996 resultados para COMPARATIVE TOXICITY


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BACKGROUND AND PURPOSE: Accurate placement of an external ventricular drain (EVD) for the treatment of hydrocephalus is of paramount importance for its functionality and in order to minimize morbidity and complications. The aim of this study was to compare two different drain insertion assistance tools with the traditional free-hand anatomical landmark method, and to measure efficacy, safety and precision. METHODS: Ten cadaver heads were prepared by opening large bone windows centered on Kocher's points on both sides. Nineteen physicians, divided in two groups (trainees and board certified neurosurgeons) performed EVD insertions. The target for the ventricular drain tip was the ipsilateral foramen of Monro. Each participant inserted the external ventricular catheter in three different ways: 1) free-hand by anatomical landmarks, 2) neuronavigation-assisted (NN), and 3) XperCT-guided (XCT). The number of ventricular hits and dangerous trajectories; time to proceed; radiation exposure of patients and physicians; distance of the catheter tip to target and size of deviations projected in the orthogonal plans were measured and compared. RESULTS: Insertion using XCT increased the probability of ventricular puncture from 69.2 to 90.2 % (p = 0.02). Non-assisted placements were significantly less precise (catheter tip to target distance 14.3 ± 7.4 mm versus 9.6 ± 7.2 mm, p = 0.0003). The insertion time to proceed increased from 3.04 ± 2.06 min. to 7.3 ± 3.6 min. (p < 0.001). The X-ray exposure for XCT was 32.23 mSv, but could be reduced to 13.9 mSv if patients were initially imaged in the hybrid-operating suite. No supplementary radiation exposure is needed for NN if patients are imaged according to a navigation protocol initially. CONCLUSION: This ex vivo study demonstrates a significantly improved accuracy and safety using either NN or XCT-assisted methods. Therefore, efforts should be undertaken to implement these new technologies into daily clinical practice. However, the accuracy versus urgency of an EVD placement has to be balanced, as the image-guided insertion technique will implicate a longer preparation time due to a specific image acquisition and trajectory planning.

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Conjugates of goat anti-HBs IgG and horseradish peroxidase (HRP) prepared by two different methods, one using NaIO4 and the other SPDP, were compared. Anti-HBs antibodies obtained from goat, rabbit and guinea-pig were tested as capture serum. The ELISA showed a sensitivity similar to RIA and a level of antigen captation ranging from 4.37 to 8.75 nanograms/ml was obtained when rabbit or guinea-pig captures were used combined with both NaIO4 or SPDP conjugates.

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The photosensitizing properties of m-tetrahydroxyphenylchlorin (mTHPC) and polyethylene glycol-derivatized mTHPC (pegylated mTHPC) were compared in nude mice bearing human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma xenografts. Laser light (20 J/cm2) at 652 nm was delivered to the tumour (surface irradiance) and to an equal-sized area of the hind leg of the animals after i.p. administration of 0.1 mg/kg body weight mTHPC and an equimolar dose of pegylated mTHPC, respectively. The extent of tumour necrosis and normal tissue injury was assessed by histology. Both mTHPC and pegylated mTHPC catalyse photosensitized necrosis in mesothelioma xenografts at drug-light intervals of 1-4 days. The onset of action of pegylated mTHPC seemed slower but significantly exceeds that of mTHPC by days 3 and 4 with the greatest difference being noted at day 4. Pegylated mTHPC also induced significantly larger photonecrosis than mTHPC in squamous cell xenografts but not in adenocarcinoma at day 4, where mTHPC showed greatest activity. The degree of necrosis induced by pegylated mTHPC was the same for all three xenografts. mTHPC led to necrosis of skin and underlying muscle at a drug-light interval of 1 day but minor histological changes only at drug-light intervals from 2-4 days. In contrast, pegylated mTHPC did not result in histologically detectable changes in normal tissues under the same treatment conditions at any drug-light interval assessed. In this study, pegylated mTHPC had advantages as a photosensitizer compared to mTHPC. Tissue concentrations of mTHPC and pegylated mTHPC were measured by high-performance liquid chromatography in non-irradiated animals 4 days after administration. There was no significant difference in tumour uptake between the two sensitizers in mesothelioma, adenocarcinoma and squamous cell carcinoma xenografts. Tissue concentration measurements were of limited use for predicting photosensitization in this model.

