基质交感分子1在载脂蛋白E基因敲除小鼠动脉粥样硬化斑块形成中的作用

目的观察基质交感分子1(STIM1)在动脉粥样硬化斑块形成过程中的改变并探讨其相关性。方法选取7~8周龄雄性载脂蛋白E基因敲除(apoE-/-)小鼠45只为模型组及野生型C57BL/6J小鼠45只为对照组,高脂饲喂至20、27和33周后,取主动脉进行HE和Masson染色,计算斑块面积占管腔面积百分比和胶原成分占斑块面积百分比;油红O染色分析斑块脂质含量;免疫组织化学染色测定平滑肌细胞阳性表达STIM1百分比,Western blot定量分析STIM1在易损斑块形成过程中的表达。结果与对照组20、27和33周龄小鼠比较,模型组STIM1相对表达量(0.2352±0.0165)vs(0.1435±0.0262)、(0.2985±0.0241)vs(0.1226±0.0270)和(0.3552±0.0340)vs(0.1385±0.0156)明显升高(P<0.01);且随着其周龄增加,STIM1表达明显升高;STIM1阳性表达面积百分比与校正斑块面积呈正相关(r=0.754,P<0.01),与校正胶原面积呈负相关(r=-0.783,P<0.01)。结论STIM1参与动脉粥样硬化斑块形成的病理过程,且与动脉粥样硬化斑块的发生、发展密切相关。     

老龄载脂蛋白E基因敲除小鼠血脂及病理组织学观察

目的:观察用普食喂养而非以往研究中的高脂饮食喂养的载脂蛋白E基因敲除小鼠(Apo E-/-)的血脂及病理组织学变化特点。方法:各选取20只8周龄雄性小鼠和同龄同性C57BL/6J小鼠为对照,普食喂养6~8个月,测定血清中总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)和高密度脂蛋白(HDL)的含量。常规制备主动脉的病理切片,进行HE染色,观察病理学变化。结果:Apo E-/-小鼠血清中TC、TG、LDL含量明显高于对照组(P0.05),且Apo E-/-小鼠主动脉根部病理切片明显脂质斑块形成。结论:普食喂养8月龄Apo E-/-小鼠是研究动脉粥样硬化(AS)的理想动物模型,为AS性心血管疾病研究者提供了参考资料。     

细胞色素P450基因对高脂饮食诱导不同周龄小鼠动脉粥样硬化的保护作用

目的研究血管内皮高表达CYP2C8基因能否改善小鼠动脉粥样硬化。方法以20和40周龄APOEKO+/-CYP2C8Tg+/-和CYP2C8Tg+/-基因(血管内皮特异性CYP2C8+/-转基因)的小鼠(n=10/组)为研究对象,相同基因背景和周龄的同窝APOEKO+/-和C57BL/6小鼠设为对照。采用PCR技术鉴定小鼠CYP2C8+/-基因;油红O染色检测APOEKO+/-CYP2C8Tg+/-、CYP2C8Tg+/-、APOEKO+/-和C57BL/6小鼠主动脉斑块形成面积;酶比色检测APOEKO+/-CYP2C8Tg+/-、CYP2C8Tg+/-、APOEKO+/-和C57BL/6小鼠血清TG、TCH、HDL。结果 20和40周龄APOEKO+/-CYP2C8Tg+/-和CYP2C8Tg+/-小鼠主动脉斑块形成面积与同周龄野生型小鼠相比明显减少,并且明显改善了血脂代谢状态。结论高表达CYP2C8基因能够改善西方饮食诱导的不同周龄小鼠的动脉粥样硬化。     

