• 【选择性动脉栓塞术对胎盘植入进行保守治疗可保留未来的生育能力,并在随后的妊娠中获得良好的结果。】 复制标题 收藏 收藏
    DOI:10.1016/j.fertnstert.2006.02.128 复制DOI
    作者列表:Alanis M,Hurst BS,Marshburn PB,Matthews ML
    BACKGROUND & AIMS: OBJECTIVE:To present a case of selective arterial embolization for the treatment of placenta increta in a patient with subsequent pregnancy. DESIGN:Case report and literature review. SETTING:Community-based hospital. PATIENT(S):A 31-year-old G2P1 woman with placenta increta presenting with delayed postpartum hemorrhage. INTERVENTION(S):Selective uterine artery embolization. MAIN OUTCOME MEASURE(S):Cessation of uterine hemorrhage, future pregnancy. RESULT(S):The patient's uterine bleeding immediately resolved. She subsequently delivered a healthy neonate at term without recurrence of abnormal placentation. CONCLUSION(S):Arterial embolization is effective for treating placenta increta in women who wish to preserve fertility. A review of the literature demonstrates a 76.9% success rate and an 11% complication rate.
    背景与目标:
  • 【早期失明会导致皮质和丘脑皮质连接异常。】 复制标题 收藏 收藏
    DOI:10.1016/j.neuroscience.2006.06.055 复制DOI
    作者列表:Karlen SJ,Kahn DM,Krubitzer L
    BACKGROUND & AIMS: :Studies in congenitally blind and bilaterally enucleated individuals show that an early loss of sensory driven activity can lead to massive functional reorganization. However, the anatomical substrate for this functional reorganization is unknown. In the present study, we examined patterns of corticocortical and thalamocortical connections in adult opossums that had been bilaterally enucleated neonatally, prior to the formation of retinogeniculate and geniculocortical connections. We show that in addition to normal thalamocortical projection patterns from visual nuclei, enucleated animals also receive input from nuclei associated with the somatosensory (ventral posterior nucleus, VP), auditory (medial geniculate nucleus, MGN), motor (ventrolateral nucleus, VL), and limbic/hippocampal systems (anterior dorsal nucleus, AD; and anterior ventral nucleus, AV). Likewise, in addition to normal corticocortical projections to area 17, bilaterally enucleated opossums also receive input from auditory, somatosensory, and multimodal cortex. These aberrant patterns of thalamocortical and corticocortical connections can account for alterations in functional organization observed in the visual cortex of bilateral enucleated animals, and indicate that factors extrinsic to the cortex play a large role in cortical field development and evolution. On the other hand, the maintenance of normal patterns of connections in the absence of visual input suggests that there are formidable constraints imposed on the developing cortex that highly restrict the types of evolutionary change possible.
    背景与目标: : 对先天性失明和双侧去核个体的研究表明,感觉驱动活动的早期丧失会导致大规模的功能重组。然而,这种功能重组的解剖基质是未知的。在本研究中,我们检查了成年负鼠的皮质和丘脑皮质连接的模式,这些负鼠在新生视网膜形成之前已被双侧摘除。我们显示,除了来自视觉核的正常丘脑皮层投射模式外,去核动物还从与体感相关的核 (腹侧后核,VP),听觉 (内侧膝状核,MGN),运动 (腹外侧核,VL) 和边缘/海马系统 (前背核,AD; 和前腹侧核,AV)。同样,除了正常的皮质皮质投射到17区外,双侧去核负鼠还从听觉,体感和多峰皮质接收输入。丘脑皮质和皮质皮质连接的这些异常模式可以解释在双侧去核动物的视觉皮质中观察到的功能组织的变化,并表明皮质外部因素在皮质场发育和进化中起着重要作用。另一方面,在没有视觉输入的情况下维持正常的连接模式表明,对发育中的皮层施加了巨大的约束,这极大地限制了进化变化的类型。
  • 【Angelchik假体治疗胃食管反流的长期结果。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Maxwell-Armstrong CA,Steele RJ,Amar SS,Evans D,Morris DL,Foster GE,Hardcastle JD
    BACKGROUND & AIMS: INTRODUCTION:Between 1982 and 1989, 46 patients had insertion of an Angelchik prosthesis for gastro-oesophageal reflux. Eleven patients (24 per cent) subsequently had the prosthesis removed, all but one for intractable dysphagia.

    METHODS:Thirty-six of the original patients were followed by questionnaire, and 32 of these had a barium marshmallow swallow investigation.

