Marked decrease in the levels of two inflammatory markers,hs-C-reactive protein and fibrinogen in patients with severe carotid atherosclerosis after eversion carotid endarterectomy

Objective and design: To study changes in the levels of two acute phase proteins, plasma fibrinogen and serum C-reactive protein (hs-CRP) in patients with severe carotid stenosis after eversion endarterectomy.Material and subjects: A total of 117 consecutive patients who underwent eversion endarterectomy were included in the study. Blood samples for acute phase protein measurement were taken before operation as well as 5.7 weeks and 13.8 months (median) post-surgery. Plasma fibrinogen and serum hs-CRP concentrations were promptly determined.Results: During the follow-up period sharp, highly significant (p < 0.0001) drop occurred in the serum concentrations of both acute phase proteins. The drop in the hs-CRP levels during the follow up period was mainly due to decrease in patients with highest baseline CRP levels.Conclusions: Our present findings indicate that removal of atherosclerotic plaques from the carotid arteries markedly decreases the production of two acute phase proteins due to the decrease of the inflammatory burden or the removal of the advanced plaques able to produce these proteins.Received 20 April 2004; returned for revision 9 June 2004; accepted by A. Falus 25 June 2004     

Changes in the plasma concentration of soluble thrombomodulin in patients with severe carotid artery stenosis after eversion endarterectomy

Objective and design: The purpose of the study was to investigate the putative role of soluble thrombomodulin (sTM) in severe carotid artery stenosis.Materials and methods: We prospectively studied 64 patients who were undergoing carotid endarterectomy (2001–2003). Plasma sTM concentration was determined in each patient before surgery and at 14 months postsurgery. −308 TNF-α promoter polymorphism was also determined.Results: Strong negative correlation was found between the preoperative duplex scan values and the plasma sTM concentrations (R = −0.418, p = 0.0006). Patients with 308 A TNF-α genotype had significantly lower (p = 0.0415) preoperative sTM values than their counterparts with no such polymorphism. Soluble TM concentrations measured in plasma samples taken at the end of the postsurgical follow-up period of 14 months duration were significantly higher compared to the preoperative values (p < 0.0001).Conclusions: Our present findings indicate that sTM may be adsorbed to the atherosclerotic plaques or inflamed endothelium in carotid arteries. The pathological significance of this adsorption remains to be determined.Received 17 November 2004; returned for revision 8 March 2005; accepted by A. Falus 11 March 2005     

Early complement activation follows eversion carotid endarterectomy and correlates with the time of clamping of the carotid artery

BACKGROUND: Complement activation plays an important role in ischemia/reperfusion (I/R) injury. The objective of the present study was to detect the presence and mechanism of complement activation in patients who underwent carotid endarterectomy (CEA). METHODS: Complement activation products C1rsC1-inhibitor, C4d, C3a and SC5b-9 and concentrations of C-reactive protein (CRP) were measured in samples serially taken from 16 patients with eversion CEA and 10 with carotid artery stenting (CAS) in the first 24h post-surgery/intervention. MBL2 genotypes were also determined. RESULTS: In patients with CEA an intense increase in C3a levels were observed immediately after surgery (p<0.001), accompanied by a slight elevation in SC5b-9 levels (p<0.05). C3a levels remained elevated until 4h post-surgery, compared with the baseline values and with CAS patients. Peak C3a levels correlated with the time of carotid clamping (r=0.5921, p=0.02). No significant changes were detected in C1rsC1-inhibitor or C4d levels following CEA, and we found no association between the generation of C3a and MBL2 genotypes or CRP levels. Complement activation was not present in patients with CAS. CONCLUSIONS: Early complement activation follows CEA and correlates with the time of I/R injury. The lack of C4d generation suggests the role of the alternative and not the lectin pathway in the process.     

Construction of knowledge of the disease by patients after carotid endarterectomy

The aim of this work was to characterize the knowledge that patients have of their disease. A special questionnaire was distributed (in 1998) to 33 patients with ischemic cerebrovascular disease who underwent carotid endarterectomy (CEA) in 1995-1996. The results show that the knowledge of patients is fragmentary, hermetic, and static, at the same time serving as their basic perceptive-cognitive filter.     

