• 【静脉溶栓在视网膜中央动脉阻塞中是否安全有效?极受好评的主题。】 复制标题 收藏 收藏
    DOI:10.1097/NRL.0000000000000129 复制DOI
    作者列表:Dumitrascu OM,Shen JF,Kurli M,Aguilar MI,Marks LA,Demaerschalk BM,Wingerchuk DM,O'Carroll CB
    BACKGROUND & AIMS: BACKGROUND:Central retinal artery occlusion (CRAO) is a neurological and ophthalmologic emergency associated with poor visual recovery. There is a dilemma regarding the appropriate treatment, as formal guidelines are lacking. Despite being considered an ocular equivalent of cerebral infarction, the time window of intravenous (IV) thrombolysis administration for maximum efficacy and safety in CRAO remains uncertain. OBJECTIVE:To critically assess the current evidence regarding the safety and effectiveness of IV thrombolysis in the treatment of patients with CRAO. METHODS:The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, and content experts in the fields of vascular neurology and ophthalmology. RESULTS:A recent patient-level meta-analysis was selected for critical appraisal. The study compared the visual recovery rates after IV thrombolysis in CRAO against the natural history of this illness and conservative therapies (ocular massage, anterior chamber paracentesis, and/or hemodilution). Time to thrombolytic therapy administration had a significant impact on visual recovery in CRAO (P<0.001). IV thrombolysis within the first 4.5 hours after symptom onset resulted in recovery of vision in 50.0% of the patients [95% confidence interval (CI), 32.4%-67.6%]. The rate of visual recovery was nearly 3 times higher than in the natural history cohort [odds ratio, 4.7 (95% CI, 2.3-9.6); P<0.001], with a 32.3% absolute risk reduction and a number needed to treat of 4.0 (95% CI, 2.6-6.6). There was no significant difference in the recovery rate after thrombolysis compared with the natural history cohort for those patients treated after 4.5 hours. No major hemorrhages occurred after alteplase administration in this meta-analysis. CONCLUSIONS:IV thrombolysis in CRAO seems to be safe and effective within the first 4.5 hours of symptom onset. A clinical decision based on this meta-analysis alone cannot be made due to several limitations. A randomized controlled clinical trial of early IV alteplase administration in CRAO is necessary to provide evidence-based therapeutic guidance.
    背景与目标: 背景:视网膜中央动脉阻塞(CRAO)是一种神经和眼科急症,伴有视力恢复不良。由于缺乏正式的指导方针,因此在适当的治疗上存在两难选择。尽管被认为是脑梗死的等效眼药,静脉溶栓治疗在CRAO中获得最大疗效和安全性的时间窗口仍然不确定。
    目的:严格评估有关IV溶栓治疗CRAO患者的安全性和有效性的现有证据。
    方法:通过制定一个严格评估的主题来解决该目标,该主题包括临床方案,结构化问题,文献检索策略,严格评估,结果评估,证据总结,评论和底线结论。参加者包括血管神经病学和眼科领域的顾问和住院神经病学家,医学馆员以及内容专家。
    结果:选择了近期的患者水平荟萃分析进行严格评估。这项研究比较了CRAO静脉溶栓后的视力恢复率与该疾病的自然病史和保守治疗方法(眼部按摩,前房穿刺和/或血液稀释)。溶栓治疗的时间对CRAO的视力恢复有显着影响(P <0.001)。在症状发作后的最初4.5小时内进行静脉溶栓治疗可导致50.0%的患者恢复视力[95%置信区间(CI),32.4%-67.6%]。视觉恢复率比自然史队列高出近3倍[赔率,比率4.7(95%CI,2.3-9.6); P <0.001],绝对危险度降低32.3%,需要治疗的数字为4.0(95%CI,2.6-6.6)。对于4.5小时后接受治疗的患者,溶栓后的恢复率与自然史队列相比无显着差异。在这项荟萃分析中,服用阿替普酶后未发生大出血。
    结论:CRAO中的IV溶栓似乎在症状发作的最初4.5小时内是安全有效的。由于一些限制,不能仅基于这种荟萃分析做出临床决定。在CRAO中早期静脉给予阿替普酶的随机对照临床试验对于提供循证治疗指导是必要的。
  • 【感染Acanthamoeba sp。的AIDS患者的生存。中枢神经系统。】 复制标题 收藏 收藏
    DOI:10.1007/s15010-017-1037-9 复制DOI
    作者列表:El Sahly H,Udayamurthy M,Parkerson G,Hasbun R
    BACKGROUND & AIMS: CASE DESCRIPTION:A 38-year-old man presented with headaches and generalized weakness. He was found to have AIDS; a ring-enhancing central nervous system lesion was found on brain imaging and he had elevated serum Toxoplasma gondii IgG levels. A diagnosis of presumptive toxoplasma encephalitis was made and he received antiretrovirals and antitoxoplasma therapy for 4 years. Intermittent headaches and evidence of disease progression on neuroimaging warranted further evaluation and cerebrospinal fluid analysis revealed amebic forms on hematoxylin and eosin staining and positive polymerase chain reaction testing for Acanthamoeba spp. He was placed on miltefosine, fluconazole, trimethoprim-sulfamethoxazole and flucytosine for 7 months. Five months after therapy discontinuation he remains asymptomatic and is taking only antiretroviral therapy. CONCLUSION:This is the first report of a patient with AIDS and granulomatous amebic encephalitis who survived with medical therapy only.
