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  • 1
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  Mainz//2011; 56. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds), 6. Jahrestagung der Deutschen Gesellschaft für Epidemiologie (DGEpi); 20110926-20110929; Mainz; DOC11gmds157 /20110920/
    Publication Date: 2011-09-20
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 2
    Abstract: We investigated the dose-response of the external beam therapy 3 (EBT3) films for proton and carbon ion clinical beams, in comparison with conventional radiotherapy beams; we also measured the film response along the energy deposition-curve in water. We performed measurements at three hadrontherapy centres by delivering monoenergetic pencil beams (protons: 63-230 MeV; carbon ions: 115-400 MeV/u), at 0.4-20 Gy dose to water, in the plateau of the depth-dose curve. We also irradiated the films to clinical MV-photon and electron beams. We placed the EBT3 films in water along the whole depth-dose curve for 148.8 MeV protons and 398.9 MeV/u carbon ions, in comparison with measurements provided by a plane-parallel ionization chamber. For protons, the response of EBT3 in the plateau of the depth-dose curve is not different from that of photons, within experimental uncertainties. For carbon ions, we observed an energy dependent under-response of EBT3 film, from 16% to 29% with respect to photon beams. Moreover, we observed an under-response in the Bragg peak region of about 10% for 148.8 MeV protons and of about 42% for 398.9 MeV/u carbon ions. For proton and carbon ion clinical beams, an under-response occurs at the Bragg peak. For carbon ions, we also observed an under-response of the EBT3 in the plateau of the depth-dose curve. This effect is the highest at the lowest initial energy of the clinical beams, a phenomenon related to the corresponding higher LET in the film sensitive layer. This behavior should be properly modeled when using EBT3 films for accurate 3D dosimetry.
    Type of Publication: Journal article published
    PubMed ID: 27997377
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  • 3
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  62. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e.V. (GMDS); 20170917-20170921; Oldenburg; DOCAbstr. 290 /20170829/
    Publication Date: 2017-08-29
    Keywords: Epidemiologie ; ddc: 610
    Language: English
    Type: conferenceObject
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  • 4
    Publication Date: 2018-07-03
    Description: Purpose: PROTECT, a phase III, randomized, placebo-controlled study, evaluated pazopanib efficacy and safety in the adjuvant renal cell carcinoma setting. The relationship between pazopanib exposure (C trough ) and efficacy and safety was evaluated. Patients and Methods: Evaluable steady-state blood trough concentrations were collected from 311 patients at week 3 or 5 (early C trough ) and 250 patients at week 16 or 20 (late C trough ). Pazopanib pharmacokinetic (PK) data were analyzed via a population model approach. Relationship between C trough or dose intensity and disease-free survival (DFS) was explored via Kaplan–Meier and multivariate analysis. Adverse events (AE) and AE-related treatment discontinuation proportions were summarized by C trough quartiles. Results: Most (〉90%) patients with early or late C trough data started on 600 mg. Mean early and late C trough overlapped across dose levels. Patients with higher early C trough quartiles achieved longer DFS (adjusted HR, 0.58; 95% confidence interval, 0.42–0.82; P = 0.002). Patients achieving early or late C trough 〉20.5 μg/mL had significantly longer DFS: not estimable (NE) versus 29.5 months, P = 0.006, and NE versus 29.9 months, P = 0.008, respectively. Dose intensity up to week 8 did not correlate with DFS, consistent with population PK model–based simulations showing overlapping pazopanib exposure with 600 and 800 mg doses. The proportion of AE-related treatment discontinuation and grade 3/4 AEs, with the exception of hypertension, was not correlated to C trough . Conclusions: In the adjuvant setting, higher pazopanib C trough was associated with improved DFS and did not increase treatment discontinuations or grade 3/4 AEs, with the exception of hypertension. Clin Cancer Res; 24(13); 3005–13. ©2018 AACR . See related commentary by Rini, p. 2979
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 5
    Publication Date: 2018-08-16
    Description: Purpose: AZD1775 is a first-in-class Wee1 inhibitor with dual function as a DNA damage sensitizer and cytotoxic agent. A phase I study of AZD1775 for solid tumors suggested activity against brain tumors, but a preclinical study indicated minimal blood–brain barrier penetration in mice. To resolve this controversy, we examined the pharmacokinetics and pharmacodynamics of AZD1775 in patients with first-recurrence, glioblastoma. Patients and Methods: Twenty adult patients received a single dose of AZD1775 prior to tumor resection and enrolled in either a dose-escalation arm or a time-escalation arm. Sparse pharmacokinetic blood samples were collected, and contrast-enhancing tumor samples were collected intraoperatively. AZD1775 total and unbound concentrations were determined by a validated LC/MS-MS method. Population pharmacokinetic analysis was performed to characterize AZD1775 plasma pharmacokinetic profiles. Pharmacodynamic endpoints were compared to matched archival tissue. Results: The AZD1775 plasma concentration–time profile following a single oral dose in patients with glioblastoma was well-described by a one-compartment model. Glomerular filtration rate was identified as a significant covariate on AZD1775 apparent clearance. AZD1775 showed good brain tumor penetration, with a median unbound tumor-to-plasma concentration ratio of 3.2, and achieved potential pharmacologically active tumor concentrations. Wee1 pathway suppression was inferred by abrogation of G 2 arrest, intensified double-strand DNA breakage, and programmed cell death. No drug-related adverse events were associated with this study. Conclusions: In contrast to recent preclinical data, our phase 0 study of AZD 1775 in recurrent glioblastoma indicates good human brain tumor penetration, provides the first evidence of clinical biological activity in human glioblastoma, and confirms the utility of phase 0 trials as part of an accelerated paradigm for drug development in patients with glioma. Clin Cancer Res; 24(16); 3820–8. ©2018 AACR . See related commentary by Vogelbaum, p. 3790
