不同药物对小鼠肝细粒棘球蚴术后感染的抑制作用

目的:探讨不同药物对小鼠肝细粒棘球蚴感染的抑制作用,了解增强宿主免疫功能对小鼠肝细粒棘球蚴感染的影响.方法:取包虫囊液成功免疫小鼠,分为药物治疗组和模型对照组.肝脏接种原头蚴前1 wk及接种后1 mo,药物治疗组分别用阿苯哒唑脂质体、槐耳浸膏及阿苯哒唑脂质体联合槐耳浸膏治疗,接种头节时各药物治疗组再分为4组,每组头节分别使用750 mL/L乙醇、200g/L高渗盐水、阿苯哒唑脂质体及平衡液处理后接种.模型对照组头节用平衡液处理后直接接种,接种后3 mo观察小鼠肝细粒棘球蚴大体和病理变化,检测小鼠脾脏指数、外周血IgG和IgE水平,并用流式细胞仪检测小鼠外周血CD4 和CD8 淋巴细胞的百分率.结果:联合治疗组中小鼠肝细粒棘球蚴生发层和角质层破坏较严重.各药物治疗组小鼠脾脏指数、IgE水平明显低于模型对照组(3.84±0.86,3.95±1.01,3.27±0.52 vs 5.46±0.52;0.06±0.08 μg/L,0.07±0.08 μg/L,0.03±0.03μg/L vs 0.20±0.02 μg/L,均P<0.01),其中联合药物治疗组降低最为明显;药物治疗组IgG水平与模型对照组相比无显著性差异.药物治疗组CD8 水平明显低于模型对照组(16.60±3.89,18.18±3.90,15.38±2.63 vs 32.90±4.71,均P<0.01),CD4 /CD8 明显高于模型对照组(3.21±0.70,3.05±0.66,3.53±0.57 vs 1.57±0.26,均尸<0.01),其中联合治疗组变化最为明显.结论:阿苯哒唑脂质体与槐耳浸膏联合用药可以明显增强小鼠免疫功能,抑制细粒棘球蚴的生长,使小鼠肝细粒棘球蚴病术后感染率降低.     

苦参碱联合阿苯达唑治疗小鼠继发性棘球蚴病效果观察

目的 评价中药苦参碱单独及联合阿苯达唑使用治疗小鼠继发性棘球蚴病的效果.方法 将感染棘球蚴的昆明小鼠分为4组:苦参碱组、阿苯达唑组、联合用药组、对照组,每组10只.在对小鼠进行药物治疗90 d后,检测各组小鼠棘球蚴湿重、抑囊率,并利用光镜、电镜对棘球蚴组织进行形态结构和超微结构观察.结果 苦参碱组、阿苯达唑组、联合用药组、对照组棘球蚴湿重分别为(0.32±0.12)、(0.31±0.10)、(0.05±0.03)、(1.16±0.43)g,苦参碱组及联合用药组对小鼠棘球蚴的抑囊率分别达到72.4%和95.7%,显示联合用药组明显优于苦参碱组(P<0.05).上述4组包囊组织Ⅲ级病理损伤率分别为40.9%(9/22)、43.5%(10/23)、91.3%(21/23)、9.5%(2/21).与对照组比较,其他3组包囊组织Ⅲ级病理损伤率明显增高(P均<0.01),且联合用药组最为明显.结论 苦参碱对小鼠棘球蚴的增长有明显的抑制作用,尤其联合阿苯达唑使用治疗效果较好,说明两种药物具有协同治疗作用.     

