模拟失重状态下大鼠抗肺炎链球菌感染能力的变化

目的 观察模拟航天失重状态下呼吸道感染肺炎链球菌后抗感染能力的变化,为航天医疗保障提供依据.方法 建立模拟失重状态下大鼠链球菌肺炎模型,将32只健康雄性清洁级Wistar大鼠按随机数字表法分为4组:悬吊注菌组(A组)、悬吊未注菌组(B组)、未悬吊注菌组(C组)及未悬吊未注菌组(D组),每组8只,采用国内外公认成熟的尾悬吊法(身体纵轴与水平面约成30°)模拟失重状态,悬吊第4天通过气管捕管法将0.4ml(细菌浓度约9.0×108 CFU/ml)的标准肺炎链球菌菌株(ATCC6303,血清型3型,美国菌种保藏中心保存)注入肺组织,建立肺炎链球菌感染模型,对照组同时注入同等量的无菌生理盐水,仅注入1次.悬吊7d后取材,测定血常规、C反应蛋白及CD4+/CD8+.观察肺组织(每组均取右肺上叶)的炎症反应,并测量实验前后动物体重的变化.结果 A组肺组织表面凹凸不平,呈颗粒样改变,光镜下可见较严重的肺淤血和小静脉、毛细血管充盈扩张,肺泡融合增多,肺泡间隔增厚及肺泡腔受压变形,B、C组也可见部分上述改变,但程度较轻.各组间白细胞总数未见明显差异(F=1.57,P=0.22);A组中性粒细胞数为(2.4±0.5)×109/L,B组为(2.0±0.3)×109/L,C组为(1.7±0.4)×109/L,均高于D组的(1.2±0.2)×109/L(u值分别为0、1.0和8.5,均P＜0.05),A组与C组比较,差异有统计学意义(u=9.0,P=0.02).中性粒细胞百分比A组为0.26±0.04,高于C组的0.19±0.05(u =8.5,P=0.01);B组为0.23±0.03,C组为0.19±0.05,均高于D组的0.15±0.02(u值分别为2.0和13.0,均P＜0.05),而B组和C组比较差异无统计学意义(u=20.0,P=0.21);各组淋巴细胞总数比较差异无统计学意义(F=0.72,P=0.55),但A组[(6.0±0.9)×109/L]低于D组[(6.3±0.6) ×109/L];淋巴细胞百分比A组为0.66±0.08,B组为0.68±0.05,均低于D组的0.79±0.02 (F=10.24,P＜0.001).A组C反应蛋白为(11.9±2.2) g/L,明显高于D组的(1.5±0.8)g/L (u =0,P =0.001);4组CD4+/CD8+比值无明显差别(F=1.23,P=0.32);与其他组比较,A组体重减轻最明显,差异有统计学意义(F=122.07,P＜0.001).结论 失重状态下大鼠机体免疫功能降低,抗肺炎链球菌感染能力降低,肺部炎症反应更强,体重减轻更明显,需要给予相应的保障措施.     

肺炎链球菌感染早期外源性白介素-18干预的实验研究

目的:探讨外源性IL-18在小鼠肺炎早期对肺组织中肺炎链球菌清除的影响.方法:经鼻灌注肺炎链球菌诱导并建立小鼠肺炎链球菌肺炎模型,将实验小鼠分3组:正常对照组、感染组、感染加IL-18干预组.培养并计数小鼠肺组织内细菌数量,检测支气管肺泡灌洗液中中性粒细胞计数,RT-PCR方法检测小鼠肺组织中TNF-α及MIP-2 mRNA表达水平.结果:①干预组小鼠肺泡灌洗液中,中性粒细胞计数明显高于感染组(P＜0.01),感染组又高于对照组(P＜0.01);②干预组小鼠肺组织中细菌计数较感染组明显降低(P＜0.01);③干预组小鼠肺组织中TNF-α及MIP-2 mRNA表达较感染组明显增高(P＜0.01),而感染组又高于对照组(P＜0.01).结论:在小鼠肺炎链球菌肺炎早期给予外源性IL-18可以上调肺组织中TNF-α及MIP-2 mRNA的表达,促进中性粒细胞在感染部位聚集,减少肺组织中细菌数量.     

