Ultrastructural Findings in Storage Pool Disease and Aspirin-Like Defects of Platelets

Previous studies have shown that abnormalities in collagen-induced platelet aggregation may be due to an impaired release of storage pool ADP, the agent ultimately responsible for platelet aggregation. In some patients and in normal subjects who ingest aspirin, the storage pool of ADP is present in normal amounts, but the mechanism for releasing it appears to be defective (“aspirin-like” defect). In these subjects, the centripetal reorientation of the platelet granules, which may be early structural changes of the release reaction, failed to occur. In one preleukemic patient with an aspirin-like defect, the elements of the open-channel system were also increased. In a second group of patients the impairment of aggregation is due to a deficiency of storage pool ADP. In these patients with storage pool disease, the initial ultrastructural changes associated with the collagen-induced release reaction were normal. The most striking abnormality was a marked decrease in the number of platelet dense bodies. Since the platelets of these patients are deficient in both serotonin and the storage pool of adenine nucleotides, the findings suggest that, in human platelets, these substances are normally stored in the dense bodies. A defect in the formation or function of the dense bodies may account for the abnormalities of platelet aggregation in storage pool disease.     

Effects on the Pulmonary Circulation of Suddenly Induced Intravascular Aggregation of Blood Platelets

When intravascular platelet aggregation was induced by intravenous infusion of collagen extract, a temporary and marked increase in pulmonary vascular resistance (PVR) was observed. The number of circulating platelets was gradually reduced after the first few infusions of collagen. After 4–6 infusions of collagen the vascular response vanished, and the platelet count in arterial blood remained fairly stable. When a vasodilator was infused simultaneously with the collagen, the pressure response could be abolished. Histological examinations of lungs at the peak of a pressor response to collagen revealed aggregated platelets in small arterial vessels and capillaries. After many infusions larger vessels were found occluded by aggregated platelets. It is concluded that platelet aggregation in the blood arriving in the lung creates a strong vasoconstriction in the pulmonary vascular bed. This response is related to release of material from the platelets.     

毛冬青甲素对血小板和血管内皮细胞功能的影响

毛冬青甲素对ADP及AA活化血小板功能的二条途径有抑制作用。本文证明毛冬青甲素对活化血小板的第三条途径TMVA也有抑制作用。提示毛冬青甲素为一广谱抗血小板药,并可抑制丙二醛的生成,但不具有刺激人工培养人脐静脉内皮细胞生成前列环素的能力。     

On the Formation and Effects of Thromboxane A2 in Human Platelets

Incubation of arachidonic acid and prostaglandin G₂ with a suspension of human platelets led to formation of an unstable (t_1/2 41 ± 7 s) compound, thromboxane A₂ Thromboxane A₂ induced irreversible aggregation of washed platelets and of platelets in platelet-rich plasma and caused release of serotonin and ADP from platelets in platelet-rich plasma.     

血小板聚集功能和尿11-脱氢血栓素B_2水平测定对评价脑梗死患者阿司匹林治疗作用的价值

目的:探讨血小板聚集功能和尿11-脱氢血栓素B2(11-DTB2)检测对评价一次及反复脑梗死患者服用阿司匹林治疗作用的价值。方法:42例反复脑梗死(≥2次)患者和50例发生一次脑梗死患者服用阿司匹林(100mg/天)至少7天后,用二磷酸腺苷(ADP)和花生四烯酸(AA)作诱导剂,测定两组血小板最大聚集率,并测定其11-DTB2的含量。结果:AA作诱导剂时,反复脑梗死患者与一次脑梗死患者比较,其血小板最大聚集率、阿司匹林半抵抗发生率明显较高(P<0.01);尿11-DTB2也是前者高于后者,差异有显著性统计学意义(P<0.01)。结论:脑梗死患者服用阿司匹林时检测血小板聚集功能和尿11-DTB2水平,可以观察阿司匹林抑制血小板功能的程度及临床疗效。     

A Personalized Diagnostic and Treatment Approach for Macrophage Activation Syndrome and Secondary Hemophagocytic Lymphohistiocytosis in Adults

Objective

We assessed the clinical features and outcomes based on therapeutic options adopted during hospital stay for adult patients with macrophage activation syndrome and secondary hemophagocytic lymphohistiocytosis (MAS/sHLH).

Methods

We conducted a retrospective chart review of all adult patients (age ≥ 18 years) diagnosed with MAS/sHLH at our center between 2010 and 2015. Inclusion criteria for patients were diagnosis of MAS/sHLH during admission and patients meeting at least 5 out of 8 of Henter’s criteria or at least 4 out of 6 of the criteria that were tested.

