福多司坦对重度阻塞性睡眠呼吸暂停综合征患者Th1、Th2细胞以及血清中IFN-γ和IL-4的影响

目的 探讨福多司坦对阻塞性睡眠呼吸暂停综合征（OSAS）患者Th1、Th2细胞的比例以及血清中γ干扰素（IFN-γ）和白细胞介素?4（IL-4）浓度的影响。方法 选择2013年4月至2014年12月在南京医科大学附属无锡市人民医院呼吸科就诊的门诊以及住院的重度OSAS患者57例和单纯打鼾患者20例,所有受试者均为男性,年龄55～76（67.0±6.4）岁。按照呼吸暂停低通气指数（AHI,次/h）将患者分为3组,即对照组（AHI≤5,n＝20）、OSAS组（AHI＞40,n＝28）和OSAS＋福多司坦组（AHI＞40,口服福多司坦片2周,n＝29）。采用流式细胞检测法测定Th1和Th2细胞所占的比例;酶联免疫吸附法测定血清中IFN-γ和IL-4的浓度。结果 研究结果表明,3组患者的年龄和体质量指数（BMI）差异无统计学意义（P＞0.05）。与对照组相比,OSAS组患者Th1细胞所占比例显著升高[F（2,74）＝85.06,P＜0.01],同时Th1细胞相关的细胞因子IFN-γ的浓度也明显上升[F（2,74）＝131.4,P＜0.01];与OSAS组相比,OSAS＋福多司坦组患者Th1细胞所占比例显著下降[F（2,74）＝85.06,P＜0.01],血清中IFN-γ的浓度也明显下调[F（2,74）＝131.4,P＜0.01];而3组患者Th2细胞的比例[F（2,74）＝2.66,P＝0.08]和血清中IL-4的水平[F（2,74）＝2.29,P＝0.11]的差异无统计学意义。结论 重度OSAS患者体内Th1细胞的激活程度显著升高,表现为相关细胞因子分泌的增多,而Th2细胞及相关细胞因子的变化不明显。福多司坦可以抑制Th1的过度激活,并降低Th1相关细胞因子的分泌。     

血小板活化对老年阻塞性睡眠呼吸暂停低通气综合征患者的影响

目的探讨血小板活化在老年人阻塞性睡眠呼吸暂停低通气综合征(OSAHS)发生发展中的作用及经鼻持续气道正压通气(nCPAP)对其影响.方法选择经多导睡眠图(PSG)确诊的老年OSAHS患者90例为试验组,据睡眠呼吸暂停低通气指数(AHI)、最低血氧饱和度(SaO2)将OSAHS患者分轻、中、重3组,其中16例重度OSAHS患者接受nCPAP治疗为治疗组,并设健康对照组20例,用酶联免疫双抗体夹心法检测各组血浆α-颗粒膜蛋白(GMP-140)、血小板膜糖蛋白Ⅱb/Ⅲa(GPⅡb/Ⅲa),比较各试验组与对照组,治疗组治疗前、后的各项指标的差异.结果 (1)中、重度老年OSAHS患者组血浆GMP-140[(16.6±2.3)μg/L、(18.9±3.1)μg/L]、GPⅡb/Ⅲa(38 468±952/49673±1037、39 867±1264/50 899±2476)均显著高于对照组[(14.8±2.1)μg/L、37672±769/48469±1672, P ＜0.05],nCPAP治疗后比治疗前明显下降(P ＜0.001);(2)GMP-140、GPⅡb/Ⅲa与AHI呈正相关(r值为0.5273、0.4829/0.4562,均为P ＜0.001),与SaO2min呈负相关(r值为-0.6481、-0.5846/-0.6264,均为P ＜0.001).结论中、重度老年OSAHS患者存在明显血小板活化,并与夜间低氧血症密切相关,其可能在OSAHS患者心脑血管栓塞性并发症高发生率中起重要作用;nCPAP治疗可有效逆转上述改变.     

