losartan-potassium and Bacterial-Infections

Sickle cell disease is numerically as common as thalassaemia. However, it affects relatively under privileged population i.e. tribal population belonging to economically poor class and having inadequate access to education and modern health facilities. A recent explosion acknowledged in understanding the pathogenesis of this disease has lead to newer dimensions in treatment. Some of these viz. prevention of overwhelming bacterial infection, present indications and controversies regarding blood transfusion, prevention of stroke, acute chest syndrome, hydroxyurea therapy--probably the best disease modifying agent at the moment, stem cell transplantation--a cure and certain promising experimental therapies including gene therapy have been discussed in this review.

Topics: Acute Disease; Adolescent; Anemia, Sickle Cell; Antisickling Agents; Bacterial Infections; Blood Transfusion; Child; Child, Preschool; Erythropoietin; Humans; Hydroxyurea; Infant; Infant, Newborn; Recombinant Proteins; Respiratory Tract Diseases; Stem Cell Transplantation; Stroke; Syndrome

Iron plays an essential role in immunosurveillance, because of its growth promoting and differentiation inducing properties for immune cells and its interference with cell mediated immune effector pathways and cytokine activities. At the same time, iron is crucial for the proliferation of tumour cells and micro-organisms, due to its role in mitochondrial respiration and DNA synthesis. Thus, gaining control over iron homeostasis is of vital importance for the course of an infection or a tumour disease, since increased iron availability or iron overload of the immune system are associated with an unfavourable course of many of these diseases. The most frequent clinical condition demonstrating this interaction of iron and immunity is anaemia of chronic disease (ACD). ACD develops in patients with chronic activation of cellular immunity such as subjects suffering from malignancies, auto-immune disorders or infections. ACD may be seen as an immune driven disease since cytokines and their products cause (i) a diversion of iron traffic into the reticuloendothelial systems, thus limiting the availability of the metal to erythroid progenitor cells for haem biosynthesis, (ii) an inhibition of erythroid progenitor cell proliferation and (iii) blunted production and activity of erythropoietin (EPO). However, ACD may also hold some benefit by reducing iron availability to invading pathogens, thus limiting their growth, and by stimulating cell mediated immune function. The latter can be referred to the correction of an inhibitory effect of iron towards IFN-gamma induced immune effector pathways in macrophages. Whereas ACD can be easily diagnosed based on the characteristic changes of iron homeostasis, therapy of ACD is much more controversial. Where a cure of the underlying disease is impossible, transfusions for rapid correction of haemoglobin levels and human recombinant EPO can be used with varying success. The sole application of iron should be strictly avoided due to promotion of pathogen growth and impairment of immune function.

Topics: Anemia, Hypochromic; Bacterial Infections; Cytokines; Erythroid Precursor Cells; Erythropoietin; Heme; Hemochromatosis; Humans; Immune Tolerance; Immunity, Cellular; Iron; Macrophages; Neoplasms

Iron overload was a common complication in patients with chronic renal failure treated with dialysis prior to the availability of recombinant human erythropoietin (rHuEPO) therapy. Iron overload was the result of hypoproliferative erythroid marrow function coupled with the need for frequent red blood cell transfusions to manage symptomatic anemia. The repetitive use of intravenous iron with or without the use of red blood cell transfusions also contributed to iron loading and was associated with iron deposition in liver parenchymal and reticuloendothelial cells; however, there were no abnormal liver function tests or evidence of cirrhosis unless viral hepatitis resulted from the transfusions. With rHuEPO therapy, the excess iron stores were shifted back into circulating red blood cells as the anemia was partially corrected, and red blood cells were lost from circulation by the hemodialysis procedure. After several years of rHuEPO therapy, most hemodialysis patients required iron supplements to replace the continuing blood losses related to hemodialysis. The potential complications of iron overload (parenchymal iron deposition, permanent organ damage, increased risk of bacterial infections, and increased free radical generation) are reviewed in the context of this setting.

