阿托伐他汀对大鼠心肌梗死后AngⅡ、TNF-α及心功能的影响

目的：探讨阿托伐他汀对大鼠心肌梗死后血管紧张素Ⅱ（AngⅡ）和肿瘤坏死因子-α（TNF-α）及心功能的影响。方法：急性心肌梗死雄性大鼠30只，随机分为心肌梗死对照组（AMI）和阿托伐他汀治疗组各15只，另设15只为假手术组，阿托伐他汀治疗组于手术后第2d起灌胃给药，假手术组及对照组只给予等量清水灌胃，6周后检测心肌AngⅡ、TNF-α及超声心动图，以了解心功能，最终获得完整资料大鼠于上述各组分别为10，11，14只。结果：与假手术组相比，心肌梗死对照组及阿托伐他汀治疗组心）lrt,AngⅡ、TNF-α和左室舒张末期内径（LVEDd）均明显升高（P均〈0．05），左室射血分数（LVEF）、短轴缩短率（FS）明显降低（P均〈0.05）。与心肌梗死对照组相比，阿托伐他汀治疗组心肌AngⅡ、TNF-α和LVEDd明显下降（P均〈0．05），LVEF、FS明显增高（P均〈0．05），左室功能改善明显。结论：阿托伐他汀能降低心肌AngⅡ，TNF-α水平，减轻心室重塑，保护心功能。     

阿托伐他汀对心肌梗死大鼠心肌纤维化和细胞外信号调节激酶表达的影响

目的观察阿托伐他汀对大鼠急性心肌梗死后心室重塑和心肌组织中细胞外信号调节激酶(ERK)1/2蛋白表达的影响。方法 20只雄性SD大鼠通过前降支动脉结扎法建立大鼠急性心肌梗死模型后随机分为心肌梗死组(AM I),心肌梗死阿托伐他汀组(ATV),另设假手术组(sham),每组n=10。阿托伐他汀组每天给予阿托伐他汀(10 mg/kg)灌胃,持续4周。假手术组和心肌梗死组每天给予同等量的0.9%氯化钠注射溶液灌胃。应用real-tim e PCR法检测梗死周边区心肌组织中Ⅰ型、Ⅲ型胶原mRNA表达,应用westernb lot方法检测p-ERK1/2、ERK1/2蛋白的表达。结果与假手术组比较,心肌梗死组和阿托伐他汀组中Ⅰ型、Ⅲ型胶原表达高于假手术组(P<0.01),阿托伐他汀组Ⅰ型、Ⅲ型胶原表达显著低于心肌梗死组(P<0.01)。心肌梗死组和阿托伐他汀组中p-ERK1/2表达高于假手术组(P<0.01),阿托伐他汀组p-ERK1/2表达低于心肌梗死组(P<0.01)。结论阿托伐他汀可以改善大鼠心肌梗死后心室重塑,其机制可能与下调心肌组织中p-ERK1/2表达有关。     

阿托伐他汀对大鼠急性心肌缺血-再灌注无复流现象的影响

目的:探讨阿托伐他汀对大鼠急性心肌缺血-再灌注无复流现象的影响。方法:8周龄健康SD大鼠48只,随机分为3组。其中缺血再灌注组(MIR)和阿托伐他汀组,进行造模;假手术组:仅穿线,不结扎。MIR组和假手术组:在造模前每日1次生理盐水2ml灌胃,连续7d。阿托伐他汀组:在造模前每日1次阿托伐他汀15mg/kg与生理盐水2ml混合灌胃,连续7d。造模完成后,血清心肌肌酸激酶同工酶(CK-MB)和乳酸脱氢酶(LDH);检测HR、主动脉收缩压(SBP)、主动脉舒张压(DBP)、左心室收缩压(LVSP)、左心室舒张压(LVEDP)。大鼠心肌采用伊文蓝染色和2,3,5-氯化三苯基四氮唑染色,计算心肌缺血率、心肌梗死率和心肌无复流率。结果:MIR组和阿托伐他汀组CK-MB、LDH、HR和LVEDP均高于假手术组,而LVSP、SBP和DBP低于假手术组(P0.01)。阿托伐他汀组HR和LVEDP高于MIR组,而CK-MB、LDH、LVSP、SBP和DBP低于MIR组(P0.05)。阿托伐他汀组心肌梗死率和心肌无复流率均小于MIR组(P0.05)。MIR组和阿托伐他汀组心肌缺血风险率比较差异无统计学意义。结论:阿托伐他汀预处理心肌缺血-再灌注大鼠,减少心肌损伤、血流动力学紊乱、心肌梗死面积。     

