Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokines play key roles in the control of hemopoiesis and immunity. As they become available in increasing quantities and purity through improved recombinant technology, cytokines hold great clinical promise. This article focuses on recent clinical experience with a wide variety of cytokines. For example, newer uses of recombinant human erythropoietin include treatment of anemia of prematurity, AIDS, and some hemoglobinopathies. The myeloid-stimulating factors have established a niche in the treatment of chemotherapy-induced neutropenias and as an adjunct to bone marrow transplantation. Combinations of cytokines that act at different levels of hemopoietic proliferation are being evaluated for the treatment of other causes of neutropenia and thrombocytopenia and also as biologic response modifiers.
 ...
PMID:The use of cytokines in children. 820 76

3'-azido-3'-deoxythymidine (AZT), the main antiviral drug used in AIDS treatment, is known to induce anemia and neutropenia. These effects have been attributed to its toxicity to hematopoietic progenitors. In this report, we present a new approach to reduce AZT hematotoxicity by using an inhibitory factor of the hematopoietic stem cells, the tetrapeptide AcSerAspLysPro (AcSDKP, Seraspenide), which has been shown to increase the survival of mice subjected to high doses of chemotherapy and to block reversibly the cycling of human granulocyte-macrophage colony forming unit (CFU-GM) and burst forming unit erythroid (BFU-E) progenitors. Normal bone marrow mononuclear cells (BMMNC) from 14 subjects were incubated with or without AcSDKP (10(-10) M) for 20 h and with or without AZT (100 microM) for another 2 h. After washing, cells were plated in methylcellulose in the presence of interleukin 3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF) and erythropoietin (EPO). Under these conditions, the preincubation of cells with AcSDKP reduced significantly the toxicity of AZT to both BFU-E and CFU-GM at least in 3 out of 8 and 4 out of 10 cases, respectively. A careful statistical analysis of these observations indicates that AcSDKP may be an efficient factor in preserving progenitors against AZT-induced hematopoietic toxicity.
 ...
PMID:The tetrapeptide AcSerAspLysPro (Seraspenide), a hematopoietic inhibitor, may reduce the in vitro toxicity of 3'-azido-3'-deoxythymidine to human hematopoietic progenitors. 824 56

The ability of combination treatment with erythropoietin (Epo) and heme to rescue hematopoietic activity in mice from the suppressive effect of azidothymidine (AZT) was determined. Exposure of mice to AZT for 5 weeks produced marked anemia, thrombocytopenia, neutropenia, and weight loss, whereas mice that received Epo and heme for 3 subsequent weeks showed significant alleviation of AZT cytotoxicity. Treatment with Epo (10 U for 5 times/week) stimulated hematopoietic recovery in the AZT-treated animals and reduced the severe anemia and thrombocytopenia by 3 weeks. Administration of a lower Epo dose (1 U Epo) resulted in only a modest retardation of AZT-induced anemia, although, when combined with heme, there was a great improvement in recovery of erythropoiesis. The combination of heme with Epo (10 U) produced the optimum response, resulting in almost normal recovery of bone marrow cellularity as well as recovery of burst-forming units-erythroid (BFU-E) and splenic hematopoietic progenitor content (colony-forming unit-spleen [CFU-S]) by the end of 3 weeks of post-AZT treatment. Treatment with heme alone markedly enhanced the recovery of BFU-E and CFU-S, as well as body weight post-AZT; however, this recovery was not to the extent seen in combination with Epo (10 U). Long-term bone marrow cultures (LTBMCs) established from mice exposed to AZT for 8 weeks showed a marked reduction in cellularity and this was completely alleviated when mice received heme and Epo (10 U) for 3 weeks after 5 weeks of AZT administration. The additive effect of heme and Epo was seen in BFU-E production, as well as in CFU-S production, in LTBMCs. Thus, heme exerts a significant protective effect on hematopoietic progenitors in vivo and may be of potential clinical use in combination with Epo to promote effective erythropoiesis in the setting of AZT therapy.
 ...
PMID:Additive effect of erythropoietin and heme on murine hematopoietic recovery after azidothymidine treatment. 820 2

