单硝酸异山梨酯片剂在健康人体的生物等效性

目的 研究单硝酸异山梨酯片的人体相对生物利用度和生物等效性.方法 健康志愿者18名,随机双交叉单剂量口服单硝酸异山梨酯片和参比制剂,剂量分别为40mg,剂间间隔为1周.分别于服药后24h内多点抽取静脉血;用高效液相色谱(HPLC)法测定血浆中单硝酸异山梨酯的浓度.用DAS药代动力学程序计算相对生物利用度并评价两种制剂生物等效性.AUC(0-24),AUC(0-∞)和Cmax经方差分析和双单侧t检验,Tmax进行秩和检验.结果 单剂量口服单硝酸异山梨酯片和参比制剂后,血浆单硝酸异山梨酯的Cmax分别为(424.28 43.09)μg·L-1和(442.48±57.78)μg·L-1;Tmax分别为(1.11±0.2)h和(1.06±0.24) h;AUC(0-24)分别为(2855.09±276.2)μg· h·L-1和(3028.28±296.0)μg· h·L-1;AUC(0-inf)分别为(3046.40±314.61)μgh·L-1和(3312.46±382.60)μg·h·L-1.AUC(0-24)、AUC(0-∞)、Cmax的90%可信区间分别为90.3%～98.5%、87.2%～97.1%和92.6%～99.9%.结论 试验与参比制剂的人体相对生物利用度为(94.79±10.14)%,2制剂具有生物学等效性.     

消旋卡多曲分散片人体相对生物利用度研究

[目的]使用HPLC-MS/MS法测定卡多曲血浆药物浓度并用于消旋卡多曲分散片人体相对生物利用度研究。[方法]采用24例健康男性志愿者随机交叉自身对照试验设计,受试者分别单剂口服国产消旋卡多曲分散片(受试制剂)400mg及消旋卡多曲颗粒(参比制剂)400mg后,用HPLC-MS/MS测定消旋卡多曲活性代谢物(Thiophine,TP)浓度,由DASver2.0程序进行生物等效性分析。[结果]24例受试者口服受试制剂消旋卡多曲分散片400mg与参比制剂400mg的AUC_(0～11)分别为(2132.8±439.6)h.μg.L~(-1)及(2384.7±615.3)h.μg.L~(-1),其相对生物利用度(F_(0～11))为(92.7±23.2)%,C_(max)分别为(661.6±158.4)μg.L~(-1)及(763.8±268.3)μg.L~(-1),T_(max)分别为(1.65±0.91)h及(1.83±0.91)h。[结论]消旋卡多曲分散片与参比制剂的AUC_(0～11)、C_(max)经双单侧t检验结果均无统计学意义,T_(max)经非参数法检验差异无统计意义。消旋卡多曲分散片与消旋卡多曲颗粒生物等效。     

罗红霉素片剂人体生物等效性研究

目的与已上市罗红霉素片为对照,考察另一国产制剂的人体生物等效性。方法18例健康受试者随机交叉单剂量口服两种制剂后,采用微生物法测定血浆中的药物浓度。结果经3P97程序拟合处理,二者的体内过程符合一室模型;试验制剂及参比制剂的罗红霉素实测平均血药峰浓度Cmax分别为(10.869±2.671)μg/ml和(11.250±3.097)μg/ml;实测平均达峰时间Tmax分别为(1.7±0.8)h和(1.6±0.8)h;t1/2(ke)分别为(13.407±2.391)和(12.496±2.231)h;血药浓度-时间曲线下面积AUC0-tn平均值分别为(127.097±32.971)μg·ml-1·h和(134.429±35.783)μg·ml-1·h;AUC0-∞平均值分别为(136.556±33.958)μg·ml-1·h和(143.483±38.052)μg·ml-1·h;试验制剂及参比制剂比较,罗红霉素的相对生物利用度F0-tn、F0-∞分别为(95.79±17.46)%、(96.58±16.66)%;对药动学参数AUC、Cmax、Tmax进行单因素方差分析及双单侧t检验,结果表明两制剂在处方与周期间P>0.05。结论试验与参比制剂的药动学参数具有生物等效性。     

