胃癌染色体17p微卫星不稳定性及突变型p53蛋白的表达

目的研究微卫星不稳定性（ＭＳＩ）及突变型ｐ５３基因在胃癌发生中的作用。方法采用ＰＣＲ为基础的方法及免疫组织化学技术检测了５０例手术切除胃癌标本染色体１７ｐ的ＭＳＩ及突变型ｐ５３蛋白的表达。结果胃癌ＭＳＩ总阳性率为３４％（１７／５０），突变型ｐ５３蛋白表达阳性率为３６％，其中高－中分化腺癌ＭＳＩ阳性率（６６．７％）显著高于低分化腺癌（１９．４％，Ｐ＜０．０１）；肠型胃癌ＭＳＩ阳性率（５５．６％）显著高于胃型胃癌（２０％，Ｐ＜０．０５）。ＭＳＩ与胃癌部位、大小、浸润、分期及突变型ｐ５３蛋白的表达无显著相关性。结论研究提示，ＭＳＩ在胃癌的发生中心能起重要作用，其作用机制可能不同于由突变型ｐ５３基因介导的致癌机制。     

卡托普利对急性心肌梗死患者早期血压、心率的影响——中国心脏研究－Ⅰ暨血管紧张素转换酶抑制剂治疗急性心肌梗死大型随机临床试验专题报告之二

探讨血管紧张素转换酶抑制剂卡托普利对急性心肌梗死病人早期血压、心率、死亡率及临床事件的影响。方法多中心随机双盲安慰剂对照临床试验，给发病３６ｈ内的急性心肌梗死病人随机口服卡托普利（ｎ＝７４６８，１２．５ｍｇ３／ｄ）或安慰剂（ｎ＝７４９４）治疗４周。结果基础血压＜１００ｍｍＨｇ或舒张压＜７０ｍｍＨｇ、心率＜７０ｍｉｎ－１者，卡托普利组４周总死亡率略高于安慰剂对照组；基础收缩压≥１００ｍｍＨｇ或舒张压≥７０ｍｍＨｇ、心率≥７０ｍｉｎ－１（尤其心率偏快）者，卡托普利组死亡率均低于对照组。用首剂（６．２５ｍｇ）药后２ｈ收缩压或舒张压较前下降１０％～１９％者卡托普利组死亡率（８．５％，７．１％）均明显低于对照组（１０．７％，Ｐ＝０．０４；１０．０％，Ｐ＝０．００３），而血压下降幅度＜１０％者两组死亡率相似。基础收缩压＜１００ｍｍＨｇ者卡托普利组休克发生率（１０．０％）高于对照组（７．８％），低血压发生率（３６．５％ｖｓ２４．０％）更高。基础心率＜６０ｍｉｎ－１者卡托普利组心力衰竭（１３．４％）、休克（５．８％）、室颤（２．８％）发生率均略高于对照组（１１．９％，３．６％，１．３％）；心率≥６０ｍｉｎ－１者卡托普利     

培哚普利与卡托普利对高血压的疗效比较

评价培哚普利治疗中度原发性高血压的有效性和安全性并与卡托普利比较。１２０例患者随机分为培哚普利组和卡托普利组，每组中４４例行偶测血压监测，１６例行动态血压监测；培为利４－６ｍｇ，１／ｄ，卡托普利１２．５－１８．７５ｍｇ，３／ｄ，疗程４周。降压总有效率培哚普利组为９１．７％，卡托普利组为７８．３％；副作用发生率培哚普利组为１１．７％，且均较轻微。     

