BXSB小鼠肾组织诱生型一氧化氮合酶的异常表达及甲泼尼龙干预效应

目的探讨诱生型一氧化氮合酶(iNOS)是否参与介导BXSB小鼠狼疮肾炎(LN)及甲泼尼龙(MPS)是否可通过影响iNOS表达而缓解LN。方法用MPS对BXSB自发狼疮小鼠进行体内实验,利用反转录-聚合酶链反应(RT-PCR)和免疫组织化学技术研究了MPS对狼疮小鼠肾脏iNOS表达的影响,并观察了狼疮小鼠MPS治疗前后24h尿蛋白和NO3-/NO2-排泄量。结果BXSB狼疮小鼠肾组织检测到了iNOSmRNA的表达,而BALB/C小鼠未见表达;免疫组织化学示iNOS表达于BXSB小鼠肾小管上皮细胞、血管内皮细胞、肾间质及肾小球浸润的炎症细胞胞质内。MPS治疗组BXSB狼疮小鼠肾组织iNOSmRNA表达量显著低于未治疗组(P<0.01);治疗组24h尿蛋白及NO3-/NO2-排泄量显著低于未治疗组(P<0.01,P<0.05)。结论iNOS及其合成的一氧化氮(NO)可能参与介导了LN。MPS可能通过抑制肾组织iNOS的表达缓解LN。     

狼疮肾炎肾组织核转录因子-κB单核细胞趋化因子-1与CD68的表达及相关分析

目的 对狼疮肾炎(LN)肾组织进行核转录因子-κB(NF-κB)、单核细胞趋化因子(MCP-1)及巨噬细胞特异性抗体(CD68)检测,探讨其与LN肾脏病理及临床指标的关系.方法 应用免疫组织化学二步法检测49例LN肾组织NF-κB、MCP-1及CD68,原位杂交法检测49例LN肾组织NF-κB,并与肾脏病理及临床指标进行分析.结果 ①LN肾组织中NF-κB、MCP-1及CD68表达均比对照组显著升高(P＜0.01);其中Ⅳ型LN肾组织中NF-κB、MCP-1及CD68的表达比非Ⅳ型LN及对照组明显增加(P＜0.01,P＜0.05).原位杂交与免疫组织化学法检测NF-κB差异无统计学意义(P＞0.05).②LN肾组织中,NF-κB的表达与肾组织活动性指数、尿蛋白定量(24 h)及血清肌酐均高于对照组,且三者之间差异有统计学意义(P＜0.01,P＜0.01,P＜0.05);MCP-1与CD68的表达在肾小球和肾小管中仅与肾组织活动性指数(r=0.447,0.532,P＜0.05)、尿蛋白定量(24 h)(r=0.357,0.368,P＜0.05)呈正相关,而与血肌酐之间差异无统计学意义(P＞0.05).结论 NF-κB通过活化MCP-1进一步诱导巨噬细胞可能是LN肾脏损害的原因之一,NF-κB信号途径有望成为抑制巨噬细胞在肾脏局部浸润和增生的一个新的治疗靶点.     

Toll样受体9在狼疮肾炎患者外周血B淋巴细胞和肾组织中的表达及临床意义

目的 探讨Toll样受体9(TLR9)在狼疮肾炎(LN)患者外周血B淋巴细胞和肾组织的表达及其临床意义.方法 分别采用细胞内流式细胞术和免疫组织化学方法对对照组和LN患者外周血B淋巴细胞及肾组织中TLR9表达情况进行比较,并对TLR9表达与临床指标相关性进行分析.结果 活动期LN患者外周血CD19+B淋巴细胞TLR9的表达率高于非活动期LN患者及对照组(P＜0.01),且其表达率与SLE疾病活动指数(SLEDAI)评分、抗双链DNA(dsDNA)抗体滴度呈正相关(P＜0.01).LN患者肾组织中肾小球、肾小管间质TLR9表达均较健康组织增高(P＜0.01),其中国际肾脏病学会/肾脏病理学会(ISN/RPS)的Ⅳ型LN肾组织TLR9表达水平较Ⅱ、Ⅲ、Ⅴ型升高(P＜0.01),且肾小球TLR9表达水平与肾小球细胞增殖程度、肾脏病理活动指数、尿蛋白定量(24 h)呈正相关(P＜0.01).与估计的肾小球滤过率(eGFR)呈负相关(P＜0.01);肾小管间质TLR9表达水平与肾脏病理活动指数、肾小管问质损害程度、尿蛋白定量(24 h)也呈正相关(P＜0.01),与eGFR呈负相关(P＜0.01).结论 TLR9参与了LN患者B淋巴细胞的异常活化及肾脏病理损伤过程.     

