丹参注射液对内皮祖细胞移植治疗大鼠心肌梗死的效应

目的探讨丹参注射液对外周血内皮祖细胞(EPCs)移植治疗大鼠急性心肌梗死后增殖分化及心功能的影响。方法 88只SD大鼠经冠状动脉左前降支结扎制造急性心肌梗死模型,随机分为心肌梗死对照组(组Ⅰ)、EPCs移植组(组Ⅱ)、丹参注射液治疗组(组Ⅲ)、EPCs移植联合丹参注射液治疗组(组Ⅳ),每组22只。复苏及培养扩增大鼠EPCs(CM-Dil标记),组Ⅱ及组Ⅳ尾静脉注射3×106个/L EPCs,组Ⅲ及组Ⅳ腹腔注射丹参注射液0. 5 g·kg~(-1)·d~(-1),连续移植及药物治疗3 d。移植后3 w及6 w超声心动图检测心功能,移植后6 w对梗死区心肌组织进行毛细血管密度测定。荧光显微镜观察心肌内移植EPCs及心肌修复情况(苏木素-伊红染色),RT-PCR检测各组心肌血管内皮生长因子(VEGF)基因表达,Western印迹法检测各组心肌中VEGF蛋白表达。结果细胞移植3 w及6 w后,组Ⅱ、组Ⅲ和组Ⅳ左室收缩舒张功能较组Ⅰ明显改善(P<0. 05),且组Ⅳ改变更显著(P<0. 01);组Ⅳ植入梗死区的EPCs可以分化为血管内皮细胞,组Ⅳ梗死心肌处血管密度较组Ⅱ明显增高(P<0. 01); VEGF基因及蛋白表达:组Ⅳ>组Ⅱ>组Ⅲ>组Ⅰ; CM-Dil标记阳性EPCs:组Ⅳ>组Ⅱ,组Ⅲ和组Ⅰ未见CM-Dil标记阳性EPCs;心肌修复情况:组Ⅳ>组Ⅱ、组Ⅲ>组Ⅰ。结论外周血EPCs移植可显著改善急性心肌梗死大鼠的心功能,EPCs移植同时予以丹参注射液优于单独应用EPCs移植,起到心肌修复的协同作用。     

远志皂苷元对内皮祖细胞移植治疗急性心肌梗死模型大鼠心功能的影响

目的探讨远志皂苷元对外周血内皮祖细胞(EPCs)移植治疗急性心肌梗死大鼠后心功能的影响。方法80只SD雄性大鼠,将冠状动脉左前降支结扎制造急性心肌梗死模型后,随机分为四组:心肌梗死对照组(组Ⅰ)、远志皂苷元治疗组(组Ⅱ)、EPCs移植组(组Ⅲ)、EPCs移植联合远志皂苷元治疗组(组Ⅳ),每组20只。复苏及培养扩增大鼠外周血EPCs(CM-Dil标记)后,移植到大鼠(组Ⅲ及组Ⅳ)急性心肌梗死模型梗死区,组Ⅱ及组Ⅳ尾静脉注射注远志皂苷元30 mg/kg(30 mg远志皂苷元溶于10 ml生理盐水),连续治疗3 d。移植后3 w及6 w,超声心动图检测大鼠心功能改变,并对梗死区心肌组织进行毛细血管密度测定,逆转录聚合酶链反应及酶联免疫吸附法测定梗死周边区血管内皮生长因子(VEGF)的表达。荧光显微镜下观察心肌梗死部位内移植的EPCs(CM-Dil标记)的数量及大鼠心肌恢复状况(HE染色)。结果细胞移植3和6 w后,组Ⅱ、组Ⅲ和组Ⅳ心功能和左室舒缩功能较对照组明显改善(P<0. 05),且组Ⅳ改变更显著(P<0. 05),组Ⅲ和组Ⅳ植入梗死区的EPCs可以分化为血管内皮细胞,组Ⅳ梗死心肌处血管密度较组Ⅲ、组Ⅱ明显增高(P<0. 05); VEGF基因及蛋白表达:组Ⅳ>组Ⅲ>组Ⅱ>组Ⅰ(P<0. 05); CM-Dil标记EPCs阳性细胞:组Ⅳ>组Ⅲ,组Ⅱ和组Ⅰ未见;心肌修复情况:组Ⅳ>组Ⅲ、组Ⅱ>组Ⅰ。结论外周血EPCs移植可以显著改善急性心肌梗死大鼠的心功能,并在EPCs移植同时予以远志皂苷元干预优于单独应用EPCs移植,起到心肌修复的协同作用。     

