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11.
C Boudier G Godeau W Hornebeck L Robert J G Bieth 《American journal of respiratory cell and molecular biology》1991,4(6):497-503
To determine whether human neutrophil cathepsin G can act by itself or in concert with human neutrophil elastase to destroy elastic fibers in vivo, we used cryostat sections of human skin as an ex vivo substrate for these leukoproteinases. Specifically stained dermal elastic fibers were quantitated using an accurate and almost entirely automatic morphometric procedure that included computerized threshold selection and elimination of non-elastic dark elements. AA, the area fraction occupied by the dermal elastic fibers, was found to be 0.100 +/- 0.014 (mean +/- SD) for 21 control skin sections originating from a single donor. Measurement of the fiber diameters in these control sections (2.4 +/- 0.8 microns [mean +/- SD]) allowed calculation of the Weibel factor used to convert AA into Vv, the volume fraction occupied by the elastic fibers: Vv was 0.028 +/- 0.004 (mean +/- SD). Incubation of skin sections with elastase, cathepsin G, or mixtures of the two enzymes resulted in an important decrease in AA accompanied by a slight increase in the average fiber diameter. The largest increase (14%) was noticed for cathepsin G and was due to a preferential attack of thin fibers and to fiber fragmentation. The AA of fibers remaining after elastolytic activity of cathepsin G was 20 to 30% that of elastase in this ex vivo assay. On the other hand, cathepsin G stimulated the elastolytic activity of elastase. For instance, the activity of a mixture of 1.1 microM elastase and 1.5 microM cathepsin G was 1.9-fold higher than the sum of the activities of the individual proteinases. The stimulation increased with the cathepsin G concentration.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Pazart L Carpentier F Durocher A Mougeot C Najean Y Godeau P 《International journal of technology assessment in health care》1999,15(3):602-607
OBJECTIVE: To assess the impact of guidelines on drug use issued by a consensus conference on polycythemia vera held in Paris in June 1993. 32Phosphorus (32P) was recommended for patients over 70 and/or at risk, whereas pipobroman and hydroxyurea were recommended for patients under 70. METHODS: A questionnaire was sent to all 119 departments of nuclear medicine in France 1 year after the conference to find out whether and how often they measured plasma volume and red cell mass (the recommended diagnostic tests for polycythemia vera). Time-series analyses were performed on sales of 32P, pipobroman (both virtually exclusively prescribed for polycythemia), and hydroxyurea over a 4-year span (January 1992-December 1995). RESULTS: The average number of plasma volume determinations per year did not change significantly after the conference (22 +/- 26 before vs 21 +/- 25 after). 32P and pipobroman sales were stable until July 1993, when 32P sales decreased while pipobroman sales rose steadily. Hydroxyurea sales increased over the whole period with no change in trend after the guidelines were published. CONCLUSIONS: The guidelines apparently influenced clinical practice since sales of drugs that are specifically used to treat polycythemia vera showed clear changes in trend after publication of the guidelines. This type of study seems to be an effective way of assessing the impact of consensus conferences. 相似文献
14.
Vincristine efficacy and safety in treating immune thrombocytopenia: a retrospective study of 35 patients
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Jérôme Stirnemann Najett Kaddouri Medhi Khellaf Anne‐Sophie Morin Virginie Prendki Marc Michel Arsène Mekinian Philippe Bierling Pierre Fenaux Bertrand Godeau Olivier Fain 《European journal of haematology》2016,96(3):269-275
Although vincristine (VCR) is sometimes prescribed for newly diagnosed immune thrombocytopenia (ITP), its efficacy in refractory ITP and sustained efficacy has yet to be demonstrated. We describe our clinical experience and recommend vincristine's correct place in ITP management. This retrospective study analysed data from 35 patients with newly diagnosed (ND), persistent (P) or chronic (C) ITP treated with VCR. The initial response rate, defined as >30 × 109 platelets/L, reached 86% after a median of 7 [interquartile range (IQR) 6–13] days. In ND and P ITP, even when previous therapies were inefficient, initial response was 87.5%, suggesting that this treatment could be used particularly in rescue. Median survival time, without failure or relapse, was 15 months (Kaplan–Meier curve). Predictive factors (univariate analysis) of an initial and long‐term response were a small number of prior treatments received. However, at 2 yr, only seven patients had sustained response. Eight (23%) patients experienced adverse events: neuropathy for seven and bowel obstruction for one. Vincristine efficacy in ITP was confirmed, and it could be a good strategy for treating resistant ITP, especially in emergencies. In this era of new therapeutics, VCR deserves to remain on the list of ITP treatments because of its initial efficacy, safety and low cost. 相似文献
15.
