Home About us Contact
|
Home About us Contact | ||
|
|
||
Mount Sinai School Of Medicine (mount + sinai_school_of_medicine)
Selected AbstractsProtein Kinase Target Discovery From Genome-Wide Messenger RNA Expression ProfilingMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 4 2010Avi Ma'ayan Abstract Genome-wide messenger RNA profiling provides a snapshot of the global state of the cell under different experimental conditions such as diseased versus normal cellular states. However, because measurements are in the form of quantitative changes in messenger RNA levels, such experimental data does not provide direct understanding of the regulatory molecular mechanisms responsible for the observed changes. Identifying potential cell signaling regulatory mechanisms responsible for changes in gene expression under different experimental conditions or in different tissues has been the focus of many computational systems biology studies. Most popular approaches include promoter analysis, gene ontology, or pathway enrichment analysis, as well as reverse engineering of networks from messenger RNA expression data. Here we present a rational approach for identifying and ranking protein kinases that are likely responsible for observed changes in gene expression. By combining promoter analysis; data from various chromatin immunoprecipitation studies such as chromatin immunoprecipitation sequencing, chromatin immunoprecipitation coupled with paired-end ditag, and chromatin immunoprecipitation-on-chip; protein-protein interactions; and kinase-protein phosphorylation reactions collected from the literature, we can identify and rank candidate protein kinases for knock-down, or other types of functional validations, based on genome-wide changes in gene expression. We describe how protein kinase candidate identification and ranking can be made robust by cross-validation with phosphoproteomics data as well as through a literature-based text-mining approach. In conclusion, data integration can produce robust candidate rankings for understanding cell regulation through identification of protein kinases responsible for gene expression changes, and thus rapidly advancing drug target discovery and unraveling drug mechanisms of action. Mt Sinai J Med 77:345,349, 2010. © 2010 Mount Sinai School of Medicine [source] Ruptured Abdominal Aortic Aneurysms: Role of Endovascular TherapyMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 3 2010Neal S. Cayne MD Abstract Ruptured abdominal aortic aneurysms historically have high mortality rates. Despite improvements in many open surgical techniques and perioperative care, these mortality rates have not significantly changed. Some of the reasons for the high mortality rates include the excessive blood loss and hypothermia that occur during open operative repair. The blood loss and hypothermia, combined with resuscitative dilutional coagulopathy, can lead to an irreversible spiraling coagulopathy that ultimately ends in the patient's demise. The availability of endovascular approaches to treat abdominal aortic aneurysms in the early 1990s offered an opportunity to substantially alter the treatment outcomes of ruptured abdominal aortic aneurysms. Endovascular repair offers many advantages, including rapid aortic control under local anesthesia, as well as an opportunity to limit the hypothermia and blood loss that occur with an open abdomen. This article will review the endovascular management of ruptured abdominal aortic aneurysms and describe the endovascular techniques for safe and effective treatment. Mt Sinai J Med 77:250,255, 2010. © 2010 Mount Sinai School of Medicine [source] Thoracic Aortic Aneurysms and Dissections: Endovascular TreatmentMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 3 2010Donald T. Baril MD Abstract The treatment of thoracic aortic disease has changed radically with the advances made in endovascular therapy since the concept of thoracic endovascular aortic repair was first described 15 years ago. Currently, there is a diverse array of endografts that are commercially available to treat the thoracic aorta. Multiple studies, including industry-sponsored and single-institution reports, have demonstrated excellent outcomes of thoracic endovascular aortic repair for the treatment of thoracic aortic aneurysms, with less reported perioperative morbidity and mortality in comparison with conventional open repair. Additionally, similar outcomes have been demonstrated for the treatment of type B dissections. However, the technology remains relatively novel, and larger studies with longer term outcomes are necessary to more fully evaluate the role of endovascular therapy for the treatment of thoracic aortic disease. This review examines the currently available thoracic endografts, preoperative planning for thoracic endovascular aortic repair, and outcomes of thoracic endovascular aortic repair for the treatment of both thoracic aortic aneurysms and type B aortic dissections. Mt Sinai J Med 77:256,269, 2010. © 2010 Mount Sinai School of Medicine [source] Minimally Invasive Vein Surgery: Latest Options for Vein DiseaseMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 3 2010FACPhArticle first published online: 20 MAY 2010, Steven Elias MD Abstract The goal of treatment for venous disease is to decrease ambulatory venous hypertension. Various strategies are employed. These can be divided into exogenous and endogenous treatments. Exogenous methods concern those employed from the outside of the limb, such as compression and elevation. Endogenous modalities treat from inside the limb the underlying venous pathology due to venous valvular dysfunction or venous obstruction. Traditional endogenous procedures include stripping, ligation, and phlebectomy. All these procedures require incisions, anesthesia, and perhaps hospitalization, and involve significant discomfort. Newer minimally invasive vein surgery procedures now exist. These are all same-day, outpatient procedures, usually involving local anesthesia. Most can be performed