炎症和凝血活化亢进在仓鼠胆囊胆固醇结石形成中作用的实验研究

目的：探讨胆囊炎症、胆汁凝血和纤溶与胆石形成之间的内在联系。 方法： 将仓鼠随机分为4组：正常组（喂养普通饲料6周），致石2周组（喂养致石饲料2周），致石6周组（喂养致石饲料6周），致石6周加阿司匹林组（喂养致石饲料和阿司匹林6周）。观察胆石形成情况、检测胆汁中D-二聚体（D-dimer）、C反应蛋白（CRP）、抗凝血酶Ⅲ抗原（AT-Ⅲ:Ag）含量、抗凝血酶Ⅲ活性（AT-Ⅲ:Ac）、凝血酶活性（F-Ⅱa:Ac）、纤溶酶活性（Plm:Ac）、纤溶酶原激活物抑制物活性（PAI:Ac）。 结果： 正常组、致石2周组、致石6周组和致石6周加阿司匹林组的胆石发病率分别为0%、20%、73%和25%。致石2周组和致石6周组胆汁的AT-Ⅲ:Ag、F-Ⅱa:Ac、D-dimer和CRP都明显高于正常组（P<0.01）；致石6周组的AT-Ⅲ:Ag、PAI:Ac、Plm:Ac、D-dimer和CRP明显高于致石2周组（P<0.01）。致石6周加阿司匹林组的D-dimer明显高于正常组（P<0.01）。致石6周加阿司匹林组的AT-Ⅲ:Ag、F-Ⅱa:Ac、PAI:Ac、D-dimer和CRP明显低于致石6周组（P<0.01）。CRP与D-dimer含量呈显著正相关（γ=0.752, P<0.01）。 结论： 胆石形成前即有凝血活化和交联纤维蛋白形成。“成石胆汁”通过刺激胆囊壁，引起胆囊壁炎症反应，从而使胆囊胆汁凝血活化，导致胆固醇结石的形成。     

临产孕妇凝血四项指标的变化及临床意义

为了解临产孕妇的凝血功能情况，本文检测了205例临产孕妇的凝血四项指标：即凝血酶原时间(FT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、凝血酶时间(TT)，结果报告如下。     

肝癌患者组织中凝血及纤溶因子的基因表达检测与分析

目的:检测组织因子（TF）、尿激酶型纤溶酶原激活物（uPA）及其受体（uPAR ）mRNA在肝细胞癌组织中的表达并探讨其临床意义。 方法:利用RT-PCR法分别检测27例肝细胞癌、癌旁及27例正常肝组织中TF、uPA、uPA mRNA表达阳性率及相对表达强度，并结合临床病理资料进行分析。 结果:TF、uPA、uPAR在肝细胞癌组织中阳性率及相对表达强度分别为62.96%（17/27）、70.37%（19/27）、77.78%（21/27）；0.567±0.268、0.964±0.458、0.784±0.322,均显著高于癌旁组织及正常组织，差异显著(P<0.05)。3者在肝癌组织中相对表达强度与肿瘤大小及部分侵袭转移指标有关，其中TF mRNA表达强度在肝内及肝外转移及门脉癌栓组高于无肝内及肝外转移及无门脉癌栓组(P<0.05) ，uPA mRNA在有包膜侵润、肝内转移及门脉癌栓组高于无包膜侵润、无肝内转移及门脉癌栓组(P<0.05)；uPAR mRNA在有肝内转移及门脉癌栓组高于无肝内转移及门脉癌栓组(P<0.05)。经Pearson检验肝细胞癌患者TF、uPA和uPAR mRNA表达呈正相关［TF-uPA：r=0.373(P<0.01)，TF-uPAR：r=0.534(P<0.01)，uPA-uPAR：r=0.365 (P<0.01)］。 结论:肝细胞癌组织中TF、uPA及uPAR的mRNA显著升高并与部分侵袭转移指标有关，提示3者可能在肝细胞癌的发生及侵袭转移起协同作用。     

妊高征患者凝血功能测定的临床评价

目的探讨凝血指标变化在妊高征患者发病过程中的作用。方法检测了80例妊高征患者的PT、APTT、Fib及国际标准化比值INR并与30例正常妊娠组结果进行比较。结果妊高征组与正常妊娠组比较,PT、INR、APTT及Fib结果均有显著性差异(P<0.01)。结论在临床工作中,如果发现妊高征患者PT、APTT明显降低,Fib含量持续升高,则需警惕发生子痫的可能。     

