Synthesis and cytotoxicity of the dihydrated complex of oxaliplatin

A new way of synthesizing the dihydrated oxaliplatin complex (DOC) is presented and its cytotoxicity is compared to that of oxaliplatin and cisplatin. By hydrolyzing oxaliplatin in aqueous sodium hydroxide at 70°C, DOC was formed in less than 1 h. Cytotoxicity was studied in the non-small cell lung cancer cell line A549 using the fluorescent microculture cytotoxic assay. Oxaliplatin and cisplatin had similar cytotoxicity profiles, whereas DOC was found to be considerably more toxic. The cytotoxicity of oxaliplatin might, at least in part, be mediated through the formation of DOC.     

Pharmacoepidemiologic implications of erroneous varicella vaccinations in pregnancy through confusion with Varicella zoster immune globulin

A series of case reports to the varicella vaccine Pregnancy Registry described inadvertent administrations during pregnancy of this live virus product instead of the intended Varicella zoster immune globulin. Cases continued to accrue despite an early publication about the pattern. The persistent problem warrants specific educational efforts to prevent further repetitions. It also has more general implications for medical product safety surveillance. First, this problem's original detection depended on the Pregnancy Registry's open-ended collection of information about pregnancy exposures. It could have escaped recognition through surveillance limited to pre specified potential risks. This need for unrestricted reporting and human vigilance to sift through case stories has particular relevance for efforts to re-think methods to monitor gestational drug exposures. In addition, the problem's persistence despite initial publicity suggests that diligent surveillance may require continued follow-up of identified safety issues. Periodic reassessments of selected preventable problems might strengthen efforts to minimize product risks.     

Botanical health products, positioning and requirements for effective and safe use

Within the group of botanical products there is a large range of variation with regard to their properties. Some products are identical to foods while others come close to or are medicines. Botanical products are regulated differently within the different member states of the European Union (EU) and globally. They are regulated either as food or as medicinal products, and in the latter case often with simplified registration procedures. These differences are caused by differences in traditional use, in cultural and historical background, in scientific substantiation and in enforcement of current legislation. One may expect that in the future differences will remain, unless EU legislation is enacted with sufficient room for different approaches. The strengths and weaknesses of the different regulatory procedures have been reviewed and evaluated as well as the current methods for quality, efficacy and safety evaluation. Criteria to categorize botanical products have been defined, such that botanical products can be regulated under the current food and medicinal regulations. Furthermore, a decision tree has been developed as a tool to distinguish herbal medicinal products from botanical health products and vice versa, and to provide a stepwise framework for the assessment of safety and efficacy.     

Infant-furniture-related injuries among preschool children in New Zealand, 1987-1996

OBJECTIVE: To describe the epidemiology of infant-furniture-related fatalities and hospitalizations in New Zealand, for children aged 0-4 years. METHODS: Infant-furniture-related deaths and hospitalizations were selected from the New Zealand Health Information Service databases for the 10-year period 1987-1996. Intentional injuries were excluded. RESULTS: Forty-three fatalities were identified. Twenty-two fatalities (51%) occurred in cots, while 13 (30%) occurred in beds. Other products involved were prams, push chairs, high chairs, car seats, portable cots and walkers. A total of 1679 infants were hospitalized through infant-furniture-related injuries. Increasing trends in hospitalizations for baby walkers, beds and bunks were observed. CONCLUSIONS: On average, four infants die each year from injuries related to infant furniture, and hospitalizations from injuries associated with infant furniture use are increasing. Mandatory standards are one measure to reduce these numbers, but education is also necessary.     