percutaneously without incisions. Patients ambulate the day of the procedure. Morbidity is less than 1%. This article summarizes the concept of minimally invasive vein surgery and summarizes new technologies to manage all forms of venous disease. Mt Sinai J Med 77:270,278, 2010. © 2010 Mount Sinai School of Medicine [source] Genetics and Asthma Disease Susceptibility in the US Latino PopulationMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 2 2010Joan Reibman MD Abstract The US Latino population is heterogeneous with diversity in environmental exposures and socioeconomic status. Moreover, the US Hispanic population derives from numerous countries previously under Spanish rule, and many Hispanics have complex proportions of European, Native American, and African ancestry. Disparities in asthma severity and control are due to complex interactions between environmental exposures, socioeconomic factors, and genetic variations. In addition, diseases within the Latino community may also differ by country of origin. Although US Census data show low asthma rates in the Hispanic population as a whole, there is a lot of variability in the prevalence and morbidity of asthma, with a prevalence of 5.0% in Mexican Americans versus 17.0% in Puerto Ricans. The diversity and population admixture make the study of the genetics of asthma complex in Latino populations. However, an understanding of the genetics of asthma in all populations, including the Latino population, can enhance risk identification, help us to target pharmacological therapy, and guide environmental regulations, all of which can promote a reduction in health disparities. The inclusion of markers of ancestral diversity and the incorporation of techniques to adjust for stratification now make these studies feasible in complex populations, including the Latino population. To date, studies using linkage analyses, genome-wide associations, or candidate gene analyses have identified an association of asthma or asthma-related phenotypes with candidate genes, including interleukin 13, ,-2 adrenergic receptor, a disintegrin and metalloproteinase 33, orosomucoid 1-like 3, and thymic stromal lymphopoietin. As reviewed here, although these genes have been identified in diverse populations, limited studies have been performed in Latino populations, and they have had variable replication. There is a need for the development of registries with well-phenotyped pediatric and adult Latino populations and subgroups for inclusion in the rapidly expanding field of genetic studies, and these studies need to be used to reduce health disparities. Mt Sinai J Med 77:140,148, 2010. © 2010 Mount Sinai School of Medicine [source] Is There a Genetic Basis for Health Disparities in Human Immunodeficiency Virus Disease?MOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 2 2010Cheryl Winkler PhD Abstract The highest global prevalence rates for human immunodeficiency virus and acquired immune deficiency syndrome have been recorded in southern Africa; in the United States, individuals of African descent are disproportionately affected by human immunodeficiency virus infection. Human immunodeficiency virus,infected individuals with African ancestry are also estimated to have a 17-fold or greater risk for developing human immunodeficiency virus,associated nephropathy in comparison with their counterparts of non-African descent. Several recent studies have implicated genetic alleles that are more frequent in populations of African descent and increase the risk of human immunodeficiency virus infection and the risk of human immunodeficiency virus,associated neuropathy (HIVAN). The supposition that persons of African descent are more susceptible to human immunodeficiency virus infection because of an underlying genetic predisposition is not supported by available evidence. However, strong, replicated data show that the increased risk for human immunodeficiency virus,associated nephropathy, as well as other major forms of kidney disease in individuals of African descent, is due in part to MYH9 (myosin, heavy chain 9, non-muscle) renal disease susceptibility alleles that are very frequent throughout sub-Saharan Africa but are infrequent or absent in non-Africans. Selection, drift, and demographic events shape the allelic architecture of the human genome: it is expected that these events will be reflected in geographic-specific differentiation in allele frequencies for a small subset of alleles that may be associated with either increased or reduced risk for complex and infectious diseases. Mt Sinai J Med 77:149,159, 2010. © 2010 Mount Sinai School of Medicine [source] Genetic and Environmental Contributions to Racial Disparities in Preterm BirthMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 2 2010Siobhan M. Dolan MD Abstract The preterm birth rate exceeds 12% in the United States, and preterm birth continues to be a clinical and public health challenge globally. Even though preterm birth is a major contributor to infant mortality and lifelong morbidity, there are few effective strategies to predict preterm birth and few clinical interventions to prevent it. Genomic research approaches that identify risk factors at the intersection of genetics and the environment will likely provide insights. Both genetic and environmental factors are known to contribute to the racial disparity seen in preterm birth. Through the identification of relevant gene-environment interactions that contribute to preterm birth and may underlie the racial disparity in preterm birth, research that will translate to clinical practice and ultimately prevent a number of preterm births is possible. Mt Sinai J Med 77:160,165, 2010. © 2010 Mount Sinai School of Medicine [source] Current Treatment and Recent Clinical Research in Alzheimer's DiseaseMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 1 2010Judith Neugroschl MD Abstract The transition from either epidemiological observation or the bench to rigorously tested clinical trials in patients with Alzheimer's disease