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991.
Annette Feigenbaum Christine Müller Christopher Yale Johannes Kleinheinz Peter Jezewski Hans Gerd Kehl Mary MacDougall Frank Rutsch Raoul C.M. Hennekam 《American journal of medical genetics. Part A》2013,161(2):360-370
In 1973, Singleton and Merten described two females with abnormal dentition, unique radiographic changes especially of the hands, and severe calcification and intimal weakening of the aortic arch and valve. Since then three additional cases with similar features have been reported and the diagnosis was suggested in another three individuals. We present an update of one case and the detailed clinical phenotype of six other cases with Singleton–Merten syndrome. The occurrence of the disorder in six members of two families and vertical male‐to‐male transmission indicate an autosomal dominant pattern of inheritance. Variability in phenotype, also within a single family, is significant. Core manifestations are marked aortic calcification, dental anomalies (delayed eruption and immature root formation of primarily the anterior permanent teeth, and early loss of permanent teeth due to short roots, acute root resorption, high caries, and aggressive alveolar bone loss), osteopenia and acro‐osteolysis, and to a lesser extend also glaucoma, psoriasis, muscle weakness, and joint laxity. Additional clinical characteristics described here include particular facial characteristics (high anterior hairline, broad forehead, smooth philtrum, thin upper vermillion) and abnormal joint and muscle ligaments. The cause and pathogenesis of this syndrome remain unknown. © 2013 Wiley Periodicals, Inc. 相似文献
992.
993.
John B. Meding MD Scott R. Small MS Mary E. Jones Michael E. Berend MD Merrill A. Ritter MD 《Clinical orthopaedics and related research》2013,471(2):403-409
Background
Press-fit acetabular components are susceptible to deformation in an underreamed socket, with excessive deformation of metal-on-metal (MOM) components potentially leading to increased torsional friction and micromotion. Specifically, however, it remains unclear how cup diameter, design, and time from implantation affect shell deformation.Questions/purposes
We asked whether (1) changes in component geometry and material altered maximum shell deformation and (2) time-dependent deformational relaxation processes occurred.Methods
Diametral deformation was quantified after press-fit implantation of metal shells into a previously validated polyurethane model. Experimental groups (n = 6–8) consisted of 48-, 54-, 60-, and 66-mm MOM cups of 6-mm wall thickness, 58-mm cups of 10-mm wall thickness, and CoCrMo and Ti6Al4V 58-mm modular cups.Results
Greater cup diameter, thinner wall construction, and Ti6Al4V modular designs generated conditions for maximum shell deformation ranging from 0.047 to 0.267 mm. Relaxation (18%–32%) was observed 120 hours postimplantation in thin-walled and modular designs.Conclusions
Our findings demonstrate a reduction of shell deformation over time and suggest, under physiologic loading, early component deformation varies with design.Clinical Relevance
Component deformation should be a design consideration regardless of bearing surface. Designs neglecting to adequately address deformational changes in vivo could be susceptible to diminished cup survival, increased wear, and premature revision. 相似文献994.
Leslie KnodEileen C. Donovan BS Artur ChernoguzKelly M. Crawford BS Mary R. DusingJason S. Frischer MD 《The Journal of surgical research》2013
Background
In the setting of inflammatory bowel disease, inflammation is associated with a simultaneous increase in angiogenesis; moreover, elevated vascular endothelial growth factor (VEGF) levels implicate angiogenesis as a pathologic contributor to disease severity. We hypothesize that selectively inhibiting vascular endothelial growth factor receptor-2 (VEGFR2) in a model of murine colitis will reduce angiogenesis, resulting in decreased inflammation and disease severity, providing mechanistic insight into the role of pathologic angiogenesis in IBD.Materials and methods
In a dextran sodium sulfate model of murine colitis, anti-VEGFR2 monoclonal antibody (DC101) or placebo was administered. Clinical assessments followed by histologic and molecular tissue analysis were performed to quantify inflammation, microvessel density (MVD), VEGF and VEGFR2 gene expression, and phosphorylated mitogen-activated protein kinase protein expression.Results
Weight loss began after d 6 with the treatment group demonstrating a more favorable percent weight change. Inflammation and MVD were similar between cohorts, both increasing in parallel toward a plateau. VEGF and VEGFR2 messenger RNA expression were not significantly different, but phosphorylated mitogen-activated protein kinase was elevated in the DC101 cohort (P = 0.03).Conclusions
Despite a more favorable weight change profile in the treated group, no difference was observed between cohorts regarding clinical disease severity. However, a parallel rise in inflammation and MVD was observed coinciding with weight loss, suggesting their relationship in IBD. VEGFR2 downstream signaling was significantly elevated in the treated cohort, possibly by VEGF-independent signal transduction. Early and effective inhibition of angiogenesis by limiting downstream VEGF signaling or targeting multiple angiogenic pathways may block angiogenesis, thereby reducing disease severity and provide evidence toward the mechanism and clinical benefit of antiangiogenics in the setting of IBD. 相似文献995.