白介素17及其受体在大鼠重症肺炎克雷伯菌肺炎中的表达

目的 探讨白介素17(interleukin-17,IL-17)及IL-17受体(interleukin-17 receptor,IL-17R)在大鼠重症肺炎克雷伯菌肺炎发病过程中的表达.方法 72只SD大鼠随机分为模型组和对照组,通过气管内注射肺炎克雷伯菌3.6×10~9cfu/只,建立大鼠重症肺炎模型,采用实时荧光定量PCR方法检测各时间点肺组织IL-17、IL-17R、IL-1β、肿瘤坏死因子α mRNA表达水平;动态观察支气管肺泡灌洗液白细胞总数和中性粒细胞分类计数,并取肺组织病理学观察.结果 IL-17及IL-17R mRNA的表达于造模后4 h开始升高,第3天达到高峰,分别为对照组的(282.32±21.22)倍、(18.01±0.67)倍(P<0.01),至第7天基本降至基础水平.IL-1β及肿瘤坏死因子α mRNA的表达高峰延迟于IL-17及IL-17R,于第5天达到高峰.IL-17 mRNA的表达量与支气管肺泡灌洗液中性粒细胞计数呈显著正相关(r=0.82,P<0.01).模型组肺组织明显充血、水肿及出血,于第3天出现显著炎症细胞浸润.结论 IL-17及其受体在重症肺炎中高表达,是参与重症肺炎克雷伯菌肺炎发生发展的重要细胞因子,其促炎作用与上调中性粒细胞聚集及刺激IL-1β、肿瘤坏死因子α等细胞因子表达有关.     

肺炎支原体肺炎患儿血清白介素17和白介素23表达的意义

目的分析并评价肺炎支原体肺炎患儿血清白介素17和白介素23表达情况。方法将我院自2014年1月至2014年7月期间收治的107例肺炎患儿按照肺炎支原体抗体检测情况分为肺炎支原体肺炎组52例(观察组)与其他肺炎组55例(对照组)。全部儿童均进行血清IL-17、IL-23、肺炎支原体抗体、白细胞计数、中性粒细胞、C反应蛋白等进行测定。结果肺炎支原体肺炎组患儿血清IL-17及IL-23含量最高(P均0.01)。其中,肺炎支原体肺炎组的血清IL-17和IL-23含量均高于其他肺炎组(P均0.05)。两组的中性粒细胞数与IL-17及IL-23含量均呈正相关(P均0.05)。结论白介素17和白介素23在肺部肺炎支原体感染过程中参与免疫应答,可能与肺炎支原体清除过程有关。     

N-乙酰半胱氨酸对人离体嗜中性粒细胞细胞内活性氧和TLR4表达的影响

目的研究抗氧化剂N-乙酰半胱氨酸(NAC)对脂多糖诱导的人嗜中性白细胞产生活性氧(ROS)和MyD88磷酸化的有影响。方法用密度梯度法分离正常健康人外周静脉血的嗜中性粒细胞。分离的人嗜中性粒细胞(1×106)分别用脂多糖(1μg/ml)和(或)不同浓度的NAC(50,100,150,200μmol/L)孵育10 min;用流式细胞仪方法测定细胞内氧自由基;用Western印迹法检测嗜中性粒细胞MyD88磷酸化的水平。结果 NAC呈剂量依赖性抑制LPS诱导的人嗜中性白细胞ROS的产生(y=-0.355x+96.96;R2=0.977 6)。浓度为100μmol/L时,可明显抑制ROS的产生可达到(55.0±6.5)%(P<0.01),在浓度为150和200μmol/L时,分别可达到(42.1±9.7)%和(30.2±13.3)%(P均<0.01)。NAC呈剂量依赖性抑制LPS诱导的人嗜中性粒细胞MyD88的磷酸化。而且NAC也呈剂量依赖性抑制MyD88的磷酸化,与抑制ROS相平行。结论抗氧化剂NAC可以通过抑制人嗜中性粒细胞TLR4的表达,抑制细胞内ROS的产生,可能与治疗肺间质纤维化有关。     