is crucial in understanding which treatments are beneficial to patients. The amyloid hypothesis has undergone scrutiny recently, as many trials aimed at reducing amyloid and plaque have been completed or are in the testing phase. Examples include modulation of the secretases involved in beta amyloid formation, anti-aggregation agents, and immunotherapeutic trials. Other therapies targeting hyperphosphorylated tau and novel targets such as enhancement of mitochondrial function, serotonin receptors, receptor for advanced glycation end products, and nerve growth factor, as well as other strategies, are discussed. A brief review of the current Food and Drug Administration,approved treatments is included. Mt Sinai J Med 77:3&–16, 2010. © 2010 Mount Sinai School of Medicine [source] Vaccination as a Therapeutic Approach to Alzheimer's DiseaseMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 1 2010Thomas Wisniewski MD Abstract Alzheimer's disease is the most common cause of dementia worldwide. Alzheimer's disease is a member of a broad range of neurodegenerative diseases characterized pathologically by the conformational change of a normal protein into a pathological conformer with a high ,-sheet content that renders it neurotoxic. In the case of Alzheimer's disease, the normal soluble amyloid , peptide is converted into oligomeric/fibrillar amyloid ,. The oligomeric forms of amyloid , have been hypothesized to be the most toxic, whereas fibrillar amyloid , becomes deposited as amyloid plaques and congophilic angiopathy, which both serve as neuropathological markers of the disease. In addition, the accumulation of abnormally phosphorylated tau as soluble toxic oligomers and as neurofibrillary tangles is a critical part of the pathology. Numerous therapeutic interventions are under investigation to prevent and treat Alzheimer's disease. Among the most exciting and advanced of these approaches is vaccination. Immunomodulation is being tried for a range of neurodegenerative disorders, with great success being reported in most model animal trials; however, the much more limited human data have shown more modest clinical success so far, with encephalitis occurring in a minority of patients treated with active immunization. The immunomodulatory approaches for neurodegenerative diseases involve targeting a self-protein, albeit in an abnormal conformation; hence, effective enhanced clearance of the disease-associated conformer has to be balanced with the potential risk of stimulating excessive toxic inflammation within the central nervous system. The design of future immunomodulatory approaches that are more focused is dependent on addressing a number of questions, including when is the best time to start immunization, what are the most appropriate targets for vaccination, and is amyloid central to the pathogenesis of Alzheimer's disease or is it critical to target tau-related pathology also. In this review, we discuss the past experience with vaccination for Alzheimer's disease and the development of possible future strategies that target both amyloid ,,related and tau-related pathologies. Mt Sinai J Med 77:17&–31, 2010. © 2010 Mount Sinai School of Medicine [source] Neuropathology of Alzheimer's DiseaseMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 1 2010Daniel P. Perl MD Abstract Alois Alzheimer first pointed out that the disease which would later bear his name has a distinct and recognizable neuropathological substrate. Since then, much has been added to our understanding of the pathological lesions associated with the condition. The 2 primary cardinal lesions associated with Alzheimer's disease are the neurofibrillary tangle and the senile plaque. The neurofibrillary tangle consists of abnormal accumulations of abnormally phosphorylated tau within the perikaryal cytoplasm of certain neurons. The senile plaque consists of a central core of beta-amyloid, a 4-kD peptide, surrounded by abnormally configured neuronal processes or neurites. Other neuropathological lesions are encountered in cases of Alzheimer's disease, but the disease is defined and recognized by these 2 cardinal lesions. Other lesions include poorly understood changes such as granulovacuolar degeneration and eosinophilic rodlike bodies (Hirano bodies). The loss of synaptic components is a change that clearly has a significant impact on cognitive function and represents another important morphological alteration. It is important to recognize that distinguishing between Alzheimer's disease, especially in its early stages, and normal aging may be very difficult, particularly if one is examining the brains of patients who died at an advanced old age. It is also noted that instances of pure forms of Alzheimer's disease, in the absence of other coexistent brain disease processes, such as infarctions or Parkinson's disease,related lesions, are relatively uncommon, and this must be taken into account by researchers who employ postmortem brain tissues for research. Mt Sinai J Med 77:32&–42, 2010. © 2010 Mount Sinai School of Medicine [source] Noninvasive Prenatal Diagnosis: Past, Present, and FutureMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 6 2009Christian Litton MD Abstract The presence of fetal cells in the maternal circulation was first noted by Georg Schmorl when he documented the presence of multinucleated syncytial giant cells of placental origin in the lung tissue of women who had died from complications of eclampsia. In the intervening century, advances in cellular and molecular biology further elucidated both the physiology and pathophysiology of communication within the fetomaternal unit. This concept is at the foundation of the rapidly expanding field of noninvasive prenatal diagnosis. However, the clinical utility of this phenomenon had been limited until the presence of cell-free fetal DNA circulating in the maternal plasma was reported in 1997 and fetal messenger RNA was demonstrated to circulate in the maternal plasma in 2000. These circulating nucleic acids are found free-floating