60Coγ射线局部辐射后小鼠非辐射区域骨髓巨核细胞的变化

目的:临床局部辐射条件下会造成非辐射区域组织及细胞功能损害,最为突出的是对造血功能的影响。实验建立60Coγ射线左半身辐射动物模型,观察局部电离辐射对其非辐射区域骨髓巨核细胞的影响。方法:实验于2003-10/2005-03在解放军第三军医大学辐照中心和全军复合伤研究所完成。①实验动物:6～8周龄SPF级雄性昆明小鼠180只,随机数字表法分为正常对照组、全身辐射组、左半身辐射组、全身屏蔽辐射组,45只/组。②实验方法:全身辐射组小鼠固定于辐射架内;左半身辐射组小鼠麻醉后固定体位,用铅砖屏蔽右半身;全身屏蔽辐射组小鼠麻醉固定体位,用铅砖屏蔽全身。以60Coγ射线一次性辐射,剂量率68.46cGy/min。正常对照组不作任何干预。③实验评估:辐射后不同时相检测小鼠血清丙二醛含量及超氧化物歧化酶活性变化,计数外周血血小板,检测骨髓巨核祖细胞集落形成单位,观察骨髓组织病理改变及CD41a、CD61的表达。结果:全身辐射组第8天死亡2只,第9天死亡4只,其余各组无脱失。①外周血血小板计数:辐射后第2,7天,左半身辐射组外周血血小板数量显著低于正常对照组(P<0.01),但高于全身辐射组(P<0.01)。②血清丙二醛含量及超氧化物歧化酶活性变化:辐射后第2,9天,左半身辐射组血清丙二醛含量显著高于正常对照组(P<0.01),低于全身辐射组(P<0.01);血清超氧化物歧化酶活性显著低于正常对照组(P<0.01),高于全身辐射组(P<0.01)。③骨髓巨核祖细胞集落形成单位的变化:与正常对照组比较,辐射后6h左半身辐射组非辐射侧的巨核祖细胞集落形成单位显著降低(P<0.01),高于全身辐射组及左半身辐射组(P<0.01)。④骨髓组织病理改变:正常对照组有核细胞比例较高,分布均匀,并见多量散在分布的细胞龛;辐射2d后,左半身辐射组非辐射侧骨髓有核细胞较正常对照组减少,但好于全身辐射组、左半身辐射组。⑤骨髓CD41a及CD61表达的变化:辐射后2d与正常对照组比较,左半身辐射组非辐射侧骨髓CD41a及CD61阳性细胞数和相对荧光强度均显著降低(P<0.01),但高于全身辐射组、左半身辐射组(P<0.01)。结论:局部电离辐射作用后,可导致小鼠非辐射区域骨髓巨核细胞增殖能力降低,血小板减少,产生功能障碍。氧自由基激活可能参与了该损伤过程。     

A crucial role for TNF-α in mediating neutrophil influx induced by endogenously generated or exogenous chemokines,KC/CXCL1 and LIX/CXCL5

Background and purpose:

Chemokines orchestrate neutrophil recruitment to inflammatory foci. In the present study, we evaluated the participation of three chemokines, KC/CXCL1, MIP-2/CXCL2 and LIX/CXCL5, which are ligands for chemokine receptor 2 (CXCR2), in mediating neutrophil recruitment in immune inflammation induced by antigen in immunized mice.

Experimental approach:

Neutrophil recruitment was assessed in immunized mice challenged with methylated bovine serum albumin, KC/CXCL1, LIX/CXCL5 or tumour necrosis factor (TNF)-α. Cytokine and chemokine levels were determined in peritoneal exudates and in supernatants of macrophages and mast cells by elisa. CXCR2 and intercellular adhesion molecule 1 (ICAM-1) expression was determined using immunohistochemistry and confocal microscopy.

Key results:

Antigen challenge induced dose- and time-dependent neutrophil recruitment and production of KC/CXCL1, LIX/CXCL5 and TNF-α, but not MIP-2/CXCL2, in peritoneal exudates. Neutrophil recruitment was inhibited by treatment with reparixin (CXCR1/2 antagonist), anti-KC/CXCL1, anti-LIX/CXCL5 or anti-TNF-α antibodies and in tumour necrosis factor receptor 1-deficient mice. Intraperitoneal injection of KC/CXCL1 and LIX/CXCL5 induced dose- and time-dependent neutrophil recruitment and TNF-α production, which were inhibited by reparixin or anti-TNF-α treatment. Macrophages and mast cells expressed CXCR2 receptors. Increased macrophage numbers enhanced, while cromolyn sodium (mast cell stabilizer) diminished, LIX/CXCL5-induced neutrophil recruitment. Macrophages and mast cells from immunized mice produced TNF-α upon LIX/CXCL5 stimulation. Methylated bovine serum albumin induced expression of ICAM-1 on mesenteric vascular endothelium, which was inhibited by anti-TNF-α or anti-LIX/CXCL5.

