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)

The cellular immunodeficiency diseases especially those with impaired IL-2 production are successfully treated by every day injection of rhIL-2. IL-2 is also effective on some patients with antibody deficiency probably caused by the lack of T cell help for B cells. Prolonged infection of EB-virus, human immunodeficiency virus, fungi and mycobacteria can be ameliorated by IL-2 treatment. Superoxide production and bacteriocidal activity of the leukocytes from some cases of chronic granulomatous disease are improved by injection of interferon gamma. Succeeding injection of G-CSF is effective to maintain the leukocyte count of congenital neutropenia to the level competent to protect bacterial infections.
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PMID:[Cytokine therapy of immunodeficiency]. 127 43

Frequent complications of human immunodeficiency virus infection are hematopoietic failure and poor tolerance of myelosuppressive drugs. Reasons for neutropenia resulting from hematopoietic failure are infection of the bone marrow and hematotoxicity of treatment with zidovudine, ganciclovir, sulfonamides, and interferons. Moreover, tumor necrosis factor-alpha, transforming growth factor-beta and interferon-gamma have been shown to suppress proliferation of bone marrow cells. Both granulocyte (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) increase neutrophil counts and ameliorate phagocytic and bactericidic function of neutrophils. We report eight cases of AIDS patients with serious infections and neutropenia (< 750 cells/microliters), who were treated concomitantly with recombinant human G-CSF (3-4 micrograms subcutaneously per kilogram body weight daily). G-CSF treatment was well tolerated in all patients and showed no side effects or disturbances of other lineages than neutrophils. Life-threatening bacterial infections were treated successfully by stimulating the neutrophil immune system. This therapy shortened the duration of subsequent treatment with antibiotics. Since human immunodeficiency virus infects CD4-positive monocytes and macrophages, which are stimulated by GM-CSF, G-CSF seems to be the cytokine of choice, if stimulation of the neutrophil lineage is warranted.
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PMID:Granulocyte colony-stimulating factor treatment in AIDS patients. 128 Apr 96

We investigated the possibility of shortening the interval between courses of the commonly prescribed 28-day MVP (mitomycin C, vindesine, and cisplatin) regimen in patients with non-small-cell lung cancer (NSCLC). We conducted a nonrandomized phase II study using recombinant human granulocyte colony-stimulating factor (G-CSF, Chugai) to explore the possibility of shortening the cycle length to 21 days and compared the results with those obtained in historical controls who had received the standard 28-day regimen. A total of 40 patients, 37 of whom were evaluable, were entered in the 21-day treatment group of the trial and were compared with 38 historical controls who had received standard 28-day cycles of MVP at our institution. Patients in the 21-day group received mitomycin C at 8 mg/m2 on day 1, vindesine at 3 mg/m2 on days 1 and 8, and cisplatin at 80 mg/m2 on day 1, with the schedule being repeated every 21 days. Controls had received the same regimen, albeit at 28-day intervals. G-CSF was given s.c. to the patients in the 21-day group at a daily dose of 2 micrograms/kg from day 2 to day 21 of every MVP cycle. The administration of G-CSF to these patients accelerated neutrophil recovery as compared with that observed in the historical controls. Significant differences were found between the two groups in terms of mean neutrophil nadirs (2666/microliters in the first cycle and 1369/microliters in the second for the G-CSF group vs 416/microliters in the first cycle and 685/microliters in the second cycle for the control group; P < 0.0001) and the mean duration of neutropenia (< or = 1000/microliters; 1.0 day in the first cycle and 1.7 days in the second for the G-CSF group vs 8.0 days in the first cycle and 6.9 days in the second for the control group; P < 0.0001). This enabled 32 (86%) of 37 patients in the G-CSF group to complete > or = 2 cycles on schedule. In 10 patients, the bone marrow aspirates taken after G-CSF administration showed increases in band neutrophil and myelocyte percentages. In conclusion, MVP treatment of patients with NSCLC at 21-day intervals is possible with the support of G-CSF.
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PMID:The use of granulocyte colony-stimulating factor to shorten the interval between cycles of mitomycin C, vindesine, and cisplatin chemotherapy in non-small-cell lung cancer. 128 46

