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Diagnostic performance of high-sensitivity troponin T, myeloperoxidase, and pregnancy-associated plasma protein A assays for triage of patients with acute myocardial infarction. 高灵敏度肌钙蛋白T、髓过氧化物酶和妊娠相关血浆蛋白A检测在急性心肌梗死患者分诊中的诊断价值
Pub Date : 2011-07-01 Epub Date: 2011-06-28 DOI: 10.3343/kjlm.2011.31.3.172
Dilshad Ahmed Khan, Mariam S Sharif, Farooq Ahmad Khan

Background: Early diagnosis is the cornerstone of management of acute myocardial infarction (AMI). We aimed to compare the diagnostic accuracy of high-sensitivity troponin T (hs-cTnT) with myeloperoxidase (MPO) and pregnancy-associated plasma protein A (PAPP-A) for early diagnosis of AMI in patients at the time of presentation to the emergency department (ED).

Methods: We enrolled 289 patients who presented at the ED of the National Institute of Heart Disease (NIHD) Rawalpindi, Pakistan, within 4 hr of onset of chest pain. Clinical assessment, electrocardiography (ECG), and angiography were carried out. Blood samples were collected at 0, 3, 6, and 12 hr. Analyses of plasma hs-cTnT, MPO, and PAPP-A were carried out using commercial kits.

Results: Out of 289 subjects who presented to the ED, we diagnosed 180 patients with coronary heart disease as having AMI (N= 61) and 119 as without AMI (stable coronary artery disease, N=61; unstable angina, N=58). Compared to non-AMI patients, the patients with AMI had significantly higher levels (represented here as median [inter quartile range]) of plasma hs-cTnT (136 [39-370] vs. 12 [7-21] ng/L), MPO (906 [564-1,631] vs. 786 [351-1,299] pmol/L) and PAPP-A (5.78 [2.67-13.4] vs. 2.8 [1.8-4.9] mIU/L). Receiver operator characteristic curves (95% CI) for hs-cTnT (0.952 [0.909-0.978]) were significantly higher (P<0.001) than those for MPO (0.886 [0.830-0.929]) and PAPP-A (0.797 [0.730-0.854]), with AMI sensitivity and specificity percentages of 87% and 98% (hs-cTnT), 82% and 84% (MPO), and 65% and 87% (PAPP-A), respectively.

Conclusions: The diagnostic performance of hs-cTnT was superior to that of MPO and PAPP-A for early triage and diagnosis of AMI among patients of coronary heart disease presenting with chest pain to the ED.

背景:早期诊断是急性心肌梗死(AMI)治疗的基石。我们的目的是比较高敏感性肌钙蛋白T (hs-cTnT)与髓过氧化物酶(MPO)和妊娠相关血浆蛋白A (PAPP-A)在急诊(ED)患者早期诊断AMI时的诊断准确性。方法:我们招募了289例在巴基斯坦拉瓦尔品第国家心脏病研究所(NIHD)急诊科就诊的胸痛发作4小时内的患者。进行临床评估、心电图和血管造影。在0、3、6和12小时采集血样。血浆hs-cTnT、MPO和PAPP-A分析使用商用试剂盒进行。结果:在289例到急诊科就诊的患者中,我们诊断出180例冠心病患者为急性心肌梗死(N= 61), 119例为无急性心肌梗死(稳定期冠心病,N=61;不稳定型心绞痛,N=58)。与非AMI患者相比,AMI患者血浆hs-cTnT (136 [39-370] vs. 12 [7-21] ng/L)、MPO (906 [564-1,631] vs. 786 [351-1,299] pmol/L)和PAPP-A (5.78 [2.67-13.4] vs. 2.8 [1.8-4.9] mIU/L)水平显著升高(以中位数[四分位数范围]表示)。hs-cTnT的受试者操作者特征曲线(95% CI)(0.952[0.909-0.978])显著高于其他指标(p < 0.05)。结论:hs-cTnT在以胸痛为主的冠心病急诊科患者的早期分诊和AMI诊断方面优于MPO和pap - a。
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引用次数: 21
Human bocavirus in patients with respiratory tract infection. 人类呼吸道感染患者中的博卡病毒。
Pub Date : 2011-07-01 Epub Date: 2011-06-28 DOI: 10.3343/kjlm.2011.31.3.179
Jang Su Kim, Chae Seung Lim, Young Kee Kim, Kap No Lee, Chang Kyu Lee

Background: Human bocavirus (HBoV) is a newly identified viral pathogen, and its clinical epidemiology and significance in respiratory infections have not yet been completely elucidated. We investigated the prevalence of HBoV infection and the association between viral (HBoV) load and clinical features of the infection in patients of all age-groups.