in the maternal plasma, unencumbered by a surrounding fetal cell. The analysis of these 3 fetal markers (fetal cells, cell-free fetal DNA, and fetal messenger RNA) for diagnostic and screening purposes is now being developed. The scope of noninvasive prenatal diagnosis is not limited to only the diagnosis of fetal genetic traits and aneuploidies. Recently, researchers have focused their investigations on the role of cell-free fetal DNA and fetal messenger RNA in preeclampsia, intrauterine growth restriction, and preterm labor. These biomarkers, the result of inherent placental dysfunction or the byproducts of placental trophoblastic apoptosis, may allow for improvements in the diagnosis and management of high-risk pregnancies. Mt Sinai J Med 76:521-528, 2009. © 2009 Mount Sinai School of Medicine [source] Achieving a Safety Culture in ObstetricsMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 6 2009Erin DuPree MD Abstract Preventable maternal and neonatal mortalities still occur, despite the wonders of today's technologically advanced healthcare system. Delivering high-quality, consistent care is the goal of every provider. Yet, obstetrical practice, in which unpredictable events and high-risk situations are the norm, is particularly vulnerable to medical errors. Obstetrics departments should be striving for a climate of patient safety, one that includes a just, reporting, and learning culture. This article discusses the various components of a safety culture as well as some of the advances that are being made in the field to improve the quality of care in obstetrics. Mt Sinai J Med 76:529-538, 2009. © 2009 Mount Sinai School of Medicine [source] Obesity and Pregnancy: Implications and Management Strategies for ProvidersMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 6 2009Taraneh Shirazian MD Abstract Obesity in pregnancy (pregravid body mass ,30) has been linked to several adverse pregnancy outcomes, including spontaneous abortion, preeclampsia, gestational diabetes, fetal macrosomia, cesarean delivery, and wound complications post,cesarean section. Intrapartum and postpartum management of obese gravidas requires multidisciplinary consultations between obstetricians, anesthesiologists, nurses, and pediatricians in order to improve the pregnancy outcomes of the mother and neonate. The American College of Obstetricians and Gynecologists currently supports risk-reducing strategies for obese pregnant patients, including limiting weight gain to 15 lb (standardized by the Institute of Medicine). Interventions to reduce gestational weight gain may be important modifiable risk factors for maternal and fetal perinatal complications. Interventions have targeted modifications of diet and exercise with educational methods such as radio broadcasts, pamphlets, and counseling. Interventions have also focused on motivational methods, such as individual and group classes, and have been implemented both before conception and immediately after birth. Effective interventions appear to be individualized in approach, but there is a lack of data to support any specific model. Prospective interventional studies are needed to demonstrate the benefits of weight limitation on pregnancy outcomes. Mt Sinai J Med 76:539-545, 2009. © 2009 Mount Sinai School of Medicine [source] The Bushmeat Trade: Increased Opportunities for Transmission of Zoonotic DiseaseMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 5 2009William B. Karesh DVM Abstract Bushmeat is a term that refers to the use of wild animals, ranging from cane rats to gorillas, for food. The term typically refers to the practice in forests of Africa. The bushmeat trade is an example of an anthropogenic factor that provides opportunities for the transmission of diseases from wildlife to humans. The expansion of the bushmeat trade over the past 2 decades has provided a venue for the emergence of zoonotic diseases by providing an increased opportunity for the transmission of organisms known to cause disease and organisms with an unknown impact on humans. Because the bushmeat trade is embedded in a complex cultural, political, and economic context, efforts to prevent the emergence of zoonoses require a multidisciplinary approach. Mt Sinai J Med 76:429,434, 2009. © 2009 Mount Sinai School of Medicine [source] Xenotransplantation, Xenogeneic Infections, Biotechnology, and Public HealthMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 5 2009Louisa E. Chapman MD Abstract Xenotransplantation is the attempt to use living biological material from nonhuman animal species in humans for therapeutic purposes. Clinical trials and preclinical studies have suggested that living cells and tissue from other species have the potential to be used in humans to ameliorate disease. However, the potential for successful xenotransplantation to cure human disease is coupled with the risk that therapeutic use of living nonhuman cells in humans may also serve to introduce xenogeneic infections of unpredictable significance. Animal husbandry practices and xenotransplantation product preparation may eliminate most exogenous infectious agents prior to transplantation. However, endogenous retroviruses are present in the genomes of all mammalian cells, have an inadequately defined ability to infect human cells, and have generated public health concern. The history of xenotransplantation, the implications for public health, the global consensus on public safeguards necessary to accompany clinical trials, and the future direction of xenotransplantation are discussed in the context of public health. Mt Sinai J Med 76:435,441, 2009. © 2009 Mount Sinai School of Medicine [source] The Utility of Simulation in Medical Education: What Is the Evidence?MOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 4 2009Yasuharu Okuda MD Abstract Medical schools and residencies are currently facing a shift in their teaching paradigm. The increasing amount of medical information and research makes it difficult for medical education to stay current in its