注射用阿奇霉素致儿童不良反应1997～2007年国内文献分析

目的:探讨注射用阿奇霉素致儿童不良反应(ADR)发生情况,为临床合理用药提供参考。方法:通过中国知网(CNKI)的中国医院知识仓库(CHKD)期刊全文数据库检索到1997～2007年国内有关儿童(≤16岁)应用注射用阿奇霉素致ADR的符合条件的文献249篇,其中临床应用220篇,个案报道29篇,按文献地区分布、性别与年龄分布、疾病种类、用法与用量、不良反应累及器官或系统及临床表现、发生时间等进行统计、分析。结果:文献分布于全国34个省、市;记载不良反应并分类的167篇9661例中,有ADR1199例,ADR发生率为12.41%;ADR类型主要有皮肤及其附件损害、消化系统损害、神经系统损害等。结论:注射用阿奇霉素对儿童是安全的,如需长疗程使用宜采用"用3停4"的方法,并注意监测肝、肾功能及听力等的变化。     

中国四地区凉拌菜中E.coli O157∶H7调查分析

目的通过对我国中南、华东、东北和西北各地区凉拌菜E.coli O157∶H7监测,了解我国凉拌菜E.coli O157∶H7的污染状况,为食源性疾病的控制提供良好的科学依据。方法采集各地区凉拌菜样本,经mEC肉汤、改良麦康凯肉汤增菌、mini-VIDAS免疫检测快速筛选和免疫磁珠富集后,接种改良山梨醇麦康凯琼脂和CHROmagar O157显色培养基分离,最后进行生化和血清学鉴定。结果在采集的1080份凉拌菜样本中检出3株E.coli O157∶H7阳性或疑似菌株。结论肉类和果蔬类凉拌菜均存在E.coli O157∶H7污染的潜在威胁;县乡级食品卫生监督工作亟需加强。     

Safety assessment of personal care products/cosmetics and their ingredients

We attempt to review the safety assessment of personal care products (PCP) and ingredients that are representative and pose complex safety issues. PCP are generally applied to human skin and mainly produce local exposure, although skin penetration or use in the oral cavity, on the face, lips, eyes and mucosa may also produce human systemic exposure. In the EU, US and Japan, the safety of PCP is regulated under cosmetic and/or drug regulations. Oxidative hair dyes contain arylamines, the most chemically reactive ingredients of PCP. Although arylamines have an allergic potential, taking into account the high number of consumers exposed, the incidence and prevalence of hair dye allergy appears to be low and stable. A recent (2001) epidemiology study suggested an association of oxidative hair dye use and increased bladder cancer risk in consumers, although this was not confirmed by subsequent or previous epidemiologic investigations. The results of genetic toxicity, carcinogenicity and reproductive toxicity studies suggest that modern hair dyes and their ingredients pose no genotoxic, carcinogenic or reproductive risk. Recent reports suggest that arylamines contained in oxidative hair dyes are N-acetylated in human or mammalian skin resulting in systemic exposure to traces of detoxified, i.e. non-genotoxic, metabolites, whereas human hepatocytes were unable to transform hair dye arylamines to potentially carcinogenic metabolites. An expert panel of the International Agency on Research of Cancer (IARC) concluded that there is no evidence for a causal association of hair dye exposure with an elevated cancer risk in consumers. Ultraviolet filters have important benefits by protecting the consumer against adverse effects of UV radiation; these substances undergo a stringent safety evaluation under current international regulations prior to their marketing. Concerns were also raised about the safety of solid nanoparticles in PCP, mainly TiO₂ and ZnO in sunscreens. However, current evidence suggests that these particles are non-toxic, do not penetrate into or through normal or compromised human skin and, therefore, pose no risk to human health. The increasing use of natural plant ingredients in personal care products raised new safety issues that require novel approaches to their safety evaluation similar to those of plant-derived food ingredients. For example, the Threshold of Toxicological Concern (TTC) is a promising tool to assess the safety of substances present at trace levels as well as minor ingredients of plant-derived substances. The potential human systemic exposure to PCP ingredients is increasingly estimated on the basis of in vitro skin penetration data. However, new evidence suggests that the in vitro test may overestimate human systemic exposure to PCP ingredients due to the absence of metabolism in cadaver skin or misclassification of skin residues that, in vivo, remain in the stratum corneum or hair follicle openings, i.e. outside the living skin. Overall, today's safety assessment of PCP and their ingredients is not only based on science, but also on their respective regulatory status as well as other issues, such as the ethics of animal testing. Nevertheless, the record shows that today's PCP are safe and offer multiple benefits to quality of life and health of the consumer. In the interest of all stakeholders, consumers, regulatory bodies and producers, there is an urgent need for an international harmonization on the status and safety requirements of these products and their ingredients.     

