5-氟尿嘧啶在胰十二指肠切除术患者血液和胰液中的动态分布

探讨５－氟尿嘧啶能否通过胰十二指肠切除术后的残留胰腺组织进入胰液中,并达有效的治疗浓度,为胰腺为临床合理化疗提供理论依据。方法通过观察胰十二指肠切除术患者胰快速推注５－氟尿嘧啶后血液和胰液中药物动态分布及相关性,术后静脉一次性快速推注５－氟尿嘧啶１．０ｇ／ｍ＾２,在给药前后按设计时间点分别采集静脉血和胰液,采用高效液相色谱法测定血浆和胰液５－氟尿嘧啶药物浓度,应用ＰＣＮＯＮＬＩＮ程序程序计算共动态     

胰腺假性囊肿治疗方法的选择

该文报告２３例胰腺假性囊肿,根据病期、囊肿大小、部位选择治疗方法,其中非手术治疗５例,外引流１例,内引流１４例,囊肿切除术３例。结果：无手术死亡,非手术治愈５例,外引流术后胰瘘１例,囊肿切除术后复发１例,内引流术后无严重并发症出现。我们认为急性囊肿应观察６周,有些病例有自行消散的可能,慢性囊肿一经确诊即可行内引流治疗,内引流是目前较理想的有效手术方式     

Novel imaging techniques for diabetic macular edema

Retinal edema should be defined as any increase of water of the retinal tissue resulting in an increase in its volume. It may be of cytotoxic or vasogenic origin. Development of vasogenic macular edema is dependent on a series of factors such as blood pressure, blood-retinal barrier permeability, retinal cell damage, retinal tissue osmotic pressure and retinal tissue compliance. Objective measurements of retinal thickness are now possible using the Retinal Thickness Analyser. Localised measurements of blood-retinal barrier permeability may also be obtained using the Retinal Leakage Analyser, a modified confocal scanning laser fluorometer, while obtaining simultaneously angiographic images of the choroid and retina. These new imaging techniques show that cytotoxic and vasogenic retinal edema may occur independently in the early stages of diabetic retinopathy. These findings offer new perpectives for designing novel therapeutic strategies. This revised version was published online in July 2006 with corrections to the Cover Date.     

Effects of selective phosphodiesterase inhibitors on platelet-activating factor- and antigen-induced airway hyperreactivity, eosinophil accumulation, and microvascular leakage in guinea pigs

There is currently interest in the potential use of selective inhibitors of cyclic nucleotide phosphodiesterases (PDE) in the treatment of asthma. In this study we examined the effects of three selective PDE inhibitors, milrinone (PDE III), rolipram (PDE IV) and zaprinast (PDE V), on the broncoconstriction produced by antigen and histamine, the airway hyperreactivity and microvascular leakage after aerosol exposure to platelet-activating factor (PAF) and antigen, and the antigen-induced eosinophil infiltration in guinea-pig lung. Inhaled rolipram (0.01–10 mg ml^–1) inhibited dose dependently the bronchospasm produced by aerosol antigen (5 mg ml^–1) an anaesthetised, ventilated guinea-pigs. Rolipram (10 mg ml^–1) produced maximal inhibition of antigen-induced bronchoconstriction but only partial inhibition of the response to aerosol histamine (1 mg ml^–1). Milrinone and zaprinast (each 10 mg ml^–1) showed weak, or no, inhibitory effects against bronchoconstriction produced by aerosol antigen or histamine. Pretreatment with rolipram (10 mg kg^–1, i.p.) prevented airway hyperreactivity to histamine which develops 24 h after exposure of conscious guinea-pigs to aerosol PAF (500 g ml^–1) or antigen (5 mg ml^–1). The pulmonary eosinophil infiltration obtained with 24 h of antigen-exposure was inhibited by rolipram. In contrast, milrinone and zaprinast (each 10 mg kg^–1, i.p.) failed to reduce either the airway hyperreactivity of the eosinophil accumulation in these animals. Rolipram (1–10 mg ml^–1) reduced the extravasation of Evans blue after aerosol PAF (500 g ml^–1) at all airway levels while a lower dose (0.1 mg ml^–1) was only effective at intrapulmonary airways. Rolipram (0.01–1 mg ml^–1) markedly reduced airway extravasation produced by inhaled antigen (5 mg ml^–1). Zaprinast (1–10 mg ml^–1) was also effective against airway microvascular leakage produced by aerosol PAF or antigen while milrinone (10 mg ml^–1) had no antiexudative effect. These data support previous suggestions that pharmacological inhibition of PDE IV results in anti-spasmogenic and anti-inflammatory effects in the airways and may be useful in the treatment of asthma.     

