奥曲肽联合阿司匹林抑制胃癌生长和转移

目的：研究阿司匹林，奥曲肽及奥曲肽联合阿司匹林对胃癌生长和转移的影响。方法：建立人胃癌裸鼠原位种植瘤模型，分别给予各组荷瘤鼠奥曲肽，阿司匹林和奥曲肽联合阿司匹林，连续给药8周。观察奥曲肽，阿司匹林及奥曲肽联合阿司匹林对胃癌生长和转移的影响及不良反应。结果：单用阿司匹林，奥曲肽治疗组以及奥曲肽，阿司匹林联合用药组的抑瘤率分别为39．3％，60．6％和85．6％，联合用药组抑瘤率明显高于单一给药组（P均＜0．01）。对照组肿瘤转移率为66．6％，奥曲肽治疗组为16．6％，阿司匹林组及联合用药组均未见转移灶。所有动物均无消化道出血及溃疡。结论：奥曲肽联合阿司匹林抑制胃癌生长和转移的效果明显优于单用其中任何一种药物，这对临床应用非细胞毒性药物治疗胃癌具有积极的意义。     

奥曲肽联合罗非昔布增强对肝癌生长的抑制作用

目的 奥曲肽和罗非昔布均能抑制肝癌生长,但2种非细胞毒性药物的抗肿瘤机制不同。从多环节发挥抗癌作用的角度考虑,我们拟探讨奥曲肽联合罗非昔布能否协同抑制人肝癌细胞生长。方法 采用^3H-胸腺嘧啶核昔掺人法探讨奥曲肽和罗非昔布单独或联合应用对肝癌细胞株SMMC—7721增殖的影响,根据中效原理分析两者之间相互作用的关系。观察奥曲肽联合罗非昔布对人肝癌裸鼠原位移植瘤生长的影响。结果 奥曲肽联合罗非昔布在体外能显著抑制肝癌细胞生长,其合用浓度与^3H0-胸腺嘧啶核昔掺人量呈显著负相关(r＝—0．997,P＜0．01)。奥曲肽联合罗非昔布在大多数效应范围的合用指数小于1,具有明显的协同作用。联合用药组的抑瘤率(97．1％)较罗非昔布组(73．2％)明显提高(P＜0．05)。且联合组肿瘤内的纤维组织增生较对照组明显增多。在各组裸鼠的体内实验中末见明显不良反应。结论 奥曲肽联合罗非昔布可协同增加对人肝癌细胞在体外生长的抑制作用,也明显提高对肝癌裸鼠原位移植瘤的抑瘤率。     

沉默G250基因对肾癌786-0细胞体内成瘤及生长的影响

目的 观察沉默G250基因对肾癌786-0细胞体内增殖的影响.方法 构建靶向G250的siRNA表达质粒pshRNA-G250并转染肾癌786-0细胞,12只BALB/c裸鼠分为阴性对照组和干扰成瘤组,干扰成瘤组每只裸鼠皮下接种5 ×106个G250基因沉默后的肾癌786-0细胞(786-0/si-G250-b),以转染空质粒的细胞(786-0/si-G250-0)为对照.观察裸鼠成瘤增时间、成瘤率、肿瘤体积变化、绘制生长曲线.成瘤3周后,处死裸鼠,称重瘤块,计算抑瘤率.结果 5×106个细胞皮下接种BALB/c裸鼠均成瘤,实验和对照组肿瘤出现时间分别为(11±1.5)、(15±2.4)d(t=3.381,P =0.007).7个不同时间点肿瘤的生长体积具有统计学意义(F=84.836,P=0.000).成瘤3 w后,肿瘤重量分别为(22.224 +5.145) mg、( 37.353±9.332) mg,(t=3.475,P =0.006),干扰组肿瘤成瘤抑制率为40.50%.结论 G250基因表达沉默抑制了肾癌细胞的体内增殖能力.     

