抗hnRNPB1单克隆抗体结合~(131)Ⅰ对肺癌小鼠靶向治疗的实验研究

目的观察131I-抗hnRNP B1MAb、抗hnRNP B1MAb对肺癌小鼠移植瘤的靶向治疗作用。方法用常规氯胺-T法合成131I-抗hnRNP B1MAb,皮下接种肺癌细胞7d后,将肺癌小鼠随机分成5组,每组6只。分别经尾静脉注射,Ⅰ组:131I-抗hnRNP B1MAb11.1MBq/只单次治疗,Ⅱ组:131I-抗hnRNP B1MAb2×11.1MBq/只强化治疗,Ⅲ组:Na131I11.1MBq/只,Ⅳ组:抗hnRNP B1MAb50μg/只,Ⅴ组:生理盐水0.12ml作为对照组。干预后每周测量一次小鼠肿瘤的长径及短径,4周后处死小鼠,分离肿瘤并称其质量,计算抑瘤率,肿瘤组织做苏木素伊红(HE)染色检查。结果治疗结束时,Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ组小鼠肿瘤的平均体积分别为(3869±192)mm3、(1987±149)mm3、(6922±532)mm3、(6962±509)mm3、(6957±521)mm3,其中I组、Ⅱ组与Ⅴ组肿瘤平均体积相比差异具有统计学意义(P<0.05),而I组、Ⅲ组治疗结束时肿瘤平均体积与Ⅴ组相比较无统计学意义(P>0.05)。治疗结束时各组小鼠平均体质量差异无统计学意义(P>0.05)。I组强化组及Ⅱ组的抑瘤率分别为69.88%和41.35%。各治疗组小鼠未发现明显的不良反应。结论抗hnRNP B1MAb结合131I对小鼠肺癌的生长具有显著抑制作用,抑制作用呈量效关系,未发现明显的毒副作用。单纯抗hnRNP B1MAb及Na131I未出现明显抑制肿瘤生长的作用。     

反义真核细胞转化生长因子βⅠ型受体与反义基质金属蛋白酶组织抑制因子-1联合作用对大鼠肝纤维化的影响

目的观察反义转化生长因子βⅠ型受体（TβRI真核表达质粒与反义基质金属蛋白酶组织抑制因子-1（TIMP-1）真核表达质粒联合作用对实验性大鼠肝纤维化的影响。方法构建大鼠反义真核细胞表达质粒，导入大鼠肝纤维化模型体内，通过I型胶原的免疫组织化学以及苦味酸-酸性品红染色观察两种反义质粒联合作用对大鼠肝纤维化的影响，用目标积分吸光度（A）值表示各实验组动物肝组织中蛋白的表达量。结果反义TβRI疗组、反义TβRI反义TIMP-1治疗组、反义TIMP-1治疗组、pcDNA3．1（＋）空质粒对照组、模型对照组、正常对照组TβRI白的A值分别为：（2．11±0．88）×10^5、（1．06±0．57）×10^5、（3．46±1．14）×10^5、（5．66±2．54）×10^5、（5．19±1．22）×10^5和（0．38±0．27）×10^5；TIMP-1蛋白的A值分别为：（1．10±0．22）×10^5、（0．30±0．12）×10^5、（0．65±0．15）×10^5、（2．05±0．36）×10^5、（1．97±0．28）×10^5和（0．10±0．12）×10^5；I型胶原的蛋白表达的A值分别为：（4．37±1．30）×10，、（0．90±0．32）×10^5、（3．40±0．91）×10^5、（6．90±1．61）×10^5、（7．34±1．68）×10^5和（0．41±0．21）×10s。反义TIMP-1治疗组TIMP-1蛋白表达量显著降低（P〈0．05），反义TβRI疗组TβRI白表达量显著降低（P〈0．05），两种反义质粒可有效抑制相应蛋白的表达；反义TIMP-1表达质粒与反义TβRI达质粒均可减少受损肝脏中I型胶原的沉积（P〈0．05），联合应用可进一步减少受损肝脏中I型胶原的沉积（P〈0．01）。在病理形态学方面的观察，反义TIMP-1表达质粒与反义TβRI达质粒均可使受损肝脏的病理形态有一定改善，联合应用可使受损肝脏的病理形态得到进一步的改善。结论反义TIMP-1表达质粒与反义TβRI达质粒对肝纤维化的发展均有一定的干预作用，联合作用可产生更有效的阻止作用。     

