MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Annual Review of Medicine' source. Wed, 08 Feb 2012 18:50:17 +0100 http://www.medworm.com/index.php?rid=5607526&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22248319%26dopt%3DAbstract Authors: Wexler NS Abstract My mother, Leonore, was diagnosed with Huntington's disease (HD) in 1968 at age 53. I was 23, my sister Alice 26, and our father, Milton Wexler, 60 years old. The same year, our father created the Hereditary Disease Foundation (HDF), dedicated to finding treatments and cures for HD. HD is an autosomal dominant, neurodegenerative disorder. Alice and I each have a 50% chance of inheriting and dying from the disorder. Over the past 43 years, we have been proud to change the face of science. Through Milton Wexler Interdisciplinary Workshops, judicious funding, and focusing on innovation and creativity, the HDF is an integral partner in key discoveries. The HDF recruited and supported >100 scientists worldwide who worked together as the Huntington's Diseas... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=5607526 Fri, 20 Jan 2012 09:01:39 +0100 5607526 http://www.medworm.com/index.php?rid=5607525&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22248320%26dopt%3DAbstract Authors: Gonzaga-Jauregui C, Lupski JR, Gibbs RA Abstract Following the "finished," euchromatic, haploid human reference genome sequence, the rapid development of novel, faster, and cheaper sequencing technologies is making possible the era of personalized human genomics. Personal diploid human genome sequences have been generated, and each has contributed to our better understanding of variation in the human genome. We have consequently begun to appreciate the vastness of individual genetic variation from single nucleotide to structural variants. Translation of genome-scale variation into medically useful information is, however, in its infancy. This review summarizes the initial steps undertaken in clinical implementation of personal genome information, and describes the applicat... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=5607525 Fri, 20 Jan 2012 09:01:29 +0100 5607525 http://www.medworm.com/index.php?rid=5607524&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22248321%26dopt%3DAbstract Authors: Carrington M, Walker BD Abstract Host genetic variation is presently estimated to account for about one-fourth of the observed differences in control of HIV across infected individuals. Genome-wide association studies have confirmed that polymorphism within the HLA class I locus is the primary host genetic contributor to determining outcome after infection. Here we progress beyond the genetic associations alone to consider the functional explanations for these correlations. In this process, the complex and multidimensional effects of HLA molecules in viral disease become apparent. PMID: 22248321 [PubMed - in process] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=5607524 Fri, 20 Jan 2012 09:01:19 +0100 5607524 http://www.medworm.com/index.php?rid=5607523&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22248322%26dopt%3DAbstract Authors: Janka GE Abstract Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome in which an uncontrolled and ineffective immune response, triggered in most cases by infectious agents, leads to severe hyperinflammation. Familial forms of HLH (FHL), which are increasingly found also in adolescents and adults, are due to genetic defects leading to impaired function of natural killer cells and cytotoxic T cells. These mutations occur either in the perforin gene or in genes important for the exocytosis of cytotoxic granules. Cytotoxic granules contain perforin and granzymes, which induce apoptosis upon entering (infected) target cells. Additionally, perforin is important for the downregulation of the immune response. Acquired forms of HLH are encountered in associatio... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=5607523 Fri, 20 Jan 2012 09:01:09 +0100 5607523 http://www.medworm.com/index.php?rid=5607522&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22248323%26dopt%3DAbstract Authors: Doig D, Brown MM Abstract Since the landmark NASCET and ECST trials demonstrated the superiority of carotid endarterectomy over medical therapy in the prevention of stroke for patients with symptomatic carotid artery stenosis, surgical intervention as a part of secondary prevention of stroke has become widespread. However, the newer technology of carotid artery angioplasty and stenting challenges this mode of intervention, promising the benefits of a procedure under local anesthesia and potentially avoiding the surgical complications of cranial nerve palsy and hematoma. Pooled evidence from randomized controlled trials of endarterectomy versus stenting shows a higher rate of stroke or death in the stenting groups-but this finding is mitigated to an extent by the lower inci... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=5607522 Fri, 20 Jan 2012 09:00:58 +0100 5607522 http://www.medworm.com/index.php?rid=5607521&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22248324%26dopt%3DAbstract Authors: Guy TS, Hill AC Abstract Mitral valve prolapse is defined as abnormal bulging of the mitral valve leaflets into the left atrium during ventricular systole. Mitral valve prolapse is a common condition that is a risk factor for mitral regurgitation, congestive heart failure, arrhythmia, and endocarditis. Myxomatous degeneration is the most common cause of mitral prolapse in the United States and Europe, and progression of myxomatous mitral prolapse is the most common cause of mitral regurgitation that requires surgical treatment. Myxomatous degeneration appears to have genetic etiology. The genetics of myxomatous degeneration is complex and not fully worked out; it appears to be heterogeneous with multi-gene, multi-chromosomal autosomal dominance with incomplete penetrance. ... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=5607521 Fri, 20 Jan 2012 09:00:47 +0100 5607521 http://www.medworm.com/index.php?rid=5607520&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22248325%26dopt%3DAbstract Authors: Verkman AS Abstract The aquaporins are a family of membrane water channels, some of which also transport glycerol. They are involved in a wide range of physiological functions (including water/salt homeostasis, exocrine fluid secretion, and epidermal hydration) and human diseases (including glaucoma, cancer, epilepsy, and obesity). At the cellular level, aquaporin-mediated osmotic water transport across cell plasma membranes facilitates transepithelial fluid transport, cell migration, and neuroexcitation; aquaporin-mediated glycerol transport regulates cell proliferation, adipocyte metabolism, and epidermal water retention. Genetic diseases caused by loss-of-function mutations in aquaporins include nephrogenic diabetes insipidus and congenital cataracts. The neuroinflammat... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=5607520 Fri, 20 Jan 2012 09:00:36 +0100 5607520 http://www.medworm.com/index.php?rid=5607519&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22248326%26dopt%3DAbstract Authors: Ozcan L, Tabas I Abstract Perturbations in the normal functions of the endoplasmic reticulum (ER) trigger a signaling network that coordinates adaptive and apoptotic responses. There is accumulating evidence implicating prolonged ER stress in the development and progression of many diseases, including neurodegeneration, atherosclerosis, type 2 diabetes, liver disease, and cancer. With the improved understanding of the underlying molecular mechanisms, therapeutic interventions that target the ER stress response would be potential strategies to treat various diseases driven by prolonged ER stress. PMID: 22248326 [PubMed - in process] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=5607519 Fri, 20 Jan 2012 09:00:25 +0100 5607519 http://www.medworm.com/index.php?rid=5607518&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22248327%26dopt%3DAbstract This article provides an overview of TBI and its neuropsychiatric sequelae in U.S. war veterans who participated in the current operations in and around Afghanistan and Iraq, with particular emphasis on blast-related mild TBI. Psychiatric disorders, particularly posttraumatic stress disorder, pain, and sensory impairments are prevalent in war veterans with TBI. Research is needed to more definitively characterize the epidemiology of TBI-related functional difficulties, the effects of blasts compared with other mechanisms of injury, recovery trajectories, and treatment outcomes in this population. PMID: 22248327 [PubMed - in process] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=5607518 Fri, 20 Jan 2012 09:00:13 +0100 5607518 http://www.medworm.com/index.php?rid=5428994&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22077719%26dopt%3DAbstract Authors: Thera MA, Plowe CV Abstract Vaccines are the most powerful public health tools mankind has created, but malaria parasites are bigger, more complicated, and wilier than the viruses and bacteria that have been conquered or controlled with vaccines. Despite decades of research toward a vaccine for malaria, this goal has remained elusive. Nevertheless, recent advances justify optimism that a licensed malaria vaccine is within reach. A subunit recombinant protein vaccine that affords in the neighborhood of 50% protective efficacy against clinical malaria is in the late stages of clinical evaluation in Africa. Incremental improvements on this successful vaccine are possible and worth pursuing, but the best hope for a highly efficacious malaria vaccine that would improve prospect... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=5428994 Tue, 26 Jul 2011 04:00:00 +0100 5428994 http://www.medworm.com/index.php?rid=5349782&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22017444%26dopt%3DAbstract Authors: Aviv A, Levy D Abstract The model we propose to explain the links between atherosclerosis and telomere dynamics (birth telomere length and its age-dependent shortening) in leukocytes takes cues from three facts: atherosclerosis is a disease of the vascular endothelium; the hematopoietic system and the vascular endothelium share a common embryonic origin; interindividual variation in leukocyte telomere length (LTL) in the general population has a genetic explanation. The model posits that LTL dynamics mirror telomere dynamics in hematopoietic stem cells (HSCs), where telomere length is an index of HSC reserves. Diminished HSC reserves at birth, their accelerated attrition rate afterward, or both are are reflected in shortened LTL during adulthood-a phenomenon that confers i... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=5349782 Tue, 26 Jul 2011 04:00:00 +0100 5349782 http://www.medworm.com/index.php?rid=4362507&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21226609%26dopt%3DAbstract Authors: Hirschhorn JN, Gajdos ZK Most common diseases and quantitative traits are heritable: determined in part by genetic variation within the population. The inheritance is typically polygenic in that combined effects of variants in numerous genes, plus nongenetic factors, determine outcome. The genes influencing common disease and quantitative traits remained largely unknown until the implementation in 2006 of genome-wide association (GWA) studies that comprehensively surveyed common genetic variation (frequency >5%). By 2010, GWA studies identified >1,000 genetic variants for polygenic traits. Typically, these variants together account for a modest fraction (10%-30%) of heritability, but they have highlighted genes in both known and new biological pathways and genes of unkno... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=4362507 Wed, 19 Jan 2011 15:00:41 +0100 4362507 http://www.medworm.com/index.php?rid=4362506&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21226610%26dopt%3DAbstract Authors: Owen DR, Lindsay AC, Choudhury RP, Fayad ZA It is now well recognized that the atherosclerotic plaques responsible for thrombus formation are not necessarily those that impinge most on the lumen of the vessel. Nevertheless, clinical investigations for atherosclerosis still focus on quantifying the degree of stenosis caused by plaques. Many of the features associated with a high-risk plaque, including a thin fibrous cap, large necrotic core, macrophage infiltration, neovascularization, and intraplaque hemorrhage, can now be probed by novel imaging techniques. Each technique has its own strengths and drawbacks. In this article, we review the various imaging modalities used for the evaluation and quantification of atherosclerosis. PMID: 21226610 [PubMed - in process] (Source:... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=4362506 Wed, 19 Jan 2011 15:00:37 +0100 4362506 http://www.medworm.com/index.php?rid=4362505&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21226611%26dopt%3DAbstract Authors: Eriksson BI, Quinlan DJ, Eikelboom JW The last decade has seen the evaluation of several new oral anticoagulants that directly target thrombin or activated factor X (FXa). All demonstrate a rapid onset of action, a low potential for food and drug interactions, and a predictable anticoagulant effect that obviates the need for routine coagulation monitoring. Those agents at the most advanced stages of clinical development are a direct thrombin inhibitor, dabigatran, and direct FXa inhibitors, rivaroxaban and apixaban. Dabigatran and rivaroxaban are approved in more than 70 countries for prevention of venous thromboembolism in patients undergoing elective hip or knee arthroplasty, and apixaban is being considered for approval by regulatory agencies for this indication. Dabigatran... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=4362505 Wed, 19 Jan 2011 15:00:32 +0100 4362505 http://www.medworm.com/index.php?rid=4362504&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21226612%26dopt%3DAbstract This article provides an overview of recent research achievements and discusses future technical challenges that must be met before the promise of stem cell applications for lung disease can be realized. PMID: 21226612 [PubMed - in process] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=4362504 Wed, 19 Jan 2011 15:00:27 +0100 4362504 http://www.medworm.com/index.php?rid=4362503&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21226613%26dopt%3DAbstract Authors: Ashlock MA, Olson ER Cystic fibrosis (CF) is a progressive genetic disease primarily involving the respiratory and gastrointestinal tracts. Multiple therapies directed at CF symptoms and clinical management strategies have emerged from iterative cycles of therapeutics development, helping to change the face of CF from a fatal childhood affliction to a disease in which nearly 50% of U.S. patients are adults. However, as a consequence of therapeutic advances, the burden of CF care is high, and despite progress, most patients succumb to respiratory failure. Addressing the basic defect in CF with systemic small molecules is evolving as a promising approach. A successful collaboration between a voluntary health organization and a pharmaceutical company, complemented by academic inv... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=4362503 Wed, 19 Jan 2011 15:00:22 +0100 4362503 http://www.medworm.com/index.php?rid=4362502&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21226614%26dopt%3DAbstract Authors: Bessho K, Bezerra JA Biliary atresia is the most common cholangiopathy of childhood. With complete obstruction of segments or the entire length of extrahepatic bile ducts, the timely pursuit of hepatoportoenterostomy is the best strategy to restore bile drainage. However, even with prompt surgical intervention, ongoing injury of intrahepatic bile ducts and progressive cholangiopathy lead to end-stage cirrhosis. The pace of disease progression is not uniform; it may relate to clinical forms of disease and/or staging of liver pathology at diagnosis. Although the etiology of disease is not yet defined, several biological processes have been linked to pathogenic mechanisms of bile duct injury. Among them, there is increasing evidence that the immune system targets the duct epithel... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=4362502 Wed, 19 Jan 2011 15:00:17 +0100 4362502 http://www.medworm.com/index.php?rid=4362501&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21226615%26dopt%3DAbstract Authors: Higgins MJ, Stearns V The selective estrogen receptor modulator tamoxifen has been used for more than three decades for the treatment, and more recently prevention, of breast cancer in women of all ages. The conversion of tamoxifen to active metabolites involves several cytochrome P450 (CYP) enzymes. CYP2D6 is the key enzyme responsible for the conversion of N-desmethyl tamoxifen to endoxifen. Single nucleotide polymorphisms in the CYP2D6 gene are not uncommon, and some alleles code for enzymes with reduced, null, or increased activity. Multiple studies suggest that women who carry one or two variant CYP2D6 alleles that encode enzymes with null or reduced activity may have an inferior breast cancer outcome when treated with tamoxifen in the adjuvant setting compared to women c... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=4362501 Wed, 19 Jan 2011 15:00:14 +0100 4362501 http://www.medworm.com/index.php?rid=4362500&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21226616%26dopt%3DAbstract Authors: Musso G, Gambino R, Cassader M Novel, culture-independent, molecular and metagenomic techniques have provided new insight into the complex interactions between the mammalian host and gut microbial species. It is increasingly evident that gut microbes may shape the host metabolic and immune network activity and ultimately influence the development of obesity and diabetes. We discuss the evidence connecting gut microflora to obesity and to type 1 and type 2 diabetes, and we present recent insights into potential mechanisms underlying this relationship: increased nutrient absorption from the diet, prolonged intestinal transit time, altered bile acid entero-hepatic cycle, increased cellular uptake of circulating triglycerides, enhanced de novo lipogenesis, reduced free fatty acid ... