巨噬细胞刺激蛋白对烟熏大鼠肺泡巨噬细胞氧化应激和细胞因子产生的影响

目的 探讨巨噬细胞刺激蛋白(MSP)对烟熏大鼠肺泡巨噬细胞氧化应激和细胞因子产生的影响.方法 培养正常和烟熏不同时间(1个月、2个月、3个月)的大鼠肺泡巨噬细胞,给予不同浓度MSP处理24 h,采用酶联免疫法检测细胞上清液中细胞因子肿瘤坏死因子α(TNF-α)、白介索8(IL-8)和IL-1β的浓度,比色法检测细胞上清液中丙二醛(MDA)和超氧化物歧化酶(SOD)的水平.结果 ①MSP呈浓度依赖性促进正常组和各烟熏组大鼠肺泡巨噬细胞分泌TNF-α、IL-8和IL-1β;经MSP处理后,各烟熏组大鼠肺泡巨噬细胞上清液中TNF-α、IL-8和n-1β浓度均高于正常组(P＜0.05);大鼠肺泡巨噬细胞上清液中TNF-α、IL-8和IL-1β浓度随烟熏时间延长呈时间依赖性增加.②MSP呈浓度依赖性促进正常组和各烟熏组大鼠肺泡巨噬细胞分泌MDA,抑制其产生SOD;烟熏2个月组和烟熏3个月组大鼠肺泡巨噬细胞上清液中MDA水平均高于正常组(P＜0.05),SOD水平均低于正常组(P＜0.05);随着烟熏时间延长,大鼠肺泡巨噬细胞上清液中MDA水平呈时间依赖性增加,SOD水平呈时间依赖性降低.结论 MSP呈浓度依赖性促进正常和烟熏大鼠肺泡巨噬细胞分泌TNF-α、IL-8、IL-1β和MDA,抑制其产生SOD.MSP促烟熏大鼠肺泡巨噬细胞分泌TNF-α、IL-8、IL-1β、MDA及抑制其产生SOD的作用较正常大鼠更显著,且烟熏时间越长此作用越明显.     

姜黄素对内毒素脂多糖诱导的库普弗细胞分泌炎症细胞因子的抑制作用

[目的]观察姜黄素对内毒素脂多糖（LPS）诱导的库普弗细胞（KC）分泌炎症细胞因子的影响。[方法]分离并培养KC48h后，分设不同浓度姜黄素组，作用于KC3h，确立无毒性的剂量范围；分正常组、LPS组、LPS加姜黄素组（分3种浓度），在添加姜黄素1h后，加LPS（0．1μg／ml培养液）刺激2h。取上清用ELISA法测定肿瘤坏死因子α（TNF-α）、放免法测白细胞介素1β（IL-1β）和IL-6水平；并以细胞免疫荧光化学法观察细胞TNF-α蛋白的表达和分布。[结果]不同浓度组姜黄素均能显著降低TNF-α、IL-1β和IL-6的水平以及细胞TNF-α蛋白的表达，量效关系显著。[结论]姜黄素对LPS诱导的KC炎症细胞因子分泌有显著的抑制作用。     

阿托伐他汀钙对扩张型心肌病患者外周血单个核细胞分泌促炎性细胞因子的影响

目的探讨不同浓度的阿托伐他汀钙对脂多糖(LPS)诱导的扩张型心肌病(DCM)心力衰竭患者的外周血单个核细胞(PBMCs)促炎性细胞因子表达的影响.方法选择心功能Ⅱ、Ⅲ、Ⅳ级的稳定期DCM患者25例,清晨采外周静脉血并分离出PBMCs,然后用细胞因子刺激剂LPS刺激PBMCs并分别加入终浓度为0、10-7、10-6、10-5mol/L的阿托伐他汀钙培养24h,离心后提取上清液并用放射免疫法测细胞因子白细胞介素-1(IL-1)β、IL-6、肿瘤坏死因子-α(TNF-α)水平.结果随着阿托伐他汀钙浓度的增加,PBMCs分泌IL-1β、IL-6、TNF-α水平呈进行性下降(P＜0.01);10-7、10-6、10-5mol/L阿托伐他汀钙组PBMCs分泌IL-1β、IL-6,TNF-α水平均显著低于0 mol/L组(均P＜0.05);10-5mol/L阿托伐他汀钙组PBMCs分泌IL-1β、IL-6、TNF-α水平均显著低于10-6、10-7mol/L组(均P＜0.05),而10-6mol/L组和10-7mol/L组IL-1β、IL-6、TNF-α水平则差异无统计学意义(均P＞0.05).结论阿托伐他汀钙呈剂量依赖性抑制LPS诱导的DCM患者外周血PBMCs促炎性细胞因子表达增加.这可能是他汀类药物对DCM有益的原因之一.     

