BACKGROUND & AIMS: :Under normoxic conditions the alpha-subunit of hypoxia-inducible factor (HIF-1alpha) protein is targeted for degradation by the von Hippel-Lindau (VHL) tumor suppressor protein acting as an E3 ubiquitin ligase. Recently, we developed a hypoxia-targeting protein, TOP3, which consisted of procaspase-3 with the VHL-mediated protein destruction motif of HIF-1alpha. This design enables procaspase-3 to be regulated similarly with HIF-1alpha, being degraded under normoxia while stabilized under hypoxia. Furthermore, stabilized TOP3 was cleaved by the hypoxic stress-induced endogenous caspases and thus the procaspase-3 was converted to active caspase-3 specifically under hypoxic conditions. These data demonstrated that the VHL-mediated protein destruction motif of HIF-1alpha endowed procaspase-3 with hypoxia-specific cytotoxicity.

背景与目标： : 在常氧条件下，低氧诱导因子 (HIF-1alpha) 蛋白的 α 亚基被作为E3泛素连接酶的von Hippel-Lindau (VHL) 肿瘤抑制蛋白靶向降解。最近，我们开发了一种低氧靶向蛋白TOP3，它由具有HIF-1alpha VHL介导的蛋白破坏基序的procaspase-3组成。该设计使procaspase-3能够与HIF-1alpha类似地调节，在常氧条件下降解，而在缺氧条件下稳定。此外，稳定的TOP3被低氧胁迫诱导的内源性半胱天冬酶裂解，因此procaspase-3在低氧条件下被特异性转化为活性caspase-3。这些数据表明，HIF-1alpha的VHL介导的蛋白质破坏基序赋予procaspase-3低氧特异性细胞毒性。

BACKGROUND & AIMS: Elderly patients with malignant glioma have a poor prognosis and the benefit of standard radical radiotherapy is equivocal. Twenty-two percent of the adult referral base with malignant glioma at our centre is of age 70 years or greater. A phase II study was undertaken to determine if a shorter course of therapy yields a comparable median survival to radical radiotherapy and thus constitutes an appropriate investigational palliative regimen. 25 patients were accrued between 1988-1995, all of whom had histologically proven malignant glioma, 23 glioblastoma multiforme and 2 anaplastic astrocytoma. The median age was 73 (range 70-78) and median Karnofsky Performance Status (KPS) was 70.40% had a stereotactic biopsy only for diagnosis. Radiotherapy was delivered to limited fields to a dose of 37.5 Gy in 15 daily fractions over 3 weeks. An intention-to-treat analysis was undertaken with survival determined from date of initial consultation. The median survival of the whole group was 8.0 months (95% CI 4.8-9.6). Patients with good performance status (KPS > 70) had a median survival of 10.4 months (95% CI 9.6-14.7). 37.5 Gy in 15 daily fractions appears to yield comparable median survival to that of other series of radical radiotherapy. A phase III study of this regimen is recommended in investigating optimal palliation of elderly malignant glioma patients.

背景与目标： 老年恶性神经胶质瘤患者的预后较差，标准的根治性放疗的益处是模棱两可的。在我们中心，患有恶性神经胶质瘤的成人转诊基地中有22% 的年龄在70岁或以上。进行了一项II期研究，以确定较短的疗程是否可以产生与根治性放疗相当的中位生存期，从而构成适当的研究性姑息治疗方案。在1988-1995之间累积了25例患者，所有这些患者均经组织学证实为恶性神经胶质瘤，23例多形性胶质母细胞瘤和2例间变性星形细胞瘤。中位年龄为73岁 (范围70-78)，中位Karnofsky表现状态 (KPS) 70.40% 仅用于诊断的立体定向活检。在3周内，将放射疗法递送到有限的区域，剂量为37.5 Gy，每天15次。进行了意向性治疗分析，从初次咨询之日起确定生存率。全组的中位生存期为8.0个月 (95% CI 4.8-9.6)。表现良好的患者 (KPS > 70) 的中位生存期为10.4个月 (95% CI 9.6-14.7)。在15个每日分数中37.5 Gy似乎产生与其他系列的根治性放疗相当的中位生存期。建议对该方案进行III期研究，以研究老年恶性神经胶质瘤患者的最佳姑息治疗。