Cristina Menni Eric Fauman Idil Erte John R.B. Perry Gabi Kastenmüller So-Youn Shin Ann-Kristin Petersen Craig Hyde Maria Psatha Kirsten J. Ward Wei Yuan Mike Milburn Colin N.A. Palmer Timothy M. Frayling Jeff Trimmer Jordana T. Bell Christian Gieger Rob P. Mohney Mary Julia Brosnan Karsten Suhre Nicole Soranzo Tim D. Spector 《Diabetes》2013,62(12):4270-4276
Using a nontargeted metabolomics approach of 447 fasting plasma metabolites, we searched for novel molecular markers that arise before and after hyperglycemia in a large population-based cohort of 2,204 females (115 type 2 diabetic [T2D] case subjects, 192 individuals with impaired fasting glucose [IFG], and 1,897 control subjects) from TwinsUK. Forty-two metabolites from three major fuel sources (carbohydrates, lipids, and proteins) were found to significantly correlate with T2D after adjusting for multiple testing; of these, 22 were previously reported as associated with T2D or insulin resistance. Fourteen metabolites were found to be associated with IFG. Among the metabolites identified, the branched-chain keto-acid metabolite 3-methyl-2-oxovalerate was the strongest predictive biomarker for IFG after glucose (odds ratio [OR] 1.65 [95% CI 1.39–1.95], P = 8.46 × 10−9) and was moderately heritable (h2 = 0.20). The association was replicated in an independent population (n = 720, OR 1.68 [ 1.34–2.11], P = 6.52 × 10−6) and validated in 189 twins with urine metabolomics taken at the same time as plasma (OR 1.87 [1.27–2.75], P = 1 × 10−3). Results confirm an important role for catabolism of branched-chain amino acids in T2D and IFG. In conclusion, this T2D-IFG biomarker study has surveyed the broadest panel of nontargeted metabolites to date, revealing both novel and known associated metabolites and providing potential novel targets for clinical prediction and a deeper understanding of causal mechanisms.Currently, stratification of individuals at risk for type 2 diabetes (T2D) within the general population is based on well-established factors such as age, BMI, and fasting glucose (1). Although these factors contribute considerably to disease risk, they may not identify at-risk individuals before the disease process is well under way.Recently, a number of studies have found several metabolites to be correlated with insulin resistance and T2D (2–6), and T2D-associated metabolic profiles have been identified 10–15 years before the diagnosis/onset of the disease (7–9). To help preventive strategies, and maximize the potential for existing effective interventions, it is important to characterize the molecular changes that take place in the development of T2D.We aim to understand other biochemical changes, in addition to hyperglycemia, that take place at the onset of T2D using the largest metabolomic screening approach to date. We assessed >400 metabolites to determine which metabolomic profiles are correlated with T2D and impaired fasting glucose (IFG) in a large cohort of females from TwinsUK with independent replication. 相似文献
996.
997.
998.
Stavros G. Memtsoudis MD PhD Mary Hargett BS Linda A. Russell MD Javad Parvizi MD William L. Cats-Baril PhD Ottokar Stundner MD Thomas P. Sculco MD 《Clinical orthopaedics and related research》2013,471(8):2649-2657
Background
Controversy exists regarding many aspects of decision making pertaining to same-day versus staged bilateral TKA (BTKAs), including patient selection, perioperative management decisions, and other important choices.Questions/purposes
In the absence of suitable randomized trials, we sought to determine areas of consensus among national experts on the following questions: (1) What are the comparative risks of same-day BTKAs compared with unilateral TKA (UTKA) and staged BTKAs? (2) Who should be considered an appropriate candidate for same-day BTKAs? (3) What constitutes appropriate workup and perioperative management for BTKAs? (4) What is the optimal time between procedures if same-day BTKAs are not deemed appropriate? (5) Are there orthopaedic or rehabilitation considerations for BTKAs that might outweigh medical contraindications?Methods
In the setting of a consensus conference of national experts in orthopaedic surgery, anesthesiology, perioperative medicine, and epidemiology, the major questions surrounding same-day BTKAs were addressed by using an extensive literature review and the modified Delphi process. The process concluded with a meeting of participants and formulation of consensus statements.Results
Eighty-one percent of participants agreed that BTKAs are more invasive and complex procedures associated with increased risk for perioperative adverse events compared with UTKA in an unselected group of patients. The consensus group agreed that physicians and hospitals should consider using more restrictive patient selection criteria and exclude those with a modified cardiac risk index greater than 3 to mitigate the potentially increased risk. The majority of the group agreed that perioperative assessment and management should reflect the higher level of acuity of same-day BTKAs. Eighty-one percent of participants agreed that if a patient is not deemed a candidate for same-day BTKAs, a second TKA should be scheduled no sooner than 3 months after the first. The entire group agreed that when there is a conflict between the orthopaedic need and the medical adequacy of same-day BTKAs, the medical concern for the patient’s safety should prevail over the orthopaedic need.Conclusions
Experts perceived that same-day BTKAs increase medical risk, and thus a systematic approach to the management of patients should be taken to minimize complications.Electronic supplementary material
The online version of this article (doi:10.1007/s11999-013-2976-9) contains supplementary material, which is available to authorized users. 相似文献999.