BACKGROUND & AIMS: BACKGROUND:Although the benefit of thrombolytic therapy in reducing mortality in acute myocardial infarction is well established, the types of bleeding and risk factors for bleeding are less well described in large trials.

METHODS AND RESULTS:We analyzed the baseline characteristics, outcomes, and incidence of bleeding by location, severity, and treatment assignment among 41,021 patients in the GUSTO-I trial of thrombolysis for acute myocardial infarction. Of the 40,903 patients for whom there were complete data, 1.2% suffered severe bleeding and 11.4% experienced moderate hemorrhage at a variety of sites. The most common sources of bleeding were procedure related. The thrombolytic regimen was strongly related to the incidence of bleeding; comparatively more bleeding was seen with the therapies of streptokinase plus intravenous heparin and the streptokinase and tissue plasminogen activator plus intravenous heparin combination. In multivariate analysis, the four most powerful independent predictors of hemorrhage were older age, lighter body weight, female sex, and African ancestry; they remained the most important predictors of bleeding when multivariate analysis was performed on patients who did not undergo invasive procedures. The presence of serious hemorrhage was associated with other undesirable outcomes (recurrent events, left ventricular dysfunction, arrhythmia, or stroke).

CONCLUSIONS:Important predictors of bleeding in this population are increased age, lighter weight, female sex, African ancestry, and experiencing invasive procedures. Other nonhemorrhagic adverse clinical outcomes were associated with moderate and severe bleeding, which was in turn associated with increased length of hospital stay and mortality at 30 days.

背景与目标： 背景 : 尽管溶栓治疗在降低急性心肌梗死死亡率方面的益处已得到充分证实，但在大型试验中，出血类型和出血危险因素的描述较少。
方法和结果 : 在GUSTO-I急性心肌梗死溶栓试验中，我们分析了41,021名患者的基线特征，结局和出血发生率，按位置，严重程度和治疗分配。在40,903例有完整数据的患者中，1.2% 例严重出血，11.4% 例在不同部位出现中度出血。最常见的出血来源与手术有关。溶栓方案与出血发生率密切相关; 链激酶加静脉肝素以及链激酶和组织型纤溶酶原激活剂加静脉肝素联合治疗的出血相对较多。在多变量分析中，出血的四个最有效的独立预测因子是年龄较大，体重较轻，女性和非洲血统; 当对未接受侵入性操作的患者进行多变量分析时，它们仍然是出血的最重要预测因子。严重出血的存在与其他不良结果 (复发事件，左心室功能障碍，心律失常或中风) 相关。
结论 : 该人群出血的重要预测因素是年龄增加，体重减轻，女性，非洲血统，经历侵入性手术。其他非出血性不良临床结局与中度和重度出血相关，而中度和重度出血又与30天时的住院时间和死亡率增加相关。

BACKGROUND & AIMS: :The oxidative deamination of serotonin (5-HT) to 5-hydroxyindoleacetic acid (5-HIAA) by rat primary astrocyte cultures was investigated in intact cells using HPLC. All detectable 5-HIAA accumulated in the extracellular medium, and its rate of production was proportional to the 5-HT concentration over the tested range of 5 x 10(-7) to 10(-4) M. At 5 x 10(-7) M 5-HT, intracellular 5-HT was detectable only in astrocytes treated with monoamine oxidase (MAO) inhibitors. These findings are consistent with the idea that 5-HT taken up into astrocytes is not stored for re-release, but is rapidly metabolized to 5-HIAA, which is then extruded from the cell. At 5 x 10(-7) M 5-HT, 5-HIAA formation in intact cells was blocked 63% by the selective high-affinity 5-HT uptake inhibitor fluoxetine. 5-HT oxidation to 5-HIAA is carried out principally by MAO-A, because clorgyline was more effective at inhibiting the production of 5-HIAA than was pargyline. Radioenzymatic determinations of MAO activity in cell homogenates supported these findings, because under these conditions clorgyline was 1,000-fold more effective than pargyline at inhibiting MAO activity toward 14C-labelled 5-HT. However, the relatively selective MAO-B substrate beta-phenylethylamine (PEA) was also oxidized, showing that these cultures also contained MAO-B activity; the Km values for MAO-A oxidation of 5-HT and MAO-B oxidation of PEA were 135 and 45 microM, and Vmax values were 88 and 91 nmol/mg of total cell protein/h, respectively. Higher concentrations of PEA (greater than 20 microM) were oxidized by both MAO-A and MAO-B isozymes.(ABSTRACT TRUNCATED AT 250 WORDS)