High-affinity IL-2 receptors are expressed by T cells activated in response to foreign histocompatibility antigens but not by normal resting T cells. To exploit this difference in IL-2R expression, anti-Tac, a murine monoclonal antibody specific for the IL-2R alpha subunit, was used to inhibit organ allograft rejection. To enhance its effector function, anti-Tac was armed by chelation with yttrium-90, a pure beta-emitting radionuclide. Animals received no immunosuppression (n = 5, group I, controls), unmodified anti-Tac (n = 5, 1 mg/kg q.o.d., group II), or 90Y-anti-Tac (n = 5, 1.6 mCi/kg divided into four doses, group III). The animals in group IV (n = 4) were treated identically to those in group III with the exception that 5 micrograms/kg/dose of granulocyte colony-stimulating factor was administered intramuscularly on the days when the yttrium-90 was given and on postoperative days 12 through 35 in order to reduce hematopoietic toxicity. Mean graft survival +/- S.E.M. for the control group was 8.2 +/- 0.5 days as compared with 13.8 +/- 2.1 days (P < 0.05) for those monkeys treated with unmodified anti-Tac. Graft survival was further prolonged in animals of group III that received 90Y-anti-Tac, with a mean graft survival of 45.0 +/- 11.8 days; however, three of the five monkeys retained viable grafts within this group but died secondary to bone marrow suppression. In comparison, the monkeys in group IV that were treated with G-CSF in conjunction with 90Y-anti-Tac had a mean graft survival of 49.2 +/- 2.9 days. In contrast to group III there were no deaths in the group (IV) receiving G-CSF. Furthermore, animals in group IV had a reduced magnitude and shortened duration of irradiation-induced neutropenia when compared with that observed in group III animals that did not receive G-CSF. Thus, treatment with 90Y-anti-Tac in conjunction with G-CSF may have potential applications in organ transplantation and the treatment of IL-2 receptor-expressing neoplastic diseases.
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PMID:Prolongation of graft survival in primate allograft transplantation by yttrium-90-labeled anti-Tac in conjunction with granulocyte colony-stimulating factor. 128 66

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

Kostmann's syndrome is a congenital disorder characterized by persistent severe neutropenia. It has a high morbidity and mortality on account of serious bacterial infection. A case which was successfully treated with G-CSF is reported.
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PMID:[Chronic congenital neutropenia treated with granulocyte colony-stimulating factor (G-CSF)]. 137 30

The haemopoietic growth factor granulocyte colony-stimulating factor (G-CSF; filgrastim) substantially shortens the period of severe neutropenia that follows high-dose chemotherapy and autologous bone-marrow infusion by stimulating granulopoiesis. Filgrastim also increases numbers of circulating progenitor cells. We have studied the ability of filgrastim to mobilise peripheral-blood progenitor cells and assessed their efficacy when infused after chemotherapy on recovery of neutrophil and platelet counts. 17 patients with non-myeloid malignant disorders received filgrastim (12 micrograms/kg daily for 6 days) by continuous subcutaneous infusion. Numbers of granulocyte-macrophage progenitors in peripheral blood increased a median of 58-fold over pretreatment values, and numbers of erythroid progenitors increased a median of 24-fold. Three leucapheresis procedures collected a mean total of 33 (SEM 5.7) x 10(4) granulocyte-macrophage progenitors per kg body weight. After high-dose chemotherapy in 14 of the patients (busulphan and cyclophosphamide), these cells were used to augment autologous bone-marrow rescue and post-transplant filgrastim treatment. Platelet recovery was significantly faster in these patients than in controls who received the same treatment apart from the infusion of peripheral-blood progenitors; the platelet count reached 50 x 10(9)/l a median of 15 days after infusion of haemopoietic cells in the study patients compared with 39 days in controls (p = 0.0006). The accelerated neutrophil recovery associated with filgrastim treatment after chemotherapy was maintained. This method may be widely applicable to aid both neutrophil and platelet recovery after high-dose chemotherapy; it will allow investigation of peripheral-blood progenitor-cell allotransplantation.
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PMID:Effect of peripheral-blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy. 137 71