    RESULTS:A high proportion of patients (20 of 26) with a prosthesis in situ had symptoms of dysphagia. On objective evaluation by marshmallow swallow, the transit time was significantly slower than that of an age-matched control group (P < 0.01), but showed no significant deterioration with time compared with previous postinsertion studies.

    CONCLUSION:The Angelchik prosthesis causes long-term dysphagia in a high proportion of patients, severe enough in one-quarter to necessitate its removal. Its continued use cannot, therefore, be recommended.

    背景与目标: 简介 : 在1982至1989之间,有46例患者插入了用于胃食管反流的Angelchik假体。11名患者 (24%) 随后切除了假体,除一名患者外,所有患者均因顽固性吞咽困难。
    方法 : 对36名原始患者进行问卷调查,其中32例进行了钡棉花糖吞咽研究。
    结果 : 在原位假体的患者中,有很大比例的患者 (26例中的20例) 有吞咽困难的症状。在棉花糖吞咽的客观评估中,通过时间明显慢于年龄匹配的对照组 (P <0.01),但与先前的插入后研究相比,随着时间的变化没有显着恶化。
    结论 : angelchik假体在很大一部分患者中引起长期吞咽困难,四分之一的患者严重到必须将其切除。因此,不建议继续使用。
  • 【腺苷A2受体在诱导大鼠海马CA1区长时程增强中的作用。】 复制标题 收藏 收藏
    DOI:10.1016/s0006-8993(97)00148-0 复制DOI
    作者列表:Kessey K,Trommer BL,Overstreet LS,Ji T,Mogul DJ
    BACKGROUND & AIMS: Although reductions in neurotransmission have been reported in response to agonist-mediated adenosine A1 receptor activation, the implications of A2 receptor activation on synaptic transmission have not been well explored. We examined the role adenosine A2 receptors play in the efficacy of neurotransmission between the Schaffer collateral-CA1 pathway in the rat transverse hippocampal slice. A2 receptor blockade in the presence of complete A1 receptor inhibition led to a reversible reduction of the field excitatory post-synaptic potential (EPSP) slope in response to low-frequency test pulses (0.033 Hz) indicating that A2 receptors can enhance synaptic transmission. A2 receptor blockade by the A2 antagonist, DMPX (3,7-dimethyl-1-propargylxanthine) prevented the induction of tetanus-induced long-term potentiation (LTP) of the EPSP. In contrast, no such effect on LTP induction was observed during A1 receptor blockade. We also examined the effects of DMPX on the induction of LTP during continued A1 receptor blockade with CPT. Under this condition, LTP was significantly reduced when compared to LTP induced in the presence of CPT alone. A similar result was found using the highly polar A2 antagonist 8-SPT (8-(p-sulfophenyl)theophylline) suggesting that the effects of DMPX on LTP were not due to a direct action on an intracellular intermediate. DMPX had no effect on LTP expression if applied 45 min following the tetanus indicating that A2 receptors play no significant role in the maintenance phase of LTP. Selective A2a receptor activation did not alter the field EPSP. Similarly, selective blockade of the A2a receptor did not interfere with tetanus-induced LTP. Increases in neuronal firing rates can result in elevations in the concentration of extracellular adenosine. Together, these results suggest that the A2 receptors may play an important role in the induction although not the maintenance of hippocampal LTP and that the effect is likely to be mediated by the A2b receptor.