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OBJECTIVE: To examine the relation between depression and substance use in adolescents and the concomitant courses of both disorders. METHODS: Four individual interviews were administered to 85 adolescent substance users aged 14-19 years (mean 17.1 years, SD 1.4) over a 3.5 year period using the Adolescent Drug Abuse Interview (ADAD) and the Beck Depression Inventory (BDI-13). RESULTS: No predictive effect was observed on one dimension over the other, but each dimension was predictive of its own course. A decrease in substance-use severity paralleled a decrease in depressive state. Similarly, stable substance-use rates, either at a low or a high level, tended to be associated with low or high levels of depression, respectively. However, an increase in substance use was not accompanied by an increase in depressive states. Moreover, depression varied greatly between adolescents, and according to gender and age. CONCLUSIONS: Depressive states and substance use in adolescents can vary considerably overtime, and are closely but rather synchronically related. Since most of the adolescents do not seek help for substance-related problems, substance use should be systematically assessed in adolescents presenting with a depressive state.

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Ce travail traite de la catégorie du « héros » et s'articule autour d'une comparaison entre les récits de la Grèce antique, principalement la poésie épique, et le Proche-Orient ancien, essentiellement les textes vétérotestamentaires - une étude dont l'objet est dès lors principalement textuel. Partant du constat, si simple mais lourd de conséquence, que le mot français « héros » vient du substantif grec rjpcoç, le texte débute par un travail de décentrement face aux référents contemporains liés à l'emploi du terme dans nos langues modernes : le « héros » n'est pas forcément le rjpcoç. Riche de cette analyse, la deuxième partie du travail se tourne vers l'Antiquité grecque, et plus précisément vers les poésies homérique et hésiodique. L'analyse de l'emploi du vocabulaire héroïque au sein de ces récits permet de cerner plus précisément les diverses figures appelées rjpcoç - figures qui semblent si différentes les unes des autres alors qu'elles partagent un qualificatif commun. Fort de cet apport quant à la compréhension du rjpcoç épique grec, une troisième partie questionne la présence de la catégorie du « héros » dans la Bible hébraïque mais aussi dans ses traductions en langues modernes. Constatant que le mot « héros » n 'apparaît jamais dans les langues anciennes que sont le grec de la LXX ou le latin de la Vulgate, les figures vétérotestamentaires sont repensées dans leur contexte proche- oriental, les voyant sous la lumière du Levant - lumière qui est la leur - et ce grâce au vocabulaire somme toute fort précis de la langue hébraïque. Finalement, une partie conclusive tente de mettre en exergue ce que la comparaison des récits grecs épiques et vétérotestamentaires a permis de soulever quant à leurs catégories « héroïques » respectives. L'enjeu est également de penser de manière critique ce que les cultures occidentales contemporaines nomment « héros », s'appuyant si souvent sur un « double héritage » gréco-romain et judéo-chrétien.

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This study aimed at identifying clinical factors for predicting hematologic toxicity after radioimmunotherapy with (90)Y-ibritumomab tiuxetan or (131)I-tositumomab in clinical practice. Hematologic data were available from 14 non-Hodgkin lymphoma patients treated with (90)Y-ibritumomab tiuxetan and 18 who received (131)I-tositumomab. The percentage baseline at nadir and 4 wk post nadir and the time to nadir were selected as the toxicity indicators for both platelets and neutrophils. Multiple linear regression analysis was performed to identify significant predictors (P < 0.05) of each indicator. For both platelets and neutrophils, pooled and separate analyses of (90)Y-ibritumomab tiuxetan and (131)I-tositumomab data yielded the time elapsed since the last chemotherapy as the only significant predictor of the percentage baseline at nadir. The extent of bone marrow involvement was not a significant factor in this study, possibly because of the short time elapsed since the last chemotherapy of the 7 patients with bone marrow involvement. Because both treatments were designed to deliver a comparable bone marrow dose, this factor also was not significant. None of the 14 factors considered was predictive of the time to nadir. The R(2) value for the model predicting percentage baseline at nadir was 0.60 for platelets and 0.40 for neutrophils. This model predicted the platelet and neutrophil toxicity grade to within ±1 for 28 and 30 of the 32 patients, respectively. For the 7 patients predicted with grade I thrombocytopenia, 6 of whom had actual grade I-II, dosing might be increased to improve treatment efficacy. The elapsed time since the last chemotherapy can be used to predict hematologic toxicity and customize the current dosing method in radioimmunotherapy.

