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

Since sera from most species contain both colony-stimulating and column-inhibitory factors, the net CSA results from a balance between these opposing substances. Studies were performed to determine whether the increased CSA noted during neutropenia or endotoxemia is due to an increase in CSF or to a decline in serum inhibitors. Rats were treated with cyclophosphamide, total body irradiation, or endotoxin and bled during the peak CSA response. By separation studies using Sephadex G150, it was shown that serum levels of high-molecular-weight inhibitors were unchanged from control values. Minimal CSA was detected in normal serum fractions; increased activity was found in fractions from neutropenic animals. During a postcyclophosphamide rebound neutrophilia, serum CSA was undetectable; inhibitor levels were similar to those measured in untreated controls. These observations show that the increased serum CSA seen with neutropenia is due to a true increase in CSF and not to a decline in circulating inhibitors.
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PMID:Serum colony-stimulating and colony-inhibitory activity in response to neutropenia. 30 46

Intravenous TMP-SMZ was used to treat 19 infectious episodes in 18 patients ranging in age from 3 weeks to 13 years. Thirteen patients with various soft tissue or skeletal infections caused by Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus. Streptococcus pyogenes, or Acinetobacter anitratus were successfully treated. Three children with four episodes of CSF shunt infections due to coagulase-negative staphylococci were treated successfully also. The only treatment failures were in two newborn infants with enteric gram-negative bacterial ventriculitis. TMP-SMZ was given at a daily dose of 10 and 50 mg/kg, respectively, every six hours. The drug was administered intravenously for a mean duration of 10 days (range 4 to 32); in 11 patients this was followed by oral administration for a mean of nine days (range 2 to 18). Half-life of TMP after intravenous administration was 5 1/4 hours; that of SMA was 8 1/2 hours. Levels determined three to four days after starting therapy were generally higher than levels obtained at corresponding times after the first dose. CSF/blood TMP and SMA ratios, determined in four patients, were 0.6 and 0.5, respectively. Side effects were observed in 14 patients, and neutropenia was the most common adverse reaction. Intravenous TMP-SMZ is an effective antimicrobic agent in the treatment of infections due to susceptible organisms. The frequent side effects, although reversible and of no major clinical consequence, suggest that future use of TMP-SMZ should be monitored closely.
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PMID:Intravenous trimethoprim-sulfamethoxazole in the treatment of serious infections in children. 38 14

Pseudomonas aeruginosa is thought to be one of the main species of bacteria producing infection in leukemic patients, especially in those with neutropenia. Although bacteremia is frequent, hematogenous spread causing secondary meningitis is rarely seen. The mortality rate is extremely high. This is believed to be the first report of a successfully treated secondary meningitis caused by Pseudomonas aeruginosa in an adult leukemic patient with a decreased neutrophil count. The patient was treated with intravenous Carbenicillin and gentamicin, and intrathecal gentamicin. The good clinical response was supported by a prompt return of the CSF to normal and by appropriate CSF antimicrobial concentration and bacteriostatic activity.
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PMID:Successful treatment of Pseudomonas meningitis and septicemia in a leukemic neutropenic adult. 80 43

Hematopoietic growth factors were found as factors stimulating hematopoietic colony formation in in vitro culture system using bone marrow cells as a source of hematopoietic progenitor cells. Erythropoietin, a growth factor stimulating erythroid lineage has now been clinically used as an therapeutic agent for anemia of chronic renal failure. Macrophage colony-stimulating factor (M-CSF), a growth factor stimulating the production of leukocytes including monocytes and neutrophils has been clinically used as an agent for leukopenic patients after anti-cancer therapy. M-CSF improves a survival rate after bone marrow transplantation (BMT) through the reduction of mortality rate associated with BMT such as bleeding, engraftment failure and GVHD. M-CSF accelerated platelet production when injected to thrombopenic patients with solid tumor after anticancer therapy. Granulocyte CSF (G-CSF) is a most powerful agent for various kinds of neutropenia such as neutropenia after anti cancer therapy, neutropenia after BMT, aplastic anemia, chronic neutropenia of children and myelodysplastic syndrome. However, since G-CSF stimulates growth of leukemic cells in vitro, careful observations should be required when clinically used on leukemic patients. Clinical studies of granulocyte-macrophage CSF (GM-CSF) and interleukin 3 (IL-3) are now in progress, in which a promoting activity of leukocyte production of these factors is evaluated.
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PMID:[Clinical application of hematopoietic growth factor (IL-3, G-CSF, GM-CSF, and EPO)]. 127 40

