咪达普利对家兔陈旧性心肌梗死远离梗死区心肌在体和离体跨室壁复极离散度的影响

目的:从在体和离体两个方面探讨咪达普利对陈旧性心肌梗死(OMI)远离梗死区心肌跨室壁复极离散度(TDR)的影响。方法:24只兔随机分为3组,两组开胸结扎左回旋支制成OMI模型,术后1周将1组给予咪达普利0.625 mg/(kg·d)口服(咪达普利组),另1组给予安慰剂口服(OMI组),第3组开胸但不结扎冠状动脉,也在术后1周给予安慰剂口服(假手术组)。3个月后分别记录3组左心室游离壁远离梗死区心外膜下、中层和心内膜下3层心肌的在体单相动作电位时程(MAPD)和离体单细胞的动作电位时程(APD),并计算TDR。结果:在体研究表明,当R-R间期为300 ms时,3层心肌的90％复极的单相动作电位时程(MAPD90)无明显差异,刺激迷走神经使R-R间期延长为800 ms时,3组的中层心肌MAPD90均较心外膜下和心内膜下心肌明显延长,TDR增加。在咪达普利组,TDR为(40.80±3.74)ms,明显小于OMI组(58.00±4.30)ms(P<0.05),与假手术组(34.06±3.31)ms相比差异无显著性意义。远离梗死区的3层心室肌酶解为单细胞后进行离体实验,在1Hz刺激下,3组中层心肌单细胞(M细胞)的APD90均较心外膜下心肌细胞和心内膜下心肌细胞明显延长,咪达普利组的跨室壁单细胞APD离散(TD-APD)为(228.45±13.94)ms,明显小于OMI组(288.32±19.66)ms(P<0.05),与假手术组(210.32±17.43)ms相比差     

盐酸咪达普利对扩张型心肌病跨室壁复极不均一性的影响

目的 :探讨咪达普利 (IMI)对扩张型心肌病 (DCM )心室肌跨室壁复极不均一性的影响及其与抑制室性心律失常的关系。方法 :32只家兔 ,随机分为DCM加IMI组、DCM组、IMI组及正常对照组 ,每组 8只。然后测定其心室颤动阈值 (VFT)以及心外膜、中层心肌和心内膜心肌细胞的单相动作电位复极 90 %时程 (APD90 )、跨室壁复极离散度 (TDR)。结果 :DCM加IMI组与DCM组相比 ,前组VFT升高 ,三层心肌APD90 均缩短 ,以中层心肌APD90 缩短更为明显 ,TDR减小。IMI组与正常对照组相比 ,VFT、三层心肌的APD90 、TDR差异均无显著性意义。结论 :IMI能抑制DCM室性心律失常的发生 ,间接地减小三层心肌跨室壁复极不均一性是重要机制     

急性心肌缺血时瞬时外向钾电流和跨壁复极离散度的变化及其计算机仿真研究

目的探讨急性心肌缺血时犬左室心肌楔形组织块瞬时外向钾电流（Ito）、跨壁复极离散度（TDR）的变化及其计算机仿真研究。方法建立冠状小动脉灌注犬左室心肌楔形组织块模型，应用浮置玻璃微电极和心电图同步记录技术，观察急性无灌流心肌缺血对内中外三层心肌细胞Ito、动作电位时程（APD）、TDR和心律失常的影响，并结合急性心肌缺血Ito离子流和TDR的变化，应用修正Luo-Rody参数进行计算机仿真。结果急性心肌缺血早期犬左室内中外三层心肌细胞的Ito离子流增大，APD缩短，均以心外膜层细胞最明显，TDR增加，诱发R-on-T早搏和室性心动过速，并经计算机仿真可以证实与临床一致的心电图特点。结论急性心肌缺血时Ito离子流增大，TDR增加，产生2位相折返，是多型性室性心动过速发生的重要机制，计算机仿真可以显示这些特点。     

急性心肌缺血犬心肌细胞瞬时外向钾电流和跨壁复极离散度变化致心律失常机制研究

目的:探讨急性心肌缺血对犬左室心肌楔形组织块瞬时外向钾电流(Ito)、跨壁复极离散度(TDR)变化及其与室性心律失常的关系。方法:建立冠状小动脉灌注犬左室心肌楔形组织块模型,应用浮置玻璃微电极和心电图同步记录技术,观察急性无灌流心肌缺血对内、中、外3层心肌细胞Ito、动作电位时程(APD)、TDR和心律失常的影响。结果:急性心肌缺血早期犬左室内、中、外3层心肌细胞的Ito增大,APD缩短,均以外膜心肌细胞最明显,TDR增加,诱发早期后除极、R-on-T期前收缩和室性心动过速。结论:急性心肌缺血时Ito增大,TDR增加,产生2相位折返,是多型性室性心动过速发生的重要机制。     

急性心肌缺血时瞬时外向钾电流和跨壁复极离散度的变化及其计算机仿真研究

目的探讨急性心肌缺血时犬左室心肌楔形组织块瞬时外向钾电流(Ito)、跨壁复极离散度(TDR)的变化及其计算机仿真研究。方法建立冠状小动脉灌注犬左室心肌楔形组织块模型,应用浮置玻璃微电极和心电图同步记录技术,观察急性无灌流心肌缺血对内中外三层心肌细胞Ito、动作电位时程(APD)、TDR和心律失常的影响,并结合急性心肌缺血Ito离子流和TDR的变化,应用修正Luo-Rody参数进行计算机仿真。结果急性心肌缺血早期犬左室内中外三层心肌细胞的Ito离子流增大,APD缩短,均以心外膜层细胞最明显,TDR增加,诱发R-on-T早搏和室性心动过速,并经计算机仿真可以证实与临床一致的心电图特点。结论急性心肌缺血时Ito离子流增大,TDR增加,产生2位相折返,是多型性室性心动过速发生的重要机制,计算机仿真可以显示这些特点。     

左心室肥厚跨室壁电不均一性及缬沙坦对其影响的实验研究

目的 :探讨肥厚心肌跨室壁复极不均一性及缬沙坦预防性给药的影响。方法 :家兔 30只 ,随机分为 3组 ,腹主动脉缩窄组 (缩窄组 )、假手术组、用药组。主动脉缩窄术制备家兔高血压心肌肥厚模型 ,胶原两步消化法分离获取左心室内膜、中层及外膜单个心肌细胞 ,以全细胞膜片钳技术记录单细胞跨膜动作电位和离子流。结果 :腹主动脉缩窄组外膜、中层、内膜 3层心肌细胞跨膜动作电位复极达 90 %时程 (APD90 )均较假手术组及用药组延长 ,有显著性差异 (P <0 0 5～ 0 0 1)。以中层心肌细胞延长最为明显 (延长比例 :中层 2 3% ,外膜 10 % ,内膜 8% ) ,使肥厚心肌跨室壁复极不均一性明显增大。用药组与假手术组间各层细胞跨膜动作电位复极达 90 %时程均无明显差异。缩窄组各层心肌细胞瞬时外向钾电流 (Ito)和延迟整流钾电流 (Iks)密度均较用药组及假手术组下降 ,有显著性差异 (P <0 0 5 ) ,以中层细胞下降的幅度最大 ,而用药组及假手术组间心肌细胞瞬时外向钾电流、延迟整流钾电流密度无显著差异。结论 :家兔心肌肥厚时中层心肌细胞跨膜动作电位复极达 90 %时程延长及心肌细胞瞬时外向钾电流、延迟整流钾电流下降较外膜和内膜细胞更为明显 ,使肥厚心肌跨室壁复极不均一性增大。缬沙坦预防性给药可抑制这一变化 ,     

咪达普利对家兔心肌梗死心肌跨室壁动作电位不均一性的影响

目的研究咪达普利对陈旧性心肌梗死家兔非梗死区心室肌复极离散度的影响。方法结扎家兔左前降支8周后,记录单相动作电位;采用二步消化法分离左室游离壁3层心肌细胞。用膜片钳全细胞模式记录单细胞动作电位。结果在体和单细胞研究结果均显示,与手术组相比,陈旧性心肌梗死家兔非心梗区心室肌中层的动作电位时程(MAPD90)明显延长(292±28msvs250±26ms,p<0.05),而内膜下和外膜下心肌细胞延长不明显,3层心肌的跨室壁复极不均一性增加。实验结果还显示在体单相动作电位的离散度较单细胞动作电位小。应用咪达普利后其复极不均一性得到改善,室颤阈值上升(13.9±1.3Vvs9.3±1.0V,p<0.05)。应用咪达普利后心肌的组织重构得到改善,复极异质性得到改善,早后除极发生率也明显降低。结论咪达普利可降低家兔非心梗区心室肌复极离散度,这可能是其减少陈旧性心肌梗死恶性心律失常发生的机制之一。     

