Clastogenic and aneugenic effects of tamoxifen and some of its analogues in hepatocytes from dosed rats and in human lymphoblastoid cells transfected with human P450 cDNAs (MCL-5 cells)

Tamoxifen and its analogues 4-hydroxytamoxifen, toremifene, 4- hydroxytoremifene, clomifene and droloxifene were tested for clastogenic effects in a human lymphoblastoid cell line (MCL-5) expressing elevated native CYP1A1 and containing transfected CYP1A2, CYP2A6, CYP2E1 and CYP3A4 and epoxide hydrolase and in a cell line containing only the viral vector (Ho1). MCL-5 or Ho1 cells were incubated with 4-hydroxytamoxifen, 4-hydroxytoremifene, clomifene or droloxifene and the incidence of micronuclei estimated. With MCL-5 cells there was an increase in micronuclei with 4-hydroxytamoxifen, 4- hydroxytoremifene and clomifene but not with droloxifene. With Ho1 cells only 4-hydroxytamoxifen and 4-hydroxytoremifene caused an increase in micronuclei. MCL-5 cells were incubated with tamoxifen, 4- hydroxytamoxifen, toremifene, droloxifene, clomifene or diethylstilbestrol (0.25-10 microg/ml) for 48 h and subjected to 3 h treatment with vinblastine (0.25 microg/ml) to arrest cells in metaphase. The incidence of cells with chromosomal numerical aberrations (aneuploidy) was increased in cells treated with tamoxifen, 4-hydroxytamoxifen, toremifene, clomifene and diethylstilbestrol but not droloxifene. The frequency of cells with structural abnormalities (excluding gaps) was increased in cells treated with tamoxifen and toremifene but not 4-hydroxytamoxifen, clomifene, droloxifene or diethylstilbestrol. The clastogenic activities of tamoxifen (35 mg/kg), toremifene (36.3 mg/kg), droloxifene (35.2 mg/kg) and diethylstilbestrol (25 mg/kg) were compared in groups of four female Wistar rats. Each chemical was dissolved in glycerol formal, administered as a single dose by gavage and hepatocytes isolated by collagenase perfusion 24 h later. The cells were cultured in the presence of epidermal growth factor (40 ng/ml) for 48 h, colchicine (10 microg/ml) being added for the final 3 h of incubation. At least 100 chromosomal spreads were examined from each animal for the presence of numerical and structural abnormalities. The incidences of aneuploidy following treatment were: tamoxifen 81%, toremifene 46%, droloxifene 9.6%, diethylstilbestrol 45.7%, vehicle control 5.3%. The incidences of chromosomal structural abnormalities excluding gaps were: tamoxifen 4.3%, toremifene 0.8%, droloxifene 0.5%, diethylstilbestrol 0.8%, control 0.5%. The incidence of chromosomal structural aberrations excluding gaps in the treated animals was not statistically significantly different from controls except in the tamoxifen-treated group. Tamoxifen (35 mg/kg per os) and toremifene (36.3 mg/kg per os) were dosed to rats for 4 weeks and chromosomal spreads made from hepatocytes. The incidences of aneuploidy were: tamoxifen 94%, toremifene 57%, control 6.5%. The incidences of chromosomal aberrations excluding gaps were: tamoxifen 12%, toremifene 1%, control 0.5%. The incidence of tamoxifen-induced chromosomal structural abnormalities was significantly elevated compared with control levels. The results demonstrate that tamoxifen and toremifene are the only two drugs tested in the study that cause chromosomal structural and numerical aberrations in vitro and tamoxifen is the only drug that induces both these effects in rat liver cells stimulated to divide in culture following oral dosing. Since chromosomal mutations require cell division for their manifestation and tamoxifen is the only compound of those tested that causes hyperplasia in the rat liver, chromosomal aberrations and aneuploidy in the rat liver would only be expected to occur following treatment with tamoxifen alone, although aneuploidy could be induced by toremifene in conjunction with a promoter such as phenobarbitone.      

老年缺血性脑血管病血瘀证患者的红细胞变形性及一氧化氮水平的检测及其意义

目的 :探讨老年缺血性脑血管病血瘀证患者的红细胞变形性及一氧化氮 ( NO)水平的变化。方法 :检测 5 5例老年缺血性脑血管病血瘀证患者的红细胞变形指数和 NO的水平。其中短暂性脑缺血发作 ( TIA) 2 5例 ,脑梗死 3 0例 ;另设 2 6例正常对照组作对比观察。结果 :血瘀证 TIA患者红细胞变形指数 ( 0 .4 67± 0 .14 5 )显著低于正常对照组 ( 0 .5 0 8± 0 .14 1) ,P<0 .0 5 ,脑梗死患者红细胞变形指数 ( 0 .4 43± 0 .15 6)降低更为明显( P<0 .0 1) ;NO水平 ,TIA患者与正常对照组比较无显著性差异 ( 79.10± 15 .3 7比 76.70± 17.10 ) ,而脑梗死患者 ( 88.5 0± 13 .68)显著升高。结论 :红细胞变形性改变及 NO水平升高在一定程度上均参与了老年缺血性脑血管病血瘀证的发生发展     

Therapeutic potential of fish oil in the treatment of ulcerative colitis

In a pilot study six patients with active ulcerative colitis and six healthy controls were given fish oil (MaxEPA) containing 3-4 g of eicosapentaenoic acid daily for a period of 12 weeks. There was a significant improvement in the patients' symptoms and histological appearance of the rectal mucosa by the end of the treatment period. There was significant fall in neutrophil chemiluminescence during treatment in patients, whereas no change was observed in the control group. Neutrophil leukotriene B4 levels fell significantly during treatment. Serum from patients receiving fish oil was significantly less chemotactic for neutrophils compared with control serum. Eicosapentaenoic acid inhibited neutrophil chemotaxis and chemiluminescence in vitro. The omega-3 fatty acids, which occur naturally in fish oils, may exert a beneficial effect by decreasing the production of inflammatory mediators.     