凝血和纤溶与缺血性脑血管病

缺血性脑血管病的ＰＬｇ含量增高，ｔ－ＰＡ活性及释放水平减低，对静脉加压阻断试验反应较差，说明ｔ－ＰＡ释放存在着暂时缺陷。而纤维蛋白肽Ａ（ＦＰＡ）水平在缺血性脑血管各期均增高，交联Ｄ二聚体（ＸＤＰ）水平在亚急性期和慢性期增高，纤维蛋白肽Ｂβ１－４２和Ｂβ１５－４２水平在各期均不增高，提示缺血性脑血管病存在着凝血功能亢进和纤溶系统受损。     

qLabs ®手持快速电化学检测仪与Sysmex CA7000凝血分析仪测定凝血四项的对比分析

目的探讨qLabs^?手持快速电化学检测仪和Sysmex CA7000凝血分析仪对凝血四项检测结果的可比性。 方法通过收集东南大学附属中大医院50例患者的血液标本,分别使用qLabs^?手持快速电化学检测仪(电化学法)和Sysmex CA7000凝血分析仪(仪器法)对同一例患者的周围静脉血和指端血进行凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)凝血四项测定,所用试剂分别为2种测定仪所指定的配套试剂。检测同一指标2种仪器所用各自试剂相关性应用二元变量相关分析;比较2种方法所测凝血四项值、采血时疼痛评分及耗时。对数据行配对t检验。 结果2种检测方法各自所用试剂具有较好的相关性,PT的相关系数(r)＝0.90,APTT的相关系数(r)＝0.88,TT的相关系数(r)＝0.80,FIB的相关系数(r)＝0.80;2种方法检测凝血四项PT、APTT、TT、FIB值比较,差异均无统计学意义(t＝1.68、0.68、0.85、1.30,P值均大于0.05);仪器法、电化学法采血所造成的的疼痛评分分别为(3.8±1.5)、(2.0±1.1)分,差异有统计学意义(t＝2.64,P<0.05);仪器法、电化学法从采样到出结果耗时分别为(195.00±10.50)、(3.00±0.30) min,差异有统计学意义(t＝2.66,P<0.05)。 结论qLabs^?手持快速电化学检测仪与Sysmex CA7000凝血分析仪配套试剂相关性良好;qLabs^?手持快速电化学检测仪在测定凝血四项时与Sysmex CA7000凝血分析仪的测定结果具有一致性,而在获取结果较快和减轻采样时疼痛方面具有一定优势。     

恶性肿瘤患者凝血功能检测的临床意义

目的:研究肺癌、乳腺癌、食道癌、胃癌、肝癌及肾癌等恶性肿瘤患者的凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、血小板计数(PLT)的变化并探讨其临床意义。方法:检测恶性肿瘤患者的PT、APTT、FIB和PLT,并与健康体检者的上述指标进行对照。结果:肝癌、肾癌组患者的PT,肝癌、肾癌、肺癌及食道癌组患者的APTT较健康对照组显著延长,差异有统计学意义(P0.05);FIB含量除肝癌组外,其他各肿瘤组均显著高于健康对照组,差异有统计学意义(P0.05);PLT在乳腺癌、肺癌、胃癌组显著增高,肝癌组显著低于健康对照组,差异有统计学意义(P0.05)。结论:与对照组相比,恶性肿瘤患者的PT、APTT时间显著延长,PLT数量及FIB含量增高,是发生血栓性疾病的高危人群,对肿瘤患者进行适当抗凝药物的使用有助于减少血栓性疾病的发生并降低远处转移的机会。     

67例早产儿凝血功能分析

目的探讨早产儿凝血功能的特点及其与早产儿出血的关系。方法于生后24h内采取股静脉防凝血,对67例早产儿、42例足月新生儿测定凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（T T）、纤维蛋白原（FIB）。结果与足月新生儿比,早产儿PT、APTT明显延长,纤维蛋白原值偏低,差异具高度统计学意义,低纤维蛋白原血症检出率比足月儿高。结论早产儿生后普遍具出血倾向,要积极防治早产儿出血。建议将凝血功能列为早产儿的常规检测指标。     