A 72 year-old woman was admitted to our hospital for hematoemesis. After admission, endoscopic examination showed esophageal varices with a red color sign which indicated endoscopic injection sclerotherapy (EIS). Concurrently, however, laboratory findings revealed severe neutropenia in peripheral blood, while bone marrow examination showed marked reduction of mature granulocytes with mild myeloid hyperplasia. As a result of those hematological abnormalities, EIS was halted. Concerning the pathogenesis of this neutropenia, immunofluorescence technique using flow cytometry disclosed the presence of anti-neutrophil autoantibody in the serum, giving a clinical diagnosis of autoimmune neutropenia (AIN). Thereafter, a conventional regimen of corticosteroids as an initial therapy and steroid pulse therapy as a succeeding maneuver were instituted, but in vain. As a last resort, 125 micrograms/body of rhG-CSF was given daily subcutaneously. As a consequence, significant increase in granulocyte count, though transient, was attained, which made EIS possible without any episodes of infections. It seems most likely that a high dose of rhG-CSF exerts beneficial effects as a prophylactic and therapeutic regimen against infections in patients with AIN.
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PMID:[The successful treatment of G-CSF in autoimmune neutropenia with liver cirrhosis complicated by esophageal varices]. 128 93

A 34-year-old female with cyclic neutropenia is reported. Family studies showed that her three sons and her mother were also involved. Oscillations in the blood neutrophil counts were almost regular, with a periodicity of 21 days. Numbers of colony-forming unit--granulocyte macrophage (CFU-GM) formed from the bone marrow cells of normal volunteers co-cultured with the patient's serum or mononuclear cell-conditioned medium (MNC-CM) were examined. Her serum prepared during the neutropenic phase inhibited the growth of CFU-GM, while her MNC-CM stimulated it. Human granulocyte colony-stimulating factor (hG-CSF) level in her serum was persistently high, with the peak occurring during the neutropenic phase. These results suggest that some inhibitory factors in the serum may be pathophysiologically important for cyclic neutropenia. To control infections, a pharmacological dose of hG-CSF was administered for 7 days around the early neutropenic phase. Her peripheral neutrophil counts oscillated from 1,200/mm3 to 17,000/mm3 with G-CSF, and from 150/mm3 to 1,800/mm3 without G-CSF.
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PMID:A case report of familial cyclic neutropenia. 128 77

We examined the effects of recombinant human granulocyte colony-stimulating factor (rG-CSF) on neutropenia induced by chemotherapy in 10 patients with non-Hodgkin's lymphoma (NHL). The numbers of peripheral blood hematopoietic progenitors were also evaluated before and after administration of rG-CSF. Six patients received an administration of 2 micrograms/kg/body weight of rG-CSF subcutaneously for 14 days after 2nd chemotherapy. Four patients received intravenous infusion of rG-CSF (300 micrograms/body/day) for 4 days from nadir state after chemotherapy. Administration of rG-CSF from the termination of chemotherapy, markedly shortend the period of bone marrow hypoplasia induced by chemotherapy. On the other hand, administration of rhG-CSF from nadir state after chemotherapy have accelerated the recovery of neutrophil counts. In addition, this type of therapy induced 26 to 60 folds increase of peripheral blood hematopoietic progenitors. These results demonstrate the validity of administration of rhG-CSF not only in the chemotherapy of NHL, but also in peripheral blood stem cell transplantation (PBSCT).
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PMID:[Clinical significance of recombinant human granulocyte colony-stimulating factor (rG-CSF) in the chemotherapy of patients with malignant lymphoma]. 128 72

