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Granulocyte Colony-stimulating Factor (granulocyte + colony-stimulating_factor)
Terms modified by Granulocyte Colony-stimulating Factor Selected AbstractsEssential role of C/EBP, in G-CSF-induced transcriptional activation and chromatin modification of myeloid-specific genesGENES TO CELLS, Issue 4 2008Satoshi Iida Granulocyte colony-stimulating factor (G-CSF) regulates the proliferation and differentiation of neutrophilic progenitor cells. Here, we investigated the roles of CCAAT/enhancer-binding protein (C/EBP), in the G-CSF-induced transcriptional activation and chromatin modification of the CCR2 and myeloperoxidase (MPO) genes in IL-3-dependent myeloid FDN1.1 cells. Chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assays revealed that G-CSF activates C/EBP, to bind target promoters. ChIP mapping experiments across the CCR2 and MPO genes showed that G-CSF induces histone H3 modifications: the acetylation of Lys9, trimethylation of Lys4 and trimethylation of Lys9. The distribution profile of the trimethylated Lys9 was distinct from that of the two other modifications. All the G-CSF-induced C/EBP, recruitment, transcriptional activation and histone modifications were reversed by re-stimulation with IL-3, and were abolished by short hairpin RNA (shRNA)-mediated knockdown of C/EBP,. These results indicate that C/EBP, is activated by G-CSF to bind target promoters, and plays critical roles in the transcriptional activation and dynamic chromatin modification of target genes during neutrophil differentiation. [source] An audit of the use of granulocyte colony-stimulating factor in septic shockINTERNAL MEDICINE JOURNAL, Issue 4 2002D. P. Stephens Abstract Background:,Granulocyte colony-stimulating factor (G-CSF) stimulates the production of neutrophils and modulates the function and activity of developing and mature neutrophils. In septic shock, the immune system can be considered one of the failing organ systems.G-CSF improves immune function and may be a useful adjunctive therapy in patients with septic shock. Aim:,To evaluate the introduction of G-CSF as an adjunct to our standard treatment for community-acquired septic shock. Methods:,We performed a prospective data collection and analysis to determine whether the addition of G-CSF to our standard treatment for community-acquired septic shock was associated with improved hospital outcome, compared with an historical cohort ofsimilar patients. We included all patients admitted to the Intensive Care Unit (ICU) with community-acquired septic shock between December 1998 and March 2000. Patients received 300 µg G-CSF intravenously daily for 10 days in addition to ourstandard treatment for community-acquired septic shock. G-CSF was discontinued early if the patient was discharged from ICU before10 days or if the absolute neutrophil count exceeded 75 × 106/mL. Results:,A total of 36 patients with community-acquired septic shock, an average Apache 2 score of 26.7, and a predictedmortality of 0.79, were treated with G-CSF from December 1998 to March 2000. Hospital mortality was 31% compared with an historical cohort of 11 similar patients with a hospital mortality of 73% (P = 0.018). In the subgroup of patients with melioidosis septic shock, the hospital survival improved from 5% to 100% (P < 0.0001). No significant adverse events occurred as a result of the administration of G-CSF. Conclusion:,G-CSF is a safe adjunctive therapy in community-acquired septic shock and may be associated with improved outcome. The use of G-CSF in septic shock should undergo further investigation to define subgroups of patients who may benefit from G-CSF. The use of G-CSF in patients with septic shock due to Burkholderia pseudomallei is recommended. (Intern Med J 2002; 32: 143,148) [source] Disseminated cutaneous Fusarium moniliforme infections in a leukemic childINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 5 2007Ching-Chi Chi MD A 5-year-old boy had a 10-month remission of acute lymphocytic leukemia (ALL) after chemotherapy. Re-induction chemotherapy was performed for relapse of ALL. Thereafter, he suffered from an episode of neutropenic fever with pneumonia. One week following control of the condition with antibiotics, a 1 × 1-cm, red, painful nodule appeared on the left thigh, which was initially suspected to be Pseudomonas infection. Parenteral ceftazidime and amikacin were administered, but persistent high fever, mild cough, and a few painful erythematous papulonodules on the face and lower extremities appeared several days later (Fig. 1). These lesions increased insidiously in diameter up to 2,5 cm with central necrosis. Hemogram showed neutropenia with a shift to the left [white blood cell (WBC) count, 2.1 × 109/L; neutrophil count, 0.21 × 109/L]. A skin biopsy showed heavy growth of hyaline branching septate hyphae in the deep dermis and subcutis, together with fat necrosis (Fig. 2). Invasion of molds into vessels and sweat glands was also seen. A culture from a lesion yielded Fusarium moniliforme, but no fungi were isolated from blood specimens. Only mild infiltrations on bilateral lower lung fields were detected by chest roentgenography. The skin lesions gradually healed and the fever subsided 2 weeks after the initiation of therapy with amphotericin B 30 mg and itraconazole 200 mg daily. Figure 1. A few painful erythematous papulonodules appeared on the face and lower extremities Figure 2. Skin biopsy showed heavy growth of hyaline branching septate hyphae in the deep dermis and subcutis along with fat necrosis (hematoxylin and eosin, ×400) Meanwhile, relapse of leukemia was detected by hemogram showing atypical leukocytosis (WBC count of 24,400 × 109/L, with blast cells representing 78%). A course of chemotherapy with cytarabine, mitoxantrone, and VP-16 was prescribed, subsequently resulting in neutropenia (WBC count, < 0.1 × 109/L; neutrophil count, 0/L) and spiking fever. Although the aforementioned antifungal therapy was continued, the centers of the originally healed lesions turned dusky red, swollen, necrotic, and ulcerative. There were more than 10 such ecthymiform lesions. After administration for 22 days, itraconazole was discontinued because of no appreciable effects. Granulocyte colony-stimulating factor (G-CSF) salvage was used, and the neutropenia gradually subsided 20 days later. In