[Rare gastroenterologic finding as a cause of hypochromic microcytic anemia]. / Seltener gastroenterologischer Befund als Ursache für eine hypochrome mikrozytäre Anämie.

CASE HISTORY: A 66-year-old woman suffering from skin paleness and weakness presented an increasing hypochromic, microcytic anemia. Diagnostic: In an ambulant setting a capsule endoscopy of the small intestine was carried out because of multiple polyps of the colon (colonoscopy) in addition to non-invasive (Hämoccult-Test) and invasive (gastroscopy) diagnostic. The patient was then admitted to hospital to clarify a suspicious ulcer of the small bowl. According to biopsies taken via balloon enteroscopy, an adenocarcinoma of the small intestine was diagnosed. THERAPY AND CLINICAL COURSE: After staging and exploratory laparotomy, histology findings showed an advanced tumour stage. A palliative chemotherapy, analogue to colon cancer treatment, was conducted. CONCLUSION: Small bowel diagnostics should be carried out if the aetiology of an anemia is not certain with an existing polyposis of the colon. Individuals with personal or family history of cumulative colorectal adenomas should undergo assessment for an adenomatous polyposis syndrom.

[Effect of hepcidin on iron metabolism in athletes]. / Efecto de la hepcidina en el metabolismo del hierro en deportistas.

The role of iron in the human body is essential, and athletes must always try to keep an adequate iron status. Hepcidin is proposed as the main hormone responsible for the control of iron reserves in the body, given its ability to induce degradation of ferroportin. The action of hepcidin on ferroportin leads to a decreased dietary iron absorption, as well as to a decrease in macrophages. Several factors such as the iron status, the amount of dietary iron, the inflammation, the hypoxia, the testosterone and the physical exercise have been pointed out as affecting the synthesis of hepcidin. This study has aimed at analysing the researches on hepcidin response to exercise, as well as designing a specific strategy to prevent a potential ferropenic status in athletes. The main findings are an association between exercise at an intensity over 65% VO2max and transient increases in the synthesis of hepcidin, and a possible regulatory effect of intermittent hypoxic stimuli in the early post-exercise recovery. Other factors such as the training volume, sex, kind of exercise or the type of surface where the training takes place do not seem to affect the response of hepcidin to exercise.

Las funciones del hierro en el organismo son esenciales, siendo uno de los objetivos del deportista mantener un estado férrico adecuado. La hepcidina, se ha propuesto como la principal hormona responsable de controlar las reservas corporales de hierro, a través de su capacidad para degradar la ferroportina. La acción de la hepcidina sobre la ferroportina provoca una disminución de la absorción del hierro proveniente de la dieta, así como de los macrófagos. Distintos factores como el estado férrico del individuo, la cantidad de hierro proveniente de la dieta, la inflamación, hipoxia, testosterona y el ejercicio, se han comprobado que afectan a la capacidad de síntesis de hepcidina. Los objetivos del presente trabajo han sido analizar las investigaciones que actualmente han estudiado la respuesta de la hepcidina al ejercicio, así como el diseño de un plan específico que tenga por objeto prevenir posibles estados ferropénicos en el deportista. Los principales hallazgos han sido una asociación entre el ejercicio a una intensidad superior al 65% VO2máx con incrementos transitorios en la síntesis de hepcidina, así como un posible efecto regulador de los estímulos de hipoxia intermitente en la recuperación temprana postejercicio. Otros factores como el volumen de entrenamiento, sexo, modalidad de ejercicio o el tipo de superficie sobre la que se practica el ejercicio no parecen afectar a la respuesta de la hepcidina al ejercicio.

Clinico-hematological and micronuclear changes induced by cypermethrin in broiler chicks: Their attenuation with vitamin E and selenium.

