Tests pharmacogénétiques: bientôt avant chaque prescription [Pharmacogenetic testing: soon before every prescription?]

Genetic polymorphisms have currently been described in more than 200 systems affecting pharmacological responses (cytochromes P450, conjugation enzymes, transporters, receptors, effectors of response, protection mechanisms, determinants of immunity). Pharmacogenetic testing, i.e. the profiling of individual patients for such variations, is about to become largely available. Recent progress in the pharmacogenetics of tamoxifen, oral anticoagulants and anti-HIV agents is reviewed to discuss critically their potential impact on prescription and contribution/limits for improving rational and safe use of pharmaceuticals. Prospective controlled trials are required to evaluate large-scale pharmacogenetic testing in therapeutics. Ethical, social and psychological issues deserve particular attention.

Effect of an I.V. bolus of phenylephrine or ephedrine on skin blood flow during spinal anesthesia

Effet d'un bolus intraveineux de phénylephrine ou d'éphedríne sur le flux sanguin cutané lors d'une anesthésie rachidienne Introduction : La phénylephrine et l'éphedrine sont des substances vaso-actives utilisées de routine pour corriger des épisodes d'hypotension artérielle induits par l'anesthésie intrarachidienne. L'influence de ces deux vasopresseurs sur le flux sanguin cutané (FSC) dans ce contexte n'a jusqu'à maintenant pas été décrite. Cette étude évalue l'effet d'une injection intraveineuse de 75 µg de phénylephrine ou de 7.5 mg d'éphedrine sur le FSC mesuré par Laser Doppler, dans les zones concernées parle bloc sympathiqué induit par l'anesthésie intrarachidienne (membres inférieurs) et dans les zones non concernées (membres supérieurs). Méthode :Après acceptation par le Comité d'Éthique, et obtention de leur accord écrit, 20 patients devant subir une intervention chirurgicale élective en décubitus dorsal sous anesthésie. intrarachidienne ont été inclus dans cette étude randomisée en double insu. Le FSC a été mesuré en continu par deux sondes fixées l'une à la cuisse (zone avec bloc sympathique) et l'autre sur l'avantbras (zone sans bloc sympathique). Les valeurs de FSC ont été enregistrées après l'anesthésie rachidienne (valeur contrôle), puis après l'injection i.v. dè phénylephrine (10 patients) ou d'éphedrine (10 patients) pour corriger une hypotension définie comme une chute de 20 mmHg de la pression artérielle systolique. Les variations de FSC exprimées en pourcentage de la valeur contrôle moyenne (+/- écart type) ont été analysées par le test t de Student. Résultats :Les données démographiques des patients et le niveau sensitif induit par l'anesthésie rachidienne sont similaires dans les deux groupes. Aux doses utilisées, seule l'éphedrine restaure la pression artérielle aux valeurs précédant l'anesthésie rachidienne. La phénylephrine augmente le FSC de l'avant-bras de 44% (+/- 79%) et de la cuisse de 34% (+/-24%), alors que l'éphedrine diminue le débit sanguin cutané de l'avant-bras de 16% (+/- 15%) et de la cuisse de 22% (+/-11%). Conclusion : L'injection intraveineuse de phénylephrine et d'éphedrine ont des effets opposés sur le flux sanguin cutané, et cette réponse n'est pas modifiée par le bloc sympathique.. Cette différence peut s'expliquer par la distribution des sous-types de récepteurs adrénergiques alpha et leur prédominance relative dans les veines et les artères de différents diamètres perfusant le tissu sous-cutané et la peau. L'éphedrine, èn raison de sa meilleure efficacité pour traiter les épisodes d'hypotension artérielle après anesthésie intrarachidienne devrait être préféré à la phénylephrine, leurs effets opposés sur le flux sanguin cutané n'étant pas pertinents en pratique clinique. SUMMARY Background: Phenylephrine or ephedrine is routinely used to correct hypotensive episodes fallowing spinal anaesthesia (SA). The influence of these two vasopressors on skin blood flow (SBF) has not yet been described. We have therefore evaluated the effects of an i.v. bolus of 75 µg phenylephrine or 7.5 mg of ephedrine on SBF measured by laser Doppler flowmetry during sympathetic blockade induced by SA. Methods: With Ethical Committee approval and written consent, 20 patients scheduled for elective procedures in supine position under SA were enrolled in this double-blind randomized study. SBF was measured continuously by two probes fixed at the thigh (area with sympathic blockade) and forearm level (area without sympathic blockade) respectively. SBF values were recorded after SA (control values) and then after a bolus administration of phenylephriné (n=10) or ephedrine (n=10) when systolic blood pressure decreased by 20 mmHg. Changes were expressed as percentage of control SBF values and analysed by Student's paired t-test. Results: Patient characteristics and dermatomal sensory levels were similar in both groups. Phenylephrine increases mean SBF at the forearm level by 44% (79%) [mean (SD)j and at the thigh by 34% (24%). Ephedrine decreases SBF at the forearm level by 16% (15%) and at the thigh by 22% (il%). Ephedrine bolus restores arterial blood pressure to pre-anaesthesia values, whereas phenylephrine does not. Conclusion: Administratión of phenylephrine and ephedrine has opposite effects on skin blood flow and sympathetic blockade does not modify this response. These findings could be explained by the distribution of the alpha-adrenoréceptor subtypes and their relative predominance among veins and arteries of different size perfusing the subcutaneous tissue and the skin. Ephedrine, due to its better efficacy to correct hypotensive episodes following SA, should be preferred, to phenylephrine, their opposite effects on SBF being not relevant for clinical practice.

