Survivin在胰腺癌组织中的表达及其与血管内皮生长因子的相关性研究

目的　探讨凋亡抑制蛋白Survivin在胰腺癌组织中的表达和血管内皮生长因子(VEGF)表达的关系。方法　用免疫组织化学Envision法对 51例胰腺导管癌Survivin和VEGF的表达进行检测。结果　 51例胰腺导管癌中Survivin蛋白的表达率为 80 4% ,VEGF的表达率为68 6% ;二者在 11例癌旁非肿瘤胰腺组织中均未发现阳性表达。Survivin的表达与组织学分级有关(P <0 0 1) ,而与临床分期和淋巴结转移关系不大 (P >0 0 5) ;VEGF的表达与临床分期、淋巴结转移有关 (P <0 0 5) ,而与组织学分级关系不大 (P >0 0 5) ;Survivin的表达与VEGF的表达密切相关(P <0 0 1)。二者的表达与病人的性别、年龄、肿瘤的大小、部位均无关。结论　Survivin和VEGF可能在胰腺癌的发生发展过程中起关键作用 ,二者在血管生成过程中密切相关 ,可能为胰腺癌的治疗提供了新的靶点     

环氧化酶-2和血管内皮生长因子在胰腺癌组织中的表达及其相关性研究

目的　探讨环氧化酶 2 (COX 2 )和血管内皮生长因子 (VEGF)在胰腺癌组织中的表达及与其生物学行为的相关性。方法　采用免疫组织化学Envision法对 5 1例胰腺导管癌组织中COX 2和VEGF的表达进行检测。结果　该 5 1例胰腺导管癌组织中COX 2和VEGF的表达阳性率分别为 74.5 %和 68.6% ,而二者在 11例癌旁胰腺组织中均未见阳性表达 ;COX 2和VEGF的表达阳性率在临床Ⅲ～Ⅳ期明显高于临床Ⅰ～Ⅱ期 ,淋巴结转移阳性组明显高于淋巴结转移阴性组 ,其差异均有显著性意义 (P<0 .0 5 ) ;COX 2和VEGF的表达与胰腺癌的组织学分级、患者的性别、年龄以及肿瘤的大小和部位无关 (P>0 .0 5 ) ;COX 2的表达与VEGF的表达呈正相关 (r =0 .411,P<0 .0 1)。结论　COX 2和VEGF可能在胰腺癌的发生、发展过程中起着关键性作用 ,二者在血管生成过程中密切相关 ,可能为胰腺癌的治疗提供新的靶点 ,值得深入探讨。     

E－钙黏附素和环氧化酶-2在胰腺癌中的表达及其临床意义

为探讨E-钙黏附素（E-cad）及环氧化酶-2（COX-2）在胰腺癌组织中的表达及其与胰腺癌临床病理特点的关系。笔者应用免疫组化技术检测56例胰腺癌组织、10例正常胰腺组织、6例癌旁组织和12例转移淋巴结组织中E-cad及COX-2的表达。结果示,正常胰腺及癌旁组织中E-cad均呈强阳性表达;正常胰腺组织中COX-2均呈阴性表达,癌旁组织中仅1例（16.7%）呈现阳性表达。胰腺癌组织中,E-cad异常表达者62.5%,COX-2表达阳性78.6%;E-cad和COX-2在癌组织中的表达与在癌旁和正常胰腺组织中的表达之间比较差异均有显著性 (P<0.01)。E-cad和COX-2在胰腺癌中的异常表达与胰腺癌的淋巴结转移、TNM分期、周围神经侵犯和1年生存率有关,组间差异有显著性(P<0.05),而与发病年龄、性别、肿块大小无相关。Kaplan-meier生存分析,E-cad和COX-2在胰腺癌中的异常表达者与正常表达者生存时间差异无显著性（P > 0.05）。提示E-cad和COX-2在胰腺癌中的异常表达可能在胰腺癌发生、发展过程中起重要作用,联合检测E-cad和COX-2可望成为评价胰腺癌生物学特性的有用指标。     

