神经外科术后患者静脉输注去甲万古霉素后血清及脑脊液药物浓度

目的了解神经外科术后患者静脉输注去甲万古霉素后血清及脑脊液内药物浓度变化特点。方法选择2014年某院神经外科手术后留置术区/脑室引流管的患者,按给药方式不同分为2组,各12例,常规给药组:去甲万古霉素0.8 g,泵入60 min,12 h重复给药;持续给药组:去甲万古霉素0.8 g,泵入60 min,再0.4 g泵入11 h,后以0.4 g持续泵入12 h,于给药后不同时间点采集患者血清和脑脊液标本,测定去甲万古霉素浓度。结果常规给药组与持续给药组去甲万古霉素血清峰浓度分别为(55.52±26.04)、(59.22±41.88)mg/L,给药24 h血清浓度分别为(8.21±6.04)、(9.11±5.09)mg/L;脑脊液峰浓度分别为(16.31±11.15)、(8.82±8.91)mg/L,给药24 h脑脊液浓度分别为(6.12±2.34)、(5.71±4.72)mg/L。常规给药组药物脑脊液穿透率以药物浓度曲线下面积比计算(AUC_(脑脊液)/AUC_(血清))0~12 h为63.3%,12~24 h为59.0%;持续给药组0~12 h为25.4%,0~24 h为47.4%。以目标细菌MRSA95%的最低抑菌浓度(MIC_(90))为2 mg/L计算,常规给药组AUC_(0-24)/MIC_(90)为192,持续给药组AUC_(0-24)/MIC_(90)为184。结论神经外科术后患者早期使用标准剂量去甲万古霉素,常规及持续给药脑脊液内药物浓度均可达目标细菌的MIC_(90)。     

阿立哌唑片在健康人体内的药代动力学研究

目的:建立测定阿立哌唑血浆药物浓度的HPLC-UV检测法,研究国产阿立哌唑片在人体的药代动力学。方法:14名健康志愿受试者多剂量口服国产阿立哌唑片20mg,采用HPLC法测定给药后不同时间点血浆中阿立哌唑浓度,用DAS1.0处理经时血药浓度数据,计算主要药代动力学参数。结果:多次口服阿立哌唑片共14 d达稳态,稳态血药浓度期间给药后(4.0±0.9)h达到峰浓度(480.3±126.2)μg.L-1,AUC0-360 h为(38166.6±13241.2)μg.h.L-1,t1/2β为(91.0±21.1)h,CL/F和V/F分别为(0.62±0.36)L.h-1和(60.9±43.7)L。结论:国产阿立哌唑的血药浓度一时间曲线符合二室开放模型,为今后的合理用药打下基础。     

鞘内注射亚胺培南/西司他丁在家兔体内的药代动力学实验研究

目的研究鞘内注射亚胺培南/西司他丁后家兔体内的药代动力学特点。方法家兔用20.0%乌拉坦耳缘静脉麻醉,给药方式为鞘内注射和静脉给药两种,每种给药方式分为低(0.35mg/kg)、中(0.7mg/kg)、高(1.4mg/kg)3种剂量组,亚胺培南/西司他丁组给药后于0、15、30min、1、2、4、8、12、24h抽取小脑延髓池脑脊液,并测定中剂量组给药后15min、2、8h的组织分布;HPLC测定脑脊液及组织中亚胺培南/西司他丁的浓度,DAS软件分析药代动力学参数。结果鞘内注射低、中、高剂量的亚胺培南/西司他丁后,脑脊液中药物分布半衰期(t1/2α)分别为(27.56±7.25)、(27.22±5.7)、(28.08±8.37)h,消除半衰期(t1/2β)分别为(26.67±3.58)、(28.23±9.23)、(29.94±6.21)h;静脉给药3种剂量后,脑脊液中药物分布半衰期分别为(6.88±0.55)、(8.25±0.24)、(7.34±0.21)h,消除半衰期(t1/2β)分别为(6.96±0.94)、(8.28±0.22)、(7.37±0.24)h;鞘内注射3种剂量后,表观分布容积(V1/F)分别为(2.58±0.42)、(2.35±0.9)、(5.13±0.63)L/kg,静脉给药3种剂量后,表观分布容积分别为(3.10±0.53)、(5.49±0.44)、(9.77±0.72)L/kg;鞘内注射3种剂量后,清除率(CL/F)分别为(0.04±0.02)、(0.08±0.01)、(0.18±0.04)L/(kg.h);静脉给药3种剂量后,清除率分别为(0.29±0.06)、(0.32±0.03)、(0.58±0.06)L/(kg.h);鞘内注射3种剂量后,曲线下面积(AUC(0-∞))分别为(9.24±0.81)、(9.8±0.69)、(10.98±0.23)mg/(L.h);静脉给药3种剂量后,曲线下面积(AUC(0-∞))分别为(1.26±0.34)、(2.21±0.19)、(2.42±0.25)mg/(L.h);鞘内给药后,心、肾、肺、脾、胃及脂肪等脑外组织药物含量2h达到峰浓度,肝、肠及肌肉组织8h药物浓度达高峰,静脉给药后,心、肝、肾、肺、脾、胃、肌肉及脂肪等脑外组织药物含量15min达到峰浓度,肠2h药物浓度达高峰,鞘内给药15min,脑组织中药物峰浓度是静脉给药的3倍。结论与静脉给药相比脑脊液中药物分布半衰期和消除半衰期延长,表观分布容积和清除率减小,曲线下面积增大;脑组织中药物峰浓度高。     