环孢素A治疗难治性肾病综合征

目的研究环孢素Ａ（ＣｓＡ）治疗难治性肾病综合征的临床疗效并探讨其机制。方法对３０例肾上腺皮质激素依赖或抵抗的肾病综合征（ＮＳ）患者联合使用了（ＣｓＡ，５ｍｇ·ｋｇ－１·ｄ－１）和泼尼松（３０ｍｇ／ｄ）治疗，并测定了ＣｓＡ治疗前后病人的血生化指标、免疫指标及２４小时尿蛋白排出量。结果２４小时尿蛋白排出量由治疗前的平均７．６７±３．００ｇ／２４ｈ降至治疗后第１、２、３个月的４．９３±３．６４ｇ／２４ｈ、３．５２±２．９４ｇ／２４ｈ、２．２３±１．６０ｇ／２４ｈ；血浆白蛋白由治疗前２７．３±６．４ｇ／Ｌ升至３０．９±８．８ｇ／Ｌ、３４．３±７．６ｇ／Ｌ、３６．０±７．２ｇ／Ｌ；治疗前后血肌酐、ＢＵＮ、尿酸、ＣＤ４／ＣＤ８和可溶性白细胞介素２（ＩＬ２）受体无明显变化，而治疗２个月后外周血单个核细胞产生血清ＩＬ２显著下降。治疗后激素抵抗组ＮＳ完全缓解、部分缓解和无效分别为２２．７％，５０．０％和２７．３％；在激素依赖组分别为５７．１％，４２９％和０。有５例患者因肝肾功能损害或严重腹泻而停用ＣｓＡ。结论本研究提示ＣｓＡ联合小剂量皮质激素治疗难治性肾病综合征，尤其是激素依赖的患者是安全和有效的。     

高血压患者心率功率谱变化及含化硝苯地平的干预作用

目的应用ＨＲＰＳＡ的方法，探讨高血压时心脏植物神经功能及压力感受器的状态和硝苯地平对其影响。方法２５例高血压患者及２１例正常人（对照组）进行心率功率谱分析（ＨＲＰＳＡ），并对其中１１例高血压给予硝苯地平１０ｍｇ舌下含化干预。结果高血压组的功率谱密度（ＰＳＤ单位［ＨＲ２／Ｈｚ］－５的低频部分（ＬＦ，１６．６２±７．７９）明显高于对照组（７．９９±４．２，Ｐ＜０．０５）；高频部分（ＨＦ，９．４７±６．３４）明显低于正常对照（１４．２±７．１２，Ｐ＜０．０５）；高血压组的ＬＦ与收缩压正相关（ｒ＝０．４６１，Ｐ＜０．０５）；含化硝苯地平后血压下降，中频部分（ＭＦ）由２．７３±１．７７增加到３．５２±２．２４，Ｐ＜０．０５），ＨＦ由９．０９±５．１９增至１４．４５±６．７５，Ｐ＜０．０１）。结论高血压除存在交感神经活性增强外，副交感神经活性减低突出，副交感神经活性减低可能与高血压患者血压不能正常调节有关     

雌激素对绝经后妇女冠心病治疗作用的观察

目的探索雌激素对绝经后妇女冠心病的防治机制及疗效。方法将１０８例绝经１年以上的女性冠心病患者随机分为三组（各３６例），甲组口服结合雌激素（倍美力）０．６２５ｍｇ１／ｄ，乙组口服７甲基异炔诺酮（利维爱）２．５ｍｇ１／ｄ，丙组口服安慰剂１片１／ｄ，于服药前及服药后第３、６个月末检测血脂谱及ＥＣＧ，并记录心绞痛发作情况。结果倍美力治疗后可使胆固醇（ＴＣ）降低１２．８％，甘油三酯（ＴＧ）降低１７．０％，低密度脂蛋白胆固醇（ＬＤＬＣ）降低２９．０％，高密度脂蛋白胆固醇（ＨＤＬＣ）上升１４６％。利维爱治疗后ＴＣ降低８．７％，ＴＧ降低１５．６～３３．８％、ＨＤＬＣ降低１９．７～２８．３％（Ｐ值均＜００１），ＬＤＬＣ无显著变化。倍美力及利维爱治疗第３、６个月后对心绞痛症状的总有效率分别为９０９％、９３５％和８３．３％和９３．１％，对ＥＣＧ缺血性改变的总有效率分别为７６．７％、８２．１％和７８．６％、８１４％，两种药物对妇女冠心病的心肌缺血疗效差异无显著性（Ｐ＞０．０５）。结论雌激素替代治疗可显著改善绝经后妇女冠心病患者的异常血脂及心肌缺血     

小剂量山朝治疗再生障碍性贫血

小剂量山地明治疗再障１７例，其中ＣＡＡ９例，ＳＡＡ－Ⅰ５例，ＳＡＡ－Ⅱ１例，ＰＴＣＡ２例。剂量为２００－３００ｍｇ／ｄ，分两次口服，平均３．５－５ｍｇ／（ｋｇ．ｄ），疗程３－６个月，除２例ＰＲＣＡ外余同时口服康力龙４－６ｍｇ／ｄ，结果：基本治愈３例，缓解１例，明显进步６例，见效７例，总有效率５８．８％     

