结核分枝杆菌MPT64抗原DNA疫苗在小鼠体内诱导的免疫应答

目的研究结核分枝杆菌MPT64抗原DNA疫苗在小鼠体内诱导的免疫应答。方法用表达MPT64的真核表达质粒pcDNA-M免疫BALB/c小鼠,ELISA法检测免疫小鼠的特异性抗体滴度和抗体亚类。分离免疫小鼠的脾淋巴细胞,检测淋巴细胞增殖、IFN-γ和IL-12产生水平、流式细胞仪计CD4+细胞和CD8+细胞数、脾淋巴细胞特异性CTL杀伤效应。结果MPT64基因免疫可诱导小鼠高水平的体液免疫应答,免疫小鼠脾淋巴增殖显著,IFN-γ和IL-12含量增加,CD4+细胞和CD8+细胞百分比明显增加,CTL杀伤效应明显。结论MPT64 DNA疫苗可诱导小鼠有效的体液和细胞免疫应答,有可能作为新型TB疫苗的组分。     

幽门螺杆菌ureI核酸疫苗免疫活性的初步研究

目的 观察幽门螺杆菌ureI核酸疫苗诱导C57BL/6小鼠产生体液免疫应答及细胞免疫应答水平.方法 重组质粒pcDNA3.1(+)/ureI、空质粒pcDNA3.1(+)及PBS分别肌注免疫C57BL/6小鼠.ELISA法检测小鼠血清中特异性IgG抗体水平以及脾淋巴细胞培养上清中IL-4和IFN-γ含量,MTT比色法检测脾淋巴细胞增殖反应,PCR和免疫荧光组化法检测ureI基因和蛋白表达.结果 pcDNA3.1(+)/ureI能够诱导小鼠产生特异性IgG抗体,该组小鼠脾淋巴细胞经UreI重组蛋白刺激后,其刺激指数和培养上清中IL-4、IFN-γ含量明显升高; ureI基因可在小鼠肌细胞中有效表达.结论 pcDNA3.1(+)/ureI核酸疫苗能刺激C57BL/6小鼠产生较强的体液免疫应答和细胞免疫应答,为进一步研究该疫苗的免疫保护作用奠定了基础.     

结核分枝杆菌重组质粒pGEX-ESAT-6构建及其在大肠埃希菌BL21(DE3)中表达效率的研究

目的构建结核分枝杆菌（MTB）重组质粒pGEX-ESAT-6，分析ESAT-6抗原在大肠埃希菌BL21（DE3）中的表达效率。方法以结核分枝杆菌H37Rv标准株基因组DNA为模板，通过PCR扩增得到ESAT-6抗原编码基因；将该基因定向克隆于含有谷胱甘肽-S-转移酶（GST）基因的高效原核表达载体pGEX-1λT，经酶切鉴定后以IPTG诱导表达ESAT-6／GST融合蛋白；SDS—PAGE及Western blot对表达产物进行鉴定。结果PCR扩增出288bp的ESAT-6基因；双酶切证实ESAT6基因成功插入pGEX-1λT中，构建了pGEX—ESAT-6穿梭表达载体。SDS—PAGE分析重组质粒pGEX-ESAT-6表达产物的分子质量单位为35ku，表达效率为20％，Western blot检测该蛋白能被活动性结核病人血清特异识别。结论结核分枝杆菌重组质粒pGEX-ESAT-6在大肠埃希菌中获得了高效融合表达，表达的ESAT-6重组蛋白具有抗原特异性。     

结核分枝杆菌早期分泌抗原靶6kDa蛋白原核载体的构建及在E．coli中的高效表达

目的获得高效表达的结核分枝杆菌早期分泌抗原靶6kDa蛋白（ESAT-6）。方法利用PCR方法扩增出ESAT-6基因片段,将酶切处理后的基因片段定向克隆到原核表达载体pET-21b（＋）,酶切分析和序列测定鉴定出ESAT-6基因的阳性重组子,将其转化入EcoliBL21（DE3）,阳性菌株经IPTG诱导,SDS-PAGE和免疫印迹分析靶蛋白的表达;重组蛋白经Ni-NTAHis·Bind Resins纯化。结果成功扩增出ESAT-6基因片段,构建了重组表达质粒pET-ESAT-6,SDS-PAGE显示表达产物分子量约为6kD,经亲和纯化后的ESAT-6重组蛋白纯度高,且能被结核病人血清所识别。结论利用pET原核表达系统成功的对结核分枝杆菌ESAT-6重组蛋白进行高效表达和纯化,重组蛋白具有良好的免疫活性。     