沙鼠肝泡球蚴组织中骨桥蛋白与IL-10的表达及相关性研究

目的 检测沙鼠肝泡状棘球蚴组织中骨桥蛋白（OPN）及白细胞介素-10（IL-10）的表达,并进一步探讨两者的相关性。方法 20%泡状棘球蚴组织混悬液开腹直视下肝脏穿刺注射感染长爪沙鼠60只,每只0.1mL,建立肝泡状棘球蚴长爪沙鼠模型。随机分为模型组（无干预,40只）和实验组（抗OPN抗体干预,20只）。感染至100 d时剖杀所有长爪沙鼠,观察泡状棘球蚴生长和转移情况,取长爪沙鼠肝泡状棘球蚴组织和转移灶标本。采用免疫组织化学SP法观察沙鼠肝泡状棘球蚴组织和转移灶中OPN及IL-10的表达情况。 结果 60只长爪沙鼠全部感染肝泡状棘球蚴。免疫组化染色显示肝泡状棘球蚴组织可见OPN及IL-10不同程度的表达。模型组中OPN和IL-10阳性细胞表达率分别为72.5%（29/40）和65%（26/40）,OPN及IL-10主要分布在肝泡状棘球蚴纤维囊壁,阳性产物均定位于细胞浆。65%（26/40）的长爪沙鼠模型经病理证实发生胸廓内淋巴结转移,伴有胸廓淋巴结转移的肝泡状棘球蚴组织中OPN及IL-10阳性细胞表达率分别为84.6% (22/26)、76.9%(20/26),均高于未发生胸廓淋巴结转移的肝泡状棘球蚴组织（50%、42.9%）（P﹤0.05）。实验组OPN和IL-10的阳性细胞表达率分别为40%（8/20）和35%(7/20)。OPN与IL-10表达呈正相关（r=0.605,P=0.000）。结论 OPN阳性表达可能与肝泡状棘球蚴的转移有关,OPN与IL-10可能在肝泡状棘球蚴的生长中起协同作用。     

阿苯达唑脂质体对小鼠细粒棘球蚴囊超微结构的影响

目的:探讨阿苯达唑脂质体(liposom alalbendazole,L-ABZ)及其联合西咪替丁(cim etidine,CTD)治疗小鼠细粒棘球蚴病的病理形态变化。方法:将阿苯达唑脂质体及西咪替丁(1.5% 乳液阿苯达唑200 m g/kg,西咪替丁100 m g/kg),经口灌喂感染小鼠3个月后,用光镜和电镜观察小鼠肝、腹细粒棘球蚴囊结构的病理改变。结果:以阿苯达唑脂质体联合西咪替丁治疗组细粒棘球蚴囊组织变性坏死改变最为显著,与对照组有显著性差异(P< 0.01)。结论:脂质体包封阿苯达唑,可提高阿苯达唑的抗细粒棘球蚴作用,西咪替丁具有明显的协同作用     

新疆伊犁河谷肝棘球蚴病临床资料分析

目的　探讨新疆伊犁河谷肝棘球蚴病流行病学特点及临床诊治方法。　方法　对 1993～ 2003年伊犁河谷多家医院经手术确诊并治疗的肝棘球蚴病病例进行回顾性分析。　结果　共 2049例肝棘球蚴病患者 ,其中细粒棘球蚴病 1965例占 96% ,泡球蚴病 84例占 4%。所有病例经棘球蚴皮内过敏试验、B超、彩超、X线检查、X线断层照相术 (CT)、磁共振成像术 (MRI)、血清学免疫试验均可确诊。确诊病例经手术治疗2 034例占 99.2 %。其中 ,行肝叶切除术、肝棘球蚴外囊膜内完整切除术、肝棘球蚴囊肿外囊外切除术共 3 0 2例占 14.7% ,无术后复发及并发症。术后服药 (吡喹酮、阿苯达唑、阿苯达唑脂质体 ) 754例占 36.7% ,均有一定疗效。肝棘球蚴病流行病学特点是沿伊犁河谷流行、散布。患者均生活在农牧区 ,均有与牛、羊、狗密切接触史 ,当地各民族人群均有发病 ,女性 1 125例占 5 4%。25～49岁发病率较高为 982例占 48%。 1993-2003年发病率呈逐年下降趋势。　结论　肝棘球蚴病是新疆伊犁地区高发病、多发病 ,沿伊犁河谷流行、散布。应进一步加强病畜管理、改良手术治疗方法 ,积累临床经验。     