    背景与目标: 病例描述:一名38岁的男性出现头痛和全身无力。他被发现患有艾滋病;在大脑成像中发现了增强环的中枢神经系统病变,他的血清弓形虫IgG水平升高。诊断为推定性弓形虫脑炎,他接受了抗逆转录病毒药物和抗弓形虫疗法治疗了4年。间歇性头痛和神经影像学上疾病进展的证据值得进一步评估,脑脊液分析显示苏木精和曙红染色中的阿米巴形式以及棘阿米巴属菌种的阳性聚合酶链反应测试。他被放置在miltefosine,fluconazole,trimethoprim-sulfamethoxazole和flucytosine上7个月。停药五个月后,他无症状,仅接受抗逆转录病毒疗法。
    结论:这是第一例仅通过药物治疗幸存下来的艾滋病和肉芽肿性阿米巴脑炎患者的报告。
  • 【中央或外周施用瘦素对确定的脂肪库中去甲肾上腺素更新的影响。】 复制标题 收藏 收藏
    DOI:10.1152/ajpregu.00368.2006 复制DOI
    作者列表:Penn DM,Jordan LC,Kelso EW,Davenport JE,Harris RB
    BACKGROUND & AIMS: :Leptin preserves lean tissue but decreases adipose tissue by increasing lipolysis and/or inhibiting lipogenesis. The sympathetic nervous system (SNS) is a primary regulator of lipolysis, but it is not known if leptin increases norepinephrine turnover (NETO) in white adipose tissue. In this study, we examined the effect of leptin administered either as a chronic physiological dose (40 microg/day for 4 days from ip miniosmotic pumps) or as an acute injection in the third ventricle (1.5 microg injected two times daily for 2 days) on NETO and the size of brown and white fat depots in male Sprague Dawley rats. NETO was determined from the decline in tissue norepinephrine (NE) during 4 h following administration of the NE synthesis inhibitor alpha-methyl-para-tryrosine. The centrally injected leptin-treated animals demonstrated more dramatic reductions in food intake, body weight, and fat pad size and an increase in NETO compared with the peripherally infused animals. Neither route of leptin administration caused a uniform increase in NETO across all fat pads tested, and in both treatment conditions leptin decreased the size of certain fat pads independent of an increase in NETO. Similar discrepancies in white fat NETO were found for rats pair fed to leptin-treated animals. These results demonstrate that leptin acting either centrally or peripherally selectively increases sympathetic outflow to white fat depots and that a leptin-induced change in fat pad weight does not require an increase in NETO.
    背景与目标: 瘦素可通过增加脂肪分解和/或抑制脂肪生成来保留瘦肉组织,但可以减少脂肪组织。交感神经系统(SNS)是脂解作用的主要调节剂,但尚不清楚瘦素是否会增加白色脂肪组织中的去甲肾上腺素周转率(NETO)。在这项研究中,我们检查了瘦素作为慢性生理剂量(腹腔镜微渗透泵每天40微克/天,连续4天)或作为急性注射在第三脑室中的作用(1.5微克,每天两次,连续2天)的效果雄性Sprague Dawley大鼠的NETO和棕色和白色脂肪储库的大小。 NETO是根据NE合成抑制剂α-甲基-对-酪氨酸给药后4小时内组织去甲肾上腺素(NE)的下降确定的。与外围注入的动物相比,以瘦素为中心注射的动物表现出食物摄入量,体重和脂肪垫尺寸的显着减少,NETO增加。瘦素的两种给药方式均不会在所有测试的脂肪垫上引起NETO的均匀增加,并且在两种治疗条件下,瘦素均会降低某些脂肪垫的大小,而与NETO的增加无关。在喂给瘦素治疗的动物中,发现白脂肪NETO的相似差异。这些结果表明,瘦素在中央或外周选择性地起作用,增加了向白色脂肪贮库的交感性流出,并且瘦素诱导的脂肪垫重量变化不需要增加NETO。
  • 【用抗感染剂治疗的中心静脉导管在预防血液感染方面的临床效果和成本效益:系统评价和经济评价。】 复制标题 收藏 收藏
    DOI:10.3310/hta12120 复制DOI
    作者列表:Hockenhull JC,Dwan K,Boland A,Smith G,Bagust A,Dündar Y,Gamble C,McLeod C,Walley T,Dickson R
    BACKGROUND & AIMS: OBJECTIVES:To assess the clinical effectiveness and cost-effectiveness of central venous catheters (CVCs) treated with anti-infective agents in preventing catheter-related bloodstream infection (CRBSI). DATA SOURCES:Major electronic databases were searched from 1985 to August 2005. REVIEW METHODS:The systematic clinical and economic reviews were conducted according to accepted procedures. Only full economic evaluations (synthesis of costs and benefits) comparing the use of anti-infective central venous catheters (AI-CVCs) with untreated CVCs or other treated catheters were selected for inclusion in the economic review. RESULTS:A total of 32 trials met the clinical inclusion criteria. Seven different types of AI-CVC were identified, with the most frequently tested being chlorhexidine and silver sulfadiazine (CHSS) (externally treated), CHSS (externally and internally treated) and minocycline rifampicin (internally and externally treated). In general, the trials were of a poor quality in terms of reported methodology, microbiological relevance and control of confounding variables. The pooled result suggests a statistically significant advantage for AI-CVCs in comparison to standard catheters in reducing CRBSI [odds ratio (OR) 0.45, 95% confidence interval (CI) 0.34 to 0.60, 24 studies, I-squared = 0%, fixed effects]. Analysis by subgroups of catheters demonstrates that antibiotic-treated catheters and catheters treated internally and externally decrease CRBSI rates significantly (OR 0.26, 95% CI 0.15 to 0.46, six studies, I-squared = 0%, fixed effects, and OR 0.43, 95% CI 0.26 to 0.70, nine studies, I-squared = 0%, fixed effects, respectively). Catheters treated only externally demonstrate a wider CI and non-significant effect (OR 0.67, 95% CI 0.43 to 1.06, nine studies, I-squared = 0%, fixed effects). A treatment effect was also found for trials with an average duration of between 5 and 12 days, and for the one study with a mean duration of over 20 days. There was a statistically significant treatment effect for both femoral and jugular insertion sites and for those studies reporting a mix of insertion sites. The treatment effect was not observed in trials using exclusively subclavian insertion sites. Of the four trials that compared treated catheters, one reported a benefit of antibiotic-treated catheters over catheters treated externally with CHSS. All three sensitivity analyses testing for study design differences reported a statistically significant treatment effect. The review was limited owing to the quality of the trials included, marked differences in the definitions and methods of diagnosis of CRBSI, and inconsistent reporting of risk factors and patient population factors. Furthermore, two-thirds of trials were commercially funded. The economic performance (cost-effectiveness and potential cost-savings) of using AI-CVCs to reduce the number of CRBSIs in patients requiring a CVC was also reviewed. Results show that the use of AI-CVCs instead of standard CVCs can lead to a reduction in CRBSIs and decreased medical costs. To complement the reviews, a basic decision-analytic model was constructed to explore a range of possible scenarios for the NHS in England and Wales. Results show that for every patient who receives an AI-CVC there is an estimated cost-saving of 138.20 pounds. The multivariate sensitivity analyses estimate potentially large cost-savings, depending on the size of the population, under a wide range of cost and clinical assumptions. However, those considering the purchase of AI-CVCs should ensure that their patient populations and the important characteristics of local clinical practice are indeed similar to those described in this economic evaluation. CONCLUSIONS:Overall, AI-CVCs are clinically effective and relatively inexpensive and therefore their integration into clinical practice can be justified. However, the use of these anti-infective catheters without the appropriate use of other practical care initiatives will have only a limited success on the prevention of CRBSIs. Comparative trials are required to determine which, if any, of the treated catheters is the most effective. Pragmatic research related to the effectiveness of bundles of care that may reduce rates of CRBSI is also warranted.
