乙交酯-丙交酯共聚物-细胞复合体移植治疗脊髓损伤

目的:观察神经干细胞、许旺细胞和组织工程支架材料乙交酯-丙交酯共聚物于大鼠髓内共移植后的生物相容性,及其对大鼠损伤脊髓形态和功能的修复作用。方法:实验于2005-05/2006-09在首都医科大学附属北京市神经外科研究所损伤修复实验室完成。①实验材料:健康成年雌性Wistar大鼠36只,随机数字表法分为单纯支架组、神经干细胞 支架复合体组、神经干细胞 许旺细胞 支架复合体组,12只/组。乙交酯-丙交酯共聚物由中科院化学研究所医用高分子材料中心提供。②实验方法:各组大鼠均建立脊髓T9半横断损伤模型。神经干细胞 许旺细胞 支架复合体组取2×1010L-1的许旺细胞、神经干细胞各10μL接种于乙交酯-丙交酯共聚物支架内,神经干细胞 支架复合体组取2×1010L-1的神经干细胞10μL接种于乙交酯-丙交酯共聚物支架内,单纯支架组取10μLDMEM培养液置于乙交酯-丙交酯共聚物支架内,于脊髓缺损处分别植入对应的复合物。③实验评估:应用电镜观察乙交酯-丙交酯共聚物支架的降解及轴突的再生状况;应用BBB评分和电生理技术检测大鼠脊髓功能性的恢复情况。结果:36只Wistar大鼠均进入结果分析。①行为学观察结果:移植术后4,12周,神经干细胞 支架复合体组、神经干细胞 许旺细胞 支架复合体组大鼠的后肢运动功能BBB评分均好于单纯支架组(P<0.01),其中神经干细胞 许旺细胞 支架复合体组尤为明显。②神经电生理检查结果:在脊髓半横断损伤后即刻,所有动物的体感诱发电位和运动诱发电位波幅都明显减低甚至消失。移植术后4周,神经干细胞 支架复合体组、神经干细胞 许旺细胞 支架复合体组大鼠的体感诱发电位和运动诱发电位波幅均有所恢复;至移植术后12周恢复明显。单纯支架组移植术后4,12周体感诱发电位和运动诱发电位波幅无明显变化。③电镜观察结果:扫描电镜下,随着时间的延长各组植入的乙交酯-丙交酯共聚物逐渐降解。透射电镜下,各组植入材料正中横断面可见新生的无髓及有髓神经纤维,至12周时神经干细胞 许旺细胞 支架复合体组最明显。结论:乙交酯-丙交酯共聚物在大鼠损伤的脊髓内具有良好的生物相容性;其与神经干细胞、许旺细胞共移植能够明显促进脊髓半横断损伤大鼠的脊髓轴突再生,并改善肢体的运动功能。     

Relationship between epicardial fat and quantitative coronary artery plaque progression: insights from computer tomography coronary angiography

Epicardial fat volume (EFV) has been suggested to promote atherosclerotic plaque development in coronary arteries, and has been correlated with both coronary stenosis and acute coronary events. Although associated with progression of coronary calcification burden, a relationship with progression of coronary atheroma volume has not been previously tested. We studied patients who had clinically indicated serial 320-row multi-detector computer tomography coronary angiography with a median 25-month interval. EFV was measured at baseline and follow-up. In vessels with coronary stenosis, quantitative analysis was performed to measure atherosclerotic plaque burden, volume and aggregate plaque volume at baseline and follow-up. The study comprised 64 patients (58.4 ± 12.2 years, 27 males, 192 vessels, 193 coronary segments). 79 (41 %) coronary segments had stenosis at baseline. Stenotic segments were associated with greater baseline EFV than those without coronary stenosis (117.4 ± 45.1 vs. 102.3 ± 51.6 cm³, P = 0.046). 46 (24 %) coronary segments displayed either new plaque formation or progression of adjusted plaque burden at follow-up. These were associated with higher baseline EFV than segments without stenosis or those segments that had stenoses that did not progress (128.7 vs. 101.0 vs. 106.7 cm³ respectively, P = 0.006). On multivariate analysis, baseline EFV was the only independent predictor of coronary atherosclerotic plaque progression or new development (P = 0.014). High baseline EFV is associated with the presence of coronary artery stenosis and plaque volume progression. Accumulation of EFV may be implicated in the evolution and progression of coronary atheroma.     

Immunosuppression among HIV‐1‐positive patients attending for care: experience from two large HIV centres in the United Kingdom

Objectives

The aim of the study was to describe the prevalence of and examine the factors associated with immunosuppression (CD4<200 cells/μL) among HIV‐infected patients attending two large inner London treatment centres.

Methods

Patients attending for care who had a CD4 count <200 cells/μL during a 6‐month period (1 January to 30 June 2007) were identified from the UK national CD4 surveillance database. Corresponding case notes were reviewed and factors associated with the most recent immunosuppressive episode examined. Patients either previously had a CD4 count >200 cells/μL at any time under follow‐up which had decreased (group A) or never had a CD4 count >200 cells/μL (group B; late presenters).

