Multi-organ failure with atypical liver granulomas following intravesical Bacillus Calmette-Guerin instillation

Bacillus Calmette-Guerin(BCG) intravesical instillation has been adopted in the treatment of patients with superficial bladder cancer.BCG-induced disseminated infection,though rare,has been associated with the histological finding of epithelioid granulomas in different organs,including the liver.We report the case of an adult patient with multi-organ failure,who developed sepsis,acute respiratory failure and acute hepatic failure with encephalopathy whose liver biopsy confirmed the presence of atypical,granulomatous-like lesions.Recovery was observed only after empirical therapy for Mycobacterium bovis with isoniazid,rifampicin,ethambutol and steroids was introduced.This case highlights the importance of a thorough patient assessment in order to exclude other more common causes of hepatic granulomas and to confirm diagnosis.Histological findings may be non-specific when the liver is involved in BCGinduced disseminated infection.

Enhancement of vitamin A combined vitamin D supplementation on immune response to Bacille Calmette-Guerin vaccine revaccinated in Chinese infants

Objective:To investigate whether there is an association between diameter of bacille CalmetteGuerin(BCG)sears and effect of purified protein derivative(PPD)reaction anil to determine whether vitamin A(VA)combined vitamin I)(VD)supplementation influences the immune response to BCG revueeinated in Chinese infants.Methods:A cross-section and 3-month community-randomised trial was conducted.A total of 5 629 infants at 3,6 and 12 months of age in Junan County of China were examined for BCG scar fonnation.Then,597 revuccinated infants were randomly assigned to supplementation(n=307)and control(n=290)groups.The supplementation group were daily assigned to 1 500 IU VA and 500 IU VD for 3 months.Then all infants were subjected to skin test with PPD.Results:The diameter of BCG sears was positively con-elated with diameter of skin indurations of PPD(r=0.17,P<0.05)in the 5 629 infants.The rate of positive response to PP1)was higher in the supplementation group than in the control group(96.1%versus 89.7%,P<0.05,prevalence ratio 1.07.95%CI 1.02-1.12).The prevalence ralio of PPD response for the supplementation group compared with that for the control group was 1.07(95%CI 1.01-1.13)for the males and 1.08(95%CI 1.00-1.17)for the females.For the supplementation group,the males got larger tuberculin induration than the females[(0.73±0.2l)cm versus(0.67±0.20)cm.P<0.05)after intervention.Conclusions:The diameter of BCG scars was effectively correlated with PPD response,which indicates BCG scar formation may be an useful tool Io evaluate the effect of tuberculosis prevention.VA combined VD supplementation may play an immunoregulatory rale in BCG revuecination.This may contribute to the prevention of childhood tuberculosis.

将生活空间延伸到室外--法国GUERIN养老中心特色

养老设施的再适应和扩建是法国当下重要的议题。养老服务的快速发展要求新的养老空间类型和设计标准相适应,而Guerin养老院正是在这一新形势背景下改扩建项目的典范。该项目拆除了多处原有的建筑,并新建特殊老人护理单元(两个14床)、养老单元(两个18床)、医护人员中心、医疗中心和日间接待中心,建筑面积为4358m^2,总规模为159床的项目正在陆续投入使用。

The Regulatory Effects of Polyporus Polysaccharide on the Nuclear Factor Kappa B Signal Pathway of Bladder Cancer Cells Stimulated by Bacillus Calmette-Guerin

Objective：To detect the effects of Polyporus polysaccharide（PPS）,Bacillus Calmette-Guerin （BCG）,and their combination on the nuclear factor kappa B（NF-κB）signaling pathway associated-gene expression and investigate the molecular mechanisms of the toxic-reducing effect of PPS in coordination with BCG against bladder cancer.Methods：After T739 cells were treated with PPS,BCG and their combination, the changes in mRNA and protein expression of inhibitor of kappa B kinase beta（IKKβ）,NF-κB subunit p65 （NF-κB p65）,intracellular adhesion molecule 1（ICAM1）and chemokine（C-c motif）ligand 2（CCL2）in bladder cancer cell line T739 were determined by relative quantitative real-time PCR,Western blot,and flow cytometry （FCM）.NF-κB p65 DNA-binding activity in T739 cell was detected by biotinylated probe-ELISA,and NF-κB p65 nuclear expression in T739 cell was observed by immunohistochemistry.Results：Compared with the T739 control group,the mRNA expression of IKBKB（IKKβ）,Rel A（NF-κB p65）,ICAM1 and CCL2 in T739 cells treated with BCG were increased obviously（Ratio2.0）,as well as the expression of IKKβ,CCL2 and ICAM1 proteins.Meanwhile,NF-κB p65 DNA-binding activity and NF-κB p65 nuclear expression in T739 cells treated with BCG were up-regulated significantly（P0.05）.Compared with the control,the increased expression in T739 cells were simultaneously down-regulated after PPS treatment,except for ICAM1 protein expression.With cells treated with a combination of BCG and PPS,the expression of genes associated with the NF-κB signaling pathway,such as IKBKB,ICAM1 and CCL2,were all down-regulated compared to the BCG group,as well as Rel A mRNA expression,NF-κB p65 DNA-binding activity and NF-κB p65 nuclear expression.Conclusions： PPS could inhibit the over-activation of the NF-κB signaling pathway induced by BCG in bladder cancer cells and accordingly attenuate the adverse reactions to BCG therapy.

