Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An evaluation of 26 surviving outpatient lung transplant recipients at one center showed that 65% (17/26) had significant anemia (hemoglobin < 11 g/L for women, < 14 g/dl for men) at a median follow-up of 13.5 months after transplantation (range, 1-41 months). There were 14 men and 12 women with a mean age of 45.1 years (range, 23.1-66.7 years). Fifteen had a double allograft and 11 had a single allograft. Anemia was normochromic and normocytic/macrocytic with a tendency to anisocytosis, with normal reticulocyte counts. Iron deficiency (transferrin saturation < 20%) was found in 35% (6/17) of anemic patients, and two of them also had ferritin levels < 15 micrograms/L. In addition, vitamin B12 was decreased in 1 patient. Folate levels were all normal. Erythropoietin levels were significantly decreased in anemic lung transplant recipients as compared with nontransplanted iron-deficient anemic patients (median, 1 mU/ml, range 1-41 mU/ml, vs. 53 mU/ml, 15-88 mU/ml; P < 0.05). In nonanemic lung transplant recipients, erythropoietin levels were decreased too, as compared with normal controls (median, 2 mU/ml, range 1-21 mU/ml, vs. 5 mU/ml, 3-32 mU/ml; P < 0.05). Investigation of peripheral stem cells in 9 patients showed normal stimulation of erythroids (burst-forming unit, erythroid; median, 573 cells/ml; range, 128-1898 cells/ml) independent of erythropoietin concentrations. Analysis of putative prognostic factors, such as age, surgical procedure (double vs. single lung allograft), indication for transplantation, time after transplantation, infection status, presence of bronchiolitis obliterans, immunosuppression (+/- azathioprine), serum creatinine, creatinine clearance, hypertension, and arterial partial pressure of oxygen, did not demonstrate any difference in erythropoietin concentrations. Only the sex variable revealed a trend to higher levels in women than in men (median, 4 mU/ml, range 1-41 mU/ml, vs. 1 mU/ml, 1-16 mU/ml; P > 0.05). The causes for low erythropoietin levels are not quite understood yet; however, they offer a rationale for the treatment of chronic anemia with recombinant human erythropoietin.
 ...
PMID:Anemia and erythropoietin levels in lung transplant recipients. 852 18

Systemic-onset juvenile chronic arthritis (SoJCA) is associated with high levels of circulating interleukin-6 (IL-6) and is frequently complicated by severe microcytic anemia whose pathogenesis is unclear. Therefore, we studied 20 consecutive SoJCA patients with hemoglobin (Hb) levels <12 g/dL, evaluating erythroid progenitor proliferation, endogenous erythropoietin production, body iron status, and iron supply for erythropoiesis. Hb concentrations ranged from 6.5 to 11.9 g/dL. Hb level was directly related to mean corpuscular volume (r = .82, P < .001) and inversely related to circulating transferrin receptor (r = -.81, P < .001) suggesting that the severity of anemia was directly proportional to the degree of iron-deficient erythropoiesis. Serum ferritin ranged from 18 to 1,660 microgram/L and was unrelated to Hb level. Bone marrow iron stores wore markedly reduced in the three children investigated, and they also showed increased serum transferrin receptor and normal-to-high serum ferritin. All 20 patients had elevated IL-6 levels and normal in vitro growth of erythroid progenitors. Endogenous erythropoietin (epo) production was appropriate for the degree of anemia as judged by both the observed to predicted log (serum epo) ratio 10.95 +/- 0.12) and a comparison of the serum epo-Hb regression found in these subjects with that of thalassemia patients. Multiple regression analysis showed that serum transferrin receptor was the parameter most closely related to hemoglobin concentration: variation in circulating transferrin receptor explained 61% of the variation in Hb level (P < .001). In 10 severely anemic patients, amelioration of anemia following intravenous iron administration resulted in normalization of serum transferrin receptor. Defective iron supply to the erythron rather than blunted epo production is the major cause of the microcytic anemia associated with SoJCA. A true body-iron deficiency caused by decreased iron absorption likely complicates long-lasting inflammation in the most anemic children, and this can be recognized by high serum transferrin receptor levels. Although oral iron is of no benefit, intravenous iron saccharate is a safe and effective means for improving iron availability for erythropoiesis and correcting this anemia. Thus, while chronically high endogenous IL-6 levels do not appear to blunt epo production, they are probably responsible for the observed abnormalities in iron metabolism. Anemia of chronic disease encompasses a variety of anemic conditions whose peculiar features may specifically correlate with the type of cytokine(s) predominantly released.
 ...
PMID:Defective iron supply for erythropoiesis and adequate endogenous erythropoietin production in the anemia associated with systemic-onset juvenile chronic arthritis. 863 55

