• 【热应激对雄性小鼠体内和体外受精能力的影响。】 复制标题 收藏 收藏
    DOI:10.1071/rd05022 复制DOI
    作者列表:Yaeram J,Setchell BP,Maddocks S
    BACKGROUND & AIMS: :A study was conducted to determine whether following exposure of male mice to high temperatures, the ability of their spermatozoa to fertilise ova was reduced, especially during the period before the males became completely infertile. Male mice placed in a microclimate chamber at 36 degrees C for two periods, each of 12 h on successive days, were less able to fertilise control females in vivo when mated and, even in those females that became pregnant, litter size was reduced. However, these effects were associated with falls in testis weight and numbers of spermatozoa in the testis and epididymis. To determine whether the effect on fertility was a result of the decreased spermatozoa numbers, spermatozoa were collected from the epididymides of heated and control males. Equal numbers of motile spermatozoa from an unselected sample or those subjected to a swim-up procedure to separate those that were motile from the immotile ones in the sample were then mixed in vitro with oocytes from superovulated normal females. Similar numbers of spermatozoa from both control and heated males bound to the zona pellucida but smaller percentages of the oocytes were fertilised by spermatozoa from the heated males and fewer of these spermatozoa penetrated the ova. The effects were first seen 7 days after the heat exposure and became more obvious after 10 or 14 days.
    背景与目标: :进行了一项研究,以确定在雄性小鼠暴露于高温之后,其精子受精卵的能力是否降低,尤其是在雄性小鼠完全不育之前的时期。将雄性小鼠在36摄氏度的小气候室内放置两次,每次连续12h,连续交配时,它们在体内不能使对照雌性小鼠受精,即使在那些怀孕的雌性小鼠中,其产仔数也会减少。然而,这些影响与睾丸重量的下降以及睾丸和附睾中精子数量的减少有关。为了确定对生育力的影响是否是精子数量减少的结果,从加热和对照雄性的附睾中收集精子。然后,将来自未选择样品的等量活动精子或经过泳动程序分离出样品中不活动精子的活动精子与来自超排卵正常雌性的卵母细胞体外混合。结合在透明带上的对照雄性和受热雄性的精子数量相似,但是受热雄性的精子受精的卵母细胞受精的百分比较小,并且这些精子很少渗透到卵子中。在暴露于热的7天后首次见到这种效果,在10或14天后更加明显。
  • 【T(2)加权的microMRI和诱发的低髓鞘转基因小鼠的发展过程中视觉系统测量的潜力。】 复制标题 收藏 收藏
    DOI:10.1007/s11064-006-9121-z 复制DOI
    作者列表:Martin M,Reyes SD,Hiltner TD,Givogri MI,Tyszka JM,Fisher R,Campagnoni AT,Fraser SE,Jacobs RE,Readhead C
    BACKGROUND & AIMS: :Our objective was to follow the course of a dysmyelinating disease followed by partial recovery in transgenic mice using non-invasive high-resolution (117 x 117 x 70 microm) magnetic resonance (microMRI) and evoked potential of the visual system (VEP) techniques. We used JOE (for J37 golli overexpressing) transgenic mice engineered to overexpress golli J37, a product of the Golli-mbp gene complex, specifically in oligodendrocytes. Individual JOE transgenics and their unaffected siblings were followed from 21 until 75-days-old using non-invasive in vivo VEPs and 3D T2-weighted microMRI on an 11.7 T scanner, performing what we believe is the first longitudinal study of its kind. The microMRI data indicated clear, global hypomyelination during the period of peak myelination (21-42 days), which was partially corrected at later ages (>60 days) in the JOE mice compared to controls. These microMRI data correlated well with [Campagnoni AT (1995) "Molecular biology of myelination". In: Ransom B, Kettenmann H (eds) Neuroglia--a Treatise. Oxford University Press, London, pp 555-570] myelin staining, [Campagnoni AT, Macklin WB (1988) Cellular and molecular aspects of myelin protein gene-expression. Mol Neurobiol 2:41-89] a transient intention tremor during the peak period of myelination, which abated at later ages, and [Lees MB, Brostoff SW (1984) Proteins in myelin. In: Morell (ed) Myelin. Plenum Press, New York and London, pp 197-224] VEPs which all indicated a significant delay of CNS myelin development and persistent hypomyelination in JOE mice. Overall these non-invasive techniques are capable of spatially resolving the increase in myelination in the normally developing and developmentally delayed mouse brain.
