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61.
Konstantinos Toutouzas Georgios Benetos Vasilis Voudris Maria Drakopoulou Konstantinos Stathogiannis George Latsios Andreas Synetos Alexios Antonopoulos Elias Kosmas Ioannis Iakovou Georgios Katsimagklis Antonios Mastrokostopoulos Sotiris Moraitis Vicki Zeniou Haim Danenberg Manolis Vavuranakis Dimitris Tousoulis 《JACC: Cardiovascular Interventions》2019,12(8):767-777
Objectives
The aim of this study was to compare the implantation of a self-expanding valve with or without balloon aortic valvuloplasty (BAV) in an open-label, noninferiority, randomized trial.Background
There are no randomized studies comparing the implantation of a self-expanding valve with (pre-BAV) or without BAV.Methods
Consecutive patients with severe aortic stenosis were randomly assigned to undergo transcatheter aortic valve replacement with the use of self-expanding prostheses with (pre-BAV) or without (no-BAV) pre-dilatation. The primary endpoint was device success according to the Valve Academic Research Consortium 2 criteria. Secondary endpoints included periprocedural mortality and stroke, new permanent pacemaker implantation, vascular complications, and 1-year mortality. The trial was scheduled to show noninferiority (Δ = 15%) of the direct versus the pre-BAV approach.Results
A total of 171 patients were randomized at 4 centers. Of these, 86 underwent transcatheter aortic valve replacement with pre-dilatation and 85 without. Device success was noninferior in the no-BAV group compared with the pre-BAV group (65 of 85 [76.5%] for no-BAV vs. 64 of 86 [74.4%] for pre-BAV; mean difference 2.1%; 90% confidence interval: ?8.9% to 13%). In the no-BAV group, 25 patients (29.4%) underwent post-balloon dilatation, and in the pre-BAV group, 13 patients (15.1%) underwent post-balloon dilatation (p = 0.03). Regarding major vascular complications and permanent pacemaker implantation, there was no difference between the 2 groups (log-rank p = 0.49, log-rank p = 0.54). In 1-month completed follow-up for all patients, there was 1 periprocedural stroke (0.5%), without any deaths.Conclusions
Direct, without balloon pre-dilatation, transcatheter aortic valve replacement with a self-expanding prosthesis system is noninferior to the pre-dilatation procedure. Lower post-dilatation rates were encountered in the group with pre-dilatation. (The Predilatation in Transcatheter Aortic Valve Implantation Trial [DIRECT]; NCT02448927) 相似文献62.
Inhibition of concanavalin A-induced acute T cell dependent hepatic damage in mice by hypothyroidism
Haim Shirin Iris Dotan Moshe Papa Yoram Maaravi Husein Aeet Lillian Zaidel Zipora Matas Rafael Bruck Steven F Moss Zamir Halpern Ran Oren 《Liver international》1999,19(3):206-211
Abstract: Aims/Background: Concanavalin A (Con A) activates T lymphocytes and causes acute T-cell-mediated hepatic injury in mice. Decreased thyroid hormonal production is associated with a variety of immunological manifestations, including inactivation of macrophages with reduced TNF production and reduced soluble IL-2 receptors in the serum. We have recently shown that hypothyroidism prevents the development of cirrhosis and also minimizes hepatic damage in rats with fulminant hepatic failure. In the present study we examined the effects of hypothyroidism on a mouse model of Con A induced T cell-mediated acute hepatitis. Methods: Hypothyroidism was induced both medically (MMI, PTU) and surgically. Eight groups of 10 mice each were studied: euthyroid controls (2 groups: water, Con A) and hypothyroid (6 groups: MMI, PTU, Surgical, MMI-Con A, PTU-Con A, Surgical-Con A). Results: Hepatic inflammation was significantly decreased in each of the Con A treated hypothyroid groups of mice. The serum transaminases, TNF-α and IL-6 levels were significantly elevated in the Con A treated group while near normal levels were found in the hypothyroid Con A treated groups (mean±SE AST: 1499±18 vs 78±10 IU/1, p<0.001; TNF: 2500±250 vs 135± 15 pg/ml. p<0.001, IL-6: 12,200±300 vs 1260±140 pg/ml, p<0.001, respectively). Conclusions: Hypothyroidism, independent of the mode of induction, can effectively inhibit the development of acute T cell-mediated liver damage in mice. These results suggest that some decrease in thyroid function might have a role in the prevention of immune mediated liver diseases. 相似文献
63.