不同剂量阿托伐他汀预处理对高脂兔心梗后hs-CRP的影响

目的：观察不同剂量阿托伐他汀预处理对高脂兔急性心肌梗死（AMI）后高敏C-反应蛋白（hs-CRP）的影响,明确其在防治心梗中的作用机制。方法：雄性高脂兔47只,随机分为对照组、AMI组、假手术组、阿托伐他汀大剂量组10 mg/（kg.d）、阿托伐他汀小剂量组5 mg/（kg.d）。灌胃给药连续14 d,末次给药后1 h结扎左冠状动脉前降支,24 h后测定hs-CRP含量。结果：与对照组比较,AMI组血清hs-CRP含量明显升高（P〈0.01）;与AMI组比较,阿托伐他汀组hs-CRP含量显著降低（P〈0.01）,以大剂量组降低显著。结论：阿托伐他汀预先给药可以降低高脂兔心梗后hs-CRP含量,对急性心梗起到预防和保护作用。     

CT-1,AngⅡ在心肌梗死大鼠心室重塑中的表达及罗格列酮对其的影响

目的:观察罗格列酮对心肌梗死后大鼠心室重塑过程中CT-1,AngⅡ表达的影响。方法:45只雄性Wistar大鼠随机分为假手术组(A组,n=15)和心肌梗死组(n=30),通过结扎左冠状动脉前降支制作急性心肌梗死模型。模型制作成功24 h后,心肌梗死组再随机分为心肌梗死对照组(B组,n=15)和罗格列酮干预组(C组,n=15)。罗格列酮干预组每日给以罗格列酮灌胃(4 mg/kg),假手术组和心肌梗死对照组每日给以等量生理盐水灌胃,持续8周。利用Real Time PCR法检测非梗死区心肌营养素-1的表达,放射免疫法检测非梗死区血管紧张素Ⅱ的含量。结果:给药8周后,B组非梗死区心肌中心肌营养素-1mRNA的表达,血管紧张素Ⅱ的含量及左心重量指数与A、C组相比显著升高,差异有统计学意义(P<0.05);C组与A组相比,非梗死区心肌中心肌营养素-1mRNA的表达,血管紧张素Ⅱ的含量及左心室重量指数显著升高,差异有统计学意义(P<0.05)。结论:罗格列酮可能通过抑制心肌营养素-1,血管紧张素Ⅱ的表达来改善大鼠心肌梗死后心室重塑。     

阿托伐他汀联合辅酶Q10对心肌梗死后心力衰竭大鼠解偶联蛋白2基因表达的影响

目的研究阿托伐他汀及辅酶Q10通过抗氧化作用改善心衰大鼠的作用机制。方法结扎大鼠左冠状动脉前降支并饲养6周的24只存活大鼠随机分为假手术组（Shamgroup,n=6）、模型组（Model group,n=6）、阿托伐他汀组（atorvastatin group,n=6）、阿托伐他汀＋辅酶Q10组（atorvastatin＋coenzyme Q10 group,n=6）,连续灌胃给药5周后测定大鼠血流动力学参数,全心及左室肥厚指数（HW/BW,LVHW/BW）,血清SOD活性及MDA含量,RT-PCR法测定非梗死区心肌组织UCP2 mRNA表达水平。结果联合应用阿托伐他汀及辅酶Q10更能明显升高左心室内压最大上升、最大下降速率（±dp/dtmax）及SOD活性,降低左心室收缩压（LVSP）、左心室舒张末压（LVEDP）、心肌肥厚指数、血清MDA的含量及下调UCP2 mRNA表达水平（P〈0.05-0.001）,但对心率（HR）、收缩压（SBP）、舒张压（DBP）无明显影响（P〉0.05）。结论阿托伐他汀联合辅酶Q10可能通过抗氧化作用,下调心肌梗死后心衰大鼠心肌细胞内UCP2 mRNA的表达水平改善心衰心室重构过程中能量代谢。     