弓形虫GRA4基因真核表达重组质粒DNA免疫小鼠的研究

目的用pVACGRA4真核表达重组质粒免疫小鼠,观察诱导的免疫应答及对弓形虫感染的保护作用。方法大量制备pVACGRA4真核表达重组质粒,经基因枪腹部皮内注射免疫BALB/c小鼠3次,以pVAC空质粒及不经任何处理的空白组为对照。于末次免疫4周后作免疫指标测定(包括MTT法测定小鼠脾脏T淋巴细胞增殖活性、间接免疫荧光法测定T淋巴细胞亚群数目、双夹心ELISA法测定细胞因子IFNγ及IL4含量、间接ELISA法测定IgG抗体滴度),并观察攻毒试验后小鼠存活情况。结果脾淋巴细胞增殖各组间差异无显著性(P>0.05);pVACGRA4组CD4+T细胞百分率无明显变化(P>0.05),CD8+T细胞百分率明显增加(与pVAC对照组比较P<0.05,与空白对照组比较P<0.01),CD4+/CD8+比值也较空白对照组明显降低(P<0.01);pVACGRA4免疫组IFNγA值比对照组略高,但差异无显著性(P>0.05),IL4A值各组间无明显变化(P>0.05);pVACGRA4组可诱导产生特异性IgG抗体,但滴度不高;pVACGRA4免疫组小鼠存活率显著高于两对照组,死亡小鼠的平均存活时间延长(与空白对照组比较P<0.05)。结论用pVACGRA4重组质粒DNA免疫小鼠,可诱导产生以细胞免疫为主的免疫应答及对弓形虫攻击感染的部分保护作用。     

结核分枝杆菌重组Bb-ESAT-6疫苗的构建、鉴定和表达及其保护力

目的构建和鉴定结核分枝杆菌(MTB)重组双歧杆菌(Bifidobacteria bifidum,Bb)-ESAT-6疫苗,研究该疫苗对鼠结核杆菌感染的免疫保护效果。方法以结核分枝杆菌H37Rv标准株基因组DNA为模板,通过PCR扩增得到ESAT-6抗原编码基因;将该基因定向克隆到大肠埃希菌-双歧杆菌穿梭表达载体pGEX-1λT,构建重组质粒pGEX-ESAT-6;用电穿孔法将该质粒导入Bb及BL21(DE3),构建结核分枝杆菌重组Bb-ESAT-6疫苗。用IPTG诱导重组BL21(DE3)菌表达ES-AT-6/GST融合蛋白;SDS-PAGE及Western blot对表达产物进行鉴定。65只BALB/c雌性小鼠,随机分为5组:A组(SC)、B组(IM)、C组(IN)、D组(Bb)、E组(PBS)。分别于免疫后8周用5×105CFU MTB H37Ra减毒株悬浮于10μL PBS中进行鼻腔粘膜接种感染。攻击感染后6w剖杀各组小鼠8只,计数肝、肺组织荷菌量,常规ELISA检测血清IgG及其亚类和IgE,MTT法检测特异性脾淋巴细胞增殖。结果PCR成功扩增出288bp的ESAT-6基因;双酶切证实ESAT6基因成功插入pGEX-1λT中;PCR证实rBb-ESAT-6疫苗构建成功。免疫印迹分析发现重组质粒pGEX-ESAT-6的表达产物在相对分子量(35kDa)处有明显的蛋白表达条带,表达效率为20%,且能被活动性结核病人血清特异识别。鼻腔内接种组的肝、肺组织荷菌量明显低于其他免疫组。疫苗接种组IgG、IgG1、IgG2a和IgG2b明显升高,IgG3和IgE无明显变化;疫苗接种组的脾淋巴细胞明显增殖。结论成功构建了结核分枝杆菌重组Bb-ESAT-6疫苗,重组Bb-ESAT-6疫苗在抗结核分枝杆菌感染过程中具有一定免疫保护作用。     

