Body Dysmorphic Disorder: Contraindication or Ethical Justification for Female Genital Cosmetic Surgery in Adolescents

Is Female Genital Cosmetic Surgery for an adolescent with Body Dysmorphic Disorder ever ethically justified? Cosmetic genital surgery (specifically labioplasty) for adolescent girls is one of the most ethically controversial forms of cosmetic surgery and Body Dysmorphic Disorder is typically seen as a contraindication for cosmetic surgery. Two key ethical concerns are (1) that Body Dysmorphic Disorder undermines whatever capacity for autonomy the adolescent has; and (2) even if there is valid parental consent, the presence of Body Dysmorphic Disorder means that cosmetic surgery will fail in its aims. In this article, we challenge, in an evidence‐based way, the standard view that Body Dysmorphic Disorder is a contraindication for genital cosmetic surgery in adolescents. Our argument gathers together and unifies a substantial amount of disparate research in the context of an ethical argument. We focus on empirical questions about benefit and harm, because these are ethically significant. Answers to these questions affect the answer to the ethical question. We question the claim that there would be no benefit from surgery in this situation, and we consider possible harms that might be done if treatment is refused. For an adolescent with Body Dysmorphic Disorder, the most important thing may be to avoid harm. We find ourselves arguing for the ethical justifiability of cosmetic labioplasty for an adolescent with Body Dysmorphic Disorder, even though we recognize that it is a counter intuitive position. We explain how we reached our conclusion.     

QALYs, age and fairness

... We can therefore conclude that either we should go for equality; and in that case QALYs are unfair because they haven't got enough of an ageist bias. Or we should accept consequentialism; and in that case QALYs have just the right sort of ageist bias. No plausible case can, however, be made for the claim that QALYs have an unfair bias against old people. Other things being equal we ought when distributing resources essential for survival favour the young. This ethical claim can be supported both by reference to equality (the life-time-view) and by reference to consequentialism (and the premises that resources generally will be more useful when given to young people).     

Unformed minds: Juveniles,neuroscience, and the law

Recently, the question of adolescent culpability has been brought before the Supreme Court of the United States for reconsideration. Neuroscience, adolescent advocates claim, is teaching us that young people cannot be found fully responsible for their actions. The reason: their brains are not fully formed. Here I consider the history of the use of scientific evidence in the courtroom, a number of adolescent murder cases, and the data now emerging from neuroscience, and argue that when it comes to brains, judges, just like the rest of us, are unnecessarily impressed. Ultimately, how we determine culpability should rest on normative and ethical considerations rather than on scientific ones.     

The roles of ASK family proteins in stress responses and diseases

The aim of palliative chemotherapy is to increase survival whilst maintaining maximum quality of life for the individual concerned. Although we are still continuing to explore the optimum use of traditional chemotherapy agents, the introduction of targeted therapies has significantly broadened the therapeutic options. Interestingly, the results from current trials put the underlying biological concept often into a new, less favorable perspective. Recent data suggested that altered pathways underlie cancer, and not just altered genes. Thus, an effective therapeutic agent will sometimes have to target downstream parts of a signaling pathway or physiological effects rather than individual genes. In addition, over the past few years increasing evidence has suggested that solid tumors represent a very heterogeneous group of cells with different susceptibility to cancer therapy. Thus, since therapeutic concepts and pathophysiological understanding are continuously evolving a combination of current concepts in tumor therapy and tumor biology is needed. This review aims to present current problems of cancer therapy by highlighting exemplary results from recent clinical trials with colorectal and pancreatic cancer patients and to discuss the current understanding of the underlying reasons.     

