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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a phase I study, the sequentially administered combination of recombinant human interleukin-3 (rhIL-3) and rhGM-CSF was compared with treatment with rhIL-3 alone in 15 patients with advanced tumors but normal hematopoiesis. Patients were initially treated with rhIL-3 for 15 days. After a treatment-free interval, the patients received a second 5-day cycle of rhIL-3 at an identical dosage, immediately followed by a 10-day course of rhGM-CSF, to assess the toxicity and biologic effects of this sequential rhIL-3/rhGM-CSF combination. rhIL-3 doses tested were 125, and 250 micrograms/m2, whereas rhGM-CSF was administered at a daily dosage of 250 micrograms/m2. Both cytokines were administered by subcutaneous (SC) bolus injection. rhIL-3/rhGM-CSF treatment was more effective than rhIL-3 but equally effective to each other in increasing peripheral leukocyte counts, especially neutrophilic and eosinophilic granulocyte counts. In contrast, both modes of cytokine therapy raised the platelet counts to the same degree. rhIL-3/GM-CSF treatment was more effective than rhIL-3 in increasing the number of circulating hematopoietic progenitor cells BFU-E and CFU-GM. High-dose rhIL-3, but not low-dose rhIL-3, was as effective as the rhIL-3/rhGM-CSF combinations in increasing the number of circulating CFU-GEMM. The increase in absolute neutrophil counts correlated with the increase in the number of circulating CFU-GM. Side effects, mainly fever, headache, flushing, and sweating, were generally mild, but in two patients the occurrence of chills, rigor, and dyspnea after initiation of GM-CSF treatment necessitated dose reduction and discontinuation, respectively. These results indicate that sequential treatment with rhIL-3 and rhGM-CSF is as effective as single-factor treatment with rhIL-3 in stimulating platelet counts, whereas the effect of combination therapy on neutrophil counts and circulating progenitor cells is superior.
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PMID:Sequential in vivo treatment with two recombinant human hematopoietic growth factors (interleukin-3 and granulocyte-macrophage colony-stimulating factor) as a new therapeutic modality to stimulate hematopoiesis: results of a phase I study. 158 11

The genes for a number of growth factors that stimulate human hematopoietic and lymphoid cells in vitro have recently been cloned and recombinant molecules provided for clinical trials. For three of these (erythropoietin, G-CSF, and GM-CSF), phase I and II studies have been completed and promising results have been obtained. Of particular relevance to the field of bone marrow transplantation (BMT) has been the finding that G-CSF and GM-CSF could shorten the period of neutropenia in patients treated with chemotherapy, including regimens requiring BMT support. Doses of up to 240 micrograms/m2 of GM-CSF have been well tolerated and have increased the peripheral blood neutrophil count in a dose-dependent manner. At higher doses, eosinophils and monocytes were also increased. A continuous infusion over at least 2 h was found to be superior to bolus administration in terms of both efficacy and reduced side effects. These have usually been mild, but bone pain, headache, fatigue and elevated temperature have been encountered. The rise in neutrophil numbers shortly after initiating treatment with GM-CSF is probably due to neutrophil demargination. After a few days increased bone marrow cellularity has also been noted. In addition to these effects on cell numbers, enhancement of granulocyte and monocyte functions has been documented. However, a major concern with the use of G-CSF and GM-CSF in cancer patients, particularly those with hematopoietic malignancies, is the potential of these molecules to stimulate malignant cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Colony stimulating factors. 245 88

The in vivo effect of yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was investigated in 29 patients with advanced malignancy in phase Ib trial. Patients were treated at six different dose levels (30-1000 micrograms/m2/day) with either daily intravenous bolus injection or 24 hours continuous infusion for 5 days or 2 weeks. Administration of rh GM-CSF resulted in a broad spectrum of dose-, route-, and schedule-dependent hematopoietic effects. Sustained infusion of rh GM-CSF elicited a maximum 17-fold average peak increase of the total white blood cell (WBC) count with mainly neutrophils, eosinophils, and monocytes accounting for this rise, and increases in bone marrow cellularity with a shift to immature myeloid elements. Elevation of lymphocytes, platelets and reticulocytes was not induced. Within one week after discontinuation of treatment the leukocytosis had disappeared. Adverse reactions encountered with rh GM-CSF seen in 65% of the patients studied were never life-threatening and always reversible. They included mild myalgias, facial flushing, low-grade fever, headache, bone discomfort, nausea, dyspnoea and transient decline of platelet counts. These results suggest that rh GM-CSF can be safely administered at the doses and schedules employed and that it can induce in vivo some of the biological effects reported in in vitro studies. Although no objective antitumour responses have been seen, the ability of rh GM-CSF to increase turnover and function of leukocytes in vivo may prevent neutropenia and infections, when GM-CSF is adjunctively added to cytotoxic cancer therapy.
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PMID:Yeast-expressed granulocyte-macrophage colony-stimulating factor in cancer patients: a phase ib clinical study. 246 45