自主神经系统对在体兔急性心肌梗死跨室壁有效不应期离散度的影响

目的为探讨自主神经系统对在体家兔急性心肌梗死（AMI）后跨室壁3层心肌细胞有效不应期（ERP）离散度的影响。方法分别在基础和心肌梗死状态下,在交感神经和迷走神经刺激的过程中,用自制复合电极结合程序电刺激法测定家兔在体基础和梗死时心外膜心肌、中层心肌和心内膜心肌的ERP,并计算跨室壁ERP的离散度（TDERP）。结果在基础状态下,交感神经刺激能缩短3层心肌细胞的ERP,中层心肌细胞的ERP缩短最明显,TDERP由（21±17）ms增加到（30±16）ms（P<0.05）;迷走神经刺激能延长3层心肌的ERP,心内膜心肌ERP增加明显,TDERP由（21±17）ms降低到（24±18）ms,差异无显著性。在AMI后30 min,交感神经刺激延长3层心肌细胞的ERP,其中中层心肌细胞的ERP增加最明显,与基础状态下交感刺激相比,TDERP由（30±16）ms增加到（38±11）ms（P<0.05）;迷走神经刺激时TDERP为（21±13）ms,与基础状态（24±18）ms迷走刺激相比,TDERP无显著变化。结论AMI后,交感神经兴奋能增加TDERP;迷走神经兴奋对TDERP无显著影响。     

胺碘酮和索他洛尔对家兔不同部位心室肌细胞电生理特性的影响

目的　观察胺碘酮和索他洛尔对家兔跨左心室壁不同部位心肌细胞电生理特性的影响 ,从组织水平探讨两种药物致尖端扭转性室性心动过速 (torsadedepointes,TdP)发生率不同的原因。方法　采用标准玻璃微电极记录技术 ,记录心外膜心肌、中层心肌和心内膜心肌的跨膜动作电位 (trans membranceactionpotential,TAP)。在不同基础周长 (basiccyclelength ,BCL)刺激下 (2 50～ 2 0 0 0ms) ,分别观察 0 3～ 3 0 μmol·L- 1 浓度的胺碘酮和 1 0～ 1 0 0 μmol·L- 1 浓度的索他洛尔对 3种心肌TAP的影响。结果　胺碘酮频率依赖性和浓度依赖性地延长 3种心肌的动作电位时限 (actionpotentialduration ,APD90 ) ,由于 3种心肌的APD90 延长程度近似 ,用药后跨心室壁复极离散度 (transmuraldispersionofre polarization ,TDR)无明显增加。索他洛尔呈逆频率依赖性和浓度依赖性地延长 3种心肌的APD90 ,与心外膜心肌和心内膜心肌相比 ,中层心肌的APD90 延长更明显 ,使TDR明显增加 ,且随着剂量的增加这种作用更为显著。在 2 0 0 0msBCL刺激时 ,1 0 0 μmol·L- 1 浓度的索他洛尔诱发早期后除极 (earlyafterde polarization ,EAD) ,胺碘酮无此作用。 结论　胺碘酮和索他洛尔对跨心室壁不同部位心肌细胞电生理特性产生不同的     

p75NTR对兔心肌梗死模型跨室壁瞬时外向钾电流异质性的作用

目的:通过干预神经营养因子p75受体(p75NTR)探讨心肌梗死(MI)后神经过度增生对心肌细胞Ito,f异质性的影响。方法:选日本大耳兔40只随机分为陈旧性心梗(HMI)组、p75 NTR激活组、p75 NTR抑制组和假手术组,每组10只(n=10)。采用酶解法制备3层心室肌单细胞,利用全细胞膜片钳技术记录电流。结果:在以+50mV的去极化刺激时,HMI组的Ito,f峰电流密度有所下降,在以p75NTR受体激活后,3层心肌Ito,f峰电流密度的下降更为明显,与假手术组比差异显著(P0.05或P0.01),其中以中层心肌Ito,f峰电流密度的下降程度最大;而应用p75NTR抑制剂后,下降的程度降低,与假手术组比无明显差异。与对照组相比,中层心肌细胞的Ito,f电压依赖性失活曲线在p75NTR激活组及HMI组均向负移,p75NTR抑制组得以恢复。Ito,f通道关闭态的τ值在4组的3层心肌细胞间存在明显差异,即p75NTR激活组及HMI组失活较快,尤以p75NTR激活组为甚,p75NTR抑制组的关闭态失活与对照组接近。结论:p75NTR激活后,3层心肌Ito,f峰电流密度下降明显,尤其以中层细胞为甚,此可能是导致跨室壁复极离散度显著增加,最终引起心律失常发生的原因之一。     

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.