冠脉搭桥术后再发急性心肌梗死冠脉造影特点和再血管化治疗

【】目的：评估冠脉搭桥术后再发急性心肌梗死冠脉造影特点和成功再血管化对预后的影响。方法：回顾性分析自2006年01月到2016年01月136例行冠脉搭桥术后再发急性心肌梗死患者(包括STEMI 和 NSTEMI)冠脉造影特点、临床表现、心电图和心脏彩超特征。结果：91.7%的STEMI患者和57.1%的NSTEMI患者罪犯血管是桥血管(P=0.001),其中,静脉桥血管是罪犯血管的比例超过动脉桥血管(210根静脉桥中82根 vs 165根动脉桥中4根。P＜0.001)。自身冠脉成功行PCI100%,桥血管成功行PCI 86.1% (P=0.002)。院内死亡率8.1%,其中STEMI患者死亡率16.7%,NSTEMI患者死亡率6.3%(p=0.104)。PCI成功患者死亡率3.3%,PCI失败患者死亡率70% (P＜0.001)。结论：冠脉搭桥术后再发急性心肌梗死患者,罪犯血管更可能是静脉桥血管,自身冠脉行PCI的成功率更高,成功行PCI能显著降低死亡率。     

血管活性药物治疗肝肾综合征

肝肾综合征(hepatorenal syndrome)是肝硬化后期的常见并发症,也可见于其他严重的肝脏疾病,如急性肝功能衰竭、酒精性肝炎等.肾功能减退为肝肾综合征的主要临床表现之一.临床上将肝肾综合征分为Ⅰ型肝肾综合征和Ⅱ型肝肾综合征两种类型.Ⅰ型肝肾综合征系指患者的血清肌酐水平在2周内升高至221μmol/L(2.5 mg/dL)以上,肾小球滤过率通常低于20 ml/min,进行性少尿,临床表现为严重的肾功能衰竭;而Ⅱ型肝肾综合征主要表现为顽固性腹水,经一段时期后病情可突然恶化,达到Ⅰ型标准.     

消化道大出血的急诊血管造影与介入治疗

目的:探讨消化道大出血的急诊血管造影与介入治疗的临床价值。方法:收集29 例消化道大出血患者,采用Seldinger技术经股动脉穿刺插管行选择性血管造影,根据出血病因及出血部位分别行出血动脉的栓塞或缩血管药物局部灌注治疗,对不能明确出血病因及出血部位者行试验性栓塞和/或灌注治疗。结果:本组血管造影有阳性发现21 例,主要表现为肿瘤性病变5 例、血管性病变5例、造影剂外溢和滞留11例。栓塞治疗18例,即刻止血率94.4%(17/18);灌注缩血管药物6例,即刻止血4 例;试验性栓塞和/或灌注治疗5 例,即刻止血2 例。结论:消化道大出血在急诊血管造影的基础上行选择性出血动脉栓塞或缩血管药物灌注治疗是安全有效的止血措施,血管造影对出血病因及出血部位的检出具有重要意义。     

冠脉支架临床及血管造影十年随访

1964年 ,Dotter和 Judkins介绍了管腔扩张后 ,在动脉段内植入管状金属构件以保持血管通畅的概念 ,直到 1986年才应用于人类。虽然长期随访研究表明 6个月冠脉造影可作为评价球囊扩张血管成形术结果的有效终点 ,但支架植入后再狭窄的时间过程是否相似未被确定。虽然 5中心造影随访患者 6个月评价 Wall-stent支架的结果已经报告 ,但未继续实施造影随访来评价在此之后支架内管腔再狭窄是否已然停止。为评价连续暴露于金属表面和承受与支架有关的压力创伤( Barotrauma)是否持续刺激新生内膜的增生 ,作者报告植入 Wallstent支架 ,6个月未发生亚…     

介入治疗及药物治疗对ACS患者预后的影响

为比较介入治疗及药物治疗对急性冠脉综合征(ACS)患者预后的影响,我们对近年来收治的113例ACS患者进行了分组观察。现报告如下。     

急性下壁心肌梗死心电图与冠脉造影对照分析

1资料与方法 1.1临床资料1995年4月-2003年8月收入我院的急性下壁心肌梗死(AIMI)病人,行冠脉造影者68例,其中男55例,女13例,年龄40岁～75岁,平均年龄55.7岁,均在入院后4周内行冠脉造影.单支病变41例(60.3%),其中右冠脉(RCA)病变26例(63.4%),左旋支(LCX)病变15例(36.6%);多支病变27例(39.7%).合并右心室梗死者8例(11.8%).以右冠脉病变单支病变或合并左旋支病变、左前降支病变77.9%,单独左旋支病变22.1%.     

