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排序方式: 共有1517条查询结果,搜索用时 140 毫秒
51.
Hume GE Fowler EV Doecke J Simms LA Huang N Palmieri O Griffiths LR Florin TH Annese V Radford-Smith GL 《Inflammatory bowel diseases》2008,14(5):585-590
BACKGROUND: The first major Crohn's disease (CD) susceptibility gene, NOD2, implicates the innate intestinal immune system and other pattern recognition receptors in the pathogenesis of this chronic, debilitating disorder. These include the Toll-like receptors, specifically TLR4 and TLR5. A variant in the TLR4 gene (A299G) has demonstrated variable association with CD. We aimed to investigate the relationship between TLR4 A299G and TLR5 N392ST, and an Australian inflammatory bowel disease cohort, and to explore the strength of association between TLR4 A299G and CD using global meta-analysis. METHODS: Cases (CD = 619, ulcerative colitis = 300) and controls (n = 360) were genotyped for TLR4 A299G, TLR5 N392ST, and the 4 major NOD2 mutations. Data were interrogated for case-control analysis prior to and after stratification by NOD2 genotype. Genotype-phenotype relationships were also sought. Meta-analysis was conducted via RevMan. RESULTS: The TLR4 A299G variant allele showed a significant association with CD compared to controls (P = 0.04) and a novel NOD2 haplotype was identified which strengthened this (P = 0.003). Furthermore, we identified that TLR4 A299G was associated with CD limited to the colon (P = 0.02). In the presence of the novel NOD2 haplotype, TLR4 A299G was more strongly associated with colonic disease (P < 0.001) and nonstricturing disease (P = 0.009). A meta-analysis of 11 CD cohorts identified a 1.5-fold increase in risk for the variant TLR4 A299G allele (P < 0.00001). CONCLUSIONS: TLR 4 A299G appears to be a significant risk factor for CD, in particular colonic, nonstricturing disease. Furthermore, we identified a novel NOD2 haplotype that strengthens the relationship between TLR4 A299G and these phenotypes. 相似文献
52.
Arjan PM de Brouwer Sander B Nabuurs Ingrid EC Verhaart Astrid R Oudakker Roel Hordijk Helger G Yntema Jannet M Hordijk-Hos Krysta Voesenek Bert BA de Vries Ton van Essen Wei Chen Hao Hu Jamel Chelly Johan T den Dunnen Vera M Kalscheuer Annemieke M Aartsma-Rus Ben CJ Hamel Hans van Bokhoven Tjitske Kleefstra 《European journal of human genetics : EJHG》2014,22(4):480-485
We have identified a deletion of 3 base pairs in the dystrophin gene (DMD), c.9711_9713del, in a family with nonspecific X-linked intellectual disability (ID) by sequencing of the exons of 86 known X-linked ID genes. This in-frame deletion results in the deletion of a single-amino-acid residue, Leu3238, in the brain-specific isoform Dp71 of dystrophin. Linkage analysis supported causality as the mutation was present in the 7.6 cM linkage interval on Xp22.11–Xp21.1 with a maximum positive LOD score of 2.41 (MRX85 locus). Molecular modeling predicts that the p.(Leu3238del) deletion results in the destabilization of the C-terminal domain of dystrophin and hence reduces the ability to interact with β-dystroglycan. Correspondingly, Dp71 protein levels in lymphoblastoid cells from the index patient are 6.7-fold lower than those in control cell lines (P=0.08). Subsequent determination of the creatine kinase levels in blood of the index patient showed a mild but significant elevation in serum creatine kinase, which is in line with impaired dystrophin function. In conclusion, we have identified the first DMD mutation in Dp71 that results in ID without muscular dystrophy. 相似文献
53.
Sebastian S Zeki Rehan Haidry Manuel Justo-Rodriguez Laurence B Lovat Nicholas A Wright Stuart A McDonald 《World journal of gastroenterology : WJG》2014,20(15):4453-4456
Barrett’s oesophagus(BO)is a usually indolent condition that occasionally requires endoscopic therapy.Radiofrequency ablation(RFA)is an effective endoscopic treatment for high grade dysplasia(HGD)and intramucosal cancer in BO.It has a good efficacy,durability and safety profile although complications can occur.Here we describe a case of RFA in a patient with high grade dysplasia.Although the response to treatment was initially very good with the development of neosquamous epithelium,the patient very rapidly developed a squamous cell cancer of the oesophagus confirmed on radiology,histology and immunohistochemistry.Sanger sequencing confirmed that the original HGD and the squamous cell cancer(SCC)were derived from separate clonal origins.The report highlights the fact that SCC of the oesophagus has been noted after endoscopic ablation for BO previously and suggest that ablation of BO may encourage the clonal expansion of cells carrying carcinogenic mutations once a dominant clonal population has been eradicated. 相似文献
54.