Pseudohypoaldosteronism type II: marked sensitivity to thiazides,hypercalciuria, normomagnesemia,and low bone mineral density 总被引:1,自引:0,他引:1
Mayan H Vered I Mouallem M Tzadok-Witkon M Pauzner R Farfel Z 《The Journal of clinical endocrinology and metabolism》2002,87(7):3248-3254
Mutations in WNK kinases cause pseudohypoaldosteronism type II (PHA II) and may represent a novel signaling pathway regulating blood pressure and K(+) and H(+) homeostasis. PHA II is an autosomal dominant disorder characterized by hypertension, hyperkalemia, and metabolic acidosis, with normal glomerular filtration rate. Thiazide diuretics correct all abnormalities. Inactivating mutations in the thiazide-sensitive NaCl cotransporter cause Gitelman syndrome, featuring hypotension, hypokalemia, and metabolic alkalosis plus hypocalciuria and hypomagnesemia. We investigated whether hypercalciuria and hypermagnesemia occurred in a large family with PHA II. Eight affected and eight unaffected members of a PHA II family with the Q565E WNK 4 mutation were studied. In affected members blood and urinary chemistry were measured on and off hydrochlorothiazide (HCTZ), and bone mineral density was determined. Marked sensitivity to HCTZ was found. A mean dose of 20 mg/d reduced mean blood pressure in the six hypertensive subjects by 54.3 (systolic) and 24.5 (diastolic) mm Hg. In affected subjects, HCTZ reduced mean serum K(+) by 1.12 mmol/liter, mean serum Cl(-) by 6.2 mmol/liter, and mean urinary calcium by 65% and elevated mean serum calcium by 0.11 mmol/liter and mean serum urate by 118 micromol/liter. Compared with the literature, this represents an increase of 6-7 in HCTZ potency. Affected members had normomagnesemia, hypercalciuria (336 +/- 113 vs. 155 +/- 39 mg/d in unaffected relatives, P = 0.0002), and decreased bone mineral density. In PHA II the observed marked sensitivity to thiazides and the hypercalciuria are consistent with increased NaCl cotransporter activity. PHA II may serve as a model to investigate thiazides' beneficial effects and side effects. 相似文献
64.
Yuval Ronen Yonatan Cohen Jung-Hyun Kang Arbel Haim Maria-Theresa Rieder Moty Heiblum Diana Mahalu Hadas Shtrikman 《Proceedings of the National Academy of Sciences of the United States of America》2016,113(7):1743-1748
Nonlinear charge transport in superconductor–insulator–superconductor (SIS) Josephson junctions has a unique signature in the shuttled charge quantum between the two superconductors. In the zero-bias limit Cooper pairs, each with twice the electron charge, carry the Josephson current. An applied bias VSD leads to multiple Andreev reflections (MAR), which in the limit of weak tunneling probability should lead to integer multiples of the electron charge ne traversing the junction, with n integer larger than 2Δ/eVSD and Δ the superconducting order parameter. Exceptionally, just above the gap eVSD ≥ 2Δ, with Andreev reflections suppressed, one would expect the current to be carried by partitioned quasiparticles, each with energy-dependent charge, being a superposition of an electron and a hole. Using shot-noise measurements in an SIS junction induced in an InAs nanowire (with noise proportional to the partitioned charge), we first observed quantization of the partitioned charge q = e*/e = n, with n = 1–4, thus reaffirming the validity of our charge interpretation. Concentrating next on the bias region eVSD ~ 2Δ, we found a reproducible and clear dip in the extracted charge to q? ~ 0.6, which, after excluding other possibilities, we attribute to the partitioned quasiparticle charge. Such dip is supported by numerical simulations of our SIS structure.Excitations in superconductors (Bogoliubov quasiparticles) can be described according to the Bardeen–Cooper–Schrieffer (BCS) theory (1) as an energy-dependent superposition of an electron with amplitude u(ε), and a hole with amplitude v(ε), where the energy ε is measured relative to the Fermi energy (2). Evidently, the expectation value of the charge operator (applied to the quasiparticle wave function), which we address as the quasiparticle charge e* = q(ε)e, is smaller than the charge of an electron, q(ε) = |u(ε)|2 ? |ν(ε)|2 (3). Solving the Bogoliubov–de Gennes equations, one finds that and , with the expected charge evolving with energy according to ––vanishing altogether at the superconductor gap edges (3). Note, however, that the quasiparticle wave function is not an eigenfunction of the charge operator (3, 4). Properties of quasiparticles, such as the excitation spectra (5), lifetime (6–10), trapping (11), and capturing by Andreev bound states (12, 13), had already been studied extensively; however, studies of their charge are lagging. In the following we present sensitive shot-noise measurements in a Josephson junction, resulting in a clear observation of the quasiparticle charge being smaller