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。     

Evaluation of ABM/P-15 versus autogenous bone in an ovine lumbar interbody fusion model

A prospective, randomized study was performed in an ovine model to compare the efficacy of an anorganic bovine-derived hydroxyapatite matrix combined with a synthetic 15 amino acid residue (ABM/P-15) in facilitating lumbar interbody fusion when compared with autogenous bone harvested from the iliac crest. P-15 is a biomimetic to the cell-binding site of Type-I collagen for bone-forming cells. When combined with ABM, it creates the necessary scaffold to initiate cell invasion, binding, and subsequent osteogenesis. In this study, six adult ewes underwent anterior-lateral interbody fusion at L3/L4 and L4/L5 using PEEK interbody rings filled with autogenous bone at one level and ABM/P-15 at the other level and no additional instrumentation. Clinical CT scans were obtained at 3 and 6 months; micro-CT scans and histomorphometry analyses were performed after euthanization at 6 months. Clinical CT scan analysis showed that all autograft and ABM/P-15 treated levels had radiographically fused outside of the rings at the 3-month study time point. Although the clinical CT scans of the autograft treatment group showed significantly better fusion within the PEEK rings than ABM/P-15 at 3 months, micro-CT scans, clinical CT scans, and histomorphometric analyses showed there were no statistical differences between the two treatment groups at 6 months. Thus, ABM/P-15 was as successful as autogenous bone graft in producing lumbar spinal fusion in an ovine model, and it should be further evaluated in clinical studies.     

Clinical and radiological outcomes of axial lumbar interbody fusion

Axial lumbar interbody fusion is a novel percutaneous alternative to common open techniques, such as anterior, posterior, and transforaminal lumbar interbody fusion. This minimally invasive technique uses the presacral space to access the L5-S1 and L4-L5 disk space. The goal of this study was to examine outcomes following axial lumbar interbody fusion. The charts of all patients who underwent axial lumbar interbody fusion surgery at our institution between 2006 and 2008 were reviewed. Clinical outcomes included visual analog scale (VAS) and Oswestry Disability Index (ODI). Radiographs were also evaluated for disk space height, L4-L5 and/or L5-S1 Cobb angle, and fusion. Of the 50 patients (32 women, 18 men; mean age, 49.29 years) treated with axial lumbar interbody fusion, 48 had preoperative VAS scores and 16 had preoperative ODI scores available. Complete radiographic data were available at the preoperative, initial postoperative, and final postoperative time points for 46 patients (92%). At last follow-up (average, 12 months), ODI scores were reduced from 46 to 22, and VAS scores were lowered from 8.1 to 3.6. Of the 49 patients with postoperative radiographs, 47 (96%) went on to a solid fusion. There were no significant differences between pre- and postoperative disk space height and lumbar lordosis angle. The most common complications were superficial infection and pseudoarthrosis. Other complications were rectal injury, hematoma, and irritation of a nerve root by a screw. Overall, we found the axial lumbar interbody fusion procedure in combination with pedicle screw placement to have good clinical and radiological outcomes.     

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.     

Comparative effects of a high-intensity interval warm-up and salbutamol on the bronchoconstrictor response to exercise in asthmatic athletes

Approximately half of all asthmatics become refractory to exercise-induced bronchoconstriction (EIB) with repeated challenges. Exercise refractoriness has been utilized by asthmatic athletes to reduce the bronchoconstrictor response to exercise prior to competition, and this has led to the observation that some asthmatic athletes can "run through" their asthma. The main aim of this study was to investigate the efficacy of short high-intensity, repeated warm-ups compared with salbutamol (a commonly used inhaled beta (2)-agonist) on the severity of EIB. Eight moderately trained (.VO(2peak), 51.9 +/- 2.3 ml . kg (-1) . min (-1)) recreational asthmatic athletes with documented EIB were tested under 4 experimental conditions: 1) control (CON) condition; 2) an interval warm-up (WU) consisting of 8 x 30-sec runs at peak treadmill speed, with 45-sec recovery between each sprint; 3) inhaling 200 microg of salbutamol (Ventolin, GlaxoSmithKline, Uxbridge, Middlesex, U.K.) (IH); and 4) combining both the WU and IH session. All 4 experimental sessions were followed by an exercise challenge test (85-90 % predicted maximum heart rate for 8 min). Pulmonary function was measured pre-exercise and at 1, 5, 10, 15 min postexercise. The mean maximum percent fall in pre- to postexercise forced expiratory volume in 1-sec (FEV (1)) for all 8 asthmatic subjects during the EIB screening test (CON session) was - 18.25 +/- 4.01 %. The mean maximum percent decrease in postexercise FEV (1) significantly decreased (p < 0.05) to only - 9.1 +/- 0.6 % following the WU condition, which is below the EIB diagnostic threshold of a 10 % fall in postexercise FEV (1). The IH and WU + IH condition resulted in a substantial postexercise bronchodilation as shown by a significant increase (p < 0.05) in the mean maximum percent change in postexercise FEV (1) following the IH (+ 8.9 +/- 6.1 %) and WU + IH (+ 15.2 +/- 4.6 %) condition. Similar changes as a result of experimental condition were observed for FEF (25-75 %). These data indicate that repeated high-intensity warm-ups can lessen the bronchoconstrictor response to exercise. In addition, combining the interval warm-up with salbutamol prior to exercise resulted in substantial bronchodilation and conferred a greater protective effect against developing EIB than either intervention alone.     

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.