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Les évidences s'accumulent concernant des problèmes de corrosion touchant les prothèses à col modulaires. Plusieurs études récentes révèlent des taux d'ions métalliques élevés. Le but de cette étude était de comparer les taux d'ions métalliques (Co, Cr, Mo, Ti), dans le sérum, chez des porteurs de prothèses à col modulaire, à tige monobloc, ainsi que sans implant. Méthodes Nous avons recruté 60 patients, dont 50 porteurs d'une PTH, unilatérale, sans aucun autre implant, non-cimentée, avec tête en céramique, à minimum 1 année postopératoire. Quarante avaient une tige SPS (Symbios) (Ti6Al4 V) modulaire (col en CoCr) et 10 une SPS monobloc (non-modulaire). Les cupules étaient toutes en alliage de Ti (Ti6Al4 V) avec insert céramique ou PE. Nous avons constitué un groupe témoin sans aucun implant. Dans le groupe o modulaires O, le col a été choisi en préopératoire sur la base d'une planification 3D et assemblé à sec avant implantation. Nous avons prélevé un échantillon sérique, un autre sanguin, qui ont été analysés par spectrométrie de masse, permettant une détermination atomique quantitative. Le résultat clinique a été estimé à l'aide du o Oxford Hip Score O. Résultats Nous avons trouvé un Co sérique moyen à 1,54 Ig L dans le groupe O modulaires O et à 0,32 Ig L dans le groupe o monobloc O avec un p < 0,001. Pour le Cr, on a 1,12 Ig L (modulaires) vs 0,60 Ig L (monoblocs) avec un p < 0,001, pour le Ti 31 Ig L (modulaires) vs 22 Ig L (monoblocs) avec p < 0,001 et pour le Mo, 0,96 Ig L (modulaires) vs 0,74 (monoblocs) avec p = 0,254. Deux patients avaient des valeurs de Co supérieures à 7 Ig L et 11 étaient au-dessus de 1 Ig L, valeur considérée comme limite. Les valeurs dans le sang complet étaient similaires. Nous n'avons pas trouvé de différence significative selon les types de col modulaires (longs vs courts et rétro vs normaux). Curieusement, le taux de Cr était significativement plus élevé chez les patients sans aucun implant que chez les porteurs de SPS monobloc, par contre les différences n'étaient pas significatives pour les autres éléments. Conclusion Les taux sériques et sanguins de ions Co, Cr et Ti étaient significativement plus élevés dans le groupe des patients avec col modulaire, avec 2 valeurs 40 extrêmement hautes et plus de la moitié (11 40) anormalement hautes. Bien que ces valeurs soient inférieures à celles d'autres études, nous avons arrêter d'utiliser de tiges à cols modulaires, et avons initié un suivi annuel des patients porteurs, similaire à celui instauré pour les grosses têtes métal-métal.

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INTRODUCTION: Many clinical practice guidelines (CPG) have been published in reply to the development of the concept of "evidence-based medicine" (EBM) and as a solution to the difficulty of synthesizing and selecting relevant medical literature. Taking into account the expansion of new CPG, the question of choice arises: which CPG to consider in a given clinical situation? It is of primary importance to evaluate the quality of the CPG, but until recently, there has been no standardized tool of evaluation or comparison of the quality of the CPG. An instrument of evaluation of the quality of the CPG, called "AGREE" for appraisal of guidelines for research and evaluation was validated in 2002. AIM OF THE STUDY: The six principal CPG concerning the treatment of schizophrenia are compared with the help of the "AGREE" instrument: (1) "the Agence nationale pour le développement de l'évaluation médicale (ANDEM) recommendations"; (2) "The American Psychiatric Association (APA) practice guideline for the treatment of patients with schizophrenia"; (3) "The quick reference guide of APA practice guideline for the treatment of patients with schizophrenia"; (4) "The schizophrenia patient outcomes research team (PORT) treatment recommendations"; (5) "The Texas medication algorithm project (T-MAP)" and (6) "The expert consensus guideline for the treatment of schizophrenia". RESULTS: The results of our study were then compared with those of a similar investigation published in 2005, structured on 24 CPG tackling the treatment of schizophrenia. The "AGREE" tool was also used by two investigators in their study. In general, the scores of the two studies differed little and the two global evaluations of the CPG converged; however, each of the six CPG is perfectible. DISCUSSION: The rigour of elaboration of the six CPG was in general average. The consideration of the opinion of potential users was incomplete, and an effort made in the presentation of the recommendations would facilitate their clinical use. Moreover, there was little consideration by the authors regarding the applicability of the recommendations. CONCLUSION: Globally, two CPG are considered as strongly recommended: "the quick reference guide of the APA practice guideline for the treatment of patients with schizophrenia" and "the T-MAP".

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This study examines the impact of globalization on cross-country inequality and poverty using a panel data set for 65 developing counties, over the period 1970-2008. With separate modelling for poverty and inequality, explicit control for financial intermediation, and comparative analysis for developing countries, the study attempts to provide a deeper understanding of cross country variations in income inequality and poverty. The major findings of the study are five fold. First, a non-monotonic relationship between income distribution and the level of economic development holds in all samples of countries. Second, both openness to trade and FDI do not have a favourable effect on income distribution in developing countries. Third, high financial liberalization exerts a negative and significant influence on income distribution in developing countries. Fourth, inflation seems to distort income distribution in all sets of countries. Finally, the government emerges as a major player in impacting income distribution in developing countries.