Cosmetic psychopharmacology and the President's Council on Bioethics

Advances in neuroscience and biotechnology have heightened the urgency of the debate over "cosmetic psychopharmacology," the use of drugs to enhance mood and temperament in the absence of illness. Beyond Therapy: Biotechnology and the Pursuit of Happiness (2003), the report of the President's Council on Bioethics, has criticized the use of cosmetic psychopharmacology. The Council claimed that cosmetic psychopharmacology will necessarily lead to "severing the link between feelings of happiness and our actions and experiences in the world," but it provided no satisfactory arguments to support this claim and ignored the possibility that cosmetic psychopharmacology might actually enhance the link between happiness and experience. The Council's arguments against cosmetic psychopharmacology depend heavily on the mistaken belief that Prozac and similar antidepressants are mood brighteners in healthy subjects. The empirical evidence, however, clearly indicates that these drugs are not forms of cosmetic psychopharmacology, thus negating much of the Council's arguments. The use of pharmaceutical agents to enhance mood or personality in normal individuals should not be rejected a priori. Instead, the effects of each agent on the individual and on society must be weighed using sound ethical reasoning and the best evidence available.     

Making efficient use of patients in designing phase III trials investigating simultaneously a set of targeted therapies with different targets

Targeted therapies are a recent development in cancer treatment research. As these therapies can only be administered to patients with certain individual characteristics, it is a straightforward idea to investigate several of such therapies simultaneously in a given patient population in order to compare each targeted therapy with the current standard therapy. This raises the question how patients satisfying several characteristics should be handled. We consider in this paper several designs to allocate treatments in a random manner to these patients, such that the evaluation of each single targeted therapy can be based on a simple comparison of patients receiving the targeted therapies versus those receiving the standard therapy within a well defined subgroup of patients satisfying the corresponding characteristic. We show how one can ensure that patients with several characteristics can contribute simultaneously to the evaluation of several targeted therapies and that this is the key point for an efficient use of the patients available. We further discuss some ethical and practical issues in applying the new designs and outline strategies to evaluate the overall effect of all targeted therapies together.     

An Eliminativist Approach to Vulnerability

The concept of vulnerability has been subject to numerous different interpretations but accounts are still beset with significant problems as to their adequacy, such as their contentious application or the lack of genuine explanatory role for the concept. The constant failure to provide a compelling conceptual analysis and satisfactory definition leaves the concept open to an eliminativist move whereby we can question whether we need the concept at all. I highlight problems with various kinds of approach and explain why a satisfactory account of vulnerability is unlikely ever to be offered if we wish the concept to play a genuinely explanatory role in bioethical contexts. I outline why an eliminativist position should be taken with regard to this concept in light of these concerns but mitigate some of the severity of this position by arguing that we can still make sense of retaining our widespread use of the term by viewing it as nothing more than a useful pragmatic linguistic device that acts as a marker to draw attention to certain kinds of issue. These issues will be entirely governed by other, better understood ethical concepts and theories.     

HOW TO CONNECT BIOETHICS AND ENVIRONMENTAL ETHICS: HEALTH, SUSTAINABILITY, AND JUSTICE

In this paper, I explore one way to bring bioethics and environmental ethics closer together. I focus on a question at the interface of health, sustainability, and justice: How well does a society promote health with the use of no more than a just share of environmental capacity? To address this question, I propose and discuss a mode of assessment that combines a measurement of population health, an estimate of environmental sustainability, and an assumption about what constitutes a fair or just share. This mode of assessment provides an estimate of the just and sustainable life expectancy of a population. It could be used to monitor how well a particular society promotes health within just environmental limits. It could also serve as a source of information that stakeholders use when they deliberate about programs, policies, and technologies. The purpose of this work is to focus attention on an ethical task: the need to fashion institutions and forms of life that promote health in ways that recognize the claims of sustainability and justice.     

Exploiting bacterial DNA gyrase as a drug target: current state and perspectives

DNA gyrase is a type II topoisomerase that can introduce negative supercoils into DNA at the expense of ATP hydrolysis. It is essential in all bacteria but absent from higher eukaryotes, making it an attractive target for antibacterials. The fluoroquinolones are examples of very successful gyrase-targeted drugs, but the rise in bacterial resistance to these agents means that we not only need to seek new compounds, but also new modes of inhibition of this enzyme. We review known gyrase-specific drugs and toxins and assess the prospects for developing new antibacterials targeted to this enzyme.     