    背景与目标: 尽管据报道,由于激动剂介导的腺苷A1受体激活,神经传递减少,但A2受体激活对突触传递的影响尚未得到很好的探讨。我们检查了腺苷A2受体在大鼠横海马切片中Schaffer collateral-CA1途径之间的神经传递功效中的作用。在完全A1受体抑制的存在下,A2受体阻断导致场兴奋性突触后电位 (EPSP) 斜率响应于低频测试脉冲 (0.033Hz) 的可逆降低,表明A2受体可以增强突触传递。A2拮抗剂DMPX (3,7-二甲基-1-炔基黄嘌呤) 对A2受体的阻断阻止了破伤风诱导的EPSP长期增强 (LTP) 的诱导。相反,在A1受体阻滞期间未观察到对LTP诱导的这种作用。我们还研究了在CPT持续阻断A1受体期间DMPX对LTP诱导的影响。在这种情况下,与单独在CPT存在下诱导的LTP相比,LTP显着降低。使用高度极性的A2拮抗剂8-SPT (8-(对磺苯基) 茶碱) 发现了类似的结果,表明DMPX对LTP的作用不是由于对细胞内中间体的直接作用。如果在破伤风后45分钟使用DMPX,则表明A2受体对LTP表达没有影响在LTP的维持阶段没有重要作用。选择性A2a受体激活不会改变EPSP。同样,选择性阻断A2a受体不会干扰破伤风诱导的LTP。神经元放电速率的增加会导致细胞外腺苷浓度的升高。这些结果表明,A2受体可能在诱导中起重要作用,尽管不是维持海马LTP,并且该作用可能是由A2b受体介导的。
  • 【前列腺素E2对足月子宫颈不利的妇女的孤立羊水过少进行引产。】 复制标题 收藏 收藏
    DOI:10.1159/000095848 复制DOI
    作者列表:Danon D,Ben-Haroush A,Yogev Y,Bar J,Hod M,Pardo J
    BACKGROUND & AIMS: OBJECTIVE:To evaluate the maternal and neonatal outcomes of pregnancies complicated with isolated oligohydramnios at term, managed by induction of labor. METHODS:We conducted a retrospective case-control study. 138 women with uncomplicated oligohydramnios at term [amniotic fluid index (AFI) < or =5 cm] and a low Bishop score (< or =6) underwent induction of labor with prostaglandin E2. These women were compared to 67 women who underwent induction of labor at 42 weeks' gestation and 276 women at low-risk pregnancy and spontaneous onset of labor, matched for parity and race. RESULTS:Cesarean section (CS) rate was similar in the study and the post-date group (17.4 and 17.9%, respectively), but significantly higher than the spontaneous labor group (5.8%, OR 3.42, 95% CI 1.75-6.68). No differences were found with other outcomes. CONCLUSION:Pregnancies with isolated oligohydramnios at term apparently are not at higher risk of perinatal complications, but induction of labor is associated with increased rate of CS.
    背景与目标:
  • 【培训后电视胸腔镜手术肺叶切除术的演变: 前30例患者的初步结果。】 复制标题 收藏 收藏
    DOI:10.1016/j.jamcollsurg.2006.06.003 复制DOI
    作者列表:Ng T,Ryder BA
    BACKGROUND & AIMS: BACKGROUND:In early-stage lung cancer, evidence is accumulating for the benefits of lobectomy by video-assisted thoracic surgery (VATS) over open lobectomy. Few thoracic training programs offer sufficient experience in this technically demanding procedure. This article describes the evolution of a new graduate's practice from open thoracotomy to VATS lobectomy. STUDY DESIGN:Our model involves a transition in technique from posterolateral thoracotomy to muscle-sparing thoracotomy and, ultimately, to VATS lobectomy. This approach was evaluated by examining outcomes of open thoracotomy patients before VATS lobectomy and outcomes of the initial 30 VATS patients. Data were collected prospectively. RESULTS:Before undertaking VATS lobectomy, 94 major pulmonary resections were performed by thoracotomy. Mortality was 1.2% for lobectomy and 0% for pneumonectomy. Use of the muscle-sparing thoracotomy increased from 17% of patients in the first half to 70% in the latter half of this group. For the first 30 VATS lobectomy patients, the mean operative time was 168 minutes. Median blood loss was 200 mL. Conversion rate to open thoracotomy was 13.3%. Mortality was 3.3% and morbidity was 26.7%. After short-term followup (mean followup 16 months), overall survival for stage I lung cancer was 96%. CONCLUSIONS:With our approach, new graduates of thoracic surgery programs can safely transition to VATS lobectomy. Gaining experience with the lateral muscle-sparing thoracotomy is an important step in the transition, as it offers similar operative exposure. Longterm disease-free and overall survival data are needed to evaluate our oncologic efficacy with this approach.