    背景与目标: 目的:评估用抗感染药治疗的中心静脉导管(CVC)在预防导管相关的血流感染(CRBSI)方面的临床效果和成本效益。
    数据来源:从1985年到2005年8月,检索了主要的电子数据库。
    审查方法:根据公认的程序进行系统的临床和经济审查。只有将将抗感染中心静脉导管(AI-CVC)与未经治疗的CVC或其他经过治疗的导管的使用进行比较的全面经济评估(成本和收益的综合)才被选入经济评估。
    结果:总共32项试验符合临床纳入标准。鉴定出七种不同类型的AI-CVC,最常测试的是洗必太和磺胺嘧啶银(CHSS)(外部治疗),CHSS(外部和内部治疗)和米诺环素利福平(内部和外部治疗)。总体而言,就报告的方法学,微生物学相关性和混杂变量的控制而言,这些试验的质量较差。汇总结果表明,与标准导管相比,AI-CVC在降低CRBSI方面具有统计学上的显着优势[比值比(OR)0.45,95%置信区间(CI)0.34至0.60,24个研究,I平方= 0%,固定效果]。导管亚组的分析表明,抗生素治疗过的导管和内外治疗过的导管显着降低了CRBSI率(OR 0.26,95%CI 0.15至0.46,六项研究,I平方= 0%,固定效应,OR 0.43,95 %CI 0.26至0.70,九项研究,I平方= 0%,分别为固定效应)。仅经外部治疗的导管显示出较宽的置信区间,且无显着影响(OR为0.67,95%置信区间为0.43至1.06,九项研究,I平方= 0%,固定效应)。对于平均持续时间为5至12天的试验以及平均持续时间超过20天的一项研究,也发现了治疗效果。股骨和颈静脉插入部位以及报告混合插入部位的研究在统计学上均具有显着的治疗效果。在仅使用锁骨下插入位点的试验中未观察到治疗效果。在比较经治疗的导管的四项试验中,有一项报告指出,与经CHSS外部治疗的导管相比,经抗生素治疗的导管有益处。针对研究设计差异的所有三个敏感性分析测试均报告了统计学上显着的治疗效果。由于包括的试验质量,CRBSI的诊断定义和诊断方法存在明显差异以及危险因素和患者人群因素的报告不一致,因此该审查受到了限制。此外,三分之二的试验是由商业资助的。还审查了使用AI-CVC减少需要CVC的患者中CRBSI数量的经济表现(成本效益和潜在的成本节省)。结果表明,使用AI-CVC代替标准CVC可以减少CRBSI并降低医疗成本。为了补充评论,构建了基本的决策分析模型,以探索英格兰和威尔士的NHS的各种可能方案。结果表明,每位接受AI-CVC的患者估计可节省138.20磅。多元敏感性分析估计,在广泛的成本和临床假设下,取决于人群的规模,可能会节省大量成本。但是,考虑购买AI-CVC的人员应确保其患者人数和当地临床实践的重要特征确实与本经济评估中所述的相似。
    结论:总体而言,AI-CVC具有临床效果且相对便宜,因此可以证明将其整合到临床实践中是合理的。但是,在没有适当使用其他实践护理措施的情况下使用这些抗感染导管在预防CRBSI方面仅会取得有限的成功。需要进行比较试验来确定哪一种治疗过的导管最有效。还必须进行与可能降低CRBSI发生率的护理捆绑的有效性相关的务实研究。
  • 【希腊中部蒂瓦盆地地下水中的六价铬污染。】 复制标题 收藏 收藏
    DOI:10.1007/s00128-012-0831-4 复制DOI
    作者列表:Tziritis E,Kelepertzis E,Korres G,Perivolaris D,Repani S
    BACKGROUND & AIMS: :There is an increasing concern regarding elevated levels of Cr(VI) in the environment due to its higher mobility and toxicity compared to the trivalent form. Anomalous hexavalent chromium concentrations (up to 212 μg/L) were determined in irrigated groundwaters from the wider area of Thiva Basin (central Greece), frequently exceeding the permissible limit for human consumption (50 μg/L for total Cr). Based on the spatial distribution of Cr(VI) values, two groups of groundwater samples were distinguished, possibly reflecting different natural and/or anthropogenic factors that govern the levels of contamination. The first group is spatially located northwards of Thiva town and is consisted of concentrations that range from 13 to 212 μg/L (median 58 μg/L), while the second group is located near Mouriki village and Cr(VI) values range from <9 to 14 μg/L. The Cr(VI) chemical anomalies represent an important social problem because the agricultural products of this region are a major vegetable supply for Greece, bringing up the urgent need to evaluate the health effects associated with Cr(VI) exposure by ingesting the potentially contaminated foods.