addition, the ecthymiform lesions gradually resolved. Amphotericin B was discontinued 1 week following neutrophil recovery. The patient died of Acinetobacter baumannii and Stenotrophomonas maltophilia sepsis 8 months later. [source] Collection of peripheral blood stem cells with granulocyte-colony-stimulating factor alone in testicular cancer patientsINTERNATIONAL JOURNAL OF UROLOGY, Issue 3 2000KISABURO HANAZAWA Abstract Background: High-dose chemotherapy with the transplantation of peripheral blood stem cells (PBSC) has been performed for the treatment of advanced testicular cancer patients. Recently, it has been reported that, in healthy donors, a large quantity of stem cells can be transferred to peripheral blood using granulocyte-colony-stimulating factor (G-CSF) alone. Therefore, it was decided to try to harvest PBSC from three patients having testicular cancers with G-CSF alone. Methods: The three patients with testicular cancer were 26, 56 and 62-years-old. They had undergone five, two and three cycles of chemotherapy, respectively, but no radiation therapy. Granulocyte colony-stimulating factor was subcutaneously injected (250 ,g) into each patient twice per day for 6 days. Peripheral blood stem cells were harvested for 3 days (days 4,6) and mononuclear cells (MNC), CD34-positive cells and colony-forming units of granulocyte-macrophage (CFU-GM) in PBSC collected by apheresis were measured. Results: Apheresis showed that the total MNC count was 20.2 × 108/kg (range, 10.6,25.9 × 108/kg), the CD34-positive cell count was 0.98 × 106/kg (range, 0.75,1.4 × 106/kg) and the total CFU-GM count was 1.36 × 105/kg (range, 0.25,3.0 × 105/kg). Conclusion: After mobilization of peripheral blood stem cells with G-CSF alone, sufficient amounts of MNC were obtained from testicular cancer patients who had undergone chemotherapy several times. However, sufficient amounts of CD34-positive cells and CFU-GM could not be obtained. These results suggested that the G-CSF dose was not adequate for harvesting sufficient amounts of CD34-positive cells and CFU-GM. [source] Granulocyte colony-stimulating factor produces a decrease in IFN, and increase in IL-4 when administrated to healthy donorsJOURNAL OF CLINICAL APHERESIS, Issue 4 2010Octavio Rodríguez-Cortés Abstract Hematopoietic stem cells transplantation (HSCT) is the leading curative therapy for a variety of hematological and hereditary diseases; however, graft versus host disease (GVHD), an immunologic phenomenon that is favored by Th1 cytokines and cytotoxic cells from donors, is present frequently and is one of the most important causes of transplant related mortality. Peripheral blood HSCT is the preferred source of stem cells in almost 100% of the cases of autologous HSCT and in 70% of allogeneic transplants. The best mobilizing agent to get the stem cells out from the bone marrow is the Granulocyte-Colony Stimulating Factor (G-CSF). In this work, our main objective was to study a possible correlation between the graft cell dose and the patient's clinical outcome. We evaluated the immunologic changes produced by G-CSF in the lymphocyte and cytokine profiles in allogeneic HSC donors. HSC from twelve donors were mobilized with G-CSF at 16 ,g/kg/day, for 5 days. Basal Peripheral Blood (BPB), Mobilized Peripheral Blood (MPB), and aphaeresis mononuclear cells (G-MNC) samples were taken from all donors. Using flow cytometry, we quantified CD19+, CD3+, CD3+CD4+, CD3+CD8+, NK, NKT, DC1, and DC2 cells. Cytokines were determined by ELISA in culture supernatants. CD19+ (p = 0.001), DC1 (p < 0.002) and DC2 (p < 0.001) cells were increased in MPB with respect to BPB. An increase in Th2 cytokines such as (IL-4) and a decrease in Th1 cytokines (IFN,, IL-2) were also found in MPB samples. In conclusion, Th1 and Th2 cytokines are relevant in predicting the clinical outcome after allogeneic peripheral blood HSCT. J. Clin. Apheresis 25:181,187, 2010. © 2010 Wiley-Liss, Inc. [source] Granulocyte Colony-stimulating Factor Suppresses Autologous Tumor Killing Activity of the Peripheral Blood Lymphocytes in the Patients with Ovarian CarcinomaAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2004Yoshiaki Ohta Problem:, Granulocyte colony-stimulating factor (G-CSF) is often administered to patients with chemotherapy-induced leukocytopenia. However, adequate attention has not been paid to its effects on cancer immunology. Reported by us and others, G-CSF often induces immunosuppression and down-regulation of response T helper (Th)2 directed immune reaction both in vivo and in vitro. In this study, we analyzed the effects of G-CSF on interferon (IFN)- , production and autologous tumor killing (ATK) activities of peripheral blood mononuclear cells (PBMCs). Methods of study:, In order to evaluate the cytokine-induced activation of peripheral T and natural killer (NK) cells, we analyzed IFN- , production by interleukin (IL)-2- and IL-12-stimulated PBMCs, using the ELISPOT assay. Specific killing of autologous tumor cells was evaluated by lactate dehydrogenase (LDH) release assay. Results:, The PBMC collected from both cancer-bearing patients and healthy subjects showed IL-2- and/or IL-12-induced IFN- , production. The frequency of IFN- , producing cells was significantly higher in the normal subjects compared with the patients with advanced ovarian carcinoma. The ATK activity was also enhanced in IL-2- and/or IL-12-stimulated PBMCs of patients with ovarian carcinoma. G-CSF almost completely abolished IFN- , production and ATK activity of PBMC stimulated with IL-2 and/or IL-12. Conclusions:, The G-CSF appears to be a suppressor of antitumor immunity. Routine administration of G-CSF to cancer patients may not be recommended, except for febrile neutropenia. [source] Incidence, Risk Factors and Clinical Consequences of Neutropenia Following Kidney Transplantation: A Retrospective StudyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009L. Zafrani Neutropenic episodes in kidney transplant patients are poorly characterized. In this retrospective study, neutropenia was experienced by 112/395 patients (28%) during the first year posttransplant. The only factor found to be significantly associated with the occurrence of neutropenia was combined tacrolimus-mycophenolate therapy (p < 0.001). Neutropenic patients experienced more bacterial infections (43% vs. 32%, p = 0.04). Grade of neutropenia