The value of ethical principles to reflect on emerging issues in epilepsy care and research.

In the age of patient participation, ethics are more important than ever to help guide clinicians in situations of uncertainty. Principles of Biomedical Ethics by James F. Childress and Thomas L. Beauchamp remains the most important reference in medical ethics. In their work, they conceptualize four principles designed to help guide clinicians in decision making, notably beneficence, non-maleficence, autonomy, and justice. While using ethical principles dates back to at least Hippocrates, the introduction by Beauchamp and Childress of the principles of autonomy and justice have helped to deal with new challenges. This contribution will discuss how the principles can help elucidate issues of patient participation in epilepsy care and research using two case studies. METHODS: In this paper, we will discuss the equilibrium to be found between two principles (beneficence and autonomy) in the context of emerging debates in epilepsy care and research. The methods section details the specificities of each principle and their relevance to epilepsy care and research. RESULTS AND DISCUSSION: Using two case studies, we will explore the potential and limits of patient participation and how the ethical principles may help to provide nuance and reflection in this emerging debate. First of all, we will explore a clinical case which involves a conflictual situation with the patient and family about psychogenic nonepileptic seizures. We will then discuss an emerging issue in epilepsy research, namely the integration of persons with severe refractory epilepsy as patient research partners.

Effect of glucose on production and release of proinsulin conversion products by cultured human islets.

Isolated human islets were examined for the rates of conversion and release of newly formed (pro)insulin-like peptides. The rate of proinsulin (PI) conversion was 2-fold slower in human beta-cells (t(1/2) = 50 min) than in rat beta-cells (t(1/2) = 25 min). During the first hour following labeling of newly synthesized proteins, PI represented the main newly formed hormonal peptide in the medium; its release was stimulated 2-fold over the basal level by 20 mmol/L glucose. During the second hour, newly synthesized hormone was mainly released as insulin, with 10- to 20-fold higher rates at 20 mmol/L glucose. Prolonged preculture of the islets at 20 mmol/L glucose did not delay PI conversion, but markedly increased the release of newly formed PI, des(31,32)-PI, and insulin at both low and high glucose levels. Our data demonstrate that 1) the release of PI provides an extracellular index for the hormone biosynthetic activity of human beta-cells; 2) an acute rise in glucose exerts a stronger amplification of the release of converted hormone than in that of nonconverted hormone; and 3) prolonged exposure to high glucose levels results in an elevated basal release of converted and nonconverted PI; this elevation is not associated with a delay in PI conversion, but is attributed to the hyperactivated state of the human beta-cell population, which was recently found to be responsible for an elevation in basal rates of hormone synthesis. These in vitro observations on human beta-cells provide a possible explanation for the altered circulating (pro)insulin levels measured in nondiabetic and noninsulin-dependent diabetic subjects.

Orthogonal projection approach applied to peak purity assessment.

The orthogonal projection approach (OPA), a stepwise approach based on an orthogonalization algorithm, is proposed. The performance of OPA for the assessment of peak purity in HPLC-DAD is described and compared with that of SIMPLISMA. The occurrence of artifacts in both approaches under nonideal situations is discussed.