Primate adult brain cell autotransplantation produces behavioral and biological recovery in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian St. Kitts monkeys.

The potential for "replacement cells" to restore function in Parkinson's disease has been widely reported over the past 3 decades, rejuvenating the central nervous system rather than just relieving symptoms. Most such experiments have used fetal or embryonic sources that may induce immunological rejection and generate ethical concerns. Autologous sources, in which the cells to be implanted are derived from recipients' own cells after reprogramming to stem cells, direct genetic modifications, or epigenetic modifications in culture, could eliminate many of these problems. In a previous study on autologous brain cell transplantation, we demonstrated that adult monkey brain cells, obtained from cortical biopsies and kept in culture for 7 weeks, exhibited potential as a method of brain repair after low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused dopaminergic cell death. The present study exposed monkeys to higher MPTP doses to produce significant parkinsonism and behavioral impairments. Cerebral cortical cells were biopsied from the animals, held in culture for 7 weeks to create an autologous neural cell "ecosystem" and reimplanted bilaterally into the striatum of the same six donor monkeys. These cells expressed neuroectodermal and progenitor markers such as nestin, doublecortin, GFAP, neurofilament, and vimentin. Five to six months after reimplantation, histological analysis with the dye PKH67 and unbiased stereology showed that reimplanted cells survived, migrated bilaterally throughout the striatum, and seemed to exert a neurorestorative effect. More tyrosine hydroxylase-immunoreactive neurons and significant behavioral improvement followed reimplantation of cultured autologous neural cells as a result of unknown trophic factors released by the grafts. J. Comp. Neurol. 522:2729-2740, 2014. © 2014 Wiley Periodicals, Inc.

Minimum requirements for application of ink dating methods based on solvent analysis in casework

Several ink dating methods based on solvents analysis using gas chromatography/mass spectrometry (GC/MS) were proposed in the last decades. These methods follow the drying of solvents from ballpoint pen inks on paper and seem very promising. However, several questions arose over the last few years among questioned documents examiners regarding the transparency and reproducibility of the proposed techniques. These questions should be carefully studied for accurate and ethical application of this methodology in casework. Inspired by a real investigation involving ink dating, the present paper discusses this particular issue throughout four main topics: aging processes, dating methods, validation procedures and data interpretation. This work presents a wide picture of the ink dating field, warns about potential shortcomings and also proposes some solutions to avoid reporting errors in court.

The response of a Swiss university hospital's palliative care consult team to assisted suicide within the institution.

In January 2006 the Centre Hospitalier Universitaire Vaudois (CHUV), a large university hospital in Lausanne, Switzerland, became the first hospital in Switzerland to allow assisted suicide (AS) in exceptional cases within its walls. However, euthanasia is illegal. This decision has posed several ethical and practical dilemmas for the hospital's palliative care consult service. To address these, the team embarked on a formal process of open dialogue amongst its members with the goal of identifying a collective response and position. This process involved meetings every 4 to 6 weeks over the course of 10 months. An iterative process unfolded. One of the principal dilemmas relates to finding a balance between the team's position against AS and the patient's autonomy and the institution's directive. Although all team members expressed opposition to AS, there were mixed opinions as to whether or not the team members should be present during the act if requested so by patients. Some thought this could be misinterpreted as complicity in the act and could send out mixed messages to the public and other health professionals about palliative care. Others felt that the team's commitment to nonabandonment obliged them to be present even if they did not provide the drug or give any advice or assistance. The implications of nonabandonment are explored, as are several other questions such as whether or not the teams are obliged to provide detailed information on AS when requested by patients.

Cyberhealth serving to support individual intake of medication.

The Internet and new communication technologies are deeply affecting healthcare systems and the provision of care. The purpose of this article is to evaluate the possibility that cyberhealth, via the development of widespread easy access to wireless personal computers, tablets and smartphones, can effectively influence intake of medication and long-term medication adherence, which is a complex, difficult and dynamic behaviour to adopt and to sustain over time. Because of its novelty, the impact of cyberhealth on drug intake has not yet been well explored. Initial results have provided some evidence, but more research is needed to determine the impact of cyberhealth resources on long-term adherence and health outcomes, its user-friendliness and its adequacy in meeting e-patient needs. The purpose of such Internet-based interventions, which provide different levels of customisation, is not to take over the roles of healthcare providers; on the contrary, cyberhealth platforms should reinforce the alliance between healthcare providers and patients by filling time-gaps between visits and allowing patients to upload and/or share feedback material to be used during the visits. This shift, however, is not easily endorsed by healthcare providers, who must master new eHealth skills, but healthcare systems have a unique opportunity to invest in the Internet and to use this powerful tool to design the future of integrated care. Before this can occur, however, important issues must be addressed and resolved, for example ethical considerations, the scientific quality of programmes, reimbursement of activity, data security and the ownership of uploaded data.

