重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白对肺间质病变大鼠TGF-β1表达的影响

目的 观察重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR-Fc,益赛普)对博来霉索(BLM)-A5所致肺间质病变大鼠转化生长因子(TGF)-β1表达的影响.方法 SD雄性大鼠45只,随机分为对照组、模型组和rhTNFR-Fc治疗组(治疗组),每组15只.各组动物于第7、14、28天随机处死5只,取肺组织进行苏木素-伊红(HE)和Masson染色,用免疫组织化学法检测肺组织TGF-β1的表达水平.结果 对照组未见明显胶原沉积、炎症及纤维化改变,治疗组各时期肺泡炎和肺纤维化程度均较模型组轻,差异有统计学意义(P<0.01).模型组各时期TGF-β1的表达较对照组增加,差异有统计学意义(P<0.01);治疗组第7、14天TGF-β1的表达较对照组增加,差异有统计学意义(P<0.01),第28天稍高于对照组,但差异无统计学意义(P>0.05).治疗组第7天比模型组减低,差异有统计学意义(P<0.05),第14、28天比模型组减低差异有统计学意义(P<0.01).结论 rhTNFR-Fc能减轻BLM-A5诱导的大鼠肺泡炎和肺纤维化,可能与抑制肺组织TGF-β1表达有关.     

丙戊酸钠对博莱霉素致肺纤维化大鼠转化生长因子β1表达的调节

目的 探讨组蛋白脱乙酰基转移酶抑制剂丙戊酸钠对博莱霉素诱导肺纤维化大鼠转化生长因子β1(TGF-β1)表达的调节.方法 54只雄性SD大鼠随机分为控制对照组、肺纤维化模型组、丙戊酸钠干预组.肺纤维化模型组、丙戊酸钠干预组均给予博莱霉素溶液按5 mg/kg气管内注入建立大鼠肺纤维化模型,控制对照组予以等体积生理盐水注射.丙戊酸钠干预组对肺纤维化大鼠予丙戊酸钠(200mg· kg-1· d-1)干预.各组随机于造模后第7、14和28天分3批处死,观察大鼠大体及HE变化和Masson染色,Szapiel评分,肺组织羟脯氨酸(HYP)检测及TGF-β1免疫组化检测.结果 与控制对照组同时间点相比,肺纤维化模型组14 d和28 d肺组织TGF-β1及HYP含量显著增高(P＜0.01),丙戊酸钠干预后增高的Szapiel评分、TGF-β1及HYP受到明显抑制.结论 予以VPA干预后肺组织Masson染色显示蓝色胶原沉积明显减少,能显著抑制博莱霉素诱导的大鼠肺纤维化的TGF-β1,VPA有抑制抗肺纤维化作用.     

