A novel algorithm for classification of interatrial communications within the oval fossa in the newborn.

BACKGROUND: An interatrial communication is present in most neonates. The majority are considered the "normal" patency of the oval foramen, while a minority are abnormal atrial septal defects. Differentiation between the two with transthoracic echocardiography may be challenging, and no generally accepted method of classification is presently available. We aimed to develop and determine the reliability of a new classification of interatrial communications in newborns. METHODS AND RESULTS: An algorithm was developed based on echocardiographic criteria from 495 newborns (median age 11[8;13] days, 51.5% females). The algorithm defines three main categories: patency of the oval foramen, atrial septal defect, and no interatrial communication as well as several subtypes. We found an interatrial communication in 414 (83.6%) newborns. Of these, 386 (93.2%) were categorised as patency of the oval foramen and 28 (6.8%) as atrial septal defects.Echocardiograms from another 50 newborns (median age 11[8;13] days, 36.0% female), reviewed by eight experts in paediatric echocardiography, were used to assess the inter- and intraobserver variation of classification of interatrial communications into patency of the oval foramen and atrial septal defect, with and without the use of the algorithm. Review with the algorithm gave a substantial interobserver agreement (kappa = 0.66), and an almost perfect intraobserver agreement (kappa = 0.82). Without the use of the algorithm, the interobserver agreement between experienced paediatric cardiologists was low (kappa = 0.20). CONCLUSION: A new algorithm for echocardiographic classification of interatrial communications in newborns produced almost perfect intraobserver and substantial interobserver agreement. The algorithm may prove useful in both research and clinical practice.

The Configuration of the Perivascular System Transporting Macromolecules in the CNS.

Large blood vessels entering the CNS are surrounded by perivascular spaces that communicate with the cerebrospinal fluid and, at their termini, with the interstitial space. Solutes and particles can translocate along these perivascular conduits, reportedly in both directions. Recently, this prompted a renewed interest in the intrathecal therapy delivery route for CNS-targeted therapeutics. However, the extent of the CNS coverage by the perivascular system is unknown, making the outcome of drug administration to the CSF uncertain. We traced the translocation of model macromolecules from the CSF into the CNS of rats and non-human primates. Conduits transporting macromolecules were found to extend throughout the parenchyma from both external and internal (fissures) CNS boundaries, excluding ventricles, in large numbers, on average ca. 40 channels per mm2 in rats and non-human primates. The high density and depth of extension of the perivascular channels suggest that the perivascular route can be suitable for delivery of therapeutics to parenchymal targets throughout the CNS.

Preparing New World monkeys for laboratory research.

New World monkeys represent an important but often poorly understood research resource. The relatively small size and low zoonotic risk of these animals make them appealing as research subjects in a number of areas. However, historic portrayal of many of these species as difficult to manage and handle is one of the factors that has limited their use. Basic guidelines are provided on management and handling approaches for the New World monkeys most commonly used in research: marmosets, squirrel monkeys, owl monkeys, and titi monkeys. Topics include transport and acclimation to a new facility, location changes within a facility, diet changes, removal from and return to social groups, capture and restraint, handling for anesthesia, postprocedural monitoring, and staff training.

Differential expression of GLUT2 in pancreatic islets and kidneys of New and Old World nonhuman primates.

Diabetes is a growing public health concern, and animal models of this disease are necessary for a full understanding of disease pathogenesis, progression, clinical sequelae, and treatment options. In particular, nonhuman primate models of diabetes are important because of their close genetic relationship to humans. Although numerous Old World primate models have been described, few studies have examined the possibility of using New World monkeys as an animal model for this disease. Streptozotocin (STZ) is a common diabetogenic drug that selectively destroys beta cells after uptake via the GLUT2 glucose transporter. Induction of diabetes using STZ was attempted in common marmosets (Callithrix jacchus). These animals showed increases in blood glucose consistent with diabetes only at STZ doses markedly greater than those used in other primate species. Additionally, all animals showed pathological evidence of acute renal and liver toxicity secondary to the treatment. In a subsequent comparative study of various nonhuman primates, GLUT2 immunostaining in pancreatic islets was used as a marker for sensitivity to STZ. Immunostaining of islets from a variety of nonhuman primate species indicated a reduced expression of pancreatic GLUT2 in New compared with Old World monkeys; this finding explains their resistance to diabetic induction with STZ. Furthermore, there were age-dependent differences in GLUT2 expression, with aged and infant macaques showing reduced expression. We conclude that New World monkeys are an inappropriate model for diabetes induction with STZ and that, with all primate species, it is important to consider the animals' age before diabetic induction with STZ is attempted.