神经外科术后患者静脉输注替考拉宁脑脊液药物浓度研究

目的了解神经外科术后患者静脉输注替考拉宁时脑脊液药物浓度,探讨神经外科手术破坏血脑屏障后是否可增加脑脊液药物浓度,以及药物持续泵入对脑脊液药物浓度的影响。方法选择神经外科术后留置术区/脑室引流管的患者,分为常规给药组(替考拉宁400 mg,30 min泵入,1次/12 h重复给药)和持续给药组(替考拉宁400 mg,30 min泵入,再以200 mg,1次/6 h持续泵入),于给药后相应时间点采集脑脊液标本检测替考拉宁浓度。结果常规给药组脑脊液替考拉宁浓度泵入后即刻浓度为(0.004±0.0123)mg/L,泵入后1 h达峰值(0.712±1.028)mg/L,后逐渐下降,泵入后12、18、24 h分别为(0.254±0.222)、(0.173±0.152)、(0.355±0.207)mg/L。持续给药组脑脊液替考拉宁泵入后即刻浓度为(0.017±0.020)mg/L,4 h后达峰值(0.587±0.255)mg/L,泵入后6、12、18、24 h分别为(0.429±0.416)、(0.325±0.254)、(0.476±0.686)、(0.318±0.464)mg/L,6 h后药物浓度相对稳定,介于(0.318±0.464)~(0.476±0.686)mg/L。常规给药组、持续给药组的AUC0—24 h分别为5.590 mg/L·h、9.082 mg/L·h。两组患者仅峰值附近区域替考拉宁浓度达到凝固酶阴性葡萄球菌(CNS)MIC50,但其浓度高于CNS MIC50的时间占整个给药时间的比例远小于50%;两组患者脑脊液替考拉宁浓度均未能达到金黄色葡萄球菌MIC50。结论持续输注替考拉宁后,患者脑脊液药物浓度较常规给药组有所增加,但仍未能达所要求的MIC;结合血药浓度的实验,血液浓度增高有利于脑脊液药物浓度增加,可考虑适当增加剂量以达到临床治疗目的。     

羊栖菜多糖复方对雄性小鼠免疫及生殖器官辐射伤的防护

目的观察羊栖菜多糖复方制剂对γ射线损伤雄性小鼠免疫器官及生殖器官的防护作用。方法将50只雄性小鼠随机分为正常对照组、模型组及低〔0.692 g/(kg.d)〕、中〔2.075 g/(kg.d)〕、高〔4.150 g/(kg.d)〕3个剂量羊栖菜多糖复方制剂组(SFPCP),每天1次灌胃给药,灌胃2周后,除正常对照组外,各组均以剂量率为0.83 Gy/h的60Coγ射线进行1次全身照射6 h,照射剂量为5 Gy。于照前1 d,照后3 d、14 d测定外周血白细胞数,照后14 d测定小鼠胸腺指数、脾指数、骨髓有核细胞数(BMNC)、睾丸质量指数、精子总数及精子畸形率。结果照后14 d,中剂量给药组外周血白细胞数为(1.4±0.2)×109/L,明显高于模型组(1.0±0.5)×109/L(P<0.05);照后14 d,低、中、高3个剂量组小鼠的胸腺指数分别为(2.21±0.63)mg/g、(2.10±0.43)mg/g及(2.03±0.32)mg/g,明显高于模型组的(1.58±0.58)mg/g(P<0.05),中、高剂量组的脾指数和骨髓有核细胞数显著高于模型组的(P<0.05);中、高剂量组睾丸质量指数分别为(3.55±0.30)mg/g和(3.57±0.31)mg/g,明显高于模型组(3.26±0.30)mg/g(P<0.05),低、中、高剂量组精子总数分别为(17.5±6.2)×104,(19.0±7.0)×104和(20.8±11.4)×104,明显高于模型组(12.2±7.4)×104(P<0.05),中、高剂量组的精子畸形率显著低于模型组(P<0.05,P<0.01)。结论羊栖菜多糖复方制剂对小鼠的免疫器官及生殖器官的辐射损伤具有一定的保护作用。     

