Frozen Ethics: Melting the Boundaries between Medical Treatment and Organ Procurement

When Renee Fox, medical sociologist and noted historian of organ transplantation, first learned of the proposal to use non-heart-beating cadavers as organ sources more than 25 years ago, she was appalled. She labeled the proposal the most elaborately macabre scheme for obtaining organs that I have encountered, adding that it borders on ghoulishness. She saw the procedure as beyond the pale of the medically decent, morally allowable, and spiritually acceptable (Fox 1993, 232). But medically decent has seldom gotten in the way of procuring organs for transplant, and we now seem to be on the verge of adopting an uncontrolled version of organ procurement from a non-heart-beating cadaver. In their commentary describing this new procedure (uncontrolled donation after circulatory determination of death or uDCDD), Arjun Prabhu, Lisa Parker, and Michael DeVita seek to normalize uDCDD by pairing it with an equally disturbing, highly experimental, long-shot emergency intervention for cardiac arrest due to exsanguination (emergency preservation and resuscitation or EPR) (Prabhu et al 2017). They argue that the central ethical question presented by uDCDD is how a hospital can avoid the appearance of conflicts of interest when proposing both uDCDD and EPR. A more fundamental ethical question, we suggest, is whether either of these procedures both done without informed consent on minority communities whose members will be used as human guinea pigs-should be done at all

Circulating cardiac troponin I levels measured by a novel highly sensitive assay in acute decompensated heart failure: insights from the ASCEND-HF trial

Background: Circulating cardiac troponin levels (cTn), representative of myocardial injury, are commonly elevated in heart failure (HF) and related to adverse clinical events. However, whether cTn represents a spectrum of risk in HF is unclear. Methods: Baseline, 48–72 hour, and 30 day plasma cTnI was measured by a novel highly-sensitive assay in 900 subjects with acute decompensated HF (ADHF) in ASCEND-HF. Multivariable models determined the relationship between cTnI and outcomes. Results: The median(interquartile range) cTnI was 16.4 (9.3-31.6) ng/L at baseline, 14.1 (7.8-29.7) ng/L at 48-72 hours, and 11.6 (6.8-22.5) ng/L at 30 days. After additional adjustment for amino terminal pro-B-type natriuretic peptide (NT-proBNP) to established risk predictors, both baseline and 48-72 hour cTnI were associated with higher risk for death or worsening HF prior to discharge (OR 1.25, P=0.03 and OR 1.43, P=0.001, respectively). However, only cTnI at 30 days was associated 180-day death (HR 1.25, P=0.007). There were no curvilinear associations between changing cTnI and clinical outcomes. Conclusions: Circulating cTnI level was associated with clinical outcomes in ADHF, but these observations diminished with additional adjustment for NT-proBNP. Although they likely represent a spectrum of risk in ADHF, these findings question the implications of changing cTnI levels during treatment

Vibrational analysis of d-PCL(530)/siloxane based hybrids doped with two lithium salts

Published online: 22 May 2013The present study has been focused on environmentally friendly sol-gel derived electrolytes based on a di-urethane cross-linked d-PCL(530)/siloxane network (where d represents di, PCL identifies the poly(ε–caprolactone) biopolymer and 530 is the average molecular weight in g.mol-1) doped with a wide range of concentration of lithium perchlorate (LiClO4) and lithium bis(trifluoromethanesulfonyl)imide (LiTFSI). Fourier Transform Infrared and Raman (FT-IR and FT-Raman, respectively) spectroscopies have been applied to evaluate the extent of ionic association. Characteristic bands of the PCL(530) segments, of the urethane cross-links and of the anions have been examined to gain insight into the cation/biopolymer, cation/anion and cation/cross-link interactions. In both electrolyte systems “free” ions and contact ions have been identified. The addition of salt modifies the hydrogen-bonded array of the host matrix, causing the destruction/formation of the urethane/urethane aggregates.Fundação para a Ciência e a Tecnologia (FCT

The contribution of dynamic stromal remodeling during mammary development to breast carcinogenesis

Breast cancer is a heterogeneous disease whose prognosis varies depending upon the developmental stage of the breast tissue at diagnosis. Notably, breast cancers associated with pregnancy exhibit increased rates of metastasis and poorer long-term survival compared to those diagnosed after menopause. However, postmenopausal breast cancers associated with obesity exhibit a more aggressive behavior and confer decreased overall patient survival compared to those diagnosed in non-obese individuals. Since the mammary gland is a dynamic tissue that undergoes significant changes throughout a woman's lifetime, especially during pregnancy and following menopause, we present evidence to support the notion that changes occurring throughout development within the mammary stromal compartment may account for some of the biological differences in breast cancer subtypes and behaviors