This study was carried out on 90 one-day-old broiler chicks to know clinico-hematological alterations, DNA damage caused by cypermethrin (CY), and attenuation of toxic effects by vitamin E (Vit E) and selenium (Se). Birds were randomly divided into five equal groups. Groups 1-4 received CY (600mlkg(-1)b.wt) daily for 30 days by crop tubing. In addition to CY, groups 2, 3 and 4 received Vit E (150mgkg(-1)b.wt), Se (0.25mgkg(-1)b.wt), and Vit E (150mgkg(-1)b.wt)+Se (0.25mgkg(-1)b.wt), respectively. Group 5 served as control. Birds were monitored twice daily for clinical signs. They were weighed and blood samples were collected at experimental days 10, 20 and 30 for hematological studies. CY-treated birds showed more prominent signs of toxicity compared to CY+Vit E, CY+Se and CY+Vit E+Se birds. Body weight in groups 1-3 was significantly (P<0.05) smaller at days 20 and 30 when compared with the control group. Significantly (P<0.001) higher numbers of micronuclei appeared in chicks treated with CY compared to CY+Vit E- and CY+Se-treated birds. Significantly decreased total erythrocyte counts (TEC), hemoglobin (Hb) concentration and packed cell volume (PCV) in all treated groups were recorded. Treated birds suffered from macrocytic hypochromic anemia. Leukocytosis in early stage and later leucopenia was seen in treated birds. It can be concluded that CY induces toxic effects in broilers chicks; however, these toxic effects can be ameliorated by Vit E or Se. Combination of Vit E and Se was more effective to ameliorate toxic effects of cypermethrin.

The effect of iron supplementation in the diet of Dasypus novemcinctus (Linnaeus, 1758) armadillos in captivity.

Armadillos of the species Dasypus novemcinctus have been used as an experimental model of leprosy. Besides non-human primates, they are the only species naturally infected with Mycobacterium leprae and when experimentally inoculated, reproduce the lepromatous form of the disease producing large quantities of bacilli. This species has been maintained in captivity by numerous researchers and specific housing and feeding requirements have been developed to guarantee their survival during long experimental periods. In the 'Lauro de Souza Lima' Institute, armadillos receive dog food, ground beef, boiled eggs and vitamin C. However, despite the balanced diet, anemia has been observed in some captive animals, especially in armadillos inoculated with M. leprae in advanced stages of infection. Thus, the objective of the present study was to evaluate the effect of iron sulfate supplementation in the feed provided for armadillos, both inoculated and non-inoculated with M. leprae, by means of the evaluation of their hematological profile. Fourteen armadillos received 10 mg/animal of iron sulfate (Hematofer(R)) diluted in sterile water mixed with their daily feed for 50 days. Hemograms and serum iron dosages for each armadillo were performed before and after supplementation. The hematocrit values increased significantly after iron supplementation, both in armadillos inoculated and non-inoculated with M. leprae. It is possible that the amount of iron in the feed is insufficient for the formation of hemoglobin, leading to microcytic anemia. Dietary supplementation with iron sulfate reversed this state, showing the importance of understanding the metabolism of exotic species for their maintenance in captivity, and thus ensuring their well-being.

The effect of iron supplementation in the diet of Dasypus novemcinctus (Linnaeus, 1758) armadillos in captivity / O efeito da suplementação com ferro na dieta de tatus Dasypus novemcinctus (Linnaeus, 1758) em cativeiro