    背景与目标:
  • 【在非常接近高压输电线路的家庭中,短期住宅测量在72h暴露于工频磁场中的预测精度。】 复制标题 收藏 收藏
    DOI:10.1038/sj.jes.7500522 复制DOI
    作者列表:Ger WJ,Chang WP,Sung FC,Li CY
    BACKGROUND & AIMS: :Between February and April 2003, a total of 80 single-dwelling households close (< 70 m) to high-tension (161 or 345 kV) power lines in a northern community of Taiwan received measurements of indoor extremely low-frequency (ELF) magnetic field for 72 h. Measurements were performed with EMDEX II meter at a sampling rate of every 300 s, yielding some 860 readings of ELF magnetic field for each household. In addition to the 72-h mean ELF magnetic field, we also calculated arithmetic means of the first 2, 6, 12, and 288 readings taken in each household to represent the information on spot, 30-min, 60-min, and 24-h exposures, respectively. The mean 72-h exposure to ELF magnetic field for the 80 study households was estimated at 0.80 micro-Tesla (microT) with a standard deviation (SD) of 1.13 microT. The mean for pot, 30-min, 60-min, and 24-h exposure was 0.88 (SD 1.38), 0.90 (SD 1.40), 0.9 (SD 1.17), and 0.83 (SD 1.17) microT, respectively. There were high agreements, indicated by a nearly perfect intra-class correlation coefficient, between 72-h mean exposure and those short-term exposure measures. Additionally, the sensitivity and specificity of various short-term exposures in the prediction of 72-h exposure greater than 0.4 microT were similar at values of 0.82-0.87 and 0.93-0.95, respectively. This study indicates that short-term measurements of indoor ELF magnetic field seem adequate to represent the mean 72-h exposure, but tended to overpredict 72-h exposure greater than 0.4 microT. Further investigation is needed to assess whether these findings can be replicated in households far away from high-tension power lines.
    背景与目标: : 在2月和2003年4月之间,台湾北部社区共有80个靠近 (< 70 m) 高压 (161或345 kV) 电力线的单户家庭接受了室内极低频 (ELF) 的测量磁场72小时。使用EMDEX II仪表以每300 s的采样率进行测量,得出每个家庭的ELF磁场的一些860读数。除了72小时的平均ELF磁场外,我们还计算了每个家庭中获取的前2、6、12和288个读数的算术平均值,以分别表示现场,30分钟,60分钟和24小时的信息。估计80个研究家庭的ELF磁场平均暴露时间为0.80微特斯拉 (microT),标准偏差 (SD) 为1.13微t。pot,30分钟,60分钟和24小时暴露的平均值分别为0.88 (SD 1.38),0.90 (SD 1.40),0.9 (SD 1.17) 和0.83 (SD 1.17) microT。在72小时平均暴露与那些短期暴露措施之间存在很高的一致性,这表明类内相关系数几乎是完美的。此外,各种短期暴露在预测大于0.4微特的72小时暴露中的敏感性和特异性分别在0.82-0.87和0.93-0.95的值处相似。这项研究表明,室内ELF磁场的短期测量似乎足以代表平均72小时暴露,但往往会高估大于0.4微特的72小时暴露。需要进一步调查,以评估这些发现是否可以在远离高压电线的家庭中复制。
  • 【关节内高分子量透明质酸注射治疗非减少颞下颌关节盘移位的短期治疗结果。】 复制标题 收藏 收藏
    DOI:10.1016/j.tripleo.2005.09.018 复制DOI
    作者列表:Yeung RW,Chow RL,Samman N,Chiu K
    BACKGROUND & AIMS: :In a patient with temporomandibular disorder who does not respond to conservative treatment, treatment with intra-articular injection of high molecular weight sodium hyaluronate can be suggested. In our study, 27 patients with nonreduced disc displacement were diagnosed clinically and confirmed by magnetic resonance imaging. The age range was from 21 to 63 years old, with a mean of 39.3 years. Two cycles of injection of high molecular weight sodium hyaluronate was performed on alternative weeks. Pain intensity was measured by the visual analog scale. Maximal mouth opening, clicking joint noise, and lateral movement were measured before and after injection for more than 6 months. Reduction of pain intensity and improvement in the maximum mouth opening parameter was statistically significant. In conclusion, this intra-articular injection using high molecular weight sodium hyaluronate looks very positive for patients affected by nonreduced disc displacement and is encouraged to be used as a primary treatment of temporomandibular joint dysfunction.