Can intravesical bacillus Calmette-Guerin reduce recurrence in patients with non-muscle invasive bladder cancer？ An update and cumulative meta-analysis

Approximately 70% of newly diagnosed bladder tumors are non-muscle invasive bladder cancer （NMIBC）. NMIBC accounts for approximately 80% of total bladder cancer cases. Bacillus Calmette-Guerin （BCG） instillation and maintenance is considered as the standard adjuvant treatment for superficial bladder cancer. A number of randomized studies have focused on the benefit of maintenance therapy following initial BCG induction. To provide further insights into the effect of intravesical instillation on recurrence in patients with NMIBC, we analyzed this relationship by conducting an updated detailed meta-analysis. Evidence suggested that adjuvant intravesical BCG with maintenance treatment is significantly effective for the prophylaxis of tumor recurrence in patients with NMIBC.

Protection of Citrullus colocynthis Fruit Extracts on Carbon Tetrachloride-induced and Bacillus Calmette-Guerin plus Lipopolysaccharide-induced Hepatotoxicity in Mice

Objective To investigate the hepatoprotective activities of the extracts from Citrullus colocynthis(ECC),a native plant used as traditional Uigur Medicine on acute liver injury in mice.Methods The activities of ECC of petroleum ether(ECCPE),chloroform(ECCC),ethyl acetate(ECCEA),n-butyl alcohol(ECCBA),and water(ECCW) were evaluated in vivo using two experimental models,carbon tetrachloride(CCl4)- and bacillus calmette-guerin(BCG) plus lipopolysaccharide(LPS)-induced acute hepatotoxicity in mice.The contents of aspartate aminotransferase(AST) and alanine aminotransferase(ALT) in serum were determined and the liver histological examination was carried out,respectively.Results The pretreatment with ECC for 7 d obviously reduced the impact of CCl4toxicity on the serum markers of liver damage,ECCEA and ECCC with a significant difference of AST(P < 0.01,0.05,respectively) and ALT(P < 0.05,0.01,respectively).The protective activity was reconfirmed against BCG + LPS-induced injury and the serum enzymatic levels were obviously elevated,for ECCEA and ECCC with a significant difference of AST(P < 0.05,0.01,respectively) and ALT(P < 0.01,0.05,respectively).Conclusion That ECCEA and ECCC are the potent hepatoprotective extracts that could protect liver against the acute injury,and this ability might be attributed to their hepatoprotective potentials.

Study of recombinant human IFN-α-2b bacilli Calmette–Guerin activated killer cells and against bladder cancer cell in vitro

Presently,one of the most potent immunothera-pies is the application of bacillus Calmette Guerin(BCG)to prevent recurrences of the superficial bladder cancer.Despite its successful use,nonresponders and certain side effects remain a major obstacle.Therefore,current studies aim at developing recombinant BCG(rBCG)strains secreting Th1-like cytokines to improve the effectiveness of the therapy.In this study,a new type of rBCG strain constructed by Tianjin institute of Urology was tested for its immunostimulatory capacity in vitro.Peripheral blood monocytes(PBMC)were stimulated by recombinant BCG and transformed into bacilli Calmette–Guerin activated killer(BAK)cells,and the effect of anticancer BAK cells was studied.Recombinant IFN-a-2b-BCG,wild-type BCG(wBCG),wild-type BCG and IFN-a-2b were coincubated with PBMCs respectively in vitro,and the proliferation of PBMC was detected with MTT in different time.BAK cells have the ability to kill bladder tumor cells,and the antitumor activity of effecter cells was determined by LDH release assay.The result of MTT showed that the proli-feration of PBMC in the recombinant BCG group was more powerful than in the other two groups(P<0.05).The result of LDH release assay showed that the antitumor activity of BAK cells stimulated by Recombinant BCG was the highest in all groups.We conclude that the recombinant BCG can activate more PBMCs to anti-bladder cancer in vitro than wild-type BCG does.