Proliferation and differentiation of hematopoietic progenitor cells are regulated by a network of stimulatory and inhibitory cytokines. An understanding of the molecular mechanisms of growth control may provide a physiologic basis for the innovative therapy of bone marrow disorders. Among various accessory cells, bone marrow T lymphocytes are capable of stimulating, as well as inhibiting, hematopoietic progenitor cells. We have now elucidated molecular mechanisms regulating the differential expression of T cell genes encoding for the stimulatory and inhibitory hematopoietic programs. Stimulation of hematopoiesis requires granulocyte-macrophage colony stimulating factor (GM-CSF), whereas inhibition requires interferon-gamma (IF gamma). Both cytokines can be induced by interleukin-2 (IL2). The T cell IL2 receptor consists of a 75 kD chain (p75) mainly expressed on a subset of resting T cells and a 55 kD chain (p55) which is strongly expressed upon T cell activation. P55 and p75 associate on activated T cells to form a dimeric receptor molecule exhibiting high affinity for IL2. The p75 monomer has an intermediate affinity for IL2. Expression of p55 in the context of the high affinity IL2 receptor constitutes a requirement for T cell IFg release. In contrast, p75 alone is capable of mediating the production of GM-CSF. Thus, T cells may be capable of selective production of cytokines with specific effects in hematopoietic growth control. Utilizing a human peripheral blood leukocyte genomic library, we identified various clones containing the entire GM-CSF gene, including coding and regulatory regions. Cloning of the GM-CSF gene allowed clinical studies utilizing recombinant DNA-derived GM-CSF. Chemotherapy-induced neutropenia contributes to both complications of cytotoxic therapy as well as increased relapse incidence of underlying disease. In a prospective randomized study, we have demonstrated that GM-CSF abrogates neutropenia following aplasiogenic chemotherapy in children and adolescents with solid tumors, and that GM-CSF may reduce the duration of infectious episodes after cytotoxic therapy. Next, we escalated the cumulative doses of cytotoxic therapy in an ablative regimen followed by hematopoietic stem cell transplantation to treat patients with poor prognosis pediatric tumors. Morbidity of this highly toxic ablative regimen depends on the duration of myeloid aplasia. Median duration of aplasia following hyper-VAMP was 13 days with CM-CSF and 29 days without GM-CSF. In addition, we have employed p55 blocking monoclonal antibody for prevention of graft vs. host disease in bone marrow transplantation. The understanding of specific molecular mechanisms of hematopoietic immuno-regulation can thus be utilized to provide novel approaches to the treatment of bone marrow failure and cancer.
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PMID:Molecular regulation of hematopoietic cytokines: implications and indications for clinical use in pediatric oncology. 130 80

RhGM-CSF is a hematopoietic growth factor which stimulates the proliferation, differentiation and functional activity of neutrophils, monocytes and macrophages. It also stimulates proliferation of endothelial cells and induces the production of other cytokines, such as interleukin (IL-1), tumor necrosis factor (TNF), interferon, prostaglandin E2, and plasminogen activating factor which affects both hematopoietic and non-hematopoietic cell activities. Initial clinical studies in 1987 generally excluded experimental therapy with rhGM-CSF in pediatric patients (age < or = 17 years) unless life threatening illness related to neutropenia and infection developed (i.e., patients with graft failure). Serious complications of patients undergoing autologous bone marrow transplantation (BMT) related to pancytopenia include infection and hemorrhage. Other regimen related complications include venooclusive disease, pneumonitis and mucositis. As a result of these complications, patients require intensive medical support including antibiotics and hyperalimentation. Initial hospital duration following marrow reinfusion is generally 4 to 5 weeks. Hematopoietic growth factors have been administered to patients undergoing autologous BMT as an attempt to reduce regimen related toxicity.
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PMID:RhGM-CSF in bone marrow transplantation: experience in pediatric patients. 130 85

It was the specific aim of this study to test the stimulatory effects of recombinant human GM-CSF (rhGM-CSF) on haemopoietic regeneration in dogs which had received total-body irradiation (TBI) with a dose of 2.4 Gy. In normal dogs rhGM-CSF given subcutaneously at 10 microgram/kg per day or 30 microgram/kg per day for 21 days caused strong but transient increases in the peripheral blood neutrophils. The monocyte counts also showed a transient rise during treatment in a dose-dependent fashion, whereas the lymphocyte counts increased only at the higher dose of rhGM-CSF and the platelet counts were transiently depressed during the course of the treatment. In the irradiated animals treatment with rhGM-CSF decreased the severity and shortened the duration of neutropenia but had no significant influence on monocyte or lymphocyte recovery. The granulocyte values showed a characteristic pattern of fluctuations with the first peak occurring at the same time (day 10 to day 13) when the abortive rise was observed in the untreated dogs. In contrast the GM-CFC in the peripheral blood remained depressed during the whole treatment course, similar to the untreated irradiated controls. These results indicate that treatment with GM-CSF can be an effective biological monotherapy for radiation-induced bone marrow failure, but that for higher radiation doses the number of GM-CSF responsive target cells will become a critical determinant of therapeutic efficacy.
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PMID:Haematological effects of rhGM-CSF in dogs exposed to total-body irradiation with a dose of 2.4 Gy. 134 34


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