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991.
992.
Mackowiak PA Billings FT Wasserman SS 《The American journal of the medical sciences》2012,343(2):146-149
Confederate general "Stonewall" Jackson has been called "one of the greatest military geniuses the world ever saw." However, on critical review of his command decisions during the course of 12 of the 20 battles he fought during the American Civil War, historians have rated his performance as poor. In this investigation, the authors examined the effect of sleep deprivation on Jackson's battle decisions in light of experimental data driving current calls for limiting the duty hours of physicians. 相似文献
993.
Langendonk JG Roos JC Angus L Williams M Karstens FP de Klerk JB Maritz C Ben-Omran T Williamson C Lachmann RH Murphy E 《Journal of inherited metabolic disease》2012,35(3):419-424
In this case series we report 12 pregnancies, in women treated at four centres, illustrating some of the issues that may be encountered during pregnancy by women with inherited metabolic disease. We discuss how specific pregnancy, labour and delivery issues for mothers with methylmalonic acidemia, homocystinuria, propionic acidemia, glutaric acidemia type 1, ornithine transcarbamylase (OTC) deficiency and 3-hydroxy-3-methylglutaric(HMG)-CoA lyase deficiency were managed and the outcome for the mother and child in each case. Eight of the 12 pregnancies resulted in the successful delivery of a liveborn infant. Several women experienced decompensation of their condition during pregnancy or the post-partum period. There was one maternal death in a women with 3-hydroxy-3-methylglutaric(HMG)-CoA lyase deficiency. Pre-pregnancy counselling and co-management of high risk medical patients by obstetricians and specialist physicians with an understanding of the relationship between pregnancy and inherited metabolic disease is essential. 相似文献
994.
Gardner JM Dandekar M Thomas D Goldblum JR Weiss SW Billings SD Lucas DR McHugh JB Patel RM 《The American journal of surgical pathology》2012,36(7):1047-1051
Pleomorphic liposarcoma (PL) is an uncommon form of liposarcoma that rarely occurs in the skin and subcutis. As its behavior in this setting is incompletely characterized, we undertook a study of a series of superficial PLs, defined as those arising or based primarily in the dermis and/or subcutis without involvement of deep structures. In addition, MDM2 gene amplification, a diagnostic signature of well-differentiated/dedifferentiated liposarcoma (WDL/DL), was evaluated to address the recent observation that this gene is amplified within PL-like areas in DL. PLs were obtained from institutional and consultation files (n=29). Cases were evaluated with respect to age, sex, location (dermis, dermis and subcutis, subcutis), size, predominant pattern (pleomorphic spindled or epithelioid), extent of lipogenic differentiation, and tumor necrosis. MDM2 amplification was analyzed using FISH on formalin-fixed, paraffin-embedded material in 26 cases. Patients ranged in age from 5 to 93 years (M:F=1.4:1). Tumors were located on the extremity (n=15), trunk (n=7), and head and neck (n=7) and involved the dermis (n=4), dermis and subcutis (n=10), and subcutis (n=15). Tumor size ranged from 0.8 to 15 cm (median=2 cm). All were mitotically active high-grade sarcomas [FNCLCC grade 2 (n=23) or 3 (n=6)] with either a pleomorphic spindled (n=24) or an epithelioid pattern (n=5) with variable extent of lipogenic differentiation [<25% (n=15), 25% to 50% (n=9), >50% (n=5)]. Necrosis was present in 3 cases. MDM2 gene amplification was present in 3 of 26 cases. Follow-up information in 24 cases (range=1 to 192 mo; median=48 mo; mean=59 mo) revealed local recurrences (4/24) but no metastasis or death from disease. We conclude that cutaneous and subcutaneous PLs, despite their high grade, have a much more favorable outcome compared with their deep-seated counterparts, most likely attributed to their small size and superficial location. The low incidence of MDM2 gene amplification in our series indicates that most superficial PLs are unrelated to WDL/DL. PL likely evolves by way of more than 1 molecular pathway. 相似文献
995.
Billings LK Hsu YH Ackerman RJ Dupuis J Voight BF Rasmussen-Torvik LJ Hercberg S Lathrop M Barnes D Langenberg C Hui J Fu M Bouatia-Naji N Lecoeur C An P Magnusson PK Surakka I Ripatti S Christiansen L Dalgård C Folkersen L Grundberg E;MAGIC Investigators;DIAGRAM + Consortium;MuTHER Consortium;ASCOT Investigators;GEFOS Consortium Eriksson P Kaprio J Ohm Kyvik K Pedersen NL Borecki IB Province MA Balkau B Froguel P Shuldiner AR Palmer LJ Wareham N Meneton P Johnson T Pankow JS Karasik D Meigs JB 《Diabetes》2012,61(8):2176-2186
Exploring genetic pleiotropy can provide clues to a mechanism underlying the observed epidemiological association between type 2 diabetes and heightened fracture risk. We examined genetic variants associated with bone mineral density (BMD) for association with type 2 diabetes and glycemic traits in large well-phenotyped and -genotyped consortia. We undertook follow-up analysis in ~19,000 individuals and assessed gene expression. We queried single nucleotide polymorphisms (SNPs) associated with BMD at levels of genome-wide significance, variants in linkage disequilibrium (r(2) > 0.5), and BMD candidate genes. SNP rs6867040, at the ITGA1 locus, was associated with a 0.0166 mmol/L (0.004) increase in fasting glucose per C allele in the combined analysis. Genetic variants in the ITGA1 locus were associated with its expression in the liver but not in adipose tissue. ITGA1 variants appeared among the top loci associated with type 2 diabetes, fasting insulin, β-cell function by homeostasis model assessment, and 2-h post-oral glucose tolerance test glucose and insulin levels. ITGA1 has demonstrated genetic pleiotropy in prior studies, and its suggested role in liver fibrosis, insulin secretion, and bone healing lends credence to its contribution to both osteoporosis and type 2 diabetes. These findings further underscore the link between skeletal and glucose metabolism and highlight a locus to direct future investigations. 相似文献
996.