OSA对不稳定型心绞痛患者炎症补体水平的影响及其与冠状动脉狭窄程度的相关性研究

目的 探讨OSA对不稳定型心绞痛患者炎症补体系统标记物水平的影响及其与冠状动脉狭窄程度的相关性。 方法 回顾性分析首都医科大学附属北京安贞医院2018年07月至2019年07月167例不稳定型心绞痛患者,所有患者均进行过睡眠呼吸监测,根据监测结果将AHI≥15的患者分为OSA组（63例）,其余为对照组（104例）,比较入院时既往病史、用药、实验室检查、血清CRP、C1q水平和冠状动脉病变Gensini评分等。 结果 OSA组Gensini评分[27.00 (26.80, 49.20）vs 20.00 (19.56, 28.19), P=0.039]、CRP[1.63 (1.43, 7.34) vs 1.42 (1.10, 4.21) mg/L, P=0.001]、C1q[(187.95±29.73) vs (176.18±29.70) mg/L, P=0.028]显著高于对照组;AHI与Gensini评分具有正相关性 (r=0.367, P<0.001);多因素回归分析发现AHI (P=0.001)、CRP (P=0.015)和C1q (P=0.006)是影响冠脉狭窄程度的独立因素。结论 OSA患者血清CRP和C1q水平显著升高,且OSA严重程度与冠心病患者冠脉狭窄程度具有相关性,CRP和C1q有望预测OSA患者冠脉狭窄程度。     

OSA患者的呼吸力学特征及血清肺泡表面活性物质水平与其胃食管反流事件的关系研究

目的通过评价阻塞性睡眠呼吸暂停(OSA)患者呼吸系统力学特征及其血清肺泡表面活性蛋白水平与其胃食管反流事件3者之间的关系,探寻OSA患者呼吸系统力学特性发生变化的可能原因。 方法对连续住院的疑似鼾症患者进行多导睡眠监测(PSG)并诊断,同时分别用脉冲振荡肺功能(IOS)测定其呼吸系统力学特征;酶联免疫吸附法测定血清肺泡表面活性物质蛋白(SP-A,-B,-C,-D)及多通道阻抗-pH监测系统,检测并分析比较胃食管及咽喉部24 h的返流状况。 结果60例经PSG确诊为不同严重程度鼾症的患者,依据其呼吸暂停低通气指数(AHI)将其分为OSAS组与非OSAS进行比较,OSAS组患者的呼吸总阻抗(Zrs5)和全部震荡频率的呼吸阻力(Rrs)显著高于非OSAS组,而呼吸电抗(Xrs)显著降低;OSAS组患者的DeMeester评分及食管近端酸反流、食管反流总值高于非OSAS组,差异具有统计学意义(P<0.01);OSAS患者的血清肺泡表面活性物质蛋白-B水平低于非OSAS组,差异有统计学意义(P<0.01)。OSAS患者的呼吸总阻抗和呼吸阻力(5～15 Hz)与总反流指数和DeMeester评分正相关(r＝0.614,P＝0.031;r＝0.668,P＝0.015;r＝0.569,P＝0.032;r＝0.563,P＝0.034);OSAS患者的Xrs5的下降与其血清肺泡表面活性物质蛋白-B水平存在相关性(r＝－0.594,P＝0.023),而与总反流指数、DeMeester评分负相关(r＝－0.821,P＝0.000;r＝－0.734,P＝0.001)。 结论随着鼾症患者阻塞性睡眠呼吸程度的加重,其呼吸阻力增加,而呼吸电抗(Xrs5)负值增大;OSAS患者的胃食管及食管近端反流与其呼吸暂停低通气指数正相关;该事件与其呼吸阻力正相关,而与其呼吸电抗显著负相关。     