Topics: Anemia; Bacterial Infections; Erythropoietin; Free Radicals; Humans; Iron; Iron Overload; Kidney Failure, Chronic; Recombinant Proteins

Anemia management using erythropoietin and intravenous iron supplementation has improved the lives of many patients with end stage renal disease (ESRD). However, because iron is an essential nutrient for microorganisms, it is plausible that iron supplementation may promote infection. This review examines the literature on the connection between iron and infection, with a focus on the relevance of these data to hemodialysis patients treated according to the National Kidney Foundation--Dialysis Outcomes Quality Initiative (NKF-DOQI) Guidelines for Anemia Management. The current evidence does not show a cause-and-effect relationship between intravenous iron administration and an increased susceptibility to infection in hemodialysis patients. Therefore, the author does not recommend changing current iron management practices in ESRD patients because of concern about infectious risk.

Topics: Anemia, Iron-Deficiency; Bacterial Infections; Erythropoietin; Evidence-Based Medicine; Humans; Iron Compounds; Kidney Failure, Chronic; Practice Guidelines as Topic; Renal Dialysis; Research Design; Risk Factors

Intravenous iron (FeIV) has been used increasingly, alone or in combination with recombinant erythropoietin, to promote red cell production as part of a blood conservation program. Given the important role that iron plays in the growth of bacteria, it has been hypothesized that this use of FeIV may promote surgical site infection. However, this hypothesis has not yet been tested appropriately. To assess this hypothesis, postoperative infection rates in patients undergoing cardiothoracic surgery were analyzed.. Data were collected on 863 patients undergoing cardiopulmonary bypass surgery in 2001. Patients were either enrolled voluntarily in a blood conservation program in which they received either postoperative FeIV and erythropoietin (n=302), as indicated, or blood transfusions and no FeIV (n=561), as indicated, to correct postoperative anemia. Infections were defined according to the U.S. Centers for Disease Control and Prevention guidelines.. Thirty-nine infections developed. The overall infection rate was 4.52%, with an infection rate of 3.97% in the iron-treated group (n=12) and a rate of 4.81% in the untreated group (n=27). When the impact of gender, age, diabetes mellitus, operating time, type of surgery, and blood transfusions were controlled for, FeIV did not increase the risk of infection (odds ratio of 1.031 for each increment of 125 mg of FeIV; 95% confidence interval 0.908, 1.170; p=0.64).. There was no impact of FeIV on the subsequent infection rate in a cardiac surgery patient cohort, indicating its safety for use in the postoperative setting.

Topics: Aged; Anemia; Bacterial Infections; Blood Loss, Surgical; Blood Transfusion; Cardiac Surgical Procedures; Drug Therapy, Combination; Erythropoietin; Female; Ferrous Compounds; Hematinics; Humans; Injections, Intravenous; Male; Prospective Studies; Recombinant Proteins; Surgical Wound Infection; Time Factors

Epidermolysis bullosa (EB) is comprised of a group of hereditary mechanobullous disorders that are characterised by extremely fragile skin and mucous membranes. This results in blister formation and non-healing wounds. This case report describes the results of an innovative treatment of two large skin lesions in a newborn with dystrophic recessive EB (DEB) who experienced bacterial superinfections and progressive anaemisation. The lesions were treated with platelet gels derived from allogeneic cord blood (cord blood platelet gel, CBPGs). The skin lesions were clinically evaluated and treated with CBPG weekly until they completely healed. The first and second lesion required CBPG applications for 2 and 4 weeks, respectively. Both lesions were monitored weekly for 6 weeks after the last CBPG application, and no significant relapses were observed during the follow-up period. This case indicates that CBPG is an effective and safe therapeutic option for managing newborns with DEB, particularly as treatment and prevention of fluid loss and superinfection.