BACKGROUND & AIMS: :The primary objectives of this study were to follow the temporal patterns of testicular LH and FSH receptor (LH-R and FSH-R) concentrations and affinity (Ka) during sexual maturation in bulls and to see if such patterns could help explain the control of rapid testicular growth that occurs after 25 weeks of age, when serum gonadotropin concentrations are low. Separate groups of Hereford x Charolais calves (n = 6) were castrated every 4 weeks from 5 to 33 weeks of age and at 56 weeks of age. A week prior to castrations, from 5 to 33 weeks of age, blood was collected every 15 min for 10 h. The transition from indifferent supporting cells to Sertoli cells in seminiferous tubules was rapid between 13 and 25 weeks and rapid testis growth occurred after 25 weeks of age. Serum LH and FSH concentrations were transiently elevated at 12 weeks of age (P < 0.05). LH-R concentrations decreased from 13 to 25 weeks of age and increased to 56 weeks of age (P < 0.05). LH-RKa decreased from 9 to 17 weeks of age, increased to 29 weeks of age and declined to 33 weeks of age (P < 0.05). FSH-R concentrations declined from 17 to 25 weeks of age then increased to 56 weeks of age (P < 0.05). FSH-RKa increased from 17 to 25 weeks of age (P < 0.05). High concentrations of gonadotropins and their receptors may be critical to initiate testis growth postnatally and support it after 25 weeks of age in the face of low serum gonadotropin concentrations.

背景与目标： : 这项研究的主要目的是跟踪公牛性成熟过程中睾丸LH和FSH受体 (lh-r和fsh-r) 浓度和亲和力 (Ka) 的时间模式，并观察这种模式是否有助于解释25周龄后睾丸快速生长的控制,当血清促性腺激素浓度较低时。从5到33周龄和56周龄，每4周对不同的Hereford x Charolais小牛 (n = 6) 进行cast割。阉割前一周，从5到33周龄，每15分钟收集一次血液，持续10小时。在13至25周之间，生精小管中从冷漠的支持细胞向Sertoli细胞的过渡迅速，并且在25周龄后睾丸迅速生长。血清LH和FSH浓度在12周龄时短暂升高 (P <0.05)。Lh-r浓度从13至25周龄降低，并增加至56周龄 (P <0.05)。Lh-rka从9周龄下降到17周龄，增加到29周龄，下降到33周龄 (P <0.05)。Fsh-r浓度从17至25周龄下降，然后增加至56周龄 (P <0.05)。Fsh-rka从17周增加到25周龄 (P <0.05)。面对低血清促性腺激素浓度，高浓度的促性腺激素及其受体对于启动出生后睾丸生长并在25周龄后支持睾丸生长可能至关重要。

BACKGROUND & AIMS: :Matrix metalloproteinase (MMPs) expression has been linked to gynecological tumor aggressiveness. The objective of this study was to determine MMP-2, MMP-7, and MMP-9 and tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 expression in endometrial malignancies and their relation to clinical and histologic parameters. Formalin-fixed, paraffin-embedded tumor samples from 50 patients with endometrial carcinoma treated between 1999 and 2004 were stained with specific monoclonal antibodies. The tumors were grouped according to the FIGO classification. The staining results were compared to histologic and clinical data. Semiquantitative analysis of MMP and TIMP expression showed a significant difference in TIMP-2 expression according to the histologic subtype (P = 0.03) and also a trend towards a difference in MMP-9 expression (P = 0.05). MMP-2 expression increased and TIMP-2 expression fell as the histologic grade increased (P = 0.0007, P < 0.0001, respectively). MMP-2 expression correlated with lymph node metastasis (P = 0.04), while TIMP-2 expression correlated with the depth of myometrial invasion (P = 0.01), vasculolymphatic space involvement (P = 0.02), and lymph node metastasis (P = 0.0003). These results support the involvement of MMPs and TIMPs in endometrial tumor growth and progression. High MMP-2 and low TIMP-2 expression were the most potent markers of endometrial tumors with a high risk of local and distant spread.