维拉帕米治疗小鼠继发性棘球蚴病的实验研究

目的通过利用钙拮抗剂维拉帕米和阿苯哒唑单独和联合用药治疗小鼠继发性棘球蚴病的疗效观察,探讨两种药协同治疗棘球蚴病的机理。方法小鼠被随机分成6组(维拉帕米、阿苯哒唑的单用组、维拉帕米和阿苯哒唑的联合用药组、对照组)。给予药物治疗90天后,解剖小鼠,检测各小鼠棘球蚴囊的湿重并且对棘球蚴囊进行病理组织学和超微结构的观察。结果治疗90天后,发现维拉帕米和阿苯哒唑单独及联合应用均对小鼠棘球蚴有明显的抑制作用(抑制率分别为47.2%、43.4%、56.6%),其中联合用药组效果明显优于单独用药组,经统计学分析差异有显著性意义。结论维拉帕米对小鼠继发性棘球蚴有一定的抑制作用,尤其维拉帕米联合阿苯哒唑的效果更好,说明维拉帕米和阿苯哒唑有协同治疗作用。     

年龄对小鼠继发性肝泡状棘球蚴模型的影响

目的 探讨不同年龄对继发性肝泡状棘球蚴的影响。方法 分别选取8周龄、18周龄、28周龄雌性昆明小鼠29、25、25只,用20%乌拉坦腹腔注射麻醉后,运用切开上腹部皮肤经腹壁肌层透视下肝穿刺方法分别对3组小鼠进行肝脏注射E. m组织混悬液,制备继发性肝泡状棘球蚴小鼠模型。接种后饲养100 d,行安乐死并解剖。结果 3组小鼠存活率分别为: 62.1%、84%、68%(P>0.05)。肝脏E. m感染率分别为:72.2%、71.4%、76.5%(P>0.05)。肝脏E. m包囊直径分别为: 0.915±0.103 cm、1.247±0.112 cm、1.215±0.197cm(P>0.05)。肝脏E. m包囊质量分别为:0.332±0.035 g、0.532±0.155 g、0.382±0.085 g(P>0.05),差异无统计学意义,小鼠肝E. m组织HE染色无差异。结论 利用18周龄小鼠作为造模动物制作继发性肝泡状棘球蚴模型,实验小鼠存活率高。     

肝泡型棘球蚴病非手术治疗的疗效评价

目的探讨非手术治疗的晚期肝泡型棘球蚴病患者的治疗方法。方法对中国人民解放军第四医院2006-2009年收治的25例无法根治性切除的肝泡型棘球蚴病患者进行回顾性调查分析,了解其治疗方法和疗效。结果 25例肝泡型棘球蚴病患者中,男性18例,女性7例,平均年龄为41岁。其中单纯药物治疗[持续服用阿苯达唑15～20 mg/(kg.d)]12例,药物结合穿刺治疗11例,药物结合介入治疗2例。阿苯达唑治疗2周为一疗程,一般持续3个疗程。治疗后1～4年共有18人获随访。其中单纯药物治疗组有效2例,改善7例;药物结合穿刺治疗组有效2例,改善5例;药物结合介入治疗组2例均无效。结论持续服用阿苯达唑可作为非手术治疗肝泡型棘球蚴病患者的主要治疗方法。     