Hume DA Lovblom LE Ahmed A Yeung E Orszag A Shin TM Bril V Perkins BA 《Diabetes research and clinical practice》2012,95(2):e37-e40
We investigated the association of CDKAL1 (rs7754840 and rs7756992) and CDKN2A/2B (rs10811661) variants with T2DM. Higher MAF of rs7754840 and rs7756992 were seen in patients, and both were associated with T2DM under additive, dominant, and recessive models. CDKAL1 rs7754840 and rs7756992, but not CDKN2A/2B rs10811661, are associated with T2DM in Lebanese. 相似文献
55.
56.
Complications of apheresis in children 总被引:1,自引:0,他引:1
Michon B Moghrabi A Winikoff R Barrette S Bernstein ML Champagne J David M Duval M Hume HA Robitaille N Bélisle A Champagne MA 《Transfusion》2007,47(10):1837-1842
BACKGROUND: Although the frequency of complications in adults undergoing therapeutic apheresis is low, there are little data in children. STUDY DESIGN AND METHODS: A retrospective study of 186 children who had undergone a total of 1632 apheresis procedures between 1994 and 2002 was conducted. Adverse reactions were prospectively documented. The procedures were plasma exchange (67%), hematopoietic progenitor cell collection (18%), red blood cell exchange (6.9%), leukodepletion (0.7%), and plasma exchange with immunoadsorption (6.7%). RESULTS: Adverse reactions, most minor, were reported in 55 percent of procedures in 82 percent of patients. The most frequent complications, per procedure and per patient during an entire course of therapy, were hypotension (14 and 48.4%), hypotension requiring fluid bolus (4.8 and 26.9%), symptomatic hypocalcemia (9.7 and 28.5%), allergic reactions (4.4 and 5.9%), catheter-related thrombosis (1.7 and 12.4%), catheter-related infection (2.1 and 16.1%), and severe anemia (hemoglobin [Hb] level, <7 g/dL; 2.5 and 17.2%). There were two deaths (1% of patients). Risk factors for complications by multivariate analysis were lower body weight, lower preapheresis Hb level, apheresis in a critical care unit, and number of procedures per patient. The 55 percent incidence of complications per procedure in our pediatric cohort is much higher than the 4.3 to 28 percent incidence reported in adults. The excess of adverse reactions in children are mostly related to citrate toxicity, higher relative vascular volume shifts, and the need for vascular access. CONCLUSION: Pediatric apheresis presents unique challenges and is associated with higher complication rate compared to adults. It is recommended that this procedure be performed in specialized centers. 相似文献
57.
McMorran BJ Patat SA Carlin JB Grimwood K Jones A Armstrong DS Galati JC Cooper PJ Byrnes CA Francis PW Robertson CF Hume DA Borchers CH Wainwright CE Wainwright BJ 《Clinical chemistry》2007,53(10):1782-1791
BACKGROUND: Airway inflammation in cystic fibrosis (CF) is exaggerated and characterized by neutrophil-mediated tissue destruction, but its genesis and mechanisms remain poorly understood. To further define the pulmonary inflammatory response, we conducted a proteome-based screen of bronchoalveolar lavage fluid (BALF) collected from young children with and without CF experiencing endobronchial infection. METHODS: We collected BALF samples from 45 children younger than 5 years and grouped them according to the presence of respiratory pathogens: > or = 1 x 10(5) colony-forming units (CFU)/mL BALF (18 and 12 samples with and without CF, respectively) and <1 x 10(5) CFU/mL (23 and 15 samples). BALF proteins were analyzed with SELDI-TOF mass spectrometry (MS) and H4 ProteinChips. Proteins were identified and characterized using trypsin digestion, tandem MS, Fourier transform ion cyclotron resonance MS, immunoblotting, and ELISA. RESULTS: The SELDI-TOF MS BALF profiles contained 53 unique, reliably detected proteins. Peak intensities of 24 proteins differed significantly between the CF and non-CF samples. They included the neutrophil proteins, alpha-defensin 1 and 2, S100A8, S100A9, and S100A12, as well as novel forms of S100A8 and S100A12 with equivalent C-terminal deletions. Peak intensities of these neutrophil proteins and immunoreactive concentrations of selected examples were significantly higher in CF than non-CF samples. CONCLUSIONS: Small neutrophil-derived BALF proteins, including novel C-terminal truncated forms of S100A proteins, are easily detected with SELDI-TOF MS. Concentrations of these molecules are abnormally high in early CF lung disease. The data provide new insights into CF lung disease and identify novel proteins strongly associated with CF airway inflammation. 相似文献
58.