    背景与目标: :由于与三价形式相比,Cr(VI)具有更高的迁移率和毒性,因此对环境中Cr(VI)含量升高的关注日益增加。在蒂瓦盆地(希腊中部)更广阔地区的灌溉地下水中确定了异常的六价铬浓度(高达212μg/ L),经常超过人类允许的摄入限量(总Cr含量为50μg/ L)。根据Cr(VI)值的空间分布,区分了两组地下水样品,可能反映了控制污染水平的不同自然和/或人为因素。第一组在空间上位于Thiva镇以北,其浓度范围为13至212μg/ L(中位数58μg/ L),而第二组位于Mouriki村附近,Cr(VI)值的范围为< 9至14μg/ L。六价铬化学异常代表了一个重要的社会问题,因为该地区的农产品是希腊的主要蔬菜供应,因此迫切需要通过摄入可能受到污染的食物来评估与六价铬暴露相关的健康影响。
  • 【奎那普利对慢性ACE的抑制作用可调节中枢血管加压素系统。】 复制标题 收藏 收藏
    DOI:10.1016/s0008-6363(97)00084-9 复制DOI
    作者列表:Muders F,Elsner D,Jandeleit K,Bahner U,Kromer EP,Kirst I,Riegger GA,Palkovits M
    BACKGROUND & AIMS: OBJECTIVE:The role of the brain as a target for angiotensin converting enzyme (ACE) inhibitors in the treatment of heart failure and hypertension is unclear. To test the hypothesis that ACE inhibitors may modulate other central neuropeptide systems such as the central vasopressin system, we studied the effects of chronic treatment with the ACE inhibitor, quinapril, on ACE activity and on central vasopressin content in specific brain areas in rats. METHODS:22 rats were chronically treated with quinapril (6 mg.kg-1 BW per gavage daily for 6 weeks; untreated controls, n = 14). ACE density in various brain regions was assessed by in vitro autoradiography using the specific ACE inhibitor, 125I-351A. Vasopressin content was determined in 19 brain areas (micropunch technique) known to be involved in cardiovascular regulation. RESULTS:Following chronic quinapril treatment ACE was significantly decreased in the thalamus (-38%), hypothalamus (-37%), hypophysis (-35%), cerebellum (-36%) choroid plexus (-20%), and locus coeruleus (-35%). Additionally, a marked reduction in serum ACE activity (-97%) was observed. Plasma levels of vasopressin were significantly decreased after quinapril treatment (0.97[s.e.m. 0.11] vs. 1.63[0.24] pg.ml-1 in controls, P < 0.05). Vasopressin content was significantly reduced in 9 of 19 specific brain areas. Regarding the hypothalamic vasopressin-producing nuclei, vasopressin was decreased in the paraventricular (292[197] vs. 2379[585] pg.mg-1 crotein in controls; P < 0.001) and supraoptic nuclei (13618[1979] vs. 24525[3894] pg.mg-1 protein; P < 0.05), but not in the suprachiasmatic nucleus. Vasopressin content was significantly reduced in brain areas connected by vasopressinergic fibres originating in the hypothalamic paraventricular nucleus: namely central gray, subcommissural organ, organum vasculosum laminae terminalis, dorsal raphe nucleus, and locus coerules. Vasopressin content was also significantly reduced in the median eminence (5887[1834] vs. 28321[4969] pg.mg-1 protein, P < 0.001), where the hormone is mainly concentrated in the hypothalamo-hypophysial tract. CONCLUSIONS:Autoradiographic studies in vitro indicate that orally administered quinapril suppresses central ACE activity after chronic treatment. ACE inhibition by quinapril strongly influences vasopressin content in important brain areas which are involved in central cardiovascular regulation. Therefore, central modulatory effects of ACE inhibitors may also contribute to overall therapeutic efficacy.
    背景与目标: 目的:尚不清楚脑作为血管紧张素转化酶(ACE)抑制剂的靶标在治疗心力衰竭和高血压中的作用。为了检验ACE抑制剂可能调节其他中枢神经肽系统(例如中枢加压素系统)的假设,我们研究了用ACE抑制剂奎纳普利进行慢性治疗对大鼠特定大脑区域ACE活性和中枢加压素含量的影响。
    方法:对22只大鼠进行喹那普利慢性治疗(每天每管饲喂6 mg.kg-1 BW,连续6周;未治疗的对照组,n = 14)。使用特定的ACE抑制剂125I-351A,通过体外放射自显影评估大脑各个区域的ACE密度。在已知参与心血管调节的19个脑区(微穿孔技术)中测定了加压素的含量。
    结果:慢性奎纳普利治疗后,丘脑(-38%),下丘脑(-37%),垂体(-35%),小脑(-36%)脉络丛(-20%)和蓝斑ACE的ACE显着降低(-35%)。另外,观察到血清ACE活性显着降低(-97%)。奎尼普利治疗后血浆血管加压素水平显着降低(对照组为0.97 [s.e.m。0.11] vs.对照组的1.63 [0.24] pg.ml-1,P <0.05)。在19个特定脑区中的9个中,加压素含量显着降低。关于下丘脑产生血管加压素的细胞核,室旁旁加压素的含量(对照组为292 [197]对2379 [585] pg.mg-1 crotein; P <0.001)和视上核(13618 [1979] vs.24525 []]降低。 [3894] pg.mg-1蛋白; P <0.05),但不在视交叉上核中。在下丘脑室旁核的血管加压能纤维连接的大脑区域中,血管加压素的含量显着降低:即中央灰色,连合下器官,椎板的末端器官,背ra核和轨迹小核。加压素的含量在中位显着性方面也显着降低(5887 [1834]对28321 [4969] pg.mg-1蛋白,P <0.001),该激素主要集中在下丘脑下垂体。
    结论:体外放射自显影研究表明,口服奎尼普利可抑制慢性治疗后的中枢ACE活性。奎那普利对ACE的抑制作用会强烈影响重要的脑部区域中血管加压素的含量,这些区域涉及中枢性心血管调节。因此,ACE抑制剂的中央调节作用也可能有助于总体治疗功效。
  • 【奥氮平和利培酮在中央杏仁核中诱导Fos表达。】 复制标题 收藏 收藏
    DOI:10.1016/j.ejphar.2019.172764 复制DOI
    作者列表:Pinna A,Costa G,Contu L,Morelli M
    BACKGROUND & AIMS: :The extended amygdala has been proposed to play an essential role in cognitive and affective processes and in neuropsychiatric disorders. In the present study, we examined the induction of Fos-like nuclei in the central amygdaloid nucleus (CeA), sublenticular extended amygdala (SLEA), interstitial nucleus of the posterior limb of the anterior commissure (IPAC), and bed nucleus of the stria terminalis (BSTL) of rodents to improve the knowledge regarding the pharmacological profile, therapeutic efficacy, and side-effects of olanzapine, an atypical antipsychotic drug and risperidone, a mixed atypical/typical antipsychotic drug in the rat brain. In addition, we evaluated the induction of Fos-like-nuclei in areas connected with these structures such as prefrontal cortex (PFCx), and nucleus accumbens shell, and in other important areas including the lateral septum and caudate-putamen that are involved in the therapeutic efficacy or side-effects of antipsychotic drugs. Fos-like-immunoreactivity induced by olanzapine and risperidone was compared with that by the atypical antipsychotic clozapine and typical antipsychotic haloperidol. Regarding the extended amygdala, and similarly to clozapine, olanzapine (5-10 mg/kg) and, with a lower efficacy, risperidone (1-3 mg/kg), induced Fos-like-nuclei in CeA, IPAC, SLEA, and BSTL. Both these drugs increased the induction of Fos-like-nuclei in PFCx, nucleus accumbens shell, lateral septum, and caudate-putamen. On the contrary, the increase of Fos-like-nuclei in the extended amygdala by haloperidol was restricted to IPAC only. These findings, consistent with the important role of extended amygdala in neuropsychiatric disorders characterized by affective disturbances, showed that olanzapine and risperidone, contrary to haloperidol, preferentially activated Fos-expression in these brain areas.