马来酸罗格列酮增强过氧化物酶体增殖剂活化受体γ1基因转染抗ApoE-/-小鼠动脉粥样硬化的作用

目的探讨过氧化物酶体增殖剂活化受体（PPAR）γ活化剂马来酸罗格列酮能否增强腺病毒介导的mPPARγ1基因转染抗ApoE-／-小鼠动脉粥样硬化的作用。方法将20周龄ApoE-／-小鼠高脂饲养20周后随机分成4组（每组n=10）,即AdPPARγ1组、AdPPARγ1＋RO组（病毒干预前1周予罗格列酮4mg·kg^-1·d^-1灌胃）、AdGFP组和PBS组。转染2周后比较各组小鼠主动脉根部斑块面积均值。Movat5色套染法和油红O染色分析主动脉根部斑块成分变化。检测斑块内PPARγ、血管平滑肌细胞（SM-actin）、巨噬细胞（MOMA-2）、MMP-9／TIMP-1、CD40／CD40L和组织因子（TF）等抗原的免疫活性。结果PBS组与AdGFP组比较,各项指标差异均无统计学意义。与AdGFP组比较,AdPPARγ1组和AdPPARγ1＋RO组ApoE-／-小鼠主动脉根部斑块面积和脂质含量减少（P〈0．05）[AdGFP组、AdPPARγ1组和AdPPARγ1＋RO组病变面积均值分别为（0．98±0．17）、（0．86±0．12）、（0．79±0．15）mm^2,油红O染色阳性面积分别为（270±49）×10^3、（150±35）×10^3、（80±21）×10^3μm^2]。Movat染色法显示PBS组和AdGFP组小鼠主动脉根部斑块成分差异不显著,而AdPPARγ1组和AdPPARγ1＋RO组纤维帽较厚、弹性纤维、胶原和蛋白聚糖含量增加。与AdGFP组比较,AdPPARγ1组和AdPPARγ1＋RO组主动脉根部斑块PPARγ、SM-actin、TIMP-1抗原免疫活性增强。而MOMA-2、MMP-9、CD40／CD40L和TF抗原免疫活性减弱,其中AdPPARγ1＋RO组作用最显著。结论腺病毒介导的mPPARγ1基因转染遏制ApoE-／-小鼠动脉粥样硬化进程,促进动脉粥样硬化斑块向稳定表型转换,PPARγ活化剂马来酸罗格列酮增强上述作用。     

榄香烯和VEGF多克隆抗体联合应用对C_6胶质瘤增殖的抑制作用

目的探讨榄香烯和VEGF多克隆抗体联合应用对昆明小鼠皮下C6胶质瘤的抑制作用。方法建立昆明小鼠皮下C6胶质瘤模型,将32只接种成瘤后的小鼠随机分成4组,每组8只,Ⅰ组生理盐水、Ⅱ组榄香烯、Ⅲ组VEGF多克隆抗体、Ⅳ组榄香烯和VEGF多克隆抗体。治疗后定期测量肿瘤的大小,计算抑制率,镜下观察肿瘤组织病理切片,流式细胞仪检测肿瘤细胞凋亡率。结果Ⅱ组、Ⅲ组、Ⅳ组的抑制率分别为（43.2&#177;3.6）%、（41.3&#177;2.9）%、（51.9&#177;4.1）%,Ⅳ组的抑制率低于Ⅱ组和Ⅲ组（P〈0.05）。实验组肿瘤标本见到较多的坏死灶,其中肿瘤细胞可见较多的核破裂,肿瘤组织坏死程度和血管的减少量Ⅳ组多于Ⅲ组和Ⅱ组。Ⅰ组、Ⅱ组、Ⅲ组、Ⅳ组细胞凋亡率分别为（0.46&#177;0.19）%、（12.9&#177;1.70）%、（11.7&#177;1.70）%、（19.4&#177;1.32）%,Ⅳ组较Ⅱ组、Ⅲ组的凋亡率高（P〈0.05）。结论榄香烯和VEGF多克隆抗体联合应用能更好抑制肿瘤组织的生长,具有协同的作用。     

