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  • 1
    Electronic Resource
    Electronic Resource
    Maximum tolerable doses of intravenous zidovudine in combination with 5-fluorouracil and leucovorin in metastatic colorectal cancer patients (1997)
    Springer
    Annals of oncology 8 (1997), S. 539-545 
    Details
    ISSN: 1569-8041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Experimental studies have demonstrated that 5-fluorouracil(5-FU) enhances zidovudine (AZT)-induced DNA strand breaks and cytotoxicity.Phase I studies have demonstrated that the maximum tolerable dose (MTD) of AZTis 8000 mg/sqm when administered i.v. over two hours after weekly 5-FU +l-leucovorin (LV), and that this combination has promising antitumor activity.The purpose of this study was therefore to evaluate the antitumor activity ofweekly bolus 5-FU + LV + AZT, administered at its MTD, and to determinewhether 5-FU enhances AZT-induced DNA strand breaks in blood nuclear cells. Patients and methods: Twenty-nine chemotherapy-naïve metastaticcolorectalcancer patients with measurable disease entered the study to evaluate theactivity of a weekly 5-FU 500 mg/m2 i.v. bolus + LV 250mg/m2 i.v. two-hour infusion + AZT 8000mg/m2 i.v. two-hour infusion. In 10 different patients, whoduring three different weeks received 5-FU + LV, AZT and 5-FU + LV + AZT, DNAstrand breaks in blood nuclear cells were determined by a fluorescent analysisof DNA unwinding. Results: Treatment was generally well tolerated and WHO grades III–IVtoxicities, consisting mostly of diarrhea (17%), were uncommon. Onepatient died of severe diarrhea with consequent hypokalemia and cardiacarrhythmia. All patients were considered evaluable for response, and 3(10%) complete and 10 (35%) partial responses were observed, foran objective response rate of 45% (95% confidence limit interval26%–64%). Both 5-FU + LV and AZT decreased the percentageof double stranded DNA in nuclear blood cells. The greatest effect wasobserved with 5-FU + LV + AZT, which reduced the percentage of double strandedDNA to 50% and 36% after 24 and 48 hours, respectively, and thisinteraction between 5-FU + LV and AZT was found to be cumulative. Conclusions: These studies demonstrate that the present dose and scheduleof AZT in combination with 5-FU + LV has significant activity in metastaticcolorectal cancer and that the combination of 5-FU + LV with AZT increases theamount of DNA damage. Therefore, AZT in combination with 5-FU + LV warrantsfurther study in colorectal cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008249803523
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    A waterborne tularemia outbreak (1987)
    Springer
    European journal of epidemiology 3 (1987), S. 35-38 
    Details
    ISSN: 1573-7284
    Keywords: Tularemia ; Epidemiology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A waterborne tularemia outbreak is described. Forty nine cases were identified in Sansepolcro, a small Medioeval town in the province of Arezzo, Tuscany, Italy. All cases had laterocervical or sub-mandibular adenitis, and occurred within a period of three weeks during March and April 1982. The study showed association between cases and the consumption of water from an unchlorinated water system. Francisella tularensis type 1 was isolated from wild hares captured in the area.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00145070
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  • 3
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    Jovian bow shock and magnetopause encounters by the Juno spacecraft (2017)
    Wiley-Blackwell
    Details
    Publication Date: 2017-05-26
    Description: The Juno spacecraft has crossed Jupiter's bow shock (BS) and magnetopause (MP) multiple times in the dawn sector (near 0600 local time), both during the approach to Jupiter and during the first three apojove periods. A survey of all of these crossings using the Juno field and particle instruments has been performed, with 51 bow shock and 97 magnetopause crossings being detected. The BS crossings ranged from 92 to 128 R J with 1 encounter during the approach, 36 during the first apojove period, 0 on the second, and 14 during the third. The MP crossings ranged from 73 to 114 R J , with 8 MP encounters during the approach, 40 encounters during the first apojove period, 24 encounters on the second, and 46 during the third. During the approach, Juno initially encountered an expanding magnetosphere resulting in a single BS and MP crossing, followed a few days later by a contracting magnetosphere, resulting in 7 more MP crossings and a BS crossing on the first outbound orbit at 92 R J . The lack of BS crossings and the limited number of MP crossings during the second apojove period suggests a long period of an expanded magnetosphere, likely caused by a prolonged period of low solar wind dynamic pressure associated with a rarefaction region. The detection of BS crossings on the third apojove period suggests another period of a highly compressed magnetosphere.
