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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic renal failure is almost invariably accompanied by symptomatic anemia. It has been demonstrated that the primary cause of this anemia is inadequate production of erythropoietin by the diseased kidneys. The isolation of erythropoietin, followed by the cloning and expression of the human erythropoietin gene, made possible clinical trials of rHuEPO in uremic patients. rHuEPO produced dramatic increases in the hematocrit in almost all patients treated and also ameliorated many symptoms, such as lethargy, dizziness, and poor appetite, that had long been attributed to the effect of uremic toxins. Adverse effects of treatment with rHuEPO noted in the early clinical trials included hypertension, seizures, arteriovenous fistula or shunt thrombosis, and hyperkalemia. Further study of rHuEPO has shown that many of these side effects may be no more frequent in patients receiving rHuEPO than in other uremic patients not receiving rHuEPO. Reduction of the rHuEPO dosage and subcutaneous administration produce less rapid increases in the hematocrit and may lessen the incidence and severity of these side effects. rHuEPO therapy places great demands on both the body's iron stores and the capacity to rapidly transfer iron from storage sites to the erythroid progenitor cells. Thus, almost all patients treated with rHuEPO become iron deficient and require oral or parenteral iron replacement. Response to rHuEPO in uremic patients is diminished if the anemia is complicated by iron deficiency, inflammatory disorders, aluminum overload, or deficiency of folate or vitamin B12. rHuEPO therapy is safe and effective in the treatment of the anemia of chronic renal failure. The use of rHuEPO leads to enhanced quality of life and eliminates the need for red cell transfusions. In addition to hemodialysis patients, predialysis patients and those on CAPD benefit from and are candidates for rHuEPO therapy.
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PMID:Anemia of renal failure. Use of erythropoietin. 157 66

This multicentre study in 142 transfusion-dependent patients with chronic renal failure maintained by haemodialysis was performed to establish the appropriate dose regimen of rHuEpo and define its long-term safety profile. Only one of 132 patients eligible for efficacy analysis did not achieve the haemoglobin target of greater than or equal to 10 g/dl; this particular patient had folate deficiency and overt hyperparathyroidism. Regular blood transfusions were no longer necessary in any patients, however five patients needed blood transfusions only once, not due to rHuEpo failure: two for iron deficiency and three for intercurrent disease. In parallel with the haemoglobin increase a statistically significant improvement in quality of life scores was observed. The weekly dose required to maintain median haemoglobin between 10 and 10.5 g/dl for 1 year (n = 79) was 200-225 U/kg, applied as two or three i.v. injections. Mean serum ferritin decreased from 1900 to 1300 ng/ml and transferrin saturation from 60% to 30%; this feature was associated with statistically significant decrease of pre-study elevated liver enzymes. The treatment had no untoward effect on the outcome of renal transplantation (n = 24). Of the 56 patients who experienced hypertensive episodes during rHuEpo therapy, 47 had a history of hypertension and nine had not. The patient incidence during the first 3 months was 28.9% and fell markedly to 4% after 1 year. Only two hypertensive episodes could not be controlled and the patients dropped out. Seizures occurred in 11 patients, most of them during early treatment; annualised incidence during the first 3 months was 7.78 per year vs 2.07 per year for seizures beyond 3 months treatment. Clinical presentation, patients' history, haemoglobin pattern, BP recordings, brain scan, and EEG indicated that the pathophysiology is multifactorial, with emphasis on rate of haemoglobin increase. Therefore a smooth haemoglobin increase rate, induced by a conservative starting dose regimen (50 U/kg thrice weekly) is recommended, to allow the circulation to adapt to changes in haematocrit/viscosity and O2 delivery. The majority of the observed adverse reactions were related to rHuEpo's therapeutic effect, i.e. increase the haematocrit. The side-effects are therefore largely predictable and can be successfully managed.
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PMID:Treatment of transfusion-dependent anaemia of chronic renal failure with recombinant human erythropoietin. A European multicentre study in 142 patients to define dose regimen and safety profile. 179 95