than e, q(eVSD∼2Δ) < 1, and evolving with energy, as expected from the BCS theory.To observe the BCS quasiparticles in transport we study a superconductor–insulator–superconductor (SIS) Josephson junction in the nonlinear regime. The overlap between the wave functions of the quasiparticles in the source and in the drain is expected to result in a tunneling current of their effective charge. This is in contrast with systems which are incoherent (14, 15) or with an isolated superconducting island, where charge conservation leads to traversal of multiples of e – Coulomb charge (16). As current transport in the nonlinear regime results from “multiple Andreev reflections” (MAR), it is prudent to make our measurements credible by first measuring the charge in this familiar regime.In short, the MAR process, described schematically in Fig. 1, carries a signature of the shuttled charge between the two superconductors (SCs), being a consequence of n traversals through the junction (as electron-like and hole-like quasiparticles), with n an integer larger than 2Δ/eVSD. A low transmission probability t (via tunneling through a barrier) in the bias range 2Δ/n < eVSD < 2Δ/(n ? 1) assures dominance of the lowest order MAR process (higher orders are suppressed as tn), with the charge evolving in nearly integer multiples of the electron charge. Although there is already a substantial body of theoretical (3, 17–23) and experimental (24–29) studies of the MAR process, charge determination without adjustable parameters is still missing. An important work by Cron et al. (27) indeed showed a staircase-like behavior of the charge using “metallic break junctions;” however, limited sensitivity and the presence of numerous conductance channels some of which with relatively high transmission probabilities did not allow exact charge quantization. Our shot-noise measurements, performed on a quasi-1D Josephson junction (single-mode nanowire) allowed clear observation of charge quantization without adjustable parameters. To count a few advantages: (i) the transmission of the SIS junction could be accurately controlled using a back-gate; (ii) this, along with our high sensitivity in noise measurements, enabled us to pinch the junction strongly (thus suppressing higher MAR orders); and (iii) with the Fermi level located near the 1D channel van Hove singularity, a rather monoenergetic distribution could be injected (SI Appendix, section S7).Open in a separate windowFig. 1.MAR. Illustrations of the leading processes contributing to the current as function of bias. In general, for 2Δ/(n ? 1) > eVSD > 2Δ/n the leading charge contribution to the current is ne. An electron-like quasiparticle is denoted by a full circle, whereas a hole-like quasiparticle is denoted by an empty circle. (A) When the bias is larger than the energy gap, eVSD > 2Δ, the leading process is a single-path tunneling of single quasiparticles from the full states (Left) to the empty states (Right). This current is proportional to the transmission coefficient t. Higher-order MAR process (dashed box), being responsible for tunneling of Cooper pairs, is suppressed as t2. (B) For 2Δ > eVSD > Δ, the main charge contributing to the current is 2e with probability t2. (C) For Δ > eVSD > 2Δ/3, the main charge contributing to the current is 3e with probability t3. 相似文献
65.
Lior Hassan Tal Pecht Nir Goldstein Yulia Haim Itai Kloog Shaked Yarza 《Journal of toxicology and environmental health. Part A》2019,82(9):564-576
ABSTRACTThe effects of particulate matter (PM) air pollution on adipose tissue have mainly been studied in animal models. The aim of this study was to examine the potential associations between PM exposure and 25 cellular markers in human omental (OM) and subcutaneous (SC) adipose tissue. The PM exposure assessments for both PM2.5 (PM <2.5 μm in diameter) and PM10 (<10 μm) were based upon a novel hybrid satellite-based spatio-temporally resolved model. We calculated the PM exposure above the background threshold for 1 week (acute phase), 3 and 6 months (intermediate phase), and 1 year (chronic phase) prior to tissue harvesting and tested the associations with adipose cell metabolic effects using multiple linear regressions and heat maps strategy. Chemokine levels were found to increase after acute and intermediate exposure duration to PM10. The levels of stress signaling biomarkers in the SC and OM tissues rose after acute exposure to PM10 and PM2.5. Macrophage and leucocyte counts were associated with severity of PM exposure in all three duration groups. Adipocyte diameter decreased in all exposure periods. Our results provide evidence for significant contribution of air pollutants exposure to adipose tissue inflammation as well as for pathophysiological mechanisms of metabolic dysregulation that may be involved in the observed responses. 相似文献
66.
