Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004610 (bacteremia)
 13,199 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seventeen patients with Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) were treated with the ICE regimen plus G-CSF with the aim of mobilizing and collecting Ph-negative peripheral stem cells (PSC) in the setting of an autotransplant program. Fifteen patients had CML in first chronic phase (CP), and two in accelerated phase (AP). Three patients had been previously treated with interferon alpha 2a (IFN). Twelve patients underwent leukaphereses and a mean of 4.7 x 10(8)/kg mononuclear cells were obtained. Four CP patients did not show a significant mobilization peak of CD34+ cells and leukapheresis was not performed; finally, one patient died before apheresis could be performed. Six of the 12 who underwent leukaphereses obtained more than 1.0 x 10(6)/kg CD34+ cells. Eight of the 12 mobilized patients (67%) obtained a major cytogenetic response, including two complete and six partial; in the remaining four patients minimal or absent cytogenetic responses were observed. A higher rate of Ph purging was obtained in patients mobilized early or showing residual Ph-negative cells before mobilization, even if they were in AP. Infectious complications were frequent with a 38% rate of bacteremia recorded and one case of pulmonary aspergillosis resulting in a toxicity similar to that occurring in acute myeloid leukemia-induction chemotherapy. The ICE regimen can promote 'in vivo' purging of the Ph+ cells in 67% of CML mobilized patients (8/12). Failure of mobilization occurs in 65% of patients (11/17), mainly because of poor CD34+ cell yield.
 ...
PMID:Mobilization of peripheral stem cells with intensive chemotherapy (ICE regimen) and G-CSF in chronic myeloid leukemia. 893 40

The p47phox-/- mouse exhibits a phenotype similar to that of human chronic granulomatous disease (CGD) and, thus, is an excellent model for the study of gene transfer technology. Using the Moloney murine leukemia virus-based retroviral vector MFG-S encoding the human form of p47phox, we performed ex vivo gene transfer into Sca-1+ p47phox-/- marrow progenitor cells without conditioning of donors with 5-fluorouracil. Transduced progenitors were transplanted into moderately irradiated (500 cGy), G-CSF preconditioned sibling p47phox-/- mice. Using the fluorescent probe dihydrorhodamine 123 (DHR), in vivo biochemical correction of the superoxide-generating NADPH oxidase system was detected by flow cytometry in 12.3% +/- 0.9% of phorbol myristate acetate-stimulated peripheral blood neutrophils at 4 weeks and 2.6% +/- 1.0% at 14 weeks after transplantation. Following gene therapy, mice were challenged with the CGD pathogen Burkholderia (formerly Pseudomonas) cepacia and bacteremia levels were assessed at 24 hours and 7 days after inoculation. At both time points, bacteremia levels in gene corrected p47phox-/- mice were significantly lower than untreated p47phox-/- mice (0.89 +/- 0.30 colonies v 237.7 +/- 83.6 colonies at 24 hours, P < .02; 4.0 +/- 2.0 colonies v 110.2 +/- 26.5 colonies at 7 days, P < .0014). More importantly, Kaplan-Meier survival analysis showed a significant survival advantage of gene corrected versus untreated p47phox-/- mice (P < .001). Thus, stem-cell-directed ex vivo gene therapy is capable of restoring phagocyte oxidant-dependent host-defense function in this mouse model of a human immune-system disorder.
 ...
PMID:Enhanced host defense after gene transfer in the murine p47phox-deficient model of chronic granulomatous disease. 911 68