Results

Of 4589 patients, 10.2% (467) had at least one CD4 count <200 cells/μL. In group A (60.1% of patients), 70.4% were not receiving antiretroviral therapy (ART) at the time at which the CD4 count fell to <200 cells/μL. Reasons included: treatment interruption (TI; 32.6%), patient declined ART (20.2%), infrequent attendance (19.1%), physician delay in offer (23.1%) and transient CD4 cell count decrease (3.9%). Among those receiving ART, one in three had poor adherence. In group B, 92.3% had started ART after presentation: most had recently started and were responding virologically. AIDS‐defining diagnoses occurred in the year preceding the decrease in CD4 cell count in 12.6% of patients in group A and 33.3% of those in group B.

Conclusion

The majority of patients became immunosuppressed while under care. Our findings suggest that, in addition to strategies aimed at earlier diagnosis, there are further opportunities to reduce severe immunosuppression in patients already attending for HIV care.     

Large femoral bone loss after hip revision using the uncemented proximally porous-coated Bi-Metric prosthesis: 22 hips followed for a mean of 6 years

Background and purpose Periprosthetic bone loss after uncemented femoral hip revision is a matter of concern. We have used a proximally porous- and hydroxyapatite-coated prosthesis (Bi-Metric) in revision since 1989 and now we report the bone changes. This prosthesis is intended to distribute the forces more evenly and to avoid proximal femoral unloading.Methods 22 patients were unilaterally reoperated because of aseptic loosening. Only patients with a healthy contralateral hip were included. Mean age at revision was 69 (55–80) years. Bone defects were graded by Gustilo-Pasternak and Endo-Klinik classifications. Clinical assessment was performed with Harris hip score. We used radiographs and dual-energy X-ray absorptiometry to evaluate migration, femoral remodeling, and bone mineral density after 72 (30–158) months.Results The mean Harris hip score was 74 (30–100) points at follow-up. Mild thigh discomfort was present in 1 patient and moderate thigh pain in 3 patients. There was no loosening or subsidence. Osteolysis seen at revision had diminished in 19 of the 22 hips at follow-up. We noted a large reduction in bone mineral density. It was most pronounced in Gruen regions 1, 2, 6, and 7.Interpretation Revision with this stem is a reliable procedure; however, we noted a large degree of proximal bone loss that could lead to later mechanical complications or fractures.     

Activity of aspirin analogues and vanillin in a human colorectal cancer cell line

Colorectal cancer is the third most common cancer and is associated with significant morbidity and mortality. Epidemiological and animal studies indicate that regular acetylsalicylic acid (aspirin) intake is associated with a reduction in the incidence of colorectal cancer. Acetylsalicylic acid (ASA) has also been shown to inhibit colorectal cancer cell proliferation in?vitro. The molecular basis for this specific cytotoxicity is an area of considerable debate. To investigate the toxicity of salicylates, the sensitivity of the DNA mismatch repair proficient SW480 human colorectal cancer cell line to four categories of compounds with varying degrees of structural similarity to acetylsalicylic acid was tested. These compounds were: i) salicylic acid analogues with substituents at the 5-position; ii) ASA analogues with extended chain lengths in the acyl group; iii) vanillin (4-hydroxy-3-methoxybenzaldehyde; and iv) bis(2-carboxyphenyl) succinate (BCS) and structurally similar derivatives thereof. It was found that compounds with amino and acetamido substituents at the salicylate 5-position were less toxic than ASA itself. Modifications to the length of the hydrocarbon chain in the acyl groups of ASA analogues also marginally reduced toxicity. Vanillin exhibited relatively limited toxicity against the SW480 colorectal cancer cell line. Commercially available and in-house synthesised BCS (diaspirin) were notably more inhibitory to cell growth than ASA itself, yet retained substantial specificity against colorectal cancer cell lines vs. non-colorectal cancer cell lines. BCS and ASA were toxic to SW480 cells through initiation of necrotic and apoptotic pathways. Fumaroyldiaspirin and benzoylaspirin exhibited greater toxicity than ASA against the SW480 cell line. A novel method for synthesis of BCS, a compound that has erratic commercial availability, is described. We propose that the anti-inflammatory and anticancer capacity of BCS and the other analogues described herein is worthy of investigation.     

Injection drug use among street-involved youth in a Canadian setting

Background  

Street-involved youth contend with an array of health and social challenges, including elevated rates of blood-borne infections and mortality. In addition, there has been growing concern regarding high-risk drug use among street-involved youth, in particular injection drug use. We undertook this study to examine the prevalence of injection drug use and associated risks among street-involved youth in Vancouver, Canada.     

Unstable housing and hepatitis C incidence among injection drug users in a Canadian setting

Background  

There has emerged growing recognition of the link between housing and health. Since Vancouver, Canada has had increasing concerns with homelessness brought about by urban renewal in the lead-up to the 2010 Winter Olympic Games, we evaluated hepatitis C virus (HCV) incidence among injection drug users (IDU) with and without stable housing.     

Needle guide in shoulder arthroscopy – a technique

Distension of joint with fluid is often used to facilitate insertion of arthroscope. This may prove difficult at times in the shoulder joint, as unlike the knee, it is deeply situated, making extravasation of fluid outside the capsule, a common occurrence. This is especially true in very tight joints and is often a problem for beginners. We describe here a very effective and simple technique where a needle is used to distend the shoulder before the insertion of the arthroscope.