单剂量阿托伐他汀对兔急性心肌梗死再灌注后内皮素-1及无复流的影响

目的：评价单剂量阿托伐他汀对兔急性心肌梗死（AMI）再灌注无复流的防治作用。方法：新西兰大白兔24只随机分成对照组、阿托伐他汀组(10mg．kg-1 )和假手术组。冠状动脉结扎60min，松解120min制备AMI再灌注模型。采用酶联免疫吸附法（ELISA）测定血清白介素-6（IL-6），用放射免疫方法测定AMI前5 min、AMI 60min和再灌注后120min血浆内皮素-1 (ET-1)的含量及正常、复流、无复流区心肌组织ET-1的变化，最终行病理学分析。结果：与对照组相比，阿托伐他汀能有效降低兔AMI再灌注后循环IL-6及ET-1(分别P < 0.01)；而心肌组织ET-1含量阿托伐他汀组仅复流区显著降低( P < 0.01) 。阿托伐他汀组与对照组相比，结扎区范围无明显差异（35.6%与36.2%，P=0.624），无复流范围显著减少(36.5％LA与75.3％LA，P < 0.001)。结论: 单剂量阿托伐他汀具有抗炎及内皮保护作用；能有效防治AMI再灌注后无复流的发生。     

阿托伐他汀早期强化抗炎作用对急性心肌梗死患者压力和化学反射敏感性的影响

目的：研究在急性心肌梗死（AMI）早期，阿托伐他汀强化治疗的抗炎作用对患者压力反射敏感性（BRS）和化学反射敏感性（ChRS）的影响。方法：将71例AMI患者分配至常规组（阿托伐他汀20mg／d，n=36）和强化组（阿托伐他汀40mg／d．n=35）。分别在入院时、用药后7d及14d检测血清超敏c反应蛋白（hsCRP）水平、白细胞介素6（IL-6）、血脂水平、BRS值、ChRS值及所有不良反应。结果：7d及14d时，两组hsCRP、IL-6水平较入院时均有明显降低；7d及14d时，强化组较常规组的hsCRP、IL-6水平均有显著降低。两组治疗后的血脂水平有显著改善，两组间差异无显著性。7d及14d时强化组BRS值、ChRS值较入院时均有明显改善；常规组仅于治疗后14d时BRS值、ChRS值有显著改善；与常规组相比，强化组治疗后BRS值、ChRS值的差异有显著性。结论：阿托伐他汀早期强化干预显著降低炎症因子水平，能更早地明显改善AMI的BRS、ChRS值。[著者文摘]     

急诊PCI术前口服阿托伐他汀对STEMI患者MCP-1、MIF及预后的影响

目的：探讨急诊PCI术前单次口服大剂量阿托伐他汀对ST段抬高性心肌梗死（STE—MI）患者外周静脉血、病变相关冠状动脉血单核细胞趋化蛋白（MCP）-1、巨噬细胞迁移抑制因子（MIF）和患者预后的影响。方法：选取稳定型心绞痛患者36例和STEMI患者69例,并将后者随机分为阿托伐他汀组（术前口服阿托伐他汀80mg,n=36）和STEMI对照组（n=33）。分别于PCI术中抽取3组患者的病变相关冠状动脉血,术后立即抽取外周静脉血,测定各组MCP—1和MIF水平;并统计术后3个月内各组心血管急性事件的发生率。结果：STEMI组外周和病变相关冠状动脉血MCP-1、MIF水平明显高于稳定型心绞痛组,阿托伐他汀组上述指标水平明显低于STEMI对照组（P〈0．05）;阿托伐他汀组和STEMI对照组患者病变相关冠状动脉血MCP-1水平明显高于静脉血（P〈0．05）,而MIF水平无明显区别;阿托伐他汀组术后3个月心血管急性事件的发生率明显低于STEMI对照组。结论：STEMI患者术前单次大剂量应用阿托伐他汀可以降低外周血和病变相关冠状动脉血MCP-1和MIF水平及3个月内急性心血管事件的发生率。     