肿瘤坏死因子α和血管紧张素Ⅱ诱导血管内皮细胞组织因子基因表达及其机制的研究

目的；研究肿瘤坏死因子α（TNFα），血管紧张素Ⅱ（AngⅡ)对内皮细胞组织因子（TF）表达的影响，并探讨TF基因5‘上游序列在TNFα，AngⅡ诱导内皮细胞该基因转录中的调控作用。方法：应用细胞原位杂交技术检测TF mRNA水平。采用基因重组技术构建含有人TF基因不同上游序列荧光毒酶报告基因质粒，经脂质体法转染内皮细胞，检测及分析报告基因活性。结果：TNFα和AngⅡ均可以诱导内皮细胞TF mRNA的表达增强。在TF基因上游序列－244／＋121bp存在时，TNFα，AngⅡ均可使转梁内皮细胞荧光素酶表达量明显增加，而在－111／＋121bp存在时TNFα，AngⅡ组与对照组荧光素酶表达量均无明显差异，而且较－244／＋121bp存在时荧光素酶表达量明显降低。结论：TF基因上游－244／－112bp序列的存在对TNFα，AngⅡ诱导内皮细胞TF基因表达起重要的调节作用。     

Differences in gallstone structure in primary common bile duct lithiasis and gallbladder lithiasis

Summary Some differences between gallbladder lithiasis and primary common bile duct lithiasis are described. Microbiological cultures and biochemical analyses were carried out on the bile of two groups of patients: 27 suffering from gallbladder and 5 from primary common duct lithiasis. The microstructure and composition of gallstones were also examined by polarized light microscopy and X-ray diffraction. Women predominated in gallbladder lithiasis but not in primary common duct lithiasis group (P<0.05) and body weight was higher in the former group (P<0.02). Primary common duct lithiasis patients had a higher, although not significant, incidence of duodenal diverticulosis (P=0.15), and a higher incidence ofE. coli-positive cultures in bile (P<0.001). No significant difference in the biochemical composition of the bile was found between the groups. Brown pigment stones predominated in primary common duct lithiasis, while cholesterol stones did in gallbladder and secondary common duct lithiasis (P<0.0001). Stones formed in the gallbladder generally show linear, radial growths of cholesterol crystals, while those from the common duct present a polystratified, concentric deposition of microgranules composed mainly of pigmentary salts.These differences should be taken into account as additional criteria in the differential diagnosis between primary and secondary common duct lithiasis, as the classical criteria for diagnosing of the former greatly underestimate its actual incidence. The distinction between primary and secondary common duct lithiasis is of practical significance, since each entity requires different treatment.Abbreviations CBD common bile duct - CBDL common bile duct lithiasis - ERCP endoscopic retrograde cholangiopancreatography - GBL gallbladder lithiasis - HDL high density lipoproteins - PCBDL primary common bile duct lithiasis - SCBDL secondary common bile duct lithiasis - SGOT serum glutamic-oxalacetic transaminase - SGPT serum glutamic-pyruvic transaminase     

Indomethacin decreases viscosity of gallbladder bile in patients with cholesterol gallstone disease

Summary There is experimental evidence that inhibition of cyclooxygenase with nonsteroidal anti-inflammatory drugs may decrease cholesterol gall-stone formation and mitigate biliary pain in gall-stone patients. The mechanisms by which NSAIDs exert these effect are unclear. In a prospective, controlled clinical trial we examined the effects of oral indomethacin on the composition of human gall-bladder bile. The study included 28 patients with symptomatic cholesterol or mixed gallstones. Of these, 8 were treated with 3 × 25 mg indomethacin daily for 7 days prior to elective cholecystectomy while 20 received no treatment and served as controls. Bile and tissue samples from the gallbladder were obtained during cholecystectomy. Indomethacin tissue levels in the gallbladder mucosa, as assessed by HPLC, were 1.05±0.4 ng/mg wet weight, a concentration known to inhibit effectively cyclooxygenase activity. Nevertheless, no differences between the treated and untreated groups were found in the concentrations of biliary mucus glycoprotein (0.94±0.27 versus 0.93±0.32 mg/ml) or total protein (5.8±0.9 versus 6.4±1.3 mg/ml), cholesterol saturation (1.3±0.2 versus 1.5±0.2), or nucleation time (2.0±3.0 versus 1.5±2.0 days). However, biliary viscosity, measured using a low-shear rotation viscosimeter, was significantly lower in patients receiving indomethacin treatment (2.9±0.6 versus 5.6±1.2 mPa.s; P < 0.02). In conclusion, in man oral indomethacin decreases bile viscosity without alteration of bile lithogenicity or biliary mucus glycoprotein content. Since mucus glycoproteins are major determinants of bile viscosity, an alteration in mucin macromolecular composition may conceivably cause the indomethacin-induced decrease in biliary viscosity and explain the beneficial effects of nonsteroidal anti-inflammatory drugs in gallstone disease.Abbreviation NSAIDs nonsteriodal anti-inflammatory drugs Dedicated to Prof. Dr. G. Paumgartner on the occasion of his 60th birthday     