Topics: Anemia; Anti-Bacterial Agents; Bacterial Infections; Blood Platelets; Epidermolysis Bullosa Dystrophica; Erythropoietin; Female; Fetal Blood; Gels; Hemorrhage; Humans; Infant, Newborn; Superinfection

Periventricular leukomalacia (PVL), a common neonatal brain white matter (WM) lesion, is frequently associated with cerebral palsy. Growing evidence has indicated that in addition to ischemia/reperfusion injury, cytokine-induced brain injury associated with maternal or fetal infection may also play an important role in the pathogenesis of PVL. Recent studies have shown that administration of lipopolysaccharide (LPS) to pregnant rats causes enhanced expression of the cytokines, i.e., IL-1 beta, TNF-alpha, and IL-6, in fetal brains. In recent years, it has been shown that erythropoietin (EPO) has a critical role in the development, maintenance, protection and repair of the nervous system. In the present study we investigated the effect of EPO on LPS-induced WM injury in Sprague-Dawley rats. LPS (500 microg/kg) suspension in pyrogen-free saline was administered intraperitoneally to pregnant rats at 18 and 19 days of gestation. The control group was treated with pyrogen-free saline. They were given 5,000 U/kg recombinant human EPO. Seven-day-old Sprague-Dawley rat pups were divided into four groups: control group, LPS-treated group, prenatal maternal EPO-treated group (5,000 U/kg, intraperitoneally given to pregnant rats at 18 and 19 days of gestation), and postnatal EPO-treated group (5,000 U/kg, intraperitoneally given to 1-day-old rat pups). Cytokine induction in the postnatal 7-day-old (P7) rat brain after maternal administration of LPS was determined by the ELISA method. The proinflammatory cytokine levels (IL-1 beta, TNF-alpha, and IL-6) in P7 rat pup brains were significantly increased in the LPS-treated group as compared with the control group. Prenatal maternal EPO treatment significantly reduced the concentration of TNF-alpha and IL-6 in the newborn rat brain following LPS injection. The concentration of IL-1 beta was decreased in the intrauterine EPO treatment group. Postnatal EPO treatment significantly decreased only the IL-6 concentration in the newborn rat brain following LPS injection. The concentration of cytokines, IL-1 beta and TNF-alpha, was reduced in the postnatal EPO treatment group. We demonstrated here that LPS administration in pregnant rats at gestational day 18 and 19 induced WM injury in P7 progeny characterized by apoptosis. Prenatal maternal and postnatal EPO treatment significantly reduced the number of apoptotic cells in the periventricular WM. Using immunohistochemistry techniques, we investigated the effects of maternal admi

Topics: Animals; Animals, Newborn; Apoptosis; Bacterial Infections; Brain; Brain Diseases; Disease Models, Animal; Erythropoietin; Female; Humans; Infant, Newborn; Interleukin-1beta; Interleukin-6; Leukomalacia, Periventricular; Lipopolysaccharides; Myelin Basic Protein; Pregnancy; Random Allocation; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

To calculate the absolute risk reduction of transfusion-related adverse events, the number of patients needed to treat, and cost to avoid one transfusion-related adverse event by using erythropoietin in critically ill patients. Number needed to treat with sensitivity analysis.. Teaching hospital.. Hypothetical cohort of critically ill patients who were candidates to receive erythropoietin.. Using vs. not using erythropoietin to reduce the need for packed red blood cell transfusions.. We used published estimates of known transfusion risks: transfusion-related acute lung injury, transfusion-related errors, hepatitis B and C, human immunodeficiency virus, human T-cell lymphotropic virus, and bacterial contamination, stratified by severity. Based on the estimated risk and frequency of transfusions with and without erythropoietin, we calculated the absolute risk reduction of transfusion-related adverse events, the number needed to treat, and cost to avoid one transfusion-related adverse event by using erythropoietin. The estimated incidence of transfusion-related adverse event was 318 permillion units transfused for all transfusion-related adverse events, 58 per million for serious transfusion-related adverse events, and 21 per million for likely fatal transfusion-related adverse events. The routine use of erythropoietin resulted in an absolute risk reduction of 191 per million for all transfusion-related adverse events, 35 per million for serious transfusion-related adverse events, and 12 per million for likely fatal transfusion-related adverse events. The number needed to treat was 5,246 to avoid one transfusion-related adverse event, 28,785 to avoid a serious transfusion-related adverse event, and 81,000 for a likely fatal transfusion-related adverse event. The total cost was $4,700,000 to avoid one transfusion-related adverse event, $25,600,000 to avoid one serious transfusion-related adverse event, and $71,800,000 to avoid a likely fatal transfusion-related adverse event. The magnitude of these results withstood extensive sensitivity analysis.. From the perspective of avoidance of adverse events, erythropoietin does not appear to be an efficient use of limited resources for routine use in critically ill patients.

