Is the cyclic GMP system underestimated by intensive care and emergency teams?

At present, the clinical management inflammatory vasoplegia associated to sepsis or anaphylaxis is symptomatic. Volume is expanded by means of administration of fluids, and low blood pressure is managed by means of administration of positive inotropes and vasoconstrictors. This therapeutic approach is mainly associated to the cyclic AMP (cAMP) and, many times the circulatory shock is refractory to high amines concentrations. However, beside of cAMP-dependent vasoreactivity mechanisms there are other two known vasoplegia involved mechanisms: cyclic GMP (cGMP) and hyperpolarization that is less clinically considered. Also, it is possible to speculate about 'probable vasopressin deficiency'. Methylene blue (MB) is the most useful and clinically safe cGMP blocker. We propose a decision tree for diagnosis and institution of this therapeutical approach many times underestimate by intensive care and emergency teams.     

A novel strategy to limit blood donor exposure and blood waste in multiply transfused premature infants

Small, premature infants require frequent small-volume transfusions. Traditional methods of transfusion expose these infants to multiple blood donors. It has recently been demonstrated that multiple donor exposures can be safely prevented in these infants by the assignment of fresh units to them and by the use of a sterile connecting device to remove blood for transfusion, as needed until the expiration of the unit. However, the program resulted in the wasting of approximately 60 percent of the blood in each unit. STUDY DESIGN AND METHODS: To minimize blood waste without compromising the goal of limiting donor exposure, a model designed to predict each infant's transfusion requirements was investigated. The model assigned infants predicted to have high transfusion requirements to receive blood from a unit dedicated to their individual use. All other infants were assigned to receive blood from a unit that could be shared among as many as four similar infants. Infant donor exposure and blood unit wastage after institution of the infant assignment model were compared with the same measurements obtained before the use of the model, during which time infants were assigned to dedicated units at the discretion of the physician. RESULTS: The numbers of transfusions per infant (3.5 +/− 2.3) and of donor exposures per infant (1.5 +/− 0.7) under the assignment model were unaltered from those in controls (4.1 +/− 2.9 transfusions and 1.6 +/− 0.8 donor exposures); however, there was significantly less blood wastage in the group assigned to shared units (32 +/− 28%) than in the group assigned to dedicated units (62 +/− 17%; p < 0.05) or than was seen in an earlier study (60 +/− 23% wasted; p < 0.05). CONCLUSION: Improved management of blood resources can be achieved within the context of a transfusion program designed to safely limit donor exposure in infants who require frequent transfusion.     

急性缺血再灌注肾损伤过程中Mg2+及K+协同胰岛素的对抗效应

目的:在肾移植术后可能发生急性缺血再灌注性肾损伤.作者前期实验表明在肾缺血再灌注期间注射胰岛素可减轻缺血再灌注肾损伤,在此基础上,在胰岛素溶液中加入天冬氨酸钾镁,观察Mg2 ,K 协同胰岛素对家兔急性肾缺血再灌注损伤的影响,并分析其可能机制.方法:实验于2002-02/04在泸州医学院生理实验室完成,动物实验方法符合动物伦理学要求.①实验材料及方法:选用健康成年日本大耳白兔27只,按随机数字表法分为3组(n=9),即缺血再灌注组、缺血再灌注胰岛素处理组及对照组,前两组采用钳夹肾动脉法建立急性肾缺血再灌注肾损伤模型,缺血再灌注胰岛素处理组再灌注的同时给予胰岛素溶液,含胰岛素3 U/kg,葡萄糖1.5 g/kg,K 4 mg/kg,Mg2 1.7 mg/kg.②实验评估:分别观察3组动物缺血再灌注2 h,48 h后,血清尿素氮、血糖、血清及肾组织中丙二醛含量以及肾组织超微结构变化.结果:23只动物进入结果分析.①肾缺血再灌注48 h后,缺血再灌注组血清尿素氮含量显著高于对照组(P＜0.01),缺血再灌注胰岛素处理组与对照组差异无显著性意义(P＞0.05).②缺血再灌注组血清及肾组织中丙二醛含量显著高于对照组(P＜0.05),缺血再灌注胰岛素处理组丙二醛含量显著低于缺血再灌注组(P＜0.05).③缺血再灌注2 h后,3组动物血糖均较术前增高,但以缺血再灌注组增高更为显著,与对照组比较差异具有显著性意义(P＜0.05),缺血再灌注胰岛素处理组与对照组差异无显著性意义(P＞0.05).④对照组肾组织超微结构正常,缺血再灌注组肾组织呈变性和坏死改变,缺血再灌注胰岛素处理组肾组织轻度变性.结论:Mg2 ,K 可协同胰岛素减轻家兔急性缺血再灌注性肾损伤,其作用途径可能和降低血糖、抗自由基损伤、改善能量代谢、减轻钙超载、防止低血钾等因素有关.     