Effects of the converting enzyme inhibitor captopril on blood coagulation and fibrinolysis in man

Summary Systematic blood coagulation analyses were conducted in 32 severely hypertensive patients treated with the angiotensin converting enzyme inhibitor captopril. Two hours after the first captopril dose, fibrin monomer complexes had already increased. This rise was even more distinct after 26 h and 1 week. Tests after 6 and 12 months of therapy showed a regression of fibrin monomer complexes to pretreatment values. In several patients with a marked increase in fibrin monomer complexes, the partial thromboplastin time (PTT) became shorter and antiplasmin activity increased. The most pronounced increase in fibrin monomer complexes was seen in patients with a rapid and excessive blood pressure reduction.The concentration of fibrin monomer complexes also rose in 15 healthy normotensive subjects, after a single oral dose of captopril (25 mg). Additionally, the PTT was shortened and antiplasmin significantly rose. An inhibition of fibrinolysis by captopril could be demonstrated by the effect on fibrin plates and thrombus weight after streptokinase. Out of 58 patients with severe hypertension and atherosclerosis treated with captopril, 7 patients suffered vascular complications during antihypertensive therapy: myocardial infarction (n=2), coronary insufficiency (1), cerebral ischemia (1), renal insufficiency (3). These ischemic lesions may be partly explained by the alterations of coagulation and fibrinolysis under captopril therapy.Dedicated to Prof. Dr. H.-J. Bretschneider on the occasion of his 60th birthday     

Abnormal blood clot formation induced by temperature responsive polymers by altered fibrin polymerization and platelet binding

Thermoresponsive polymers (TRPs) have been extensively investigated as smart devices, drug delivery systems and protein conjugates due to their unique phase transition properties. Here, we report the unusual influence of TRPs in blood clotting and the mechanism by which TRPs change the three dimensional organization of blood clot structure. Ten different TRPs with lower critical solution temperatures ranged from 26 to 80 °C are studied. TRPs altered the fibrin polymerization by increasing the rate of protofibril aggregation, decreased the fibrin fiber diameter and changed the platelet integration within the clot. The mechanical properties of the clot decreased considerably in presence of TRPs due to the poor platelet binding. The poor integration of platelets within the clot is not due to the inhibition of platelet activation by TRPs but may due to the unusual organization of fibrin structure. The plasma phase of the blood coagulation is not affected in presence of TRPs. We anticipate that our results will have significant implications on the use of TRPs in applications where blood contact is essential. These observations may also open up new avenues, for example, in the design of new generation antithrombotics.     

Immunohistochemical study on the liver in autopsy cases with disseminated intravascular coagulation (DIC) with reference to clinicopathological analysis

Summary Immunohistochemical and clinicopathological studies were performed in 27 autopsy cases with indisputable DIC, which had been selected from 1,800 autopsy cases of elderly people based on the following two criteria; 1. presence of fibrin thrombi in glomeruli, and 2. presence of fresh patchy necrotic foci in myocardium and/or fibrin thrombi in splenic sinuses. A high incidence of liver lesions (22/27) was revealed in autopsy cases with indisputable DIC. The liver lesions could be classified into four groups. Group-I (Central degeneration) was characterized by massive precipitation of fibrin irregularly around the central vein, causing parenchymal damage. Group-II (Central necrosis), showed coagulation necrosis in the cental zone due to circulatory disturbance caused by either shock as a cause of DIC or abrupt cessation of blood flow into the lobules following fibrin thrombus formation in vessels of Glisson's sheath. Both group-I and -II showed a short clinical duration of DIC. Group-III (Sinusoidal thrombosis), showed the presence of fibrin thrombi in sinusoids with mild parenchymal damage and long clinical duration of DIC. Group-IV (No thrombosis), showed neither parenchymal damage nor fibrin thrombi in sinusoids, but a long clinical duration of DIC.     