Results

Nineteen adult patients with MAS/sHLH met the inclusion criteria from January 2010 to October 2015 (median age 48 years; female 68.4%). Treatment had been personalized, depending on the clinical presentation and course of disease. Majority of the patients received anakinra, cyclosporine, intravenous immunoglobulins (IVIG), and steroids. Fourteen (74%) patients survived, with clinical improvement by the time of discharge. After excluding the three patients with underlying leukemia/lymphoma who opted for palliative care and subsequently died, the survival rate was 88%.

Conclusion

A modified diagnostic and treatment protocol for adult patients with MAS/sHLH that incorporated graded introduction of medications based on clinical presentation and cytokine profile resulted in the best adult survival rate reported in literature.

     

标本类型及存放时间对心衰患者BNP和NT-proBNP检测结果的影响

目的:探讨标本类型及存放时间对心衰患者B型尿钠肽(BNP)和氨基末端B型尿钠肽前体(NT-proBNP)检测结果的影响。方法:取37例心衰患者静脉血,制备EDTA-K2抗凝血浆、肝素钠抗凝血浆和血清标本,同时进行BNP与NT-proBNP平行测定,并将EDTA-K2抗凝血浆标本于室温(22℃±3℃)监测上述指标在0～24h的水平稳定性。结果:采用血清及EDTA-K2和肝素钠抗凝血浆标本检测NT-proBNP结果重复性好,而BNP结果的重复性较差;EDTA-K2抗凝血浆在室温下放置0～24h,BNP浓度逐渐下降,24h与0h、2h比较,差异显著(P0.05);而NT-proBNP浓度在0～24h维持不变。结论:NT-proBNP测定的适用标本类型较多,且检测结果比BNP稳定,建议诊断心衰时选择NT-proBNP作为辅助检测指标。     

Effects of Large Latex Particle Uptake on the Surface Connected Canalicular System of Blood Platelets: A Freeze-Fracture and Cytochemical Study

The complex structural organization of the platelet's surface-connected or open canalicular system (OCS) and close physical relationships to the dense tubular system have been described in previous cytochemical and freeze-fracture ultrastructural studies. Despite observations that suggest that channels of the OCS are seldom, if ever, single, tubelike invaginations of the surface, others have indicated that the OCS is a readily available source of membrane for evagination onto the exposed surface of the platelet after activation or during phagocytosis. In the present investigation we have utilized freeze-fracture for the first time to evaluate the uptake of large (0.312 μm, SD ± 0.0022) latex particles by platelets. Results of the study leave no doubt that channels of the OCS serve as the major route for latex ingestion in the unstirred system employed. Prolonged exposure to latex and uptake of many spherules cause marked changes in platelet surface contour and internal organization. The OCS is transformed from a spiderweb of intercommunicating channels into one or two large vacuoles filled with latex. Conversion of the OCS into large sacs is associated with disk-to-sphere transformation and a decrease in the number of openings of the OCS on the platelet surface. Thus, the OCS appears to be effectively interiorized by the process of phagocytosis, rather than evaginated as others have suggested.     

Effects of Large Latex Particle Uptake on the Surface Connected Canalicular System of Blood Platelets: A Freeze-Fracture and Cytochemical Study

The complex structural organization of the platelet's surface-connected or open canalicular system (OCS) and close physical relationships to the dense tubular system have been described in previous cytochemical and freeze-fracture ultrastructural studies. Despite observations that suggest that channels of the OCS are seldom, if ever, single, tubelike invaginations of the surface, others have indicated that the OCS is a readily available source of membrane for evagination onto the exposed surface of the platelet after activation or during phagocytosis. In the present investigation we have utilized freeze-fracture for the first time to evaluate the uptake of large (0.312 μm, SD ± 0.0022) latex particles by platelets. Results of the study leave no doubt that channels of the OCS serve as the major route for latex ingestion in the unstirred system employed. Prolonged exposure to latex and uptake of many spherules cause marked changes in platelet surface contour and internal organization. The OCS is transformed from a spiderweb of intercommunicating channels into one or two large vacuoles filled with latex. Conversion of the OCS into large sacs is associated with disk-to-sphere transformation and a decrease in the number of openings of the OCS on the platelet surface. Thus, the OCS appears to be effectively interiorized by the process of phagocytosis, rather than evaginated as others have suggested.     