    背景与目标: : 对于对保守治疗无反应的颞下颌疾病患者,建议使用关节内注射高分子量透明质酸钠进行治疗。在我们的研究中,临床诊断出27例椎间盘移位未减少的患者,并通过磁共振成像证实。年龄范围为21至63岁,平均39.3岁。在其他星期进行了两个周期的高分子量透明质酸钠注射。疼痛强度通过视觉模拟量表测量。注射前后6个月以上,测量最大张口,点击关节噪声和侧向运动。疼痛强度的降低和最大张口参数的改善具有统计学意义。总之,这种使用高分子量透明质酸钠的关节内注射对于受椎间盘移位不全影响的患者看起来非常积极,并被鼓励用作颞下颌关节功能障碍的主要治疗方法。
  • 【B细胞慢性淋巴细胞白血病患者T细胞中的信号分子和细胞因子产生: 氟达拉滨和阿仑单抗治疗的长期影响。】 复制标题 收藏 收藏
    DOI:10.1080/10428190600565503 复制DOI
    作者列表:Kiaii S,Choudhury A,Mozaffari F,Rezvany R,Lundin J,Mellstedt H,Osterborg A
    BACKGROUND & AIMS: :Fludarabine and alemtuzumab are routinely used for treatment of B-cell chronic lymphocytic leukemia (B-CLL). The present study aimed to compare the expression of signaling molecules and cytokine production by T cells of B-CLL patients in long-term unmaintained remission/plateau phase following fludarabine or alemtuzumab treatment with that of indolent/untreated B-CLL patients and healthy donors. The frequency and intensity of TCR-CD3zeta chain, p56lck, p59fyn, ZAP-70, PI3-kinase and interferon (IFN)-gamma/interleukin (IL)-4 production in CD4 and CD8 T cells was examined by flow cytometry. T-cell function was assessed by stimulation with purified protein derivative (PPD) and phytohemagglutinin (PHA). Despite a reduction in number, the expression of IFN-gamma/IL-4 in T-cells in patients was significantly higher than in healthy donors. The intensity of most signaling molecules in treated patients was relatively unaffected vs. healthy donors but lower than untreated-indolent patients. However, the total number of T cells which expressed each of the signaling molecules was decreased in patients, with no difference between fludarabine- and alemtuzumab-treated patients. The T-cell response to PHA but not PPD was reduced in treated patients. The results suggest that, despite some alterations in signaling molecules and a reduction in T-cell number, overall T-cell functions may be relatively well preserved long-term after treatment with fludarabine and alemtuzumab.
    背景与目标: : 氟达拉滨和阿仑单抗通常用于治疗b细胞慢性淋巴细胞白血病 (b-cll)。本研究旨在比较在氟达拉滨或阿仑单抗治疗后长期未维持缓解/平台期的b-cll患者的T细胞与惰性/未治疗的b-cll患者和健康的T细胞的信号分子表达和细胞因子产生供体。通过流式细胞术检查CD4和CD8 T细胞中TCR-CD3zeta链,p56lck,p59fyn,ZAP-70,PI3-kinase和干扰素 (IFN)-γ/白细胞介素 (IL)-4产生的频率和强度。通过纯化蛋白衍生物 (PPD) 和植物血凝素 (PHA) 刺激来评估T细胞功能。尽管数量减少,但患者T细胞中IFN-γ/IL-4的表达显着高于健康供体。与健康供体相比,接受治疗的患者中大多数信号分子的强度相对不受影响,但低于未经治疗的惰性患者。然而,在患者中表达每种信号分子的T细胞总数减少,而氟达拉滨和阿仑单抗治疗的患者之间没有差异。在治疗的患者中,T细胞对PHA的反应降低,但对PPD的反应降低。结果表明,尽管信号分子发生了一些变化,T细胞数量减少,但在用氟达拉滨和阿仑单抗治疗后,总体T细胞功能可能长期保持良好。
  • 【人前脑成神经细胞对成年大鼠中枢神经系统长轴突通路的改造。】 复制标题 收藏 收藏
    DOI:10.1038/347556a0 复制DOI
    作者列表:Wictorin K,Brundin P,Gustavii B,Lindvall O,Björklund A
    BACKGROUND & AIMS: :The failure of lesioned axons to regenerate over long distances in the mammalian central nervous system (CNS) is not due to an inability of central neurons to regenerate, but rather to the non-permissive nature of the CNS tissue environment. Regenerating CNS axons, which grow well within a peripheral nerve, for example, fail to penetrate mature CNS tissue by more than about 1 mm. Recent evidence indicates that this may be due to inhibitory membrane proteins associated with CNS oligodendrocytes and myelin. We report here that human telencephalic neuroblasts implanted into the excitotoxically lesioned striatum of adult rats can escape or neutralize this inhibitory influence of the adult CNS environment and extend axons along major myelinated fibre tracts for distances of up to approximately 20 mm. The axons were seen to elongate along the paths of the striato-nigral and cortico-spinal tracts to reach the substantia nigra, the pontine nuclei and the cervical spinal cord, which are the normal targets for the striatal and cortical projection neurons likely to be present in these implants.