correlated with the global risk of infection. Discontinuation of mycophenolic acid (MPA) due to neutropenia was associated with an increased incidence of acute rejection (odds ratios per day 1.11, 95% confidence intervals 1.02,1.22) but not with reduced renal function at 1 year. The time from onset of neutropenia to MPA discontinuation correlated with the duration of neutropenia. Granulocyte colony-stimulating factor (G-CSF) administration was safe and effective in severely neutropenic kidney graft recipients, with absolute neutrophil count >1000/,L achieved in a mean of 1.5±0.5 days. Neutropenia is an important and frequent laboratory finding that may exert a significant influence on outcomes in kidney transplantation. As well as leading to an increased incidence of infection, it is associated with a higher rate of allograft rejection if MPA is discontinued for >6 days (p = 0.02). G-CSF accelerates recovery of neutropenia and may be a good therapeutic alternative for severely neutropenic patients. [source] Low-dose lenograstim is as effective as standard dose in shortening neutrophil engraftment time following myeloablative chemotherapy and peripheral blood progenitor cell rescueBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2007L. Nolan Summary Granulocyte colony-stimulating factor (G-CSF) is widely used following myeloablative chemotherapy (high-dose therapy; HDT) and peripheral blood progenitor cell rescue (PBPCR) to reduce neutrophil engraftment time. The dose and duration required to gain maximum clinical and economic benefit has not been fully investigated. This double blind placebo-controlled randomised trial was performed to determine whether short course low-dose or standard-dose Lenograstim (L) would influence recovery of haematopoiesis following HDT and PBPCR. Sixty-one patients were randomised between May 1999 and November 2004, to receive standard-dose lenograstim (263 ,g/d), low-dose lenograstim (105 ,g/d) or placebo injections. These commenced on day +5 following PBPCR and continued until neutrophil engraftment [absolute neutrophil count (ANC)] , 0·5 × 109/l. Patients received standard supportive care until haemopoietic recovery. Both standard- and low-dose lenograstim resulted in a significantly shorter median time to neutrophil recovery (ANC , 0·1 × 109/l:10·0 vs. 11·0 d, P = 0·025; ANC , 0·5 × 109/l:11·0 vs. 14·0 d, P = 0·0002) compared with placebo. There was no significant difference in blood product support, antibiotic usage, documented infection, overall survival or relapse-free survival between the groups. Short course low-dose lenograstim is as effective as standard-dose in reducing neutrophil engraftment time following HDT and PBPCR. [source] Due to low infection rates no routine anti-infective prophylaxis is required in younger patients with chronic lymphocytic leukaemia during fludarabine-based first line therapyBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2007Barbara F. Eichhorst Summary The impact of the combination therapy fludarabine plus cyclophosphamide (FC) in comparison with fludarabine alone regarding the incidence and severity of infections among previously untreated patients with chronic lymphocytic leukaemia (CLL) was evaluated within a multicentre phase III study. A total of 375 patients, up to 65 years old, were randomised between fludarabine or FC for first line therapy. No routine anti-infective prophylaxis was provided. A total of 196 infectious episodes, including 33 severe infections, were documented. In the fludarabine arm, 32·9% of the patients developed an infectious complication compared with 39·9% in the FC arm (P = 0·2). No difference was observed in the rate of severe infections (Common Toxicity Crtieria grades III and IV) between both treatment arms. Dose reductions were performed more frequently in FC-treated patients. Granulocyte colony-stimulating factor (G-CSF) was administered due to leucopenia in 5% of all patients. A multivariate regression model identified only elevated thymidine kinase, but not the treatment arm, as a statistically independent risk factor for infections. In summary, FC was not associated with a higher rate of infections compared with fludarabine alone. No routine antibiotic or virostatic prophylaxis, or pre-emptive treatment with G-CSF, is necessary in first line therapy with fludarabine-based regimens in younger patients with CLL, if adequate dose reduction is performed. The combination therapy FC is not associated with a higher rate of infections compared with fludarabine alone. No routine antibiotic or virostatic prophylaxis as well as pre-emptive treatment with G-CSF is necessary in first line therapy with fludarabine-based regimen in younger patients with CLL, if adequate dose reductions due to cytopenia or previous infections are performed. [source] Heterogeneous expression pattern of pro- and anti-apoptotic factors in myeloid progenitor cells of patients with severe congenital neutropenia treated with granulocyte colony-stimulating factorBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2005Gunnar Cario Summary Apoptosis is accelerated in the myeloid progenitor cells of patients with severe congenital neutropenia (CN). Granulocyte colony-stimulating factor (G-CSF) increases neutrophil numbers in most CN patients. The effect of G-CSF on apoptosis in CN was analysed by apoptosis rate and expression of anti- and pro-apoptotic factors. G-CSF-treated patients showed higher apoptosis frequency, lower expression of bcl-2 and bcl-xL, but higher expression of bfl-1/A1 and mcl-1. Caspase 9 was highly expressed in patients and controls after G-CSF administration. Thus, G-CSF acts on apoptosis regulation, but additional mechanisms leading to the increase of neutrophil numbers must be assumed. [source] Crohn's-like ileo-colitis in patients affected by glycogen storage disease Ib: two years'follow-up of patients with a wide spectrum of gastrointestinal signsACTA PAEDIATRICA, Issue 12 2003D Melis Aim: To investigate the presence of inflammatory bowel disease (IBD) and to evaluate the progression of bowel involvement after two years'follow-up in seven patients affected by glycogen storage disease type Ib (GSDIb). Methods: Seven patients (5F, 2M, aged 4.5,20.6 y) entered the study. Bowel involvement was evaluated by ileocolonoscopy and specific IBD serologic markers. To evaluate disease activity, Paediatric