The prognostic significance of neutropenic fever in lung cancer patients receiving chemotherapy with or without radiotherapy was investigated. Male patients and patients with squamous cell lung cancer had a higher incidence of febrile episodes than female patients and patients with other cell types, but the differences were not significant. Patients with a poor performance status had a significantly higher incidence of febrile episodes. An indwelling central venous catheter was an important risk factor for febrile episodes, indicating that bacteremia was one of the major causes of fever. The median survival time of the patients who developed febrile episodes during chemotherapy was significantly shorter than that of patients without fever (6.1 vs 12.0 months), whether or not cases of early death within 3 months were excluded (8.9 vs 13.1 months). The prevention of infectious complications during anticancer treatment by the use of rh G-CSF and the early initiation of antimicrobial chemotherapy, although the results are inconclusive, may be worthwhile.
 ...
PMID:Prognostic significance of febrile episodes in lung cancer patients receiving chemotherapy. 969 9

In this retrospective study, 23 recipients of peripheral blood progenitor cells (PBPC) were compared to 23 recipients of bone marrow (BM). The donors were 12 HLA-A-B-DR identical siblings and 11 HLA-A-B-DR identical unrelated donors in the PBPC and BM groups, respectively. Diagnoses in the PBPC group were CML seven, AML, nine, ALL three, lymphoma one, myeloma two and aspartylglucosaminuria (AGU) one. The median age was 40 (5-55) years. The BM group was matched for diagnosis, age, conditioning therapy, GVHD prophylaxis and G-CSF treatment after BMT. A higher number of MNC (P<0.001), CD34+ (P = 0.05), CD3+ (P<0.001) and CD56+ (P<0.001) cells in the graft, a reduced number of platelet transfusions (P = 0.03) and a significant hastening of neutrophil and platelet recovery were seen in the PBPC group compared to the BM group. In logistic regression analysis, the following factors were important for engraftment of ANC >0.5 x 10(9)/l: peripheral blood progenitor cell transplantation (PBPCT) (P = 0.003) and mononuclear cells (MNC) > or =2.5 x 10(8)/kg recipient in the graft (above median) (P = 0.009) in univariate analysis. For recovery of platelets >30 x 10(9)/l: PBPCT (P = 0.03) and HLA-identical sibling donors (P = 0.05) were significant in multivariate analysis. A trend towards a lower incidence of bacteremia was seen in the PBPC group, ie 22 vs 48% (P = 0.06) in the BM group. GVHD, TRM and survival did not differ between the two groups.
 ...
PMID:Faster neutrophil and platelet engraftment, but no differences in acute GVHD or survival, using peripheral blood stem cells from related and unrelated donors, compared to bone marrow. 970 19

Infectious complications after autologous peripheral blood progenitor cell transplantation (PBPCT) have been reported in a few studies including small patient numbers. The present study was performed to assess the incidence, types, outcome and factors affecting early and late infections in 150 patients aged 18 to 68 years (median 46.5) who underwent high-dose therapy, with G-CSF. Patients were kept in reverse isolation rooms and received antimicrobial chemoprophylaxis with oral quinolone and fluconazole. One hundred and fifteen patients (76.7%) developed fever (median 3 days, range 1-29); 20 patients (55.5%) had Gram-positive and 13 (36. 2%) Gram-negative bacterial infections. There were no fungal infections or infection-related deaths. Mucositis grade II-IV (P = 0. 0001; odds ratio 3.4) and >5 days on ANC <100/microl (P = 0.0001; odds ratio 2.3) correlated with development of infection. Only days with ANC <100/microl affected infection outcome (P = 0.0024) whereas the antibiotic regimen did not. After day +30 there were four cases of bacterial pneumonitis (2.7%), one case of fatal CMV pneumonia (0. 8%) and 20 of localized VZV infection (13.3%). Reduction of neutropenia duration with PBPCT and G-CSF is not enough to prevent early infectious complications since only a few days of severe neutropenia and mucositis are related to development of early infections. However, no infection-related deaths were seen. Although Gram-positive organisms were the major cause of bacteremia, a glycopeptide in the empirical antibiotic regimen did not affect infection outcome. In PBPCT recipients, early and late opportunistic infections were notably absent, which was at variance with what was seen with bone marrow recipients. Efforts should be made to prevent mucositis and neutropenia and identify new strategies of antibacterial prophylaxis.
 ...
PMID:Infectious complications after autologous peripheral blood progenitor cell transplantation followed by G-CSF. 1057 58

