心脏直视术中应用抑肽酶引发过敏反应的临床观察及处理

抑肽酶是从牛肺中提取的碱性多肽，体外循环手术中抑肽酶可增加术后血小板功能、抑制纤溶、提高术后凝血因子含量等，从而减少了术后出血，对心肌具有保护作用，并对患者手术后的免疫系统及补体的恢复有促进作用。但是，作为牛肺中提取的碱性多肽，抑肽酶可导致过敏反应，我科1998年元月～2003年元月在心脏直观手术中应用抑肽酶1000人次，其中有5例发生严重过敏反应，经及时抢救均治愈，现报告如下：     

抑肽酶抑制体外循环中炎症反应的应用研究

目的:总结抑肽酶抑制体外循环心脏直视手术中炎性反应的研究和临床应用.方法:自2001年1月至11月,因心脏瓣膜病变而施行心脏瓣膜置换手术的患者随机分为研究组和对照组,术中应用抑肽酶的患者作为研究组.两组患者的体外循环、麻醉方法、预充液配制及手术方式间无差异.分别在体外循环前、中、后监测IL-6、IL-8和TNF-α变化.结果:两组患者CPB开始前的各炎性因子浓度间无显著性差异(P＞0.05),而体外循环开始至结束后对照组患者的各炎性因子浓度均比研究组患者显著增加(P＜0.05).结论:抑肽酶能有效的抑制体外循环术中IL-6、IL-8和TNF-α的释放,减轻体外循环术后炎性反应的程度,这对促进患者术后恢复、减少术后并发症具有重要的意义.     

益生菌对婴儿体外循环心脏手术后胃肠功能的影响

目的:观察益生菌对婴儿体外循环心脏手术后胃肠功能的影响。方法:将某三甲医院2019-07—2019-12行体外循环心脏手术后的58例患儿随机分为对照组(n=28)和观察组(n=30),对照组于术后24h内常规早期肠内营养,观察组在对照组的基础上加用酪酸梭菌制剂(米雅)。观察并记录两组患儿术后首次排便时间和胃肠功能紊乱发生情况,并比较术前、术后第7天两组患儿血清超敏C反应蛋白(CRP)和降钙素原(PCT)水平的变化。结果:观察组患儿胃肠道功能恢复时间较对照组短,术后第7天CRP和PCT指标明显低于对照组(P均<0.05)。结论:益生菌可减轻婴儿体外循环心脏手术后炎症反应,促进胃肠道功能恢复。     

常温及低温体外循环对机体免疫功能影响的对比研究

目的探讨常温体外循环对机体免疫功能的影响，以寻找减轻免疫损伤的方法，提高手术效果，减少术后并发症发生。方法选择先天性或风湿性心脏病患者40例，随机分为两组，常温组及低温组，每组20例。分别于术晨、转机末及术后1、4、7、14天抽取静脉血标本，测定血浆IgA、IgM、IgG、TNF-α、IL-2、CD3、CIM、C3、CA含量。结果与术前相比，手术后IgA、IgG、IgM、IL-2、C3、CA、CD3、CD4均有不同程度地降低，TNF-α、CD8均有不同程度地升高；组间相比，两组术前各项指标相似，术后IgA、IgM、IgG、IL-2、CD3、CIM、C3、CA均有一个以上的时间点高于低温组，TNF-α低于低温组，CD8两组相似，无显著性差异。结论常温体外循环心脏直视手术对免疫系统的影响较低温方法轻；常温体外循环对补体及细胞因子的影响显著轻于低温方法。因此，常温方法有利于术后机体的恢复及抗感染作用。     

