高血压病人血小板L—精氨酸／一氧化氮系统的改变

目的原发性高血压（ＥＨ）病人（２３例）与健康成年人（１４）例作对照，观察高血压时血小板（Ｐｔ）左旋精氨酸（Ｌ－Ａｒｇ）－一氧化氮（ＮＯ）系统的改变及Ｌ－Ａｒｇ转运的特征。方法微盘测定法测定血小板孵育液中亚硝酸盐（ＮＯ２－）的含量来反映ＮＯ产生量、ＡＤＰ刺激下ＮＯ的产生量；采用张新波等建立的一氧化氮合酶（ＮＯＳ）测定改良法测定血小板ＮＯＳ活性；放射性同位素标记测定血小板３Ｈ－Ｌ－Ａｒｇ转运的动力学特征。结果ＥＨ患者Ｐｔ的ＮＯ产生量及ＮＯＳ活性较对照组明显降低（Ｐ＜０．０１），用ＡＤＰ刺激后，ＥＨ患者Ｐｔ的ＮＯ增加量仅为正常对照组增加量的６０％，其Ｌ－Ａｒｇ转运能力亦显著低于正常人（各浓度点Ｐ均＜０．０１）。最大转运速率（Ｖｍａｘ）仅为正常人的７９％（Ｐ＜０．０１），而米氏常数（Ｋｍ）则无明显改变（Ｐ＞０．０５）。结论高血压时Ｐｔ的Ｌ－Ａｒｇ－ＮＯ系统存在明显异常，提示对ＥＨ患者，在降压的同时，联合应用改善Ｌ－Ａｒｇ－ＮＯ系统的药物，对预防和治疗高血压减少并发症可能会有更好的效果。     

同型半胱氨酸对正常人血小板L-精氨酸/一氧化氮途径的影响

目的通过观察同型半胱氨酸（Ｈｃｙ）对血小板Ｌ精氨酸（ＬＡｒｇ）／一氧化氮（ＮＯ）系统的影响,探讨Ｈｃｙ对血小板损伤的机制。方法健康成人６例,平均年龄（３３±７）岁。晨取静脉血,将每例血样分为对照组及加Ｈｃｙ组,分别测定血小板ＬＡｒｇ转运功能;同时将上述两组分别设立加乙酰胆碱（Ａｃｈ）与不加Ａｃｈ组,测定血小板ＮＯ合酶（ＮＯＳ）活性、ＮＯ生成量和ｃＧＭＰ含量。结果（１）在不同浓度的Ｌ－Ａｒｇ时,Ｈｃｙ组ＬＡｒｇ转运速率均低于对照组（Ｐ＜００１）。（２）在Ａｃｈ刺激下,ＮＯＳ活性明显提高,但Ｈｃｙ组提高的程度明显低于对照组（Ｐ＜００１）。（３）在Ａｃｈ刺激下,ＮＯ生成及ｃＧＭＰ含量明显提高（Ｐ＜００１）,但Ｈｃｙ组仍明显低于对照组（Ｐ＜００５）。结论Ｈｃｙ影响血小板功能可能与ＬＡｒｇ／ＮＯ系统改变有关。     

胰岛素抵抗高血压大鼠血小板L—精氨酸／一氧化氮系统的改变

目的 观察胰岛素抵抗高血压大鼠血小板Ｌ－精氨酸／一氧化氮系统的改变。方法 自发性高血压大鼠（ＳＨＲ）自第５周至第１０周喂信果糖,制备胰岛素抵抗高血压大鼠（ＩＲ）模型。在此模型上,检测血小板一氧化氮合酶（ＮＯＳ）活性、一氧化氮（ＮＯ）产生量及Ｌ－精氨酸（Ｌ－Ａｒｇ）转运特征,同时观察了血浆Ｌ－Ａｒｇ水平、心纳素（ＮＡＰ）、ＮＯ水平及ｃＧＭＰ水平。结果 ＳＨＲ大鼠收缩压（ＳＢＰ）（Ｐ〈０．０１）,血浆     

左旋精氨酸对家兔心肌缺血再灌注损伤的保护作用

目的探讨左旋精氨酸（Ｌ－Ａｒｇ）对心肌缺血再灌注损伤（ＭＩＲＩ）的保护作用。方法制备家兔ＭＩＲＩ模型,观察Ｌ－Ａｒｇ对血清中和心肌组织中一氧化氮代谢产物（ＮＯＰ）含量、乳酸脱氢酶（ＬＤＨ）活性及心肌细胞形态学变化的影响。结果Ｌ－Ａｒｇ保护组和非保护组比较,血清及心肌ＮＯＰ明显升高（Ｐ＜０．０５）;心肌ＬＤＨ显著增高（Ｐ＜０．０５）,而血清ＬＤＨ无明显变化;心肌细胞形态学异常改变明显减轻。结论Ｌ－Ａｒｇ通过提高机体一氧化氮水平而保护缺血再灌注损伤的心肌。     