背景与目标： : 基质金属蛋白酶 (MMPs) 的表达与妇科肿瘤的侵袭性有关。这项研究的目的是确定子宫内膜恶性肿瘤中金属蛋白酶 (TIMP)-1和TIMP-2的MMP-2，MMP-7，MMP-9和组织抑制剂及其与临床和组织学参数的关系。用特异性单克隆抗体对来自50例1999年和2004例子宫内膜癌患者的福尔马林固定，石蜡包埋的肿瘤样品进行染色。根据FIGO分类对肿瘤进行分组。将染色结果与组织学和临床数据进行比较。MMP和TIMP表达的半定量分析显示，根据组织学亚型，TIMP-2表达存在显着差异 (P = 0.03)，并且MMP-9表达存在差异的趋势 (P = 0.05)。随着组织学分级的增加，MMP-2表达增加，TIMP-2表达下降 (分别为P = 0.0007，P <0.0001)。MMP-2表达与淋巴结转移相关 (P = 0.04)，而TIMP-2表达与肌层浸润深度相关 (P = 0.01)，血管淋巴间隙受累 (P = 0.02) 和淋巴结转移 (P = 0.0003)。这些结果支持MMPs和TIMPs参与子宫内膜肿瘤的生长和进展。高MMP-2和低TIMP-2表达是子宫内膜肿瘤的最有效标志物，具有局部和远处扩散的高风险。

BACKGROUND & AIMS: The effect of nutritional status on IGF-I mRNA expression in the liver and brain of juvenile barramundi (Lates calcarifer) was investigated. Fish were either fed a satiety ration (SAT) or starved (STV) for 6 weeks. Starved fish demonstrated significantly lower condition factor and hepatic IGF-I mRNA expression at 3 and 6 weeks, when compared with the SAT group. IGF-I mRNA expression in the brain was 10 fold lower than the liver and was not affected by ration size. These results suggest the liver is the major site of IGF-I mRNA synthesis and hepatic but not brain IGF-I mRNA expression is regulated by food availability in juvenile barramundi.

背景与目标： 研究了营养状况对幼年barramundi (Lates calcarifer) 肝脏和大脑中igf-i mRNA表达的影响。对鱼喂食饱腹感 (SAT) 或饥饿 (STV) 6周。与SAT组相比，饥饿的鱼在3周和6周时表现出明显较低的条件因子和肝igf-i mRNA表达。大脑中igf-i mRNA的表达比肝脏低10倍，不受日粮大小的影响。这些结果表明，肝脏是igf-i mRNA合成的主要部位，而肝脏而不是大脑igf-i mRNA的表达受幼年barramundi食物的调节。

BACKGROUND & AIMS: :The objective of this study was to confirm whether hemoglobin (Hb) levels during chemoradiotherapy are associated with survival in patients with locally advanced cervical carcinoma and to assess impact of the Hb level on survival according to lymph node (LN) metastasis. A retrospective review of 85 cervical carcinoma patients treated with concurrent chemoradiotherapy was conducted. The stage of disease ranged between FIGO stage IB and stage IVA. Disease-free and overall survivals were evaluated by univariate and multivariate analyses. After median follow-up of 35.7 months, 24 patients developed recurrence of disease and 14 patients died from their disease. Stage, LN metastasis, and squamous cell carcinoma antigen and Hb levels during chemoradiation were correlated significantly with survival (P < 0.05). Maintenance of Hb above 10.0 g/dL was associated with better survival (P < 0.05). However, no such benefits were observed in patients with LN metastasis by magnetic resonance imaging (MRI). Multivariate Cox regression hazard model showed that Hb levels during chemoradiation were an independent prognostic factor in patients without LN metastasis by MRI. Maintenance of Hb during chemoradiation is of benefit in cervical carcinoma patients without LN metastasis but not with LN metastasis by MRI.