三条补体通路在IgA肾病血液中的活化及致病作用

目的:研究不同的补体活化类型在Ig A肾病(Ig A nephropathy,Ig AN)中的活化及其致病作用,拓展Ig AN的发病机制理论。方法:设立Ig AN疾病组30例,疾病对照组狼疮性肾炎(Lupus nephritis,LN)患者8例作阳性对照,本院查体中心筛选健康人30例作正常对照。采用商品化的ELISA试剂盒检测Ig AN患者及对照者血清中三条补体激活渠道的标志性成分:三条补体活化通路中的共同裂解产物C3a、C5a,及溶解型终末期膜攻击复合物s C5b-9,经典途径标志物C1q,凝集素途径标志物L-ficolin(FCN2),经典途径及凝集素途径激活后的共同标志物C4d,替代途径标志物补体Bb因子。分析血清中的补体浓度与临床生化指标的相关性。结果:所有因子三组间的比较均有显著差异(P0.05)。补体因子与临床指标间存在不同程度的相关性,其中Bb、C3a等补体裂解产物与血肌酐间呈正相关关系,FCN2与尿红细胞计数间呈负相关关系,而C1q与临床指标间无相关性。结论:Ig AN患者血液中或许存在补体经典途径、凝集素途径及替代途径的活化,并且补体激活参与临床及肾脏病理损伤,补体激活程度影响临床及病理损伤程度。     

超声引导下星状神经节阻滞应用于头面部手术患者的效果观察

目的 探讨超声引导下星状神经节阻滞对头面部手术患者呼吸、循环、免疫功能、炎症反应、镇痛效果及麻醉相关并发症的影响。方法 选取行头面部手术的患者80例,随机分为对照组与观察组,每组40例。观察组在麻醉诱导前行超声引导下星状神经节阻滞,对照组麻醉诱导前不进行任何阻滞麻醉干预。比较2组患者围术期呼吸、循环、免疫功能及炎症指标变化情况,术后不同时点视觉模拟量表(VAS)评分,围术期麻醉相关并发症发生情况。结果 2组患者术前1 d、麻醉诱导前、拔管时及术后1 h的呼吸频率组间及组内比较差异均无统计学意义(P 0. 05)。2组患者术前1 d、麻醉诱导前的心率比较差异无统计学意义(P 0. 05),拔管时及术后1 h的心率比较差异有统计学意义(P 0. 05);观察组不同时点的心率组内比较差异无统计学意义(P 0. 05),对照组不同时点的心率组内比较差异有统计学意义(P 0. 05)。2组患者术前1 d的免疫球蛋白(Ig) G、Ig A、Ig M比较差异无统计学意义(P 0. 05); 2组患者术后3 d的Ig G、Ig A、Ig M均低于术前1 d(P 0. 05);对照组术后3 d的Ig G、Ig A、Ig M低于观察组(P 0. 05)。2组患者术前1 d血清肿瘤坏死因子-α(TNF-α)及白细胞介素-6(IL-6)比较差异无统计学意义(P 0. 05),2组患者术后3 d血清TNF-α及IL-6高于术前1 d(P 0. 05),对照组术后3 d血清TNF-α及IL-6高于观察组(P 0. 05)。术后24 h、48 h,观察组疼痛VAS评分低于对照组(P 0. 05)。2组患者围术期麻醉相关并发症发生率比较差异无统计学意义(P 0. 05)。结论 头面部手术患者术前实施超声引导下星状神经节阻滞有助于维持术中循环稳定,减轻围术期免疫抑制及炎症反应,提高术后镇痛效果,对呼吸功能影响较小,且不会增加围术期麻醉相关并发症。     

老年股骨头骨折患者围手术期凝血功能变化

目的:观察老年股骨头骨折患者围手术期凝血功能变化,为术后下肢深静脉血栓形成(DVT)提供早期实验诊断依据。方法:老年股骨头骨折患者(骨折组,n=87)于手术前及手术后第1天和第3天检测血浆凝血酶原时间(PT)、血浆部分凝血活酶时间(APTT)、凝血酶时间(TT)、血浆D-二聚体(D-D)和血浆纤维蛋白原降解产物(FDP)水平变化,并与健康对照人群(对照组,n=43)进行比较分析。结果:与对照组比较,骨折组手术前凝血功能水平差异无统计学意义(P>0.05)。手术后第1天、第3天,骨折组患者D-D、FDP较术前及对照组显著升高(P<0.05),而PT、APTT和TT与术前和对照组水平差异无统计学意义(P>0.05)。结论:凝血功能检查对早期诊断和防治老年股骨头骨折手术后DVT有重要临床价值。     

