799 research outputs found

    The effects of 5-fluorouracil and interferon-alpha on early healing of experimental intestinal anastomoses.

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    The continuing search for effective adjuvant therapy after resection of intestinal malignancies has prompted a growing interest in both immediate post-operative regional chemotherapy and the combination of 5-fluorouracil (5-FU) and interferon-alpha as drugs of choice. We have compared the effects of both compounds, alone and together, on early healing of intestinal anastomoses. Four groups (n = 26 each) of rats underwent resection and anastomosis of both ileum and colon: a control group and three groups receiving intraperitoneal 5-FU, interferon-alpha or both on the day of surgery and the next 2 days. Animals were killed 3 or 7 days (n = 10 each) after operation in order to measure anastomotic strength and hydroxyproline content. The remaining six animals in each group were used to study anastomotic collagen synthetic capacity at day 3. Three days after operation, ileal anastomotic bursting pressure was lowered by 37% in the 5-FU/interferon-alpha group (P = 0.0104). At day 7, anastomotic breaking strength was reduced significantly in ileum (P = 0.0221) and colon (P = 0.0054) of the 5-FU/interferon-alpha group and in colon of the interferon-alpha group (P = 0.0221). Collagen synthetic capacity was strongly suppressed by 5-FU but not by interferon-alpha. However, no differences in anastomotic hydroxyproline content were observed between groups at both days 3 and 7. Thus, post-operative use of interferon-alpha, in particular in combination with 5-FU, may be detrimental to anastomotic repair in the intestine

    Bewijsrechtelijke grenzen voor rapporten van de Onderzoeksraad voor veiligheid

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    Als er een ramp plaatsvindt, wil iedereen die zich er bij betrokken voelt, antwoord op de vraag hoe dat heeft kunnen gebeuren. Maar niet iedereen die dat wil weten heeft dezelfde motieven. Wil men een schuldige kunnen aanwijzen, of wil men voorkomen dat een dergelijke ramp zich zal herhalen? Wat de Onderzoeksraad voor veiligheid betreft is de opdracht duidelijk: de blik van de Onderzoeksraad is op de toekomst gericht. In een gerechtelijke procedure mogen (onder meer) ‘verklaringen van personen, afgelegd in het kader van het onderzoek van de raad’ dan ook niet als bewijs worden gebruikt. Het zou namelijk onwenselijk zijn als betrokkenen bevreesd zouden zijn openheid van zaken te geven uit vrees voor aansprakelijkstelling of vervolging. De betekenis van dit in artikel 69 Rijkswet Onderzoeksraad voor veiligheid neergelegde verbod blijkt, niettegenstaande de heldere ratio ervan, tamelijk gecompliceerd te zijn

    Engaging Preuniversity Students in Sustainability and Life Cycle Assessment in Upper-Secondary Chemistry Education: The Case of Polylactic Acid (PLA)

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    This article reports about a lesson series that focuses on engaging students in sustainability, plastics, and life cycle assessment (LCA). The purpose of the lesson series is to give students insights into sustainability in the context of plastics and to foster awareness of and insights into the benefits of the LCA method. The lesson series introduces students to sustainability by enabling them to watch a video, answer questions, read articles, conduct laboratory experiments, and experience the four stages of LCA. In general, the findings reveal that the lesson series evoked in students a more critical view of the life cycle of plastics. The students showed increasing awareness of the complexity of the sustainability issue at hand. In addition, students used their acquired knowledge about LCA and mentioned impact categories in their argumentation. The lesson series evoked predominantly life cycle thinking, and the qualitative part of an LCA, and might thus serve as a stepping stone toward the quantitative assessment. The preliminary results show that the lesson series is effective for evoking life cycle thinking among students and serves as a stepping stone towards life cycle assessment. Future research could focus on setting the goal and scope of the process to be assessed, with emphasis on the functional unit in the context of plastics, and providing students a complete and coherent understanding of the entire cycle of production, use and recycling of plastics

    Exploring the effect of glaucomatous visual field defects of current drivers on a neuropsychological test battery

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    Purpose This study explores the effect of glaucomatous visual field defects on several neuropsychological tests that are often used in research and in clinical settings.Methods Nineteen glaucoma patients and nineteen healthy participants, which are current drivers and older than 65 years old were included. All participants completed the Montreal Cognitive Assessment (MoCA), the Trail Making Test (TMT), the Benton Visual Retention Test (BVRT), the Snellgrove Maze Task (SMT) and the Digit Span Test (DST). All participants were also tested on contrast sensitivity and near and far visual acuity. For the glaucoma patients, visual field tests were downloaded from hospital servers.Results On the MoCA test, glaucoma patients scored lower than the healthy group, but not significantly. On the MoCA-Blind, the difference was statistically significant. Glaucoma patients also had lower percentile scores on the TMT, with a significant difference in the TMT-A, but this difference largely disappeared in the calculated TMT B-A index, which isolates the cognitive component. The BVRT and SMT showed no significant differences between both groups. In the only non-visual test, the DST, glaucoma patients outperformed the healthy group. Glaucoma severity did not influence results, except for the BVRT on which the moderate/severe group has better scores.Conclusion Using visual items might lead to conclusions about cognition when it should be one about vision. Therefore, careful selection of tests is needed when examining cognition in glaucoma patients.</p

    CLSM as Quantitative Method to Determine the Size of Drug Crystals in a Solid Dispersion