Crohn's Disease Activity Index (PCDAI), terminal ileum wall thickness detected at ultrasonography (US), 99mTechnetium labelled autologous White Cell Scan (Tc-WCS) and barium meal with follow-through were investigated. Results: Ileocolonoscopy and histology examination revealed variable degrees of bowel involvement in all patients. The results of serologic markers were indicative of a Crohn's-like ileocolitis. US and Tc-WCS, could clearly define patients with severe inflammatory involvement, but failed to identify all patients with mild to moderate disease. For the most severely affected patients, anti-inflammatory agents and steroids were prescribed, whereas nutritional therapy with polymeric formula and antibiotics were assumed by two other patients and antibiotics only by one patient. Granulocyte colony-stimulating factor (G-CSF) was prescribed to all patients. Ileocolonoscopy and histology data improved in all patients. The assumption of G-CSF and/or gastric drip feeding (g.d.f.) was inversely associated with the PCDAI results (p < 0.05). Conclusion: IBD is common in patients affected by GSDIb independently of the severity of gastrointestinal signs and symptoms. Different therapeutic approaches can be used according to the severity of IBD. G-CSF treatment and g.d.f. can be protective factors for IBD. [source] Acceleration of granulocyte colony-stimulating factor-induced neutrophilic nuclear lobulation by overexpression of Lyn tyrosine kinaseFEBS JOURNAL, Issue 1 2002Tomomi Omura Stimulation with granulocyte colony-stimulating factor (G-CSF) induces myeloid precursor cells to differentiate into neutrophils, and tyrosine phosphorylation of certain cellular proteins is crucial to this process. However, the signaling pathways for neutrophil differentiation are still obscure. As the Src-like tyrosine kinase, Lyn, has been reported to play a role in G-CSF-induced proliferation in avian lymphoid cells, we examined its involvement in G-CSF-induced signal transduction in mammalian cells. Expression plasmids for wild-type Lyn (Lyn) and kinase-negative Lyn (LynKN) were introduced into a murine granulocyte precursor cell line, GM-I62M, that can respond to G-CSF with neutrophil differentiation, and cell lines that overexpressed these molecules (GM-Lyn, GM-LynKN) were established. Upon G-CSF stimulation, both the GM-Lyn and GM-LynKN cells began to differentiate into neutrophils, showing early morphological changes within a few days, much more rapidly than did the parental cells, which started to exhibit nuclear lobulation about 10 days after the cells were transferred to G-CSF-containing medium. However, the time course of expression of the myeloperoxidase gene, another neutrophil differentiation marker, was not affected by the overexpression of Lyn or LynKN. Therefore, in normal cells, protein interactions with Lyn, but not its kinase activity, are important for the induction of G-CSF-induced neutrophilic nuclear lobulation in mammalian granulopoiesis. [source] Ifosamide, epirubicin and granulocyte colony-stimulating factor: a regimen for successful mobilization of peripheral blood progenitor cells in patients with multiple myelomaHEMATOLOGICAL ONCOLOGY, Issue 2 2001M. Arland Abstract In general, the mobilization of peripheral blood progenitor cells (PBPC) in multiple myeloma (MM) patients is poor and is achieved in most cases by combined cyclophosphamide and G-CSF. This study was performed to examine the efficacy of combined ifosfamide/epirubicine and G-CSF for PBPC mobilization and purging. Sixteen patients suffering from multiple myeloma in stage II/A and III/A according to Durie and Salmon underwent chemotherapy consisting of a total of three cycles of ifosfamide (3,g/m2 on days 1 and 2 and epirubicine 80,mg/m2 on day 1) and G-CSF (10 or 20,µg/kg body weight (BW) daily until harvesting). PBPC harvesting was performed after the first and third cycle of chemotherapy. The median number of PBPC after the first cycle of chemotherapy was 7.79×106 CD34+ cells/kg BW (ranging from 0.94,26.36×106) and 6.38×106 CD34+ cells/kg BW (ranging from 0.79,29.31×106) after the third cycle of chemotherapy. Clinical re-evaluation after three cycles of chemotherapy showed 13 (81 per cent) patients in partial remission (PR), two (12 per cent) in complete remission (CR) and one (6.25 per cent) in stable disease (SD). No major side-effects were observed, six patients developed hematological toxicity stage IV WHO for a median of 3.9 days but no serious infection episodes occurred. Combined ifosfamide/epirubicin and standard G-CSF is able to mobilize sufficient PBPC without serious side-effects for patients with MM and for purging procedures resulting in a high proportion of complete remissions after tandem high-dose melphalan chemotherapy. Copyright © 2001 John Wiley & Sons, Ltd. [source] Neutrophil mobilization and clearance in the bone marrowIMMUNOLOGY, Issue 3 2008Rebecca C. Furze Summary The bone marrow is the site of neutrophil production, a process that is regulated by the cytokine granulocyte colony-stimulating factor (G-CSF). Mature neutrophils are continually released into the circulation, with an estimated 1011 neutrophils exiting the bone marrow daily under basal conditions. These leucocytes have a short half-life in the blood of ,6·5 hr, and are subsequently destroyed in the spleen, liver and indeed the bone marrow itself. Additionally, mature neutrophils are retained in the bone marrow by the stromal cell-derived factor (SDF-1,)/chemokine (C-X-C motif) receptor 4 (CXCR4) chemokine axis and form the bone marrow reserve. Following infection or inflammatory insult, neutrophil release from the bone marrow reserve is substantially elevated and this process is mediated by the co-ordinated actions of cytokines and chemokines. In this review we discuss the factors and molecular mechanisms regulating the neutrophil mobilization and consider the mechanisms and functional significance of neutrophil clearance via the bone marrow. [source] An audit of the use of granulocyte colony-stimulating factor in septic shockINTERNAL MEDICINE JOURNAL, Issue 4 2002D. P. Stephens Abstract Background:,Granulocyte colony-stimulating factor (G-CSF) stimulates the production of neutrophils and modulates the function and activity of developing and mature neutrophils. In septic shock, the immune system can be considered one of the failing organ systems.G-CSF improves immune function and may be a useful adjunctive therapy in patients with septic shock. Aim:,To evaluate the introduction of G-CSF as an adjunct to our standard treatment for community-acquired septic shock. Methods:,We performed a prospective data collection and analysis to determine whether the addition of G-CSF to our standard treatment for community-acquired septic shock was associated with improved hospital outcome, compared with an historical cohort ofsimilar patients. We included all patients admitted to the Intensive Care Unit (ICU) with community-acquired septic shock between December 1998 and March 2000. Patients received 300 µg G-CSF intravenously daily for 10 days in addition to ourstandard treatment for community-acquired septic shock. G-CSF was discontinued early if the patient was discharged from ICU before10 days or if the absolute neutrophil count exceeded 75 × 106/mL. Results:,A total of 36 patients with community-acquired septic shock, an average Apache 2 score of 26.7, and a predictedmortality of 0.79, were treated with G-CSF from December 1998 to March 2000. Hospital mortality was 31% compared with an historical cohort of 11 similar patients with a hospital mortality of 73% (P = 0.018). In the subgroup of patients with melioidosis septic shock, the hospital survival improved from 5% to 100% (P < 0.0001). No significant adverse events occurred as a result of the administration of G-CSF. Conclusion:,G-CSF is a safe adjunctive therapy in community-acquired septic shock and may be associated with improved outcome. The use of G-CSF in septic shock should undergo further investigation to define subgroups of patients who may benefit from G-CSF. The use of G-CSF in patients with septic shock due to Burkholderia pseudomallei is recommended. (Intern Med J 2002; 32: 143,148) [source] Exacerbation of palmoplantar pustulosis by granulocyte colony-stimulating factorINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 6 2005Ichiro Kurokawa MD No abstract is available for this article. [source] Dyskeratosis congenita with isolated neutropenia and granulocyte colony-stimulating factor treatmentINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2002Kutluhan Yilmaz A 3-year-old Turkish boy with a history of chronic cough, recurrent bronchopneumonia, and a borderline sweat chloride test (40 mEq/L) was referred for further evaluation to our department. He was born at term (2100 g) to a marriage with no consanguinity. His mother and father were 40 and 46 years old, respectively. Physical examination (Fig. 1) revealed hypopigmented, atrophic, and hyperkeratotic skin lesions surrounded by reticulate hyperpigmentation on the entire body, predominantly on the face, neck, arms, shoulders, and legs, which had been noticed initially at the age of 18 months. Dystrophic toenails, sparse and thin hair, and phimosis were also observed. Laboratory tests disclosed an isolated neutropenia (white blood cell count, 1800/mm3). Bone marrow (BM) aspiration showed a decreased myelopoiesis without myelodysplastic changes, but normal erythropoiesis, megakaryopoiesis, and normal stroma. Lymphocyte subgroups containing CD4, CD5, CD6, CD8, CD19, CD23, and CD25, and immunoglobulin G (IgG), IgM, IgA, and IgE, were in the normal range; hemoglobin F (HbF), 2.8%. Spontaneous and clastogen-induced chromosome breaks were not increased. A skin biopsy showed increased pigmentation at the basal layer, dyskeratotic epidermal cells, and marked IgM deposition and cytoid bodies and mild IgA and IgG deposits at the dermo-epidermal junction. Lactate response to glucose challenge, amino acid chromatography, and urine organic acid analysis were normal. Figure 1. Hypopigmented, atrophic, and hyperkeratotic skin lesions surrounded by reticulate hyperpigmentation involving predominantly the face, neck, arms, shoulders, and legs, dystrophic toenails, and sparse and thin hair A diagnosis of dyskeratosis congenita (DC) was made with typical skin lesions, dystrophic toenails, thin and sparse hair, and neutropenia with decreased myelopoiesis in BM. Treatment with granulocyte colony-stimulating factor (G-CSF) was considered for the neutropenia. As the increase in neutrophil count at a dose of 5 µg/kg was not adequate, 10 µg/kg G-CSF was tried (Fig. 2). With 10 µg/kg once to three times a week, a 1.8,4.8-fold increase in the absolute neutrophil count (ANC) was achieved with no side-effects. Treatment was more frequent during infection (days 22,28). Figure 2. Response of absolute neutrophil count (ANC) to granulocyte colony-stimulating factor (G-CSF) administration (5 µg/kg on days 1 and 3; 10 µg/kg on days 5, 10, 16, 23, 26, 28, 34, 40, 48, 54) [source] Severe antibody-mediated agranulocytosisINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1 2008H. JOHNSEN Summary A 56-year-old female with Crohn's disease was admitted to the hospital with malaise, fever, and a low white blood cell count (0.8 × 109/l) with no granulocytes or myeloid precursor cells in the bone marrow. The leucopenia was initially thought to be the result of an infection and she was treated with antibiotics and granulocyte colony-stimulating factor (G-CSF, filgrastim). However, the bacterial cultures and viral tests were all negative. The patient's condition deteriorated and she became morbidly ill, but recovered after high dose steroid treatment. Six weeks later she relapsed whilst receiving 7.5 mg daily dose of prednisolone. She recovered quickly after being given high dose methylprednisolone in combination with filgrastim. A high maintenance dose of prednisolone was tapered over 5 months. She has not relapsed since and is currently well. Antibodies to the human neutrophil antigen (HNA)-3a were detected, but these antibodies could not easily explain her agranulocytosis as she had a HNA-3a negative phenotype. It seems plausible that her agranulocytosis was immune mediated through autoantibodies directed towards the early myeloid cells. [source] Low cost autologous peripheral blood stem cell transplantation performed in a municipal hospital for a patient with plasma cell leukaemiaINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 3 2002K. Ghosh Autologous peripheral blood stem cell transplantation (PBSCT) is a costly procedure. In India, the cost varies from US$20 000 to 25 000 and most patients cannot afford it. Using several cost-cutting