心房颤动病人血栓形成与一氧化氮、血小板P-选择素表达关系研究

目的研究慢性心房颤动(房颤)病人血栓形成与血浆一氧化氮(NO)水平、血小板活化的关系.方法应用流式细胞仪分析窦性心律及房颤病人血小板P-选择素、糖蛋白Ⅱb/Ⅲa(GPⅡb/Ⅲa)表达,同时测定血浆NO、血栓素B2(TXB2)、6-keto-前列腺素F1α(6-keto-PGF1a)含量,计算TXB2/6-keto-PGF1a.应用N-硝基-L-精氨酸甲基酯(N-nitro-L-arginine methyl ester,L-NAME)抑制一氧化氮合酶(NOS),流式细胞仪分析其对血小板P-选择素表达的影响及L-精氨酸(L-arginine,L-Arg)预处理后L-NAME对血小板P-选择素表达的影响.结果房颤组血浆NO水平明显低于窦性心律组[(22.68±9.38)μmol/L对(31.25±14.91)μmol/L,P＜0.05];血小板P-选择素表达明显高于窦性心律组[(6.76±3.36)%对(4.86±2.09)%,P＜0.05];血小板GPⅡb/Ⅲa表达明显增高P＜0.05;血浆TXB2及TXB2/6-keto-PGF1a含量均显著增高(P＜0.001).房颤血栓形成组与房颤无血栓组血小板P-选择素表达差异无显著性[(7.77±2.90)%对(6.53±3.17)%,P＞0.05].应用L-NAME抑制NOS后,血小板P-选择素表达增加,L-Arg预处理可明显阻断这一效应.结论房颤引起的不规则心律能抑制NO合成,使血浆NO水平降低,这可能是房颤病人血小板P-选择素表达增加,血栓形成的原因之一.NO及NO前体可能预防房颤病人的血栓形成.     

持续缓慢选择性与单纯血浆置换治疗高胆红素血症

目的探讨持续缓慢选择性血浆置换（CPPE）和单纯血浆置换（SPE）治疗高胆红素血症的临床疗效。方法分析71例（139例次）接受CPPE的患者（CPPE组）治疗前、治疗结束时及治疗后48h时血清清蛋白（ALB）、球蛋白（GLO）、凝血酶原活动度（PTA）及总胆红素（TBIL）的变化情况,并与36例（79例次）接受SPE的患者（SPE组）做比较。结果①同治疗前相比,2组患者治疗结束时及治疗结束48h时血PTA值均明显升高（P均〈0．01）,但2组问比较差异无统计学意义（P〉0．05）;②同治疗前比较,CPPE组治疗结束时及治疗后48h时血清ALB、GLO差异均无统计学意义（P〉0．05）,而SPE组则明显减少（P均〈0．01）;③同治疗前比较,2组治疗结束时TBIL下降幅度差异无统计学意义（P〉0．05）,但同治疗结束时比,CPPE组治疗结束48h时血TBIL上升幅度为22．91％±12．50％,而SPE组为39．30％±25．42％,差异有统计学意义（P〈0．05）;@CPPE组患者临床治愈好转率为59．16％（42／71）,高于SPE组的38．89％（14／36）,差异有统计学意义（x^2=3．933,P〈0．05）。结论CPPE治疗高胆红素血症时,可减少新鲜冰冻血浆的用量,减少血清ALB、GLO、纤维蛋白原及凝血因子等有益物质的丢失,延缓治疗后血清TBIL反弹的幅度和速度,提高高胆红素血症患者临床治愈好转率。因此,CPPE是治疗高胆红素血症有效且安全的方法。     

