from the mother to the fetus. It is concluded, that there is no easy exchange of EPO across the human placenta between maternal and fetal compartments. Changes in EPO concentration in the fetal compartment therefore could serve as indicator of fetal hypoxia. A therapeutic application of EPO in the mother for the treatment of chronic anemia would not have any effect on fetal tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lack of permeability of the human placenta for erythropoietin. 765 24

We studied the effects of recombinant human erythropoietin (rHuEPO) on anemic W/WV mice which manifested severe anemia accompanied by mutation of the W gene encoding tyrosine kinase type receptor (c-kit gene) of bone marrow hematopoietic cells. Nine-week-old male W/WV mice or normal littermates (+/+) were used. Since serum EPO concentration in W/WV mice increased in proportion to severity of anemia, EPO production in the kidneys of these animals was found to be regulated normally. Hematocrit in +/+ mice increased and a maximal response was also obtained with 2,000 IU/kg of rHuEPO. On the other hand, hematocrit in W/WV mice increased in a dose-responsive manner by administration with 2,000 and 10,000 IU/kg, showing different responses to rHuEPO in these two types of mice. The responsiveness of W/WV mice to rHuEPO was low in terms of increases in erythroblastic precursor cells (CFU-E), and immature cells in the bone marrow. Scatchard analysis of the specific binding of 125I-rHuEPO against bone marrow cells revealed that the different responsiveness to rHuEPO between W/WV and +/+ mice may be correlated with differences in affinity of EPO receptor of bone marrow cells in these mice. From these results, a high dose of rHuEPO is capable of improving the anemia in W/WV mice that had EPO receptors with lowered affinity, indicating the possible effectiveness of rHuEPO in anemic patients with EPO receptor abnormality.
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PMID:Improvement of anemia in W/WV mice by recombinant human erythropoietin (rHuEPO) mediated through EPO receptors with lowered affinity. 765 14

In the attempt to prevent malnutrition, a seven year longitudinal evaluation was carried out in 24 RDT patients in order to assess the efficacy of the following strategy: 1) Counseling for an adequate physical activity and a high caloric intake limiting dietary restrictions to fluids, salt and fruit. 2) Improvement of anemia by increasing dialysis dose and/or by administering EPO. 3) The use of high UF HDF in order to employ more biocompatible membranes and to improve small and middle molecules removal. Nutritional status was assessed by a biochemical screening and by evaluating the variations of dry body weight (BW), which had to be also confirmed by a normal cardiac volume. Moreover in all patients a 4 consecutive days dietary record was obtained one year before the end of the observation period. During this period the mean dry BW increased significantly except in the two last years, when it remained stable. The increase of BW was associated with a reduced incidence of hypertension, a significant increase of Hb and reduction of BUN and sCr. The remaining biochemical parameters were constantly in the normal range. The dietary record showed a mean caloric-proteic intake similar to that recommended for the general population. These data point out that the above strategy can prevent malnutrition in patients on RDT. It must be confirmed whether the use of more biocompatible membranes and the removal of the middle molecules can play an important role in this setting.
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PMID:[Can malnutrition be prevented in patients on chronic extracorporeal dialysis?]. 770 10

Nine B-chronic lymphocytic leukaemia (B-CLL) patients suffering from anaemia, due to no obvious cause except their disease, were treated with recombinant human erythropoietin (r-HuEPO). The treatment protocol provided a closed label phase of 3 months duration, during which the patients received r-HuEPO or placebo in a ratio of 2:1, followed by an open label phase, also of 3 months duration, during which r-HuEPO was administered to all patients three times a week s.c. r-HuEPO was given a dose of 150 U/kg of body weight with an escalation of 50 U/kg up to a maximum of 300 U/kg three times a week. Complete response was achieved in 5/9 (55%) patients and partial response in 3/9 (33%). The response obtained was independent of the pretreatment serum EPO levels, the duration of anaemia, the concomitant administration of chemotherapy, the presence of splenomegaly, or the degree of bone marrow infiltration by lymphocytes. It appears that r-HuEPO is very effective in reversing the disease-related anaemia of B-CLL patients.
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PMID:Effective treatment of disease-related anaemia in B-chronic lymphocytic leukaemia patients with recombinant human erythropoietin. 773 64

Chronic anemia of cancer can be corrected in approximately 50% of the cases by treatment with recombinant human erythropoietin (rHuEPO). Early prediction of responsiveness would avoid the emotional and financial burden of ineffective medical intervention. Eighty patients with chronic anemia of cancer undergoing treatment with rHuEPO (150 U/kg, 3 times per week by subcutaneous injection; after 6 weeks without response, 300 U/kg) participated in this study. Response was defined as a gain of at least 2 g/dL hemoglobin (Hb) within 12 weeks. Multivariate discriminant analysis and logistic regression analysis of response were performed on routine blood tests; serum levels of EPO, iron, ferritin, transferrin, and its receptor; World Health Organization (WHO) performance status; various cytokines; neopterin; stem cell factor; C-reactive protein; and alpha 1-antitrypsin. At baseline, none of these factors showed sufficient prognostic power. The following predictive algorithm was developed: (1) If after 2 weeks of therapy both the serum EPO level is > or = 100 mU/mL and Hb concentration has not increased by at least 0.5 g/dL, unresponsiveness of the patient is very likely (predictive power, 93%); otherwise, response may be predicted with an accuracy of 80%. (2) If both the serum level of EPO is less than 100 mU/mL and Hb concentration has increased by > or = 0.5 g/dL, response is highly probable (predictive power, 95%). (3) Alternatively, a serum ferritin level of > or = 400 ng/mL after 2 weeks of rHuEPO therapy strongly indicates unresponsiveness (predictive power, 88%), whereas a level less than 400 ng/mL suggests response in 3 of 4 patients.
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PMID:Prediction of response to erythropoietin treatment in chronic anemia of cancer. 788 86