急性冠脉综合征的冠脉造影评价

目的 观察急性冠脉综合征（ACS）冠脉血管病变的特点。方法 对36例ACS病人进行了冠状动脉造影，并对其冠状动脉复杂病变及血栓存在的情况进行了研究。结果 ACS多发性于冠脉血管的复杂病变，且与血栓形成密切相关。结论 冠脉血管病变复杂较易发生ACS，且粥样斑块的破裂及血栓形成在ACS的形成过程中起着重要作用，从而为选择有效方法冠脉综合征提供客观依据。     

急性脑动脉闭塞的血管造影分级及溶栓治疗疗效评估系统

重组组织型纤溶酶原激活剂（rt-PA）静脉内溶栓治疗已成为公认的治疗急性缺血性卒中的有效方法，但该治疗方法仅限于发病3h以内的患者，且有较高的颅内出血发生率，治疗时间窗很窄，因此，其临床应用受到很大限制，只有一小部分患者能得到及时治疗。而现代医学影像技术指导下的动脉溶栓治疗，能够确定是否存在可逆性缺血脑组织，使溶栓治疗适应证选择更科学，显著延长溶栓治疗的时间窗，提高血管再通率和改善神经功能预后。研究表明，急性期全脑血管造影（DSA）所反映的脑血管闭塞的部位、程度、侧支循环、血管再通和血流灌注情况等诸多因素均与预后密切相关。因此，对急性脑缺血患者全面、客观的血管造影分级对介入治疗适应证选择、预测血管再通率及临床疗效具有重要作用。现就目前常用的急性缺血性卒中DSA分级标准进行综述如下。     

TAMI心肌梗死的溶栓治疗和血管成形术

标　　题　急性心肌梗死患者静脉组织纤溶酶原激活剂后行即刻延迟选择性血管成形术的随机试验。作　　者　ＴｏｐｏｌＥＪ ,ＣａｌｉｆｆＲＭ ,ＧｅｏｒｇｅＢＳ ,ｅｔａｌ　　参考文献　ＮＥｎｇｌＪＭｅｄ ,1987,3 71:5 81～ 5 88　　疾　　病　急性心肌梗死。目　　的　为了比较急性心肌梗死患者经组织型纤溶酶原激活剂静脉溶栓进行即刻或延迟 (7～ 10ｄ)冠状动脉成形术的疗效。设　　计　随机 ,公开 ,多中心。病　　例　 3 86例 ,年龄≤ 75岁 ,出现急性心肌梗死症状 <4ｈ(如果存在严重进行性胸痛则 <6ｈ) ,2个导联ＳＴ段抬高≥ 1ｍｍ。…     

多发大动脉炎的血管造影87例特点分析

目的:探讨多发性大动脉炎的血管造影影像表现特点,评价血管造影对受累动脉管腔狭窄程度及病情的判断。方法:回顾性分析我院2003年6月至2011年6月,87例临床诊断多发大动脉炎入院患者。临床表现不是十分典型,入院进行常规血管造影检查,进行分析。结果:血管造影证实的大动脉炎患者的血管影像资料,均是多部位血管累及,累及主动脉及其主要分支,临床以头臂型最为多见。此组病例病变累及锁骨下动脉病变38根;颈总动脉28根;腹主动脉14根;肾动脉16根,多血管同时累及多见。结论:多发大动脉炎综合征血管造影以多部位血管受累多见,以狭窄阻塞型常见,常是多血管同时受累。冠状动脉也可以同时受累。     