Molecular diagnosis of exocrine pancreatic cancer using a percutaneous technique

Background: The K-ras oncogene is activated by point mutations at codon 12 in most patients with exocrine pancreatic cancer. Mutant-enriched polymerase chain reaction (PCR) amplification can enhance the detection of mutated K-ras. This technique was applied to patients undergoing percutaneous fine-needle aspiration (FNA) biopsy of suspect pancreatic lesions. Methods: Twenty-five patients underwent percutaneous FNA of the pancreas for cytologic and molecular analysis. After preparing cytologic smears, the 22-gauge needle and syringe used for FNA were rinsed in RPMI-1640. The specimen was centrifuged, and DNA was extracted from the supernatant and subjected to mutant-enriched PCR using appropriate mismatched primers that introduce a BstNI restriction endonuclease cleavage site at codon 12 of wild-type, but not mutant, K-ras. After digestion with BstNI, the DNA was reamplified. To increase assay sensitivity, the final five PCR cycles were completed incorporating 5 μCi of (α-32P)dCTP. The DNA was then redigested and subjected to gel electrophoresis and autoradiography. Results: The median amount of DNA retrieved per specimen was 3.33 μg. Mutant K-ras was detected as a band of 143 bps; residual wild-type DNA was seen as a 114-bp fragment. Twenty-one of 25 specimens demonstrated mutated K-ras DNA. Two patients with nondiagnostic cytology results had mutated K-ras DNA; adenocarcinoma of pancreatic origin was confirmed in both cases after pancreatectomy. Conclusion: The molecular diagnosis of pancreatic cancer through identification of mutations in K-ras can be readily performed on specimens obtained by percutaneous FNA. As aggressive multimodality management of this disease becomes more common, pretreatment analysis of molecular determinants may have greater clinical significance. Presented at the 48th Cancer Symposium of The Society of Surgical Oncology, Boston, Massachusetts, March 23–26, 1995.     

Phosphate and thiophosphate group donating adenine and guanine nucleotides inhibit glibenclamide binding to membranes from pancreatic islets

Summary In microsomes obtained from mouse pancreatic islets, the Mg complex of adenosine 5-triphosphate (MgATP) increased the dissociation constant (K _D) for binding of [³H]glibenclamide by sixfold. In the presence of Mg²⁺, not only ATP but also adenosine 5-0-(3-thiotriphosphate) (ATPS), adenosine 5-diphosphate (ADP), guanosine 5-triphosphate (GTP), guanosine 5-diphosphate (GDP), guanosine 5-0-(3-thiotriphosphate) (GTPTS) and guanosine 5-0-(2-thiodiphosphate) (GDP S) inhibited binding of [³H]glibenclamide. These effects were not observed in the absence of Mg²⁺. Half maximally effective concentrations of the Mg complexes of ATP, ADP, ATPS and GDP were 11.6, 19.0, 62.3 and 90.1 mol/l, respectively. The non-hydrolyzable analogues adenosine 5-(,-imidotriphosphate) (AMP-PNP) and guanosine 5-(,-imidotriphosphate) (GMP-PNP) did not alter [³H]glibenclamide binding in the presence of Mg²⁺. MgADP acted much more slowly than MgATP and both MgADP and MgADP did not inhibit [³H]glibenclamide binding when the concentrations of MgATP and MgATP were kept low by the hexokinase reaction. Development of MgATP-induced inhibition of [³H]glibenclamide binding and dissociation of [³H]-glibenclamide binding occurred at similar rates. However, the reversal of MgATP-induced inhibition of [³H]glibenclamide binding was slower than the association of [³H]glibenclamide with its binding site. Exogenous alkaline phosphatase accelerated the reversal of MgATP-induced inhibition of [³H]glibenclamide binding. MgATP enhanced displacement of [³H]glibenclamide binding by diazoxide. The data suggest that sulfonylureas and diazoxide exert their effects by interaction with the same binding site at the sulfonylurea receptor and that protein phosphorylation modulates the affinity of the receptor.Some of the results described here are part of the medical theses of S. Löser and I. Rietze Send offprint requests to M. Schwanstecher at the above address     

胰腺囊实性肿瘤8例临床病理学分析

目的 观察胰腺囊实性肿瘤(CSTP)的临床病理及免疫组化特点。方法 组织学HE、PAS法，免疫组化SP法。结果 8例CSTP中，女性7例，男性1例；年龄19～32岁，平均26岁。手术后均无复发；肿瘤平均直径9cm，有包膜、囊实性相问。镜检：肿瘤由乳头和囊实性区混合而成，细胞大小形态较一致，核圆、卵圆，异形不明显，核分裂罕见。免疫组化8例al抗胰蛋白酶、VIMENTIN弥漫阳性，2例CK阳性，3例CgA、Syn局灶阳性；Insulin、EMA阴性。结论 胰腺囊实性肿瘤多发生于年轻女性，具有独特临床病理特点。预后好，应视为低度恶性肿瘤。     