洗涤式自体血回输对心脏手术患者凝血和携氧功能的影响

目的:观察洗涤式自体血回输对心脏手术患者凝血功能和红细胞携氧功能相关指标的影响。方法:61例手术患者采用美国美敦力血液回输机进行洗涤式自体血回输,分别测定术前、术后当天、术后第1天、术后第7天血液凝固指标:血小板计数(PLT)、血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)、D-二聚体(D-D)和红细胞携氧功能相关指标:血氧分压(PaO2)、血氧饱和度(SaO2)、血酸碱度(pH)、红细胞计数(RBC)、血红蛋白含量(HGB)、红细胞压积(Hct)。结果:61例患者术中回收原血和"机血"共84912ml,平均每例患者回输浓缩红细胞465ml。与术前比较,术后当天和术后第1天凝血功能指标PLT、FIB显著降低(P<0.01),PT显著延长(P<0.05或P<0.01),术后当天D-D明显升高(P<0.05);携氧功能指标PaO2在术后当天和术后第1天显著升高(P<0.01),RBC、HGB、Hct均显著降低(P<0.01,P<0.05)。术后第7天所有异常指标均恢复至术前水平。结论:洗涤式自体血回输不影响血液凝固和携氧功能,可安全应用于心脏手术。     

抑肽酶在体外循环心脏直视手术中的肺保护作用研究

目的:体外循环中,血液与异物表面直接接触,导致许多炎性介质和血管活性物质的形成及释放,形成的肺损伤是手术患者的一个重要而危险的并发症.本文总结了CPB中应用抑肽酶进行肺保护的研究和临床应用.方法:2001年1月至11月,在本院施行二尖瓣置换手术的患者随机分为研究组和对照组,手术中应用抑肽酶的患者作为研究组,未用抑肽酶的患者作为对照组.记录两组患者术前、麻醉诱导时、体外循环结束时的气道压力(Paw)、肺泡--动脉血氧分压差[(A-a)DO2]、两组患者回病房后的机械通气时间.结果:两组患者的术前、前中情况均无显著性差异.而研究组患者体外循环结束时的气道压力和肺泡-动脉血氧分压差的升高幅度明显小于对照组患者(P＜0.05),预示着研究组患者的肺功能在体外循环过程中受到的损伤程度显著小于对照组患者.研究组患者的机械通气时间比对照组患者显著减少(P＜0.05),说明研究组患者术后肺功能比对照组患者恢复得快.结论:在体外循环心内直视手术中应用抑肽酶,充分发挥其血液麻醉作用,可有效减轻肺损伤,促进术后恢复,取得良好的肺保护效果,而且简便易行、安全实用,对医患双方都有着积极意义.     

体外受精-胚胎移植患者卵泡液中免疫球蛋白的测定

目的　了解体外受精 -胚胎移植患者卵泡液中是否存在免疫球蛋白 (Ig)及补体C3,及其与所获卵子数、受精率、卵裂率及妊娠成功率的关系。方法　体外受精 -胚胎移植 (IVF -ET)患者 50例 ,分为两组 :妊娠组与非妊娠组 ,利用速率散射比浊法测定每例患者血清及卵泡中的IgG、IgA、IgM、C3水平及记录各个病人的卵子数、受精数、卵裂数。结果　卵泡液中Ig、C3比血液中的显著降低 (P <0 0 1 )且卵泡液中IgA、IgM与血液中IgA、IgM有相关性。卵泡液中Ig、C3与所获卵子数、受精率、卵裂率、妊娠率无相关性。结论　卵泡液中存在免疫球蛋白 (Ig)及补体C3且不影响妊娠的成功。     