慢性移植物抗宿主病狼疮样小鼠肾组织CTGF表达及氟伐他汀的干预作用

目的观察结缔组织生长凶子(CTGF)在慢性移植物抗宿主病(cGVHD)狼疮样小鼠。肾组织中的表达情况及氟伐他汀的调节作用。方法建立cGVHD狼疮样小鼠模型。按随机设计原则将模型小鼠分为3组,即模型对照组(A组)、氟伐他汀干预组(B组)及正常对照组(C组),每组均有6只小鼠。CTGF蛋白检测采用免疫组织化学方法及免疫荧光法．mRNA表达采用反转录-聚合酶链反应(RT-PCR)检测：留取24 h尿,测定尿蛋白排泄量。结果模型对照组小鼠24 h尿蛋门总量明显高于氟伐他汀干预组(P＜0．05)及正常对照组小鼠(P＜0．01)；RT-PCR检测到模型对照组小鼠肾组织CTGF mRNA表达较氟伐他汀干预组小鼠明显升高(P＜0．05),而正常对照组小鼠表达量少；免疫组织化学及免疫荧光表明正常对照组小鼠仅在少数肾小管有微量CTGF表达,而模型对照组及氟伐他汀干预组小鼠肾小管及问质均有CTGF蛋白表达,且模型对照组小鼠表达量显著高于氟伐他汀干预组小鼠(P＜0．01)。结论CTGF可能参与介导狼疮肾炎的发生、发展；cGVHD狼疮样小鼠模型肾组织中CTGF蛋白及mRNA表达明显上调,提示CTGF可能在狼疮肾炎(LN)肾小球硬化及肾间质纤维化的进程中起重要作用；氟伐他汀可能通过降低CTGF表达及减少尿蛋白排泄从而缓解LN,延缓肾纤维化进程。     

TLR4及相关炎性因子在糖尿病肾病中的表达及临床意义

目的探讨糖尿病肾病(DN)中Toll样受体4(TLR4)与相关炎性因子的关系在DN进展中的作用。方法选取DN患者27例,对照组10例,测定24 h尿蛋白含量、血清肌酐含量;免疫组化法检测肾组织中TLR4及单核细胞趋化蛋白(MCP-1)、白细胞介素(IL)-18的表达,并分析TLR4与相关炎性因子的相关性。结果与对照组比较,DN组患者的24 h尿蛋白定量及血肌肝(Scr)水平显著高于对照组(P<0.01);肾小管上皮细胞TLR4、MCP-1、IL-18的表达显著升高(P<0.01);TLR4的表达水平与MCP-1、IL-18、24 h尿蛋白定量及Scr水平呈显著正相关(R=0.683 39,0.613 31,0.645,0.571 2,P<0.05)。结论 DN组患者肾组织TLR4的表达上调,且与MCP-1、IL-18有显著相关性,可能是DN炎症介质活化的一个重要机制。     