非那雄胺国产与进口制剂生物利用度和生物等效性比较

对18名健康男性志愿受试者采用交叉试验,随机单剂量口服非那雄胺试验片、胶囊或参比片后,按时采集肘静脉血,用HPLC-MS法测定非那雄胺的血浆浓度。试验制剂AUC0→24,AUC0→∞,Cm ax经对数转换后进行双单侧t检验,AUC0→24,AUC0→∞,Cm ax的90%可信区间均落在参比片的80%~120%范围内;试验片和试验胶囊相对参比片的生物利用度分别为(101.5±11.0)%和(99.2±11.3)%。结果表明,试验制剂与参比制剂生物等效。     

高效液相色谱法考察头孢克肟的生物等效性

目的研究头孢克肟干混悬剂(代号A)、胶囊剂(代号B)和参比制剂(世福素,代号C)的人体生物等效性。方法采用高效液相色谱法测定18名健康受试者三交叉单剂量口服被试制剂或参比制剂200mg后血浆中头孢克肟的浓度。结果经三交叉生物利用度计算和生物等效性分析程序(BIO3)拟合,头孢克肟采用梯形法计算的A、B、C三者AUC0-t均值分别为(18.54±6.31)μg.h.mL-1、(16.10±5.51)μg.h.mLn-1和(17.16±5.96)μg.h.mLn-1;实测Cmax均值分别为(2.63±0.76)μg.mLn-1、(2.43±0.78)μg.mLn-1和(2.57±0.90)μg.mLn-1;实测Tmax均值分别为(4.11±0.58)h、(4.56±0.11)h和(4.56±0.70)h,头孢克肟干混悬剂、胶囊剂与参比制剂的相对生物利用度分别为(108.8±12.3)%和(95.7±15.9)%。结论经统计学分析,被试制剂A和参比制剂C、被试制剂B和参比制剂C具有生物等效性。     

兰索拉唑肠溶胶囊在健康人体的药代动力学和生物等效性

目的研究兰索拉唑肠溶胶囊在健康人体的药代动力学与相对生物利用度,评价其生物等效性。方法18名健康男性志愿者采用自身对照随机交叉给药方案,分别单次口服兰索拉唑受试制剂和参比制剂各30mg,HPLC法测定给药后不同时间点血浆中的药物浓度,比较两药主要药动学参数的差异,进行生物等效性评价。结果兰索拉唑受试制剂和参比制荆的药代动力学参数：Cmax分别为898．0±352．5μg·L-1、878．7±312．4μg·L-1;Tmax分别为2．5±0．7h、2．8±0．7h;AUC0→12分别为3515．2±2115．0μg·L-1、3539．9±2009．8μg·L-1;AUC0→∞分别为3678．3±2314．9μg·h·L-1、3777．0±2255．4μg·h·L-1：T1／2分别为1．9±0．5h、2．2±0．9h。与参比制剂相比,受试制剂的相对生物利用度（以AUC0→12作为评价依据）为98．0±9．7％。结论受试制剂与参比制剂为生物等效制剂。     

高效复合干扰素人体药动学及生物等效性的研究

[目的]以美国安进公司生产的干复津注射液(Infergen)为参比制剂,对四川辉阳生命工程股份有限公司研制的冻干重组高效复合干扰素粉针剂(rSIFN-co)人体药动学和生物等效性进行比较研究.[方法]对18名健康男性志愿受试者采用随机双交叉自身对照试验,受试者分别单剂皮下注射试验制剂9μg和参比制剂9μg后,用放射免疫法测定干扰素诱生的2',5',-寡腺苷酸合成酶(2'5'-0AS)浓度,由DAS verl.0程序计算药代动力学参数并进行生物等效性分析.[结果]试验制剂rSIFN-co 9μg峙与参比制剂lnfergen 9μg的AUC0-48分别为(4184.1±1938.7)pmol·h/dL,及(3336.8±1365.5)pmol·h/dL,Cmax分别为(204.42±100.16)pmol·dL-1及(271.77±150.53)pmol.dL-1,Tmax分别为(23.00±1.03)h及(23.22±1.0)h.参比制剂和试验制剂Tmax的差异无统计学意义(P=0.163),Cmax和AUC0-48差异有统计学意义(P=0.031,P=0.014),其相对生物利用度为125.4%.[结论]两制剂生物等效.冻干重组高效复合干扰素粉针剂(rSIFN-co)具有临床推广价值.     