99mTc-MDP联合胶体磷酸铬32P与单一疗法对大鼠佐剂型关节炎治疗效果比较

目的用^99mTc-亚甲基二膦酸盐（^99mTc-MDP）联合胶体磷酸铬^32P治疗大鼠佐剂型关节炎，探讨其疗效并与单一使用^99mTc-MDP或胶体磷酸铬^32P治疗进行比较。方法利用佐剂诱导SD大鼠的关节炎模型（AA），给予胶体磷酸铬^32P踝关节腔内注射以及^99mTc-MDP腹腔注射，在不同的时间点观察大鼠左踝关节的左右径宽度、血清肿瘤坏死因子（TNF）和白细胞介素-1β（IL-1β）水平及关节病理的变化。结果联合治疗组大鼠左踝关节左右径宽度较^32P胶体治疗组小[第4周（7．11±0．34）mm vs（7．57±0．29）mm，P〈0．01]。联合治疗较^32P胶体治疗更能有效地降低血清TNF[第4周时（1．6±0．4）ng／ml vs（2．0±0.3）ng／ml，P〈0．051和IL-1β[第4周时（0．271±0．033）ng／ml vs（0.308±0.024）ng／ml，P〈0．05；第6周时（0．209±0．023）ng／ml vs（0．255±0．016）ng／ml，P〈0.01]的水平。在病理检查上，联合治疗组滑膜增生程度较^99mTc-MDP治疗组轻，而炎细胞浸润程度较^32P胶体治疗组轻。结论^99mTc-MDP联合胶体磷酸铬^32P治疗大鼠佐剂型关节炎较单用^99mTc-MDP或胶体磷酸铬^32P治疗效果更好。     

骨髓源性心肌干细胞移植治疗心肌梗死的实验研究

目的研究骨髓源性心肌干细胞（MCSC）移植对心肌梗死的治疗作用。方法通过单细胞克隆培养技术从雄性SD大鼠骨髓间充质干细胞（MMSC）中筛选MCSC。结扎雌性SD大鼠的左冠状动脉前降支,建立心肌梗死模型,1周后于梗死区边缘移植MMSC和MCSC。移植后4周,用超声心动图检测心功能变化。取心肌组织作冷冻切片,用HE和Masson染色法显示瘢痕区的组织结构变化,通过免疫组织化学染色标记血管内皮生长因子受体-1阳性（VEGFR-1^＋）微血管,用图像分析系统测量瘢痕面积和微血管密度。利用原位荧光杂交标记含有Y染色体的MCSC,并检测心肌特异性肌钙蛋白T（cTnT）的表达。结果筛选的MCSC表达c—kit,心肌早期转录因子Nkx2．5呈低表达。细胞移植后4周,MCSC移植组的左室短轴缩短分数（62．9％±2．2％）和左室射血分数（32．8％±1．1％）高于MMSC移植组（分别为55．7％±1．6％和28．2％±1．6％）和对照组（分别为42．4％±2．1％和23．6％±1．2％）;MCSC组心肌梗死面积比率（8．7％±0．7％）低于MMSC组（12．0％±1．1％）和对照组（16．8％±0．9％）。含有Y染色体的MCSC表达cTnT,与受体心肌相续。MCSC移植组的梗死区周围微血管密度[（101．8±6．2）条／mm^2]大于对照组[（68．4±4．9）条／mm^2],与MMSC组[（97．2±3．2）条／mm^2]比较,差异无统计学意义。结论移植入心肌梗死模型的MCSC能够分化为功能性心肌,明显改善心功能,并诱导血管新生。MCSC的移植治疗效果优于MMSC。     

