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The role of iron status markers in predicting response to intravenous iron in haemodialysis patients on maintenance erythropoietin.

BACKGROUND: Iron deficiency (ID) is the main cause of hyporesponsiveness to erythropoietin in haemodialysis patients and its detection is of value since it is easily corrected by intravenous iron. Markers of iron supply to the erythron, including erythrocyte zinc protoporphyrin (Er-ZPP), percentage of hypochromic erythrocytes (Hypo), reticulocyte haemoglobin content (CHr) and soluble transferrin receptor (sTfR), may be more accurate predictors of ID than ferritin (Fer) and transferrin saturation (TSat), but relative diagnostic power and best threshold values are not yet established. METHODS: In 125 haemodialysis patients on maintenance erythropoietin, the diagnostic power of the above parameters was evaluated by ROC curve, multivariate regression, and stepwise discriminant analyses. Diagnosis of ID was based on haemoglobin response to intravenous iron (992 mg as sodium ferric gluconate complex over an 8-week period). RESULTS: Fifty-one patients were considered iron deficient (haemoglobin increase by 1.9+/-0.5 g/dl) and 74 as iron replete (haemoglobin increase by 0.4+/-0.3 g/dl). ROC curve analysis showed that all tests had discriminative ability with the following hierarchy: Hypo (area under curve W=0.930, efficiency 89.6% at cut-off >6%), CHr (W=0.798, efficiency 78.4% at cut-off < or =29 pg), sTfR (W=0.783, efficiency 72.4% at cut-off >1.5 mg/l), Er-ZPP (W=0.773, efficiency 73.0% at cut-off >52 micromol/mol haem), TSat (W=0.758, efficiency 70.4% at cut-off <19%) and ferritin (W=0.633, efficiency 64.0% at cut-off <50 ng/ml). Stepwise discriminant analysis identified Hypo as the only variable with independent diagnostic value, able to classify 87.2% of patients correctly. Additional tests did not substantially improve diagnostic efficiency of Hypo >6% alone. CONCLUSIONS: In haemodialysis patients on maintenance erythropoietin, Hypo >6% is the best currently available marker to identify those who will improve their response after intravenous iron. Cost-effectiveness suggests that this parameter should be a first-line tool to monitor iron requirements in clinical practice.

Biomarkers↗

Autologous blood transfusions in children and young adults with low body weight undergoing spinal surgery.

The perioperative course of 118 patients weighing less than 45.5 kg (100.1 pounds) who participated in a predeposited autologous blood program from 1979-1984 is reviewed. Average age was 13 years 11 months (range 6 years 4 months to 20 years 4 months) and the average weight, 41 kg (range 30-45.4 kg). All underwent spinal surgery, 96% for scoliosis. The program involved preoperative donation of blood that was stored and subsequently retransfused to replace operative blood losses. Patients donated an average of 811 ml (range 208-1,320 ml) blood. Operation and hospitalization were completed by 63% without receiving any homologous blood, and the need for donor blood was reduced in the remaining 37%. Preoperative blood donation and retransfusion led to no significant complications. We describe an autologous blood transfusion program and show that autotransfusion is a safe and preferred method of blood replacement for children and young adults with low body weight undergoing elective surgery.

Adolescent↗

Iron deficiency and infant development.

It has been shown that iron-deficient anemic infants are not as successful in tests of mental and motor development as their iron-sufficient age-matched counterparts. A recent study has confirmed that iron intervention can reverse developmental delays, while placebo-treated anemic infants showed no such improvement. The etiology of the developmental delay and its effect on later performance remain to be elucidated.

Anemia, Hypochromic↗

The interaction of papain with polycations.

An investigation has been made of the interactions of the enzyme papain with the polycations protamine, polybrene, poly(L-lysine), spermine, spermidine and the neutral polymer polyvinylpyrrolidone (PVP). At low concentrations, each behaves as an inhibitor of the enzyme. As their concentrations increased above a certain level, the activity of the systems increased, and their inhibition of the enzyme appeared to be less pronounced. When acting by themselves in the presence of the substrate haemoglobin, each of the polycations was a weak proteolytic catalyst with a ranking of catalytic effectiveness of protamine greater than polybrene greater than poly(L-lysine) greater than polyvinyl-pyrrolidone greater than spermidine greater than spermine. This effect could explain the anomalous inhibition of papain by these polycations. The interaction of papain with dansyl protamine (DNSP) and the extent of complex formation were studied using a fluorescence polarization technique and the results showed that there was a strong interaction occurred. The strength of binding was assessed by determination of the critical electrolyte concentration (0.2 M, NaNO3). The stoichiometry of the DNSP-papain complex was found to be 63 base moles of DNSP to one mole of papain.

Catalysis↗

Iron deficiency in adolescent female dancers.