    背景与目标: :已提出扩大杏仁核在认知和情感过程以及神经精神疾病中起重要作用。在本研究中,我们检查了中央杏仁核(CeA),扁桃体下杏仁核(SLEA),前连合后肢的间质核(IPAC)和纹状体床核的Fos状核的诱导啮齿类动物的终末期(BSTL),以提高有关奥氮平(一种非典型的抗精神病药物)和利培酮(一种混合的非典型/典型的抗精神病药物)在大鼠脑中的药理作用,疗效和副作用的知识。此外,我们评估了与这些结构相关的区域(如前额叶皮层(PFCx)和伏隔核壳)以及其他重要区域(包括外侧中隔和尾状丘脑)的Fos样核的诱导。抗精神病药的治疗功效或副作用。将奥氮平和利培酮诱导的Fos样免疫反应性与非典型抗精神病药氯氮平和典型的抗精神病药物氟哌啶醇进行了比较。关于扩大的杏仁核,与氯氮平相似,奥氮平(5-10mg / kg)和利培酮(1-3mg / kg)疗效较差,在CeA,IPAC,SLEA和BSTL。这两种药物都增加了PFCx,伏隔核壳,外侧中隔和尾状壳-丘脑中Fos样核的诱导。相反,氟哌啶醇增加杏仁核中Fos样核的数量仅限于IPAC。这些发现与杏仁核延长在以情感障碍为特征的神经精神疾病中的重要作用一致,表明奥氮平和利培酮与氟哌啶醇相反,优先激活了这些大脑区域的Fos表达。
  • 【中央模式生成器固有地为运动产生的最佳搜索行为。】 复制标题 收藏 收藏
    DOI:10.7554/eLife.50316 复制DOI
    作者列表:Sims DW,Humphries NE,Hu N,Medan V,Berni J
    BACKGROUND & AIMS: :Efficient searching for resources such as food by animals is key to their survival. It has been proposed that diverse animals from insects to sharks and humans adopt searching patterns that resemble a simple Lévy random walk, which is theoretically optimal for 'blind foragers' to locate sparse, patchy resources. To test if such patterns are generated intrinsically, or arise via environmental interactions, we tracked free-moving Drosophila larvae with (and without) blocked synaptic activity in the brain, suboesophageal ganglion (SOG) and sensory neurons. In brain-blocked larvae, we found that extended substrate exploration emerges as multi-scale movement paths similar to truncated Lévy walks. Strikingly, power-law exponents of brain/SOG/sensory-blocked larvae averaged 1.96, close to a theoretical optimum (µ ≅ 2.0) for locating sparse resources. Thus, efficient spatial exploration can emerge from autonomous patterns in neural activity. Our results provide the strongest evidence so far for the intrinsic generation of Lévy-like movement patterns.
    背景与目标: :有效地寻找动物的食物等资源是动物赖以生存的关键。已经提出,从昆虫到鲨鱼再到人类的各种动物都采用类似于简单的Lévy随机行走的搜索方式,从理论上讲,这对于“盲目的觅食者”定位稀疏的零散资源是最佳的。为了测试这种模式是固有产生的还是通过环境相互作用产生的,我们追踪了果蝇幼虫在大脑,食管下神经节(SOG)和感觉神经元中具有(有或没有)突触活动受阻的果蝇幼虫。在大脑受阻的幼虫中,我们发现延长的底物探索以类似于截断的Lévy行走的多尺度运动路径出现。令人惊讶的是,大脑/ SOG /受感官阻断的幼虫的幂律指数平均为1.96,接近用于稀疏资源定位的理论最佳值(µ≅2.0)。因此,有效的空间探索可以从神经活动的自主模式中产生。迄今为止,我们的结果为Lévy样运动模式的内在生成提供了最有力的证据。
  • 【一种新型的血压计的评估,该血压计通过分析肱动脉上收缩压波来估算中心主动脉血压。】 复制标题 收藏 收藏
    DOI:10.1097/HJH.0b013e3283567b94 复制DOI
    作者列表:Lin AC,Lowe A,Sidhu K,Harrison W,Ruygrok P,Stewart R
    BACKGROUND & AIMS: BACKGROUND:Central arterial pressure is a better predictor of adverse cardiovascular outcomes than brachial blood pressure, but noninvasive measurement by applanation tonometry is technically demanding. METHOD:Pulsecor R6.5 is a novel device adapted from a standard sphygmomanometer which estimates the central aortic pressure from analysis of low-frequency suprasystolic waveforms at the occluded brachial artery. A physics-based model, which simulates the arterial system using elastic, thin-walled tube elements and Navier-Stokes equations, is used to calculate arterial pressure and flow propagation. To determine the reliability of the device, we compared 94 central systolic pressures estimated by Pulsecor to the simultaneous directly measured central aortic pressures at the time of coronary angiography in 37 individuals. RESULTS:There was good correlation in central SBP between catheter measurements and Pulsecor estimates by either invasive or noninvasive calibration methods (r = 0.99, P < 0.0001 and r = 0.95, P < 0.0001, respectively). The mean difference in central systolic pressure was 2.78 (SD 3.90) mmHg and coefficient of variation was 0.03 when the invasive calibration method was used.When the noninvasive calibration method was used, the mean difference in central systolic pressure was 0.25 (SD 6.31) mmHg and coefficient of variation was 0.05. CONCLUSION:We concluded that Pulsecor R6.5 provides a simple and easy method to noninvasively estimate central SBP, which has highly acceptable accuracy.