Training in endoscopic submucosal dissection

Endoscopic submucosal dissection (ESD) represents an important advancement in the therapy of early neoplastic gastrointestinal lesions by providing higher en-bloc curative resection rate with lower recurrence compared to endoscopic mucosal resection (EMR) and by sparing the involved organ and protecting patient’ s quality of life. Despite these advantages ESD is associated with long procedure times and a higher rate of complications, making ESD a challenging procedure which requires advanced endoscopic skills. Thus, there has been a recognized need for structured training system for ESD to enhance trainee experience and, to reduce the risks of complications and inadequate treatment. ESD has a very flat learning curve. However, we do not have uniformly accepted benchmarks for competency. Nevertheless, it appears that, in Japan, more than 30 supervised gastric ESD procedures are required to achieve technical proficiency and minimize complications. A number of training algorithms have been pro-posed in Japan with the aim to standardize ESD training. These algorithms cannot be directly applied in the West due to substantial differences including the availability of highly qualified mentors, the type of pathology seen, choice of devices, and trainee’s background. We propose a training algorithm for Western physicians which integrates both hands-on training courses, animal model work as well as visits to expert centers. No specific preceptor training programs have been yet developed but there is a consensus that these programs are important for permeation of ESD worldwide.     

阿司匹林和塞莱昔布对幽门螺杆菌的体外影响

目的:探讨阿斯匹林和选择性COX-2抑制剂塞莱昔布对体外培养的幽门螺杆菌(H pylori)生长、毒力因子及外膜蛋白的影响．方法:不同浓度的阿司匹林及塞莱昔布与H pylori共同培养,以活菌计数、分光光度计法检测H pylori的生长状态,分光光度计检测A 560nm值判断尿素酶活性,Hela细胞空泡变性实验和中性红吸收试验检测空泡毒素的活性,以SDS-PAGE电泳检测H pylori外膜蛋白的变化．结果:阿司匹林及塞莱昔布可以抑制H pylori的生长,此过程为剂量依赖性效应．阿司匹林0．5 mmol／L及塞莱昔布0．01 mmol／L时与DMSO对照相比H pylori24 h和48 h的菌落计数开始降低,随着两药剂量的加大菌落计数降低得更加明显,阿司匹林2．0 mmol/L和塞莱昔布0．04 mmol／L时H pylori被完全杀灭．阿司匹林及塞莱昔布可剂量依赖性的抑制H pylori的尿素酶活性及空泡毒素的活性．在对H pylori外膜蛋白的研究中发现,NSAIDs可能对H pylori的某种外膜蛋白表达有影响．结论:阿司匹林和塞莱昔布可抑制H pylori的生长、毒力因子的活性,并可能改变H pylori外膜蛋白的表达．     

Hyperfunctioning and nonhyperfunctioning benign adrenal cortical lesions: characterization and comparison with MR imaging

The authors evaluated the potential of magnetic resonance (MR) imaging at 0.35 T to permit differentiation of nine hyperfunctioning adrenal cortical lesions from 21 nonhyperfunctioning adrenal cortical adenomas. Both qualitative data (visual assessment) and quantitative data (signal intensity ratios, T1, and T2) were used for tissue characterization. With a 2,000/56-100 sequence (repetition time msec/echo time msec), the majority of lesions were visually isointense to liver. Of 34 quantitative measures, only lesion-liver and lesion-kidney intensity ratios at 2,000/150 showed statistically significant differences among nonhyperfunctioning adenomas, aldosterone-producing lesions, and corticosteroid-producing lesions; however, the authors question the significance of these differences because of the abundant noise associated with the 2,000/150 sequence. The results suggest that nonhyperfunctioning adrenal cortical adenomas cannot be distinguished from benign hyperfunctioning cortical lesions with use of MR imaging at 0.35 T.     