β-catenin基因的异常表达与胰腺癌发生和生物学行为的关系

目的　研究β- catenin基因的异常表达与胰腺癌发生和生物学行为的关系。方法　应用免疫组织化学 Pic Ture TM二步法 ,检测 4 7例胰腺癌组织、12例胰腺导管内肿瘤 (上皮中度不典型增生 )和 8例正常胰腺组织中β- catenin的表达 ;同时检测胰腺癌增殖细胞核原 (PCNA)作为胰腺癌增殖状态的指标。结果　β- catenin蛋白主要定位于正常胰腺腺泡和导管上皮细胞的连结处 ,8例正常胰腺组织均呈正常表达 ;胰腺导管内肿瘤异常表达率为 5 0 % (6 / 12 ) ;胰腺癌异常表达率为 6 8.1% (32 /4 7) ,与胰周淋巴结和肝脏癌转移和 1年生存率显著相关 (分别 P<0 .0 5 ,0 .0 1和 0 .0 5 ) ,而与胰腺癌大小、分化程度、增殖状态及浸润无关 (P>0 .0 5 )。结论　β- catenin基因的异常表达是胰腺癌发生的分子机制之一 ,也是判断胰腺癌转移和预后的良好指标。     

胰腺癌组织中雌激素受体表达及临床应用其拮抗剂三苯氧胺的疗效观察

我们检测了 5 0例患者胰腺癌组织中雌激素受体 (ＥＲ)的表达 ,探讨其与胰腺癌生物学行为的关系 ,并对 15例患者行三苯氧胺 (ＴＡＭ)治疗 ,现将结果报告如下。资料与方法1.一般资料 :收集我院 5 0例胰腺癌患者 ,其中男 33例 ,女 17例 ;年龄 10～ 72岁 ,中位年龄 5 7岁。病理组织学分型包括胰腺导管癌 35例 ,胰腺腺泡细胞癌 15例 ,其中高分化癌2 9例 ,低分化癌 2 1例 ;ＴＮＭ分期Ⅰ期 4例 ,Ⅱ期 8例 ,Ⅲ期 14例 ,Ⅳ期 2 4例。诊断标准按照ＵＩＣＣ胰腺癌ＴＮＭ分期 (1987年第Ⅳ版 )。本组行手术切除 18例 ,姑息性手术 32例 ,无手术死亡。2 .方…     

COX-2及Ki67在乳腺浸润性导管癌组织中的表达及临床意义

目的探讨COX-2和Ki67在乳腺浸润性导管癌组织中的表达情况及其临床意义。方法采用免疫组化SP方法检测82例乳腺浸润性导管癌组织与癌旁正常组织中COX．2和Ki67的表达,并结合临床病理特点进行分析。结果82例乳腺浸润性导管癌组织中COX-2和Ki67的表达分别为71．95％和64．63％,与癌旁正常组织相比均明显增高（均P〈0．001）;COX-2和Ki67的表达与肿瘤TNM分期、淋巴结转移、脉管侵犯及组织学分级呈正相关（均P〈0．05）;Ki67的表达与肿瘤大小呈正相关（P〈0．01）;Spearman等级相关分析法显示两者表达呈正相关（P〈O．05）。结论在乳腺浸润性导管癌组织中COX-2和Ki67的表达均增高,两者与乳腺浸润性导管癌临床病理特征密切相关,对两者进行联合检测可反映乳腺浸润性导管癌的生物学行为。     

环氧化酶-2基因在膀胱移行细胞癌组织中的表达及其意义

目的　探讨环氧化酶 2 (COX 2 )基因在膀胱移行细胞癌组织中的表达及其临床意义。方法　采用免疫组织化学酶标记链霉素亲和生物素法 (LSAB)对 78例膀胱移行细胞癌组织进行COX 2基因表达的检测。结果　在膀胱癌中COX 2主要呈胞核表达 ,染色阳性率为 5 6.41% ;COX 2表达与膀胱移行细胞癌组织分级、分期和预后呈高度正相关 (P <0 .0 1)。结论　膀胱移行细胞癌中COX 2异常表达与肿瘤分级、分期和疾病进展等生物学行为密切相关。     

ki67和cyclin D1在肾癌组织中的表达及其临床意义

目的:探讨ki67和cyclin D1在肾细胞癌(RCC)组织中的表达及意义。方法:利用免疫组化方法检测ki67和cyclin D1在50例RCC组织中的表达情况。50例的病理分级G111例,G230例,G39例;TNM分期Ⅰ期24例,Ⅱ期16例,Ⅲ期5例,Ⅳ期5例。结果:RCC组织中ki67标记指数为(14.0±10.95)%,cyclin D1的阳性率为80%;ki67在RCC病理分级G1与G3,G2与G3之间表达差异显著,在Ⅰ期与Ⅲ期、Ⅳ期之间表达差异显著,Ⅱ期与Ⅲ期、Ⅳ期之间表达亦差异显著,ki67和cyclinD1在RCC及正常肾组织中的表达差异有统计学意义(均P<0.05)。结论:ki67和cyclinD1在RCC组织中存在着高表达,RCC组织中ki67标记指数随着病理分级和临床分期的增高而增高,与肿瘤的生物学行为有一定关系。     

