• 【麻醉师心输出量储备和输血可能性术前评估的差异: 一项初步研究。】 复制标题 收藏 收藏
    DOI:10.1177/0310057X0603400407 复制DOI
    作者列表:Harrison MJ
    BACKGROUND & AIMS: :The aim of this pilot study was to investigate anaesthetists' assessment of the ability of patients to increase cardiac output over a range of clinical scenarios and of their perceived 'likelihood of transfusion' in these scenarios. Specialist anaesthetists were given a questionnaire with clinical cues in the form of diagnoses about theoretical patients. They were asked to use 100 mm visual analogue scales (VAS) for their assessments of each patient's cardiac reserve and their 'likelihood of transfusion' of these patients; the endpoints of the VAS being 'Very low' (0 mm) to 'High' (100 mm), and 'Do not transfuse' (0 mm) to 'Transfuse' (100 mm) respectively. The assessment of patients' cardiac output reserve by anaesthetists (n = 54) showed great variation; for example, a patient with severe aortic stenosis was perceived overall to have a limited ability to increase cardiac output (mean VAS 16 mm) but there was considerable variation between anaesthetists (25-75 percentiles 10 mm to 21 mm). Assessment of 'likelihood of transfusion' (n = 42) also had great variation; as an example a patient with 'angina' with a haemoglobin of 95 g l(-1) was perceived overall to have an average likelihood of transfusion of 50 mm, but the 25-75 percentiles ranged from 33 mm to 71 mm. This study suggests that inter-anaesthetist variability in the assessment of a patient's 'cardiac output reserve' and his 'likelihood of transfusion' is large.
    背景与目标: : 这项初步研究的目的是调查麻醉师对患者在一系列临床情况下增加心输出量的能力的评估,以及他们在这些情况下感知到的 “输血可能性”。以理论患者的诊断形式向专科麻醉师提供了一份带有临床线索的问卷。他们被要求使用100毫米视觉模拟量表 (VAS) 来评估每个患者的心脏储备和这些患者的 “输血可能性”; VAS的终点是 “非常低” (0毫米) 到 “高” (100毫米),和 “不输血” (0毫米) 分别转换为 “输血” (100毫米)。麻醉师 (n = 54) 对患者心输出量储备的评估显示出很大的差异; 例如,总体上认为患有严重主动脉瓣狭窄的患者增加心输出量的能力有限 (平均VAS 16毫米),但麻醉师之间存在相当大的差异 (25-75个百分位数10毫米至21毫米)。“输血可能性” 的评估 (n = 42) 也有很大的差异; 例如,具有95g l(-1) 血红蛋白的 “angina” 患者总体上被认为平均输血可能性为50毫米,但25-75个百分位数范围为33毫米至71毫米。这项研究表明,在评估患者的 “心输出量储备” 和他的 “输血可能性” 时,麻醉师间的变异性很大。
  • 【严重脑外伤的白质损伤和预后评估: 一个前瞻性多中心队列。】 复制标题 收藏 收藏
    DOI:10.1097/ALN.0b013e3182755558 复制DOI
    作者列表:
    BACKGROUND & AIMS: BACKGROUND:Existing methods to predict recovery after severe traumatic brain injury lack accuracy. The aim of this study is to determine the prognostic value of quantitative diffusion tensor imaging (DTI). METHODS:In a multicenter study, the authors prospectively enrolled 105 patients who remained comatose at least 7 days after traumatic brain injury. Patients underwent brain magnetic resonance imaging, including DTI in 20 preselected white matter tracts. Patients were evaluated at 1 yr with a modified Glasgow Outcome Scale. A composite DTI score was constructed for outcome prognostication on this training database and then validated on an independent database (n=38). DTI score was compared with the International Mission for Prognosis and Analysis of Clinical Trials Score. RESULTS:Using the DTI score for prediction of unfavorable outcome on the training database, the area under the receiver operating characteristic curve was 0.84 (95% CI: 0.75-0.91). The DTI score had a sensitivity of 64% and a specificity of 95% for the prediction of unfavorable outcome. On the validation-independent database, the area under the receiver operating characteristic curve was 0.80 (95% CI: 0.54-0.94). On the training database, reclassification methods showed significant improvement of classification accuracy (P < 0.05) compared with the International Mission for Prognosis and Analysis of Clinical Trials score. Similar results were observed on the validation database. CONCLUSIONS:White matter assessment with quantitative DTI increases the accuracy of long-term outcome prediction compared with the available clinical/radiographic prognostic score.