Methods: Nasopharyngeal aspirates from patients with symptoms of respiratory infection were tested for presence of HBoV by using real-time polymerase chain reaction. HBoV-positive patients were categorized into low- and high-viral-load groups using 1.0×10(6) copies/mL as the threshold value of viral load.

Results: Detection rate of HBoV was 4.8% (N=93) in a total of 1,926 samples with peak incidence of infection being observed in patients aged 6-12 months. HBoV infection was more frequently observed in young children, especially, in children aged less than 5 yr, and the HBoV load decreased with increase in age. HBoV was codetected with other respiratory viruses in 17 (18.3%) of the 93 HBoV-positive patients and 15 patients (88.2%) belonged to the low-viral-load group. Patients infected with HBoV alone showed a higher viral load than those patients in whom HBoV was codetected with other respiratory viruses (median load, 3.78×10(5) copies/mL vs. 1.94×10(4) copies/mL, P=0.014). Higher pulse rate (P=0.007) and respiratory rate (P=0.021) were observed in patients with a high-viral-load.

Conclusions: Our results suggest that HBoV may be the causative agent of respiratory infection in the high-viral-load group.

背景:人bocavavirus (HBoV)是一种新发现的病毒性病原体,其临床流行病学及其在呼吸道感染中的意义尚未完全阐明。我们调查了所有年龄组患者HBoV感染的患病率以及病毒(HBoV)载量与感染临床特征之间的关系。方法:采用实时聚合酶链反应法对有呼吸道感染症状的患者鼻咽吸出物进行HBoV检测。以1.0×10(6) copies/mL作为病毒载量阈值,将hbov阳性患者分为低病毒载量组和高病毒载量组。结果:1926份样本HBoV检出率为4.8% (N=93), 6 ~ 12月龄为感染高峰。HBoV感染在幼儿中更为常见,特别是在5岁以下的儿童中,HBoV载量随着年龄的增长而下降。93例HBoV阳性患者中17例(18.3%)与其他呼吸道病毒共检出HBoV, 15例(88.2%)属于低病毒载量组。单独感染HBoV的患者的病毒载量高于同时感染其他呼吸道病毒的患者(中位载量,3.78×10(5) copies/mL vs. 1.94×10(4) copies/mL, P=0.014)。高病毒载量患者脉搏率(P=0.007)和呼吸率(P=0.021)较高。结论:我们的结果提示HBoV可能是高病毒载量组呼吸道感染的病原体。
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引用次数: 26
Comparative quantitative analysis of cluster of differentiation 45 antigen expression on lymphocyte subsets. 分化簇45抗原在淋巴细胞亚群上表达的比较定量分析。
Pub Date : 2011-07-01 Epub Date: 2011-06-28 DOI: 10.3343/kjlm.2011.31.3.148
Mijeong Im, Hyojin Chae, Taehoon Kim, Hun-Hee Park, Jihyang Lim, Eun-Jee Oh, Yonggoo Kim, Yeon-Joon Park, Kyungja Han

Background: Since the recent introduction of radioimmunotherapy (RIT) using antibodies against cluster of differentiation (CD) 45 for the treatment of lymphoma, the clinical significance of the CD45 antigen has been increasing steadily. Here, we analyzed CD45 expression on lymphocyte subsets using flow cytometry in order to predict the susceptibility of normal lymphocytes to RIT.

Methods: Peripheral blood specimens were collected from 14 healthy individuals aged 25-54 yr. The mean fluorescence intensity (MFI) of the cell surface antigens was measured using a FACSCanto II system (Becton Dickinson Bioscience, USA). MFI values were converted into antibody binding capacity values using a Quantum Simply Cellular microbead kit (Bangs Laboratories, Inc., USA).