Bacterially-Derived Nanocells for Tumor-Targeted Delivery of Chemotherapeutics and Cell Cycle Inhibitors

Chemotherapeutic drug therapy in cancer is seriously hampered by severe toxicity primarily due to indiscriminate drug distribution and consequent collateral damage to normal cells. Molecularly targeted drugs such as cell cycle inhibitors are being developed to achieve a higher degree of tumor cell specificity and reduce toxic side effects. Unfortunately, relative to the cytotoxics, many of the molecularly targeted drugs are less potent and the target protein is expressed only at certain stages of the cell cycle thus necessitating regimens like continuous infusion therapy to arrest a significant number of tumor cells in a heterogeneous tumor mass. Here we discuss targeted drug delivery nanovectors and a recently reported bacterially-derived 400nm sized minicell that can be packaged with therapeutically significant concentrations of chemotherapeutic drugs, targeted to tumor cell surface receptors and effect intracellular drug delivery with highly significant anti-tumor effects in-vivo. We also report that molecularly targeted drugs can also be packaged in minicells and targeted to tumor cells with highly significant tumor growth-inhibition and regression in mouse xenografts despite administration of minute amounts of drug. This targeted intracellular drug delivery may overcome many of the hurdles associated with the delivery of cytotoxic and molecularly targeted drugs.     

The need for systematic reviews of reasons

There are many ethical decisions in the practice of health research and care, and in the creation of policy and guidelines. We argue that those charged with making such decisions need a new genre of review. The new genre is an application of the systematic review, which was developed over decades to inform medical decision-makers about what the totality of studies that investigate links between smoking and cancer, for example, implies about whether smoking causes cancer. We argue that there is a need for similarly inclusive and rigorous reviews of reason-based bioethics, which uses reasoning to address ethical questions. After presenting a brief history of the systematic review, we reject the only existing model for writing a systematic review of reason-based bioethics, which holds that such a review should address an ethical question. We argue that such a systematic review may mislead decision-makers when a literature is incomplete, or when there are mutually incompatible but individually reasonable answers to the ethical question. Furthermore, such a review can be written without identifying all the reasons given when the ethical questions are discussed, their alleged implications for the ethical question, and the attitudes taken to the reasons. The reviews we propose address instead the empirical question of which reasons have been given when addressing a specified ethical question, and present such detailed information on the reasons. We argue that this information is likely to improve decision-making, both directly and indirectly, and also the academic literature. We explain the limitations of our alternative model for systematic reviews.     

Prioritising Healthcare Workers for Ebola Treatment: Treating Those at Greatest Risk to Confer Greatest Benefit

The Ebola epidemic in Western Africa has highlighted issues related to weak health systems, the politics of drug and vaccine development and the need for transparent and ethical criteria for use of scarce local and global resources during public health emergency. In this paper we explore two key themes. First, we argue that independent of any use of experimental drugs or vaccine interventions, simultaneous implementation of proven public health principles, community engagement and culturally sensitive communication are critical as these measures represent the most cost‐effective and fair utilization of available resources. Second, we attempt to clarify the ethical issues related to use of scarce experimental drugs or vaccines and explore in detail the most critical ethical question related to Ebola drug or vaccine distribution in the current outbreak: who among those infected or at risk should be prioritized to receive any new experimental drugs or vaccines? We conclude that healthcare workers should be prioritised for these experimental interventions, for a variety of reasons.     