L－精氨酸逆转一氧化氮抑制后的犬冠脉血流动力学改变和内皮素－1含量升高

观察了犬冠脉内灌注Ｎ－单甲基左旋精氨酸（Ｌ－ＮＭＭＡ）后再灌注Ｌ－精氨酸（Ｌ－Ａｒｇ）和单独灌注Ｌ－ＮＭＭＡ前后冠脉血流动力学、冠脉血流储备以及冠脉对不同浓度的乙酰胆碱（Ａｃｈ）反应的变化，同时用放免法测定冠脉前降支（ＬＡＤ）伴行静脉血中内皮素－１（ＥＴ－１）含量。结果发现，Ｌ－Ａｒｇ完全逆转了灌注Ｌ－ＮＭＭＡ引起的血流动力学改变，使心率回升，下降的基础冠脉流量（ＣＢＦ），从２０±８ｍｌ／ｍｉｎ回升至２８±７ｍｌ／ｍｉｎ，Ｐ＜０．０５），降低的冠脉储备恢复，从５１±１０ｍｌ／ｍｉｎ升至９４±１５ｍｌ／ｍｉｎ，Ｐ〈０．０１），ＥＴ－１的含量不再升高，从１５．５±３．０ｎｇ／Ｌ下降至５．０±２．０ｎｇ／Ｌ，Ｐ〈０．０１），Ａｃｈ介导的ＣＢＦ增加不再受到抑制（Ｐ〈０．０１）。结果提示提供外源性Ｌ－Ａｒｇ可增加一氧化氮（ＮＯ）的产生，使由于ＮＯ抑制而产生的血流动力学改变和ＥＴ－１升高发生逆转。     

L－精氨酸逆转一氧化氮抑制后的犬冠脉血流动力学改变和内皮素－1含量升高

观察了犬冠脉内灌注Ｎ－单甲基左旋精氨酸（Ｌ－ＮＭＭＡ）后再灌注Ｌ－精氨酸（Ｌ－Ａｒｇ）和单独灌注Ｌ－ＮＭＭＡ前后冠脉血流动力学、冠脉血流储备以及冠脉对不同浓度的乙酰胆碱（Ａｃｈ）反应的变化，同时用放免法测定冠脉前降支（ＬＡＤ）伴行静脉血中内皮素－１（ＥＴ－１）含量。结果发现，Ｌ－Ａｒｇ完全逆转了灌注Ｌ－ＮＭＭＡ引起的血流动力学改变，使心率回升，下降的基础冠脉流量（ＣＢＦ），从２０±８ｍｌ／ｍｉｎ回升至２８±７ｍｌ／ｍｉｎ，Ｐ＜０．０５)，降低的冠脉储备恢复，从５１±１０ｍｌ／ｍｉｎ升至９４±１５ｍｌ／ｍｉｎ，Ｐ〈０．０１)，ＥＴ－１的含量不再升高，从１５．５±３．０ｎｇ／Ｌ下降至５．０±２．０ｎｇ／Ｌ，Ｐ〈０．０１)，Ａｃｈ介导的ＣＢＦ增加不再受到抑制（Ｐ〈０．０１）。结果提示提供外源性Ｌ－Ａｒｇ可增加一氧化氮（ＮＯ）的产生，使由于ＮＯ抑制而产生的血流动力学改变和ＥＴ－１升高发生逆转。     

一氧化氮在高脂饲养兔胸主动脉的变化和意义

观察高脂饲养兔胸主动脉血管环对去甲肾上腺素（ＮＥ）的反应性及环磷酸鸟苷（ｃＧＭＰ）含量的变化。结果表明其对ＮＥ的反应性降低，组织ｃＧＭＰ的含量减少。左旋精氨酸（Ｌ－Ａｒｇ）和硝普钠（ＳＮＰ）可恢复此反应性，而一氧化氮合成酶（ＮＯＳ）阻滞剂Ｌ－硝基精氨酸（Ｌ－ＮＮＡ）却加重其降低的反应性。提示高脂饲养兔血管环中的一氧化氮（ＮＯ）减少，Ｌ－Ａｒｇ及ＳＮＰ可以逆转之，暗示Ｌ－Ａｒｇ／ＮＯ通路障碍可能是动脉粥样硬化的又一机理。     