LPS对体外培养的人冠状动脉平滑肌细胞炎症因子表达的影响——对建立支架内再狭窄炎症细胞模型的探索

目的探索LPS作用不同时间对体外培养的人冠状动脉平滑肌细胞(HCASMC)炎症因子表达的影响,为支架置入术后再狭窄炎症细胞活化模型的建立提供实验数据支持。方法体外培养的HCASMC 3~5代,接种于6孔细胞培养板,用不同浓度(0.01,0.1,0.5,1.0,10)μg/ml的LPS作用不同时间(6 h,24 h,48 h),通过酶联免疫吸附实验(ELISA)检测细胞培养上清液中炎症因子白介素6(IL-6)、白介素1β(IL-1β)以及肿瘤坏死因子α(TNF-α)的表达变化。结果对照组只有少量的IL-1β分泌。加入不同浓度LPS刺激后,与对照组比较,干预6 h的各LPS浓度组IL-1β表达量无明显变化,差异无统计学意义(P均0.05)。而干预24 h或48 h的各LPS浓度组与对照组相比IL-1β表达量明显增加,差异有统计学意义(P均0.05)。对照组有少量IL-6分泌。加入不同浓度LPS刺激后,与对照组比较,0.5μg/ml浓度组LPS干预6 h、24 h、48 h均可显著诱导IL-6的表达增加,1μg/ml浓度组则在24 h、48 h刺激条件下表达增加,差异有统计学意义(P均0.05)。对照组有少量TNF-α的分泌,加入LPS干预后,TNF-α的变化趋势与IL-6相一致。结论 0.5μg/ml和1μg/ml浓度的LPS刺激24 h或48 h使HCASMC的IL-6、IL-1β和TNF-α表达增加,可作为构建HCASMC炎症活化模型的参考。     

甲氨蝶呤联合4-氢过氧环磷酰胺对干燥综合征患者单个核细胞的作用

目的研究甲氨蝶呤（MTX）联合4-氢过氧环磷酰胺（4HC）对体外培养的干燥综合征（SS）患者外周血单个核细胞（PBMC）的周期、凋亡及分泌白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）的影响。方法 MTX、4HC、MTX联合4HC的3组药物在4个浓度水平0、1、10、100μg/ml,与体外培养的SS患者PBMC作用48h。用流式细胞术（FCM）检测细胞周期、凋亡,用酶联免疫吸附试验（ELISA法）检测IL-1β、TNF-α分泌水平。对MTX、4HC在0、1、10μg/ml浓度水平进行析因设计。结果细胞周期：与对照组相比,MTX10组、MTX100组PBMC的G0/G1期比例增加,S期及G2/M期比例减少;不同药物浓度4HC组对细胞各周期影响多数无统计学意义;联合组中MTX1＋4HC1组、MTX10＋4HC10组及MTX100＋4HC100组G0/G1期细胞比例减少,S期及G2/M期比例增加。细胞凋亡：MTX10组、MTX100组、4HC10组、4HC100组和联合组PBMC凋亡率高于对照组。同一药物浓度水平时,MTX1＋4HC1组凋亡率高于MTX1组,MTX10＋4HC10组凋亡率高于MTX10组及4HC10组,MTX100＋4HC100组凋亡率高于MTX100组及4HC100组。细胞因子：不同药物浓度的MTX组、4HC组和联合组IL-1β分泌水平均低于对照组;除MTX10外,各药物组TNF-α分泌水平均低于对照组。比较同一药物浓度水平时,不同组的IL-1β、TNF-α分泌水平,混合组均低于单用药组。交互作用：MTX联合4HC在0、1、10μg/ml3个浓度对G0/G1期比例、凋亡率、IL-1β及TNF-α分泌水平4个方面的F值分别为：4.68、45.19、4.44及3.392,P值均〈0.05,提示MTX和4HC存在交互作用。结论 MTX和4HC联合作用具有协同效应。MTX和4HC联合作用于体外培养的SS患者的PBMC,可有效抑制其G0/G1期的细胞凋亡,降低促炎因子IL-1β、TNF-α的分泌水平。     

