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Victor R.G.,Cedars Sinai Medical Center
Nature Reviews Cardiology | Year: 2015

Arterial baroreceptors are mechanosensitive sensory nerve endings in the walls of the carotid sinuses and aortic arch that buffer the increases and decreases in arterial blood pressure. Electrical field stimulation of the carotid sinus, known as carotid baroreflex activation therapy, holds promise as a novel device-based intervention to supplement, but not replace, drug therapy for patients with resistant hypertension. Acute electrical field stimulation of even one carotid sinus can cause a sufficiently large reflex decrease in blood pressure to overcome offsetting reflexes from the contralateral carotid baroreceptors and aortic baroreceptors that are not paced. However, the initial phase III Rheos Pivotal Trial on continuous carotid baroreceptor pacing for resistant hypertension with the first-generation baroreceptor pacemaker yielded equivocal data on efficacy and adverse effects due to facial nerve injury during surgical implantation. A miniaturized second-generation pacing electrode has seemingly overcome the safety issue, and early results with the new device suggest efficacy of unilateral carotid sinus stimulation in heart failure. A phase III trial of this new device for resistant hypertension has been registered. © 2015 Macmillan Publishers Limited. Source

Almost exactly 20 years after their discovery, the BRCA1 and BRCA2 genes have become the target of the first "personalized" therapy available for patients with ovarian cancer. In December 2014, a poly(ADP-ribose) polymerase (PARP) inhibitorwas granted expedited approved by the United States Food and Drug Administration for use in advanced ovarian cancer patients with germline BRCA1/2 mutations who have received three or more prior lines of chemotherapy. This review article will discuss (1) the BRCA1 and BRCA2 genes within the larger context of homologous recombination deficiency; (2) the advances in our understanding of hereditary cancer risk and the dramatic shifts that have occurred in the genetic testing landscape since the landmark 2013 Supreme Court ruling invalidating patents on BRCA1 and BRCA2 genetic testing; and (3) the clinical trials leading to the approval of olaparib, the first in human PARP inhibitor. © 2015 Elsevier Inc. Source

Svendsen C.N.,Cedars Sinai Medical Center
Human Molecular Genetics | Year: 2013

Based on cloning studies in mammals, all adulthumancells theoretically containDNAthat is capable of creating a whole new person. Cells are maintained in their differentiated state by selectively activating some genes and silencing. The dogma until recently was that cell differentiation was largely fixed unless exposed to the environment of an activated oocyte. However, it is now possible to activate primitive pluripotent genes within adult human cells that take them back in time to a pluripotent state (termed induced pluripotent stem cells). This technology has grown at an exponential rate over the past few years, culminating in the Nobel Prize in medicine. Discussed here are recent developments in the field as they relate to regenerative medicine, with an emphasis on creating functional cells, editing their genome, autologous transplantation and how this ground-breaking field may eventually impact human aging. © The Author 2013. Published by Oxford University Press. Source

Forrester J.S.,Cedars Sinai Medical Center
Journal of the American College of Cardiology | Year: 2010

The new Adult Treatment Panel guidelines will be published in 2011. This paper suggests the consideration of major changes in the existing management guidelines for low-density lipoprotein cholesterol management based on 2 fundamental principles: return the low-density lipoprotein cholesterol level to the normal range and begin treatment closer to disease onset. These principles suggest the value of rethinking all 3 of the principal features of the Adult Treatment Panel III guidelines for low-density lipoprotein cholesterol management: the initiation criteria, the use of variable targets, and the level of the treatment target. Because the principal issue surrounding guideline change is likely to be uncertainty concerning cost and toxicity, the text of new guidelines would have to completely satisfy this concern by strong emphasis on a prudent conservative approach to implementation and would include both cautionary data and caveats concerning the tradeoffs between the potency, cost, and toxicity of statins. The proposed changes in the guidelines, if combined with effective implementation, would likely lead to the displacement of atherosclerotic disease as the nation's number 1 killer. This review provides a logical rationale and discusses the pros and cons for each of the proposed changes. © 2010 American College of Cardiology Foundation. Source

Wallace D.J.,Cedars Sinai Medical Center
Nature Reviews Rheumatology | Year: 2015

Drug discovery in systemic lupus erythematosus (SLE) has lagged behind other rheumatic diseases, in large part because of difficulty in measuring change or improvement in a disorder that involves multiple organ systems to varying degrees at different times. The metrics currently used as primary endpoints are composite indices that rely mainly on disease assessment measures derived before the era of clinical trials of targeted therapies. Only one agent has been approved for the treatment of SLE since 1957. This monograph reviews the evolution of drug development for SLE, problems and pitfalls that have been encountered, and outlines the domains used to evaluate SLE in the clinic. Finally, several initiatives underway to improve clinical trial design are outlined. © 2015 Macmillan Publishers Limited. Source

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