    背景与目标: : 受损的轴突在哺乳动物中枢神经系统 (CNS) 中无法长距离再生不是由于中枢神经元无法再生,而是由于CNS组织环境的非宽松性质。例如,在周围神经内良好生长的再生CNS轴突不能穿透成熟的CNS组织超过约1毫米。最近的证据表明,这可能是由于与CNS少突胶质细胞和髓磷脂相关的抑制性膜蛋白所致。我们在此报告,植入成年大鼠兴奋性毒性病变纹状体的人类端脑神经母细胞可以逃避或中和成年CNS环境的这种抑制作用,并沿主要有髓纤维束延伸轴突,距离可达约20毫米。可以看到轴突沿着纹状体-黑质和皮质-脊髓束的路径伸长,到达黑质,桥脑核和颈脊髓,这是纹状体和皮质投射神经元的正常目标。这些植入物。
  • 11 Who recommends long-term care matters. 复制标题 收藏 收藏

    【世卫组织建议长期护理事宜。】 复制标题 收藏 收藏
    DOI:10.1093/geront/46.4.474 复制DOI
    作者列表:Kane RL,Bershadsky B,Bershadsky J
    BACKGROUND & AIMS: PURPOSE:Making good consumer decisions requires having good information. This study compared long-term-care recommendations among various types of health professionals. DESIGN AND METHODS:We gave randomly varied scenarios to a convenience national sample of 211 professionals from varying disciplines and work locations. For each scenario, we asked the professional to recommend the appropriate forms of long-term care. RESULTS:Although the professional respondents used the full spectrum of options offered to them, some professionals tended to favor the sector they worked in. Advanced practice nurses recommended day care and homemaking more and adult foster care less. Gerontologists used skilled nursing-facility placement more actively and rehabilitation, homemaking, and home health care less actively. Geriatricians and primary care physicians both favored rehabilitation and skilled nursing-facility care and were both less enthusiastic about assisted living, homemaking, and informal care, but the geriatricians favored day care more than did the primary care physicians. Registered nurses were highly supportive of assisted living, adult foster care, homemaking, and home health care, and they opposed skilled nursing-facility care. Social workers were less likely than other participants to endorse rehabilitation and adult foster care. IMPLICATIONS:Because consumer preference should be a major factor in making long-term-care decisions, many consumers need information about what options may best fit their situation. In the absence of empirical data on which types of long-term care work best for whom, consumers have to rely on expert judgment-but that judgment varies. Clients should be aware that an expert's background (as defined by discipline and work situation) may affect his or her recommendations. Each discipline appears to have its own set of experiences and beliefs that may influence recommendations.
    背景与目标:
  • 【吸入类固醇/长效 β2激动剂组合产品可改善成人哮喘患者的24小时肺功能。】 复制标题 收藏 收藏
    DOI:10.1186/1465-9921-7-110 复制DOI
    作者列表:Lötvall J,Langley S,Woodcock A
    BACKGROUND & AIMS: BACKGROUND:The combination of inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA) is recommended by treatment guidelines for the treatment of persistent asthma. Two such combination products, salmeterol/fluticasone propionate (SFC, Seretide GSK, UK) and formoterol/budesonide (FBC, Symbicort, AstraZeneca, UK) are commercially available. OBJECTIVES:The purpose of these studies was to evaluate and compare the duration of bronchodilation of both combination products up to 24 hours after a single dose. METHODS:Two randomised, double blind, placebo-controlled, crossover studies were performed. Study A was conducted in 33 asthmatic adults receiving 400-1200 mcg of budesonide or equivalent. Serial forced expiratory volume in one second (FEV1) was measured over 24 hours to determine the duration of effect of both SFC (50/100 mcg) and FBC (4.5/160 mcg). Study B was conducted in 75 asthmatic adults receiving 800-1200 mcg of budesonide or equivalent and comprised a 4 week run-in of 400 mcg bd Becotide followed by 4 weeks treatment with either SFC 50/100 mcg bd or FBC 4.5/160 mcg bd taken in a cross-over manner. Serial 24-hour FEV1 was measured after the first dose and the last dose after each 4-weeks treatment period to determine the offset of action of each treatment. RESULTS:In study A, a single inhalation of SFC and FBC produced a sustained bronchodilation at 16 hours with an adjusted mean increase in FEV1 from pre-dose of 0.22 L (95% CI 0.19, 0.35 L) for SFC and 0.25 L (95% CI 0.21, 0.37 L) for FBC, which was significantly greater than placebo for both treatments (-0.05 L; p < 0.001). In study B, the slope of decline in FEV1 from 2-24 hours post dose was -16.0 ml/hr for SFC and -14.2 ml/hr for FBC. The weighted mean AUC over 24 hours was 0.21 Lxmin and 0.22 Lxmin and mean change from pre-dose FEV1 at 12 hours was 0.21 L for SFC and 0.20 L for FBC respectively CONCLUSION:Both SFC and FBC produced a similar sustained bronchodilator effect which was prolonged beyond 12 hours post dose and was clearly measurable at 24 h.