奥曲肽抑制胃癌生长的实验研究

目的:研究生长抑素类似物奥曲肽在体内和体外对胃癌生长的影响及初步作用环节。方法:采用3H-胸腺嘧啶核苷(3H-TdR)掺入法及TdT介导的dUTP缺口末端标记(TUNEL)法检测奥曲肽对体外培养的SGC-7901胃癌细胞生长的影响及凋亡的诱导作用。建立裸鼠人胃癌原位移植瘤模型,给予奥曲肽治疗8周,观察其对裸鼠体内胃癌生长的影响。用免疫组化法检测奥曲肽对胃癌细胞及组织中增殖细胞核抗原(PCNA)表达的影响。用逆转录聚合酶链反应(RT-PCR)法检测胃癌细胞及组织中生长抑素受体(SSTR)-2和SSTR-3基因的表达。结果:奥曲肽可明显降低胃癌细胞的3H-TdR掺入,其效应与药物剂量呈明显正相关。奥曲肽可诱导SGC-7901胃癌细胞凋亡,其发生率为18.3%±2.7%。奥曲肽可抑制裸鼠人胃癌原位移植瘤的生长,其抑瘤率为62.3%。胃癌细胞及组织中PCNA的表达因奥曲肽的干预而明显下调。无论是胃癌细胞还是胃癌组织,均有SSTR-2和SSTR-3基因表达。结论:在体内及体外,奥曲肽通过SSTR-2和SSTR-3的介导可有效抑制胃癌生长。     

SN50联合5-氟尿嘧啶通过调节NF-κB信号通路抑制人胃癌裸鼠移植瘤生长的研究

目的探讨NF-κB通路抑制剂SN50联合5-氟尿嘧啶(5-FU)对人胃癌裸鼠移植瘤生长的影响及机制。方法建立荧光素酶标记的人胃癌细胞株SGC7901,常规传代培养,采用对数生长期细胞建立人胃癌裸鼠皮下移植瘤模型。14 d后随机分为4组:对照组、5-FU干预组、SN50干预组、5-FU+SN50干预组。每组8只动物,共给药4周。观察并记录各组裸鼠皮下移植瘤的生长情况,游标卡尺测量瘤体长短径,于停药次日处死裸鼠,称取瘤重,计算肿瘤体积、肿瘤生长抑制率、绘制肿瘤生长曲线。通过体内可见光成像技术分别于第1、7、14、21、28天对裸鼠进行活体成像,记录移植瘤光子数,绘制皮下移植瘤光子数曲线图。免疫组化方法检测移植瘤中NF-κBp65表达情况。结果与其他三组相比,5-FU+SN50干预组肿瘤体积、抑瘤率及光子数差异均有统计学意义(P0.05);与对照组及SN50干预组比较,5-FU干预组肿瘤体积和光子数明显减少(P0.05),抑瘤率明显增加(P0.05);SN50干预组与对照组相比,肿瘤体积、抑瘤率及光子数差异无统计学意义(P0.05)。NF-κBp65阳性率依次为对照组47.4%、5-FU组57.1%、SN50组11.8%、5-FU+SN50组25.0%。结论 5-FU单药及5-FU+SN50均能抑制裸鼠胃癌皮下移植瘤的生长,而联合应用效果更明显;SN50可通过抑制NF-κB信号转导通路的活化,显著增强5-FU对裸鼠胃癌皮下移植瘤的抑制作用。     

