瑞舒伐他汀和阿托伐他汀对氯吡格雷抗血小板活性的影响

目的观察瑞舒伐他汀和阿托伐他汀对氯吡格雷抗血小板活性的影响。方法选择60例冠心病患者接受阿司匹林100mg/d、氯吡格雷75 mg/d及低分子肝素5000 U/12 h治疗,5 d后随机分为阿托伐他汀20mg/d(阿托伐他汀组,30例)和瑞舒伐他汀10 mg/d(瑞舒伐他汀组,30例)。在服用氯吡格雷之前(基线值)、加用他汀类药物之前及服用他汀类药物3d后,用全血阻抗法分别测定不同浓度二磷酸腺苷(5、10、20μmol/L)诱导的血小板聚集率。结果与基线值比较,服用氯吡格雷5 d后和加服他汀类药物治疗3 d后,2组患者血小板聚集率明显降低,差异有统计学意义(P<0.05);与治疗前比较,阿托伐他汀组患者血小板聚集率有所升高,而瑞舒伐他汀组患者血小板聚集率有所下降,但差异无统计学意义(P>0.05)。结论经细胞色素3A4途径代谢的阿托伐他汀及不经细胞色素3A4代谢的瑞舒伐他汀,短期内对氯吡格雷抗血小板活性无影响。     

阿托伐他汀可以消弱氯吡格雷抗血小板聚集的能力

氯吡格雷 (Clopidogrel)是一种无活性的前体药物 ,需要在肝脏内转化成活性物质 ,并通过与血小板P2YacADP受体结合而发挥其抗血小板聚集的作用。而氯吡格雷在人体肝内活性转化的机制 ,目前仍不清楚。在用一种新型的床旁血小板聚集度计测定氯吡格雷对血小板的功能影响时 ,该文的作者发现当患者同时服用阿托伐他汀 (Atorvastatin)时 ,氯吡格雷的抗血小板聚集作用就会显著降低。由于阿托伐他汀通过肝内的CyP3 A4酶代谢 ,因此该文的作者推测 ,阿托伐他汀可能抑制氯吡格雷通过P45 0CyP3 A4酶进行活性转化这一过程 ,从而消弱氯吡格雷抗血小板…     

他汀类药对氯吡格雷抗血小板作用的影响

目的 前瞻性评价普伐他汀、氟伐他汀、阿托伐他汀对氯吡格雷抗血小板作用的影响.方法 人选连续1015例急性冠状动脉综合征或稳定性心绞痛行冠状动脉造影和(或)支架术患者,分为普伐他汀组(228例)、氟伐他汀组(179例)、阿托伐他汀组(481例)和对照组(127例).比较各组术后支架内血栓发生率、不同浓度(2、5、10、20 μmol)二磷酸腺苷(ADP)诱导的1 min(ADP-1)、5 min(ADP-5)和最大血小板聚集力(ADP-M)及其影响因素.结果 4组患者基础临床情况(除年龄、高血压及冠状动脉造影复查率外)和冠状动脉病变和(或)支架术情况相似,术后支架内血栓发生率(普伐他汀组0.9%、氟伐他汀组1.1%、阿托伐他汀组1.0%、对照组0.8%,P>0.05)和ADP-1、ADP-5、ADP-M与对照组相比差异均无统计学意义(P均>0.05).多因素回归分析显示,年龄(B=0.21,P=0.001)、氯吡格雷总量(B=7.30,P=0.002)及低分子肝素的使用(OR=6.71,P=0.01)是影响氯吡格雷抗血小板作用的独立决定因素.结论 普伐他汀、氟伐他汀和阿托伐他汀对氯吡格雷的抗血小板作用无明显影响,而年龄、氯吡格雷总量及低分子肝素使用是决定氯吡格雷抗血小板作用的独立因素.     