达肝素对载脂蛋白E基因缺陷小鼠肾动脉粥样硬化病变的影响

目的在动脉粥样硬化模型鼠中,观察达肝素对肾动脉粥样硬化病变进展及对植物血凝素样氧化型低密度脂蛋白受体1(LOX-1)和血管内皮生长因子(VEGF)的表达影响,探讨达肝素可能的抗动脉粥样硬化机制。方法以6周龄雄性C57BL/6J小鼠24只为对照,随机分为普通饲料组及高脂饲料组。雄性6周龄载脂蛋白E基因缺陷(Apo E-/-)小鼠36只,均予高脂饲料喂养至12周龄,随机分为模型组、低剂量肝素组[达肝素钠100 IU/(kg.d)]、高剂量肝素组[达肝素钠200 IU/(kg.d)],皮下注射连续4周(16周龄)后各组随机取6只处死。分离肾动脉,制成石蜡切片行HE及免疫组织化学染色,观察斑块情况及LOX-1蛋白的表达。用RT-PCR方法,检测肾动脉LOX-1 mRNA及VEGF mRNA的表达。用Western Blot分析法,检测肾动脉中LOX-1蛋白的表达。剩余小鼠继续原方案喂养4周(20周龄)后处死,肾动脉石蜡切片行HE染色,观察斑块情况。结果 Apo E-/-模型组在16周龄时出现轻度肾动脉粥样硬化。低剂量及高剂量达肝素均抑制肾动脉粥样硬化的形成(P<0.05)。Apo E-/-模型组LOX-1 mRNA、VEGF mRNA及LOX-1蛋白的表达水平较C57BL/6J普通饲料组的表达水平明显升高(P<0.05)。低剂量及高剂量达肝素治疗后,LOX-1 mRNA、VEGF mRNA及LOX-1蛋白的表达水平表达较模型组明显下降(P<0.05)。结论达肝素钠可能通过抑制LOX-1蛋白及VEGF表达的途径,抑制肾动脉粥样硬化的进展。     

胆汁酸衍生物INT-767激活FXR及TGR5降低小鼠动脉粥样硬化风险

目的探讨胆汁酸衍生物INT-767激活FXR及TGR5及其对小鼠动脉粥样硬化风险的影响。方法选取8周龄载脂蛋白(Apo)E-/-和低密度脂蛋白(LDL)R-/-的C57BL/6J小鼠分别用含INT-767(30 mg/kg)高纯度饲料(D12079B)喂养12 w和16 w,收集样本后进行组织生化分析(主动脉窦组织生化分析),对CD68和MCP1进行免疫荧光检测,血清样本进行快速蛋白液相色谱分析;血清胆汁酸水平通过q TRAP LC-MS/MS法检测。血清炎性细胞因子水平通过酶联免疫吸附(ELISA)试剂盒检测。采用电泳迁移率实验(EMSA)测定核转录因子(NF)-κB与DNA的结合活性。结果 INT-767可降低Apo E-/-和LDLR-/-小鼠血清胆固醇和甘油三酯水平,抑制肝CYPB1表达下调血清胆酸和去氧胆酸水平,从而抑制LDLR-/-和APOE-/-小鼠动脉粥样硬化斑块形成、降低Apo E-/-小鼠巨噬细胞浸润和炎症水平;INT-767主要是通过激活TGR5降低巨噬细胞细胞因子表达水平。结论胆汁酸的类似物INT-767可通过双激活TGR5和FXR调控靶基因,降低和减缓动脉粥样硬化的风险。     

肺炎衣原体感染对C57BL/6J小鼠动脉粥样硬化形成的影响

目的:研究肺炎衣原体(CP)感染对C57BL/6J小鼠动脉粥样硬化(AS)形成的影响。方法:48只8周龄雄性C57BL/6J小鼠分为感染-高脂组、高脂组和感染组和对照组,喂养40周,取主动脉根部标本分析AS斑块面积,采用直接免疫荧光法检查血管壁CP抗原,微量免疫荧光法(Micro-IFA)检测CP特异性抗体IgG。结果:感染-高脂组小鼠平均AS斑块面积较高脂组增大[(135249±43748)μm2∶(96378±30945)μm2,P<0·05],感染组和对照组小鼠无AS样斑块形成。结论:CP感染可加速高脂饮食C57BL/6J小鼠的主动脉AS发展。     