背景与目标： : 使用HPLC在完整细胞中研究了大鼠原代星形胶质细胞培养物将5-羟色胺 (5-HT) 氧化脱氨为5-羟基吲哚乙酸 (5-HIAA)。所有可检测到的5-HIAA都积累在细胞外培养基中，在5x10(-7) 至10(-4) M的测试范围内，其产生速率与5-HT浓度成正比。在5x10(-7) M 5-HT时，仅在用单胺氧化酶 (MAO) 抑制剂处理的星形胶质细胞中可检测到细胞内5-HT。这些发现与以下观点一致: 吸收到星形胶质细胞中的5-HT不会储存以重新释放，而是会迅速代谢为5-HIAA，然后从细胞中挤出。在5 × 10(-7) m5-ht时，选择性高亲和力5-HT摄取抑制剂氟西汀63% 阻断完整细胞中的5-HIAA形成。5-HT氧化为5-HIAA主要由MAO-A进行，因为clorgyline比pargyline更有效地抑制5-HIAA的产生。细胞匀浆中MAO活性的放射酶测定支持了这些发现，因为在这些条件下，clorgyline在抑制针对14c标记的5-HT的MAO活性方面比pargyline有效1,000倍。然而，相对选择性的MAO-B底物 β-苯乙胺 (PEA) 也被氧化，表明这些培养物也含有MAO-B活性; 5-HT的MAO-A氧化和PEA的MAO-B氧化的Km值分别为135和45微米，vmax值分别为88和91 nmol/mg的总细胞蛋白/h。较高浓度的豌豆 (大于20微米) 被MAO-A和MAO-B同工酶氧化。(摘要截短于250字)

BACKGROUND & AIMS: An important step in the processing of visual patterns is the segmentation of the retinal image. Neuronal responses evoked by the contours of individual objects need to be identified and associated for further joint processing. These grouping operations are based on a number of Gestalt criteria. Here we report that connections in the visual cortex of the cat exhibit a highly significant anisotropy, preferentially linking neurons activated by contours that have similar orientation and are aligned colinearly. These anatomical data suggest a close relation between the perceptual grouping criterion of colinearity and the topology of tangential intracortical connections. We propose that tangential intracortical connections support perceptual grouping by modulating the saliency of distributed cortical responses in a context-dependent way. The present data are compatible with the hypothesis that the criteria for this grouping operation are determined by the architecture of the tangential connections.

背景与目标： 视觉图案处理中的一个重要步骤是视网膜图像的分割。需要识别并关联单个物体轮廓引起的神经元反应，以进行进一步的关节处理。这些分组操作基于许多格式塔标准。在这里，我们报告说，猫的视觉皮层中的连接表现出高度显着的各向异性，优先连接由具有相似方向且对齐的轮廓激活的神经元。这些解剖学数据表明共线性的感知分组标准与切向皮质内连接的拓扑之间存在密切关系。我们建议，切向皮质内连接通过以上下文相关的方式调节分布式皮质反应的显着性来支持感知分组。当前数据与以下假设兼容: 该分组操作的标准由切向连接的体系结构确定。

BACKGROUND & AIMS: :In Escherichia coli at least five enzyme activities required for the beta-oxidation of fatty acids are associated with a multienzyme complex composed of two subunits in alpha 2 beta 2 conformation (A. Pramanik et al., J. Bacteriol. 137:469-473, 1979). In the present work, the DNA sequence of the genes encoding these two subunits, fadB and fadA, has been determined. The direction of transcription was from fadB to fadA rather than from fadA to fadB, as suggested previously (S. K. Spratt et al., J. Bacteriol. 158:535-542, 1984). Only 10 nucleotides separated the coding sequences for the two peptides, confirming the suggestion that these genes form an operon. The peptides encoded by fadB and fadA were 729 amino acids and 387 amino acids, respectively, in length. The larger and smaller peptides had predicted molecular masses of 79,678 and 40,876 Da, respectively. Recently, the sequence of the fadA gene was published in a separate report (Yang et al., J. Biol. Chem. 265:10424-10429, 1990). In this work, most of the DNA sequence for fadA was confirmed, and 10 errors were corrected. Three of these nucleotide changes resulted in five amino acid residue changes predicted in the carboxy terminus of the fadA-encoded peptide. By comparison to other peptide sequences, the alpha subunit encoded within fadB had 31% perfect identity with the rat peroxisomal enoyl-coenzyme A:hydratase-3-hydroxyacyl-coenzyme A dehydrogenase trifunctional enzyme over the entire length of the two peptides. In agreement with the work of Yang et al., the beta subunit encoded within fadA had 35 to 45% perfect identity with five thiolase genes from different eucaryotic sources over the entire length of the peptide.

