Alterations in serum sodium in relation to atrial natriuretic factor and other neuroendocrine variables in experimental pacing-induced heart failure

The pathophysiologic role of atrial natriuretic factor and other neuroendocrine variables in relation to serum sodium and renal function was evaluated in 15 conscious dogs with severe chronic ventricular pacing-induced heart failure (250 beats/min for 5.1 +/- 0.4 weeks). Six sham-operated dogs observed over an 8 week period served as controls. Development of heart failure was characterized by a progressive increase in plasma norepinephrine, renin activity and aldosterone from control values of 293 +/- 15 pg/ml, 1.4 +/- 0.4 ng/ml per h and 124 +/- 42 pg/ml, respectively, to 1,066 +/- 96 pg/ml, 10.2 +/- 2.4 ng/ml per h and 577 +/- 151 pg/ml (all p less than 0.01), respectively, at severe heart failure. In contrast to other neuroendocrine variables, plasma atrial natriuretic factor increased from a control level of 243 +/- 74 pg/ml to a peak concentration of 724 +/- 149 pg/ml (p less than 0.01) at 2 weeks, then declined and plateaued at twice the level of the control value as severe heart failure developed. At severe heart failure, serum sodium decreased from 147 +/- 0.6 to 141.8 +/- 2.1 mmol/liter (p less than 0.05), whereas urea increased from 6.0 +/- 0.5 to 7.8 +/- 0.6 mmol/liter (p less than 0.05). The change in serum sodium concentration correlated with plasma renin activity and aldosterone (r = -0.77, -0.88, respectively, both p less than 0.01), but not with norepinephrine or atrial natriuretic factor. When sinus rhythm was restored, 14 dogs were observed for 48 to 72 h and 8 dogs were followed up for another 4 weeks after cessation of pacing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Continuity and Change in the Genetic and Environmental Etiology of Youth Antisocial Behavior

Behavior Genetics - Trajectories of youth antisocial behavior (ASB) are characterized by both continuity and change. Twin studies have further indicated that genetic factors underlie continuity,...     

Hepatitis C recurrence: the Achilles heel of liver transplantation

Hepatitis C virus (HCV) infection is the most common indication for liver transplantation worldwide; however, recurrence post transplant is almost universal and follows an accelerated course. Around 30% of patients develop aggressive HCV recurrence, leading to rapid fibrosis progression (RFP) and culminating in liver failure and either death or retransplantation. Despite many advances in our knowledge of clinical risks for HCV RFP, we are still unable to accurately predict those most at risk of adverse outcomes, and no clear consensus exists on the best approach to management. This review presents a critical overview of clinical factors shown to influence the course of HCV recurrence post transplant, with particular focus on recent data identifying the important role of metabolic factors, such as insulin resistance, in HCV recurrence. Emerging data for genetic markers of HCV recurrence and their usefulness for predicting adverse outcomes will also be explored.     

