Fast Image-Based Model of Mitral Valve Closure for Surgical Planning

Surgical repair of the mitral valve results in better outcomes than valve replacement, yet diseased valves are often replaced due to the technical difficulty of the repair process. A surgical planning system based on patient-specific medical images that allows surgeons to simulate and compare potential repair strategies could greatly improve surgical outcomes. The system must simulate valve closure quickly and handle the complex boundary conditions imposed by the chords that tether the valve leaflets. We have developed a process for generating a triangulated mesh of the valve surface from volumetric image data of the opened valve. The closed position of the mesh is then computed using a mass-spring model of dynamics. In the mass-spring model, triangle sides are treated as linear springs supporting only tension. Chords are also treated as linear springs, and self-collisions are detected and handled inelastically. The equations of motion are solved using implicit numerical integration. The simulated closed state is compared with an image of the same valve taken in the closed state to assess accuracy of the model. The model exhibits rapid valve closure and is able to predict the closed state of the valve with reasonable accuracy.Engineering and Applied Science

Cleft closure and undersizing annuloplasty improve mitral repair in atrioventricular canal defects

ObjectiveReoperation rates to correct left atrioventricular valve regurgitation after primary repair of atrioventricular canal defects remain relatively high. The causes of valvular regurgitation are likely multifactorial, and simple cleft closure is often insufficient to prevent recurrence.MethodsTo elucidate the mechanisms leading to regurgitation, we conducted hemodynamic studies using isolated native mitral valves. Anatomy of these valves was altered to mimic atrioventricular canal type valves and studied under pediatric hemodynamic conditions. The impact of subvalvular geometry, cleft closure, annular dilatation, and annular undersizing on regurgitation were investigated.ResultsPapillary muscle position did not have a significant effect on regurgitation. Cleft closure had a significant impact on valvular competence, with reduction in regurgitation volume with increased cleft closure. Regurgitation volume decreased from 12.5 ± 2.4 mL/beat for an open cleft to 4.9 ± 1.9 mL/beat for a partially closed cleft and to 1.4 ± 1.6 mL/beat when the cleft was completely closed. Annular dilatation had a significant impact on regurgitation even after cleft closure. A 40% increase in annular size increased regurgitation by 59% for a partially closed cleft and by 84% for a fully closed cleft. Reducing the annular size by 20% from the physiologic level decreased the regurgitation volume by 12% for a fully open cleft and by 58% for the partially closed cleft case.ConclusionsAnnular dilatation after primary repair has a potentially significant role in the recurrence of atrioventricular valve regurgitation. Reducing the annular size and restricting dilatation as an adjunct to cleft closure is a promising surgical approach in such valve anatomies

A decade (1982 to 1992) of pediatric cardiac transplantation and the impact of FK 506 immunosuppression

