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| 1 | Arrhythmogenic mechanisms in ryanodine receptor channelopathies显示文摘Ryanodine receptors(Ry Rs) are the calcium release channels of sarcoplasmic reticulum(SR) that provide the majority of calcium ions(Ca2+) necessary to induce contraction of cardiac and skeletal muscle cells.In their intracellular environment,Ry R channels are regulated by a variety of cytosolic and luminal factors so that their output signal(Ca2+) induces finely-graded cell contraction without igniting cellular processes that may lead to aberrant electrical activity(ventricular arrhythmias) or cellular remodeling.The importance of Ry R dysfunction has been recently highlighted with the demonstration that point mutations in RYR2,the gene encoding for the cardiac isoform of the Ry R(Ry R2),are associated with catecholaminergic polymorphic ventricular tachycardia(CPVT),an arrhythmogenic syndrome characterized by the development of adrenergically-mediated ventricular tachycardia in individuals with an apparently normal heart.Here we summarize the state of the field in regards to the main arrhythmogenic mechanisms triggered by Ry R2 channels harboring mutations linked to CPVT.Most CPVT mutations characterized to date endow Ry R2 channels with a gain of function,resulting in hyperactive channels that release Ca2+ spontaneously,especially during diastole.The spontaneous Ca2+ release is extruded by the electrogenic Na+/Ca2+ exchanger,which depolarizes the external membrane(delayed afterdepolarization or DAD) and may trigger untimely action potentials.However,a rare set of CPVT mutations yield Ry R2 channels that are intrinsically hypo-active and hypo-responsive to stimuli,and it is unclear whether these channels release Ca2+ spontaneously during diastole.We discuss novel cellular mechanisms that appear more suitable to explain ventricular arrhythmias due to Ry R2 loss-of-function mutations. | ZHAO Yan-Ting VALDIVIA Carmen R. GURROLA Georgina B. HERNNDEZ Jonathan J. VALDIVIA Héctor H. | 2015 | Science China(Life Sciences)2015，58，1： | 14 |
| 2 | Recombinant streptokinase vs hydrocortisone suppositories in acute hemorrhoids:A randomized controlled trial显示文摘AIM: To compare the efficacy and safety of recombinant streptokinase(rSK) vs hydrocortisone acetate-based suppositories in acute hemorrhoidal disease.METHODS: A multicenter(11 sites), randomized(1:1:1), open, controlled trial with parallel groups was performed. All participating patients gave their written,informed consent. After inclusion, patients with acute symptoms of hemorrhoids were centrally randomized to receive, as outpatients, by the rectal route, suppositories of rSK 200000 IU of one unit every 8 h(first 3 units)and afterwards every 12 h until 8 administrations were completed(schedule A), one unit every 8 h until 6 units were completed(schedule B), or 25 mg hydrocortisone acetate once every 8 h up to a maximum of 24 administrations. Evaluations were performed at 3, 5,and 10 d post-inclusion. The main end-point was the 5thday response(disappearance of pain and bleeding, and≥ 70% reduction of the lesion size). Time to response and need for thrombectomy were secondary efficacy variables. Adverse events were also evaluated.RESULTS: Groups were homogeneous with regards to demographic and baseline characteristics. Fifth day complete response rates were 156/170(91.8%; 95%CI:87.3-96.2), 155/170(91.2%; 95%CI: 86.6%-95.7%),and 46/170(27.1%; 95%CI: 20.1%-34.0%) with rSK(schedule A and B) and hydrocortisone acetate suppositories, respectively. These 64.6% and 63.9%differences(95%CI: 56.7%-72.2% and 55.7%-72.0%)were highly significant(P < 0.001). This advantage was detected since the early 3rd day evaluation(68.8% and64.1% vs 7.1% for the rSK and active control groups,respectively; P < 0.001) and was maintained even at the late 10 th day assessment(97.1% and 93.5% vs67.1% for rSK and hydrocortisone acetate, respectively;P < 0.001). Time to response was 3 d(95%CI: 2.9-3.1)for both rSK groups and 10 d(95%CI: 9.3-10.7) in the hydrocortisone acetate group. This difference was highly significant(P < 0.001). All subgroup stratified analyses(with or without thrombosis and hemorrhoid classification) showed a statistically significant advantage for the rSK groups. Thrombectomy was necessary in4/251 and 14/133 patients with baseline thrombosis in the rSK and hydrocortisone acetate groups, respectively(P < 0.001). There were no adverse events attributable to the experimental treatment.CONCLUSION: rSK suppositories showed a significant advantage over a widely-used over-the-counter hydrocortisone acetate preparation for the treatment of acute hemorrhoidal illness, as well as having an adequate safety profile. | Francisco Hernández-Bernal Georgina Castellanos-Sierra Carmen M Valenzuela-Silva Karem M Catasús-Alvarez Osmany Martínez-Serrano Odalys C Lazo-Diago Cimara H Bermúdez-Badell José R Causa-García Juan E Domínguez-Suárez Pedro A López-Saura 无 | 2015 | World Journal of Gastroenterology2015，21，23： | 2 |
| 3 | Apoptosis inhibition plays a greater role than necrosis inhibition in decreasing bacterial transloca- tion in experimental intestinal transplantation 显示文摘 | Daniel A Anna S Georgina H | 2005 | Surgery2005，137，1： | 1 |
| 4 | Corrall,Revisiting the subject librarian:a study of English,Law and Chemistry 显示文摘 | Georgina H | 2007 | Joumal of Librarianship and Information Science2007，，2： | 1 |
| 5 | Water-harvesting beetle显示文摘 | ANDREW R P GEORGINA H | 2002 | Nature Australia2002，27，： | 1 |
| 6 | Inhibition effects of nitrogen compounds on the hydrodesulfurization of dibenzothiophen显示文摘 | Laredo Georgina C Antonio De los Reyes H J Luis Cano D J | 2001 | Applied Catalysis A: General2001，207，1： | 1 |
| 7 | Pre-diagnosis body mass index, post-diagnosis weight change, and prognosis among women with early stage breast cancer 显示文摘 | Bette J C Marilyn L K Georgina H | 2008 | Cancer Causes Control2008，19，10： | 1 |
| 8 | New synchronization method for Plasmodium falciparum显示文摘 | Lisa RC Abhinav S Georgina H | 2010 | Malaria J2010，9，： | 1 |
| 9 | Assessment of microbial diversity in human colonic samp les by 16S rDNA sequence analysis显示文摘 | GEORGINA H PRYDE S E RUSSELL V J | 2002 | FEMS Microbiol Ecol2002，39，： | 1 |
| 10 | Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial显示文摘 | Gerald S Falchook Georgina V Long Razelle Kurzrock Kevin B Kim Tobias H Arkenau Michael P Brown Omid Hamid Jeffrey R Infante Michael Millward Anna C Pavlick Steven J O’Day Samuel C Blackman C Martin Curtis Peter Lebowitz Bo Ma Daniele Ouellet Richard F Ke | 2012 | The Lancet . 2012 (9829)2012，，9829： | 1 |
| 11 | A 3D motion analysis study comparing the effectiveness of cervical spine orthoses at restricting spinal motion through physiological ranges显示文摘 | Nicholas R E Georgina H Rachel E | 2013 | Eur Spine J2013，22，1： | 1 |
| 12 | Automatic recognition of quarantine citrus diseases显示文摘 | GEORGINA S DIEGO H M SERGIO G | 2013 | Expert Systems with Applications2013，40，9： | 1 |
| 13 | Assessment of microbial diversity in human colonic samples by 16S rDNAsequence analysis显示文摘 | GEORGINA H PRYDE S E RUSSELL V J | 2002 | FEMS Microbiol Ecol2002，39，： | 1 |
| 14 | Inhibition effects of nitrogen compounds on the hydrodesulfurization of dibenzothiophen 显示文摘 | Laredo Georgina C Antonio De los Reyes H J Luis Cano D J | 2001 | Applied Catalysis A: General2001，207，1： | 1 |