阻塞性睡眠呼吸暂停综合征严重度与血小板参数相关性的探讨

目的:探讨阻塞性睡眠呼吸暂停综合征(obstructive sleep apnea syndrome, OSAS)的程度与血小板参数如血小板计数、平均血小板体积(mean platelet volume,MPV)、血小板分布宽度(platelet distribution width,PDW)及血小板压积的关系。方法:纳入166例受试者,分为轻度OSAS组[睡眠呼吸暂停低通气指数(apnea-hypopnea index, AHI)(5.0～14.9,n=40)]、中度OSAS组(AHI 15.0～29.9,n=43)和重度OSAS组(AHI≥30,n=42),及正常对照(AHI5,n=41),并对重度OSAS组中的32例实施持续气道正压通气(continuous positive airway pressure,CPAP)治疗3个月。比较各组间以及治疗前后血小板计数、MPV、PDW及血小板压积等血小板参数的变化。结果:血小板计数、MPV及血小板压积在各组患者中差异无统计学意义(均P0.05)。PDW在正常对照和轻度OSAS组间以及在中度和重度OSAS组间差异无统计学意义(均P0.05),但中度和重度OSAS组PDW明显高于正常对照组和轻度OSAS组(均P0.05)。重度OSAS患者CPAP治疗后PDW较治疗前显著降低(P0.05)。但血小板计数、MPV及血小板压积治疗前后差异无统计学意义。相关性分析显示PDW与AHI呈正相关(r=0.758,P=0.034),PDW与最低脉搏氧饱和度(minimal pulse oxygen saturation,miniSpO_2)呈负相关(r=-0.579,P=0.012)。结论:PDW可随着OSAS程度的加重而增高,可能作为OSAS严重度评估的潜在辅助指标。     

PCI术后血小板聚集功能影响因素的临床分析

目的探讨经皮冠状动脉介入(PCI)术后患者血小板聚集功能的影响因素。方法 266例冠心病行PCI的患者,均予以氯吡格雷和阿司匹林双联抗血小板及冠心病标准治疗,根据术后血小板聚集率(PAR)分为0%~29%、30%~49%、50%~69%、70%~100%等4组,比较4组患者的CYP2C19基因型、一般临床信息、冠状动脉病变情况及生化指标,并通过Logistic回归分析,找出PAR升高的危险因素。结果患者的性别构成比、年龄、脑钠肽(BNP)、CYP2C19基因型在不同PAR分组间存在差异(P0.05)。Logistic回归分析显示,PAR升高≥50%的危险因素是女性(OR=2.713,P=0.027)、高BNP(OR=1.002,P=0.007)、CYP2C19呈慢代谢型(OR=5.159,P0.001);PAR升高≥70%的独立危险因素是女性(OR=5.716,P=0.008)、CYP2C19呈慢代谢型(OR=3.149,P=0.049)。结论 PAR50%的患者以CYP2C19快代谢基因型为主,而慢代谢基因型的患者PAR多为50%以上,CYP2C19基因多态性对PAR影响显著。另外,女性、高BNP可能是冠心病患者PCI术后PAR升高的危险因素。     

高血压患者阻塞性睡眠呼吸暂停综合征的炎症因子

背景 阻塞性睡眠呼吸暂停综合征(OSAS)是一种常见病,其患高血压的发病率远高于无高血压的人群.目的 旨在通过检测炎症因子的变化探究OSAS导致高血压发生发展的机制.方法 根据睡眠呼吸暂停低通气指数(AHI,＜5次/h为无呼吸暂停)将136例入选者共分为5组.①高血压 轻度OSAS组:22例,AHI 5～20次/h;⑦高血压 中重度OSAS组:58例,AHI＞20次/h;③高血压组;20例,为高血压不合并OSAS患者;④OSAS组:16例,为中重度OSAS不合并高血压患者,AHI＞20次/h;⑤正常对照组:20例,为没有高血压和OSAS的健康人.用酶联免疫吸附法(ELISA)测定白介索6(IL-6)、血清可溶性CD40配体(sCD40L)、高敏C反应蛋白(hsCRP)、可溶性胞间黏附分子1(sICAM-1)及血管细胞黏附分子(VCAM-1)的浓度.结果 ①单独OSAS组和单独高血压组的IL-6、sCD40L、hsCRP、sICAM-1、VCAM-1浓度高于正常对照组,(P＜0.05);②高血压 OSAS组的IL-6、sCD40L、hsCRP、sICAM-1、VACM-1浓度明显商于单独OSAS组、单独高血压组和正常对照组;③高血压 OSAS组的hsCRP、sICAM-1、VCAM-1浓度变化与呼吸紊乱指数、血氧饱和度下降程度正相关;④hsCRP与平均动脉压正相关.结论 炎症反应参与高血压的发生发展,OSAS可能是通过炎症反应而促发高血压.     