血浆置换对重症肝病患者血浆vWF水平的影响

目的观察血浆置换对重症肝病患者血浆vWF水平的影响。方法前瞻性收集血浆置换治疗的重症患者临床资料及转归;采用ELISA法检测血浆置换前后血浆中vWF的含量。结果共收集73例重症肝病患者,其中50例患者出院时病情好转,23例恶化。重症肝病组血浆vWF水平为60 215.0(19 412.4,127 995.0)ng/mL,显著高于正常对照组22 500.00(5 760.00,44 700.00)ng/mL(P0.05)。血浆置换后患者血浆vWF水平为42 855.1(12 714.5,115 684.7)ng/mL,与血浆置换前比较,差异有统计学意义(P0.05)。好转组患者血浆vWF水平治疗后下降18 650.65(1727.93,81 110.42)ng/mL,显著高于恶化组7 517.82(-25 045.33,22 718.17)ng/mL(P=0.005)。结论血浆置换能够有效降低重症肝病患者血浆vWF水平,提示血浆置换有助于改善患者肝脏微循环状态,促进肝功能恢复。     

血浆吸附灌流联合血浆置换加用恩替卡韦治疗乙型肝炎相关慢加急性肝衰竭的临床疗效

目的观察血浆吸附灌流(PP)联合血浆置换(PE)的组合型人工肝方法加恩替卡韦抗病毒治疗乙型肝炎相关慢加急性肝衰竭(HBV-ACLF)的临床疗效。方法将PP和使用少量血浆的PE联合在1次治疗模式中完成,治疗35例68例次肝衰竭患者,检测治疗前、结束时及治疗结束72 h时患者血清总胆红素(TBil)、凝血酶原活动度(PTA)、血清白蛋白(Alb),与同期进行的34例66例次单纯PE治疗患者做对照,两组患者皆予恩替卡韦抗病毒治疗。结果 (1)治疗1个月时并发症发生率2组间差异无统计学意义(P>0.05)。治疗1个月时HBV DNA下降超过100倍的患者比率分别为治疗组68.6%,对照组61.8%,2者差异无统计学意义(P>0.05)。(2)治疗组和对照组患者治疗1个月时好转率(62.9%,61.8%),生存率(68.6%,64.7%),累积3个月生存率(65.7%,64.7%),6个月生存率(65.7%,61.8%),差异皆无统计学意义(P均>0.05)。(3)2组患者治疗结束及治疗结束72 h时TBil均明显低于治疗前水平(P均<0.05),治疗组在治疗结束时TBil下降幅度更大(P<0.05),在治疗结束72 h时2组间比较差异无统计学意义(P>0.05)。治疗组患者在治疗结束时PTA无明显升高(P>0.05),而对照组在治疗结束时PTA升高(P<0.05)。治疗组患者在治疗结束时Alb较治疗前无明显变化(P>0.05),而对照组在治疗结束时Alb显著升高(P<0.05)。结论本研究建立的PP联合PE及恩替卡韦抗病毒治疗方法,血浆用量少,抗病毒疗效好,治疗HBV-ACLF患者安全有效。     

MELD在评价血浆置换治疗重型肝炎疗效中的作用

目的应用终末期肝病评分模型评价血浆置换治疗重型肝炎的临床疗效。方法 62例重型肝炎患者在内科综合治疗基础上联合血浆置换治疗,分析血浆置换治疗前后实验室指标的变化,并随访所有患者3个月内的临床转归。结果血浆置换治疗明显降低胆红素、胆汁酸、丙氨酸氨基转移酶水平;血浆置换治疗后患者3个月实际病死率是56.5%,显著低于预期病死率75.8%(P0.05),尤其在MELD30分的患者中疗效显著。而对于MELD≥30分组血浆置换治疗并不能改善预后。结论血浆置换是治疗重型肝炎的有效、安全的肝脏支持装置,对MELD30分以下者能显著改善预后。     