curriculum. As patients become increasingly concerned that students and residents are "practicing" on them, clinical medicine is becoming focused more on patient safety and quality than on bedside teaching and education. Educators have faced these challenges by restructuring curricula, developing small-group sessions, and increasing self-directed learning and independent research. Nevertheless, a disconnect still exists between the classroom and the clinical environment. Many students feel that they are inadequately trained in history taking, physical examination, diagnosis, and management. Medical simulation has been proposed as a technique to bridge this educational gap. This article reviews the evidence for the utility of simulation in medical education. We conducted a MEDLINE search of original articles and review articles related to simulation in education with key words such as simulation, mannequin simulator, partial task simulator, graduate medical education, undergraduate medical education, and continuing medical education. Articles, related to undergraduate medical education, graduate medical education, and continuing medical education were used in the review. One hundred thirteen articles were included in this review. Simulation-based training was demonstrated to lead to clinical improvement in 2 areas of simulation research. Residents trained on laparoscopic surgery simulators showed improvement in procedural performance in the operating room. The other study showed that residents trained on simulators were more likely to adhere to the advanced cardiac life support protocol than those who received standard training for cardiac arrest patients. In other areas of medical training, simulation has been demonstrated to lead to improvements in medical knowledge, comfort in procedures, and improvements in performance during retesting in simulated scenarios. Simulation has also been shown to be a reliable tool for assessing learners and for teaching topics such as teamwork and communication. Only a few studies have shown direct improvements in clinical outcomes from the use of simulation for training. Multiple studies have demonstrated the effectiveness of simulation in the teaching of basic science and clinical knowledge, procedural skills, teamwork, and communication as well as assessment at the undergraduate and graduate medical education levels. As simulation becomes increasingly prevalent in medical school and resident education, more studies are needed to see if simulation training improves patient outcomes. Mt Sinai J Med 76:330,343, 2009. © 2008 Mount Sinai School of Medicine [source] Student-Run Health Clinic: Novel Arena to Educate Medical Students on Systems-Based PracticeMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 4 2009Yasmin S. Meah MD Abstract In recent decades, the United States has experienced substantial growth in the number of student-run clinics for the indigent. Today, over 49 medical schools across the country operate over 110 student-run outreach clinics that provide primary care services to the poor and uninsured. Despite this development, little research has been published on the educational value of such student-led endeavors. Although much has been surmised, no general methodology for categorizing the learning experience in these clinics has been established. This article represents the first literature review of the novel method of educating students through the operation of a clinic for the underserved. It highlights the student-run clinic as a unique enhancement of medical education that may supplant current curricular arenas in teaching students about systems-based practice principles such as cost containment and financing, resource allocation, interdisciplinary collaboration, patient advocacy, and monitoring and delivery of quality care. The novelty of the student-run clinic is that students place themselves at the forefront of problem solving and system navigation to effectively care for severely disadvantaged populations. This article underscores the student-run clinic as a potentially ideal experiential learning method for preparing young physicians to confront a US healthcare system currently facing crises in cost, quality of care, and high rates of uninsurance. The article stresses the need for outcomes research on the long-term effectiveness of the student-run clinic experience in affecting medical student practice behaviors and attitudes in patient care settings that extend beyond the student-run clinic. Mt Sinai J Med 76:344,356, 2009. © 2008 Mount Sinai School of Medicine [source] Emerging Concepts in the Pathophysiology of Type 2 Diabetes MellitusMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 3 2009Prasanth N. Surampudi MD Abstract Type 2 diabetes mellitus is a multifactorial metabolic disorder. It is characterized by chronic hyperglycemia, insulin resistance, and a relative insulin secretion defect. The prevalence of type 2 diabetes mellitus has risen worldwide in large part because of an increase in obesity and sedentary lifestyles. The underlying pathophysiology and complications of type 2 diabetes mellitus are still being elucidated. Recent advances in diabetes research have helped us to gain a better understanding about insulin resistance and insulin secretion defects. The evolving understanding about the influence of the incretin effect, insulin signal transduction, adipose tissue, intra,islet cell communication, and inflammation is changing the way in which we view type 2 diabetes mellitus. This new understanding will eventually provide us with new treatment approaches to help patients who have type 2 diabetes mellitus. This article gives a review of the current and emerging concepts of the pathophysiology of type 2 diabetes mellitus. Mt Sinai J Med 76: 216,226, 2009. © 2009 Mount Sinai School of Medicine [source] Glycemic Targets for Patients with Type 2 Diabetes MellitusMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 3 2009Ole-Petter R. Hamnvik MB Abstract Cardiovascular disease is the predominant