Identification of an abnormal gene for the GPIIIa subunit of the platelet fibrinogen receptor resulting in Glanzmann's thrombasthenia

The platelet fibrinogen receptor, which is composed of glycoproteins IIb (GPIIb) and IIIa (GPIIIa), belongs to a large family of receptors that participate in a multitude of biologically important adhesive interactions. Platelets from most patients with the autosomal recessive bleeding disorder, Glanzmann's thrombasthenia, are deficient in GPIIb and GPIIIa. We have used cDNA probes to analyze the GPIIb and GPIIIa genes in four patients from three kindreds with Glanzmann's thrombasthenia. Southern analysis of their DNA was identical to that observed in normals when probed with a full-length GPIIb cDNA or a 3' GPIIIa cDNA. However, in one family, a 5' 2.0 kb GPIIIa cDNA identified abnormal DNA fragments in the father and two affected siblings' genes. A series of restriction digests resulting in small genomic fragments were probed with portions of the 5' 2.0 kb GPIIIa cDNA and indicated that the abnormal sequences are flanked by normal fragments of the GPIIIa gene. To analyze further the genetic defect in this family, RNA was prepared from their platelets. Northern analysis revealed normal levels of GPIIb mRNA compared to control platelets. We were unable to identify GPIIIa mRNA of any size in the clinically affected family members. We also identified an EcoRI restriction fragment length polymorphism (RFLP) that permitted carrier status determination in the clinically unaffected siblings. These studies indicate that Glanzmann's thrombasthenia can be caused by heterogeneous defects in the GPIIIa gene. Furthermore, we have shown that platelets can be used to characterize normal and abnormal GPIIIa and GPIIb mRNA, and RFLPs may be used to determine the carrier status in some families with Glanzmann's thrombasthenia. The specific gene abnormality in this family appears to represent an example of an insertional mutation resulting in a human disease.     

Quantitation of activated factor VII levels in plasma using a tissue factor mutant selectively deficient in promoting factor VII activation

Although the majority of factor VII (FVII) circulates in the zymogen form, low levels of activated factor VII (FVIIa) have been postulated to exist in plasma and to serve a priming function for triggering of the clotting cascade. However, direct measurement of plasma FVIIa has not previously been possible. We have quantified plasma FVIIa levels using a novel, highly sensitive assay that is free from interference by FVII. Specificity of this clot-based assay results from the use of a mutant tissue factor that is selectively deficient in promoting FVII activation, but retains FVIIa cofactor function. In normal adults, FVIIa was found to be present in plasma (mean: 3.6 ng/mL) with considerable variation between individuals (range: 0.5 to 8.4 ng/mL). FVIIa levels were only loosely correlated with FVII coagulant activity, but were elevated in pregnancy and reduced with oral anticoagulant therapy. Incubation of plasma on ice in glass containers (cold activation) resulted in substantial FVIIa generation. Measurement of plasma forms of factor VII is of potential clinical importance because elevated FVII coagulant activity has been implicated as a significant risk predictor for ischemic heart disease. Clinically, this new assay will now permit direct assessment of the role of plasma FVIIa in thrombotic disorders.     

人工股骨头假体置换治疗高龄股骨转子部骨折的特点

目的:观察人工股骨头假体置换对75岁以上股骨转子间骨折患者的治疗效果,以及治疗过程中的早期并发症和不良反应。方法:选择解放军总医院骨科2001-06/2005-12收治的75岁以上股骨转子间骨折患者98例(100髋),患者或家属知情同意。骨折按照EVANS分型:Ⅱ型12髋,Ⅲ型53髋,Ⅳ型32髋。全麻或硬膜外麻醉下手术,术中复位大、小转子骨折块,以钢丝固定,股骨距部位骨缺损以骨水泥充填,重塑股骨距,人工股骨头(北京京航公司或Link公司,钛合金股骨头)以骨水泥固定。复位后中立位或稍内收屈曲90°及伸直位外旋90°无脱位,认为关节安装合适。关节腔内置负压引流管。注意围手术期处理,术后患者早期下地功能锻炼。人工股骨头置换的疗效评估标准:疼痛完全消失、关节功能好、恢复生活自理者为优;活动时髋部或大腿有轻微疼痛、基本恢复生活自理者为良;活动时髋部或大腿疼痛,但可扶拐行走、生活部分自理者为可;髋部疼痛明显、不能行走、生活基本不能自理者为差。结果:98例患者中术后住院期间死亡1例;随访过程中死亡2例,原因与手术无关;失访3例,进入结果分析共92例。①术后随访6-24个月,其中6-12个月23例,13-18个月48例,19-24个月21例,平均13个月。按照疗效评估标准,优30例,良45例,可16例,差1例,优良率为82%。②术后发生早期并发症15例,包括肺部感染、深静脉血栓形成等,发生率为16%。结论:人工股骨头假体置换治疗75岁以上股骨转子间骨折患者,术后髋关节活动功能恢复率较高,并发症发生率较低。     

Serum eosinophil cationic protein (ECP) is a sensitive measure for disease activity in atopic dermatitis

Atopic dermatitis (AD) is characterized by alterations in cellular and humoral immunity including elevated serum levels of IgE, IL-2 receptor (IL-2R) and eosinophil cationic protein (ECP). In order to evaluate the relevance of these serum parameters as indicators of disease activity, the concentrations of IgE, IL-2R and ECP were measured in serum samples of patients with an acute exacerbation of AD (n = 19) on admission to hospital and every 6 days up to discharge, and compared with those from normal non-atopic controls (n = 15). The severity of the disease in the AD patients was examined using an established clinical scoring system. On admission, AD patients showed significantly elevated serum levels of IgE, IL-2R and ECP compared with normal controls (P less than or equal to 0.0001). Clinical improvement was associated with a decrease of both the clinical score (P less than or equal to 0.001) and serum ECP levels (P less than or equal to 0.005). No significant changes in serum IgE and serum IL-2R were observed. In addition, there was a significant correlation between serum ECP and the clinical score (R = 0.67, P less than or equal to 0.001). These data indicate that serum ECP may be a helpful tool for monitoring disease activity in AD.     

新型输送型球囊扩张导管在颅内动脉狭窄治疗中的临床应用研究

目的：探讨新型输送型球囊扩张导管(Fastunnel)在颅内动脉粥样硬化狭窄介入治疗中的应用效果。方法：2021年11月至2022年2月,我们使用新型输送型球囊扩张导管对10例颅内动脉粥样硬化狭窄的患者进行了球囊扩张+支架成形术。收集并分析了患者的基线情况、影像学特点、治疗情况及围手术期情况。结果：男6例,女性4例,平均年龄(62.7±6.7)岁。10例患者均成功接受手术治疗,手术时长为16~65(37.3±18.2)min,治疗过程所受辐射剂量为1381~4901(2643.7±1131.7)mGy,剂量面积乘积(DAP)值为5707~38112(17526.8±10809.5)μGym₂^。围手术期无出血及缺血相关并发症。结论：输送型球囊扩张导管具有较好的安全性,能有效地简化手术步骤、缩短手术时间,对减少患者及医生所受射线剂量。