Armadillos of the species Dasypus novemcinctus have been used as an experimental model of leprosy. Besides non-human primates, they are the only species naturally infected with Mycobacterium leprae and when experimentally inoculated, reproduce the lepromatous form of the disease producing large quantities of bacilli. This species has been maintained in captivity by numerous researchers and specific housing and feeding requirements have been developed to guarantee their survival during long experimental periods. In the "Lauro de Souza Lima" Institute, armadillos receive dog food, ground beef, boiled eggs and vitamin C. However, despite the balanced diet, anemia has been observed in some captive animals, especially in armadillos inoculated with M. leprae in advanced stages of infection. Thus, the objective of the present study was to evaluate the effect of iron sulfate supplementation in the feed provided for armadillos, both inoculated and non-inoculated with M. leprae, by means of the evaluation of their hematological profile. Fourteen armadillos received 10 mg/animal of iron sulfate (Hematofer®) diluted in sterile water mixed with their daily feed for 50 days. Hemograms and serum iron dosages for each armadillo were performed before and after supplementation. The hematocrit values increased significantly after iron supplementation, both in armadillos inoculated and non-inoculated with M. leprae. It is possible that the amount of iron in the feed is insufficient for the formation of hemoglobin, leading to microcytic anemia. Dietary supplementation with iron sulfate reversed this state, showing the importance of understanding the metabolism of exotic species for their maintenance in captivity, and thus ensuring their well-being.

O tatu da espécie Dasypus novemcinctus tem sido utilizado como modelo experimental para a hanseníase. Eles são a única espécie, além de primatas não humanos, que se apresentam naturalmente infectados pelo Mycobacterium leprae. Estes tatus, quando experimentalmente inoculados, reproduzem a forma virchoviana da hanseníase produzindo grandes quantidades de bacilos. Esta espécie tem sido mantida em cativeiro por vários pesquisadores, no entanto, alguns cuidados são necessários para garantir a sobrevivência destes por longos períodos experimentais, tais como alojamento e alimentação. No Instituto Lauro de Souza Lima, os animais em cativeiro recebem ração canina, carne bovina, ovos cozidos e vitamina C, mesmo assim, tem-se observado o desenvolvimento de quadros de anemia nestes animais, principalmente nos inoculados com o M. leprae, em estados avançados da infecção. Sendo assim, o objetivo deste estudo foi avaliar o efeito da suplementação com sulfato ferroso na alimentação fornecida aos tatus, inoculados e não inoculados com M. leprae, por meio de avaliação de seu perfil hematológico. Foram utilizados 14 animais que receberam 10 mg/animal de sulfato ferroso (Hematofer®) diluídos em água estéril e misturados diariamente à ração por 50 dias. Foram feitos hemograma e dosagem de ferro sérico de cada animal antes e após a suplementação. Os valores de hematócrito aumentaram significativamente após a suplementação, tanto nos animais inoculados como nos não inoculados com M. leprae. É possível que a quantidade de ferro na alimentação seja insuficiente para a formação da hemoglobina, levando a um quadro de anemia microcítica. A suplementação da dieta com sulfato ferroso reverteu este quadro, mostrando a importância de se conhecer o metabolismo de espécies exóticas para manutenção destas em cativeiro, assegurando seu bem estar.

Increased microerythrocyte count in homozygous alpha(+)-thalassaemia contributes to protection against severe malarial anaemia.

BACKGROUND: The heritable haemoglobinopathy alpha(+)-thalassaemia is caused by the reduced synthesis of alpha-globin chains that form part of normal adult haemoglobin (Hb). Individuals homozygous for alpha(+)-thalassaemia have microcytosis and an increased erythrocyte count. Alpha(+)-thalassaemia homozygosity confers considerable protection against severe malaria, including severe malarial anaemia (SMA) (Hb concentration < 50 g/l), but does not influence parasite count. We tested the hypothesis that the erythrocyte indices associated with alpha(+)-thalassaemia homozygosity provide a haematological benefit during acute malaria. METHODS AND FINDINGS: Data from children living on the north coast of Papua New Guinea who had participated in a case-control study of the protection afforded by alpha(+)-thalassaemia against severe malaria were reanalysed to assess the genotype-specific reduction in erythrocyte count and Hb levels associated with acute malarial disease. We observed a reduction in median erythrocyte count of approximately 1.5 x 10(12)/l in all children with acute falciparum malaria relative to values in community children (p < 0.001). We developed a simple mathematical model of the linear relationship between Hb concentration and erythrocyte count. This model predicted that children homozygous for alpha(+)-thalassaemia lose less Hb than children of normal genotype for a reduction in erythrocyte count of >1.1 x 10(12)/l as a result of the reduced mean cell Hb in homozygous alpha(+)-thalassaemia. In addition, children homozygous for alpha(+)-thalassaemia require a 10% greater reduction in erythrocyte count than children of normal genotype (p = 0.02) for Hb concentration to fall to 50 g/l, the cutoff for SMA. We estimated that the haematological profile in children homozygous for alpha(+)-thalassaemia reduces the risk of SMA during acute malaria compared to children of normal genotype (relative risk 0.52; 95% confidence interval [CI] 0.24-1.12, p = 0.09). CONCLUSIONS: The increased erythrocyte count and microcytosis in children homozygous for alpha(+)-thalassaemia may contribute substantially to their protection against SMA. A lower concentration of Hb per erythrocyte and a larger population of erythrocytes may be a biologically advantageous strategy against the significant reduction in erythrocyte count that occurs during acute infection with the malaria parasite Plasmodium falciparum. This haematological profile may reduce the risk of anaemia by other Plasmodium species, as well as other causes of anaemia. Other host polymorphisms that induce an increased erythrocyte count and microcytosis may confer a similar advantage.

