BACKGROUND & AIMS: The analysis of brain extracellular fluid can provide essential information about both the physiology and the pathology of the human nervous system. The introduction of microdialysis into the clinical sciences has provided a new opportunity to study this environment. Using microdialysis, endogenous substances can be obtained and drugs can be delivered in very close proximity to the receptors and ion channels on neuronal membranes. In this sense, microdialysis can be regarded as a novel technique since it can continuously measure interstitial brain activity in living tissue while causing minimal adverse effects. Although it has been well established as an experimental technique for neurochemistry, the true utility of microdialysis as a clinical tool is still being defined. The potential clinical applications of microdialysis to characterize the human brain extracellular environment in patients with pathologic conditions has grown rapidly. The number of publications in which microdialysis has been performed in clinical studies has been increasing during recent years and this article gives a summary of those reports where microdialysis was applied in the study of human brain disorders.

背景与目标： 脑细胞外液的分析可以提供有关人类神经系统的生理和病理的基本信息。将微透析引入临床科学为研究这种环境提供了新的机会。使用微透析，可以获得内源性物质，并且可以非常靠近神经元膜上的受体和离子通道递送药物。从这个意义上讲，微透析可以被视为一种新技术，因为它可以连续测量活体组织中的间质脑活动，同时引起最小的不良影响。尽管它已被确立为神经化学的实验技术，但微透析作为临床工具的真正用途仍在定义中。微透析在病理条件下表征人脑细胞外环境的潜在临床应用已迅速发展。近年来，在临床研究中进行微透析的出版物数量一直在增加，本文总结了将微透析应用于人脑疾病研究的报道。

BACKGROUND & AIMS: Levodopa-induced psychosis can complicate the treatment of Parkinson's disease (PD). In this retrospective, uncontrolled report, we describe our experience treating PD-related psychosis with clozapine, emphasizing those patients treated for longer than 1 year. Twenty-seven patients were treated, 14 for longer than 1 year. Most patients showed a rapid improvement from baseline within 1 month using the Clinical Global Impression and Global Psychosis Rating Scores. Five patients discontinued the drug due to side effects, but only two patients reported side effects after 6 months of treatment. Clozapine appears to be effective in treating PD related psychotic symptoms while not interfering with motor function.

背景与目标： 左旋多巴引起的精神病会使帕金森氏病 (PD) 的治疗复杂化。在这份回顾性，不受控制的报告中，我们描述了我们用氯氮平治疗PD相关精神病的经验，强调了那些治疗时间超过1年的患者。27例患者接受了治疗，其中14例超过1年。使用临床总体印象和总体精神病评分，大多数患者在1个月内从基线显示出快速改善。五名患者因副作用而停药，但只有两名患者在治疗6个月后报告副作用。氯氮平似乎可有效治疗PD相关的精神病性症状，同时不干扰运动功能。

BACKGROUND & AIMS: OBJECTIVE:To review the data on the efficacy of oxcarbazepine (OXC) in bipolar disorder (BD) and to provide recommendations for clinicians on the use of this medication in treating BD. METHOD:Using the terms oxcarbazepine and bipolar disorder, oxcarbazepine and mania, or oxcarbazepine and bipolar depression, we conducted a computer-aided search of MEDLINE for the years 1950 to 2005. RESULTS:Case reports, retrospective chart reviews, open prospective studies, and double-blind studies reported the efficacy and effectiveness of OXC in treating BD. The data indicate that OXC has efficacy in treating acute mania and may be a useful add-on in treating acute bipolar depression and in BD prophylaxis. OXC is generally well-tolerated. CONCLUSION:We recommend using OXC as monotherapy or as add-on therapy in refractory mania, but we recommend it be used predominantly as an add-on treatment for other phases of BD in patients who have not improved with well-established treatments or in patients who have difficulty tolerating adequate dosages.

背景与目标：

BACKGROUND & AIMS: Marked increases in case rates of drug-resistant tuberculosis and nontuberculous mycobacterial infections have brought renewed urgency to the development of new treatment regimens for mycobacterial infections. Preclinical data, such as in vitro measures of drug activity and pharmacokinetics, are used in the design of new treatment regimens. This review surveys the extensive published clinical experience concerning the treatment of drug-susceptible tuberculosis to evaluate the use of these preclinical measures in predicting clinical outcomes of antimycobacterial therapy. In vitro measures of drug activity predict the potency of a drug to prevent the emergence of resistance to other antimycobacterial drugs but do not predict the sterilizing activity of a drug or the activity of drug combinations. In vitro measures of drug activity do not allow reliable predictions of the level at which an organism should be considered resistant. Assays of drug penetration in tissues and activity against intracellular bacilli add modestly to the predictive value of in vitro measures of drug activity but still do not predict sterilizing activity. In contrast, animal models of tuberculosis have predicted relative drug potency (including sterilizing activity), the efficacy of multidrug regimens, and the duration of therapy needed. Despite pharmacokinetic parameters that would suggest the need for multiple doses per day, all of the first-line antituberculous drugs are active when given as infrequently as twice weekly. It is difficult to predict the efficacy of therapy for an intracellular pathogen that has the capacity for dormancy. Better in vitro models are needed, particularly ones that predict sterilizing activity.