血浆置换对肝衰竭患者细胞因子表达的影响

目的观察人工肝血浆置换术治疗对肝衰竭患者血清白细胞介素(IL)6、肿瘤坏死因子(TNF)α及干扰素(IFN)γ的清除效果,进一步探讨人工肝支持系统在肝衰竭治疗中的意义。方法收集2012年2月至2013年2月在蚌埠医学院第一附属医院住院的36例肝衰竭患者,分别在血浆置换术前及多次治疗后的次日清晨采集血标本。用ELISA法测定血浆TNFα、IL-6、IFNγ的含量,计量资料治疗前后组间比较采用t检验,多组间比较采用方差分析,进一步两两比较采用SNK-q检验。结果 36例肝衰竭患者TNFα、IL-6、IFNγ治疗前分别为(381.23±190.57)ng/L、(77.9±83.09)ng/L、(534.65±471.19)ng/L,治疗后分别为(274.12±212.30)ng/L、(54.8±63.32)ng/L、(259.65±312.26)ng/L,治疗前后比较,差异均有统计学意义(P值均0.05)。亚急性肝衰竭和慢加急性(亚急性)肝衰竭患者根据临床表现的严重程度又分为早期、中期和晚期。结果发现,IL-6、TNFα在早、中、晚期组比较差异均有统计学意义(P值均0.05);IFNγ早、中、晚期组差异有统计学意义(P0.05);进一步两两比较IFNγ早期组与晚期组、中期组与晚期组相比,差异均有统计学意义(P值均0.05)。经过人工肝血浆置换治疗,其中有29例肝衰竭患者好转痊愈,余7例恶化,TNFα、IL-6、IFNγ在好转痊愈组降低程度分别为(122.58±57.64)ng/L、(26.93±7.25)ng/L、(284.06±94.31)ng/L,均显著高于恶化组下降水平(P值均0.05)。急性肝衰竭有效率为66.67%,亚急性肝衰竭有效率为85.71%,慢加急性(亚急性)肝衰竭有效率为86.36%,慢性肝衰竭有效率为50.00%。结论连续的人工肝血浆置换术治疗,能有效清除肝衰竭患者血浆促炎性细胞因子水平,改善患者临床症状。     

血浆置换治疗对急性肝衰竭患者血清炎性细胞因子水平的影响

不少研究证实急性肝衰竭及伴随的多器官功能衰竭与体内多种炎性细胞因子的异常升高密切相关。如何降低炎性细胞因子水平,调节机体免疫状态成为治疗急性肝衰竭的重要措施之一。常规内科药物治疗较难有效清除体内蓄积的毒性物质、降低炎性细胞因子水平。人工肝支持治疗是近年发展迅速的终末期肝病的非内科治疗手段。[第一段]     

Efficacy of liver assisting in patients with hepatic encephalopathy with special focus on plasma exchange

Severe liver injury result in development of hepatic encephalopathy (HE) and often also in brain edema that is a potentially fatal complication. HE and brain edema are correlated to the level and persistence of hyperammonemia and the presence of systemic inflammation. Treatment of HE and brain edema is based on restoring and keeping normal physiological variables including tonicity, blood gasses, lactate, temperature and vascular resistance by a wide variety of interventions. In addition liver support devices improve the stage of HE, cerebral metabolic rate for oxygen and glucose, and are used either as a bridge to liver transplantation or liver recovery in patients with fulminant hepatic failure and in patients with acute-on-chronic liver failure. This short review will mainly focus on the management and efficacy of doing plasma exchange on HE in patients with acute HE.     

血浆置换治疗慢性重型肝炎

目的：探讨血浆置换治疗慢性重肝炎的疗效机制。方法：将25例慢性重型肝炎患者分为治疗组与对照组，对照组入院后给予内科综合治疗，治疗组在内科综合治疗的基础上加血浆置换治疗。检测两组治疗前后的血氨、血浆内毒素、肿瘤坏死因子α（TNF－α）、转化生长因子β1（TGF－β1）、肝细胞生长因子（HGF）、血清氨基酸水平的变化。结果：治疗组血氨、血浆内毒素、TNF－α、TGF－β1治疗前后下降幅度较对照组明显（P＜0．05），而HGF浓度呈上升趋势；治疗组甲硫氨酸浓度下降较对照组明显（P＜0．05），其他氨基酸差异无显著性（P＞0．05），支链氨基酸与芳香族氨基酸比值无明显上升。结论：血浆置换可降低血氨、内毒素、TNF－α、甲硫氨酸等有害物质，抑制TGF－β1上升，而HGF上升，缓解炎症，抑制肝脏纤维化、促进肝细胞再生，为患者的自然恢复争取机会。     