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    PURPOSE: To test whether confocal laser scanning microscopy (CLSM) can be used as an analytical tool to determine the drug crystal size in a powder mixture or a crystalline solid dispersion. METHODS: Crystals of the autofluorescent drug dipyridamole were incorporated in a matrix of crystalline mannitol by physical mixing or freeze-drying. Laser diffraction analysis and dissolution testing were used to validate the particle size that was found by CLSM. RESULTS: The particle size of the pure drug as determined by laser diffraction and CLSM were similar (D(50) of approximately 22 μm). CLSM showed that the dipyridamole crystals in the crystalline dispersion obtained by freeze-drying of less concentrated solutions were of sub-micron size (0.7 μm), whereas the crystals obtained by freeze-drying of more concentrated solutions were larger (1.3 μm). This trend in drug crystal size was in agreement with the dissolution behavior of the tablets prepared from these products. CONCLUSION: CLSM is a useful technique to determine the particle size in a powder mixture. Furthermore, CLSM can be used to determine the drug crystal size over a broad size distribution. A limitation of the method is that the drug should be autofluorescent

    Challenges while MOOCifying a HE eLearning course on Universal Accessibility

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    There are some similarities in developing a traditional Higher Education (HE) eLearning course and MOOCs (Massive Open Online Courses), due to the use of the basis of eLearning instructional design. But in MOOCs, students should be continually influenced by information, social interactions and experiences forcing the faculty to come up with new approaches and ideas to develop a really engaging course. In this paper, the process of MOOCifying an online course on Universal Accessibility is detailed. The needed quality model is based upon the one used for all online degree programs at our university and on a variable metric specially designed for UNED MOOC courses making possible to control how each course was structured, what kind of resources were used and how activities, interaction and assessment were included. The learning activities were completely adapted, along with the content itself and the on-line assessment. For this purpose, the Gardner's Multiple Intelligences Product Grid has been selected

    Identification of a methylation panel as an alternative triage to detect CIN3+ in hrHPV-positive self-samples from the population-based cervical cancer screening programme

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    Background: The Dutch population-based cervical cancer screening programme (PBS) consists of primary high-risk human papilloma virus (hrHPV) testing with cytology as triage test. In addition to cervical scraping by a general practitioner (GP), women are offered self-sampling to increase participation. Because cytological examination on self-sampled material is not feasible, collection of cervical samples from hrHPV-positive women by a GP is required. This study aims to design a methylation marker panel to detect CIN3 or worse (CIN3+) in hrHPV-positive self-samples from the Dutch PBS as an alternative triage test for cytology.Methods: Fifteen individual host DNA methylation markers with high sensitivity and specificity for CIN3+ were selected from literature and analysed using quantitative methylation-specific PCR (QMSP) on DNA from hrHPV-positive self-samples from 208 women with CIN2 or less (&lt; CIN2) and 96 women with CIN3+. Diagnostic performance was determined by area under the curve (AUC) of receiver operating characteristic (ROC) analysis. Self-samples were divided into a train and test set. Hierarchical clustering analysis to identify input methylation markers, followed by model-based recursive partitioning and robustness analysis to construct a predictive model, was applied to design the best marker panel.Results: QMSP analysis of the 15 individual methylation markers showed discriminative DNA methylation levels between &lt; CIN2 and CIN3+ for all markers (p &lt; 0.05). The diagnostic performance analysis for CIN3+ showed an AUC of ≥ 0.7 (p &lt; 0.001) for nine markers. Hierarchical clustering analysis resulted in seven clusters with methylation markers with similar methylation patterns (Spearman correlation&gt; 0.5). Decision tree modeling revealed the best and most robust panel to contain ANKRD18CP, LHX8 and EPB41L3 with an AUC of 0.83 in the training set and 0.84 in the test set. Sensitivity to detect CIN3+ was 82% in the training set and 84% in the test set, with a specificity of 74% and 71%, respectively. Furthermore, all cancer cases (n = 5) were identified.Conclusion: The combination of ANKRD18CP, LHX8 and EPB41L3 revealed good diagnostic performance in real-life self-sampled material. This panel shows clinical applicability to replace cytology in women using self-sampling in the Dutch PBS programme and avoids the extra GP visit after a hrHPV-positive self-sampling test.</p

    Exploring Large Document Repositories with RDF Technology: The DOPE Project

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    This thesaurus-based search system uses automatic indexing, RDF-based querying, and concept-based visualization of results to support exploration of large online document repositories

    Plasminogen Activator Inhibitor-Type I Gene Deficient Mice Show Reduced Influx of Neutrophils in Ventilator-Induced Lung Injury

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    Ventilator-induced lung injury (VILI) is associated with inhibition of the fibrinolytic system secondary to increased production of plasminogen activator inhibitor- (PAI-)1. To determine the role of PAI-1 on pulmonary coagulopathy and inflammation during mechanical ventilation, PAI-1 gene-deficient mice and their wild-type littermates were anesthetized (control), or anesthetized, tracheotomized and subsequently ventilated for 5 hours with either low tidal volumes (LVT) or high tidal volumes (HVT). VILI was assessed by pulmonary coagulopathy, lung wet-to-dry ratios, total protein level in bronchoalveolar lavage fluid, neutrophil influx, histopathology, and pulmonary and plasma cytokine levels. Ventilation resulted in pulmonary coagulopathy and inflammation, with more injury following ventilation with HVT as compared to LVT. In PAI-1 gene-deficient mice, the influx of neutrophils in the pulmonary compartment was attenuated, while increased levels of pulmonary cytokines were found. Other endpoints of VILI were not different between PAI-1 gene-deficient and wild-type mice. These data indicate that a defect fibrinolytic response attenuates recruitment of neutrophils in VILI
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