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Pilot study of an HLA-A2 peptide vaccine using flt3 ligand as a systemic vaccine adjuvant 总被引:5,自引:0,他引:5
McNeel DG Knutson KL Schiffman K Davis DR Caron D Disis ML 《Journal of clinical immunology》2003,23(1):62-72
A pilot vaccine study was conducted to test the safety and immunological efficacy of four monthly immunizations of an MHC class I peptide vaccine, the E75 HLA-A2 epitope from HER-2/neu, using flt3 ligand as a systemic vaccine adjuvant. Twenty HLA-A2-expressing subjects with advanced stage prostate cancer were randomly assigned to one of four immunization or treatment schedules: (a) Flt3 ligand (20 g/kg per day) administered subcutaneously daily for 14 days on a 28-day cycle, monthly for four months; (b) flt3 ligand course as above with the E75 peptide vaccine administered on day 7 of each flt3 ligand cycle; (c) flt3 ligand course as above with the E75 peptide vaccine administered on day 14 of each flt3 ligand cycle; or (d) E75 peptide admixed with granulocyte–macrophage colony-stimulating factor and administered intradermally once every 28 days, as has previously been reported. The primary endpoints of the study were the determination of safety and immunological efficacy in generating E75-specific T cells as determined by peptide-specific interferon-gamma ELIspot. Adverse events included one grade 3 skin reaction and the development of grade 2 autoimmune hypothyroidism in two subjects with preexisting subclinical autoimmune hypothyroidism. Dendritic cells were markedly increased in the peripheral blood of subjects receiving flt3 ligand with each repetitive cycle, but augmentation of antigen-presenting cells within the dermis was not observed. Apart from a single subject, no significant peptide-specific T-cell responses were detected by ELIspot, whereas delayed-type hypersensitivity responses were detectable in control subjects and in subjects receiving peptide vaccine early in the course of flt3 ligand administration. The absence of robust peripheral immune responses in the current study may be attributable to the small numbers of subjects or differences in the subject population. In addition, the inability of flt3 ligand to augment the number of peripheral skin antigen-presenting cells may have contributed to the absence of robust peptide-specific immunity detectable in the peripheral blood of immunized subjects treated with flt3 ligand. 相似文献
3.
Dania Genobile Joanna Gaston Graham F Tallis Joy E Gregory Julia M Griffith Mary Valcanis Diane Lightfoot John A Marshall 《Communicable diseases intelligence》2004,28(2):225-229
Outbreaks of shigellosis in child care are not commonly reported in Australia, however Shigella bacteria can easily spread in these settings. We report an outbreak of shigellosis in a child care centre and discuss the control measures implemented. This investigation identified 20 confirmed cases of Shigella sonnei biotype g and a further 47 probable cases in children and staff who attended a child care centre, and their household contacts. The investigation highlighted the importance of stringent control measures and protocols for dealing with outbreaks of Shigella and other enteric infections in the child care setting, and the importance of prompt notification by both doctors and child care centres, of suspected outbreaks. 相似文献
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Lin Z. Li Stephen Kadlececk He N. Xu Dania Daye Benjamin Pullinger Harrilla Profka Lewis Chodosh Rahim Rizi 《NMR in biomedicine》2013,26(10):1308-1320
Conventional methods for the analysis of in vivo hyperpolarized 13C NMR data from the lactate dehydrogenase (LDH) reaction usually make assumptions on the stability of rate constants and/or the validity of the two‐site exchange model. In this study, we developed a framework to test the validity of the assumption of stable reaction rate constants and the two‐site exchange model in vivo via ratiometric fitting of the time courses of the signal ratio L(t)/P(t). Our analysis provided evidence that the LDH enzymatic kinetics observed by hyperpolarized NMR are in near‐equilibrium and satisfy the two‐site exchange model for only a specific time window. In addition, we quantified both the forward and reverse exchange rate constants of the LDH reaction for the transgenic and mouse xenograft models of breast cancer using the ratio fitting method developed, which includes only two modeling parameters and is less sensitive to the influence of instrument settings/protocols, such as flip angles, degree of polarization and tracer dosage. We further compared the ratio fitting method with a conventional two‐site exchange modeling method, i.e. the differential equation fitting method, using both the experimental and simulated hyperpolarized NMR data. The ratio fitting method appeared to fit better than the differential equation fitting method for the reverse rate constant on the mouse tumor data, with less relative errors on average, whereas the differential equation fitting method also resulted in a negative reverse rate constant for one tumor. The simulation results indicated that the accuracy of both methods depends on the width of the transport function, noise level and rate constant ratio; one method may be more accurate than the other based on the experimental/biological conditions aforementioned. We were able to categorize our tumor models into specific conditions of the computer simulation and to estimate the errors of rate quantification. We also discussed possible approaches to the development of more accurate rate quantification methods for hyperpolarized NMR. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
