苦参碱抗大鼠胰腺纤维化作用及机制研究

目的 探讨苦参碱对胰腺纤维化的干预作用,为其临床应用提供实验依据.方法 48只雄性Wistar大鼠随机分为正常组、模型组和治疗组,每组16只.以腹腔注射DDC(750 mg/kg体重)每周2次,共6周建立胰腺纤维化动物模型,治疗组于DDC注射后2周起每日腹腔注射苦参碱(100 mg/kg体重),6周后处死动物.采用放射免疫法检测血清透明质酸.胰腺常规病理检查、评分,Masson染色判断胶原纤维量.免疫组化和RT-PCR法检测胰腺组织生长因子β1(TGF-β1)及Smad3、Smad7的蛋白和mRNA表达.结果 治疗组血清透明质酸浓度、病理积分及胶原纤维的表达量分别为(105.85 ± 25.69)ng/ml、3.16 ± 1.15及(19.16 ± 4.27)%,TGF-β1和Smad3蛋白表达分别为(23.16 ± 7.68)%和(18.65 ± 9.82)%,TGF-β1 mRNA和Smad3 mRNA表达分别为0.33 ± 0.10和0.23 ± 0.03,均较模型组明显降低(P ＜ 0.01).而Smad7的表达与模型组无显著差异.结论 大鼠腹腔注射DDC可建立胰腺纤维化动物模型.苦参碱具有显著的抗胰腺纤维化的作用,其机制可能与抑制TGF-β1的产生、抑制TGF-β/Smads信号转导通路活性有关.     

骨形成蛋白-7在慢性胰腺炎中的表达及意义

目的研究骨形成蛋白-7(BMP-7)在大鼠CP组织中的表达,探讨其在胰腺纤维化形成中的意义。方法每周2次腹腔内注射二乙基二硫代氨基甲酸盐(diethyldithiocarbamate,DDC)建立大鼠CP模型。HE染色观察正常组及造模后2、4、6、8周时大鼠胰腺病理学变化,VG染色观察胶原纤维含量,免疫组化检测BMP-7、TGF-β1、Smad2/3的表达。结果(1)正常组BMP-7在腺泡细胞的胞质中表达。造模后4周腺泡细胞及部分炎性细胞BMP-7阳性面积比及阳性灰度值较正常组减少(P<0.05)。造模后8周腺体萎缩几乎无BMP-7表达,残留腺泡中表达量较正常胰腺显著减少[阳性面积比:(5.63±1.65)%vs(36.51±3.76)%,P<0.01;灰度值:144.20±5.67vs174.54±1.22,P<0.01]。(2)TGF-β1和Smad2/3的表达在纤维化进展中变化一致。对照组小叶间结缔组织和部分腺泡间有少量表达。8周时小叶内纤维化区域及残留腺泡细胞间可见大量TGF-β1和Smad2/3表达,TGF-β1为(22.66±6.73)%;Smad2/3为(24.58±4.35)%,较正常组增加(P<0.01)。(3)TGF-β1与Smad2/3表达呈正相关(r=0.61,P=0.005),BMP-7与TGF-β1、Smad2/3表达均呈负相关(r值分别为-0.69和-0.68,P=0.001)。结论胰腺纤维化过程中TGF-β1/Smad2/3信号通路活化,可促进细胞外基质沉积和腺泡细胞萎缩。BMP-7的表达量可反映残存腺泡细胞的数量,可能对CP的进展具有潜在的保护作用。     