中学生考试综合征及相关因素的调查

目的探讨中学生考试综合征的现状及其与相关因素之间的关系.方法采用分层抽样法,对4所中学6个年级的学生进行了考试综合征的流行病学调查和相关量表的测试.结果发现中学生考试综合征的总检出率为21.9%.文科理科、不同年级的学生考试综合征检出率差异有显著性.患考试综合征学生的个性更为内向,情绪趋向不稳定,学习压力相对较大.结论考试综合征的产生既有自身的心理因素,也有外界的环境因素,其危害很大,可通过减轻考生的心理压力,提高应试技能,培养考生良好的个性品质,心理咨询等手段矫治.     

Effect of Normal Human Serum on the Binding of Specific Antibodies and Platelet-unrelated Immune Complexes to Human Platelets

Radiolabelled staphylococcal protein A was used to quantitate the binding of IgG on stored human platelets from human sera containing specific antibodies reactive with platelets and rabbit serum containing immune complexes (IC). Normal human serum (NHS) inhibited the binding of IC onto platelets and to various extents also the binding of specific antibodies. The attachment of inhibitors to platelets seemed to be reversible. The considerable difference in the inhibitory capacities of IgG-deficient sera and monomeric IgG indicates that IgG is the major inhibitory component of NHS. The binding of IgG from NHS onto platelets evidently hampers the detection of weak platelet antibodies even with the most sensitive tests. Purified Clq, known to modify the reactions of IC with fresh platelets did not alter the binding of IC onto stored platelets. A monoclonal, antiglobulin-active rheumatoid factor of IgM class displayed only moderate inhibition. Therefore, the application of RF or Clq for the differentiation of the binding induced by IC or antibodies is not useful in this assay system. The heterogeneity of immunologic receptors of platelets provides an explanation of the inhibitory inefficiency of Clq.     

新生儿高胆红素血症患者血小板功能测定

报告了30例新生儿高咀红素血症患儿和17例正常新生儿的血小板粘附率、聚集率、血小板，第3因子有效性测定结果．经统计学分析新生儿高胆红素血症时血小板粘附率升高．取集率下降．血小板第3因子活性减低与年龄有关而与黄疸无关．光疗时血小板粘附率．聚集串无影响．但能提高血小板第3因子的活性．并提示新生儿高胆红素血症时应慎用抗凝药．     

Sibling Aggregation for Psychopathology in Offspring of Opiate Addicts: Effects of Parental Comorbidity

Applied a new analytic approach within the high-risk paradigm, the analysis of sibling aggregation, to identify homogeneous subtypes of familial risk for psychopathology and addiction. All sibling pairs participating in a study of offspring of opiate-addicted parents were identified and their aggregation for psychiatric disorders was determined using pairwise odds ratios, an analytic technique used in genetic epidemiology. Sibling aggregation was most notable for depressive and anxiety disorders but only in the presence of comorbid depressive disorders in the parents. Parental comorbid alcoholism did not impact sibling aggregation. We emphasize methodological implications of this approach for addressing issues of phenotypic and etiologic heterogeneity in the study of developmental risk for substance abuse.     

Uptake of Serotonin in Blood Platelets in vitro. II: Further Studies on the Effects of Small Anions

According to previous reports, serotonin (5HT) uptake in human blood platelets in vitro requires the presence of chloride. Chloride can be replaced by other small univalent, but unphysiological anions, such as (in decreasing order of effectiveness) bromide, nitrite, iodide, nitrate, and formate, However, the effect of nitrite, especially, is kinetically different from that of chloride. Whereas the effect of chloride obeys simple Michaelis-Menten type kinetics, increasing concentrations of nitrite give a sigmoidal 5HT uptake curve. Moreover, the effects of nitrite and chloride are partly additive. It is suggested that these effects of nitrite can be explained by assuming that nitrite, besides being able to replace chloride in the so-called “anionic site” of the carrier, also has an effect on a hypothetical “activating site”. This simple model cannot, however, easily explain all the complex interactions between chloride and nitrite. It is also reported that preincubation with different anions affects the uptake rate to very varying degrees, and that the anions have somewhat different effects on spontaneous 5HT outflux.     

Effects of Sample Collection and Storage Methods on Antipneumococcal Immunoglobulin A in Saliva

Saliva contains components of both the mucosal and systemic immune systems. Variable flow rates, immunoglobulin proteases, and variation in collection and storage methods all introduce differences in the estimated concentrations of antibodies. We evaluated the effect of four collection methods and three storage protocols on the concentrations of immunoglobulin A (IgA) antibodies to pneumococcal capsular antigens 1, 5, 6B, and 14 and to pneumococcal surface adhesin A (PsaA) in saliva. Specimens were collected from 30 healthy Kenyan adults by collecting drool, by pipette suction, and with two commercial kits, OraSure and Oracol. Aliquots from each specimen were snap-frozen with glycerol in liquid nitrogen or stored for 4 to 8 h at +4°C either with or without the addition of protease enzyme inhibitors prior to storage at −70°C. Anticapsular IgA concentrations were not significantly different with different collection methods, but snap-freezing the specimens in liquid nitrogen led to concentrations 41 to 47% higher than those of specimens stored by the other methods (P < 0.0005).     