背景与目标： 在大肠杆菌中，脂肪酸的 β-氧化所需的至少五种酶活性与由 α2β2构象中的两个亚基组成的多酶复合物相关 (a.Pramanik等人，J. Bacteriol. 137:469-473，1979)。在本工作中，已经确定了编码这两个亚基fadB和fadA的基因的DNA序列。转录的方向是从fadB到fadA，而不是从fadA到fadB，如前所述 (S. K. Spratt等人，J. Bacteriol. 158:535-542，1984)。只有10个核苷酸分离了两个肽的编码序列，证实了这些基因形成操纵子的暗示。fadB和fadA编码的肽长度分别为729个氨基酸和387个氨基酸。较大和较小的肽分别预测79,678和40,876 Da的分子量。最近，fadA基因的序列发表在单独的报告中 (Yang等人，J. Biol. Chem. 265:10424-10429，1990)。在这项工作中，fadA的大部分DNA序列得到了确认，并纠正了10个错误。这些核苷酸变化中的三个导致fadA编码肽的羧基末端预测的五个氨基酸残基变化。与其他肽序列相比，fadB内编码的 α 亚基与大鼠过氧化物酶体烯酰辅酶a具有31% 完美的同一性: 在两个肽的整个长度上hydratase-3-hydroxyacyl-coenzyme脱氢酶三官能酶。与Yang等人的工作一致，在fadA内编码的 β 亚基在肽的整个长度上与来自不同真核来源的五个硫解酶基因具有35至45% 完美的同一性。

BACKGROUND & AIMS: :Descriptions of primary HIV-1 infection have so far been based on Caucasians living in industrialized nations. Due to studies of leptospirosis in the predominantly black population of Barbados, serum was available for patients admitted with acute febrile illnesses to the Queen Elizabeth Hospital (QEH). By searching the medical records of 510 adult patients with known HIV-1 infection we identified 10 patients who had stored serum from an admission for an acute febrile illness that predated or coincided with their first HIV-1-positive test. Serological testing confirmed primary HIV-1 infection in 9 and was suggestive in the 10th patient. The clinical features of these 10 patients were in keeping with previous descriptions of primary HIV-1 infection but differed from leptospirosis cases seen at the QEH. One patient died during his seroconversion illness and another died 3 months after seroconversion. The findings suggest that severe primary HIV-1 infection could be a relatively uncommon occurrence, that the condition may be misdiagnosed, and that cases may not occur until the AIDS epidemic is established. :A retrospective review was conducted of the medical records of 510 HIV-1-positive adult patients who had attended the Queen Elizabeth Hospital (QEH) to determine whether any had been admitted for an illness compatible with a diagnosis of primary HIV-1 infection. A serum bank, created from patients who had been admitted with acute febrile illnesses and investigated for leptospirosis, provided serological evidence for primary HIV-1 infection in 10 patients. Serological testing of the serum samples confirmed primary HIV-1 infection in nine patients and was suggestive in the tenth. The clinical features of the 10 patients fit the earlier descriptions of primary HIV-1 infection, but differed from the leptospirosis cases seen at the QEH. One patient died during his seroconversion illness and another died 3 months after seroconversion. These findings suggest that severe primary HIV-1 infection could be a relatively uncommon occurrence, that the condition may be misdiagnosed, and that cases may not occur until the AIDS epidemic is established.

背景与目标：

BACKGROUND & AIMS: The expression and localization of hepatocyte growth factor/scatter factor (HGF/SF) were examined immunohistochemically in 59 human coronary artery lesions retrieved by directional coronary atherectomy and compared with the localization of transforming growth factor beta isoforms (TGF-beta 1, -beta 2, and -beta 3). In 21 of the 59 specimens (35.6%) HGF-like immunoreactivity (HGF-IR) was revealed. The HGF immunopositivity rate of 45% (14/31) in thrombotic tissue was significantly (P < 0.05) higher than the rates of 7.3% (4/55), 7.1% (3/42), and 0% (0/14) in fibrous tissue, neointimal hyperplasia and atheromatous gruel, respectively. Immunoreactivity for HGF was much weaker than that for TGF-beta isoforms in these components except in thrombotic tissue. These cells exhibiting strong HGF-IR were inflammatory cells such as monocytes/macrophages in thrombotic tissue, in tissue lesions adjacent to a thrombus, and outside the capillary walls in a portion of the neovascularized lesions. Smooth muscle cells (SMCs) hardly demonstrated HGF-IR. In contrast, in control coronary arteries obtained at autopsy, the HGF-IR was strongly expressed in SMCs. These findings suggest that HGF produced by macrophages play a part in the process of coronary plaque formation attributable to thrombus in man.