硝唑尼特和阿苯达唑联合治疗小鼠原发性和继发性泡状棘球蚴病的机制探讨

目的观察硝唑尼特、阿苯达唑及硝唑尼特／阿苯达唑联合治疗原发性和继发性泡状棘球蚴病小鼠的疗效。方法分别通过腹腔注射泡状棘球蚴原头节和口服泡状棘球蚴虫卵的方式建立继发性和原发性泡状棘球蚴病小鼠模型,建模2个月后分别进行药物治疗,药物经口灌胃,疗程持续35d后,检测各组小鼠泡状棘球蚴囊湿重及病理改变并检测血清IL-2、IL-4、TNF—α和Ig—E的含量。结果治疗35d后,继发性泡球蚴感染小鼠用药组与模型对照组比较,用药组泡球蚴的平均湿重显著下降（P〈0．01）,结果现示硝唑尼特单独及联合均有明显抑制小鼠泡状棘球蚴生长的作用（抑囊率分别为51．56％、67．68％、88．06％）,其中联合用药明显优于单独用药。继发性和原发性泡球蚴感染实验小鼠血清IL-2、IL-4及Ig-E的含量,用药组和模型对照组比较差异有统计学意义（P〈0．01）,与空白对照组比较差异无统计学意义（P〉0．05）;TNF—α含量用药组和模型对照组与空白对照组比较差异有统计学意义（P〈0．05）,用药组与模型对照组比较差异有统计学意义（P〈0．05）。结论硝唑尼特及硝唑尼特／阿苯达唑联合用药对小鼠泡状棘球蚴感染有一定的抑制作用。     

肝泡状棘球蚴病的超声及病理表现

目的: 分析肝泡状棘球蚴病患者的临床、病理及超声图像特征.方法: 回顾性分析2002-2007年我院经手术病理证实的肝泡状棘球蚴病患者15例的超声图像特征并分型.结果: 15例肝泡状棘球蚴病单发12例,多发3例,共发现肿块20个;超声特征:多位于左肝,大小多为5 cm以上,形态多不规则,边界多清晰,内部回声多呈高回声、不均匀、无液化、无钙化,后方回声多衰减,无声晕、无内部血流多见,未见肝门及腹腔淋巴结肿大;根据声像图特征分为:实性肿块型(13个,65%)、肿块液化型(7个,35%)、肿块钙化型(8个,40%).结论: 超声检查肝泡球蚴病超声影像具有特征性,是肝泡球蚴病重要的影像学检查方法.     

Continuous albendazole therapy in alveolar echinococcosis--evaluation of therapeutic effect with computerized tomography and ultrasonography]

Fifteen cases of alveolar echinococcosis were treated with albendazole in a dosage of 20 mg/kg/d x 30 days for 12-60 courses (25.8 courses in average) and were followed up 1-7 years (48 months in average) with computerized tomography and ultrasonography. Abdominal pain in all the cases, jaundice in 4 and hemoptysis in disappeared 2. In 13 of the 15 cases, the hepatic lesions reduced in size. Among 9 cases examined with computerized tomography, the hepatic lesions were completely calcified in 5 and enclosed with calcified walls in 3. Only one patient with huge and extensive hepatic lesions showed no apparent improvement. No severe adverse reaction was observed. Evidently albendazole was effective in the treatment of alveolar echinococcosis.     

肝泡型棘球蚴病并发肺泡型棘球蚴病相关危险因素分析

目的 探讨肝泡型棘球蚴病并发肺泡型棘球蚴病的相关危险因素。 方法 收集青海大学附属医院肝胆胰外科 2017 年 10 月至 2019 年 4 月收治的肝泡型棘球蚴病并发肺泡型棘球蚴病的患者(并发组)以及肝泡型棘球蚴病未并发肺泡型棘球蚴病患者(对照组)的一般资料、实验室和影像学检查资料,分析并发肺泡型棘球蚴病发生的影响因素。 结果 共收集肝泡型棘球蚴病并发肺泡型棘球蚴病患者 49 例,肝泡型棘球蚴病未并发肺泡型棘球蚴病患者 55 例,两组间性别及年龄构成差异均无统计学意义( χ2 = 2. 164、2. 780, P均>0. 05)。 单因素分析结果提示,HBeAg 以及肝内病灶侵犯肝后下腔静脉、肝动脉、肝静脉和门静脉情况是肝泡型棘球蚴病并发肺泡型棘球蚴病的影响因素。 二元多因素 Logistic 回归分析结果提示,肝内病灶侵犯肝后下腔静脉和肝内病灶侵犯肝静脉是肝泡型棘球蚴病并发肺泡型棘球蚴病的独立危险因素。 结论 对于肺部病灶界定不明确的肝泡型棘球蚴病患者,可以根据术前肝内病灶影像学特征并结合肺部病灶影像学结果作出判断,进而采取有针对性的干预措施,实现患者临床受益最大化。     