乳房保健方对苯甲酸雌二醇联合黄体酮建立大鼠乳腺增生模型的影响及抗氧化作用研究

目的观察评价乳房保健方对大鼠乳腺增生的治疗作用及对D-半乳糖致大鼠衰老的抗氧化作用。方法 SD雌性大鼠,随机均分为分别为空白对照组,模型对照组,乳房保健方高、中、低剂量组,阳性对照药组,每组10只。1除空白对照组外其余各组大鼠肌肉注射苯甲酸雌二醇0.5 mg/kg,1次/d,连续25 d。随后改用肌肉注射黄体酮4mg/kg,1次/d,连续5 d,同时各给药组按剂量灌胃给药,每天1次,连续30 d。实验结束后测量第2对乳头的直径及高度,测定大鼠血清中相关激素含量。取第2对乳腺作组织病理学观察。2造模组大鼠用D-半乳糖125 mg/kg腹腔注射造模,注射量为0.2 m L/100 g,每日1次,连续造模6周。各给药组灌胃给予不同浓度受试样品,每天1次,连续30天。实验结束后取血测定血清相关抗氧化物质的含量。结果 1乳房保健方组对乳腺增生模型大鼠异常升高的E_2、P、PRL、LH、FSH及乳头直径和高度均有明显的下降作用(P<0.01)。2乳房保健方大鼠T-AOC显著提高(P<0.05),GSH-PX活力、SOD活性明显上升(P<0.01),LPO、MDA含量显著降低(P<0.01)。结论乳房保健方对雌激素过度刺激所致的乳腺增生大鼠的乳腺组织有较好的保护作用,且具有一定的抗氧化作用。     

肠杆菌科细菌对头孢吡肟药敏折点引入剂量依赖性敏感的临床意义北大核心CSCD

目的评估美国临床实验室标准化研究所文件中肠杆菌科细菌对头孢吡肟药敏折点引入剂量依赖性敏感的临床意义,为合理使用抗菌药物提供参考依据。方法采用Phoenix WinNonlin 5.2和Matlab软件进行头孢吡肟药物代谢动力学模型建模和计算不同给药方案T>MIC%结果,进一步结合临床分离肠杆菌科致病菌体外药敏数据评估头孢吡肟药敏折点引入剂量依赖性敏感的临床意义。结果药物代谢动力学曲线显示,不同给药方案有不同的最高血药浓度和T>MIC%;增加单次给药剂量可显著提高最高血药浓度,单次给药1g和2g,Cmax分别为75μg/ml和150μg/ml,1g/12h方案64.68%时间血药浓度>8μg/ml、2g/12h方案81.65%时间血药浓度>8μg/ml;而缩短给药间隔则可以显著提升T>MIC%,1g/6h方案可以维持血药浓度一直>8μg/ml。结论肠杆菌科细菌对头孢吡肟药敏折点引入剂量依赖性敏感可以帮助临床医师更合理使用头孢吡肟。     

肠杆菌科细菌对头孢吡肟药敏折点引入剂量依赖性敏感的临床意义

目的 评估美国临床实验室标准化研究所文件中肠杆菌科细菌对头孢吡肟药敏折点引入剂量依赖性敏感的临床意义,为合理使用抗菌药物提供参考依据。方法 采用Phoenix WinNonlin 5.2和Matlab软件进行头孢吡肟药物代谢动力学模型建模和计算不同给药方案T>MIC%结果,进一步结合临床分离肠杆菌科致病菌体外药敏数据评估头孢吡肟药敏折点引入剂量依赖性敏感的临床意义。结果 药物代谢动力学曲线显示,不同给药方案有不同的最高血药浓度和T>MIC%;增加单次给药剂量可显著提高最高血药浓度,单次给药1g和2g,Cmax分别为75μg/ml和150μg/ml,1g/12h方案64.68%时间血药浓度>8μg/ml、2g/12h方案81.65%时间血药浓度>8μg/ml;而缩短给药间隔则可以显著提升T>MIC%,1g/6h方案可以维持血药浓度一直>8μg/ml。结论 肠杆菌科细菌对头孢吡肟药敏折点引入剂量依赖性敏感可以帮助临床医师更合理使用头孢吡肟。     