Jair Bar Arnold Cyjon Dov Flex Hadas Sorotsky Haim Biran Julia Dudnik Nili Peylan-Ramu Nir Peled Hovav Nechushtan Maya Gips Rivka Katsnelson Shoshana Keren Rosenberg Ofer Merimsky Amir Onn Maya Gottfried 《Lung》2014,192(5):759-763
Purpose
Testing tumor samples for the presence of a mutation in the epithelial growth factor receptor (EGFR) gene is recommended for advanced non-squamous non-small cell lung cancer (NSCLC) patients. We aimed to collect data about common practice among Medical Oncologists treating lung cancer patients, regarding EGFR mutation testing in advanced NSCLC patients.Methods
An internet-based survey was conducted among members of the Israeli Society for Clinical Oncology and Radiotherapy involved in the treatment of lung cancer patients.Results
24 Oncologists participated in the survey. The participants encompass the Oncologists treating most of the lung cancer patients in Israel. 79 % of them use EGFR testing routinely for all advanced NSCLC patients. Opinions were split regarding the preferable biopsy site for EGFR testing material. 60 % of participants recommend waiting for EGFR test results prior to initiation of first-line therapy.Conclusions
EGFR testing is requested in Israel routinely by most treating Oncologists for all advanced NSCLC patients, regardless of histology. In most cases, systemic treatment is deferred until the results of this test are received. 相似文献67.
Shaye Kivity Yaron Zafrir Ronen Loebstein Rachel Pauzner Meir Mouallem Haim Mayan 《Autoimmunity reviews》2014,13(11):1109-1113
Objective
Low dose (10–25 mg/week) methotrexate is widely used for the management of systemic inflammatory diseases, and is considered to be relatively safe. Toxicity due to low dose MTX has been reported but is poorly characterized. We describe the clinical features, risk factors, and outcomes of low dose MTX toxicity in a large case series at our center.Patients and methods
We conducted a retrospective case series of all adult (> 18 years) patients hospitalized at Sheba Medical Center, between 2005 and 2012 for low dose MTX toxicity.Results
We identified 28 patients (age: 70.4 ± 13.7 years, range: 33–88; 20 (71%) females) hospitalized for low dose MTX toxicity. Indications for MTX therapy included: rheumatoid arthritis (39.2%), psoriasis ± arthritis (21.5%), polymyalgia rheumatica (10.8%) and other inflammatory conditions (28.5%). Pancytopenia was the most common manifestation of low dose MTX toxicity detected in 78.5% of the patients. Potential risk factors included acute renal failure, hypoalbuminemia, concurrent use of drugs known to interact with MTX, and dose errors. Serum MTX concentrations (n = 20, mean 0.04 ± 0.07 μg/mL range: 0–0.3) did not correlate with the degree of either neutropenia (r = − 0.36; p = 0.18) or thrombocytopenia (r = 0.44; p = 0.10). Seven (25%) patients died, all from pancytopenia followed by sepsis. Serum MTX concentrations did not differ between the patients who died from MTX toxicity (n = 6; mean: 0.05 ± 0.04 μg/mL) and those who survived the toxicity (n = 14 mean 0.04 ± 0.08; p = 0.45).Conclusions
Low-dose MTX toxicity can be life threatening, mainly due to myelosuppression. There is no rationale for MTX therapeutic drug monitoring in the setting of low-dose toxicity. 相似文献68.
69.
70.
Gafner Michal Borovich Adi Gimpel Ariel Peled Yoav Meshulam Moshe Krissi Haim 《Archives of gynecology and obstetrics》2020,301(5):1207-1212
Archives of Gynecology and Obstetrics - To characterize the population of women who underwent mid-trimester preterm premature rupture of membrane (PPROM) in a country where mid-trimester abortions... 相似文献