Complement as a predictor of further miscarriage in couples with recurrent miscarriages

BACKGROUND: The clinical significance of complement is unclear in patients with unexplained recurrent miscarriage, though low levels of complement 3 (C3) and/or complement 4 (C4) are reported to be associated with the antiphospholipid syndrome (aPS). We therefore investigated whether C3 and C4 have a predictive value for subsequent miscarriages. METHODS: In total, 215 patients with a history of two consecutive first-trimester miscarriages and no abnormal chromosomes in either partner, no uterine anomalies and no antiphospholipid (aPL) antibodies were examined. Blood tests for C3, C4, total haemolytic complement (CH50), immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) were performed before subsequent pregnancy. Patients were then followed up without treatment, and their pregnancy outcomes were compared with their previous blood test results. RESULTS: From 215 pregnant patients, 45 subsequently miscarried, whereas the remainder had a live birth. There was no relation with serum CH50, IgG, IgA and IgM levels, but C3 and C4 levels in patients with subsequent miscarriage were significantly higher than in those whose pregnancy was successful. CONCLUSION: In patients with two previous miscarriages, C3 and C4 levels were higher in those women who had a third miscarriage, than in women that went on to have a live birth.     

体外循环对患者血清免疫球蛋白和补体的影响

测定了35例体外循环心脏手术患者围术期不同时间血清免疫球蛋白(IgS)和补体水平。结果显示术后IgS和补体水平均较术前显著下降,且持续至术后3～8d。提示:体外循环系统可损害机体体液免疫功能。     

Isolation of rat IgM to IgG hybridoma isotype switch variants and analysis of the efficiency of rat Ig in complement activation

Sequential sublining was used in combination with enzyme-linked immunosorbent assays to isolate mu----gamma isotype switch variants of the rat IgM secreting mouse-rat B cell hybridoma line BA1.8. Switch variants to all four subclasses of IgG were obtained. The variant antibodies retained the antigen specificity of the parental IgM for the O18 (lipopolysaccharide) antigen of Escherichia coli. In sodium dodecyl sulfate-polyacrylamide gels the apparent molecular mass of the gamma heavy chains decreased in the order gamma 2b greater than gamma 1 greater than gamma 2c greater than gamma 2a. IgM, IgG1, IgG2a, IgG2b and IgG2c of the BA1.8 variant family and IgG2b, IgE and IgA of the previously described BA1.2 family were used for a comparative analysis of the capacity of rat Ig to activate complement. Efficient lysis of sheep erythrocytes coated with the O18 antigen was observed with IgM and all IgG subclasses, but no lysis was triggered by IgE or IgA. One hundred to 1000 IgG molecules were required to mediate the same hemolytic activity as one IgM molecule. The four IgG subclasses were equally efficient at mediating lysis by rat or human complement, while IgG2a was less efficient with guinea pig complement than the other three IgG subclasses. Antibody-triggered binding of C3 to pathogenic O18:K1 E. coli bacteria was measured using serum containing 125I-labeled C3. K1-encapsulated strains did not fix C3 efficiently in the absence of specific antibodies while acapsular mutants fixed C3 via the alternative pathway. IgM and all IgG subclasses triggered C3 binding to the K1 encapsulated bacteria. The capacity of IgM to mediate C3 fixation was not greater than that observed with IgG.     