The in vivo effect of yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) was investigated in 30 patients with advanced malignancy in a phase Ib trial. Patients were treated at four different dose levels (120 to 1,000 micrograms/m2/d) by either daily intravenous (IV) bolus injection or 24-hour continuous infusion. Administration of rh GM-CSF resulted in a broad spectrum of dose- and schedule-dependent hematopoietic effects. Sustained infusion of rh GM-CSF elicited a maximum 17-fold average peak increase of the total WBC count with mainly neutrophils, eosinophils, and monocytes accounting for this rise, and increases in bone marrow cellularity with a shift to immature myeloid elements. Elevation of lymphocytes, platelets, and reticulocytes was not induced. Within five days after discontinuation of treatment the leukocytosis had disappeared. Adverse reactions encountered with rh GM-CSF seen in 65% of the patients studied were never life-threatening and always rapidly reversible. They included mild myalgias, facial flushing, low-grade fever, headache, bone discomfort, nausea, dyspnea, and transient decline of platelet counts. These results suggest that rh GM-CSF can be safely administered at the doses and schedules used and that it can induce in vivo some of the biological effects reported in in vitro studies. Although no objective antitumour responses have been seen, the ability of rh GM-CSF to increase number and function of leukocytes in vivo may prevent neutropenia and infections when GM-CSF is added to cytotoxic cancer therapy.
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PMID:Hematopoietic responses in patients with advanced malignancy treated with recombinant human granulocyte-macrophage colony-stimulating factor. 264 95

Seventeen patients with aplastic anaemia were treated with recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) for 14 d. Nonresponding patients were then treated with anti-human thymocyte globulin (ATG), methylprednisolone and oxymetholone. Side-effects of rhGM-CSF included fever, nausea and vomiting, diarrhoea, bone pain, headache and chills. Two patients had sustained trilineage haemopoietic recovery after receiving only rhGM-CSF. Of 11 patients who received immunosuppressive therapy, there was one complete response, two partial responses, one minimal response, and seven nonresponses. Actuarial survival at 2 years is 64%. Early administration of rhGM-CSF had no apparent effect on subsequent response to immunosuppressive therapy.
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PMID:Recombinant granulocyte-macrophage colony stimulating factor followed by immunosuppressive therapy for aplastic anaemia. 825 89

Human immunodeficiency virus (HIV), is able to replicate in many human cells such as helper lymphocytes, monocytes/macrophages and glial cells. Monocytes/macrophages must be considered an important reservoir of HIV in vivo and a producer of cytokines such as Interleukin-1 (IL1) and tumor necrosis factor (TNF). These substances lead to an autocrine feedback loop that produces an increased virus replication and a secondary induction of other cytokines such as Interleukin 6 (IL6) and granulocyte-macrophage colony stimulating factor (GM-CSF). These cytokines all together may be responsible for many clinical aspects of the disease such as headache, fever, anorexia, subtle cognitive changes, motor disfunctions and cachexia. The future strategies in the treatment of AIDS must be a combination of drugs acting on different points of viral replication and with synergistic potential. Omega 3 polyunsaturated fatty acids (omega-3) can be considered a candidate for their pleiotropic effects on immunological and metabolic systems. In particular, their use is considered for their ability to decrease IL1 and TNF production by monocytes/macrophages, as demonstrated by many authors. The decreased induction of these cytokines and consequently of IL6 and acute phase proteins may have beneficial effects on many clinical manifestations of AIDS such as cachexia.
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PMID:Omega-3 fatty acids as coadjuvant treatment in AIDS. 828 91

This investigation is devoted to the study of the time-course of a cytokines panel (IL-4, IL-6, IFN-gamma, GM-CSF) in plasma samples from migraine patients. The data obtained during challenged migraine crises was compared to the baseline values. Time-data series analysis showed a fall after a challenge test for IL-4 and IL-6 plasma levels and an opposite trend for gamma-IFN and GM-CSF levels. The implication of this phenomenon in dietary migraine is not readily evident. There may possibly be an activation of this cytokine network together with the well-known impairment in the neuropeptidergic system, considering the close links between interleukins and other cytokines and the neuro-mediators of pain, such as histamine and 5-HT.
Headache
PMID:Disruption of the immunopeptidergic network in dietary migraine. 829 90