肺炎克雷伯菌肺炎对大鼠胸腺细胞凋亡的影响及机制

目的研究肺炎克雷伯菌肺炎对大鼠胸腺细胞凋亡的影响及机制。方法选择10只6周龄健康SPF级Sprague Dawleg雄性大鼠,构建肺炎克雷伯菌肺炎大鼠模型,另外10只SD大鼠尾对照组。造模第6天取腹腔静脉血进行白细胞和中性粒细胞计数。电镜观察大鼠胸腺组织切片,流式细胞术检测胸腺细胞凋亡情况。免疫组织化学法检测胸腺组织中IL-23、Bcl-2和Caspase-3蛋白水平,免疫共沉淀检测Bcl-2泛素化水平。结果模型组大鼠胸腺组织中白细胞和中性粒细胞数目显著高于对照组(P0.05)。电镜观察显示模型组大鼠胸腺细胞凋亡情况明显,而对照组无显著凋亡情况,模型组胸腺细胞凋亡指数高于对照组,且具有显著性差异(P0.05)。模型组大鼠胸腺组织中IL-23和Caspase-3蛋白水平高于对照组、Bcl-2蛋白水平低于对照组,且泛素化水平高于对照组。结论肺炎克雷伯菌肺炎会导致大鼠胸腺细胞凋亡,IL-23/Bcl-2/Caspase-3的级联反应参与其中。     

肺炎支原体感染儿童血清MCP-1与IL-10水平及临床意义

目的研究肺炎支原体(MP)感染儿童急性期血清单核细胞趋化蛋白-1(MCP-1)与白细胞介素-10(IL-10)水平,探讨其临床意义。方法将160例研究对象分为3组:MP肺炎组(A组,80例)、非MP肺炎组(B组,40例)和对照组(C组,40例)。A组按照重症支原体肺炎诊断标准,分成普通型组(52例)和重症组(28例);普通型组按有无蛋白尿分成蛋白尿组(30例)和无蛋白尿组(22例)。采用ELISA法检测MCP-l与IL-10水平。结果 1 A组MCP-1、IL-10水平均高于B组和C组(P0.05);2重症组MCP-1水平明显高于普通型组(t=9.9031,P0.05);3蛋白尿组与无蛋白尿组MCP-1水平差异无统计学意义(t=0.0605,P0.05)。结论 MP肺炎患儿血清MCP-1及IL-10水平均显著升高,且与其他原因所致肺炎差异明显,提示血清MCP-1及IL-10水平可作为早期诊断MP肺炎的依据之一。     

大鼠大肠杆菌肺炎模型自由基和前列腺素代谢变化

目的从自由基和前列腺素代谢研究老年肺炎的病理生理特点.方法将大鼠复制大肠杆菌肺炎模型,分为青年对照组和模型组,老龄对照组和模型组.观察肺脏组织病理改变,外周血前列腺素代谢产物,肺泡灌洗液中性粒细胞计数、超氧化物歧化酶(SOD)活性、一氧化氮(NO)和丙二醛(MDA)含量.结果肺炎的肺组织损伤老龄大鼠较青年大鼠严重.青年模型组和老龄模型组中性粒细胞和血栓素B2(TXB2)的增高和6-酮-前列腺素F1α(6-Keto-PGF1α)的降低均较青年对照组和老龄对照组显著.与青年对照组比较,青年模型组血清SOD活性降低和MDA含量增高,肺泡灌洗液SOD活性减低和NO、MDA含量升高.老龄对照组和老龄模型组肺泡灌洗液SOD活性的降低及血清与肺泡灌洗液MDA含量升高分别较青年对照组和青年模型组显著.老龄模型组血清和肺泡灌洗液SOD活性的降低和NO、MDA含量的增高较老龄对照组显著.结论中性粒细胞和前列腺素及自由基介导的损伤参与肺炎的发生发展.肺炎老龄大鼠自由基损伤尤为严重.     