Postoperative Intensive Care Treatment after Esophageal Resection

The aim of this article is to give a short review of problems associated with the intensive caretreatment of patients after esophageal resection.Pulmonary dysfunction,supraventricular tachyarrhyth-mia,anastomotie leakage and mental disorders are the topics covered.Systemic inflammatory reaction andsepsis is the linking topic between these specific complications.Pulmonary dysfunction having an incidenceof up to 40% is the most important complication.Low tidal volume ventilation,pain management includingepidural analgesia and early tracheostomy are the mainstay of therapy.Supraventricular tachyarrhythmiais an early indicator of emerging complications.Its symptomatic treatment is standardized using electriccardioversion,beta-blockers and amiodarone.Anastomotic leakage must be suspect in any septic episode.Endoscopy and contrast studies allow for precise diagnosis.Interventional endoscopy is increasingly suc-cessful in the therapy of these leakages.Microbiological surveillance and specific antibiotic therapy ensurethat a complication does not cause a septic cascade leading to multiorgan failure.The workload on ICUcaused by a patient after esophageal resection still exceeds that of most other patients with gastrointestinalsurgery.     

吉西他滨联合顺铂或氟尿嘧啶治疗晚期胰腺癌临床疗效的比较

目的　比较GP方案 (吉西他滨 顺铂 )与GF方案 (吉西他滨 氟尿嘧啶 )治疗晚期胰腺癌的近期疗效和毒副作用。方法　经病理组织学或细胞学检查证实的 60例胰腺癌患者 ,随机分为GP组和GF组 ,各 3 0例。GP组给予吉西他滨 10 0 0mg/m2加生理盐水 10 0ml,静脉滴注 3 0min ,第 1、8、15天 ;顺铂 40mg ,静脉滴注 ,第 15、16、17天。GF组给予吉西他滨 10 0 0mg/m2 加生理盐水 10 0ml ,静脉点滴 3 0min ,第 1、8、15天 ;氟尿嘧啶 5 0 0mg/m2 加 5 %GS 5 0 0ml ,静脉滴注时间超过 6h ,第 1～ 5天。结果　GP组PR 3例 ,MR 5例 ,NC 12例 ,PD 5例 ,PR MR为 3 2 .0 % ,中位生存期为 8.7个月 ,临床受益反应率 (CBR )为 5 7.7% (15 /2 6) ,CA 19 9水平下降超过 5 0 %者达 48.1% (13 /2 7)。GF组PR 3例 ,MR 8例 ,NC 9例 ,PD 4例 ,PR MR为 45 .8% ,中位生存期为 10 .1个月 ,CBR 82 .1% (2 3 /2 8) ,CA19 9水平下降超过 5 0 %者达 5 3 .6% (15 /2 8)。 2组比较 ,CBR有显著性差异 (P <0 .0 5 ) ,GF疗效较佳。不良反应主要为白细胞减少和血小板减少 ,2组无显著性差异。结论　含吉西他滨的联合化疗方案与以往单药方案比较 ,疗效高、副作用小、患者中位生存期长 ,临床受益反应率 (CBR )高 ;GP方案和GF方案比较 ,后者CBR更高 (5     

高强度体外聚焦超声热疗治疗局部晚期胰腺癌的多中心临床研究

目的：探讨临床单用HIFU治疗局部晚期胰腺癌(local advanced pancreatic carcinoma，APC)的可能性。方法：4个中心共41例患者入选进行非随机病例对照研究，其中HIFU组24例，单用HIFU治疗；对照组17例，接受HIFU及吉西他滨综合治疗。比较两组的疗效、治疗费用及安全性，采用Cox回归分析进一步确定吉西他滨化疗对生存期的影响。结果：HIFU组临床受益率、平均生存期与对照组相似，分别为66．7％比76．5％(P=10．740)和141．5天比176．5天(P=0．3510)；而治疗费用较低，为20500元比51805元(P=0．000)；安全性更高。Cox回归分析显示仅体力状态、HIFU次数及临床受益进入方程(P=0．000)，化疗对生存期无影响。结论：单用HIFU治疗APC，其疗效等同于HIFU和吉西他滨的综合治疗，但较综合治疗经济、安全。推测可以单独应用HIFU治疗局部晚期胰腺癌．值得临床进一步验证。