三氧化二砷联合Ad-IκBαM诱导胃癌细胞凋亡的研究

目的研究三氧化二砷（As2O3）对胃癌SGC-7901细胞作用过程中细胞内核转录因子KB（NF-κB）的激活及重组腺病毒Ad—IκBαM通过抑制NF-κB的活化增强As2O3的诱导凋亡作用。方法培养胃癌SGC-7901细胞,以非感染组及感染Ad—IκBα组为对照,采用凝胶电泳迁移率实验（EMSA）及免疫组化法检测As2O3处理后细胞核内NF-κB的激活情况,以及感染Ad—IκBαM对NF-κB活性的影响;四甲基偶氮唑盐（MTT）法、Hoechest染色、原位末端标记（TUNEL）法分别检测感染Ad—IκBαM对As2O3诱导细胞凋亡的影响。结果EMSA及免疫组化法显示As2O3作用于胃癌细胞可使细胞内NF-κB激活,感染Ad—IκBαM使NF-κB活性受到明显抑制;MTT法证明,As2O3作用后,感染Ad—IκBαM细胞的凋亡率（59．2±2．5）％较感染Ad-IκBα组（47．5±2．3）％及未感染组（40．0±1．2）％明显升高,各组间比较P〈0．01;Hoechest法显示,感染Ad—IκBαM组的凋亡率为（27.7±2．6）％,明显高于感染Ad—IκBα组（18．3±1．5）％及未感染组（11.0±1．7）％（P〈0．05）。TUNEL法结果与Hoechest法一致,感染Ad—IκBαM组的凋亡率为（31．1±2．5）％,高于感染Ad-IκBα组（20.7±2．1）％及未感染组（13.0±1、7）％（P〈0．05）。可见,感染Ad—IκBαM可明显提高As2O3诱导的细胞凋亡。结论As2O3作用于胃癌细胞可使细胞内NF-κB激活,从而表明NF-κB激活可能为胃癌细胞抗诱导凋亡作用的重要机制;感染Ad．IKBctM可有效抑制NF-κB的活性,并增强As2O3的诱导凋亡作用。     

马来酸曲美布汀治疗功能性消化不良与腹泻型肠易激综合征重叠的随机对照研究

目的 观察马来酸曲美布汀片（曲美布汀）治疗功能性消化不良（FD）与腹泻型肠易激综合征（IBS—D）重叠的疗效和不良反应。方法 采用随机、病例对照的前瞻性研究,129例患者随机分为A组（曲美布汀和地衣芽孢杆菌）、B组（曲美布汀）和C组（地衣芽孢杆菌）。各症状采用分级记分进行描述,疗效评价参照症状积分的变化。结果 A、B组治疗前后的评分,分别为腹胀[A组（4．55±0．85）分,（1．26±0．52）分;B组（4．36±0．66）分,（1．48±0．61）分]、早饱[A组（4．05±0．96）分,（1．01±0．51）分;B组（3．89±0．81）分,（1．25±0．76）分]、腹痛[A组（9．26±0．68）分,（0．68±0．43）分;B组（9．57±1．60）分,（0．76±0．54）分],症状总积分[A组（20．00±1．25）分,（3．06±0．91）分;B组（19．05±2．28）分,（3．89±2．12）分],治疗后较治疗前均有显著下降（P〈0．05）,而C组治疗前后差异无统计学意义（P〉0．05）;3组治疗前后的腹泻评分[A组（4．78±0．76）,（0．65±0．53）;B组（4．13±0．65）,（1．25±0．62）;C组（4．65±0．88）,（1．45±0．70）]均有显著性下降（P〈0．05）。治疗4周后,腹胀、早饱、腹痛的评分和症状总积分,A、B组与C组比较,差异有统计学意义（P〈0．05）。A、B组的各症状的疗效和总疗效均优于C组（P〈0．05）。3组的费用一效果比（C／E）分别为4．07、1．19、6．65,以B组最佳。A、B组的不良反应发生率分别为22．9％和23．7％,主要为轻度的口干和便秘。结论 曲美布汀治疗FD与IBS—D重叠的患者,具有疗效高,价廉,不良反应少的特点。     