Billings FT Pretorius M Schildcrout JS Mercaldo ND Byrne JG Ikizler TA Brown NJ 《Journal of the American Society of Nephrology : JASN》2012,23(7):1221-1228
Obesity increases oxidative stress, endothelial dysfunction, and inflammation, but the effect of obesity on postoperative AKI is not known. We examined the relationship between body mass index (BMI) and AKI in 445 patients undergoing cardiac surgery and whether oxidative stress (F(2)-isoprostanes), inflammation (IL-6), or antifibrinolysis (plasminogen activator inhibitor-1 [PAI-1]) contribute to any identified relationship. Overall, 112 (25%) of the 445 patients developed AKI. Higher BMI was independently associated with increased odds of AKI (26.5% increase per 5 kg/m(2) [95% confidence interval, 4.3%-53.4%]; P=0.02). Baseline F(2)-isoprostane (P=0.04), intraoperative F(2)-isoprostane (P=0.003), and intraoperative PAI-1 (P=0.04) concentrations also independently predicted AKI. BMI no longer predicted AKI after adjustment for the effect of F(2)-isoprostanes, suggesting that obesity may affect AKI via effects on oxidative stress. In contrast, adjustment for IL-6 or PAI-1 did not substantially alter the association between BMI and AKI. Further, deconstruction of the obesity-AKI relationship into direct (i.e., independent of candidate pathways) and indirect (i.e., effect of BMI on AKI via each candidate pathway) effects indicated that F(2)-isoprostanes, but not IL-6 or PAI-1, partially mediate the relationship between obesity and AKI (P=0.001). In conclusion, obesity independently predicts AKI after cardiac surgery, and oxidative stress may partially mediate this association. 相似文献
997.
The Intelence aNd pRezista Once A Day Study (INROADS): a multicentre,single‐arm,open‐label study of etravirine and darunavir/ritonavir as dual therapy in HIV‐1‐infected early treatment‐experienced subjects
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PJ Ruane C Brinson M Ramgopal R Ryan B Coate M Cho TN Kakuda D Anderson 《HIV medicine》2015,16(5):288-296
998.
Knecht H; Raphael M; McQuain C; Rothenberger S; Pihan G; Camilleri-Broet S; Bachmann E; Kershaw GR; Ryan S; Kittler EL; Quesenberry PJ; Schlaifer D; Woda BA; Brousset P 《Blood》1996,87(3):876-881
This sequencing study of 17 acquired immunodeficiency syndrome-related lymphomas (9 primary brain, 8 systemic) and 8 human immunodeficiency virus-negative atypical lymphoproliferations expressing large amounts of the latent membrane protein 1 (LMP1) of Epstein-Barr virus was performed to characterize the carboxy terminal NF-kappa B activation domain of LMP1 at the molecular level in an immunocompromised host. In- frame deletions within the NF-kappa B activation domain were identified in all but 2 primary brain lymphomas, 4 systemic lymphomas, and 4 atypical lymphoproliferations, ie, in 60% of cases. In addition, non silent point mutations (range 1 to 5, mean 3.3) were detected in all cases. Although all changes occurred within the first 100 nucleotides of the carboxy terminal NF-kappa B activation domain--a critical sequence for the protein half-life--not a single point mutation was found in the remaining 62 nucleotides, necessary for malignant transformation. Such a clustering of nonrandom sequence variations, associated with a high oncoprotein expression in immunocompromised hosts, suggests that this part of the LMP1 oncogene behaves as a hypervariable region with natural selection of growth-promoting variants through prolongation of the protein half-life. 相似文献
999.
Specific antibody-blocking activities in antilymphocyte globulin as correlates of efficacy for the treatment of aplastic anemia 总被引:1,自引:0,他引:1
Horse anti-human thoracic duct lymphocyte globulin (ATDLG) has been used successfully for the treatment of severe aplastic anemia, although not all lots have comparable efficacy. We have characterized the antibody specificities contained in one lot of Swiss ATDLG found to provide a response rate of 69% and another lot that provided only a 31% response rate. Antibody specificities were analyzed quantitatively by competitive inhibition assays with the use of a panel of fluorescein- conjugated murine monoclonal antibodies that recognize T cell antigens, common leukocyte antigens, and "la-like" antigens. Although there was wide variation in the amounts of individual antibody specificities within each lot, the effective lot of ATDLG contained an average of 2 1/2 times as much of each antibody specificity as the less effective lot. There were only two antibody specificities that differed remarkably from this pattern; and these deviations did not appear sufficient to account for the variation in ATDLG efficacy. It is possible that antibody specificities other than those tested were responsible for therapeutic efficacy. Alternatively, the data suggest that it might be possible to achieve improved results for the treatment of severe aplastic anemia with higher doses of less effective lots of ATDLG. 相似文献
1000.