阿托伐他汀对大鼠心肌梗死后心室重塑和心功能的影响

目的观察阿托伐他汀对大鼠急性心肌梗死后心室重塑和心功能的影响。方法 20只雄性SD大鼠通过前降支动脉结扎法建立大鼠急性心肌梗死模型后随机分为心肌梗死组(AMI),阿托伐他汀组(ATV),另设假手术组,每组n=10。阿托伐他汀组每天给予阿托伐他汀钙片(10 mg.kg-1.d-1)灌胃,持续4周。假手术组和心肌梗死组每天给予同等量的0.9%氯化钠注射溶液灌胃。治疗前后分别测量3组大鼠的左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、左室射血分数(LVEF)和短轴缩短率(LVFS)。大鼠处死后,测量左心室重量及左心重量指数。采用羟胺氧化法测定大鼠血清超氧化物歧化酶活力(SOD)。采用TBA法测定血清丙二醛(MDA)水平。结果治疗4周后,与正常组比较,心肌梗死组和阿托伐他汀组的左心室重量及左心室重量指数均显著增加。与心肌梗死组比较,阿托伐他汀组的左心室重量及左心室重量指数均显著降低,LVEDD、LVESD明显降低,LVEF显著升高。血清超氧化物歧化酶活力显著增强,血清丙二醛水平下降。结论阿托伐他汀可能通过抗氧化作用,改善心肌梗死后大鼠心室重构和左心室功能,防治心室重塑。     

Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Activity kinetics and diagnostic significance in myocardial infarction.

This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.     

俯卧位通气对高海拔地区肺复张治疗无效急性呼吸窘迫综合征患者氧合的影响

目的 探讨俯卧位通气对高海拔地区肺复张术(RM)治疗无效急性呼吸窘迫综合征(ARDS)患者的治疗作用.方法 从海拔2260m的地区医院筛选RM治疗无效的41例ARDS患者[平均氧合指数( PaO2/FiO2)较RM前升高＜20％视为RM无效],依不同病因分为肺内源性ARDS组(ARDSp组)和肺外源性ARDS组(ARDSexp组),每组再按信封法随机分为俯卧位组和仰卧位组,即ARDSp俯卧位组(11例)、ARDSp仰卧位组(9例)、ARDSexp俯卧位组(10例)、ARDSexp仰卧位组(11例).在通气前及通气1、2、3、4h监测动脉血氧分压( PaO2)、PaO2/FiO2、静态顺应性(Cst)、气道阻力(Raw)的变化.结果 通气lh时,ARDSexp俯卧位组PaO2/FiO2( mm Hg,l mm Hg=0.133 kPa)即较通气前显著升高(157.4±40.6比129.3±48.7,P＜0.05),并随通气时间延长呈持续增高趋势,4h达峰值(219.1 ±41.1);且ARDSexp俯卧位组通气3h内PaO2/FiO2较其他3组显著增高,另3组间则差异无统计学意义.ARDSp俯卧位组、ARDSexp俯卧位组通气4h时PaO2/FiO2均较相应仰卧位组显著增高(208.8±39.7比127.4±47.1,219.1±41.1比124.9±50.8,均P＜0.05).4组通气前后Cst无显著改变,各组间差异也无统计学意义.ARDSp俯卧位组通气4h时Raw(cmH2O·L-1·s-1)较通气前显著降低(6.8±1.7比10.7±1.8,P＜0.05),且明显低于其他3组;其他3组各时间点Raw组内及组间比较差异均无统计学意义.结论 俯卧位通气作为ARDS机械通气重要策略之一,可以改善RM无效高原ARDS患者的氧合,为抢救患者赢得宝贵的时间.     