SARS冠状病毒E蛋白DNA疫苗的构建及其实验免疫研究

目的构建SARS冠状病毒(SARS-CoV)小囊膜蛋白(E蛋白)的DNA疫苗pVAC-E,观察其在小鼠中诱导的免疫应答。方法采用PCR方法体外扩增SARS冠状病毒E蛋白的基因片段,克隆入真核表达载体pVAC,构建pVAC-E重组质粒。通过脂质体介导瞬时转染非洲绿猴肾(Vero)细胞,Western-blot鉴定E蛋白在细胞中的表达。以基因枪方式免疫小鼠,ELISA检测小鼠血清特异性抗体,MTT法测定淋巴细胞转化率,流式细胞仪检测小鼠脾脏T淋巴细胞亚群分布。结果成功构建SARS-CoVDNA疫苗pVAC-E。Western-blot结果示,转染后的Vero细胞可表达一约9kD大小能被SARS病人血清特异识别的蛋白条带。免疫小鼠中未检测到明显的抗体滴度升高。淋巴细胞转化率在免疫组和对照组间无差别(P>0.05)。脾脏T淋巴细胞亚群分析示免疫组小鼠CD4+细胞显著升高(P<0.05),CD8+细胞与对照组相比无显著差异。结论构建的真核表达质粒pVAC-E能在Vero细胞中表达,表达产物具免疫活性,免疫小鼠后能诱导一定的细胞免疫应答。     

结核分枝杆菌ESAT6、CFP10基因DNA疫苗对小鼠免疫原性的初步研究

目的 研究ESAT6、CFP10基因DNA疫苗分别与卡介苗联合免疫小鼠,以诱导免疫效果.方法 以构建的真核表达载体pEGFP-N1ESAT6、pEGFP-N1-CFP10与卡介苗共同免疫随机分成8组的80只小鼠,分别标记为：生理盐水组（SLYS）、卡介苗组（KJM）、pEGFP N1组（P-N1）、pEGFP-N1 ESAT6组（P-N1-E）、pEGFP N1-CFP10组（P-N1-C）、卡介苗加pEGFP-N1组（K＋P-N1）、卡介苗加pEGFP-N1-ESAT6组（K＋P-N1-E）和卡介苗加pEGFP-N1 CFP10组（K＋P-N1-C）.每只小鼠皮内注射100μL卡介苗,每只小鼠肌肉注射50μg质粒,每组共注射3次.以纯化的ESAT6、CFP10蛋白作为抗原,用DOT ELISA方法检测小鼠血清中的抗体;用ELISA方法检测小鼠血清中IFN-γ的变化.结果 免疫3次后的小鼠血清中检测到针对CFP10蛋白的抗体,未检测到针对ESAT6蛋白的抗体.但二者血清中IFNγ水平都有显著上升,K＋P N1-C和K＋P-N1-E免疫3次后,测得的IFN-γ平均含量为（107.591±7.3281）pg/mL和（95.7503±9.0184） pg/mL,显著高于免前、一免、二免（P＜0.01）.结论 结核分枝杆菌ESAT6,CFP10基因DNA疫苗和卡介苗联合应用后可诱导小鼠产生有效的细胞免疫应答,为DNA疫苗的研究奠定一定的基础.     