Ian F. Caplan Eric Winter Gregory Glauser Stephen Goodrich Scott D. McClintock Eric L. Hume Neil R. Malhotra 《Journal of orthopaedic research》2020,38(10):2189-2196
The LACE+ (Length of stay, Acuity of admission, Charlson Comorbidity Index score, and Emergency department visits in the past 6 months) risk-prediction tool has never been tested in an orthopedic surgery population. LACE+ may help physicians more effectively identify and support high-risk orthopedics patients after hospital discharge. LACE+ scores were retrospectively calculated for all consecutive orthopedic surgery patients (n = 18 893) at a multi-center health system over 3 years (2016-2018). Coarsened exact matching was employed to create “matched” study groups with different LACE+ score quartiles (Q1, Q2, Q3, Q4). Outcomes were compared between quartiles. In all, 1444 patients were matched between Q1 and Q4 (n = 2888); 2079 patients between Q2 and Q4 (n = 4158); 3032 patients between Q3 and Q4 (n = 6064). Higher LACE+ scores significantly predicted 30D readmission risk for Q4 vs Q1 and Q4 vs Q3 (P < .001). Larger LACE+ scores also significantly predicted 30D risk of ED visits for Q4 vs Q1, Q4 vs Q2, and Q4 vs Q3 (P < .001). Increased LACE+ score also significantly predicted 30D risk of reoperation for Q4 vs Q1 (P = .018), Q4 vs Q2 (P < .001), and Q4 vs Q3 (P < .001). 相似文献
59.
P. Maxwell Courtney Colin M. Whitaker Jacob T. Gutsche Eric L. Hume Gwo-Chin Lee 《The Journal of arthroplasty》2014
Based on our previously published risk stratification model, 295 (19%) of a consecutive series of 1594 TJA patients were triaged to the ICU. However, only 67 patients (22%) required intensive care interventions. We identified 5 independent multivariate predictors (P < 0.001) including COPD, CAD, CHF (1 point each), EBL > 1000 mL, and intraoperative vasopressors (2 points each) to form the Penn Arthroplasty Risk Score (PARS). Patients with a score of 0 through 7 had a probability of requiring critical care of 7.0%, 13.2%, 23.5%, 38.1%, 55.4%, 71.4%, 83.4%, and 91.1% respectively. Based on these results, our previous risk stratification protocol is overly sensitive and non-specific. Any risk stratification algorithm for ICU admission should include intraoperative risk factors in order to be fully predictive. 相似文献
60.
Michael P. Bogenschutz Samara L. Rice J. Scott Tonigan Howard S. Vogel Joseph Nowinski Donald Hume Pamela B. Arenella 《Journal of substance abuse treatment》2014
There are few clinical trials of 12-step treatments for individuals with serious mental illness and alcohol or drug dependence. This randomized trial assessed the effects of adding a 12-session 12-step facilitation therapy (TSF), adapted from that used in Project MATCH, to treatment as usual in an outpatient dual diagnosis program. Participants were 121 individuals dually diagnosed with alcohol dependence and a serious mental disorder, followed during 12 weeks of treatment and 36 weeks post-treatment. Participants receiving TSF had greater participation in 12-step programs, but did not demonstrate greater improvement in alcohol and drug use. However, considered dimensionally, greater participation in TSF was associated with greater improvement in substance use, and greater 12-step participation predicted decreases in frequency and intensity of drinking. Findings suggest that future work with TSF in this population should focus on maximizing exposure to TSF, and maximizing the effect of TSF on 12-step participation. 相似文献