双氯芬酸钠胶浆剂与栓剂治疗肾绞痛的对比研究

目的 比较双氯芬酸钠胶浆剂与栓剂治疗肾绞痛的效果.方法 将160例肾绞痛患者随机分为双氯芬酸钠胶浆剂组(双氯芬酸钠胶浆10 ml,肛门上5 cm处直肠内灌注)和双氯芬酸钠栓剂组(双氯芬酸钠栓50 mg,肛门上5 cm处直肠内塞入),每组80例,观察对比两组用药60min后的止痛效果.结果 双氯芬酸钠胶浆剂组止痛效果优于双氯芬酸钠栓剂组,总有效率分别为97.5%和77.5%(P＜0.01),显效率分别为92.5%和58.8%(P＜0.001).双氯芬酸钠胶浆剂组止痛持续时间为(18.2±4.5)h,长于双氯芬酸钠栓剂组的(12.0±3.6)h,P＜0.001.结论 双氯芬酸钠胶浆剂治疗肾绞痛疗效满意,优于双氯芬酸钠栓剂.     

双氯芬酸钠透皮控释制剂的研究

目的：探讨不同双氯芬酸钠透皮控释制剂对药物的影响。方法：采用正交设计实验,考察双氯芬酸钠制备过程中乙醇含量、磷脂浓度、柔性辅料的用量及超声处理时间等对包封率的影响;采用正交设计实验,考察丙烯酸树脂为主要成分、琥珀酸为交联剂、柠檬酸三乙酯为增塑剂制对体外透皮率和体外释药性的影响;采用健康大鼠进行药动学实验,研究双氯芬酸钠醇质体在大鼠体内的药动学特征和生物利用度。结果：乙醇含量(A)、磷脂浓度(B)、柔性辅料(D)的用量及超声处理时间(C)四个影响因素对透皮控释贴剂包封率的综合影响效果为B＞A＞C＞D,根据评分,得最佳处方为：A3B2C2D1;得出的最优处方组成为：双氯芬酸钠醇脂质体溶液含量10%、丙烯酸树脂Ⅳ号0.4g,柠檬酸三乙酯0.25g,琥珀酸0.052g,氮酮含量5%;计算得出双氯芬酸钠透皮控释贴剂的相对生物利用度为167.20%,说明采用本研究优化后工艺制备的双氯芬酸钠透皮控释贴剂具有较高的生物利用度。结论：双氯芬酸钠应用醇质体制成透皮控释制剂,透皮吸收的效果好,控释作用显著,相对生物利用度高。     

阿魏酸钠联合金水宝治疗2型糖尿病肾病临床疗效观察

目的 探讨阿魏酸钠注射液联合金水宝胶囊治疗2型糖尿病肾病的疗效.方法 2型糖尿病肾病患者178例按随机数字表法分为阿魏酸钠治疗组(对照组,87例)和阿魏酸钠联合金水宝治疗组(治疗组,91例).对照组应用阿魏酸钠注射液0.4 g+0.9％氯化钠注射液250ml,静脉滴注,每日一次;治疗组应用阿魏酸钠注射液0.4 g+0.9％氯化钠注射液250ml,静脉滴注,每日一次,同时口服金水宝胶囊,每次6粒,每日3次.疗程均为21 d.治疗前后观察两组尿白蛋白排泄率(UAER)、尿白蛋白/肌酐比值(ACR)变化情况.结果 对照组治疗后UAER、ACR水平均较治疗前有明显下降[(142.7±10.3μg/min比191.7±13.4μg/min、23.7±3.8 mg/g比28.7±3.8 mg/g),P＜0.05],治疗组治疗后UAER、ACR水平均较治疗前同样明显下降[(110.2±9.8)μg/min比(195.9±12.3)μg/min、(20.4±2.2) mg/g比(29.0±4.0) mg/g),P＜0.05],治疗后UAER、ACR水平治疗组与对照组比较差异有统计学意义(P＜0.05).结论 阿魏酸钠注射液联合金水宝胶囊治疗2型糖尿病肾病,可明显减少尿白蛋白的排泄,更好地保护肾脏功能.     