Topics: Bacterial Infections; Blood Group Incompatibility; Blood Transfusion; Cost-Benefit Analysis; Critical Illness; Erythropoietin; Health Care Costs; Humans; Incidence; Medical Errors; Morbidity; Pharmacoepidemiology; Recombinant Proteins; Risk; Transfusion Reaction; United States; Virus Diseases

To evaluate the pattern of erythropoietin (EPO) and some proinflammatory cytokines in the anemia of chronic disorders (ACD) secondary to infection.. Sequential determination in serum of interleukin-1 beta (IL-1 beta), necrosis tumoral factor alpha (TNF-alpha), gamma interferon (IFN-gamma), interleukin-6 (IL-6), and erythropoietin (EPO) in 25 patients with chronic bacterial infectious diseases and ACD criteria. We evaluated the relationship of these mediators with the anemia and the iron metabolism.. Serum EPO levels significatively decreased compared with initial values, and the last control was in normal rank (18.04 +/- 19.10 vs. 8.56 +/- 4.72 UI/mL; p < 0.001; normal rank: 4-15 mUI/mL). In the first control, there was a negative and non significative correlation between the EPO levels and the hemoglobin concentration (r = -0.115, NS), reaching significance in the last control (r = -0.446; p < 0.05). There was negative correlation between the hematocrit and TNF-alpha levels (r = 0.467; p < 0.05) and between the haemoglobin values and the log of serum TNF-alpha (r = 0.424; p < 0.001). An inverse correlation between the IL-6 levels and both, the hemoglobin concentration and the serum iron was found, and there was a direct correlation between this cytokine values and the EPO levels.. Blunted response of erythropoietin and the action of TNF may contribute to the pathogenesis of ACD secondary to infection. Positive correlation between IL-6 and EPO suggest a proerythropoietic action of IL-6 in response to the anemia.

Topics: Adult; Aged; Anemia; Bacterial Infections; Chronic Disease; Cytokines; Erythropoietin; Female; Fever; Hematocrit; Hemoglobinometry; Humans; Interferon-gamma; Interleukin-1; Interleukin-6; Male; Middle Aged; Tumor Necrosis Factor-alpha

Most patients receiving anemia therapy respond well, with a significant rise in hemoglobin concentration. However, approximately 5%-10% of patients fail to show a satisfactory response despite high doses of erythropoietin. The definition of hyporesponsiveness to anemia therapy is somewhat arbitrary, but it is generally regarded as a failure to achieve a hemoglobin concentration of 10-11 g/dL despite a dose of erythropoietin in excess of 200 U/kg weekly. The condition has many causes, the most important ones being iron deficiency, infection or inflammation, and underdialysis. Investigating a patient's poor response to erythropoietin should begin with a check for compliance, followed by screening for iron deficiency. If doubt exists about the presence of iron deficiency, then a trial of intravenous iron may be given. A reticulocyte count may be helpful. A significantly elevated count suggests the presence of blood loss or hemolysis. The level of C-reactive protein (CRP) may be useful as an indicator of underlying inflammation, and underdialysis may be corrected by increasing the dialysis prescription. If other, minor causes of hyporesponsiveness to erythropoietin have been excluded, then a bone marrow biopsy should be performed. Some patients may require higher doses of erythropoietin, and it is not unreasonable to increase the dose to 10,000 U thrice weekly. Some causes of hyporesponsiveness to erythropoietin, such as iron deficiency and underdialysis, are easily corrected; but others, such as primary bone marrow disorders and hemoglobinopathies, are not possible to overcome.

Topics: Anemia; Anemia, Iron-Deficiency; Bacterial Infections; C-Reactive Protein; Erythropoietin; Hemoglobins; Humans; Kidney Failure, Chronic; Patient Compliance; Peritoneal Dialysis; Recombinant Proteins; Reticulocyte Count; Treatment Failure

The low plasma erythropoietic (Epo) activity which is non-adequate to manifestation of anemia, and the lack of correlation between Epo activity and the degree of anemia and hypoxia were found in children with sepsis. The lowest Epo activity was determined in plasma of patients after repeatedly blood transfusion and in emaciated children. The non-specific Epo activity inhibitor was determined in acute period of sepsis in majority of patients. We suppose that the low Epo activity was due to the violation of Epo synthesis regulation mechanism or was connected with the presence of non-specific inhibitors. These results suggest recombinant Epo for the treatment of anemia in children with sepsis.