Results: Among the lymphocyte subsets, the expression of CD45 was the highest (725,368±42,763) on natural killer T (NKT) cells, 674,030±48,187 on cytotoxic/suppressor T cells, 588,750±48,090 on natural killer (NK) cells, 580,211±29,168 on helper T (Th) cells, and 499,436±21,737 on B cells. The Th cells and NK cells expressed a similar level of CD45 (P=0.502). Forward scatter was the highest in NKT cells (P<0.05), whereas side scatter differed significantly between each of the lymphocyte subsets (P<0.05). CD3 expression was highest in the Th and NKT cells.

Conclusions: NKT cells express the highest levels of CD45 antigen. Therefore, this lymphocyte subset would be most profoundly affected by RIT or pretargeted RIT. The monitoring of this lymphocyte subset during and after RIT should prove helpful.

背景:自从最近引入使用抗分化簇(CD45)抗体的放射免疫疗法(RIT)治疗淋巴瘤以来,CD45抗原的临床意义一直在稳步增加。在这里,我们使用流式细胞术分析CD45在淋巴细胞亚群上的表达,以预测正常淋巴细胞对RIT的易感性。方法:收集14例25-54岁健康人外周血标本,采用FACSCanto II系统(Becton Dickinson Bioscience, USA)测定细胞表面抗原的平均荧光强度(MFI)。使用Quantum simple Cellular微珠试剂盒(Bangs Laboratories, Inc., USA)将MFI值转换为抗体结合能力值。结果:在淋巴细胞亚群中,CD45在自然杀伤T (NKT)细胞中表达最高(725,368±42,763),在细胞毒/抑制T细胞中表达最高(674,030±48,187),在自然杀伤(NK)细胞中表达最高(588,750±48,090),在辅助T (Th)细胞中表达最高(580,211±29,168),在B细胞中表达最高(499,436±21,737)。Th细胞和NK细胞表达CD45水平相近(P=0.502)。结论:NKT细胞表达CD45抗原水平最高。因此,RIT或预靶向RIT对这一淋巴细胞亚群的影响最为深远。在RIT期间和之后对这个淋巴细胞亚群的监测应该是有帮助的。
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引用次数: 15
Evaluation of the diagnostic performance of fibrin monomer in disseminated intravascular coagulation. 纤维蛋白单体在弥散性血管内凝血诊断中的价值评价。
Pub Date : 2011-07-01 Epub Date: 2011-06-28 DOI: 10.3343/kjlm.2011.31.3.143
Kyoung-Jin Park, Eui-Hoon Kwon, Hee-Jin Kim, Sun-Hee Kim

Background: Fibrin-related markers (FRM) such as fibrin monomer (FM) and D-dimer (DD) are considered useful biological markers for the diagnosis of disseminated intravascular coagulation (DIC). However, no studies on the diagnostic performance of different FRMs have been published in Korea. The aim of this study was to evaluate the diagnostic performance of FM for DIC in comparison with DD.

Methods: The reference limit of FM was determined based on plasma sample data obtained from 210 control individuals. To evaluate diagnostic performance, FM data from the plasma samples of 139 patients with DIC-associated diseases were obtained for DIC scoring. FM was measured by immunoturbidimetry using STA-LIATEST FM (Diagnostica Stago, France). Patients were classified according to the DIC score as non-DIC, non-overt DIC, or overt DIC. ROC curve analyses were performed.

Results: The reference limit in the control individuals was determined to be 7.80 µg/mL. Patients with DIC-associated diseases were categorized as non-DIC (N=43), non-overt DIC (N=80), and overt DIC (N=16). ROC curve analyses showed that the diagnostic performance of FM was comparable to DD in both non-overt DIC and overt DIC (P=0.596 and 0.553, respectively). In addition, FM had higher sensitivity, specificity, positive predictive value, and negative predictive value than DD for differentiating overt DIC from non-DIC.

Conclusions: This study demonstrated that the diagnostic performance of FM for DIC was comparable to DD. FM might be more sensitive and more specific than DD in the diagnosis of overt DIC, but not non-overt DIC.