细胞色素P450基因降低动脉粥样硬化小鼠MMP-9表达

目的研究血管内皮高表达CYP2C8基因能否降低动脉粥样硬化小鼠的MMP-9的表达。方法以20周龄APOEKO+/-CYP2C8Tg+/-和CYP2C8Tg+/-小鼠(n=10/组)为研究对象,相同基因背景和周龄的同窝APOEKO+/-和C57BL/6小鼠设为对照。采用PCR技术鉴定小鼠CYP2C8+/-基因;油红O染色检测APOEKO+/-CYP2C8Tg+/-、CYP2C8Tg+/-、APOEKO+/-和C57BL/6小鼠主动脉斑块形成面积;用Real-time PCR法检测各组小鼠的主动脉MMP-9基因表达水平,Western blot分析各组小鼠的主动脉MMP-9蛋白的表达情况。用ELISA法检测各组小鼠的血浆IL-1β和IL-10。结果 APOEKO+/-CYP2C8Tg+/-和CYP2C8Tg+/-小鼠主动脉斑块形成面积明显减少,Real-time PCR分析显示高表达CYP2C8在主动脉中明显下调MMP-9基因的表达,Western blot分析结果显示:高表达CYP2C8在主动脉中明显下调MMP-9蛋白的活性。在血清学上,高表达CYP2C8明显上调IL-10而下调IL-1β。结论高表达CYP2C8基因能够降低小鼠的MMP-9的活性、减低炎性介质水平,通过抗炎和稳定粥样斑块而发挥抗粥样硬化作用。     

冠脉宁口服液干预ApoE基因敲除小鼠动脉粥样硬化的实验研究

目的探讨冠脉宁口服液对Apo E基因敲除小鼠(Apo E-/-小鼠)动脉粥样硬化病变(AS)的影响及其机制。方法 30只以C57BL/6J为背景的10周龄Apo E-/-小鼠,高脂饲料喂养12周后随机分为3组:模型组、冠脉宁组、复方丹参组,每组10只。冠脉宁组给予冠脉宁口服液20 g/(kg·d)灌服;复方丹参组给予复方丹参溶液3.5 g/(kg·d)灌服;模型组给予等量生理盐水灌服。另设10只相同背景和周龄的普通饲料喂养的C57BL/6J小鼠作为空白对照组。分别给药12周后小鼠摘除眼球采血,酶法检测血脂水平,ELISA方法检测血清中内脏脂肪素(visfatin)、白介素-6(IL-6)水平。HE染色观察小鼠主动脉病理形态学变化。结果空白对照组主动脉未见动脉粥样硬化改变,模型组有较明显的主动脉内膜增厚及粥样斑块的形成。模型组血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平及血清中visfatin、IL-6的表达显著高于空白对照组,而高密度脂蛋白胆固醇(HDL-C)水平则显著低于空白对照组(P0.05)。与模型组比较,冠脉宁组、复方丹参组TC、TG、LDL-C水平及血清中visfatin、IL-6水平显著降低(P0.05),而HDL-C水平显著升高(P0.05),且病理损伤程度减轻。冠脉宁组与复方丹参组比较,血脂指标、visfatin、IL-6水平差异无统计学意义(P0.05)。结论冠脉宁口服液可降低Apo E-/-小鼠的血脂水平及血清中visfatin、IL-6水平,具有一定的抗动脉粥样硬化作用,可能通过调节血脂代谢、降低炎症细胞因子水平达到抑制动脉粥样硬化进展、稳定动脉粥样硬化斑块的目的。     