Immunoglobulins in certain CNS disorders: a study of CSF Ig classes G, A, M, D, and E concentrations

Concentrations of cerebrospinal fluid (CSF) Ig classes G, A, M, D, and E have been reported in various neurologic disorders, viz, aseptic meningitis, multiple sclerosis, benign tumor, malignant tumor, and hydrocephalus. In aseptic meningitis, IgG and IgM were found to be either normal or elevated, whereas concentrations of IgA, IgD, and IgE were normal. Multiple sclerosis patients had IgG, IgA, and IgM, either normal or elevated, but IgD and IgE were on the lower end of the normal. Malignant tumor patients had elevated concentrations of IgG, IgA, IgM, and IgE, but their IgD was on the lower end of the normal. In benign tumor population IgA and IgE, and in hydrocephalus IgG and IgA, were found to be elevated in most of the patients. On statistical analysis, significant differences were observed between the means of the normal group and that of the patients' group for all the five immunoglobulins. By linear regression, a statistical relationship was observed between IgA - IgG, IgM - IgG, IgA - IgM and IgA + IgM - IgG in these neurologic disorders.     

T cell dependent differentiation of human B cells: direct switch from IgM to IgE, and sequential switch from IgM via IgG to IgA production.

Ig production by splenic human B cells that express different surface Ig isotypes were analysed in limiting dilution cultures. Therefore, FACS sorted IgM+, IgG+ and IgA1+ B cells were stimulated with PMA-activated EL4 thymoma cells as helper cells in the presence of IL-2 and IL-4. We found that at least every second B cell responded in vitro and secreted the antibody corresponding to its surface Ig isotype. IgE secreting cells developed from surface IgM+ D+ cells (1/31 to 1/167), but not from IgG+ or IgA1+ cells (much less than 1/5000). Negative signalling of the IgM+ B cells by addition of anti-IgM antibodies into the cultures reduced the number of single IgM producing cells by greater than 85%, and completely inhibited IgE switch. In contrast, anti-IgG and anti-IgA antibodies did not reduce the IgE response. The results indicate a direct switch from IgM to IgE secretion in vitro. In contrast to IgE, IgA secreting cells developed from IgM+D+ (1/30 to 1/51) and from IgG+ B cells (1/14 to 1/25). Negative signalling of the IgG+ B cell subset within total B cells by anti-IgG antibodies suppressed the development of IgG as well as IgA producing cells, but did not inhibit IgM and IgE responses. This indicates a sequential switch from IgM via IgG to IgA. Taken together, this study indicates that IgE secreting cells are derived directly from IgM+D+ B cells by non-sequential switching, whereas IgA producing cells preferentially develop by sequential switching via IgG+ B cells.     

Isotypic analysis of grass-pollen-specific antibodies in human plasma. III. Relationship to autoantibodies to IgE

Since it has been shown that autoanti-IgE may be mistaken for antiallergen antibodies, thus appearing as pseudo-allergen-specific antibodies, it is crucial to separate true- from pseudo-allergen-specific antibodies and to determine to what extent autoanti-IgE appeared as pseudo-allergen-specific antibodies. For this purpose, human Ig pools were affinity-purified successively on a grass-pollen column and then on an antihuman-IgE column. IgG1–4, IgA, and IgM antibodies that were eluted from the grass-pollen column separated into pseudo- (∼30–40%) and true-allergen-specific antibodies that were coretained and not coretained, respectively, with the IgE on the anti-IgE column. Levels of autoanti-IgE were determined in individual plasma samples by surface plasmon resonance and statistically compared to the concentrations of allergen-specific antibodies obtained previously in the same plasma samples. A positive correlation between IgM autoanti-IgE levels and grass-pollen-"specific" IgM concentrations ( P < 0.0002), and negative correlations between IgA autoanti-IgE and both IgE anti-grass pollen and IgG2 autoanti-IgE levels ( P < 0.03, in both cases) were observed for the first time. This supports the contentions that: (1) autoanti-IgE antibodies appeared as pseudo-grass-pollen-specific antibodies, (2) they hid IgE antibodies when the latter were measured, and (3) they compete with one another in binding IgE. Lastly, a model of large Ig complexes is discussed.     