背景:纤维蛋白相关标志物(FRM),如纤维蛋白单体(FM)和d -二聚体(DD)被认为是诊断弥散性血管内凝血(DIC)的有用生物标志物。然而,韩国尚未发表关于不同FRMs诊断性能的研究。本研究的目的是评价FM对DIC的诊断价值,并与dd进行比较。方法:根据210例对照患者的血浆样本数据确定FM的参考限。为了评估诊断性能,从139例DIC相关疾病患者的血浆样本中获取FM数据进行DIC评分。FM采用STA-LIATEST FM (Diagnostica Stago, France)的免疫比浊法测定。根据DIC评分将患者分为非DIC、非显性DIC和显性DIC。进行ROC曲线分析。结果:确定对照个体的参考限为7.80µg/mL。伴有DIC相关疾病的患者分为非DIC (N=43)、非显性DIC (N=80)和显性DIC (N=16)。ROC曲线分析显示FM对非显性DIC和显性DIC的诊断效果与DD相当(P值分别为0.596和0.553)。此外,FM在区分显性DIC与非DIC的敏感性、特异性、阳性预测值和阴性预测值均高于DD。结论:本研究表明FM对DIC的诊断性能与DD相当,FM对显性DIC的诊断可能比DD更敏感、更特异,但对非显性DIC的诊断则不然。
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引用次数: 20
Erythroleukemia relapsing as precursor B-cell lymphoblastic leukemia. 作为前体b细胞淋巴细胞白血病复发的红白血病。
Pub Date : 2011-04-01 DOI: 10.3343/kjlm.2011.31.2.81
Borae G Park, Chan-Jeoung Park, Seongsoo Jang, Eul Ju Seo, Hyun-Sook Chi, Jung-Hee Lee

AML relapsing as ALL has rarely been reported. We describe the case of a 62-yr-old man who was diagnosed with erythroleukemia with a complex karyotype and achieved complete hematologic and cytogenetic remission after induction chemotherapy. However, 4 months after the initial diagnosis, he showed relapse with blasts showing a different morphology and immunophenotype and was diagnosed with precursor B-cell ALL. The relapsing precursor B-cell ALL presented with the same leukemic clones as the primary erythroleukemia. Cytogenetic analysis of his bone marrow (BM) at the time of the primary erythroleukemia showed complex karyotypic abnormalities, including monosomy 5 and monosomy 7. At relapse, his BM showed reemergence of these leukemic clones of complex karyotypic abnormalities with clonal switch. To our knowledge, this is the first case of a lineage switch from erythroleukemia to ALL.

AML复发为ALL的报道很少。我们描述了一个62岁的男子谁被诊断为红细胞白血病与复杂核型和实现完全血液学和细胞遗传学化疗后缓解。然而,在最初诊断4个月后,他复发,原始细胞表现出不同的形态和免疫表型,并被诊断为前体b细胞ALL。复发的前体b细胞ALL表现出与原发性红细胞白血病相同的白血病克隆。原发性红细胞白血病时骨髓细胞遗传学分析显示复杂的核型异常,包括单体5和单体7。在复发时,他的BM显示这些复杂核型异常的白血病克隆与克隆开关重新出现。据我们所知,这是第一例从红细胞白血病到ALL的谱系转换。
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引用次数: 10
Effects of long-term use of depo-medroxyprogesterone acetate on lipid metabolism in Nepalese women. 长期使用醋酸甲羟孕酮对尼泊尔妇女脂质代谢的影响。
Pub Date : 2011-04-01 DOI: 10.3343/kjlm.2011.31.2.95
Binod Kumar Yadav, Rajesh Kumar Gupta, Prajwal Gyawali, Rojeet Shrestha, Bibek Poudel, Manoj Sigdel, Bharat Jha

Various synthetic progestogens that are used as contraceptives have been reported to influence lipid and lipoprotein fractions differently. Depo-medroxyprogesterone acetate (DMPA), a synthetic progestogen, is used by Nepalese women as a contraceptive agent. Our study aims to determine the effects of long-term use of DMPA on lipid metabolism. We performed this study on 60 healthy Nepalese women who had been using DMPA for more than 2 yr and age- and weight-matched control subjects who were not using hormonal contraceptives. Fasting blood samples were collected from the subjects for the estimation of total cholesterol (TC) and triglyceride (TG) levels, and the levels of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were estimated using the Friedewald's equation. TC and LDL-C levels in DMPA users were significantly higher than those in non-users. Our study concluded that DMPA use induces lipid metabolism changes that can increase the risk of cardiovascular diseases.