Treatment of human alveolar echinococcosis with flubendazole. Clinical, morphological and immunological study

Flubendazole has been given at a daily dosage of 50 mg/kg for 16 months (extremes 10 and 24 months) to 10 patients with hepatic alveolar echinococcosis. Clinical, morphological and immunological evaluations have been performed every 2 months during the treatment, and in 6 patients after discontinuation of the drug for 24 months. Jaundice persisted or occurred in 7 patients; infectious complications were observed in 4 patients; portal hypertension appeared in 5 patients; metastatic spread was suspected in 2 patients. Subjective improvement and weight gain were reported by 6 patients during the first 4 months of treatment. Severe complications occurring during the period of FZ therapy or within 2 months after withdrawal of the drug led to surgery in 6 patients, and death occurred in 3 cases. These observations demonstrate the inefficacy of FZ in this series of 10 patients with alveolar echinococcosis, possibly related to the extremely poor bioavailability of FZ. Higher plasma concentrations obtained with mebendazole and albendazole could explain the better efficacy of these two drugs despite their similar chemical structures and experimental toxicity upon larval cestodes.     

Effect of dose increase or cimetidine co-administration on albendazole bioavailability.

The low bioavailability of albendazole affects the therapeutic response in patients with echinococcosis. Cimetidine co-administration is reported to improve bioavailability. To analyze the assumed dose-dependent bioavailability of albendazole, we administered 5 to 30 mg/kg albendazole to 6 male volunteers in a randomized cross-over study. To assess the effect of cimetidine (10 mg/kg twice daily), the drug was given with albendazole (20 mg/kg). A dose-dependent bioavailability was not observed. This was due to inter-individual variability of the maximal concentration (Cmax 38%-72%) of albendazole sulphoxide (ABZSX), the active metabolite of albendazole. Cmax was 0.21+/-0.14 mg/L after 5 mg/kg and 0.39+/-0.19 mg/L after 30 mg/kg albendazole (P = 0.217). Cimetidine tended to decrease Cmax by 52% (P = 0.109) and significantly inhibited ABZSX breakdown as indicated by the prolongation of ABZSX elimination half-life from 7.4+/-3.3 hr to 19.0+/-11.7 hr (P = 0.028). Remarkably, the inter-individual variability of Cmax was significantly lower during cimetidine co-administration: 14% versus 72%.     

Endemic alveolar echinococcosis in Southern Belgium?

Until now, Belgium has been considered as a low-risk country for alveolar echinococcosis. However it was recently demonstrated by necropsy series that, in some parts of southern Belgium (Wallonia), up to 51% of the red foxes (Vulpes vulpes) may be infected by E. multilocaris. The authors, working in a university hospital in southern Belgium, described in 2002 the first autochthonous Belgian case of hepatic alveolar echinococcosis. More importantly, in 2004, they diagnosed three other patients with alveolar echinococcosis. One underwent surgical resection, but two others had bilateral pulmonary involvement at time of definite diagnosis. Palliative albendazole therapy was initiated. These patients had been diagnosed with hepatic mass from unknown origin for several months. The previous experience with the first case allowed the authors to consider and to confirm alveolar echinococcosis diagnosis, made by pathology and/or serological tests and imaging. These four patients with alveolar echinococcosis were living either in the Liege or the Luxembourg province. Considering the high prevalence of E. multilocaris infection of red foxes and the recent increase of the fox population due to rabies vaccination in southern Belgium, and also the presence of E. multilocaris infection of red foxes in northern Belgium, it is likely that not only Wallonia, but also maybe the whole Belgium, may face endemic alveolar echinococcosis in the next years.     

