Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The recent production of recombinant human growth factors has expanded the neonatal clinician's armamentarium for treating sepsis and anemia of prematurity (AOP). Agents that may prove useful in the premature neonate include recombinant human erythropoietin (rh-EPO), granulocyte colony-stimulating factor (rhG-CSF), and CSF). Within the neonatal population, research utilizing these agents is still relatively new. Appropriate clinical trials are still needed to elucidate the optimal dosing regimen for both rhG-CSF and rh-EPO, as are studies to address the issue of long-term safety. Use of rhG-CSF in sepsis and of rh-EPO for AOP is still considered experimental, but in instances where conventional treatments are not proving beneficial, these agents may provide a therapeutic alternative. Their potential for improving care of the premature neonate must also be assessed.
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PMID:Hematopoietic growth factors: Part I. 893 67

Administration of large doses of recombinant granulocyte colony-stimulating factor (rG-CSF) to mice results in diminished erythropoiesis. Hyporegenerative anemia does not occur in adult humans as a consequence of treatment with rG-CSF, but it is not clear whether this will be a problem in neonates. Because rG-CSF is currently being tested as a treatment for neutropenia in neonates, we assessed the possibility that such treatment will diminish their erythropoiesis. To do this, we added rG-CSF, in vitro, to clonogenic cultures of hematopoietic progenitors obtained from the bone marrow and liver of seven human fetuses and from the umbilical cord blood of five term and five preterm infants. The range of rG-CSF concentrations tested (0.1-10.0 ng/mL) included the peak concentrations measured in the blood of neonates receiving rG-CSF treatment on experimental protocols. Inclusion of rG-CSF in the cultures did not diminish clonal maturation of fetal erythroid (erythroid colony-forming and burst-forming unit) progenitors, nor did it reduce the number of normoblasts generated per erythroid progenitor cell colony. On the basis of these studies we predict that administration of rG-CSF to neonates will not result in down-modulation of erythropoiesis.
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PMID:Effect of recombinant granulocyte colony-stimulating factor on erythropoiesis in the human fetus and neonate. 894 65

Thrombopoietin, the endogenous c-Mpl ligand, is a novel lineage-specific hematopoietic factor that plays a pivotal role in the regulation of megakaryocytopoiesis and thrombopoiesis. In this study, we examined the effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), a truncated molecule of recombinant human c-Mpl ligand derivatized with polyethylene glycol, on myelosuppressive chemotherapy-induced thrombocytopenia in mice. We developed a new murine model of thrombocytopenia induced by i.v. injections of mitomycin C (MMC) for two consecutive days. In control mice, platelet counts began to decrease on day 6, reached a nadir of less than 5% of basal level on day 14, and could not recover to basal level by day 26. Administration of PEG-rHuMGDF greatly enhanced recovery of the number of megakaryocyte progenitor cells and the megakaryocytes in bone marrow, and markedly reduced the severity of thrombocytopenia; it also accelerated platelet recovery in a dose-dependent manner in myelosuppressed mice. Mice receiving consecutive administration of higher doses of PEG-rHuMGDF showed no thrombocytopenia but rather had platelet counts being increased over basal level. Although absolute neutrophil counts and red cell counts also were decreased following MMC treatment, administration of PEG-rHuMGDF also improved neutropenia and anemia. Administration of PEG-rHuMGDF on alternate days or once a week after chemotherapy was almost as effective as consecutive administration in improving thrombocytopenia. Combined administration of PEG-rHuMGDF and rHuG-CSF had an additive effect on improvement of thrombocytopenia and neutropenia. These results suggest that PEG-rHuMGDF is a therapeutically effective agent in the treatment of thrombocytopenia associated with chemotherapy.
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PMID:Effects of pegylated recombinant human megakaryocyte growth and development factor on thrombocytopenia induced by a new myelosuppressive chemotherapy regimen in mice. 894 25