背景与目标： : 本研究的目的是确认放化疗期间血红蛋白 (Hb) 水平是否与局部晚期宫颈癌患者的生存相关，并根据淋巴结 (LN) 转移评估Hb水平对生存的影响。回顾性分析了85例同期放化疗治疗的宫颈癌患者。疾病的阶段介于FIGO IB期和IVA期之间。通过单变量和多变量分析评估无病生存率和总体生存率。中位随访35.7个月后，24例患者出现疾病复发，14例患者死于疾病。分期、LN转移、放化疗期间鳞状细胞癌抗原和Hb水平与生存率显著相关 (P <0.05)。Hb维持在10.0g/dL以上与较好的生存率相关 (P <0.05)。然而，通过磁共振成像 (MRI) 在LN转移患者中未观察到这种益处。多因素Cox回归风险模型显示，放化疗期间的Hb水平是MRI无LN转移患者的独立预后因素。化疗期间维持血红蛋白对无LN转移但无LN转移的宫颈癌患者有好处。

BACKGROUND & AIMS: OBJECTIVE:In the absence of immunodeficiency, only microchimerism (<0.1%) has been achieved in human fetal recipients or nonhuman primates following in utero hematopoietic cell transplantation (IUHCT). We hypothesized that enhanced long-term engraftment might be more reliably achieved in microchimeric systems if higher levels of chimerism existed during development of adaptive immunity. To evaluate this hypothesis, we stimulated the donor cells with vascular endothelial growth factor (VEGF) and stem cell factor (SCF) prior to IUHCT in a chimerism-resistant murine strain combination. METHODS:Donor Balb/c marrow was cultured in media with or without VEGF and SCF supplementation for 12 hours prior to IUHCT into B6 fetuses at 14 days postcoitum (dpc). Donor cell phenotype, homing, and chimerism were assessed at short and long-term time points and transplanted animals received skin allografts at 8 weeks. RESULTS:In pretreated allogeneic recipients, early chimerism rates were more than double that of controls (71% vs 33%, p = 0.01). These differences were associated with higher numbers of pretransplant donor cell colony-forming cells without change in donor cell homing. Despite prolonged skin allograft survival for pretreated recipients compared with controls (mean survival = 20.8 vs 8.2 days, p < 0.001), long-term engraftment was unchanged. CONCLUSIONS:These findings demonstrate that higher levels of early chimerism in recipients of cytokine-stimulated marrow result in improved short-term chimerism and tolerance. Future studies are needed to confirm the existence of a "threshold" level of chimerism necessary to sustain long-term engraftment.

背景与目标：

BACKGROUND & AIMS: :The objective of this study was to determine whether paclitaxel and a strong antioxidant, pyrrolidinedithiocarbamate (PDTC), can affect the activation of nuclear factor-kappa B (NF-kappaB) in SKOV-3 human ovarian cancer cell line and the effect of these two agents on the growth and apoptosis of the cancer cells. The cells were treated with various concentrations of paclitaxel and/or PDTC at various time intervals. Following treatments, cell growth and apoptosis were determined by 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulphonyl)-2H-tetrazolium (WST-8) (WST) assay and flow cytometry, respectively. Western blot assay was used to determine the nuclear p65 protein and cytoplasmic IkappaB-alpha protein. High doses of PDTC significantly inhibited the growth of SKOV-3 cells and caused apoptosis. Paclitaxel and lower doses of PDTC combined demonstrated additive inhibition of cell growth and increased levels of apoptosis. Treatment of paclitaxel alone showed increased nuclear p65 protein and decreased cytoplasmic IkappaB-alpha protein expression, while pretreatment of PDTC reversed this function. PDTC blocks the paclitaxel-induced activation of NF-kappaB leading to increased chemosensitivity to paclitaxel and enhanced apoptosis. Combining antioxidants and paclitaxel has significant potential to overcome the risk of paclitaxel resistance.