Chemotherapy-induced anemia in children with cancer is usually of acute onset. To investigate an alternate treatment to transfusion (Tx), we undertook a phase I-II clinical trial of daily administrations of recombinant erythropoietin (rHuEPO). Patients with a hemoglobin (Hgb) value < 75 g/l were treated for 14 days in cohorts of 3 at escalating daily doses of 25, 50, 70, 80, 90, and 100 U/kg respectively. The maximum-tolerated dose was not encountered. Of 18 courses given to 15 children aged 0.5-18 years, 7 (39%) were associated with increased or stable Hgb levels (courses without Tx), while 11 (61%) were terminated by a Tx, without evidence of a dose-response relationship. Changes in mean Hgb levels and absolute reticulocyte counts were paralleled by those of mean white blood cell, platelet, and absolute neutrophil counts during the first 7 days and when the end-points of the study were reached. Numbers of circulating burst-forming units-erythroid remained low throughout courses without Tx. No cumulative increase of serially determined serum EPO levels was observed and serum ferritin levels were elevated in both groups of courses. We conclude that daily administration of rHuEPO were safe but ineffective in our trial. Recovery of chemotherapy-induced myelosuppression appeared to be the rate-limiting factor for the outcome, without evidence of an enhanced stimulation of erythropoiesis. The lack of a proliferative response of specific progenitor cells suggested a mechanism of transient primary resistance to rHuEPO.
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PMID:Recombinant erythropoietin in acute chemotherapy-induced anemia of children with cancer. 775 97

The superimposition of human immunodeficiency virus (HIV) infection, associated opportunistic infections, and anti-retroviral therapy further worsens the severity of anemia in patients also suffering from end-stage renal disease. A major cause of anemia in renal failure is a deficiency of erythropoietin. The causes of anemia in HIV disease include direct and indirect stem cell inhibition by the virus, increased peripheral destruction of red blood cells, and bone marrow suppression by various opportunistic infections and therapeutic drugs, particularly zidovudine. We compared the efficacy of recombinant human erythropoietin (rHuEPO) therapy in improving the anemia in HIV-infected end-stage renal disease patients (group I) with that in nondiabetic (group II) and diabetic (group III) hemodialysis patients without HIV infection. All three groups of patients were comparable in dialysis prescription and serum iron studies. Iron supplementation was prescribed to all patients, and none received blood transfusions. After 8 weeks of rHuEPO therapy (administered intravenously in a dose of 100 U/kg body weight thrice weekly), the mean increase in hematocrit was similar in all responders (5.8% increase in hematocrit in 23 of 30 HIV patients and 6.7% increase in 24 of 30 non-HIV patients). Response in hematocrit was noted in HIV patients despite the presence of opportunistic infections in 15 and zidovudine administration in 11. Seven HIV-positive patients and six non-HIV patients failed to respond to rHuEPO. Irrespective of the HIV status, the baseline serum EPO levels in patients responding to rHuEPO were significantly lower than those in nonresponders.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The efficacy of erythropoietin in human immunodeficiency virus-infected end-stage renal disease patients treated by maintenance hemodialysis. 777 87

Eight young children with renal failure, undergoing continuous peritoneal dialysis (CDP) and presenting an anemia (hemoglobin level [Hb] 57 to 89 g/l) were treated by subcutaneous recombinant human erythropoietin (rHu EPO) twice weekly. The initial dose of 75 U/kg was adjusted to induce progressive increase of Hb with a target level of 100-120 g/l. Treatment duration was 24 weeks in five of these children and 10 to 13 weeks in the three others. In seven cases out of eight, anemia was corrected. The target Hb level was reached in 3 to 21 weeks with rHu EPO doses of 150 to 300 U/kg/w (mean: 200 U/kg/w) for four children without recent transfusion; then the median maintenance dose was 135 U/kg/w (range: 50-300 U/kg/w). In only one patient, Hb never reached a level higher than 77 g/l despite weekly dose of 350 U/kg, a reticulocytosis of 5.6%, rHu EPO treatment lasting up to 24 weeks and the absence of iron deficiency. In any case, no transfusion was necessary after the first day of rHu EPO treatment. In three patients, the increase of a preexisting hypertension required the adaptation of antihypertensive treatments. One patient presented a marked thrombocytosis. In conclusion, twice-a-week subcutaneous injections of 75 to 150 U/kg of rHu EPO appear to be well tolerated and effective in the treatment of anemia of CPD children.
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PMID:[Effectiveness of and tolerance to human recombinant erythropoietin in the treatment of kidney failure anemia in children undergoing continuous peritoneal dialysis. Multicenter study]. 777 95

Anemia was induced in rats by the development of a hemorrhagic ascites. These animals also bore solid tumors (DS-sarcomas) on the hind foot dorsum. The effects of two methods for anemia correction on oxygenation in the solid tumors were compared in this study. Anemia was corrected either chronically by erythropoietin administration (1000 IU/kg) over 14 days (EPO) or acutely by transfusion with red blood cells (TR). Non-anemic and untreated anemic animals served as controls. Tumor oxygenation was determined in anesthetized animals using polarographic needle electrodes and pO2 histography. The reduction in hematocrit and hemoglobin content found in anemic animals could successfully be corrected either by EPO or by TR. Anemia resulted in a worsening of tumor oxygenation which could partially be reversed by EPO or TR in small tumors (< 1.4 ml). In larger tumors (> or = 1.4 ml), neither method of anemia correction resulted in significant changes in tumor oxygenation.
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PMID:Tumor oxygenation in anemic rats: effects of erythropoietin treatment versus red blood cell transfusion. 777 26


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