cause of death in diabetic patients, and reducing the risk of cardiovascular disease in diabetics has recently been the focus of several highly publicized large trials, including ACCORD (Action To Control Cardiovascular Risk in Diabetes), ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation), and VADT (Veterans Affairs Diabetes Trial). These studies randomized high-risk diabetic patients into either intensive treatment or standard treatment. The glycemic control arm of ACCORD was terminated 17 months before the planned end of the study because of a finding of significantly increased all-cause and cardiovascular mortality in the intensive treatment group. These findings were not duplicated in either ADVANCE or VADT. Multiple possible explanations have been brought forward, including a higher incidence of death from unrecognized hypoglycemia, effects due to increased exposure to particular antidiabetic medications, adverse effects of rapid correction of hyperglycemia, weight gain, and differences in baseline characteristics. None of these were validated in post hoc analyses of the trial data, and the cause of the increased mortality remains elusive. Subgroup analyses suggest that those who start off with better control of their diabetes or without preexisting cardiovascular disease may have the most to gain from tight glycemic control. Reducing the risk of macrovascular disease and death in diabetic patients requires not only attention to glucose control but also meticulous attention to control of nonglycemic risk factors, including hypertension, hyperlipidemia, smoking, lack of exercise, and unhealthy diet as well as timely prescription of medications with proven preventative benefits, such as aspirin and statins. Mt Sinai J Med 76:227,233, 2009. © 2009 Mount Sinai School of Medicine [source] Balancing Risk and Benefit with Oral Hypoglycemic DrugsMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 3 2009Ole-Petter R. Hamnvik MB Abstract Clinicians are faced with an expansive array of treatment choices when caring for patients with type 2 diabetes. Because patient compliance may be affected when media sensationalism about controversial findings is misunderstood, we sought to clarify the recent controversy surrounding the cardiovascular and bone-health risks of thiazolidinediones, the risk of lactic acidosis with metformin, and the risk of hypoglycemia with oral therapies. The side effect profile of thiazolidinediones includes fluid retention, heart failure; and an increased risk of fracture. A recent controversial meta-analysis suggested that rosiglitazone increases the risk of myocardial infarction, which is possibly related to thiazolidinedione-induced lipid changes, weight gain, congestive heart failure, and anemia. Metformin is restricted to patients with normal renal function because of concerns that metformin may cause lactic acidosis. However, few cases of metformin-associated lactic acidosis have been reported, and most have occurred in patients with other reasons for developing lactic acidosis, such as sepsis or renal failure. Although the use of metformin continues to increase, observational studies have not been able to demonstrate an increased incidence of lactic acidosis in metformin-treated patients, even when it is used in populations with relative contraindications. Some oral hypoglycemic medications can cause hypoglycemia. Hypoglycemia is especially common in older patients, alcoholics, and patients with liver or renal disease. Patients on sulfonylureas and meglitinides have the highest incidence of hypoglycemia because of their pharmacological action of increasing insulin secretion. Of the sulfonylureas, glyburide presents the highest risk of hypoglycemia. Combination therapies, especially those regimens containing a sulfonylurea, increase the risk of hypoglycemia. Mt Sinai J Med 76:234,243, 2009. © 2009 Mount Sinai School of Medicine [source] Traumatic brain injury in the United States: an epidemiologic overviewMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 2 2009Carl R. Summers PhD Abstract A basic description of severity and frequency is needed for planning healthcare delivery for any disease process. In the case of traumatic brain injury, severity is typically categorized into mild, moderate, and severe with information from a combination of clinical observation and self-report methodologies. Recent US civilian epidemiological findings measuring the frequency of mortality and morbidity of traumatic brain injury are presented, including demographic and etiological breakdowns of the data. Falls, motor vehicle accidents, and being struck by objects are the major etiologies of traumatic brain injury. US civilian and Army hospitalization trends are discussed and compared. Features of traumatic brain injuries from Operation Iraqi Freedom and Operation Enduring Freedom are discussed. Mt Sinai J Med 76:105,110, 2009. © 2009 Mount Sinai School of Medicine [source] Blast-related mild traumatic brain injury: mechanisms of injury and impact on clinical careMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 2 2009Gregory A. Elder MD Abstract Mild traumatic brain injury has been called the signature injury of the wars in Iraq and Afghanistan. In both theaters of operation, traumatic brain injury has been a significant cause of mortality and morbidity, with blast-related injury the most common cause. Improvised explosive devices have been the major cause of blast injuries. It is estimated that 10% to 20% of veterans returning from these operations have suffered a traumatic brain injury, and there is concern that blast-related injury may produce adverse long-term health affects and affect the resilience and in-theater performance of troops. Blast-related injury occurs through several mechanisms related to the nature of the blast overpressure wave itself as well as secondary and tertiary injuries. Animal studies clearly show that blast overpressure waves are transmitted to the brain and can cause changes that neuropathologically are most