慢性移植物抗宿主病狼疮样小鼠肾组织集落刺激因子-1表达及泼尼松的调控作用

目的　观察集落刺激因子 1(CSF 1)在慢性移植物抗宿主病 (GvHD)狼疮样小鼠肾组织中的表达及泼尼松的调控作用。方法　GvHD狼疮样小鼠模型参照有关文献建立。按随机设计原则将模型动物分两组即模型组 (A组 )和泼尼松治疗组 (B组 ) ,另设正常对照组 (C组 ) ,每组均有 8只动物。CSF 1蛋白检测采用免疫组织化学方法 ,mRNA表达采用原位杂交技术检测。结果　①A组肾组织中CSF 1蛋白表达显著高于C组 (P <0 0 5 ) ,肾小球、肾小管 间质中均有表达 ,尤以肾小管 间质表达更为丰富 ,而B组CSF 1在肾小球、肾小管 间质表达均显著减少 (P <0 0 5 )。②A组肾组织中CSF 1mRNA表达显著高于C组 (P <0 0 5 ) ,经泼尼松治疗后CSF 1mRNA受到明显抑制。③A组中CSF 1蛋白和mRNA表达呈正相关关系 (r =0 6 15 ,P <0 0 5 ) ,A组肾组织中CSF 1蛋白表达和 2 4h尿蛋白排泄呈正相关 (r =0 5 78,P <0 0 5 )。结论　慢性GvHD狼疮样小鼠肾组织特别在肾小管 间质中CSF 1蛋白和mRNA表达均显著增高 ,泼尼松在改善肾组织病理改变的同时 ,对CSF 1表达亦起抑制作用 ,提示CSF 1参与狼疮肾炎的发生和发展 ,泼尼松抑制CSF 1过度表达可能是其在狼疮肾炎中发挥治疗作用的机制之一。     

IgA肾病患者肾脏MCP-1的表达及意义

目的观察Ig A肾病患者肾脏单核细胞趋化蛋白-1（MCP-1）表达变化,并探讨其作用。方法用免疫组织化学染色法检测34例同步行肾活检诊断明确的Ig A肾病患者肾脏MCP-1表达,用肌氨酸氧化酶法检测血清肌酐（Scr）,比较不同程度肾小管间质病变及不同血清肌酐水平患者MCP-1的差异。用SDS-PAGE法检测尿蛋白分子量,并进一步分型,对不同分子量尿蛋白患者的MCP-1水平进行比较。采用Pearson相关分析Ig A肾病患者的MCP-1及24 h尿蛋白的相关性。结果 Ig A肾病患者肾组织MCP-1主要表达在肾小管上皮细胞内,与24 h尿蛋白定量呈正相关（r=0.34,P〈0.05）。肾小管间质病变分级重度组肾组织MCP-1表达较轻度组升高（P〈0.05）,Scr〉140μmol/L的Ig A肾病患者较Scr≤140μmol/L者升高（P均〈0.05）,混合性尿蛋白10 k D的Ig A肾病患者较23 k D者升高（P〈0.05）。结论肾组织MCP-1表达增加在Ig A肾病患者肾小管间质病变及肾功能损害中起重要作用。尿蛋白为10 k D的Ig A肾病患者肾组织MCP-1表达增加明显。     

脂多糖对小鼠肾脏炎症因子、过氧化物酶体增殖物活化受体γ及其辅调节因子表达的影响

目的:观察腹腔注射脂多糖(LPS)对小鼠肾脏单核细胞趋化蛋白1(MCP-1)、诱导型一氧化氮合酶(iNOS)、过氧化物酶体增殖物活化受体γ(PPAR-γ)及其辅调节因子表达的影响。方法:雄性云南昆明小白鼠[(20±2)g]随机分成两组:LPS组,腹腔注射LPS(5mg/kg);对照组,腹腔注射等体积磷酸盐缓冲液。分别于0～72h后处死小鼠,检测血清尿素氮和肌酐变化;留取肾脏,EMSA法检测NF-κB及PPAR-γ的DNA结合活性;Real-time PCR法检测肾组织MCP-1、iNOS、PPAR-γ及其辅激活因子1(PGC-1)、类固醇受体辅激活因子1(SRC-1)、SRC-2、SRC-3及核辅抑制因子(NCoR)mRNA的表达;ELISA检测肾组织MCP-1蛋白表达,Western Blot检测肾组织核蛋白PPAR-γ表达;HE染色观察病理改变,免疫组织化学法观察肾组织巨噬细胞的浸润情况。结果:小鼠腹腔注射LPS后血清尿素氮升高明显(P<0.05),但血肌酐无明显变化。肾组织NF-κB的DNA结合活性在0.5h后即明显增高,而PPAR-γ的DNA结合活性早期增强,8h后开始减弱。与同时间点对照组及基础值相比,小鼠腹腔注射LPS后6h,12h及24h,肾组织MCP-1 mRNA及蛋白表达均显著增加(P<0.01);而iNOS mRNA表达在6h及12h后显著增加(P<0.01)。PPAR-γ及PGC-1 mRNA表达则显著下调(P<0.01),核内PPAR-γ蛋白含量早期升高,24h时显著下降(P<0.01)。SRC-1、SRC-2、SRC-3及NCoR mRNA的表达与对照组相比无显著差异。LPS作用后肾组织HE染色未见显著改变,免疫组化可见肾组织巨噬细胞浸润,最初主要分布在髓质肾小管周围,在48h及72h浸润更为明显,皮质肾小球周围也可见巨噬细胞浸润。结论:小鼠腹腔注射LPS后肾组织中NF-κB活性及相关炎症因子MCP-1和iNOS表达上调,肾组织内有明显的巨噬细胞浸润,表明处于炎症状态,而PPAR-γ及其辅激活因子PGC-1的表达下调可能与炎症发展相关。     

