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Emmi Helle Aldo Córdova-Palomera Tiina Ojala Priyanka Saha Praneetha Potiny Stefan Gustafsson Erik Ingelsson Michael Bamshad Deborah Nickerson Jessica X. Chong University of Washington Center for Mendelian Genomics Euan Ashley James R. Priest 《Genetic epidemiology》2019,43(2):215-226
Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes. 相似文献
16.
A study for evaluating the effect of the deltoid-flap repair in massive rotator cuff defects 总被引:2,自引:1,他引:1
Gunter Spahn Stefan Kirschbaum Hans Michael Klinger 《Knee surgery, sports traumatology, arthroscopy》2006,14(4):365-372
The repair of massive cuff defects by direct suture often is impossible. In these cases, a repair by musculo–tendineous flaps (latissimus-dorsi, pectoralis or deltoideus) is required. It was the goal of this study to evaluate the result of delta-flap repair in case of massive cuff defects with a diameter of 5 cm or more. Between 1998 and 2000 for all patients who were suffering from a massive rotator cuff tear more than 5 cm a deltoid transfer was performed. A total of 20 patients (14 male, 6 female; age: 60.9 ± 8.7 years) were available for a follow-up after 47.2 ± 8.0 (range, 36 to 60) month. The operation included an arthroscopic evaluation, acromioplasty with resection of the lateral clavicular end, and biceps tenodesis. The cuff defect was repaired by transfer a muscular flap from the anterior part of the deltoid (about 2×6 cm) into the defect. The patients subjectively rated their result—10 excellent, 9 good, and 1 poor. Preoperatively, the Constant amounted 26.3 ± 5.1 points. At follow-up, the score significantly increased to 74.5 ± 8.5 points. The acromiohumeral distance increased from 4.9 ± 1.1 to 9.2 ± 1.7 mm. In MRI examination of 11 patients all had an intact flap. Two complications (a wound hematoma and a deep infection) did not influence the result. The repair of massive rotator cuff tears by a deltoid transfer produces acceptable clinical and radiological results. 相似文献
17.
Detailed pathological changes of human lumbar facet joints L1–L5 in elderly individuals 总被引:4,自引:1,他引:3
Facet joints play an important role in intervertebral load transmission and are crucial for rotational kinematics. Clinically, the role of facet joints as a possible source of low back pain is seen as controversial and at present is not sufficiently investigated. In this study, human lumbar facet (zygapopyhysial) joints from donors with advanced age were analyzed macroscopically, for degenerative changes. The aim was to determine the extent and morphology of degenerative changes in these joints. Lumbar facet joints (L1–L5) of 32 donors were studied (mean age 80.1±11.2 years). Joint capsules were carefully removed and joint surfaces (5 zones) examined using magnifying glasses and probes. In the result, the majority of facet joints showed cartilage defects of varying extent. Defects were located mostly at the margins of the articular surface, the central zone being relatively well preserved. Defect localization was different between superior (most cartilage defects in superior zone) and inferior (most defects inferiorly) facets. Further, defects were more severe caudal (level of L5) and in older persons. Osteophytes were present in up to 30%, located mostly at the latero-dorsal enthesis of the joint capsule on the superior facet. In conclusion, most margins of the articular facets are subject to degenerative changes in the lumbar spine of elderly persons, the topographical pattern being different in superior and inferior facets. This observation can be explained by the segmental motion patterns during extension/flexion movements of the facets. Sometimes, due to the marginal extension, it is obvious that not all changes can be assessed by CT or MRI. 相似文献
18.
The vagal nerve as a link between the nervous and immune system in the instance of polymicrobial sepsis 总被引:5,自引:0,他引:5
Wolfram Kessler Tobias Traeger Alexandra Westerholt Friederike Neher Marlene Mikulcak Antje Müller Stefan Maier Claus-Dieter Heidecke 《Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie》2006,391(2):83-87
Background The role of the vagal nerve in the autonomic nervous system is widely well known. Recently, an additional function was revealed
serving as a connector between the nervous and immune system. This connection is called the “cholinergic inflammatory pathway.”