阻塞性睡眠呼吸暂停患者血清瘦素水平的研究

目的　探讨瘦素在阻塞性睡眠呼吸暂停综合征 (OSAS)患者体内的变化。方法　选择年龄及体重指数 (BMI)差异无显著性的OSAS患者 5 8例和单纯肥胖者 2 1例 ,用多导睡眠呼吸监测仪进行监测 ,用放射免疫法测定所有对象的血清瘦素。结果　 (1)无论男性还是女性 ,OSAS患者瘦素水平 [(6 1± 1 7) μg/L ,(19 5± 9 9) μg/L]平均高于单纯肥胖者 [(4 5± 1 7) μg/L ,(10 5± 2 4) μg/L](P <0 0 1,P <0 0 5 )。 (2 )单纯肥胖者及OSAS患者血清瘦素水平分别与BMI呈显著正相关 (r=0 5 9,P <0 0 1;r=0 6 4,P <0 0 1) ,同时OSAS患者血清瘦素水平分别与呼吸暂停及低通气指数 (AHI) (r=0 47,P <0 0 1)和颈围 (r=0 6 4,P <0 0 1)也有明显的正相关。结论　OSAS患者血清瘦素水平比单纯肥胖者更高 ,除了肥胖、颈围宽外 ,OSAS本身也是引起瘦素水平升高的原因。     

血小板压积对非ST段抬高型心肌梗死严重病变的预测价值

目的 探讨血小板压积(PCT)与非ST段抬高型心肌梗死(NSTEMI)患者急性冠状动脉事件全球登记(GRACE)评分的相关性及对严重病变的预测价值。方法 回顾性分析2019年1月至2020年1月武汉亚心总医院收治的193例NSTEMI患者的临床资料。根据冠状动脉造影结果,累及3支冠状动脉和(或)左主干者为严重病变组(96例),余为非严重病变组(97例)。采用Spearman分析PCT与GRACE评分的相关性,采用受试者工作特征(ROC)曲线分析PCT对NSTEMI严重病变的预测价值。结果 严重病变组PCT显著高于非严重病变组[(0.32%±0.05%)比(0.24%±0.04%),P＜0.001],血小板计数(PC)显著低于非严重病变组[(180.46±19.46)×10⁹/L比(212.54±30.17)×10⁹/L,P＜0.001]。Spearman相关分析结果显示,无论非严重病变组还是严重病变组,PCT与GRACE评分均呈正相关(r＝0.288,P＝0.004;r＝0.777,P＜0.001),PC与GRACE评分均呈负相关(r＝－0.846,P＜0.001;r＝－0.822,P＜0.001)。ROC曲线下面积PCT最大(0.858),其次是PC(0.802);PCT诊断NSTEMI严重病变的临界值为0.275,敏感度为81.3%,特异度为84.5%。结论 PCT与GRACE评分呈正相关,对NSTEMI严重病变具有较好的预测价值。     

阿托伐他汀对阻塞性睡眠呼吸暂停综合征患者臂-踝脉搏波传递速度的影响

目的 评价阿托伐他汀对阻塞性睡眠呼吸暂停综合征（obstructive sleep apnea syndrome,OSAS）患者臂-踝脉搏波传递速度（brachial-ankle pulse wave velocity,baPWV）的影响.方法 利用多导睡眠图（PSG）入选165例OSAS患者,分为单纯OSAS组（B组）80例和OSAS合并高血压组（C组）85例.入选患者服用阿托伐他汀,在服药前和3个月后应用科林波形分析仪测量患者的baPWV.另外,选择同期81名健康体检者为正常对照组（A组）.结果 B、C两组基础状态如腹围、颈围、体质量指数、呼吸暂停低通气指数（apnea hypopnea index,AHI）、低密度脂蛋白胆固醇、超敏C反应蛋白均明显高于A组,差异有统计学意义（P＜0.05）.B、C两组治疗3个月后血清低密度脂蛋白胆固醇、超敏C反应蛋白浓度均明显降低,与治疗前比较,差异有统计学意义（P＜0.001）.B、C两组baPWV较基础状态明显下降,差异有统计学意义[B组：（1 562±414）cm/s vs.（1 840±463） cm/s,P＜0.001;C组：（1 596±433）cm/svs.（1 866±428）cm/s,P＜0.001].结论 阿托伐他汀不仅显著降低低密度脂蛋白胆固醇,抑制炎症反应,还对动脉弹性有明显的改善作用.     