Cutaneous calcinosis in erythromelanosis follicularis faciei et colli

A case of erythromelanosis follicularis faciei et colli is described which showed deposition of calcium in the lesional skin on the face.     

Improved Short-Term Outcomes of Primary Coronary Stenting Compared to Primary Balloon Angioplasty in Acute Myocardial Infarction at Experienced Centers: The PAMI Study Group Experience

To study the additive benefits of routine stent implantation in patients undergoing primary percutaneous transluminal coronary angioplasty (PTCA) at experienced centers, we compared the outcomes of the 982 patients undergoing PTCA for acute myocardial infarction (AMI) in the Primary Angioplasty in Myocardial Infarction-2 (PAMI-2) trial (only 1% of whom were stented) to the 312 patients in the PAMI Stent Pilot Trial (236 [76%] of whom were stented). The inclusion and exclusion criteria, PTCA methodology, and definitions used were prespecified to be identical between the two trials. Compared to the primary PTCA approach in PAMI-2, the strategy of stenting all eligible lesions in the PAMI Stent Pilot Trial was associated with reduced rates of in-hospital death (0.6% vs 2.7%, P = 0.03), reinfarction (1.3% vs 4.6%, P = 0.008), recurrent ischemia (3.5% vs 11.6%, P < 0.0001), target vessel revascularization (7.3% vs 11.4%, P = 0.04), and a shorter hospital stay (6.4 ± 4.4 vs 7.1 ± 6.2 days, P = 0.01). By multiple logistic regression analysis in 1,294 patients, stent implantation versus PTCA only was the strongest predictor of freedom from the composite in-hospital end point of death, reinfarction, or target vessel revascularization (TVR) (8.3% vs 15.0%, multivariate odds ratio = 0.4, P < 0.0001). These data strongly suggest that despite the excellent results achieved when primary PTCA is performed by experienced operators, the short-term outcomes of mechanical reperfusion can be further improved by a primary stent strategy.     

Glycemic Control of Surgical Patients. What is Correct,What is Not

Perioperative hyperglycemia is very common among critically ill patients with or without diabetes mellitus (DM). Perioperative elevated levels of blood glucose (BG) have been linked with increases in morbidity, infections, anastomotic failure, autoimmune dysfunction, and raised mortality and prolongation of hospitalization. A variety of different approaches have been taken for the control of BG in the perioperative period, and different methods of measurement have been proposed, among which, point of care (POC) meters, arterial blood gas analysis and venous plasma analysis prevail. The aim of this literature review was to provide evidence-based answers as to how BG levels should be monitored. We conclude that more conservative glycemic control is preferable to “tight glycemic control” (TGC), in order to avoid complications associated with episodes of hypoglycemia.     

The place of premedication in pediatric practice

Behind the multiple arguments for and against the use of premedication, sedative drugs in children is a noble principle that of minimizing psychological trauma related to anesthesia and surgery. However, several confounding factors make it very difficult to reach didactic evidence-based conclusions. One of the key confounding issues is that the nature of expectations and responses for both parent and child vary greatly in different environments around the world. Studies applicable to one culture and to one hospital system (albeit multicultural) may not apply elsewhere. Moreover, the study of hospital-related distress begins at the start of the patient's journey and ends long after hospital discharge; it cannot be focused completely on just the moment of anesthetic induction. Taking an example from actual practice experience, the trauma caused by the actual giving of a premedication to a child who absolutely does not want it and may struggle may not be recorded in a study but could form a significant component of overall effect and later psychological pathology. Clearly, attitudes by health professionals and parents to the practice of routine pediatric premedication, vary considerably, often provoking strong opinions. In this pro–con article we highlight two very different approaches to premedication. It is hoped that this helps the reader to critically re-evaluate a practice, which was universal historically and now in many centers is more selective.     

学龄前儿童普通话平均句子长度的多因素研究

【目的】探讨影响学龄前儿童普通话平均句子长度的因素,为促进儿童语言发育提供参考意见。【方法】以65名3~6岁学龄前儿童为研究对象并对其父母进行问卷调查。问卷内容包括儿童发育情况、家庭社会环境因素等39个变量。利用计算机程序计算每名儿童自然语言样本的平均句子长度。【结果】年龄、边看图书边自己讲述、父亲的文化程度、看广告、看电视后家长(或保姆)与儿童谈论电视内容与学龄前儿童平均句子长度呈正相关;边看图书边听家长讲述和语言障碍家族史与学龄前平均句子长度呈负相关。【结论】年龄、遗传因素和家庭语言环境为学龄前儿童语言发育的重要影响因素。