Topics: Anemia, Hypochromic; Animals; Bacterial Infections; Blood Transfusion; Cells, Cultured; Erythropoietin; Hemoglobins; Humans; Hypoxia; Infant; Mice; Mice, Inbred BALB C; Reference Values

PURPOSE AND RATIONALE: There has been no previously published experience with granulocyte-macrophage colony-stimulating factor (GM-CSF) at doses less than 15 micrograms/m2/d in patients with aplastic anemia, and most observations have been made at doses of 100 to 500 micrograms/m2/d (2.5 to 12.5 micrograms/kg/d). The benefits of using considerably lower doses, if effective, should include a decrease in cost and in side effects. We have therefore used very low doses of GM-CSF to treat a group of patients with aplastic anemia. Additionally, since severe anemia is often a problem in these patients, we recently started administering erythropoietin along with the GM-CSF. Herein we report the results of very-low-dose GM-CSF therapy in patients with aplastic anemia and our preliminary findings in those individuals who received combination therapy.. We administered recombinant human GM-CSF subcutaneously at doses of 5 to 20 micrograms/m2/d ("very-low-dose GM-CSF") to 12 patients with aplastic anemia. In addition, a 13th patient received erythropoietin together with the GM-CSF regimen, and three of the 12 individuals who initially received 1 or more months of GM-CSF alone were later also given erythropoietin (4,000 U/d subcutaneously).. In five of 12 patients (42%) treated with very-low-dose GM-CSF, an increase in neutrophil counts (2.0- to 6.7-fold) was noted, and one of these subjects attained a bilineage response (neutrophil counts, 0.3 to 1.75 x 10(9)/L; platelet counts, 8 to 169 x 10(9)/L). Moreover, a sixth patient showed a rise in platelet counts (19 to 80 x 10(9)/L) without a concomitant increase in neutrophils. Constitutional side effects were minimal. Combining erythropoietin and very-low-dose GM-CSF produced a bilineage response (neutrophils, 1.0 to 3.0 x 10(9)/L; hemoglobin, 7.4 to 9.4 g/dL) in the one patient who received erythropoietin together with the GM-CSF from the time that GM-CSF was initiated. In one of the other patients who were given combination therapy, the addition of erythropoietin appeared to enhance the response; this patient demonstrated a neutrophil response to GM-CSF alone and a trilineage response (neutrophils, 0.8 to 3.75 x 10(9)/L; hemoglobin, 7.0 to 13.1 g/dL; and platelets, 10 to 34 x 10(9)/L) to the combination. No toxicity was associated with the addition of erythropoietin.. Our observations suggest that (1) very low doses of GM-CSF (5 to 20 micrograms/m2/d subcutaneously) may be used initially in neutropenic patients with aplastic anemia, and the dose subsequently increased only in patients who do not respond; and (2) the administration of erythropoietin together with GM-CSF is well tolerated, can augment responsiveness in some patients, and deserves further study.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Aplastic; Bacterial Infections; Bone Marrow; Erythropoietin; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Hemoglobins; Humans; Injections, Subcutaneous; Leukocyte Count; Lymphocytes; Male; Middle Aged; Neutropenia; Neutrophils; Platelet Count; Recombinant Proteins; Thrombocytopenia; Time Factors

