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81.
London GM Asmar RG O'Rourke MF Safar ME;REASON Project Investigators 《Journal of the American College of Cardiology》2004,43(1):92-99
OBJECTIVES: The goal of this study was to determine if a low-dose combination of the angiotensin-converting enzyme inhibitor perindopril (Per) and the diuretic indapamide (Ind) reduces central (thoracic aorta, carotid artery) as well as brachial systolic blood pressure (SBP) more than the beta-blocker atenolol and to determine the hemodynamic factors influencing independently brachial and central SBP: pulse wave velocity (PWV) and pattern of wave reflections. BACKGROUND: In high cardiovascular risk populations, angiotensin blockade improves survival without affecting brachial SBP and diastolic blood pressure (DBP). Whether central SBP, which is physiologically lower than brachial SBP, is significantly reduced has never been investigated. METHODS: This study was a double-blind randomized trial for one year in patients with essential hypertension. RESULTS: For a similar DBP reduction, Per/Ind decreased SBP significantly more than atenolol, with a more pronounced reduction for central than for brachial SBP. After one year, the difference between brachial and central SBP was maintained by Per/Ind (8.28 +/- 1.53 mm Hg) and significantly attenuated by atenolol (0.29 +/- 1.61 mm Hg). Under atenolol, the principal factor modulating SBP reduction was mean blood pressure. Under Per/Ind, this parameter played a minor role, and the central SBP reduction implied a major role for disturbed PWV and wave reflections. CONCLUSIONS: Under Per/Ind, but not atenolol, normalization of brachial SBP is achieved with a significantly greater reduction of central SBP. This hemodynamic profile reflects changes of wave reflections issued from distal arterial and arteriolar territory, where Per/Ind, but not atenolol, is known to improve vessel wall structure. 相似文献
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84.
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
85.
Adam D Farmer Sahar D Mohammed George E Dukes S Mark Scott Anthony R Hobson 《World journal of gastroenterology : WJG》2014,(17):5000-5007
AIM:To ascertain whether caecal pH is different in patients with irritable bowel syndrome(IBS),whose primary symptoms are bloating and distension,to healthy controls.METHODS:Motility and pH data were reviewed from16 patients with RomeⅢdefined IBS and 16 healthy controls,who had undergone a wireless motility capsule(WMC)study using a standardized protocol.Motility measures were anchored around known anatomical landmarks as identified by compartmental pH changes.Sixty-minute epochs were used to quantify antral,duodenal,ileal,caecal and distal colonic contractility.The maximum and minimum pH was measured either side of the ileo-caecal junction.RESULTS:No differences were seen in motility parameters,compartmental transit times or maximal ileal pH between the two groups.Caecal pH was significantly lower in patients compared to controls(5.12±0.05vs 6.16±0.15,P<0.0001).The ileal:caecalΔchange was greater in patients than controls(-2.63±0.08 vs-1.42±0.11,P<0.0001).There was a significant correlation between caecal pH and right colonic contractility(r=0.54,P=0.002).CONCLUSION:Patients with bloating and distension have a lower caecal pH compared to controls.The measurement of caecal pH using the WMC provides a quantifiable biomarker of fermentation potentially identifying those patients that may preferentially benefit from antibiotic or dietary interventions. 相似文献
86.
Refaat MM Tanaka T Kormos RL McNamara D Teuteberg J Winowich S London B Simon MA 《Journal of cardiac failure》2012,18(2):140-145
BackgroundImplantable cardioverter-defibrillators (ICDs) reduce mortality in heart failure (HF). In patients requiring a ventricular assist device (VAD), the benefit from ICD therapy is not well established. The aim of this study was to define the impact of ICD on outcomes in VAD-supported patients.Methods and ResultsWe reviewed data for consecutive adult HF patients receiving VAD as a bridge to transplantation from 1996 to 2003. The primary outcome was survival to transplantation. A total of 144 VADs were implanted [85 left ventricular (LVAD), 59 biventricular (BIVAD), mean age 50 ± 12 years, 77% male, left ventricular ejection fraction 18 ± 9%, 54% ischemic]. Mean length of support was 119 days (range 1–670); 103 patients (72%) survived to transplantation. Forty-five patients had an ICD (33 LVAD, 12 BIVAD). More LVAD patients had an appropriate ICD shock before implantation than after (16 vs 7; P = .02). There was a trend toward higher shock frequency before LVAD implant than after (3.3 ± 5.2 vs 1.1 ± 3.8 shocks/y; P = .06). Mean time to first shock after VAD implant was 129 ± 109 days. LVAD-supported patients with an ICD were significantly more likely to survive to transplantation [1-y actuarial survival to transplantation: LVAD: 91% with ICD vs 57% without ICD (log-rank P = .01); BIVAD: 54% vs 47% (log-rank P = NS)]. An ICD was associated with significantly increased survival in a multivariate model controlling for confounding variables (odds ratio 2.54, 95% confidence interval 1.04–6.21; P = .04).ConclusionsShock frequency decreases after VAD implantation, likely owing to ventricular unloading, but appropriate ICD shocks still occur in 21% of patients. An ICD is associated with improved survival in LVAD-supported HF patients. 相似文献
87.
