ISSN:0192-8562    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Erythropoietin is a glycoprotein hormone that plays a vital role in erythropoiesis. It is mainly produced in the fetal liver till the third trimester of pregnancy. At that point, the kidney interstitium takes over this function and be-comes the main source of erythropoietin. Hypoxia stimulates erythropoietin production by a mechanism that may require a heme protein as a second messenger. Erythropoietin stimulates the maturation of erythroid precursors (colony-forming unit-erythroid and burst-forming unit-erythroid) via at least two types of cell surface receptors. The higher-affinity receptors appear to be more important in modulating the effects of erythropoietin in vivo. Changes in intracellular calcium may ultimately mediate the action of erythropoietin on erythroid precursors. A specific and sensitive radioimmunoassay is now available for accurately measuring erythropoietin levels. All forms of erythrocytosis except polycythemia vera are associated with elevated erythropoietin levels. Levels are also high in cord blood obtained following fetal asphyxia. Reduced levels are seen in patients with anemia due to renal diseases. The response of erythropoietin to the degree of anemia appears to be attenuated in patients with cancer, chronic diseases, and human immunodeficiency virus (HIV) infection. Erythropoietin has been successfully used for treating patients with anemia due to renal failure. Its use has also been approved for the treatment of anemia patients receiving zidovudine for HIV infection. Encouraging results have been observed when erythropoietin was used to treat anemia due to rheumatoid arthritis, hematological malignancies, and prematurity. It has also been used to increase the yield of autologous blood collected prior to an elective surgical procedure. However, it has not proved to be useful in sickle cell anemia and myelodysplastic syndromes.

ISSN:0192-8562    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Granulocyte-macrophage colony-stimulating factor (GMCSF) is a glycoprotein necessary for the growth, differentiation, and function of cells of the granulocyte-macrophage lineage. This agent has been molecularly cloned and expressed in bacteria, yeast, and mammalian cell lines, providing a limitless source of the pure human protein for use in children. Here, we briefly review the discovery, biologic characterization, gene identification and cloning, and clinical experience to date with this new agent, focusing where possible on the use of recombinant GM-CSF in children.

ISSN:0192-8562    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Human granulocyte colony-stimulating factor (G-CSF), a 20 KD glycoprotein consisting of 174 amino acids, is one of the physiological regulators mainly produced by endothelial cells, monocytes-macrophages and fibroblasts, under various stimulations such as infections. The molecule specifically and markedly stimulates the production of neutrophils associated with an expansion of the hematopoietic stem cells/progenitor cells and elevates the functional activities of neutrophils. Under favor of the unique biological activities, recombinant human G-CSF (rhG-CSF) has now become an epoch-making agent for the purposes of reduction of bacterial/fungal infections, particularly in neutropenias of various causes, increased dose intensity of chemotherapeutic drugs in cancers, and solving various problems in hematopoietic stem cell transplantation.

ISSN:0192-8562    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The hematopoietic growth factor interleukin (IL)-3 is a potent regulator of blood cell proliferation. It promotes the survival, proliferation, and development of hematopoietic stem cells and committed progenitor cells of the granulocyte-macrophage, erythrocyte, eosinophil, basophil, megakaryocyte, mast cell, and lymphocyte lineages. In addition, IL-3 enhances mature myeloid cell functions such as phagocytosis and activation of basophils and eosinophils, as well as monocyte cytotoxicity. The first phase of clinical trials suggested that IL-3 may augment myelopoiesis in a number of clinical conditions. It may be efficacious for treatment of primary marrow disorders, including myelodysplastic syndromes and aplastic anemia. However, replacement therapy with IL-3 alone is probably not sufficient to obtain maximal stimulation of myelopoiesis. Preclinical and clinical studies published to date suggest that sequential use or combinations of growth factors will be needed to obtain optimal hematopoietic responses.

ISSN:0192-8562    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Cisplatin (CDDP) has been implicated in the development of anemia via several mechanisms of action, including shortening of red cell (RBC) survival and direct toxicity of the drug on RBC bone marrow precursors. Recent studies and case reports suggest an association between CDDP and the development of hyporegenerative anemia as a consequence of relative erythropoietin (EPO) deficiency. To study the effects of CDDP on the relationship between serum EPO and hemoglobin (Hb) concentration, we measured levels of EPO in 12 patients (1–21 years of age) who were treated with cumulative doses of CDDP ranging from 300 to 720 mg/m2for a variety of pediatric malignancies. Post-CDDP glomerular filtration rates (GFR) varied from 29 to 143 ml/min/1.73 m2for 11 of the 12 patients studied. At the completion of CDDP therapy, an inverse linear relationship between log10serum EPO and Hb was noted among those patients who retained at least 40–50% of their pre-CDDP therapy GFR. One patient with chronic renal failure at the completion of CDDP therapy (GFR 25–35 ml/min/1.73 m2) exhibited a chronic transfusion-dependent, hyporegenerative anemia that was due to persistently low levels of EPO. Institution of recombinant human (r-Hu) EPO therapy resulted in an abrupt cessation of this patient's RBC transfusion dependency. Additional studies are needed to further characterize the effects of CDDP on EPO production and secretion and to determine optimal dosing schedules for r-Hu EPO in pediatric patients who receive CDDP and other myelosuppressive chemotherapy.