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 6
    Publication Date: 2018-09-05
    Description: Purpose: This large two-part, three-arm phase I study examined the safety and tolerability of CC-486 (an oral formulation of azacitidine, a hypomethylating agent) alone or in combination with the cytotoxic agents, carboplatin or nab-paclitaxel, in patients with advanced unresectable solid tumors. Patients and Methods: Part 1 ( n = 57) was a dose escalation of CC-486 alone (arm C) or with carboplatin (arm A) or nab-paclitaxel (arm B). The primary endpoint was safety, MTD, and recommended part 2 dose (RP2D) of CC-486. In part 2 ( n = 112), the primary endpoint was the safety and tolerability of CC-486 administered at the RP2D for each treatment arm, in tumor-specific expansion cohorts. Secondary endpoints included pharmacokinetics, pharmacodynamics, and antitumor activity of CC-486. Results: At pharmacologically active doses CC-486 in combination with carboplatin or nab-paclitaxel had a tolerable safety profile and no drug–drug interactions. The CC-486 RP2D was determined as 300 mg (every day, days 1–14/21) in combination with carboplatin (arm A) or as monotherapy (arm C); and 200 mg in the same dosing regimen in combination with nab-paclitaxel (arm B). Albeit limited by the small sample size, CC-486 monotherapy resulted in partial responses (three/eight) and stable disease (four/eight) in patients with nasopharyngeal cancer. Three of the stable disease responses lasted more than 150 days. Conclusions: CC-486 is well tolerated alone or in combination with carboplatin or nab-paclitaxel. Exploratory analyses suggest clinical activity of CC-486 monotherapy in nasopharyngeal cancer and provided the basis for an ongoing phase II clinical trial (ClinicalTrials.gov identifier: NCT02269943). Clin Cancer Res; 24(17); 4072–80. ©2018 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Neurological sciences 13 (1992), S. 357-359 
    ISSN: 1590-3478
    Keywords: Acute intermittent porphyria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Sommario Viene riportato il caso di una paziente di 58 anni affetta da polineuropatia, disturbi vegetativi e dolori addominali. La diagnosi di porfiria acuta intermittente venne sospettata e la conferma scaturì dal riscontro di elevati livelli urinari di porfobilinogeno e di acido delta-aminolevulinico.
    Notes: Abstract We report the case of a 58-year-old woman affected by polyneuropathy, vegetative disturbances and abdominal pain. A provisional diagnosis of acute intermittent porphyria was made and was confirmed by the increased levels of urinary deltaaminolevulinic acid (ALA) and porphobilinogen (PBG).
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1588-2780
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract A physics-based approach to gamma-ray response-function generation is presented in which the response of CdZnTe detectors is modeled from first principles. Numerical modeling is used to generate response functions needed for spectrum analysis for general detector configurations (e.g., electrode design, detector materials and geometry, and operating conditions). With numerical modeling, requirements for calibration and characterization are significantly reduced. Elements of the physics-based model, including gamma-ray transport, charge carrier drift and diffusion, and circuit response, are presented. Calculated and experimental gamma-ray spectra are compared for a coplanar-grid CdZnTe detector.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1590-3478
    Keywords: Botulism ; SFEMG ; cardiovascular reflexes ; autonomic tests
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Sommario Un paziente affetto da botulismo è stato studiato a vari intervalli di tempo dall'intossicazione mediante tests di esplorazione vegetativa ed elettromiografia di singole fibre. Si è osservata nella prima fase della malattia una marcata compromissione del controllo della pressione arteriosa e della frequenza cardiaca, oltrechè una notevole anormalità funzionale della placca motrice. La ripresa della funzionalità vegetativa è apparsa più lenta di quella della trasmissione neuromuscolare. Il monitoraggio delle alterazioni vegetative nel botulismo può permettere di selezionare i pazienti a rischio per un improvviso arresto cardiaco o respiratorio.
    Notes: Abstract A patient with botulism was studied at different times after intoxication using various autonomic tests of the cardiovascular reflexes, and by single fiber EMG (SFEMG). The control of heart rate and blood pressure appeared markedly impaired in the early stage of the disease as well as SFEMG. Autonomic function recovered more slowly as neuromuscolar transmission. Monitoring autonomic derangement in botulism may give the opportunity to select patients at risk for cardiac or respiratory arrest.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1612-1112
    Keywords: Pyrolysis-gas chromatography-mass spectrometry ; Pyrolysis/methylation ; Painting layer ; Proteinaceous binder
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary Thirty standard painting layers were analysed by pyrolysis-gas chromatography/mass spectrometry (Py-GC-MS) and by Py-GC-MS in the presence of tetramethylammonium hydroxide (pyrolysis/methylation). Painting layers were prepared according to Renaissance recipes for tempera, employing proteinaceous binders (egg, glue and casein) and six different pigments. Thermal degradation products of proteins, carbohydrates and lipids were selected for semiquantitative analysis based on single/summed ion monitoring (SIM) mode. The relative distribution of these products was used to characterise binding media for the purpose of their identification in painting layers.
    Type of Medium: Electronic Resource
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