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As most metabolic studies are conducted in male animals, understanding the sex specificity of the underlying molecular pathways has been broadly neglected; for example, whether PPARs elicit sex-dependent responses has not been determined. Here we show that in mice, PPARalpha has broad female-dependent repressive actions on hepatic genes involved in steroid metabolism and immunity. In male mice, this effect was reproduced by the administration of a synthetic PPARalpha ligand. Using the steroid oxysterol 7alpha-hydroxylase cytochrome P4507b1 (Cyp7b1) gene as a model, we elucidated the molecular mechanism of this sex-specific PPARalpha-dependent repression. Initial sumoylation of the ligand-binding domain of PPARalpha triggered the interaction of PPARalpha with GA-binding protein alpha (GABPalpha) bound to the target Cyp7b1 promoter. Histone deacetylase and DNA and histone methylases were then recruited, and the adjacent Sp1-binding site and histones were methylated. These events resulted in loss of Sp1-stimulated expression and thus downregulation of Cyp7b1. Physiologically, this repression conferred on female mice protection against estrogen-induced intrahepatic cholestasis, the most common hepatic disease during pregnancy, suggesting a therapeutic target for prevention of this disease.

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Report for the scientific sojourn at the National Institute for Public Health and the Environment (RIVM), Netherlands, from 2006 to 2008. This project aimed at creating scientific elements that could help deriving an integrated testing strategy for reproductive toxicity. Part of the project focused on the use of alternative tests for regulatory purposes. An in vitro-in vivo extrapolation method for embryotoxicity was proposed and evaluated. In vitro and in vivo dose descriptors were correlated; however, the scatter in the correlation was too large to allow an accurate estimation of an in vivo dose from an in vitro dose. The in vitro-in vivo extrapolation method together with toxicokinetic data was also applied to a category of substances (phthalates). Although based on a limited number of substances, the results suggested that in vitro-in vivo extrapolation for embryotoxicity is possible within a category of compounds if adequate toxicokinetic data is available. Because of the limitations that still remain in the use of alternative tests for reproductive toxicicity, other approaches to reduce animal testing were explored. Thus, a database of reproductive toxicity studies was created to retrospectively evaluate the comparative value of some studies or elements in a particular study. When compared to the subchronic toxicity study, the rat two-generation reproductive toxicity study had a considerable impact on the identification of hazard for reproductive toxicity, but not on the overall NOAEL. Among the two-generation studies included in our database, the second generation affected neither the overall NOAEL nor the critical effect. The rat and the rabbit developmental toxicity studies were, on average, similarly sensitive. However, for certain substances the developmental study in either one of the two species appeared to be more sensitive than in the other species.

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This paper extends previous research and discussion on the use of multivariate continuous data, which are about to become more prevalent in forensic science. As an illustrative example, attention is drawn here on the area of comparative handwriting examinations. Multivariate continuous data can be obtained in this field by analysing the contour shape of loop characters through Fourier analysis. This methodology, based on existing research in this area, allows one describe in detail the morphology of character contours throughout a set of variables. This paper uses data collected from female and male writers to conduct a comparative analysis of likelihood ratio based evidence assessment procedures in both, evaluative and investigative proceedings. While the use of likelihood ratios in the former situation is now rather well established (typically, in order to discriminate between propositions of authorship of a given individual versus another, unknown individual), focus on the investigative setting still remains rather beyond considerations in practice. This paper seeks to highlight that investigative settings, too, can represent an area of application for which the likelihood ratio can offer a logical support. As an example, the inference of gender of the writer of an incriminated handwritten text is forwarded, analysed and discussed in this paper. The more general viewpoint according to which likelihood ratio analyses can be helpful for investigative proceedings is supported here through various simulations. These offer a characterisation of the robustness of the proposed likelihood ratio methodology.

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Currently, financial economics is unable to predict changes in asset prices with respect to changes in the underlying risk factors, even when an asset's dividend is independent of a given factor. This paper takes steps towards addressing this issue by highlighting a crucial component of wealth effects on asset prices hitherto ignored by the literature. Changes in wealth do not only alter an agents risk aversion, but also her perceived 'riskiness' of a security. The latter enhances significantly the extent to which market- clearing leads to endogenously-generated correlation across asset prices, over and above that induced by correlation between payoffs, giving the appearance of 'contagion.'