    Print ISSN: 0094-8276
    Electronic ISSN: 1944-8007
    Topics: Geosciences , Physics
    Published by Wiley-Blackwell on behalf of American Geophysical Union (AGU).
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  • 4
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    A comprehensive suite of suprathermal ion sensors (2016)
    Wiley-Blackwell
    Details
    Publication Date: 2016-12-13
    Description: Ions with energies from a few times the solar wind plasma thermal energy up to 100 s of keV/e are called suprathermal (ST) ions. ST ions are ubiquitous throughout the heliosphere and comprise material from many sources that vary in time and space. ST ions constitute a key source of material for solar energetic particles and other higher energy interplanetary particle populations. Measuring the energy spectra and composition (ionic charge and elemental) of ST ions in the heliosphere has proved to be rather difficult. This is because their energy region lies between that sampled by solar wind instruments, which require long integration times to acquire adequate statistics at these energies, and that by the energetic particle instruments, which typically do not extend down into the lower part of the ST regime due to the low-energy thresholds (~25-50 keV) of solid-state detectors. We present two novel concepts that, when combined, measure ST ions with high time, mass, and charge state resolution to address these challenges. Both use electrostatic analyzers (ESAs) that essentially serve as spectrographs. They simultaneously select ions over a broad range of energy-per-charge (E/q), thus requiring fewer voltage steps to cover the entire energy range. Their sensitivity is large compared to current instruments because each E/q is sampled for a longer period of time while the geometric factor is comparable. We describe the results obtained with laboratory prototypes. We also present a list of potential options for the detector section.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley-Blackwell on behalf of American Geophysical Union (AGU).
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  • 5
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    Diamond-graphite pixel array for particles detection (2013)
    Institute of Physics Publishing (IOP)
    Details
    Publication Date: 2013-10-26
    Description: The response of graphite-diamond pixel detectors to 90 Sr β-particles is reported. Laser induced graphitization was used to realize 200 μm × 200 μm square conductive graphite pads on one detector side whereas a large area graphite contact was realized on the other face for biasing. A board with nine hybrid charge sensitive pre-amplifier channels was used to test homogeneity of response of nine pixels at a time. In the dark the current is Ohmic up to 100 V where the current increases with a power law. While the bulk pixel resistance is 2.5 × 10 12 Ω, the resistance between adjacent pixels depends on voltage following a power law. Under irradiation a resolved β-spectrum well separated from the noise contribution was observed on each pixel. The most probable value of the collected charge distribution is voltage dependent and saturates around ±300 V (0.6 V/μm) with a value of 0.70±0.05 fC (4300±300 equivalent electrons charge).
