Hemocompatibility studies of surface-treated polyurethane-based chronic indwelling catheters

The objectives of this research were to evaluate and compare the interactions of several polyurethane-based central venous catheter materials with blood. Specifically, measurements of fibrinogen adsorption, platelet adhesion, kallikrein generation, and fibrinopeptide A (FPA) release were performed. The catheter materials examined in this study included: platinum-cured, 50 shore A durometer, barium sulfate-filled, silicone (SI); Tecoflex EG85A-B20 polyurethane (PU); PU catheters whose outer surface had been impregnated with ion beam-deposited silver atoms (AgI and AgII); PU catheters coated with a hydrophilic, polyacrylic acid polymer (UC); PU catheters coated with an air-cured PTFE emulsion (CS); and PU catheters coated with an aminofunctional dimethylsiloxane copolymer (JG). The time course of fibrinogen adsorption from plasma to the SI, JG, PU, and CS materials was similar, with CS exhibiting the least amount of adsorbed fibrinogen after 1 h (65±4.7 ng cm^-2) and PU the greatest (144±16.5 ng cm^-2). After 90 min of contact, AgI and AgII exhibited the greatest number of adherent platelets, levels that were approximately two to three times higher than those on the other catheter materials. With the exception of UC and PU, which caused kallikrein generation levels approximately half that of the positive (glass) control, little kallikrein formation was observed for any of the materials relative to the negative control. Finally, FPA generation was greatest using the SI, CS, and PU materials, with the latter causing the production of almost four times the amount of FPA as the negative control. This preliminary assessment of the hemocompatibility of the various catheters suggests that the surface treatments did not adversely affect their interactions with blood components; further investigations of these materials are therefore warranted in order to completely characterize their behavior prior to use in clinical situations.     

新型FGG基因突变导致遗传性纤维蛋白原缺陷症的研究

目的:对临床发现的1例遗传性纤维蛋白原缺陷症患者及其家属进行凝血相关指标检测和基因型分析,并探讨可能的分子发病机制。方法:采集先证者及其家属共4人的外周血,检测凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(Fg)、D-二聚体及8项凝血因子指标。对编码纤维蛋白原3条肽链的FGA、FGB和FGG基因的所有外显子和侧翼序列进行测序并进行生物信息学分析。结果:先证者及其长姐的8项凝血因子中FⅤ、FⅧ稍高,TT明显延长,Fg明显降低;测序结果显示FGG基因存在c.901C>T杂合突变。生物信息学分析显示,突变改变了原有的蛋白结构,减少了氢键数目。结论:纤维蛋白原γ链c.901C>T杂合突变是引起该家系遗传性纤维蛋白原缺陷的主要原因,该突变是首次在国内外报道。     

术前纤维蛋白水平与结肠癌预后的关系

目的探讨术前纤维蛋白水平对结肠癌患者预后的预测价值,寻求结肠癌预后的新的预测指标。方法收集自2007年1月至2008年12月于我科就诊,并行根治性手术的结肠癌患者的临床资料。分别按照体重指数、肿瘤大小、分期、分化程度、大体分型、血管浸润情况、CEA水平、mGPS评分对患者进行分组,比较组间患者术前纤维蛋白水平的差异及术后生存情况的差异。结果本次研究共纳入结肠癌患者255例,患者的术前平均纤维蛋白水平为(3.17±0.88)g/L。不同肿瘤大小、分期、分化程度、大体分型、血管浸润情况、CEA、mGPS评分组患者术前纤维蛋白水平相比差异有统计学意义(P0.05)。单因素分析结果显示术前纤维蛋白水平与结肠癌患者术后总体生存情况有关(P0.05)。结论术前纤维蛋白水平与结肠癌患者临床病理特征有关,可作为预测患者预后的指标之一。     

Liposuction in Dercum's disease: impact on haemostatic factors associated with cardiovascular disease and insulin sensitivity

Berntorp E, Berntorp K, Brorson H, Frick K (University of Lund, Malmö, Sweden). Liposuction in Dercum's disease: impact on haemostatic factors associated with cardiovascular disease and insulin sensitivity. J Intern Med 1998; 243 : 197–201.

Objective

To study the impact of adipose tissue removal by liposuction on factors associated with increased risk of cardiovascular atherosclerotic disease within the coagulation and fibrinolytic system and glucose metabolism.