Association of intracellular pro- and anti-inflammatory cytokines in peripheral blood with the clinical or ultrasound indications for carotid endarterectomy in patients with carotid atherosclerosis

Early non-invasive diagnostic information would be useful in identifying patients at risk of progressive carotid atherosclerosis, despite an apparently harmless plaque on ultrasound imaging. In this study, we assessed the possible association of intracellular cytokines in peripheral blood with the ultrasound (stenosis > or = 70%) and clinical indications (transient ischaemic attack, amaurosis fugax or stroke) for carotid endarterectomy (CEA) in patients. Intracellular cytokine expression was determined in 106 patients (67 undergoing and 39 not undergoing CEA). Cells primed for the proinflammatory cytokines tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1beta, IL-6, IL-8 and the anti-inflammatory cytokines IL-4 and IL-10 were found in significantly higher percentages in patients undergoing CEA than in patients who were not (P < 0.05). Intracellular cytokine expression was significantly higher in patients undergoing CEA who had stenosis > or = 70% (TNF-alpha, IFN-gamma, IL-1beta, IL-6, IL-4 and IL-10), with previous stroke (IFN-gamma, IL-1beta, IL-6, IL-8, IL-4 and IL-10) and with amaurosis fugax (IFN-gamma, IL-6, IL-4 and IL-10) than in patients not undergoing CEA. Increased intracellular cytokines in patients' peripheral blood might be a warning signal indicating progressive atherosclerosis. If so, intracellular cytokine monitoring could help in selecting patients at high risk of future clinical cardiovascular events and therefore most likely to benefit from CEA or adjustment of pharmacological therapy.     

Plasma levels of endothelin and early carotid atherosclerosis in diabetic patients.

An increased thickness of the carotid artery wall is thought to be a sign of early atherosclerosis. Since plasma endothelin concentrations were released from vascular endothelial cells, we have investigated the possible relationship between endothelin 1 (ET-1) and arterial wall thickness. Ninety-eight patients with Type 2 diabetes without evidence of macroangiopathy, hypertension, proteinuria or proliferative retinopathy, and 50 non-diabetic subjects were studied. After an overnight fast, blood was taken for ET-1, glucose, HbA1c, lipids, insulin and C-peptide. Arterial wall thickness was measured as the mean of the maximum intimal-medial thickness (IMT) in 16 carotid segments by B-mode ultrasound. ET-1 levels were significantly elevated in diabetic patients with IMT>1100 microm, 8.3 pmol/l (5.2-12.9) compared with control subjects, 7.6 pmol/l (5.0-11.0), p<0.01 and with diabetic subjects with IMT<500 microm, 7.43 pmol/l (4.8-11.1), p<0.01. The diabetic (IMT>1100 microm) study group had also significantly higher levels of insulin, 102.8 +/- 46.4 pmol/l vs control subjects, 77.5 +/- 32.4 pmol/l, p<0.01. In diabetic subjects, no correlation was found between ET-1 and IMT with glucose, HbA1c, lipids, age or duration of diabetes, respectively. We conclude that ET-1 levels are elevated in Type 2 diabetic patients with increased IMT. Thus providing further support for the role of endothelin in atherosclerosis.     

Anti-endothelial cell antibodies in patients with coronary atherosclerosis

Anti-endothelial cell antibodies (AECA) have been shown to possess endothelial cell activation properties and to harbor pathogenic potential in experimental animal models of autoimmune systemic disorders. Atherosclerosis is a form of an inflammatory condition in which the immune system has been shown to be involved. The aim of the present study was to assess the presence of AECA in patients with coronary atherosclerosis. A total of 134 patients admitted for chest pain of suspected anginal origin were evaluated for coronary artery atherosclerosis by angiography. Sera were drawn prior to the procedure for the determination of AECA employing cyto-ELISA. AECA positive sera were further evaluated for its ability to promote in vitro E-selectin expression by HUVEC using a cell-based ELISA. Patients with no coronary artery involvement had levels of AECA that did not differ from those obtained for patients with confirmed coronary atherosclerosis (one, two or three vessel disease). Furthermore, AECA positive sera from patients, with or without coronary atherosclerosis displayed similar capacity of inducing E-selectin expression by endothelial cells. AECA may not stand as an optimal mean of discriminating atherosclerotic from non-atherosclerotic patients. The ability of AECA to activate endothelial cells is also not unique to patients with atherosclerosis and is evident also in age-matched control subjects.     

