白细胞介素6对豚鼠离体近端结肠平滑肌收缩的影响

目的:研究白细胞介素6(IL-6)对豚鼠近端结肠平滑肌的影响及其机制.方法:观察IL-6对结肠收缩的影响;用河豚毒素(TTX)阻断肠神经后观察不同浓度IL-6对结肠平滑肌收缩的影响;损伤Cajal间质细胞(ICC)后观察IL-6对结肠平滑肌收缩的影响.结果:在带有ICC的近端结肠纵行肌加入IL-6后,结肠平滑肌的收缩振幅增加和频率加快,呈浓度依赖性:加入TTX后,收缩的幅度和频率,同拮抗前相比分别降低和减慢(0.206±0.027 g vs 0.300±0.039 g;9.770±1.711 s vs 8.483±1.113 s:P<0.01,P<0.05):TTX阻断后加入IL-6(80μg/L),振幅增加和频率加快(P<0.01,P<0.05):破坏结肠ICC,收缩幅度和频率分别与损伤ICC后加入IL-6无显著性差异(80μg/L),而与正常结肠收缩振幅和频率有显著性差异(P<0.01).结论:IL-6对豚鼠近端结肠平滑肌的收缩活动有兴奋作用,其兴奋效应主要是通过肠神经元介导.ICC是IL-6对平滑肌兴奋途径的一个不可缺少的中间环节.     

防风对大鼠结肠平滑肌收缩的抑制作用及其机制

目的: 观察防风(RS)对离体大鼠结肠平滑肌的影响,并探讨其机制.方法: 制备大鼠结肠平滑肌肌条,以9 g/LNaCl溶液为对照,观察防风对肌条自发收缩以及对乙酰胆碱(Ach)引起的肌每收缩的影响.并观察防风对用3种工具药,即纳络酮(NLT)、心得安(XDA)和酚妥拉明(FTLM)充分孵育后的平滑肌肌条的抑制作用.结果: RS各组较NS组均对离体大鼠结肠平滑肌收缩有一定程度的抑制(振幅:F=8.388,P<0.01;面积:F=33.390,P<0.01),在10-40 g/L范围内随浓度的增大而增强.RS可以抑制Ach引起的离体大鼠结肠平滑肌收缩,加入Ach后加入不同浓度的RS平滑肌收缩振幅和面积均可部分抑制(F=6.093,P<0.0l:F=15.383,P<0.01).与对照组(NS RS)比较,FTLM组对平滑肌收缩的振幅(88.92%±9.93%)和面积(91.5%±12.59%)均可抑制(均P<0.01),NIT RS组面积有差异(72.6%±15.26%,P<0.05),而XDA组振幅和面积均无统计学意义.结论: 防风能够抑制离体大鼠结肠平滑肌收缩,其机制与肾上腺素能α-受体、M胆碱受体有关.     