    背景与目标: :我们的目标是通过非侵入性高分辨率(117 x 117 x 70 microm)磁共振(microMRI)和诱发视觉系统(VEP)技术追踪转基因小鼠的运动异常,然后部分恢复。我们使用经工程改造过表达Golli-mbp基因复合物产物Golli J37(特别是在少突胶质细胞中)的JOE(用于J​​37 golli过表达)转基因小鼠。从21岁到75天大,使用11.7 T扫描仪上的非侵入性体内VEP和3D T2加权显微MRI对个体JOE转基因及其未受影响的兄弟姐妹进行跟踪研究,我们认为这是同类研究中的首次纵向研究。显微MRI数据表明,在峰值髓鞘形成期(21-42天)期间出现了明显的整体性低髓鞘形成,与对照组相比,JOE小鼠在以后的年龄(> 60天)中得到了部分纠正。这些显微MRI数据与[Campagnoni AT(1995)“髓鞘形成的分子生物学”)有很好的相关性。在:Ransom B,Kettenmann H(eds)Neuroglia-专着中。牛津大学出版社,伦敦,第555-570页]髓磷脂染色,[Campagnoni AT,Macklin WB(1988)髓磷脂蛋白基因表达的细胞和分子方面。 [Mol Neurobiol 2:41-89]在髓鞘形成高峰期发生短暂的意向性震颤,此现象在以后的年龄有所减轻,[Lees MB,Brostoff SW(1984)Proteins in髓磷脂。在:莫雷尔(编辑)髓磷脂。 [Plenum Press,纽约和伦敦,第197-224页] VEP均表明JOE小鼠的CNS髓磷脂发育显着延迟和持续性髓鞘减少。总体而言,这些非侵入性技术能够在空间上解决正常发育和发育迟缓的小鼠大脑中髓鞘形成的增加。
  • 【先天性心脏病中的心脏T1定位:用于测量心肌细胞外体积分数的推注与输注方案。】 复制标题 收藏 收藏
    DOI:10.1007/s10554-017-1191-2 复制DOI
    作者列表:Al-Wakeel-Marquard N,Rastin S,Muench F,O H-Ici D,Yilmaz S,Berger F,Kuehne T,Messroghli DR
    BACKGROUND & AIMS: :Myocardial extracellular volume fraction (ECV) reflecting diffuse myocardial fibrosis can be measured with T1 mapping cardiovascular magnetic resonance (CMR) before and after the application of a gadolinium-based extracellular contrast agent. The equilibrium between blood and myocardium contrast concentration required for ECV measurements can be obtained with a primed contrast infusion (equilibrium contrast-CMR). We hypothesized that equilibrium can also be achieved with a single contrast bolus to accurately measure diffuse myocardial fibrosis in patients with congenital heart disease (CHD). Healthy controls (n = 17; median age 24.0 years) and patients with CHD (n = 19; 25.0 years) were prospectively enrolled. Using modified Look-Locker inversion recovery T1 mapping before, 15 min after bolus injection, and during constant infusion of gadolinium-DOTA, T1 values were obtained for blood pool and myocardium of the left ventricle (LV), the interventricular septum (IVS), and the right ventricle (RV) in a single midventricular plane in short axis or in transverse orientation. ECV of LV, IVS and RV by bolus-only and bolus-infusion correlated significantly in CHD patients (r = 0.94, 0.95, and 0.74; p < 0.01, respectively) and healthy controls (r = 0.96, 0.89, and 0.64; p < 0.05, respectively). Bland-Altman plots revealed no significant bias between the techniques for any of the analyzed regions. ECV of LV and RV myocardium measured by bolus-only T1 mapping agrees well with bolus-infusion measurements in patients with CHD. The use of a bolus-only approach facilitates the integration of ECV measurements into existing CMR imaging protocols, allowing for assessment of diffuse myocardial fibrosis in CHD in clinical routine.
    背景与目标: :应用基于g的细胞外造影剂前后,可通过T1映射心血管磁共振(CMR)来测量反映弥漫性心肌纤维化的心肌细胞外体积分数(ECV)。 ECV测量所需的血液和心肌造影剂浓度之间的平衡可通过灌注造影剂(平衡造影剂CMR)获得。我们假设通过单次对比推注也可以达到平衡,以准确测量先天性心脏病(CHD)患者的弥漫性心肌纤维化。前瞻性纳入健康对照组(n = 17);中位年龄24.0岁; CHD患者(n = 19; 25.0岁)。使用改良的Look-Locker反转恢复T1映射,在推注大剂量,之后15分钟以及在持续输注--DOTA期间,获得了左心室(LV),心室间隔(IVS)的血池和心肌的T1值,右心室(RV)在短心轴或横向方向的单个心室中平面内。仅推注和推注输注的LV,IVS和RV的ECV在CHD患者(分别为r = 0.94、0.95和0.74; p <0.01)和健康对照者(r = 0.96、0.89和0.64; p中显着相关)分别<0.05)。布兰德-奥特曼(Bland-Altman)图显示,任何被分析区域的技术之间均无明显偏差。通过仅推注T1测绘测得的LV和RV心肌的ECV与CHD患者的推注量测量非常吻合。仅推注方法的使用有助于将ECV测量值集成到现有的CMR成像协议中,从而可以在临床常规中评估CHD中弥漫性心肌纤维化。
  • 【血浆中瘦素和脂联素的单次或连续测量对肺动脉高压有预后价值吗?】 复制标题 收藏 收藏
    DOI:10.1177/2045893217717219 复制DOI
    作者列表:Tonelli AR,Fares WH,Dakkak W,Rao Y,Zhou X,Dweik RA
    BACKGROUND & AIMS: :Leptin (a neuroendocrine peptide that enhances metabolism and acts on the hypothalamus to suppress appetite) and adiponectin (a protein that has insulin-sensitizing, anti-inflammatory, and antiproliferative properties) are involved in the pathobiology of pulmonary arterial hypertension (PAH). We hypothesized that plasma leptin and adiponectin as well as the leptin/adiponectin ratio are abnormal in PAH patients and their levels track with disease severity and functional changes during follow-up. We tested this hypothesis in a cohort of patients included in the 16-week, international, multicenter, double-blind, placebo-controlled FREEDOM-C2 study. Blood was collected at baseline and week 16 in 178 out of 310 randomized patients with PAH. Baseline plasma leptin and adiponectin concentrations were 25 ± 31 ng/mL and 7.8 ± 6.1 ug/mL, respectively. Leptin, adiponectin, and leptin/adiponectin (mean ± SD) changes at 16 week were of small magnitude. Leptin at baseline was significantly associated with older age, higher BMI, higher Borg dyspnea index, and lower NT-pro BNP. Women had higher levels of leptin than men (30.5 ± 33.2 versus 7.2 ± 6.4 ng/mL), even when adjusting for background therapy and etiology (linear regression: β = 21.8, P < 0.001). Adiponectin was negatively associated with BMI and positively associated with NT-pro BNP. Changes in leptin, adiponectin, and leptin/adiponectin ratio adjusted for weight at 16 weeks did not predict functional class, distance walk in 6 min or survival at one, two, three, or four years. Plasma leptin and adiponectin at baseline and their change at 16-week do not appear to significantly impact prognosis in PAH.
