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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Granulocyte transfusions may be beneficial in neutropenic patients with progressive infections despite appropriate antibiotics. In order to evaluate both the feasibility of granulocyte collection in normal donors receiving granulocyte colony-stimulating factor (G-CSF) and the efficacy of infusing these cells into neutropenic patients with progressive sepsis, four donors received between 5-10 micrograms/kg G-CSF per day and underwent leucapheresis within a day of the first dose. Different red cell sedimenting agents and interface settings were evaluated to determine the optimal method of granulocyte collection. The number of granulocytes collected, the peripheral blood granulocyte level in the recipient at various time points after infusion, and the clinical response were evaluated. Results showed that G-CSF and the leucaphereses caused mild to moderate fatigue in two donors and profound fatigue and a brief episode of hypoxia in one donor. Efficient granulocyte collections were only obtained using dextran 40 or dextran 70 as the sedimenting agent and a deep interface setting which extended sampling into the upper red cell layer. Infusion of granulocytes obtained with this technique resulted in a sustained increase in circulating granulocyte numbers in three recipients, one of whom gained significant clinical benefit. In conclusion, granulocyte transfusions from donors given G-CSF are feasible and may be clinically beneficial, particularly if given early in the course of infection in neutropenic patients.
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PMID:G-CSF stimulated donor granulocyte collections for neutropenic sepsis. 853 1

We have previously reported that recombinant human granulocyte colony-stimulating factor was well tolerated and resulted in sustained neutrophilia and improvement of neutrophil functions in newborn infants with presumed sepsis. We now report a 2-year follow-up on 21 of the initial cohort of 28 patients. Treatment with recombinant human granulocyte colony-stimulating factor in neonates with presumed sepsis was not associated with any long-term adverse hematologic, immunologic, or developmental effects.
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PMID:A two-year follow-up of neonates with presumed sepsis treated with recombinant human granulocyte colony-stimulating factor during the first week of life. 855 4

To investigate the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on sepsis, chronically catheterized conscious pigs were challenged with Pseudomonas aeruginosa (8 x 10(7) colony-forming units kg-1 h-1) for 84 h (Group A, n = 8). Group B (n = 7) also received rhG-CSF at 5 micrograms kg-1 d-1, the first dose being given 30 min before starting bacterial infusion. Two of the animals in Group A died from pulmonary failure, whereas all those treated with rh-GCSF survived. Fever, severe pulmonary hypertension and systemic hypotension--the latter accompanied at first by a transient hypodynamic, and later a hyperdynamic response--were observed in all of the animals. In Group B, however, the rise in temperature, mean pulmonary arterial pressure (at a later stage of the observation), plasma levels of tumor necrosis factor, and endotoxin were significantly less than in Group A. In the rhG-CSF-treated pigs, an initial leukopenia completely recovered within 24 h (p < .05 vs. Group A). These data suggest that rhG-CSF might be beneficial in the treatment of sepsis.
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PMID:Effect of recombinant human granulocyte colony-stimulating factor on hemodynamic and cytokine response in a porcine model of Pseudomonas sepsis. 857 58

Eighteen patients with metastatic non-small cell lung cancer were treated with a combination of intravenous vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France) 25 mg/m2 on days 1 and 8 and intravenous paclitaxel 175 mg/m2 on day 2 every 3 weeks. All patients were given granulocyte colony-stimulating factor 5 micrograms/kg/d subcutaneously on days 3 through 7 and 9 through 17 or until the absolute neutrophil count reached 10 x 10(9)/L or higher. One patient was enrolled in this study too recently to be assessed. The mean age of the remaining 17 patients was 59 years (age range, 33 to 75 years); all but one patient had refractory disease, mostly to cisplatin-containing regimens. Four patients were ineligible (two because of poor performance status and two because of previous exposure to vinblastine). Three partial responses were observed, with durations of 46, 64, and 140+ days. Four patients had stable disease and four had progressive disease. The most common side effect was neutropenia (five grade 4 and one grade 3); two patients died of leukopenic sepsis in the first cycle. Peripheral neuropathy was also common (four grade 1 and one grade 2 sensory neuropathy). Other toxic effects were anemia and nausea and vomiting. The median survival was 153 days in all patients and 179 days in eligible patients. The preliminary results in this ongoing study of combination vinorelbine and paclitaxel as second-line therapy for metastatic non-small cell lung cancer are promising, and using this regimen as first-line therapy is warranted.
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PMID:Pilot study of vinorelbine (navelbine) and paclitaxel in patients with refractory non-small cell lung cancer. 861 Feb 31