阿托伐他汀可能抑制经皮冠脉介入治疗后氯吡格雷的抗血小板作用

加拿大蒙特利尔皇家维多利亚医院Brophy报道,经皮冠脉介入治疗（PCI）术后服用氯吡格雷的患者,如果同时接受阿托伐他汀治疗,可能导致心血管事件发生危险增加。氯吡格雷是一种抗血小板药物，为无活性的药物前体，在体内经细胞色素P4503A4酶（CYP3A4）的作用转化为活性成分。在PCI术后，氯吡格雷是常用的预防支架内血栓形成的抗血小板药物，阿托伐他汀可能与氯吡格雷的无活性药物前体竞争性结合CYP3A4，从而影响氯吡格雷的抗血小板作用。     

阿托伐他汀联合氯吡格雷治疗老年急性脑梗死的1年短期疗效及对患者预后运动能力的影响

目的 探讨阿托伐他汀联合氯吡格雷治疗老年急性脑梗死(ACI)的1年短期疗效及对患者预后运动能力的影响。方法 选取2018年1月至2021年1月海口市第三人民医院收治的200例老年ACI患者。应用病历号单双分组将患者分为研究组(n=100,采用阿托伐他汀联合氯吡格雷治疗)和对照组(n=100,采用阿托伐他治疗),比较两组临床效果。结果 研究组治疗有效率(98.00%)显著高于对照组(88.00%,P<0.05);研究组治疗后凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)水平显著高于对照组，纤维蛋白原(FIB)水平显著低于对照组(P<0.05);研究组治疗后血小板活化功能指标血小板-单核细胞聚集体(PMA)、a颗粒膜糖蛋白(CD)62p水平显著低于对照组(P<0.05);研究组治疗后总胆固醇(TC)、三酰甘油(TG)水平显著低于对照组(P<0.05);研究组治疗后运动功能评分(Fugl-Meyer)量表显著高于对照组(P<0.05)。结论 阿托伐他汀联合氯吡格雷治疗老年ACI的1年短期疗效显著，经过治疗后血脂、凝血功能、血小板活化功能均得到一定的改善，...     

阿托伐他汀与氯吡格雷对ACS患者氯吡格雷羧酸衍生物血浓度与血小板聚集率的影响

目的:测定急性冠状动脉综合征(ACS)患者氯吡格雷羧酸衍生物血浓度和血小板聚集率,观察阿托伐他汀和氯吡格雷有无相互作用。方法:对照组为25例健康受试者,ACS组为66例ACS患者。均口服阿司匹林100mg/d、氯吡格雷75mg/d、阿托伐他汀20mg/d,5d后暂停阿托伐他汀,继续氯吡格雷和阿司匹林口服4d,分别于第5天、第9天采用液相色谱串联质谱法测量氯吡格雷羧酸衍生物血浓度,流式细胞仪测定血小板聚集率,比较两组差异。结果:对照组第5天和第9天氯吡格雷羧酸衍生物血浓度分别为(5.76±0.87)ng/dl和(5.67±0.88)ng/dl(P=0.351),血小板聚集率分别为(44.25±16.37)%与(47.61±16.67)%(P=0.083)。ACS组第5天和第9天氯吡格雷羧酸衍生物血浓度分别为(5.96±0.87)ng/dl和(5.86±0.97)ng/dl(P=0.115),血小板聚集率分别为(47.70±15.07)%与(47.02±15.45)%(P=0.622)。相关性分析显示,血氯吡格雷羧酸衍生物浓度和血小板聚集率呈正相关。结论:氯吡格雷羧酸衍生物血浓度和血小板聚集率相关性良好,氯吡格雷和阿托伐他汀未见相互作用。     

西洛他唑与氯吡格雷对ACS患者抗炎作用研究

目的探讨抗血小板药西洛他唑、氯吡格雷对急性冠脉综合征(ACS)患者斑块稳定性和炎症抑制的作用机制,以及与他汀类药物的协同作用。方法入选82例ACS患者随机分成A组(常规用药+阿托伐他汀)、B组(氯吡格雷常规用药)和C组(西洛他唑+常规用药),观察治疗3周后血脂、白细胞(WBC)计数和高敏C反应蛋白(hs-CRP)、肿瘤坏死因子-a(TNF-a)、白介素-1β(IL-1β)水平变化、临床疗效和不良反应。结果 3组在治疗后WBC计数、三酰甘油(TG)、胆固醇(TC)、低密度脂蛋白(LDL-C)较治疗前均下降(P<0.05),下降幅度组间比较无统计学意义;3组治疗后高密度脂蛋白(HDL-C)上升(P<0.05);3组治疗后TNF-a、IL-1β和hs-CRP水平均下降(P<0.05),氯吡格雷、西洛他唑两组下降幅度均大于常规用药(P<0.05)。治疗前后TNF-a、IL-1β变化值与HDL-C变化值呈负相关(r=-0.38,P=0.04;r=-0.39,P=0.03)。结论予ACS患者阿托伐他汀联用西洛他唑或氯吡格雷较单用阿托伐他汀均可进一步降低致炎因子水平,抑制血小板活化。     