大黄素对脂多糖诱导单核细胞分泌白细胞介素-1β、白细胞介素-6及肿瘤坏死因子-α的抑制作用

目的研究大黄素对内毒素诱导单核细胞分泌白细胞介素(IL)-1β、IL-6和肿瘤坏死因子(TNF)-α的抑制作用。方法采用人外周血分离培养单核细胞,25μg/ml内毒素作为刺激因子,观察0.1,0.5,1,5,10,25μg/ml 6种质量浓度的大黄素对单核细胞分泌IL-1β、IL-6和TNF-α活性的影响,以酶联免疫吸附法(ELISA)测定IL-1β、IL-6和TNF-α的水平。结果大黄素对内毒素诱导单核细胞分泌IL-1β和TNF-α均有一定影响,大黄素浓度在0.5~10μg/ml可显著抑制LPS诱导单核细胞分泌IL-1β,并在1μg/ml时达到最大抑制作用;大黄素在较低浓度时(0.1,0.5μg/ml)对单核细胞分泌TNF-α具有显著抑制作用,但当浓度升高时,抑制作用减弱。大黄素对内毒素诱导单核细胞分泌IL-6没有明显影响。结论大黄素在一定浓度范围内对内毒素诱导单核细胞分泌IL-1β及TNF-α均有显著抑制作用,这可能是大黄素治疗牙周炎的机制之一。     

血脂康胶囊对LPS诱导大鼠肝脏Kupffer细胞NF-κB表达的影响

目的探讨血脂康胶囊对脂多糖(LPS)诱导大鼠肝脏Kupffer细胞NF-κB表达的影响。方法将分离的Kupffer细胞按1×105个/ml接种于24孔板内培养48 h后,对照组:常规培养;LPS组:给予终浓度为100 ng/ml的LPS培养8 h;血脂康胶囊组:血脂康胶囊用生理盐水溶解,90 mg·kg-1·d-1,其余处理同LPS组。ELISA法检测上清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)水平。Western blotting检测胞浆IκBα、p-IκBα及胞核NF-κB p65蛋白表达水平。结果 LPS组细胞上清TNF-α、IL-1β和IL-6表达高于对照组(P0.05)。血脂康胶囊组细胞上清TNF-α、IL-1β和IL-6低于LPS组(P0.05),但高于对照组(P0.05)。对照组胞浆蛋白IκBα表达显著高于LPS组和血脂康胶囊组(P0.05),但LPS组明显低于血脂康胶囊组(P0.05)。LPS组胞核NF-κB p65和p-IκBα表达高于对照组和血脂康胶囊组(P0.05),但血脂康胶囊组表达低于LPS组(P0.05)。结论血脂康胶囊对LPS诱导的Kupffer细胞炎症因子分泌有一定的抑制作用。     

幽门螺杆菌Tipα蛋白激活NLRP3炎性小体诱导THP-1细胞分泌IL-1β和IL-18

目的以佛波酯(PMA)诱导分化的THP-1巨噬细胞为模型,探讨NLRP3炎性小体在幽门螺杆菌Tipα蛋白诱导炎性细胞因子分泌中的作用。方法采用重组纯化Tipα蛋白刺激巨噬细胞,ELISA检测其促炎细胞因子TNF-α、IL-1β和IL-18的分泌水平。分别用NF-κB通路阻断剂PDTC和ROS清除剂NAC预处理细胞,ELISA检测预处理前后Tipα诱导细胞分泌促炎细胞因子水平差异,Western Blot检测NLRP3和Caspase-1分子的表达水平差异。结果 Tipα蛋白可显著诱导巨噬细胞产生TNF-α、IL-1β和IL-18;Tipα蛋白浓度为40μg/mL时,刺激细胞6h后,TNF-α、IL-18和IL-1β表达水平接近峰值(P0.05)。特异性阻断NF-κB信号通路后,巨噬细胞分泌的促炎细胞因子及Caspase-1和NLRP3分子的表达水平均较阻断前明显降低,ROS清除剂NAC预处理细胞后,巨噬细胞分泌的IL-18和IL-1β较处理前有明显降低(P0.05),TNF-α无明显变化;Western Blot结果显示Caspase-1和NLRP3分子的表达水平较阻断前均有明显降低。结论 Tipα能够促进巨噬细胞产生促炎细胞因子IL-1β和IL-18;NLRP3/Caspase-1途径可能参与了Tipα诱导的IL-1β和IL-18分泌。     