    背景与目标:
  • 【用水痘病毒抗原进行皮肤试验以预测带状疱疹的风险。】 复制标题 收藏 收藏
    DOI:10.1017/S0950268812002671 复制DOI
    作者列表:Okuno Y,Takao Y,Miyazaki Y,Ohnishi F,Okeda M,Yano S,Kumihashi H,Gomi Y,Maeda K,Ishikawa T,Mori Y,Asada H,Iso H,Yamanishi K,Shozu Herpes Zoster (SHEZ) Study Group.
    BACKGROUND & AIMS: :The Shozu Herpes Zoster (SHEZ) Study was designed to clarify the incidence of and predictive and immunological factors for herpes zoster in a defined community-based Japanese population. As part of this series, a total of 5683 residents aged ≥50 years received a varicella-zoster virus (VZV) skin test with VZV antigen, and 48 h later, the erythema and oedema were assessed by measuring the longest diameter. The diameters of both the erythema and oedema decreased with the increasing age of the subject. Sixty-three subjects contracted herpes zoster within a year after receiving the VZV skin test. Analysis of the herpes zoster incidence rate vs. the skin test reaction revealed that the shorter the diameter of erythema or oedema, the greater the likelihood of herpes zoster. These results demonstrated that the VZV skin test is an excellent surrogate marker for predicting the risk of herpes zoster.
    背景与目标: : Shozu带状疱疹 (SHEZ) 研究旨在阐明以社区为基础的日本人群中带状疱疹的发生率以及预测和免疫学因素。作为本系列的一部分,共有5683名年龄 ≥ 50岁的居民接受了VZV抗原的水痘病毒 (VZV) 皮肤测试,48小时后,通过测量最长直径来评估红斑和水肿。随着受试者年龄的增长,红斑和水肿的直径均减小。接受VZV皮肤测试后一年内,有63名受试者感染了带状疱疹。对带状疱疹发病率与皮肤测试反应的分析表明,红斑或水肿的直径越短,带状疱疹的可能性越大。这些结果表明,VZV皮肤测试是预测带状疱疹风险的出色替代指标。
  • 【英国肾移植资源评估。】 复制标题 收藏 收藏
    DOI:10.1016/s0140-6736(85)91508-9 复制DOI
    作者列表:Sells RA,Macpherson S,Salaman JR
    BACKGROUND & AIMS: :Statistics on treatment rates for patients with end stage renal disease (ESRD) show that the number of ESRD patients per million population in the United Kingdom has increased slowly in recent years. The British Transplantation Society issued questionnaires in 1983 and 1984 to determine the number of patients transplanted, the number of suitable patients, and the facilities needed to enable all suitable patients to receive treatment. While there is a high transplant rate, the percentage of ESRD patients on dialysis is low, and there is a "socially unacceptable deficit" with respect to treatment of diabetics and the elderly.
    背景与目标: : 有关终末期肾病 (ESRD) 患者治疗率的统计数据表明,英国每百万人口中ESRD患者的数量近年来增长缓慢。英国移植学会1983年和1984发放了问卷,以确定移植的患者人数、合适的患者人数以及使所有合适的患者都能接受治疗所需的设施。尽管移植率很高,但接受透析的ESRD患者的百分比却很低,并且在糖尿病患者和老年人的治疗方面存在 “社会上不可接受的缺陷”。
  • 【药房抗肿瘤药物污染水平定期环境监测的应用和评估-MEWIP项目。】 复制标题 收藏 收藏
    DOI:10.1093/annhyg/mes081 复制DOI
    作者列表:Kiffmeyer TK,Tuerk J,Hahn M,Stuetzer H,Hadtstein C,Heinemann A,Eickmann U
    BACKGROUND & AIMS: :A large-scale study was carried out in order to determine the contamination level of antineoplastic drugs in pharmacies and to investigate the suitability and effects of wipe sample monitoring at regular intervals. A specific study design was developed. The 130 participating pharmacies were divided into a study and a control group, carrying out five and two wipe sampling cycles, respectively. The work practice was analyzed using questionnaires to identify factors that influence the contamination level. From 1269 wipe samples, 774 (61%) were contaminated with at least one of the analyzed cytotoxic drugs: cyclophosphamide, docetaxel, etoposide, 5-fluorouracil, gemcitabine, ifosfamide, methotrexate, and paclitaxel. A significant decrease of the contamination with cyclophosphamide and 5-fluorouracil was observed in the study group. The Monitoring-Effect Study of Wipe Sampling in Pharmacies method has proven to be a reliable and affordable tool for contamination control. Based on the 90th percentile of the contamination values, a substance-independent performance-based guidance value of 0.1ng cm(-2) has been derived.