    背景与目标: :瘦素(一种增强神经代谢的神经内分泌肽,作用于下丘脑以抑制食欲)和脂连蛋白(一种具有胰岛素敏感性,抗炎和抗增殖特性的蛋白质)参与了肺动脉高压(PAH)的病理生物学研究。我们假设PAH患者的血浆瘦素和脂联素以及瘦素/脂联素比值异常,并且其水平随随访期间的疾病严重程度和功能变化而变化。我们在16周,国际,多中心,双盲,安慰剂对照的FREEDOM-C2研究中对一组患者进行了检验。在310位随机分组的PAH患者中,有178位在基线和第16周采集了血液。基线血浆瘦素和脂联素浓度分别为25±±31μng/ mL和7.8±±6.1μg/ mL。瘦素,脂联素和瘦素/脂联素在16周时的变化很小。基线时的瘦素与年龄增加,BMI升高,Borg呼吸困难指数升高和NT-pro BNP降低显着相关。即使调整背景治疗和病因,女性的瘦素水平也比男性高(30.5±33.2 vs 7.2±6.4μng/ mL)(线性回归:β≥21.8,P <0.001)。脂联素与BMI负相关,与NT-pro BNP正相关。瘦体重,脂联素和瘦素/脂联素之比的变化(按体重在16周时调整)不能预测功能等级,6分钟步行距离或一,二,三年或四年的生存率。基线时血浆瘦素和脂联素及其在16周时的变化似乎并未显着影响PAH的预后。
  • 【乳酸和丙酮酸测量值对评估大鼠心脏细胞质中游离烟酰胺-腺嘌呤二核苷酸氧化还原状态的价值。】 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,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。研究的疾病包括心脏工作增加,缺氧,胰岛素的添加,急性四氧嘧啶糖尿病,慢性链脲佐菌素糖尿病和酮体的添加。真实的细胞内乳酸值(从乳酸和山梨糖醇空间估算)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,乳酸梯度降低。由细胞外乳酸盐/丙酮酸盐比率计算出的细胞质游离NAD / NADH比率与在非糖尿病性心脏中由组织α-甘油磷酸酯/二羟基丙酮磷酸盐比率计算出的NAD / NADH比率相似并且在相同的方向上改变。在糖尿病心脏中,细胞外和组织中乳酸/丙酮酸的比率与组织α-甘油-磷酸盐/二羟基丙酮磷酸盐的比率给出的细胞质游离NAD / NADH比率值不同。这些差异与丙酮酸在灌注液和组织中的积累有关。细胞外乳酸/丙酮酸比的变化比心脏乳酸/丙酮酸比的变化更好地区分了急性心脏功和急性缺氧。这些观察结果支持在评估心肌氧合状态时使用细胞外乳酸/丙酮酸的测量结果,但要考虑到营养因素并且排除糖尿病状态。
  • 【关于生育治疗的生育知识和信念:《国际生育决策研究》的发现。】 复制标题 收藏 收藏
    DOI:10.1093/humrep/des402 复制DOI
    作者列表:Bunting L,Tsibulsky I,Boivin J
    BACKGROUND & AIMS: STUDY QUESTION:How good is fertility knowledge and what are treatment beliefs in an international sample of men and women currently trying to conceive? SUMMARY ANSWER:The study population had a modest level of fertility knowledge and held positive and negative views of treatment. WHAT IS KNOWN ALREADY:Few studies have examined general fertility treatment attitudes but studies of specific interventions show that attitudes are related to characteristics of the patient, doctor and context. Further, research shows that fertility knowledge is poor. However, the majority of these studies have examined the prevalence of infertility, the optimal fertile period and/or age-related infertility in women, in university students and/or people from high-resource countries making it difficult to generalize findings. STUDY DESIGN, SIZE, DURATION:A cross-sectional sample completed the International Fertility Decision-making Study (IFDMS) over a 9-month period, online or via social research panels and in fertility clinics. PARTICIPANTS/MATERIALS, SETTING, METHODS:Participants were 10 045 people (8355 women, 1690 men) who were on average 31.8 years old, had been trying to conceive for 2.8 years with 53.9% university educated. From a total of 79 countries, sample size was >100 in 18 countries. All 79 countries were assigned to either a very high Human Development Index (VH HDI) or a not very high HDI (NVH HDI). The IFDMS was a 45-min, 64-item English survey translated into 12 languages. The inclusion criteria were the age between 18 and 50 years and currently trying to conceive for at least 6 months. Fertility knowledge was assessed using a 13-item correct/incorrect scale concerned with risk factors, misconceptions and basic fertility facts (range: 0-100% correct). Treatment beliefs were assessed with positive and negative statements about fertility treatment rated on a five-point agree/disagree response scale. MAIN RESULTS AND THE ROLE OF CHANCE:Average correct score for Fertility Knowledge was 56.9%, with greater knowledge significantly related to female gender, university education, paid employment, VH HDI and prior medical consultation for infertility (all P < 0.001). The mean agreement scores for treatment beliefs showed that agreement for positive items (safety, efficacy) was correlated with agreement for negative items (short/long-term physical/emotional effects) (P > 0.001). People who had given birth/fathered a child, been trying to conceive for less than 12 months, who had never consulted for a fertility problem and who lived in a country with an NVH HDI agreed less with negative beliefs. HDI, duration of trying to conceive and help-seeking were also correlates of higher positive beliefs, alongside younger age, living in an urban area and having stepchildren. Greater fertility knowledge was associated with stronger agreement on negative treatment beliefs items (P < 0.001) but was unrelated to positive treatment beliefs items. LIMITATIONS, REASONS FOR CAUTION:There was volunteer bias insofar as more women, people of higher education and people with fertility problems (i.e. met criteria for infertility, had consulted a medical doctor, had conceived with fertility treatment) participated and this was true in VH and NVH HDI countries. The bias may mean that people in this sample had better fertility knowledge and less favourable treatment beliefs than is the case in the general population. WIDER IMPLICATIONS OF THE FINDINGS:Educational interventions should be directed at improving knowledge of fertility health. Future prospective research should be aimed at investigating how fertility knowledge and treatment beliefs affect childbearing and help-seeking decision-making.