High levels of immunoglobulin E and a continuous increase in immunoglobulin G and immunoglobulin M by age in children with newly diagnosed type 1 diabetes

The incidence of type 1 diabetes (T1D) is increasing, either because of environmental factors accelerating onset of the disease or because of inducement of autoimmune diabetes in children who previously were at lower risk. High levels of immunoglobulin (Ig), specifically, IgM and IgA, and a low level of IgG were reported in adult patients; however no studies have analyzed the increasing incidence in relation to Ig levels. Our aim was to describe Ig in children newly diagnosed with diabetes and in their healthy siblings. Children with T1D expressed significantly lower IgG (p < 0.01) and higher IgA levels (p = 0.045), whereas no differences in IgE or IgM (p > 0.5) levels were found. Age-specific levels were unchanged over a 9-year period. In patients and siblings IgG, IgA and IgE increased by age (p < 0.001); which was in contrast to IgM (p > 0.05). The continued increase in IgG levels by age indicates that adult levels are reached later than in previously studied cohorts, thereby indicating a slower maturation of the immune system.     

Immunoglobulin isotype production by cycling human B lymphocytes in response to recombinant cytokines and anti-IgM

Actively cycling populations of purified human tonsilar B lymphocytes were examined for their capacity to secrete IgM, IgA, IgE and IgG of all four subclasses in direct response to recombinant cytokines; in some experiments, monoclonal antibody to IgM (anti-mu) was included in order to explore the influence of antigen receptor ligation on immunoglobulin (Ig) production. Enhanced IgM release was seen on culture of the cycling cells with either interleukin-2 (IL-2), IL-4 or interferon-alpha (IFN-alpha). IL-2 and IFN-alpha also augmented IgA production, whereas IL-4 had no effect on this isotype. IL-4 did, however, encourage the production of the IgG subclasses IgG1, IgG2 and IgG3, while IL-2 augmented IgG1 and IgG3 release and IFN-alpha increased IgG1 levels. IgG4 production, and that of IgE, failed to be perturbed by any of the cytokines assayed. Neither IL-1 alpha, IL-1 beta, IL-5 nor IFN-gamma significantly altered the profile of Ig isotype release. When confronted with anti-mu, cycling B cells demonstrated a marked suppression in IgM production. Suppression could not be overcome by the addition to culture of the normally IgM-promoting IL-4. Concomitant with the reduction in IgM levels, an increase in IgG release was observed. This was comprised of elevations in IgG1 and IgG3. Although not influencing IgA release directly, anti-mu was found to promote increased IgA production in co-culture with either IL-2 or IFN-alpha. The findings are discussed in the context of recent findings on Ig isotype control in both human and murine systems.     

Low immunoglobulin E flags two distinct types of immune dysregulation

During the last two decades, hyper‐immunoglobulin (Ig)E syndromes have been characterized clinically and molecularly in patients with genetically determined primary immunodeficiencies. However, the detection of low IgE levels, defined here as below detection limit in the routine clinical immunology laboratory, has received little attention. We analysed the association of serum IgA, IgM and IgG levels (including IgG subclasses) with low, normal or high serum IgE levels in patients evaluated in a single‐centre out‐patient immunodeficiency and allergy clinic. The correlation of serum IgE levels with IgG subclasses depended on the clinical phenotype. In patients with immunodeficiencies, IgE correlated with IgG2 and IgG4 but not with IgG3. In contrast, in patients referred for signs of allergy, IgE correlated with IgG3 but not with IgG2. A low IgE result was associated with low IgG3 and IgG4 in allergy referrals, while immunodeficiency referrals with a low IgE result had significantly lower IgG1, IgG2 and IgG4 levels. Hierarchical clustering of non‐IgE immunoglobulin profiles (IgM, IgA, IgG, IgG1–4) validated that non‐IgE immunoglobulin levels predict the clinic referral, i.e. phenotype, of low‐IgE patients. These results suggesto guide the clinical management of patients with low serum IgE levels.