The iron balance of 25 adolescent dancers and 23 control females of the same age were studied. The concentrations of fasting blood haemoglobin, serum iron, serum transferrin and serum ferritin were determined. Iron supplementation (ferrous sulphate corresponding to 100 mg of elemental iron per day) was instigated if body iron stores were low (serum ferritin less than 30 micrograms.l-1). Blood samples were drawn again after ten weeks. Low haemoglobin concentration (blood haemoglobin less than 125 g.l-1) was more prevalent among dancers than among control subjects. Reduced iron stores as well as completely absent iron stores (serum ferritin concentration less than 12 micrograms.l-1) were equally common in both groups (25% of the subjects). Iron supplementation reduced the number of anaemic girls from 16 to 4 and the highly significant difference in haemoglobin level between the treated and untreated groups disappeared. Ten weeks of iron therapy was not, however, long enough to increase iron stores.

Adolescent↗

Analysis of the factors influencing peritubular PCO2 in the rat.

We have developed a mathematical model to assess the relative contributions of several factors to the high CO2 partial pressures observed in rat peritubular capillaries. This model is based on a single nephron and focuses specifically on the CO2 partial pressure differences (delta PCO2) between peritubular capillaries and the afferent arteriole. The model is formulated by writing steady-state mass balances for the glomerulus, proximal tubule, and peritubular capillaries in addition to equilibrium relationships for CO2, HCO3-, blood protein buffers, and hemoglobin carbamino compounds. Principal input parameters include glomerular blood flow rate, rates of HCO3- and water reabsorption, and the rate of metabolic CO2 production. Under conditions representative of normal Munich-Wistar rats, the model predicts delta PCO2 to be 4.1 mmHg, in approximate agreement with experimental observations reported elsewhere. Metabolic CO2 production is responsible for roughly half of this predicted delta PCO2, the remainder being attributable to reabsorption processes. In examining the sensitivity of delta PCO2 to changes in physiological conditions, we consistently found it to be inversely related to glomerular blood flow rate. The influence of changes in HCO3- reabsorption on delta PCO2 is variable and highly dependent on the arterial acid-base status and the ratio of HCO3- reabsorption to water reabsorption.

Acid-Base Equilibrium↗

Ironstrene (ferric sodium edetate) treatment of anaemic infants.

This study deals with haemoglobin (Hb) measurements of healthy 1-year-old children in one district in central Norway. The aim was to study the Hb levels, to treat any children having iron deficiency anaemia (Hb less than or equal to 10.8 g/100 ml), and to evaluate the effect of sodium iron edetate after 4 weeks of treatment, with a follow-up after 1 year. A total of 141 children were examined, of whom 40 had Hb less than or equal to 10.8 g/100 ml (28.4%). The study showed that the Hb levels in healthy 1-year-olds have a normal distribution. Thirty-four children with Hb less than or equal to 10.8 g/100 ml were treated for 4 weeks with sodium iron edetate (six drop-outs). The study showed a significant increase in Hb levels immediately after the treatment period as well as 4 weeks later. Hb decreases significantly immediately after ceasing treatment and continues to do so during the control period of 1 year. The Hb levels probably increase to a maximum 2 weeks after the treatment period.

Anemia, Hypochromic↗

Coprophagy in iron-deficient rats: II. 2 novel methods of prevention.

2 novel methods of coprophagy prevention were used in iron-deficient rats to measure their effect on haemoglobin regeneration during the feeding of ferrous sulphate or several soya proteins. Neck collars produced considerable weight loss and depression in food intake compared to aluminium anal cups which were tolerated well. Both methods of coprophagy prevention reduced iron availability from a range of soya proteins and ferrous sulphate and it is suggested that the practice of coprophagy in iron-deficient and possibly iron-replete rats may overestimate iron (and possibly other mineral) absorption (retention) studies.

Anemia, Hypochromic↗

Alteration of substrate specificity of fructosyl-amino acid oxidase from Ulocladium sp. JS-103.

We showed by random mutagenesis that one-amino-acid substitution at Arg94 in fructosyl-amino acid oxidase from Ulocladium sp. JS-103 enhanced substrate specificity toward fructosyl valine (FV), a model compound of hemoglobin A(1c). Kinetic analysis showed that the specificity of the R94W mutant enzyme toward FV was 14-fold that of the wild-type enzyme. The mutant enzyme obtained will be useful in developing an enzymatic measurement method for hemoglobin A(1c).

Amino Acid Oxidoreductases↗

The effect of iron supplementation on the level of haemoglobin after lower limb arthroplasty.

We randomised 120 patients who were undergoing either primary total hip or knee arthroplasty to receive either ferrous sulphate or a placebo for three weeks after surgery. The level of haemoglobin and absolute reticulocyte count were measured at one and five days, and three and six weeks after operation. Ninety-nine patients (ferrous sulphate 50, placebo 49) completed the study. The two groups differed only in the treatment administered. Recovery of level of haemoglobin was similar at five days and three weeks and returned to 85% of the pre-operative level, irrespective of the treatment group. A small, albeit greater recovery in the level of haemoglobin was identified at six weeks in the ferrous sulphate group in both men (ferrous sulphate 5%, placebo 1.5%) and women (ferrous sulphate 6%, placebo 3%). The clinical significance of this is questionable and may be outweighed by the high incidence of reported side effects of oral iron and the cost of the medication. Administration of iron supplements after elective total hip or total knee arthroplasty does not appear to be worthwhile.