Digital imaging among medical facilities

The Department of Veterans Affairs (VA) in the USA operates a network of 172 medical centres which all utilize a hospital information system (HIS) which has been developed and is currently maintained by the VA. During the past several years, an image management and communication module has been developed, installed and clinically utilized at the Washington DC and Maryland VA Medical Centres. This image management and communication system, referred to as the decentralized hospital computer program (DHCP) imaging system, is fully integrated with a commercial picture archiving and communication system (PACS). The system is utilized to capture, archive, and display all images generated within the hospital including radiology, nuclear medicine, pathology, endoscopy, bronchoscopy, and dermatology, intraoperative photographs, ECG data, and a limited number of paper documents. The ultimate goal of the project is to have all patient text and image data available at any clinical workstation to any authorized user anywhere within the network of medical centres. Clinical requirements for an imaging workstation include ease of use, rapid and reliable access to the complete set of patient information, and images which are of acceptable quality to meet the requirements of the user and the subspecialty. Patient confidentiality and data security must be safeguarded at all times. Integration of the images with the remainder of the patient's database was found to be critical to the success of the project. The experience at the Washington and Maryland facilities suggests that an imaging system that is successfully integrated with a hospital information system can provide substantial clinical and economic benefits both within and among medical centres. Clinical acceptance and utilization of the system has been excellent, particularly in diagnostic radiology where DHCP Imaging has been interfaced to a commercial PAC system. Based upon this initial experience, the VA has begun to deploy the system throughout its large network of medical centres.     

Myocardial elastography at both high temporal and spatial resolution for the detection of infarcts

Myocardial elastography is a novel method for noninvasively assessing regional myocardial function, with the advantages of high spatial and temporal resolution and high signal-to-noise ratio (SNR). In this paper, in-vivo experiments were performed in anesthetized normal and infarcted mice (one day after left anterior descending coronary artery [LAD] ligation) using a high-resolution (30 MHz) ultrasound system (Vevo 770, VisualSonics Inc., Toronto, ON, Canada). Radiofrequency (RF) signals of the left ventricle (LV) in longitudinal (long-axis) view and the associated electrocardiogram (ECG) were simultaneously acquired. Using a retrospective ECG gating technique, 2-D full field-of-view RF frames were acquired at an extremely high frame rate (8 kHz) that resulted in high-quality incremental displacement and strain estimation of the myocardium. The incremental results were further accumulated to obtain the cumulative displacements and strains. Two-dimensional and M-mode displacement images and strain images (elastograms), as well as displacement and strain profiles as a function of time, were compared between normal and infarcted mice. Incremental results clearly depicted cardiac events including LV contraction, LV relaxation and isovolumetric phases in both normal and infarcted mice, and also evidently indicated reduced motion and deformation in the infarcted myocardium. The elastograms indicated that the infarcted regions underwent thinning during systole rather than thickening, as in the normal case. The cumulative elastograms were found to have higher elastographic SNR (SNR(e)) than the incremental elastograms (e.g., 10.6 vs. 4.7 in a normal myocardium, and 6.0 vs. 2.4 in an infarcted myocardium). Finally, preliminary statistical results from nine normal (m = 9) and seven infarcted (n = 7) mice indicated the capability of the cumulative strain in differentiating infracted from normal myocardia. In conclusion, myocardial elastography could provide regional strain information at simultaneously high temporal (>/=0.125 ms) and spatial ( approximately 55 microm) resolution as well as high precision ( approximately 0.05 microm displacement). This technique was thus capable of accurately characterizing normal myocardial function throughout an entire cardiac cycle, at the same high resolution, and detecting and localizing myocardial infarction in vivo.     

Clinical Pharmacokinetics of Morphine

Morphine, the most widely used mu-opioid analgesic for acute and chronic pain, is the standard against which new analgesics are measured. A thorough understanding of the pharmacokinetics of morphine is required in order to safely and effectively use this analgesic in a wide variety of patients with different levels of organ function. A MEDLINE search was conducted to identify literature published between 1966 and January 2002 relevant to the pharmacokinetics of morphine. These publications were reviewed and the literature summarized regarding unique and clinically important elements of morphine disposition relative to its parenteral administration (including intravenous, intramuscular, subcutaneous, epidural and intrathecal administration), absorption profile (immediate release, controlled release, and sublingual/buccal, and rectal administration), distribution, and its metabolism/ excretion. Special populations, including infants, elderly, and those with renal/liver failure, have a unique morphine pharmacokinetic profile that must be taken into account in order to maximize analgesic efficacy and reduce the risk of adverse events.     

