适配体介导的MRI-As靶向造影剂的动物体内实验

目的合成一种靶向于动脉粥样硬化(As)病变的核磁共振成像(MRI)纳米造影剂,为开发新型动脉粥样硬化MRI诊断技术提供实验依据。方法运用自主研发的对泡沫细胞具有靶向性的寡合苷酸适配体PM1,与四氧化三铁(Fe_3O_4)纳米粒耦联,制备出具有靶向作用的MRI造影剂,命名为MRI-As。用高脂饲料饲养建立载脂蛋白E基因敲除(ApoE~(-/-))小鼠As动物模型,苏丹红Ⅳ染色鉴定主动脉As病变。MRI成像仪检测MRI-As造影剂对As小鼠斑块MRI成像的影响。结果 ApoE~(-/-)小鼠模型动物MRI显像可以观察到主动脉壁毛糙,As病灶呈高信号亮点,与周围组织形成良好对比,中心信号较高,较均匀,边缘较清楚。注射MRI-As造影剂后,As病变区信号强度呈下降趋势,管壁不光滑,呈多发斑点状信号的缺损。对照组动物注射MRI-As造影剂后,血管壁信号强度无明显变化。结论 MRI-As造影剂对As病变能起到主动靶向作用,利用Fe_3O_4纳米粒对As病变的阴性对比效果,显著提高了As病变的MRI图像分辨率,具有As MRI影像的新型、快速、高效、无创、无辐射造影剂的潜质。     

老年人腹主动脉瘤血管平滑肌细胞相关蛋白表达及巨噬细胞浸润的病理学特点

目的 观察血管平滑肌细胞(VSMC)表达变化及巨噬细胞浸润在老年人腹主动脉瘤中的病理学特点. 方法 对15例老年人腹主动脉瘤与6例正常腹主动脉组织行HE染色、VanGieson法染色和免疫组织化学染色.用免疫组织化学染色检测α-平滑肌肌动蛋白(α-SMA)、组织蛋白酶B及CD68蛋白表达. 结果 老年人腹主动脉瘤病变处胶原容积百分比(9.3±1.9)%,较正常主动脉的(5.3±1.8)%增高(P＜0.05).老年人腹主动脉瘤中组织蛋白酶B和CD68的表达增强分别为0.38+0.07和0.51±0.12,α-SMA表达减弱为0.23±0.05,与正常腹主动脉(分别为0.13±0.06和0.01±0.01,0.33±0.05)比较.差异有统计学意义(P＜0.05). 结论 VSMC相关蛋白表达水平改变及巨噬细胞浸润可能参与了老年人腹主动脉瘤血管壁的破坏.     

兔VX2肝癌模型的建立及纳米微泡造影剂在模型早期检测中的应用

目的通过建立一个原发性或转移性兔肝癌模型并应用纳米微泡造影剂对肿瘤进行早期检测,探讨纳米材料在肝癌超声诊断中的应用。方法通过肿瘤组织块接种法制备兔肝癌模型并利用门静脉插管注射微泡造影剂对比增强显影。结果模型建立后检测原位成瘤率为83．3％,采用5MHz的发射频率,肝内主要血管及瘤块1min内显影得到增强。结论靶向超声纳米对比剂具有特异性和敏感性,纳米级微泡造影剂用于超声造影增强是完全可行的。     

原发性肝细胞癌抗血管生成治疗后血管内皮生长因子及血流灌注参数变化

背景血管靶向药物是临床治疗肝脏肿瘤所取得的重大进步之一,尤其对于不能行手术切除的晚期原发性肝细胞癌(hepatocellular carcinoma, HCC)患者,其疗效确切.超声造影是一种无创性血流灌注显示方法,能实时动态反映肿瘤组织的微循环血流灌注,可为临床评估HCC抗血管生成疗效提供血流动力学参考信息.目的探讨超声造影在评估HCC抗血管生成疗效中的应用价值.方法选取经肝穿刺活检病理证实的72例HCC患者作为研究对象(共72个病灶),随机分为A组(36例)和B组(36例). A组接受经肝动脉化疗栓塞术(transcatheter arterial chemoembolization,TACE)治疗,B组接受TACE联合沙利度胺治疗.所有患者分别于治疗前、治疗12 wk后行超声造影检查,测量病灶血流灌注参数:曲线下面积(area under curve, AUC)、峰值强度(peak intensity,PI),同期测定血清血管内皮生长因子(vascular endothelial growth factor, VEGF)水平作比较分析.结果B组治疗后AUC、PI以及血清VEGF水平分别低于各组治疗前,差异有统计学意义(P0.05); B组治疗后AUC、PI以及血清VEGF水平明显低于A组治疗后,差异有统计学意义(P0.05).结论超声造影能定量分析HCC抗血管生成治疗后血流灌注参数变化,有效评估HCC抗血管生成疗效,具有一定应用价值.     