血浆吸附灌流联合血浆置换治疗肝衰竭和高胆红素血症的临床研究

目的观察血浆吸附灌流（plasma perfusion,PP）联合血浆置换（plasma exchange,PE）的组合型人工肝方法治疗肝衰竭和高胆红素血症的临床疗效。方法将PP和使用少量血浆的PE联合在1次治疗模式（联合组）中完成,治疗51例66例次肝衰竭和高胆红素血症患者,检测治疗前、结束时及治疗结束48h时患者血总胆红素、总胆汁酸、VIA、ALB及WBC水平,并观察不良反应发生情况,与同期进行的36例79例次单纯PE治疗患者（PE组）做对照。结果①联合组治疗的总有效率为60．87％,高于PE组的52．78％,但差异无统计学意义（P〉0．05）;②2组患者治疗结束及治疗结束48h时血清总胆红素均明显低于治疗前水平（P〈0．05）,联合组治疗结束时血清总胆红素下降幅度高于PE组（P〈0．05）;③2组患者治疗结束时血清总胆汁酸均低于治疗前水平（P〈0．05）,但2组间比较差异无统计学意义（P〉0．05）;④2组治疗结束时PTA值均高于治疗前水平（P〈0．05）;⑤同治疗前比较,联合组治疗结束时及治疗结束48h时血清ALB、GLO均无明显变化（P〉0．05）。而PE组则明显减少（P均〈0．05）;⑥同治疗前比,2组治疗结束时及治疗结束48h时血WBC总数均无明显变化（P〉0．05）,丝且治疗结束时血Pn总数均明显减少（P均〈0105）;⑦联合组平均使用血浆量明显少于PE组;⑧未发生严重不良反应。结论本研究建立的PP联合PE的人工肝方法血浆用量少,治疗肝衰竭和高胆红素血症安全有效。     

Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura

Therapeutic plasma exchange is an effective empiric treatment for thrombotic thrombocytopenic purpura (TTP), but how therapy affects the level of a disintegrin and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) or inhibitor has not been reported in many patients. We prospectively analyzed ADAMTS13 activity and inhibitor levels in 37 adults with TTP. ADAMTS13 level at presentation was lower than 5% in 16 of 20 patients with idiopathic TTP and in none of 17 patients with TTP associated with hematopoietic stem cell transplantation, cancer, drugs, or pregnancy (P <.00001). Seven of the 16 patients with ADAMTS13 activity lower than 5% ( approximately 44%) had inhibitors. For 8 patients followed serially with ADAMTS13 activity lower than 5% but no inhibitor at presentation, plasma exchange led to complete clinical remission and a rise in ADAMTS13 level. In contrast, 4 patients with low ADAMTS13 activity but high-titer inhibitor (> 5 units/mL) had neither a rise in ADAMTS13 activity nor a reduction in the inhibitor titer: 3 had recurrent disease and 1 died. Among 17 patients with AD-AMTS13 activity at presentation higher than 25%, 10 died. Mortality rate for idiopathic TTP was 15%, whereas mortality for nonidiopathic TTP was 59% (P <.02). We conclude that assays of ADAMTS13 activity and inhibitors in addition to the clinical categories (idiopathic TTP and nonidiopathic TTP) are predictive of outcome and may be useful to tailor patient treatment.     

Interactions of plasma proteins with group A,B, C and G streptococci

Streptococci of serological groups A, B, C and G displayed different binding activities for plasma proteins. Most of the streptococci studied, except those of group B, bound immunoglobulin G. All streptococci reacted with fibrinogen and, except those of group B, with fibronectin. The majority of streptococci, but none of group B, had an affinity for α2-macroglobulin. Albumin was bound by all cultures of group G and a few of group C. Haptoglobulin interacted with only 1 group A culture. None of the streptococci bound transferrin.The specificity of binding sites for ¹²⁵I-labelled plasma proteins was revealed in a series of inhibition experiments with the unlabelled proteins. The binding sites on streptococci of group G showed different sensitivities to trypsin and pepsin. Reactivities for immunoglobulin G, however, remained unaffected after treatments of the streptococci with trypsin. Exposure to heat (30 min, 80°C) partially inactivated binding activities for the plasma proteins. Sodium dodecyl-sulphate and acetylimidazole strongly reduced binding of albumin and to a lesser extent that of α₂-macroglobulin. They had no or little effect on the interaction with the other plasma proteins. Dioxane decreased almost all binding activities. Ethanol partially diminished the binding of immunoglobulin G, fibrinogen, fibronectin and α₂-macroglobulin. Treatments of group G streptococci with guanidine, urea, formamide or methanol-HCl did not affect their plasma protein binding activities.     