Rokitansky-Aschoff sinuses of the gallbladder are associated with black pigment gallstone formation: a scanning electron microscopy study

Rokitansky-Aschoff sinuses are the result of hyperplasia and herniation of epithelial cells through the fibromuscular layer of the gallbladder wall and are usually referred to as adenomyomatosis. The role of this study is to demonstrate that Rokitansky-Aschoff sinuses of the gallbladder are a risk factor for the formation of black pigment gallstones. A total of 179 removed gallbladders, were hystologically examinated. Sixty-four of the 179 consecutive cholecystomized patients had typical adenomyomatosis. Thirty-eight of the 64 patients with adenomyomatosis had black pigment gallstones, alone ( n =22) or in association with single ( n =12) or multiple ( n =4) cholesterol gallstones in the same gallbladder. Twelve of these patients did not have the typical risk factors for black stones (hemolysis, cirrhoses, gastrectomy, etc). Gallstones were examined by infrared spectroscopy and X-ray diffractometry. In addition, in a subset of 14 patients, the gallstones and the gallbladder wall were examined by scanning electron microscopy. At least in the initial phases of formation, Rokitansky-Aschoff sinuses were found close to small intraparietal vessels and sometimes they contained black pigment microstones. After the fourth to fifth decades of life, black gallstones can be found in the Rokitansky-Aschoff sinuses and in the main gallbladder lumen. Black pigment gallstones can form in Rokitansky-Aschoff sinuses of the gallbladder in absence of the typical risk factors for bilirubin suprasaturation of bile.     

肝外胆道动力学因素在胆囊结石形成中的作用

目的：探讨肝外胆道动力学因素在胆囊结石形成中的作用。方法：选用家兔４７只随机分为４组。对照组（ｎ＝１３），成石组（ｎ＝１４），消炎痛组（ｎ＝１０），红霉素组（ｎ＝１０）。饲养４周后检测成石情况、胆总管压力等指标。结果：成石组１２／１４只形成结石，消炎痛组４／１０只形成结石，红霉素组无一只形成结石。成石组胆汁中胆固醇和粘蛋白含量显著增高，胆囊管阻力和胆总管压力显著增高，胆囊排空率显著降低。消炎痛组较成石组胆汁中粘蛋白浓度降低，胆囊管阻力下降，胆总管压力下降，胆囊排空率无显著改善。红霉素组较成石组胆汁粘蛋白含量下降，胆囊管阻力下降，胆囊排空率增加而胆总管压力无显著变化。结论：除胆汁成分异常外，肝外胆道动力学因素参与了胆囊结石形成，改变肝外胆道动力学因素以促进胆囊排空，能有效地防止胆囊结石形成     

The orbital venous plexus as a sampling site for coagulation testing: The continuing saga

Papers have recently been published regarding the acceptability of samples obtained from the orbital venous plexus for coagulation testing (Dameron et al. 1992; Edwards and Fuller 1993; Matsuzawa et al. 1994; Salemink et al. 1994). Meetings of the committee for International Harmonisation for Clinical Pathology Testing (IHCPT) have highlighted the concerns of sampling from the orbital venous plexus (OVP), both ethical considerations and validity of data. In response to a letter to the editor (Weingand, 1994) and to enable informed and objective discussion of this topic, this paper presents coagulation data on samples obtained from the OVP, collected by several pharmaceutical companies using a variety of systems.     

Effect of bleeding site on coagulation results in the Charles river outbred albino SD rat

The UK Home Office currently advises that the amount of blood to be taken during a toxicology study is limited to 15% of an animal's blood volume (equivalent to approximately 1 ml per 100 g of the animal's bodyweight) in a 28 day period. At SmithKline Beecham, blood samples for routine haemtology and clinical chemistry analyses during a study have been obtained from the orbital sinus (OS). Adequate samples can be obtained for all routine assays with the exception of coagulation tests, and the possibility has been investigated of taking terminal coagulation samples from the posterior vena cava (PVC) as part of the post-mortem procedures, and compared the prothrombin (PT) and activated partial thromboplastin (APTT) times obtained on blood samples from each source. There was no biologically significant difference between samples taken from OS and PVC.Originally presented at ECCP 93.