Medical Ethics and Human Rights : Legacies of Nuremberg

Many of our most important human rights documents are the product of the world\u27s horror during the carnage of World War II. The broadest and most powerful declaration of human rights, the Universal Declaration of Human Rights, was adopted by the membership of the new United Nations in 1948. But there are also much more specific statements of the world\u27s aspirations for all of its inhabitants. August 1997 marked the 50th anniversary of the conclusion of the trial of Nazi physicians at Nuremberg, a trial which has been variously designated as the Doctors\u27 Trial and the Medical Case. 2 In addition to documenting atrocities committed by physicians and scientists during the war, the primary product of the trial has come to be known as the Nuremberg Code, a judicial codification of ten prerequisites for the moral and legal use of human beings in experiments. Anniversaries provide us with an opportunity to reflect on the past, but also to renew our efforts to plan for the future. Have we learned the lessons of the Doctors\u27 Trial? What can we do to make those lessons real for physicians and medical researchers 50 years later

Frozen Ethics: Melting the Boundaries between Medical Treatment and Organ Procurement

When Renee Fox, medical sociologist and noted historian of organ transplantation, first learned of the proposal to use non-heart-beating cadavers as organ sources more than 25 years ago, she was appalled. She labeled the proposal the most elaborately macabre scheme for obtaining organs that I have encountered, adding that it borders on ghoulishness. She saw the procedure as beyond the pale of the medically decent, morally allowable, and spiritually acceptable (Fox 1993, 232). But medically decent has seldom gotten in the way of procuring organs for transplant, and we now seem to be on the verge of adopting an uncontrolled version of organ procurement from a non-heart-beating cadaver. In their commentary describing this new procedure (uncontrolled donation after circulatory determination of death or uDCDD), Arjun Prabhu, Lisa Parker, and Michael DeVita seek to normalize uDCDD by pairing it with an equally disturbing, highly experimental, long-shot emergency intervention for cardiac arrest due to exsanguination (emergency preservation and resuscitation or EPR) (Prabhu et al 2017). They argue that the central ethical question presented by uDCDD is how a hospital can avoid the appearance of conflicts of interest when proposing both uDCDD and EPR. A more fundamental ethical question, we suggest, is whether either of these procedures both done without informed consent on minority communities whose members will be used as human guinea pigs-should be done at all

On the path toward personalized medicine: implications of pharmacogenetic studies of alcohol use disorder medications

IntroductionThe heritability of alcohol use disorder (AUD) is estimated to be ~50%; however, the genetic basis of the disease is still poorly understood. The genetic variants identified thus far only explain a small percentage of AUD phenotypic variability. While genome-wide association studies (GWAS) are impacted by technical and methodological limitations, genetic variants that have been identified independently of GWAS findings can moderate the efficacy of AUD medications.Areas coveredThis review discusses findings from clinical pharmacogenetic studies of AUD medications. While the pharmacogenetic studies reviewed involve several genetic variants in the major neurotransmitter systems, genetic loci in the opioid system have garnered the most attention.Expert opinionThe clinical utility of pharmacogenetics in AUD populations is uncertain at this time. There are several ongoing prospective clinical trials that will enhance knowledge regarding the applicability of pharmacogenetics in clinical populations. We recommend that future work in this area consider reverse translating from genotype to phenotype, mapping genes to stages of the addiction cycle, mapping genes to neural circuits, and harnessing large population-based cohorts

Chapter 13: The politics of immigrant and refugee health in the United States

Over 25 years of experience from the field have resulted in important lessons learned concerning how to best approach the multifaceted, complex treatment of immigrants and refugees. Continuing this work, it is important to educate medical communities about tried-and-true best practices and cultural sensitivity, as well as the integration of culturally-related practices in different clinical contexts. The medical model is inadequate to address the systematic challenges inherent in caring for displaced and traumatized populations. Beyond the clinical realm, systems are needed to advocate on behalf of immigrant and refugee communities using policy and law instruments; system-level intervention is the most effective way to address structural barriers to the highest possible standard of health and human rights

Evaluation of the Addictions Neuroclinical Assessment (ANA) framework through deep phenotyping of problem drinkers.

BackgroundTo advance the development of a neuroscience-informed understanding of alcohol use disorder (AUD) through the Addictions Neuroclinical Assessment (ANA) framework, the present study reports on deep phenotyping of a large sample of problem drinkers.MethodsParticipants (n = 1679) were primarily heavy drinkers with and without AUD, who completed a phenotypic battery of well-validated scales and behavioral measures of alcohol use and problems, mood, attention, and impulsivity. These scales were subjected to sequential factor analytic work in order to derive a factor solution that explains biobehavioral variation in the sample. To assess the construct validity of the resulting factor solution, scores on each factor were associated with demographic and clinical indicators.ResultsFactor analysis techniques using indicators of alcohol use and problems, mood, attention, and impulsivity implicated four functional domains that compliment and extend the proposed ANA domains: negative alcohol-related consequences, incentive salience, negative emotionality, and executive function. Demographic and clinical variables significantly predicted scores on all ANA domains.ConclusionsThis study provides an independent test of the recently proposed neuroscience-based ANA framework. Results largely support the novel approach in identifying four core constructs in problem drinkers. Future studies can deepen our understanding of how these domains are relevant to AUD by incorporating biomarkers