超声辐照载紫杉醇微泡对大鼠血管平滑肌细胞凋亡的影响

目的 探讨超声辐照载紫杉醇微泡对大鼠血管平滑肌细胞(VSMCs)凋亡的影响及其作用机制.方法 将体外培养的大鼠胸主动脉VSMCs用血小板衍生生长因子-BB刺激后分组如下:对照组(A组)、超声辐照+微泡组(B组)、超声辐照+载紫杉醇微泡组(C组)、单纯载紫杉醇微泡组(D组)和紫杉醇组(E组).采用频率1MHz、声强0.3W/cm2的连续波超声辐照VSMCs 120s,用流式细胞仪、Annexin V/PI染色和免疫细胞化学技术检测各组细胞周期、细胞凋亡以及凋亡相关蛋白表达的变化.结果 与A组比较,各组S期细胞比例均显著降低(P＜0.01),B组G0/G1期细胞比例显著增高(P＜0.01),D组和E组G2/M细胞比例显著增高(P＜0.01),C组G0/G1期细胞比例和G2/M细胞比例均显著增高(P＜0.01).与A组比较,B组和C组VSMCs凋亡率显著增高(P＜0.01),Bax蛋白表达显著上调、而Bcl-2蛋白表达则显著降低(P＜0.01).结论 超声辐照载紫杉醇微泡可诱导VSMCs凋亡,其机制可能是微泡介导的超声空化效应,致Bax蛋白表达上调及Bcl-2蛋白表达下调.     

原肌球蛋白4抗体靶向动脉粥样硬化合成型血管平滑肌细胞体内磁共振成像的实验研究

目的 观察合成型血管平滑肌细胞(VSMC)标记蛋白原肌球蛋白4(TPM-4)在动脉粥样硬化斑块形成过程中的表达变化及分布，探讨靶向合成型VSMC体内MRI的可行性。方法 选择雄性载脂蛋白E(apoE^-/-)小鼠45只为实验组(高脂饲料喂养),雄性6周龄C57BL/6小鼠25只为对照组(普通饲料喂养)。2组小鼠分别于不同时间点取腹主动脉进行苏木精-伊红、免疫组织化学及Masson染色。从实验组随机选取建模成功apoE^-/-小鼠各10只分别为靶向探针组[anti-TPM-4-单纯超微超顺磁性氧化铁纳米颗粒(USPIO)]及单纯USPIO组，在探针注射前及注射24 h后采用7.0 T磁共振采集腹主动脉图像，观察信号变化，扫描完成后取腹主动脉标本进行病理学验证。结果 对照组小鼠无斑块形成，实验组小鼠不同时间点斑块内均可见TPM-4表达，阳性表达主要在斑块周围及胶原纤维分布区域。斑块内TPM-4和胶原纤维阳性面积与斑块面积呈正相关(r=0.875,P<0.01;r=0.811,P<0.01)。靶向探针组腹主动脉斑块T₂...     

超声介导微泡造影剂携带肝细胞生长因子基因靶向治疗大鼠急性心肌梗死

目的 研究急性心肌梗死时超声介导微泡造影剂携带肝细胞生长因子(HGF)基因靶向治疗的可行性.方法 将54只雄性SD大鼠建立心肌梗死模型并随机分成3组(每组18只):US/MB-HGF组,予超声照射及尾静脉注射携带HGF质粒基因(pcDNA3.1-HGF)的微泡造影剂;US-HGF组,予超声照射及尾静脉注射PCDNA3.1-HGF,无微泡造影剂;US/MB-P组:即对照组,予超声照射及尾静脉注射携带空质粒的微泡造影剂.并按大鼠被处死的时间顺序,将每组分为3个亚组(每组6只):24 h组、7 d组和14 d组,分别取心肌组织做石蜡切片并做免疫组织化学染色,包括抗凋亡蛋白(bcl-2)的表达、HGF蛋白表达和CD34标记的毛细血管计数情况.结果 (1)心肌组织HGF蛋白表达:US/MB.HGF7 d亚组有明显的HGF蛋白表达,24 h组未见有明显的HGF的表达颗粒.US-HGF7d和14 d亚组可见少量HGF表达.US/MB-P组各亚组均未见HGF表达.(2)CDM标记的毛细血管计数:US/MB-HGF 14 d亚组为(367.6±17.6)个/高倍视野,明显高于US-HGF组[(268.9±0.8)个/高倍视野]和US/MB-P组[(186.8±11.8)个/高倍视野,均P＜0.05],各组24 h和7 d亚组的毛细血管计数均低于其14 d亚组.(3)梗死区bcl-2的表达:US/MB-HGF 7 d亚组为9.9%±0.5%,明显高于US-HGF组(6.3%±1.0%)和uS/MB-P组(3.5%±0.8%,均P＜0.05);US/MB-HGF 14 d亚组为6.7%±0.9%,明显高于US-HGF组(4.5%±0.8%)和US/MB-P组(2.1%±0.9%,均P＜0.05);3组24 h亚组均未见明显表达.结论 超声介导造影剂微泡破裂可以使静脉注射的HGF基因在心肌局部浓度增高,增强其转染和表达,且可明显促进心肌新生血管的生长,减少急性梗死区心肌细胞的凋亡.     