| 15 | Inhibition effects of nitrogen compounds on the hydrodesulfurization of dibenzothiophene显示文摘 | GEORGINA C LAREDO S ANTONIO DE LOS REYES H J J LUIS CANO D | 2001 | Appl Catal A:Gen2001，207，： | 1 |
| 16 | The microbiology of butyrate formation in the human colon显示文摘 | Susan E Pryde Sylvia H Duncan Georgina L Hold Colin S Stewart Harry J Flint | 2002 | FEMS Microbiology Letters2002，，2： | 1 |
| 17 | Inhibition effects of nitrogen compounds on the hydrodesulfurization of dibenzothiophene 显示文摘 | GEORGINA C L S ANTONIO J R H LUIS J C D | 2001 | Applied Catalysis A2001，207，12： | 1 |
| 18 | Prediagnosis body mass index,postdiagnosis weight change,and prognosis among women with early stage breast cancer显示文摘 | Bette JC Marilyn LK Georgina H | | 0，，10： | 1 |
| 19 | Prospective application of a bleeding and ischemic risks-adjusted antithrombotic protocol in elderly patients revascularized with everolimus-eluting stents:EPIC05-Sierra75 study显示文摘OBJECTIVES Elderly patients show a higher incidence of ischemic and bleeding events after percutaneous transluminal coron-ary intervention(PCI).We sought to investigate outcomes in elderly patients treated with antithrombotic strategy guided by bleeding and ischemic risks after revascularization with last generation everolimus-eluting stent(EES).METHODS Prospective multicenter registry including patients over 75 years revascularized with EES and antithrombotic ther-apy guided by clinical presentation,PCI complexity and PRECISE DAPT score.Co-primary safety endpoints were:(1)composite of cardiac death,myocardial infarction and stent thrombosis and;(2)bleeding(BARC 2-5).Primary efficacy endpoint was target lesion revascularization.A matched group of patients revascularized with current drug-eluting stents and no such tailored antith-rombotic therapy was used as control.RESULTS Finally,1064 patients were included in SIERRA-75 cohort,80.8±4.2 years,36.6%women,71%acute coronary syn-dromes(ACS)and 53.6%complex PCI.Co-primary safety endpoint of major adverse cardiovascular events was met in 6.2%,co-primary safety endpoint of bleeding in 7.8%and primary efficacy endpoint of TKLR in 1.5%.The multivariable adjusted model showed no significant association of the prescribed short/long dual antiplatelet therapy(DAPT)durations with any endpoint suggesting a well tailored therapy.No stent thrombosis reported in the subgroup with 1-3 months DAPT duration.As compared to control group,bleeding BARC 2-5 was significantly lower in SIERRA-75 group(7.4%vs.10.2%,P=0.04)as well as the net safety-efficacy endpoint(14.3%vs.18.5%,P=0.02).CONCLUSIONS In elderly population,the application of this risks-adjusted antithrombotic protocol after revascularization with last generation EES seems to be associated with an improved prognosis in terms of ischemic and bleeding outcomes. | Jose M de la Torre Hernandez Ramon Lopez Palop Jesus M Jimenez Mazuecos Pilar Carrillo Sáez Alejandro Gutierez-Barrios Eduardo Pinar Belen Cid Luis Fernandez Tamara Garcia Camarero Cristóbal Urbano-Carrillo Juan F Oteo Dominguez Victor A Jimenez Diaz Antonio EGomez Menchero Eladio Galindo Fernández Juan GCórdoba Soriano Raymundo Ocaranza Eduardo ArroyoÚcar Koldobika Garcia San Roman Silvio Leal Ginés Martínez Cáceres Jose A Linares Vicente Georgina Fuertes Ferre Xavier Carrillo Juan CRama Merchán Catia Costa Juan Sanchis Renato Fernandes Alberto Rodrigues Jose M Vegas Valle Hélder Pereira Armando Perez de Prado | 2022 | Journal of Geriatric Cardiology2022，19，5： | 0 |
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