    背景与目标: : 进行了大规模研究,以确定药房中抗肿瘤药物的污染水平,并调查定期擦拭样品监测的适用性和效果。开发了一个特定的研究设计。将130家参与的药房分为研究组和对照组,分别进行了五个和两个擦拭采样周期。使用问卷调查对工作实践进行了分析,以确定影响污染水平的因素。从1269擦拭样品中,774 (61%) 被至少一种分析的细胞毒性药物污染: 环磷酰胺,多西他赛,依托泊苷,5-氟尿嘧啶,吉西他滨,异环磷酰胺,甲氨蝶呤和紫杉醇。在研究组中观察到环磷酰胺和5-氟尿嘧啶的污染显着减少。药房擦拭采样方法的监测效果研究已被证明是控制污染的可靠且负担得起的工具。根据污染值的第90个百分位数,得出了与物质无关的基于性能的指导值0.1ng cm(-2)。
  • 【用傅立叶域光学相干断层扫描评估超声介导的葡萄糖对正常,良性和癌性人肺组织通透性的影响。】 复制标题 收藏 收藏
    DOI:10.1117/1.JBO.17.11.116006 复制DOI
    作者列表:Wei H,Wu G,Guo Z,Yang H,He Y,Xie S,Guo X
    BACKGROUND & AIMS: :The objective of this study was to evaluate the effects of ultrasound-mediated analyte diffusion on permeability of normal, benign, and cancerous human lung tissue in vitro and to find more effective sonophoretic (SP) delivery in combination with the optical clearing agents (OCAs) method to distinguish normal and diseased lung tissues. The permeability coefficients of SP in combination with OCAs diffusion in lung tissue were measured with Fourier-domain optical coherence tomography (FD-OCT). 30% glucose and SP with a frequency of 1 MHz and an intensity of 0.80  W/cm2 over a 3 cm probe was simultaneously applied for 15 min. Experimental results show that the mean permeability coefficients of 30% glucose/SP were found to be (2.01±0.21)×10(-5)  cm/s from normal lung (NL) tissue, (2.75±0.28)×10(-5)  cm/s from lung benign granulomatosis (LBG) tissue, (4.53±0.49)×10(-5)  cm/s from lung adenocarcinoma tumor (LAT) tissue, and (5.81±0.62)×10(-5)  cm/s from lung squamous cell carcinoma (LSCC) tissue, respectively. The permeability coefficients of 30% glucose/SP increase approximately 36.8%, 125.4%, and 189.1% for the LBG, LAT, and LSCC tissue compared with that for the NL tissue, respectively. There were statistically significant differences in permeability coefficients of 30% glucose/SP between LBG and NL tissue (p<0.05), between LAT and NL tissue (p<0.05), and between LSCC and NL tissue (p<0.05). The results suggest that the OCT functional imaging technique to combine an ultrasound-OCAs combination method could become a powerful tool in early diagnosis and monitoring of changed microstructure of pathologic human lung tissue.
    背景与目标: : 这项研究的目的是评估超声介导的分析物扩散对体外正常,良性和癌性人肺组织通透性的影响,并找到与光学清除剂 (OCAs) 结合更有效的超声电泳 (SP) 递送方法,以区分正常和患病的肺组织。用傅里叶域光学相干断层扫描 (fd-oct) 测量SP与OCAs扩散在肺组织中的渗透系数。在3厘米探针上同时施加频率为1 MHz且强度为0.80   W w/cm2的30% 葡萄糖和SP 15分钟。实验结果表明,30% 葡萄糖/SP对正常肺 (NL) 组织的平均渗透系数为 (2.01 ± 0.21)× 10(-5)  cm cm/s,肺良性肉芽肿 (LBG) 组织 (2.75 ± 0.28)× 10(-5)  cm/s,肺腺癌肿瘤 (LAT) 组织 (4.53 ± 0.49)× 10(-5)  cm/s,和 (5.81 ± 0.62)× 10(-5)  cm cm/s分别来自肺鳞状细胞癌 (LSCC) 组织。与NL组织相比,LBG、LAT和LSCC组织的30% 葡萄糖/SP的渗透系数分别增加约36.8% 、125.4% 和189.1%。LBG与NL组织之间 (p<0.05),LAT与NL组织之间 (p<0.05) 以及LSCC与NL组织之间 (p<0.05) 的30% 葡萄糖/SP的渗透系数差异有统计学意义。结果表明,OCT功能成像技术结合超声-OCAs组合方法可以成为早期诊断和监测病理性人肺组织微观结构变化的有力工具。
  • 【发展中国家蛋白质充足性评估: 质量问题。】 复制标题 收藏 收藏
    DOI:10.1017/S0007114512002577 复制DOI
    作者列表:Ghosh S,Suri D,Uauy R
    BACKGROUND & AIMS: :Dietary protein and amino acid requirement recommendations for normal "healthy" children and adults have varied considerably with 2007 FAO/WHO protein requirement estimates for children lower, but dietary essential AA requirements for adults more than doubled. Requirement estimates as presented do not account for common living conditions, which are prevalent in developing countries such as energy deficit, infection burden and added functional demands for protein and AAs. This study examined the effect of adjusting total dietary protein for quality and digestibility (PDCAAS) and of correcting current protein and AA requirements for the effect of infection and a mild energy deficit to estimate utilizable protein (total protein corrected for biological value and digestibility) and the risk/prevalence of protein inadequacy. The relationship between utilizable protein/prevalence of protein inadequacy and stunting across regions and countries was examined. Data