Erythropoietin (EPO) plays a central role in the regulation of red blood cell (RBC) production. Since iron is an essential element for erythropoiesis and hemoglobin (Hb) synthesis, its importance is heightened in patients treated with epoetin alfa. Stimulation of erythropoiesis following the administration of epoetin alfa is associated with several changes in iron metabolism; indeed, plasma ferritin levels fall as a result of increased utilization of iron by the expanding erythroid marrow. The administration of epoetin alfa can therefore lead to a state of relative iron deficiency. Thus, iron supplementation is essential to maximize the effect of epoetin alfa-induced erythropoiesis.
 ...
PMID:Erythropoietin, iron metabolism, and red blood cell production. 872 73

Anaemia is a common manifestation of juvenile rheumatoid arthritis (JCA). We have evaluated 26 JCA patients with anaemia and compared their laboratory parameters to those without anaemia. In the patients with anaemia, activation criteria such as erythrocyte sedimentation rate (ESR) and CRP were significantly higher than in those without anaemia. Anaemia was present in all systemic JCA patients and was present in 42% and 78% of the oligoarticular and polyarticular types, respectively. Serum iron levels and transferrin saturations were low in all, whereas serum iron-binding capacities of the patients were normal. Mean ferritin level was 249pg/l (range 8.46-1000pg/l). There was a significant correlation between ferritin levels and CRP and ESR (r = 0.48 and r = 0.55 respectively) (both p < 0.05). Epo levels were normal. Twelve (60%) of the bone marrow aspiration specimens stained positive for iron whereas 40% stained negative; there were also changes suggestive of myelodysplasia. Sideroblasts were also decreased in number. Thus, in these patients iron is not sufficiently transferred to the erythroid series and/or cannot be used by erythroblasts, accompanied by a possible absolute iron deficiency. Thus we suggest that the iron in JCA tends to be stored in the form of ferritin, not in an accessible form and impaired metabolism along with other factors are effective in the anaemia of JCA.
 ...
PMID:Anaemia in juvenile chronic arthritis. 879 53

Ten patients, who received cadaveric kidneys, were followed for 24 wk with serial measurements of serum erythropoietin (S-Epo), transferrin receptor (S-TfR) and iron variables. The mean pretransplant creatinine clearance was 8.2 (range 0-22) ml/min and the mean haemoglobin (Hb) level was 99 +/- 18.6 (range 66-124) g/l. Nine patients demonstrated a gradual increase in S-Epo levels, which reached a peak, and was accompanied by a parallel increase in S-TfR levels with a median lag period of 3 wk between both peaks. Hb correction followed the S-TfR peak after a second lag period (median 7 wk). Elevated S-Epo and S-TfR did not result in correction of anaemia in 1 patient due to impaired graft function. Within 4 months, S-Epo levels reached the normal range while TfR levels were higher than normal. Follow-up of iron status demonstrated the development of iron deficiency in 5 patients, which was corrected spontaneously. Improvement in erythropoiesis after renal transplantation seems to occur by means of expansion of the erythroid marrow, as detected by increasing S-TfR levels, subsequent to a S-Epo peak. This expansion precedes Hb normalization. A nonuraemic environment is probably a prerequisite for the correction of anaemia but not for the increase in S-Epo or S-TfR levels. Iron deficiency may occur after transplantation due to an increase in iron utilization.
 ...
PMID:Assessment of erythropoiesis following renal transplantation. 915 Jul 10

Recombinant erythropoietin (r-EPO) was administered to 37 patients with advanced, transfusion-dependent and chemo-resistant multiple myeloma (MM), at the fixed dose of 10,000/U s.c., 3 times a week, for 2 months. Thirteen patients (35.1%) achieved a significant response in terms of complete abolition of red cell transfusions. Factors significantly predictive of response were: a) inappropriate production of endogenous EPO, as expressed by a reduced observed/predicted ratio; b) presence of a consistent number of circulating erythroid precursors BFU-E; c) low serum levels of tumor necrosis factor (TNF) and interleukin-1 (IL-1), cytokines with inhibitory activity on erythropoiesis; d) a single line of previously received chemotherapy. Renal failure, bone marrow plasma cell infiltration, serum levels of IL-6 and other main clinical and laboratory parameters did not affect significantly the response to r-EPO. High fluorescence reticulocytes (HFR) and soluble transferrin receptor (sTfR) values were useful to detect an early stimulation of erythropoiesis in responders, while a high percentage of circulating hypochromic erythrocytes (HE), as assessed by an automated counter, identified those patients developing functional iron deficiency during r-EPO treatment. We conclude that about one-third of severely anemic patients with advanced MM, unresponsive to chemotherapy, may benefit by r-EPO therapy. The clinical management of these patients can be accomplished using non-invasive parameters, such as sTfR, HFR and HE.
 ...
PMID:Clinical results of recombinant erythropoietin in transfusion-dependent patients with refractory multiple myeloma: role of cytokines and monitoring of erythropoiesis. 922 86