Structures of a Na+-coupled,substrate-bound MATE multidrug transporter

Multidrug transporters belonging to the multidrug and toxic compound extrusion (MATE) family expel dissimilar lipophilic and cationic drugs across cell membranes by dissipating a preexisting Na⁺ or H⁺ gradient. Despite its clinical relevance, the transport mechanism of MATE proteins remains poorly understood, largely owing to a lack of structural information on the substrate-bound transporter. Here we report crystal structures of a Na⁺-coupled MATE transporter NorM from Neisseria gonorrheae in complexes with three distinct translocation substrates (ethidium, rhodamine 6G, and tetraphenylphosphonium), as well as Cs⁺ (a Na⁺ congener), all captured in extracellular-facing and drug-bound states. The structures revealed a multidrug-binding cavity festooned with four negatively charged amino acids and surprisingly limited hydrophobic moieties, in stark contrast to the general belief that aromatic amino acids play a prominent role in multidrug recognition. Furthermore, we discovered an uncommon cation–π interaction in the Na⁺-binding site located outside the drug-binding cavity and validated the biological relevance of both the substrate- and cation-binding sites by conducting drug resistance and transport assays. Additionally, we uncovered potential rearrangement of at least two transmembrane helices upon Na⁺-induced drug export. Based on our structural and functional analyses, we suggest that Na⁺ triggers multidrug extrusion by inducing protein conformational changes rather than by directly competing for the substrate-binding amino acids. This scenario is distinct from the canonical antiport mechanism, in which both substrate and counterion compete for a shared binding site in the transporter. Collectively, our findings provide an important step toward a detailed and mechanistic understanding of multidrug transport.     

MATE1的功能及其对二甲双胍代谢的影响

二甲双胍是2型糖尿病患者最常用的口服药物之一,疗效因人而异,其代谢与多种转运蛋白相关.多药物和毒素排出转运蛋白1 (MATE1)是最近研究的热点,其在二甲双胍排泄入胆汁和尿液的最后一步中起关键作用,其基因多态性是二甲双胍代谢和疗效差异的重要因素.     

Aluminum tolerance in maize is associated with higher MATE1 gene copy number

Genome structure variation, including copy number variation and presence/absence variation, comprises a large extent of maize genetic diversity; however, its effect on phenotypes remains largely unexplored. Here, we describe how copy number variation underlies a rare allele that contributes to maize aluminum (Al) tolerance. Al toxicity is the primary limitation for crop production on acid soils, which make up 50% of the world’s potentially arable lands. In a recombinant inbred line mapping population, copy number variation of the Al tolerance gene multidrug and toxic compound extrusion 1 (MATE1) is the basis for the quantitative trait locus of largest effect on phenotypic variation. This expansion in MATE1 copy number is associated with higher MATE1 expression, which in turn results in superior Al tolerance. The three MATE1 copies are identical and are part of a tandem triplication. Only three maize inbred lines carrying the three-copy allele were identified from maize and teosinte diversity panels, indicating that copy number variation for MATE1 is a rare, and quite likely recent, event. These maize lines with higher MATE1 copy number are also Al-tolerant, have high MATE1 expression, and originate from regions of highly acidic soils. Our findings show a role for copy number variation in the adaptation of maize to acidic soils in the tropics and suggest that genome structural changes may be a rapid evolutionary response to new environments.     

A time-to-treatment analysis in the medicine versus angiography in thrombolytic exclusion (MATE) trial

Patients with acute coronary syndromes who are considered ineligible for thrombolytic therapy are at high risk of recurrent ischemia and death. This trial randomized 201 patients to triage angiography in the first 24 hours of hospital admission versus conventional medical care. Of the 165 patients who underwent angiography that was either protocol-driven or on the basis of physician preference, those who underwent angiography within 6 hours of symptom onset had a reduction in early and late adverse events. The rates of in-hospital recurrent ischemia were 15.4%, 15.4%, 17.5%, 32.4%, and 38.5%, respectively (P = 0.01 for trend), and rates of cumulative recurrent myocardial infarction or death were 0%, 12.8%, 10.0%, 11.8%, and 7.7%, respectively (P = 0.48 for trend) for patients who underwent angiography at 0-6, 6-12, 12-24, 24-48, and over 48 hours, respectively from symptom onset. Future trials of invasive versus conservative therapy should focus on performing angiography within 6 hours of symptom onset.     

