The nitric oxide pathway in pre-eclampsia: pathophysiological implications

Pre-eclampsia, one of the most significant health problems inhuman pregnancy, complicates 6-7% of all gestations and is theleading cause of fetal growth retardation, infant morbidityand mortality, premature birth and maternal death. Recent researchimplicates free radicals in the pathophysiology of pre-eclampsia.This review covers the biochemistry of nitric oxide (NO) andpossible interactions with other free radicals. Studies in therat show that pregnancy is associated with enhanced productionand responsiveness to NO in both reproductive tissues and bloodvessels. Rats infused with N^G-nitro-L-arginine methyl ester(L-NAME, a NO synthase inhibitor) have been used as an animalmodel of pre-eclampsia, and the effects of steroid hormoneson blood pressure in this model have been tested. Results suggestthat pre-eclampsia may be a state of NO deficiency. However,in humans there seem to be contradictions regarding the involvementof NO in maternal adaptation to pregnancy. It is suggested thatNO may be one of several systems that act in concert to maintaina symbiotic relationship between mother and fetus. However,the input of each system may be genetically determined.     

Surgical sperm retrieval and intracytoplasmic sperm injection as treatment of obstructive azoospermia

Male genital tract obstructions may result from infections, previous inguinal and scrotal surgery (vasectomy) and congenital bilateral absence of the vas deferens (CBAVD). Microsurgery can sometimes be successful in treating the obstruction. In other cases and in cases of failed surgical intervention, the patient can be treated by microsurgical or percutaneous epididymal sperm aspiration (MESA, PESA) or testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI). We present the results of 39 ICSI procedures for obstructive azoospermia in 24 couples. The aetiology of the obstruction was failed microsurgery in 11 patients, CBAVD in nine and genital infections in four. Sperm retrieval was accomplished via MESA in four cases, PESA in 18 cases and via TESE in 11 cases. TESE was only applied when PESA failed to produce enough spermatozoa for simultaneous ICSI. In six patients, the ICSI procedure was performed with cryopreserved spermatozoa after an initial PESA procedure. Fertilization occurred in 47% of the metaphase II oocytes; embryo transfer was performed in 92% of procedures and resulted in a clinical pregnancy in 13/39 procedures. Ongoing pregnancy was achieved in 10/39 procedures. One pregnancy was terminated early after prenatal investigation showed a cytogenetic abnormality (47,XX+18, Edwards syndrome). The other nine pregnancies resulted in the live birth of 10 children, without any congenital abnormalities. Epididymal and testicular retrieved spermatozoa were successfully used for ICSI to treat obstructive azoospermia, and resulted in an ongoing pregnancy in 10 of 24 couples (41.6%) after 39 ICSI procedures, a success rate of 25.6% per treatment cycle and of 27.7% per embryo transfer.      

Immunological aspects of clinical renal transplantation

Improved facilities for treating patients with end-stage renal failure have resulted in more elderly and debilitated patients being accepted for treatment. Renal transplantation is now the optimum form of treatment but organ procurement has failed to match clinical demand. Future developments may focus on further non-specific immunosuppressive agents. As one year survival rates for first cadaver allografts now exceed 85% in many units, the significance of new developments will be increasingly difficult to evaluate.     

Association of the platelet glycoprotein IIb HPA-3 polymorphism with survival after acute ischemic stroke

BACKGROUND AND PURPOSE: The role of polymorphisms of the platelet glycoprotein (GP) IIb/IIIa receptor in the development of cardiovascular disease has been the subject of intensive research. The aim of this study was to determine the association of the HPA-3 polymorphism of platelet GPIIb with ischemic stroke and subsequent survival and to identify possible interactions of HPA-3 with classic risk factors. METHODS: HPA-3 genotype was determined by restriction fragment length polymorphism in 515 patients with ischemic stroke and 423 healthy, age-matched control subjects. RESULTS: There was no significant difference in the genotype distribution of patients and controls, nor was there any difference when patients were subclassified into small- and large-vessel disease. The genotype distribution of the 231 patients subsequently dying during 2.8 years of follow-up (aa=45.0%, ab=46.8%, bb=8.2%) was significantly different from that of those still alive (aa=37.0%, ab=48.2%, bb=14. 8%) (P=0.03). In a Cox regression model, the relative risks for poststroke mortality in patients of aa and ab genotype compared with those of bb genotype were 2.42 (95% CI, 1.24 to 4.71) and 2.13 (95% CI, 1.09 to 4.17), respectively, after we accounted for confounding factors. In addition, significant interactions of HPA-3 with the Pl(A) polymorphism of GPIIIa (P=0.002) and with fibrinogen (P=0.01) were identified in relation to mortality. CONCLUSIONS: HPA-3 is related to poststroke mortality, and the significant interaction of HPA-3 with Pl(A) and fibrinogen suggests that it may in some way influence the interaction of GPIIb/IIIa with fibrinogen, particularly in the presence of high fibrinogen.     