measures, we were able to treat a patient with plasma cell leukaemia by autologous PBSCT. A 42-year-old-male presented with plasma cell leukaemia. He was treated with VAD therapy, followed by high-dose cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) for mobilization of peripheral blood stem cells. The patient was conditioned with high dose melphalan, followed by autologous PBSCT. The procedure was performed in a municipal hospital in which there was no prior experience with stem cell transplantation. Costs were reduced by: (i) using oral medication whenever possible; (ii) having a relative of the patient prepare his food under medical guidance; (iii) starting G,CSF on day 7 rather than on day 1; (iv) short-term storage of the PBSC in an ordinary refrigerator at 4 °C without cryopreservation; (v) infusing a large number of CD34+ cells, which shortened the time to engraftment; (vi) delegating many of the functions of a marrow transplant nurse to a resident physician. The cost of transplantation was thereby reduced to about US$ 6000, with successful engraftment by day +13. The patient remained in remission for 7 months, after which he relapsed and was treated with chemotherapy and electron beam radiation to the skin. [source] Inverse relation between plasma G-CSF levels and neutrophil counts in a patient with autoimmune neutropenia treated with G-CSFINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2000L.tH. Vlasveld Summary The pharmacokinetic characteristics of granulocyte colony-stimulating factor (G-CSF) appears to be related to the neutrophil count. We report the case of an 81-year-old male with acquired antibody induced neutropenia treated with G-CSF. This produced a rapid increase in the neutrophil count which appeared to be associated with diminished trough plasma G-CSF levels. Our data appears to indicate that mature neutrophils may play a part in the clearance of G-CSF from plasma. [source] Paclitaxel, ifosfamide, and nedaplatin (TIN) salvage chemotherapy for patients with advanced germ cell tumorsINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2007Norio Nonomura Background: The paclitaxel, ifosfamide, and cisplatin regimen has been used to treat metastatic testicular cancer with successful results. We investigated the usefulness of a paclitaxel, ifosfamide, and nedaplatin (TIN) regimen as salvage therapy for patients with advanced testicular germ cell tumors (GCTs). Methods: Eight patients with advanced GCTs were treated with TIN. The treatment was performed as salvage therapy for cases refractory to therapies, such as bleomycin, etoposide and cisplatin, and irinotecan with nedaplatin. The TIN regimen consisted of paclitaxel (200 mg/m2) by 24-h infusion on day 1, followed by ifosfamide (1.2 g/m2) infusions over 2 h on days 2,6, and nedaplatin (100 mg/m2) given over 2 h on day 2. Results: Seven out of eight patients achieved a disease-free status after chemotherapy, followed by surgical resection of the residual tumor. Six of the seven patients have continued to show no evidence of disease after salvage therapy, with a median follow-up period of 27 months, but one patient developed a ,growing teratoma syndrome' in the mediastinum 31 months after TIN chemotherapy. All patients developed grade 4 leukocytopenia. However, it could be managed by using granulocyte colony-stimulating factor. Only one patient developed grade 2 sensory neuropathy and no patient developed nephrotoxicity. Conclusion: The TIN regimen was efficacious and well-tolerated as salvage chemotherapy for Japanese patients with advanced GCTs. [source] Intravesical instillation therapy with bacillus Calmette-Guérin for superficial bladder cancer: Study of the mechanism of bacillus Calmette-Guérin immunotherapyINTERNATIONAL JOURNAL OF UROLOGY, Issue 2 2007Yasuyo Shintani Aim: In order to clarify the initial step of the mechanism by which bacillus Calmette-Guérin (BCG) exhibits antitumor activity via the immune response induced in the bladder submucosa after intravesical BCG therapy for human bladder cancer, various cytokines secreted in the urine after BCG instillation were measured. Methods: After transurethral resection of bladder cancer, a 6-week course of BCG instillation was performed. At the first and sixth weeks' dosings, spontaneously excreted urine was collected before and 4, 8, and 24 h after BCG instillation. The urinary cytokines were determined by Sandwich enzyme-linked immunosorbent assay using monoclonal antibodies against granulocyte,macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-,, granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-1,, IL-8, interferon (IFN)-,, and IL-12. Results: After the BCG therapy, various cytokines, such as GM-CSF, TNF-,, G-CSF, IL-1,, IL-8, IFN-,, and IL-12 were secreted, comprising the immune response cascade. The mean urinary excretions of GM-CSF and TNF-, 4 h after the sixth week's instillation were significantly higher than the pre-instillation levels. There were no significant increases in the urinary IFN-, or IL-12 levels between 4 and 24 h after the sixth week's instillation. The TNF-, level 4 h after the sixth week's instillation had a strong tendency towards the absence of recurrence, with a mean follow-up of 54.1 months. The Kaplan-Meier curve showed the 2, 5, and 10-year recurrence-free survival rates were 72.4%, 65.8%, and 56.4%, respectively. Conclusions: We suggested that the urinary levels of TNF-, might be essential in antitumor activity after BCG therapy and might play an important role in the prevention of bladder tumor recurrence. [source] Ex vivo expansion of apheresis-derived peripheral blood hematopoietic progenitorsJOURNAL OF CLINICAL APHERESIS, Issue 1 2002Zeev Estrov Because the administration of hematopoietic growth factors and the use of stem cell support often fails to alleviate the neutropenic phase induced by cytotoxic drugs, several investigators have attempted to expand ex vivo hematopoietic progenitors for clinical use. These attempts have clearly shown that the cultured cells are functional and can be safely administered to patients, but that the in vivo performance is disappointing and the concept as a whole is not yet clinically useful. The major reasons for these unsuccessful attempts are thought to be cumbersome cell fractionation techniques, contamination, prolonged incubation, and the use of less than ideal cytokine