Therapeutic apheresis: use of human serum albumin, fresh frozen plasma and cryosupernatant plasma in therapeutic plasma exchange

In therapeutic plasma exchange, patient plasma is removed and a colloid replacement solution is infused in its stead. A solution of 4-5% human serum albumin in saline is the recommended replacement solution in most instances, even though it leads to transient mild deficiencies of most plasma proteins. Albumin solutions are pasteurized to inactivate viruses, carry a very low risk of febrile and allergic reactions, and are convenient to store and administer. Fresh frozen plasma, which must be type specific and needs to be ordered in advance and thawed before use, carries a higher risk of reactions; however, it replaces all plasma constituents and is appropriate for patients with thrombotic thrombocytopenic purpura or a pre-existing coagulopathy. Neither cryosupernatant plasma, which is relatively depleted of the proteins in cryoprecipitate, nor pooled plasma that has been virally inactivated with organic solvents and detergents has been shown to be superior to fresh frozen plasma for any indication.     

低置换量血浆置换联合血浆吸附治疗42例重型肝炎疗效观察

目的探讨低置换量(2000ml)血浆置换联合血浆吸附治疗重型肝炎的临床疗效。方法选择42例重型肝炎患者在内科治疗的基础上采用低置换量血浆置换联合血浆吸附治疗,同期40例未进行人工肝治疗的重型肝炎为对照组,观察两组在临床症状、实验室检测指标及存活率的差异。结果低置换量血浆置换联合血浆吸附治疗组较对照组患者的临床症状,实验室指标及存活率均有明显改善,在统计学上有显著性差异(P<0.05)。结论低置换量血浆置换联合血浆吸附治疗重型肝炎是一种有效的方法。     

血浆置换联合血浆灌流治疗肝衰竭患者临床疗效分析*

目的探讨血浆置换（PE）联合血浆灌流（PP）治疗肝衰竭患者的临床疗效。方法选择2012年6月~2015年7月我科治疗的肝衰竭患者46例为观察组,行PE联合PP治疗;以2007年1月~2008年5月治疗的肝衰竭患者46例为对照组,行单纯PE治疗。采用日本OLYMPUS AU5400全自动生化分析仪检测肝功能指标;采用酶联免疫吸附法检测CRP、TNF-α、IL-6水平。结果观察组显效率和总有效率（分别为41.3%和93.47%）均明显高于单纯PE组（21.74%和78.26%,P<0.05）;治疗后,观察组患者血清TBIL、INR、NH₃、CRP、TNF-α和IL-6水平分别为（308.3±35.3）μmol/L、（1.6±0.2）、（214.3±22.7）μmol/L、（7.4±1.1）mg/L、（1128.3±345.3）ng/L和（115.5±12.0）ng/L,明显低于对照组【分别为（326.1±38.4）μmol/L、（1.9±0.8）、（267.5±26.1）μmol/L、（10.3±1.3）mg/L、（2012.3±318.4）ng/L和（184.3±20.1）ng/L,P<0.05】;观察组ALB水平为（34.3±4.9）g/L,明显高于对照组【（31.4±3.9）g/L,P<0.05】;观察组并发症发生率为19.6%,显著低于对照组的36.1%（P<0.05）。结论血浆置换联合血浆灌流治疗肝衰竭患者有助于清除炎性因子,改善肝功能,提高治疗效果。     

Lack of effect of calcium infusion on blood glucose and plasma insulin levels in patients with insulinoma