Trichostatin A对博莱霉素诱导的大鼠肺纤维化的抑制作用

目的 观察非选择性组蛋白去乙酰化酶抑制剂Trichostatin A(TSA)对博莱霉素诱导大鼠肺纤维化的影响以及肺组织中α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原含量及转化生长因子β1(TGF-β1)mRNA表达的变化.方法 将46只SPF级雄性160～180 g SD大鼠随机分为正常对照组、模型组Ⅰ、模型组Ⅱ、治疗组,其中正常对照组10只,模型组Ⅰ 14只,模型组Ⅱ12只,治疗组10只.模型组Ⅰ、模型组Ⅱ及治疗组经气管内注入盐酸博莱霉素(5mg/kg),制备肺纤维化大鼠模型.正常对照组气管内注入相同体积生理盐水.治疗组在造模次日起腹腔内注射TSA 2 mg/kg溶于二甲基亚砜(DMSO) 60μl,并稀释于生理盐水1.2 ml中,每天1次,连续3d;模型组Ⅱ在造模次日起腹腔内注射DMSO 60 μl稀释于生理盐水1.2 ml中,每天1次,连续3 d；模型组Ⅰ及正常对照组在造模次日起腹腔内注射生理盐水1.2 ml,每天1次,连续3d.其中模型组Ⅰ大鼠死亡5只,模型组Ⅱ大鼠死亡4只,治疗组大鼠死亡2只.于造模第21天处死全部存活大鼠.取肺组织进行HE染色及Masson三色染色,评估肺纤维化程度.碱水解法测定肺组织羟脯氨酸(HYP)含量.酶联免疫吸附法(ELISA)测定肺组织匀浆中α-SMA及Ⅰ型胶原的含量.real-time PCR检测肺组织TGF-β1mRNA表达的变化.结果 ①HE染色分析:模型组Ⅰ及模型组Ⅱ肺泡炎程度较正常对照组增高(P＜0.05),模型组Ⅰ及模型组Ⅱ之间肺泡炎程度差异无统计学意义(P＞0.05),治疗组肺泡炎程度均较模型组Ⅰ及模型组Ⅱ减轻(P＜0.05),与正常对照组比较肺泡炎程度差异无统计学意义(P＞0.05).②Masson染色分析:模型组Ⅰ及模型组Ⅱ肺组织纤维化程度较正常对照组增高(P＜0.05),模型组Ⅰ及模型组Ⅱ之间肺纤维化程度差异无统计学意义(P＞0.05),治疗组肺纤维化程度较模型组Ⅰ及模型组Ⅱ减轻(P＜0.05),与正常对照组比较肺纤维化程度差异无统计学意义(P＞0.05).③肺组织HYP含量:模型组Ⅰ及模型组Ⅱ的HYP含量较正常对照组高(P＜0.05),模型组Ⅰ及模型组Ⅱ的HYP含量无明显变化(P＞0.05).治疗组的HYP含量较模型组Ⅰ及模型组Ⅱ降低(P＜0.05),与正常对照组比较差异无统计学意义(P＞0.05).④肺组织匀浆中α-SMA蛋白浓度:模型组Ⅰ及模型组Ⅱ的α-SMA含量较正常对照组高(P＜0.05),模型组Ⅰ及模型组Ⅱ的α-SMA含量差异无统计学意义(P＞0.05),治疗组的α-SMA含量较模型组Ⅰ及模型组Ⅱ降低(P＜0.05),与正常对照组比较差异无统计学意义(P＞0.05).⑤肺组织匀浆中Ⅰ型胶原蛋白浓度:模型组Ⅰ及模型组Ⅱ的Ⅰ型胶原含量较正常对照组高(P＜0.05),模型组Ⅰ及模型组Ⅱ的Ⅰ型胶原含量差异无统计学意义(P＞0.05),治疗组的Ⅰ型胶原含量较模型组Ⅰ及模型组Ⅱ降低(P＜0.05),与正常对照组比较差异无统计学意义(P＞0.05).⑥肺组织TGF-β1 mRNA:模型组Ⅰ及模型组Ⅱ的TGF-β1 mRNA表达较正常对照组升高(P＜0.05),模型组Ⅰ及模型组Ⅱ的TGF-β1 mRNA表达差异无统计学意义(P＞0.05),治疗组的TGF-β1mRNA表达较模型组Ⅰ及模型组Ⅱ降低(P＜0.05),但高于正常对照组(P＜0.05).结论 气管内注入博莱霉素成功构建肺纤维化大鼠模型.非选择性组蛋白去乙酰化酶抑制剂TSA能减轻博莱霉素诱导大鼠肺纤维化,降低肺组织中纤维化相关蛋白α-SMA、Ⅰ型胶原含量以及TGF-β1 mRNA表达.     

肺纤维化大鼠肺组织血小板源性生长因子和纤溶酶原激活物抑制剂1表达的研究

目的 观察肺纤维化大鼠肺组织中血小板源性生长因子(PDGF)和纤溶酶原激活物抑制剂1(PAI-1)表达的变化,探讨其在肺纤维化中的作用机制.方法 30只 Wistar大鼠随机分为博莱霉素组(BLM组)和对照组(NS组):①BLM组,气管内灌注BLM(5 mg/kg)诱导肺纤维化;②NS组,气管内灌注NS(剂量与用法同上).于气管内灌注后第7、14和28天各分别处死5只大鼠,取右肺支气管肺泡灌洗液(BALF),进行细胞分类、计数;留取左肺组织匀浆测定羟脯氨酸含量;采用免疫组织化学法测定PDGF和PAI-l蛋白的表达.结果 ①BLM组肺组织中胶原含量在第7天开始升高,第14、28天进行性增高,明显高于NS组(P＜0.01);②BLM组肺组织中PDGF蛋白表达在第7天达高峰,之后下降,第28天时仍高于NS组(P ＜0.05),与BALF中的细胞总数密切相关;③BLM组肺组织中PAI-1的表达在第7天开始升高,第28天达到高峰,与肺组织中胶原的含量密切相关(r=0.952,P＜0.01).结论 PDGF和PAI-1可能通过影响细胞外基质的代谢及胶原的沉积促进肺纤维化的发生.     