Organisms belonging to the Mycobacterium avium complex (MAC) cause life-threatening bacteremia in immunocompromised patients. Monocytes and macrophages are thought to be responsible for ingestion and killing of MAC. However, it has been suggested that neutrophils may play a role in the early immune response to MAC infection. Here, neutrophils in autologous plasma were incubated (at 0 and 37 degrees C) with M. avium labeled with Auramine O, a potent fluorochrome. Neutrophil phagocytosis was measured by flow cytometry. Neutrophils incubated at 37 degrees C showed an increase in fluorescence over time with a maximum at 15 min, whereas neutrophils on ice showed no time-dependent increase in FL1. At 15 min Fl 1 at 37 degrees C was twice as high as FL1 at 0 degrees C. Examination under the fluorescent microscope showed multiple intracellular fluorescent mycobacteria. Results in nine independent experiments showed time-dependent decrease of colony-forming units in neutrophil-associated live M. avium. Significant killing was observed within 30 min and was complete by 120 min. Observation by electron microscopy clearly confirmed the presence of intraphagosomal MAC, both intact and with evidence of degradation. These data demonstrate that MAC is rapidly phagocytized and killed by human neutrophils. The newly established flow cytometry method should be useful in further studies of neutrophil function and of the role of G-CSF and other cytokines in MAC disease.
 ...
PMID:Phagocytosis and killing of Mycobacterium avium complex by human neutrophils. 1126 86

At the workshop on infections after stem cell transplantation (SCT) in children, the following topics were introduced by invited speakers and discussed with the audience: empirical antimicrobial therapy in the pre-engraftment period, early diagnosis of fungal and viral infections and possibilities to treat them and the possible role of G-CSF early post-SCT. Episodes of fever in the pre-engraftment period mostly are unexplained, and in about one quarter due to bacteremia, mostly by Gram-positive cocci. No single drug or combination of drugs used for antimicrobial therapy is superior, neither does it cover 100% of the pathogens. Close microbiological surveillance of the patients and knowledge of the local microbial epidemiology are requested for optimal therapy. Early fungal infections are reactivations of pre-SCT infections, late fungal infections mostly are associated with failure of engraftment or GvHD and its treatment. Except for suggestive ultrasound or CT-scan abnormalities, the possibilities for early diagnosis are limited c.q. not reliable. Fluconazol prophylaxis is recommended to prevent Candida albicans invasion. A number of new antifungal drugs are being tested in phase I and II studies. CMV, EBV and adenoviruses may reactivate after SCT, causing severe disease with a high mortality, especially in non-HLA-identical donor-recipient combinations. Frequent surveillance cultures for CMV and adenoviruses, pp65-CMV antigen detection in WBC and PCR techniques for CMV, EBV and adenoviruses all have their own contribution to the early diagnosis of dissemination of the viral infection. Therapeutical possibilities, except with respect to ganciclovir and foscarnet for CMV infection, are still limited. The effectiveness of cidofovir is under study. Adoptive therapy with virus-specific CTL's probably represents the new frontier. G-CSF administration early after SCT has a beneficial effect on PMN recovery, hospitalization time, use of antibiotics and total parenteral nutrition requirement in children undergoing allogeneic and autologous BMT. No benefit is observed in children undergoing peripheral blood SCT. The routine use of G-CSF in the latter group of patients is not justified.
 ...
PMID:Infections after stem cell transplantation in children: state of the art and recommendations. 1157 29