In vitro calcium plays a fundamental role in regulating insulin secretion. On the other hand, the influence of calcium excess on insulin release in vivo is not clearly defined. Recently, calcium infusion has been proposed as a provocative test for the diagnosis of insulin-secreting tumors. A 2-h infusion of calcium gluconate was performed (4 mg/kg . h) in six patients with islet cell adenoma. As a result, mean calcium plasma levels increased from 9.6 +/- 0.4 to 11.6 +/- 0.8 mg/100 ml. During calcium infusion, blood glucose and plasma insulin concentrations remained unchanged. These observations suggest that calcium fails to stimulate basal insulin secretion even in cases of organic hyperinsulinism. They show that calcium infusion is not helpful as a provocative test in the diagnosis of insulinoma.     

Lack of elevation of platelet factor IV in plasma from patients with myocardial infarction

Platelet factor IV and beta-thromboglobulin are protein constituents of platelet granules. Elevated levels of these proteins in plasma have been used as sensitive indicators of platelet degranulation. Clearance of platelet factor IV is much faster than that of beta-thromboglobulin after release of the proteins in vivo. Although increases of platelet factor IV have been observed in patients with infarction, the implication that they reflect pathogenetic phenomena such as coronary thrombosis has not been assessed explicitly. Accordingly, plasma samples obtained serially from 52 patients with acute myocardial infarction under rigorous conditions verified to minimize platelet degranulation in vitro were evaluated prospectively. Correlative studies were performed to detect left ventricular mural thrombus, and coronary thrombosis was assessed independently in selected patients with indium-111 platelet scintigraphy. Platelet factor IV was normal at the time of admission in patients with infarction, averaging 6.3 +/- 3.3 ng/ml, similar to values in 44 other patients with chest pain without subsequent infarction (5.7 +/- 2.7 ng/ml) and in 25 normal subjects (4.3 +/- 1.6 ng/ml). Platelet factor IV generally did not increase during hospitalization in patients with infarction despite recurrent chest pain, development of left ventricular thrombus or documented recurrent infarction. However, platelet factor IV increased consistently after invasive procedures, accounting for 104 of the total of 110 increases due to platelet activation in vivo as reflected by persistence of elevated levels of beta-thromboglobulin. Thus, platelet factor IV values generally remain normal despite acute myocardial infarction. Rare increases that occur reflect platelet degranulation in vitro due to sampling artifact or perturbations of platelets in vivo due to invasive procedures.(ABSTRACT TRUNCATED AT 250 WORDS)     

Proteomic study of plasma proteins in pregnant women with asthma

OBJECTIVE AND BACKGROUND: The course of asthma may be altered during pregnancy with at least one-third of women experiencing a worsening of asthma and 20% having an exacerbation during pregnancy. This study used the novel proteomic technique, surface-enhanced laser desorption ionization-time of flight mass spectrometry to determine if the presence of asthma during pregnancy was associated with alterations in plasma proteins. METHODS: Plasma collected from healthy (n = 23) and asthmatic (n = 27) pregnant women at 18 and 30 weeks gestation was applied to strong anion exchange (SAX2), weak cation exchange (WCX2) and immobilized metal affinity capture (IMAC-Cu(2+)) chips. Mass analysis was conducted using Ciphergen Protein Biology System IIc and significant differences in individual peak intensities between groups determined. RESULTS: At 18 weeks gestation, 91 peaks were significantly different between pregnant women with and without asthma, representing 28% of the total peaks identified. At 30 weeks gestation, 51 peaks were significantly different. There were two peaks that were significantly different between groups at both 18 and 30 weeks gestation and expressed at a similar level at both time points. One was increased in asthmatics (MW = 6444 Da) whereas the other decreased in asthmatics compared with non-asthmatic women (MW = 1846 Da). CONCLUSIONS: This study demonstrated that there are differences in protein patterns between pregnant women with and without asthma. Other techniques are needed to define the molecular species and classify pathophysiological significance. Surface-enhanced laser desorption ionization-time of flight mass spectrometry has potential as a tool to monitor disease progression in situations such as pregnancy.