Calcium intake in the elderly: validation of a dietary questionnaire

Epidemiological studies of calcium and osteoporosis have been hampered by the lack of a suitable tool for assessing calcium intake. This report describes a new frequency and amount questionnaire for measuring present and past calcium intake in the elderly. The validity of the questionnaire was tested against two commonly used standards of dietary assessment, five-day duplicate diets and seven-day weighed dietary inventories. The resulting correlation coefficients were, respectively, r = 0.76 and r = 0.69, while that for repeatability was r = 0.84. Furthermore, the questionnaire categorized subjects into thirds of the distribution of intake with almost no gross misclassification. It is suggested that the present findings may be extended to the majority of normal, healthy elderly subjects, implying wide application for the questionnaire in the assessment of calcium intake in the elderly.     

The human drama of genetics: 'hard' and 'soft' media representations of inherited breast cancer

This paper examines media coverage of 'breast cancer genetics', and explores its implications for public understanding. We present a content analysis of coverage in British newspapers and look at a variety of popular forms, including women's magazines, television soap opera and radio drama. Genetic/inherited risk receives a great deal of coverage across a wide range of media formats and outlets. Much of this attention has focused on individuals from 'high risk families' and dilemmas around prophylactic mastectomies. Through examining media coverage, combined with interviews with media personnel and their sources, we show why this story proved so attractive to the media and highlight the different production values which influence coverage. Finally, we introduce preliminary findings from focus group discussions to demonstrate how such 'human interest' framing has engaged audience attention and influenced public understandings. The paper concludes by highlighting the implications for analysing, predicting, and engaging with, media representations of science.     

Worker education in the primary prevention of occupational dermatoses

This paper reports the evaluation of a skin care education programmeconducted on a fine chemicals manufacturing site where over1,000 employees are located. Approximately 60% are involvedin chemical manufacture. Over a 12 month period production staffreceived training in prevention of occupational dermatoses linkedto a site-wide poster initiative. The incidence of new casesof occupational dermatoses fell from 0.055 (70 cases in 1,277employees) to 0.021 (27 cases in 1,277 employees) before andafter the intervention respectively (p<0.0001). After otherfactors such as chemicals handled, observer bias and changesin reporting related to socioeconomic climate were taken intoaccount it is concluded that this study demonstrates the importanceof worker education as a tool for primary prevention of disease.Training materials such as video and poster presentations maybe effectively used in the chemical manufacturing industry asan adjunct to prevention and control of exposure to substanceshazardous to the skin. Such methods may also be used in otherindustries where there are significant risks of dermatoses.     

Regional Variation in Travel-related Illness acquired in Africa,March 1997–May 2011

To understand geographic variation in travel-related illness acquired in distinct African regions, we used the GeoSentinel Surveillance Network database to analyze records for 16,893 ill travelers returning from Africa over a 14-year period. Travelers to northern Africa most commonly reported gastrointestinal illnesses and dog bites. Febrile illnesses were more common in travelers returning from sub-Saharan countries. Eleven travelers died, 9 of malaria; these deaths occurred mainly among male business travelers to sub-Saharan Africa. The profile of illness varied substantially by region: malaria predominated in travelers returning from Central and Western Africa; schistosomiasis, strongyloidiasis, and dengue from Eastern and Western Africa; and loaisis from Central Africa. There were few reports of vaccine-preventable infections, HIV infection, and tuberculosis. Geographic profiling of illness acquired during travel to Africa guides targeted pretravel advice, expedites diagnosis in ill returning travelers, and may influence destination choices in tourism.     