Genotoxicity studies on fucoidan from Sporophyll of Undaria pinnatifida

The sulfated seaweed extract, fucoidan, has anticoagulant, antithrombotic, and antiviral activities. Despite extensive work on the biological activities of fucoidan, detailed studies on the genotoxicity of fucoidan from Sporophyll of Undaria pinnatifida sources have not been tested before. The objective of this study was to investigate the genotoxicity effects of fucoidan extracted from Sporophyll of U. pinnatifida using a test battery of three different methods. In a reverse mutation assay using four Salmonella typhimurium strains and Escherichia coli, fucoidan did not increase the number of revertant colonies in any tester strain regardless of metabolic activation by S9 mix, and did not cause chromosomal aberration in short tests with S9 mix or in the continuous (24 h) test. A bone marrow micronucleus test in ICR mice dosed by oral gavage at doses up to 2000 mg/kg bw/day showed no significant or dose-dependent increases in the frequency of micronucleated polychromatic erythrocytes (MNPCE), and the high dose suppressed the ratio of polychromatic erythrocytes (PCE) to total erythrocytes. We conclude that fucoidan presents no significant genotoxic concern under the anticipated conditions of use.     

Scientific evaluation of the chronic toxicity of the herbal medicine CGX in beagle dogs

CGX is a potential hepatoprotective herbal medicine used to treat various chronic liver disorders. The purpose of the study was to evaluate the pharmaceutical safety of CGX via a systemic 13-week repeated dose toxicity test in beagle dogs. Male and female beagle dogs were divided into four groups and two animals each from the control and high-dose group (400 mg/kg) were allocated into recovery groups. The dogs were administered with CGX (0, 100, 200, 400 mg/kg) for 13 weeks. During the experimental period, the dogs were observed for signs of gross toxicity and for behavioral changes; body weight and food consumption were measured. An ophthalmologic examination and urinalysis were performed at 0 and 13th week and blood biochemistry and hematological parameters analyses were performed at 0, 6th, and 13th week. A histopathological examination was also performed at the end of the experiment. There were no CGX-induced abnormalities in clinical signs, organ weights, food consumption, hematological, urine, and blood biochemical parameters, or histopathological findings in any of the groups during or after the 13 weeks. We demonstrated the safety of CGX for 13-week repeated dose and considered that it is safe for chronic clinical use.     

Acute and repeated dose (4 weeks) oral toxicity studies of two antihypertensive peptides,RYLGY and AYFYPEL,that correspond to fragments (90–94) and (143–149) from αs1-casein

The Lowpept® is a powdered casein hydrolysate containing the antihypertensive peptides RYLGY and AYFYPEL, two sequences that correspond to α_s1-casein f (90–94) (RYLGY) ¹ and α_s1-casein f (143–149) (AYFYPEL) ¹. To support the safety, Lowpept® has been examined in an acute and in a 4-week repeated dose oral toxicity studies in rats. Powdered casein hydrolysate administered in a single oral gavage dose of 2000 mg/kg resulted in no adverse events or mortality. Also, casein hydrolysate administered as a daily dose of 1000 mg/kg for 4 weeks by gavage resulted in no adverse events or mortality. No evidence or treatment-related toxicity was detected during both studies. Data analysis of body weight gain, food consumption, clinical observations, blood biochemical, haematology, organ weight ratios and histopathological findings did not show significant differences between control and treated groups. It is concluded that the casein hydrolysate containing the peptides RYLGY and AYFYPEL orally administered to rats was safe and that not treatment-related toxicity was detected even at the highest doses investigated in both acute (2000 mg/kg of body weight) and repeated dose (4 weeks) oral (1000 mg/kg of body weight) toxicity studies.     

