With the exponential growth of cardiovascular implantable electronic devices (CIEDs) in pediatric patients, a new method of long-term surveillance, remote monitoring (RM), has become the standard of care. The purpose of this study was to determine the usefulness of RM as a monitoring tool in the pediatric population. A retrospective review was performed of 198 patients at the University of Iowa Children’s Hospital who had CIEDs. Data transmitted by RM were analyzed. The following data were examined: patient demographics; median interval between transmissions; detection of adverse events requiring corrective measures, including detection of lead failure; detection of arrhythmias and device malfunctions independent of symptoms; time gained in the detection of events using RM versus standard practice; the validity of RM; and the impact of RM on data management. Of 198 patients, 162 submitted 615 RM transmissions. The median time between remote transmissions was 91 days. Of 615 total transmissions, 16 % had true adverse events with 11 % prompting clinical intervention. Of those events requiring clinical response, 61 % of patients reported symptoms. The median interval between last follow-up and occurrence of events detected by RM was 46 days, representing a gain of 134 days for patients followed-up at 6-month intervals and 44 days for patients followed-up at 3 month-intervals. The sensitivity and specificity of RM were found to be 99 and 72 %, respectively. The positive and negative predictive values were found to be 41 and 99 %, respectively. RM allows for early identification of arrhythmias and device malfunctions, thus prompting earlier corrective measures and improving care and safety in pediatric patients.
Photoreceptor morphogenesis in the sensory retina of chicks of 2 to 20 days incubation age was studied by scanning electron microscopy (SEM) and correlative transmission electron microscopy (TEM). At 9.5 days spherical inner segments extend into the subretinal space (optic ventricle). They are randomly arranged with chiefly smooth surfaces and contain centrioles, polyribosomes and microtubules. Microvilli project primarily from Müller cells. By the twelfth day immature ellipsoid and myoid regions have formed. Microvilli are abundant on the lateral surfaces of inner segments and extend over the entire spherical surface by the fifteenth day. Occasional cilia with surrounding depressions at their bases were also observed. Inner segments are more symmetrically arranged due to close proximity of photoreceptor cells. Inner segments elongate during the sixteenth day; many display a transitional ovoid form. Microvilli become less numerous but some persist as calycal processes. By the eighteenth day, conical shaped outer segments appear. Thereafter, all photoreceptor cells are comparable to those in the mature retina. Abundant microvilli on the external surface of the sensory retina suggest a supportive role in supplying adequate nutrition to the sensory retina during morphogenesis. The establishment and continual development of the ellipsoid and myoid appear to be primarily responsible for the elongation of photoreceptor cells.
Recent evidence has suggested that prolactin (PRL), internalized by lactogen-dependent Nb2 lymphoma cells, is actively translocated to the nucleus where it binds to PRL receptors. Moreover, the mitogenic action of PRL in these cells has been separately linked to protein tyrosyl phosphorylation and activation of protein kinase C (PKC). Therefore, the coupling of PRL internalization and nuclear translocation to the activation of these signal transduction pathways was investigated. Results from control experiments indicated that 30% of internalized and 5% total cell-associated 125I-rat PRL could be recovered within nuclei obtained from Nb2 cells previously incubated with the radiolabel for 3 h at 37 degrees C. Furthermore, internalized PRL was found to be intact and not associated with any carrier proteins. Addition of tyrosine kinase (TK) antagonists, genistein or tyrphostin, significantly reduced cell surface binding, internalization, and nuclear translocation of 125I-rat PRL. In contrast, neither the level of cell-associated nor internalized hormone differed between cells treated with the PKC antagonists, staurosporine or calphostin C, and control cultures. Instead, PKC inhibition significantly reduced nuclear PRL translocation. The inhibitory effects of the TK and PKC antagonists on PRL internalization and nuclear translocation in intact Nb2 cells were verified by immunofluorescence microscopy in parallel experiments. In other experiments, each of the kinase inhibitors blocked PRL-stimulated Nb2 cell proliferation in a concentration-dependent manner. It is concluded that activated TK and PKC collaborate in the process of PRL internalization and translocation to the nucleus. TK activation may participate in PRL receptor binding or hormone internalization while activation of PKC appears to be required for its nuclear targeting. Since TK and PKC activation are required for lactogen-stimulated Nb2 cell proliferation, we suggest that a component of the mitogenic pathway in these cells is a direct nuclear interaction of PRL.
This study presents scanning electron microscopic (SEM) observations of topographical changes that occur during morphogenesis of rod cells in the albino rat. Correlative transmission electron microscopy (TEM) was also utilized. Albino rats ranging in age from birth to three weeks were used for the study. Tissues were prepared by conventional methods for SEM and TEM. At birth, numerous irregularly arranged inner segments extend from the external surface of the sensory retina. They are spherical, smooth surfaced and possess a randomly oriented cilium. The internal morphology of these immature inner segments is comparable to that observed in other vertebrate species. Statistical analysis reveals a rapid increse in the number of rod cells during the first week. This period is characterized by the elongation of inner segments and their associated cilia. Microvilli project from the apices of Müller cells, but not from adjacent inner segments. By day 5, cilia occasionally display small bulbous outer segments. They are more numerous by day 8 and are usually eccentrically positioned at the tips of cilia. By day 11, outer segments are abundant and frequently obscure from view the underlying inner segments and associated cilia. Elongated cylindrical outer segments are present within the posterior retina at the end of the second week. However, rod cell morphogenesis lags in the peripheral retina. Topographical variations between developing photoreceptor cells in mammalian and non-mammalian retinas are discussed.
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