1,721,048 research outputs found

    Systemic Absorption and Pharmacokinetics of Single-dose Intravesical Gemcitabine After Transurethral Resection of the Bladder in Non-muscle-invasive Bladder Cancer

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    OBJECTIVES To evaluate the systemic quantitative absorption, pharmacokinetics, and toxicities of gemcitabine administered intravesically at the recommended, high-concentration dose of 40 mg/mL, immediately after transurethral resection. METHODS For a single intravesical instillation of gemcitabine after resection, 15 consecutive patients with recurrent, low-, or intermediate-risk non-muscle-invasive bladder cancer candidates were selected. The extent of resection was defined as "small" if 6 excursions were needed to eliminate lesions. Eight and 7 patients, underwent a small and a large resection, respectively. Immediately after surgery 2000 mg of gemcitabine in 50 mL saline was instilled and held in the bladder for I hour. Pharmacokinetics of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine were determined in plasma by high-performance liquid chromatography. Local and systemic toxicity were assessed. RESULTS The highest mean gemcitabine concentrations were 1.38 mu g/mL in small and 2.47 mu g/mL in large resections. The difference was largest at 15 minutes after instillation (1.10 vs 2.47 mu g/mL, P = .001). A significant difference was found between time and type of resection for gemcitabine plasma levels (P = .02) but not for 2',2'-difluorodeoxyuridine. Toxicity never exceeded grade 2. At a mean follow-up of 2 years, 9 patients (60%) were found to be recurrence-free. CONCLUSIONS The systemic absorption of a single postoperative intravesical instillation of high concentration gemicitabine is proportional to the extent of resection; peak plasma concentrations reached at 15 minutes are below the levels of intravenous administration

    Exemestane for Breast Cancer Prevention: A Critical Shift?

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    The Mammary Prevention 3 (MAP.3) placebo-controlled randomized trial in 4,560 high-risk postmenopausal women showed a 65% reduction in invasive breast cancer with the use of exemestane at 35 months median follow-up. Few differences in adverse events were observed between the arms, suggesting a promising risk: benefit balance with exemestane for use in chemoprevention. Yet, the MAP. 3 design and implementation raise concerns regarding limited data maturity and not prospectively including key bone-related and other toxicities as study end points. Exemestane for prevention is juxtaposed against selective estrogen receptor modulators and the other aromatase inhibitors. Additional issues for prevention, including the influence of obesity, alternative dosing, and biomarker use in phase III trials, are addressed. Significance: The recently completed MAP. 3 trial of exemestane for breast cancer prevention offers a potential new standard for pharmaceutical risk reduction in high-risk postmenopausal women. In addition to describing key findings from the publication of MAP. 3 and related trials, our review undertakes a detailed analysis of the strengths and weaknesses of MAP. 3 as well as the implications for future prevention research. Cancer Discovery; 2(1); 25-40. (C) 2012 AACR

    Age Is Predictive of Immediate Postoperative Urinary Continence after Radical Retropubic Prostatectomy

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    Introduction: Immediate continence is a goal to take into consideration for better patient satisfaction after radical prostatectomy. Factors predicting urinary continence at catheter removal were investigated. Materials and Methods: We evaluated preoperative, operative, clinical, hormonal and pathological variables in a homogeneous series of radical retropubic prostatectomies (RRPs) following the principles of urinary sphincter restoration technique. Results: The study included 201 patients who underwent RRP. The overall immediate continence rate at catheter removal was 67.7% (136 patients); 28.8% (58 patients) were using one protective pad daily and 3.5% (7 patients) were incontinent. At 6-month follow-up incontinence had reached the lowest level of 2.5% (5 patients) and at 12 months the patients using one pad daily had decreased to 11.9% (24 patients). Multivariate logistic analysis showed that the only two factors independently associated with immediate continence were age <65 years (OR = 2.63, 95% CI 1.13-5.88, p = 0.02) and potency (OR = 3.6, 95% CI 1.2-10.7, p = 0.01) adjusting for D'Amico risk group, surgical margins, extracapsular extension, clinical stage, PSA, testosterone, LH and FSH. No significant association was noted for PSA, hormonal levels, hospital stay, prostate size, clinical stage, risk group, TNM stage, pathological Gleason score or extracapsular extension. Conclusions: In our series age <65 years was associated with immediate continence after RRP. Moreover, patients who were immediately continent had a 3.6-fold probability to be potent within 12 months

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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