Platelet calmodulin correlates with platelet turnover

We measured the calmodulin content in platelets in 13 normal persons and in 62 patients with hematological diseases. The level of platelet calmodulin was higher in patients with idiopathic thrombocytopenic purpura (ITP), systemic lupus erythematosus, myeloproliferative disorders, acute leukemia in a recovery phase, aplastic anemia, thrombosis and hypersplenism as compared to the controls. Among the patients with ITP, calmodulin was lower in responders than in nonresponders and those at the initial diagnosis. We also measured the volume, life-span and aggregation of the platelets and demonstrated a significant relationship between the calmodulin level and the platelet volume, and a negative relationship between the calmodulin level and platelet life-span, there was no correlation between the calmodulin level and platelet aggregation. We thus conclude that platelet calmodulin is inversely correlated with platelet turnover.     

Evidence that platelet buoyant density,but not size,correlates with platelet age in man

Following infusion of ⁵¹Cr-labeled autologous platelets into normal subjects, high-density (HD) and low-density (LD) platelet cohorts were isolated by prolonged centrifugation in isosmotic arabino-galactan (Stractan). Specific radioactivity of LD platelets declined rapidly post-infusion (T_1/2 = 1.5 days), but specific radioactivity of HD platelets remained constant or increased over a 3–4-day period and gradually declined for 6–7 days thereafter. These differences were exaggerated when platelet cohorts enriched in LD or HD cells by slow centrifugation in high-density albumin were labeled and transfused. Mean survival of a platelet cohort enriched with HD cells was significantly (P < 0.02) shorter (7.73 days) than that of a cohort enriched with LD cells (9.33 days). In normal subjects treated with aspirin, capacity for thromboxane synthesis was regained more rapidly (P < 0.05) in LD than in HD platelets. HD and LD platelets differed only slightly in mean volume (HD platelets = 7.57 μ³, LD platelets = 6.87 μ³, 0.05 < P < 0.01). We believe the most logical interpretation of these findings is that under normal conditions in man, newly formed platelets are less dense on the average than total platelets and become more dense as they age in the circulation. Thus, specific radioactivity of LD platelets declines rapidly as these platelets move into a more dense compartment and are replaced by newly formed, un-labelled cells; specific radioactivity of HD platelets remains constant or increases as labelled platelets enter this compartment in numbers equal to or greater than the number leaving it at the end of their life span. The similarity in mean volumes of LD and HD platelets suggests that platelet size is unrelated to platelet age under normal conditions.     

In vitro quality of platelets during prolonged storage after washing with three platelet additive solutions

Background and Objectives Patients with anaphylactic transfusion reactions require washed platelet concentrates (PCs) for subsequent platelet (PLT) transfusions. New PLT additive solutions (PASs) contain substances that might be beneficial for the preservation of PLT function during storage. This study compares the quality of PLTs washed and stored with T‐Sol, Composol or SSP+. Study Design and Methods Fifteen buffy coats were pooled and divided into three parts. PCs with 30% plasma and 70% PAS (T‐Sol, Composol or SSP+) were prepared. Washing was performed on day 5 of storage. Ten PCs were prepared and washed with each PAS. In vitro variables including haemostatic function (clotting time and clot retraction) were analysed on day 5 before, directly after and up to 2 days after washing. Results Swirling was well preserved, and pH was within acceptable limits (6·4–7·4) during storage for all PASs. The PLT number was reduced by washing for all PASs, and T‐Sol PCs had a further decrease during storage. PLTs in T‐Sol were spontaneously more activated and had lower capacity to respond to an agonist than Composol or SSP+ PLTs. The haemostatic function was only slightly changed by washing and during postwashing storage. Conclusion PLTs washed with T‐Sol, Composol or SSP+ had good in vitro quality for two days after washing despite absence of glucose. PLTs in T‐Sol were more affected by the washing procedure and subsequent storage than Composol or SSP+ PLTs as judged by higher spontaneous activation.     