There are differences between young and adult organisms regarding toxokinetic aspects and clinical manifestations of heavy metal intoxications. Chronically, toxic Cd intake causes a microcytotic hypochromic anemia in young rats at lower exposure levels and after shorter exposure periods than in adult animals. Cd absorption is increased by co-administration of milk and in conjunction with iron deficiency. After long exposure periods toxic Cd concentrations accumulate in the kidney cortex; this process starts very early in life. In 3-year-old children Cd concentrations in the kidney can reach up to one-third of those found in adults. Hg++ and methyl-Hg can cause Hg encephalopathia, and frequently cause mental retardation in adults. Correspondingly, Hg++ accumulation in the brains of suckling rats is approx. 10 times higher than in grown animals. Milk increases the bioavailability of Hg++. In suckling rats Hg is bound to a greater extent to ligands in the erythrocytes. Methyl-Hg concentrations in breast milk reach 5% of those in maternal plasma and that is a severe hazard for breastfed children of exposed mothers. Toxic Pb concentrations can lead to Pb encephalopathia. A high percentage of surviving children have seizures and show signs of mental retardation. Anemia and reduced intelligence scores were recently observed in children after exposure to very low levels of Pb. Pb absorption is increased in children and after co-administration of milk. There are no definite proofs for carcinogenesis or mutagenesis after oral exposure to Cd, Hg, and Pb in man. Heavy metal concentrations were found in the same order of magnitude in commercial infant formulas and in breast milk. When infant formulas are reconstituted with contaminated tap water, however, Pb and Cd concentrations can be much higher. The average heavy metal uptake from such diets exceeds the provisional tolerable weekly intake levels set by the WHO for adults, calculated on the basis of an average food intake and a downscaled body weight. These considerations do not even provide for differences in absorption and distribution or for the increased sensitivity of children to heavy metal exposure. However, dilution effects for essential heavy metals were observed in fast-growing young children; this effect might be extrapolated to toxic metals. These theoretical considerations are compared with epidemiological evidence. A health statistic from Baltimore shows a decline of Pb intoxications in infants. This observation correlates with a simultaneous decline in exposure to Pb which was due, for example, to decreased use of lead dyes in house paints and the abolition of tin cans for infant food.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[The toxicological estimation of the heavy metal content (Cd, Hg, Pb) in food for infants and small children]. 218

Therapy with recombinant human erythropoietin (rHuEPO) can reverse anemia and improve the quality of life in anemic hemodialysis patients. However, therapy is costly and must be used efficiently. An initial rHuEPO dose less than 50 U/kg intravenously three times weekly may be adequate to achieve a hematocrit of 30-33% in many patients. Acquired iron deficiency is a common problem during rHuEPO therapy and must be prevented with oral and parenteral iron replacement to maintain the efficacy of rHuEPO. Patients should be monitored carefully for additional problems including: an increase in blood pressure; onset of seizures or headaches; increased blood potassium, phosphate, and creatinine concentrations; enhanced coagulability resulting in dialyzer and vascular access clotting; and myalgias with a 'flu-like' syndrome.
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PMID:Practical approach to initiation of recombinant human erythropoietin therapy and prevention and management of adverse effects. 226 Jun 19

Extensive testing has proven that recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) corrects the anemia of end-stage renal disease and eliminates the need for transfusions in virtually all patients. Patients whose hematocrit levels are less than 0.30 or who are transfusion dependent are candidates for therapy. A dosage of 50 to 150 U/kg body weight intravenously three times a week produces an increase in hematocrit by approximately 0.01 to 0.02 per week. Once the hematocrit reaches 0.30 the dose is adjusted so that a target hematocrit of 0.32 to 0.38 is maintained. Eighty percent of patients need maintenance doses of r-HuEPO of less than or equal to 150 U/kg; the other 20% of patients require larger doses. Reasons for poor responses include iron deficiency, inflammation due to surgery or infection, and osteitis fibrosa. Most patients require iron supplementation to prevent functional iron deficiency. BP increased in one third of patients, and in 3% seizures occurred during the initial phase of therapy, often associated with a sudden increase in BP. This hypertension can be controlled with medication. Increased dialyzer clotting may occur, which is prevented when heparin doses are adjusted, and dialyzer solute clearances may decrease slightly. Treatment with r-HuEPO does not elicit an antibody response. The mechanism of action of r-HuEPO is identical to that of natural erythropoietin, and therefore is an appropriate therapy for the long-term management of anemia in chronic renal failure.
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PMID:Guidelines for recombinant human erythropoietin therapy. 266 49

Postmortem human brain analyses have been performed to further evaluate pathogenetic aspects of the Rett syndrome. While there are no significant abnormalities with respect to amino acid concentrations in putamen, caudate nucleus, red nucleus and thalamus, the concentration of kynurenine is increased in putamen, caudate nucleus, gl. pallidus, raphe and amygdaloid n. In contrast, serotonin and its metabolite 5-hydroxyindole acetic acid are below normal levels. D2-receptor number is decreased and there is a significant drop in the concentration of the iron-binding protein ferritin. It can be concluded, that reduction of D2-receptors is due to loss of cholinergic and GABA-ergic cell bodies in the striatum or may be a response to iron deficiency. Low serotonergic and high kynurenergic activity may be of pathogenetic importance in the frequently observed cerebral seizures in Rett syndrome.
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PMID:Preliminary brain autopsy findings in progredient Rett syndrome. 308 91

