Tamoxifen induces resistance to activated protein C

Introduction

The estrogen antagonist tamoxifen (TAM) increases the thrombotic risk similar to estrogen containing oral contraceptives (OC). In OC users this risk is attributed to alterations of hemostasis resulting in acquired resistance to activated protein C (APC). TAM-induced APC resistance has not been reported yet.

Materials and Methods

Blood samples were collected prospectively from women with breast cancer before (n = 25) and monthly after start of adjuvant TAM treatment (n = 75). APC resistance was evaluated on basis of the effect of APC on the endogenous thrombin generation potential. To detect increased in vivo APC generation APC plasma levels were measured using a highly sensitive oligonucleotide-based enzyme capture assay. Routine hemostasis parameters were measured additionally.

Results

APC sensitivity decreased by 41% (p = 0.001) compared to baseline after one month of TAM application and remained significantly decreased during the study period. Free protein S increased (p = 0.008) while other analyzed procoagulant factors, inhibitors, and activation markers of coagulation decreased or did not change significantly. In five patients the APC concentration increased to non-physiological levels but an overall significant increase of APC was not observed.

Conclusions

This is the first study showing acquired APC resistance under TAM therapy. Acquired APC resistance might explain the increased thrombotic risk during TAM treatment. Observed changes of hemostasis parameters suggest different determinants of TAM-induced APC resistance than in OC-induced APC resistance. The presence of acquired APC resistance in TAM patients warrants further evaluation if these patients may benefit from antithrombotic prophylaxis in the presence of additional thrombotic risk factors.     

45例老年冠心病介入治疗临床分析

目的评价老年冠心病患者经皮冠状动脉介入治疗（PCI）的临床疗效和安全性。方法本组行PCI（PTCA／PTCA＋支架术）共45例,其中PTCA＋支架术34例,直接支架置入7例,PTCA4例（补救性介入和延迟的PCI治疗各2例）。结果手术成功率为95．6％。45例患者中,术中发生室颤1例,经电复律成功。3例发生频发室早及短阵室速,2例自行消失,1例经静脉推注利多卡因后消失,2例发生股动脉穿刺处血肿,局部治疗后血肿消失。结论70岁以上的高龄冠心病患者的介入治疗成功率高、并发症的发生率也是可以接受的。     

伴焦虑抑郁的冠状动脉粥样硬化性心脏病介入治疗患者药物干预治疗的研究

目的探讨心理药物干预对伴有焦虑抑郁症状冠状动脉粥样硬化性心脏病（冠心病）介入治疗患者的临床疗效。方法对入选的168例冠心病介入治疗患者,通过症状自评量表（SCL-90）、Zung抑郁自评量表（SDS）、Zung焦虑自评量表（SAS）的测评对SDS得分粗分大于41以及SAS得分粗分大于40,定为有抑郁和焦虑倾向,共59人入选。将入选患者随分为干预组36例,对照组23例。干预组在冠心病介入治疗后常规心内科治疗的基础上＋抗精神药物＋心理干预。对照组在冠心病介入治疗后常规心内科治疗基础上＋安慰剂。2组治疗前后SAS、SDS、SCL-90评分,心绞痛分级和心电图ST段进行比较。结果（1）干预组不同时段SAS、SDS评分明显低于对照组（P〈0.01）。（2）干预组治疗后SCL-90评分除躯体症状人际关系敌对性外其余评分高于治疗前（P〈0.01）。（3）干预组治疗后与常模均值心理健康状况的差异无统计学意义（P〉0.05）（除躯体症状、人际关系、敌对性）。（4）干预组治疗后总有效率高于对照组（P〈0.05）。结论（1）冠心病介入治疗患者存在抑郁、焦虑、躯体化、人际关系、敌对性、精神病性等心理健康问题。（2）精神药物＋心理干预可明显改善伴有焦虑抑郁症状的冠心病介入治疗患者心理健康水平。通过认知的改变,可以减轻负性情绪对躯体状态的影响,抑制已改变的病理生理过程,从而提高临床疗效。     