sources (n = 116 countries) included FAO FBS (food supply), UNICEF (stunting prevalence), UNDP (GDP) and UNSTATS (IMR) and USDA nutrient tables. Statistical analyses included Pearson correlations, paired-sample/non-parametric t-tests and linear regression. Statistically significant differences were observed in risk/prevalence estimates of protein inadequacy using total protein and the current protein requirements versus utilizable protein and the adjusted protein requirements for all regions (p < 0·05). Total protein, utilizable protein, GDP per capita and total energy were each highly correlated with the prevalence of stunting. Energy, protein and utilizable protein availability were independently and negatively associated with stunting (p < 0·001), explaining 41 %, 34 % and 40 % of variation respectively. Controlling for energy, total protein was not a statistically significant factor but utilizable protein remained significant explaining~45 % of the variance (p = 0·017). Dietary utilizable protein provides a better index of population impact of risk/prevalence of protein inadequacy than crude protein intake. We conclude that the increased demand for protein due to infections and mild to moderate energy deficits, should be appropriately considered in assessing needs of populations where those conditions still prevail.
    背景与目标: : 正常 “健康” 儿童和成人的膳食蛋白质和氨基酸需求建议差异很大,2007粮农组织/世卫组织儿童的蛋白质需求估计值较低,但成人的膳食必需AA需求增加了一倍以上。所提出的需求估计数没有考虑到发展中国家普遍存在的共同生活条件,例如能源短缺,感染负担以及对蛋白质和AAs的功能需求增加。这项研究检查了调整膳食总蛋白质的质量和消化率 (PDCAAS) 以及纠正当前蛋白质和AA对感染和轻度能量不足的影响,以估计可利用的蛋白质 (根据生物学价值和消化率校正的总蛋白质) 和蛋白质不足的风险/患病率。研究了可利用的蛋白质/蛋白质不足的患病率与跨地区和国家的发育迟缓之间的关系。数据来源 (n = 116个国家) 包括粮农组织FBS (粮食供应) 、儿童基金会 (发育迟缓流行率) 、开发署 (国内生产总值) 和统计司 (IMR) 以及USDA营养表。统计分析包括Pearson相关性,配对样本/非参数t检验和线性回归。在使用总蛋白质和当前蛋白质需求与可利用蛋白质和所有区域的调整后蛋白质需求的风险/患病率估计中,观察到统计学上的显着差异 (p <0·05)。总蛋白质,可利用蛋白质,人均GDP和总能量均与发育迟缓的患病率高度相关。能量,蛋白质和可利用的蛋白质利用率与发育迟缓独立且负相关 (p <0·001),分别解释了变异的41%,34% 和40%。控制能量,总蛋白不是统计学上的显着因素,但可利用的蛋白质仍然显着解释了约45% 的方差 (p = 0.017)。与粗蛋白摄入相比,饮食中可利用的蛋白质提供了更好的人口对蛋白质不足风险/患病率的影响指数。我们得出的结论是,在评估仍然存在这些疾病的人群的需求时,应适当考虑由于感染和轻度至中度能量不足而导致的蛋白质需求增加。
  • 【乳酸和丙酮酸测量在评估灌注大鼠心脏细胞质中游离烟酰胺-腺嘌呤二核苷酸的氧化还原状态中的价值。】 复制标题 收藏 收藏
    DOI:10.1111/eci.1971.1.4.295 复制DOI
    作者列表:Opie LH,Mansford KRL
    BACKGROUND & AIMS: :In the isolated rat heart perfused with glucose as substrate, measurements were made of perfusate and tissue lactate and pyruvate concentrations, and of tissue α-glycerophosphate and dihydroxyacetone phosphate concentrations. The conditions studied included increased heart work, anoxia, the addition of insulin, acute alloxan diabetes, chronic streptozotocin diabetes, and the addition of ketone bodies. True intracellular lactate values (estimated from the lactate and sorbitol spaces) and apparent tissue values exceeded perfusate values, showing the existence of a lactate concentration gradient. During anoxia, the lactate gradient diminished. Cytoplasmic free NAD+/NADH ratios calculated from the extracellular lactate/pyruvate ratio were similar to and changed in the same direction as the NAD+/NADH ratios calculated from the tissue α-glycerophosphate/dihydroxyacetone phosphate ratios in non-diabetic hearts. In diabetio hearts, extracellular and tissue lactate/pyruvate ratios gave different values for the cytoplasmic free NAD+/NADH ratios than did tissue α-glycero-phoaphate/dihydroxyacetone phosphate ratios. These discrepancies were associated with accumulation of pyruvate in the perfusate and the tissue. Changes in the extracellular lactate/pyruvate ratio gave a better differentiation between acute heart work and acute anoxia than did changes in the heart lactate/pyruvate ratio. The use of extracellular lactate/ pyruvate measurements in assessing the state of myocardial oxygenation is supported by these observations, provided that nutritional factors are taken into account and the diabetic state is excluded.