Proactive safety surveillance

Growth in health information systems presents opportunities to enhance postmarketing safety surveillance of medical products. Spontaneous suspected side effect reports provide the foundation, but we need to 'proactively' improve their quality and our strategies to seek signals. In our more familiar 'reactive' mode, we examine hypotheses from inquiries or publicity. Such responsive evaluations remain essential but may miss latent information on unsuspected risks. Efficient techniques to disclose hidden clusters and associations may emerge through adaptation of approaches from industrial quality control and other disciplines. Data-driven techniques like exploratory analysis, control charts, and time series modeling may help in sifting through accumulated data and in screening consecutive submissions to discern hints of new product hazards or of more specific understanding about previously identified potential side effects. We also need to cultivate non-spontaneous data for hypothesis generation as well as testing, the systematic epidemiologic evaluation of questions and concerns. This hypothesis testing function will assume greater importance if proactive safety surveillance methods yield larger numbers of putatively positive findings. Whether from spontaneous reports or other sources, signals that could have arisen by chance alone usually represent only clues to potential hazards until or unless they can be verified through independent studies.     

LC-MS/MS法检测西维来司他原料药中的降解产物

目的：探讨应用液相色谱-串联质谱法（LC-MS/MS）检测西维来司他原料药中的降解产物.方法：以乙腈-水-甲酸（40：60：0.1）为流动相,待测物经Hypersil C18柱分离,电喷雾串联质谱在线检测,获得相关的色谱和质谱信息.结果：在所应用的条件下,西维来司他与其降解产物达到了很好分离,主成分和其降解产物峰的保留时间分别为18.46和3.36min,同时通过两者的质谱特征获得了降解产物的结构信息.结论：所建立的方法能快速、准确地分离鉴定西维来司他原料药中的降解产物,从而可以对其原料药进行质量控制.     

Retinoblastoma Gene Product and P21 (WAF1, CIP1) Protein Expression in Non Hodgkin's Lymphomas: A Multivariate Survival Analysis

We evaluated immunohistochemically the expression of two negative regulators of the cell cycle, namely retinoblastoma gene product (pRb) and WAF1/Cip1 gene product (p21), in paraffin sections from 93 patients with non-Hodgkin's lymphomas (NHL) and related it to clinicopathological parameters, proliferative fraction, p53 expression and survival. Patients were followed until death (n=33) or for an average of 52 months (60-160). Rb labelling index (LI) increased with malignancy grade and proliferative activity but was unrelated to other clinicopathological parameters. In 33% of cases, especially those of the aggressive groups, we observed diminished pRb expression (i.e. low pRb/Ki-67 ratio). p21 expression on the other hand correlated only with histological grade, Rb LI and p53 LI. In multivariate analysis, Rb LI was a negative predictor of disease-free survival but was linked to a higher probability of complete response. However, diminished pRb expression as well as p21 expression were not statistically significant prognostic indicators. Our results suggest that pRb as a cell cycle related molecule may play an important role in determining prognosis and therapeutic response in NHL patients.     

美国FDA《植物药品产业指南》的技术要求与我国中药新药技术要求的比较研究

本文通过将美国FDA于2000年8月10日发布的《植物药产业指南》与我国中药新药审批技术要求进行对照,指出在植物药新药审批方面SDA与FDA的异同。并对中药作为药品进入美国市场提出了一些有价值的建议。     

天麻饮片中天麻素的含量测定方法的研究

目的测定天麻饮片中天麻素的含量.方法采用高效液相色谱法.色谱柱为Hypersil C18柱(300×4.6mm,10μm),流动相为乙腈-甲醇-磷酸盐缓冲液-水(101530945),流速1mL·min-1,检测波长为220nm.结果天麻素在0.7～3.8μg范围内呈良好的线性关系,平均加样回收率为97.66%,RSD=2.2%(n=5).结论含量测定方法快速、准确.适用于天麻中天麻素的含量测定.     

S市水质有机物成分分析及遗传毒性研究

分别采集S市两处自来水厂入口处源水与自来水各120L,经XAD－2树脂柱收集其中的有机物,采用GC／MS定性与定量分析有机物成分,同时采用Ames与小鼠骨髓微核试验从基因水平与染色体水平检测其遗传毒性,结果源水与自来水均检出多种有机物,自来水中有机物种类较源水为少。遗传毒性试验表明源水与自来水有不同程度的致突变性,且自来水较源水为强,两种试验结果之间有一定的相关性,说明S市水质受到一定程度的有机物污染,氯化消毒可使水质遗传毒性增加,其机理可能与氯化消毒副产物有关。