VEGF基因转染同种异体骨髓间充质干细胞对心肌梗死的治疗作用

目的研究血管内皮生长因子（VEGF）基因转染同种异体骨髓间充质干细胞（MSCs）对猪急性心肌梗死（AMI）的治疗作用。方法体外分离、纯化、培养猪骨髓MSCs,以PCNA染色标记细胞;制备、抽提、纯化质粒pd-VEGF。用球囊堵闭及拉伤冠状动脉法建立AMI模型1周后,随机将其分为4组,每组4只,进行经冠状动脉途径移植MSCs和/或VEGF转染。Ⅰ组给予转染VEGF腺病毒的MSCs移植;Ⅱ组单纯MSCs移植;Ⅲ组VEGF基因质粒;Ⅳ组DMEM对照组。4周后行免疫组化和超声心动图检查。结果Ⅰ组及Ⅱ组在梗死区及缺血区均可见较大量的PCNA标记的移植细胞。Ⅷ因子染色阳性的新生血管密度：Ⅰ组〉Ⅲ组〉Ⅱ组〉Ⅳ组。4周后LVEF值：Ⅰ组〉Ⅱ组〉Ⅲ组〉Ⅳ组（P〈0.05或P〈0.01）。结论VEGF基因转染同种异体骨髓MSCs移植猪心肌梗死区及缺血区可以提高缺血心肌的心功能,这可能和骨髓MSCs促进血管和心肌细胞的再生有关。     

自体外周血内皮祖细胞移植联合PPAR激动剂治疗大鼠急性心肌梗死的实验研究

目的探讨自体外周血内皮祖细胞（EPCs）移植联合PPAR激动剂罗格列酮、非诺贝特治疗大鼠急性心肌梗死的可行性和疗效。方法40只SD雄性大鼠随机分为四组：心肌梗死对照组（组Ⅰ）、单纯EPCs移植组（组Ⅱ）、EPCs移植联合罗格列酮治疗组（组Ⅲ）、内皮祖细胞移植联合非诺贝特治疗组（组Ⅳ）,每组10只。应用密度梯度离心法获得大鼠外周血单个核细胞,体外培养扩增获得较纯的EPCs后,移植到大鼠急性心肌梗死模型梗死区,罗格列酮组、非诺贝特组分别以罗格列酮（20mg·kg^-1·d^-1）和非诺贝特（20mg·kg^-1·d^-1）灌胃。8周后超声心动图检测大鼠心功能改变,测定血流动力学指标,免疫组化观察心肌内移植EPCs及大鼠心肌修复情况。结果细胞移植8周后,组Ⅱ、组Ⅲ和组Ⅳ大鼠心功能,左室收缩舒张功能较组Ⅰ明显改善（P〈0．05）,且组Ⅲ和组Ⅳ改变更显著（P〈0．05）。结论EPCs移植可以显著改善急性心肌梗死大鼠的心功能,EPCs移植联用罗格列酮和非诺贝特,优于单独应用EPCs移植。     

内皮祖细胞移植治疗大鼠急性心肌梗死的实验研究

目的探讨大鼠内皮祖细胞(EPCs)移植于梗死心肌的增殖分化情况及对心功能的影响。方法分离培养大鼠EPCs,免疫荧光法检测其CD34+、CD133+和Flk-1+的表达。将SD大鼠冠状动脉左前降支结扎制造急性心肌梗死模型后,在梗死心肌处植入DAPI标记的EPCs(实验组)或M 199培养液(对照组)。移植后1周及4周,心脏超声检查心功能,并对梗死区心肌组织进行移植细胞形态学检查及毛细血管密度测定,逆转录聚合酶链反应及酶联免疫吸附测定梗死周边区血管内皮生长因子(VEGF)的表达。结果培养获得EPCs,其表型为CD34+、CD133+和Flk-1+。植入梗死区的EPCs可以分化为血管内皮细胞,实验组梗死心肌处血管密度较对照组明显增高(P<0.01),并且VEGF基因及蛋白表达在移植后1周均较对照组明显增高(P<0.01)。移植后4周,实验组大鼠左心室射血分数及左心室短轴缩短率较对照组明显提高(P<0.01);而移植后1周,两组大鼠超声检测心功能各指标变化不明显。结论同种异体EPCs移植到梗死心肌大鼠缺血心肌能分化为毛细血管内皮细胞,促进梗死后心肌血管新生,改善心功能。     