Self-reported health problems among Swedish miners one year after unemployment

Unemployment is considered to be a public health concern sincedeterioration in the health of the unemployed is often anticipated.However, for some groups, such as miners, unemployment mightimprove health due to a cessation of potentially harmful occupationalexposures. This study evaluates the health of 79 miners in oneSwedish iron-ore mine, and 226 age-matched controls from thegeneral population, during one year after the closure of themine. The participants received a questionnaire regarding medicalhistory and subjective symptoms at the beginning of the studyperiod, and after one year. Statistically significant negativeeffects on self-reported health attributable to unemploymentwere not found, although neuropsychiatric symptoms were morecommon among the unemployed miners. The miners reported a statisticallysignificant improvement in grip force (p=0.031). They had asignificantly higher prevalence of symptoms associated withmining related exposures when compared with the population controls;pain in the upper extremities [relative risk (RR)=2.27, 95%confidence interval (Cl)=1.44–3.59), back pain (RR=1.84;Cl=1.237–2.75), vasospastic disease of the fingers (RR=2.05;Cl=1.18–3.57) and obstructive respiratory symptoms (attacksof dyspnea and wheezing: RR=3.67; Cl=1.167–11.6).     

Excès de cas humains et animaux de tularémie en France au cours de l’hiver 2007–2008 : émergence ou phénomène isolé ?

Context

Tularemia is a zoonosis affecting humans and hares in France. We describe the results of surveillance in both species, in 2007 and 2008.

Methods

Human tularemia cases are mandatorily notifiable in France since 2003. In hares, surveillance relies on volunteer hunter associations in all districts of the country. Data from mandatory reports and volunteer surveillance in 2007/2008 were analyzed and compared with previous results.

Results

In 2007/2008, 144 cases were reported in humans and 117 cases in hares. This was a 100% increase compared to previous years. Human cases differed from those of previous years only by the frequency of contact with breeding animals. Human cases without any documented risk exposure were also more frequent.

Conclusion

An increase of tularemia cases occurred in 2007/2008 in both species. Complementary studies are needed to identify the species reservoir in France to understand the causes of this peak of cases.     

深圳公立医院管理体制改革制度设计

深圳公立医院管理体制改革实行政事分开、管办分开,在理事会架构下按法定机构模式组建市医管中心,落实公立医院运营管理自主权.作者从当前公立医院管理体制的弊端入手,介绍了深圳市进行公立医院管理体制改革的基本思路及改革方案设计的主要举措,深入剖析了的改革方案的特点,并对改革效果进行了预测.     

Effects of nitrogen dioxide on red blood cells of rats: Changes in components of red cell membranes during in vivo exposure to NO2

Red cell membranes, prepared from red blood cells of rats exposed to 4, 10, or 20 ppm nitrogen dioxide (NO₂) for 1 to 10 days, were examined for evidence of changes in membrane components. Appreciable changes were not found in contents of phospholipid and cholesterol during exposure to 10 ppm NO₂. By contrast, protein content altered with the time of exposure. Moreover, changes in protein composition were observed by employing sodium dodecyl sulfate — polyacrylamide gel electrophoresis. Twenty-four-hour exposure to NO₂ at the concentration above 10 ppm resulted in a marked increase in the percentage of lysophosphatidylethanolamine (LysoPE) to the total phospholipids. The prolonged exposure to 10 ppm NO₂ gave rise to a further increase in LysoPE, whereas the percentage of phosphatidylethanolamine (PE) showed a gradual decrease. A 1-day exposure to 4.0 ppm NO₂ also caused an increase in sialic acid content and decreases in those of PE and hexose. In addition to contents of these components the percentage of LysoPE increased 5 days after exposure and the elevated values were maintained up to the end of exposure period. These results demonstrate that red blood cells in circulation exhibit different membrane properties in terms of lipid and carbohydrate composition during 10 days of exposure to 4.0 ppm NO₂.     

The design of hazard risk assessment matrices for ranking occupational health risks and their application in mining and minerals processing

Two hazard risk assessment matrices for the ranking of occupational health risks are described. The qualitative matrix uses qualitative measures of probability and consequence to determine risk assessment codes for hazard-disease combinations. A walk-through survey of an underground metalliferous mine and concentrator is used to demonstrate how the qualitative matrix can be applied to determine priorities for the control of occupational health hazards. The semi-quantitative matrix uses attributable risk as a quantitative measure of probability and uses qualitative measures of consequence. A practical application of this matrix is the determination of occupational health priorities using existing epidemiological studies. Calculated attributable risks from epidemiological studies of hazard-disease combinations in mining and minerals processing are used as examples. These historic response data do not reflect the risks associated with current exposures. A method using current exposure data, known exposure-response relationships and the semi-quantitative matrix is proposed for more accurate and current risk rankings.