    Electronic ISSN: 1748-0221
    Topics: Physics
    Published by Institute of Physics Publishing (IOP)
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  • 6
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    FOLFOXIRI or FOLFOXIRI plus bevacizumab as first-line treatment of metastatic colorectal cancer: a propensity score-adjusted analysis from two randomized clinical trials (2016)
    Oxford University Press
    Details
    Publication Date: 2016-04-26
    Description: Background FOLFOXIRI plus bevacizumab is a valid option as upfront treatment for metastatic colorectal cancer (mCRC) patients. While several trials investigated the effect of combining bevacizumab with different chemotherapy regimens, including fluoropyrimidines monotherapy and oxaliplatin- or irinotecan-containing doublets, no randomized comparison assessing the impact of the addition of bevacizumab to FOLFOXIRI is available. Patients and methods A total of 122 mCRC patients received first-line FOLFOXIRI in the phase III trial by the GONO (FOLFOXIRI group) and 252 patients received first-line FOLFOXIRI plus bevacizumab in the TRIBE trial (FOLFOXIRI plus bevacizumab group). A propensity score-adjusted method was adopted to provide an estimation of the benefit from the addition of bevacizumab to FOLFOXIRI in terms of survival and activity parameters. Results Patients in the FOLFOXIRI group had more frequently Eastern Cooperative Oncology Group performance status of one or two, high Köhne score, metachronous and liver-limited disease, had previously received adjuvant treatments and had their primary tumors resected. The median progression-free survival (PFS) was 12.3 months in the FOLFOXIRI plus bevacizumab group compared with 10.0 months in the FOLFOXIRI group {propensity score-adjusted hazard ratio (HR) 0.74 [95% confidence interval (CI) 0.59–0.94], P = 0.013}. This association was significant also in the multivariable model ( P = 0.024). The median OS was 29.8 months in the FOLFOXIRI plus bevacizumab group compared with 23.6 months in the FOLFOXIRI group [propensity score-adjusted HR: 0.72 (95% CI 0.56–0.93), P = 0.014]. At the multivariable model, the addition of bevacizumab was still associated with significantly longer OS ( P = 0.030). No significant differences in RECIST response rate (RR) [65.1% versus 55.7%; propensity score-adjusted odds ratio (OR): 1.29 (95% CI 0.81–2.05), P = 0.280], early RR [62.7% versus 57.8%; OR: 1.14 (95% CI 0.68–1.93), P = 0.619] and median depth of response (42.2% versus 53.8%, P = 0.259) were reported. Conclusions Though in the absence of a randomized comparison, the addition of bevacizumab to FOLFOXIRI provides significant benefit in PFS and OS, thus supporting the use of FOLFOXIRI plus bevacizumab as upfront treatment for mCRC patients. Trials’ numbers NCT01219920 and NCT00719797
    Print ISSN: 0923-7534
    Electronic ISSN: 1569-8041
    Topics: Medicine
    Published by Oxford University Press
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  • 7
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    Continuation or reintroduction of bevacizumab beyond progression to first-line therapy in metastatic colorectal cancer: final results of the randomized BEBYP trial (2015)
    Oxford University Press
    Details
    Publication Date: 2015-03-27
    Description: Background The combination of bevacizumab with fluorouracil-based chemotherapy is a standard first-line treatment option in metastatic colorectal cancer (mCRC). We studied the efficacy of continuing or reintroducing bevacizumab in combination with second-line chemotherapy after progression to bevacizumab-based first-line therapy. Patients and methods In this phase III study, patients with mCRC treated with fluoropyrimidine-based first-line chemotherapy plus bevacizumab were randomized to receive in second-line mFOLFOX-6 or FOLFIRI (depending on first-line regimen) with or without bevacizumab. The primary end point was progression-free survival. To detect a hazard ratio (HR) for progression of 0.70 with an α and β error of 0.05 and 0.20, respectively, 262 patients were required. Results In consideration of the results of the ML18147 trial, the study was prematurely stopped. Between April 2008 and May 2012, a total of 185 patients were randomized. Bevacizumab-free interval was longer than 3 months in 43% of patients in chemotherapy alone arm and in 50% of patients in the bevacizumab arm. At a median follow-up of 45.3 months, the median progression-free survival was 5.0 months in the chemotherapy group and 6.8 months in the bevacizumab group [adjusted HR = 0.70; 95% confidence interval (CI) 0.52–0.95; stratified log-rank P = 0.010]. Subgroup analyses showed a consistent benefit in all subgroups analyzed and in particular in patients who had continued or reintroduced bevacizumab. An improved overall survival was also observed in the bevacizumab arm (adjusted HR = 0.77; 95% CI 0.56–1.06; stratified log-rank P = 0.043). Responses (RECIST 1.0) were similar in the chemotherapy and bevacizumab groups (17% and 21%; P = 0.573). Toxicity profile was consistent with previously reported data. Conclusions This study demonstrates that the continuation or the reintroduction of bevacizumab with second-line chemotherapy beyond first progression improves the outcome and supports the use of this strategy in the treatment of mCRC. Clinical Trials.gov number NCT00720512.
    Print ISSN: 0923-7534
    Electronic ISSN: 1569-8041
    Topics: Medicine
    Published by Oxford University Press
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