胰腺良恶性疾病中HOX A9 mRNA的表达及其临床意义

目的　探讨胰腺良、恶性病变组织中HOXA9mRNA的表达及其临床意义。方法　采用常规石蜡包埋切片 ,HOXA9mRNA原位杂交检测 ,对 5 3例胰腺癌及 2 0例慢性胰腺炎手术切除标本进行对比研究。结果　胰腺癌组HOXA9mRNA表达阳性率和评分〔49% ,(3 .3± 2 .1)分〕均明显低于慢性胰腺炎组〔95 % ,(5 .4± 0 .8)分〕和癌旁上皮组〔80 % ,(4 .6± 1.2 )分 ,n =2 5〕 ,而且其差异均有显著性 (P<0 .0 1) ;慢性胰腺炎组和癌旁上皮组HOXA9mRNA表达阴性 (n =5 )病例的导管上皮均呈中至重度不典型增生 ;高分化腺癌 (n =3 0 )和未转移癌 (n =2 2 )的HOXA9mRNA表达阳性率及其评分分别为 63 % ,(4 .0± 2 .2 )分和 64 % ,(4 .1± 2 .2 )分 ,均明显高于低分化腺癌〔3 2 % ,(2 .6± 2 .3 )分 ,n =19〕和转移癌〔3 2 % ,(2 .7± 2 .2 )分 ,n =2 5〕 ,其差异也有显著性意义 (P<0 .0 5或P<0 .0 1)。结论　该研究结果提示 ,HOXA9mRNA表达可能与胰腺癌的发生、发展、生物学行为及预后有密切关系 ,检测胰腺良、恶性病变组织中HOXA9mRNA的表达 ,对预防和早期发现胰腺癌可能具有重要的临床意义 ,值得深入研究。     

胰腺癌中血管形成因子和细胞粘附分子的表达研究

目的　探讨CD3 4 和血管内皮生长因子 (VEGF)、细胞间粘附分子 (ICAM 1)在胰腺癌(pancreaticadenocarcinoma ,PAC)组织、慢性胰腺炎组织 (chronicpancreatitis ,CP)中的表达及病理意义 ,明确血管形成在胰腺癌演化过程中所起的重要作用。方法　应用免疫组化Envission方法对 2 4例胰腺癌组织、2 4例慢性胰腺炎组织、7例正常胰腺组织 ,进行了CD3 4 、VEGF、ICAM 1的表达情况的检测。对CD3 4 阳性血管进行MVD计数 ,并结合胰腺癌的病理特征进行分析。结果　癌组织 (4 7 2±9 4 )和慢性胰腺炎组织 (4 0 8± 7 93)中微血管密度明显高于对照组 (9 85± 2 86 ) (P <0 0 1)。VEGF在正常胰腺组织中不表达 ,在胰腺癌组织中VEGF主要表达于肿瘤细胞和导管细胞的胞质中 ,在慢性胰腺炎组织中VEGF在叶间及叶内导管细胞均高表达。细胞间粘附分子ICAM 1在正常对照胰腺组织中未见表达 ,仅见于某些内皮细胞着色 ,在胰腺癌组织及慢性胰腺炎组织中 ,除内皮细胞高表达外 ,肿瘤细胞阳性表达亦较高 ,慢性胰腺炎中ICAM 1亦在叶间及小叶内导管细胞中高表达。结论　我们发现微血管形成及其调控因子、细胞粘附分子与慢性胰腺炎、胰腺癌的生物学行为密切相关 ,在胰腺癌的演变中亦起了不可低估的作用 ,抗血管形成治疗无论是对胰腺癌抑     