背景与目标： : 这项研究的目的是确定紫杉醇和强抗氧化剂吡咯烷二硫代氨基甲酸酯 (PDTC) 是否会影响SKOV-3人卵巢癌细胞系中核因子-κ B (NF-κ B) 的活化以及这两种药物对癌细胞生长和凋亡的影响。在不同的时间间隔用各种浓度的紫杉醇和/或PDTC处理细胞。处理后，通过2-(2-甲氧基-4-硝基苯基)-3-(4-硝基苯基)-5-(2,4-二硫酰基)-2h-四唑 (WST-8) (WST) 测定和流式细胞仪测定细胞生长和凋亡。Western blot测定法用于测定核p65蛋白和细胞质IkappaB-α 蛋白。高剂量的PDTC显著抑制SKOV-3细胞的生长并引起细胞凋亡。紫杉醇和较低剂量的PDTC组合显示出对细胞生长的加性抑制和凋亡水平的增加。单独治疗紫杉醇显示核p65蛋白增加，胞质IkappaB-α 蛋白表达降低，而PDTC的预处理逆转了这一功能。PDTC阻断紫杉醇诱导的NF-κ b激活，从而增加对紫杉醇的化学敏感性并增强细胞凋亡。结合抗氧化剂和紫杉醇具有克服紫杉醇耐药性风险的巨大潜力。

BACKGROUND & AIMS: Studies concerned with the efficacy of cochlear implants have traditionally focused on measuring enhancements in speech perception associated with implantation. This paper reports the findings of a study concerned with qualitative and quantitative measures of psychosocial benefit associated with the adult cochlear implant programme. Cochlear implants enhanced implantees' interpersonal communication skills and social confidence, and were associated with a reduction in the user's social anxiety. Broader socioeconomic gains were not achieved by implantees, mainly because of an absence of adequate employment and community education programmes associated with implant programmes.

背景与目标： 传统上，与人工耳蜗的功效有关的研究集中在测量与植入相关的语音感知的增强。本文报告了一项研究的结果，该研究涉及与成人人工耳蜗计划相关的社会心理益处的定性和定量测量。人工耳蜗增强了植入者的人际沟通技巧和社交信心，并与减少用户的社交焦虑有关。植入者没有实现更广泛的社会经济收益，这主要是因为缺乏与植入计划相关的适当就业和社区教育计划。

BACKGROUND & AIMS: The driving behaviors of dementia patients have received little in the way of empirical scrutiny except through retrospective reports of crash rates. Understanding the driving errors of dementia patients and how they differ from those of normal older and younger drivers is important. This knowledge is basic to the development of road tests and scoring procedures to evaluate the driving competence of older, experienced drivers, especially those whose fitness to drive may have been compromised by a medical illness that alters their mental abilities. We have drive tested over 100 currently driving elderly patients with clinically significant cognitive decline (mostly diagnosed as the early stages of Alzheimer disease) and compared their performance with that of normal drivers. The study identified the types of driving errors that distinguish and differentiate the cognitively impaired group as well as a set of driving errors typical of both cognitively impaired and normal experienced drivers but differing in the number and severity of errors. A set of errors was also identified that did not differentiate the groups and should not be used in evaluating a person's competence to drive.

背景与目标： 痴呆症患者的驾驶行为很少受到经验审查，除非通过回顾性报告撞车率。了解痴呆症患者的驾驶错误以及它们与正常的老年和年轻驾驶员的区别非常重要。这些知识是道路测试和评分程序的发展的基础，以评估年龄较大，经验丰富的驾驶员的驾驶能力，尤其是那些适合驾驶的人可能因改变其心理能力的医疗疾病而受到损害。我们已经对100多名目前驾驶具有临床显著认知能力下降 (主要被诊断为阿尔茨海默病的早期阶段) 的老年患者进行了驾驶测试，并将他们的表现与正常驾驶员的表现进行了比较。该研究确定了区分和区分认知障碍组的驾驶错误类型，以及一组认知障碍和正常经验驾驶员的典型驾驶错误，但错误的数量和严重程度不同。还发现了一组错误，这些错误不能区分群体，不应用于评估一个人的驾驶能力。

