Stergiopoulos K.,Stony Brook University Medical Center
Journal of the American College of Cardiology | Year: 2011
To varying extents, women with pre-existing cardiomyopathies have a limited cardiovascular reserve. The hemodynamic challenges of pregnancy, labor, and delivery pose unique risks to this group of patients, which can result in clinical decompensation with overt heart failure, arrhythmias, and rarely, maternal death. A multidisciplinary team approach and a controlled delivery are crucial to adequate management of patients with underlying heart disease. Pre-conception planning and risk assessment are essential, and proper counseling should be offered to expectant mothers with regard to both the risks that pregnancy poses and the implications for future offspring. In this article, we will review the hemodynamic stressors that pregnancy places upon women with pre-existing cardiomyopathies and risk assessment and discuss what evidence exists with regard to the management of 2 forms of cardiomyopathy during pregnancy, labor, and delivery: dilated and hypertrophic cardiomyopathy. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Stanat S.J.C.,Stony Brook University Medical Center |
Capozzi J.D.,Winthrop University
Journal of Arthroplasty | Year: 2012
Postoperative squeaking in ceramic-on-ceramic total hip arthroplasty is a recently emerging phenomenon. We performed a meta-analysis of published data to examine patient and procedural risk factors. Twelve studies (6137 patients, total) were analyzed, with 150 patients (2.4%) complaining of squeaking. The only significant patient risk factor was increasing body mass index (P =.03, n = 2957). There was no significance found with patient age, sex, height, weight, or procedural laterality for squeak incidence. For implant type, the presence of a Stryker Accolade femoral stem (beta-titanium; Stryker Orthopedics, Mahwah, NJ) was significantly found to increase squeak (P <.0001, n = 4654). The presence of a raised metallic lip on the acetabular component was not found to be associated with squeak. Acetabular cup position was also not found to have a significant bearing on the incidence of squeaking. © 2012 Elsevier Inc.
Lieberthal W.,Stony Brook University Medical Center |
Levine J.S.,University of Illinois at Chicago
American Journal of Physiology - Renal Physiology | Year: 2012
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays a fundamental role in regulating cellular homeostasis and metabolism. In a two-part review, we examine the complex molecular events involved in the regulation and downstream effects of mTOR, as well as the pivotal role played by this kinase in many renal diseases, particularly acute kidney injury, diabetic nephropathy, and polycystic kidney diseases. Here, in the first part of the review, we provide an overview of the complex signaling events and pathways governing mTOR activity and action. mTOR is a key component of two multiprotein complexes, known as mTOR complex 1 (mTORC1) and 2 (mTORC2). Some proteins are found in both mTORC1 and mTORC2, while others are unique to one or the other complex. Activation of mTORC1 promotes cell growth (increased cellular mass or size) and cell proliferation (increased cell number). mTORC1 acts as a metabolic "sensor," ensuring that conditions are optimal for both cell growth and proliferation. Its activity is tightly regulated by the availability of amino acids, growth factors, energy stores, and oxygen. The effects of mTORC2 activation are distinct from those of mTORC1. Cellular processes modulated by mTORC2 include cell survival, cell polarity, cytoskeletal organization, and activity of the aldosteronesensitive sodium channel. Upstream events controlling mTORC2 activity are less well understood than those controlling mTORC1, although growth factors appear to stimulate both complexes. Rapamycin and its analogs inhibit the activity of mTORC1 only, and not that of mTORC2, while the newer "catalytic" mTOR inhibitors affect both complexes. © 2012 the American Physiological Society.
Coyle P.K.,Stony Brook University Medical Center
CNS Drugs | Year: 2013
There are currently nine approved disease modifying therapies for relapsing forms of multiple sclerosis, with six distinct mechanisms of action. All have side effects, and none are cures. When a patient cannot tolerate therapy, or there is unacceptable breakthrough disease activity, the most common approach is to change drug. No universal guidelines exist for switching therapy. This overview will propose switch principles and suggestions. © 2013 Springer International Publishing Switzerland.
Mathison M.,Stony Brook University Medical Center
Journal of the American Heart Association | Year: 2012
In situ cellular reprogramming offers the possibility of regenerating functional cardiomyocytes directly from scar fibroblasts, obviating the challenges of cell implantation. We hypothesized that pretreating scar with gene transfer of the angiogenic vascular endothelial growth factor (VEGF) would enhance the efficacy of this strategy. Gata4, Mef2c, and Tbx5 (GMT) administration via lentiviral transduction was demonstrated to transdifferentiate rat fibroblasts into (induced) cardiomyocytes in vitro by cardiomyocyte marker studies. Fisher 344 rats underwent coronary ligation and intramyocardial administration of an adenovirus encoding all 3 major isoforms of VEGF (AdVEGF-All6A(+)) or an AdNull control vector (n=12/group). Lentivirus encoding GMT or a GFP control was administered to each animal 3 weeks later, followed by histologic and echocardiographic analyses. GMT administration reduced the extent of fibrosis by half compared with GFP controls (12 ± 2% vs 24 ± 3%, P<0.01) and reduced the number of myofibroblasts detected in the infarct zone by 4-fold. GMT-treated animals also demonstrated greater density of cardiomyocyte-specific marker beta myosin heavy chain 7(+) cells compared with animals receiving GFP with or without VEGF (P<0.01). Ejection fraction was significantly improved after GMT vs GFP administration (12 ± 3% vs -7 ± 3%, P<0.01). Eight (73%) GFP animals but no GMT animals demonstrated decreased ejection fraction during this interval (P<0.01). Also, improvement in ejection fraction was 4-fold greater in GMT/VEGF vs GMT/null animals (17 ± 2% vs 4 ± 1%, P<0.05). VEGF administration to infarcted myocardium enhances the efficacy of GMT-mediated cellular reprogramming in improving myocardial function and reducing the extent of myocardial fibrosis compared with the use of GMT or VEGF alone.