    背景与目标: 背景:与肱动脉血压相比,中央动脉压是心血管不良预后的更好预测指标,但是压平眼压计的无创测量在技术上要求很高。
    方法:Pulsecor R6.5是一种采用标准血压计的新型装置,该血压计通过分析闭塞的肱动脉的超搏动上的波形来估计中心主动脉压。基于物理的模型使用弹性薄壁管元件和Navier-Stokes方程模拟动脉系统,用于计算动脉压力和流量传播。为了确定设备的可靠性,我们比较了Pulsecor估计的94例中心收缩压与37例冠状动脉造影时同时直接测量的中心主动脉压。
    结果:通过有创或无创校准方法,导管测量值与Pulsecor估计之间的中央SBP均具有良好的相关性(分别为r = 0.99,P <0.0001和r = 0.95,P <0.0001)。使用有创校准方法时,收缩压的中心平均差异为2.78(SD 3.90)mmHg,采用无创校准法时的变异系数为0.03;使用无创校准方法时,收缩压的平均差异为0.25(SD 6.31)mmHg。变异系数为0.05。
    结论:我们得出结论,Pulsecor R6.5提供了一种简单且简便的方法来无创地估计中心性SBP,其准确度非常高。
  • 【托斯卡纳地区108例男性乳腺癌病例的BRCA1 / BRCA2突变状况和临床病理特征:在意大利中部的一项基于人群的研究。】 复制标题 收藏 收藏
    DOI:10.1007/s10549-008-0194-z 复制DOI
    作者列表:Ottini L,Rizzolo P,Zanna I,Falchetti M,Masala G,Ceccarelli K,Vezzosi V,Gulino A,Giannini G,Bianchi S,Sera F,Palli D
    BACKGROUND & AIMS: BACKGROUND:Male breast cancer (MBC) is a rare and scarcely investigated disease. The strongest genetic risk factor for MBC is represented by inherited BRCA2 mutations, whereas the association between MBC and BRCA1 mutations is less clear. MBC appears to be biologically similar to breast cancer in females, however the phenotypic characteristics of BRCA1/2-related MBCs are not yet well elucidated. OBJECTIVE:To investigate the genetic and phenotypic characteristics of MBC in a large and well-characterized population-based series of 108 MBCs from Tuscany (Central Italy) and to evaluate associations between BRCA1/BRCA2 mutation status and clinical-pathological features including breast/ovarian cancer first-degree family history, tumor histology and grade, proliferative activity, estrogen/progesterone receptors (ER/PR) and epidermal growth factor receptor 2 (HER2) expression. Results BRCA1/BRCA2 mutations were identified in ten MBCs, in particular, two cases (1.9%) carried BRCA1 and eight cases (7.4%) carried BRCA2 mutations. The same BRCA1 mutation (3347delAG) was detected in two unrelated MBC cases. Three novel BRCA2 pathogenic mutations were found. Statistically significant associations emerged between BRCA2-related tumors and absence of PR expression (P = 0.008), HER2 over-expression (P = 0.002) and high tumor grade (P = 0.005). Conclusions Here, we (i) reported that in our population about 9% of MBC cases are accounted for by BRCA1/BRCA2 mutations; (ii) enlarged the BRCA2 mutational spectrum and (iii) characterized a specific phenotype associated with BRCA2-related MBCs suggestive of aggressive behavior. Overall, our results may have important implications on clinical management for this rare disease.
    背景与目标: 背景:男性乳腺癌(MBC)是一种罕见且鲜有研究的疾病。 MBC的最强遗传风险因子由遗传的BRCA2突变代表,而MBC和BRCA1突变之间的关联尚不清楚。在女性中,MBC在生物学上似乎与乳腺癌相似,但是与BRCA1 / 2相关的MBC的表型特征尚未得到很好的阐明。
    目的:研究来自托斯卡纳(意大利中部)的一个大型且特征明确的基于人群的108 MBCs系列中MBC的遗传和表型特征,并评估BRCA1 / BRCA2突变状态与临床病理特征(包括乳腺癌/卵巢癌)之间的关联癌症一级家族史,肿瘤组织学和等级,增殖活性,雌激素/孕激素受体(ER / PR)和表皮生长因子受体2(HER2)的表达。结果在10个MBCs中鉴定出BRCA1 / BRCA2突变,特别是2例(1.9%)携带BRCA1,8例(7.4%)携带BRCA2突变。在两个无关MBC病例中检测到相同的BRCA1突变(3347delAG)。发现了三个新的BRCA2致病突变。在与BRCA2相关的肿瘤与PR表达缺失(P = 0.008),HER2过表达(P = 0.002)和高肿瘤分级(P = 0.005)之间,出现了统计学上显着的关联。结论在这里,我们(i)报告说,在我们的人群中,约9%的MBC病例是由BRCA1 / BRCA2突变引起的; (ii)扩大了BRCA2突变谱,并且(iii)表征了与BRCA2相关的MBC相关的特定表型,暗示了攻击行为。总体而言,我们的结果可能会对这种罕见疾病的临床治疗产生重要影响。
  • 【吡格列酮减弱小鼠脂多糖诱导的抑郁样行为,调节小鼠的NF-κB/ IL-6 / STAT3,CREB ​​/ BDNF途径和中枢5-羟色胺能神经传递。】 复制标题 收藏 收藏
    DOI:10.1016/j.intimp.2017.05.036 复制DOI
    作者列表:Liao L,Zhang XD,Li J,Zhang ZW,Yang CC,Rao CL,Zhou CJ,Zeng L,Zhao LB,Fang L,Yang DY,Xie P
    BACKGROUND & AIMS: :Immune activation and inflammation are closely associated with the development of depression. Pioglitazone (PIO), a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, has exhibited antidepressant-like effects in a couple of studies. However, the underlying mechanisms are far from being fully elucidated. The study aimed to investigate the effects of PIO on depression-like behaviors induced by lipopolysaccharide (LPS) and to explore the possible underlying mechanisms. The results showed that PIO pretreatment attenuated the depression-like behaviors in mice challenged with intracerebroventricular (i.c.v.) LPS administration. Moreover, Western blot analysis revealed the effects of PIO on inhibiting activation of the nuclear factor kappa B/interleukin 6/signal transducer and activator of transcription 3 (NF-κB/IL-6/STAT3) pathway, improving down-regulation of the cAMP response-element-binding protein/brain derived neurotrophic factor (CREB/BDNF) pathway, as well as regulating disturbed expression of proteins involved in central serotonergic neurotransmission following LPS administration. The beneficial effects of PIO, at both the behavioral and molecular level, were significantly inhibited by the PPAR-γ specific antagonist GW9662. In summary, our data reveals for the first time that the modulation of the NF-κB/IL-6/STAT3 and CREB/BDNF pathways, as well as the potential impact on central serotonergic neurotransmission, may be involved in the PPAR-γ-dependent effects of PIO on depression-like behaviors induced by LPS. Additionally, our findings may provide a novel therapeutic target for the treatment of depression-like behaviors in patients with inflammatory status.