In humans, interleukin 3 (IL-3) administration increases the cellularity and cycling of bone marrow progenitor cell populations. Initially, in primates and then in humans, IL-3 in sequence with GM-CSF has been shown to stimulate multilineage hematopoiesis. Based upon these effects, we designed a phase I trial of daily IL-3 administered subcutaneously for 10 days at dose levels of 2.5, 5.0, 10.0, 12.5, and 15.0 micrograms/kg followed within 72 h by bone marrow harvest, high-dose chemotherapy, and following chemotherapy, a fixed dose (5.0 micrograms/kg/day) of GM-CSF and bone marrow rescue. The study was designed to assess the toxicity and biological effects of IL-3 administered alone prior to bone marrow harvest and to determine the safety and clinical effects of IL-3 stimulated bone marrow with GM-CSF following high-dose combination chemotherapy. A total of 19 patients with chemotherapy-sensitive non-hematologic malignancies (13 breast, five ovarian, and one testicular cancer) were enrolled. IL-3 up to 15.0 micrograms/kg/day could be administered without dose-limiting toxicities. Flu-like symptoms and headaches were common and poorly tolerated at the highest IL-3 dose. Significant increases in neutrophil counts (P = 0.018) were observed following IL-3. Overall, IL-3 administration was associated with a modest, but significant increase in CFU-GM within the bone marrow (P = 0.034). IL-3 administration had no consistent effect on CD34+ cell number within bone marrow. For the entire group, engraftment of neutrophils to greater than 0.5 x 10(9)/l occurred at a median of 21 days (range of 13-63 days) and platelet independence occurred at a median of 17 days (range 11-120 days). When IL-3 dose levels were analyzed separately, engraftment of neutrophils and platelets, blood product (platelets and packed RBCs) utilization, and discharge date were not superior in those treated with the higher dose (15.0 micrograms/kg) of IL-3. While higher doses of IL-3 were associated with more toxicity, they did not appear to enhance the stem cell pool or speed engraftment later. The effects of pre-bone marrow harvest IL-3 are modest and likely not as impressive as other approaches aimed at enhancing hematologic recovery following high-dose chemotherapy.
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PMID:A phase I trial of interleukin 3 (IL-3) pre-bone marrow harvest with granulocyte-macrophage colony-stimulating factor (GM-CSF) post-stem cell infusion in patients with solid tumors receiving high-dose combination chemotherapy. 854 62

We performed a pilot study of human recombinant IL-6 (SDZ ILs 969) in 6 patients with poor prognosis Hodgkin's disease following autologous bone marrow transplantation (ABMT) to determine its safety and tolerability. IL-6 was administered the day following bone marrow infusion by subcutaneous injection once daily at a dose of 1 micro/kg/day to 3 patients and 2.5 microg/kg/day to 3 patients and was continued for 6 weeks or until platelet engraftment (>50 x 10(9)/L independent of transfusion). No severe or life threatening toxicities were seen at either dose level. A reversible elevation in alkaline phosphatase occurred in 4 patients and all patients complained of headache, myalgias, and fever. Gastrointestinal toxicity was low, grade 3-4 mucositis occured less frequently than in similarly-treated historical controls receiving GM-CSF. Serum concentrations of other cytokines such as IL-3 and G-CSF after ABMT differed from results obtained in transplant recipients given GM-CSF. The median time to an ANC >0.5 x 10(9)/L was 25.5 days and to a platelet count of >20 x 10(9)/L independat of transfusion was 35.5 days. Engraftment was no different from controls. Five patients relapsed at a median of 5 months post-ABMT and four remain alive at a median of 12 months post-ABMT. We conclude that IL-6 administration is safe and well tolerated in patients following ABMT. Further efforts to evaluate its effect on hematopietic recovery as well as relapse following transplantation in a larger patient series are warranted.
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PMID:A phase I study of interleukin-6 after autologous bone marrow transplantation for patients with poor prognosis Hodgkin's disease. 925 Aug 27

A 33 years old immunocompromised woman was admitted for a fever of unknown origin during the last five months. She referred a body temperature up to 38.3 degrees C, headache, weakness. The physical examination revealed right homonymous hemianopia, hyperreflexia and Babinski on her right side. A TC scan and a following bioptic specimen showed multiple cerebral tuberculomas. A conventional therapy was started but no significative improvement was observed. She was finally treated with interferon gamma and GM-CSF in addition to the therapy with an important regression of the lesions and significative improvement of the fever and neurological findings.
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PMID:[Multiple cerebral tuberculomas resistant to conventional therapy in an immunocompromised subject]. 1499 22


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