    背景与目标: : 在以葡萄糖为底物灌注的离体大鼠心脏中,测量灌注液和组织乳酸和丙酮酸的浓度,以及组织 α-甘油磷酸和二羟基丙酮磷酸的浓度。研究的条件包括增加心脏工作,缺氧,添加胰岛素,急性四氧嘧啶糖尿病,慢性链脲佐菌素糖尿病和添加酮体。真实的细胞内乳酸值 (从乳酸和山梨醇空间估算) 和表观组织值超过灌注液值,表明存在乳酸浓度梯度。在缺氧期间,乳酸梯度减小。在非糖尿病心脏中,由细胞外乳酸/丙酮酸比率计算出的无细胞质NAD/NADH比率与由组织 α-甘油磷酸/二羟基丙酮磷酸盐比率计算出的NAD/NADH比率相似,并沿相同方向变化。在糖尿病心脏中,细胞外和组织乳酸/丙酮酸比率给出的细胞质游离NAD/NADH比率与组织 α-甘油磷酸酯/二羟基丙酮磷酸盐比率不同。这些差异与灌注液和组织中丙酮酸的积累有关。细胞外乳酸/丙酮酸比率的变化比心脏乳酸/丙酮酸比率的变化更好地区分了急性心脏工作和急性缺氧。这些观察结果支持使用细胞外乳酸/丙酮酸测量来评估心肌氧合状态,前提是要考虑营养因素并排除糖尿病状态。
  • 【关于微生物风险评估在国际贸易中的潜在用途的监管观点。】 复制标题 收藏 收藏
    DOI:10.1016/s0168-1605(97)01263-4 复制DOI
    作者列表:Hathaway SC,Cook RL
    BACKGROUND & AIMS: The recent ratification of the World Trade Organisation Agreement will arguably be the most important factor in developing new sanitary measures for the international trade in food over the next decade. There is a markedly increased desire for quantitative data on the microbial risks associated with different classes of foods, and traditional good manufacturing practice (GMP)-based food hygiene requirements are coming under increasing challenge. As the risk assessment paradigm is increasing applied and as decision-making criteria for risk management become established, more emphasis will be placed on predictive microbiology as a means of generating exposure data and establishing critical limits for Hazard Analysis Critical Control Point (HACCP) plans. In this respect, developing international guidelines for risk management arguably presents the greatest challenge in establishing and maintaining quantitative Sanitary and Phytosanitary (SP) measures for food in international trade, and for judging their equivalence. Where specific industry sectors and regulators do not have jurisdiction over the entire food chain, from production of raw materials through to consumption, it will be difficult to apply the risk assessment paradigm in the design of HACCP plans. Thus, it appears that default to food safety objectives for many segments of food production chains subject to application of HACCP plans is inevitable in the medium term.

