Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over a period of 14 days a longitudinal analysis was performed on the effects of filgrastim (recombinant human granulocyte colony stimulating factor, rhG-CSF) administered to 20 postoperative/posttraumatic patients at risk of or with sepsis. The following parameters were determined: leukocyte counts, serum cytokine levels and the surface expression of functional antigens and adhesion molecules. Filgrastim (1 mu g/kg.day) was infused continuously on the first 3 days and tapered to 0.5 mu g/kg.day on the following 4 days or until discharge from the surgical intensive care unit. During infusion of filgrastim, G-CSF levels increased in 16 out of the 20 patients within 48 h. In these 16 patients, leukocyte counts increased in 15 out of 16 patients. Expression of CD64 was upregulated within 24 h. The expression of CD32 was upregulated in 8 out of 9 patients with an initial expression < 55%. LAM-1 expression was downregulated in all patients revealing an initial expression of LAM-1 > 40%. Soluble ICAM increased in 9 out of 11 patients. IL-8 decreased in all 6 patients presenting initial values of IL-8 > 90 pg/ml. IL-1RA increased in 10 patients. Filgrastim had no effect on the expression of CD14, CD16 and CD34 and on the levels of TNF-alpha and sTNF-R type I (p55). In conclusion, infusion of filgrastim in postoperative/post traumatic patients at risk of and with sepsis resulted in improved generation and function of neutrophils and appeared to counterregulate hyperactivation of proinflammatory processes.
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PMID:Filgrastim (RHG-CSF) related modulation of the inflammatory response in patients at risk of sepsis or with sepsis. 883 41

Thymoma with agranulocytosis is a rare association. We describe two cases of agranulocytosis presenting with sepsis which were both found to have coincident benign spindle cell thymomas. One case, associated with promyelocyte arrest and hypogammaglobulinaemia, was treated successfully with granulocyte colony-stimulating factor (G-CSF). Thymectomy had no effect. The other case, associated with complete myeloid aplasia, proceeded to a fatal outcome after failure of treatment with granulocyte-macrophage colony stimulating factor (GM-CSF), plasmapheresis, thymectomy, intravenous immunoglobulin, cyclophosphamide and methylprednisolone. We also review the literature of thymoma in association with agranulocytosis.
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PMID:Thymoma and agranulocytosis: two case reports and literature review. 885 38

The recent production of recombinant human growth factors has expanded the neonatal clinician's armamentarium for treating sepsis and anemia of prematurity (AOP). Agents that may prove useful in the premature neonate include recombinant human erythropoietin (rh-EPO), granulocyte colony-stimulating factor (rhG-CSF), and CSF). Within the neonatal population, research utilizing these agents is still relatively new. Appropriate clinical trials are still needed to elucidate the optimal dosing regimen for both rhG-CSF and rh-EPO, as are studies to address the issue of long-term safety. Use of rhG-CSF in sepsis and of rh-EPO for AOP is still considered experimental, but in instances where conventional treatments are not proving beneficial, these agents may provide a therapeutic alternative. Their potential for improving care of the premature neonate must also be assessed.
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PMID:Hematopoietic growth factors: Part I. 893 67

Nasopharyngeal carcinoma (NPC) has been shown to be highly responsive to chemotherapy. The major limiting toxicity was myelotoxicity. Recently, the role of granulocyte colony-stimulating factor (G-CSF) in reducing chemotherapy-induced neutropenic sepsis has been well established. In this study, we tested whether recombinant human G-CSF (rhG-CSF) could effectively support the bone marrow function in both previously untreated and pretreated metastatic NPC patients receiving intensive chemotherapy. Twelve patients with distant metastatic disease, 5 newly diagnosed (group A) and 7 pretreated patients (group B), were enrolled to receive BEC (bleomycin, epirubicin and cisplatin), followed by rhG-CSF support (50 microg/m2 s.c. daily for 10 days) every 4 weeks for two cycles. Four patients in group A completed the treatment as scheduled while only 2 patients in group B did. After the first treatment cycle, 6 patients (50%) had grade III-IV myelosuppression. Five of the patients were from group B. The mean values of the white cell count nadir were 2,680 (range 1,200-3,700) in group A and 1,343 (range 400-2,900) in group B (p = 0.0386). Neutropenia-associated fever occurred in 7 patients, 6 of whom had received previous treatment. There were 2 deaths due to toxicity, and both patients had liver metastases within 6 months following radiation. After 24 months of follow-up, only 1 patient is still alive. Our preliminary results suggest that in previously treated metastatic NPC patients, bone marrow suppression is still the major limiting toxic side effect of aggressive chemotherapy, especially for those patients with liver recurrences within 6 months after irradiation and despite rhG-CSF support.
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PMID:Intensive chemotherapy plus recombinant human granulocyte-colony stimulating factor support for distant metastatic nasopharyngeal carcinoma. A preliminary report. 897 90

