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)

Tumor necrosis factor-alpha (TNF) is a monokine produced by activated macrophages that has cytotoxic and cytostatic effects on erythroid progenitor cells. We have recently shown that Chinese hamster ovary cells transfected with the human TNF gene and which constitutively express TNF induced a hypoproliferative anemia, mild thrombocytopenia, and mild leukocytosis when injected into nude mice. We have used this murine model to determine if treatment with recombinant human erythropoietin can prevent or ameliorate the anemia seen with long-term continuous exposure to high concentrations of TNF. Mice bearing TNF-producing tumors became anemic with hematocrits ranging from 30% to 32%. Treatment with recombinant human erythropoietin (100-1000 U/kg body weight three times per week) increased the reticulocyte counts initially in mice bearing TNF-producing tumors but failed to reverse the anemia seen in these animals. Erythropoietin did not significantly increase the number of marrow erythroid colony-forming units (CFU-E) or erythroid burst-forming units (BFU-E) in mice bearing TNF-producing tumors. The data suggest that erythropoietin could not sufficiently overcome the decreased number of erythroid progenitors in mice bearing tumors producing high levels of TNF to correct their anemia.
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PMID:Erythropoietin fails to reverse the anemia in mice continuously exposed to tumor necrosis factor-alpha in vivo. 233 32

Epoetin alfa (recombinant human erythropoietin) effectively diminishes the anemia associated with end-stage renal disease (ESRD). Although many clinical manifestations of ESRD have been attributed to uremic toxins, the ability of epoetin alfa therapy to improve several of these conditions, such as diminished energy levels, appetite, cold tolerance, sexual function, and cognitive abilities, suggests that anemia may be an important factor in uremia-associated symptoms. Correction of this anemia results in improvements in the patient's quality of life. These improvements can be measured by objective criteria such as exercise tolerance tests, or by subjective standards such as patient response to questionnaires. In studies to date, both subjective and objective data show that epoetin alfa therapy significantly improves the quality of life of patients with ESRD.
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PMID:Perspectives on the improvement of quality of life with epoetin alfa therapy. 234 8

An increase in bone marrow blood flow has been previously described in anaemic rabbits and dogs. We examined the effect of haemorrhage and haemolysis in female Sprague-Dawley rats, with the hypothesis that high blood flow was related to hyperplasia of bone marrow tissue and that the increase would affect bone as well. Blood flow was measured in tibia and femur by the microspheres trapping method. Chronic anaemia was accompanied at day 32 by a marked increase (factor of 1.7-1.9) in blood flow to bone marrow and to bone. On the other hand, no increase in blood flow was observed in chronic compensated anaemia, showing that anaemia per se and not stimulation of erythropoiesis was responsible for the increase. We then explored the effect on blood flow of two factors associated with anaemia. Erythropoietin 4 U/d for 4 d failed to induce any increase in bone and marrow blood flow. Systemic hypoxia (76 mmHg for 3 d) reduced the fraction of cardiac output conveyed to bone and marrow by 40-50%, but this decrease was more than compensated by an increase in cardiac output. We conclude that neither erythropoietin nor low tissue pO2 is the direct cause for the increase in bone and marrow blood flow observed in anaemia.
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PMID:Anaemia and marrow blood flow in the rat. 234 30

Treatment of renal anemia with recombinant human erythropoietin in chronic hemodialysis patients has been reported to lead to increased appetite, and in several studies, to an increase in predialysis serum urea, potassium and creatinine values. We recorded dietary intake, and dialysis clearances for creatinine, urea and uric acid in a group of 12 anemic hemodialysis patients treated with recombinant erythropoietin (epoetin beta). A gradual increase was noted in dietary intake of calories, carbohydrate and sodium during the study period, attaining statistical significance after 10-12 months of therapy. A trend toward increased dietary intake of protein, lipid and potassium was observed, but the differences did not achieve statistical significance. Although a trend toward decreased dialysis clearance at higher hematocrits was found for creatinine clearances did not change significantly for any of the solutes examined, and linear regression analysis did not demonstrate a strong relationship between dialyzer clearance and hematocrit values within the range observed in this study.
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PMID:Effect of erythropoietin therapy on diet and dialysis clearances in hemodialysis patients. 237 50