多房棘球绦虫重组BCG-EmⅡ/3疫苗诱导小鼠脾细胞亚群变化的研究

目的 探讨多房棘球绦虫重组BCG—EmⅡ／3疫苗免疫和多房棘球绦虫（Em）原头节攻击后小鼠脾CD4^＋和CD8^＋T淋巴细胞亚群的变化。方法 Balb／c小鼠随机分为疫苗皮下注射组、鼻腔接种组、空载体对照组、卡介苗（BCG）对照组和磷酸缓冲液（PBS）对照组。疫苗免疫8周时用Em原头节进行攻击，感染后18周杀鼠取脾，分离脾细胞，流式细胞仪检测脾CD4^＋和CD8^＋T淋巴细胞亚群的百分比。结果 疫苗皮下注射组和鼻腔接种组的脾CD4^＋T细胞亚群比值分别为0．345±0．018、0．314±0．014，与PBS对照组（0．216±0．027）比较明显增高（q值分别为3．93、3．76，P〈0．01）；CD8^＋T细胞亚群比值分别为0．091±0．005、0．083±0．007，与PBS对照组（0．085±0．018）比较无明显变化（q值分别为0．92、0．89，P〉0．05）；CD4^＋／CD8^＋亚群比值分别为3．81±0．30、3．80±0．44，与PBS对照组（2．75±1．08）比较明显增高（q值分别为3.25、3．06，P〈0．01）。皮下注射组的CD4^＋和CD8^＋T细胞亚群数目显著高于鼻腔内接种组（q值分别为3．52、2．63，P〈0．01或〈0．05）。结论 CD4^＋T细胞亚群在多房棘球绦虫重组BCG-EmⅡ／3疫苗诱导的小鼠抗Em原头节攻击感染的保护性免疫机制中起关键作用。     

激活蛋白1和肿瘤坏死因子α在早期被动吸烟小鼠肺部表达增加

目的观察早期被动吸烟小鼠肺功能及肺组织的病理变化,核转录因子κB（NF-κB）和激活蛋白-1（AP-1）的活性变化以及炎症因子IL-8、IL-6和肿瘤坏死因子α（TNF-α）的表达变化,探讨转录因子与炎症介质的关系,为慢性阻塞性肺疾病发病机制的研究提供参考。方法将C57/BL6雄性小鼠随机分为被动吸烟组（10只）和健康对照组（10只）,被动吸烟2h,2次/d（间隔时间至少6h）,连续30d。用小动物呼吸机连接PowerLab压力传导器测定各组肺功能,HE染色法比较各组肺组织的病理变化,凝胶迁移检测（electrophoretic mobility shift assay,EMSA）观察肺组织中NF-κB和AP-1的活性,用酶链免疫吸附试验（ELISA）测定支气管肺泡灌洗液（BALF）中IL-8、IL-6和TNF-α的浓度。结果健康组小鼠肺功能和吸烟组相比未见显著性差异,[吸气峰流速度（PIF）分别为（1.8244±0.4907）ml/s和（1.8675±0.4187）ml/s（P=0.6244）,呼气峰流速度（PEF）分别为（6.1369±0.5753）ml/s和（6.1689±0.7669）ml/s（P=0.3598）],肺组织病理观察可见终末细支气管和血管周围有大量淋巴细胞浸润,肺泡中有大量巨噬细胞聚集。肺组织EMSA结果显示NF-κB活性变化不明显,吸烟组AP-1活性明显增强。ELISA结果表明BALF中吸烟组较健康组TNF-α显著性增高[分别为（241.44±239.47）pg/mg和（106.58±64.229）pg/mg,P=0.0243],IL-8和IL-6无明显改变[IL-8分别为（20.404±24.204）pg/mg和（13.018±11.289）pg/mg,P=0.4392;IL-6分别为（75.612±89.278）pg/mg和（43.863±35.899）pg/mg,P=0.1206]。结论小鼠早期被动吸烟可以引起终末细支气管和血管旁淋巴细胞浸润,巨噬细胞肺泡腔内聚集。气道内TNF-α表达增加。肺组织AP-1活性增加,可能参与了吸烟引起的早期炎症变化。     

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.