[Human recombinant erythropoietin-alpha increases the efficacy of irradiation in preclinical model]. / A rekombináns humán erythropoietin-alfa fokozza a humán laphámrák sugárérzékenységét preklinikai modellben.

According to recent data erythropoietin receptor (EPOR) is expressed not only by bone marrow erythroid progenitors but by endothelial- and cancer cells and it was suggested that erythropoietin (EPO) may affect their functions as well. We have analyzed the effects of recombinant human erythropoietin-alpha (rHuEPOalpha) on radiation sensitivity of EPOR+ human epidermoid carcinoma (A431) xenograft model. In vivo rHuEPOalpha treatment was started after tumor cell inoculation into SCID mice. 5 Gy irradiation was performed on day 14, the effect of which was measured on day 22. Hemoglobin level, tumor-associated microvessels and HIF-1alpha expression of the xenograft were monitored during the experiment. rHuEPOalpha administration prevented the development of tumor-induced anemia of SCID mice and reduced the level of HIF-1alpha expression of the xenograft tumor without affecting tumor growth. We have found that rHuEPOalpha treatment significantly increased the efficacy of antitumor effect of irradiation which was partly mediated by complex effects on tumor-associated microvessels. In vitro rHuEPOalpha did not affect proliferation of A431 cells but enhanced the antiproliferative and proapoptotic effects of irradiation. We concluded that rHuEPOalpha administration positively modulated the antitumoral effects of irradiation at least by two pathways, decreasing systemic hypoxia resulting in decreased tumoral HIF-1alpha expression and enhancing direct effects on tumor-associated microvessels.

Every-three-week administration of darbepoetin alfa in women with chemotherapy-associated anemia.

PURPOSE: The effectiveness of every-three-week administration of darbepoetin alfa in women with chemotherapy-associated anemia was evaluated. METHODS: Women receiving chemotherapy for gynecological tumors who had a hemoglobin concentration of <10 g/dL were recruited from an obstetrics and gynecology service. Study patients received subcutaneous darbepoetin alfa 6.75 microg/kg, followed by 4.5 microg/kg every three weeks for a total of up to six doses. Hematopoietic response and mean changes in hemoglobin concentrations were evaluated. The Functional Assessment in Cancer Therapy-Anemia (FACT-An) survey was self-administered before and after study completion to evaluate the patients' quality of life. RESULTS: The mean+/-S.D. age and weight for the 14 patients recruited (12 of whom were assessable) were 52.1+/-14 years and 64.6+/-19.8 kg, respectively. The mean initial and maintenance doses were 442 and 301.6 microg, respectively. The overall hematopoietic response was 64.3%, of which 35.7% were complete and 28.6% were partial. Peak response occurred at weeks 9 and 12. The mean+/-S.D. change in hemoglobin concentration was 1.6+/-1.51 g/dL. Treatment failure was predicted by week 9 (n=2). Maintenance doses were withheld if a patient's hemoglobin concentration exceeded 12 g/dL (n=3). The mean+/-S.D. point differential for FACT-An pretreatment and posttreatment scores was 5.8+/-4.71 (n=6). CONCLUSION: Every-three-week administration of subcutaneous darbepoetin alfa produced a complete or partial hematopoietic response in 11 of 14 women with chemotherapy- associated anemia. A quality-of-life indicator generally improved among the 6 patients for whom posttreatment quality-of-life data were available.

Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients.

This is an updated systematic review of 57 trials and 9353 cancer patients from articles, abstracts, and reports published between January 1, 1985, and April 30, 2005, on the effects of epoetin alfa and beta (i.e., epoetin) and darbepoetin alfa (i.e., darbepoetin). We included randomized controlled trials comparing epoetin or darbepoetin plus red blood cell transfusion with red blood cell transfusion alone for prophylaxis or treatment of anemia in cancer patients with or without concurrent antineoplastic therapy. The Cochrane Library, MEDLINE, EMBASE, and conference proceedings were searched. Effect estimates and 95% confidence intervals (CIs) were calculated with fixed-effects models. Treatment with epoetin or darbepoetin statistically significantly reduced the risk for red blood cell transfusions (relative risk [RR] = 0.64, 95% CI = 0.60 to 0.68; 42 trials and 6510 patients) and improved hematologic response (RR = 3.43, 95% CI = 3.07 to 3.84; 22 trials and 4307 patients). Treatment with epoetin or darbepoetin increased the risk of thrombo-embolic events (RR = 1.67, 95% CI = 1.35 to 2.06; 35 trials and 6769 patients). Uncertainties remain as to whether and how epoetin or darbepoetin affects overall survival (hazard ratio = 1.08, 95% CI = 0.99 to 1.18; 42 trials and 8167 patients). Caution is advised when using epoetin or darbepoetin in combination with thrombogenic chemotherapeutic agents or for cancer patients who are at high risk for thrombo-embolic events.

Independent risk factors for anemia in cancer patients receiving chemotherapy: results from the European Cancer Anaemia Survey.

OBJECTIVES: To develop a hitherto unavailable risk factor model for accurately predicting anemia development in cancer patients before chemotherapy (CT) administration. METHODS: 2,070 nonanemic patients from the European Cancer Anaemia Survey (ECAS) with hemoglobin (Hb) > or =12 g/dl at enrollment who received their first CT during ECAS and underwent at least two CT cycles were divided randomly into split half (SH) 1 and SH2 (n = 1,035 each). The model was developed on SH1 using logistic regression to simultaneously evaluate predictive factors, and was validated using SH2 and an additional similar subpopulation of 5,901 ECAS patients. Anemia risk values were assigned to the predictive factors and the sum of the predictive factors gave the total anemia risk score; lower-, higher-, and highest-risk cutoff points of the total anemia risk score were determined. RESULTS: Variables ultimately identified as significant predictive factors for anemia were: lower initial Hb (< or =12.9 g/dl in females, and < or =13.4 g/dl in males); having lung or gynecologic cancer versus gastrointestinal (GI)/colorectal cancer; cancer at any other site versus GI/colorectal cancer; treatment with platinum CT, and female gender. CONCLUSION: Using this evidence-based risk model, nonanemic patients who are at the highest risk of developing anemia prior to receiving CT can be identified clinically, allowing appropriate anemia management to be planned.

Administration of intravenous iron sucrose as a 2-minute push to CKD patients: a prospective evaluation of 2,297 injections.