背景与目标： 通过免疫组织化学检查了通过定向冠状动脉粥样斑块切除术检索的59例人冠状动脉病变中肝细胞生长因子/散射因子 (HGF/SF) 的表达和定位，并将其与转化生长因子 β 亚型 (tgf-β1，-β2和-β3) 的定位进行了比较。在59个标本中的21个 (35.6%) 中，HGF样免疫反应性 (hgf-ir) 被揭示。血栓组织中45% (14/31) 的HGF免疫阳性率显着 (P < 0.05) 高于纤维组织，新内膜增生和动脉粥样硬化稀粥中的7.3% (4/55)，7.1% (3/42) 和0% (0/14)。分别。除血栓形成组织外，这些成分中HGF的免疫反应性比TGF-β 同工型的免疫反应性弱得多。这些表现出强hgf-ir的细胞是炎性细胞，例如血栓形成组织中，与血栓相邻的组织病变以及部分新生血管病变的毛细血管壁外部的单核细胞/巨噬细胞。平滑肌细胞 (smc) 几乎不显示HGF-IR。相反，在尸检获得的对照冠状动脉中，hgf-ir在smc中强烈表达。这些发现表明，巨噬细胞产生的HGF在人类血栓形成引起的冠状动脉斑块形成过程中发挥了作用。

BACKGROUND & AIMS: :A major problem in the search for new cancer drug targets is that the drugs are often toxic to normal tissues and require high doses to kill tumor cells. Therefore cellular targets which appear to involve low dose responses to cancer therapy are especially interesting since they could selectively target normal tissues which are not targeted by the treatment and thus may be responsible for unpleasant side effects or may be amenable to exploitation in order to improve the therapeutic ratio. One such target, which is the subject of this review, is radiation-induced bystander effects [RIBE], which result in the observation of radiation like responses in cells which have not been irradiated. RIBE is a novel phenomenon which indicates that at low doses, cell signaling is more important than direct DNA damage. Historically, DNA has always been considered to be the target for radiation therapy. The growing realization that signaling is important opens up several important therapeutic strategies which will be discussed in this review. RIBE appears to be the result of a generalized stress response in tissues or cells which is expressed at the level of the tissue, organ or organism rather than at the level of the individual cell. The signals may be produced by all exposed cells, but the response may require a quorum of cells in order to be expressed. The major response involving low LET (x- or gamma-ray) radiation exposure discussed in the existing literature is a death response. This has many characteristics of apoptosis but may be detected in cell lines without p53 expression, although the death response is suppressed in many tumor cell lines. While a death response in unirradiated normal cells around a tumor might appear to be adverse, it can in fact be protective and remove damaged cells from the population. If harnessed correctly, it could lead to the development of new drugs aimed not at tissue destruction but at enabling homeostatic mechanisms to control tumor expansion. In this scenario, the level of harmful or beneficial response will be related to the background damage, carried by the cell population, and the genetic programme determining response to damage. This focus may be important when attempting to predict the consequences of mixed therapies involving radiation and other cytotoxic agents. In this review, our current knowledge of the mechanisms underlying the induction of bystander effects by ionizing radiation is reviewed, and the question of how bystander effects may be harnessed to produce a new generation of anti-cancer drugs aimed at stabilization of tissue homeostasis rather than tissue destruction is considered.