Administration, Oral↗

Studies on the interference by haemoglobin in the determination of bilirubin.

Haemoglobin interference in the determination of bilirubin was compared in 7 different methods using the Jendrassik-Grof procedure, the Jendrassik-Grof-Nosslin modification, and the more recent procedures using nitrophenyldiazonium, 2,5-dichlorophenyldiazonium, 2,4-dichloraniline, and a direct reading method. To a variable degree, haemoglobin decreased the apparent absorption of the reaction product in all procedures. The extent of this decrease depended on the reagent used, the wavelength, incubation time, bilirubin concentration and the type of blank used. In an attempt to elucidate the mechanism of interference, haemoglobin was found to destroy the bilirubin diazo-compound whereas haemoglobin was ineffective. Likewise, storage of haemolytic samples for several days led to a disappearance of haemoglobin. H2O2, which had no effect in the absence of haemoglobin, potentiated the action of haemoglobin on diazobilirubin coupling. From our observations it can be concluded that haemoglobin disturbs the diazo-bilirubin reaction by a dual mechanism. H2O2, formed from oxyhaemoglobin by autoxidation, destroys the diazo bilirubin colour. In accordance with this explanation, potassium iodide stabilized the diazo compound against the peroxidative effect of oxyhaemoglobin; stabilization was not effective with superoxide dismutase, mannitol or ascorbate.

Bilirubin↗

[Comparative studies on wholebody retention of iron(II)-sulfate and a combination of iron(II)-sulfate and DL-serine].

The wholebody retention of an 59iron-sulphate-DL-serin combination (group B) was compared to that of 59iron-sulphate in healthy female volunteers. Mean 59Fe-retention of group B(n = 9) was found to be 40% higher than that of group A(n = 10); however, this difference was mathematically statistically not significant--especially because of the high standard deviation of group B.

Absorption↗

Serum leptin levels in patients with sideropenic and pernicious anemia: the influence of anemia treatment.

Leptin is a 16 kDa protein hormone involved in food intake, energy expenditure regulation and numerous other physiological processes. Recently, leptin has been demonstrated to stimulate hematopoietic stem cells in vitro. The aim of our study was to measure serum leptin and erythropoietin levels in patients with sideropenic (n = 18) and pernicious anemia (n=7) before and during anemia treatment. Blood samples for the blood count, leptin and erythropoietin determinations were obtained by venepunction at the time of the diagnosis of anemia and after partial and complete anemia recovery. The relationships of serum leptin levels to erythropoietin levels and blood count parameters were also studied. No significant differences in serum leptin levels between the groups studied were found. The serum leptin levels in none of groups were modified by treatment of anemia (basal levels, the levels during treatment and after anemia recovery were 13.1+/-14.5 vs 12.8+/-15.6 vs 12.0+/-14.8 ng/ml in patients with sideropenic anemia and 7.8+/-8.5 vs 9.5+/-10.0 vs 8.9+/-6.6 ng/ml in patients with pernicious anemia). The erythropoietin levels were higher at the time of anemia in both groups and decreased significantly after partial or complete recovery. Serum leptin levels in both groups correlated positively with the body mass index. No significant relationships were found between serum leptin levels and erythropoietin values or various parameters of the peripheral blood count. We conclude that serum leptin levels in patients with sideropenic and pernicious anemia positively correlate with the body mass index but are not influenced by the treatment of anemia.

Adult↗

Iron deficiency anemia.

Iron deficiency anemia is the most common cause of anemia worldwide and results from inadequate iron supply for erythropoiesis. Iron deficiency is most prevalent during periods of rapid body growth: in infancy and again at puberty. Insufficient intake accounts for most cases. The clinical manifestations of iron deficiency anemia can be subtle, but irreversible delayed psychomotor development may occur if the anemia is severe and prolonged. The optimal approach is prevention and early treatment.

Adolescent↗

[Effect of iron chloride (III) on hematological status of the Planorbarius corneus (Mollusca: Gastropoda: Bulinidae) in normal snails and during infection with trematode parthenites].

The effect of three ferric chloride concentrations (100, 200, 300 mg/l) on the acid-alkaline balance of haemolymph and haemoglobin content in Planorbarius corneus under normal conditions and in the case of infection with parthenites and larvae of Echinoparichium aconiatum was examined. In the medium with an effective concentration of ferric chloride, all snail specimens proved to have acidified haemolymph, by 40-50% in infected samples and 80-85% in uninfected ones. Statistically reliable differences in the haemoglobin content in the haemolymph of infected and uninfected specimens between the control and test media were absent, that proves a weak toxic effect of ferric ions on P. corneus.

Animals↗