BACKGROUND: Intravenous iron supplementation is an integral part of the management of anemia in patients with chronic kidney disease. Traditionally, this has been administered as an infusion over 1 or more hours, which requires the use of intravenous fluids and administration tubing, along with extra demands on patient and nursing time. METHODS: We prospectively investigated the safety and practicality of administering iron sucrose, 200 mg, as a bolus injection over 2 minutes in patients with chronic kidney disease. A total of 2,297 injections were administered to 657 patients. Any adverse events were recorded, including acute anaphylactoid reactions to the iron injection, along with the presence or absence of metallic taste and phlebitis, and these were classified as "serious" and "nonserious." RESULTS: The most common adverse event was a mild and transient metallic taste that occurred during 412 injections (17.9%); in no case was this of significant distress to the patient. Excluding this, 2,240 injections (97.5%) proceeded uneventfully, and no case of phlebitis was recorded. Adverse events other than metallic taste were recorded in association with 57 injections (2.5%). Seven of these were caused by an acute anaphylactoid reaction to the intravenous iron. All 7 acute reactions resolved completely within 30 minutes with no sequelae, and none required hospitalization. The remaining 50 adverse events consisted of pain during the injection (n = 31), pain after the injection with or without some bruising (n = 9), nausea/gastrointestinal symptoms (n = 3), lethargy (n = 4), and lightheadedness (n = 3). CONCLUSION: Administration of 200 mg of iron sucrose as an intravenous bolus injection over 2 minutes is a practical dosing regimen in patients with chronic kidney disease, resulting in considerable savings in time and cost.

Cancer-related anemia: pathogenesis, prevalence and treatment.

Cancer-related anemia is a cytokine-mediated disorder resulting from complex interactions between tumor cells and the immune system. Overexpression of certain inflammatory cytokines results in shortened survival of red blood cells, suppression of erythroid progenitor cells, impaired iron utilization, and inadequate erythropoietin production. Numerous other factors may also contribute to the development of anemia in cancer patients. The European Cancer Anaemia Survey (ECAS) has provided the most current, comprehensive, prospectively collected data on the incidence and prevalence of anemia among cancer patients, as well as important perspectives on anemia treatment and relationship of hemoglobin and performance status. ECAS enrolled over 15,000 treated and untreated patients with various malignancies from cancer centers in 24 European countries and followed them for up to 6 months. The initial analysis of the ECAS data revealed that 39% of the total cancer patient population was anemic (hemoglobin <12.0 g/dl) at enrollment, although the rate varied according to tumor type, disease status, and cancer treatment status. Of the patients who were not anemic at enrollment and started cancer treatment during the survey, those undergoing chemotherapy--either alone or in combination with radiotherapy--had the highest incidence of anemia (63 and 42%, respectively). Low hemoglobin levels correlated with poor performance status and only 40% of patients who were anemic at some time during the survey received treatment for their anemia. These findings are noteworthy, since a growing body of clinical evidence indicates that the treatment of anemia can significantly improve patients' quality of life and may also improve the clinical outcome.

Evolving treatment strategies for anaemia in cancer: experience with epoetin beta.

Epoetin represents the standard of care in the management of cancer therapy-related anaemia, increasing haemoglobin levels, reducing transfusion need and improving patient quality of life (QoL). Recent research aimed at improving convenience and ease of use has involved all epoetins. In particular, it has confirmed that epoetin beta 30,000 IU once weekly is equally effective as the conventional 10,000 IU three-times weekly regimen in alleviating cancer-related anaemia. Ongoing research aimed at improving still further the effectiveness of epoetins in anaemia treatment is examining the role of concomitant intravenous iron during epoetin beta therapy. With the recent debate over whether epoetin therapy has an effect on treatment outcome and survival, well-designed trials specifically powered to assess survival are required. The BReast cancer-Anaemia and the Value of Erythropoietin (BRAVE) trial is such a study, assessing the impact of epoetin beta on survival and QoL of patients with metastatic breast cancer scheduled to receive anthracycline- and/or taxane-based chemotherapy. The findings of such studies are expected to lead to a greater understanding of the optimal use of epoetins in cancer-related anaemia.