The effects of angiotensin converting enzyme (ACE) inhibitors and their combined use with an antiestrogenic steroid on erythropoiesis were investigated in patients on chronic hemodialysis (CHD). Hematocrit was decreased by 10% or more in 6 of 12 patients who received either captopril or enalapril for 2-6 months. Erythropoietin (Epo) and angiotensin II (AII) were significantly reduced in these patients. When treatment with mepitiostane was combined with ACE inhibitor, anemia was significantly improved but without evidence of changes in circulating Epo concentrations or indices of renin-angiotensin activity. The reduction of AII and Epo formation by ACE inhibitors seems to play an important role in the worsening of anemia in patients on CHD; addition of an antiestrogenic steroid should be considered.
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PMID:Worsening of anemia by angiotensin converting enzyme inhibitors and its prevention by antiestrogenic steroid in chronic hemodialysis patients. 247 97

Five glycoprotein growth factors capable of stimulating the proliferation and differentiation of haemopoietic progenitor cells in vitro have been identified and sequenced over the past ten years. Recombinant DNA technology has recently enabled the production of sufficient amounts of these agents for preclinical testing. Erythropoietin (EPO), granulocyte-macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF) have already entered clinical studies in humans. Interleukin-3 (IL-3) and macrophage colony-stimulating factor (M-CSF) should soon be available for use in humans. EPO corrects the anaemia of end stage renal failure, improving the quality of life for such patients and preventing the need for red cell transfusions. At high dose it increases platelet production in vitro and in vivo and may be of value in humans to prevent the thrombocytopaenia associated with chemotherapy. G-CSF and GM-CSF have been used in several clinical studies. Administration of both growth factors results in a leucocytosis, G-CSF predominantly increasing neutrophil production and GM-CSF increasing production of neutrophils, eosinophils and monocytes. The optimal administration of these agents is via continuous intravenous infusion or daily subcutaneous injections at doses of 3-10 micrograms/kg/24 h. GM-CSF has shown promising results in patients with AIDS and the myelodysplastic syndrome and both G-CSF and GM-CSF have reduced the duration of neutropaenia and incidence of infection associated with chemotherapy. These agents may allow an escalation of the dose-intensity of chemotherapy in the future and thereby, hopefully, increase the response rate and survival for patients with a variety of neoplasms. Several other potential roles for these haemopoietic growth factors are discussed.
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PMID:Clinical trials with haemopoietic growth factors. 249 Dec 51

Data presented in this study suggest existence of hyperendorphinism in uraemic patients. This hyperendorphinism may be regarded both as a primary beneficial compensatory mechanism counteracting disturbances of the internal environment, while causing secondary harmful side effects, which contribute to the uraemic state. Erythropoietin treatment of uraemic, haemodialyzed patients is followed by marked endocrine alterations (suppression of plasma levels of STH, ACTH, prolactin, glucagon, aldosterone, cortisol and plasma renin activity, elevation of plasma insulin and atrial natriuretic levels, lack of influence on plasma PTH, CT and AVP). It remains to be clarified whether the erythropoietin induced endocrine alterations are due to correction of the existing anaemia or reflect a specific effect of this hormone.
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PMID:Endocrine abnormalities in patients with endstage renal failure. 256 Mar 46