据报道,用作避孕药的各种合成孕激素对脂质和脂蛋白组分的影响不同。醋酸甲羟孕酮(DMPA)是一种合成孕激素,被尼泊尔妇女用作避孕药。我们的研究旨在确定长期使用DMPA对脂质代谢的影响。我们对60名使用DMPA超过2年的健康尼泊尔妇女和年龄和体重匹配的未使用激素避孕药的对照组进行了这项研究。收集受试者空腹血液样本,估算总胆固醇(TC)和甘油三酯(TG)水平,并使用Friedewald方程估算高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)水平。DMPA服用者TC和LDL-C水平明显高于非服用者。我们的研究得出结论,使用DMPA会引起脂质代谢的变化,从而增加心血管疾病的风险。
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引用次数: 20
Streptococcus suis causes septic arthritis and bacteremia: phenotypic characterization and molecular confirmation. 猪链球菌引起脓毒性关节炎和菌血症:表型表征和分子证实。
Pub Date : 2011-04-01 DOI: 10.3343/kjlm.2011.31.2.115
Hanah Kim, Sang Hoon Lee, Hee-Won Moon, Ji Young Kim, Sun Hwa Lee, Mina Hur, Yeo-Min Yun

Streptococcus suis is a swine pathogen that causes meningitis, septicemia, pneumonia, and endocarditis. The first case of human S. suis infection was reported in Denmark in 1968, and since then, this infection with has been reported in many countries, especially in Southeast Asia because of the high density of pigs in this region. We report the case of a patient with septic arthritis and bacteremia caused by S. suis. Cases in which S. suis is isolated from the joint fluid are very rare, and to the best of our knowledge, this is first case report of S. suis infection in Korea. The identity of this organism was confirmed by phenotypic characterization and 16S rRNA sequence analysis. An 81-yr-old Korean woman who presented with fever, arthralgia, and headache was admitted to a secondary referral center in Korea. Culture of aspirated joint fluid and blood samples showed the growth of S. suis biotype II, which was identified by the Vitek2 GPI and API 20 Strep systems (bioMérieux, USA), and this organism was susceptible to penicillin G and vancomycin. The 16S rRNA sequences of the blood culture isolates showed 99% homology with those of S. suis subsp. suis, which are reported in GenBank. The patient's fever subsided, and blood and joint cultures were negative for bacterial growth after antibiotic therapy; however, the swelling and pain in her left knee joint persisted. She plans to undergo total knee replacement.

猪链球菌是一种猪病原体,可引起脑膜炎、败血症、肺炎和心内膜炎。丹麦于1968年报告了第一例人类猪链球菌感染病例,自那时以来,许多国家都报告了这种感染,特别是在东南亚,因为该地区的猪密度很高。我们报告的情况下,病人与化脓性关节炎和菌血症引起的猪链球菌。从关节液中分离出猪链球菌的病例非常罕见,据我们所知,这是韩国首例猪链球菌感染病例。通过表型鉴定和16S rRNA序列分析证实了该菌的身份。一名81岁韩国妇女以发热、关节痛、头痛等症状被送往韩国二级转诊中心。经Vitek2 GPI和API 20链球菌检测系统(biomsamrieux, USA)鉴定,该菌对青霉素G和万古霉素敏感。血培养分离株的16S rRNA序列与猪链球菌亚种的同源性达99%。在GenBank中有报道。患者发热消退,抗生素治疗后血液和关节培养细菌生长阴性;然而,左膝关节的肿胀和疼痛持续存在。她计划接受全膝关节置换术。
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引用次数: 16
The path to clinical proteomics research: integration of proteomics, genomics, clinical laboratory and regulatory science. 临床蛋白质组学研究之路:蛋白质组学、基因组学、临床实验室和监管科学的整合。
Pub Date : 2011-04-01 DOI: 10.3343/kjlm.2011.31.2.61
Emily S Boja, Henry Rodriguez