延续护理对冠心病PCI患者术后康复的应用效果分析

目的 针对延续护理对冠心病PCI术后康复中的应用效果进行研究。方法 选取2015年5月~2017年5月到我院进行PCI治疗的126例冠心病患者,随机分为对照组和观察组,每组63例。对照组采取常规PCI术后康复健康教育,观察组采取延续护理干预。对比两组患者出院时及出院1年后的自我管理行为。结果 观察组患者的治疗依从性[（31.64±2.45）分vs（27.35±2.34）分]、生活改良[（28.64±2.76）分vs（26.34±2.18）分]、应急处理[（26.85±2.44）分vs（24.12±2.82）分]、自我管理[（86.15±8.08）分vs（78.31±7.39）分]等指标均优于对照组,差异具有统计学意义（P＜0.05）。结论 对冠心病PCI术后患者采取延续护理,能够提升康复效果,改善患者自我管理行为。     

肝素与高龄PCI术后上消化道大出血

目的:探讨高龄患者PCI术后使用肝素发生上消化道出血的危险性及注意事项.方法:比较普通肝素与低分子肝素的使用剂量、观测指标及各自特点.结果:高龄患者,尤合并消化道疾病者,PCI术后使用肝素易发生上消化道出血.结论:拟行PCI术的患者,尤高龄者,应行全面的评估,特别是消化道疾病史.在应用肝素时应酌减剂量及严密监测实验室指标,以便及时防治,避免发生严重并发症.     

A quantitative real-time PCR method for tissue factor mRNA

BACKGROUND: Tissue factor (TF) is primarily known for its function to initiate blood coagulation. The range of in vivo expression of TF is wide and requires a dynamic assay for monitoring. A general method for TF mRNA quantitation that is dynamic, sensitive and applicable to a variety of experimental systems or clinical situations is therefore desirable. OBJECTIVES: To develop a method for sensitive and dynamic quantitation of TF mRNA in human blood cells. METHODS: TF mRNA expression was analysed and evaluated in monocyte isolations, in whole blood (healthy volunteers and patients scheduled for percutaneous coronary intervention, PCI) and in a panel of human cell lines. RNA was extracted, reverse transcribed and subjected to real-time PCR amplification, according to the TaqMan technology. A TF plasmid was constructed as calibrator of the assay. Two housekeeping genes used as endogenous controls for cDNA quality and integrity were evaluated. RESULTS: The assay was linear by seven orders of magnitude and detected down to 10(2) copies of the TF plasmid. The coefficient of variation was 4% intra-assay and 28% between the assays when using beta2MG as endogenous control. The beta-actin gene expression was induced by treatment with lipopolysaccharide (LPS) in blood leukocytes and could not be used as an endogenous control. However, beta2MG showed only minor variations upon treatment with LPS. The TF mRNA and antigen expression, measured in a Western blot, correlated well (R(2)=0.903) in a panel of 11 human cell lines. CONCLUSIONS: We have established a method for sensitive and dynamic quantitation of TF mRNA in experimental systems and for clinical situations.     

曲美他嗪对PCI患者的心肌保护作用

目的 探讨曲美他嗪对经皮冠状动脉介入治疗(PCI)患者的心肌保护作用.方法 47例因急性心肌梗死(AMI)而行急诊PCI的患者随机分为曲美他嗪组(A组)和对照组(B组),A组在常规治疗的基础上于急诊PCI前后给予曲美他嗪口服,B组不用曲美他嗪.比较两组患者问血肌钙蛋白I(cTnI)、肌酸激酶同工酶(CK-MB)峰值浓度、CK-MB恢复正常的时间、再灌注心律失常及2W后的左室功能.结果 (1)A组和B组患者分别为24例和23例,两组临床基线资料无统计学差异.(2)A组cTnI峰值浓度和CK-MB峰值浓度分别为(1.23±0.98)ng/mL和(114±67)U/L,显著低于B组的(2.36±1.28)ng/mL和(159±72)U/L(P<0.05);A组CK-MB峰值时间和恢复正常的时间均显著短于B组(P<0.05或0.01).(3)A组33%(8例)发生再灌注心律失常,显著低于B组的65%(15例)(P<0.05).(4)2W后超声心动图检测的左室射血分数A组为(58±10)%,显著高于B组的(51±10)%(P<0.05).结论 对急诊PCI的急性心肌梗死患者,曲美他嗪可能缩小梗死面积.减轻再灌注损伤.保护心脏功能.     