Early osteonecrosis of the femoral head: detection in high-risk patients with MR imaging

To determine whether magnetic resonance (MR) imaging can demonstrate the early stages of osteonecrosis that are not detectable radiographically, the authors compared radiologic findings with histologic results in seven patients at high risk for osteonecrosis of the femoral head. Radiography and MR imaging were performed, and proximal femoral intramedullary pressures were measured in all patients, even if results from imaging studies were normal. If the pressures were elevated, core decompression with biopsy was performed. Seven patients had elevated pressures in 11 hips. Of 11 hips from which biopsy specimens were taken, all had histologic evidence of osteonecrosis. However, in only five were the MR imaging findings consistent with osteonecrosis. In the remaining six hips with osteonecrosis, MR imaging findings were normal. Sensitivity of MR imaging in detection of osteonecrosis was 46%. The authors conclude that normal MR imaging results in high-risk patients do not rule out the presence of osteonecrosis.     

2,3-epoxy-4-hydroxynonanal, a potential lipid peroxidation product for etheno adduct formation, is not a substrate of human epoxide hydrolase

Our previous studies have shown that 2,3-epoxy-4-hydroxynonanal, a reactive epoxy aldehyde capable of forming etheno adducts with DNA bases, is mutagenic and tumorigenic (Carcinogenesis, 14, 2073). The epoxy aldehyde can be generated from trans-4-hydroxy-2-nonenal, a lipid peroxidation product of omega-6 polyunsaturated fatty acids, by autoxidation or by incubation with fatty acid hydroperoxides or hydrogen peroxides (Chem. Res. Toxicol., 9, 306). These are plausible in vivo pathways for the formation of 2,3-epoxy-4-hydroxynonanal. The possibility that 2,3-epoxy-4-hydroxynonanal is a tumorigen of endogenous origin is suggested by recent observations that etheno bases are detected as background DNA lesions in untreated rodents and humans. A metabolic pathway critical for detoxification of 2,3-epoxy-4- hydroxynonanal involves the ring-opening by epoxide hydrolase, which abolishes its ability to form cyclic etheno DNA adducts. In this study, we examined whether 2,3-epoxy-4-hydroxynonanal is a substrate of cDNA expressed human epoxide hydrolase. Human epoxide hydrolase was expressed in TK- 143 cells (thymidine kinase-deficient human embryoblast) infected with recombinant vaccinia virus encoding human epoxide hydrolase cDNA. Controls consisted of the cells infected with vaccinia virus in the absence of human epoxide hydrolase cDNA. No hydrolysis occurred when [2,3-(3)H]2,3-epoxy-4-hydroxynonanal was incubated at 37 degrees C for 30 min at pH 7.4 with cells expressing human epoxide hydrolase, as indicated by the presence of a pair of radioactive peaks in reversed-phase HPLC chromatography, which comigrated with the UV standards of the two diastereomers of the epoxy aldehyde. The identity of these compounds as the intact epoxy aldehyde was further supported by derivatization to the 2,4- dinitrophenylhydrazones followed by reversed phase HPLC analysis. Similar results were observed with the control cells or with the heat deactivated human epoxide hydrolase. The epoxide hydrolase activity in the expressed cells was demonstrated by their ability to convert benzo[a]pyrene-4,5-dihydroepoxide to benzo[a]pyrene-trans-4,5- dihydrodiol under the same conditions. These results clearly indicate that 2,3-epoxy-4-hydroxynonanal is not a substrate of human epoxide hydrolase, and, thus strengthen its possible endogenous role in the formation of promutagenic exocyclic etheno adducts in vivo.