BACKGROUND & AIMS: BACKGROUND:Germ cells are the only cell type that can penetrate from one generation to next generation. At the early embryonic developmental stages, germ cells originally stem from primordial germ cells, and finally differentiate into functional gametes, sperm in male or oocyte in female, after sexual maturity. This study was conducted to investigate a large-scale expressed sequence tag (EST) analysis in chicken PGCs and compare the expression of the PGC ESTs with that of embryonic gonad. RESULTS:We constructed 10,851 ESTs from a chicken cDNA library of a collection of highly separated embryonic PGCs. After chimeric and problematic sequences were filtered out using the chicken genomic sequences, there were 5,093 resulting unique sequences consisting of 156 contigs and 4,937 singlets. Pearson chi-square tests of gene ontology terms in the 2nd level between PGC and embryonic gonad set showed no significance. However, digital gene expression profiling using the Audic's test showed that there were 2 genes expressed significantly with higher number of transcripts in PGCs compared with the embryonic gonads set. On the other hand, 17 genes in embryonic gonads were up-regulated higher than those in the PGC set. CONCLUSION:Our results in this study contribute to knowledge of mining novel transcripts and genes involved in germline cell proliferation and differentiation at the early embryonic stages.

背景与目标：

BACKGROUND & AIMS: Various practice parameters have emphasized a step-wise approach to the treatment of asthma utilizing high doses of inhaled corticosteroids, i.e., 2000 ug per day for the most difficult-to-manage asthmatic patient, along with maximum bronchodilator therapy. The use of such vigorous therapy presupposes that various triggers that perpetuate asthma have been considered and hopefully eliminated or diminished, such as occupational incitants, gastroesophageal reflux, and concomitant medication such as beta blockers and perhaps difficult-to-recognize allergen stimulation. As new therapies emerge, their role in the treatment of a severe subgroup of the population remains uncategorized and will only be clarified with personal experience and appropriate double-blind studies. For example, there are data to support the concept that salmeterol plus moderate dose aerosol corticosteroids is superior to high dose corticosteroid aerosols. Theoretically, the use of anti-leukotrienes for a patient with aspirin idiosyncrasy may be superior to other combinations as would be conjectured from aspirin challenge data. Lidocaine has recently been employed in severe asthmatics, and preliminary data suggest benefit. The purpose of this review is to summarize some of our knowledge regarding medications that are either steroid-sparing or that might be useful in a subgroup of asthmatic patients with severe asthma.

背景与目标： 各种实践参数强调了使用高剂量的吸入皮质类固醇治疗哮喘的逐步方法，即对于最难管理的哮喘患者，每天2000微克，以及最大的支气管扩张剂治疗。使用这种剧烈疗法的前提是，已经考虑并希望消除或减少了使哮喘持续存在的各种诱因，例如职业性诱因，胃食管反流以及伴随药物 (例如 β 受体阻滞剂和可能难以识别的过敏原刺激)。随着新疗法的出现，它们在严重人群亚组治疗中的作用仍然未分类，只有通过个人经验和适当的双盲研究才能阐明。例如，有数据支持沙美特罗加中等剂量气雾剂皮质类固醇优于高剂量皮质类固醇气雾剂的概念。从理论上讲，阿司匹林特质患者使用抗白三烯可能优于其他组合，这可以从阿司匹林激发数据中推测。利多卡因最近被用于严重哮喘患者，初步数据表明有益。这篇综述的目的是总结我们有关保留类固醇或可能对患有严重哮喘的哮喘患者亚组有用的药物的一些知识。

BACKGROUND & AIMS: :A mouse perfusion model using fluorescently labeled dextran has been developed to investigate the functionality of blood vessels during cutaneous wound healing. By immunostaining cryostat sections of perfused wounds with antibodies that identify vessels, we were able to assess their functionality. There was an increase in the proportion of CD31(+)-perfused vessels in all wound regions with time, although the vessels of the wound margins and superficial granulation tissue (GT) took the longest to become perfused. More than 50% of the latter vessels were not perfused at 10 days postwounding. This is consistent with the growth of functional vessels from the wound base proceeding to the more superficial GT. The CD34 marker was expressed by a subpopulation of CD31(+) vessels. However, in contrast to CD31(+) vessels, the functionality of CD34(+) vessels did not change significantly with time and 50-75% of CD34(+) vessels in the GT and wound margins were nonfunctional. This might be explained either by apoptosis of the CD34(+) vessels or the loss of the marker with time. This study has important implications for assays of wound-healing angiogenesis based on histology and immunohistochemical markers for vessels, because vessel functionality differs both spatially and temporally during wound healing.