Atorvastatin reduces thrombin generation after percutaneous coronary intervention independent of soluble tissue factor

INTRODUCTION: Statins were previously shown to suppress cellular tissue factor (TF) in vitro. Here, we investigated the effect of atorvastatin on the TF-pathway and thrombin generation after coronary angioplasty and stenting in vivo. MATERIALS AND METHODS: A cohort of 30 patients with coronary artery disease (CAD) was randomised to treatment with either none (n=10), 10 mg (n=10) or 80 mg (n=10) atorvastatin per day for the postinterventional period of 6 months starting the day before percutaneous coronary intervention (PCI). Fasting blood samples were collected on admission and after 6 weeks and 6 months of statin therapy to determine sTF, free tissue factor pathway inhibitor (TFPI) and prothrombin fragment F1.2 by immunoassay. RESULTS: Soluble TF (sTF) significantly correlated with thrombin generation as measured by prothrombin fragment F1.2 at baseline. This correlation was lost 6 weeks and 6 months after initiation of statin therapy. In vivo, F1.2 was significantly lowered after 6 months of statin therapy by both, low dose (0 vs. 10 mg: 1.3+/-0.3 vs. 0.7+/-0.2 ng/ml; P<0.05) and high dose (0 vs. 80 mg: 1.2+/-0.3 vs. 0.6+/-0.2 ng/ml; P=0.01) atorvastatin compared to control. However, sTF and free TFPI did not change significantly with atorvastatin therapy when compared to baseline or control. CONCLUSIONS: Our results demonstrate reduced in vivo generation of thrombin six months after percutaneous coronary intervention and statin therapy independent of sTF and free TFPI.     

In vitro evaluation of 56 coronary artery stents by 256-slice multi-detector coronary CT

Objective

We sought to investigate stent lumen visibility of 56 coronary stents with the newest 256-multi-slice-CT (256-MDCT) technology for different reconstruction algorithms in an in vitro model.

Background

Early identification of in-stent restenosis (ISR) is important to avoid recurrent ischemia and prevent acute myocardial infarction (AMI). Since angiography has the disadvantage of high costs and its invasiveness, MDCT could be a convenient and safe non-invasive alternative for detection of ISR.

Material and methods

Percentages of in-stent lumen diameter and in-stent signal attenuation (measured as contrast-to-noise ratio (CNR)) of 56 coronary stents (group A ≤2.5 mm; group B = 2.75–3.0 mm; group C = 3.5–4.0 mm) were evaluated in a coronary vessel in vitro phantom (iodine-filled plastic tubes) employing four different reconstruction algorithms (XCD, CC, CD, XCB) on a novel 256-MDCT (Philips-iCT, collimation = 128 mm × 0.625 mm; rotation time = 270 ms; tube current = 800 mA s with 120 kV). Analysis was conducted with the semi-automatical full-width-at-half-maximum (FWHM) method. P-values <0.05 were regarded statistically significant.

Results

In-stent lumen diameter >60% for group C stents was significantly larger and CNR was significantly lower (both p < 0.05) for sharp kernels (CD; XCD) when compared to groups A/B. The FWHM-method showed significantly smaller in-stent lumen diameter (p < 0.05) when compared to the manual method.

Conclusion

256-MDCT could potentially be employed for clinical assessment of stent patency in stents >3.0 mm when analysed with cardio-dedicated sharp kernels, although clinical studies corroborating this claim should be performed. However, stents ≤3.0 mm reconstructed by soft kernels revealed insufficient in-stent lumen visualisation and should not be used in clinical practice.Further improvements in spatial and temporal image resolution as well as reductions of radiation exposure and image noise have to be accomplished for the ambitious goal of characterising both CT coronary artery anatomy and in-stent lumen.