La médecine interne generate: un terrain propice à l'exercice de l'éthique au quotidien [Everyday bioethics in general internal medicine]

The knowledge of the national legislation and the key concepts of bioethics are necessary for medical practice. The four principles of bioethics are autonomy, beneficence, non-maleficence, and justice. General internal medicine is the speciality of comprehensive care for often elderly patients with multiple chronic illnesses. This care is related to many ethically difficult decisions. In our article, we discuss common ethical problems in general internal medicine, including ethical aspects of the patient-physician relationship and medical decision making, the ethical significance of time management, research in bioethics and medical education.

Good practice in authoring manuscripts on geomorphology

This article aims to help potential authors of geomorphological articles to get their work published. It identifies the basic characteristics of a good manuscript in geomorphology in terms of: (a) originality and significance; and (b) rigour. It uses these characteristics to define how an author should structure a conventional' manuscript in geomorphology by successfully identifying and justifying the motivation for the research; clearly and fully explaining the methods used; and presenting and discussing the results obtained. The article considers the importance of published literature in sustaining all elements of a manuscript in geomorphology. It also presents the natural symmetry that should exist between parts of a manuscript. These practical elements regarding the form and content of a manuscript are then developed through: (a) flagging some of the common mistakes made by authors drawing upon my experience as Managing Editor of the journal Earth Surface Processes and Landforms; (b) discussing the ethical and legal issues, including plagiarism, that relate to manuscript submission; (c) exploring the review process from the perspective of an author, including guidance on how best to respond to review comments in revising a manuscript. Copyright (c) 2013 John Wiley & Sons, Ltd.

Peut-on accepter les progrès en sciences biomèdicales sans progrès en éthique ? [Can we take for granted medical progress without progress in ethics ?].

Since the mid 20th century progress in biomedical science has been punctuated by the emergence of bioethics which has fashioned the moral framework of its application to both research and clinical practice. Can we, however, consider the advent of bioethics as a form of progress marking the advances made in biomedical science with an adequate ethical stamp? The argument put forward in this chapter is based on the observation that, far from being a mark of progess, the development of bioethics runs the risk of favouring, like modern science, a dissolution of the links that unite ethics and medicine, and so of depriving the latter of the humanist dimensions that underlie the responsibilities that fall to it. Faced with this possible pitfall, this contribution proposes to envisage as a figure of moral progress, consubstantial with the development of biomedical science, an ethical approach conceived as a means of social intervention which takes the first steps towards an ethics of responsibility integrating the bioethical perspective within a hermeneutic and deliberative approach. By the yardstick of a prudential approach, it would pay particular attention to the diverse sources of normativity in medical acts. It is suggested that this ethical approach is a source of progress insofar as it constitutes an indispensable attitude of watchfulness, which biomedical science can lean on as it advances, with a view to ensuring that the fundamental link uniting ethics and medicine is maintained.

Kitcher's Revolutionary Reasoning Inversion in Ethics

This paper examines three specific issues raised by The Ethical Project. First, I discuss the varieties of altruism and spell out the differences between the definitions proposed by Kitcher and the ways altruism is usually conceived in biology, philosophy, psychology, and economics literature. Second, with the example of Kitcher's account, I take a critical look at evolutionary stories of the emergence of human ethical practices. Third, I point to the revolutionary implications of the Darwinian methodology when it is thoughtfully applied to ethics.

Recherche scientifique en médecine de famille: expériences, barrières et besoins des praticiens [Scientific research in family medicine: practitioners' experience, barriers and needs].

Scientific data from family medicine are relevant for the majority of the population. They are therefore essential from an ethical and public health perspective. We need to promote quality research in family medicine despite methodological, financial and logistic barriers. To highlight the strengths and weaknesses of research in family medicine in the French-speaking part of Switzerland we asked practitioners from this region to share their experience, critics and needs in relation to research. This article summarizes their contribution in light of the international literature.

Wage cuts and managers' empathy: How a positive emotion can contribute to positive organizational ethics in difficult times

Using the lens of positive organizational ethics, we theorized that empathy affects decisions in ethical dilemmas that concern the well-being of not only the organization but also other stakeholders. We hypothesized and found that empathetic managers were less likely to comply with requests by an authority figure to cut the wages of their employees than were non-empathetic managers. However, when an authority figure requested to hold wages constant, empathy did not affect wage cut decisions. These findings imply that empathy can serve as a safeguard for ethical decision making in organizations during trying times without generally undermining organizational effectiveness. We conclude by discussing the implications of our research.