背景与目标： : 已经开发了使用荧光标记的葡聚糖的小鼠灌注模型，以研究皮肤伤口愈合过程中血管的功能。通过用识别血管的抗体对灌注伤口的低温恒温器切片进行免疫染色，我们能够评估其功能。尽管伤口边缘和浅表肉芽组织 (GT) 的血管灌注时间最长，但所有伤口区域中CD31 () 灌注血管的比例随时间增加。超过50% 的后一种血管在伤后10天没有灌注。这与从伤口基部到更浅表的GT的功能性血管的生长是一致的。CD34标记由CD31 () 血管的亚群表达。然而，与CD31(+) 血管相反，CD34(+) 血管的功能没有随时间显着变化，并且GT和伤口边缘中的50-75% CD34(+) 血管无功能。这可以通过CD34 () 血管的凋亡或标记物随时间的丢失来解释。这项研究对基于血管的组织学和免疫组织化学标记的伤口愈合血管生成测定具有重要意义，因为在伤口愈合过程中，血管功能在空间和时间上均不同。

BACKGROUND & AIMS: :There is a substantial need for a diagnostic tool to aid in the early diagnosis of heart failure and in the recognition of those at risk for its development, as well as in guidance of therapy. Testing for amino-terminal pro-brain natriuretic peptide (NT-proBNP) has been recognized to have utility in the diagnosis, prognosis and management of heart failure. In addition, numerous other applications for NT-proBNP testing are now recognized, such as evaluation of patients with heart disease in the absence of heart failure, as well as the diagnostic and prognostic evaluation of patients with acute coronary syndromes or pulmonary thromboembolism.

背景与目标： : 迫切需要一种诊断工具来帮助早期诊断心力衰竭，识别有发展风险的人以及指导治疗。氨基末端脑钠肽前体 (NT-proBNP) 的检测已被认为可用于心力衰竭的诊断，预后和管理。此外，NT-proBNP检测的许多其他应用现已得到认可，例如在没有心力衰竭的情况下评估心脏病患者，以及对急性冠状动脉综合征或肺血栓栓塞患者的诊断和预后评估。

BACKGROUND & AIMS: AIMS:Falling in older persons is a frequent and serious clinical problem. Several drugs have been associated with increased fall risk. The objective of this study was to identify differences in the incidence of falls after withdrawal (discontinuation or dose reduction) of fall-risk-increasing drugs as a single intervention in older fallers. METHODS:In a prospective cohort study of geriatric outpatients, we included 139 patients presenting with one or more falls during the previous year. Fall-risk-increasing drugs were withdrawn, if possible. The incidence of falls was assessed within 2 months of follow-up after a set 1 month period of drug withdrawal. Multivariate adjustment for potential confounders was performed with a Cox proportional hazards model. RESULTS:In 67 patients, we were able to discontinue a fall-risk-increasing drug, and in eight patients to reduce its dose. The total number of fall incidents during follow-up was significantly lower in these 75 patients, than in those who continued treatment (mean number of falls: 0.3 vs. 3.6; P value 0.025). The hazard ratio of a fall during follow-up was 0.48 (95% confidence interval (CI) 0.23, 0.99) for overall drug withdrawal, 0.35 (95% CI 0.15, 0.82) for cardiovascular drug withdrawal and 0.56 (95% CI 0.23, 1.38) for psychotropic drug withdrawal, after adjustment for age, gender, use of fall-risk-increasing drugs, baseline falls frequency, comorbidity, Mini-Mental State Examination score, and reason for referral. CONCLUSIONS:Withdrawal of fall-risk-increasing drugs appears to be effective as a single intervention for falls prevention in a geriatric outpatient setting. The effect was greatest for withdrawal of cardiovascular drugs.

背景与目标：