复方肝毒清对二甲基亚硝胺诱导小鼠肝损伤模型的保护作用

[目的]探讨复方肝毒清对二甲基亚硝胺（Dimethylnitrosamine,DMN）诱导小鼠肝损伤模型的保护作用。[方法]将60只小鼠随机分为空白对照组、模型组、联苯双酯组及复方肝毒清高、中、低剂量组。空白对照组予0.85%氯化钠10 ml/kg灌胃,其他各组以15 mg/kg DMN腹腔注射建立小鼠肝损伤模型,同时后4组分别按150mg/kg联苯双酯滴丸和20、10、5 g/kg复方肝毒清灌胃,每12 h给药1次,共4次。赖氏法检测血清丙氨酸氨基转移酶（ALT）、天冬氨酸转氨酶（AST）、清蛋白水平;ELISA法检测血清肿瘤坏死因子α（TNF-α）、白细胞介素1β（IL-1β）水平;定量PCR法检测肝组织TNF-α、IL-1βmRNA的表达。[结果]复方肝毒清不仅能够显著改善肝功能和肝组织病理,而且能明显降低血清TNF-α、IL-1β水平和肝组织TNF-α、IL-1βmRNA的表达。[结论]复方肝毒清可能是通过减少炎症细胞因子的分泌而达到保护肝脏的作用。     

二甲双胍对脂多糖诱导的THP-1细胞相关炎症因子及凋亡的影响

目的 通过观察二甲双胍对脂多糖诱导的人单核细胞(THP-1)相关炎症因子分泌及凋亡影响的剂量效应关系,探讨二甲双胍的直接抗炎作用.方法 体外培养人THP-1细胞,以1μg/ml脂多糖和不同浓度二甲双胍分别孵育6、24和48 h,收集细胞及培养液上清进行检测.应用乳酸脱氢酶微量释放法检测不同浓度二甲双胍对THP-1细胞的毒性作用,酶联免疫吸附法检测上清白细胞介素(IL)-1β、IL-6、IL-8和肿瘤坏死因子α(TNF-α)水平,流式细胞仪Annexin V/碘化丙啶双染色法测定THP-1细胞早期凋亡率.结果 二甲双胍可剂量依赖性地降低上清IL-1β、IL-6、IL-8和TNF-α水平,且48 h作用最为显著.1和5 mmol/L二甲双胍显著降低脂多糖刺激的IL-1β、IL-6、IL-8和TNF-α的分泌(P＜0.05或P＜0.01).并且二甲双胍可剂量依赖性地减少THP-1细胞早期凋亡数目(F=4.696,P=0.036);1、5 mmol/L二甲双胍组细胞早期凋亡率明显低于脂多糖组(37.47％、33.35％对49.90％,P＜0.05或P＜0.01).结论 二甲双胍可剂量依赖地降低脂多糖诱导的THP-1细胞炎症因子分泌及早期凋亡率,提示其有一定的直接抗炎作用.     

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.     

治疗高血压药物的经济学评价

重视高血压治疗中的经济学评价,对利用我国有限的卫生资源来遏制高血压对人民群众的危害有着重要的现实意义。药物经济学对于药物治疗的成本和治疗的结果给予同样的关注。因为治疗高血压的费用,不仅涉及药物价格,还包括患者的危险水平,降压疗效和对临床终点事件的影响,以及治疗的依从性和安全性。因此药物经济学更强调整体成本和价-效比。低危病人,若非药价低廉,治疗的价-效比不够理想。而在高危的患者,价-效比越小越经济而不是药费越便宜越好。