Mice mounting an acute phase response, induced by sterile inflammation after a single s.c. injection of casein 24 h beforehand, were remarkably protected against lethal infection with Gram-positive or Gram-negative bacteria. This was associated with enhanced early clearance of bacteremia, greater phagocytosis and oxidative burst responses by neutrophils, and enhanced recruitment of neutrophils into tissues compared with control, nonacute phase mice. Casein-induced inflammation was also associated with increased concentrations of G-CSF in serum, and administration of neutralizing Ab to this cytokine completely abrogated protection against Escherichia coli infection after casein pretreatment. Injection of recombinant murine G-CSF between 3 and 24 h before infection conferred the same protection as casein injection. In contrast, the casein-induced acute phase response affected neither serum values of TNF-alpha, IL-1 beta, or IL-6 after E. coli infection nor susceptibility to LPS toxicity. Furthermore, protection against infection was unaffected in IL-1R knockout mice, which have deficient acute phase plasma protein responses, or after nonspecific inhibition of acute phase protein synthesis by D-galactosamine or specific depletion of complement C3 by cobra venom factor. Increased production of G-CSF in the acute phase response is thus a key physiological component of host defense, and pretreatment with G-CSF to prevent bacterial infection in at-risk patients now merits further study, especially in view of increasing bacterial resistance to antibiotics.
 ...
PMID:Production of granulocyte colony-stimulating factor in the nonspecific acute phase response enhances host resistance to bacterial infection. 1209 96

The authors overviewed 239 febrile neutropenia (FN) episodes in 82 pediatric leukemia cases treated with BFM treatment protocols. FN was observed mostly during consolidation therapy. Mucositis was the most identified focus; gram-negative microorganisms were the most identified pathogens. Five patients developed invasive fungal infections. Fever resolved after mean 5.3 days and mean antibiotic administration time was 12.7 days. Addition of G-CSF to antimicrobial therapy shortened the duration of neutropenia, but it did not affect duration of fever resolution and antibiotic administration. The duration of neutropenia, fever resolution, and antibiotic administration was significantly longer in children with acute myeloid leukemia. The authors conclude that children with acute leukemia have severe prolonged neutropenia and are in high risk. In these patients, prediction of the risk of bacteremia based on clinical and laboratory features is important for immediate empiric broad-spectrum antimicrobial therapy and for higher survival rate.
 ...
PMID:Assessment of febrile neutropenia episodes in children with acute leukemia treated with BFM protocols. 1843 2

Abstract Although it is documented that concurrent wounding increases mortality from radiation injury, the molecular mechanism of combined injury is unknown. In this study, mice were exposed to gamma radiation followed by skin wounding. Wound trauma exacerbated radiation-induced mortality, reducing the LD(50/30) from 9.65 Gy to 8.95 Gy. Analyses of histopathology, inducible nitric oxide synthase (iNOS), and serum cytokines were performed on mouse ileum and skin at various times after 9.75 Gy and/or wounding. In the ileum, the villi were significantly shortened 3 days postirradiation but not after wounding; combined injury resulted in decreased villus width and tunica muscularis thickness. The skin of mice subjected to combined injury was less cellular and had a smaller healing bud than the skin of mice subjected to wounding alone. Combined injury significantly delayed wound closure times; it also prolonged the increased levels of iNOS protein in the skin and ileum. iNOS up-regulation was correlated with increases in transcription factors, including NF-kappaB and NF-IL6. The increase in NF-IL6 may be due to increases in cytokines, including IL-1beta, -6, -8, -9, -10 and -13, G-CSF, eotaxin, INF-gamma, MCP-1, MIP-1alpha and MIP-1beta. Combined injury resulted in early detection of bacteria in the blood of the heart and liver, whereas radiation alone resulted in later detection of bacteria; only a transient bacteremia occurred after wounding alone. Results suggest that enhancement of iNOS, cytokines and bacterial infection triggered by combined injury may contribute to mortality. Agents that inhibit these responses may prove to be therapeutic for combined injury and may reduce related mortality.
 ...
PMID:Wound trauma increases radiation-induced mortality by activation of iNOS pathway and elevation of cytokine concentrations and bacterial infection. 2019 17


1 2 Next >>