骨形成蛋白-7在慢性胰腺炎中的表达及意义

目的 研究骨形成蛋白-7(BMP-7)在大鼠CP组织中的表达,探讨其在胰腺纤维化形成中的意义.方法 每周2次腹腔内注射二乙基二硫代氨基甲酸盐(diethyldithiocarbamate, DDC)建立大鼠CP模型.HE染色观察正常组及造模后2、4、6、8周时大鼠胰腺病理学变化,VG染色观察胶原纤维含量,免疫组化检测BMP-7、TGF-β1、Smad2/3的表达.结果 (1)正常组BMP-7在腺泡细胞的胞质中表达.造模后4周腺泡细胞及部分炎性细胞BMP-7阳性面积比及阳性灰度值较正常组减少(P＜0.05).造模后8周腺体萎缩几乎无BMP-7表达,残留腺泡中表达量较正常胰腺显著减少[阳性面积比:(5.63±1.65)% vs (36.51±3.76)%, P＜0.01;灰度值:144.20±5.67 vs 174.54±1.22, P＜0.01].(2)TGF-β1和Smad2/3的表达在纤维化进展中变化一致.对照组小叶间结缔组织和部分腺泡间有少量表达.8周时小叶内纤维化区域及残留腺泡细胞间可见大量TGF-β1和Smad2/3表达,TGF-β1为(22.66±6.73)%;Smad2/3为(24.58±4.35)%,较正常组增加(P＜0.01).(3)TGF-β1与Smad2/3表达呈正相关(r = 0.61, P = 0.005), BMP-7与TGF-β1、Smad2/3表达均呈负相关(r值分别为-0.69和-0.68,P = 0.001).结论 胰腺纤维化过程中TGF-β1/Smad2/3信号通路活化,可促进细胞外基质沉积和腺泡细胞萎缩.BMP-7的表达量可反映残存腺泡细胞的数量,可能对CP的进展具有潜在的保护作用.     

姜黄素对大鼠慢性酒精性胰腺炎的作用和机制研究

目的 观察姜黄素对大鼠实验性慢性胰腺炎的干预作用.方法 18只1月龄雄性SD大鼠按数字表法随机分为对照组、ANP组和姜黄素组,每组6只.以25％乙醇代水饮12周后每周1次腹腔注射脂多糖(2 mg/kg体重)、共4次的方法建立慢性胰腺炎模型.姜黄素组制模同时饲以姜黄素.17周后处死动物.测血糖浓度,常规胰腺病理检查及胶原纤维染色,检测胰腺组织淀粉酶和脂肪酶水平.采用RT-PCR法检测胰腺组织转化生长因子β1(TGF-β1) mRNA表达.结果 对照组、ANP组和姜黄素组胰腺病理评分分别为1.17±0.41、7.33±2.58和3.50±1.05,姜黄素组较ANP组降低(P＜0.01),但仍高于对照组(P＜0.05).各组血糖值无统计学差异.姜黄素组胰腺组织匀浆淀粉酶和脂肪酶含量分别为(7348±102)、(14135±1272)U/g,均高于ANP组的(5428±547)和(9123±1250) U/g(P值均＜0.05).对照组、ANP组和姜黄素组胰腺TGF-β1 mRNA表达量分别为0.618±0.019、0.818±0.012、0.745±0.088,ANP组显著高于对照组和姜黄素组(P值均＜0.01).结论 在长期摄入乙醇的基础上反复腹腔注射脂多糖可诱导慢性胰腺炎;姜黄素可能通过抑制TGF-β1表达而产生抗胰腺纤维化的作用.     

脂质过氧化在胰腺纤维化形成中的作用

目的研究脂质过氧化对胰腺星状细胞(pancreatic stellate cells,PSC)活化的影响及其在胰腺纤维化形成中的作用。方法实验大鼠每周2次腹腔内注射二乙基二硫代氨基甲酸盐(diethyldithiocarbamate,DDC),共10周建立胰腺纤维化模型。分别于注射后第2,4,6,8,10周处死大鼠,检测胰腺组织中丙二醛(MDA)含量,各时间点胰腺组织α-平滑肌肌动蛋白(α-SMA)、转化生长因子-β1(TGF-β1)的表达,逆转录聚合酶链反应(RT-PCR)检测α1-型胶原(Colα1)、TGF-β1 mRNA水平。结果注射DDC后,胰腺组织内MDA含量逐步升高,8周时高达(6.21±0.70)nmol/mg prot(P<0.01)。4周时可见明显的细胞外基质沉积和纤维化形成,8周时小叶及小叶内广泛纤维化,大量腺体萎缩,形成瘢疤组织。α-SMA、TGF-β1的阳性表达在2周时已出现,4周时明显增加,且阳性细胞多位于胰腺小叶间及腺泡旁纤维化区域。胰腺组织Colα1 mRNA在造模2周时少量表达,4周表达增加,8周后维持在较高水平;对照组TGF-β1mRNA表达水平较低,TGF-β1 mRNA在造模4周时表达明显增强,与对照组相比有显著性差异(P<0.05),6周后表达增加不明显。结论随着造模时间的延长,胰腺组织MDA含量的增加与胶原纤维形成、TGF-β1表达及活化PSC的增加相一致,提示脂质过氧化产物通过激活PSC及刺激TGF-β1的分泌,增加胰腺组织中胶原的沉积,促进胰腺纤维化的形成。     