卡介苗膀胱灌注相关肝炎临床病理特征分析

目的 阐明卡介苗膀胱灌注相关肝炎的临床病理特征。方法 2023年北京友谊医院诊治的卡介苗膀胱灌注相关肝损伤患者2例,通过文献检索卡介苗膀胱灌注相关肝损伤21例。总结患者性别、年龄、卡介苗膀胱灌注次数、肝脏生化结果、肝脏病理活检、结核杆菌检测结果、治疗方案、预后等信息。结果 本中心共诊治2例、文献共报道21例资料较为齐全的卡介苗膀胱灌注相关肝损伤。23例患者均为男性,年龄66(34~88)岁,接受卡介苗膀胱灌注次数为6(1~17)次。主要表现为ALP和(或)GGT明显升高,伴或不伴ALT和AST升高,52.2%(12/23)患者血清TBil升高。结核菌检测阳性6例,阴性14例,检测结果不详3例。共20例接受肝穿刺活检,其中19例呈肉芽肿性肝炎,1例呈汇管区扩大及炎症细胞浸润,未见肉芽肿形成。7例接受抗结核治疗,14例接受抗结核+激素治疗,2例只接受激素治疗。87.0%(20/23)患者痊愈,2例患者好转后没有继续随访,死亡2例。结论 卡介苗膀胱灌注相关肝炎表现为ALP和(或)GGT明显升高,约半数患者可出现黄疸,绝大部分呈肉芽肿性肝炎,少数患者可找到结核分枝杆菌。部分患者经过抗结核治疗痊愈,大部分患者抗结核联合激素治疗、部分患者只接受激素治疗后痊愈,提示免疫反应参与了疾病的发生发展。

播散性卡介菌病1例

卡介苗是一种预防结核病的减毒活疫苗,健康新生儿出生时即予以接种。轻度不良反应为接种2~3 d后,接种部位皮肤发红,触之无硬结,数日后自行消退。播散性卡介菌病是最严重的不良反应,临床表现主要为接种部位红肿、破溃和溢脓,全身多发性淋巴结肿大、皮肤包块形成和肺部病变,也可累及肝脏、脾脏和骨骼。该病致死率高,早期诊断及治疗方法的选择仍是难题。现就我科诊治的1例临床诊断的播散性卡介菌病诊治过程及相关文献复习总结如下,以期为相应专业的临床医师提供一定帮助。

森林的社会、文化和景观功能及巴黎的城市森林

“森林和树木的社会、文化和景观功能”是第十届世界林业大会讨论领域C中的第十个专题。这个专题的主报告人是法国巴黎农村工程、林业和水利局的总工程师J.C.Guerin先生。他指出,随着城市人口的急剧增多,城市建筑越来越密集和拥挤,城市居民对于回归较舒适的自然环境的要求越来越迫切,因此,城市林业(urban for-estry)的概念应运而生。

对BCG预防结核病的评估

Calmeue和Guerin于1921年首次用牛型弱毒分枝杆菌制备出抗结核的活菌苗后,迄今已70年了。当时为纪念这两位发明者,将此菌苗称之为BCG菌苗。今天我们为纪念它的问世70周年,对其所作的历史性贡献作一综述。一、BCG苗的问世人类结核病在19世纪已为人所认识,如Koch等人曾试图注射死菌制成的旧结核菌素治疗病人,结果不理想,很多人死于治疗。这一失败,导致人们设想制备一种减毒活菌苗。

卡介苗多糖核酸与减毒活卡介苗治疗哮喘患儿疗效比较及治疗前后细胞因子的变化

目的探讨卡介苗多糖核酸(BCG-PSN)与减毒活卡介苗治疗儿童哮喘临床疗效及其对哮喘患儿TH1/TH2调节的差异。方法急性发作期哮喘患儿60例随机分A、B、C3组,每组20例。A组予全球哮喘防治创议(GI NA方案)+BCG-PSN0.5mg/次,肌注,1次/隔日,共36次;B组予GI NA方案+减毒活卡介苗0.1mL,皮内注射,仅1次;C组单纯GI NA方案治疗。酶联法检测治疗前后血清IgE及外周血单个核细胞(PBMC)诱生的IL-4、IL-5及IFN-γ。结果1.疗效:A组优于B组,B组优于C组(P均<0.05)。2.治疗组治疗后IFN-γ均高于治疗前,IL-4、IL-5、IgE均低于治疗前。对于调整IL-5,A组优于B组和C组(P<0.05,0.01);对于上调IFN-γ及下调IL-4、IgE,A与B组比较无显著差异(P>0.05)。结论1.BCG-PSN的疗效优于减毒活卡介苗。2.减毒活卡介苗一次性小剂量接种对哮喘儿IL-4、IFN-γ、IgE失衡的调节与BCG-PSN多次肌注效果相当,对IL-5失衡的调节不及BCG-PSN。