颈动脉内膜剥脱术后颈部神经损伤的危险因素分析

目的:探讨颈动脉内膜剥脱术(CEA)后颈部神经损伤(CNI)的相关危险因素。方法:采用回顾性研究方法。纳入天坛医院2012年4月—2015年5月209例CEA患者的临床资料,其中男177(84.69%)例、女32(15.31%)例,年龄42～80(67.5±8.8)岁。(1)统计患者术后CNI的发生率及临床表现。(2)...     

血清IL-6、CRP和PCT水平对严重多发伤后MODS的预测价值

目的探讨多发伤患者外周血血清白细胞介素-6(IL-6)、C反应蛋白(CRP)和降钙素原(PCT)对多器官功能障碍综合征(MODS)的预测价值。方法 87例多发伤患者按治疗过程中有无发生MODS分为MODS组和非MODS组。采用ELISA法测定患者伤后第1、2、3、5、和7天血清IL-6和PCT的含量,采用免疫比浊法测定血清CRP的水平,并与20例健康对照比较,应用受试者工作特征曲线(ROC曲线)进行统计学分析。结果与健康对照组相比,多发伤患者血清IL-6、CRP和PCT水平伤后早期均出现不同程度的升高(P<0.01),其中PCT水平升高最早;与非MODS组比较,MODS组各项指标均有显著差异(P<0.01)。IL-6、CRP和PCT的ROC曲线下面积分别为0.686、0.854和0.914。PCT对严重多发伤后发生MODS的诊断价值高于IL-6和CRP。结论 PCT是严重多发伤后预测MODS发生的较好辅助诊断指标,其诊断价值优于IL-6和CRP。     

Changes in circulating levels of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 after carotid endarterectomy

It has been shown that vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2) are upregulated in severe carotid stenosis. However, it is unknown whether carotid endarterectomy (CEA) affects serum level of these molecules. We investigated changes in concentration of VEGF and VEGFR-2 in patients undergoing carotid endarterectomy. Forty-three patients with extracranial carotid stenosis (>70%), were studied. Patients with severe vertebrobasilar stenosis, recent (<1 month) vascular event (stroke, coronary infarction, arterial thromboembolism), critical ischemia of lower extremity, recent infection, autoimmune disease or malignancy were excluded from the study. Blood samples were taken before CEA and on the second post-operative day. Thirty healthy blood donors served as a control group. We used enzyme linked immuno-absorbent assay as a method for the determination of VEGF and VEGFR-2. Pre-operative levels of VEGF (371+/-42 pg/ml) and VEGFR-2 (8424+/-356 pg/ml) were significantly elevated. There was significant decrease in both VEGF (152 pg/ml) and VEGFR-2 (1297 pg/ml) after CEA, without however reaching normal values. In asymptomatic patients and in patients with a contralateral carotid stenosis of >50%, however, the observed reduction of VEGF did not reach statistical significance. On the other hand, in the same subgroups, a major decrease of VEGFR-2 values was observed. VEGF and VEGFR-2 showed a very significant increase in serum of patients with severe carotid stenosis. These pre-operative levels decreased significantly after endarterectomy, and the changes emphasize the importance of these molecules in carotid disease progression.     

不同孕周子痫前期患者血清胱抑素C水平变化的研究

目的探讨子痫前期患者血清胱抑素C水平变化。方法选取2011年5月-2012年12月在广州医学院附属深圳沙井医院产检子痫前期病例50例纳入研究组,同期选择健康孕妇50例作为对照组,所有观察对象于孕20周、孕24周、孕28周、孕30周、孕34周、孕36周产检时记录血压及尿蛋白结果,同时测量外周血清胱抑素C水平。结果①子痫前期组孕20周时血清胱抑素C水平为0．75±0．12mg／L,对照组为0．59±0．33mg／L,两组间比较P〈0．05,差异有统计学意义。此后,随孕周增加,两组病例间血清胱抑素c水平均有上升趋势,且相同孕周相比均有统计学差异（P〈0．05）。②子痫前期组孕28周时收缩压为145．2±19．1mmHg,舒张压为89．5±15．7mmHg,对照组孕28周时收缩压为133．1±17．2mmHg,舒张压为80．4±17．3mmHg,此后随孕周增加,两组病例收缩压及舒张压均呈进行性上升,且相同孕周相比具有统计学差异（P〈0．05）。孕20周、孕24周时子痫前期组及对照组相比,舒张压及收缩压无统计学差异（P〉0．05）。③子痫前期组首次出现尿蛋白时间为1例28周,10例30周,21例34周,18例36周,对照组没有尿蛋白。结论子痫前期患者孕20周后胱抑素C升高,早于临床血压及尿蛋白改变时间,胱抑素C可能是子痫前期发生预测及肾功能早期损害的敏感指标。     