    背景与目标: 研究问题:在目前试图受孕的国际男女样本中,生育知识的水平如何?对治疗的看法是什么?
    总结答案:该研究人群对生育的知识水平不高,对治疗持正面和负面的看法。
    已有的知识:很少有研究检查一般的生育治疗态度,但是对特定干预措施的研究表明,态度与患者,医生和环境的特征有关。此外,研究表明生育知识很差。但是,这些研究中的大多数都检查了大学生和/或资源丰富国家的人中女性的不育症患病率,最佳生育期和/或与年龄相关的不育症,因此难以一概而论。
    研究设计,规模,期限:一个横断面样本在9个月的时间内通过在线或通过社会研究小组以及在生育诊所完成了国际生育力决策研究(IFDMS)。
    参与者/材料,环境,方法:参与者为10045人(8355名女性,1690名男性),平均年龄31.8岁,尝试受孕2.8年,大学学历占53.9%。在总共79个国家中,有18个国家的样本量大于100。所有79个国家/地区都被分配为人类发展指数(VH HDI)很高或不是很高的HDI(NVH HDI)。 IFDMS是一项长达45分钟,包含64个项目的英语调查问卷,被翻译成12种语言。纳入标准为18至50岁之间的年龄,目前试图怀孕至少6个月。使用与危险因素,误解和基本生育率有关的13项正确/不正确的量表评估了生育知识(正确范围为0-100%)。用五点同意/不同意反应量表对有关生育力治疗的正面和负面陈述对治疗信念进行了评估。
    主要结果和机会的作用:生育知识的平均正确分数为56.9%,其中更多知识与女性,大学教育,有偿就业,VH HDI和不育相关的医学咨询密切相关(所有P <0.001)。治疗信念的平均协议得分显示,阳性项目(安全性,有效性)的一致性与阴性项目(短期/长期的身体/情绪影响)的一致性相关(P> 0.001)。生育/生过孩子,试图怀孕少于12个月,从未就生育问题进行咨询并且生活在NVH HDI的国家的人不同意否定。人类发展指数(HDI),尝试受孕的时间和寻求帮助的时间也与较高的积极信念,较年轻的年龄,居住在市区和有继子女的信念相关。较高的生育知识与对消极治疗信念项目达成更强的共识有关(P <0.001),但与积极治疗信念项目无关。
    局限性,注意事项的原因:自愿参加者的偏见涉及更多的妇女,受过高等教育的人和有生育问题的人(即达到不育标准,咨询医生,接受过生育治疗的人),这在VH中是正确的和NVH HDI国家。这种偏见可能意味着与一般人群相比,该样本中的人具有更好的生育知识和较差的治疗信念。
    结论的教育意义:教育干预措施应旨在提高对生育健康的认识。未来的前瞻性研究应旨在调查生育知识和治疗观念如何影响生育和寻求帮助的决策。
  • 【肽基精氨酸脱亚氨酶(PAD)6对于卵母细胞细胞骨架片的形成和女性的生育能力至关重要。】 复制标题 收藏 收藏
    DOI:10.1016/j.mce.2007.05.005 复制DOI
    作者列表:Esposito G,Vitale AM,Leijten FP,Strik AM,Koonen-Reemst AM,Yurttas P,Robben TJ,Coonrod S,Gossen JA
    BACKGROUND & AIMS: :Peptidylarginine deiminase 6 (PAD6) is an enzyme that is uniquely expressed in male and female germ cells. To study the function of this enzyme in vivo we generated mice deficient for PAD6. Here we show that inactivation of the PAD6 gene in mice leads to female infertility whereas male fertility is not affected. The absence of the PAD6 protein and consequently absence of citrullination activity in oocytes results in dispersal of the cytoskeletal sheets in oocytes, indicating an essential role of these germ cell-specific structures in zygote/embryo development. PAD6 deficient mice do not show any other overt phenotype. Thus, we identify citrullination as a new regulator of fertility.