similar to diffuse axonal injury. One striking feature of the mild traumatic brain injury cases being seen in veterans of the wars in Iraq and Afghanistan is the high association of mild traumatic brain injury with posttraumatic stress disorder. The overlap in symptoms between the disorders has made distinguishing them clinically challenging. The high rates of mild traumatic brain injury and posttraumatic stress disorder in the current operations are of significant concern for the long-term health of US veterans with associated economic implications. Mt Sinai J Med 76:111,118, 2009. © 2009 Mount Sinai School of Medicine [source] Severe traumatic brain injury: maximizing outcomesMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 2 2009Mary E. Tang MD Abstract Severe traumatic brain injury is one of the leading causes of death and disability in the United States. The initial management of traumatic brain injury involves early resuscitation, computed tomography scanning, and surgical evacuation of mass lesions, when indicated. Recent research suggests that the prevention and treatment of secondary brain injury decrease mortality and improve outcomes. Specifically, treatment should address not only cerebral protection but also prevention of injury to other organ systems. To achieve the best outcomes, attention must be focused on optimizing blood pressure and brain tissue oxygenation, maintaining adequate cerebral perfusion pressures, and preventing seizures. In addition, maximizing good outcomes depends on proactively addressing the risk of common sequelae of brain injury, including infection, deep venous thrombosis, and inadequate nutrition. Guidelines developed for the management of severe traumatic brain injury have dramatically improved functional neurological outcomes. Mt Sinai J Med 76:119,128, 2009. © 2009 Mount Sinai School of Medicine [source] Spectrum of Fibrosing Diffuse Parenchymal Lung DiseaseMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 1 2009Adam S. Morgenthau MD Abstract The interstitial lung diseases are a heterogeneous group of disorders characterized by inflammation and/or fibrosis of the pulmonary interstitium. In 2002, the American Thoracic Society and the European Respiratory Society revised the classification of interstitial lung diseases and introduced the term diffuse parenchymal lung disease. The idiopathic interstitial pneumonias are a subtype of diffuse parenchymal lung disease. The idiopathic interstitial pneumonias are subdivided into usual interstitial pneumonia (with its clinical counterpart idiopathic interstitial pneumonia), nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, desquamative interstitial pneumonia, respiratory bronchiolitis interstitial lung disease, and lymphocytic pneumonia. Sarcoidosis and hypersensitivity pneumonitis are the 2 most common granulomatous diffuse parenchymal lung diseases. Rheumatoid arthritis, systemic sclerosis, and dermatomyositis/polymyositis (causing antisynthetase syndrome) are diffuse parenchymal lung diseases of known association because these conditions are associated with connective tissue disease. Hermansky-Pudlak syndrome is a rare genetic diffuse parenchymal lung disease characterized by the clinical triad of pulmonary disease, oculocutaneous albinism, and bleeding diathesis. This review provides an overview of the chronic fibrosing diffuse parenchymal lung diseases. Its primary objective is to illuminate the clinical challenges encountered by clinicians who manage the diffuse parenchymal lung diseases regularly and to offer potential solutions to those challenges. Treatment for the diffuse parenchymal lung diseases is limited, and for many patients with end-stage disease, lung transplantation remains the best option. Although much has been learned about the diffuse parenchymal lung diseases during the past decade, research in these diseases is urgently needed. Mt Sinai J Med 76:2,23, © 2009 Mount Sinai School of Medicine [source] Gastroesophageal Reflux Disease and Idiopathic Pulmonary FibrosisMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 1 2009Yevgenia Y. Pashinsky MD Abstract Gastroesophageal reflux disease occurs with a higher prevalence in patients with idiopathic pulmonary fibrosis than in matched controls. Silent reflux occurs in about a third of patients with significant gastroesophageal reflux disease; thus, objective measurements are required to evaluate gastroesophageal reflux disease in patients with advanced lung diseases. We provide here a detailed description of acid and non-acid reflux and the diagnostic evaluation for pulmonologists and lung transplant surgeons suspecting reflux as a contributing factor in advanced lung diseases. We review the evidence for gastroesophageal reflux disease causing idiopathic pulmonary fibrosis and other select pulmonary diseases and the potential role of antireflux surgery in the management of advanced lung disease and transplant patients. Mt Sinai J Med 76:24,29, © 2009 Mount Sinai School of Medicine [source] "End-stage" Pulmonary Fibrosis in SarcoidosisMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 1 2009Alvin T. Teirstein MD Abstract Pulmonary fibrosis is an unusual "end stage" in patients with sarcoidosis. Fibrosis occurs in a minority of patients, and presents with a unique physiologic combination of airways dysfunction (obstruction) superimposed on the more common restrictive dysfunction. Imagin techniques are essential to the diagnosis, assessment and treatment of pulmonary fibrosis. Standard chest radiographs and CT scans may reveal streaks, bullae, cephalad retraction of the hilar areas, deviation of the trachea and tented diaphragm. Positive gallium and PET scans indicate residual reversible granulomatous disease and are important guides to therapy decisions. Treatment, usually with corticosteroids, is effective in those patients with positive scans, but fibrosis does not improve with any treatment. With severe functional impariment and patient disability, pulmonary hypertension and right heart