氯吡格雷联合阿司匹林治疗急性冠脉综合征疗效与 安全性的Meta分析

目的 系统评价氯吡格雷联合阿司匹林治疗急性冠脉综合征的疗效。方法 计算机检索英文数据库Embase、Pubmed、The Cochrane Library以及中文数据库CBM、CNKI和WanFang Data,搜集有关氯吡格雷联合阿司匹林治疗急性冠脉综合征的相关临床研究,且研究必须为随机对照试验（RCT）。检索时限从2008年1月~2019年1月。由三位评价员独立筛选文献、提取资料并评价纳入的各项临床研究之间的偏移风险[Tau2=0.00;Chi2=3.35;df=10（P=0.97）;I2=0]后,运用RevMan 5.3软件进行Meta分析。结果 最终纳入11项临床研究,包括2518名患者。Meta分析结果显示:与单用阿司匹林相比,氯吡格雷联合阿司匹林能明显提高治疗的有效率[OR=3.12,95%CI（2.20,4.42）,P<0.00001],其中部分研究报道了氯吡格雷联合 阿司匹林治疗急性冠脉综合征的同时,肌钙蛋白的含量出现了降低[OR=4.94,95%CI（1.77,13.79）,P=0.002];对报道中的不良反应（包括心血管事件的发生、血小板的降低、出血等）进行分析,差异无统计学意义（P＞0.05）。结论 氯吡格雷联合阿司匹林能提高对患有急性冠脉综合征的患者的疗效,并且可能不增加不良反应的发生率。由于受纳入的临床研究质量的限制,上述结论还需通过更多的质量更高的研究予以验证。     

气质和教养方式对青少年攻击行为的交互效应检验

目的:考察气质间及气质与教养方式对青少年直接攻击和间接攻击的交互效应。方法:采用气质问卷、教养方式问卷和青少年攻击行为问卷,对1266名青少年进行调查。结果:①意志控制可缓冲感觉寻求对青少年直接攻击的风险作用。②权威教养可缓冲感觉寻求对青少年直接攻击的风险作用,而专制教养可增强意志控制对青少年直接攻击的保护作用;专制教养可减弱感觉寻求对青少年间接攻击的抑制作用。结论:气质间及气质与教养方式的交互效应对青少年直接攻击效应显著;气质与教养方式的交互效应对青少年间接攻击效应显著。     

Tourmaline纤维抑制高黏血症家兔血小板聚集的实验研究

目的 研究Tourmaline纤维对高黏血症家兔血小板聚集的影响。方法 用静脉注射高分子右旋糖酐(MW>140000)的方法复制高黏血症家兔模型,测定应用Tourmaline纤维(实验组,n=6)及对照纤维(对照组,n=6)前后血小板聚集率(1分钟聚集率A1和最大聚集率Amax)的变化。并分析TXA_2水平的变化与血小板Amax间的相关关系。结果 与对照组比,实验组高黏血症家兔在应用Tourmaline纤维后6、12h血小板A1和Amax明显降低,与应用前比,差异有显著意义(P<0.05),12h时TXA_2降低与A-max间呈显著负相关(r=-0.94),24h无显著差异(与对照组比)。结论 使用Tourmaline纤维6h和12h后,高黏血症家兔的血小板聚集明显被抑制,此作用与血浆TXA_2的降低相关。     

阿斯匹林对冠心病患者血小板活性和聚集的影响

对冠心病患者服用阿斯匹林（ＡＳＡ）前后的血小板α－颗粒膜蛋白１４０（ＧＭＰ－１４０）水平和血小板聚集进行了测定。结果显示：冠心病患者治疗前血小板ＧＭＰ－１４０水平和聚集率显著高于正常人（Ｐ〈０．００１）,使用阿斯匹林（ＡＳＡ）治疗后两种指标明显下降（Ｐ〈０．００１）,达到正常人水平（Ｐ〉０．０５）,提示ＡＳＡ能直接降低ＧＭＰ－１４０水平,抑制血小板活化和聚集,有效地防止冠状血管的进一步损害。