造血干细胞移植与临床感染的防治

学术背景:造血干细胞移植技术在临床上已得到广泛应用,移植后感染是关系到移植成败的重要因素。目的:探讨造血干细胞移植后各阶段的感染的特点、预防及治疗,以进一步减低造血干细胞移植后感染的发生率及死亡率。检索策略:由作者应用计算机检Medline 1994-01/2007-05关于造血干细胞移植及移植后感染的文章,检索词为"hematopoietic stem cell transplantation,infection",限定语言种类为"English";同时检索中国期刊全文数据库1994-01/2007-05相关文章,检索词"造血干细胞移植,感染,防治",限定语言种类为中文。纳入标准:随机对照研究;实验或临床研究包含平行对照组。排除标准:重复性研究文献评价:初检得到212篇文献,初审后选取与造血干细胞移植后感染有关的文章126篇,删除明显无关及相关性不强的文章,进一步查找全文,29个实验符合标准,予以纳入。29个研究包括324例患者和140个实验动物,分别阐述了造血干细胞移植后感染的原因、途径、特点、种类及各种感染的预防及治疗措施。资料综合:造血干细胞移植后感染发病隐匿,由于患者免疫力低下,感染不易控制,在不同阶段致病菌的种类有所不同,细菌感染普遍,在移植后各个时期均可出现,真菌感染和病毒感染致死性强,故预防和治疗感染至关重要,其治疗分为预防治疗、抢先治疗、经验性治疗和针对治疗。结论:造血干细胞移植后感染的治疗已成为影响移植疗效的一个重要原因,及早的诊断及正确的治疗将成为移植后感染治疗成功的关键。     

STRA-MI-VT (STereotactic RadioAblation by Multimodal Imaging for Ventricular Tachycardia): rationale and design of an Italian experimental prospective study

Background

Ventricular tachycardia (VT) is a life-threatening condition, which usually implies the need of an implantable cardioverter defibrillator in combination with antiarrhythmic drugs and catheter ablation. Stereotactic body radiotherapy (SBRT) represents a common form of therapy in oncology, which has emerged as a well-tolerated and promising alternative option for the treatment of refractory VT in patients with structural heart disease.

Objective

In the STRA-MI-VT trial, we will investigate as primary endpoints safety and efficacy of SBRT for the treatment of recurrent VT in patients not eligible for catheter ablation. Secondary aim will be to evaluate SBRT effects on global mortality, changes in heart function, and in the quality of life during follow-up.

Methods

This is a spontaneous, prospective, experimental (phase Ib/II), open-label study (NCT04066517); 15 patients with structural heart disease and intractable VT will be enrolled within a 2-year period. Advanced multimodal cardiac imaging preceding chest CT-simulation will serve to elaborate the treatment plan on different linear accelerators with target and organs-at-risk definition. SBRT will consist in a single radioablation session of 25 Gy. Follow-up will last up to 12 months.

Conclusions

We test the hypothesis that SBRT reduces the VT burden in a safe and effective way, leading to an improvement in quality of life and survival. If the results will be favorable, radioablation will turn into a potential alternative option for selected patients with an indication to VT ablation, based on the opportunity to treat ventricular arrhythmogenic substrates in a convenient and less-invasive manner.

     

In vitro and in vivo studies of the effect of artemether on Schistosoma mansoni.

To determine whether artemether, a derivative of the antimalarial agent qinghaosu, is therapeutically active against Schistosoma mansoni, we determined the in vitro, in vivo, and histopathologic effects of the drug on S. mansoni worms. In vitro, toxic effects of artemether on S. mansoni were not seen at concentrations of less than 100 micrograms/ml. However, in vivo, 30 and 50% reductions in the lengths of male and female worms, respectively, were observed 14 days after treatment. By 56 days worm dimensions had returned to control values. Similar reversible effects on male testes and female ovaries were seen. In vivo, a single oral dose of artemether (300 mg/kg) induced a shift of worms towards the liver within 8 h after treatment. By 3 and 14 days after treatment, 99 and 76%, respectively, of worms were still in the liver. In vivo, the therapeutic effect of artemether on adult S. mansoni treated on day 56 after infection was modest. Doses as high as 1,200 mg (200 mg/kg per day, six doses) resulted in a worm reduction rate of only 39%. However, in infected mice treated on day 14 or 21 after infection, worm reduction rates of 83 to 98% were obtained. Thus, artemether exhibited modest in vitro and in vivo activities against adult S. mansoni but was twofold more active against 2- to 3-week-old liver-stage parasites.