丹参多糖对小鼠免疫性肝损伤的保护作用

目的探讨丹参多糖对卡介苗(BCG)和脂多糖(LPS)诱导的小鼠免疫性肝损伤的保护作用。方法尾静脉注射BCG和LPS诱导小鼠免疫性肝损伤,对比小鼠脏器系数,检测血清谷草转氨酶(AST)、谷丙转氨酶(ALT)、一氧化氮(NO)的水平以及比较肝组织匀浆中肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)的含量。结果丹参多糖可显著改善免疫性肝损伤小鼠的胸腺、肝脏、脾脏系数,降低血清中ALT、AST、NO的活性以及肝组织匀浆中TNF-α、IL-1β的含量。结论丹参多糖对免疫性肝损伤具有显著的保护作用。

卡介苗接种对儿童结核病预防保护作用的探讨

目的 结核病的发病率近年有所回升 ,临床对结核病的治疗研究较多 ,但卡介苗接种后对机体的保护作用如何 ,持续时间长短 ,何时复种等研究不多。鉴于此 ,该文研究卡介苗接种对儿童的保护作用。方法 对该市城乡 96 0 8例 0～ 14岁接种卡介苗 (简称种卡 )的儿童进行卡痕、PPD试验 (结核菌纯蛋白衍化物 )普查。结果3个月～组小儿PPD阳性率最高 ,为 91.5 % ;1岁～组次之 ,为 81.6 % ;3岁～组最低 ,为 5 7.1% ;7～ 14岁组PPD阳性率又有回升 ,为 74 .2 % ,各组间差异有显著性 (P <0 .0 1)。城市儿童PPD阳性率为 78.8% ,高于乡村儿童(6 2 .4 % ) ;卡痕阳性率为 90 .3% ,高于乡村儿童 (5 6 .1% ) ,P <0 .0 1;结核自然感染率低于乡村儿童 (1.7%vs3.4 % ) ,P <0 .0 5。 <3岁儿童结核自然感染率最低 (0 .5 % ) ,低于 3～ 7岁和 7～ 14岁 ,7～ 14岁儿童自感率最高。结论 卡介苗对 0～ 3岁儿童保护作用明显 ,对 4岁以上儿童保护作用渐减弱 ;且城市儿童PPD阳性率和卡痕阳性率明显高于乡村儿童 。

福建叶下珠抗小鼠免疫性肝损伤的实验研究

目的评价福建叶下珠对小鼠免疫性肝损伤的保护作用。方法48只NIH小鼠随机分为叶下珠高、低剂量组、联苯双酯组、正常对照组及模型组。于造模之日起,叶下珠高、低剂量组分别以20 g/kg、10 g/kg叶下珠药液灌胃,联苯双酯组以0.15 g/kg联苯双酯药液灌胃,正常对照组及模型组每天给予等量生理盐水。每天灌胃1次,连用12 d。检测血清谷丙转氨酶(ALT)和肝、脾脏器指数,并做肝脏病理学检查。结果联苯双酯组、叶下珠高、低剂量组小鼠血清ALT、肝指数、脾指数值较模型组有不同程度的改善(P<0.05,P<0.01)。炎症坏死程度:5组间比较,差异有非常显著性意义(P<0.005);模型组与正常组、联苯双酯组、福建叶下珠高、低剂量组与模型组间两两比较,差异有显著性意义(P值均<0.05);联苯双酯组与福建叶下珠大、小剂量组间比较,差异无显著性意义(P>0.05)。结论福建叶下珠能显著降低血清转氨酶活力和肝脾脏器指数,对肝细胞坏死有一定的改善作用,具有较好的抗小鼠免疫性肝损伤作用。