    背景与目标: 免疫激活和炎症与抑郁症的发展密切相关。吡格列酮(PIO)是一种过氧化物酶体增殖物激活的受体γ(PPAR-γ)激动剂,在两项研究中显示出抗抑郁样作用。但是,远未完全阐明其基本机制。这项研究旨在调查PIO对脂多糖(LPS)诱导的抑郁样行为的影响,并探讨可能的潜在机制。结果表明,PIO预处理可减轻经脑室内(i.c.v.)LPS给药攻击的小鼠的抑郁样行为。此外,蛋白质印迹分析揭示了PIO对抑制核因子κB/白介素6 /信号转导子和转录激活子3(NF-κB/ IL-6 / STAT3)通路的激活,改善了cAMP的下调响应元素结合蛋白/脑源性神经营养因子(CREB ​​/ BDNF)途径,以及在LPS给药后调节参与中枢5-羟色胺能神经传递的蛋白的表达紊乱。 PIO在行为和分子水平上的有益作用均被PPAR-γ特异性拮抗剂GW9662显着抑制。总而言之,我们的数据首次揭示了NF-κB/ IL-6 / STAT3和CREB ​​/ BDNF信号通路的调节,以及对中枢5-羟色胺能神经传递的潜在影响,可能与PPAR-γ-有关。 PIO对LPS诱导的抑郁样行为的依赖效应。此外,我们的发现可能为炎症状态患者的抑郁症样行为的治疗提供新的治疗目标。
  • 【[CYTED-RITMOS网络:寻求在拉丁美洲促进移动医疗的解决方案]。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Saigí-Rubió F,Novillo-Ortiz D,Piette JD
    BACKGROUND & AIMS: :The area of mobile technologies applied to health (mHealth) is a growing worldwide trend that has generated enormous expectations for the mitigation of problems related to medical services delivery and public health stemming from a lack of resources and the limited number of specialists. The numerous opportunities offered by mobile technologies, together with their ease of use, have attracted the interest both of governments and universities. This is the case of the Ibero-American Mobile Technologies and Health Network (CYTED-RITMOS, Spanish acronym). As a result of the network's first year of activity, in October 2015 the RITMOS International Workshop was held in Barcelona to present the priority areas in Latin America where research, development, and innovation (R&D+i) projects on mobile health could be carried out and possible solutions found. The objective of this article is to present the potentialities and applicability of mHealth in the Region of the Americas.
    背景与目标: :应用于健康的移动技术(mHealth)领域是一个日益发展的全球趋势,人们对缓解由于缺乏资源和专家人数有限而导致的与医疗服务提供和公共卫生有关的问题抱有极大的期望。移动技术所带来的众多机遇及其易用性吸引了政府和大学的兴趣。伊比利亚美洲移动技术和卫生网络(CYTED-RITMOS,西班牙首字母缩写)就是这种情况。作为网络第一年活动的结果,2015年10月,RITMOS国际研讨会在巴塞罗那举行,介绍了拉丁美洲的优先领域,可以在该领域开展有关移动医疗的研究,开发和创新(R&D i)项目,以及找到可能的解决方案。本文的目的是介绍移动医疗在美洲地区的潜力和适用性。
  • 【在北美和欧洲,具有潜在危险因素的儿童的侵袭性肺炎球菌疾病负担。】 复制标题 收藏 收藏
    DOI:10.1111/ijcp.12234 复制DOI
    作者列表:Rose MA,Christopoulou D,Myint TT,de Schutter I
    BACKGROUND & AIMS: BACKGROUND:Characterisation of risk groups who may benefit from pneumococcal vaccination is essential for the generation of recommendations and policy. METHODS:We reviewed the literature to provide information on the incidence and risk of invasive pneumococcal disease (IPD) in at-risk children in Europe and North America. The PubMed database was searched using predefined search terms and inclusion/exclusion criteria for papers reporting European or North American data on the incidence or risk of IPD in children with underlying medical conditions. RESULTS:Eighteen references were identified, 11 from North America and 7 from Europe, with heterogeneous study methods, periods and populations. The highest incidence was seen in US children positive for human immunodeficiency virus infection, peaking at 4167 per 100,000 patient-years in 2000. Studies investigating changes in incidence over time reported decreases in the incidence of IPD between the late 1990s and early 2000s. The highest risk of IPD was observed in children with haematological cancers or immunosuppression. Overall, data on IPD in at-risk children were limited, lacking incidence data for a wide range of predisposing conditions. There was, however, a clear decrease in the incidence of IPD in at-risk children after the introduction of 7-valent pneumococcal conjugate vaccine into immunisation programmes, as previously demonstrated in the general population. CONCLUSION:Despite the heterogeneity of the studies identified, the available data show a substantial incidence of IPD in at-risk children, particularly those who are immunocompromised. Further research is needed to determine the true risk of IPD in at-risk children, particularly in the post-PCV period, and to understand the benefits of vaccination and optimal vaccination schedules.