背景与目标： 耐药结核病和非结核分枝杆菌感染的病例率显着增加，为开发新的分枝杆菌感染治疗方案带来了新的紧迫性。临床前数据，例如药物活性和药代动力学的体外测量，用于设计新的治疗方案。这篇综述调查了有关药物敏感结核病治疗的广泛已发表的临床经验，以评估这些临床前措施在预测抗细菌治疗临床结果中的应用。药物活性的体外测量可以预测药物的效力，以防止对其他抗细菌药物的耐药性出现，但不能预测药物的灭菌活性或药物组合的活性。药物活性的体外测量无法可靠地预测生物体应被认为具有抗性的水平。药物在组织中的渗透和对细胞内杆菌的活性的测定适度增加了药物活性的体外测量的预测值，但仍不能预测灭菌活性。相反，结核病的动物模型已经预测了相对的药物效力 (包括灭菌活性)，多药疗法的功效以及所需的治疗持续时间。尽管药代动力学参数表明每天需要多次剂量，但所有一线抗结核药物在每周两次的情况下均具有活性。很难预测具有休眠能力的细胞内病原体的治疗效果。需要更好的体外模型，尤其是可以预测灭菌活性的模型。

BACKGROUND & AIMS: INTRODUCTION:Ethics committees are a necessary resource to guarantee ethical integrity in human research; they must apply international standards in their ethical evaluation of research projects involving human subjects. OBJECTIVE:The ethics committees for human research of Colombia were characterized, and recommendations for strengthening them were formulated. MATERIALS AND METHODS:In 2003, 280 groups with research projects involving human subjects were selected from a list of research groups which form part of the science and technology network of Colciencias. (Colciencias is the Colombian national agency that promotes and funds science and technology.) Eighty percent (224) of the projects were associated with 40 institutions, consisting of universities, hospitals, and public or private research centers. Thirty of these institutions had at least one ethics committee for evaluating use of human subjects. A questionnaire was mailed to each of these Committees, requesting information concerning its their compostition, regulations, multidisciplinarity, plurality, representativity and independence. The World Health Organization's Operational Guidelines for Ethic Committees that Evaluate Biomedical Research (TDR/PRD/ETHICS/2000) was used as reference for the analysis. In 5 of the cities, supplemental information was obtained by direct discussions with members of the ethics committees. RESULTS:Twenty-six committees responded to the questionnaire. The results indicated that 47% of the committee members were physicians, but only 23% of the committees had representatives from the community. In 60% of the Committees, members were not independent from the organization in which it was based. Seventy percent had established operating procedures. Lack of national regulations and limited education in research ethics were mentioned as the main drawbacks in providing effective guidance. CONCLUSIONS:These observations led to the conclusion that national guidelines must be established for ethics committees that correspond to international standards. Committee members must be trained before accepting committee responsibilities. Finally, new committees must be created along with the improvement of the currently existing committees for reinforcing and promoting the importance of ethical integrity in research.

背景与目标：

BACKGROUND & AIMS: AIM:This paper reviews how the interpreter's role is described in empirically based, qualitative cross-cultural interview studies and how trustworthiness is determined. BACKGROUND:Increased immigration during the past decades has created a multiethnic society in many countries. This development poses a challenge to healthcare staff, in that they need to understand how people from different cultures experience health and illness. One way to assess immigrants' experiences is through cross-cultural interview studies, involving an interpreter. Thorough knowledge of the interpreter's role is needed in order to increase the trustworthiness of this kind of nursing research. METHOD:Literature searches were conducted from October to November 2004 using PubMed, CINAHL, Psycinfo, Sociological abstract, Your Journals@ovid, and Eric databases. Qualitative interview studies written in English and performed with an interpreter were included. The Matrix Method was used to review the literature. FINDINGS:In almost all of the 13 relevant papers found, the role of the interpreter(s) in the research process was only sparsely described. In addition, all studies except one employed different techniques to established trustworthiness. The most common techniques were prolonged engagement, member check or triangulation, the latter performed either on the data, investigators or methods. CONCLUSION:Methodological issues with respect to interpreters have received only limited attention in cross-cultural interview studies. Researchers in the field of nursing need to consider (1) the interpreter's role/involvement in the research process; (2) the interpreter's competence and the style of interpreting; (3) the interpreter's impact on the findings. This information is a prerequisite when trying to determine the trustworthiness of a cross-cultural study.