Liposomes targeting tumour stromal cells

Liposomes have found clinical application in cancer therapy in the delivery of cytostatic agents. As a result of the targeted delivery of these toxic molecules to the tumour cells coupled to avoidance of toxicity-sensitive tissues, the therapeutic window is widened. Over the past years the focus of cancer therapy has shifted towards the stromal cells that are present in the tumour. It appears that clinically relevant tumours have acquired the ability to modulate the microenvironment in such a way that a chronic pro-inflammatory and pro-angiogenic state is achieved that contributes to invasion and metastasis and continued proliferation. Over the past years, liposomal formulations have been designed that target key stromal cell types that contribute to tumour growth. At the same time, many promising cell types have not been targeted yet and most of the studies employ drugs that aim at depleting stromal cells rather than modulating their activity towards an anti-tumour phenotype. In this review these target cell types will be addressed. Complementing these targeted formulations with the appropriate drugs to optimally suppress tumour-promoting signals while preserving anti-tumour action will be the challenge for the future.     

Learning from the voiceless

This article is concerned with understanding what is at stake in the everyday lives of family members facing Huntington's Disease (HD). The methodological and analytical point of departure is German critical psychology, particularly the category of conduct of everyday life (Holzkamp, 1995; Dreier, 1999). Specifically, I address questions of accessing and understanding the conduct of everyday life of persons facing HD who are not visibly active with respect to this circumstance. The question of access is not merely about getting in touch with persons who are not known to the research, professional and HD communities, but also about the consequences of establishing contact with persons who have not made an entry into any of these public areanas themselves. The question of understanding is about developing an analysis from a first-person perspective on the personal conduct of everyday life that is not visibly active. The development of such an understanding has broader implications, not just for further research and health care practices, but importantly also for the prevailing moral and ethical demands made on persons living at risk of hereditary diseases.     

Ethics and severe pandemic influenza: maintaining essential functions through a fair and considered response

The response to severe pandemic influenza will be managed by experts in public health and infectious disease and by government officials to whom the public will turn for information and direction. Nonetheless, there remain important ethical considerations that can shape what goals are given priority, how scarce resources are distributed, how the public is included, and how we treat the most vulnerable in our response to a pandemic. This article assumes that the secondary consequences of severe pandemic influenza could be greater than deaths and illness from influenza itself. Response plans, then, must consider threats to societal as well as medical infrastructures. While some have suggested that scarce medical countermeasures be allocated primarily to first responders and then to the sickest, we suggest that an ethical public health response should set priorities based on essential functions. An ethical response also will engage the public, will coordinate interdependent sectors as a core preparedness priority, and will address how plans affect and can be understood by the least well off.     

Welfarism versus 'free enterprise': considerations of power and justice in the Philippine healthcare system

The just distribution of benefits and burdens of healthcare, at least in the contemporary Philippine context, is an issue that gravitates towards two opposing doctrines of welfarism and 'free enterprise.' Supported largely by popular opinion, welfarism maintains that social welfare and healthcare are primarily the responsibility of the government. Free enterprise (FE) doctrine, on the other hand, maintains that social welfare is basically a market function and that healthcare should be a private industry that operates under competitive conditions with minimal government control. I will examine the ethical implications of these two doctrines as they inform healthcare programmes by business and government, namely: (a) the Devolution of Health Services and (b) the Philippine Health Maintenance Organization (HMO). I will argue that these doctrines and the health programmes they inform are deficient in following respects: (1) equitable access to healthcare, (2) individual needs for premium healthcare, (3) optimal utilisation of health resources, and (4) the equitable assignment of burdens that healthcare entails. These respects, as considerations of justice, are consistent with an operational definition of 'power' proposed here as 'access to and control of resources.'     

Are Phase 1 Trials Therapeutic? Risk,Ethics, and Division of Labor

Despite their crucial role in the translation of pre‐clinical research into new clinical applications, phase 1 trials involving patients continue to prompt ethical debate. At the heart of the controversy is the question of whether risks of administering experimental drugs are therapeutically justified. We suggest that prior attempts to address this question have been muddled, in part because it cannot be answered adequately without first attending to the way labor is divided in managing risk in clinical trials. In what follows, we approach the question of therapeutic justification for phase 1 trials from the viewpoint of five different stakeholders: the drug regulatory authority, the IRB, the clinical investigator, the referring physician, and the patient. Our analysis shows that the question of therapeutic justification actually raises multiple questions corresponding to the roles and responsibilities of the different stakeholders involved. By attending to these contextual differences, we provide more coherent guidance for the ethical negotiation of risk in phase 1 trials involving patients. We close by discussing the implications of our argument for various perennial controversies in phase 1 trial practice.     