背景与目标： : 寻找新的癌症药物靶标的一个主要问题是，这些药物通常对正常组织有毒，需要高剂量才能杀死肿瘤细胞。因此，似乎涉及对癌症治疗的低剂量反应的细胞靶标是特别令人感兴趣的，因为它们可以选择性地靶向不被治疗靶向的正常组织，并且因此可能导致令人不快的副作用或可能易于利用以提高治疗比率。作为本综述主题的一个这样的目标是辐射诱导的旁观者效应 [RIBE]，该效应导致在未辐照的细胞中观察到类似辐射的反应。RIBE是一种新现象，表明在低剂量下，细胞信号传导比直接DNA损伤更重要。从历史上看，DNA一直被认为是放射治疗的目标。越来越多的意识到信号很重要，这开辟了一些重要的治疗策略，这些策略将在本文中进行讨论。RIBE似乎是组织或细胞中普遍应激反应的结果，该应激反应在组织，器官或生物体的水平而不是单个细胞的水平上表达。信号可能由所有暴露的细胞产生，但是响应可能需要一定数量的细胞才能表达。现有文献中讨论的涉及低LET (x射线或伽马射线) 辐射暴露的主要反应是死亡反应。这具有许多凋亡特征，但可以在没有p53表达的细胞系中检测到，尽管在许多肿瘤细胞系中死亡反应受到抑制。虽然肿瘤周围未照射的正常细胞的死亡反应似乎是不利的，但实际上它可以起到保护作用并从人群中清除受损的细胞。如果正确使用，它可能会导致新药的开发，其目的不是组织破坏，而是使稳态机制能够控制肿瘤的扩张。在这种情况下，有害或有益反应的水平将与细胞群体携带的背景损害以及确定对损害反应的遗传程序有关。在尝试预测涉及辐射和其他细胞毒性药物的混合疗法的后果时，此重点可能很重要。在这篇综述中，我们对电离辐射诱导旁观者效应的潜在机制的当前知识进行了综述，并讨论了如何利用旁观者效应来生产旨在稳定组织稳态而不是组织破坏的新一代抗癌药物的问题。

BACKGROUND & AIMS: In the study presented, knee joint proprioception of 17 patients with primary degenerative joint disease of the knee joint was evaluated. As a control group, the proprioception of 30 healthy volunteers with clinical and anamnestically inconspicuous knee joints was examined. We tested the proprioceptive capability of the subjects with an angle reproduction test. Additionally, all knee joints were measured with and without an elastic knee bandage. The study showed significantly more deterioration in knee joint proprioception in patients with gonarthrosis than in the control group. Even the proprioception of the contralateral, healthy knee joint was worse than the results of the control group. However, after using an elastic knee bandage, significant improvement in the proprioceptive abilities of the injured knee joint was documented.

背景与目标： 在提出的研究中，对17例原发性退行性膝关节疾病患者的膝关节本体感觉进行了评估。作为对照组，检查了30名健康志愿者的临床和记忆不明显的膝关节的本体感觉。我们通过角度再现测试测试了受试者的本体感受能力。此外，在使用和不使用弹性膝盖绷带的情况下测量所有膝关节。研究表明，与对照组相比，淋病患者的膝关节本体感觉明显恶化。甚至对侧健康膝关节的本体感觉也比对照组的结果差。但是，在使用弹性膝盖绷带后，记录了受伤膝关节本体感受能力的显着改善。

BACKGROUND & AIMS: :Our recent study demonstrated that defects in p110delta result in B-cell immunodeficiency that is very similar to that observed in BTK-deficient mice. We revealed that the p110delta fit the B-cell signal transduction complex and played a non-redundant role in the development and function of B cells. In humans, most children with primary B-cell immunodeficiency have mutations in the BTK, whereas a few have defects in the components of the B-cell signal transduction complex. But little is known about the genetic variation of p110delta in children with defects in B-cell immunodeficiency of unknown aetiology. Sixteen patients from 15 unrelated families and 112 normal controls underwent sequence analysis to identify genetic variations of the p110delta. Allele frequency in each group was also analysed and compared. We identified five single base-pair polymorphic nucleotide exchanges in both patient and control groups with similar allele frequencies, which did not contribute to the immunodeficiency. Three of them are novel (m.953A>G, m.1200C>T and m.1561A>G), and the m.953A>G and m.1561A>G nucleotide exchanges are non-synonymous (N253S and T456A, respectively). The novel m.1561A>G was in complete linkage disequilibrium with the known m.873A>G in our study of Taiwanese group. In addition, one novel single base-pair missense mutation, m.3256G>A (E1021K), was identified in one boy with typical clinical features of primary B-cell immunodeficiency and could not be found in either his family or the normal control population. By atomic structural analysis of the amino acid as well as the alignment comparison between species, it resulted in the replacement of the negative-charged amino acid E with the positive-charged amino acid K at codon 1021, located in the highly conservative and important catalytic functional domain. Our findings could shed light on further understanding the polymorphisms of p110delta in B-cell immunodeficiency and different populations. Moreover, the 3256G>A missense mutation raised the attention and warranted further extensive analysis to elucidate the role of p110delta in human immunodeficiency.