    背景与目标: :肽基精氨酸脱亚氨酶6(PAD6)是一种在雄性和雌性生殖细胞中独特表达的酶。为了研究该酶在体内的功能,我们产生了PAD6缺陷的小鼠。在这里,我们显示,小鼠中PAD6基因的失活导致女性不育,而男性不育不受影响。卵母细胞中缺乏PAD6蛋白,因此缺乏瓜氨酸化活性,导致卵母细胞中细胞骨架片的分散,表明这些生殖细胞特异性结构在合子/胚胎发育中起着至关重要的作用。 PAD6缺陷的小鼠没有显示任何其他明显的表型。因此,我们确定瓜氨酸化是生育的新调节剂。
  • 【在急诊科室中解释尿液中三环抗抑郁药的测定:两种定性的护理现场尿液三环抗抑郁药免疫分析与定量血清色谱分析的比较。】 复制标题 收藏 收藏
    DOI:10.1093/jat/31.5.270 复制DOI
    作者列表:Melanson SE,Lewandrowski EL,Griggs DA,Flood JG
    BACKGROUND & AIMS: :Patients taking tricyclic antidepressants (TCA) can experience toxicity or severe side effects. As a rapid and less technically demanding alternative to quantitative serum analysis, most laboratories offer qualitative immunoassays to assist in the evaluation of a suspected TCA overdose. However, the relationship between quantitative serum and qualitative urine levels of TCA-related compounds and their metabolites has not been comprehensively studied. Serum high-performance liquid chromatography results were compared to the qualitative urine results using the Syva Rapid Test and the Biosite Triage. Serum concentrations of amitriptyline, desipramine, doxepin, imipramine, and nortriptyline ranging from subtherapeutic to toxic triggered a positive response on both urine immunoassay devices. On the other hand, neither immunoassay uniformly detected clomipramine, even at serum levels greater than the therapeutic range. False positives due to cyclobenzaprine were more common with the Biosite assay. For virtually all positive urine TCA findings, it was not possible to determine whether the positive results corresponded to subtherapeutic, therapeutic, supratherapeutic, or toxic serum concentrations. Because urine immunoassays are the only option for many laboratories analyzing specimens for TCAs (especially in an emergency setting), clinicians must understand the limitations and interpret results in conjunction with clinical findings and/or quantitation of serum levels.
    背景与目标: :服用三环抗抑郁药(TCA)的患者可能会出现毒性或严重的副作用。作为定量血清分析的一种快速且对技术要求不高的替代方法,大多数实验室提供定性免疫测定,以协助评估可疑的TCA过量。但是,尚未对TCA相关化合物及其代谢产物的定量血清与定性尿液水平之间的关系进行全面研究。使用Syva快速测试和Biosite Triage将血清高效液相色谱结果与定性尿液结果进行比较。从亚治疗到有毒的血清阿米替林,地昔帕明,多塞平,丙咪嗪和去甲替林的血清浓度在两种尿液免疫测定装置上均引发阳性反应。另一方面,即使在血清水平大于治疗范围的情况下,也没有一种免疫测定能够统一检测到氯米帕明。在Biosite分析中,环苯扎林引起的假阳性更为常见。对于几乎所有尿液TCA阳性结果,都无法确定阳性结果是否对应于亚治疗,治疗,超治疗或有毒血清浓度。由于尿液免疫分析是许多实验室分析TCA样本的唯一选择(尤其是在紧急情况下),因此临床医生必须了解局限性,并结合临床发现和/或血清水平定量来解释结果。
  • 【鼻窦区域肿瘤的动态IMRT治疗:蒙特卡罗计算与治疗计划系统计算和离子室测量的比较。】 复制标题 收藏 收藏
    DOI:10.1177/153303460600500505 复制DOI
    作者列表:Court LE,Jahnke L,Chin D,Song J,Cormack R,Zygmanski P,Tishler RB,Chin L
    BACKGROUND & AIMS: :Results are presented comparing Monte Carlo (MC) calculations for dynamic IMRT treatments of tumors in the sinus region with Eclipse treatment planning system dose calculations, and ion chamber measurements. The EGS4nrc MC code, BEAMnrc, was commissioned to simulate a Varian 21Ex Linac for both open and IMRT fields. The accuracy of the simulation for IMRT plans was evaluated using a head phantom by comparing MC, Eclipse, TLD results, and ion chamber in solid water phantom measurements. The MC code was then used to simulate dose distributions for five patients who were treated using dynamic IMRT for tumors in the sinus region. The results were compared with absolute and relative dose distributions calculated using Eclipse (pencil beam, modified-Batho inhomogeneity correction). Absolute dose differences were also compared with ion chamber results. Comparison of the doses calculated on the head phantom using MC, compared with Eclipse, ion chamber, and TLD measurements showed differences of -3.9%, -1.4%, and -2.0%, respectively (MC is colder). Relative dose distributions for the patient plans calculated using MC agreed well with those calculated using Eclipse with respect to targets and critical organs, indicating the modified-Batho correction is adequate. Average agreement for mean absolute target doses between MC and Eclipse was -3.0 +/-; 2.3% (1 s.d.). Agreement between ion chamber and Eclipse for these patients was -2.2 +/- 1.9%, compared with 0.2 +/- 2.0% for all head and neck IMRT patients. When Eclipse doses were corrected based on ion chamber results, agreement between MC and Eclipse was -0.7 +/- 2.0%, indicating a small systematic uncertainty in the doses calculated using the treatment planning system for this subset of patients.