阿托伐他汀对兔动脉粥样硬化斑块稳定性及斑块内血管新生的影响

目的探讨阿托伐他汀对兔动脉粥样硬化(AS)斑块稳定性及斑块内血管新生的影响。方法将80只新西兰大白兔按随机数字表法随机分为无药物干预常规超声造影组(A组),无药物干预超声微泡造影组(B组),阿托伐他汀干预超声常规造影组(C组),阿托伐他汀干预超声微泡造影组(D组),每组20只;建立AS模型后,利用免疫组化法检测斑块组织血管内皮生长因子(VEGF)、白细胞分化抗原40配体(CD40L),第8因子相关抗原(FVⅢRAg)及基质金属蛋白酶(MMP)-3的蛋白表达;利用超声造影技术对斑块进行常规超声及微泡造影检查,并采用ACQ分析软件得到斑块的始增时间(AT)、到达时间(TTP)、峰值时间(PI)以及基础强度(BI),计算增强强度(EI);利用病理组织学检查以及抗CD34免疫组化染色法,算出微血管密度(MVD),并与造影参数进行相关性分析。结果所有模型高脂喂养后,相对于A组+B组,C组+D组的内皮细胞肿胀、变性减轻,且脂质沉积和泡沫细胞也减少;同时C组+D组AS斑块内VEGF,FVⅢRAg,MMP-3和CD40L的阳性染色面积以及MVB值也均明显低于A组+B组(均P<0.01);另外D组AS斑块EI值与MVD值呈正相关(r=0.665,P<0.01),高于C组AS的EI值与MVD值相关性(r=0.401,P<0.01)。结论阿托伐他汀具有稳定AS斑块的作用,抑制斑块内血管新生可能为其机制之一,而超声微泡造影剂有助于评价AS斑块新生血管情况。     

利用超声彩色多普勒技术评价大鼠腹主动脉狭窄模型

目的利用超声彩色多普勒技术对构建的大鼠腹主动脉缩窄(abdominal aortic constriction,AAC)模型进行检测,评价动物模型的心脏结构、功能变化。方法以0.3 mm银夹缩窄双侧肾动脉上段(约0.5 cm处)的腹主动脉制备压力超负荷大鼠模型36只,按时间分为AAC-2周组、AAC-4周组和AAC-8周组及假手术(Sham)组(每组12只)。建模后2周、4周和8周时,用Vevo 2100型动物微小超声心动图仪进行M-mode超声检测心功能指标,如射血分数(ejection fraction,EF)、左心室短轴缩短率(fractional shortening,FS)、左心室舒张期前壁厚度(left ventricular end-diastolic anterior wall thickness,LVAWd)、左心室收缩期前壁厚度(left ventricular endsystolic anterior wall thickness,LVAWs)、左心室舒张期后壁厚度(left ventricular end-diastolic posterior wall thickness,LVPWd)、左心室收缩期后壁厚度(left ventricular end-systolic posterior wall thickness,LVPWs)、左心室舒张末期内径(left ventricular end-diastolic internal dimension,LVEDd)、左心室收缩末期内径(left ventricular endsystolic internal dimension,LVEDs);和超声彩色多普勒测量腹主动脉缩窄前、后的血流量,二尖瓣E/A值;测量左心室质量指数(left ventricular mass index,LVMI)等。结果(1)同Sbam组比较,AAC-2周组的EF、FS、LVEDd、LVEDs明显降低(P0.01),而LVAWd、LVAWs、LVPWd、LVPWs均明显增加(P0.05);腹主动脉缩窄前段血流量与管腔增大,缩窄后段血流量和管腔显著变小;且出现E/A值和LV MI改变明显(P0.01),AAC-2周组左心室肥厚明显。(2)同AAC-2周组比较,AAC-4周和AAC-8周组EF、FS、LVAWd、LVAWs、LVPWd、LVPWs明显降低,而LVEDd、LVEDs明显增加,且缩窄后段血流速度、血流量明显变小,而E/A值及LVMI增加明显(P0.05)。AAC-4周组与AAC-8周组心脏体积、左心室腔明显增大呈心力衰竭病变。结论利用动物微小彩色多普勒技术能直观、准确地检测和评价以银夹缩窄腹主动脉的大鼠模型;AAC模型2周时心肌肥厚明显、4周时出现心力衰竭,8周时心力衰竭严重。     

超声声学造影诊断腹主动脉穿透性粥样硬化性溃疡的临床价值

目的探讨超声声学造影在诊断腹主动脉穿透性粥样硬化性溃疡的临床价值。方法对6例常规彩色多普勒超声检查怀疑腹主动脉穿透性粥样硬化性溃疡患者行超声声学造影检查,与CT血管造影检查结果进行对比。结果 6例患者中,超声声学造影和CT血管造影均显示,腹主动脉穿透性粥样硬化性溃疡4例,腹主动脉夹层2例。彩色多普勒超声检查显示6例均为腹主动脉穿透性粥样硬化性溃疡。与CT血管造影检查比较,单独使用彩色多普勒超声的符合率为66.7%,联合使用超声声学造影的符合率为100%。结论超声声学造影可以为腹主动脉穿透性粥样硬化性溃疡的诊断和鉴别诊断提供重要的影像学信息。     

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.