    背景与目标:
  • 【猕猴髓核内的远距离中间神经元。】 复制标题 收藏 收藏
    DOI:10.1002/cne.21085 复制DOI
    作者列表:Imura K,Rockland KS
    BACKGROUND & AIMS: :Like other thalamic nuclei, the primate pulvinar is considered not to have long-range intrinsic connections, either excitatory or inhibitory. Injections of biotinylated dextran amine (BDA) in the medial pulvinar, however, reveal retrogradely filled neurons up to 2.0 mm from the injection edge. Serial section reconstruction (n = 18) confirmed that retrogradely filled neurons projected to the injection site and showed that they had additional long-range collaterals within the posterior pulvinar. Arrays of small, beaded terminations occurred in multiple foci along the collaterals. Terminal arrays were up to 1.0 mm in length; foci were separated by about 0.7 mm. Somata were large (average area = 220 microm2), and dendritic arbors were radiate and also large (about 1.0 mm in diameter), but without either the appendages of classical interneurons or the hairlike spines characteristic of radiate pulvinocortical projection neurons. Double labeling for BDA and parvalbumin (PV) or BDA and gamma-aminobutyric acid (GABA) indicated that these large neurons were positive for both PV and GABA. Double labeling for PV and GABA, or PV and glutamic acid decarboxylase 67 (GAD67) revealed a small number of similarly large neurons in the posterior pulvinar that were positive for both substances. Thus, we propose that these neurons are a novel class of inhibitory interneuron, longer range than the classic thalamic local circuit interneurons. Future questions include how these neurons relate to other inhibitory systems and specific postsynaptic populations and whether they are located preferentially within the posterior pulvinar, possibly related to the multimodal character of this thalamic region.
    背景与目标: : 与其他丘脑核一样,灵长类脉冲被认为不具有兴奋性或抑制性的远距离内在联系。然而,在内侧髓中注射生物素化的葡聚糖胺 (BDA) 显示出从注射边缘到2.0毫米的逆行填充的神经元。连续切片重建 (n = 18) 证实,逆行填充的神经元投射到注射部位,并显示它们在后牙髓内有其他远距离侧支。沿侧支的多个病灶中出现了一系列小的串珠末端。末端阵列的长度可达1.0毫米; 病灶间隔约0.7毫米。躯体很大 (平均面积 = 220 microm2),树突状乔木辐射且也很大 (直径约1.0毫米),但没有经典中间神经元的附属物或辐射的皮质投射神经元的毛状刺特征。BDA和小白蛋白 (PV) 或BDA和 γ-氨基丁酸 (GABA) 的双重标记表明,这些大神经元对PV和GABA均为阳性。对PV和GABA或PV和谷氨酸脱羧酶67 (GAD67) 的双重标记显示,后牙髓中少量类似的大神经元对两种物质均呈阳性。因此,我们建议这些神经元是一类新型的抑制性中间神经元,其范围比经典的丘脑局部电路中间神经元更长。未来的问题包括这些神经元与其他抑制系统和特定的突触后种群之间的关系,以及它们是否优先位于后牙髓内,这可能与该丘脑区域的多模式特征有关。
  • 【[肉毒杆菌毒素治疗痉挛性婴儿脑瘫: 一年内27例结果]。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Sánchez-Carpintero R,Narbona J
    BACKGROUND & AIMS: INTRODUCTION AND OBJECTIVES:Positive outcome of patients with spastic cerebral palsy treated with botulinum toxin reported in the last three years has led us to perform this study with the aim to show our experience in the management of spastic cerebral palsy with the toxin, determine its indications, analyze the results and propose new possible indications in the future.

    MATERIAL AND METHODS:We include 10 hemiplegic and 17 diplegic patients with an average age of 6 years and 7 months, followed up between 5 and 17 months. Clinical improvement was monitored using the PRS and EVFEL scales and articular motion range was measured 6 months before and after the injection while continuing physiotherapy. The injected muscles were adductor, hamstrings, triceps and posterior tibialis, and the doses were 1-2 U/muscle/kg body weight.