脂质过氧化在胰腺纤维化形成中的作用

目的 研究脂质过氧化对胰腺星状细胞(pancreatic stellate cells, PSC)活化的影响及其在胰腺纤维化形成中的作用.方法 实验大鼠每周2次腹腔内注射二乙基二硫代氨基甲酸盐(diethyldithiocarbamate, DDC),共10周建立胰腺纤维化模型.分别于注射后第2,4,6,8,10周处死大鼠,检测胰腺组织中丙二醛(MDA)含量,各时间点胰腺组织α-平滑肌肌动蛋白(α-SMA)、转化生长因子-β1(TGF-β1)的表达,逆转录聚合酶链反应(RT-PCR)检测α1-Ⅰ型胶原(ColⅠα1)、TGF-β1 mRNA水平.结果 注射DDC后,胰腺组织内MDA含量逐步升高,8周时高达(6.21 ± 0.70)nmol/mg prot(P ＜ 0.01).4周时可见明显的细胞外基质沉积和纤维化形成,8周时小叶及小叶内广泛纤维化,大量腺体萎缩,形成瘢疤组织.α-SMA、TGF-β1的阳性表达在2周时已出现,4周时明显增加,且阳性细胞多位于胰腺小叶间及腺泡旁纤维化区域.胰腺组织ColⅠα1 mRNA在造模2周时少量表达,4周表达增加,8周后维持在较高水平;对照组TGF-β1 mRNA表达水平较低,TGF-β1 mRNA在造模4周时表达明显增强,与对照组相比有显著性差异(P ＜ 0.05),6周后表达增加不明显.结论 随着造模时间的延长,胰腺组织MDA含量的增加与胶原纤维形成、TGF-β1表达及活化PSC的增加相一致,提示脂质过氧化产物通过激活PSC及刺激TGF-β1的分泌,增加胰腺组织中胶原的沉积,促进胰腺纤维化的形成.     

转化生长因子β1Ⅱ型受体在大鼠慢性胰腺炎中的表达及氧化苦参碱对其的影响

目的:探讨转化生长因子β1Ⅱ型受体(TβRⅡ)在慢性胰腺炎(CP)纤维化病理进程中的作用,研究氧化苦参碱(OM)对胰腺纤维化的作用机制.方法:40只Wistar♂大鼠随机分为4组,即阴性对照组(NC组,n=10),CP模型组(CP组,n=10),OM干预组(OP组,n=10)和OM治疗组(OT组,n=10).NC组隔日给予腹腔注射生理盐水300mg/kg;其他每组均隔日腹腔注射二乙基硫代氨基甲酸盐(DDC)700mg/kg,30d停止.另外OP组于注射DDC同日开始每日腹腔注射OM100mg/kg,OT组于注射DDC1wk后开始每日腹腔注射OM100mg/kg,分别于注射DDC20d、40d后处死动物.胰腺组织行HE染色和Masson胶原染色并进行病理学评分,Western blot检测胰腺组织TβRⅡ的表达.结果:Masson染色测定结果显示,在20d、40d时CP组胶原纤维含量显著高于其余各组(20d:22.54%±4.45%vs13.16%±1.84%,19.58%±2.78%,2.45±0.24%;40d:35.14%±3.27%vs25.14%±3.67%,28.68%±2.55%,3.0%±0.3...     

DDC递增法诱导大鼠胰腺纤维化动物模型的研究

目的建立DDC剂量递增腹腔内注射诱发大鼠胰腺纤维化动物模型方法,并与常规恒量DDC腹腔内注射方法比较。方法70只Wistar大鼠随机分为4组:生理盐水注射组、低剂量DDC恒量注射组(600 mg/kg/次。每周2次,共8次)、高剂量DDC恒量注射组(1 000 mg/kg/次,每周2次,共8 次)及DDC剂量递增注射组(首次400 mg/kg/次,以10%浓度连续递增,每周2次,共8次)。每周于注射后2d h、48 h、1周、2周、3周、4周6个时间点分别随机处死3只大鼠,并对胰、肝、肾组织进行病理学诊断与胶原纤维测定。实验中观察动物并发症(鼻出血,尿失禁,震颤)的发生率及死亡率。结果DDC递增组大鼠并发症较少,但成模时间及纤维化程度与恒量注射组无显著性差异,纤维化程度增加过程较为渐进,提示更为接近胰腺纤维化的发展过程。结论DDC注射递增法可以建立大鼠胰腺纤维化动物模型, 此模型较常规恒定DDC腹腔注射法更为优越。     