Design, setting and subjects

Liposuction was performed in 53 patients with Dercum's disease. The levels of fibrinogen, von Willebrand factor antigen (VWF:Ag) and plasminogen activator inhibitor type 1 activity (PAI-1) were measured preoperatively, and 2 weeks, 4 weeks and 3 months postoperatively. In a subsample of 10 patients, insulin sensitivity was determined before and 2–4 weeks after surgery using the 2-h euglycaemic hyperinsulinaemic clamp technique. The study was performed as a single-centre study.

Main outcome measure

Fibrinogen, PAI-1 and VWF:Ag levels, and glucose uptake before and after removal of adipose tissue.

Results

Weight reduction was sustained throughout the follow-up period with a mean decrease from 90.7 to 86.6 kg (P < 0.0001). There was a slight increase in levels of coagulation factors 2 and 4 weeks postoperatively, probably in reaction to the surgical trauma. After 3 months the values had returned to preoperative levels except for PAI-1, which still showed a slight increase (P < 0.05). In the subsample of 10 patients, glucose uptake was improved (P < 0.05) from a short-term perspective after surgery.

Conclusion

Surgical removal of adipose tissue, without change in lifestyle, does not seem to improve the levels of coagulation and fibrinolytic factors associated with cardiovascular atherosclerotic disease, whereas glucose takeup may be facilitated and insulin sensitivity increases from a short-term perspective.

     

Treatment of acute myocardial infarction with subcutaneous heparin at low doses

Heparin has been used intensively in the treatment of acute myocardial infarction and preinfarction angina (PA) at full doses as a single drug by us. However, heparin may be used at smaller doses for similar purposes. These doses are not exactly anticoagulant, even though they reduce blood hypercoagulability, and act mainly in an antithrombotic capacity. We studied 529 patients with acute myocardial infarction, of whom 262 were treated with subcutaneous heparin at low doses (5000 IU every 12 h) and 267 received conventional therapy without antithrombotic drugs. Heparin used was Heparina (Abbott) and Liquemine (Roche), in vials with the equivalence 1 cm3 = 50 mg = 5000 IU. Blood rheologic factors (thromboelastography, platelet adhesiveness, total blood viscosity, and number of platelets) were determined in all patients, those treated with heparin at low doses and also the control group, before and after the 30-day treatment period. Diagnosis was based on clinical symptoms, laboratory studies, and electrocardiogram examination. In both the 262 patients treated with heparin at low doses and in the control group of 267 patients, baseline values of rheological factors were high. After 30 days (i.e., after study completion) these high values which are statistically significant compared with normal values, with p less than 0.0001 for both groups, remained constant in the control group who did not receive heparin. On the contrary, in the group treated with heparin at low doses, all these factors changed. Heparin provides protection against thrombosis by increasing the negative charge of the vessel wall and by other reactions at the endothelial surface. Heparin requires a plasmatic component called antithrombine III.(ABSTRACT TRUNCATED AT 250 WORDS)     

Platelet and haemorheological markers in 'high risk' hypertensives are improved by tighter blood pressure control and cardiovascular risk management: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)

OBJECTIVE: To investigate the impact of intensified cardiovascular risk management on soluble markers of platelet, endothelial and rheological function in a population of middle-aged hypertensive patients at high risk of cardiovascular complications. DESIGN: Prospective follow-up study. SUBJECTS AND METHODS: A total of 159 hypertensive patients [138 male, mean age 64 (+/-8) years] and 80 healthy controls were studied. Plasma levels of soluble P-selectin (sP-sel, a marker of platelet function), von Willebrand factor (vWF, an index of endothelial damage/dysfunction) and rheological indices [fibrinogen (Fib), plasma viscosity (PV), haematocrit (HCT), white blood count (WBC) and platelet count] were measured at baseline and again (in the patients) after 6 months' treatment. RESULTS: As expected, 6 months of intensified cardiovascular risk management resulted in a significant fall in mean blood pressure (BP) and total cholesterol. It also resulted in reduced haematocrit, vWF, sP-sel, WBC and PV levels (all P < 0.001), but not plasma fibrinogen. There were no correlations between the fall in BP and the improvement in any of the research indices. CONCLUSIONS: Intensified cardiovascular risk management results in significant improvements in indices of endothelial, platelet and rheological function in a population of hypertensives at high risk of cardiovascular events. These improvements appear to be independent of the degree of change in BP. Given the fundamental role of interactions between the endothelium and circulating blood components in the pathogenesis of hypertensive complications this may be of importance in preventing adverse cardiovascular outcomes.     