背景与目标： : 我们最近的研究表明，p110delta的缺陷导致b细胞免疫缺陷，这与BTK缺陷小鼠中观察到的非常相似。我们揭示了p110delta符合b细胞信号转导复合物，并且在b细胞的发育和功能中起着非冗余的作用。在人类中，大多数患有原发性b细胞免疫缺陷的儿童在BTK中存在突变，而少数儿童在b细胞信号转导复合物的成分中存在缺陷。但是，对于病因不明的b细胞免疫缺陷儿童中p110delta的遗传变异知之甚少。来自15个无关家庭和112个正常对照的16名患者进行了序列分析，以鉴定p110delta的遗传变异。还对各组的等位基因频率进行了分析和比较。我们在患者组和对照组中鉴定出五个具有相似等位基因频率的单碱基对多态性核苷酸交换，这对免疫缺陷没有贡献。其中三个是新颖的 (m.953A>G，m.1200C>T和m.1561A>G)，而m.953A>G和m.1561A>G核苷酸交换是非同义的 (分别为N253S和T456A)。在我们对台湾组的研究中，新颖的m.1561A>G与已知的m.873A>G完全处于连锁不平衡状态。此外，在一名具有原发性b细胞免疫缺陷典型临床特征的男孩中鉴定出一个新的单碱基对错义突变m.3256G>A (E1021K)，在其家人或正常对照人群中均找不到。通过氨基酸的原子结构分析以及物种之间的比对比较，它导致负电荷氨基酸E被密码子1021位的正电荷氨基酸K取代，位于高度保守和重要的催化功能域。我们的发现可能有助于进一步了解b细胞免疫缺陷和不同人群中p110delta的多态性。此外，3256G>A错义突变引起了人们的注意，并需要进一步广泛的分析来阐明p110delta在人类免疫缺陷中的作用。

BACKGROUND & AIMS: OBJECTIVE:To investigate clinically relevant intra-individual and mean changes in health-related quality of life (HRQoL) with the Short Form-36 Health Survey (SF-36) need to acknowledge that SF-36 is trademarked ie: SF-36(R) following cardiac intervention for Australian and Danish patients. DESIGN:Prospective observational study in tertiary cardiac centres in Townsville, Queensland, Australia and Copenhagen, Denmark. Two hundred coronary artery bypass graft surgery (CABG) patients of two Townsville hospitals, and 47 CABG or percutaneous coronary intervention (PCI) patients of a Copenhagen hospital. The main outcome measures are eight SF-36 health subscales at baseline and six months post-intervention. RESULTS:Australian and Danish patients experienced similar HRQoL pre-intervention. By six months post-intervention, patients experienced a significant mean improvement in all subscales of the SF-36 survey (p < or = 0.05), although up to 27% of patients had a clinically significant decline in HRQoL from baseline. CONCLUSIONS:These results demonstrate that it is necessary to investigate intra-individual changes in HRQoL as well as group mean changes as they produce different conclusions. In addition, establishing clinically significant intra-individual change standards may assist researchers and clinicians in determining whether an individual may benefit from therapy or intervention.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Surveys of the population are commonly used to obtain information on health status. Increasingly, researchers are linking self-reported health status information to primary care consultation data. However, it is not known how participating in a health-related survey affects consultation behaviour. The objective of this study was to assess whether completion of a health-related questionnaire changes primary care consultation behaviour. METHODS:Participants were 3402 adults aged 50 and over from the general population in North Staffordshire, UK, who completed a health-related postal survey received in April 2003. The survey was predominantly about occurrence and severity of knee pain in the last year. Primary care attendance for the three months following response was compared to three control periods: i) the three months prior to the survey, ii) the same time period in the previous year and iii) the same time period in the following year. Comparisons were made on consultations for any problem, consultations for musculoskeletal disorders and consultations for knee problems. RESULTS:The percentage of subjects consulting for any condition was marginally higher for the three months directly after receipt of the questionnaire but the difference was only statistically significant in comparison to the three months before the survey (64% v. 62%, p = 0.05). There was little difference in consultation prevalence for musculoskeletal problems immediately after the survey compared to the three control periods. There was an increase of 37% in knee disorder consultations for the three months after the survey compared to the three months directly before the survey (p = 0.02). However, consultation prevalence for knee problems was identical for the three months after the survey to the same time periods in the years prior to and following the survey (both p = 0.94). CONCLUSION:The results from this study suggests that questionnaires related to physical health do not affect the standard consulting behaviour of patients, even for the symptom under investigation. This should reassure researchers who wish to link self-reported health status and medical care utilisation and clinicians whose patients are involved in such research.