VEGF基因转染同种异体骨髓间充质干细胞治疗心肌梗死的实验研究

目的探讨血管内皮生长因子（VEGF）基因转染同种异体骨髓间充质干细胞（MSCs）对猪急性心肌梗死（AMI）血管再生和心功能的影响。方法体外分离、纯化、培养猪骨髓MSCs，以PCNA染色标记细胞；制备、抽提、纯化质粒pd—VEGF。用球囊堵闭及拉伤冠状动脉法建立AMI模型1W后，随机将其分为4组（n=4），进行经冠状动脉途径移植MSCs和／或Ⅵ犯F转染。组Ⅰ：给予转染VEGF腺病毒的MSCs移植；组Ⅱ：单纯MSCs移植；组Ⅲ：VEGF转染；组Ⅳ：DMEM对照组。4W后行免疫组化和超声心动图检查。结果组Ⅰ及组Ⅱ在梗死区及缺血区均可见较大量的PCNA标记的移植细胞。Ⅶ因子染色阳性的新生血管密度：组Ⅰ〉组Ⅲ〉组Ⅱ〉组Ⅳ。4W后LVEF值：组Ⅰ〉组Ⅱ〉组Ⅲ〉组Ⅳ（均P〈0．01）。结论VEGF基因转染同种异体骨髓MSCs移植猪心肌梗死区及缺血区促进血管再生及心肌细胞的再生，改善心功能。     

t-PA基因修饰的内皮祖细胞对大鼠急性心肌梗死的治疗作用

目的探讨组织型纤溶酶原激活物(t-PA)基因修饰的脐血内皮祖细胞(EPCs)移植治疗对大鼠急性心肌梗死的治疗作用。方法体外扩增EPCs,将构建的t-PA基因慢病毒表达载体转染脐血EPCs,建立大鼠心肌梗死模型,实验随机分为PBS组、空载体EPCs组、单纯EPCs组和t-PA EPCs组。大鼠急性心肌梗死术后3 h开始移植治疗,t-PA EPCs组、EPCs组和空载体EPCs组静脉注射t-PA基因转染的EPCs、单纯EPCs和空载体EPCs。移植4周后,采用心脏超声评价心脏功能及检测血浆N末端B型脑钠钛前体(NT-Pro-BNP)的表达水平,Western-blot检测心肌组织中血管内皮生长因子(VEGF)、基质金属蛋白酶2/基质金属蛋白酶9(MMP-2/MMP-9)及基质金属蛋白酶组织抑制因子(TIMP-1)的表达水平;移植8 h后,ELISA法检测血清中t-PA、D-二聚体、纤溶酶原激活物抑制物1(PAI-1)和纤维蛋白原(Fib)表达情况。结果与PBS组、空载体EPCs组以及单纯EPCs组比较,t-PA基因修饰EPCs可明显改善心肌梗死后大鼠的心肌组织病理改变,大鼠急性心肌梗死心功能各参数改善最为显著; t-PA EPCs组NT-Pro-BNP的表达水平显著低于其他各组; t-PA EPCs组VEGF和TIMP的表达水平显著高于其他各组;相反,基质金属蛋白酶(MMP-2/MMP-9)的表达水平显著低于其他各组。t-PA EPCs组t-PA、D-二聚体表达均显著高于其他各组,而PAI-1、Fib表达均显著低于其他各组。结论 t-PA基因修饰的EPCs移植能有效治疗大鼠急性心肌梗死,其具体治疗作用与其改善心脏功能、促进血管新生、抑制心室重构、抑制血栓形成或增加溶栓作用等有关。     

腺相关病毒介导的血管内皮生长因子基因与骨髓间充质干细胞联合治疗大鼠肢体缺血的研究

目的 探讨腺相关病毒(rAAV)介导的人血管内皮生长因子(VEGF)165基因转染大鼠骨髓间充质干细胞(MSC)移植对血管新生的影响.比较单纯干细胞移植与联合基因治疗的疗效.方法 全骨髓培养法提取培养MSC;rAAV-VEGF165转染MSC中,酶联免疫吸附试验(ELISA)及反转录-聚合酶链反应(RT-PCR)检测VEGF的表达;以近交系大鼠建立骨骼肌缺血模型,40只大鼠随机分为4组,每组10只.对照组注射磷酸盐缓冲液(PBS);干细胞组移植等量MSC,转染术后7 d组和转染术后10 d组分别于结扎7 d和10 d后的缺血区移植转染VEGF基因的MSC,移植6周后做Ⅷ因子染色检测血管新生情况.结果成功培养出MSC,免疫组化CD44阳性表达,CD34阴性表达;流式细胞术CD90阳性表达.在转染rAAV-VEGF165后转染组1、3、5、7、9 d上清液中VEGF165分泌水平分别为(131.98±6.00)、(263.96±4.58)、(540.85±5.97)、(208.98±5.06)、(174.45±5.00)ng/L,明显高于未转染组的(68.72±1.99)、(76.47±4.98)、(89.86±1.99)、(84.93±8.97)、(68.71±5.98)ng/L[t值分别为14.14、51.16、79.28、27.56、26.07,(均P＜0.05)],且5 d时达到高峰,此后表达开始下降.琼脂糖凝胶电泳可见在579 bp处见到高亮度条带,证明rAAV-VEGF165成功转染进MSC细胞中.转染后的生长曲线及细胞形态较未转染组无明显变化.Ⅷ因子染色示转染术后10 d组动物缺血区毛细血管密度[(9.35±2.72)条/视野]明显高于对照组[(1.05±0.50)条/视野]和干细胞组[(3.10±1.43)条/视野](均P＜0.01),较转染术后7 d组[(6.95±1.69)条/视野]亦有一定程度的升高(P＜0.05).结论 MSC有利于VEGF基因的稳定表达,可作为VEGF基因的良好细胞载体,且联合应用效果高于单独移植MSC,移植最佳时间为术后10 d.     