外源性H_2S对肺纤维化大鼠肺组织转化生长因子-β1及结缔组织生长因子的干预作用

目的动态观察硫化氢(H2S)对博莱霉素(BLM)致肺纤维化大鼠肺组织转化生长因子(TGF-β1)及结缔组织生长因子(CTGF)表达的影响。方法采用气管内一次注射BLM 5 mg/kg致大鼠肺纤维化的造模方法,将健康雄性Wistar大鼠54只随机分为对照组、肺纤维化组和NaHS(H2S供体)+肺纤维化组,造模后第2天开始:NaHS+肺纤维化组每天腹腔注射0.5 ml NaHS(28μmol/kg),对照组及肺纤维化组每天腹腔内注射等量生理盐水。各组在给药后7、14、28 d分别随机处死6只取材,碱水解法检测肺组织羟脯氨酸(HYP)水平的变化,免疫组化法检测TGF-β1及CTGF蛋白在肺组织的表达。结果与对照组相比,肺纤维化组各期大鼠肺组织HYP含量、TGF-β1及CTGF蛋白表达均显著升高(P<0.01);与肺纤维化相比,NaHS+肺纤维化各组大鼠HYP含量、TGF-β1及CTGF蛋白表达在各期均显著降低(P<0.01、0.05)。各组各期肺组织TGF-β1与CTGF呈显著正相关(r=0.891⁰.968,P均<0.01)。结论外源性H2S可以通过抑制TGF-β1信号通路,下调CTGF蛋白表达发挥抗纤维化作用。     

TGF-β/Smads信号传导通路在实验性大鼠肺间质纤维化中的作用

目的 研究化瘀理肺方对肺间质纤维化大鼠肺组织中转化生长因子β(TGF-β)、Smad3、Smad7蛋白表达的影响.方法 对照组在气管插管内注入生理盐水,其余大鼠注入博莱霉素建立肺纤维化模型.分别给予大鼠化瘀理肺方药物(中药组)、生理盐水灌胃(模型组、对照组)、氢化可的松琥珀酸钠腹腔注射(激素组)进行干预,并于给药后14、28 d处死,取肺组织行HE染色观察病理变化,免疫组化法测定肺组织TGF-β、Smad3、Smad7蛋白表达情况.结果 与模型组和激素组比较,中药组肺泡炎和肺纤维化程度及TGF-β、Smad3蛋白表达均明显降低,Smad7蛋白表达升高.结论 TGF-β、Smad3、Smad7在实验性大鼠肺纤维化的形成中起重要作用,化瘀理肺方可通过调节这些蛋白的表达,从而起到防治肺纤维化的作用.     