Better biomarkers are urgently needed to cancer detection, diagnosis, and prognosis. While the genomics community is making significant advances in understanding the molecular basis of disease, proteomics will delineate the functional units of a cell, proteins and their intricate interaction network and signaling pathways for the underlying disease. Great progress has been made to characterize thousands of proteins qualitatively and quantitatively in complex biological systems by utilizing multi-dimensional sample fractionation strategies, mass spectrometry and protein microarrays. Comparative/quantitative analysis of high-quality clinical biospecimen (e.g., tissue and biofluids) of human cancer proteome landscape has the potential to reveal protein/peptide biomarkers responsible for this disease by means of their altered levels of expression, post-translational modifications as well as different forms of protein variants. Despite technological advances in proteomics, major hurdles still exist in every step of the biomarker development pipeline. The National Cancer Institute's Clinical Proteomic Technologies for Cancer initiative (NCI-CPTC) has taken a critical step to close the gap between biomarker discovery and qualification by introducing a pre-clinical "verification" stage in the pipeline, partnering with clinical laboratory organizations to develop and implement common standards, and developing regulatory science documents with the US Food and Drug Administration to educate the proteomics community on analytical evaluation requirements for multiplex assays in order to ensure the safety and effectiveness of these tests for their intended use.

癌症检测、诊断和预后迫切需要更好的生物标志物。虽然基因组学界在了解疾病的分子基础方面取得了重大进展,但蛋白质组学将勾勒出细胞的功能单元、蛋白质及其错综复杂的相互作用网络和潜在疾病的信号通路。利用多维样品分馏策略、质谱法和蛋白质微阵列,在定性和定量分析复杂生物系统中成千上万种蛋白质的特征方面取得了巨大进展。对人类癌症蛋白质组图谱的高质量临床生物样本(如组织和生物流体)进行比较/定量分析,有可能通过其表达水平的改变、翻译后修饰以及不同形式的蛋白质变体,揭示导致这种疾病的蛋白质/肽生物标志物。尽管蛋白质组学的技术不断进步,但生物标记物开发管道的每一步仍然存在重大障碍。美国国家癌症研究所(NCI)的癌症临床蛋白质组技术计划(NCI-CPTC)已经迈出了关键的一步,通过在管道中引入临床前 "验证 "阶段、与临床实验室组织合作开发和实施通用标准,以及与美国食品药品管理局合作开发监管科学文件,向蛋白质组学界介绍多重检测的分析评估要求,以确保这些检测在预期用途上的安全性和有效性,从而缩小生物标记物发现和鉴定之间的差距。
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引用次数: 0
New biomarkers of acute kidney injury and the cardio-renal syndrome. 急性肾损伤和心肾综合征的新生物标志物。
Pub Date : 2011-04-01 DOI: 10.3343/kjlm.2011.31.2.72
Robert Hawkins

Changes in renal function are one of the most common manifestations of severe illness. There is a clinical need to intervene early with proven treatments in patients with potentially deleterious changes in renal function. Unfortunately progress has been hindered by poor definitions of renal dysfunction and a lack of early biomarkers of renal injury. In recent years, the definitional problem has been addressed with the establishment of a new well-defined diagnostic entity, acute kidney injury (AKI), which encompasses the wide spectrum of kidney dysfunction, together with clearer definition and sub-classification of the cardio-renal syndromes. From the laboratory have emerged new biomarkers which allow early detection of AKI, including neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C. This review describes the new concepts of AKI and the cardio-renal syndromes as well as novel biomarkers which allow early detection of AKI. Panels of AKI biomarker tests are likely to revolutionize the diagnosis and management of critically ill patients in the coming years. Earlier diagnosis and intervention should significantly reduce the morbidity and mortality associated with acute kidney damage.