Serum erythropoietin (S-EPO) levels were measured in 50 patients with anaemia of chronic disorders (ACD), classified into three groups according to their aetiology: inflammatory (n = 20), infectious (n = 15) and neoplastic (n = 15). The inflammatory group showed a higher mean S-EPO level (mean value +/- SEM, 69 +/- 11 mU ml-1) than the neoplastic (43 +/- 5 mU ml-1; P less than 0.05) and infectious groups (27 +/- 4 mU ml-1; P less than 0.01). The S-EPO level in the inflammatory group also differed from that of 32 healthy controls (36 +/- 3 mU ml-1; P less than 0.05). Fourteen patients with added iron deficiency (12 subjects from the inflammatory group) showed the highest S-EPO concentration (72 +/- 17 mU ml-1). Conversely, S-EPO levels were lower in febrile subjects (12 patients with infection and five with malignancy) than in non-febrile patients (28 +/- 4 mU ml-1 vs. 55 +/- 7 mU ml-1; P less than 0.01). In the infectious group, the logarithm of S-EPO correlated directly with the haemoglobin and haematocrit values. We conclude that differences in S-EPO concentration in ACD may be further related to the patient's iron stores and temperature. A decrease in EPO production may contribute to the pathogenesis of ACD secondary to infection.

Topics: Anemia; Anemia, Hypochromic; Arthritis, Rheumatoid; Bacterial Infections; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms

Iron overload increases the risk of bacterial infection in dialysis patients, partly by impairing functions of the polymorphonuclear granulocytes (PMNs). PMN defence was studied sequentially in haemodialysis patients with transfusional haemosiderosis, treated for 6 +/- 1.5 months (n = 8) to 13 +/- 1.7 months (n = 4) with recombinant human erythropoietin (rHuEpo). Over this period, signs of iron overload (increased serum ferritin and serum iron) improved, and stainable iron disappeared in PMNs. Simultaneously, phagocytosis of Yersinia enterocolitica by PMNs improved. The decrease in serum ferritin was significantly related to the improved phagocytosis. Killing of Y. enterocolitica by PMNs also improved. It is anticipated that rHuEpo therapy in iron-overloaded dialysis patients could decrease the incidence of bacterial infection by improving PMN functions in these patients.

Topics: Adult; Aged; Bacterial Infections; Blood Bactericidal Activity; Erythropoietin; Female; Hemosiderosis; Humans; Iron; Male; Middle Aged; Neutrophils; Phagocytosis; Recombinant Proteins; Renal Dialysis; Yersinia enterocolitica

Although anemia of chronic disease is a common hematologic disorder, the pathogenesis of the disease is still not well understood. Various workers have demonstrated decreased red cell life span, decreased erythropoietin levels, and inappropriate response of the bone marrow to the degree of anemia. The iron metabolism in the anemia of chronic disease is abnormal in that the macrophages in the bone marrow hold onto iron and do not release it for reutilization by the erythroid precursors. More recent studies have focused attention on cytokines produced by macrophages. These are interleukin-1 and tumor necrosis factor. These cytokines appear to be involved in both red cell production and ferrokinetics. Greater understanding of the biology of the cytokines may be the key to understanding the pathogenesis of anemia of chronic disease.

Topics: Anemia; Bacterial Infections; Chronic Disease; Erythropoiesis; Erythropoietin; Humans; Interleukin-1; Neoplasms; Tumor Necrosis Factor-alpha

Anemia is invariably seen in patients who have been severely burned, and a number of factors have been implicated in its etiology. Prior studies have suggested that a depressed rate of erythropoiesis is involved. In order to study this, we evaluated the effect of serum from burned patients on red cell and white cell colony growth in vitro. We found that these sera were capable of inhibiting red cell, but not white cell, colony growth. Additional experiments indicated that this was related to the presence of some substance in the burned serum rather than the absence of a factor required for colony formation. Further studies, including review of clinical data, suggested that this effect was not due to topical medications nor to episodes of bacterial sepsis. Serial studies showed that inhibition was often not present in the immediate postburn period but developed gradually, reaching maximum intensity approximately 20 to 30 days following the burn and then returning toward normal as patients healed their injury. Our studies permit the hypothesis that inhibition of erythropoiesis plays a role in the pathogenesis of the anemia of thermal injury.

Topics: Adult; Aged; Anemia; Animals; Bacterial Infections; Burns; Cells, Cultured; Erythropoiesis; Erythropoietin; Female; Humans; Mice

Topics: Anemia, Hypochromic; Animals; Bacterial Infections; Cell Division; Erythroblasts; Erythrocyte Aging; Erythrocytes; Erythropoiesis; Erythropoietin; Humans; Neoplasms