No satisfactory treatment exists to treat or prevent malignant ascites secondary to nonovarian intraperitoneal (IP) disseminated malignancies. A Phase I/II clinical trial combining radical cytoreductive surgery (CS) and IP hyperthermic chemotherapy (IPHC) with mitomycin C is presented. Between December 9, 1992 and July 31, 1995, 39 patients (pts) were explored for IP cancer. Five pts with known liver metastases were excluded, leaving 34 pts (15 female, 19 male) of median age 53 (range, 17-76). The majority of pts had disseminated IP cancers of gastrointestinal origin (80%). Prior therapy included the following: chemotherapy, 20 pts (59%); surgery, 29 pts (85%); and radiation, 2 pts (6%). Following CS, IPHC with mitomycin C was done. At surgery, 12 pts (35.3%) had frank ascites, and 12 pts (35.3%) had positive IP cytology without ascites. The median hospital stay was 9 days (range, 5-65) with no 30-day mortality. Complications for 36 treatments included: thrombocytopenia Eastern Cooperative Oncology Group grade 3 or 4, two cases (5.6%); neutropenia requiring granulocyte colony-stimulating factor, seven cases (19.4%); sepsis, four cases (11.1%); bowel leak, two cases (5.6%); and serous wound leak, two cases (5.6%). Ascites correlated with worse resection status (P = 0.025). Ascites was controlled in 9 of 12 (75.0%) pts, with failures at 1, 4, and 14 months (median follow-up, 7.5 months). No cytology-positive ascites-negative pts developed clinical ascites (median follow-up, 9.4 months). The median survival time in pts with ascites was 10.1 months versus 32.7 for patients without ascites (P = 0.013). For the entire study population, the 1- and 2-year survival rates were 74.6 and 48.5 per cent, respectively (median follow-up, 18.2 months). In this study, malignant ascites was controlled in 75 per cent of cases and prevented in all pts with positive IP cytology. CS plus IPHC appears to be relatively well tolerated and may be effective for the treatment and prevention of malignant ascites.
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PMID:Treatment and prevention of malignant ascites associated with disseminated intraperitoneal malignancies by aggressive combined-modality therapy. 901 27

The presence of certain defects in both cellular and humoral immunity after thermal injury has been established. Likewise, the translocation of enteric bacteria to the mesenteric lymph nodes and to distant organs has also been observed following serious thermal injury. The effects of granulocyte colony-stimulating factor (G-CSF) on bacterial translocation, the small bowel mucosa, and cecal bacterial content were investigated in a rat model of burn wound sepsis in which albino Wistar rats were scalded over 30% of their bodies, after which the lesions were infected by 1 x 10(8) colony-forming units (cfu) Pseudomonas aeruginosa. The control group was treated with 5% dextrose solution subcutaneously starting 2 days preburn, while the treatment group received 100 microg/kg human G-CSF subcutaneously. On the 4th day post burn all animals were killed to examine the bowel and culture of the mesenteric lymph nodes (MLN), livers, and spleens. No significant differences were observed between the groups regarding the cecal bacterial content and small bowel; however, a difference was seen in the ratio of translocation in the MLN liver and spleen and quantitative MLN cultures. Based on these findings, G-CSF was thus found to be significantly effective in reducing bacterial translocation due to burn wound sepsis.
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PMID:Effects of granulocyte colony-stimulating factor on bacterial translocation due to burn wound sepsis. 901 94