生长素对载脂蛋白E基因敲除小鼠动脉粥样硬化斑块与炎症因子的影响

目的观察生长素对载脂蛋白E基因敲除(ApoE~(-/-))小鼠血浆白细胞介素8(IL-8)、单核细胞趋化因子1(MCP-1)、肿瘤坏死因子α(TNF-α)水平和血管壁核转录因子κBp65(NFκBp65)表达及动脉粥样斑块的影响。方法8周龄雄性ApoE~(-/-)小鼠12只饲以西方类型膳食12周建立动脉粥样硬化模型,遗传背景相同的6只8周龄雄性C57BL/6J小鼠饲以同类型膳食作对照。第8周时模型组分为腹腔内注射生长素(100μg/kg)组(n=6)和注射生理盐水(0.1mL)组(n=6),C57BL/6J小鼠亦给予生理盐水(0.1mL)腹腔内注射。第12周时眼眶取血,分离血浆,酶联免疫吸附试验(ELISA)法检测IL-8、MCP-1、TNF-α水平。取小鼠主动脉进行苏丹Ⅳ染色,观察主动脉粥样硬化病变面积占主动脉内膜面积的比例,行主动脉窦HE及油红O染色,观察主动脉窦动脉粥样斑块面积占管腔总面积的比例,行主动脉免疫组化染色,观察NFκBp65的表达。结果与C57BL/6J小鼠比较,ApoE~(-/-)小鼠和ApoE~(-/-)+生长素小鼠总胆固醇和低密度脂蛋白胆固醇高[(6.7±0.5),(7.6±2.0)比(5.5±0.2)mmol/L,(5.6±0.3),(6.0±0.5)比(2.2±0.1)mmol/L,均P0.05],ApoE~(-/-)+生长素小鼠高密度脂蛋白胆固醇比ApoE~(-/-)组高[(0.5±0.1)比(0.3±0.1)mmol/L,P0.05]。与C57BL/6J小鼠比较,ApoE~(-/-)小鼠主动脉粥样硬化病变面积占主动脉内膜面积比例增加[(15.1±1.7)%比0],ApoE~(-/-)+生长素小鼠主动脉粥样病变面积占主动脉内膜面积比例较ApoE~(-/-)小鼠降低[(10.1±0.5)%比(15.1±1.7)%,P0.05];C56BL/6J小鼠主动脉窦无动脉斑块形成(0%),ApoE~(-/-)组和ApoE~(-/-)+生长素组均有动脉斑块形成,但ApoE~(-/-)+生长素组小鼠主动脉窦斑块面积占管腔总面积的比例较ApoE~(-/-)组低[(22.6±2.2)%比(32.4±3.2)%,P0.01]。ApoE~(-/-)小鼠TNF-α、IL-8和MCP-1水平较C57BL/6J小鼠增高[分别为(24.5±1.7)比(10.1±0.5)ng/L,(33.5±16.7)比(16.8±8.8)ng/L,(78.0±5.6)比(13.5±1.8)ng/L;均P0.05],ApoE~(-/-)+生长素组TNF-α、IL-8和MCP-1水平较ApoE~(-/-)组降低[分别为(15.5±1.0)比(24.5±1.7)ng/L,(22.0±1.2)比(33.5±16.7)ng/L,(45.5±4.5)比(78.0±5.6)ng/L;均P0.05]。ApoE~(-/-)小鼠血管壁NF-κBp65表达较C57BL/6J增高,ApoE~(-/-)小鼠+生长素组血管壁NF-κBp65表达较ApoE~(-/-)小鼠组降低(P0.05)。结论生长素通过抑制炎症反应减少ApoE~(-/-)小鼠动脉粥样斑块形成。     

艾塞那肽部分通过抑制聚二磷酸腺苷核糖聚合酶1途径延缓糖尿病动脉粥样硬化的发展

目的探讨艾塞那肽对糖尿病动脉粥样硬化的影响。方法将雄性Apo E基因敲除(Apo E-/-)小鼠分为对照组、糖尿病组和艾塞那肽组(糖尿病+艾塞那肽)三组,6周后测量小鼠体重、心脏重量,检测其血糖及血脂水平,HE染色、油红O染色及免疫组织化学法测量主动脉斑块面积大小、组分及其稳定指数,Western Blot检测聚二磷酸腺苷核糖聚合酶1及诱导型一氧化氮合酶的表达。结果与对照组相比,糖尿病组小鼠的血清总胆固醇、甘油三酯和血糖水平明显升高,主动脉根部斑块面积占血管管腔面积的百分比明显增高,斑块稳定性明显降低,聚二磷酸腺苷核糖聚合酶1及诱导型一氧化氮合酶表达增高。与糖尿病组相比,艾塞那肽组小鼠的血清总胆固醇水平明显降低,甘油三酯降低,主动脉根部斑块面积百分比显著降低,斑块稳定性明显增高,聚二磷酸腺苷核糖聚合酶1及诱导型一氧化氮合酶表达降低。结论艾塞那肽可以部分通过抑制聚二磷酸腺苷核糖聚合酶1途径减少糖尿病小鼠动脉粥样硬化斑块的面积,增加斑块的稳定性。     

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.     

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.