背景与目标：

BACKGROUND & AIMS: :There is strong evidence for an association between overgrowth disorders such as Beckwith-Wiedemann syndrome and the development of neoplasia. An increased cancer risk has also been observed in individuals with isolated hemihyperplasia. We critically review the evidence for tumour surveillance in Beckwith-Wiedemann syndrome and isolated hemihyperplasia and suggest local practice guidelines.

背景与目标： : 有强有力的证据表明，Beckwith-Wiedemann综合征等过度生长性疾病与肿瘤的发展之间存在关联。在孤立的半增生个体中也观察到癌症风险增加。我们严格审查了Beckwith-Wiedemann综合征和孤立性半增生中肿瘤监测的证据，并提出了当地实践指南。

BACKGROUND & AIMS: :The course of untreated localized prostate cancer after 10 years of follow-up is at large unknown. As curative treatment is usually only offered patients with a life expectancy exceeding 10 Years, the expected course of the disease if left untreated is of the utmost interest. This paper aims to describe the outcome for patients who survive for more than 10 years when treated without curative intent. The results indicate that cancer specific mortality in patients with localized prostate cancer increases steadily over time and is approximately 50% after 15 years. This is a much higher figure than in reported series on radical prostatectomy. Even if many deaths occur at an old age, prostate cancer death is shown to be associated with a significant morbidity, need for palliative treatment, hospital care and cost. Preventing prostate cancer death is therefore not only a matter of saving year of life but also to prevent suffering caused by the disease. Modern diagnostic tools, such as prostate specific antigen, seem to detect clinically significant cancers in the vast majority of patients. Over diagnosis seems to be uncommon if diagnostic procedures are restricted to patients with a long life expectancy. Localized prostate cancer is a slow-growing but progressive neoplastic disease. When diagnosed in a man with a longer life expectancy it should be handled as such.

背景与目标： : 经过10年的随访，未经治疗的局部前列腺癌的病程尚不清楚。由于通常只为预期寿命超过10年的患者提供治愈性治疗，因此，如果不及时治疗，该疾病的预期病程是最大的利益。本文旨在描述无治疗意图治疗后存活10年以上的患者的结果。结果表明，局部前列腺癌患者的癌症特异性死亡率随着时间的推移而稳定增加，并且在15年后约为50%。这比报道的根治性前列腺切除术系列要高得多。即使许多死亡发生在老年，前列腺癌的死亡也被证明与显着的发病率，姑息治疗的需求，医院护理和费用有关。因此，预防前列腺癌死亡不仅是挽救生命的问题，而且还可以防止疾病造成的痛苦。现代诊断工具 (例如前列腺特异性抗原) 似乎可以在绝大多数患者中检测到临床上重要的癌症。如果诊断程序仅限于预期寿命长的患者，则过度诊断似乎并不常见。局限性前列腺癌是一种生长缓慢但进行性的肿瘤性疾病。当被诊断为预期寿命较长的男性时，应该这样处理。

BACKGROUND & AIMS: :Malignant transformation of synovial chondromatosis into chondrosarcoma is unusual. Thirteen cases and one series have been reported; only four of them developed in the hip. The overall survival is about 50%, possibly because of the difficulty of arriving at a correct early diagnosis (radiographically and histologically) and subsequent adequate surgical therapy. We report two patients (ages 30 and 50 years) in whom synovial chondrosarcoma developed in previously excised synovial chondromatosis of the hip. The diagnosis was made with modern imaging techniques (computed tomography and magnetic resonance imaging) and verified by open biopsy. The early recognition allowed a wide limb-saving resection; both patients are disease free 3 and 2 years after surgery.

背景与目标： : 滑膜软骨瘤病向软骨肉瘤的恶性转化是不常见的。已报告了13例和一系列; 其中只有四例在臀部发育。总生存率约为50%，可能是因为难以获得正确的早期诊断 (放射学和组织学) 以及随后的适当手术治疗。我们报告了两名患者 (年龄分别为30岁和50岁)，其中滑膜软骨肉瘤是在先前切除的髋关节滑膜软骨瘤中发展的。诊断是通过现代成像技术 (计算机断层扫描和磁共振成像) 进行的，并通过开放活检进行了验证。早期识别允许广泛的肢体切除; 两名患者在手术后3年和2年均无病。

BACKGROUND & AIMS: :The materials that have been reported as causing allergic contact dermatitis within spectacle frames are identified, and their most likely location on the frame is highlighted. The lack of any real control over spectacle frame quality and content is indicated to be a problem, as is the difficulty in determining the true source of many frames. Much of the information must be obtained from anonymous sources in the industry, historical 'common knowledge' of indeterminate source or reports of dermatological problems.