经沉默免疫负调控基因技术处理的树突状细胞联同细胞毒性T淋巴细胞对HepG2细胞移植瘤的抑制作用

目的观察经沉默免疫负调控基因(iAPA)技术处理的树突状细胞(DC)联同细胞毒性T淋巴细胞(CTL)(iAPA-DC/CTL)对HepG2细胞移植瘤的抑制作用。方法利用人肝癌细胞系HepG2建立裸鼠皮下移植瘤模型,将12只裸鼠随机分为2组:生理盐水对照组(C组)和iAPA-DC/CTL组(DC组),每组6只,行iAPA-DC/CTL治疗4次(1周/次)后处死。实验期间观察各组裸鼠的肿瘤生长,测量肿瘤长短径并描绘肿瘤生长曲线,称量瘤重并计算抑瘤率,病理检测。两组间均数比较采用成组t检验。结果造模成功率为92.31%。C组和DC组肿瘤体积分别为:(697.69±143.99)、(485.64±188.75)mm3,DC组生长相对缓慢(t=2.28,P0.05);C组和DC组肿瘤重量分别为:(0.32±0.07)、(0.22±0.08)g,DC组肿瘤重量小于对照组(t=2.31,P0.05),抑瘤率为30.39%。肿瘤免疫组化染色后T淋巴细胞计数分别为:C组未见、DC组(39.74±5.11)个/高倍视野,DC组肿瘤内T细胞数多于对照组(t=19.05,P0.05)。结论 iAPA-DC/CTL能够有效抑制HepG2细胞裸鼠皮下移植瘤的生长。     

奥曲肽与奥美拉唑联合治疗儿童急性上消化道出血的疗效及安全性分析

目的探讨奥曲肽与奥美拉唑联合治疗儿童急性上消化道出血的疗效及安全性。方法回顾性分析2007年8月至2017年2月南京医科大学附属儿童医院收治的120例急性上消化道出血患儿的临床资料,按治疗方法的不同分为奥曲肽组、奥美拉唑组与联合组,每组各40例。所有患儿入院后均给予常规治疗,在此基础上,奥曲肽组给予单药奥曲肽治疗,奥美拉唑组给予单药奥美拉唑治疗,联合组给予奥曲肽联合奥美拉唑治疗。观察三组患儿治疗后的临床疗效、止血时间、住院时间及药物安全性。结果联合组临床总有效率(95. 00%)显著高于奥曲肽组(77. 50%)、奥美拉唑组(70. 00%),P均0. 05。联合组平均止血时间、平均住院时间显著短于奥曲肽组、奥美拉唑组(P均0. 05);奥曲肽组平均止血时间、平均住院时间显著短于奥美拉唑组(P均0. 05)。奥曲肽组、奥美拉唑组、联合组药物治疗期间不良反应总发生率分别为5. 00%、7. 50%、7. 50%,差异无统计学意义(P 0. 05)。结论应用奥曲肽与奥美拉唑联合治疗儿童急性上消化道出血较单药治疗更有利于提升临床疗效,显著缩短患儿止血时间及住院时间,且不明显增加药物不良反应,安全性较高,可作为临床治疗急性上消化道出血的常用方案。     

吉西他滨联合光动力疗法治疗人胰腺癌裸鼠移植瘤的研究

目的 探讨细胞毒药物吉西他滨(gemcitabine)联合光动力疗法(PDT)对人胰腺癌裸鼠移植瘤的疗效.方法 成功造模胰腺癌裸鼠60只,均分为5组:对照组、光敏剂组(光敏素2 mg/kg,腹腔内注射)、化学治疗组(吉西他滨50 mg/kg,腹腔内注射)、光动力组(光敏素2 mg/kg,腹腔内注射+激光照射)和联合治疗组(吉西他滨50 mg/kg+光敏素2 mg/kg+激光照射).光动力组和联合治疗组在光敏素注射48 h后激光照射(630 nm,120 J/cm2),照射时间为20 min;联合治疗组在激光照射前1 h及照射后第3、6、9天腹腔内注射吉西他滨,共4次;化学治疗组吉西他滨剂量、时间与联合治疗组相同.每周2次测虽肿瘤大小,术后21 d处死所有裸鼠,计算瘤体体积,分析各组时一效关系、抑瘤率以及治疗前、后裸鼠体重变化.结果 对照组、光敏剂组和化学治疗组各时段肿瘤体积随时间延长而增长,差异均有统计学意义(P值均＜0.05).光动力组治疗后第6、9、12、15、18和21天肿瘤体积显著小于同时间段的对照组和光敏剂组(P值均＜0.05);联合治疗组第18和21天肿瘤体积明显较光动力组小(P值均＜0.05).联合治疗组和光动力组瘤重分别为(0.29±0.20)g和(0.69±0.23)g,联合治疗组瘤重明显低于光动力组(P＜0.05);以上两组瘤重均比对照组、光敏剂组和化学治疗组低[(1.65±0.21)、(1.62±0.12)和(1.37±0.19)g,P＜0.05].联合治疗组和光动力组抑瘤率分别为82.42%和58.18%,两组比较差异有统计学意义(P＜0.05);且以上两组抑瘤率均高于光敏剂组和化学治疗组(1.80%和17.00%,P＜0.05).结论 PDT能抑制小鼠胰腺癌生长,但维持时间较短;吉西他滨联合PDT能显著抑制小鼠胰腺癌生长,且有协同增效作用.     

