Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

We analyzed the use of non-tunneled (polyurethane, double lumen) central venous catheters (CVCs) for the collection, conditioning, transplantation and immediate post-transplantation periods in 56 children with various malignant diseases. A total of 71 leukaphereses were performed, with a mean of 1.2 apheresis per patient, following administration of granulocyte colony-stimulating factor (G-CSF) using a continuous flow blood cell separator (Cobe Spectra). The mean TBV (total blood volume) processed was 4.5 +/- 1.2 s.d. (range 2.4-7). The mean flow rate was 30.6 ml/min and the duration of a single apheresis was 327 +/- 84 s.d. (range 175-511 min). The mean purities and efficacies of collections were 77.38 +/- s.d. (range 42-100) and 42.78 +/- s.d. (range 24-80), respectively. The mean numbers of mononuclear cells (MNC) and CD34+ cells collected were 9.3 +/- 6.9 s.d. x 10(8)/kg (range 2-49) and 6.2 +/- 7.2 s.d. x 10(6)/kg (range 1-42), respectively. We observed the following complications during catheter insertion for collection: pneumothorax (1.7%), mechanical dysfunction (3.5%) that resolved with thrombolytic therapy. Complications during conditioning, transplantation and immediate post-transplantation periods were entry site infection in five patients (8.92%), catheter-related infection in two (3.57%) and catheter-related sepsis in three (5.35%). Our results indicate that the collection of PBSC with non-tunneled catheters is safe, effective and dis associated with a low incidence of complications.
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PMID:Non-tunneled catheters for the collection and transplantation of peripheral blood stem cells in children. 923 57

A 40-year-old patient with long-standing Crohn's ileocolitis in remission experienced cyclic neutropenia with a periodicity of 14 days. He was not receiving immunosuppressive or myelosuppressive therapy. The patient had Staphylococcus aureus bacteremia resulting from central catheter infection, which was refractory to antibiotic therapy during the period of severe neutropenia. When granulocyte colony-stimulating factor (G-CSF) was administered, the cyclic neutropenia rapidly disappeared, the neutrophil and leukocyte counts normalized, and the sepsis resolved. When G-CSF therapy was discontinued, the leukocyte and absolute neutrophil counts again declined. With reinstitution of therapy, the leukocyte and absolute neutrophil counts recovered and normalized. Crohn's ileocolitis remained in remission during G-CSF therapy. This report confirms and extends one previous report of cyclic neutropenia associated with Crohn's disease and demonstrates in one patient the efficacy and safety of G-CSF on the hematologic, bacteriologic, and clinical manifestations of cyclic neutropenia associated with Crohn's disease.
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PMID:Cyclic neutropenia in Crohn's ileocolitis: efficacy of granulocyte colony-stimulating factor. 925 52

Interfering with the endotoxin-mediated cytokine cascade is thought to be a promising approach to prevent septic complications in gram-negative infections. The synthetic lipid A analog SDZ MRL 953 has been shown to be protective against endotoxic shock and bacterial infection in preclinical in vivo models. As part of a trial of unspecific immunostimulation in cancer patients, we conducted a double-blind, randomized, vehicle-controlled phase I trial of SDZ MRL 953 to investigate, first, its biologic effects and safety of administration in humans and, second, its influence on reactions to a subsequent challenge of endotoxin (Salmonella abortus equi). Twenty patients were treated intravenously with escalating doses of SDZ MRL 953 or vehicle control, followed by an intravenous application of endotoxin (2 ng/kg of body weight [BW]). Administration of SDZ MRL 953 was safe and well-tolerated. SDZ MRL 953 itself increased granulocyte counts and serum levels of granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6), but not of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), IL-1beta, and IL-8. Compared with vehicle control, pretreatment with SDZ MRL 953 markedly reduced the release of TNF-alpha, IL-1beta, IL-8, IL-6, and G-CSF, but augmented the increase in granulocyte counts to endotoxin. Induction of tolerance to the endotoxin-mediated cascade of proinflammatory cytokines by pretreatment with SDZ MRL 953 in patients at risk may help to prevent complications of gram-negative sepsis.
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PMID:Downregulation of the proinflammatory cytokine response to endotoxin by pretreatment with the nontoxic lipid A analog SDZ MRL 953 in cancer patients. 926 88


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