Liposomes targeting tumour stromal cells

Abstract

Liposomes have found clinical application in cancer therapy in the delivery of cytostatic agents. As a result of the targeted delivery of these toxic molecules to the tumour cells coupled to avoidance of toxicity-sensitive tissues, the therapeutic window is widened. Over the past years the focus of cancer therapy has shifted towards the stromal cells that are present in the tumour. It appears that clinically relevant tumours have acquired the ability to modulate the microenvironment in such a way that a chronic pro-inflammatory and pro-angiogenic state is achieved that contributes to invasion and metastasis and continued proliferation. Over the past years, liposomal formulations have been designed that target key stromal cell types that contribute to tumour growth. At the same time, many promising cell types have not been targeted yet and most of the studies employ drugs that aim at depleting stromal cells rather than modulating their activity towards an anti-tumour phenotype. In this review these target cell types will be addressed. Complementing these targeted formulations with the appropriate drugs to optimally suppress tumour-promoting signals while preserving anti-tumour action will be the challenge for the future.     

Breast cancer at bone metastatic sites: recent discoveries and treatment targets

Breast carcinoma is the most common cancer of women. Bones are often involved with breast carcinoma metastases with the resulting morbidity and reduced quality of life. Breast cancer cells arriving at bone tissues mount supportive microenvironment by recruiting and modulating the activity of several host tissue cell types including the specialized bone cells osteoblasts and osteoclasts. Pathologically activated osteoclasts produce osteolytic lesions associated with bone pain, pathological fractures, cord compression and other complications of metastatic breast carcinoma at bone. Over the last decade there has been enormous growth of knowledge in the field of osteoclasts biology both in the physiological state and in the tumor microenvironment. This knowledge allowed the development and implementation of several targeted therapeutics that expanded the armamentarium of the oncologists dealing with the metastases-associated osteolytic disease. While the interactions of cancer cells with resident bone cells at the established metastatic gross lesions are well-studied, the preclinical events that underlie the progression of disseminated tumor cells into micrometastases and then into clinically-overt macrometastases are just starting to be uncovered. In this review, we discuss the established information and the most recent discoveries in the pathogenesis of osteolytic metastases of breast cancer, as well as the corresponding investigational drugs that have been introduced into clinical development.     

遗传伦理问题起源的研究与对策

遗传伦理问题是生命科学领域最具争议并最难以妥善解决的问题之一。近年来, 此类问题的研究主要是围绕遗传伦理问题的种类及解决方法进行的。但关于遗传伦理问题起源的系统研究尚不多见, 这也使相应对策的提出显得缺乏理论支撑。文章从人类生物进化与文化进化的双重角度深入探讨了遗传伦理问题发生的进化根源和演化规律。人类是生物进化与文化进化的双重产物, 是地球上唯一既具有生物属性又具有文化属性的物种。通过对人类生物进化与文化进化及其生物属性与文化属性特点的比较研究, 文章提出了任何伦理问题都可以从人类的生物进化与文化进化之间相互作用所产生的冲突中找到其发生根源的观点, 其目的是为研究遗传伦理问题及其对策的提出寻求理论和实践上的依据。同时, 提出了一系列关于遗传伦理问题的对应策略。文章的最终目的并非仅仅为某种观点能被接受, 而是希望通过对遗传伦理问题及其起源的了解和认识, 使遗传学领域的决策者和研究者更具使命感与责任感, 使一般公众对遗传学研究及其应用少一些误解, 多一些理性, 从而使遗传学事业能健康、持续发展, 造福人类。