Sage Hahn Scott Mackey Janna Cousijn John J. Foxe Andreas Heinz Robert Hester Kent Hutchinson Falk Kiefer Ozlem Korucuoglu Tristram Lett Chiang-Shan R. Li Edythe London Valentina Lorenzetti Luijten Maartje Reza Momenan Catherine Orr Martin Paulus Lianne Schmaal Rajita Sinha Zsuzsika Sjoerds Dan J. Stein Elliot Stein Ruth J. van Holst Dick Veltman Henrik Walter Reinout W. Wiers Murat Yucel Paul M. Thompson Patricia Conrod Nicholas Allgaier Hugh Garavan 《Human brain mapping》2022,43(1):555-565
To identify neuroimaging biomarkers of alcohol dependence (AD) from structural magnetic resonance imaging, it may be useful to develop classification models that are explicitly generalizable to unseen sites and populations. This problem was explored in a mega-analysis of previously published datasets from 2,034 AD and comparison participants spanning 27 sites curated by the ENIGMA Addiction Working Group. Data were grouped into a training set used for internal validation including 1,652 participants (692 AD, 24 sites), and a test set used for external validation with 382 participants (146 AD, 3 sites). An exploratory data analysis was first conducted, followed by an evolutionary search based feature selection to site generalizable and high performing subsets of brain measurements. Exploratory data analysis revealed that inclusion of case- and control-only sites led to the inadvertent learning of site-effects. Cross validation methods that do not properly account for site can drastically overestimate results. Evolutionary-based feature selection leveraging leave-one-site-out cross-validation, to combat unintentional learning, identified cortical thickness in the left superior frontal gyrus and right lateral orbitofrontal cortex, cortical surface area in the right transverse temporal gyrus, and left putamen volume as final features. Ridge regression restricted to these features yielded a test-set area under the receiver operating characteristic curve of 0.768. These findings evaluate strategies for handling multi-site data with varied underlying class distributions and identify potential biomarkers for individuals with current AD. 相似文献
88.
Wu H Romieu I Sienra-Monge JJ Estela Del Rio-Navarro B Anderson DM Jenchura CA Li H Ramirez-Aguilar M Del Carmen Lara-Sanchez I London SJ 《The Journal of allergy and clinical immunology》2007,120(2):322-328
BACKGROUND: S-nitrosothiols are potent endogenous bronchodilators depleted in asthmatic airway lining fluid. S-nitrosoglutathione reductase (GSNOR; also known as alcohol dehydrogenase 5 or formaldehyde dehydrogenase) catalyzes the metabolism of S-nitrosoglutathione (GSNO) and controls intracellular levels of S-nitrosothiols. GSNOR knockout mice have increased lung S-nitrosothiol levels and are therefore protected from airway hyperresponsiveness after methacholine or allergen challenge. OBJECTIVE: We sought to investigate whether genetic variation in GSNOR is associated with childhood asthma and atopy. METHODS: We genotyped 5 tagging and 2 additional single nucleotide polymorphisms (SNPs) in GSNOR in 532 nuclear families consisting of asthmatic children aged 4 to 17 years and both parents in Mexico City. Atopy was determined by means of skin prick testing. RESULTS: Carrying 1 or 2 copies of the minor allele of SNP rs1,154,404 was associated with decreased risk of asthma (relative risk [RR], 0.77; 95% CI, 0.61-0.97; P = .028 for 1 copy and RR, 0.66; 95% CI, 0.44-0.99; P = .046 for 2 copies). Homozygosity for the minor allele of SNP rs28,730,619 was associated with increased risk of asthma (RR, 1.60; 95% CI, 1.13-2.26; P = .0077). Haplotype analyses supported the single SNP findings. GSNOR SNPs were not associated with the degree of atopy. CONCLUSION: This is the first study of genetic polymorphisms in GSNOR and asthma. These data suggest that genetic variation in GSNOR might play a role in asthma susceptibility. CLINICAL IMPLICATIONS: The association of GSNOR polymorphisms with asthma suggests a potential therapeutic target. 相似文献
89.
Keri A. Streby Marguerite T. Parisi Barry L. Shulkin Brian LaBarre Rochelle Bagatell Lisa Diller Stephan A. Grupp Katherine K. Matthay Stephan D. Voss Alice L. Yu Wendy B. London Julie R. Park Gregory A. Yanik Arlene Naranjo 《Pediatric blood & cancer》2023,70(8):e30418
Background
Diagnostic mIBG (meta-iodobenzylguanidine) scans are an integral component of response assessment in children with high-risk neuroblastoma. The role of end-of-induction (EOI) Curie scores (CS) was previously described in patients undergoing a single course of high-dose chemotherapy (HDC) and autologous hematopoietic cell transplant (AHCT) as consolidation therapy.Objective
We now examine the prognostic significance of CS in patients randomized to tandem HDC and AHCT on the Children's Oncology Group (COG) trial ANBL0532.Study design
A retrospective analysis of mIBG scans obtained from patients enrolled in COG ANBL0532 was performed. Evaluable patients had mIBG-avid, International Neuroblastoma Staging System (INSS) stage 4 disease, did not progress during induction therapy, consented to consolidation randomization, and received either single or tandem HDC (n = 80). Optimal CS cut points maximized the outcome difference (≤CS vs. >CS cut-off) according to the Youden index.Results
For recipients of tandem HDC, the optimal cut point at diagnosis was CS = 12, with superior event-free survival (EFS) from study enrollment for patients with CS ≤ 12 (3-year EFS 74.2% ± 7.9%) versus CS > 12 (59.2% ± 7.1%) (p = .002). At EOI, the optimal cut point was CS = 0, with superior EOI EFS for patients with CS = 0 (72.9% ± 6.4%) versus CS > 0 (46.5% ± 9.1%) (p = .002).Conclusion
In the setting of tandem transplantation for children with high-risk neuroblastoma, CS at diagnosis and EOI may identify a more favorable patient group. Patients treated with tandem HDC who exhibited a CS ≤ 12 at diagnosis or CS = 0 at EOI had superior EFS compared to those with CS above these cut points. 相似文献90.