combinations. In response, we have developed a simple procedure for ex vivo expansion of myeloid progenitor cells. In this assay, unfractionated mononuclear cells from apheresis donors are incubated in nonpyrogenic plastic bags for 7 days in the presence of culture medium either containing fetal calf serum or human plasma, granulocyte colony-stimulating factor, and stem cell factor. We have demonstrated that under these conditions the number of colony-forming units (CFU) granulocyte-macrophage (CFU-GM) and of CFU-granulocyte-macrophage-erythroid-megakaryocyte (CFU-GEMM) increased 7- and 9-fold, respectively, by day 7 and the number of burst-forming units-erythroid (BFU-E) increased 2.7-fold by day 5 of culture. Significant increases in the numbers of cells expressing CD34+, CD34+/CD38+, CD34+/CD33+, CD34+/CD15+, and CD34+/CD90+ and significant declines in the numbers of cells expressing CD34+/CD38- and CD19 surface antigens were also observed. The relative numbers of cells expressing T-cell markers and CD56 surface antigen did not change. By using different concentrations of various hematopoietic growth factor combinations, we can increase the number of mature and immature cells of different hematopoietic lineages. J. Clin. Apheresis 17:7,16, 2002. © 2002 Wiley-Liss, Inc. [source] Severe chronic neutropenia in Chinese children in Hong KongJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 2 2001TF Leung Objective: Severe chronic neutropenia (SCN) is a rare and heterogeneous disorder in children. The epidemiology, clinical features and outcomes of SCN in Chinese children were reviewed. Methodology: A retrospective analysis of case records was undertaken for 18 children with SCN managed during a 12-year period in a university teaching hospital in Hong Kong. Results: The median (range) age of the patients at initial presentation was 6.5 months (4 days,19 months). The initial and lowest median absolute neutrophil counts (ANC) were 0.29 × 109 /L and 0.06 × 109 /L, respectively. Patients with congenital SCN had significantly fewer neutrophils in peripheral blood at diagnosis. Only five subjects received granulocyte colony-stimulating factor (G-CSF) treatment. All children were free from serious infection on follow up for 51 months. Only one child suffered from long-term infection-related morbidity. One patient with chronic neutropenia was subsequently shown to have common variable immunodeficiency. Conclusions: Most children with SCN in our series had favourable clinical outcomes. Our results support the recommendation that G-CSF should be used only in those with recurrent or severe infections. [source] Principles of Peripheral Blood Mononuclear Cell Apheresis in a Preclinical Canine Model of Hematopoietic Cell TransplantationJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2008M. Lupu Background: Preclinical studies of peripheral blood mononuclear cell (PBMC) transplantation conducted in a well-established canine hematopoietic cell transplantation (HCT) model have been successfully translated to human patients over the past 5 decades. Objective: We retrospectively investigated the safety and feasibility of PBMC apheresis in the canine model of HCT by analyzing apheresis parameters, cell yields, and the impacts of donor-related and apheresis-related variables on collection yields and donor stability. Animals: One hundred and twenty dogs that underwent PBMC aphereses were evaluated. Methods: Aphereses were performed with a COBE Spectra blood separator and a central dual-lumen catheter, with or without recombinant canine granulocyte colony-stimulating factor (rcG-CSF) stem cell mobilization. Results: Aphereses from dogs not given rcG-CSF yielded an average volume of 280 ± 42 mL containing an average of 15,086 ± 9,834 leukocytes/mL. Aphereses from dogs given rcG-CSF yielded an average volume of 261 ± 55 mL containing an average of 39,711 ± 24,488 leukocytes/mL. Higher pre-apheresis white blood cell (WBC) counts correlated with higher apheresis WBC yields (R=0.50, P<.0001). The correlations of collection time, inlet volume, and collection flow rate on WBC yields were statistically significant but only weak to moderate in magnitude (R=0.34, P=.0001; R=0.38, P=.0006; R=0.26, P=.002, respectively) as were the correlations of collection time and inlet volume on collection volumes (R=0.30, P=.002; R=0.42, P<.0001, respectively). All dogs recovered promptly after PBMC aphereses and catheter removal, without complications. Conclusions and Clinical Importance: These data may be useful for translating PBMC apheresis technology to the field of veterinary oncology for the treatment of dogs with hematologic malignancies. [source] An open-labelled study of granulocyte colony-stimulating factor in the treatment of active Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2005J. R. Korzenik Summary Background :,Immunodeficiency syndromes associated with a Crohn's-like illness suggest innate immune defects may lead to Crohn's disease. Anecdotal cases using haemopoietic colony-stimulating factors report improvement in intestinal disease associated with these syndromes. Aim :,To test the safety and efficacy of recombinant human granulocyte colony-stimulating factor in active Crohn's disease. Methods :,In an open-labelled 12-week trial, patients with a Crohn's Disease Activity Index between 220 and 450 were treated with recombinant human granulocyte colony-stimulating factor (filgrastim, Neupogen). Concomitant immunosuppressants were prohibited except prednisone ,20 mg/day. Patient's received recombinant human granulocyte colony-stimulating factor 300 mcg daily subcutaneously adjusted to achieve an absolute neutrophil count between 25 and 35 × 109/L. Results :,Twenty patients were enrolled with a mean initial Crohn's Disease Activity Index of 307 (range: 234,428). Fifteen patients (75%) completed 8 weeks; 13 patients (65%) completed 12 weeks with the mean Crohn's Disease Activity Index for patients continuing through those times of 196 (range: 36,343) and 162 (range: 20,308), respectively. At week 12, 11 patients (55%) demonstrated a decrease of at least 70 points; five (25%) achieved a sustained remission. The mean decrease was statistically significant at each assessment time-point. Three of four patients with fistulae had a positive response. Adverse effects included bone pain, mostly mild resolving with continued