Frank?K.?Brown Farida?Kopti Charlie??Chang Scott?A.?Johnson Meir?Glick Chris?L.?Waller 《The AAPS journal》2017,19(5):1255-1263
Merck & Co., Inc., Kenilworth, NJ, USA, is undergoing a transformation in the way that it prosecutes R&D programs. Through the adoption of a “model-driven” culture, enhanced R&D productivity is anticipated, both in the form of decreased attrition at each stage of the process and by providing a rational framework for understanding and learning from the data generated along the way. This new approach focuses on the concept of a “Design Cycle” that makes use of all the data possible, internally and externally, to drive decision-making. These data can take the form of bioactivity, 3D structures, genomics, pathway, PK/PD, safety data, etc. Synthesis of high-quality data into models utilizing both well-established and cutting-edge methods has been shown to yield high confidence predictions to prioritize decision-making and efficiently reposition resources within R&D. The goal is to design an adaptive research operating plan that uses both modeled data and experiments, rather than just testing, to drive project decision-making. To support this emerging culture, an ambitious information management (IT) program has been initiated to implement a harmonized platform to facilitate the construction of cross-domain workflows to enable data-driven decision-making and the construction and validation of predictive models. These goals are achieved through depositing model-ready data, agile persona-driven access to data, a unified cross-domain predictive model lifecycle management platform, and support for flexible scientist-developed workflows that simplify data manipulation and consume model services. The end-to-end nature of the platform, in turn, not only supports but also drives the culture change by enabling scientists to apply predictive sciences throughout their work and over the lifetime of a project. This shift in mindset for both scientists and IT was driven by an early impactful demonstration of the potential benefits of the platform, in which expert-level early discovery predictive models were made available from familiar desktop tools, such as ChemDraw. This was built using a workflow-driven service-oriented architecture (SOA) on top of the rigorous registration of all underlying model entities. 相似文献
16.
M. Hussein Gasem Helmia Farida Ahmed Ahmed Juli?te A. Severin Agus Suryanto Bambang Isbandrio Henri A. Verbrugh Rudy A. Hartskeerl Peterhans J. van den Broek 《Journal of clinical microbiology》2016,54(1):197-199
We report four Indonesian cases meeting the clinical and radiological criteria for community-acquired pneumonia and other findings suggestive of leptospirosis. Quantitative PCR (qPCR) analyses of serum and urine samples and serology confirmed the diagnosis of leptospirosis in each. Results of qPCR analysis of throat swabs were concordant with those obtained with acute-phase serum samples, which suggests its potential for use as a noninvasive diagnostic tool for leptospirosis. 相似文献
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18.
D u Le Thi Huong B Wechsler J Cabane S Herson P Godeau G Chomette 《Annales de médecine interne》1984,135(3):181-188
Splenic involvement is a classical complication of infective endocarditis (IE). Clinical manifestations are rare, 5 out of 100 IE: unexpected rupture (1 case), abscess causing reinfection (2 cases), pseudo-tumour (1 case) and terminal infarction (1 case). In addition to a review of the literature, a post mortem histological study of the spleen of 78 cases of IE was undertaken. Splenic involvement did not seem to be the direct cause of death. Three types of lesions which may or may not be associated were observed: congestive inflammatory lesions, infarction (48 p. 100), abscess (6 p. 100). Splenic infarction usually results in scarring but may progress to abscess formation. Rupture was not observed in this autopsy series. Although splenic involvement is common at post mortem it gives rise to few symptoms. Persistant pyrexia and the appearance of local signs should lead to investigation of splenic complications and eventually, to surgical ablation. 相似文献
19.
Christine T. Kovner Maja Djukic Jin Jun Jason Fletcher Farida K. Fatehi Carol S. Brewer 《Nursing outlook》2018,66(2):160-167
Background
The Institute of Medicine (IOM) report, The Future of Nursing, included recommendations to increase nurse diversity, the percent of nurses obtaining a bachelor’s degree, and inter-professional education.Purpose
The purpose of this paper is to report the progress toward achievement of these recommendations.Methods
We used a longitudinal, multi-state data from four cohorts of nurses newly licensed in 2004 to 2005, 2007 to 2008, 2010 to 2011, and 2014 to 2015 to examine and compare the trends.Finding
The percentage of males who became licensed increased, from 8.8% in 2004 to 2005 cohort to 13.6% in the 2014 to 2015 cohort. The percentage of white-non-Hispanic nurses who were licensed decreased from 78.9% in 2007 to 2008 to 73.8% in 2014 to 2015. These differences primarily reflect an increase in white-Hispanic nurses. More nurses are obtaining a bachelor’s degree as their first professional degree, from 36.6% in 2004 to 2005 cohort to 48.5% in 2014 to 2015 cohort. About 40% of the 2014 to 2015 cohort reported that they learned to work in inter-professional teams. Collegial nurse-physician relations had an upward positive trajectory over time increasing almost 7%.Discussion
The diversity and education of new nurses have increased, but are short of meeting the IOM recommendations. 相似文献20.