Terminal renal dysfunction (TRD) was induced in 2 groups of dogs by partial surgical ablation of the kidney. Dogs of a control group and of 1 of the TRD groups were maintained on a diet containing normal phosphorus concentration, whereas dogs of the other TRD group were maintained on a low-phosphorus diet. Mild anemia developed in dogs of both TRD groups and could not be attributed to iron deficiency, increased erythrocyte concentration of 2,3-diphosphoglycerate, or absolute deficiency of erythropoietin (EP). Subsequently, all dogs were acutely depleted of approximately 25% of their blood volume. Erythropoietin concentration in dogs of the TRD groups was lower than that of controls, however, erythroid regenerative capacity was comparable with that of control dogs when plasma parathyroid hormone (PTH) concentration was lowered by reduced dietary intake of phosphorus. The PCV in dogs of the chronic TRD groups had a slight positive correlation with serum EP concentration, and a significant (P less than 0.05) negative correlation with plasma PTH and serum phosphorus and creatinine concentrations, using a correlation matrix. There was no longer a significant correlation between plasma PTH concentration and PCV after controlling for serum creatinine concentration by use of a multiple linear regression analysis. A significant (P less than 0.05) negative correlation also was observed between plasma PTH and serum EP concentrations, but not between serum EP and phosphorus or creatinine concentrations. Significance of the EP and PTH association was reduced when analyzed, using a multiple linear regression analysis that included serum creatinine values.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of parathyroid hormone in the anemia of chronic terminal renal dysfunction in dogs. 261 21

Hematologic growth factors are now assessible in recombinant forms, and thus available in amounts making cliical use possible. Erythropoietin, which induces differentiation and proliferation of the red blood cells, is produced by recombinant techniques. Clinical trials have shown the effectiveness of erythropoietin in correcting the anaemia of end stage renal diseare in patients maintained by haemodialysis. One of the growth factors for white blood cells, so called colony stimulating factors (CSF) has been given to patients suffering from AIDS. The growth factor given (GM-CSF) has a stimulatory effect upon granulocytes as well as monocytes. The clinical trial showed that the low white cell counts of the patients were normalized in a dose-dependent manner after GM-CSF administration. Clinical studies are under way. Erythropoietin, GM-CSF and G-CSF (stimulates granulocytes) are now being tested at medical centers in patients with AIDS, various forms of anemia, cancer and bone marrow transplants.
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PMID:[Factors influencing hematopoiesis--a new therapeutic alternative?]. 264 79

Haemopoietic growth factors have for over two decades allowed experimentalists to grow haemopoietic bone marrow cells in vitro. With refinements in technique and the discovery of novel growth factors, all of the known haemopoietic lineages can now be grown in vitro. This has allowed a much greater understanding of the complex process of haemopoiesis from the haemopoietic stem cell to the mature, functioning end-cell. The in vivo action of these growth factors has been harder to investigate. Although recombinant technology has afforded us the much greater quantities necessary for in vivo work, problems remain with administration because of effects on other tissues. Interpretation of results is difficult because of the complex inter-relationships which exist between factors. Some of these have been defined in vitro and it appears likely that they also operate in vivo. Erythropoietin is a physiological regulator of erythropoiesis. It has been detected in vivo with levels responding appropriately to stress (i.e. elevated in anaemia) and, when administered in pharmacological doses, has been shown to correct anaemia. Granulocyte/macrophage colony-stimulating factor (GM-CSF) has been detected in vivo and may influence the production and function of granulocytes and macrophages, although how it is regulated is unknown. Granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor are ore lineage-specific. Interleukin 3 (IL-3), although it has not been detected in vivo, may act on a primitive marrow precursor by expanding the population and making these cells more susceptible to other growth factors, such as GM-CSF. Interleukin 1 (IL-1) has been detected in vivo, does not appear to have any isolated action on bone marrow (except possibly radioprotection) but probably acts synergistically with other growth factors, such as G-CSF. Interleukins 2, 4, 5 and 6 have not been detected in vivo. All have effects on B-cells. In addition IL-2 is an essential factor for the in vitro growth of T-cells and may have antitumour effects in vivo. IL-5 is an eosinophil growth factor in vitro. Megakaryocytopoiesis is also affected by humoral factors. Factors, alone or in combination, may be useful to restore functional granulopoiesis when used therapeutically. Some can be used as anticancer agents, although there may be a risk of induction of haematological malignancy. Increased understanding of their physiological roles will allow a more rational use.
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PMID:Growth factors in haemopoiesis. 264 65


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