大鼠大肠杆菌肺炎模型自由基和前列腺素代谢变化

目的 从自由基和前列腺素代谢研究老年肺炎的病理生物特点。方法 将大鼠复制大肠杆菌肺炎模型,分为青年对照组和模型组,老龄对照组和模型组。观察肺脏组织病理改变,外周血前列腺素代谢产物,肺泡灌洗液中性粒细胞计数,超氧化物歧化酶（SOD）活性,一氧化氮（NO）和丙二醛（MDA）含量。结果 肺炎的肺组织损伤老龄大鼠较青年大鼠严重,青年模型组和老龄模型组中性粒细胞和血栓素B2（TXB2)物增高和6－酮－前列腺素F1α(6-Keto-PGF1a)的降低均较青年对照组和老龄对照组显著。与青年对照组比较,青年模型组血清SOD活性降低和MDA含量增高,肺泡灌洗液SOD活性减低和NO,MDA含量量升高。老龄对照组和老年模型组肺泡灌洗液SOD活性的降低及血清与肺泡灌洗液MDA含量升高分别较青年对照组和青年模型组显著。老龄模型血清和肺泡灌洗液SOD活性的降低和NO,MDA含量的增高较老对照组显著。结论 中性粒细胞和前列腺素及自由基介导的损伤参与肺炎的发生发展,肺炎老年大鼠自由基损伤尤为严重。     

TIMP1基因对肺炎链球菌诱导的肺泡上皮细胞HEPApiC凋亡的影响及机制研究

目的探讨基质金属蛋白酶抑制剂1(TIMP1)基因对肺炎链球菌诱导的人肺泡上皮细胞HEPApiC凋亡的影响及其可能的机制。方法体外培养人肺泡上皮细胞HEPApiC,采用肺炎链球菌感染HEPApiC细胞,实时荧光定量PCR(QPCR)和Western blot检测细胞中TIMP1的表达水平。将HEPApiC细胞分为4组,空白对照组(未做任何处理的细胞)、感染组(肺炎链球菌感染的细胞)、阴性对照组(转染siRNA control+肺炎链球菌感染的细胞)和干扰组(转染TIMP1 siRNA+肺炎链球菌感染的细胞)。CCK-8法检测各组HEPApiC细胞活力,流式细胞术检测各组HEPApiC细胞凋亡情况,Western blot检测细胞中B细胞淋巴瘤/白血病-2(Bcl-2)和Bcl-2相关X蛋白(Bax)表达水平,ELISA检测上清中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)的含量。结果肺炎链球菌感染后HEPApiC细胞中TIMP1 mRNA和蛋白表达水平均明显上调。转染TIMP1 siRNA后HEPApiC细胞中TIMP1 mRNA和蛋白表达水平均明显下调。感染组细胞凋亡率、Bax表达水平、TNF-α、IL-1β和IL-6含量均明显高于空白对照组(P0.05),而细胞活力和Bcl-2表达水平低于空白对照组(P0.05);干扰组细胞凋亡率、Bax表达水平、TNF-α、IL-1β和IL-6含量均明显低于感染组和阴性对照组(P0.05),而细胞活力和Bcl-2表达水平高于感染组和阴性对照组(P0.05)。结论敲低TIMP1基因表达能够抑制肺炎链球菌诱导的HEPApiC细胞凋亡,其作用机制可能与抑制炎性因子TNF-α、IL-1β和IL-6的表达有关。     

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.     

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.