血红素氧合酶的干预对糖尿病大鼠结肠动力障碍的影响

目的:探讨血红素氧合酶(heme oxygenase,HO)的干预对糖尿病(diabetes mellitus,DM)大鼠结肠动力障碍的影响.方法:链脲佐菌素ip建立DM模型,饲养6 wk时以碳沫推进实验证实DM大鼠存在胃肠慢传输运动后,所有大鼠分为正常对照组、DM未干预组、DM Hemin组[予HO诱导剂正铁血红素(Hemin)]及DM ZnPP组[予HO阻滞剂锌原卟啉(zinc protoporphyrin Ⅸ,ZnPP Ⅸ)];监测体质量、血糖.饲养9 wk时再测胃肠推进率,离体肌条实验记录结肠平滑肌条自发收缩反应及对Ach的反应性,Western blot及免疫组化检测近、远端结肠HO的表达.结果:6 wk时DM大鼠胃肠慢传输运动模型建立.HO干预对DM大鼠体质量、血糖无影响(P＞0.05).9 wk时Western blot示DM未干预组(1.20±0.09)、DM Hemin组(1.08±0.11)及DM ZnPP组(1.10±0.08)近端结肠HO-2表达无显著差异(P＞0.05),但均较正常对照组(1.66±0.14)显著减少(P＜0.05);各实验组远端结肠HO-2表达无差异.正常对照组与DM未干预组近、远端结肠HO-1的表达无差异(Western blot示HO-1/α-tubulin:近端结肠0.22±0.02 vs 0.22±0.03;远端结肠0.23±0.03 vs 0.23±0.03,P＞0.05);DM Hemin组结肠HO-1的表达(近端结肠0.66±0.09;远端结肠0.47±0.07)较前两组显著增多(P＜0.05);DM ZnPP组结肠HO-1基本无表达.DM Hemin组胃肠推进指数(54.4%±2.9% vs 63.0%±1.2%,P＜0.05)、结肠平滑肌条自发收缩频率、波幅和对Ach的反应性较DM未干预组显著下降(P＜0.05),而DM ZnPP组胃肠推进指数(72.5%±2.6% vs 63.0%±1.2%,P＜0.05)、结肠平滑肌条自发收缩频率、波幅和对Ach的反应性较DM未干预组明显改善(P＜0.05).结论:HO干预(诱导或阻断),对DM大鼠体质量、血糖无影响.诱导HO-1使DM大鼠慢传输型结肠动力障碍加重,而阻断HO-1可能改善DM大鼠慢传输型结肠动力障碍.     

莪术对大鼠结肠平滑肌收缩的促进作用及机制

目的:观察莪术对离体大鼠结肠平滑肌收缩运动的影响,并初步探讨其作用机制.方法:制备大鼠结肠平滑肌肌条,以9 g/LNaCl溶液(NS)为对照组,观察不同浓度莪术对结肠平滑肌的收缩效应;以莪术为对照组.分别观察酚妥拉明、维拉帕米和阿托品3种阻断剂孵育肌条后,莪术对肌条的收缩效应.结果:莪术高浓度组对离体大鼠结肠平滑肌的促进作用明显,与NS对照组比较,莪术1g/L、10 g/L组引起的肌条最大收缩振幅和曲线下面积均有统计学意义(63.92±2.06,76.27±2.28vs100%;44.09±11.10,55.66±10.29vs100%,P<0.05或<0.01);与单独莪术组比较,阻断剂维拉帕米和阿托品对莪术引起的肌条收缩有抑制作用,其最大收缩振幅和曲线下面积均有统计学意义(87.35%±50.49%,73.80%±9.37%vs 100%,33.97%±15.18%,27.55%±11.56% vs 100%,P<0.05或<0.01).结论:莪术对大鼠结肠平滑肌的收缩活动有兴奋作用,且与剂量呈正相关,其引起的收缩效应可被阿托品和维拉帕米阻断,而未能被酚妥拉明阻断.     

芒柄花素对兔离体肠平滑肌舒张作用的影响

目的观察芒柄花素对兔离体肠平滑肌肌张力的影响并探讨其作用机制。方法采用经典的离体小肠灌流技术,观察芒柄花素对肠平滑肌收缩活动以及乙酰胆碱(Ach)、氯化钡(BaCl2)及组胺(HA)所致痉挛性收缩肠平滑肌的影响。应用L型钙通道开放剂Bay K8644、肌浆网ryanodine受体阻断剂钌红(RR)和一氧化氮(NO)合酶抑制剂左旋硝基精氨酸甲酯(L-NAME),研究芒柄花素舒张肠平滑肌的作用机制。结果芒柄花素(10、20、40、60、80、100μmol/L)能剂量依赖性的抑制家兔离体小肠平滑肌自发性收缩,对Ach,HA和BaCl2所致的兔离体肠痉挛性收缩也具有剂量依赖性抑制作用,且与无刺激肠平滑肌比较有显著性差异(P<0.05或P<0.01)。芒柄花素可明显抑制Bay K8644(0.5μmol/L),阻断RR引起肠平滑肌舒张作用,但L-NAME不能够抑制芒柄花素舒张肠平滑肌作用。结论芒柄花素显著抑制家兔小肠平滑肌的收缩活动,其抑制可能与抑制细胞外钙内流和内钙释放,从而使细胞内钙浓度降低有关,但与小肠平滑肌一氧化氮(NO)浓度无关。     