硝酸甘油联合奥曲肽治疗肝硬化并上消化道出血疗效和安全性的Meta分析

目的系统评价硝酸甘油联合奥曲肽治疗肝硬化继发上消化道出血与单用奥曲肽治疗方法疗效差异。方法应用计算机检索电子数据库PubMed、SinoMed、CNKI、WanFang、VIP关于硝酸甘油联合奥曲肽与单用奥曲肽治疗肝硬化并上消化道出血疗效的随机对照试验(RCTs),并对纳入文献进行Meta分析。结果共有11篇文献纳入研究,包括受试者947例(观察组481例,对照组466例)。Meta分析结果示:硝酸甘油联合奥曲肽治疗在总有效率、治愈率、显效时间、止血时间方面均优于单用奥曲肽治疗,差异有统计学意义(P0.001);治疗后,观察组门静脉、脾静脉血流量低于对照组,差异有统计学意义(P0.001);在不良反应发生率方面,两组差异无统计学意义(P=0.71)。结论硝酸甘油联合奥曲肽治疗优于单用奥曲肽,且不良反应少,值得在临床上推广使用。     

索拉非尼联合奥曲肽对HepG2细胞的抑制作用

目的 观察索拉非尼联合奥曲肽在体外对人肝癌细胞株HepG2的抑制作用,并探讨其机制. 方法 采用不同浓度梯度的索拉非尼、奥曲肽单独和联合作用于人肝癌细胞株HepG2,分别于24、48、72 h用CCK-8试剂盒测定各组细胞的杀伤效应,流式细胞术检测HepG2细胞的凋亡率,荧光显微镜观察细胞的凋亡情况;并用酶联免疫吸附法检测细胞培养上清液中血管内皮生长因子(VEGF)的水平,Western blot法测定细胞中髓样细胞白血病-1(Mcl-1)、细胞外信号调节激酶(ERK) 1/2、磷酸化ERK1/2的表达.数据采用均数±标准差((x)±s)表示,用SPSS17.0软件对数据进行单因素方差分析. 结果 索拉非尼、奥曲肽单独使用和联合使用均对HepG2细胞具有抑制作用,并诱导其凋亡,联合用药组抑制效果优于单独用药组F=200.398,(P＜0.05).荧光显微镜观察显示,联合用药组和单独用药组细胞膜上均出现代表细胞早期凋亡的标志物磷脂酰丝氨酸.联合用药组VEGF表达水平为(10.31±4.69) pg/ml,低于索拉非尼组[(22.73±5.88)pg/ml]、奥曲肽组[(25.46±3.45) pg/ml]及正常对照组[(57.15±6.32) pg/ml],F=1019.725,P值均＜0.05.Western blot 法结果显示,各组ERK1/2表达水平差异并无统计学意义(P＞0.05);与正常对照相组比,索拉非尼、奥曲肽及联合用药组的磷酸化ERK1/2表达均减少(F=2.401,P＜0.05),联合用药组表达水平低于单独用药组(P值均＜0.05);奥曲肽组Mcl-1的表达水平与对照组差异无统计学意义,索拉非尼组和联合用药组的表达水平低于正常对照组(P值均＜ 0.05),联合用药组的Mcl-1表达水平低于各单独用药组(P值均＜ 0.05).结论 索拉非尼、奥曲肽均可抑制人肝癌细胞HepG2增殖,并诱导其凋亡,联合应用效果更为显著;其机制可能与二者协同抑制VEGF的表达,并下调抗凋亡蛋白Mcl-1及磷酸化ERK1/2的表达有关.     

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。