Ifosfamide, carboplatin, cisplatin, etoposide, and paclitaxel are chemotherapeutic agents active in treating many malignant diseases. The ICE combination (ifosfamide/carboplatin [or cisplatin]/etoposide) has been studied in breast cancer, small cell and non-small cell lung cancer, testicular cancer, lymphoma, and other malignancies with promising results. We conducted a dose-escalation study of paclitaxel in combination with ICE (ICE-T) to evaluate the toxicity and define the maximum tolerated dose of paclitaxel. To date, 24 patients have been treated with ICE-T. Patients had to have no or minimal prior chemotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate bone marrow, liver, and kidney function. The doses of ICE were as follows: ifosfamide 1.25 g/m2/d days 1 to 3, carboplatin 300 mg/m2 day 1, and etoposide 80 mg/m2/d days 1 to 3. Paclitaxel was given at a dose of 120 mg/m2 to five patients, 135 mg/m2 to five patients, 150 mg/m2 to three patients, and 175 mg/m2 to 11 patients. All patients received granulocyte colony-stimulating factor support. The most common side effect was neutropenia. Grade 4 neutropenia and thrombocytopenia occurred during 34% and 20% of 94 cycles, respectively, with leukopenic fever occurring during 14% of cycles. No treatment-related death or sepsis occurred due to brief nadir durations of 3.5 days for neutropenia and thrombocytopenia. Other toxicities were mostly mild to moderate and did not require dose modification, although alopecia was universal. Nine patients (100%) with metastatic breast cancer and four (67%) with soft tissue sarcoma have attained documented objective responses with four complete remissions (one breast cancer and three sarcoma patients). The maximum tolerated dose of paclitaxel has not yet been defined, and the study is ongoing. In conclusion, this pilot study showed that ICE-T is safe and tolerable. The response to ICE-T is encouraging and warrants further study with this regimen.
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PMID:Ifosfamide, carboplatin, etoposide, and paclitaxel chemotherapy: a dose-escalation study. 867 54

Thirty-one patients (median age, 44 years) with advanced hematologic malignancies were given thiotepa 15 mg/kg, and cyclophosphamide 120 (n = 14) or 150 (n = 17) mg/kg followed by unfractionated peripheral blood stem cell transplants (PBSCT) from genotypically identical siblings (n = 28) or one antigen mismatched family donor (n = 3). Donors were mobilized with granulocyte colony-stimulating factor 5 to 10 microgram/kg/d for 6 days and underwent two to three leukapheresis on days +5, +6, +7. The median cell yield per donor expressed/kg of recipients body weight was as follows: nucleated cells 13 x 10(8)/kg; CD34+ cells 6 x 10(6)/kg; colony-forming unit-granulocyte macrophage 38 x 10(4)/kg, and CD3+ cells 449 x 10(6)/kg. The diagnoses were chronic myeloid leukemia (n = 4), acute myeloid (n = 9) or lymphoid leukemia (n = 2), acute myelofibrosis (n = 2), multiple myeloma (n = 1), lymphoma (n = 6), chronic lymphocytic leukemia (n = 1) myelodysplasia (n = 6). Twenty-eight patients had advanced disease, 29 patients were first grafts, and 2 were second transplants 3 and 9 years after the first. Neutrophil counts of 0.5 x 10(9)/L and platelet counts of 30 x 10(9)/L platelets were both achieved on day +14 (median). Engraftment could be proven by sex markers or DNA polymorphism in 29 of 31 patients: one had early leukemia relapse and one patient was unevaluable because of early death. Acute graft-versus-host disease (GVHD) was scored as minimal or absent (grade 0 to 1) in 14 patients, moderate (grade II) in 13, and severe (grade III to IV) in four. Causes of death were leukemia (n = 4), acute GVHD (n = 4, with associated cytomegalovirus infections in three), sepsis (n = 1), liver failure (n = 1), multiorgan failure (n = 1), and hemorrhage (n = 1). The actuarial transplant mortality is 29%, the actuarial relapse rate 22%. Nineteen patients survive with a median follow up of 288 days (100-690). The actuarial 2-year survival is 57%. Three patients received PBSCT from family donors mismatched for one class II antigen: all engrafted, one developed grade I aGVHD; one died of leukemia on day +155; two are alive disease free 267 to 290 days postgraft. This study suggests that thiotepa cyclophosphamide followed by unfractionated PBSC allograft may be an alternative form of transplant for adults with advanced leukemia, also in the setting of one antigen mismatched donor. The engraftment is rapid with acceptable GVHD and relatively low transplant-related mortality.
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PMID:Thiotepa cyclophosphamide followed by granulocyte colony-stimulating factor mobilized allogeneic peripheral blood cells in adults with advanced leukemia. 870 95