血管内皮生长因子基因转染骨髓间充质干细胞移植促进缺血心肌血管生成的研究

目的研究血管内皮生长因子(vascularendothelial growth factor,VEGF)基因转染骨髓间充质干细胞(mesenchymalstem cells,MSCs)移植对缺血心肌的血管生成作用。方法于2004年5月至2005年8月取第四军医大学西京医院分离、培养Wistar大鼠的MSCs,用真核表达载体pcDNA3.1(-)/hVEGF165转染MSCs。45只近交系Wistar大鼠随机均分为转染组(MSCs/VEGF组)、对照组(MSCs组)、无血清培养基组(DMEM组),结扎前降支建立急性心肌梗死模型后在梗死区边缘区行5×106细胞移植,DMEM组行等量培养基注射。细胞移植前行CM-DiI标记。移植1个月后行心脏B超测量射血分数值,组织化学染色评价新生血管密度。结果培养的MSCs呈典型贴壁生长成纤维样外观,pcDNA3.1(-)/hVEGF165能有效转染大鼠MSCs,移植1个月后MSCs/VEGF组较其余各组左室射血分数(LVEF),再生血管密度明显增加,差异均有显著性(P<0.01)。结论VEGF基因转染MSCs移植能显著促进缺血心肌血管再生,进而改善心脏功能。     

粒细胞集落刺激因子动员内皮祖细胞治疗大鼠急性心肌梗死的疗效观察

目的 通过对心脏在体心功能和离体心肌储备功能测定,评价粒细胞集落刺激因子(G-CSF)动员内皮祖细胞(EPCs)对心肌梗死(MI)大鼠心功能改善的作用。方法 雄性Wistar大鼠36只,随机分为对照组、MI组和G-CSF组(每组12只),MI组和G-CSF组采用冠脉左前降支结扎法制作MI模型后,分别腹腔注射生理盐水和G-CSF连续5 d。给药后第7天,球后静脉采血,测定EPCs的数目和血浆血管内皮生长因子(VEGF)及C反应蛋白(CRP)的浓度。第4周时,进行在体心功能和离体心肌储备功能的测定,对MI大鼠的心功能进行全面评价。结果 G-CSF可增加外周血中EPCs的数目,提高血浆中VEGF的浓度。同时在体心功能和离体心肌储备功能测定的结果显示,MI大鼠的心功能得到改善。结论 G-CSF能够促进心梗大鼠EPCs的动员,增强VEGF的释放,改善MI大鼠的心功能。因此,G-CSF用于EPCs动员治疗AMI在临床上是有应用前景的。     

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     

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.     

Angiographic diagnosis of the degree of serosal invasion of carcinoma of the colon

Angiography using Prostaglandin El^® was performed on 38 patients with carcinoma of the colon in order to diagnose the degree of serosal cancer invasion. The findings at angiography were classified into four groups:1) AG-S3, abnormal change (irregularity and/or encasement) up to marginal vessels; 2) AG-S2, abnormality up to vasa recta; 3) AG-S1, abnormality of penetrating branches of vasa recta within the wall of the colon; and 4) AG-S0, no distinct findings of abovementioned vessels. These angiographic findings were compared with both macroscopic and microscopic serosal cancer invasion. Angiographic diagnosis is in accord with the macroscopic findings in 84.2 percent of cases. Angiographic diagnosis is in accord with the microscopic findings in 32.4 percent of cases. Macroscopic findings confirm the angiographic diagnosis precisely but the conflict with microscopic findings should not be overlooked. This may be the result of inflammatory change, adhesion, and fibrosis around carcinoma of the colon.     

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.