    背景与目标: :结果比较了用蒙特卡洛(MC)计算窦道区域肿瘤的动态IMRT治疗与Eclipse治疗计划系统剂量计算和离子室测量值的比较结果。委托EGS4nrc MC代码BEAMnrc模拟开放域和IMRT域的Varian 21Ex Linac。通过比较MC,Eclipse,TLD结果和固体水体模测量中的离子室,使用头部体模评估了IMRT计划仿真的准确性。然后,将MC代码用于模拟五名使用动态IMRT进行鼻窦区域肿瘤治疗的患者的剂量分布。将结果与使用Eclipse计算出的绝对和相对剂量分布(铅笔束,改良的Batho不均匀性校正)进行比较。还将绝对剂量差异与离子室结果进行了比较。与使用Eclipse,离子室和TLD进行测量相比,使用MC在头部模型上计算的剂量进行了比较,分别显示出-3.9%,-1.4%和-2.0%的差异(MC更冷)。对于目标和关键器官,使用MC计算的患者计划的相对剂量分布与使用Eclipse计算的相对剂量分布非常吻合,表明改良的Batho校正是足够的。 MC和Eclipse之间的平均绝对目标剂量的平均一致性为-3.0 /-; 2.3%(1 s.d.)。对于这些患者,离子室和Eclipse之间的一致性为-2.2 /-1.9%,而所有头颈部IMRT患者的一致性为0.2 /-2.0%。根据离子室结果校正Eclipse剂量后,MC和Eclipse之间的一致性为-0.7 /-2.0%,这表明使用治疗计划系统为该患者子集计算的剂量存在系统性的不确定性。
  • 【姿势稳定性和姿势测量重复性的白天变化。】 复制标题 收藏 收藏
    DOI:10.1097/JOM.0b013e3180577796 复制DOI
    作者列表:Forsman P,Haeggström E,Wallin A,Toppila E,Pyykkö I
    BACKGROUND & AIMS: OBJECTIVE:Daytime sleepiness correlates with sleep-related accidents, but convenient tests for occupational sleepiness monitoring are scarce. The effect of daytime on balance, on posturographic measurements, and on their repeatability was investigated in 30 healthy volunteers as part of our work to develop such a test. METHODS:The daytime effect was assessed by measuring balance at 8:30 am, 10:30 am, and 1:30 pm. The repeatability was assessed with morning trials once a week for 1 month. The posturographic test was performed on a static force platform, and the balance was evaluated from a fractal dimension of sway, most common sway amplitude, and time interval for open-loop stance control. RESULTS:The balance worsened during the day, and it was possible to determine whether the measurement was performed in the morning or in the afternoon. The morning balance remained unchanged during the month-long test. CONCLUSIONS:Posturographic measurements are repeatable and have a circadian effect, which may be influenced by sleepiness.
    背景与目标: 目的:白天嗜睡与睡眠相关的事故有关,但缺乏方便的职业嗜睡监测测试。作为我们开展此类测试工作的一部分,我们在30名健康志愿者中研究了白天对平衡,姿势测量和重复性的影响。
    方法:通过测量上午8:30,上午10:30和下午1:30的平衡来评估白天的效果。通过每周一次的晨间试验评估可重复性,持续1个月。在静态力平台上进行后路测验,并通过摇摆的分形维数,最常见的摇摆幅度和开环姿态控制的时间间隔来评估平衡。
    结果:白天的平衡恶化,可以确定是在上午还是在下午进行测量。在为期一个月的测试中,上午余额保持不变。
    结论:姿势测量可重复并具有昼夜节律效应,这可能会受到困倦的影响。
  • 【每日滴入变应原后的介体测量:IL-5升高,IFN-γ降低。】 复制标题 收藏 收藏
    DOI:10.2500/aap.2008.29.3094 复制DOI
    作者列表:McDermott RA,Nelson HS,Dreskin SC
    BACKGROUND & AIMS: :This study was designed to measure symptoms, IL-4, IL-5, IFN-gamma, and eosinophilic cationic protein (ECP) in nasal secretions from subjects experiencing an artificial allergy season and to look for evidence of priming. Clinically relevant allergen was administered intranasally out of season to 12 asymptomatic individuals with seasonal allergic rhinitis. These individuals were then randomized to receive allergen or saline daily for the next 7 days. Nasal secretions and scrapings of nasal epithelium were obtained at baseline (day 1), 24 hours after the initial allergen administration (day 2), and 24 hours after the last instillation of allergen or saline (day 9). Nasal symptom scores (p < 0.0002), IL-5 mRNA (p = 0.03), and ECP (p < 0.02) increased after receiving the first challenge (day 2 compared with day 1). In the six subjects randomized to receive seven sequential daily challenges with allergen, symptom scores remained elevated (p < 0.02), IL-5 protein increased (p = 0.02), and IFN-gamma (p = 0.02) levels decreased (day 9 compared with day 1). In the six subjects randomized to receive seven sequential daily challenges with placebo, symptom scores, IL-5, and IFN-gamma levels were not significantly different (day 9 compared with day 1). Compared with the findings at day 2 (n = 12), the treated subjects (n = 6) had no further increase in symptoms but did show a further increase in IL-5 (p = 0.01) and a decrease in IFN-gamma (p = 0.02) at day 9. Daily instillation of moderate doses of allergen intranasally is characterized by persistent symptoms, elevation of IL-5, and reduced levels of IFN-gamma.