Treatment of cancer-related anemia with epoetin alfa: a review.

Erythropoietin (EPO) is a hematopoietic growth hormone that regulates survival, proliferation, and differentiation of erythroid progenitor cells. A reduction in tissue oxygenation stimulates EPO production, through a complex feedback mechanism. Patients with cancer-related anemia have an inadequate EPO response that is further impaired by cancer treatments such as chemotherapy. Cancer-related anemia substantially impairs patient functioning and may contribute to poor treatment outcomes. A significant number of studies demonstrates that treatment of anemia in cancer patients using recombinant human EPO (rHuEPO, epoetin alfa) significantly increases haemoglobin (Hb) levels, reduces transfusion requirements, and improves quality of life, particularly by relieving fatigue. Recent data also show that epoetin alfa therapy may improve cognitive function in patients receiving chemotherapy. In addition, the correction of anemia may prolong survival by enhancing tumor oxygenation, thus increasing tumor sensitivity to chemotherapy or radiation. The indicated dose of epoetin alfa is 150-300 IU/kg three times per week, but it is commonly dosed at 40,000-60,000 IU once weekly based on trial data and extensive clinical use. Determining the timing of initiation of epoetin alfa is a clinical judgement; however, data suggest that patient functioning declines and the risk of transfusion increases when the Hb level falls under 12 g/dL.

An Hfe-dependent pathway mediates hyposideremia in response to lipopolysaccharide-induced inflammation in mice.

Inflammation influences iron balance in the whole organism. A common clinical manifestation of these changes is anemia of chronic disease (ACD; also called anemia of inflammation). Inflammation reduces duodenal iron absorption and increases macrophage iron retention, resulting in low serum iron concentrations (hyposideremia). Despite the protection hyposideremia provides against proliferating microorganisms, this 'iron withholding' reduces the iron available to maturing red blood cells and eventually contributes to the development of anemia. Hepcidin antimicrobial peptide (Hamp) is a hepatic defensin-like peptide hormone that inhibits duodenal iron absorption and macrophage iron release. Hamp is part of the type II acute phase response and is thought to have a crucial regulatory role in sequestering iron in the context of ACD. Mice with deficiencies in the hemochromatosis gene product, Hfe, mounted a general inflammatory response after injection of lipopolysaccharide but lacked appropriate Hamp expression and did not develop hyposideremia. These data suggest a previously unidentified role for Hfe in innate immunity and ACD.

Behavioral and developmental effects of preventing iron-deficiency anemia in healthy full-term infants.

OBJECTIVE: To determine the behavioral and developmental effects of preventing iron-deficiency anemia in infancy. METHODS: Healthy full-term Chilean infants who were free of iron-deficiency anemia at 6 months were assigned to high- or low-iron groups or to high- or no-added-iron groups. Behavioral/developmental outcomes at 12 months of age included overall mental and motor test scores and specific measures of motor functioning, cognitive processing, and behavior. There were no differences between high- and low-iron groups in the prevalence of iron-deficiency anemia or behavioral/developmental outcome, and they were combined to form an iron-supplemented group (n = 1123) for comparison with the no-added-iron group (n = 534). RESULTS: At 12 months, iron-deficiency anemia was present in 3.1% and 22.6% of the supplemented and unsupplemented groups, respectively. The groups differed in specific behavioral/developmental outcomes but not on global test scores. Infants who did not receive supplemental iron processed information slower. They were less likely to show positive affect, interact socially, or check their caregivers' reactions. A smaller proportion of them resisted giving up toys and test materials, and more could not be soothed by words or objects when upset. They crawled somewhat later and were more likely to be tremulous. CONCLUSIONS: The results suggest that unsupplemented infants responded less positively to the physical and social environment. The observed differences seem to be congruent with current understanding of the effects of iron deficiency on the developing brain. The study shows that healthy full-term infants may receive developmental and behavioral benefits from iron supplementation in the first year of life.