Through stimulation of the acetylcholine receptors located upon the macrophages, the “unspecific” immune system can be directly
influenced.
Methods The vagal nerve was completely transected directly posterior to its passage through the diaphragm. The effect of complete
vagotomy was analyzed using a murine model of polymicrobial peritonitis (colon ascendens stent peritonitis, CASP). Survival
and clinical course of vagotomized or sham-operated mice were analyzed in the CASP model.
Results After CASP surgery, vagotomy led to a significantly increased mortality (64.7%) in comparison to sham-vagotomized animals
(34%). No difference in the bacterial load of various tissues (lung, liver, spleen, blood, lavage fluid, and kidney) from
septic animals with or without vagotomy was observed. Vagotomized animals reveal elevated serum cytokine levels (TNF, IL-6,
IL-10, and MCP-1) 20 h after the induction of polymicrobial peritonitis.
Conclusion The vagal nerve is therefore an important modulator of the immune system.
W. Kessler and T. Traeger contributed equally to this work
Best of Forum Papers presented at the Annual Meeting of the German Society of Surgery, 2–5 May 2006, Berlin, Germany 相似文献
19.
Prevalence of H pylori associated 'high risk gastritis' for development of gastric cancer in patients with normal endoscopic findings 总被引:1,自引:0,他引:1
Andreas Leodolter Matthias P Ebert Ulrich Peitz Kathlen Wolle Stefan Kahl Peter Malfertheiner 《World journal of gastroenterology : WJG》2006,(34)
INTRODUCTION H pylori infection is an established risk factor for development of gastric cancer[1,2]. According to the model of carcinogenesis of the intestinal type adenocarcinoma proposed by Correa, the multi-step development starts from the condition o… 相似文献
20.
Educating African American men about the prostate cancer screening dilemma: a randomized intervention. 总被引:1,自引:0,他引:1
Kathryn L Taylor Jackson L Davis Ralph O Turner Lenora Johnson Marc D Schwartz Jon F Kerner Chikarlo Leak 《Cancer epidemiology, biomarkers & prevention》2006,15(11):2179-2188
BACKGROUND: Until there is a definitive demonstration that early diagnosis and treatment of prostate cancer reduces disease-related mortality, it is imperative to promote informed screening decisions by providing balanced information about the potential benefits and risks of prostate cancer screening. Within a community/academic collaboration, we conducted a randomized trial of a printed booklet and a videotape that were designed for African American (AA) men. The purpose of the trial was to determine the effect of the interventions on knowledge, decisional conflict, satisfaction with the screening decision, and self-reported screening. METHODS: Participants were 238 AA men, ages 40 to 70 years, who were members of the Prince Hall Masons in Washington, DC. Men were randomly assigned to the (a) video-based information study arm, (b) print-based information study arm, or (c) wait list control study arm. Intervention materials were mailed to men at home. Assessments were conducted at baseline, 1 month, and 12 months postintervention. Multivariate analyses, including ANCOVA and logistic regression, were used to analyze group differences. RESULTS: The booklet and video resulted in a significant improvement in knowledge and a reduction in decisional conflict about prostate cancer screening, relative to the wait list control. Satisfaction with the screening decision was not affected by the interventions. Self-reported screening rates increased between the baseline and the 1-year assessment, although screening was not differentially associated with either of the interventions. In exploratory analyses, prostate-specific antigen testing at 1 year was more likely among previously screened men and was associated with having low baseline decisional conflict. CONCLUSIONS: This study represents one of the first randomized intervention trials specifically designed to address AA men's informed decision making about prostate cancer screening. We have developed and evaluated culturally sensitive, balanced, and disseminable materials that improved knowledge and reduced decisional conflict about prostate cancer screening among AA men. Due to the high incidence and mortality rates among AA men, there is a need for targeted educational materials, particularly materials that are balanced in terms of the benefits and risks of screening. 相似文献