HYPNOTIC AND ANAESTHETIC ACTION OF THIOPENTONE AND MIDAZOLAM ALONE AND IN COMBINATION

This study examined the interaction between i.v. administeredmidazolam and thiopentone on the loss of response to verbalcommand ("hypnosis") and the loss of response to transcutaneouselectrical stimulation of the ulnar nerve ("anaesthesia") inpatients presenting for minor elective surgery. Dose-responsecurves for thiopentone and midazolam individually and in combinationwere determined using the two end-points in 300 unpremedicatedpatients. For hypnosis a highly significant (P < 0.001) supraaddictive(synergistic) interaction was found, the combination having1.8 times the expected potency of the individual agents. Althoughmidazolam failed to produce anaesthesia in the dose range used,the dose of thiopentone required to produce anaesthesia wasreduced by 50% in the presence of midazolam. The mechanism ofinteraction and the potential role of benzodiazepine-barbituratecombinations are discussed and the observed synergistic anaesthesiainteraction is used to explain the potentially dangerous combinationof benzodiazepines with other potent CNS depressants such asbarbiturates and alcohol. ^*Present address: Prince of Wales Hospital, Shatin, Hong Kong.     

THIOPENTONE AND ETOMIDATE CONCENTRATIONS IN MATERNAL AND UMBILICAL PLASMA, AND IN COLOSTRUM

We have measured concentrations of etomidate and thiopentonein maternal plasma, umbilical venous plasma and colostrum afterinduction of anaesthesia in 40 patients undergoing Caesareansection. Mean plasma etomidate concentration declined rapidly(1242.0 ng ml^–1 at 5 min, 434.0 ng mt1 at 15 min, 64.2ng ml^–1 at 30 min, 7.0 ng ml^–1 at 60 min and undetectable2 h after the injection). Mean plasma concentrations of thiopentonedeclined more slowly (6.09 µg ml^–1 at 5 min, 2.64µg ml^–1 at 2 h, 1.35 ng ml^–1 at 4 h, 0.86ng ml^–1 at 9 h and 0.59 ng ml^–1 at 12.h). Mean umbilicalvenous thiopentone concentration was 4.72 µg ml^–1.whereas the thiopentone concentration in the maternal sampleat 5 min was 6.09 g ml^–1, giving an umbilical.maternalvein ratio of 1:1.3. Mean umbilical etomidate concentrationwas 51.7 ng ml^–1 and the corresponding maternal vein sample(5 min) was 1242.0 ng ml^–1 (P < 0.001), giving an umbilical:maternal vein ratio of 1:24. Mean concetrations of thioptonein colostrum were 1.98 µg mt^–1 at 30 min, 0.91 gmt1 at 4 h and 0.59 µg ml^–1 at 9 h, colostrum .plasmaratios at 4 h and 9 h being 0.67 and 0.68, respectively. Meanconcentrations of etomidate in colostrum were 79.2 ng ml^–1at 30 min and 16.3 ng ml^–1 at 2 h. being undetectableat 4 h. The colostrum:plasma etomidate concentration ratio was1.2 at 30 min. We conclude that, although plasma and colostrumconcentrations of thiopentone and etomidate declined rapidly,the decrease was faster with etomidate.     

RESPIRATORY AND HYPNOTIC EFFECTS OF NITRAZEPAM, DIAZEPAM AND PENTOBARBITONE AND THEIR SOLVENTS IN THE RABBIT AND THE MOUSE

Nitrazepam and diazepam only cause significant depression ofrespiratory rate and loss or righting reflex, in mice, at lethaldoses. In sub-lethal doses they induce a stage of deep but rousablesleep which is quite distinct from the intermittent dozing ofcontrol mice and the comatose state of mice injected with pentobarbitone.However, the respiratory effects of nitrazepam and diazepamin high doses in mice and low doses in rabbits are modifiedby the presence of solvent. Furthermore the solvent itself causesa loss of righting reflex in mice and the lethal dose of nitrazepamand diazepam is greatly reduced when the drugs are administeredin solvent     