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=4362500 Wed, 19 Jan 2011 15:00:10 +0100 4362500 http://www.medworm.com/index.php?rid=4362499&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21226617%26dopt%3DAbstract Authors: Peterson BS, Weissman MM We have identified a brain-based endophenotype for major depressive disorder (MDD) that includes thinning of the cortex of the lateral aspect of the right hemisphere and the medial aspect of the left, as well as bilateral hypoplasia of frontal and parietal white matter. The endophenotype status of these abnormalities is supported by their presence in a multigenerational cohort of persons who themselves do not have MDD but who are at increased familial risk for developing the illness. Those who have the endophenotype but who are not ill nevertheless still suffer from inattention and poor visual memory for social stimuli in direct proportion to the magnitude of cortical thinning and white matter hypoplasia within the endophenotype. Identification of this... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=4362499 Wed, 19 Jan 2011 15:00:07 +0100 4362499 http://www.medworm.com/index.php?rid=4206368&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21090963%26dopt%3DAbstract Authors: Weidemann F, Niemann M, Warnock DG, Ertl G, Wanner C Fabry disease is an X-linked lysosomal storage disorder caused by α- galactosidase A deficiency. Intracellular accumulation of globotriaosylceramide starts in utero and progressively develops in various tissues and organs. Cardiac involvement is frequent, and its presentation as concentric nonobstructive left ventricular hypertrophy serves as a model for other hypertrophic cardiomyopathies. This review describes the Fabry cardiomyopathy, its treatment, and multidisciplinary patient care models. These models will help clinicians in diagnosing, assessing, and treating patients with Fabry disease. As the models can be extrapolated to other diseases, they might contribute to more optimal clinical management of patients with oth... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=4206368 Wed, 17 Nov 2010 00:00:00 +0100 4206368 http://www.medworm.com/index.php?rid=4174395&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21073335%26dopt%3DAbstract Authors: Karsenty G The molecular elucidation of two human skeletal dysplasias revealed that they are caused by an increase or a decrease in the synthesis of serotonin by enterochromaffin cells of the gut. This observation revealed a novel and powerful endocrine means to regulate bone mass. Exploiting these findings in the pharmacological arena led to the demonstration that inhibiting synthesis of gut-derived serotonin could be an effective means to treat low-bone-mass diseases such as osteoporosis. Expected final online publication date for the Annual Review of Medicine Volume 62 is January 07, 2011. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates. PMID: 21073335 [PubMed - as supplied by publisher] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=4174395 Wed, 10 Nov 2010 00:00:00 +0100 4174395 http://www.medworm.com/index.php?rid=3904223&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20731602%26dopt%3DAbstract Authors: Dodson S, Baracos VE, Jatoi A, Evans WJ, Cella D, Dalton JT, Steiner MS Cancer cachexia is a complex metabolic condition characterized by loss of skeletal muscle. Common clinical manifestations include muscle wasting, anemia, reduced caloric intake, and altered immune function, which contribute to increased disability, fatigue, diminished quality of life, and reduced survival. The prevalence of cachexia and the impact of this disorder on the patient and family underscore the need for effective management strategies. Dietary supplementation and appetite stimulation alone are inadequate to reverse the underlying metabolic abnormalities of cancer cachexia and have limited long-term impact on patient quality of life and survival. Therapies that can increase muscle mass and physica... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3904223 Sun, 15 Aug 2010 23:00:00 +0100 3904223 http://www.medworm.com/index.php?rid=3858907&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20690826%26dopt%3DAbstract Authors: Rowley AH Kawasaki disease (KD) is a vasculitis of young childhood that particularly affects the coronary arteries. Molecular analysis of the oligoclonal IgA response in acute KD led to production of synthetic KD antibodies. These antibodies identify intracytoplasmic inclusion bodies in acute KD tissues. Light and electron microscopic studies indicate that the inclusion bodies are consistent with aggregates of viral proteins and RNA. Advances in molecular genetic analysis and completion of the Human Genome Project have sparked a worldwide effort to identify genes associated with KD. A polymorphism of one such gene, ITPKC, a negative regulator of T cell activation, confers susceptibility to KD in Japanese populations and increases the risk of developing coronary artery abnormal... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3858907 Mon, 02 Aug 2010 23:00:00 +0100 3858907 http://www.medworm.com/index.php?rid=3858906&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20690827%26dopt%3DAbstract This article provides a brief overview of the conceptual and practical components of cognitive therapy and highlights some of the empirical evidence regarding its efficacy. Cognitive therapy (often labeled generically as cognitive behavior therapy) is efficacious either alone or as an adjunct to medication and provides a prophylaxis against relapse and recurrence. Expected final online publication date for the Annual Review of Medicine Volume 62 is January 07, 2011. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates. PMID: 20690827 [PubMed - as supplied by publisher] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3858906 Mon, 02 Aug 2010 23:00:00 +0100 3858906 http://www.medworm.com/index.php?rid=3167755&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20059330%26dopt%3DAbstract Authors: Grosser T, Yu Y, Fitzgerald GA Nonsteroidal antinflammatory drugs (NSAIDs) inhibit prostaglandin formation by cyclooxygenases (COX) 1 and 2. NSAIDs selective for inhibition of COX-2 are less likely than traditional drugs to cause serious gastrointestinal adverse effects, but predispose to adverse cardiovascular events, such as heart failure, myocardial infarction, and stroke. Evidence from human pharmacology and genetics, genetically manipulated rodents, and other animal models and randomized trials indicates that this is consequent to suppression of COX-2-dependent cardioprotective prostagladins, particularly prostacyclin. Lessons drawn from how this saga unfolded are relevant to how we approach drug surveillance and regulation, integrate diversifed forms of information and m... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3167755 Wed, 13 Jan 2010 20:32:03 +0100 3167755 http://www.medworm.com/index.php?rid=3167754&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20059331%26dopt%3DAbstract Authors: Patrono C, Rocca B Mechanisms of platelet inhibition are reviewed with emphasis on the pharmacokinetic and pharmacodynamic determinants of clinical efficacy and safety of antiplatelet drugs. Current developments in antiplatelet therapy are discussed in relation to both primary and secondary prevention of atherothrombotic complications. Interindividual variability in response to antiplatelet agents and new drug targets are outlined within the context of optimizing the balance between the cardiovascular benefits and bleeding risks of antiplatelet therapy. Recent advances in the pharmacogenetics of thienopyridines open the realistic prospect of a personalized choice of the most appropriate antiplatelet agent and tailored dose adjustment for an individual patient. PMID: 200593... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3167754 Wed, 13 Jan 2010 20:32:03 +0100 3167754 http://www.medworm.com/index.php?rid=3167753&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20059332%26dopt%3DAbstract Authors: Arepally GM, Ortel TL Heparin-induced thrombocytopenia (HIT) is an immune-mediated hypercoagulable disorder caused by antibodies to platelet factor 4 (PF4) and heparin. HIT develops in temporal association with heparin therapy and manifests either as an unexplained thrombocytopenia or thrombocytopenia complicated by thrombosis. The propensity for thrombosis distinguishes HIT from other common drug-induced thrombocytopenias. Diagnosing HIT in hospitalized patients is often challenging because of the frequency of heparin use, occurrence of thrombocytopenia from other causes, and development of asymptomatic PF4/heparin antibodies in patients treated with heparin. This review summarizes our current understanding of the pathogenesis, clinical features, diagnostic criteria, and mana... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3167753 Wed, 13 Jan 2010 20:32:03 +0100 3167753 http://www.medworm.com/index.php?rid=3167752&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20059333%26dopt%3DAbstract Authors: Bergwitz C, Jüppner H In contrast to the regulation of calcium homeostasis, which has been extensively studied over the past several decades, relatively little is known about the regulation of phosphate homeostasis. Fibroblast growth factor 23 (FGF23) is part of a previously unrecognized hormonal bone-parathyroid-kidney axis, which is modulated by PTH, 1,25(OH)(2)-vitamin D (1,25(OH)(2)D), dietary and serum phosphorus levels. Synthesis and secretion of FGF23 by osteocytes are positively regulated by 1,25(OH)(2)D and serum phosphorus and negatively regulated, through yet unknown mechanisms, by the phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and by dentin matrix protein 1 (DMP1). In turn, FGF23 inhibits the synthesis of 1,25(OH)(2)... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3167752 Wed, 13 Jan 2010 20:32:03 +0100 3167752 http://www.medworm.com/index.php?rid=3167751&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20059334%26dopt%3DAbstract Authors: Barouch DH, Korber B Despite more than 25 years of concerted worldwide research, the development of a safe and effective HIV-1 vaccine remains elusive. Prototype antibody-based and T cell-based HIV-1 vaccines have failed to show efficacy in clinical trials to date. Next-generation HIV-1 vaccine candidates are in various stages of preclinical and clinical development, but key scientific obstacles pose major challenges for the field. Critical hurdles include the enormous global diversity of the virus and the challenges associated with generating broadly reactive neutralizing antibody and cellular immune responses. We review the current state of the HIV-1 vaccine field and outline strategies that are being explored to overcome these roadblocks. PMID: 20059334 [PubMed - in pro... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3167751 Wed, 13 Jan 2010 20:32:03 +0100 3167751 http://www.medworm.com/index.php?rid=3167750&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20059335%26dopt%3DAbstract Authors: Sambhara S, Poland GA Avian influenza H5N1 viruses that have spread to a number of countries in Asia, the Middle East, and Africa have the potential to cause a pandemic. The most effective public health intervention strategy is to combine preventive vaccination with nonpharmaceutical intervention strategies and enhanced surveillance activities. H5N1 vaccines are poorly immunogenic even at high doses; an adjuvant is needed for enhancement of immunogenicity and for dose-sparing. Lack of effective, yet safe, adjuvants is the limiting factor for candidate vaccines that utilize egg-dependent or egg-independent manufacturing technologies. Hence, developing novel adjuvants is crucial for pandemic influenza vaccine development. Although the use of antiviral drugs is also an important ... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3167750 Wed, 13 Jan 2010 20:32:03 +0100 3167750 http://www.medworm.com/index.php?rid=3167749&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20059336%26dopt%3DAbstract Authors: Sakhuja R, Mauri L Acute myocardial infarction is a common and life-threatening presentation of coronary artery disease in adults. In the settings of ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction, significant mortality benefit has been observed in randomized trials of coronary stent procedures compared with medical therapy alone. However, data regarding procedural choices, and particularly stent choices, are limited, and significant controversy exists. Drug-eluting stents were introduced in the United States in 2003 and have been widely adopted based on profound reduction in restenosis. Yet recent years have witnessed a decline in use of drug-eluting stents in the setting of myocardial infarction due to long-term safety concerns.... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3167749 Wed, 13 Jan 2010 20:32:03 +0100 3167749 http://www.medworm.com/index.php?rid=3167748&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20059337%26dopt%3DAbstract Authors: Sen-Chowdhry S, Morgan RD, Chambers JC, McKenna WJ Arrhythmogenic right ventricular cardiomyopathy (ARVC) has a prevalence of at least 1 in 1000, is a leading cause of sudden cardiac death in people aged < or =35 years, and accounts for up to 10% of deaths from undiagnosed cardiac disease in the <65 age group. The classic form of the disease has an early predilection for the right ventricle, but recognition of left-dominant and biventricular subtypes has prompted proposal of the broader term arrhythmogenic cardiomyopathy. The clinical profile of the disease bridges the gap between the cardiomyopathies and inherited arrhythmia syndromes. The early "concealed" phase is characterized by propensity toward ventricular tachyarrhythmia in the setting of well-preserved morpholog... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3167748 Wed, 13 Jan 2010 20:32:03 +0100 3167748 http://www.medworm.com/index.php?rid=3167747&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20059338%26dopt%3DAbstract Authors: Terracciano CM, Miller LW, Yacoub MH The introduction of the heart lung machine more than 50 years ago proved in principle that heart function can be replaced, albeit for short periods. This was followed by attempts to produce total or partial artificial hearts that could function for prolonged periods of time. Progress in this field has been intermittent but has accelerated considerably in the past 10 years, with ventricular assist devices (VADs) reaching an impressive degree of sophistication and complexity owing to the contributions from clinicians, engineers, scientists, industrialists, and others. This review describes the currently available types of VADs, their current clinical use, the patient selection process, the trend toward use of VADs in patients with less severe... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3167747 Wed, 13 Jan 2010 20:32:03 +0100 3167747 http://www.medworm.com/index.php?rid=3167746&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20059339%26dopt%3DAbstract Authors: Janssens S Progenitor cells residing in bone marrow, adipose tissue, and skeletal muscle or circulating in the blood are capable of improving myocardial function in preclinical models. In contrast, early clinical studies using bone marrow cells have shown mixed results and reflect our incomplete understanding of underlying mechanisms. Recent identification of various cardiac precursor cells has suggested an endogenous reservoir for cell-based repair. However, confronted with massive cardiac cell loss, inventive strategies and enabling technologies are required to mobilize or deliver functionally competent progenitor cells to sites of injury or to effectively stimulate endogenous repair. We review our present knowledge in this promising and rapidly evolving development in cardi... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3167746 Wed, 13 Jan 2010 20:32:03 +0100 3167746 http://www.medworm.com/index.php?rid=3167745&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20059340%26dopt%3DAbstract Authors: Villanueva A, Minguez B, Forner A, Reig M, Llovet JM The genomic era is changing the understanding of cancer, although translation of the vast amount of data available into decision-making algorithms is far from reality. Molecular profiling of hepatocellular carcinoma (HCC), the most common cause of death among cirrhotic patients and a fast-growing malignancy in Western countries, is enabling the advancement of novel approaches to disease diagnosis and management. Most HCCs arise on a cirrhotic liver, and predictably, an accurate genomic characterization will allow the identification of procarcinogenic signals amenable to selective targeting by chemopreventive strategies. Molecular diagnosis is currently feasible for small tumors, but it has not yet been formalized by scientif... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3167745 Wed, 13 Jan 2010 20:32:03 +0100 3167745 http://www.medworm.com/index.php?rid=3167744&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20059341%26dopt%3DAbstract Authors: Linehan WM, Bratslavsky G, Pinto PA, Schmidt LS, Neckers L, Bottaro DP, Srinivasan R Kidney cancer is not a single disease; it is made up of a number of cancers that occur in the kidney, each having a different histology, following a different clinical course, responding differently to therapy, and caused by a different gene. Study of the genes underlying kidney cancer has revealed that it is fundamentally a metabolic disorder. Understanding the genetic basis of cancer of the kidney has significant implications for diagnosis and management of this disease. VHL is the gene for clear cell kidney cancer. The VHL protein forms a complex that targets the hypoxia-inducible factors for ubiquitin-mediated degradation. Knowledge of this pathway provided the foundation for the developme... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3167744 Wed, 13 Jan 2010 20:32:03 +0100 3167744 http://www.medworm.com/index.php?rid=3167743&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20059342%26dopt%3DAbstract Authors: Scott BL, Deeg HJ Myelodysplastic syndromes (MDS) represent a collection of stem cell disorders characterized by impaired hematopoiesis resulting in low peripheral blood counts. The majority of patients with MDS present with symptoms related to anemia; however, bleeding and infection are the most common causes of death. The median age of diagnosis is 72 and the median survival is 2.5 years. Lenalidomide, azacitidine, and decitabine are all FDA-approved agents to treat MDS; however, the only potential cure for MDS remains stem cell transplantation. PMID: 20059342 [PubMed - in process] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3167743 Wed, 13 Jan 2010 20:32:03 +0100 3167743 http://www.medworm.com/index.php?rid=3167742&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20059343%26dopt%3DAbstract Authors: Singhal S, Nie S, Wang MD Surgery is currently the most effective and widely used procedure in treating human cancers, and the single most important predictor of patient survival is a complete surgical resection. Major opportunities exist to develop new and innovative technologies that could help the surgeon to delineate tumor margins, to identify residual tumor cells and micrometastases, and to determine if the tumor has been completely removed. Here we discuss recent advances in nanotechnology and optical instrumentation, and how these advances can be integrated for applications in surgical oncology. A fundamental rationale is that nanometer-sized particles such as quantum dots and colloidal gold have functional and structural properties that are not available from either di... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3167742 Wed, 13 Jan 2010 20:32:03 +0100 3167742 http://www.medworm.com/index.php?rid=3167741&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20059344%26dopt%3DAbstract Authors: Musso G, Gambino R, Cassader M Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic fat accumulation in the absence of significant ethanol consumption, viral infection, or other specific causes of liver disease. Currently the most common chronic liver disease, affecting 30% of the Western world, NAFLD may progress to cirrhosis and end-stage liver disease and may increase the risk of developing diabetes and cardiovascular disease. Although its pathogenesis is unclear, NAFLD is tightly associated with insulin resistance and the metabolic syndrome. No established treatment exists, and current research is targeting new molecular mechanisms that underlie NAFLD and associated cardiometabolic disorders. This review discusses some of these emerging molecular mechanisms... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3167741 Wed, 13 Jan 2010 20:32:03 +0100 3167741 http://www.medworm.com/index.php?rid=3167740&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20059345%26dopt%3DAbstract Authors: Rubino F, Schauer PR, Kaplan LM, Cummings DE Several gastrointestinal (GI) operations that were designed to promote weight loss can powerfully ameliorate type 2 diabetes mellitus (T2DM). Although T2DM is traditionally viewed as a chronic, relentless disease in which delay of end-organ complications is the major treatment goal, GI surgery offers a novel endpoint: complete disease remission. Ample data confirm the excellent safety and efficacy of conventional bariatric operations-especially Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding-to treat T2DM in severely obese patients. Use of experimental procedures as well as conventional bariatric operations is increasingly being explored in less obese diabetic patients, with generally favorable results, although... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3167740 Wed, 13 Jan 2010 20:32:03 +0100 3167740 http://www.medworm.com/index.php?rid=3167739&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20059346%26dopt%3DAbstract Authors: Whitcomb DC Acute pancreatitis and chronic pancreatitis are complex inflammatory disorders of the pancreas with unpredictable severity, complications, and clinical courses. Growing evidence for genetic risk and modifying factors, plus strong evidence that only a minority of patients with these disorders are heavy alcohol drinkers, has revolutionized our concept of these diseases. Once considered a self-inflicted injury, pancreatitis is now recognized as a complex inflammatory condition like inflammatory bowel disease. Genetic linkage and candidate gene studies have identified six pancreas-targeting factors that are associated with changes in susceptibility to acute and/or chronic pancreatitis, including cationic trypsinogen (PRSS1), anionic trypsinogen (PRSS2), serine protease... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3167739 Wed, 13 Jan 2010 20:32:03 +0100 3167739 http://www.medworm.com/index.php?rid=3167738&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20059347%26dopt%3DAbstract Authors: Stankiewicz P, Lupski JR During the last quarter of the twentieth century, our knowledge about human genetic variation was limited mainly to the heterochromatin polymorphisms, large enough to be visible in the light microscope, and the single nucleotide polymorphisms (SNPs) identified by traditional PCR-based DNA sequencing. In the past five years, the rapid development and expanded use of microarray technologies, including oligonucleotide array comparative genomic hybridization and SNP genotyping arrays, as well as next-generation sequencing with "paired-end" methods, has enabled a whole-genome analysis with essentially unlimited resolution. The discovery of submicroscopic copy-number variations (CNVs) present in our genomes has changed dramatically our perspective on DNA str... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3167738 Wed, 13 Jan 2010 20:32:03 +0100 3167738 http://www.medworm.com/index.php?rid=3167737&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20059348%26dopt%3DAbstract Authors: Ling GS, Rhee P, Ecklund JM The delivery of combat casualty care poses numerous challenges including austere conditions, limited supplies and medical personnel, and multiple simultaneous patients. However, the exigent circumstances of the battlefield compel the development of research and the advancement of adaptive, practical medical technologies to support and sustain military health. In Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF), modern changes in medical management, coupled with improved protective gear and evacuation capabilities, have facilitated the highest survival rate in combat history. PMID: 20059348 [PubMed - in process] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3167737 Wed, 13 Jan 2010 20:32:03 +0100 3167737 http://www.medworm.com/index.php?rid=3167736&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20059349%26dopt%3DAbstract Authors: Jacobson G, Anderson G The Medicare Modernization Act was intended to improve access to prescription drugs for millions of seniors, by providing a range of benefit packages with different prices and different formularies for beneficiaries to choose from. The major challenge for physicians has been to recognize when a Medicare beneficiary has coverage versus when that patient is in the "doughnut hole" where Medicare beneficiaries do not have coverage and therefore have to pay the full cost of the drugs out-of-pocket. A second challenge is that different Medicare beneficiaries are enrolled in different drug plans, and drugs that are covered in some plans are not covered in other plans. PMID: 20059349 [PubMed - in process] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=3167736 Wed, 13 Jan 2010 20:32:03 +0100 3167736 http://www.medworm.com/index.php?rid=2899516&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19824825%26dopt%3DAbstract Authors: King Iii SB, Marshall JJ, Tummala PE Coronary artery disease (CAD) is one manifestation of ischemic heart disease, which is the leading cause of mortality in the world. In addition to preventive medical therapy and lifestyle changes, consideration of revascularization of obstructed arteries to reduce ischemia, alleviate angina, and improve quality of life is a mainstay of current practice. However, the benefits of different methods of revascularization in particular patient populations are debated. Percutaneous coronary intervention (PCI), which involves placement of intracoronary stents in most patients, is a less invasive procedure than coronary artery bypass graft (CABG) surgery. Although it is generally accepted that patients with single-vessel obstructive CAD are best tre... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2899516 Mon, 12 Oct 2009 23:00:00 +0100 2899516 http://www.medworm.com/index.php?rid=2899515&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19824826%26dopt%3DAbstract Authors: Hoxie JA Developing an HIV-1 vaccine that can elicit antibodies to prevent infection has been a formidable challenge. Although no single immunogen has generated antibodies that can neutralize diverse isolates, progress has been made in understanding (a) the structure of the HIV-1 envelope glycoprotein, which is targeted by neutralizing antibodies, (b) how HIV-1 evades antibodies made by an infected host, and (c) how rare monoclonal antibodies can exhibit broadly neutralizing activity. Advances in structural and molecular biology coupled with new approaches to isolate neutralizing antibodies from HIV-1-infected individuals are enhancing our understanding of what humoral immune responses will be required for a vaccine. This review summarizes progress in understanding the host an... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2899515 Mon, 12 Oct 2009 23:00:00 +0100 2899515 http://www.medworm.com/index.php?rid=2899519&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19824816%26dopt%3DAbstract Authors: Taber KH, Hurley RA, Yudofsky SC Neuropsychiatry is the subspecialty of psychiatry that deals with disorders at the intersection of neurology and psychiatry. Neuropsychiatric disorders are complex and incompletely understood. Neuroscience research is beginning to elucidate the biological underpinnings of many of these disorders. These advances have the potential to improve diagnosis, inform treatment selection, and facilitate development of new and better interventions. Expected final online publication date for the Annual Review of Medicine Volume 61 is January 07, 2010. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates. PMID: 19824816 [PubMed - as supplied by publisher] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2899519 Sun, 11 Oct 2009 23:00:00 +0100 2899519 http://www.medworm.com/index.php?rid=2899517&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19824818%26dopt%3DAbstract Authors: Caskey CT Humans have considerable genetic variation, as shown by their DNA sequence differences. Drug responsiveness and toxicity are affected by this variability. Genetic variation affects prodrug activation, drug target, downstream activation pathways, drug elimination, and toxicity activation. Molecular diagnostic methods have discovered the genetic basis of these "outlier" drug responses. By predicting a patient's response, such diagnostics can improve both the safety and efficacy of drugs. The article illustrates the matching of molecular diagnosis to drug therapy for improved patient outcomes. Expected final online publication date for the Annual Review of Medicine Volume 61 is January 07, 2010. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised e... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2899517 Sun, 11 Oct 2009 23:00:00 +0100 2899517 http://www.medworm.com/index.php?rid=2899520&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19824815%26dopt%3DAbstract Authors: Whitsett JA, Wert SE, Weaver TE The alveolar region of the lung creates an extensive epithelial surface that mediates the transfer of oxygen and carbon dioxide required for respiration after birth. Maintenance of pulmonary function depends on the function of type II epithelial cells that synthesize and secrete pulmonary surfactant lipids and proteins, reducing the collapsing forces created at the air-liquid interface in the alveoli. Genetic and acquired disorders associated with the surfactant system cause both acute and chronic lung disease. Mutations in the ABCA3, SFTPA, SFTPB, SFTPC, SCL34A2, and TERT genes disrupt type II cell function and/or surfactant homeostasis, causing neonatal respiratory failure and chronic interstitial lung disease. Defects in GM-CSF receptor funct... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2899520 Tue, 06 Oct 2009 23:00:00 +0100 2899520 http://www.medworm.com/index.php?rid=2899518&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19824817%26dopt%3DAbstract Authors: Roberts DL, Dive C, Renehan AG Body mass index, as an approximation of body adiposity, is associated with increased risk of several common and less common malignancies in a sex- and site-specific manner. These findings implicate sex- and cancer site-specific biological mechanisms underpinning these associations, and it is unlikely that there is a "one system fits all" mechanism. Three main candidate systems have been proposed-insulin and the insulin-like growth factor-I axis, sex steroids, and adipokines-but there are shortfalls to these hypotheses. In this review, three novel candidate mechanisms are proposed: obesity-induced hypoxia, shared genetic susceptibility, and migrating adipose stromal cells. While public health policies aimed at curbing the underlying causes of the ... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2899518 Tue, 06 Oct 2009 23:00:00 +0100 2899518 http://www.medworm.com/index.php?rid=2753290&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19719397%26dopt%3DAbstract Authors: Major EO Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the white matter of the human brain caused by lytic infection of oligodendrocytes with the human polyomavirus JCV. Although the majority of PML cases occur in severely immune-suppressed individuals, with HIV-1 infection as the predominant factor, PML has been increasingly diagnosed in patients treated with biological therapies such as monoclonal antibodies that modulate immune system functions. Monoclonal antibodies that target the cell adhesion molecules VLA-4 (natalizumab; Tysabri(R) for multiple sclerosis and Crohn's disease) or LFA-1 (efalizumab; Raptiva(R) for severe forms of plaque psoriasis) to prevent extravasation of inflammatory T cells into tissues, or target the cell surface mar... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2753290 Sun, 30 Aug 2009 23:00:00 +0100 2753290 http://www.medworm.com/index.php?rid=2753289&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19719398%26dopt%3DAbstract Authors: Attia E Anorexia nervosa (AN) is a serious mental illness categorized by a failure to maintain a minimally normal weight, a fear of gaining weight or becoming fat, and preoccupations about body shape or weight. AN is associated with significant morbidity and a mortality rate as high as that seen in any psychiatric illness. Biological factors, including genetic predisposition, appear to play a role in the development of AN. Treatment is challenging both because interventions with clear empirical support have not been identified and because individuals affected by AN are typically reluctant to undergo weight restoration. Preliminary studies suggest that family-based treatment may be useful for younger patients with AN. Treatment development for adults with AN and pursuit of neur... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2753289 Sun, 30 Aug 2009 23:00:00 +0100 2753289 http://www.medworm.com/index.php?rid=2716721&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19686083%26dopt%3DAbstract Authors: Kamali F, Wynne H Warfarin is a drug with a narrow therapeutic index and a wide interindividual variability in dose requirement. Because it is difficult to predict an accurate dose for an individual, patients starting the drug are at risk of thromboembolism or bleeding associated with underdosing or overdosing, respectively. Single nucleotide polymorphisms in the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKOR) genes have been shown to have a significant effect on warfarin dose requirement. Other genes mediating the action of warfarin make either little or no contribution to dose requirement. Although the polymorphisms in CYP2C9 and VKORC1 explain a significant proportion of the interindividual variability in warfarin dose requirement, currently available ev... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2716721 Sun, 16 Aug 2009 23:00:00 +0100 2716721 http://www.medworm.com/index.php?rid=2716720&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19686084%26dopt%3DAbstract Authors: Akashi YJ, Nef HM, Möllmann H, Ueyama T Recently, an increasing number of cases of stress cardiomyopathy, mainly occurring in elderly women, have been documented in many parts of the world. In Japan, this disease is known as takotsubo cardiomyopathy (named after the fishing pot used for trapping octopus). Symptoms of this condition are akin to those of acute myocardial infarction, but no obstructive lesions are found in the coronary arteries, and left ventricular apical ballooning is present. Stress cardiomyopathy is now a well-recognized cause of acute heart failure, lethal ventricular arrhythmias, and ventricular rupture. Although the precise mechanism of onset of this condition is still controversial, two major pathogenic mechanisms have been proposed: catecholamine ca... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2716720 Sun, 16 Aug 2009 23:00:00 +0100 2716720 http://www.medworm.com/index.php?rid=2661338&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19642221%26dopt%3DAbstract Authors: Kuter DJ Although the thrombopoietin receptor was discovered in 1991 and thrombopoietin (TPO) was purified in 1994, the development of a clinically useful TPO was hampered by the appearance of neutralizing antibodies to some forms of recombinant TPO. However, in 2008 two new drugs that mimic the effect of TPO became available to treat thrombocytopenia. Romiplostim is a TPO peptide mimetic given by subcutaneous injection that activates the TPO receptor by binding to the distal hematopoietic receptor domain just like TPO. Eltrombopag is a TPO nonpeptide mimetic administered orally that activates the TPO receptor by binding to the transmembrane domain. Both increase the platelet count in healthy humans as well as in >80% of patients with immune thrombocytopenic purpura (ITP). ... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2661338 Sun, 02 Aug 2009 07:12:03 +0100 2661338 http://www.medworm.com/index.php?rid=2649484&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19630568%26dopt%3DAbstract Authors: Cappellini MD, Pattoneri P Deferoxamine (DFO) was the standard of care for transfusional iron overload for >40 years, requiring subcutaneous infusion for 8-12 h/day, 5-7 days/week. Oral iron chelators are an important development, offering the potential to improve compliance and patients' quality of life. The oral, three-times-daily agent deferiprone appeared to be a promising advance; however, its use has been limited owing to serious adverse events, such as neutropenia and agranulocytosis. Therapy combining deferiprone with DFO has proved effective in the management of severe cardiac siderosis. Deferasirox is a novel, orally active agent that provides 24-h chelation with a once-daily dose. An extensive clinical trial program has demonstrated that deferasirox at appropriat... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2649484 Wed, 29 Jul 2009 14:40:03 +0100 2649484 http://www.medworm.com/index.php?rid=2649483&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19630569%26dopt%3DAbstract Authors: Morrow PK, Hortobagyi GN The genomic era has been characterized by an exponential increase in the number of targets in the management of breast cancer. Prognostic profiling has helped to determine which tumors are more likely to be associated with poor disease-free survival. Gene expression profiles are being studied in order to improve predictions of response and toxicity. Epigenetics is being evaluated for its ability to influence estrogen receptor expression. However, these fields require further validation. This review discusses the advances in the management of breast cancer through genomic evaluation. PMID: 19630569 [PubMed - in process] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2649483 Wed, 29 Jul 2009 14:40:03 +0100 2649483 http://www.medworm.com/index.php?rid=2649482&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19630570%26dopt%3DAbstract Authors: Garzon R, Calin GA, Croce CM MicroRNAs (miRNAs) are small, noncoding RNAs with important functions in development, cell differentiation, and regulation of cell cycle and apoptosis. MiRNA expression is deregulated in cancer by a variety of mechanisms including amplification, deletion, mutation, and epigenetic silencing. Several studies have now shown that miRNAs are involved in the initiation and progression of cancer. In this review, we briefly describe miRNA biogenesis and discuss how miRNAs can act as oncogenes and tumor suppressors. We also address the role of miRNAs in the diagnosis, prognosis, and treatment of cancer. PMID: 19630570 [PubMed - in process] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2649482 Wed, 29 Jul 2009 14:40:03 +0100 2649482 http://www.medworm.com/index.php?rid=2649481&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19630571%26dopt%3DAbstract We present in detail these recent advances and provide some insight into several promising future strategies. PMID: 19630571 [PubMed - in process] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2649481 Wed, 29 Jul 2009 14:40:03 +0100 2649481 http://www.medworm.com/index.php?rid=2649480&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19630572%26dopt%3DAbstract This article reviews the epidemiology, assessment, neurobiology, genetic etiology, and treatment of nicotine dependence. Enhanced understanding of these dimensions of nicotine dependence may help to advance progress toward lowering the prevalence rate of tobacco use in the U.S. and lowering the rate of tobacco-related morbidity and mortality. PMID: 19630572 [PubMed - in process] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2649480 Wed, 29 Jul 2009 14:40:03 +0100 2649480 http://www.medworm.com/index.php?rid=2649479&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19630573%26dopt%3DAbstract Authors: Broide DH This review focuses on sublingual immunotherapy (SLIT), toll-like receptor-9 (TLR-9) vaccines using cytosine phosphorothioate guanosine (CpG)-allergen conjugates, and anti-IL-5 as novel immunomodulating therapies in allergy. At present, all three approaches are investigational in the United States and require further study to determine their safety and effectiveness. SLIT provides a novel oral route of administering an allergen to induce tolerance to inhaled allergens. Studies of SLIT in allergic rhinitis demonstrate that it reduces symptoms and medication use and is associated with a low incidence of systemic allergic reactions. Initial phase II studies with TLR-9 vaccines conjugated to a ragweed allergen demonstrate that they reduce symptoms of allergic rhinitis du... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2649479 Wed, 29 Jul 2009 14:40:03 +0100 2649479 http://www.medworm.com/index.php?rid=2649478&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19630574%26dopt%3DAbstract Authors: Klion A Hypereosinophilic syndrome is a heterogeneous group of rare disorders characterized by marked blood or tissue eosinophilia resulting in a wide variety of clinical manifestations. Although the existence of clinical subtypes (or variants) of HES has been appreciated for some time, the recent characterization of some of these variants at the molecular and immunologic levels has demonstrated dramatic differences in disease pathogenesis, response to treatment, and prognosis depending on the etiology of the eosinophilia. This, together with the availability of novel targeted therapies, including tyrosine kinase inhibitors and monoclonal antibodies, has fundamentally altered the approach to the diagnosis and treatment of HES. PMID: 19630574 [PubMed - in process] (Source: ... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2649478 Wed, 29 Jul 2009 14:40:03 +0100 2649478 http://www.medworm.com/index.php?rid=2649477&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19630575%26dopt%3DAbstract Authors: Shenoi S, Friedland G The presence and consequences of resistance to drugs used for the treatment of tuberculosis have long been neglected. The recent detection and recognition of widespread multiple-drug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis have raised interest and concern among clinicians and public health authorities globally. In this article, we describe the current global status of drug-resistant tuberculosis. We discuss the development of resistance, current management, and strategies for control. PMID: 19630575 [PubMed - in process] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2649477 Wed, 29 Jul 2009 14:40:03 +0100 2649477 http://www.medworm.com/index.php?rid=2649476&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19630576%26dopt%3DAbstract Authors: Berger M, Gray JA, Roth BL Serotonin is perhaps best known as a neurotransmitter that modulates neural activity and a wide range of neuropsychological processes, and drugs that target serotonin receptors are used widely in psychiatry and neurology. However, most serotonin is found outside the central nervous system, and virtually all of the 15 serotonin receptors are expressed outside as well as within the brain. Serotonin regulates numerous biological processes including cardiovascular function, bowel motility, ejaculatory latency, and bladder control. Additionally, new work suggests that serotonin may regulate some processes, including platelet aggregation, by receptor-independent, transglutaminase-dependent covalent linkage to cellular proteins. We review this new "expanded... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2649476 Wed, 29 Jul 2009 14:40:03 +0100 2649476 http://www.medworm.com/index.php?rid=2649475&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19630577%26dopt%3DAbstract Authors: Geschwind DH Autism is a common childhood neurodevelopmental disorder with strong genetic liability. It is not a unitary entity but a clinical syndrome, with variable deficits in social behavior and language, restrictive interests, and repetitive behaviors. Recent advances in the genetics of autism emphasize its etiological heterogeneity, with each genetic susceptibility locus accounting for only a small fraction of cases or having a small effect. Therefore, it is not surprising that no unifying structural or neuropathological features have been conclusively identified. Given the heterogeneity of autism spectrum disorder (ASD), approaches based on studying heritable components of the disorder, or endophenotypes, such as language or social cognition, provide promising avenues f... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2649475 Wed, 29 Jul 2009 14:40:03 +0100 2649475 http://www.medworm.com/index.php?rid=2649474&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19630578%26dopt%3DAbstract Authors: Bernat JL Although philosophers and cognitive neuroscientists have struggled to define human consciousness, physicians can identify and assess its two clinical dimensions: wakefulness and awareness. A comatose patient has neither wakefulness nor awareness; a patient in a vegetative state has wakefulness without awareness; and a minimally conscious patient has both, but awareness is impaired. Syndromes of unconsciousness have established diagnostic criteria, but they encompass a spectrum of severity of brain damage and have indistinct boundaries. Functional neuroimaging using PET and fMRI have provided a new and complementary way to assess consciousness. Several recent provocative studies suggest that fMRI in unresponsive patients may detect evidence of conscious awareness when... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2649474 Wed, 29 Jul 2009 14:40:03 +0100 2649474 http://www.medworm.com/index.php?rid=2649473&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19630579%26dopt%3DAbstract Authors: Jolesz FA MRI-guided focused ultrasound (MRgFUS) surgery is a noninvasive thermal ablation method that uses magnetic resonance imaging (MRI) for target definition, treatment planning, and closed-loop control of energy deposition. Integrating FUS and MRI as a therapy delivery system allows us to localize, target, and monitor in real time, and thus to ablate targeted tissue without damaging normal structures. This precision makes MRgFUS an attractive alternative to surgical resection or radiation therapy of benign and malignant tumors. Already approved for the treatment of uterine fibroids, MRgFUS is in ongoing clinical trials for the treatment of breast, liver, prostate, and brain cancer and for the palliation of pain in bone metastasis. In addition to thermal ablation, FUS, wi... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2649473 Wed, 29 Jul 2009 14:40:03 +0100 2649473 http://www.medworm.com/index.php?rid=2649472&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19630580%26dopt%3DAbstract Authors: Manolio TA, Collins FS The International HapMap Project produced a genome-wide database of human genetic variation for use in genetic association studies of common diseases. The initial output of these studies has been overwhelming, with over 150 risk loci identified in studies of more than 60 common diseases and traits. These associations have suggested previously unsuspected etiologic pathways for common diseases that will be of use in identifying new therapeutic targets and developing targeted interventions based on genetically defined risk. Here we examine the development and application of the HapMap to genome-wide association (GWA) studies; present and future technologies for GWA research; current major efforts in GWA studies; successes and limitations of the GWA approac... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2649472 Wed, 29 Jul 2009 14:40:03 +0100 2649472 http://www.medworm.com/index.php?rid=2649471&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19630581%26dopt%3DAbstract Authors: Paiardini M, Pandrea I, Apetrei C, Silvestri G The fact that human immunodeficiency virus (HIV) causes a deadly disease in humans whereas its simian counterparts, the simian immunodeficiency viruses (SIVs), are virtually nonpathogenic in their natural hosts remains a fundamental mystery of modern medicine. Arguably, the pathogenesis of HIV infection will remain poorly understood until the mechanisms responsible for the AIDS resistance of natural SIV hosts are fully explained. Over the past few years, some key features of natural SIV infections have been described in studies conducted predominantly in sooty mangabeys (SMs), African green monkeys (AGMs), and mandrills. Natural SIV hosts are able to avoid the chronic, generalized immune system activation that is associated with d... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2649471 Wed, 29 Jul 2009 14:40:03 +0100 2649471 http://www.medworm.com/index.php?rid=2631099&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19622036%26dopt%3DAbstract Authors: Hazra R, Siberry GK, Mofenson LM Tremendous success in the prevention and treatment of pediatric HIV in high-resource countries has changed the face of the epidemic. A perinatally HIV-infected child now faces a chronic disease rather than a progressive, fatal one. However, these successes pose new challenges as perinatally HIV-infected youth survive into adulthood. These include maintaining adherence to long-term, likely life-long therapy; selecting successive antiretroviral drug regimens, given the limited availability of pediatric formulations and the lack of pharmacokinetic and safety data in children; and overcoming extensive drug resistance in multi-drugexperienced children. Pediatric HIV care now focuses on morbidity related to long-term HIV infection and its treatment. ... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=2631099 Mon, 20 Jul 2009 23:00:00 +0100 2631099 http://www.medworm.com/index.php?rid=1970387&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19012475%26dopt%3DAbstract Authors: Kodali S, Schwartz A There is significant interest in developing transcatheter therapy for valvular heart disease (VHD). Numerous devices have been developed for the percutaneous treatment of pulmonary and aortic stenosis as well as mitral regurgitation. Several of these devices have progressed to randomized clinical trials. These ongoing trials for aortic stenosis and mitral regurgitation will provide important insights into the durability of these therapies as well as the results following standard surgical repair. The field of transcatheter valve therapy is rapidly evolving, and this review aims to summarize the current status of the field. Expected final online publication date for the Annual Review of Medicine Volume 60 is January 07, 2009. Please see http://www.annualrev... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1970387 Fri, 14 Nov 2008 05:00:00 +0100 1970387 http://www.medworm.com/index.php?rid=1934946&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18980468%26dopt%3DAbstract Authors: Glaspy JA Therapy with erythropoiesis-stimulating agents (ESAs) is associated with well-documented benefits to anemic cancer patients undergoing chemotherapy, most importantly a reduction in the likelihood of needing red cell transfusions. One challenge in supportive cancer care is a relative resistance to ESAs, requiring high doses with a significant rate of nonresponse. Recent advances in our understanding of iron metabolism in patients with chronic illness and the results of clinical trials indicate that parenteral iron improves ESA response in this setting. Another issue is the safety of ESA treatment in cancer patients. There is an increased risk of venous thrombosis that must be considered in clinical decision making. There are also recent data raising concerns that ESAs... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1934946 Mon, 03 Nov 2008 05:00:00 +0100 1934946 http://www.medworm.com/index.php?rid=1931134&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18976050%26dopt%3DAbstract Authors: Abraham C, Cho JH The intestinal immune system has the challenge of maintaining both a state of tolerance toward intestinal antigens and the ability to combat pathogens. This balance is partially achieved by reciprocal regulation of proinflammatory, effector CD4(+) T cells, and tolerizing, suppressive Treg subsets. Inflammatory bowel disease (IBD) comprises Crohn's disease (CD) and ulcerative colitis (UC). Genome-wide association studies have linked CD to a number of IL-23 pathway genes, notably IL23R (interleukin 23 receptor). Similar associations in IL-23 pathway genes have been observed in UC. IL23R is a key differentiation feature of CD4(+) Th17 cells, effector cells that are critical in mediating antimicrobial defenses. However, IL-23 and Th17 cell dysregulation can lead ... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1931134 Fri, 31 Oct 2008 04:00:00 +0100 1931134 http://www.medworm.com/index.php?rid=1931133&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18976115%26dopt%3DAbstract Authors: Torban E, Goodyer P The association between renal dysplasia and minor malformations of the external ear is weak. However, there is a remarkable list of syndromes that link the kidney to the inner ear. To organize these seemingly disparate syndromes, we cluster representative examples into three groups: (a) syndromes that share pathways regulating development; (b) syndromes involving dysfunction of the primary cilium, which normally provides critical information to epithelial cells about the fluid in which they are bathed; (c) syndromes arising from dysfunction of specialized proteins that transport ions and drugs in and out of the extracellular fluid or provide structural support. Expected final online publication date for the Annual Review of Medicine Volume 60 is January 07,... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1931133 Fri, 31 Oct 2008 04:00:00 +0100 1931133 http://www.medworm.com/index.php?rid=1906719&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18947294%26dopt%3DAbstract Authors: Abdel-Wahab OI, Levine RL Primary myelofibrosis (PMF) is a clonal stem cell disorder that manifests clinically as anemia, splenomegaly due to extramedullary hematopoiesis, leukoerythroblastosis, and constitutional symptoms, which are the clinical hallmarks of PMF.Within the past three years it has been determined that a single, recurrent, somatic mutation in the gene encoding the cytoplasmic tyrosine kinase Janus kinase 2 ( JAK2) occurs in the majority of patients with PMF, and more recently, activating mutations in the gene encoding the thrombopoietin receptor MPL have also been identified in a subset of PMF patients. These discoveries have yielded important insights into the pathogenesis of PMF and have brought about the first opportunity for rationally targeted therapy for ... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1906719 Thu, 23 Oct 2008 04:00:00 +0100 1906719 http://www.medworm.com/index.php?rid=1906718&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18947296%26dopt%3DAbstract Authors: Douek DC, Roederer M, Koup RA There is an intense interplay between HIV and the immune system, and the literature is replete with studies describing various immunological phenomena associated with HIV infection. Many of these phenomena seem too broad in scope to be attributable either to HIV-infected cells or to the HIV-specific immune response. Recently, a more fundamental understanding of how HIV affects various T cells and T cell compartments has emerged. This review covers the role of immune activation in HIV immunopathogenesis, how that activation could be mediated directly by HIV replicating within and damaging the gut mucosal barrier, how HIV affects multiple T cell functions and phenotypes, and how chronic HIV replication induces immune modulatory pathways to negativel... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1906718 Thu, 23 Oct 2008 04:00:00 +0100 1906718 http://www.medworm.com/index.php?rid=1906717&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18947298%26dopt%3DAbstract Authors: Makarov DV, Loeb S, Getzenberg RH, Partin AW The development of biomarkers for prostate cancer screening, detection, and prognostication has revolutionized the management of this disease. Prostate-specific antigen (PSA) is a useful, though not specific, biomarker for detecting prostate cancer.We review the literature on prostate cancer biomarkers, including serum markers (PAP, tPSA, fPSA, proPSA, PSAD, PSAV, PSADT, EPCA, and EPCA-2), tissue markers (AMACR, methylated GSTP1, and the TMPRSS2-ETS gene rearrangement), and a urine marker (DD3PCA3/UPM-3). Future research should focus on validation of already existing biomarkers and the discovery of new markers to identify men with aggressive prostate cancer. Expected final online publication date for the Annual Review of Medicine Vo... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1906717 Thu, 23 Oct 2008 04:00:00 +0100 1906717 http://www.medworm.com/index.php?rid=1906716&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18947299%26dopt%3DAbstract Authors: Harris PC, Torres VE A number of inherited disorders result in renal cyst development. The most common form, autosomal dominant polycystic kidney disease (ADPKD), is a disorder most often diagnosed in adults and caused by mutation in PKD1 or PKD2. The PKD1 protein, polycystin-1, is a large receptor-like protein, whereas polycystin-2 is a transient receptor potential channel. The polycystin complex localizes to primary cilia and may act as a mechanosensor essential for maintaining the differentiated state of epithelia lining tubules in the kidney and biliary tract. Elucidation of defective cellular processes has highlighted potential therapies, many of which are now being tested in clinical trials. ARPKD is the neonatal form of PKD and is associated with enlarged kidneys and bi... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1906716 Thu, 23 Oct 2008 04:00:00 +0100 1906716 http://www.medworm.com/index.php?rid=1906715&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18947300%26dopt%3DAbstract Authors: Lamberts SW, Uitterlinden AG In the practice of internal medicine, the value of genetic testing in common (mono)genetic diseases such as familial hemochromatosis, hypercholesterolemia, Mediterranean fever, and thrombophilia is limited. The genotype insufficiently predicts the phenotype because of the powerful effects of other modifying genes, environmental influences, and lifestyle factors. Many common diseases, including diabetes mellitus, osteoporosis, and cardiovascular disease, have strong genetic influences but are called complex genetic traits. The underlying genetic factors are currently investigated using new molecular tools such as genome-wide association studies, analyzing up to 500,000 markers in huge number of patients. Many new (often unexpected) markers have been... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1906715 Thu, 23 Oct 2008 04:00:00 +0100 1906715 http://www.medworm.com/index.php?rid=1896551&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18928333%26dopt%3DAbstract Authors: O'Dell MW, Lin CC, Harrison V Recent evidence indicates that the brain can remodel after stroke, primarily through synaptogenesis.Task-specific and repetitive exercise appear to be key factors in promoting synaptogenesis and are central elements in rehabilitation of motor weakness following stroke. Expert medical management ensures a patient is well enough to participate in rehabilitation with minimal distractions due to pain or depression. Contraint-induced motor therapy and body-weight-supported ambulation are forms of exercise that "force use" of an impaired upper extremity. Technologies now in common use include robotics, functional electrical stimulation, and, to a lesser degree, transcranial magnetic stimulation and virtual reality. The data on pharmacological interventi... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1896551 Fri, 17 Oct 2008 04:00:00 +0100 1896551 http://www.medworm.com/index.php?rid=1896550&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18928334%26dopt%3DAbstract Authors: Tester DJ, Ackerman M In the past decade there has been an increasing awareness of distinct, potentially lethal heritable cardiomyopathic and channelopathic syndromes as they pertain to sudden cardiac death in infants and children. This review highlights current clinical and molecular findings of two highly relevant structural cardiac abnormalities evident at autopsy, namely hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy, as well as the cardiac channelopathies of long QTsyndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, and short QT syndrome, which may account for one third of autopsy-negative sudden unexplained deaths (SUDs) during childhood and adolescence. We also explore the role of postmortem genetic analysi... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1896550 Fri, 17 Oct 2008 04:00:00 +0100 1896550 http://www.medworm.com/index.php?rid=1896549&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18928335%26dopt%3DAbstract Authors: Ruggiero SL, Mehrotra B Bisphosphonate therapy has been considered standard therapy in the management and care of cancer patients with metastatic bone disease and patients with osteoporosis. The efficacy of these drugs is due to their ability to inhibit osteoclast-mediated bone resorption. However, the postmarketing experience with intravenous and, to a much lesser extent, oral bisphosphonates has raised concerns about potential side effects related to profound bone remodeling inhibition and osteonecrosis isolated to the jaws. We review the risk factors, incidence, pathogenesis, prevention strategies, and management of this new complication. Expected final online publication date for the Annual Review of Medicine Volume 60 is January 07, 2009. Please see http://www.annualrevie... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1896549 Fri, 17 Oct 2008 04:00:00 +0100 1896549 http://www.medworm.com/index.php?rid=1833849&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18817460%26dopt%3DAbstract Authors: Sierra F, Hadley E, Suzman R, Hodes R Life expectancy has increased dramatically in the United States and in much of the world in recent years and decades. The factors underlying this increase are incompletely understood and are undoubtedly complex. A question that drives current research is whether life expectancy can be further extended using current knowledge of modifiable risk factors. A still more challenging research focus is on the possibility that life expectancy might be further increased through knowledge gained from studies of the basic biology of aging and its genetic and environmental modifiers. Expected final online publication date for the Annual Review of Medicine Volume 60 is January 07, 2009. Please see http://www.annualreviews.org/catalog/pubdates.aspx for r... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1833849 Thu, 25 Sep 2008 04:00:00 +0100 1833849 http://www.medworm.com/index.php?rid=1833848&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18817461%26dopt%3DAbstract Authors: Henry MC, Moss LR Necrotizing enterocolitis (NEC) remains a major cause of neonatal morbidity and death. The pathophysiology is poorly understood. Prevailing evidence suggests that NEC is due to an inappropriate inflammatory response of the immature gut to some undefined insult. The mortality rate (15%-25%) for affected infants has not changed appreciably in 30 years. Many infants with NEC recover uneventfully with medical therapy and have long-term outcomes similar to unaffected infants of matched gestational age. Infants with progressive disease requiring surgical intervention suffer almost all of the mortality and morbidity. Of these, 30%-40% will die of their disease and most of the remainder will develop long-term neurodevelopmental and gastrointestinal morbidity. Recent ... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1833848 Thu, 25 Sep 2008 04:00:00 +0100 1833848 http://www.medworm.com/index.php?rid=1816490&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18803476%26dopt%3DAbstract This article explains these biases and other common confounders in cancer screening. The most direct and reliable way to avoid being led astray by intuitions is through the use of randomized controlled trials. Expected final online publication date for the Annual Review of Medicine Volume 60 is January 07, 2009. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates. PMID: 18803476 [PubMed - as supplied by publisher] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1816490 Fri, 19 Sep 2008 04:00:00 +0100 1816490 http://www.medworm.com/index.php?rid=1786645&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18783330%26dopt%3DAbstract Authors: Bresalier RS The incidence of esophageal adenocarcinoma (EAC) has risen dramatically over the past three decades in western countries. The importance of Barrett's esophagus (BE) derives from its potential to transform to adenocarcinoma. BE is characterized by endoscopically recognized displacement of the squamocolumnar junction proximal to the gastroesophageal junction, with replacement of squamous mucosa with columnar lined mucosa. Adenocarcinomas of the esophagus appear to arise from Barrett's mucosa through progressive degrees of dysplasia, but the pathogenesis and natural history of this process are still unclear. Much of our knowledge regarding BE and the risk of EAC is based on observational and cross-sectional analyses, and recommendations regarding management have trad... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1786645 Wed, 10 Sep 2008 04:00:00 +0100 1786645 http://www.medworm.com/index.php?rid=1760827&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18764741%26dopt%3DAbstract This article briefly reviews preclinical data and the current status of ETRAs in the clinical management of PAH. Expected final online publication date for the Annual Review of Medicine Volume 60 is January 07, 2009. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates. PMID: 18764741 [PubMed - as supplied by publisher] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1760827 Tue, 02 Sep 2008 04:00:00 +0100 1760827 http://www.medworm.com/index.php?rid=1751414&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18759554%26dopt%3DAbstract Authors: Birkmeyer JD, Dimick JB Surgical mortality varies widely across hospitals and surgeons, more so than would be predicted by chance alone or differences in case mix. Although a large body of research has suggested the importance of procedure volume, clinical mechanisms underlying variation in surgical mortality remain largely unknown. Payers, policy makers, and professional organizations have implemented a variety of large-scale strategies aimed at improving outcomes. Selective referral, process compliance, and outcomes measurement reflect different philosophies on how best to improve surgical quality and have distinct advantages and disadvantages. The optimal strategy may depend on both the clinical context (e.g., which procedure) and political realities. Expected final online ... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1751414 Fri, 29 Aug 2008 04:00:00 +0100 1751414 http://www.medworm.com/index.php?rid=1743731&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18729729%26dopt%3DAbstract Authors: Sicherer SH, Sampson HA Food allergies, defined as an adverse immune response to food proteins, affect as many as 6% of young children and 3%-4% of adults in westernized countries, and their prevalence appears to be rising. In addition to well-recognized acute allergic reactions and anaphylaxis triggered by IgE antibody-mediated immune responses to food proteins, there is an increasing recognition of cell-mediated disorders such as eosinophilic gastroenteropathies and food protein-induced enterocolitis syndrome. We are gaining an increasing understanding of the pathophysiology of food allergic disorders and are beginning to comprehend how this disease results from a failure to establish or maintain normal oral tolerance. Many food allergens have been characterized at a molecul... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1743731 Tue, 19 Aug 2008 04:00:00 +0100 1743731 http://www.medworm.com/index.php?rid=1743730&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18729730%26dopt%3DAbstract Authors: Sharfstein SS The purpose of the psychiatric hospital changed dramatically during the twentieth century. Formerly the primary location for psychiatric treatment, the hospital now plays a more circumscribed role within a community-based system of care. Crisis stabilization, safety, and a focus on rapid discharge are the critical components of the acute inpatient stay. Subspecialized units focus on geriatrics, children, adolescents, dual diagnosis (substance abuse and mental illness), trauma disorders, eating disorders, and forensics. When integrated with the general medical system and a comprehensive base of community-delivered day treatment, residential sevices, and outpatient services, psychiatric hospitalization is a humane alternative to long-term institutional care. Expect... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1743730 Tue, 19 Aug 2008 04:00:00 +0100 1743730 http://www.medworm.com/index.php?rid=1743729&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18729731%26dopt%3DAbstract Authors: Maron BA, Loscalzo J The unique biochemical profile of homocysteine is characterized by chemical reactivity supporting a wide range of molecular effects and by a tendency to promote oxidant stress-induced cellular toxicity. Numerous epidemiological reports have established hyperhomocysteinemia as an independent risk factor for cardiovascular disease, cerebrovascular disease, dementia-type disorders, and osteoporosis-associated fractures. Although combined folic acid and B-vitamin therapy substantially reduces homocysteine levels, results from randomized placebo-controlled clinical trials testing the effect of vitamin therapy on outcome in these diseases have generally fallen short of expectations. These results have led some to abandon homocysteine monitoring in the management... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1743729 Tue, 19 Aug 2008 04:00:00 +0100 1743729 http://www.medworm.com/index.php?rid=1583828&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17705684%26dopt%3DAbstract Authors: Kavanagh D, Richards A, Atkinson J Hemolytic uremic syndrome is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. It is one of a group of conditions termed the thrombotic microangiopathies, which are characterized by prominent endothelial cell injury. It may be diarrheal-associated or atypical (aHUS). Evidence for a pathogenic role of the alternative pathway of complement was first suggested in 1974. Mutations in the complement regulatory proteins factor H, membrane cofactor protein (CD46), and factor I predispose to aHUS development. Mutations of the activating components factor B and complement C3 have also been reported. Penetrance is approximately 50%, suggesting other genetic and environmental modifiers are needed for disease express... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583828 Mon, 07 Jul 2008 14:12:35 +0100 1583828 http://www.medworm.com/index.php?rid=1583827&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17716024%26dopt%3DAbstract Authors: Emanuel LL Most patients want some control over their medical care, including-or even especially-when they are too sick to participate in decisions. Clinicians who have to make decisions for patients who are unable to participate often would appreciate guidance from patients' wishes. Advance care planning responds to these needs. The process provides for discussions about goals in different scenarios and allows inclusion of the family and physician as well as the patient. It helps to have the patient and family complete validated worksheets that walk them through the various considerations and result in expressions of preference that are clinically meaningful. For the clinician, scenario-based goals for care and personal thresholds for when desired care shifts from primarily c... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583827 Mon, 07 Jul 2008 14:12:35 +0100 1583827 http://www.medworm.com/index.php?rid=1583826&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17716025%26dopt%3DAbstract Authors: Sequist LV, Lynch TJ Drugs that target the epidermal growth factor receptor (EGFR) have had a major impact on the treatment of non-small cell lung cancer (NSCLC). The use of these drugs has also motivated pivotal advances in the understanding of the molecular biology of NSCLC, including the discovery that mutations in EGFR are associated with dramatic and sustained responses to anti-EGFR treatments. This review summarizes the clinical development of EGFR tyrosine kinase inhibitors, the discovery of molecular predictors of response, and the future directions for research in the field. PMID: 17716025 [PubMed - indexed for MEDLINE] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583826 Mon, 07 Jul 2008 14:12:35 +0100 1583826 http://www.medworm.com/index.php?rid=1583825&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17845134%26dopt%3DAbstract Authors: Guerra S, Martinez FD Asthma risk has a clear hereditary component but, unexpectedly, the majority of reported associations between genetic variants and asthma have not been consistently replicated across studies. Methodological flaws have been indicated as a possible explanation for these inconsistencies. However, an alternative explanation is that the effects of genetic variants depend on other factors whose frequency and distribution vary, both across individuals and across populations. Within this framework, we review recent advances in asthma genetics and conclude that a paradigm shift is needed, because a static model in which the DNA sequence is associated with disease risk in a linear fashion fails to consider the interdependence of the diverse components of asthma ris... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583825 Mon, 07 Jul 2008 14:12:35 +0100 1583825 http://www.medworm.com/index.php?rid=1583824&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17845135%26dopt%3DAbstract Childhood obesity: adrift in the "limbic triangle". Annu Rev Med. 2008;59:147-62 Authors: Mietus-Snyder ML, Lustig RH The prevalence and severity of childhood obesity have increased steadily over the past three decades. The human species evolved to rigorously defend its lower limit for weight and adiposity but is tolerant of the upper limit, which, until recent times, was rarely approached. Neuroendocrine mechanisms within the limbic core of the brain prevent starvation (ventromedial hypothalamus), heighten reward (ventral tegmental area and nucleus accumbens), and attenuate stress (amygdala), in order to promote food-seeking and ingestive behavior and to conserve energy output. In a stressful modern environment with ready access to calorie-dense, highly palatable foods and lim... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583824 Mon, 07 Jul 2008 14:12:35 +0100 1583824 http://www.medworm.com/index.php?rid=1583823&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17845136%26dopt%3DAbstract Authors: Hedner U, Ezban M For hemophilia patients with inhibitors against FVIII or FIX, the development of recombinant factor VIIa (rFVIIa) raises the possibility of a therapeutic alternative whose availability and convenience of treatment are comparable to those of FVIII or FIX. In support of this new concept for the treatment of bleeding episodes, pharmacological doses of FVIIa have been shown to induce hemostasis. Pharmacological doses of rFVIIa enhance thrombin generation on thrombin-activated platelets, thereby facilitating the formation of strong, well-structured fibrin plugs resistant to premature proteolysis. Modified rFVIIa molecules with a stronger hemostatic potential have been produced. Inhibition of the FVII-TF-dependent pathway (TFPI and rFVIIai) has been tried in attemp... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583823 Mon, 07 Jul 2008 14:12:35 +0100 1583823 http://www.medworm.com/index.php?rid=1583822&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17845137%26dopt%3DAbstract Authors: Judge DP, Dietz HC Marfan syndrome is a common inherited disorder of connective tissue caused by deficiency of the matrix protein fibrillin-1. Effective surgical therapy for the most life-threatening manifestation, aortic root aneurysm, has led to a nearly normal lifespan for affected individuals who are appropriately recognized and treated. Traditional medical therapies, such as beta-adrenergic receptor blockade, are used to slow pathologic aortic growth and decrease the risk of aortic dissection by decreasing hemodynamic stress. New insights regarding the pathogenesis of Marfan syndrome have developed from investigation of murine models of this disorder. Fibrillin-1 deficiency is associated with excess signaling by transforming growth factor beta (TGFbeta). TGFbeta antagonis... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583822 Mon, 07 Jul 2008 14:12:35 +0100 1583822 http://www.medworm.com/index.php?rid=1583821&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17845138%26dopt%3DAbstract Authors: Geeraert L, Kraus G, Pomerantz RJ The success of highly active antiretroviral therapy (HAART) for HIV-1 infection has sparked interest in mechanisms by which the virus can persist despite effectively suppressive therapy. Latent HIV-1 reservoirs established early during infection not only prevent sterilizing immunity but also represent a major obstacle to virus eradication. When HIV-1 gains a foothold in the immunologic memory or in certain inaccessible compartments of the human body, it cannot be easily purged by HAART and is able to replenish systemic infection on treatment interruption. Because latently infected cells are indistinguishable from uninfected cells, deliberate activation of latent infection combined with intensified HAART seems to be the best strategy to combat ... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583821 Mon, 07 Jul 2008 14:12:35 +0100 1583821 http://www.medworm.com/index.php?rid=1583820&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17845139%26dopt%3DAbstract Authors: Garantziotis S, Hollingsworth JW, Zaas AK, Schwartz DA Toll-like receptors (TLRs) enable innate immune recognition of endogenous and exogenous prototypic ligands. They also orchestrate innate and adaptive immune response to infection, inflammation, and tissue injury. Given their significance in the immune response, it is not surprising that genetic variations of TLRs can affect their function and by extension affect the response of the organism to environmental stimuli. The genetics of TLRs provides important insights in gene-environment interactions in health and disease, and it may enable scientists to assess patients' susceptibility to diseases or predict their response to treatments. PMID: 17845139 [PubMed - indexed for MEDLINE] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583820 Mon, 07 Jul 2008 14:12:35 +0100 1583820 http://www.medworm.com/index.php?rid=1583819&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17883367%26dopt%3DAbstract Authors: Leeman BA, Cole AJ Diagnostic tools and treatment options for epilepsy have expanded in recent years. Imaging techniques once confined to research laboratories are now routinely used for clinical purposes. Medications that were unavailable a few years ago are now first-line agents. Patients with refractory seizures push for earlier surgical intervention, consider treatment with medical devices, and actively seek nonpharmacologic alternatives. We review some of these recent advances in the management of epilepsy. PMID: 17883367 [PubMed - indexed for MEDLINE] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583819 Mon, 07 Jul 2008 14:12:35 +0100 1583819 http://www.medworm.com/index.php?rid=1583818&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17892433%26dopt%3DAbstract Authors: Copeland WC Mitochondrial genetic diseases can result from defects in mitochondrial DNA (mtDNA) in the form of deletions, point mutations, or depletion, which ultimately cause loss of oxidative phosphorylation. These mutations may be spontaneous, maternally inherited, or a result of inherited nuclear defects in genes that maintain mtDNA. This review focuses on our current understanding of nuclear gene mutations that produce mtDNA alterations and cause mitochondrial depletion syndrome (MDS), progressive external ophthalmoplegia (PEO), ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). To date, all of these etiologic nuclear genes fall into one of two categories: genes whose products function directly at the mtDNA replication fork, such as POLG,... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583818 Mon, 07 Jul 2008 14:12:35 +0100 1583818 http://www.medworm.com/index.php?rid=1583817&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17892435%26dopt%3DAbstract Authors: Klasse PJ, Shattock R, Moore JP The development of a vaginal (and perhaps a rectal) microbicide would be of major benefit for slowing the global spread of human immunodeficiency virus type 1 (HIV-1). A microbicide is a gel or related device that, when inserted vaginally or rectally, acts to prevent infection of a woman or a man by HIV-1 during sexual intercourse. A practical microbicide must be not only effective, safe, and user-friendly but also economically affordable in the developing world. To date, the performance of microbicide candidates in efficacy trials has been disappointing, but next-generation concepts now in or approaching clinical trials offer improved prospects for efficacy. The most plausible approaches involve topical application of antiretroviral agents with... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583817 Mon, 07 Jul 2008 14:12:35 +0100 1583817 http://www.medworm.com/index.php?rid=1583816&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17914924%26dopt%3DAbstract Authors: Lavori PW, Dawson R An adaptive treatment strategy (ATS) is a rule for adapting a treatment plan to a patient's history of previous treatments and the response to those treatments. The ongoing management of chronic disease defines an ATS, which may be implicit and hidden or explicit and well-specified. The ATS is characterized by the use of intermediate, early markers of response to dynamically alter treatment decisions, in order to achieve a favorable ultimate outcome. We illustrate the ATS concept and describe how the effect of initial treatment decisions depends on the performance of subsequent decisions at later stages. We show how to compare two or more ATSs, or to determine an optimal ATS, using a sequential multiple assignment randomized (SMAR) trial. Designers of clini... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583816 Mon, 07 Jul 2008 14:12:35 +0100 1583816 http://www.medworm.com/index.php?rid=1583815&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17914925%26dopt%3DAbstract Authors: Ventura AC, Merajver SD The development and spread of breast and other human cancers are caused by the overexpression, mutation, and/or deletion of specific genes that drive these events. Finding genetic and molecular differences between cancerous and healthy cells can reveal the genetic determinants of cancer. This knowledge results in a better understanding of the carcinogenic process and improved predictive power, with implications for identifying new drug targets, designing novel therapies, and improving preclinical and clinical studies. We review the concepts of biomarker, genetic marker, and genetic determinant in cancer, with particular focus on the most aggressive and lethal form of breast cancer, termed inflammatory breast cancer (IBC). Using IBC as an example, we des... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583815 Mon, 07 Jul 2008 14:12:35 +0100 1583815 http://www.medworm.com/index.php?rid=1583814&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17914926%26dopt%3DAbstract Authors: Humphreys BD, Bonventre JV The potential role of mesenchymal stem cells (MSCs, also called mesenchymal stromal cells) in endogenous repair and cell-based therapies for acute kidney injury (AKI) is under intensive investigation. Preclinical studies indicate that administered MSCs both ameliorate renal injury and accelerate repair. These versatile cells home to sites of injury, where they modulate the repair process. The mechanisms responsible for their protective and regenerative effects are incompletely understood. Some have reported that MSCs are capable of direct engraftment into injured nephrons under certain circumstances. This is highly controversial, however, and even those who argue there is engraftment acknowledge that the primary means of repair by these cells most li... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583814 Mon, 07 Jul 2008 14:12:35 +0100 1583814 http://www.medworm.com/index.php?rid=1583813&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17919086%26dopt%3DAbstract Authors: Morgan KJ, Gilliland DG Myeloproliferative disorders (MPDs) are characterized by a clonal expansion of myeloid cells. Over the past two years, the identification of the JAK2V617F mutation in most cases of polycythemia vera (PV) as well as approximately 50% of patients with essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF) has greatly advanced our understanding of MPDs. The JAK2V617F mutation alters the JAK2 tyrosine kinase to confer constitutive activation and affect downstream signaling pathways. Data from mouse models demonstrate that the mutation is sufficient for development of PV, but additional work is needed to better understand how this allele functions in ET and IMF. Regardless of the various pathologies, the JAK2V617F discovery highlights the importan... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583813 Mon, 07 Jul 2008 14:12:35 +0100 1583813 http://www.medworm.com/index.php?rid=1583812&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17937586%26dopt%3DAbstract Authors: Lynch AS, Robertson GT Biofilms are communal structures of microorganisms encased in an exopolymeric coat that form on both natural and abiotic surfaces and have been associated with a variety of persistent infections that respond poorly to conventional antibiotic chemotherapy. Biofilm infections of certain indwelling medical devices by common pathogens such as staphylococci are not only associated with increased morbidity and mortality but are also significant contributors to the emergence and dissemination of antibiotic resistance traits in the nosocomial setting. Current treatment paradigms for biofilm-associated infections of semipermanent indwelling devices typically involve surgical replacement of the device combined with long-term antibiotic therapy and incur high healt... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583812 Mon, 07 Jul 2008 14:12:35 +0100 1583812 http://www.medworm.com/index.php?rid=1583811&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17937587%26dopt%3DAbstract Authors: Maynard S, Epstein FH, Karumanchi SA Preeclampsia is a systemic syndrome of pregnancy that originates in the placenta and is characterized by widespread maternal endothelial dysfunction. Until recently, the molecular pathogenesis of preeclampsia was largely unknown, but recent work suggests a key role for altered expression of placental antiangiogenic factors. Soluble Flt1 and soluble endoglin, secreted by the placenta, are increased in the maternal circulation weeks before the onset of preeclampsia. These antiangiogenic factors produce systemic endothelial dysfunction, resulting in hypertension, proteinuria, and the other systemic manifestations of preeclampsia. The molecular basis for placental dysregulation of these pathogenic factors remains unknown, and the role of angiog... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583811 Mon, 07 Jul 2008 14:12:35 +0100 1583811 http://www.medworm.com/index.php?rid=1583810&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17937588%26dopt%3DAbstract Authors: Heath JR, Davis ME The biological picture of cancer is rapidly advancing from models built from phenomenological descriptions to network models derived from systems biology, which can capture the evolving pathophysiology of the disease at the molecular level. The translation of this (still academic) picture into a clinically relevant framework can be enabling for the war on cancer, but it is a scientific and technological challenge. In this review, we discuss emerging in vitro diagnostic technologies and therapeutic approaches that are being developed to handle this challenge. Our discussion of in vitro diagnostics is guided by the theme of making large numbers of measurements accurately, sensitively, and at very low cost. We discuss diagnostic approaches based on microfluidic... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583810 Mon, 07 Jul 2008 14:12:35 +0100 1583810 http://www.medworm.com/index.php?rid=1583809&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17937589%26dopt%3DAbstract Authors: Meyer EH, DeKruyff RH, Umetsu DT Asthma is an immunological disease with multiple inflammatory and clinical phenotypes, characterized by symptoms of wheezing, shortness of breath, and coughing due to airway hyperreactivity (AHR) and reversible airway obstruction. In allergic asthma, the most common form of asthma, airway inflammation is mediated by adaptive immune recognition of protein allergens by Th2 cells, resulting in airway eosinophilia. However, in other forms of asthma, inflammation is associated with immune responses to respiratory infections and airway neutrophilia. A central feature common to all forms of asthma is AHR, the heightened responsiveness of the airways to nonspecific stimuli. AHR has been shown recently in animal models of asthma to require the presence ... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583809 Mon, 07 Jul 2008 14:12:35 +0100 1583809 http://www.medworm.com/index.php?rid=1583808&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17937590%26dopt%3DAbstract Authors: Gal-Yam EN, Saito Y, Egger G, Jones PA Deregulation of gene expression is a hallmark of cancer. Although genetic lesions have been the focus of cancer research for many years, it has become increasingly recognized that aberrant epigenetic modifications also play major roles in the tumorigenic process. These modifications are imposed on chromatin, do not change the nucleotide sequence of DNA, and are manifested by specific patterns of gene expression that are heritable through many cell divisions. We review these modifications in normal and cancer cells and the evolving approaches used to study them. Additionally, we outline advances in their potential use for cancer diagnostics and targeted epigenetic therapy. PMID: 17937590 [PubMed - indexed for MEDLINE] (Source: Annual R... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583808 Mon, 07 Jul 2008 14:12:35 +0100 1583808 http://www.medworm.com/index.php?rid=1583807&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17937591%26dopt%3DAbstract Authors: Glassberg H, Rader DJ Lipid-modifying therapy has been proven to significantly reduce cardiovascular events and total mortality. Most of the data have come from statin trials. Statin therapy is generally well-tolerated and safe, and for patients who are at higher than average risk of cardiovascular disease, the benefit of lipid-modifying therapy far exceeds the risk. Careful risk assessment is a critical component of effective lipid-modifying therapy. In the foreseeable future, low-density lipoprotein cholesterol (LDL-C) will remain the primary therapeutic target, and combination therapy is likely to become the norm. The major questions are how low to treat and how to achieve increasingly aggressive targets in lipid-lowering therapy. Many patients on LDL-lowering therapy conti... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583807 Mon, 07 Jul 2008 14:12:35 +0100 1583807 http://www.medworm.com/index.php?rid=1583806&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17937592%26dopt%3DAbstract Authors: Moore AF, Florez JC Despite major advances in our knowledge of glycemic pathophysiology and the availability of multiple therapeutic options to confront type 2 diabetes, unraveling the complex link between genetic risk and environmental factors in this burgeoning epidemic has proven difficult. Linkage approaches have clarified the etiology of monogenic diabetic syndromes and congenital lipodystrophies, and candidate gene association studies have identified a number of common variants implicated in type 2 diabetes. This year we have witnessed the advent of genome-wide association scanning: As many as nine genetic loci have now been reproducibly associated with type 2 diabetes in five genome-wide scans. Of particular interest are preliminary explorations of the connections betwe... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583806 Mon, 07 Jul 2008 14:12:35 +0100 1583806 http://www.medworm.com/index.php?rid=1583805&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17939760%26dopt%3DAbstract Authors: Moscona A Antiviral drugs are important in the management of seasonal influenza and critical to pandemic planning. Although several other classes of anti-influenza compounds exist, the neuraminidase (NA) inhibitors are currently the only option in most clinical settings. These drugs, zanamivir and oseltamivir, prevent the release of newly replicated influenza virions from infected cells. They are highly effective when used for treatment of seasonal influenza early in the course of infection, or for prevention when given soon after exposure. Treatment strategies for avian influenza infections in humans are still provisional owing to inadequate clinical data. As predicted by molecular studies, resistance to the NA inhibitors is now emerging, although at a level less significant ... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583805 Mon, 07 Jul 2008 14:12:35 +0100 1583805 http://www.medworm.com/index.php?rid=1583804&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17961075%26dopt%3DAbstract Authors: Beaudet AL, Belmont JW Advances in the fabrication of DNA microarrays as well as transformations in detection chemistries have vastly increased the throughput for genotyping, DNA sequencing, and array-based copy number analysis (ABCNA). Rapid changes in technology are not only affecting research but also revolutionizing DNA diagnostics. Here we focus on the application of high-throughput ABCNA and genotyping. Targeted and genome-wide ABCNA has led to the discovery of extensive DNA copy number variation in the population and the delineation of many previously unrecognized submicroscopic chromosomal aberrations (genomic disorders). High-throughput single-nucleotide polymorphism (SNP) genotyping is being widely applied in genome-wide association studies (GWASs) with recent succes... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583804 Mon, 07 Jul 2008 14:12:35 +0100 1583804 http://www.medworm.com/index.php?rid=1583803&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17967129%26dopt%3DAbstract Authors: Sable CA, Strohmaier KM, Chodakewitz JA The prevalence of invasive fungal infections (IFIs) has increased over the past three decades owing to the increasing numbers of immunocompromised hosts. These infections are associated with significant morbidity and mortality. Recent significant advances in antifungal therapy include the broad-spectrum triazoles (voriconazole and posaconazole) and a new class of antifungals, the echinocandins (caspofungin, micafungin, and anidulafungin). New treatment strategies, such as combination therapy and pre-emptive therapy, are being investigated. There have also been significant improvements in diagnostics; the galactomannan enzyme immunoassay and the beta-glucan test are now part of the EORTC/MSG criteria for diagnosis of IFI. Despite these ad... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583803 Mon, 07 Jul 2008 14:12:35 +0100 1583803 http://www.medworm.com/index.php?rid=1583802&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18186700%26dopt%3DAbstract This article explicates the reasoning behind the Critical Path Initiative and discusses examples of successful consortia. PMID: 18186700 [PubMed - indexed for MEDLINE] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583802 Mon, 07 Jul 2008 14:12:35 +0100 1583802 http://www.medworm.com/index.php?rid=1583801&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18186701%26dopt%3DAbstract Authors: Kaye DM, Hoshijima M, Chien KR Heart failure is a major cardiovascular disease, characterized by considerable morbidity and mortality. Despite major advances in the pharmacotherapy of heart failure, the options for patients with severe end-stage symptoms remain limited. However, recent developments in the identification of the molecular basis for the progressive nature of heart failure have identified a number of potentially important new therapeutic targets. In particular, key components of the cardiomyocyte calcium-handling pathway show characteristic changes in heart failure. A body of research examining the effect of restoration of these defects in experimental models of heart failure, whether in genetically engineered mouse models or by myocardial gene transfer, very stro... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583801 Mon, 07 Jul 2008 14:12:35 +0100 1583801 http://www.medworm.com/index.php?rid=1583800&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18186702%26dopt%3DAbstract Authors: McCabe LL, McCabe ER Newborn screening (NBS) represents the largest volume of genetic testing. The 45-year history of NBS has demonstrated its benefits, as well as the importance of an evidence base. The recent addition of tandem mass spectrometry (MS/MS) resulted in a fivefold increase in the number of tests. Experience with MS/MS also showed that laboratory tests are just one part of the NBS system. The lessons learned from NBS will provide important insights as we move into the predictive, preventive, and personalized era of genomic medicine. PMID: 18186702 [PubMed - indexed for MEDLINE] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583800 Mon, 07 Jul 2008 14:12:35 +0100 1583800 http://www.medworm.com/index.php?rid=1583799&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18186703%26dopt%3DAbstract Authors: Lee CC The induction of hypometabolism in cells and organs to reduce ischemia damage holds enormous clinical promise in diverse fields, including treatment of stroke and heart attack. However, the thought that humans can undergo a severe hypometabolic state analogous to hibernation borders on science fiction. Some mammals can enter a severe hypothermic state during hibernation in which metabolic activity is extremely low, and yet full viability is restored when the animal arouses from such a state. To date, the underlying mechanism for hibernation or similar behaviors remains an enigma. The beneficial effect of hypothermia, which reduces cellular metabolic demands, has many well-established clinical applications. However, severe hypothermia induced by clinical drugs is extreme... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583799 Mon, 07 Jul 2008 14:12:35 +0100 1583799 http://www.medworm.com/index.php?rid=1583798&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18186704%26dopt%3DAbstract Authors: Zimet GD, Shew ML, Kahn JA Human papillomavirus (HPV) is a necessary, though not sufficient, cause of cervical cancer. Two vaccines have been developed that prevent two HPV types associated with 70% of cervical cancers. One of the vaccines (a quadrivalent vaccine) also prevents two HPV types associated with 90% of genital warts. Both HPV vaccines have shown very good efficacy and safety. This review summarizes the guidelines for use of the quadrivalent vaccine published by the Advisory Committee on Immunization Practices, presents data on vaccine efficacy and safety, and gives an overview of the findings of cost-effectiveness studies. In addition, we summarize the research on the attitudes of parents and health care providers toward HPV vaccine and critically evaluate controve... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583798 Mon, 07 Jul 2008 14:12:35 +0100 1583798 http://www.medworm.com/index.php?rid=1583797&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18186705%26dopt%3DAbstract Authors: Molina A The anti-CD20 monoclonal antibody rituximab, first approved for clinical use in 1997, has changed the standard of care for many patients with non-Hodgkin's lymphoma (NHL). Recent data from large randomized clinical trials confirm that the addition of rituximab to standard chemotherapy regimens (chemoimmunotherapy) improves both response rates and survival outcomes in patients with follicular NHL and diffuse large B cell lymphoma (DLBCL), the two most common subtypes of NHL. Population-based analyses have found substantial improvements in NHL survival over the past decade; studies indicate that rituximab has favorably altered the long-term prognosis of follicular NHL and DLBCL patients. This review discusses the clinical development of rituximab-based therapies for pat... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583797 Mon, 07 Jul 2008 14:12:35 +0100 1583797 http://www.medworm.com/index.php?rid=1583796&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18186706%26dopt%3DAbstract Authors: Koelle DM, Corey L Abstract Herpes simplex viruses are evolutionarily ancient and ubiquitous. In the past 20 years, there has been increasing recognition of a worldwide pandemic of HSV-2 infection. Moreover, HSV-2 prevalence has increased despite fairly widespread use of antiviral drugs for HSV. The success of HSV-1 and HSV-2 stems from latency within long-lived neurons and frequent mucocutaneous shedding. The generally mild medical consequences of HSV infection reflect a functional equilibrium between host and microbe in most immunocompetent persons. However, significant gaps in our knowledge of the correlates of disease severity and HSV immune evasion are limiting rational advances in these areas. Human genetic studies are gradually outlining important innate responses, whil... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583796 Mon, 07 Jul 2008 14:12:35 +0100 1583796 http://www.medworm.com/index.php?rid=1583795&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18186707%26dopt%3DAbstract Authors: Thomas DL Hepatitis C virus (HCV) coinfection occurs in an estimated one quarter of HIV-infected persons in Europe, Australia, and the United States. As use of highly active antiretroviral drugs has markedly reduced opportunistic infections, HCV-related liver disease has emerged as a leading cause of death. HIV infection adversely affects both the natural history and the treatment of hepatitis C. Because there are no experimental models of coinfection and because the pathogenesis of each infection is incompletely understood, how HIV infection alters hepatitis C is not clear. This review considers the epidemiology, natural history, treatment, and pathogenesis of hepatitis C in HIV-infected persons. PMID: 18186707 [PubMed - indexed for MEDLINE] (Source: Annual Review of Medi... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583795 Mon, 07 Jul 2008 14:12:35 +0100 1583795 http://www.medworm.com/index.php?rid=1583861&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16886904%26dopt%3DAbstract Authors: Gomperts BN, Strieter RM Stem cells have been shown to contribute to the repair and regeneration of injured lungs. These stem cells are resident in specific protected niches in the lung, or they can be mobilized from the bone marrow and recruited from the circulation in the setting of severe injury. Normal repair of the airway involves regeneration of the airway epithelium by stem cells in both the proximal airway and distal airspace, whereas aberrant repair of the lung may result from stem cells that lead to fibrosis. The stem cell niche in the lung is probably critical in determining whether "good" or "bad" stem cells are involved in local repair, and therefore whether fibrosis predominates. There is much excitement about the possibility of harnessing stem cells for repair a... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583861 Mon, 01 Jan 2007 05:00:00 +0100 1583861 http://www.medworm.com/index.php?rid=1583860&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16886905%26dopt%3DAbstract Authors: de Kruif J, Bakker AB, Marissen WE, Kramer RA, Throsby M, Rupprecht CE, Goudsmit J The currently recommended treatment for individuals exposed to rabies virus is the combined administration of rabies vaccine and rabies immune globulin (RIG). This review sets out the criteria used to guide development of a cocktail of human monoclonal antibodies as a replacement for RIG. Using this process as a model, the general requirements for development of safe and efficacious monoclonal antibody alternatives to currently used polyclonal serum products are discussed. PMID: 16886905 [PubMed - indexed for MEDLINE] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583860 Mon, 01 Jan 2007 05:00:00 +0100 1583860 http://www.medworm.com/index.php?rid=1583859&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16903799%26dopt%3DAbstract Authors: Jarskog LF, Miyamoto S, Lieberman JA The neurodevelopmental hypothesis of schizophrenia posits an interaction between multiple susceptibility genes and one or more environmental insults in early life, resulting in altered brain development and the emergence of psychosis in early adulthood. Based on this framework, it has been argued that most neuropathological deficits observed in post mortem and neuroimaging studies of schizophrenia represent one or more lesions that originated in early life and remained static thereafter. However, recent longitudinal neuroimaging studies demonstrate a progressive component to the neuropathology of new-onset schizophrenia. This opens the possibility that the functional decline seen in many patients following the onset of illness may be halted... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583859 Mon, 01 Jan 2007 05:00:00 +0100 1583859 http://www.medworm.com/index.php?rid=1583858&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16907639%26dopt%3DAbstract Authors: Bossé Y, Hudson TJ Epidemiological and twin studies have demonstrated that asthma is under genetic and environmental influences. Numerous candidate gene association studies as well as genome-wide linkage scans have followed, aiming to elucidate the genetic architecture underlying this complex disease. Several promising asthma susceptibility genes were identified, and a comprehensive catalogue of these genes seems a realistic goal within 5 to 10 years. However, a key challenge is to understand the combination of genes and environmental factors that gives rise to the disease in a specific individual. Currently, most of the reports of asthma susceptibility genes are either preliminary or controversial, with little knowledge about the genetic mechanisms leading to abnormal fu... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583858 Mon, 01 Jan 2007 05:00:00 +0100 1583858 http://www.medworm.com/index.php?rid=1583857&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16922634%26dopt%3DAbstract Authors: Stone EM Macular degeneration is a term that describes a large group of conditions that are collectively the most common cause of irreversible vision loss in the developed world. Approximately one in three people will be affected to some degree by the time they reach 75 years of age. Many forms of macular degeneration have a significant genetic component, and a large amount of progress has recently been made in understanding the genes involved. In the future, genetic testing may allow specific preventive treatments to be delivered to individuals at risk, decades before the disease would ordinarily become manifest. PMID: 16922634 [PubMed - indexed for MEDLINE] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583857 Mon, 01 Jan 2007 05:00:00 +0100 1583857 http://www.medworm.com/index.php?rid=1583856&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16958560%26dopt%3DAbstract Authors: Tsibris AM, Kuritzkes DR Human immunodeficiency virus type 1 (HIV-1) entry into target cells is a multistep process involving the interaction of viral envelope proteins with cell surface receptors. Binding to CD4 is followed by engagement of specific chemokine receptors (CCR5 or CXCR4), triggering molecular rearrangements in the envelope transmembrane subunit that result in membrane fusion. Chemokine receptor antagonists that block the interaction of the HIV-1 envelope with CCR5 or CXCR4 potently inhibit HIV-1 in vitro. Pilot studies of orally bioavailable small-molecule CCR5 inhibitors in HIV-1-infected subjects have provided proof of concept for this novel drug class; phase III safety and efficacy trials are under way. PMID: 16958560 [PubMed - indexed for MEDLINE] (Sourc... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583856 Mon, 01 Jan 2007 05:00:00 +0100 1583856 http://www.medworm.com/index.php?rid=1583855&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16958561%26dopt%3DAbstract Authors: Ulrich RG The therapeutic margin for any drug is based on both toxicity and efficacy. Generally, toxicity is dose-dependent and is driven either by the therapeutic target or by an untoward target. However, idiosyncratic toxicities are usually not observed until a drug has been on the market and has gained broad exposure. Except in the case of pharmacokinetic interactions, these toxicities are not driven solely by drug exposure but rather depend on several drug- and patient-related risk factors. Drug-related risk factors include metabolism, bioactivation and covalent binding, and the inhibition of key cell functions. Patient-related risk factors include underlying disease, age, gender, comedications, nutritional status, activation of the innate immune system, physical activity,... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583855 Mon, 01 Jan 2007 05:00:00 +0100 1583855 http://www.medworm.com/index.php?rid=1583854&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16987079%26dopt%3DAbstract Authors: St Clair EW, Turka LA, Saxon A, Matthews JB, Sayegh MH, Eisenbarth GS, Bluestone J Recent advances in immunology and a growing arsenal of new drugs are bringing the focus of tolerance research from animal models into the clinical setting. The conceptual framework for therapeutic tolerance induction has shifted from a "sledgehammer" approach that relies solely on cellular depletion and cytokine targeting, to a strategy directed toward restoring a functional balance across the immune system, namely the different populations of naive cells, effector and memory cells, and regulatory cells. Unlocking the key to tolerance induction in the future will likely depend on our ability to harness the functions of T regulatory cells. Also, dendritic cells are strategically positioned at the... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583854 Mon, 01 Jan 2007 05:00:00 +0100 1583854 http://www.medworm.com/index.php?rid=1583853&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16987080%26dopt%3DAbstract Authors: Hasan A, Abraham WT Cardiac resynchronization therapy (CRT) is well established as a treatment for patients with moderate to severe heart failure on optimal medical therapy. Early studies demonstrated improved functional capacity and evidence of reverse remodeling; more recently, CRT has been associated with a survival benefit in advanced heart failure both with and without a defibrillator. We review the eight landmark trials in CRT. To date, criteria have focused on electrical delay, but echocardiographic parameters emphasize the importance of mechanical delay or ventricular dyssynchrony. With the exponential rise in implants, new issues have emerged, such as optimal device programming, identifying appropriate candidates, and accounting for cases without clinical benefit from... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583853 Mon, 01 Jan 2007 05:00:00 +0100 1583853 http://www.medworm.com/index.php?rid=1583852&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16987081%26dopt%3DAbstract Authors: Pomerantz M, Kantoff P Several recent advances have been made in the management of prostate cancer. Active surveillance is an increasingly attractive and reasonable approach for those with low-volume, low-risk disease. For locally advanced or localized high-risk disease, neoadjuvant and adjuvant therapies are emerging as the standard of care. Innovative uses of traditional hormonal treatments can potentially limit common side effects. Recent data also support the utility of second-line hormonal therapy. For the first time, a survival advantage with the use of chemotherapy has been established. Much work is under way to augment its efficacy with novel agents such as targeted therapeutics and tumor vaccines. Recent scientific breakthroughs suggest additional strategies in treati... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583852 Mon, 01 Jan 2007 05:00:00 +0100 1583852 http://www.medworm.com/index.php?rid=1583851&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16987082%26dopt%3DAbstract Authors: Stead WW Health care information technology changes the ecosystem of a practice. Human roles, process work flow, and technology infrastructure are tightly interrelated. Medical errors may increase if a change in one is not accommodated by a change in the others. Introduction of information technology should be approached as an iterative process of care improvement rather than as a one-time insertion of an information system into established practice. Information technology supports a family of technological approaches, each with distinct mechanisms of action, benefits, and side effects. By matching technological approach to task and staging introduction into practice, initial benefit can be obtained more quickly, at reduced cost, while managing risk of a misfit. A staged appro... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583851 Mon, 01 Jan 2007 05:00:00 +0100 1583851 http://www.medworm.com/index.php?rid=1583850&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16987083%26dopt%3DAbstract Authors: Cho JH, Abraham C The inflammatory bowel diseases (IBD) are comprised of two major subphenotypes, Crohn's disease (CD) and ulcerative colitis (UC). A significant role for genetic factors in IBD was established from epidemiologic studies and, more recently, the identification of well-established disease associations, notably the association of Nod2 (CARD15) polymorphisms with CD. The mapping to CD of Nod2 variants that alter protein function represents one of the earliest, most well-established, associations in complex genetic disorders. Since the initial discovery, genotype-phenotype correlations, definition of Nod2 expression and signaling pathways, association studies in other, related disorders, and features of Nod2 deficiency in murine models have been reported. Taken toge... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583850 Mon, 01 Jan 2007 05:00:00 +0100 1583850 http://www.medworm.com/index.php?rid=1583849&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17002551%26dopt%3DAbstract Authors: Tantravahi J, Womer KL, Kaplan B Although patients with end-stage renal disease can be maintained with dialysis therapy, the superiority of patient survival with renal transplantation makes transplantation the preferred method of renal replacement. Potent immunosuppressive therapies, particularly calcineurin inhibitors, have greatly reduced the incidence of acute rejection. However, long-term allograft survival remains limited. We discuss the impact of acute rejection on long-term allograft survival and discuss other factors leading to late allograft loss, including calcineurin inhibitor toxicity, chronic allograft nephropathy, and BK virus nephropathy, as well as donor and recipient factors associated with long-term allograft loss. PMID: 17002551 [PubMed - indexed for MED... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583849 Mon, 01 Jan 2007 05:00:00 +0100 1583849 http://www.medworm.com/index.php?rid=1583848&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17002552%26dopt%3DAbstract Authors: Dalerba P, Cho RW, Clarke MF Although monoclonal in origin, most tumors appear to contain a heterogeneous population of cancer cells. This observation is traditionally explained by postulating variations in tumor microenvironment and coexistence of multiple genetic subclones, created by progressive and divergent accumulation of independent somatic mutations. An additional explanation, however, envisages human tumors not as mere monoclonal expansions of transformed cells, but rather as complex tridimensional tissues where cancer cells become functionally heterogeneous as a result of differentiation. According to this second scenario, tumors act as caricatures of their corresponding normal tissues and are sustained in their growth by a pathological counterpart of normal adult st... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583848 Mon, 01 Jan 2007 05:00:00 +0100 1583848 http://www.medworm.com/index.php?rid=1583847&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17020493%26dopt%3DAbstract Authors: Vincenti F, Luggen M T cells are central mediators of adaptive immunity. As such, they are involved in both normal immune responses (e.g., rejection of a transplanted organ) and abnormal ones (e.g., rheumatoid arthritis). T cells require both antigen-specific and costimulatory signals for their full activation. Advances in protein engineering and an increased understanding of the immune response have culminated in the evolution and creation of protein therapeutics that target specific costimulatory molecules. The selective costimulation modulator abatacept (CTLA-4Ig) binds to CD80 and CD86, blocking interaction with CD28, and is approved for the treatment of moderate to severe rheumatoid arthritis. Belatacept, currently enrolling phase III trials in renal transplantation, was ... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583847 Mon, 01 Jan 2007 05:00:00 +0100 1583847 http://www.medworm.com/index.php?rid=1583846&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17037976%26dopt%3DAbstract Authors: Lakhani VT, You YN, Wells SA Multiple endocrine neoplasia (MEN) type 1 and type 2 exhibit an autosomal dominant pattern of inheritance. In the past two decades the germline mutations that cause these inherited syndromes have been identified. The large majority of patients with MEN1 have mutations in the menin gene. Mutations in the REarranged during Transfection (RET) gene cause MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC). Specific codon mutations within RET correlate with disease phenotype and severity. Also, children from families with MEN2A, MEN2B, or FMTC, who are found to have inherited a mutated RET allele, can be managed by prophylactic thyroidectomy, thus preventing the development of medullary thyroid carcinoma (MTC), the dominant endocrinopathy in p... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583846 Mon, 01 Jan 2007 05:00:00 +0100 1583846 http://www.medworm.com/index.php?rid=1583845&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17052163%26dopt%3DAbstract Authors: Ferrara N, Mass RD, Campa C, Kim R Inhibiting angiogenesis is a promising strategy to treat cancer and several other disorders, including intraocular neovascular syndromes. The identification of vascular endothelial growth factor (VEGF)-A as a major regulator of normal and pathological angiogenesis has enabled significant progress toward effective treatments for such disorders. Several VEGF inhibitors have been recently approved by the U.S. Food and Drug Administration for the treatment of cancer and the neovascular form of age-related macular degeneration. This review summarizes the basic biology of VEGF-A and illustrates the clinical progress in targeting this molecule. PMID: 17052163 [PubMed - indexed for MEDLINE] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583845 Mon, 01 Jan 2007 05:00:00 +0100 1583845 http://www.medworm.com/index.php?rid=1583844&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17059361%26dopt%3DAbstract Authors: Avila PC Omalizumab, a humanized monoclonal antibody against IgE, is clinically efficacious when it neutralizes almost all free IgE and reduces IgE receptors on basophils and mast cells. Asthmatic subjects on inhaled corticosteroids who are treated with omalizumab as an add-on therapy experience only modest benefits in symptoms and perhaps in quality of life, but the most significant effects are reductions in airway inflammation and in exacerbation rate. Airway obstruction and hyperresponsiveness do not change significantly. Although the magnitude of the beneficial effects is small, they are observed even in the most severe cases, particularly the reduction in exacerbation rate. The safety profile of omalizumab is very encouraging, although phase IV studies are ongoing to clar... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583844 Mon, 01 Jan 2007 05:00:00 +0100 1583844 http://www.medworm.com/index.php?rid=1583843&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17059362%26dopt%3DAbstract This article focuses on technologic methods for improving drug development efficiency. These technologies include high-content cell screening, expression profiling, mass spectroscopy, mouse models of disease, and a post-launch screening program that enables investigations of adverse drug effects. Implementation of these new technologies promises to improve performance in drug development and safety. PMID: 17059362 [PubMed - indexed for MEDLINE] (Source: Annual Review of Medicine) Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583843 Mon, 01 Jan 2007 05:00:00 +0100 1583843 http://www.medworm.com/index.php?rid=1583842&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17059365%26dopt%3DAbstract Authors: Pastan I, Hassan R, FitzGerald DJ, Kreitman RJ Immunotoxins are proteins used to treat cancer that are composed of an antibody fragment linked to a toxin. The immunotoxin binds to a surface antigen on a cancer cell, enters the cell by endocytosis, and kills it. The most potent immunotoxins are made from bacterial and plant toxins. Refinements over many years have produced recombinant immunotoxins; these therapeutic proteins are made using protein engineering. Individual immunotoxins are designed to treat specific cancers. To date, most success has been achieved treating hematologic tumors. Obstacles to successful treatment of solid tumors include poor penetration into tumor masses and the immune response to the toxin component of the immunotoxin, which limits the number of cyc... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583842 Mon, 01 Jan 2007 05:00:00 +0100 1583842 http://www.medworm.com/index.php?rid=1583841&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17076602%26dopt%3DAbstract Authors: Gurtner GC, Callaghan MJ, Longaker MT Regenerative medicine focuses on new therapies to replace or restore lost, damaged, or aging cells in the human body to restore function. This goal is being realized by collaborative efforts in nonmammalian and human development, stem cell biology, genetics, materials science, bioengineering, and tissue engineering. At present, understanding existing reparative processes in humans and exploring the latent ability to regenerate tissue remains the focus in this field. This review covers recent work in limb regeneration, fetal wound healing, stem cell biology, somatic nuclear transfer, and tissue engineering as a foundation for developing new clinical therapies to augment and stimulate human regeneration. PMID: 17076602 [PubMed - indexed ... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583841 Mon, 01 Jan 2007 05:00:00 +0100 1583841 http://www.medworm.com/index.php?rid=1583840&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17081079%26dopt%3DAbstract Authors: Tonelli M, Pfeffer MA Kidney failure and chronic kidney disease (CKD) are associated with accelerated cardiovascular disease, apparently because of a high burden of traditional vascular risk factors and possibly nontraditional risk factors such as inflammation, chronic volume overload, and abnormal calcium-phosphate metabolism. Although the burden of cardiovascular disease in CKD patients is well documented, potentially beneficial therapies appear to be underused in mild to moderate CKD and are relatively understudied in those with kidney failure. This review describes the epidemiology and pathophysiology of cardiovascular disease in CKD. We also discuss the clinical and public health implications of current knowledge and outline opportunities for further research. PMID: 1... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583840 Mon, 01 Jan 2007 05:00:00 +0100 1583840 http://www.medworm.com/index.php?rid=1583839&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17100552%26dopt%3DAbstract Authors: Cha YI, DuBois RN Preclinical and clinical studies have clearly shown a benefit of nonsteroidal anti-inflammatory drug (NSAID) use in reducing cancer risk. However, the adverse gastrointestinal and cardiovascular side effects associated with NSAIDs and COX-2 selective inhibitors (coxibs) have provoked more scrutiny of the precise role of specific downstream mediators in the prostaglandin (PG) signaling cascade. NSAIDs and coxibs inhibit PG biosynthesis. One of the PGs produced at high levels in the tumor microenvironment is PGE(2), which is thought to play a major role in cancer progression. Thus, a better understanding of PGE(2) signaling could enable identification of novel and safer therapeutic targets downstream of the cyclooxygenase enzymes. We review the emerging molecul... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583839 Mon, 01 Jan 2007 05:00:00 +0100 1583839 http://www.medworm.com/index.php?rid=1583838&cid=s_37529_22_f&fid=37529&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17100553%26dopt%3DAbstract Authors: Singec I, Jandial R, Crain A, Nikkhah G, Snyder EY Stem cells, by virtue of their defining property of self-renewal, represent an unlimited source of potentially functional human cells for basic research and regenerative medicine. Having validated the feasibility of cell-based therapeutic strategies over the past decade, mostly through the use of rodent cells, the stem cell field has now embarked upon a detailed characterization of human cells. Recent progress has included improved cell culture conditions, long-term propagation, directed differentiation, and transplantation of both human embryonic and somatic stem cells. Continued progress in understanding basic human stem cell biology, combined with a better handle on the fundamental pathophysiology of human diseases one wish... Annual Review of Medicine journals http://www.medworm.com/rss/comments.php?id=1583838 Mon, 01 Jan 2007 05:00:00 +0100 1583838