ACES (Ara-C, carboplatin, etoposide, steroids) therapy using granulocyte-colony stimulating factor (G-CSF) was designed for relapsed or refractory non-Hodgkin's lymphoma (NHL), and the therapeutic effects and adverse reactions were studied. The subjects were 40 patients, including 19 relapsed cases and 21 refractory cases, subjected to chemotherapy using anthracycline type agents. The ACES therapy consisted of carboplatin at 100 mg/m2 and etoposide at 80 mg/m2 for 4 d from the first day, Ara-C at 2 g/m2 on the fifth day, solumedrol at 500 mg for 5 d from the first day and G-CSF at 2 micrograms/kg from the seventh day. This therapy was performed every 3 weeks, in principle. The doses were reduced to 70% of the above values for patients aged 70 yr or older. Among the 40 patients, complete remission (CR) was achieved in 14 (35%) and partial remission (PR) in 14 (35%) for a response of 70%. The 50% survival period was 526 d, and the 2-yr disease-free survival rate was 58.3%. Adverse reactions of grade 3 or higher included granulocytopenia in 62.5%, anemia in 17.5% and thrombocytopenia in 50%, but there was no death related to treatment. Four patients underwent transplantation of hematopoietic stem cells and have survived for long periods. This treatment was effective against relapsed NHL and could be performed safely with few adverse reactions.
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PMID:Salvage chemotherapy for relapsed or refractory non-Hodgkin's lymphoma with a combination of ACES (high-dose Ara C, carboplatin, etoposide and steroids) therapy. 898 96

This study was aimed to evaluate the effect of ifosfamide, cisplatin and etoposide (ICE) combined chemotherapy in small cell lung cancer (SCLC), and to test the feasibility of adding recombinant human granulocyte colony-stimulating factor (rhG-CSF) to aggressive chemotherapy. Thirty consecutive, previously untreated, patients with SCLC (17 with limited disease and 13 with extensive disease) entered this study. The ICE regimen consisted of ifosfamide (I) 4 g/m2 i.v. with same dose mesna i.v. on first day, cisplatin (C) 25 mg/m2 i.v. on days 1 to 3 and etoposide (E) 100 mg/m2 i.v. on days 1 to 3. A total of 30 MU rhG-CSF i.v. were given from day 7 to 14 if WBC were lower than 3000 x 10(6)/L, neutrophils were lower than 1000 x 10(6)/L. Overall response (OR) rate was 93% with a complete response (CR) rate of 23%. Median survival was 12 months [95% confidence interval (CI): 11-14] and median response duration was 10 months [95% CI: 8-10]. Thirty-seven percent of patients had grade 3 neutropenia, 40% had grade 3 anemia, and 1% had grade 2 thrombocytopenia. Nonhematologic toxicity was mild with nausea and vomiting being the most common. RhG-CSF, which reduced leukopenic nadirs and shortened the neutropenic period, was also well tolerated. This chemotherapy protocol seems to be active, well tolerated and is currently being compared with various conventional chemotherapies.
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PMID:Ifosfamide, cisplatin and etoposide (ICE) combined chemotherapy with recombinant human granulocyte colony-stimulating factor support in small cell lung cancer. 910 21

Clinical and laboratory features of acute meningococcal meningitis according to age were studied in 255 patients. Whereas males accounted for three out of five patients aged 0-4 years, females accounted for three out of four patients older than 50 years of age. All patients had clinical signs of nuchal rigidity and fever. Patients older than 30 years of age had less frequent petechiae (62%) than younger patients (81%). Furthermore, elderly patients above 50 years of age were prone to an obtunded mental state and a prolonged disease course with fever. Without relation to age, 2/3 had purulent meningitis and 2/3 had marked peripheral leucocytosis (> 15 x 10(9) cells/l); 90% of patients had at least one of these findings. The cellular inflammatory response in peripheral blood indicated a bacterial aetiology in > 95% of the cases. More than 80% of children and adults had abnormal CSF biochemical findings, but the level of protein and the glucose ratio (CSF/serum) were positively and negatively correlated to increasing age of the patient, respectively: thus, in children these biochemical markers may be unreliable in the differentiation between a bacterial and non-bacterial aetiology. Thrombocytopenia (< 100.000 x 10(9)/I) was not associated with age, though the lowest platelet count was found in elderly patients. The case fatality rate was 7.5%, but neither age, sex nor sign of septicaemia was associated with fatality. Thrombocytopenia, a lowered coagulation index (< 0.5, factors II, VII, X), a moderate anaemia (haemoglobin < 11 g/dl), an obtunded mental state and a history of convulsions were poor prognostic factors; only anaemia was independently correlated to fatality so this should be considered as an important prognostic marker in the acute phase of meningococcal meningitis.
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PMID:Acute meningococcal meningitis: analysis of features of the disease according to the age of 255 patients. Copenhagen Meningitis Study Group. 920 30