肾功能改变是严重疾病最常见的表现之一。临床需要对有潜在有害的肾功能改变的患者进行早期干预。不幸的是,肾功能不全的定义和缺乏肾损伤的早期生物标志物阻碍了进展。近年来,随着一个新的定义明确的诊断实体——急性肾损伤(AKI)的建立,定义问题得到了解决,该诊断实体涵盖了广泛的肾功能障碍,以及更清晰的心肾综合征的定义和分类。从实验室已经出现了新的生物标志物,允许AKI的早期检测,包括中性粒细胞明胶酶相关脂钙蛋白(NGAL)和胱抑素c。本文综述了AKI和心肾综合征的新概念以及允许AKI早期检测的新生物标志物。未来几年,AKI生物标志物测试可能会彻底改变危重患者的诊断和管理。早期诊断和干预应显著降低与急性肾损害相关的发病率和死亡率。
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引用次数: 55
Clinical, pharmacokinetic, and pharmacogenetic determinants of clopidogrel resistance in Korean patients with acute coronary syndrome. 韩国急性冠脉综合征患者氯吡格雷耐药的临床、药代动力学和药物遗传学决定因素。
Pub Date : 2011-04-01 DOI: 10.3343/kjlm.2011.31.2.91
Kyoung-Jin Park, Hae-Sun Chung, Suk-Ran Kim, Hee-Jin Kim, Ju-Yong Han, Soo-Youn Lee

Background: Clopidogrel has been widely used to prevent recurrent ischemia in patients with acute coronary syndrome (ACS). However, inter-individual variability in response to clopidogrel has been a problem in the clinical setting. The aim of the present study was to investigate the frequency of clopidogrel resistance and to determine the clinical, pharmacokinetic, and pharmacogenetic factors for clopidogrel resistance in Korean patients with ACS.

Methods: Clinical information, such as the underlying diseases and concurrent medications, of 114 patients with ACS who received clopidogrel therapy was studied. The degree of inhibition of platelets was assessed using the VerifyNow assay (Accumetrics, USA). The patients who showed less than 20% inhibition of platelets were defined as non-responders to clopidogrel treatment. Steady state plasma concentrations of clopidogrel were measured using HPLC/tandem mass spectrometry. CYP2C19 genotyping was also performed.

Results: A wide inter-individual variability was observed in platelet inhibition (0-76%); 56 patients (49%) showed less than 20% inhibition. There were no differences between the patients' history of diabetes mellitus and concurrent medications as well as the plasma concentrations of clopidogrel of the responders and non-responders. CYP2C19 variants, including CYP2C19*2 and CYP2C19*3, were more commonly observed in the non-responders than in the responders (P value < 0.0001).

Conclusions: The response to clopidogrel was highly variable in Korean patients with ACS. The results of the present study confirmed that the genetic polymorphism of CYP2C19 could be important in clopidogrel response. However, further studies are required to investigate other likely factors involved in clopidogrel resistance.

背景:氯吡格雷已被广泛用于预防急性冠脉综合征(ACS)患者复发性缺血。然而,个体间对氯吡格雷反应的差异一直是临床环境中的一个问题。本研究的目的是调查氯吡格雷耐药的频率,并确定韩国ACS患者氯吡格雷耐药的临床、药代动力学和药物遗传因素。方法:对114例接受氯吡格雷治疗的ACS患者的基础疾病、并发用药等临床资料进行分析。使用VerifyNow测定法(Accumetrics,美国)评估血小板抑制程度。血小板抑制低于20%的患者被定义为对氯吡格雷治疗无反应。采用HPLC/串联质谱法测定氯吡格雷稳态血药浓度。同时进行CYP2C19基因分型。结果:在血小板抑制方面存在广泛的个体差异(0-76%);56例(49%)患者抑制率低于20%。有反应者与无反应者的血浆氯吡格雷浓度、糖尿病史及同时用药无差异。CYP2C19变异,包括CYP2C19*2和CYP2C19*3,在无应答者中比在应答者中更常见(P值< 0.0001)。结论:韩国ACS患者对氯吡格雷的反应差异很大。本研究结果证实CYP2C19基因多态性可能在氯吡格雷反应中起重要作用。然而,需要进一步的研究来调查与氯吡格雷耐药有关的其他可能因素。
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引用次数: 23
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Korean Journal of Laboratory Medicine
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