急性冠脉综合征病人氯吡格雷抵抗与他汀类药物的相关性研究

目的探讨他汀类药物是否影响氯吡格雷抗血小板作用。方法选取76例急性冠脉综合征病人,所有病人均连续口服双联抗血小板药物(阿司匹林肠溶片与硫酸氢氯吡格雷片)及他汀药物不少于7 d。39例病人口服经CYP3A4途径代谢的降脂药物(阿托伐他汀钙或辛伐他汀片)为CYP3A4途径代谢组,37例病人口服非CYP3A4途径代谢的降脂药物(氟伐他汀缓释片)为非CYP3A4途径代谢组。采用比浊法测定两组二磷酸腺苷(ADP)(5μmol/L)诱导的血小板聚集率。结果两组平均血小板聚集率比较差异无统计学意义(P0.05)。结论氯吡格雷抵抗现象发生机制与不同代谢途径他汀药物相互作用无明显关联。     

阿托伐他汀联合氯吡格雷在冠心病心绞痛治疗中对血脂、血液流变学及心功能的影响

目的 探讨阿托伐他汀联合氯吡格雷在冠心病心绞痛治疗中作用。方法 回顾性分析冠心病心绞痛患者74例,随机分为：对照组(n=37)应用传统治疗,观察组(n=37)应用阿托伐他汀联合氯吡格雷,观察两组血脂、血液流变学及心功能指标。结果 干预后,观察组总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、三酰甘油(TG)显著低于对照组(P<0.05),高密度脂蛋白胆固醇(HDL-C)显著高于对照组(P<0.05);干预后,观察组血液流变学指标显著低于对照组(P<0.05);干预后,观察组心功能显著高于对照组(P<0.05)。结论 阿托伐他汀联合氯吡格雷可改善冠心病心绞痛患者血脂、血液流变学及心功能指标。     

两种他汀类药物对不同细胞色素P450酶2C19基因型患者氯吡格雷抗血小板作用的影响

目的观察2种他汀类药物对不同细胞色素P450酶(CYP)2C19基因型的急性冠状动脉综合征(ACS)患者氯吡格雷抗血小板作用的影响。方法选取接受CYP2C19基因型检测的老年ACS患者200例,根据服用他汀类药物及CYP2C19基因型分为6组:阿托伐他汀+快代谢组(A组)40例,瑞舒伐他汀+快代谢组(B组)40例;阿托伐他汀+中代谢组(C组)46例,瑞舒伐他汀+中代谢组(D组)46例;阿托伐他汀+慢代谢组(E组)14例,瑞舒伐他汀+慢代谢组(F组)14例。在使用氯吡格雷前(基线)、联合服用他汀类药物前(治疗前)及服用他汀类药物7 d(治疗后),测定二磷酸腺苷诱导的血小板聚集率;随访6个月,观察主要不良心血管事件(MACE)的发生率。结果与基线比较,治疗前和治疗后A组、B组、C组、D组、E组和F组血小板聚集率明显降低(P<0.05),且治疗后较治疗前更低[(3.9±0.2)%vs(5.2±0.3)%;(3.8±0.2)%vs(5.3±0.3)%;(4.9±0.4)%vs(5.3±0.3)%;(5.0±0.3)%vs(5.1±0.4)%;(5.0±0.4)%vs(5.2±0.3)%;(4.9±0.5)%vs(5.1±0.4)%,P<0.05];治疗后在相同基因代谢类型中,A组与B组、C组与D组、E组与F组血小板聚集率比较,无统计学差异(P>0.05);治疗后在不同基因代谢类型中,A组血小板聚集率明显低于C组和E组(P<0.05),B组血小板聚集率明显低于D组和F组,差异有统计学意义(P<0.05);C组与E组,D组与F组血小板聚集率比较,差异无统计学意义(P>0.05)。6组MACE发生率比较,差异无统计学意义(P>0.05)。结论2种他汀类药物对于同一代谢基因型组氯吡格雷抗血小板活性没有影响,对于不同代谢基因型患者氯吡格雷抗血小板活性有影响,氯吡格雷抗血小板活性受到CYP2C19基因多态性的影响。     