Recombinant human granulocyte colony-stimulating factor (rHuG-CSF) has been shown to stimulate the production and function of neutrophils in vitro and in vivo. Clinical studies in patients receiving myelosuppressive chemotherapy showed earlier neutrophil recovery, a reduction in infectious complications of neutropenia, and the use of fewer antibiotics. Its use has also been established for mitigating the infectious complications associated with severe chronic neutropenia (SCN). Data are emerging that neutropenia also contributes to the risk of infections in patients with acquired immunodeficiency syndrome (AIDS) and in neonates with presumed sepsis, and that rHuG-CSF may be a useful adjunct therapy in these patients. More recent studies have focused on enhancing neutrophil number and function in patients with infections not associated with neutropenia. These studies were approached cautiously because of the suggestion that neutrophils might non-selectively amplify the body's inflammatory response in the immunocompetent host and lead to inadvertent tissue injury. Preclinical models have provided a strong rationale for clinical studies to determine whether rHuG-CSF lessens the severity or duration of serious infections or their complications in patients with suboptimal outcome from antibiotics. These studies suggest that elevation of neutrophil levels in these settings is not only safe but has clinical benefit.
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PMID:Clinical benefits of improving host defences with rHuG-CSF. 910 12

The capacity of filgrastim to reduce the myelotoxicity of a 16-week intensive chemotherapy regimen has been investigated in 24 operable breast cancer patients with > or = 10 metastatic axillary nodes. Five patients were treated with chemotherapy alone (control group); 19 patients were treated with chemotherapy and filgrastim, 5 microg/kg/day s.c. Six patients in the latter group were treated from day 4 to day 7 (level 1), seven from day 10 to day 13 (level 2), and six from day 4 to day 7 and day 10 to day 13 (level 3). A total of 135 courses were administered: neutropenia was the most severe toxicity, and the prophylactic use of filgrastim does not reduce its severity. Moreover, the dose intensities of antiblastic drugs actually received by the patients were not significantly different in the four study groups. Among the patients treated at level 3, there were three toxic deaths: one patient died because of febrile neutropenia and sepsis, two patients because of ischemic colitis. At a median follow-up of 15 months, 17 patients were alive, and 15 patients were disease free. The use of filgrastim does not ameliorate myelotoxicity and does not allow the administration of the planned doses of antiblastic drugs of a 16-week intensive chemotherapy regimen.
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PMID:Filgrastim and lack of support of intensive adjuvant chemotherapy for high-risk breast cancer patients. 912 94

Bacterial infections remain an important cause of neonatal mortality and morbidity. Pathogenesis of the neonate's predilection to infection are multifactorial. Factors directly attributable to the infant include humoral, phagocytic, and cellular deficiencies. Septic neonates may have reduced neutrophil storage pools that cause profound neutropenia. Both correlate with poor prognosis. Antibiotic administration is mandatory in neonatal sepsis. Supplementary treatments may be useful. Granulocyte transfusions, when available, provide neutrophils, improving the neonate's neutrophil count and neutrophil function. The efficacy of intravenous immunoglobulin (i.v.IG) is questionable because the prophylactic and therapeutic administration of i.v.IG fails to reduce the incidence of bacterial infections or affect the overall survival rate. Hyperimmune preparations seem to be more effective. The administration of granulocyte colony-stimulating factor induces myeloid progenitor proliferation, enhances the neutrophil storage pool, produces neutrophilia, and improves neutrophil function. More extensive, well-designed, and carefully control trials are needed to determine the benefit of supportive therapies for neonatal sepsis.
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PMID:Neonatal sepsis: pathogenesis and supportive therapy. 919 31

This phase I dose-finding study examined the effects of the combination of doxorubicin and docetaxel (Taxotere) in 42 women with metastatic breast cancer. The combination was studied at six different dosing levels. The maximum tolerated doses were defined as doxorubicin, 50 mg/m2, and docetaxel, 85 mg/m2, with sepsis as the dose-limiting toxicity. Activity was observed at all dose levels, especially at the highest dose levels (50/60, 50/75, 50/85, and 60/60 mg/m2), with a response rate of 81% (95%; confidence interval, 62.5% to 92.5%) in patients treated at these dose levels. The response rate in patients with visceral disease was 74%, and 82% in patients with liver metastasis. Adjuvant chemotherapy with or without anthracyclines did not affect the response rate. The recommended doses were doxorubicin, 50 mg/m2, and docetaxel, 75 mg/m2, or 60 mg/m2 of both drugs, administered on day 1 every 3 weeks, without granulocyte-colony stimulating factor (G-CSF, filgrastim [Neupogen]) support. Neutropenia was the only grade 3 or 4 adverse event. There were no cases of congestive heart failure, a significant decrease in left-ventricular ejection fraction, or interruption of treatment because of fluid retention.
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PMID:Docetaxel in combination with doxorubicin: a phase I dose-finding study. 921 22


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