    背景与目标: 背景:可能从肺炎球菌疫苗接种中受益的风险人群的表征对于产生建议和政策至关重要。
    方法:我们回顾了文献,以提供有关欧洲和北美高危儿童的侵袭性肺炎球菌疾病(IPD)的发生率和风险的信息。使用预定义的搜索词和纳入/排除标准对PubMed数据库进行了搜索,以检索报告欧洲或北美患有基础疾病的儿童中IPD发生率或风险的数据。
    结果:共确定了18篇参考文献,其中11篇来自北美,7篇来自欧洲,其研究方法,时期和人群各不相同。在人类免疫缺陷病毒感染呈阳性的美国儿童中发生率最高,在2000年达到峰值,每10万患者年中有4167名。调查随时间变化的研究报告说,在1990年代末至2000年代初,IPD发生率下降。在患有血液系统癌症或免疫抑制的儿童中,发生IPD的风险最高。总体而言,高危儿童的IPD数据有限,缺乏各种易患病情况的发病率数据。但是,将7价肺炎球菌结合疫苗引入免疫接种计划后,高危儿童IPD发生率明显下降,这在以前的一般人群中已得到证实。
    结论:尽管已确定研究的异质性,但现有数据显示高危儿童,特别是免疫受损儿童的IPD发生率很高。需要进一步的研究来确定高危儿童中IPD的真正风险,尤其是在PCV后时期,并了解疫苗接种的好处和最佳的疫苗接种时间表。
  • 【乌干达姆巴拉拉儿童的中枢神经系统疑似感染的病因学和预后。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-017-02741-w 复制DOI
    作者列表:Page AL,Boum Ii Y,Kemigisha E,Salez N,Nanjebe D,Langendorf C,Aberrane S,Nyehangane D,Nackers F,Baron E,Charrel R,Mwanga-Amumpaire J
    BACKGROUND & AIMS: :Infections of the central nervous system (CNS) are severe conditions, leading to neurological sequelae or death. Knowledge of the causative agents is essential to develop guidelines for case management in resource-limited settings. Between August 2009 and October 2012, we conducted a prospective descriptive study of the aetiology of suspected CNS infections in children two months to 12 years old, with fever and at least one sign of CNS involvement in Mbarara Hospital, Uganda. Children were clinically evaluated on admission and discharge, and followed-up for 6 months for neurological sequelae. Pathogens were identified from cerebrospinal fluid (CSF) and blood using microbiological and molecular methods. We enrolled 459 children. Plasmodium falciparum (36.2%) and bacteria in CSF (13.3%) or blood (3.3%) were the most detected pathogens. Viruses were found in 27 (5.9%) children. No pathogen was isolated in 207 (45.1%) children. Patterns varied by age and HIV status. Eighty-three (18.1%) children died during hospitalisation, and 23 (5.0%) during follow-up. Forty-one (13.5%) children had neurological sequelae at the last visit. While malaria remains the main aetiology in children with suspected CNS infections, no pathogen was isolated in many children. The high mortality and high rate of neurological sequelae highlight the need for efficient diagnosis.
    背景与目标: :中枢神经系统(CNS)的感染是严重的状况,导致神经系统后遗症或死亡。对病原体的知识对于在资源有限的环境中制定案例管理指南至关重要。在2009年8月至2012年10月之间,我们对乌干达姆巴拉拉医院发烧且至少有一个中枢神经系统受累迹象的2个月至12岁儿童中疑似中枢神经系统感染的病因进行了前瞻性描述研究。对儿童的入院和出院进行了临床评估,并随访了6个月的神经系统后遗症。使用微生物学和分子方法从脑脊液(CSF)和血液中鉴定出病原体。我们招收了459名儿童。恶性疟原虫(36.2%)和脑脊液(13.3%)或血液(3.3%)中的细菌是检测到最多的病原体。在27名(5.9%)儿童中发现了病毒。 207名(45.1%)儿童中没有分离出病原体。模式因年龄和艾滋病毒感染状况而异。住院期间有83名(18.1%)儿童死亡,随访期间有23名(5.0%)儿童死亡。上次访问时有41(13.5%)个儿童患有神经系统后遗症。尽管怀疑是中枢神经系统感染的儿童中疟疾仍然是主要病因,但在许多儿童中没有分离出病原体。神经系统后遗症的高死亡率和高发生率突出了对有效诊断的需求。
  • 【在爱泼斯坦-巴尔病毒感染后,伴有视神经炎和中央白质局灶性病变的吉兰-巴雷综合征。】 复制标题 收藏 收藏
    DOI:10.2169/internalmedicine.47.1224 复制DOI
    作者列表:An JY,Yoon B,Kim JS,Song IU,Lee KS,Kim YI
    BACKGROUND & AIMS: :We report a case of Guillain-Barré syndrome (GBS) accompanied by optic neuritis and a central white matter lesion subsequent to Epstein-Barr virus (EBV) infection. A 49-year-old man presented with visual disturbance and hemiparesis one week after developing cold-like symptoms. T2- and diffusion-weighted brain MRI showed a high-signal intensity lesion in the left internal capsule. The patient's visual acuity improved during steroid pulse therapy, but his hemiparesis progressed to quadriparesis. Nerve conduction studies showed demyelination predominant in the distal nerve terminals, consistent with GBS. Serological testing suggested EBV reinfection. Our findings indicate that EBV-related central and peripheral demyelination can occur simultaneously and can be successfully treated with a combination of corticosteroids and immunoglobulin.
    背景与目标: :我们报告了一例伴有视神经炎和继发爱泼斯坦-巴尔病毒(EBV)感染的中央白质病变的吉兰-巴雷综合征(GBS)。一名49岁的男子在出现感冒状症状后一周出现视觉障碍和偏瘫。 T2和弥散加权脑MRI显示左内囊有高信号强度病变。在类固醇脉冲治疗期间,患者的视力有所改善,但他的偏瘫进展为四肢瘫痪。神经传导研究显示,远端神经末梢主要发生脱髓鞘,与GBS一致。血清学检查提示EBV再感染。我们的研究结果表明,与EBV相关的中枢和外周脱髓鞘可以同时发生,并且可以通过联合使用糖皮质激素和免疫球蛋白成功治疗。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录