    RESULTS:The values on PRS improved an average of 24%, adductor angle 66% (p < 0.01), knee angle 40% (p = 0.05) and ankle angle 52% (p < 0.01); 96% of patients could get more physiological static or walking patterns because of the decrease of spasticity and those persisted after the effect of the toxin had worn off. It was maximum at 2 months, stabilized 4 to 6 months later and decreased during further 2 months.

    CONCLUSIONS:This experience leads us to propose higher starting dosage and to take into account the stability of postural pattern of each patient to choice the muscle to be injected. Other therapeutic possibilities are also proposed in children with fixed shortening e.g. combining the toxin with stretching casts.

    背景与目标: 简介和目标 : 最近三年报道的肉毒杆菌毒素治疗痉挛性脑瘫患者的积极结果导致我们进行这项研究,目的是展示我们在治疗痉挛性脑瘫方面的经验毒素,确定其适应症,分析结果并在将来提出新的可能适应症。
    材料和方法 : 我们包括10例偏瘫和17例双瘫患者,平均年龄为6岁7个月,随访5至17个月。使用PRS和EVFEL量表监测临床改善,并在注射前和注射后6个月测量关节运动范围,同时继续理疗。注射的肌肉是内收肌,绳肌,三头肌和胫后肌,剂量为1-2 U/肌肉/kg体重。
    结果 : PRS上的值平均提高了24%,内收角66% (p <0.01),膝角40% (p = 0.05) 和踝角52% (p < 0.01); 96% 患者由于痉挛程度的降低而获得更多的生理静态或行走模式,并且在毒素作用消失后持续存在。在2个月时达到最大值,在4到6个月后稳定下来,在接下来的2个月内下降。
    结论 : 这种经验使我们提出更高的起始剂量,并考虑到每位患者的姿势模式的稳定性,以选择要注射的肌肉。对于固定缩短的儿童,还提出了其他治疗可能性,例如将毒素与拉伸铸型结合使用。
  • 【具有长dsrna表达的哺乳动物细胞中的特异性和无毒沉默。】 复制标题 收藏 收藏
    DOI:10.1093/nar/gkl532 复制DOI
    作者列表:Strat A,Gao L,Utsuki T,Cheng B,Nuthalapaty S,Mathis JM,Odaka Y,Giordano T
    BACKGROUND & AIMS: :A number of groups have developed libraries of siRNAs to identify genes through functional genomics. While these studies have validated the approach of making functional RNAi libraries to understand fundamental cellular mechanisms, they require information and knowledge of existing sequences since the RNAi sequences are generated synthetically. An alternative strategy would be to create an RNAi library from cDNA. Unfortunately, the complexity of such a library of siRNAs would make screening difficult. To reduce the complexity, longer dsRNAs could be used; however, concerns of induction of the interferon response and off-target effects of long dsRNAs have prevented their use. As a first step in creating such libraries, long dsRNA was expressed in mammalian cells. The 250 nt dsRNAs were capable of efficiently silencing a luciferase reporter gene that was stably transfected in MDA-MB-231 cells without inducing the interferon response or off-target effects any more than reported for siRNAs. In addition, a long dsRNA expressed in the same cell line was capable of silencing endogenous c-met expression and inhibited cell migration, whereas the dsRNA against luciferase had no effect on c-met or cell migration. The studies suggest that large dsRNA libraries are feasible and that functional selection of genes will be possible.
    背景与目标: : 许多小组已经开发了sirna文库,以通过功能基因组学鉴定基因。尽管这些研究已经验证了制作功能性RNAi文库以了解基本细胞机制的方法,但由于RNAi序列是合成生成的,因此它们需要现有序列的信息和知识。另一种策略是从cDNA创建RNAi文库。不幸的是,这种sirna库的复杂性将使筛选变得困难。为了降低复杂性,可以使用更长的dsrna; 然而,对干扰素反应的诱导和长dsrna的脱靶效应的担忧阻止了它们的使用。作为创建此类文库的第一步,长dsRNA在哺乳动物细胞中表达。250 nt dsrna能够有效地沉默在MDA-MB-231细胞中稳定转染的荧光素酶报告基因,而不会比sirna所报道的更多诱导干扰素应答或脱靶效应。此外,在同一细胞系中表达的长dsRNA能够沉默内源性c-met表达并抑制细胞迁移,而针对荧光素酶的dsRNA对c-met或细胞迁移没有影响。研究表明,大型dsRNA文库是可行的,并且基因的功能选择将是可能的。

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