抑制NO合酶上调大鼠血管α1—肾上腺素受体和三磷酸肌醇受体

探讨ＮＯ系统和血管α１－肾上腺素受体α１－ＡＲ）及三磷酸肌醇受体（ＩＰ３Ｒ）系统在高血压发病中的相互作用。方法在常规饲食中加入Ｌ－ＮＡＭＥ喂饲大鼠１或４周制备大鼠高血压模型；应用放射性配基结合实验观察α１－ＡＲ及ＩＰ３Ｒ的变化。结果应用Ｌ－ＮＡＭＥ处理一周，大鼠动脉血压升高３０（２ｍｍＨｇ（Ｐ＜０．０５），血浆ＮＯｘ含量则下降２５％（Ｐ＜０．０５）。主动脉肌膜α１－ＡＲ及肌浆网ＩＰ３Ｒ密度分别增加１２％和４０％。Ｌ－ＮＡＭＥ处理４周，大鼠血压升高７５±８ｍｍＨｇ（Ｐ＜０．０１），血浆ＮＯｘ含量下降５０％（Ｐ＜０．０１），主动脉肌膜α１－ＡＲ及肌浆网ＩＰ３Ｒ密度分别较对照组高７３％和１３７％（Ｐ＜０．０１），此时尾动脉肌膜ＡＲ及肌浆网ＩＰ３Ｒ密度亦较对照组增加５５％和５６％（Ｐ＜０．０１）。结论提示长期抑制ＮＯＳ引起大鼠持续性高血压的同时，可致大鼠血管α１－ＡＲ及ＩＰ３Ｒ明显上调。     

L-精氨酸对肾性高血压心肌肥厚大鼠左心室肌原癌基c-fos蛋白表达及血浆NO含量的影响

目的：探讨Ｌ－精氨酸对肾性高血压心肌肥厚大鼠左室肌原癌基因 ｃ－ｆｏｓ表达及血浆 ＮＯ含量的影响。方法：采用免疫组织化学方法测定左室肌原癌基因ｃ－ｆｏｓ蛋白表达,用比色法测定血浆一氧化氮含量。结果：通过８周治疗后,Ｌ－Ａｒｇ使高血压心肌肥厚大鼠ｃ－ｆｏｓ蛋白表达显著减少（Ｐ＜０．００５）,使血浆中ＮＯ含量显著升高（Ｐ＜０,００１）结论： Ｌ－Ａｒｇ治疗高血压心肌肥厚大鼠能减轻 ｃ－ｆｏｓ表达和提高血浆中ＮＯ含量。     

和胃胶囊对实验大鼠胃动力的影响

目的：探讨和胃胶囊对胃动力障碍的改善作用。方法：给大鼠腹腔注射盐酸左旋精氨酸（Ｌ－Ａｒｇ）造成胃电、胃肠激素的异常，同时给予和胃胶囊灌胃，观察和胃胶囊对Ｌ－Ａｒｇ所致大鼠胃电、胃肠激素异常的改善作用。结果：和胃胶囊能有效抑制Ｌ－Ａｒｇ引起大鼠血清及胃粘膜一氧化氮含量的升高（Ｐ〈０．０５），对Ｌ－Ａｒｇ所致的大鼠胃电地血浆胃动素水平下降和血清胃泌素水平升高有明显的对抗作用（Ｐ〈０．０５～０．０１）。结论：和胃胶囊对Ｌ－Ａｒｇ所致大鼠胃动力障碍有明显的改善作用，其作用机制是多途径的。     

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。     

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。     

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。     

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.     

Angiographic diagnosis of the degree of serosal invasion of carcinoma of the colon

Angiography using Prostaglandin El^® was performed on 38 patients with carcinoma of the colon in order to diagnose the degree of serosal cancer invasion. The findings at angiography were classified into four groups:1) AG-S3, abnormal change (irregularity and/or encasement) up to marginal vessels; 2) AG-S2, abnormality up to vasa recta; 3) AG-S1, abnormality of penetrating branches of vasa recta within the wall of the colon; and 4) AG-S0, no distinct findings of abovementioned vessels. These angiographic findings were compared with both macroscopic and microscopic serosal cancer invasion. Angiographic diagnosis is in accord with the macroscopic findings in 84.2 percent of cases. Angiographic diagnosis is in accord with the microscopic findings in 32.4 percent of cases. Macroscopic findings confirm the angiographic diagnosis precisely but the conflict with microscopic findings should not be overlooked. This may be the result of inflammatory change, adhesion, and fibrosis around carcinoma of the colon.