胰岛素瘤的解剖分布特点分析

目的胰岛素瘤是最常见的胰腺神经内分泌肿瘤，因其临床表现多样，导致诊断困难。影像学诊断尤其是超声内镜(EUS)在胰岛素瘤的诊断中起着重要作用，拥有较高的敏感性和特异性。本研究拟通过明确胰岛素瘤的解剖分布特点，以期有助于提高影像学的诊断准确率和降低漏诊率，尤其是在教育和培训实践中对于EUS的学习者更具有指导价值。 方法回顾性分析解放军总医院第一医学中心病案资料数据库1993年1月至2019年11月经外科手术、病理确诊为胰岛素瘤的患者的临床资料，检索方法采取搜索术后病理诊断为"胰岛素瘤"的病例，通过查阅病例的方法，提取出胰岛素瘤的大小和解剖分布等数据，进一步分析其特点。 结果共检索到确诊为胰岛素瘤的患者116例，其中，男45例、女71例，年龄13～76岁，平均年龄(44.4±14.85)岁。胰岛素瘤单发110例(94.8%)、多发6例(5.2%)。位置分布：头颈部46例(39.7%)，单发45例、多发1例；体尾部68例(58.6%)，单发65例、多发3例；全胰腺多发2例(1.7%)。病变大小特点：最大径0.4～3.4 cm，平均大小(1.53±0.58)cm。≤1 cm 29例、>1 cm而≤1.5 cm41例、>1.5 cm而≤2.0 cm28例，≤3 cm 15例，>3 cm 3例。年龄与肿瘤的大小相关，≤44岁患者肿瘤平均大小为(1.36±0.51)cm、>44岁患者肿瘤平均大小为(1.70±0.60)cm，P<0.05。头颈部的肿瘤大于体尾部的肿瘤，头颈部肿瘤平均大小(1.66±0.63)cm，体尾部(1.42±0.52)cm，P<0.05。 结论胰岛素瘤在胰腺体尾部较头颈部更好发；绝大多数单发，但可以全胰腺多发；多数小于1.5 cm，肿瘤的大小与患者年龄和肿瘤的解剖分布相关。     

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7?, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20?, MUC2?). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Demonstration of the mechanism of action of biguanides

Summary Palmitic acid oxidation in rat diaphragm homogenate is depressed by biguanide concentrations that are still incapable of inhibiting oxidative phosphorylation. Glucose oxidation is not directly effected by the same biguanide concentrations: however, the inhibitory effect of palmitic acid on glucose oxidation is partly removed by biguanides. Inhibition of fatty acid oxidation, which accounts for most of the metabolic effects caused by these drugs, can be regarded as the fundamental mechanism of action of biguanides. There is some evidence suggesting that these drugs might interact with carnitine, thus preventing long-chain fatty acids from being transported across the mitochondrial membrane to the site of oxidation. Traduzione a cura degli AA.     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

血吸虫童虫生长发育及其机制的研究进展

血吸虫童虫是宿主免疫系统攻击的重要靶标,包括皮肤型、肺型和肝门型童虫。宿主分子对童虫生长发育具有重要作用。童虫生长发育机制包括免疫调节、信号转导、性别发育及凋亡等。肌动蛋白、组织蛋白酶、烯醇化酶和葡萄糖基转移酶等分子为血吸虫童虫生长发育的重要分子。本文对血吸虫童虫生长发育及其机制的研究进展做一综述。     

124例耐多药结核分枝杆菌基因突变特征分析

目的对临床分离的耐多药结核分枝杆菌相关基因的突变特征进行分析。方法对124例耐多药结核分枝杆菌以及50株敏感株的耐药相关基因(包括异烟肼inh A、kat G、oxyR-ahp C间隔区以及利福平rpo B)进行序列测定,分析其基因突变情况。结果异烟肼耐药inh A基因突变率为14.5%;kat G基因突变率为70.2%(87/124),主要位于315位;oxyR-ahp C间隔区突变率为15.3%;inh A、kat G两种基因同时突变率75.0%,三种基因同时突变率为89.5%。利福平rpo B基因突变的检出率高达95.2%,突变主要发生在531、526、516位点。结论我省耐多药菌异烟肼耐药相关基因最常见突变为kat G 315、inh A C-T(-15)、axyR-ahp C间隔区(-10)C-T,利福平为rpo B531、526、516。结合MDR-TB耐药相关基因的特征分析,可以建立一种快速、准确、特异的适合于我省的检测结核菌耐多药性的新方法。     