Vacuolar transport of nicotine is mediated by a multidrug and toxic compound extrusion (MATE) transporter in Nicotiana tabacum

Alkaloids play a key role in plant defense mechanisms against pathogens and herbivores, but the plants themselves need to cope with their toxicity as well. The major alkaloid of the Nicotiana species, nicotine, is translocated via xylem transport from the root tissues where it is biosynthesized to the accumulation sites, the vacuoles of leaves. To unravel the molecular mechanisms behind this membrane transport, we characterized one transporter, the tobacco (Nicotiana tabacum) jasmonate-inducible alkaloid transporter 1 (Nt-JAT1), whose expression was coregulated with that of nicotine biosynthetic genes in methyl jasmonate-treated tobacco cells. Nt-JAT1, belonging to the family of multidrug and toxic compound extrusion transporters, was expressed in roots, stems, and leaves, and localized in the tonoplast of leaf cells. When produced in yeast cells, Nt-JAT1 occurred mainly in the plasma membrane and showed nicotine efflux activity. Biochemical analysis with proteoliposomes reconstituted with purified Nt-JAT1 and bacterial F₀F₁-ATPase revealed that Nt-JAT1 functioned as a proton antiporter and recognized endogenous tobacco alkaloids, such as nicotine and anabasine, and other alkaloids, such as hyoscyamine and berberine, but not flavonoids. These findings strongly suggest that Nt-JAT1 plays an important role in the nicotine translocation by acting as a secondary transporter responsible for unloading of alkaloids in the aerial parts and deposition in the vacuoles.     

The structure of the Aquifex aeolicus MATE family multidrug resistance transporter and sequence comparisons suggest the existence of a new subfamily

Multidrug and toxic compound extrusion (MATE) transporters are widespread in all domains of life. Bacterial MATE transporters confer multidrug resistance by utilizing an electrochemical gradient of H⁺ or Na⁺ to export xenobiotics across the membrane. Despite the availability of X-ray structures of several MATE transporters, a detailed understanding of the transport mechanism has remained elusive. Here we report the crystal structure of a MATE transporter from Aquifex aeolicus at 2.0-Å resolution. In light of its phylogenetic placement outside of the diversity of hitherto-described MATE transporters and the lack of conserved acidic residues, this protein may represent a subfamily of prokaryotic MATE transporters, which was proven by phylogenetic analysis. Furthermore, the crystal structure and substrate docking results indicate that the substrate binding site is located in the N bundle. The importance of residues surrounding this binding site was demonstrated by structure-based site-directed mutagenesis. We suggest that Aq_128 is functionally similar but structurally diverse from DinF subfamily transporters. Our results provide structural insights into the MATE transporter, which further advances our global understanding of this important transporter family.