All cases of transient erythroblastopenia in children less than 10 years of age, diagnosed in Sweden during the years 1987-89, were identified. Almost all (51/53) were less than 3 years of age. In this group, the incidence was 4.3/100 000, which is the same as that of acute lymphatic leukaemia. No geographical, but a possible temporal, cluster was seen in 1989. The anaemia was severe in some cases; haemoglobin concentration was less than 40 g/l in 8 of 53 children. Thrombocytosis and neutropenia were common and were attributed to high endogenous erythropoietin activity. Thirty-seven of 53 children were given a blood transfusion. All children recovered and no complications or relapses were seen. Transient erythroblastopenia of childhood is a benign disease, and it is important to make a correct diagnosis to prevent unnecessary anxiety for leukaemia or aplastic anaemia.
 ...
PMID:Transient erythroblastopenia of childhood in Sweden: incidence and findings at the time of diagnosis. 833 93

Haematological complications frequently occur in patients treated with chemotherapeutic agents. The degree and duration of bone marrow suppression depends upon the type of agent used. In general, agents that are cell cycle phase-specific tend to cause early myelosuppression with rapid marrow recovery, as compared to the non-phase-specific agents. Host factors including patient age, nutritional status, marrow infiltration or damage, and hepatic and renal function also affect haemotoxicity. Chemotherapeutic agents suppress proliferating or potentially proliferating precursors of neutrophils, platelets and red blood cells to the same extent. With most drugs, neutropenia tends to be dose limiting and more severe than thrombocytopenia. Because of the longer life span of red blood cells, severe anaemia is rarely a problem. The management of myelosuppression is multifaceted, and consists of aggressive antibiotic therapy to treat or prevent the infections that occur with neutropenia, as well as red blood cell and platelet transfusion support to correct anaemia and prevent bleeding. The role of the haemopoietic growth factors including erythropoietin, colony-stimulating factors and the interleukins is currently being evaluated in clinical trials. Haemolytic uraemic syndrome, haemolytic anaemia and therapy-induced myelodysplasia and/or acute leukaemia are uncommon and potentially severe complications of chemotherapeutic agents.
 ...
PMID:Adverse haematological complications of anticancer drugs. Clinical presentation, management and avoidance. 845 62

The drug zidovudine (AZT), a synthetic thymidine analog, has been used in the treatment of acquired immunodeficiency syndrome (AIDS). Clinical use of zidovudine has induced hematopoietic toxicity manifested by anemia, neutropenia and on occasion thrombocytopenia. Such toxicity has stimulated the development of alternative dideoxynucleoside drugs capable of exerting anti-viral potency while minimizing the risk for inducing organ toxicities. One such alternative dideoxynucleoside drug is 2',3'-dideoxyinosine (ddI). Recent therapeutic anti-viral strategy, now undergoing clinical trial, is the evaluation of combined zidovudine ddI treatment. Unfortunately a complete assessment of their potential toxicity using this drug regimen has not been thoroughly examined. We report here the results of studies comparing the toxicity profile of zidovudine versus ddI on their ability to influence several classes of hematopoietic progenitor stem cells, e.g. granulocyte--macrophage (CFU-GM), megakaryocyte (CFU-Meg) and erythroid (CFU-E/BFU-E) following in vitro co-culture with normal human bone marrow. Since the main clinical toxicity associated with zidovudine in vivo is the development of anemia, additional in vitro studies compared the dose-escalation effect of erythropoietin in the presence of combined zidovudine and ddI. CFU-GM, CFU-Meg, CFU-E and BFU-E were all reduced (P < 0.05) following incubation with either zidovudine or ddI thus determining their ID50 concentrations for these classes of hematopoietic progenitors; however, the extent of toxicity associated with ddI was lower than what was observed with zidovudine. More importantly, dose-escalation of erythropoietin was effective in reversing the inhibition observed for ddI on erythroid progenitors CFU-E and BFU-E (P < 0.05), an effect not reported with zidovudine in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Comparison of dideoxynucleoside drugs (DDI and zidovudine) and induction of hematopoietic toxicity using normal human bone marrow cells in vitro. 846 23