    背景与目标: 世界贸易组织最近批准的协议可以说是在未来十年为国际食品贸易制定新的卫生措施的最重要因素。对与不同类别食品相关的微生物风险的定量数据的需求明显增加,并且基于传统良好生产规范 (GMP) 的食品卫生要求正面临越来越大的挑战。随着风险评估范式的应用越来越多,随着风险管理决策标准的建立,将更加重视预测微生物学,作为生成暴露数据和建立危害分析关键控制点 (HACCP) 计划关键限值的一种手段。在这方面,制定国际风险管理准则可以说是建立和维持国际贸易中食品定量卫生和植物检疫措施以及判断其等效性的最大挑战。如果特定的行业部门和监管机构对从原材料生产到消费的整个食物链没有管辖权,那么将很难在HACCP计划的设计中应用风险评估范式。因此,在中期看来,受HACCP计划约束的食品生产链的许多部分默认食品安全目标是不可避免的。
  • 【甲醛致癌与大鼠鼻腔病理和人类健康风险评估的关系的简要综述。】 复制标题 收藏 收藏
    DOI:10.1177/019262339702500307 复制DOI
    作者列表:Morgan KT
    BACKGROUND & AIMS: The 1980 report that inhaled formaldehyde induced nasal squamous cell carcinomas in rats had a significant societal impact and resulted in extensive research in the fields of rodent nasal pathology and human cancer risk assessment. This article presents an overview of the evolution of these events. It is concluded that the nasal passages of humans and rats are fundamentally identical biological target organs. Nevertheless, in the case of human health risk assessment, minor differences between these species may be critically important. Special attention should be paid to interspecies differences in nasal dosimetry and local metabolism; thus, chemical toxicity data derived from rats require careful interpretation when used for human risk assessments. In the case of formaldehyde, it is recommended that low-concentration (< or = 2 ppm airborne exposure) extrapolation, where no tissue damage is observed, be uncoupled from the responses at high concentrations (> or = 6 ppm), where epithelial degeneration, regenerative cell replication, and inflammation appear to be essential driving forces in formaldehyde carcinogenesis. The presence of treatment-related nasal lesions in rats following exposure to chemicals should always be treated as an indication of a potential human health risk, whether exposure is by the inhalation, oral, or dermal route.

    背景与目标: 1980报告说,吸入甲醛诱导的大鼠鼻鳞状细胞癌具有重大的社会影响,并导致在啮齿动物鼻病理学和人类癌症风险评估领域的广泛研究。本文概述了这些事件的演变。结论人和大鼠的鼻腔通道是基本相同的生物靶器官。然而,就人类健康风险评估而言,这些物种之间的微小差异可能至关重要。应特别注意鼻剂量测定和局部代谢的种间差异; 因此,从大鼠获得的化学毒性数据在用于人类风险评估时需要仔细解释。在甲醛的情况下,建议低浓度 (< or = 2 ppm空气传播暴露) 外推,在没有观察到组织损伤的情况下,与高浓度 (> or = 6 ppm) 的反应分离,在高浓度 (> or = 6 ppm),上皮变性,再生细胞复制,炎症似乎是甲醛致癌的重要驱动力。无论是通过吸入,口服还是通过皮肤途径暴露,都应始终将暴露于化学物质后的大鼠中与治疗相关的鼻部病变视为潜在的人类健康风险的指示。
  • 【评估有害物质经皮渗透的不同大鼠模型之间的差异。】 复制标题 收藏 收藏
    DOI:10.1007/s00204-007-0221-6 复制DOI
    作者列表:Korinth G,Göen T,Schaller KH,Drexler H
    BACKGROUND & AIMS: :By regulatory authorities the rat is considered to be a suitable animal model to predict the percutaneous absorption of hazardous substances in humans. In our study, the percutaneous penetration of 2-butoxyethanol (BE) and toluene was compared in different rat models. Intradermal microdialysis and static diffusion cells were used in in vivo and in vitro experiments with haired Wistar and hairless Lewis rats. Microdialysis experiments showed a steady-state penetration for BE and a penetration maximum for toluene in both rat strains at approximately 60 min after beginning of exposure. However, in diffusion cell experiments the penetration of the test compounds in both rat strains increased until the end of exposure (4 h). Additionally, in microdialysis experiments BE penetrated in hairless rats in a higher amount than in haired rats (factor: 1.4; P < 0.01), for toluene it was just the opposite (factor: 1.9; P < 0.001). In diffusion cell experiments, the penetrated amounts of both compounds were higher in hairless rats compared to haired rats. The fluxes for BE were in diffusion cell experiments at a factor of 14.5 (haired rat) and 18.1 (hairless rat) higher than in microdialysis experiments, the difference factor for toluene was 2.6 (haired rat) and 12.9 (hairless rat). The lag times indicate a significantly faster penetration in microdialysis experiments compared with diffusion cell experiments (P < 0.001). There are great differences in percutaneous penetration behaviour between the techniques and the rat strains. The diffusion cell method has difficulties to describe the percutaneous penetration kinetics, whereas microdialysis describes it more reliable. Due to these differences the reliability of a conversion factor for the transfer of percutaneous absorption data from rat to human skin, as proposed in the literature, is questionable.