STRESS AND AROUSAL CIRCADIAN RHYTHMS IN SMOKERS AND NON-SMOKERS WORKING DAY AND NIGHT SHIFTS

Twenty smokers and twenty non-smokers completed a brief Mood State Questionnaire every 2 hours, over one day shift and one night shift. The subjects comprised male police officers and factory workers, aged 23–57 years. Cigarette smokers reported significantly higher stress levels than non-smokers on both day and night shifts (p<0.05). This confirms previous findings that smokers are often more stressed than non-smokers. Stress levels varied over time within each shift (p<0.001), but the circadian patterns did not differ between smokers and non-smokers. Thus smoking did not alter circadian mood rhythms, nor did it facilitate stress control. Self-rated levels of arousal showed the archetypal inverted-U pattern over time in both smokers and non-smokers. There was no difference in mean arousal levels between subgroups, indicating that cigarettes did not lead to greater alertness. The shift×time interaction was significant for both stress (p<0.001) and arousal (p<0.003), indicating different circadian rhythms during the day shift and the night shift. Finally, while smokers consumed slightly more cigarettes during the night shift than day shift (22.3, 19.4 respectively, p<0.05), mean stress and arousal levels did not differ between shifts. The implications of these findings for smoking behaviour are discussed. © 1997 by John Wiley & Sons, Ltd.     

OBSERVATIONS OF BLOOD LACTATE AND PYRUVATE LEVELS AND EXCESS LACTATE PRODUCTION DURING AND AFTER ANAESTHESIA WITH AND WITHOUT HYPERVENTILATION

Arterial blood levels of lactate and pyruvate and the productionof excess lactate were studied in two groups of patients. Onegroup of ten patients was anaesthetized with <1 per centhalothane, nitrous oxide and oxygen and allowed to breathe spontaneously.The second group of twelve patients was anaesthetized with nitrousoxide and oxygen, and additional trichloroethylene or papaveretum,and deliberately hyperventilated. No significant changes werefound in lactate or pyruvate during anaesthesia in the firstgroup, but there was a significant increase in the lactate:pyruvate ratio half an hour after recovery from the anaesthetic.Significant excess lactate production occurred during anaesthesiain the second group after hyperventilation had been in progressfor half an hour. The excess lactate increased after 1 hourof hyperventilation and further increases were found half anhour after recovery from the anaesthetic. These findings arediscussed in relation to the observed changes in blood-gas levelsand acid-base balance and to the current knowledge of carbohydratemetabolism.     

多发、复杂肝内胆管结石的诊治

目的探讨多发性、复杂性肝内胆管结石的诊治方法。方法对我院近8年来的23例多发复杂性肝内胆管结石的病人诊治经验结合文献进行分析。结果这些病例手术后残留结石率高达65．2％,比一般的肝内胆管结石术后残留率30．36％高得多,且严重并发症发生并死亡率高达17．4％。结论多发、复杂性的肝内胆管结石病人的诊治是长期来难以突破的重大临床问题,术前的“个体化”诊疗方案和术式选择是提高疗效的关键。     

VENTILATION AND GAS EXCHANGE DURING ANAESTHESIA AND SURGERY IN SPONTANEOUSLY BREATHING INFANTS AND CHILDREN

Minute ventilation (VE) (mlmin^–1), respiratory frequency(f), mixed expired carbon dioxide fraction (FCO₂ and end-tidalcarbon dioxide concentration E'CO₂) (%) were measured, and alveolarventilation (VA), deadspace (VD), deadspace/tidal volume ratio(VD/VT) and carbon dioxide output (VCO₂) calculated in 58 anaesthetized,spontaneously breathing infants and children weighing 2.8–20.5kg.Although minute volumes varied, tidal volume correlated wellwith weight (r = 0.83), with a mean tidal volume (± ISD)of 5.2±1.2mlkg^–1. It was concluded that, by theuse of mean VT + ISD (approximated to 6 ml kg^–1) the freshgas flow in mlmin^–1 should be set at 2.5x6xkgxf(15xkgxf)to avoid rebreathing in various T-piece systems in anaesthetized,intubated and spontaneously breathing infants up to a body weightof 20 kg. End-tidal carbon dioxide concentration was lower inyounger patients who were premedicated with atropine alone thanin the older ones who received opioid premedication also. Respiratoryfrequency, VD/VT and total VD per minute were higher in theyounger age group, which explained the finding of a high VEin relation to VCO₂ for these patients. This inefficiency ofventilation emphasizes the need to minimize apparatus deadspacein breathing systems used for small infants. ^*Department of Anaesthesia, University Hospital, S-22185 Lund,Sweden. Department of Anaesthesia, St George's Hospital, Blackshaw Road,London SW17.