    背景与目标: :本研究旨在测量经历了人工过敏季节的受试者的鼻分泌物中的症状,IL-4,IL-5,IFN-γ和嗜酸性阳离子蛋白(ECP),并寻找引发的证据。临床相关的变应原是在季节外鼻内给予12例季节性变应性鼻炎的无症状个体。然后将这些个体随机分组,在接下来的7天中每天接受过敏原或生理盐水。在基线(第1天),首次施用过敏原后24小时(第2天)和最后滴入过敏原或生理盐水后第24小时(第9天)获得鼻腔分泌物和鼻上皮的刮痕。接受首次攻击后(第2天与第1天相比),鼻症状评分(p <0.0002),IL-5 mRNA(p = 0.03)和ECP(p <0.02)升高。在随机接受每日7次连续性过敏原攻击的6名受试者中,症状评分保持升高(p <0.02),IL-5蛋白升高(p = 0.02),IFN-γ(p = 0.02)水平降低(比较第9天)与第1天)。在随机接受安慰剂的七个连续每日挑战的六名受试者中,症状评分,IL-5和IFN-γ水平无显着差异(第9天与第1天相比)。与第2天的结果(n = 12)相比,接受治疗的受试者(n = 6)的症状没有进一步增加,但确实表现出IL-5进一步增加(p = 0.01)和IFN-γ降低( p = 0.02)在第9天。鼻内每日滴入中等剂量的过敏原的特征是持续症状,IL-5升高和IFN-γ水平降低。
  • 【左,右,近壁或远壁常见颈动脉内膜中层厚度测量:与心血管疾病和下肢动脉粥样硬化的关系。】 复制标题 收藏 收藏
    DOI:10.1016/s0895-4356(97)00059-0 复制DOI
    作者列表:Bots ML,de Jong PT,Hofman A,Grobbee DE
    BACKGROUND & AIMS: :We evaluated the differences in strength of the associations of prevalent cardiovascular disease and lower extremity arterial atherosclerosis to common carotid intima-media thickness, assessed by near wall measurements only, by far wall measurements only, and by the average of near and far wall measurements. The study was based on data from 1500 participants of the Rotterdam Study, a single-center-population-based prospective follow-up study among 7983 subjects, aged 55 years or over. Comparison of the strength of the associations of near wall intima-media thickness and of combined near and far wall intima-media thickness to cardiovascular disease and lower extremity arterial atherosclerosis revealed significantly stronger associations compared to associations observed for far wall intima-media thickness, in particular for stroke and lower extremity arterial disease. We conclude that near wall common carotid intima-media thickness measurement provides at least as good an indicator of atherosclerosis elsewhere and of cardiovascular risk as the far wall intima-media thickness measurement.
    背景与目标: :我们评估了常见心血管疾病和下肢动脉粥样硬化与颈总动脉内膜中层厚度之间的关联强度差异,仅通过近壁测量,仅远壁测量以及近壁和远壁测量的平均值来评估。该研究基于来自鹿特丹研究的1500名参与者的数据,鹿特丹研究是一项基于单中心人群的前瞻性随访研究,涉及对象为7983名年龄在55岁以上的受试者。比较近壁内膜-中层厚度和近,远壁内膜-中层厚度联合对心血管疾病和下肢动脉粥样硬化的强度,发现与远壁内膜-中层厚度相关的关联明显更强。特别适用于中风和下肢动脉疾病。我们得出的结论是,近壁普通颈动脉内膜中层厚度测量至少可以提供与远壁内膜中层厚度测量一样好的动脉粥样硬化和心血管风险的指标。
  • 【果蝇的精子成熟和雄性繁殖需要简单串联重复的RNA。】 复制标题 收藏 收藏
    DOI:10.7554/eLife.48940 复制DOI
    作者列表:Mills WK,Lee YCG,Kochendoerfer AM,Dunleavy EM,Karpen GH
    BACKGROUND & AIMS: :Tandemly-repeated DNAs, or satellites, are enriched in heterochromatic regions of eukaryotic genomes and contribute to nuclear structure and function. Some satellites are transcribed, but we lack direct evidence that specific satellite RNAs are required for normal organismal functions. Here, we show satellite RNAs derived from AAGAG tandem repeats are transcribed in many cells throughout Drosophila melanogaster development, enriched in neurons and testes, often localized within heterochromatic regions, and important for viability. Strikingly, we find AAGAG transcripts are necessary for male fertility, and that AAGAG RNA depletion results in defective histone-protamine exchange, sperm maturation and chromatin organization. Since these events happen late in spermatogenesis when the transcripts are not detected, we speculate that AAGAG RNA in primary spermatocytes 'primes' post-meiosis steps for sperm maturation. In addition to demonstrating essential functions for AAGAG RNAs, comparisons between closely related Drosophila species suggest that satellites and their transcription evolve quickly to generate new functions.