背景与目标：

BACKGROUND & AIMS: Epoxyeicosatrienoic acids (EETs) are endothelium-derived arachidonic acid metabolites of cytochrome P450. They dilate coronary arteries, open K+ channels, and hyperpolarize vascular smooth muscles. However, the mechanisms of these smooth muscle actions remain unknown. This study examined the effects of EETs on the large-conductance Ca(2+)-activated K+ channel (KCa) in smooth muscle cells of small bovine coronary arteries. In cell-attached patch-clamp experiments, 11,12-EET produced a 0.5- to 10-fold increase in the activity of the KCa channels when added in concentrations of 1, 10, and 100 nmol/L. In the inside-out excised membrane patch mode, 11,12-EET was without effect on the activity of the KCa channel unless GTP (0.5 mmol/L) or GTP and ATP (1 mmol/L) were added to the bath solution. In the presence of GTP and ATP, the increase in the KCa channel activity with 11,12-EET in inside-out patches was comparable to that in cell-attached patches. This effect of 11,12-EET in inside-out patches was blocked by the addition of GDP-beta-S (100 mumol/L). In outside-out patches, 11,12-EET also increased the KCa channel activity when GTP and ATP were added to the pipette solution. The addition of a specific anti-Gs alpha antibody (100 nmol/L) in the pipette solution completely blocked the activation of the KCa channels induced by 11,12-EET. An anti-G beta gamma or anti-Gi alpha antibody was without effect. We conclude that 11,12-EET activates the KCa channels by a Gs alpha-mediated mechanism. This mechanism contributes to the effects of EETs as endothelium-derived hyperpolarizing factors to hyperpolarize and relax arterial smooth muscle.

背景与目标： 环氧二十碳三烯酸 (EETs) 是细胞色素p450的内皮衍生的花生四烯酸代谢产物。它们扩张冠状动脉，打开K通道，并使血管平滑肌超极化。然而，这些平滑肌作用的机制仍然未知。这项研究检查了EETs对小冠状动脉平滑肌细胞中大电导Ca(2) 激活的K通道 (KCa) 的影响。在细胞附着的膜片钳实验中，当以1、10和100 nmol/L的浓度添加时，11,12-eet使KCa通道的活性增加了0.5至10倍。在由内向外切除的膜贴片模式中，11,12-eet对KCa通道的活性没有影响，除非将GTP (0.5 mmol/L) 或GTP和ATP (1 mmol/L) 添加到浴液中。在存在GTP和ATP的情况下，由内而外的贴片中11,12-eet的KCa通道活性增加与细胞附着的贴片相当。由内而外的贴片中11,12-eet的这种作用被添加GDP-β-S (100 mumol/L) 所阻断。在向外贴剂中，当将GTP和ATP添加到移液器溶液中时，11,12-eet也会增加KCa通道活性。在移液器溶液中添加特异性抗Gs α 抗体 (100 nmol/L) 完全阻断了由11,12-eet诱导的KCa通道的激活。抗G β γ 或抗Gi α 抗体无效。我们得出的结论是，11,12-eet通过Gs α 介导的机制激活了KCa通道。该机制有助于EETs作为内皮衍生的超极化因子，使动脉平滑肌超极化和松弛。

BACKGROUND & AIMS: :Surgically correctable forms of primary aldosteronism are generally held to be less common than forms requiring medical therapy. However, with the availability of improved diagnostic techniques and the adoption of a systematic and thorough diagnostic work-up they can be identified more commonly than expected. Adrenal vein sampling (AVS) for measurement of cortisol and aldosterone has emerged as the 'gold standard' diagnostic test for identifying unilateral causes of primary aldosteronism that are amenable to surgical cure. Adrenalectomy can provide long-term normalisation of blood pressure and correction of primary aldosteronism in about 55% of patients with an aldosterone-producing adenoma and can markedly ameliorate blood pressure control in the rest. This chapter summarises the diagnostic work-up suggested for identifying these forms and examines the other diseases mimicking mineralocorticoid excess that enter into the differential diagnosis of surgically curable primary aldosteronism.