The Role of Renin－Angiotensin Systemin

目的研究压力负荷产生的心肌肥厚过程中的肾素－血管紧张素系统（ＲＡＳ）作用。方法应用ｌｏｓａｒｔａｎ（Ｌｏｓ）及卡托普利（Ｃａｐ）研究心肌ＲＡＳ在压力超荷大鼠心肌肥厚中的作用。狭窄大鼠腹主动脉造成压力超荷（ＣｏＡ），术后第二天给予ＣｏＡ大鼠亚降压量Ｌｏｓ（３ｍｇ／ｋｇ·ｄ－１）与Ｃａｐ（３０ｍｇ／ｋｇ·ｄ－１）。结果不影响动脉血压，但左室重分别减少５８．３％及６２．５％，左室／体重比值显著低于ＣｏＡ组（４．１２±０．１７及３．９２±０．２３ｖｓ４．８６±０．１８，Ｐ＜０．０５），但左室重与假手术组比仍有差异。高血压肥厚２周大鼠，经亚降压量Ｌｏｓ及Ｃａｐ治疗２周后，左室重较治疗前分别减少６０％及６４％，蛋白质含量显著低于ＣｏＡ组（１０２．１±１４及９８．５±１５ｍｇｖｓ１４３．３±１９ｍｇ，Ｐ＜０．０５），但高于正常组。结论Ｌｏｓ与Ｃａｐ逆转肥厚的机制除降压外，阻断心肌ＲＡＳ活性起重要作用     

大剂量静脉用胺碘酮治疗顽固性、持续性室性心律失常的临床疗效及安全性

目的：评价静脉用胺碘酮（ａｍｉｏｄａｒｏｎｅ）对顽固性、持续性室性心动过速（ＳＶＴ）、心室颤动（ＶＦ）患者的临床疗效。方法：２４例ＳＶＴ和（或）ＶＦ患者，其中男１９例，女５例，平均年龄４９．２±１２．４岁；冠心病陈旧性心肌梗死１４例，心肌病７例，心肌炎２例，先天性心脏病１例。静脉注射胺碘酮首剂３～５ｍｇ／ｋｇ，１０分钟内注入，继之以１．０～１．５ｍｇ／ｍｉｎ维持静脉滴注，第１个２４小时总量平均２１６５．０±３８５．４ｍｇ（包括口服量），以后依病情渐减，维持静脉滴注平均４．２±２．５天。静脉应用同时加用口服胺碘酮６００～１２００ｍｇ／ｄ。第１次负荷量后，若心律失常控制不理想，可每隔１５～３０分钟再给１．５～３．０ｍｇ／ｋｇ的追加负荷量。疗效判断以ＳＶＴ和（或）ＶＦ消失为有效。结果：总有效率８３．３％。２例静脉用胺碘酮期间出现窦性心动过缓、窦性停搏及一过性Ⅱ度房室传导阻滞。经减量后恢复。结论：静脉应用大剂量胺碘酮治疗快速性室性心律失常安全有效。     

高血压病患者血清甲状腺激素的水平及药物干预的变化

目的：探讨高血压病（ＥＨ）患者血清甲状腺激素的水平及药物干预后的影响。方法：用放射免疫法测定了６６例ＥＨ患者和３６例正常血压对照者及４１例ＥＨ患者服药（２５例服吲达帕胺２．５ｍｇ／ｄ或１６例服卡托普利１８．７５～７５ｍｇ／ｄ）８周后血清Ｔ３、Ｔ４的变化。结果：ＥＨ患者血清Ｔ３、Ｔ４水平显著高于对照组,均Ｐ〈０．０１;服吲达帕胺组或卡托普利组８周后血压,Ｔ３、Ｔ４水平较服药前均显著降低（Ｐ〈０．０５）。结论：ＥＨ患者血清Ｔ３、Ｔ４水平增高;吲达帕胺,卡托普利有效降血的同时均能显著降低血清Ｔ３、Ｔ４水平,甲状腺激素的失控可能参与高血压的形成或维持。     

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.     

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.