A 50-year-old woman with anorexia nervosa was admitted for evaluation of neutropenia (WBC 1,600/microliters). Her bone marrow was gelatinous, and myeloid cells had decreased. Homogeneous substance deposited in the marrow, stained by alcian blue (pH 2.5), indicative of acid mucopolysaccharides. CFU-G and CFU-GM were decreased in number and myeloid pool in the bone marrow also decreased. Anti-neutrophilic antibody was negative. Neutropenia may be related to myeloid hypoplasia, due to increase of acid mucopolysaccharides replacing adipose cells in the bone marrow under long-term mal-nutritional state. Neutrophils markedly increased by administration of rhG-CSF 5.0 micrograms/kg/day for 14 days without the first peak. Serum G-CSF level did not increase (less than 60 pg/ml). It is effective to administer G-CSF to anorexia nervosa with neutropenia.
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PMID:[Anorexia nervosa with neutropenia--response of neutrophils to G-CSF]. 137 86

Recombinant canine granulocyte colony-stimulating factor (rcG-CSF) was administered to clinically normal dogs, cyclic-hematopoietic dogs, and dogs undergoing autologous bone marrow transplantation, to determine whether rcG-CSF could be used to stimulate WBC production and function in normal and neutropenic dogs. To the normal dogs, rcG-CSF was administered by SC injection at rates of 1 microgram/kg of body weight, q 12 h; 2 micrograms/kg, q 12 h; or 5 micrograms/kg, q 12 h. A significant dose-dependent increase in the WBC count resulted from the stimulation of bone marrow progenitor cells. The increased WBC count was characterized by mature neutrophilia and monocytosis. Neutrophil myeloperoxidase and phagocytic activity were normal in rcG-CSF-treated normal dogs, demonstrating the production of normal functional neutrophils in response to rcG-CSF treatment. Recombinant canine G-CSF prevented neutropenia and associated clinical signs but did not completely eliminate the cycling of neutrophils in cyclic-hematopoietic dogs when it was administered at rates of 1 microgram/kg, q 12 h, and 2.5 micrograms/kg, q 12 h. The time to bone marrow reconstitution was not decreased in dogs treated with rcG-CSF at a rate of 2.5 micrograms/kg, q 12 h, for 13 days following autologous bone marrow transplantation. On the basis of our findings, we suggest that treatment with rcG-CSF is an effective way to stimulate myelopoiesis in dogs, but that the dose of rcG-CSF required to stimulate WBC production will vary depending on the cause of neutropenia. Recombinant canine G-CSF should be useful in stimulating production and maintaining function of WBC for treatment of clinical diseases seen commonly in veterinary practice.
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PMID:Effects of recombinant canine granulocyte colony-stimulating factor on white blood cell production in clinically normal and neutropenic dogs. 137 21

Neutropenias, especially extended an long-lasting stages, lead to life-threatening endogenous infection. Therefore, after taking off materials for bacteriological investigations an empirical schedule of a combined high dose, treatment with broad-band antibiotics and/or antimycotics has immediately to be introduced and to continue until the body temperature and the peripheral blood granulocytes are normalized. In case of treatment failure one should complete the therapy by other additional antibiotics or correct the combination of its in respect to the results of the microbiological investigations. Supplements of this antimicrobial treatments are immunoglobulins and growth factors (G-CSF, GM-CSF). In case of an expected neutropenica the use of the selective gut decontamination or the reverse isolation of the patient can be of essential advantage.
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PMID:[Therapy of bacterial infections in neutropenic and immunocompromised patients]. 144 70


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