Conclusion and implications:

Following antigen challenge, CXCR2 ligands are produced and act on macrophages and mast cells triggering the production of TNF-α, which synergistically contribute to neutrophil recruitment through induction of the expression of ICAM-1.     

Noninsertional Achilles tendinopathy: Pathology and management

Many patients present to their physician's office with the chief complaint of pain at the Achilles tendon. This review discusses the pathology, diagnosis, and treatment of Achilles tendinopathy. Achilles tendinopathy is generally caused by chronic stress to the tendon, leading to a defective arrangement of collagen fibers in the Achilles tendon. This then results in pain and limited function. Ultrasound imaging can help identify the abnormal portion of the tendon. Various treatments are available for Achilles tendinopathy, the most current of which are discussed in this article. Appropriate treatment can potentially lead to a full recovery.     

Community-Based Services for Homeless Adults Experiencing Concurrent Mental Health and Substance Use Disorders: A Realist Approach to Synthesizing Evidence

Consultations with community-based service providers in Toronto identified a lack of strong research evidence about successful community-based interventions that address the needs of homeless clients experiencing concurrent mental health and substance use disorders. We undertook a collaborative research effort between academic-based and community-based partners to conduct a systematic evidence synthesis drawing heavily from Pawson’s realist review methodology to focus on both whether programs are successful and why and how they lead to improved outcomes. We examined scholarly and nonscholarly literature to explore program approaches and program elements that lead to improvements in mental health and substance use disorders among homeless individuals with concurrent disorders (CD). Information related to program contexts, elements, and successes and failures were extracted and further supplemented by key informant interviews and author communication regarding reviewed published studies. From the ten programs that we reviewed, we identified six important and promising program strategies that reduce mental health and, to a far lesser degree, substance use problems: client choice in treatment decision-making, positive interpersonal relationships between client and provider, assertive community treatment approaches, providing supportive housing, providing supports for instrumental needs, and nonrestrictive program approaches. These promising program strategies function, in part, by promoting and supporting autonomy among homeless adults experiencing CD. Our realist informed review is a useful methodology for synthesizing complex programming information on community-based interventions.     

Frozen Section Analysis for Intraoperative Margin Assessment During Breast-Conserving Surgery Results in Low Rates of Re-excision and Local Recurrence

Background Negative surgical margins minimize the risk of local recurrence after breast-conserving surgery. Intraoperative frozen section analysis (FSA) is one method for margin evaluation. We retrospectively analyzed records of patients who received breast-conserving therapy with intraoperative FSA of the lumpectomy cavity to assess re-excision rates and local control. Methods Records were retrospectively reviewed for individuals who underwent breast-conserving surgery for ductal carcinoma in situ (DCIS) or invasive carcinoma between 1993 and 2003. Inclusion criteria were a minimum of 2 years follow-up and intact tumor at the time of operation. The major outcome measure was local recurrence. The Kaplan-Meier test was used to evaluate local recurrence rates between groups. Results 290 subjects with an average age of 57.2 years (range 27–89) underwent 292 lumpectomies with FSA. 11.3% had DCIS, 73.3% had infiltrating ductal, 5.8% had infiltrating lobular, and 9.6% exhibited other forms of invasive carcinoma. 70 subjects underwent additional resection at the time of breast surgery, 16 underwent subsequent re-excision, and 17 underwent subsequent mastectomy. At a median follow-up of 53.4 months (range 5.8–137.8), there were six local recurrences (2.74%) in patients who had breast-conserving procedures and two local recurrences in patients who underwent mastectomy. There were no statistically significant associations among local recurrence rate, tumor size, nodal status, or overall stage. Local recurrences were higher in patients with DCIS compared with invasive carcinoma, and tumors >2cm. Conclusions Intraoperative FSA allows resection of suspicious or positive margins at the time of lumpectomy and results in low rates of local recurrence and re-excision. The low local recurrence rate reported here is comparable to those reported with other margin assessment techniques.     

Critical Care of Nursing in Nebraska

(Ed. note) The University of Nebraska School of Nursing has two campuses: one, the Medical Center in Omaha; the other, the Lincoln Division campus, an hour or so away. The worsening economy of Nebraska agriculture forced the State to examine its expenses, and the Chancellor proposed elimination of the Lincoln nursing program. The Regents voted not to close it. The details of the issues and the concepts of strategy and negotiation used by the College of Nursing to effect this change of policy will be published in Nursing and Health Care in articles by the Dean, Rosalee Yeaworth, and the then Associate Dean, Nancy Langs ton. In an unusual editorial collaboration, IMAGE presents the rest of the story in this piece by the faculty and students—the "grassroots."     

一阶导数差示脉冲极谱法的建立及在药物分析中的应用

本文研究了一阶导数差示脉冲极谱法,并将其运用于扑尔敏、氟哌啶醇、维生素B₆及其制剂的定量分析中。方法简便、快速、灵敏、结果准确。