背景与目标： : 确定了已报告在眼镜架内引起过敏性接触性皮炎的材料，并突出显示了它们在镜架上的最可能位置。缺乏对眼镜架质量和内容的真正控制是一个问题，确定许多镜架的真正来源也是一个困难。许多信息必须从行业中的匿名来源，不确定来源的历史 “常识” 或皮肤病学问题报告中获得。

BACKGROUND & AIMS: :Women of African descent have a lower incidence of breast cancer than their white counterparts; however, the overall age-adjusted breast cancer mortality rates are higher. They also present at a younger age, and have more advanced disease that exhibits poor prognostic features including significantly larger tumors of higher grade, higher rates of estrogen receptor and progesterone receptor negativity and a higher rate of p53 mutations and HRAS1 proto-oncogene expression, all of which confer a poor prognosis. While there are many possible contributory factors to the discrepancies in outcome in women of African descent, there is no satisfactory explanation as to why women of African origin tend to present at a younger age with hormone receptor-negative tumors and more adverse prognostic features.

背景与目标： : 非洲裔妇女的乳腺癌发病率低于白人妇女; 然而，总体年龄调整后的乳腺癌死亡率较高。他们的年龄也较小，并且患有更晚期的疾病，表现出较差的预后特征，包括较高级别的明显更大的肿瘤，较高的雌激素受体和孕激素受体阴性率以及较高的p53突变和HRAS1原癌基因表达率，所有这些都导致不良的预后。尽管有许多可能导致非洲裔妇女结局差异的因素，但对于为什么非洲裔妇女倾向于在年轻时出现激素受体阴性肿瘤和更多不良预后特征，尚无令人满意的解释。

BACKGROUND & AIMS: :The loss and fragmentation of natural habitats by human activities are pervasive phenomena in terrestrial ecosystems across the Earth and the main driving forces behind current biodiversity loss. Animal-mediated pollination is a key process for the sexual reproduction of most extant flowering plants, and the one most consistently studied in the context of habitat fragmentation. By means of a meta-analysis we quantitatively reviewed the results from independent fragmentation studies throughout the last two decades, with the aim of testing whether pollination and reproduction of plant species may be differentially susceptible to habitat fragmentation depending on certain reproductive traits that typify the relationship with and the degree of dependence on their pollinators. We found an overall large and negative effect of fragmentation on pollination and on plant reproduction. The compatibility system of plants, which reflects the degree of dependence on pollinator mutualism, was the only reproductive trait that explained the differences among the species' effect sizes. Furthermore, a highly significant correlation between the effect sizes of fragmentation on pollination and reproductive success suggests that the most proximate cause of reproductive impairment in fragmented habitats may be pollination limitation. We discuss the conservation implications of these findings and give some suggestions for future research into this area.

背景与目标： : 人类活动造成的自然栖息地的丧失和破碎是地球上陆地生态系统中普遍存在的现象，也是当前生物多样性丧失的主要驱动力。动物介导的授粉是大多数现存开花植物有性繁殖的关键过程，也是在栖息地破碎化的背景下研究最一致的过程。通过荟萃分析，我们定量回顾了过去二十年来独立破碎化研究的结果，目的是测试植物物种的授粉和繁殖是否可能对栖息地破碎化有不同的敏感性，这取决于某些生殖特征，这些特征代表了与传粉者的关系和对传粉者的依赖程度。我们发现碎片化对授粉和植物繁殖的总体影响很大。植物的相容性系统反映了对传粉媒介互惠关系的依赖程度，是解释物种效应大小差异的唯一繁殖性状。此外，碎片化对授粉的影响大小与生殖成功之间的高度显着相关性表明，碎片化生境中生殖障碍的最直接原因可能是授粉限制。我们讨论了这些发现的保护意义，并为该领域的未来研究提供了一些建议。