Living organisms have evolved a wide range of mechanisms to protect themselves against external environmental stress factors such as toxins and xenobiotics or internal metabolic waste products (1, 2). Multidrug resistance (MDR) transporters confer resistance against antibiotics and anticancer drugs to infectious pathogens and cancer cells (2–5), making them a central factor in two serious global health threats. Currently known MDR transporters belong to seven families (4): the adenosine triphosphate–binding cassette (ABC) superfamily, multidrug and toxic compound extrusion (MATE) family (6), major facilitator superfamily, resistance–nodulation–division superfamily, small MDR family, p-aminobenzoyl-glutamate transporter family (7), and the recently identified proteobacterial antimicrobial compound efflux family (8). Apart from primary-active ABC transporters, the other six families contain secondary-active transporters utilizing transmembrane electrochemical ion gradients to drive transport.MATE transporters can use either Na⁺ or H⁺ as coupling ions to drive the extrusion of various structurally diverse, usually polyaromatic and cationic compounds, which can diffuse into the cytosol across the cell membrane (9–15). Members of the MATE transporter family are widely distributed in all three domains of life. Human MATE transporters, which are highly expressed in kidney and liver, mediate the proton-dependent excretion of various cationic drugs into urine and bile (16–19), thereby decreasing the plasma concentrations of these drugs and thus lowering their therapeutic efficacies (20). On the other hand, they help to reduce drug-induced nephrotoxicity by affecting the pharmacokinetics of anticancer agents in platinum-based chemotherapy (5, 21). In plants, MATE transporters are involved in the secretion of a variety of secondary metabolites for detoxification or as a defense strategy against herbivores and pathogens (22, 23). Bacterial MATE transporters are primarily employed as xenobiotic efflux pumps, contributing to the MDR phenotype of important human pathogens (24, 25).The MATE family belongs to the multidrug/oligosaccharidyl-lipid/polysaccharide exporter superfamily (26). On the basis of amino acid sequence similarity, the MATE transporters have been previously classified into three major subfamilies: the NorM, DNA damage–inducible protein F (DinF), and eukaryotic MATE (eMATE) subfamilies (6, 25, 27). Bacterial and archaeal MATE transporters, subdivided into the NorM and DinF subfamilies, harness energy from transmembrane H⁺ and/or Na⁺ gradients, while eMATE transporters appear to be exclusively H⁺-coupled. Since the first crystal structure of a MATE transporter, that from Vibrio cholerae (NorM-VC), was determined (28), the structures of several MATE homologs including representatives from all three subfamilies have become available (9, 23, 29–33). All structures show the MATE transporters to be present in a monomeric state consisting of 12 transmembrane helices (TMs) with two 6-helix bundles (N and C bundles) arranged pseudosymmetrically. These bundles are linked by a large intracellular loop between TM6 and TM7. The drug- and cation-bound structures of a NorM transporter from Neisseria gonorrhoeae (NorM-NG) suggested that several conserved acidic residues in both N and C bundles are responsible for the allosteric regulation of uptake and efflux of substrates (9, 34). In contrast, atomic structures of the DinF transporter from Bacillus halodurans demonstrated the presence of only one competitive binding site in the N bundle and highlighted the importance of one highly conserved aspartate residue (D40^DinF-BH) for transport activity (29). In addition, a pH-dependent protonation/deprotonation of this aspartate residue was proposed to drive a bent–straight conformational change of TM1 in DinF transporters (30, 31), although this proposal still remains a matter of controversy (34, 35). Furthermore, a corresponding aspartate residue is absent in the N bundle of eMATE transporters. The crystal structure of AtDTX14, an eMATE transporter from Arabidopsis thaliana, revealed a direct competition between H⁺ and substrate that occurs in the C bundle (23). The crystal structure of the DinF subfamily transporter from Pyrococcus furiosus (PfMATE) in an inward-facing state was solved with bound native lipids (36), indicating a function as a lipid transporter. The transition between the two states is enabled by conformational flexibility and loose binding of TM1 and TM7 to their respective bundles.Here we purified and characterized the MATE transporter Aq_128 from the hyperthermophilic bacterium Aquifex aeolicus. Our phylogenetic analyses indicate that Aq_128 belongs to a previously unknown subfamily of the MATE transporter family, which also comprises transporters from ε-Proteobacteria and Archaea so far. The phylogenetic placement of Aq_128 outside the known diversity of MATE transporters is consistent with the fact that Aq_128 lacks the conserved acidic residues which are crucial for the transport activity of other MATE transporters. X-ray structural and functional analyses characterize Aq_128 as an Na⁺-dependent drug transporter, and our data show that the cation and substrate binding site are located in the N bundle. A detailed structural and functional comparison between Aq_128 and the MATE transporters from other subfamilies is presented.     

Measurements in the Addictions for Triage and Evaluation (MATE): an instrument based on the World Health Organization family of international classifications

Aims To present and evaluate a measurement tool for assessing characteristics of people with drug and/or alcohol problems for triage and evaluation in treatment. Measurements in the Addictions for Triage and Evaluation (MATE) is composed of 10 modules, selected on the basis of a detailed set of specifications. Conceptually, the MATE was constructed according to the ICD and International Classification of Functioning (ICF) in the World Health Organization (WHO) classification system. Two of the ICF‐related modules were newly designed. Design Monitoring feasibility and field‐testing in a treatment‐seeking population with researcher and clinician‐administered test–retest interviews, construct validation with related instruments and evaluation of the dimensional structure of the ICF‐related modules. Setting The research was conducted in a large, regional substance abuse treatment centre in the Netherlands and at the Municipal Health Service of Amsterdam. Participants A total of 945 treatment‐seeking patients were recruited during routine intakes, 159 of whom were interviewed twice; 32 problem drug users were also recruited from the Amsterdam cohort studies among problem drug users. Findings Completion time was reasonably short, and there were relatively few missing data. The factor structure of the ICF‐related modules revealed a three‐factor model with an acceptable fit. Inter‐rater reliability ranged between 0.75 and 0.92 and was satisfactory, but interviewer reliability ranged between 0.34 and 0.73, indicating that some of subscales need to be improved. Concurrent validity was indicated by significant correlations (>0.50) between the ICF‐related modules and the WHO Disability Assessment Schedule II (WHODAS II) and WHO Quality of Life brief version (WHOQOL‐BREF). Conclusions The MATE can be used to allocate patients to substance abuse treatment. Because it is a comprehensive but flexible measurement tool that is also practical to use, the MATE is well suited for use in a heterogeneous population.     