手转胎头术失败的原因与分娩结局临床分析

目的 探讨手转胎头术失败的原因与分娩结局.方法 选择2008年1月至2010年12月于我院住院分娩的持续性枕横位、枕后位产妇198例,根据行手转胎头术后结果分为成功组126例、失败组72例.比较两组分娩结局,对比分析失败原因.结果 失败组胎儿体质量≥3500 g的发生率[76.4％(55/72)]明显高于成功组[31.7％(40/126)],差异有统计学意义(x2=30.177,P=0.001)、失败组宫缩乏力发生率[58.3％(42/72)]高于成功组[38.1％ (48/126)],差异有统计学意义(x2=7.569,P=0.006)、失败组骨盆临界或轻度狭窄发生率[38.9％ (28/72)]高于成功组[23.8％(30/126)],差异有统计学意义(x2 =5.030,P=0.002)、失败组手转胎头时机不当(宫口开大＜6 cm、胎头位于坐骨棘上及宫口开大8～10 cm、胎头位于坐骨棘下≥2 cm)发生率[61.1％(44/72)]高于成功组[38.9％(49/126)],差异有统计学意义(x2=9.084,P=0.003).失败组母儿并发症(产后出血、产褥病率、胎儿窘迫、新生儿窒息)发生率高于成功组(x2 =9.586,P=0.002、x2=9.334,P=0.002、x2=5.910,P=0.015、x2=5.240,P=0.022)、失败组剖宫产发生率[72.2％(52/72)]明显高于成功组[34.1 ％(43/126),x2=26.641,P=0.001)].结论 手转胎头术能使难产变顺产,降低剖宫产率,减少母儿并发症,但须积极预防、处理导致手转胎头术失败的原因,对矫正失败后继续矫正及试产应慎重.     

Evidence-Based Pain Management and Palliative Care in Issue Four for 2009 of The Cochrane Library

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly. Issue 4 for 2009 contains 4027 complete reviews, 1906 protocols for reviews in production, and 11447 one-page summaries of systematic reviews published in the general medical literature. In addition, there are citations of 600,000 randomized controlled trials, and 12,200 cited papers in the Cochrane methodology register. The health technology assessment database contains over 7500 citations. This edition of the Library contains 90 new reviews, of which 19 have potential relevance for practitioners in pain and palliative medicine.     

Wie zuverlässig sind Angaben zu nichtentzündlichen ausgedehnten Schmerzen?

ZusammenfassungFragestellung Es wurde geprüft, wie sich der Differenziertheitsgrad zweier Schmerzmessmethoden auf Angaben zur Ausgedehntheit klinischer Schmerzen auswirkt. Zugleich wurde der Referenzzeitraum variiert, über den die Patienten berichten sollten.Methode Erfasst wurde der Einfluss zu Lasten der Befragungsdifferenziertheit durch den Vergleich zweier Körperschema-Bildvorlagen. Drei Referenzzeiträume (Schmerz aktuell, letzte Woche, letztes halbes Jahr) wurden vorgegeben.Ergebnisse Patienten mit ausgedehnten Schmerzen gaben bei differenzierter Befragung um so mehr Schmerzen an, je weiter die Schmerzen zurück lagen und je größer der Berichtszeitraum war. Patienten mit gelenknahen Schmerzen gaben bei hoch differenzierter Befragung weniger ausgedehnte Schmerzen in der Vergangenheit an als bei globaler Einschätzung. Patienten mit Rückenschmerzen berichteten bei differenzierter Befragung zum aktuellen Schmerz über weniger ausgedehnte Schmerzen als bei globaler Befragung.Schlussfolgerung Die Angaben zur Schmerzausdehnung variieren vor allem bei Patienten mit ausgedehnten Schmerzen in Abhängigkeit von der Differenziertheit der Befragung. In diesen Fällen ist die Wahrscheinlichkeit erhöht, dass sich die Beschwerdesymptomatik zumindest teilweise erst in der Reaktion auf die situativen Befragungsbedingungen konstituiert und daher nicht auf andere Befragungsbedingungen generalisiert werden kann.