    背景与目标: :串联重复的DNA或卫星在真核生物基因组的异色区域富集,并有助于核结构和功能。一些卫星被转录,但我们缺乏直接证据证明正常机体功能需要特定的卫星RNA。在这里,我们显示了源自AAGAG串联重复序列的卫星RNA在果蝇整个发育过程中的许多细胞中转录,富含神经元和睾丸,通常位于异色区域内,对生存力很重要。令人惊讶的是,我们发现AAGAG转录本对于男性的生育能力是必需的,并且AAGAG RNA耗尽会导致组蛋白-鱼精蛋白交换缺陷,精子成熟和染色质组织缺陷。由于这些事件发生在精子发生的后期,但未检测到转录本,因此我们推测原代精子细胞中的AAGAG RNA会“引发”减数分裂后的精子成熟步骤。除了证明AAGAG RNA的基本功能外,密切相关的果蝇物种之间的比较还表明,卫星及其转录迅速发展以产生新的功能。
  • 【测量肌肉和大脑的散射和吸收变化。】 复制标题 收藏 收藏
    DOI:10.1098/rstb.1997.0055 复制DOI
    作者列表:Gratton E,Fantini S,Franceschini MA,Gratton G,Fabiani M
    BACKGROUND & AIMS: :Non-invasive techniques for the study of human brain function based on changes of the haemoglobin content or on changes of haemoglobin saturation have recently been proposed. Among the new methods, near-infrared transmission measurements may have significant advantages and complement well-established methods such as functional magnetic resonance imaging and positron emission tomography. Near-infrared measurements can be very fast, comparable in speed to electrophysiological measurements, bur are better localized. We will present the demonstration of measurements of millisecond signals due to brain activity in humans following stimulation of the visual cortex. However, major unresolved questions remain about the origin of the signals observed. Optical measurements on exposed cortex in animals show that both the absorption and the scattering coefficient are affected by neural activity. Model calculations show that the signals we detected may originate from rapid changes of the scattering coefficient in a region about 1 to 2 cm below the scalp. We discuss our measurement protocol, which is based on a frequency-domain instrument, and the algorithm to separate the absorption from the scattering contribution in the overall response. Our method produces excellent separation between scattering and absorption in relatively homogeneous masses such as large muscles. The extrapolation of our measurement protocol to a complex structure such as the human head is critically evaluated.
    背景与目标: :最近提出了基于血红蛋白含量变化或血红蛋白饱和度变化来研究人脑功能的非侵入性技术。在这些新方法中,近红外透射测量可能具有显着优势,并且可以完善功能性磁共振成像和正电子发射断层扫描等公认的方法。近红外测量可以非常快,在速度上可与电生理学测量相媲美,bur的定位更好。在视觉皮层刺激后,我们将演示由于人类大脑活动而导致的毫秒信号测量的演示。但是,关于观察到的信号的起源,仍然存在主要的未解决问题。对动物裸露皮层的光学测量表明,吸收和散射系数均受神经活动的影响。模型计算表明,我们检测到的信号可能源于头皮以下约1至2 cm的区域中散射系数的快速变化。我们讨论了基于频域仪器的测量协议以及将吸收与总响应中的散射贡献区分开的算法。我们的方法在相对均匀的质量(例如大块肌肉)中产生了散射和吸收之间的出色分离。我们严格地评估了将我们的测量协议外推到复杂结构(例如人头)的过程。
  • 【通过热致发光和闪光诱导的叶绿素荧光测量研究了在无球藻滨中光系统II电荷重组的能量学。】 复制标题 收藏 收藏
    DOI:10.1007/s11120-008-9373-3 复制DOI
    作者列表:Cser K,Deák Z,Telfer A,Barber J,Vass I
    BACKGROUND & AIMS: :We studied the charge recombination characteristics of Photosystem II (PSII) redox components in whole cells of the chlorophyll (Chl) d-dominated cyanobacterium, Acaryochloris marina, by flash-induced chlorophyll fluorescence and thermoluminescence measurements. Flash-induced chlorophyll fluorescence decay was retarded in the mus and ms time ranges and accelerated in the s time range in Acaryochloris marina relative to that in the Chl a-containing cyanobacterium, Synechocystis PCC 6803. In the presence of 3-(3,4-dichlorophenyl)-1, 1-dimethylurea, which blocks the Q(B) site, the relaxation of fluorescence decay arising from S(2)Q(A)(-) recombination was somewhat faster in Acaryochloris marina than in Synechocystis PCC 6803. Thermoluminescence intensity of the so called B band, arising from the recombination of the S(2)Q(B)(-) charge separated state, was enhanced significantly (2.5 fold) on the basis of equal amounts of PSII in Acaryochloris marina as compared with Synechocystis 6803. Our data show that the energetics of charge recombination is modified in Acaryochloris marina leading to a approximately 15 meV decrease of the free energy gap between the Q(A) and Q(B) acceptors. In addition, the total free energy gap between the ground state and the excited state of the reaction center chlorophyll is at least approximately 25-30 meV smaller in Acaryochloris marina, suggesting that the primary donor species cannot consist entirely of Chl a in Acaryochloris marina, and there is a contribution from Chl d as well.
    背景与目标: :我们通过闪光诱导的叶绿素荧光和热致发光测量研究了叶绿素(Chl)d为主的蓝细菌,无核小球藻的整个细胞中光系统II(PSII)氧化还原组分的电荷重组特性。相对于含Chla的蓝藻细菌(Synechochocystis PCC 6803)而言,在无花果滨海中,闪光诱导的叶绿素荧光衰减在mus和ms时间范围内被延迟,并在s时间范围内加速。在存在3-(3,4)的情况下-二氯苯基)-1,1-二甲基脲,阻止Q(B)站点,由S(2)Q(A)(-)重组引起的荧光衰减的弛豫比拟蓝藻PCC 6803快一点。由于在S.2Q(B)(-)电荷分离状态的重组下产生的所谓的B带的热致发光强度与无毒双杀藻码头中等量的PSII相比显着提高了(2.5倍)与拟南芥6803。我们的数据显示,电荷重组的能量在滨蛇纲中被修饰,导致Q(A)和Q(B)受体之间的自由能隙减小了约15 meV。此外,在无核小球藻的基态和反应中心叶绿素的激发态之间的总自由能隙至少小25-30 meV,这表明主要的供体物种不能完全由无毒无味的Chla组成, Chl d也有贡献。

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