Oxidative stress and endothelial damage in patients with asymptomatic carotid atherosclerosis

It is know that oxidative stress can be able to induce cytotoxicity of blood cells, stimulate release of inflammatory cytokines, and induce the production of growth factors. The aim of this study was to investigate oxidative stress and endothelial dysfunction in patients with asymptomatic carotid artery disease and healthy controls. Native low-density lipoproteins, oxidised low-density lipoproteins, malondialdehyde, nitrates, glutathione peroxidase activity and endothelin-1 were determined in patients without severe (range between 30% and 50%) carotid artery stenosis. Native low-density lipoproteins, oxidized low-density lipoproteins, malondialdehyde, glutathione peroxydase, and endothelin-1 concentrations were higher in patients than in health controls (P<0.001). No difference was observed in nitrate values (P<0.8). Our results revealed oxidative stress in patients without severe carotid artery stenosis and clinical symptoms. This was shown by the elevated malondialdehyde and oxidized low-density lipoprotein levels. Received: 6 July 2000 / Accepted: 2 February 2001     

颈部推拿对兔颈动脉粥样硬化重度狭窄病变的#br#血管拉伸力学特性的影响颈部推拿对兔颈动脉粥样硬化重度狭窄病变的血管拉伸力学特性的影响

目的　探讨颈部推拿手法对兔颈动脉粥样硬化（CAS）重度狭窄的血管拉伸力学特性的影响。 方法　45只新西兰兔随机分为颈椎旋转组（n=12）、推桥弓组（n=12）、模型对照组（n=12）和空白对照组（n=9）,在颈椎旋转组、推桥弓组和模型对照组建立左侧CAS模型,并分别接受颈椎旋转手法、推桥弓手法干预3周,模型对照组和空白对照组不作手法干预。取左侧颈动脉进行单轴拉伸试验和病理观察,比较四组兔颈动脉的拉伸力学特性。 结果　（1）26只兔造模成功,其中颈椎旋转组、推桥弓组、模型对照组兔颈动脉的最大载荷显著高于空白对照组,同时最大应变显著低于空白对照组(P<0.05);（2）颈椎旋转组兔颈动脉的弹性模量显著高于模型对照组、推桥弓组和空白对照组（P<0.05）,而推桥弓组兔颈动脉的弹性模量与模型对照组相比差异无统计学意义(P>0.05)。 结论　动脉粥样硬化病变可致兔颈动脉血管拉伸力学特性下降,而颈部旋转推拿治疗可导致严重粥样硬化病变并重度狭窄的兔颈动脉弹性下降,为临床安全应用颈部推拿手法提供了参考。     

高血压合并颈动脉粥样硬化患者外周血效应性T细胞亚群的变化及意义

目的:探讨高血压合并颈动脉粥样硬化患者外周血效应性T细胞各亚群Th1、Th2和Th17细胞活性的变化。方法:行颈动脉超声检查选择20例高血压合并颈动脉粥样硬化患者(CA组),颈动脉正常的25例高血压患者(EH组)以及20例性别、年龄匹配的健康体检者作为对照组(Control组)。清晨空腹抽血。以流式细胞术检测外周血中Th1、Th2和Th17细胞比例,实时定量RT-PCR方法检测T-bet、GATA3和RORγt mRNA,ELISA法检测血浆中IFN-γ、IL-4和IL-17水平。结果:与EH组和Control组相比较,CA组Th1、Th17细胞比例显著升高,T-bet和RORγt mRNA表达增加,血浆IFN-γ和IL-17水平显著升高。与Control组相比较,EH组Th1、Th17细胞比例、T-bet和RORγt mRNA、血浆IFN-γ和IL-17水平均无统计学差异。三组间Th2细胞比例、GATA3 mRNA和血浆IL-4水平均无统计学差异。结论:高血压病患者的Th1、Th17细胞活性升高,这种改变可能与颈动脉粥样硬化的发生发展有关。     

Total serum IgE levels in a large cohort of patients with severe or difficult-to-treat asthma.