32 cases (21 acute severe malaria and 11 chronic malaria syndrome), who developed unusual complications and/or manifestations are reported. The acute manifestations were unexplained tachypnoea 4, pulmonary oedema 5 and shock due to multiple organ dysfunction syndrome 3, melena 2 and E coli septicaemia in one. The other features were concomitant salmonellosis 2, meningitis 1, renal failure 3, hepatorenal syndrome 2, hepatitis like illness 7, neck stiffness with normal CSF 3, urticaria and subconiunctival haemorrhage 2 each, apyrexial spell with anaemia 4, thromocytopenia 3, and hypoglycaemia 3 (two pretreatment and one while on quinine in 5% glucose drip). The chronic syndrome noted were hyperreactive malaria syndrome (Tropical splenomegaly) 3, repeated haemolysis 2, chronic simple malaria with positive parasitaemia and normal Igm levels 4, and cerebellar ataxia with tremors 3. Bone marrow in these cases was hypercullular with increase plasma cells. Liver biopsy revealed lymphocytic infiltration. There was no case with permanent neurogical deficit. All patients with pulmonary oedema and multiple organ dysfunction died but chronic syndrome patients recovered fully. Early recoginition of atypical manifestation and prompt treatment will decrease the mortality and morbidity due to malaria.
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PMID:Unusual acute and chronic complications of malaria. 928 1

Previous studies have shown that approximately 40% of patients with myelodysplastic syndrome (MDS) and anaemia respond to treatment with human recombinant granulocyte-CSF (G-CSF) plus erythropoietin (epo). The present study was designed to investigate pre-treatment variables for their ability to predict erythroid responses to this treatment. 98 patients with MDS (30 RA, 31 RARS, 32 RAEB, five RAEB-t) were treated with a combination of G-CSF (0.3-3.0 microg/kg/d, s.c.) and epo (60-300 U/kg/d, s.c.) for at least 10 weeks. Minimum criteria for erythroid response was a 100% reduction of red blood cell (RBC) transfusion need or an increase in haemoglobin level of > or = 1.5 g/dl. 35 patients (36%) showed responses to treatment. Medium duration of response was 11-24 months. In multivariate analysis, serum erythropoietin levels and initial RBC-transfusion need retained high statistical significance (P < 0.01). Using pre-treatment serum epo levels as a ternary variable (< 100, 100-500 or > 500 U/l) and RBC transfusion need as a binary variable (< 2 or > or = 2 units per month), the analysis provided a predictive score for erythroid response. This score divided patients into three groups: one group with a high probability of erythroid responses (74%), one intermediate group (23%) and one group with poor responses to treatment (7%). This predictive scoring system could be used in decisions regarding use of these cytokines for treating the anaemia of MDS, both for defining patients who should not be given the treatment and for selecting patients for inclusion in prospective trials.
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PMID:Erythroid response to treatment with G-CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model. 937 52