BACKGROUND & AIMS: PROBLEM:Lymphocyte immunotherapy (LIT) is applied in infertility treatment. Moreover, it has been suggested for prevention of rhesus D-hemolytic disease and as a vaccine for reduction of human immunodeficiency virus-1 susceptibility. Although transfusion-related problems have been rarely reported they were a matter of debate. Here we discuss extensive single-center experience with intradermal LIT for implantation failure and recurrent miscarriages. METHOD OF STUDY:Retrospective 2- to 3-year follow-up of in vitro fertilization couples treated during 1996-2002 (feedback 2,848/3,041 = 93%), registering 930 deliveries. Prospective survey for acute reactions for 2000-2003 (feedback 2,687/3,246 = 83%). Review of the literature. RESULTS:Infections of the patient and transplant rejection later in life are minor residual risks. Post-transfusion purpura was suspected once but not verified. Anaphylaxis or malignancy were not promoted. Fetal/newborn alloimmune disease (severe hemolytic disease, thrombocytopenia, neutropenia) were not observed. CONCLUSION:Based on microbiological, immunological, and hematological testing the risks of intradermal LIT are low.

背景与目标：

BACKGROUND & AIMS: The sonographic features of 22 patients with histologically benign intraductal papillomas are presented, with clinical, mammographic, galactographic, and histopathologic correlation. The most common presenting feature in this series is a palpable central breast mass in an elderly woman. Sonography was abnormal in all 22 patients. The typical sonographic features include a well-defined, smooth-walled, solid, hypoechoic nodule or a lobulated, smooth-walled, cystic lesion with solid components. Dilated ducts are a common feature, often with visible solid intraluminal echoes. These findings suggest the diagnosis of an intraductal papilloma. The differential diagnosis includes fibroadenoma and phyllodes tumor (for large solid lesions) and intracystic carcinoma (for complex cystic lesions). Mammograms are frequently normal (36% of patients). When abnormal, the mammographic features are of a smooth-walled, well-defined mass or increased retroareolar opacity. Contrary to the reported literature, calcification was seen infrequently. We conclude that ultrasonography is useful in the detection and delineation of intraductal papillomas.

背景与目标： 介绍了22例组织学良性导管内乳头状瘤患者的超声特征，并具有临床，乳房x线，乳腺造影和组织病理学相关性。这个系列中最常见的表现特征是一名老年妇女明显的中央乳房肿块。所有22例患者的超声检查均异常。典型的超声特征包括明确的，光滑壁的，固体的，低回声结节或带有固体成分的分叶状，光滑壁的囊性病变。扩张的导管是一个常见的特征，通常具有可见的管腔内固体回声。这些发现提示诊断为导管内乳头状瘤。鉴别诊断疾病包括纤维腺瘤和叶状肿瘤 (用于大的实体病变) 和囊内癌 (用于复杂的囊性病变)。乳房x线照片通常是正常的 (36% 的患者)。异常时，乳房x线照片特征为光滑壁，清晰的肿块或乳晕后混浊增加。与报道的文献相反，钙化很少出现。我们得出的结论是，超声检查可用于检测和描绘导管内乳头状瘤。

BACKGROUND & AIMS: :Debt among Canadian university graduates is increasing, while money apportioned to federal and provincial needs-based student assistance programs has been decreasing since the 1990s. Dental students have had to absorb increased tuition fees at both the undergraduate and post-baccalaureate levels. Existing debt and high tuition fees may adversely influence a potential candidate"s decision to enroll in dental school. Likewise, debt incurred during the minimum 2 years of pre-dental education adds to the future debt load of dental graduates. It seems that few dental students can remain debt-free during their dental education, although data are lacking about the extent of debt among dental students and its impact on their career decisions. Government statistics focus primarily on tuition costs for baccalaureate-degree students. Tuition and clinic-related fees constitute a significant proportion of costs for dental students; moreover, university administrations perceive dentistry as an expensive curriculum. This first article of a 4-part series examines debt among dental students, both nationally and internationally.

背景与目标： : 自20世纪90年代以来，加拿大大学毕业生的债务正在增加，而分配给联邦和省级基于需求的学生援助计划的资金却在减少。牙科学生不得不在本科和学士学位后水平上吸收增加的学费。现有的债务和高昂的学费可能会对潜在候选人就读牙科学校的决定产生不利影响。同样，在至少2年的牙科前教育期间产生的债务增加了牙科毕业生未来的债务负担。尽管缺乏有关牙科学生的债务程度及其对职业决定的影响的数据，但似乎很少有牙科学生在牙科教育期间能够保持无债务状态。政府统计数据主要集中在学士学位学生的学费上。学费和诊所相关费用占牙科学生费用的很大一部分; 此外，大学管理部门认为牙科是一项昂贵的课程。由4部分组成的系列文章的第一篇文章研究了国内外牙科学生的债务。