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Lebanon, NH, United States

Finlayson S.R.G.,One Medical Center Drive | Finlayson S.R.G.,White River Junction Outcomes Group
Annals of Surgery | Year: 2010

Objective: To examine the use of surgical procedures for Crohn's disease since the introduction of infliximab. Summary background data: Prior studies have shown that the overall rate of surgery for Crohn's disease has not changed significantly since the introduction of infliximab, an immunomodulator considered particularly effective in treating Crohn's fistulas. How infliximab has affected individual rates of specific types of procedures, particularly surgery for intestinal fistulas, is unknown. Methods: We used the Nationwide Inpatient Sample to identify all hospital admissions for Crohn's disease for each year from 1993 through 2004. Cases of Crohn's disease and relevant surgical interventions were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes. Using US Census data to establish population denominators, trends in population-based rates of use of these procedures were examined over time. Trends were tested for significance with Spearman rank correlation tests. Results: From 1993 to 2004, there was no statistically significant change in population-based rates of small bowel and right colon resection, while rates of left colon resection, other colon resection, and rectal resection declined moderately. However, rates of surgical repair of fistulas of the small intestine, the most commonly performed fistula operation, increased by 60%, from 1.5 per 1,000,000 in 1993 to 2.4 per 1,000,000 in 2004 (P = 0.04). Conclusions: During the period of adoption of infliximab as a novel treatment for Crohn's disease, overall rates of bowel resections have either remained relatively stable or decreased moderately, while rates of small bowel fistula repair have increased significantly. These findings call into question the effectiveness of infliximab in preventing the need for surgery for Crohn's disease at the population level. Copyright © 2010 by Lippincott Williams & Wilkins. Source

McAllister T.W.,One Medical Center Drive
PM and R | Year: 2010

Wide variation in outcomes after neurotrauma, despite apparently similar injury severity, suggests that host factors may influence the recovery process. Genetically determined individual differences might be one such factor. The study of the genetic modulation of outcome after neurotrauma is at an early stage. Nevertheless, several important components of the response to neurotrauma can be identified in which genetic differences contribute to variability in outcome. These components include genetic modulators of pre- and postinjury cognitive reserve and behavioral homeostasis, and processes that modulate cytotoxic injury cascades (extent of injury) and injury repair. This work reviews what is knownof the role of genetic variation in outcome after neurotrauma with a focus on clinical outcomes after traumatic brain injury. Polymorphisms reported to influence outcome after traumatic brain injury that illustrate important underlying mechanisms are emphasized. Source

Mulligan-Kehoe M.J.,One Medical Center Drive
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2010

The vasa vasorum form a network of microvasculature that originate primarily in the adventitial layer of large arteries. These vessels supply oxygen and nutrients to the outer layers of the arterial wall. The expansion of the vasa vasorum to the second order is associated with neovascularization related to progression of atherosclerosis. Immunohistological analysis of human plaques from autopsied aortas have defined plaque progression and show a significant correlation with vasa vasorum neovascularization. Recent technological advances in microcomputed tomography have enabled investigation of vasa vasorum structure and function in nondiseased large arteries from pigs and dogs. Smaller mammals, particularly mice with genetic modifications that enable disease development, have been used extensively to study the vasa vasorum in diseased vessels. Despite the fact that most mouse models that are used to study atherosclerosis are unable to develop plaque to the extent found in humans, studies in both humans and mice underscore the importance of angiogenic vasa vasorum in progression of atherosclerosis. Those who have examined the vasa vasorum in occluded vessels of nondiseased pigs and dogs find that inhibition of the vasa vasorum makes the animals atheroprone. Atherosclerosis is a multifactorial disease. There is increasing evidence that factors, produced in response to changes in the arterial wall, collaborate with the vasa vasorum to enhance the disease process. Copyright © 2010 the American Physiological Society. Source

Penrod N.M.,Dartmouth College | Cowper-Sal-Lari R.,Dartmouth College | Moore J.H.,One Medical Center Drive | Moore J.H.,Dartmouth College
Trends in Pharmacological Sciences | Year: 2011

The collection and analysis of genomic data has the potential to reveal novel druggable targets by providing insight into the genetic basis of disease. However, the number of drugs targeting new molecular entities, approved by the US Food and Drug Administration has not increased in the years since the collection of genomic data has become commonplace. The paucity of translatable results can be partly attributed to conventional analysis methods that test one gene at a time in an effort to identify disease-associated factors as candidate drug targets. By disengaging genetic factors from their position within the genetic regulatory system, much of the information stored within the genomic data set is lost. Here we discuss how genomic data is used to identify disease-associated genes or genomic regions, how disease-associated regions are validated as functional targets, and the role network analysis can play in bridging the gap between data generation and effective drug target identification. © 2011 Elsevier Ltd. Source

Leib D.A.,One Medical Center Drive
Cell Host and Microbe | Year: 2012

Herpes simplex encephalitis (HSE) is a devastating infection of the central nervous system (CNS). Lafaille et al. (2012) show that susceptibility to HSE is due to mutations in Toll-like receptor response pathways that directly reduce the intrinsic resistance of neurons and other cells in the CNS to HSV infection. © 2012 Elsevier Inc. Source

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