别嘌醇对2型糖尿病小鼠肾小管间质prohibitin表达与细胞凋亡的影响

目的探讨抑制尿酸药物别嘌醇对2型糖尿病db/db小鼠肾小管上皮细胞prohibitin表达及细胞凋亡的影响。方法将T2DM db/db小鼠随机分为:db/db小鼠对照组(db/db组)、db/db小鼠+别嘌醇50 mg·kg-1·d-1治疗组(db/db+A组);将db/m小鼠作为对照组(db/m组),干预12 w后检测血糖、血尿素氮、血尿酸、血甘油三酯、24 h尿蛋白定量水平;电镜下观察肾小管上皮细胞病理改变;Western印迹及免疫组化法检测肾皮质抗增殖因子(prohibitin)、凋亡诱导因子(AIF)的定位与表达水平;分光光度计检测肾皮质丙二醛(MDA)的含量;原位末端脱氧核糖核酸转移酶介导的脱氧尿苷三磷酸标记法(TUNEL法)检测肾小管间质细胞凋亡情况。结果①12 w末,db/db组小鼠血糖、血尿酸、血甘油三酯、血尿素氮、24 h尿蛋白定量、肾组织匀浆MDA含量较db/m组均有不同程度的升高(P<0.05),而db/db+A组血尿酸、血尿素氮、24 h尿蛋白定量、肾组织MDA含量均较同时期db/db组降低(P<0.05)。②免疫组化与Western印迹检测结果均提示,db/db组肾皮质prohibitin蛋白表达量较db/m组明显降低(P<0.01),db/db+A组表达比db/db组有所增强(P<0.01)。db/db组肾皮质AIF蛋白表达明显高于db/m组(P<0.01),db/db+A组表达比db/db组有所降低(P<0.01)。③电镜下db/db组小鼠肾小管上皮细胞线粒体可见肿胀、空泡变,嵴结构消失等病变,db/db+A组上述病变减轻。④TUNEL检测结果:db/db组小鼠肾小管上皮细胞及间质细胞凋亡数量较db/m组明显增多,db/db+A组肾小管上皮细胞凋亡率较db/db组降低。结论别嘌醇可抑制T2DM小鼠肾小管间质细胞凋亡,其机制可能与其降低血尿酸水平后提高肾组织prohibitin的表达,减少局部氧化应激反应,抑制AIF增多并向核内转位有关。     

Bcl-2、Bax在狼疮肾炎患者肾组织中的表达及意义

目的研究细胞凋亡调节蛋白(Bcl-2及Bax)在狼疮肾炎(LN)患者肾组织的表达情况及与LN肾脏病理改变的关系。方法2003-012003-04对广西医科大学第一附属医院的44例活动期LN患者用免疫组化方法检测肾组织中Bcl-2、Bax的表达,观察它们与LN肾脏病理改变的关系。结果(1)LN肾小球Bcl-2及Bax表达均增高,与肾小球细胞增殖程度及增殖细胞核抗原(PCNA)阳性细胞数呈正相关。(2)LN肾间质Bcl-2表达增高,与间质炎症细胞浸润程度正相关。(3)LN肾小管Bax表达增高,与肾小管间质病变呈正相关。结论LN肾组织存在Bcl-2、Bax蛋白异常表达。Bcl-2高表达在LN肾小球细胞增殖及肾间质炎症细胞浸润过程中可能起重要作用。Bax在肾小管过度表达与肾小管间质病变有关。     

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。     

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。     

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.     

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.