Rapid advances were made in understanding the molecular and cellular bases of iron metabolism and its disorders. Molecular mechanisms for the cellular uptake, storage, and utilization of iron were clarified in investigations of the structure and functions of transferrin, transferrin receptor, ferritin, erythroid delta-aminolevulinic acid synthase, and the RNA-binding protein termed the iron responsive-element binding protein. Evidence was obtained that a nuclear DNA-binding protein, NF-E2, may be involved in the regulation of both hemoglobin synthesis in erythroid cells and of iron absorption in the intestine. Clinically, progress was made in improving the diagnosis and management of both iron deficiency and iron overload, with studies of the usefulness of serum transferrin receptor measurements, of a new therapeutic preparation of iron using a "gastric delivery system," and of the development of new orally active iron-chelating agents.
 ...
PMID:New advances in iron metabolism, iron deficiency, and iron overload. 937 Dec 67

The expression of transferrin receptors on the cell membrane of erythroblasts was analysed with flow cytometry in patients with different forms of anaemia. At the same time the concentration of soluble transferrin receptors (sTfRs) was analysed in serum. It was shown that only in iron deficiency a high concentration of sTfRs in serum could be explained with an increased expression of transferrin receptors on the erythroblastic membrane. In anaemia of chronic disease and myelodysplasia a discrepancy between a low expression on the cell membrane and normal or elevated serum values was seen. From this study we conclude that the concentration of sTfRs in serum does not only depend on the expression of transferrin receptors on the erythroblasts but also on the erythroid activity.
 ...
PMID:Relationship between soluble transferrin receptors in serum and membrane-bound transferrin receptors. 949 May 71

Recombinant human erythropoietin is used in clinical practice mainly for treatment of anemia of renal failure. In the past years, however, its use has been approved for other indications, including prevention of anemia in surgical patients or in patients undergoing platinum-based chemotherapy, treatment of anemia of prematurity, of anemia induced by zidovudine therapy in HIV-infected patients, and of anemia induced by chemotherapy of nonmyeloid malignancies. Erythropoietin should routinely be given subcutaneously to maximize its effects. Most patients undergoing rHuEpo treatment develop functional iron deficiency, a situation in which iron supply to the erythroid marrow is inadequate for the erythrocyte precursor demand. Iron supplementation should, therefore, be given to all individuals receiving rHuEpo except for those patients with increased serum iron and transferrin saturation. Outside the setting of uremia, only a portion of patients can clearly benefit from erythropoietin therapy; therefore, the use of rHuEpo should be individualized in nonrenal applications.
 ...
PMID:How and when to use erythropoietin. 957 Jul 2

Automated counting of reticulocytes has markedly increased the precision and accuracy of this assay compared with the traditional manual counts. In addition, several new reticulocyte parameters are now available to clinicians and pathologists. This review examines the potential role of these parameters in the diagnosis and management of anemias. Reticulocyte maturity can now be assessed based on the staining intensity of reticulocytes, which is proportional to their RNA content. However, the clinical value of the numerical estimate of the immature reticulocyte fraction has not been yet demonstrated. In the bone marrow transplant setting, there is no clear evidence that the use of this index results in improved care of these patients, and many studies have failed to show its superiority compared with the traditional white cell count, especially for autologous transplants. Direct measurement of reticulocyte volume, hemoglobin concentration, and hemoglobin content are now available. Studies have shown that these parameters, and hemoglobin content in particular, allow a real-time assessment of the functional state of the erythroid marrow. In the setting of recombinant human erythropoietin therapy, studies of hemoglobin content have shown that this index allows an early detection of functional iron deficiency. Preliminary studies have also shown that this index may be helpful in the diagnosis of iron deficiency and in the monitoring of iron replacement therapy.
 ...
PMID:Use of reticulocyte cellular indices in the diagnosis and treatment of hematological disorders. 959 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>