Hypoxemia and anemia are associated with increased CBF, but the mechanisms that link the changes in PaO2 or arterial O2 content (CaO2) with CBF are unclear. These experiments were intended to examine the contribution of nitric oxide. CaO2 in pentobarbital-anesthetized rabbits was reduced to approximately 6.5 mL O2/dL by hypoxemia (PaO2 approximately 24 to 26 mm Hg) or hemodilution with hetastarch (hematocrit approximately 14% to 15%). Animals with normal CaO2 (approximately 17.5 to 18 mL O2/dL) served as controls. In part I, each animal was given 3, 10, and 30 mg/kg N omega-nitro-L-arginine methyl ester (L-NAME) intravenously (total 43 mg/kg) to inhibit production of nitric oxide. Forebrain CBF was measured with radioactive microspheres approximately 15 to 20 minutes after each dose. Baseline CBF was greater in hypoxemic rabbits (111 +/- 31 mL x 100 g-1 x min-1, mean +/- SD) than in hemodiluted (70 +/- 22 mL x 100 g-1 min-1) or control animals (39 +/- 12 mL x 100 g-1 min-1). L-NAME (which reduced brain tissue nitric oxide synthase activity by approximately 65%) reduced CBF in hypoxemic animals to 80 +/- 23 mL x 100 g-1 x min-1 (P < 0.0001), but had no significant effect on CBF in either anemic or control animals. In four additional rabbits, further hemodilution to a CaO2 of approximately 3.5 mL O2/dL increased baseline CBF to 126 +/- 21 mL x 100 g-1 min-1, but again there was no effect of L-NAME. In part II, animals were anesthetized as above, and a close cranial window was prepared. The cyclic GMP (cGMP) content of the artificial CSF superfusate was measured under baseline conditions, and then after the reduction of CaO2 to approximately 6.5 mL O2/dL by either hypoxemia or hemodilution. Concentrations of cGMP did not change during either control conditions or after hemodilution. However, cGMP increased significantly with the induction of hypoxemia. The cGMP increase in hypoxemic animals could be blocked with L-NAME. These results suggest that nitric oxide plays some role in hypoxemic vasodilation, but not during hemodilution.
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PMID:Cerebral blood flow during hypoxemia and hemodilution in rabbits: different roles for nitric oxide? 939 31

Previous studies have shown that daily multiple administration of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) markedly stimulates thrombopoiesis and effectively ameliorates thrombocytopenia, and in most cases anemia and neutropenia, in myelosuppressed animals. In this study, we evaluated the effects of a single intravenous injection of PEG-rHuMGDF on hematopoietic recovery after sublethal total-body irradiation in mice. A single injection of PEG-rHuMGDF (1 to 640 microg/kg) 1 hour after irradiation accelerated platelet, red blood cell (RBC), and white blood cell (WBC) recovery in a dose-dependent fashion. In the bone marrow of vehicle-treated mice, megakaryocytic, erythroid, and myeloid progenitors, as well as day 12 colony-forming unit-spleen (CFU-S), were dramatically decreased much earlier than the nadirs of peripheral blood cells, whereas megakaryocytes were modestly decreased. Treatment with PEG-rHuMGDF (80 microg/kg, an optimal dose) 1 hour after irradiation resulted in more rapid recovery of these four hematopoietic progenitors and also significantly facilitated megakaryocyte recovery. In addition, the same PEG-rHuMGDF administration schedule expanded bone marrow cells capable of rescuing lethally irradiated recipient mice. As the interval between irradiation and PEG-rHuMGDF treatment was longer, its effects on hematopoietic recovery were attenuated. In contrast to the effects of PEG-rHuMGDF, a single injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF) 1 hour after irradiation exclusively accelerated WBC recovery, but only to a similar extent as PEG-rHuMGDF (80 microg/kg) treatment even when rhG-CSF doses were escalated to 1,000 microg/kg. This appeared related to different pharmacokinetics of these two factors after a single injection in irradiated mice. The concentrations of PEG-rHuMGDF after injection persisted in the plasma for a longer time compared with rhG-CSF. These results indicate that a single injection of PEG-rHuMGDF at an early time after irradiation is able to effectively improve thrombocytopenia, anemia, and leukopenia with concomitant accelerated recovery of both primitive and committed hematopoietic progenitors in irradiated mice. Our data also show that compared with the rhG-CSF shown to exert multilineage effects on hematopoiesis, PEG-rHuMGDF has more wide-ranging effects on peripheral blood cell recovery.
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PMID:Multilineage hematopoietic recovery by a single injection of pegylated recombinant human megakaryocyte growth and development factor in myelosuppressed mice. 941 67


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