结核分枝杆菌Rv0033的原核表达及其免疫原性研究

目的表达重组结核分枝杆菌(Mycobacterium tuberculosis,M.tb)Rv0033,并观察其免疫原性,为结核病(Tuberculosis, TB)新型疫苗的研发筛选优势靶抗原。方法构建重组载体pET30b-Rv0033并表达重组Rv0033。以全血干扰素释放技术(Whole blood IFN-γrelease assay, WBIA)检测M.tb感染者的T细胞是否特异性识别重组载体pET30b-Rv0033。取纯化的rRv0033混合佐剂DMT后免疫小鼠,ELISA法检测血清特异性抗体IgG、IgG1及IgG2a水平,并计算IgG2a/IgG1比值;同时检测小鼠脾细胞中特异性IFN-γ、TNF-α、IL-2水平。结果成功构建原核表达载体pET30b-Rv0033,重组Rv0033的诱导表达、纯化和鉴定结果均符合预期。人群外周血淋巴细胞经rRv0033蛋白刺激后,非典型结核(Atypical tuberculosis, ATB)及潜伏性结核感染(Latent tuberculosis infection, LTBI)受试者IFN-γ水平显著高于健康对照人群(P0.01);ATB受试者IFN-γ水平显著高于LTBI受试者(P0.05)。BCG+Rv0033/DMT免疫小鼠产生的特异性抗体(IgG、IgG1和IgG2a)滴度水平显著高于Rv0033/DMT组和BCG组(均P0.01);Rv0033/DMT组和BCG+Rv0033/DMT组小鼠的IgG2a/IgG1比值显著高于DMT组和BCG组,且1,提示rRv0033可诱导以Th1细胞免疫应答为主的免疫应答。接受PPD刺激或rRv0033蛋白刺激的BCG+Rv0033/DMT组小鼠IFN-γ、TNF-α及IL-2水平较高,其次分别是BCG组、Rv0033/DMT组、DMT组,PBS组水平较低,且rRv0033蛋白混合DMT佐剂组高于单纯DMT佐剂组(P0.05)。结论制备的rRv0033蛋白可被M.tb感染者外周血T细胞特异性识别,联合佐剂DMT免疫小鼠能够诱导高水平的抗原特异性Th1型免疫应答,可能与rRv0033蛋白提供的免疫保护力密切相关。     

周期型马来丝虫3-磷酸甘油醛脱氢酶基因真核表达载体的构建及DNA免疫研究

目的 构建周期型马来丝虫3-磷酸甘油醛脱氢酶(BmGAPDH)真核表达载体pcDNA3.1-BmGAPDH,并观察其在小鼠体内的细胞免疫应答效应.方法 以周期型马来丝虫总RNA为模板,RT-PCR方法扩增目的 基因片段.与pGEM-T Easy克隆载体连接,筛选出阳性克隆.经PCR和双酶切鉴定后,亚克隆至真核表达质粒pcDNA3.1,构建pcDNA3-BmGAPDH表达载体,将纯化的pcDNA3.1-BmGAPDH和CpG经后腿胫前肌免疫BALB/c小鼠,并设PBS对照组及空质粒对照组,共免疫3次,每次免疫间隔2周.用RT-PCR方法检测肌肉组织内目的 基因;用噻唑蓝(MTT)法、ELISA方法分别检测免疫小鼠T淋巴细胞刺激增殖指数和血清中细胞因子IFN-γ、IL-4水平.应用SPSS统计学软件进行样本均数的t检验.结果 成功构建了pcDNA3.1-BmGAPDH真核表达载体,基因片段全长为1020 bp.DNA序列分析与基因库已知基因序列同源性为99%.该真核表达载体免疫小鼠后,从小鼠肌肉组织扩增出目的 基因重组质粒组小鼠淋巴细胞刺激增殖指数显著高于PBS对照组及空质粒对照组,淋巴细胞刺激增殖指数分别为1.398、1. 006和1.017(P<0.05).重组质粒组IFN-γ、IL-4细胞因子水平均高于PBS对照组及空质粒对照组,分别为163.905、58.589、51.317 ng/L和107.906、27.111、34.627 ng/L(P<0.05).免疫佐剂CpG与疫苗同时注射可增强机体的免疫应答,表现为IFN-γ水平和免疫4周后淋巴细胞刺激增殖指数显著上升.结论 pcDNA3.1-BmGAPDH真核表达载体能在小鼠体内表达并可诱导相关的细胞免疫应答.     

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.     

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.     

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.     

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。     

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     

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。     

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。