We studied the effect of erythropoietin (EPO) and interleukin 3 (IL-3), either alone or in combination, on the hematopoietic toxicity associated with zidovudine in vivo, as determined by peripheral blood indices, and assay of hematopoietic progenitors, i.e. erythroid (CFU-E/BFU-E), myeloid (CFU-GM) and megakaryocyte (CFU-Meg) from bone marrow and spleen. Previous studies from this laboratory have established that dose escalation of zidovudine to normal mice induced a dose-dependent decrease in hematocrit, white blood cells and platelets with altered populations of marrow and splenic erythroid, myeloid and megakaryocyte progenitors. Daily administration of EPO (50 U/animal, i.p.) and/or IL-3 (5 U/animal, i.p.) was associated with altered peripheral blood indices and progenitor cells. In general, use of EPO and IL-3 alone reduced zidovudine-induced toxicity, notably in erythropoiesis; however, combination EPO/IL-3 was associated with enhanced toxicity with an observed rebound only with the use of < 2.5 mg/ml drug; 2.5 mg/ml drug in the presence of combination EPO/IL-3 accelerated zidovudine-erythroid toxicity. A similar response was noted with circulating platelets and megakaryocyte progenitors. Use of EPO or IL-3, either alone or in combination, failed to reverse zidovudine-induced neutropenia. These studies demonstrate that use of EPO or IL-3, either alone or in combination may serve as an effective adjuvant therapy to modulate the erythroid toxicity associated with lower doses of zidovudine; however, this cytokine therapy was ineffective modulating zidovudine-induced myelosuppression when used in vivo. A reversal in zidovudine-induced myeloid toxicity, therefore may require the use of a myelopoiesis inducing cytokine.
 ...
PMID:In-vivo effect of interleukin 3 and erythropoietin, either alone or in combination, on the hematopoietic toxicity associated with zidovudine. 848 6

Myelodysplastic syndromes [MDS] are clonal disorders of hematopoietic stem cells leading to a deregulation of proliferation and differentiation of the bone marrow cells. Clinically the patients present with symptoms and signs of anemia, thrombocytopenia, and neutropenia. About a third of the patients will develop acute myeloid leukemia. Supportive care is the mainstay of therapy in these mostly elderly patients. G-CSF should only be given in cases of neutropenia and infection, but not prophylactically. Selected patients with severe or transfusion-dependent anemia will respond to treatment with erythropoietin. In advanced MDS aggressive chemotherapy should be considered, while in patients below 50 years of age and an HLA-identical sibling donor allogeneic bone marrow transplantation is the treatment of choice.
 ...
PMID:[Myeloproliferative syndromes]. 862 70

Patients with myelodysplastic syndromes (MDS) have refractory cytopenias leading to transfusion requirements and infectious complications. In vitro marrow culture data have indicated that granulocyte colony stimulating factor (G-CSF) synergizes with erythropoietin (EPO) for the production of erythroid precursors. In an effort to treat the anemia and neutropenia in this disorder, MDS patients were treated with a combination of recombinant human EPO and recombinant human G-CSF. Fifty-five patients were enrolled in the study of which 53 (96%) had a neutrophil response. Forty-four patients were evaluable for an erythroid response of which 21 (48%) responded. An erythroid response was significantly more likely in those patients with relatively low serum EPO levels, higher absolute basal reticulocyte counts and normal cytogenetics at study entry. Seventeen (81%) of the patients who responded to combined G-CSF plus EPO therapy continued to respond during an 8-week maintenance phase. G-CSF was then discontinued and all patients' neutrophil responses were diminished, whereas 8 continued to have an erythroid response to EPO alone. In 7 of the remaining 9 patients, resumption of G-CSF was required for recurrent erythroid responses. The median duration of erythroid responses to these cytokines was 11 months, with 6 patients having relatively prolonged and durable responses for 15 to 36 months. Our results also indicate that approximately one half of responding patients require both G-CSF and EPO to maintain an effective erythroid response, suggesting that synergy between G-CSF and EPO exists in vivo for the production of red blood cells in MDS.
 ...
PMID:Maintenance treatment of the anemia of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor and erythropoietin: evidence for in vivo synergy. 1153 40

To determine whether granulocyte-colony stimulating factor and erythropoietin are effective in the therapy of neutropenia and anaemia related to human immunodeficiency virus (HIV) infection and to anti-retroviral agents, we recruited 11 HIV-infected children (mean age 4 years 10 months). All the children were given granulocyte-colony stimulating factor at a dosage of 5 micrograms/kg twice or three times a week while erythropoietin was administered additionally to three patients at a dosage of 50 U/kg twice a week. Both agents were administered subcutaneously for at least 4 months. Leukocyte and neutrophil counts significantly increased during the treatment (after 1 months, P = 0.003 and P = 0.009, respectively). Erythropoietin prevented blood transfusions and increased haemoglobin levels in the three children treated. No side-effects were recorded during the administration of either agent. Granulocyte-colony stimulating factor and erythropoietin appear to be safe and useful agents in the management of HIV-infected children.
 ...
PMID:Granulocyte-colony stimulating factor and erythropoietin therapy in children with human immunodeficiency virus infection. 867 88


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>