骨髓间充质干细胞对大鼠肺纤维化的抑制作用

目的分析大鼠气管内注入博来霉素(BLMS)后,观察不同时间点移入骨髓间充质干细胞(MSC)的分化行为,分析细胞因子表达规律及其与病理变化的相关性,确定MSC移植治疗实验性肺纤维化大鼠的最佳时间窗及标准,旨在为临床上干细胞移植治疗肺纤维化的时机提供可靠参考依据。方法体外分离和培养雄性Wistar大鼠的MSC。将60只雌性Wistar大鼠随机分为4组:A组为生理盐水对照组,气管内注入PBS50μL;B组为博来霉素模型组,向气管内注入BLMS 5mg/kg;C组气管内注入BLMS后立即尾静脉注射移植MSC 1×10~7/mL,200μL;D组气管内注入BLMS 14d后移植MSC 1×107/mL,200μL。于实验7d、14d、28d(D组于28d)分别处死大鼠5只,取肺组织病理切片行HE及Masson染色,观察肺部炎症和纤维化情况及羟脯氨酸(HYP)含量测定;提取肺组织通过聚合酶链反应(PCR)检测雄性鼠的性别决定基因(SRY);提取肺组织免疫组织化学法检测转化生长因子-β1(TGF-β1)蛋白表达。结果病理切片观察:B组第7天肺泡炎最明显,28d时肺纤维化最严重,与其他3组比较有统计学意义(P0.05或P0.01);C组、D组肺泡炎及肺纤维化程度均较B组显著减轻(P0.05),但仍较A组严重(P0.05或P0.01),其中D组较C组严重(P0.05)。Y染色体性别决定区SRY基因的检测:A组及B组检测不到SRY基因,但C组和D组各时间点均能检测到SRY基因。HYP含量:B组第7天HYP含量开始升高,28d达到最高峰,高于其他3组(P0.05或P0.01),与A组相比各时间点HYP含量的差异均具有统计学意义(P0.01);C组与D组大鼠HYP含量均呈低水平升高趋势,造模后7d、14d、28dHYP含量均显著低于B组(P0.05)。TGF-β1:B组TGF-β1在14d时表达最高,28d时逐渐下降,各组之间比较均有统计学意义(P0.05)。结论气管内注入博来霉素可成功复制大鼠肺纤维化模型;MSC可减轻肺泡炎、肺纤维化的程度;MSC到达损伤肺后可能抑制TGF-β1的表达,从而抑制博来霉素诱导肺纤维化的形成。     

罗格列酮对肺纤维化大鼠TGF-β1 表达的影响

将45只SD雄性大鼠随机分为对照组、模型组和治疗组,模型组和治疗组大鼠气管内一次性滴注博莱霉素-A5(BLM-A5),对照组大鼠滴注等体积生理盐水.注药后治疗组灌服罗格列酮8 mg/(kg·d),对照组、模型组给予等体积生理盐水.各组动物于7、14、28 d随机处死5只,取肺组织进行HE和Masson染色,免疫组化法检测肺组织转化生长因子β1(TGF-β1)的表达水平.HE染色示治疗组各时期肺泡炎和肺纤维化程度均较模型组轻;Masson 染色示治疗组胶原沉积明显少于模型组.治疗组与模型组各时期TGF-β1表达水平均有统计学差异.提示罗格列酮能减轻BLM-A5诱导的肺纤维化大鼠肺泡炎和肺纤维化,其机制可能与抑制肺组织TGF-β1表达有关.     

ADAMTS-1在肺纤维化大鼠肺组织中的表达及意义

目的 探讨ADAMTS-1在肺纤维化大鼠肺组织中的表达及意义.方法 40只SD大鼠气管内注射博莱霉素A5建立实验性大鼠肺纤维化模型(模型组),10只SD大鼠气管内注入生理盐水作为对照组,模型组于第7、14、21和28天分别处死10只大鼠,对照组于第28天全部处死,采用HE染色、Masson三联染色检测肺纤维化的病理变化,用免疫组织化学和RT-PCR分别测定肺组织ADAMTS-1蛋白及mRNA水平.结果 模型组7～28 d各时点肺组织ADAMTS-1蛋白和mRNA表达水平均低于对照组(P ＜0.05或P＜0.01).结论 ADAMTS-1表达下调可能在肺纤维化的发病过程中起重要作用.     

黄芪糖蛋白对博莱霉素诱导小鼠肺纤维化的干预作用及机制

目的观察黄芪糖蛋白(HQGP)干预肺纤维化小鼠的病理学改变及并分析机制。方法将60只健康ICR小鼠随机分为对照组、模型组及治疗组,每组20只。采用鼻腔滴入博莱霉素建立小鼠肺纤维化模型,造模次日起治疗组每天腹腔注射HQGP,模型组及对照组腹腔注射等体积的生理盐水,连续14 d;造模后第7、14、28天取材,取肺组织进行HE、Masson染色,观察肺泡炎及纤维化程度;免疫组化法检测肺组织转化生长因子(TGF)-β1表达。结果与模型组比较,第7、14、28天治疗组肺泡炎、肺纤维化程度明显减轻;肺组织TGF-β1蛋白表达明显降低(P0.05)。结论 HQGP抑制小鼠肺纤维化的发展,其作用机制可能与降低肺组织中TGF-β1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.     

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.