银杏天宝对大鼠实验性结肠炎抗氧化作用的影响

目的:在三硝基苯磺酸灌肠诱导大鼠实验性结肠炎模型中,研究银杏天宝(EGB)的治疗作用及其抗氧化损伤作用的机制.方法:应用三硝基苯磺酸(TNBS)/乙醇灌肠制备大鼠实验性结肠炎模型.实验设正常对照组,三硝基苯磺酸模型组,阳性药物对照组(5-ASA group,100 mg/kg),EGB组(200 mg/kg) 4组.观察大鼠肠组织大体形态和组织学评分.生化法检测大鼠肠组织超氧化物歧化酶(SOD),谷胱苷肽过氧化物酶(GSH-Px)活性及丙二醛(MDA),一氧化氮(NO)含量.免疫组化检测肠组织诱导型一氧化氮合酶(iNOS)蛋白的表达.结果:与模型组相比,EGB组结肠组织iNOS表达明显减少,NO、MDA明显降低(iNOS:19.60%±3.17% vs 81.36%±1.71%;NO:9.20±0.81μmol/g vs 14.77±1.34μmol/g;MDA:3.96±0_35 umol/g vs 6.06±0.39 umol/g;P<0.01):SOD、GSH-Px活性明显升高(SOD:32.52±1.82 kU/g vs 21.90±2.22 kU/g;GSH- Px:49.91±2.59 kU/g vs 41.26±2.90 kU/g;P<0.01).EGB能明显减少大鼠实验性结肠炎模型组大体形态和组织学评分(2.10±0.57vs 3.10±0.57:3.50±0.85 vs 4.7±0.82;P<0.01).结论:EGB可能通过抑制氧自由基反应,抗氧化损伤,抑制NO生成,来减轻结肠炎炎症反应.     

促结肠动力中药筛选及其机制

目的:探讨中药生白术、小茴香、蒲公英、莱菔子、大腹皮、莪术的促结肠动力作用,以筛选出具有开发价值的促结肠动力药物,并探讨其初步机制.方法:制备豚鼠结肠纵肌,以9g/L氯化钠溶液和乙酰胆碱为对照,观察6味中药对离体结肠肌条收缩活性的效应.实验结果以振幅(g)、时间(s)和曲线下面积(g·s)表示.分析对象为加药后5min内出现的最大波形.结果:该6味中药对肌条均有不同程度的兴奋效应,中药组(依次为大腹皮、莱菔子、蒲公英、小茴香、莪术、生白术)与生理盐水组相比,振幅峰值(0.97±0.40,0.95±0.26,0.87±0.49,0.85±0.26,0.78±0.39,0.60±0.25vs0.03±0.04,P<0.01)和曲线下面积(1.40±1.00,0.75±0.79,0.62±0.54,0.64±0.59,0.40±0.37,0.29±0.15vs0.11±0.06,P<0.05或P<0.01)均有显著性差异,以大腹皮作用最强,时间长达175±238.07s.在阿托品和维拉帕米分别预孵育情况下,加入各中药后与单独中药组的肌条收缩幅度增强的幅度明显减弱,两组间差异有显著性(中药 拮抗剂组vs中药组,P<0.05).结论:该6味中药对结肠平滑肌均有不同程度的兴奋效应,引起的收缩效应可被M受体阻断剂阿托品部分阻断,通过细胞外Ca2 内流介导.     