    背景与目标: : 监管机构认为该大鼠是预测人体内有害物质经皮吸收的合适动物模型。在我们的研究中,比较了2-丁氧基乙醇 (BE) 和甲苯在不同大鼠模型中的经皮渗透。皮内微透析和静态扩散细胞用于有毛Wistar和无毛Lewis大鼠的体内和体外实验。微透析实验显示,在暴露开始后约60分钟,两种大鼠菌株中BE的稳态渗透和甲苯的最大渗透。然而,在扩散细胞实验中,测试化合物在两种大鼠品系中的渗透增加,直到暴露结束 (4小时)。此外,在微透析实验中,无毛大鼠的渗透量高于毛发大鼠 (因子: 1.4; P <0.01),对于甲苯则相反 (因子: 1.9; P <0.001)。在扩散细胞实验中,与无毛大鼠相比,无毛大鼠中两种化合物的渗透量更高。在扩散池实验中,BE的通量为14.5 (毛大鼠) 和18.1 (无毛大鼠) 高于微透析实验中的系数,甲苯的差异系数为2.6 (毛大鼠) 和12.9 (无毛大鼠)。滞后时间表明与扩散池实验相比,微透析实验中的渗透明显更快 (P <0.001)。该技术与大鼠品系之间的经皮穿透行为存在很大差异。扩散池方法难以描述经皮渗透动力学,而微透析则描述其更可靠。由于这些差异,如文献中所述,将经皮吸收数据从大鼠转移到人皮肤的转换因子的可靠性值得怀疑。
  • 【妊娠唾液皮质醇分泌模式及其对评估方案的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.biopsycho.2006.07.005 复制DOI
    作者列表:Harville EW,Savitz DA,Dole N,Herring AH,Thorp JM,Light KC
    BACKGROUND & AIMS: :Cortisol is used in research as a biomarker of psychological stress. Logistical considerations argue for collecting as few samples as possible, balanced against diurnal rhythms and intra-individual variations. 100 pregnant women gave five saliva samples a day for 3 days, at waking, 30 min after waking, and 11:00 a.m., 5:00 p.m., and 9:00 p.m. Timing of collection was confirmed by monitors. Another sample was taken during a clinic visit. Using the 15 measures as the gold standard, correlations and mean area under the curve (AUC) were compared with subsets and the single clinic sample to evaluate alternate collection protocols. Five samples in 1 day, or protocols involving morning and night samples, had the highest correlations with mean AUC (correlation coefficient ranging from 0.82 to 0.88). Standardizing the clinic measurement to a single time of day did not substantially improve correlations with mean AUC. Correlations with measures of reported stress were also not strong.
    背景与目标: : 皮质醇在研究中被用作心理压力的生物标志物。后勤方面的考虑主张收集尽可能少的样本,并与昼夜节律和个体内部变化保持平衡。100名孕妇每天在醒来时,醒来后30分钟以及上午11:00,下午5:00和下午9:00时每天提供五个唾液样本收集时间由监视器确认。在诊所就诊时采集了另一个样本。使用15项措施作为金标准,将相关性和曲线下平均面积 (AUC) 与子集和单个临床样本进行比较,以评估替代收集方案。1天内的5个样品或涉及早晨和夜间样品的方案与平均AUC的相关性最高 (相关系数范围从0.82到0.88)。将临床测量标准化为一天中的单个时间并没有显着改善与平均AUC的相关性。与报告的压力度量的相关性也不强。
  • 【美国睡眠实验室活动的定量评估。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Tachibana N,Ayas NT,White DP
    BACKGROUND & AIMS: STUDY OBJECTIVES:To determine the total number of active sleep laboratories in the United States and the number of polysomnograms conducted on a yearly basis in these laboratories. METHODS:All members of the AASM and all AASM accredited sleep laboratory directors received a questionnaire addressing their laboratory and its volume. In three states, multiple telephone calls to AASM members were used to correctly identify the absolute number of labs and their PSG volume in those states. Extrapolating from the number of labs studies identified per questionnaire relative to the correct number (per calls) in those states and, then applying this ratio to the entire US, the total number of labs and studies was determined. RESULTS:Our data suggests that there are, in the year 2001, 1,292 sleep laboratories conducting 1,165,135 polysomnograms per year. This comes to 427 PSG's/year per 100,000 population in the United States. CONCLUSIONS:These data suggest that there are a relatively large number of sleep laboratories in the US conducting a substantial number of PSG's. However, there was considerable variability in this volume between states that did not relate to known markers of healthcare utilization. These numbers have likely increased since 2001.