failure may supervene for which the patient will require treatment. Oxygen, careful diuresis, sildenafil and bosentan may be salutary. These patients are candidates for lung transplantation. Mt Sinai J Med 76:30,36, © 2009 Mount Sinai School of Medicine [source] Diversity in academic medicine no. 1 case for minority faculty development todayMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 6 2008Diversity in academic medicine no. Abstract For the past 20 years, the percentage of the American population consisting of nonwhite minorities has been steadily increasing. By 2050, these nonwhite minorities, taken together, are expected to become the majority. Meanwhile, despite almost 50 years of efforts to increase the representation of minorities in the healthcare professions, such representation remains grossly deficient. Among the underrepresented minorities are African and Hispanic Americans; Native Americans, Alaskans, and Pacific Islanders (including Hawaiians); and certain Asians (including Hmong, Vietnamese, and Cambodians). The underrepresentation of underrepresented minorities in the healthcare professions has a profoundly negative effect on public health, including serious racial and ethnic health disparities. These can be reduced only by increased recruitment and development of both underrepresented minority medical students and underrepresented minority medical school administrators and faculty. Underrepresented minority faculty development is deterred by barriers resulting from years of systematic segregation, discrimination, tradition, culture, and elitism in academic medicine. If these barriers can be overcome, the rewards will be great: improvements in public health, an expansion of the contemporary medical research agenda, and improvements in the teaching of both underrepresented minority and non,underrepresented minority students. Mt Sinai J Med 75:491,498, © 2008 Mount Sinai School of Medicine [source] Diversity in academic medicine no. 2 history of battles lost and wonMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 6 2008Diversity in academic medicine no. Abstract Spurred by its rapidly changing demographics, the United States is striving to reduce and eliminate racial and ethnic health disparities. To do so, it must overcome the legacy of individual, institutional, and structural racism and resolve conflicts in related political and social ideologies. This has moved the struggle over diversity in the health professions outside the laboratories and ivy-covered walls of academic medicine into the halls of Congress and chambers of the US Supreme Court. Although equal employment opportunity and affirmative action programs began as legal remedies for distinct histories of legally sanctioned racial and gender discrimination, they also became effective means for increasing the representation of underrepresented minorities in higher education and the health professions. Beginning in the 1970s and continuing today, legal challenges to measures for realizing equal opportunity and leveling the playing field have reached the US Supreme Court and state-wide ballot initiatives. These historical challenges and successes are the subject of this article. Although the history is not exhaustive, it aims to provide an important context for the struggles of advocates to improve the representation of underrepresented minorities in medicine and reduce racial and ethnic health disparities. Mt Sinai J Med 75:499,503, © 2008 Mount Sinai School of Medicine [source] Diversity in academic medicine no. 3 struggle for survival among leading diversity programsMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 6 2008A. Hal Strelnick MD Abstract Since efforts to increase the diversity of academic medicine began shortly after the Civil War, the efforts have been characterized by a ceaseless struggle of old and new programs to survive. In the 40 years after the Civil War, the number of minority-serving institutions grew from 2 to 9, and then the number fell again to 2 in response to an adverse evaluation by the Carnegie Foundation for the Advancement of Teaching. For 50 years, the programs grew slowly, picking up speed only after the passage of landmark civil rights legislation in the 1960s. From 1987 through 2005, they expanded rapidly, fueled by such new federal programs as the Centers of Excellence and Health Careers Opportunity Programs. Encompassing majority-white institutions as well as minority-serving institutions, the number of Centers of Excellence grew to 34, and the number of Health Careers Opportunity Programs grew to 74. Then, in 2006, the federal government cut its funding abruptly and drastically, reducing the number of Centers of Excellence and Health Careers Opportunity Programs to 4 each. Several advocacy groups, supported by think tanks, have striven to restore federal funding to previous levels, so far to no avail. Meanwhile, the struggle to increase the representation of underrepresented minorities in the health professions is carried on by the surviving programs, including the remaining Centers of Excellence and Health Careers Opportunity Programs and new programs that, funded by state, local, and private agencies, have arisen from the ashes. Mt Sinai J Med 75:504,516, © 2008 Mount Sinai School of Medicine [source] Economic and healthcare forces of hospitalist movementMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 5 2008Tara F. Bishop MD Abstract The field of hospital medicine has become a widely accepted model for inpatient care and has grown rapidly in the past ten years. The impetus for growth has largely been pressure to contain costs for inpatient care and improve efficiency in the hospital. Studies have shown that care by hospitalists is generally more cost-effective than care by faculty or private practice physicians without affecting quality. The field faces challenges in continuity of patient care and retention of physicians in the workforce. Mt Sinai J Med 75:424,429, 2008. © 2008 Mount Sinai School of Medicine [source] | ||||||||||