Life insurance: genomic stratification and risk classification

With the development and increasing accessibility of new genomic tools such as next-generation sequencing, genome-wide association studies, and genomic stratification models, the debate on genetic discrimination in the context of life insurance became even more complex, requiring a review of current practices and the exploration of new scenarios. In this perspective, a multidisciplinary group of international experts representing different interests revisited the genetics and life insurance debate during a 2-day symposium ‘Life insurance: breast cancer research and genetic risk prediction seminar'' held in Quebec City, Canada on 24 and 25 September 2012. Having reviewed the current legal, social, and ethical issues on the use of genomic information in the context of life insurance, the Expert Group identified four main questions: (1) Have recent developments in genomics and related sciences changed the contours of the genetics and life insurance debate? (2) Are genomic results obtained in a research context relevant for life insurance underwriting? (3) Should predictive risk assessment and risk stratification models based on genomic data also be used for life insurance underwriting? (4) What positive actions could stakeholders in the debate take to alleviate concerns over the use of genomic information by life insurance underwriters? This paper presents a summary of the discussions and the specific action items recommended by the Expert Group.Access to genetic information by life insurers has been a topic of discussion for many years.¹ The possibility of using genetic data to underwrite an applicant''s insurance policy has given rise to concerns about the emergence of ‘genetic discrimination''. Genetic discrimination in the field of life insurance is not necessarily illegal in that in insurance underwriting questions about health, family history of disease, or genetic information may constitute legal exceptions to antidiscrimination legislation.^{2, 3} Nevertheless, the expression ‘genetic discrimination'' has acquired public notoriety⁴ and we will use more neutral language in this paper.Countries including Canada, the United States, Russia, and Japan⁵ have chosen not to adopt laws specifically prohibiting access to genetic data for underwriting by life insurers.⁶ In these countries, life insurance underwriters treat genetic data like other types of medical or lifestyle data. However, a growing number of countries such as Belgium, France, and Norway⁵ have chosen to adopt laws to prevent or limit insurers'' access to genetic data for life insurance underwriting. Other countries including Finland and the United Kingdom have developed voluntary arrangements with the industry (ie moratoria) with similar objectives.⁷Life insurance is a private contract between the policy-holder and the insurer. Its principal role is to provide financial security to the beneficiaries in the event of the insured''s death.⁸ Because of this important role, life insurance is often required, or strongly recommended for those seeking loans to acquire primary social goods, like housing or cars.⁹ In Europe, a consequence of the advent of the welfare state is that private insurance has increasingly played a complementary and supplementary role to social insurance by offering additional security and protection to the population. Thus, in this region, insurance is often considered as a social good that allows individuals to live a comfortable life and as a tool to promote social integration.¹⁰ In other regions of the world, this social role of life insurance is also recognized to a lesser extent. Given this social role, equitable access to life insurance is perceived as a sensitive issue and cases of denial looked upon negatively in popular media. Although documented incidents of denial or of increased premiums on the basis of genetic information have remained limited to the context of a few relatively well known, highly penetrant, familial, adult-onset, genetic conditions,¹¹ they have nevertheless generated significant public concern. Fear that insurers will have access to genetic information generated in a clinical or research setting for use in underwriting has been reported by several studies as a reason for non-participation in genetic research or recommended clinical genetic testing.^{12, 13, 14}The clinical utility of genetic testing for monogenic disorders such as Huntington disease, and hereditary forms of cancer are well established.¹⁵ However, genomic risk profiles based on the known common susceptibility variants have limited utility in risk prediction at the individual level, although they could be used for risk stratification in prevention programmes in populations.¹⁶ Today, a new era of genomic research has made it increasingly affordable to scan the entire genome of an individual. Researchers and physicians can interpret these data together with medical and lifestyle information in the form of sophisticated risk prediction models.¹⁷ Moreover, improvement in computing technologies coupled with the Internet make predictive information increasingly available, whether through direct-to-consumer marketing of genetic tests, genetic data sharing online communities, or international research database projects. Given these important technological and scientific changes, and their impact on various stakeholders. The term ‘stakeholders'' is used in this text to refer to the following groups of individuals: actuaries (person who computes insurance risk and premium rates based on statistical data), academic researchers, community representatives, ethics committees, genetic counsellors, genomic researchers, human rights experts, insurers, governmental representatives, non-governmental organisations, patient representatives, physicians, policy makers, popular media, reinsurers (company in charge of calculating the risk and premium amount for insuring a particular customer), research participants, and underwriters (company or person in charge of calculating the risk involved in providing insurance for a particular customer and to decide how much should be paid for the premium). This list is not meant to be exhaustive as relevant new groups may emerge as this topic further develops in the coming years. A multidisciplinary group of international experts representing different interests (hereinafter ‘the Expert Group'') revisited the genetics and life insurance debate. The following text presents a summary of the issues discussed and the ‘Action Items'' agreed upon by the Expert Group at the ‘Life Insurance, Risk Stratification, and Personalized Medicine Symposium''.