Alveolar echinococcosis of the liver: percutaneous stent therapy in Budd-Chiari syndrome.

BACKGROUND AND AIMS: Infiltration of the hepatic veins in the alveolar echinococcosis can lead to the development of the Budd-Chiari syndrome. The medical and surgical treatment of this condition is generally unsatisfactory. The results of successful interventional treatment with percutaneous stent implantation in the hepatic veins are reported. METHODS: Using a transjugular approach, metal mesh stents (Boston Scientific, Medi-Tech Accuflex 8/60 mm) were placed in the median and left hepatic veins of a 53 year old woman. After the intervention, oral chemotherapy with albendazole (2 x 400 mg/day) was continued, but no anticoagulants were given. RESULTS: Stent placement was performed without complications. The clinical picture improved rapidly: normalisation of portal blood flow was confirmed by Doppler ultrasound and there was improvement of liver function, reduction of oesophageal varices, and disappearance of ascites. A follow-up examination at 15 months showed no evidence of stent occlusion. CONCLUSIONS: Treatment of portal hypertension in alveolar echinococcosis of the liver is problematic. In selected patients with portal hypertension secondary to hepatic vein stenoses but no cirrhosis, percutaneous stent placement in the hepatic veins represents a promising treatment alternative.     

阿苯达唑治疗多房棘球蚴病研究进展

多房棘球蚴病是由多房棘球绦虫感染引起的一种高致死率人兽共患寄生虫病。阿苯达唑为苯并咪唑类化合物之一,具有强大的杀灭寄生虫作用,且驱虫谱较广。对于不愿接受手术治疗、失去手术机会或身体状态差而无法耐受手术的多房棘球蚴病患者,使用阿苯达唑药物治疗可一定程度上延缓疾病进展。近年来,多房棘球蚴病相关实验研究取得大量成果。本文回顾了相关文献并对阿苯达唑治疗多房棘球蚴病研究进展进行综述,以期增加对阿苯达唑治疗多房棘球蚴病效果的认识,为未来用于临床治疗奠定基础。     

转移性脑多房棘球蚴病1例

本文报道了1例转移性脑多房棘球蚴病病例。该患者经过10年抗棘球蚴病治疗,前后经过肝脏、右肾及脑部等3次手术治疗。患者虽经过多次手术及口服阿苯达唑治疗,仍出现肝棘球蚴病复发及远处转移。本病例提示,早期预防、早期诊断、早期规律治疗和必要时行手术根治是治疗棘球蚴病的关键所在。     

阿苯达唑乳剂治疗肝囊型包虫病212例临床疗效观察

目的　验证新剂型阿苯达唑乳剂对肝囊型包虫病患者的临床疗效。　方法　对 2 12例肝囊型包虫病患者用阿苯达唑 10 m g/ (kg· d)和 12 .5 mg/ (kg· d)两种剂量进行治疗。服药 3个月复查 1次为 1个疗程 ,各疗程之间不间断连续用药。以 B超影像特征为主判定疗效 ,观察不同疗程的效果。以停药时的检查结果为近期疗效。停药后随访 1～ 4年的结果为远期疗效。　结果　两个剂量组共 2 12例患者的平均近期疗效 :治愈率为74.5 % ,有效率为 99.1% ,无效率为 0 .9%。平均远期疗效 :治愈率为 83.1% ,有效率为 89.3% ,无效率为 0 .6 % ,复发率为 10 .2 %。以 12 .5 mg/ (kg· d)连续治疗 9个月的疗效较好。复发病例再治疗的效果良好。　结论　阿苯达唑乳剂对肝囊型包虫病的临床疗效超过当前包虫病药物治疗的最好水平 ,疗效稳定可靠 ,不良反应轻微 ,可成为治疗包虫病的首选药物。