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Rima Moghnieh Dania Abdallah Lyn Awad Tamima Jisr Anas Mugharbil Ali Youssef Hani Tamim Samer Khaldieh Oula Massri Najat Rashini Youssef Hamdan Ahmad Ibrahim 《Infection》2018,46(6):823-835
Purpose
In this study, we assessed the incidence, contributing factors and outcome of prolonged neutropenia above 7 days and of bacteraemia in patients with lymphoma and multiple myeloma who underwent autologous haematopoietic stem cell transplantation (AHSCT) without antibacterial prophylaxis.Methods
This is a retrospective chart review of 190 adult patients who underwent AHSCT between 2005 and 2015 at a Lebanese hospital.Results
Neutropenia of 7 days duration and longer was documented in 66% of the patient population. Through univariate analysis, patients with lymphoma were significantly more likely to have prolonged neutropenia (≥?7 days) compared to those with myeloma. Mucositis above grade 3, diarrhoea and fever were more likely to occur in patients with prolonged neutropenia. Bacteraemia was documented in 12.6% of the patients. Total mortality rate was 3.7%, and that attributed to bacteraemia was 12.5% in the bacteraemia subgroup. Among bacterial isolates recovered from clinical specimens (89 isolates), 70% were Gram-negative, of which 57% were fluoroquinolone susceptible. Ninety-five percent of the Gram-negative bacteria causing bacteraemia were susceptible to fluoroquinolones.Conclusion
Bacterial pathogens causing bacteraemia were still highly susceptible to fluoroquinolones, despite the high prevalence of fluoroquinolone-resistant strains in the general bacterial ecology. Accordingly, the pertinence of fluoroquinolone prophylaxis in the AHSCT setting warrants further investigation. Moreover, continuous surveillance of local antibiograms in this patient population has become a must in an era of preponderant antibiotic resistance.7.
PPARgamma inhibits GH synthesis and secretion and increases apoptosis of pituitary GH-secreting adenomas 总被引:4,自引:0,他引:4
8.
Andreea-Iuliana Ceanga Mihai Ceanga Maria Eveslage Edwin Herrmann Dania Fischer Axel Haferkamp Maria Wittmann Stefan Müller Hugo Van Aken Andrea Ulrike Steinbicker 《Transfusion and apheresis science》2018,57(6):739-745
Background
Preoperative anemia and allogeneic blood transfusions (ABTs) may affect outcomes in cancer surgery. The prevalence of anemia, the use of ABTs, the risks of transfusions, lengths of stay and mortality of oncological patients undergoing radical cystectomy were investigated in three University Hospitals in Germany.Patients and Methods
Hospital records of 220 consecutive patients undergoing radical cystectomy from 2010 to 2012 were retrospectively analyzed for independent risk factors of ABT and unfavorable outcomes (readmission, increased length of stay (LOS) or death) using multivariate regression analysis.Results
Preoperative anemia was present in 40%. 70% of patients received blood transfusions. Low preoperative and intraoperative nadir hemoglobin levels were associated with receipt of ABT (OR 1.33, P?=?0.04 and OR 2.94, P?<?0.001 respectively). Transfusion of ten or more red blood cell units (RBCs) during the entire hospital stay was a predictor of an increased LOS (P?<?0.001) and death (OR 52, 95%CI [5.9, 461.3], P?<?0.001), compared to non-transfused patients. Preoperative ABT and ASA scores were associated with ≥10RBCs.Conclusion
Anemic patients undergoing radical cystectomy had a high risk to receive ABTs. Preoperative transfusions and transfusion of ≥10RBCs during the entire hospital stay may increase patient`s mortality.Prospective, randomized controlled studies have to follow this study. 相似文献9.
Giancarlo Cicolini Carlo Della Pelle Valentina Simonetti Dania Comparcini Gianna Sepede Francesco Cipollone 《Archives of Psychiatric Nursing》2018,32(2):305-309
Purpose
To investigate the role of psychiatric dimensions, behavioral or substance addictions and demographical variables as determinants of pathological gambling among nursing students.Design
Multicenter cross-sectional study.Methods
From June to October 2015 a survey was carried out among Italian Nursing students. Data were collected using a six-section tool.Findings
Nursing students who completed the survey numbered 1083, 902 (83.3%) had some problems with gambling and 29 (2.7%) showed pathological gambling. Percentage of pathological gambling was significantly associate with illicit drug/alcohol use (65.5%; p = 0.001) and with male gender (58.6%) comparing to student nurse with non-pathological gambling (20%) and those with some problem (24.2%). Significant main effect was observed for IAT score (Beta = 0.119, t = 3.28, p = 0.001): higher IAT scores were associated with higher SOGS scores.Conclusions
Italian nursing students have some problems with gambling and pathological gambling problem, and males are those who have more problems. Results might be useful for faculties of health professionals to identify students at risk in an early stage, to direct prevention tailored interventions.Clinical relevance
Nursing faculties should be aware of the prevalence of Gambling among students.Prevention interventions should be planned to minimize the risk of gambling behavior in the future nurses' health care workers. 相似文献10.