不同剂量阿托伐他汀对急性冠状动脉综合征患者sCD40L及其预后影响

目的探讨早期应用不同剂量阿托伐他汀对急性冠状动脉综合征患者血清sCD40L水平及其预后的影响。方法168例急性冠状动脉综合征患者随机分为阿托伐他汀小剂量(10mg/d,56例)、中剂量(40mg/d,55例)和大剂量(80mg/d,57例)组。测定治疗前后血清sCD40L和血脂水平。并随访(平均7.6±3.2个月)主要心血管事件。结果血清sCD40L水平在阿托伐他汀小剂量组治疗前后差异无显著性,而大、中剂量组治疗后分别降低52.4%和52.2%(P均<0.05);主要心血管事件发生率大、中剂量组比小剂量组分别减少29.1%和30.1%(P均<0.05),但大、中剂量组间差异无显著性。结论阿托伐他汀呈剂量依赖性通过抗炎作用稳定冠脉斑块,减少急性冠脉综合征患者心血管事件的发生,效应以中剂量(40mg/d)为佳。     

枸杞子、淫羊藿的提取物与海参、牡蛎肉的冻干粉合用缓解体力疲劳作用研究

目的研究枸杞子、淫羊藿的提取物与海参、牡蛎肉的冻干粉合用缓解体力疲劳的作用效果。方法按《保健食品检验与评价技术规范》缓解体力疲劳检测评价方法,将192只ICR(institute of cancer research)雄性小鼠随机分为阴性溶剂对照组、低(0.14g/kg·bw)、中(0.27g/kg·bw)、高剂量(0.80g/kg·bw)组,每组48只,连续灌胃给药30d后,测定小鼠负重游泳时间、游泳后血清尿素、血乳酸含量和肝糖原含量。结果中、高剂量组小鼠负重游泳时间分别为(549±97)s、(541±91)s,较对照组(408±75)s明显增加(P0.01);中、高剂量组小鼠血清尿素分别为(12.43±0.69)mmol/L、(12.53±0.85)mmol/L,较对照组(13.49±0.79)mmol/L明显降低(P0.01);低、中、高剂量组肝糖原分别为(5.61±0.55)、(6.33±0.71)、(6.38±0.75)g/100g,均高于对照组(P0.01)。中剂量组小鼠运动血乳酸含量显著低于对照组(P0.01)。结论枸杞子、淫羊藿的提取物与海参、牡蛎肉的冻干粉合用具有缓解体力疲劳的作用。     

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.     

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.     

Occupational health hazards in mining: an overview

This review article outlines the physical, chemical, biological, ergonomic and psychosocial occupational health hazards of mining and associated metallurgical processes. Mining remains an important industrial sector in many parts of the world and although substantial progress has been made in the control of occupational health hazards, there remains room for further risk reduction. This applies particularly to traumatic injury hazards, ergonomic hazards and noise. Vigilance is also required to ensure exposures to coal dust and crystalline silica remain effectively controlled.     

Manufacture and use of nanomaterials: current status in the UK and global trends

This paper provides an overview of the production and use of nanomaterials (NMs), particularly in the UK. Currently, relatively few companies in the UK are identifiable as NM manufacturers, the main emphasis being the bulk markets in metals and metal oxides, and some niche markets such as carbon nanotubes and quantum dots. NM manufacturing in the UK does not reflect the global emphasis on fullerenes, nanotubes and fibres. Some assumptions have been made about the types of NM that are likely to be imported into the UK, which currently include fullerenes, modified fullerenes and other carbon-based NMs including nanotubes. Many university departments, spin-offs and private companies have developed processes for the manufacture of NMs but may only be producing small quantities for research and development (R&D) purposes. However, some have the potential to scale up to produce large quantities. The nanotechnology industry in the UK has strong R&D backup from universities and related institutions. This review has covered R&D trends at such institutions, and appropriate information has been added to a searchable database. While several companies are including NMs in their products, only a few (e.g. manufacturers of paints, coatings, cosmetics, catalysts, polymer composites) are using nanoparticles (NPs) in any significant quantities. However, this situation is likely to change rapidly. There is a need to collect more information about exposure to NPs in both manufacturing and user scenarios. As the market grows, and as manufacturers switch from the micro- to the nanoscale, the potential for exposure will increase. More research is required to quantify any risks to workers and consumers.     

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.     

Investigating clusters in the workplace and beyond

Clusters of disease are common and occur in the workplace and in the general community. They often arouse considerable concern among the population. Investigations have sometimes lead to exciting new knowledge, but in general the investigation of clusters is difficult and often unrewarding, especially for community clusters. In the workplace, investigations are more likely to find associations and even new causes, but still many clusters remain enigmatic. Despite this, there are many reasons for investigating clusters, including allaying community concern and identifying uncontrolled exposures. A structure for investigating clusters in the workplace is suggested.