Identification of simultaneous mutation of fibrinogen alpha chain and protein C genes in a Japanese kindred

Afibrinogenaemia usually induces a bleeding tendency during infancy, whereas protein C deficiency increases susceptibility to thrombosis in children or adolescence. Mutations of these genes have been, therefore, established as independent risk factors for coagulation disorders. We describe the homozygous mutation of the fibrinogen alpha chain gene and additional heterozygous mutation of the protein C gene in a male infant who showed prolonged umbilical bleeding after birth. On examination, the plasma fibrinogen was undetectable, and the activity and antigen level of protein C were reduced. The patient showed no fibrinogen Aalpha chain as well as Bbeta and gamma chains by Western blotting. The sequencing analysis showed the homozygous deletion of 1238 bases from intron 3 at position 2008 to intron 4 at position 3245 in the fibrinogen alpha chain gene. Both parents were heterozygous carriers of this mutation. In this patient, an additional mutation was also detected in the protein C gene: the heterozygous deletion of exon 7 at position 6161-6163 or 6164-6166, resulting the deletion of one amino acid (Lys150 or 151). His mother was also a carrier of this mutation. As the simultaneous mutation of the fibrinogen alpha chain and protein C genes has not been previously reported, the influence of the interaction between these two mutations on the clinical manifestations of this patient should be carefully monitored for a long period.     

老年2型糖尿病患者颅内动脉粥样硬化与亚临床甲状腺功能减退的关系

目的探讨老年2型糖尿病(T2DM)患者颅内动脉粥样硬化与亚临床甲状腺功能减退(SCH)的相关性。方法选择老年T2DM患者404例,其中甲状腺功能正常组(甲功正常组)291例,SCH组113例,比较2组一般情况及各生化指标的差异。分析促甲状腺激素(TSH)与各临床指标的相关性。结果 SCH组女性、颅内动脉粥样硬化、TC、TG、LDL-C、脂蛋白(a)、纤维蛋白原、C反应蛋白、血尿酸、同型半胱氨酸较甲功正常组明显升高,空腹血糖[(6.03±1.32)mmol/L vs(7.61±0.93)mmol/L]、HDL-C[(1.25±0.46)mmol/L vs(1.41±0.49)mmol/L]、D-二聚体[(0.23±0.11)mg/L vs(0.55±0.27)mg/L]显著降低(P<0.05)。TSH、年龄、收缩压、LDL-C、纤维蛋白原、血尿酸、同型半胱氨酸是颅内动脉粥样硬化独立的危险因素,且TSH与纤维蛋白原、TC、TG、LDL-C、脂蛋白(a)、C反应蛋白、血尿酸、同型半胱氨酸呈正相关,与空腹血糖、D-二聚体、HDL-C呈负相关(P<0.05)。结论老年T2DM合并SCH发生颅内动脉粥样硬化风险增加,高TSH是T2DM患者颅内动脉粥样硬化的独立危险因素。     

冠状动脉药物洗脱支架置入术后再狭窄与胆红素和纤维蛋白原关系探讨

目的探讨冠状动脉药物洗脱支架术后支架内再狭窄与血清总胆红素(TB)和纤维蛋白原(Fib)的关系。方法收集PCI置入药物洗脱支架术后1年行冠状动脉造影随访的782例患者,分为再狭窄组130例和对照组652例。回顾性分析2组患者临床资料的差异。结果再狭窄组与无再狭窄组患者血清TB[(11.82±4.53)μmol/Lvs(12.95±5.06)μmol/L]、Fib[(3.04±0.65)g/L vs(2.83±0.60)g/L]比较,差异有统计学意义(P<0.05,P<0.01)。支架内再狭窄与糖尿病(OR=1.763,95%CI:1.158².683)、Fib(OR=1.678,95%CI:1.2422.683)、Fib(OR=1.678,95%CI:1.242².266)呈正相关,与血清TB(OR=0.922,95%CI:0.8602.266)呈正相关,与血清TB(OR=0.922,95%CI:0.860⁰.988)、支架直径(OR=0.615,95%CI:0.4440.988)、支架直径(OR=0.615,95%CI:0.444⁰.850)呈负相关。结论糖尿病、Fib为支架内再狭窄的危险因素,支架直径和血清TB为支架内再狭窄保护因素。