ISSN:0192-8562    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Thrombocytopenia has a variable incidence in the May-Hegglin anomaly, a rare congenital syndrome characterized by inclusions resembling Dohle bodies within leukocytes, thrombocytopenia, and giant platelets. We studied a 16-year-old girl and three relatives with the syndrome to elucidate the pathogenesis of the thrombocytopenia and the degree of impaired hemostasis. On confirmation of automated platelet counts by manual techniques we found that both aperture-impedence and light-scatter instruments tended to undercount the actual number of platelets by 30–50%. An enzyme immunoassay for platelet-associated IgG showed elevated levels in all patients (mean of 2.3 ± 0.6 ng/106platelets versus 0.8 ± 0.6 in normals, p < 0.0001). Bleeding time and platelet aggregation in response to adenosine diphosphate, arachidonic acid, epinephrine, ristocetin, and collagen were all normal. No clinical bleeding was observed in any of the patients in the face of major surgery or childbirth. The findings suggest the possibility of a peripheral destructive and perhaps an immune pathogenesis of the thrombocytopenia of May-Hegglin anomaly and confirm that clinical bleeding may not accompany the severe thrombocytopenia seen in this disorder.

ISSN:0192-8562    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Desmopressin and ethamsylate were evaluated for possible synergistic effects on the bleeding time. The drugs were administered individually and together to 12 patients with markedly prolonged bleeding times known to be relatively or absolutely unresponsive to desmopressin alone. The bleeding disorders studied included Glanzmann's thrombasthenia (one), other disorders of platelet function (four), pseudo-von Willebrand disease (one), and von Willebrand disease type I (three), type II (two), and type III (one). Desmopressin alone shortened the bleeding time from 23.9 -± 1.5 to 19.5 ± 2.3 min (p = 0.03). Ethamsylate alone was without effect. Desmopressin and ethamsylate together shortened the bleeding time to 11.2 ± 1.4 min (p < 0.01 compared to baseline, p = 0.02 compared to desmopressin alone). The combination was ineffective in three patients, with Glanzmann's thrombasthenia (one), and von Willebrand disease type I (one) and type III (one). Toxic effects of the drugs were not observed. Five patients received desmopressin and ethamsylate prior to dental work with mandibular block (one), heart surgery requiring cardiopulmonary bypass (two), and adenotonsillectomy surgery (two). Normal hemostasis was achieved in each case. A synergistic shortening of the bleeding time was observed with the combination of desmopressin and ethamsylate in a wide range of bleeding disorders.

ISSN:0192-8562    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Eighty-nine pediatric oncology patients, in remission and off treatment for at least 4 years, were reviewed annually in the Late Effects Clinic of Princess Margaret Hospital for Children in Perth, Western Australia. Interval from time of diagnosis to follow-up ranged from 4 to 23 years (mean 10.8 years). Acute lymphoblastic leukemia (ALL) (40%) and Wilms' tumor (27%) were the most common primary malignancies in this group. Late sequelae included musculoskeletal abnormalities (23 children), growth hormone deficiency (11), second tumors (9), learning difficulties (7), puberty and fertility problems (4), and hypothyroidism (4). These complications were most often related to radiation therapy. The need for pro-longed, regular follow-up of survivors of childhood malignancy for early detection of late sequelae and subsequent intervention is stressed.

ISSN:0192-8562    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The Pediatric Oncology Group compared two regimens that employed involved field radiotherapy 3,500 rad and either MOPP + Bleo or A-COPP chemotherapy, given in a sandwich fashion, as treatments for stage III Hodgkin's disease in children under the age of 18 years. Eighty-four surgically staged children from the United States and Mexico who had been randomly assigned to treatment during the period from July 1976 through October 1982 were evaluated. Unfavorable disease characteristics were distributed equally between the treatment groups. The percentages of children achieving complete remission by regimen were 84% for MOPP + Bleo and 92% for A-COPP. For those continuing in complete remission, the percentages were 71% for MOPP + Bleo and 72% for A-COPP. For those surviving 9 years, the percentage was 84% for MOPP + Bleo and 85% for A-COPP. The presence of low abdominal disease at diagnosis did not adversely influence response to therapy or survival. All deaths among MOPP + Bleo cases occurred within 4 years of study entry; 3 late deaths in A-COPP cases at 8–10 years were due to osteosarcoma, cardiopathy, and recurrent Hodgkin's disease. The preferred treatment regimen for future use cannot be determined until the cardiotoxicity of Adriamycin is eliminated by the development of drug delivery techniques that reduce cardiotoxicity or anthacycline congeners that are not cardiotoxic.

ISSN:0192-8562    

出版商:OVID    

年代:1991

数据来源: OVID