    背景与目标:
  • 【造影剂血流储备分数在日常实践中冠心病功能评估中的效用。】 复制标题 收藏 收藏
    DOI:10.1016/j.hlc.2017.03.158 复制DOI
    作者列表:Van Wyk P,Puri A,Blake J,Elliott JM,McClean D,Arshad M,Sutherland J,Thacker O,Bailey T,Yi M,Smyth D
    BACKGROUND & AIMS: BACKGROUND:Adenosine induced hyperaemic fractional flow reserve (aFFR) is a validated predictor of clinical outcome and part of routine interventional practice. Protocol issues associated with the adenosine infusion limit the use of aFFR in clinical practice. Contrast medium induced hyperaemic FFR (cFFR) is a simpler procedure from a practical standpoint. We compared the two in a real world setting. METHODS:We analysed 76 patients that had both cFFR and aFFR assessment of 100 angiographically indeterminate coronary stenosis. cFFR was performed with intracoronary contrast medium injections (10ml for left coronary lesions and 8ml for right coronary lesions). The diagnostic performance of cFFR was analysed and compared to the gold standard aFFR. RESULTS:Mean cFFR was 0.87 (±0.07) and mean aFFR was 0.84 (±0.08). Bland-Altman analysis revealed a close agreement between cFFR and aFFR (0.035±0.032; 95% CI: -0.028 to 0.098) and good linear correlation (r=0.92, r2=0.86; p<0.0001). Using cFFR cut-off values of ≤0.83 in predicting an aFFR value of ≤0.80 or a cFFR value ≥0.88, predicting an aFFR value of >0.80 yielded a sensitivity of 100%, specificity of 96.1%, positive predictive value of 92.3%, negative predictive value of 100% and diagnostic accuracy of 96%. Only 24% of cFFR values were in the 0.84 to 0.87 range. CONCLUSION:Contrast medium induced hyperaemic FFR as an initial assessment may limit the need for adenosine to when cFFR falls in the 0.84 to 0.87 range. The use of adenosine infusion potentially could have been avoided in the majority of patients in this study.
    背景与目标:
  • 【“芯片上的人” 的发展: 实验室动物和人类物质的系统安全评估和效率评估的转化前沿替代方案?】 复制标题 收藏 收藏
    DOI:10.1177/026119291204000504 复制DOI
    作者列表:Marx U,Walles H,Hoffmann S,Lindner G,Horland R,Sonntag F,Klotzbach U,Sakharov D,Tonevitsky A,Lauster R
    BACKGROUND & AIMS: :Various factors, including the phylogenetic distance between laboratory animals and humans, the discrepancy between current in vitro systems and the human body, and the restrictions of in silico modelling, have generated the need for new solutions to the ever-increasing worldwide dilemma of substance testing. This review provides a historical sketch on the accentuation of this dilemma, and highlights fundamental limitations to the countermeasures taken so far. It describes the potential of recently-introduced microsystems to emulate human organs in 'organ-on-a-chip' devices. Finally, it focuses on an in-depth analysis of the first devices that aimed to mimic human systemic organ interactions in 'human-on-a-chip' systems. Their potential to replace acute systemic toxicity testing in animals, and their inability to provide alternatives to repeated dose long-term testing, are discussed. Inspired by the latest discoveries in human biology, tissue engineering and micro-systems technology, this review proposes a paradigm shift to overcome the apparent challenges. A roadmap is outlined to create a new homeostatic level of biology in 'human-on-a-chip' systems in order to, in the long run, replace systemic repeated dose safety evaluation and disease modelling in animals.
    背景与目标: : 各种因素,包括实验动物与人类之间的系统发育距离,当前的体外系统与人体之间的差异以及计算机模拟的限制,都需要新的解决方案来解决全球范围内不断增长的难题。物质测试。这篇评论提供了关于这一困境加剧的历史草图,并强调了迄今为止采取的对策的根本局限性。它描述了最近引入的微系统在 “芯片上的器官” 设备中模拟人体器官的潜力。最后,它着重于对旨在模仿 “芯片上的人” 系统中人体全身器官相互作用的第一批设备的深入分析。讨论了它们替代动物急性全身毒性测试的潜力,以及它们无法提供重复剂量长期测试的替代方法。受人类生物学,组织工程和微系统技术的最新发现的启发,这篇评论提出了一种范式转变,以克服明显的挑战。概述了在 “芯片上的人” 系统中创建新的生物稳态水平的路线图,以便从长远来看取代动物的系统重复剂量安全性评估和疾病建模。

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