Erythropoietin, a glycoprotein, is synthesized mainly in the kidney. With the destruction of renal tissue, erythropoietin production decreases; this is a major factor in the development of anemia in patients with renal failure. For about ten years now, recombinant human erythropoietin has been available for the treatment of renal anemia. All patients with renal insufficiency, independent of their plan for future renal replacement therapy, may benefit from erythropoietin. At what extent of anemia erythropoietin therapy should be started is still discussed and is certainly dependent on the degree of the patient's impairment by his anemia. Before beginning a therapy with erythropoietin, other forms of anemia observed in patients with renal failure, i.e. mainly iron deficiency, have to be excluded. A strict monitoring of hematocrit during treatment with erythropoietin is mandatory. Hypertension, seizures and cardiovascular complications have been observed with overdosing of erythropoietin. Special emphasis of this review is therefore put on the discussion of the dynamics of the erythropoietin-red cell system.
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PMID:[Erythropoietin, a milestone in the history of nephrology]. 748 78

In a patient with celiac disease, folate and iron deficiency, and epilepsy, CT over a 4-month period showed parietoocipital calcifications in the corticomedullary junctions. The calcification was progressive, but it and the seizures stabilized after institution of a gluten-free diet and iron and folic acid supplements.
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PMID:Bilateral occipital calcification associated with celiac disease, folate deficiency, and epilepsy. 748 40

To determine the effect of iron status on the seizure threshold, measures of iron sufficiency were prospectively evaluated in 51 children presenting to a pediatric emergency department with a febrile illness with (26) or without (25) an associated febrile seizure. A higher proportion of children from the febrile seizure group had a family history of mental retardation (5/26 versus 0/25, P = .02) or of previous febrile seizures (10/26 versus 2/23, P = .01). The two groups were otherwise comparable for age, sex, race, family history of afebrile seizures, temperature at presentation, white blood cell count, differential, and vitamin and antibiotic use. Patients with febrile seizures were less frequently iron deficient as defined by a free erythrocyte protoporphyrin level above 0.80 ng/L (2/23 versus 10/25, P < .01), hemoglobin concentration less than 110 g/L (1/26 versus 6/25, P < .03), hematocrit less than 0.30 L/L (0/22 versus 4/25, P < .02), mean corpuscular hemoglobin less than 20 pg (0/25 versus 3/24, P < .04), mean corpuscular volume less than 65 fL (0/26 versus 4/24, P < .02), and platelet count higher than 550 x 10(9)/L (0/26 versus 3/25, P < .04). This association was even stronger when adjusted for differences in family history. None of the patients in the febrile seizure group was being treated for iron deficiency at presentation, whereas three of 25 controls used an iron supplement (P < .04). Iron deficiency may protect against the development of febrile seizures.
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PMID:Does iron deficiency raise the seizure threshold? 778 98

We examined the hypothesis that administering epoetin to maintain a lower target haemoglobin (Hb) results in a reduced side effect profile and a lower maintenance epoetin dose. We report a prospective study of 14 haemodialysis patients assessing epoetin dose efficiency and side effect profile of partially correcting dialysis-associated anaemia. Initial Hb was 6.2 +/- 0.6 g/dl (mean +/- 1 SD). Intravenous epoetin was commenced at 120 IU/kg/week in 3 divided doses and titrated to achieve a target Hb of 8 g/dl. Follow-up was 24 weeks. The final Hb was 8.7 +/- 0.8 g/dl. The peak epoetin dose was 196 +/- 86 IU/kg/week with a maintenance dose of 141 +/- 71 IU/kg/week. Therapy was associated with hypertension--5 patients (32%); seizures--1 patient (6%) (withdrawn from therapy), and temporary iron deficiency--4 patients (35%). Iron deficiency was corrected with oral therapy. There was 1 treatment failure. Comparable conventional regimens use 100-200 IU/kg to maintain the Hb at 10-13 g/dl and have a similar incidence of side effects. We concluded that reducing the target Hb in order to decrease epoetin requirements is not justified as it offers no benefit over conventional Hb targets in terms of dose requirements or side effects.
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PMID:Partial correction of dialysis-associated anaemia does not reduce erythropoietin dose or the incidence of side effects. 834 95


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