卡介菌多糖核酸的抗炎和抗过敏作用

目的 研究卡介菌多糖核酸 (BCG PSN)的抗炎、抗过敏作用。方法 观察对磷酸组胺所致豚鼠皮肤瘙痒的影响 ;采用二甲苯所致小鼠耳廓肿胀及角叉菜胶所致大鼠足跖肿胀实验观察抗炎作用 ;以 2 ,4 二硝基氟苯所致小鼠皮肤迟发型变态反应、大鼠同种被动皮肤过敏反应及小鼠异种被动皮肤过敏反应 ,探讨抗过敏作用。结果 豚鼠隔日肌内注射BCG PSN(0 1,0 2 ,0 4mg·kg-1) 3wk ,对磷酸组胺所致皮肤瘙痒无明显影响。小鼠隔日肌内注射BCG PSN(0 15 ,0 30 ,0 6 0mg·kg-1) 3wk ,可剂量依赖性地抑制二甲苯所致耳廓肿胀和耳异种被动皮肤过敏反应 ,高剂量时也可显著抑制 2 ,4 二硝基氟苯诱导的迟发型变态反应。大鼠隔日肌内注射BCG PSN(0 1,0 2 ,0 4mg·kg-1) 3wk ,可剂量依赖性地抑制角叉菜胶所致足跖肿胀和同种被动皮肤过敏反应。收稿日期 :2 0 0 3 -12 -2 4,修回日期 :2 0 0 4-0 2 -12作者简介 :刘桂珍 ( 1965 -) ,女 ,主管实验师 ,研究方向 :心血管药理学。Tel:0 73 1 2 3 5 5 0 77;胡长平 ( 1969-) ,男 ,博士 ,副教授 ,通迅作者 ,研究方向 :心血管药理学 ,Tel:0 73 1 2 3 5 5 0 77,E mail:huchangping2 0 0 1@yahoo .com .cn结论 BCG PSN对急性炎症、速发型变态反应和迟发型变态反应具有抑制作用。

卡介苗联合化疗药物交替膀胱灌注预防表浅性膀胱癌TURB-t术后复发的系统评价

目的系统评价卡介苗联合化疗药物交替膀胱灌注与单用卡介苗膀胱灌注预防表浅性膀胱癌TURB-t术后复发的临床疗效和不良反应。方法电子检索PubMed(1950～2006.12)﹑OVID(1966～2006.12)﹑EMbase(1984～2006.12)﹑Cochrane图书馆(2006年第4期)、中国生物医学文献数据库(1978～2006)和维普中文科技期刊数据库(1989～2006),并手工检索已发表和未发表文献,纳入卡介苗联合化疗药物交替膀胱灌注预防表浅性膀胱癌TURB-t术后复发的随机对照试验,按Cochrane系统评价方法对纳入研究进行质量评价,并采用RevMan4.2.9软件进行Meta分析。结果共纳入4个随机对照试验,包括681例表浅性膀胱癌患者。Meta分析结果显示,卡介苗联合化疗药物交替膀胱灌注与单用卡介苗膀胱灌注相比,①对于Ta和T1期表浅性膀胱癌,复发率差异有统计学意义[RR合并0.69,95%CI(0.53,0.90)];②对于Tis期表浅性膀胱癌,复发率差异无统计学意义[RR1.22,95%CI(0.97,1.54)];③不良反应发生率差异无统计学意义[RR合并0.85,95%CI(0.70,1.03)]。结论卡介苗联合化疗药物交替膀胱灌注与单用卡介苗膀胱灌注相比,对于Ta和T1期表浅性膀胱癌,前者能有效降低TURB-t术后肿瘤复发率;对于Tis期膀胱癌,两者在TURB-t术后肿瘤复发率差异无统计学意义;在副作用发生率方面,两者差异也无统计学意义。但由于本系统评价纳入研究数量少,且存在选择偏倚、实施偏倚以及发表偏倚的中度可能性,很可能影响结果的可靠性,故应谨慎看待以上结论,期待更多高质量的随机对照试验提供更可靠的证据。

红背叶根对小鼠免疫性肝损伤的保护作用

目的探讨红背叶根对卡介苗和脂多糖诱导的小鼠免疫性肝损伤的保护作用。方法尾静脉注射卡介苗+脂多糖诱导小鼠免疫性肝损伤。称重并计算小鼠的胸腺、肝脏、脾脏系数,检测血清谷丙转氨酶、谷草转氨酶、一氧化氮的活性以及测定肝组织匀浆中TNF-α、IL-1β的含量。结果红背叶根可显著改善免疫性肝损伤小鼠的胸腺、肝脏、脾脏系数,降低血清中谷丙转氨酯、谷草转氨酶、一氧化氮的活性以及肝组织匀浆中TNF-α、IL-1β的含量。结论红背叶根对免疫性肝损伤具有显著的保护作用。

长足大竹象成虫前胸背板及鞘翅超微结构观察

利用扫描电镜对长足大竹象成虫前胸背板和鞘翅的超微结构进行观察。结果表明:前胸背板和鞘翅表面均不光滑,前胸背板有零星分布的芽型感器和大量的凹陷;鞘翅上肩部有毛,在点刻沟部位遍布大量芽型感器。