BACKGROUND: Limited data are available on levels of IgE in large cohorts of patients with severe or difficult-to-treat asthma. OBJECTIVE: To examine IgE levels and disease in patients from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. METHODS: From January 2001 to October 2001, 4,923 patients were screened for inclusion in the study. Of these, 4,756 patients 6 years or older with severe or difficult-to-treat asthma were enrolled and completed a baseline study visit. Total serum IgE levels were measured at the baseline visit and are summarized by geometric means. RESULTS: The mean total IgE level of the population is 106.6 IU/mL (95% confidence interval, 101.5-112.0 IU/mL). Children (6-12 years old) and adolescents (13-17 years old) have higher mean IgE levels than adults (> or =18 years old) (P < .001). Males have a higher mean IgE level than females (P < .001). IgE levels are higher among nonwhite patients than white patients (P < .001). Current smokers have higher IgE levels than past smokers or never smokers (P < .001). Among children, patients with severe asthma have a higher mean IgE level (280.2 IU/mL) than patients with moderate (145.8 IU/mL) or mild (137.8 IU/mL) asthma (P < .001). Among adults, patients with childhood-onset asthma have higher IgE levels (124.3 IU/mL [n = 1,348]) than patients with adult-onset asthma (65.7 IU/mL [n = 1,956]) (P < .001). CONCLUSION: In patients with severe or difficult-to-treat asthma from the TENOR study, higher total IgE levels were observed in males, children, smokers, nonwhite racial/ethnic groups, and adults with childhood-onset disease. In addition, IgE levels are associated with asthma severity among younger patients.     

Serial cytokine levels in patients with severe sepsis

Objective and design  The serial or dynamic changes of cytokine levels in severely septic patients, between shock and no shock, survivors and non-survivors are still unclear. Methods  Seventy-six patients with severe sepsis were enrolled to our study. Plasma levels of interferon-γ, interleukin (IL)-6, IL-10, IL-12 and transforming growth factor-β1 from day 1 to day 7 were determined. Results  IL-6 level in non-survivors was higher than that in survivors on day 1. IL-10 level in non-survivors was higher than that in survivors on day 1, 2, and 3. IL-6 level in shock patients was higher than that in non-shock patients on day 1, 2, 6 and 7. IL-10 level in shock patients was higher than that in non-shock patients from day 1 to day 7. Plasma time-course curves of IL-6 and IL-10 were different between survivors and non-survivors. Plasma time-course curve of IL-6 was different between patients with shock and without shock. Regression analysis found that IL-6 was correlated with IL-10 and shock. IL-10 was correlated with IL-6 and mortality. Conclusion  IL-6 and IL-10 were the key cytokines in the pathogenesis of severe sepsis. IL-6 was comparatively more associated with septic shock and IL-10 was comparatively more associated with mortality.     

颈动脉的形态与动脉粥样硬化的解剖学观测

目的研究颈动脉的形态与动脉粥样硬化的情况,为颈总、颈内动脉狭窄的诊治提供形态学基础。方法解剖观测成尸30(男24、女6)侧颈动脉,观测颈动脉的形态及动脉粥样硬化情况。结果①颈总动脉中段外径,左侧(8.75±1.56)mm;右侧(8.31±0.99)mm。②颈内动脉根部外径,左侧(8.15±1.42)mm;右侧(7.51±1.63)mm。③颈外动脉中段外径,左侧(4.87±1.09)mm;右侧(4.39±0.89)mm。④颈动脉粥样硬化发生率占60%(18侧),其中颈内动脉根部四壁明显动脉硬化,内腔直径1.6mm严重狭窄1侧,占总数的3.33%。结论颈动脉粥样硬化发生率最高为颈动脉窦,占颈动脉硬化标本的100%,可致颈内动脉内腔狭窄。