DDC递增法诱导大鼠胰腺纤维化动物模型的研究

目的建立DDC剂量递增腹腔内注射诱发大鼠胰腺纤维化动物模型方法,并与常规恒量DDC腹腔内注射方法比较.方法 70只Wistar大鼠随机分为4组:生理盐水注射组、低剂量DDC恒量注射组(600 mg/kg/次,每周2次,共8次)、高剂量DDC恒量注射组(1 000 mg/kg/次,每周2次,共8次)及DDC剂量递增注射组(首次400 mg/kg/次,以10%浓度连续递增,每周2次,共8次).每周于注射后24 h、48 h、1周、2周、3周、4周6个时间点分别随机处死3只大鼠,并对胰、肝、肾组织进行病理学诊断与胶原纤维测定.实验中观察动物并发症(鼻出血,尿失禁,震颤)的发生率及死亡率.结果 DDC递增组大鼠并发症较少,但成模时间及纤维化程度与恒量注射组无显著性差异,纤维化程度增加过程较为渐进,提示更为接近胰腺纤维化的发展过程.结论 DDC注射递增法可以建立大鼠胰腺纤维化动物模型,此模型较常规恒定DDC腹腔注射法更为优越.     

虾青素对肝纤维化大鼠的保护作用及机制研究

目的研究虾青素抑制肝纤维化作用是否与影响TGF-β1/Smad/ERK通路有关。方法将50只大鼠随机分为正常组、模型组、秋水仙碱组(0.1 mg·g~(-1))、虾青素Ⅰ组(2 mg·g~(-1))和虾青素Ⅱ组(4 mg·g~(-1)),每组10只。采用皮下注射CCl_4法制备肝纤维化大鼠模型。在造模成功后,给予正常组和模型组动物生理盐水、而在药物干预组则分别给予秋水仙碱和虾青素灌胃,连续给药6 w。分别采用免疫组化法和Western blot法检测肝组织Ⅰ型胶原、Smad2、转化生长因子-β1(TGF-β1)和p-ERK蛋白表达,采用RT-PCR法检测肝组织CollagenⅠ、Smad2、TGF-β1和p-ERK mRNA水平。结果正常组、虾青素Ⅰ组和虾青素Ⅱ组肝组织Ⅰ型胶原蛋白分别为(0.4±0.1)、(1.4±0.3)和(1.2±0.3),均显著低于模型组[(1.7±0.4),P0.05],Smad2分别为(0.5±0.1)、(1.3±0.4)和(0.8±0.4),显著低于模型组[(1.6±0.3),P0.05],TGF-β1蛋白分别为(0.5±0.1)、(1.4±0.4)和(1.2±0.3),显著低于模型组[(1.7±0.4),P0.05],p-ERK蛋白分别为(0.4±0.1)、(1.3±0.4)和(0.9±0.3),显著低于模型组[(1.6±0.5),P0.05];正常组、虾青素Ⅰ组和虾青素Ⅱ肝组织Ⅰ型胶原mRNA水平分别为(1.0±0.1)、(2.0±0.4)和(1.8±0.5),均显著低于模型组[(2.4±0.4),P0.05],Smad2 mRNA水平分别为(1.0±0.1)、(2.0±0.5)和(1.8±0.4),显著低于模型组[(2.5±0.6),P0.05],TGF-β1 mRNA水平分别为(1.0±0.1)、(2.1±0.4)和(1.6±0.3),均显著低于模型组[(2.5±0.5),P0.05],p-ERK mRNA水平分别为(1.1±0.1)、(2.1±0.4)和(1.8±0.3),均明显低于模型组[(2.6±0.5),P0.05]。结论虾青素可抑制肝纤维化进展,其机制可能与调控TGF-β1/Smad/ERK通路表达有关。     

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。     

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.