Peripheral blood progenitor cell (PBPC) autografts have a number of advantages over autologous bone marrow transplantation (ABMT) as haematopoietic support after high-dose chemotherapy in patients with breast cancer. These may include less contamination by tumour cells, reduced morbidity and mortality and additional dose escalation of chemotherapy. A dose-escalation study is described using recombinant granulocyte colony-stimulating factor (G-CSF; filgrastim) primed PBPC support and post-infusion filgrastim for patients with high-risk or metastatic breast cancer. The regimen involved the use of cyclophosphamide, thiotepa and carboplatin at five dose levels. The main problem to emerge was organ toxicity induced by chemotherapy or sepsis. Patients receiving higher levels of chemotherapy were therefore allocated or not to an additional regimen involving pentoxifylline, ciprofloxacin and dexamethasone in an attempt to inhibit tumour necrosis factor alpha (TNF-alpha) which is believed to be one of the principal mediators of chemotherapy-related organ toxicity. The incidence of bilirubin elevations, weight gain > 5% and veno-occlusive disease (VOD) was lower in patients receiving the 'anti-TNF' therapy. The simultaneous use of PBPC support and 'anti-TNF' therapy therefore allows a substantial increase in chemotherapy dosage. Further studies with larger patient numbers are required to show whether this decreased toxicity also produces increased patient survival.
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PMID:High-dose chemotherapy for breast cancer: clinical advantages of autologous peripheral blood progenitor cells (PBPC) compared with autologous bone marrow transplantation (ABMT). 875 Jan 43

We report the case of a 34 year old woman with acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC) due to methicillin-resistant Staphylococcus aureus (MRSA) sepsis with hyperimmunoglobulin E syndrome (HIES). Although chemotactic activity of neutrophils was impaired in this patient, neutrophils accumulated in the lungs as assessed by bronchoalveolar lavage fluid (BALF) counts. In addition to antibiotics and oxygen therapy, the administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) resulted in a remarkable recovery.
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PMID:Acute respiratory distress syndrome due to methicillin-resistant Staphylococcus aureus sepsis in hyper-IgE syndrome. 877 83

Although antimicrobial therapy has been the central clinical strategy for patients with sepsis and multiple organ failure, the survival rate in these patients remains low because their host defense mechanisms usually are compromised. Various inflammatory cytokines recently have been shown to play important roles in normal host defense mechanisms and in sepsis and its sequelae. Cytokine modulation therapies, which have focused on the downregulation of the inflammatory response, have not been shown to benefit these patients. This article examines the role of granulocyte colony-stimulating factor as a proinflammatory mediator and a potential adjuvant treatment in patients with severe infection.
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PMID:Granulocyte colony-stimulating factor and modulation of inflammatory cells in sepsis. 879 69

The ribonucleotide reductase inhibitor, hydroxyurea (HU), augments the cytotoxic effects of 5-fluorouracil (5FU) in vitro; both drugs are synergistic with interferon-alpha (IFN) in vitro. The aim of this phase I study was to determine the maximal duration of HU, 4.3 g/m2, administered as a parenteral infusion in combination with 5FU, 2.6 g/m2 administered over 24 hrs each week, + IFN, 9 MU, subcutaneously three times per week. There were 26 patients enrolled and evaluable. This included 14 patients with colorectal cancer of whom 13 had been previously treated, and 12 patients with other refractory malignancies (pancreas, cholangiocarcinoma, hepatocellular carcinoma, renal cell carcinoma, and others), of whom 10 were previously untreated. The dose-limiting toxicity of this regimen was myelosuppression. This prohibited dose escalation of HU above the starting dose (24 hrs) on a 6-weeks-on, 2-weeks-off therapy schedule. When filgrastim, 480 microg, was administered subcutaneously on days 3-6, the duration of HU could be extended to 48 hrs on a 2-weeks-on, 1-week-off therapy schedule. There were two instances of fatal infection, one in a patient with a rectovaginal fistula with neutropenic sepsis and the second in a patient with non-neutropenic Clostridium septicum sepsis. All therapy was administered in the ambulatory setting. There were three responders, all among previously untreated patients. High-dose parenteral hydroxyurea, 4.3 g/m2 administered over 24 hrs, can be safely combined with high-dose weekly 5FU, 2.6 g/m2 over 24 hrs + IFN, 9 MU subcutaneously three times per week, without filgrastim in the ambulatory setting. Parenteral hydroxyurea, 4.3 g/m2 over 24 hrs daily x 2 can also be combined with high-dose 5FU + IFN, but requires the addition of filgrastim to avoid severe myelosuppression.
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PMID:Phase I trial of high-dose infusional hydroxyurea, high-dose infusional 5-fluorouracil and recombinant interferon-alpha-2a in patients with advanced malignancies. 882 49


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