treatment. One patient was hospitalized with a viral-like syndrome but it is uncertain if this was treatment related. Conclusion :,Recombinant human granulocyte colony-stimulating factor is safe and potentially effective therapy for active Crohn's disease. [source] Hematopoietic stem cells mobilized by granulocyte colony-stimulating factor partly contribute to liver graft regeneration after partial orthotopic liver transplantationLIVER TRANSPLANTATION, Issue 7 2006Feng Liu On the basis of the recently recognized potential of hematopoietic stem cells (HSCs) to give rise to hepatocytes, we investigated whether HSCs mobilized by granulocyte colony-stimulating factor (G-CSF) or G-CSF per se could contribute to faster recovery and promote tissue reparation after rats' (cross-sex) partial orthotopic liver transplantation (PLTx). Sex-mismatched (female to male) syngeneic rat PLTx was established. The recipients were repeatedly administrated recombinant G-CSF for 5 consecutive days before (G-CSF + PLTx group) and after PLTx (PLTx + G-CSF group). Compared with those in PLTx group, CD34+ cells in peripheral blood and portal tract region increased from day 1 to 7 after transplantation in G-CSF + PLTx group and from day 3 to 14 after transplantation in PLTx + G-CSF group, respectively, which suggested that CD34+ HSCs were mobilized and migrated into liver graft. Compared with that in G-CSF + PLTx and PLTx groups, there was a higher survival rate in the PLTx + G-CSF group. On day 3 after surgery, the level of aspartate aminotransferase and alanine aminotransferase were lower, whereas the mitosis index, proliferating cell nuclear antigen,positive nuclei, bromodeoxyuridine (BrdU) incorporation, and graft-to-recipient weight ratio were higher in the PLTx + G-CSF group. In contrast, these parameters had no significant difference between G-CSF + PLTx and PLTx groups. To define the origin of proliferating cells reconstituting liver after injury, sry+ (sex-determining region for Y chromosome) and sry+/cytokeratin 19+ (CK19) cells were quantitated. Higher percentage of sry+ and sry+/CK19+ cells in PLTx + G-CSF was detected than in G-CSF + PLTx groups on day 14 after surgery, although the liver engraftment rate still remained rather low. Some of the sry+/CK19+ cells in the portal tract areas were similar to hepatic oval cells/cholangiocytes. In conclusion, G-CSF administration after PLTx greatly improved survival rate and liver regeneration of partial graft, partly by its mobilizing HSCs into the injured liver to differentiate into hepatocytes through hepatic oval cells'/cholangiocytes' engraftment. Liver Transpl 12:1129,1137, 2006. © 2006 AASLD. [source] Neutrophil dysplasia induced by granulocyte colony-stimulating factor,AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2010Barbara J. Bain No abstract is available for this article. [source] Long-term posaconazole treatment and follow-up of rhino-orbital-cerebral mucormycosis in a diabetic girlPEDIATRIC DIABETES, Issue 4 2009Luigi Tarani Abstract:, To demonstrate that the 2-yr clinical follow-up of our patient strongly suggests that long-term therapy with posaconazole (POS) is safe and beneficial in treatment and prevention of relapses of, otherwise fatal, central nervous system mucormycosis. Mucormycosis is a very rare opportunistic mycotic infection of diabetic children. We present the 30-month follow-up of a 12-yr-old girl affected by diabetic ketoacidotic coma, complicated by rhinocerebral mucormycosis and successfully treated with POS at the initial daily dose of 5 mg/kg t.i.d. with fatty food for 3 wk, followed by a daily dose of 10 mg/kg in four doses for 2 months and then 20 mg/kg/d in four doses for 16 months and in two doses for further 5 months. The previous amphotericin B, granulocyte colony-stimulating factor, hyperbaric oxygen and nasal and left maxillary sinus surgical debridement therapy was ineffective in stopping the progression of the infection to the brain. The patient improved within 10 d with reduced ocular swelling and pain, and 6 months after therapy stop, she is in good health and cultures are sterile. This article demonstrates that POS may be a useful drug in mucormycosis in children. We also strongly draw the attention to the main preventive procedure against invasive fungal infection that is the correct management of antidiabetic therapy that prevents the predisposing temporary neutrophils activity deficit, contributing to a better survival rate of diabetic children. [source] Protein microarray analysis as a tool for monitoring cellular autoreactivity in type 1 diabetes patients and their relativesPEDIATRIC DIABETES, Issue 5 2007Zuzana Vrabelova Background:, Autoreactive T cells have a crucial role in type 1 diabetes (T1D) pathogenesis. Objectives:, The aim of our study was to monitor the in vitro production of cytokines by peripheral blood mononuclear cells (PBMCs) after stimulation with diabetogenic autoantigens. Subjects:, Ten T1D patients (tested at the time of diagnosis and 6 and 12 months later), 10 first-degree relatives of the T1D patients, and 10 controls underwent the study. Methods:, PBMCs were stimulated with glutamic acid decarboxylase 65 (GAD65) amino acids (a.a.) 247,279, 509,528, and 524,543; proinsulin a.a. 9,23; and tyrosine phosphatase (islet antigen-2)/R2 a.a. 853,872. Interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, IL-13, interferon (IFN)-,, tumor necrosis factor ,, transforming growth factor ,1, and granulocyte colony-stimulating factor (GCSF) were analyzed by protein microarray. Results:, Differences in cytokine(s) poststimulatory and mainly in basal production were observed in all groups. The most prominent findings were in controls, the higher basal levels of IL-2, IL-4, IL-5, IL-13, and GCSF were observed when compared with relatives (p < 0.05, for all). After stimulation in controls, there was a significant decrease in IL-2, IL-13, GCSF, and IFN-, (p < 0.05, for all). The group of relatives was the most variable in poststimulatory production. A strong correlation between cytokines production was found but groups differed in this aspect. Conclusion:, By multiplex analysis, it may be possible, for example, to define the risk immunological response pattern among relatives or to monitor the immune response in patients on immune modulation therapy. 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