Inhibition of the multidrug and toxin extrusion (MATE) transporter by pyrimethamine increases the plasma concentration of metformin but does not increase antihyperglycaemic activity in humans

We hypothesized that the pharmacodynamic (PD) characteristics of metformin would change with inhibition of the multidrug and toxin extrusion (MATE) transporter, which mediates renal elimination of metformin. Twenty healthy male subjects received two doses (750/500 mg) of metformin, with and without 50 mg of pyrimethamine (a potent MATE inhibitor), with 1 week of washout in between each dose. The PD characteristics of metformin were assessed using oral glucose tolerance tests (OGTTs) before and after the metformin dose. Metformin concentrations in plasma and urine were determined using liquid chromatography‐electrospray ionization‐tandem mass spectrometry. When metformin was co‐administered with pyrimethamine, its area under the concentration–time curve from 0 to 12 h was 2.58‐fold greater (p < 0.05), whereas the antihyperglycaemic effects of metformin were decreased. The mean differences (90% confidence interval) in mean and maximum serum glucose concentrations and in 2‐h‐post‐OGTT serum glucose concentration were ?0.6 (?1, ?0.2), ?0.9 (?1.6, ?0.3) and ?0.5 (?1.1, 0.1) mmol/l, respectively. These findings indicate that the response to metformin is not only related to the plasma exposure of metformin but is also related to other factors, such as inhibition of uptake transporters and the gastrointestinal‐based pharmacology of metformin.     

A prospective randomized trial of triage angiography in acute coronary syndromes ineligible for thrombolytic therapy: Results of the medicine versus angiography in thrombolytic exclusion (MATE) trial

Objectives. The purpose of this study was to determine if early triage angiography with revascularization, if indicated, favorably affects clinical outcomes in patients with suspected acute myocardial infarction who are ineligible for thrombolysis.Background. The majority of patients with acute myocardial infarction and other acute coronary syndromes are considered ineligible for thrombolysis and therefore are not afforded the opportunity for early reperfusion.Methods. This multicenter, prospective, randomized trial evaluated in a controlled fashion the outcomes following triage angiography in acute coronary syndromes ineligible for thrombolytic therapy. Eligible patients (n = 201) with <24 h of symptoms were randomized to early triage angiography and subsequent therapies based on the angiogram versus conventional medical therapy consisting of aspirin, intravenous heparin, nitroglycerin, beta-blockers, and analgesics.Results. In the triage angiography group, 109 patients underwent early angiography and 64 (58%) received revascularization, whereas in the conservative group, 54 (60%) subsequently underwent nonprotocol angiography in response to recurrent ischemia and 33 (37%) received revascularization (p = 0.004). The mean time to revascularization was 27 ± 32 versus 88 ± 98 h (p = 0.0001) and the primary endpoint of recurrent ischemic events or death occurred in 14 (13%) versus 31 (34%) of the triage angiography and conservative groups, respectively (45% risk reduction, 95% CI 27–59%, p = 0.0002). There were no differences between the groups with respect to initial hospital costs or length of stay. Long-term follow-up at a median of 21 months revealed no significant differences in the endpoints of late revascularization, recurrent myocardial infarction, or all-cause mortality.Conclusions. Early triage angiography in patients with acute coronary syndromes who are not eligible for thrombolytics reduced the composite of recurrent ischemic events or death and shortened the time to definitive revascularization during the index hospitalization. Despite more frequent early revascularization after triage angiography, we found no long-term benefit in cardiac outcomes compared with conservative medical therapy with revascularization prompted by recurrent ischemia.