氯硝柳胺悬浮剂的毒性评价

目的评价氯硝柳胺悬浮剂的毒性，为现场大规模应用灭螺提供依据。方法按照中华人民共和国国家标准GB 15670-1995《农药登记毒理学试验方法》和鱼类毒性试验方法进行。结果经口、经皮肤的LDso雌、雄性大鼠均>5 000 mg/kg，经呼吸道的LCso雌、雄性大鼠均>5 000mg/m3，该药经口、经皮肤、经呼吸道毒性均属微毒类药物；兔眼用药后，观察期内无不良反应，对眼无刺激性；皮肤用药后对皮肤无刺激性。与氯硝柳胺原药、氯硝柳胺乙醇胺盐原药和氯硝柳胺乙醇胺盐可湿性粉剂相比，氯硝柳胺悬浮剂对鱼急性毒性最低。结论氯硝柳胺悬浮剂属微毒类药物，对鱼的毒性低于其乙醇胺盐可湿性粉剂，适合于现场应用。     

Assessment of quality of life of parents of children with juvenile chronic arthritis

The aim of the study was to assess the quality of life (QOL) and the psychological status of parents of children with juvenile chronic arthritis (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA were evaluated and compared to those of the parents of 28 healthy children. Mothers of JCA children and mothers of healthy children reported similar QOL. The reported anxiety and depression levels were similar for mothers and fathers in both groups. The parents of children with pauciarticular-type JCA reported lower QOL and higher levels of anxiety and depression than the parents of children with other types, namely polyarticular and systemic JCA. These findings may be explained by the fact that the pauciarticular patients had shorter disease duration and were less frequently seen in the outpatient clinic. The QOL of mothers of children with JCA was found to be slightly impaired in the group of children with pauciarticular JCA. Future larger studies are needed to confirm these results, as the number of subjects in the three groups was rather low. Received: 26 September 2001 / Accepted: 8 February 2002     

Numerical Simulation of the Effect of Rate of Change of Glucose on Measurement Error of Continuous Glucose Monitors

Background

A 5-day in-patient study designed to assess the accuracy of the FreeStyle Navigator® Continuous Glucose Monitoring System revealed that the level of accuracy of the continuous sensor measurements was dependent on the rate of glucose change. When the absolute rate of change was less than 1 mg•dl⁻¹•min⁻¹ (75% of the time), the median absolute relative difference (ARD) was 8.5%, with 85% of all points falling within the A zone of the Clarke error grid. When the absolute rate of change was greater than 2 mg•dl⁻¹•min⁻¹ (8% of the time), the median ARD was 17.5%, with 59% of all points falling within the Clarke A zone.

Method

Numerical simulations were performed to investigate effects of the rate of change of glucose on sensor measurement error. This approach enabled physiologically relevant distributions of glucose values to be reordered to explore the effect of different glucose rate-of-change distributions on apparent sensor accuracy.

Results

The physiological lag between blood and interstitial fluid glucose levels is sufficient to account for the observed difference in sensor accuracy between periods of stable glucose and periods of rapidly changing glucose.

Conclusions

The role of physiological lag on the apparent decrease in sensor accuracy at high glucose rates of change has implications for clinical study design, regulatory review of continuous glucose sensors, and development of performance standards for this new technology. This work demonstrates the difficulty in comparing accuracy measures between different clinical studies and highlights the need for studies to include both relevant glucose distributions and relevant glucose rate-of-change distributions.     

Study of constancy of hydrogen-consuming flora of human colon

The constancy of the hydrogen consuming flora of the human colon was studied in 15 healthy subjects via two measurements obtained 18 to 36 months apart. Hydrogen disappearance rate and the major products of H₂-consuming bacteria, methane and sulfide, were measured during incubation of fecal homogenates with excess hydrogen and sulfate. In 11/15, the hydrogen consumption rate and the predominant hydrogen-consuming pathway (methanogenesis, sulfate reduction, or neither) remained constant. However, major shifts in these pathways were observed in four subjects, with two losing and two gaining the ability to produce methane. Methanogenesis was associated with the highest hydrogen consumption rate. This study demonstrates that clinically unrecognizable, major alterations of the colonic flora occur in healthy subjects. Understanding of the factors responsible for these alterations might allow for therapeutic manipulation of the colonic flora.Supported in part by the Department of Veterans Affairs and NIDDKD RO1 DK 13309-25.