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Gap junctions play a fundamental role in intercellular communication in cardiac tissue. Various types of heart disease including hypertrophy and ischemia are associated with alterations of the spatial arrangement of gap junctions. Previous studies applied two-dimensional optical and electron-microscopy to visualize gap junction arrangements. In normal cardiomyocytes, gap junctions were primarily found at cell ends, but can be found also in more central regions. In this study, we extended these approaches toward three-dimensional reconstruction of gap junction distributions based on high-resolution scanning confocal microscopy and image processing. We developed methods for quantitative characterization of gap junction distributions based on analysis of intensity profiles along the principal axes of myocytes. The analyses characterized gap junction polarization at cell ends and higher-order statistical image moments of intensity profiles. The methodology was tested in rat ventricular myocardium. Our analysis yielded novel quantitative data on gap junction distributions. In particular, the analysis demonstrated that the distributions exhibit significant variability with respect to polarization, skewness, and kurtosis. We suggest that this methodology provides a quantitative alternative to current approaches based on visual inspection, with applications in particular in characterization of engineered and diseased myocardium. Furthermore, we propose that these data provide improved input for computational modeling of cardiac conduction.

During the 1990s, bioethicists raised questions about certain clinical trials conducted in developing countries. These inquiries led to revisions in the Declaration of Helsinki and recommendations from the US National Bioethics Advisory Commission. This article raises doubts about the original questions and subsequent recommendations. It is possible that impractical solutions have been proposed for nonexistent ethical problems.

Several ethicists have raised criticisms of various placebo-controlled clinical trials conducted in developing countries between 1995 and 1998. This essay reviews and rejects the arguments that these trials violated basic canons of medical ethics, or constituted exploitation by scientists in advanced countries of subjects in developing countries. A uniform international standard for the evaluation of such trials is proposed, replacing the old standard of voluntary and informed consent with a more focused standard of uncoerced and undeceived consent.