背景与目标： : 手术可纠正的原发性醛固酮增多症的形式通常被认为比需要药物治疗的形式不常见。但是，随着改进的诊断技术的可用性以及系统而彻底的诊断工作的采用，可以比预期的更普遍地识别它们。用于测量皮质醇和醛固酮的肾上腺静脉采样 (AVS) 已成为 “金标准” 诊断测试，用于确定可手术治愈的原发性醛固酮增多症的单侧原因。肾上腺切除术可提供约55% 的产生醛固酮的腺瘤患者的血压长期正常化和原发性醛固酮增多症的纠正，并可显着改善其余患者的血压控制。本章总结了建议用于识别这些形式的诊断工作，并检查了其他模仿盐皮质激素过量的疾病，这些疾病进入了手术可治愈的原发性醛固酮增多症的鉴别诊断疾病。

BACKGROUND & AIMS: :In the present pilot study, the feasibility of a site-of-care cervicovaginal self-sampling methodology for HPV-based screening was tested in 346 women residing in underserved rural areas of Northern Greece. These women provided self-collected cervicovaginal sample along with a study questionnaire. Following molecular testing, using the cobas® HPV Test, Roche®, HPV positive women, were referred to colposcopy and upon abnormal findings, to biopsy and treatment. Participation rate was 100%. Regular pap-test examination was reported for 17.1%. Among hrHPV testing, 11.9% were positive and colposcopy/biopsy revealed 2 CIN3 cases. Non-compliance was the most prevalent reason for no previous attendance. Most women reported non-difficulty and non-discomfort in self-sampling (77.6% and 82.4%, respectively). They would choose self-sampling over clinician-sampling (86.2%), and should self-sampling being available, they would test themselves more regularly (92.3%). In conclusion, self-sampling is feasible and well-accepted for HPV-based screening, and could increase population coverage in underserved areas, helping towards successful prevention.

背景与目标： : 在本试点研究中，对居住在希腊北部服务不足的农村地区的346名妇女进行了基于HPV筛查的护理现场宫颈阴道自采样方法的可行性进行了测试。这些妇女提供了自我收集的宫颈阴道样本以及研究问卷。在分子测试之后，使用cobas®罗氏HPV检测®HPV阳性女性被转诊至阴道镜检查和异常发现后，进行活检和治疗。参与率为100%。报告定期进行17.1% 巴氏试验检查。在hrHPV检测中，11.9% 例为阳性，阴道镜/活检显示2例CIN3。不遵守是以前没有出席的最普遍原因。大多数妇女报告说，自我取样没有困难，也没有不适 (分别为77.6% 和82.4%)。他们将选择自采样而不是临床医生采样 (86.2%)，并且如果自采样可用，他们将更定期地测试自己 (92.3%)。总之，自我采样对于基于HPV的筛查是可行的且被广泛接受，并且可以增加服务不足地区的人口覆盖率，从而有助于成功预防。

BACKGROUND & AIMS: :Genetic factors are important for developing primary and subsequent malignancies in children. This study investigated the role of genetic factors involved in DNA-repair. Designed as a feasibility study, it addressed the possibility of obtaining samples for genetic analyses from former patients through the German Childhood Cancer Registry. Testing feasibility was as important as the biological question itself. We analyzed the expression of DNA-repair genes in untreated primary fibroblasts of 20 individuals with a second neoplasm compared to 20 matched single neoplasm cases using customized cDNA microarrays (1344 gene sequences, about 800 genes). Matching was by first neoplasm, age, and year of first diagnosis. Forty-six percent of the 52 contacted second neoplasm cases and 18% of the 132 single neoplasm patients participated in the study. The DNA-repair gene results show small differences in the basal gene expression of FTH1 and CDKN1A. To our knowledge, this is the first study using gene expression arrays in untreated primary fibroblasts regarding second neoplasms after a childhood neoplasm. We were able to recruit childhood cancer patients for genetic analyses long after diagnosis. The biological importance of the differences in the DNA-repair gene expression has to be elucidated yet.

背景与目标： : 遗传因素对于发展儿童原发性和继发恶性肿瘤很重要。这项研究调查了参与DNA修复的遗传因素的作用。作为一项可行性研究，它解决了通过德国儿童癌症登记处从以前的患者那里获得用于基因分析的样本的可能性。测试可行性与生物学问题本身一样重要。我们使用定制的cDNA微阵列 (1344个基因序列，约800个基因) 分析了20个具有第二个肿瘤的个体的未处理的原代成纤维细胞中DNA修复基因的表达，与20个匹配的单个肿瘤病例相比。根据首次肿瘤，年龄和首次诊断的年份进行匹配。52例接触第二肿瘤病例中的6% 例和132例单一肿瘤患者中的18% 例参加了研究。DNA修复基因结果显示FTH1和CDKN1A的基础基因表达差异很小。据我们所知，这是第一项使用基因表达阵列在未经治疗的原发性成纤维细胞中进行的关于儿童肿瘤后第二次肿瘤的研究。我们能够在诊断后很长时间招募儿童癌症患者进行基因分析。必须阐明DNA修复基因表达差异的生物学重要性。