Intravascular and total body platelet equilibrium in healthy volunteers and in thrombocytopenic patients transfused with single donor platelets

Instrument platelet counts used in corrected count increment (CCI) and percent platelet recovery (PPR) formulas presume the transfused platelets are in equilibrium during the first hour after platelet transfusion. The timing of the pre-transfusion count affects CCI results, and we postulate that timing of CCI post transfusion affects CCI results. Platelet equilibrium using indium-111 platelet transfusions has not been reported. Platelet redistribution was studied in 16 healthy volunteers and 12 thrombocytopenic patients by generally infusing less than 72-hr stored single-donor platelets along with an aliquot of indium-111-labeled platelets by intravenous push. Counts were measured at 10, 15, 20, 60, and 120 min, and 24, 48, 72 hr along with continuous body scanning for 2 hr in healthy volunteers, and static organ scanning in patients and volunteers. Results indicated transfused platelets do not reach intravascular equilibrium for 60 min post-infusion and that the 10-min count cannot detect platelet refractoriness. However, total body equilibrium varies considerably between normal volunteers and thrombocytopenic patients. It is recommended to continue with the 1-hr post transfusion count. Am. J. Hematol. 58:165–176, 1998. © 1998 Wiley-Liss, Inc.     

Studies of platelet volume, chemistry and function in patients with essential thrombocythaemia treated with Anagrelide

Anagrelide (imidazoquinazolin derivative) is a new compound proposed for the treatment of myeloproliferative disorders. In this study, Anagrelide was given to patients with essential thrombocythaemia (ET) in a compassionate-use protocol. The aim of this study was to test the effect of this drug not only on the platelet count but also on platelet volume, chemistry and function, which has not previously been reported. Thus, in ET, different functional or structural platelet abnormalities were reported: a shortening of the bleeding time, hypoaggregation to several agonists, and in particular a lack of response to adrenalin, an increase in the amount of total platelet glycoprotein IV (or CD36), and an abnormal migration of thrombospondin on electrophoresis. These different parameters were studied before and during therapy with Anagrelide. Although the platelet count was corrected, no functional or chemical abnormality was improved. Furthermore, platelet volume was shown to be constantly increased under Anagrelide. Thus, Anagrelide, in reducing the platelet count, may possibly decrease the risk of thrombosis and haemorrhage. Nevertheless, if the risk of thromboses and/or myelofibrosis is related not only to the platelet count but also to the platelet abnormalities, the persistence of a thrombocytopathy in patients treated with Anagrelide must be taken in consideration. Our data suggest that thromboses and myelofibrosis are clinical end-points which should be included in future large-scale use of Anagrelide.     

Congenital Deficiency of Cyclo-Oxygenase in a Woman with Generalized Atherosclerosis

The case of a 52-year-old woman with congenital cyclo-oxygenase deficiency, signs of generalized atherosclerosis and a moderate bleeding tendency is reported. Secondary platelet aggregation was absent. Platelet aggregation induced by arachidonic acid failed totally while that induced by calcium ionophore was normal. No malondialdehyde formation could be detected in her platelet-rich-plasma. The life-long deficiency of cyclo-oxygenase had not protected her from progressive vascular disease. This case suggests that the chronic intake of large doses of aspirin cannot prevent arterial disorders.     

A review of inherited platelet disorders with guidelines for their management on behalf of the UKHCDO

The inherited platelet disorders are an uncommon cause of symptomatic bleeding. They may be difficult to diagnose (and are likely to be under-diagnosed) and pose problems in management. This review discusses the inherited platelet disorders summarising the current state of the art with respect to investigation and diagnosis and suggests how to manage bleeding manifestations with particular attention to surgical interventions and the management of pregnancy.     

Platelets are not hyperreactive in patients with ovarian cancer

Paraneoplastic thrombocytosis has been reported in different types of solid tumors, including ovarian epithelial cancer, and found to be associated with a worse outcome. Although the effect of cancer on increasing platelet counts is well documented, the effect of cancer on platelet functions is not well known. We compared in vitro aggregation response of platelets isolated from 34 patients with ovarian cancer to those of platelets from 19 patients with benign ovarian tumors. Aggregation studies were conducted in a light transmission aggregometer, using both a high and a low dose of ADP and collagen. We evaluated platelet preactivation by measuring the plasma concentration of β-thromboglobulin (β-TG) and platelet factor-4 (PF-4) as markers of platelet α granule secretion, using ELISA. We found that ovarian cancer is not associated with an enhanced aggregation response of platelets to ADP or collagen, and plasma concentration of β-TG and PF-4 is not higher in patients with ovarian cancer compared to those in patients with benign ovarian tumors.