雷公藤多甙片联合地氯雷他定治疗慢性特发性荨麻疹疗效观察

目的观察雷公藤多甙片联合地氯雷他定治疗慢性特发性荨麻疹的临床疗效和安全性。方法共入选180例患者,将其随机分成两组,每组各90例,治疗组予雷公藤多甙片10mg口服,3次/d,地氯雷他定5mg口服,1次/d,均连用28天;对照组仅予地氯雷他定5mg口服,1次/d,连用28天。结果治疗第7天时治疗组有效率为69.77%,对照组为54.02%;第14天时治疗组有效率82.56%,对照组59.77%;第28天时治疗组有效率93.02%,对照组67.82%。两组患者在治疗第7,14和28天时有效率比较,差异均有统计学意义(P均<0.05)。患者主观生活质量评估在治疗14天后DLQI和睡眠情况改善明显好于对照组,28天后DLQI、睡眠情况和日常活动评分也明显好于对照组(P均<0.05)。不良反应:治疗组发生率为8.14%,对照组为6.90%,两组差异无统计学意义。停药6周后进行随访和复诊,试验组复发率低于对照组,差异有统计学意义(P<0.05)。结论雷公藤多甙片联合地氯雷他定治疗慢性特发性荨麻疹的临床疗效比单纯应用地氯雷他定治疗的疗效好,停药后复发率低。     

如何制定临床试验的数据和安全监察计划

在临床试验中实施数据和安全监察是为了确保参加临床试验的受试者安全和采集的数据有效、完整、准确,每一个临床试验都有必要制定数据和安全监察计划,并经伦理委员会批准。数据和安全监察计划的内容包括方案概要、试验管理、数据管理和分析、质量保证、法规、试验安全、试验的有效性、数据和安全监察计划的实施、必要时制定数据和安全监察委员会计划。制定数据和安全监察计划时需要考虑试验的风险、研究期、试验设计、干预研究的疾病/症状、研究人群、干预措施、终点/结果指标等,监察的程度需与试验的风险、规模和复杂程度一致。     

Excluding pulmonary embolism at the bedside with low pre-test probability and D-dimer: safety and clinical utility of 4 methods to assign pre-test probability

INTRODUCTION: Less than 35% of patients suspected of having pulmonary embolism (PE) actually have PE. Safe bedside methods to exclude PE could save scarce health care resources if they exclude large proportions of patients with suspected PE and are widely applicable. Non-Elisa D-dimer in combination with pre-test probability of suspected PE can safely exclude PE at the bedside. Pre-test probability can be assigned by gestalt or by using clinical models (Wells, Wicki, Rodger). MATERIALS AND METHODS: We combined two databases from studies of patients with suspected PE and retrospectively compared the diagnostic test characteristics of the different methods of assigning pre-test probability. RESULTS: 535 patients were studied. PE was confirmed in 20.8% of study patients. Two clinical predictive models (Rodger and Wells) and overall diagnostic impression have similar sensitivities ranging from 96% (95% confidence interval (CI) 89-99%) to 99% (93-100%). Wicki's model has a sensitivity of 89% (77-96%). The Wells' model with a cutoff of less than 2 points in association with semi-quantitative D-dimer has a specificity of 11% (CI 7-15%). The specificities for the other clinical predictive model are ranging from 21% (17-25%) to 49% (CI 42-55%). CONCLUSION: Semi-quantitative D-dimer must be combined with safe clinical probability assessment to safely exclude PE in a significant proportion of patients. Wicki's model in association with semi-quantitative D-dimer has the lowest sensitivity and should be used carefully to exclude PE at the bedside. The Wells' model with a cutoff of less than 2 points when combined with semi-quantitative D-dimer excluded very few patients and therefore limits its clinical utility.