1,721,021 research outputs found
Investigation of the association between 5-HT3A receptor gene polymorphisms and efficiency of antiemetic treatment with 5-HT3 receptor antagonists
No full textObjectives Acute cytostatic drug induced nausea and vomiting is provoked by a release of endogenous serotonin that mediates its effect by binding to the 5-hydroxytryptamine type 3 (5-HT3) receptors. The most effective antiemetic drugs are the 5-HT3 receptor antagonists. Nevertheless about 30% of the patients do not respond satisfactorily. Five 5-HT3 receptor genes (-5HT(3A-E)) with high sequence homology have been identified. Two subunits, the 5-HT3A and 5-HT3B are expressed in anatomical structures known to be involved in the mechanism of acute cytostatic drug induced emesis. Methods We included 242 cancer patients at their first day of chemotherapy to investigate the influence of genetic polymorphisms of the 5-HT3A receptor gene on the intensity of nausea and vomiting which was documented using standardized interviews and visual analog scales. Results Sequencing of the entire 5-HT3A receptor gene of all patients revealed 21 polymorphisms, two of them were amino acid substitutions (Ala33Thr, Met257Ile). Linkage disequilibrium analysis revealed that 15 polymorphisms of the 5-HT3A receptor gene are partially linked to each other. However, none of the haplotypes was significantly associated with the intensity of cytostatic induced nausea and vomiting. Conclusion Polymorphisms and haplotype analysis of the 5-HT3A receptor gene may not serve as a pharmacogenetic predictor of the antiemetic treatment with 5-HT3 receptor antagonists in cancer patients. (C) 2004 Lippincott Williams Wilkins
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
Patient-tailored antiemetic treatment with 5-hydroxytryptamine type 3 receptor antagonists according to cytochrome P-450 2D6 genotypes
No full textPurpose: The use of serotonin 5-hydroxytryptamine type 3 receptor antagonists has substantially reduced, but not eliminated, nausea and vomiting in cancer chemotherapy. This study sought to investigate whether efficacy of antiemetic treatment with ondansetron and tropisetron depends on cytochrome P-450 2D6 (CYP2D6) genotype, hypothesizing that the rapid and particularly the ultrarapid metabolizers of these drugs are at risk of being undertreated. Patients and Methods: Included in the study were 270 cancer patients receiving their first day of chemotherapy. Nausea and vomiting were documented using standardized interviews. The intensity of nausea was measured with visual analog scales before and twice during the chemotherapy. The relationship between the CYP2D6 genotypes and the tropisetron serum concentrations 3 and 6 hours after drug administration was analyzed in a subgroup of 42 patients. CYP2D6 genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism analysis. Results: Genetically defined poor metabolizers had higher serum concentrations of tropisetron than all other patients (P < .03). Approximately 30% of all patients receiving chemotherapy experienced nausea and vomiting. Genetically defined ultrarapid metabolizers of CYP2D6 substrates had higher frequency of vomiting within the first 4 hours (P < .001) and within the period 5 to 24 hours (P < .03) after treatment than all the other patients; the tendency for nausea was similar. This difference was more pronounced in patients treated with tropisetron than in those treated with ondansetron. Conclusion: Antiemetic treatment with tropisetron or ondansetron could be improved by adjustment for the CYP2D6 genotype; approximately 50 subjects would have to be genotyped to protect one patient from severe emesis
Variations of the 5-hydroxytryptamine type 3B receptor gene and intensity of nausea and vomiting in cancer patients
No full textVariations in the 5-hydroxytryptamine type 3B receptor gene as predictors of the efficacy of antiemetic treatment in cancer patients
No full textPurpose : Serotonin (5-hydroxytryptamine type 3 [5-HT3]) receptor antagonists have substantially reduced but not eliminated nausea and vomiting in patients undergoing cancer chemotherapy. They act through specific binding to the 5-HT3A, 5-HT3B receptor complex. The 5-HT3B subunit seems to be most important for its functionality. We hypothesized that patients with genetic variations in the 5-HT3B receptor gene might respond differently to antiemetic treatment. Patients and Methods: We included 242 cancer patients on their first day of chemotherapy. Nausea and vomiting were documented before and twice during the chemotherapy using standardized interviews and visual analog scales. We sequenced the entire 5-HT3B receptor gene, including the 5' flanking region and at least a 20-base pair intronic sequence of each intron-exon splice site of all patients. Results : Approximately 30% of all patients suffered from nausea or vomiting. Sequencing of the 5-HT3B receptor gene revealed 13 polymorphisms: two of them were amino acid exchanges (Tyr129Ser, Ala223Thr) and two were deletion variants. In both observation periods, patients homozygous for the -100 -102delAAG deletion variant of the promotor region experienced vomiting more frequently than did all the other patients. Conclusion: A more efficient antiemetic treatment with 5-HT3 receptor antagonists might be possible on a pharmacogenetic basis. However, only a small fraction of the therapeutic failure is explained by the -AAG deletion variant of the 5-HT3B, receptor gene. Additional clinical and biochemical studies are needed to confirm the association. (C) 2003 by American Society of Clinical Oncology
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