The decade from 1982 through 1992 witnessed tremendous growth in pediatric cardiac transplantation. At Children's Hospital of Pittsburgh 66 cardiac transplants were performed during this period (age range 7 hours to 18 years). The cause of cardiomyopathy was congenital (n = 30), cardiomyopathy (n = 29), myocarditis (n = 2), doxorubicin toxicity (n = 2), ischemic (n = 1), valvular (n = 1), and cardiac angiosarcoma (n = 1). Nine children (14 %) required mechanical circulatory support before transplantation: extracorporeal membrane oxygenation (n = 8) and Novacor left ventricular assist system (n = 1) (Baxter Healthcare Corp., Novacor Div., Oakland, Calif.). The mean follow-up time was 2 years (range 4 months to 8 years). The overall survival in the group was 67 %. In children with congenital heart disease (>6 months of age) the perioperative (30 day) mortality was 66 % before mid-1988 (n = 10) and 0 % since mid-1988 (n = 11). The late mortality (>30 days) in children with cardiomyopathy transplanted prior to mid-1988 was 66 % (n = 14) and 7 % since mid-1988 (n = 15). Since mid-1988 1- and 3-year survival was 82 % in children with congenital heart disease and 90 % in children with cardiomyopathy. Twenty-six children have had FK 506 as their primary immunosuppressive therapy since November 1989. Survival in this group was 82 % at 1 and 3 years. The actuarial freedom from grade 3A rejection in the FK group was 60 % at 3 and 6 months after transplantation versus 20 % and 12 %, respectively, in the 15 children operated on before the advent of FK 506, who were treated with cyclosporine-based triple-drug therapy (p < 0.001, Mantel-Cox and Breslow). Twenty of 24 children (83 %) in the FK 506 group are receiving no steroids. The prevalence of posttransplantation hypertension was 4 % in the FK 506 group versus 70 % in the cyclosporine group (p < 0.001, Fisher). Renal toxicity in children treated with FK 506 has been mild. Additionally, eight children have been switched to FK 506 because of refractory rejection and drug toxicity. FK 506 has not produced hirsutism, gingival hyperplasia, or abnormal facial bone growth. The absence of these debilitating side effects, together with the observed immune advantage and steroid-sparing effects of FK 506, hold tremendous promise for the young patient facing cardiac transplantation and a future wedded to immunosuppression

Contribución de la Paleofitogeografía a la interpretación del paisaje vegetal ibérico: estado de conocimientos y nuevas perspectivas de investigación

The palaeobotanical studies that have been accomplished in the Iberian Peninsula during the last two decades have provided a great amount of data that can be applied in geobotanical knowledge. In most of the cases, those results have contributed to solve classical scientific debates regarding vegetal landscapes interpretations. One of the most relevant discussions is related to the aloctonous or non-aloctonous origin of much of the Iberian pine forests, on diverse Iberian habitats. The main contributions of Palaeobotany to the processes that explain the present distribution of plants are reviewed in a spatial and temporal framework, from old geological periods (Mesozoic, Tertiary) to the recent ones (Pleistocene, Holocene). Linked to the history of our vegetal landscapes, Pleistocene and Holocene epochs have been treated from two different points of view: firstly the problems within extensive territorial environments and, secondly, the problems related to the interpretation of the evolution and/or behaviour of taxa. In the last part, some new investigation trends related to palaeophytogeography are exposed, focusing on the high potential interest on being applied to Iberian ecosystems.Los trabajos de car&aacute;cter paleobot&aacute;nico realizados en la pen&iacute;nsula Ib&eacute;rica en las dos &uacute;ltimas d&eacute;cadas han proporcionado un importante volumen de resultados con aplicaci&oacute;n en el &aacute;mbito del conocimiento geobot&aacute;nico. En muchos casos, esos resultados han aportado soluciones a debates cl&aacute;sicos relativos a la interpretaci&oacute;n del paisaje vegetal. Uno de los m&aacute;s conocidos es el de la consideraci&oacute;n, como espont&aacute;neos o no, de muchos de los pinares ib&eacute;ricos en diferentes &aacute;mbitos del territorio peninsular. Se revisan las contribuciones m&aacute;s importantes de la Paleobot&aacute;nica a los procesos que explican la actual distribuci&oacute;n de las plantas, en un marco tanto espacial como temporal, desde periodos geol&oacute;gicos antiguos (Mesozoico, Terciario) a los m&aacute;s recientes (Pleistoceno, Holoceno). Dentro de estos &uacute;ltimos nos hemos referido, por una parte, a problemas planteados en &aacute;mbitos territoriales extensos y, por otra, a problemas vinculados a la interpretaci&oacute;n de la evoluci&oacute;n y/o comportamiento de taxones concretos. Por &uacute;ltimo se hace referencia a las tendencias recientes y nuevas metodolog&iacute;as de aplicaci&oacute;n en paleofitogeograf&iacute;a, aludiendo a los primeros resultados que hayan podido proporcionar en el marco peninsular

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field