内脏脂肪素在大鼠结肠平滑肌收缩障碍中的作用及其机制研究

背景:肥胖与多种功能性胃肠病相关,肥胖者常存在胃肠动力障碍,且血清脂肪细胞因子内脏脂肪素(VF)水平明显升高。既往研究显示VF可抑制子宫、血管平滑肌收缩。目的:探讨VF对大鼠结肠平滑肌收缩的影响及其可能机制。方法:取正常Sprague-Dawley(SD)大鼠远端结肠制备成0. 3 cm×0. 8 cm的肌条,使用生物信号分析系统记录VF对肌条收缩活动的影响。体外培养SD乳大鼠结肠平滑肌细胞,予VF干预,以蛋白质印迹法检测肌球蛋白轻链(MLC)磷酸化水平和钙通道Cav1. 2(α1亚基)表达;以激光共聚焦显微镜观察细胞外有或无Ca~(2+)的情况下乙酰胆碱刺激引起的细胞内Ca~(2+)浓度变化。结果:在肌条收缩实验中,VF(200 ng/mL)可显著减弱正常大鼠结肠平滑肌肌条的收缩张力(P 0. 05)。在结肠平滑肌细胞实验中,VF(200 ng/mL)可下调Cav1. 2通道表达,降低细胞内Ca~(2+)浓度和MLC磷酸化水平(P 0. 05)。结论:VF可能通过下调结肠平滑肌细胞膜Cav1. 2通道表达降低细胞内Ca~(2+)浓度,引起结肠平滑肌收缩障碍,从而参与结肠动力障碍的发生。     

一氧化氮抑制大鼠空肠平滑肌收缩

目的 观察神经性一氧化氮合酶(nNOs)在空肠组织内的分布和一氧化氮(NO)对空肠平滑肌相位性收缩的抑制作用,初步探讨其作用机制。方法 利用免疫组织化学技术和张力换能器分别测定nNOS在空肠组织内的分布和空肠平滑肌的收缩张力。结果 空肠平滑肌胞浆内有大量的nNOS分布,NO对大鼠空肠平滑肌收缩张力幅度的抑制呈浓度依赖性,对张力频率和时程没有明显影响。阻断β受体时,NO抑制张力的幅度,不影响频率和时程。阻断α或M受体时,NO对张力的幅度、频率和时程均抑制,并且阻断M受体时,NO对张力的频率和时程抑制有时间依赖性。正常张力幅度2.83±0.57mN,频率26.97±6.28次／min,时程2.25±0.24s,propranolol+L-Arg分别为1.47±0.46mN(P<0.01),25.53±2.99次／min(P>0.05),2.48±0.22 s,(P>0.05)。phen-tolamine+L-Arg分别为1.29±0.53 mN(P<0.01),22.93±1.75次／min(P<0.05),2.80±0.23s,(P<0.05)。atropine+L-Arg分别为1.72±0.74mN(P<0.05),17.92±4.93次／min(P<0.01),3.68±1.11 s,(P<0.01)。结论 空肠平滑肌胞浆内有大量的nNOS分布,NO对空肠平滑肌相位性收缩有抑制作用,这种作用与α、β、M受体有关。     

维生素K3通过延迟整流钾通道影响豚鼠结肠平滑肌收缩

目的研究维生素K3对豚鼠结肠平滑肌肌条自发性收缩频率和平均张力的影响,和对细胞膜延迟整流钾通道的影响,并初步探讨其治疗肠痉挛的机制。方法将豚鼠处死后取5cm左右长的结肠,用张力换能器测量(40,100,400)μmol/L维生素K3对肌条收缩频率和平均张力的影响,再将肌条消化得到单个豚鼠结肠平滑肌细胞,用K(v)电级内液充灌玻璃微电级,分别用台氏液和含40μmol/L,100μmol/L,400μmol/L的维生素K3的台氏液灌流。以-40mV为钳制电压钳制细胞,20mV为阶跃,检测K(v)。每检测1个浓度维生素K3后均用台氏液洗脱1min。结果40μmol/L,100μmol/L,400μmol/L维生素K3可减弱豚鼠结肠平滑肌的收缩频率和平均张力(40,100,400)μmol/L,维生素K3相对正常组的频率分别下降了(21.4±2.16)%,(42.3±3.24)%,(66.5±3.67)%(P<0.05),张力分别减少了(23.6±2.64)%,(46.7±2.96)%,(69.7±3.23)%(P<0.05)。40μmol/L,100μmol/L,400μmol/L维生素K3作用下延迟整流钾电流的峰值相对正常组分别增加了(44.04±4.36)%,(92.05±6.34)%,(115.89±6.41)%,(P<0.05)。结论维生素K3能浓度依赖性的减弱平滑肌条的收缩频率和平均张力,并增强延迟整流钾通道的开放,这可能是其治疗胃肠痉挛的机制之一。     

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.