Balance and gait improved in patients with MS after physiotherapy based on the Bobath concept

Background and Purpose . Patients with multiple sclerosis (MS) tend to have movement difficulties, and the effect of physiotherapy for this group of patients has been subjected to limited systematic research. In the present study physiotherapy based on the Bobath concept, applied to MS patients with balance and gait problems, was evaluated. The ability of different functional tests to demonstrate change was evaluated. Method . A single‐subject experimental study design with ABAA phases was used, and two patients with relapsing–remitting MS in stable phase were treated. Tests were performed 12 times, three at each phase: A (at baseline); B (during treatment); A (immediately after treatment); and A (after two months). The key feature of treatment was facilitation of postural activity and selective control of movement. Several performance and self‐report measures and interviews were used. Results . After intervention, improved balance was shown by the Berg Balance Scale (BBS) in both patients, and improved quality of gait was indicated by the Rivermead Visual Gait Assessment (RVGA). The patients also reported improved balance and gait function in the interviews and scored their condition as ‘much improved’. Gait parameters, recorded by an electronic walkway, changed, but differently in the two patients. Among the physical performance tests the BBS and the RVGA demonstrated the highest change, while no or minimal change was demonstrated by the Rivermead Mobility Index (RMI) and Ratings of Perceived Exertion (RPE). Conclusion . The findings indicate that balance and gait can be improved after physiotherapy based on the Bobath concept, but this should be further evaluated in larger controlled trials of patients with MS. Copyright © 2006 John Wiley & Sons, Ltd.     

B cells as a target of immune modulation

B cells have recently been identified as an integral component of the immune system; they play a part in autoimmunity through antigen presentation, antibody secretion, and complement activation. Animal models of multiple sclerosis (MS) suggest that myelin destruction is partly mediated through B cell activation (and plasmablasts). MS patients with evidence of B cell involvement, as compared to those without, tend to have a worse prognosis. Finally, the significant decrease in new gadolinium-enhancing lesions, new T2 lesions, and relapses in MS patients treated with rituximab (a monoclonal antibody against CD20 on B cells) leads us to the conclusion that B cells play an important role in MS and that immune modulation of these cells may ameliorate the disease. This article will explore the role of B cells in MS and the rationale for the development of B cell–targeted therapeutics. MS is an immune-mediated disease that affects over 2 million people worldwide and is the number one cause of disability in young patients. Most therapeutic targets have focused on T cells; however, recently, the focus has shifted to the role of B cells in the pathogenesis of MS and the potential of B cells as a therapeutic target.     

Simultaneous versus sequential optimal design for pharmacokinetic-pharmacodynamic models with FO and FOCE considerations

We consider nested multiple response models which are used extensively in the area of pharmacometrics. Given the conditional nature of such models, differences in predicted responses are a consequence of different assumptions about how the models interact. As such, sequential versus simultaneous and First Order (FO) versus First Order Conditional Estimation (FOCE) techniques have been explored in the literature where it was found that the sequential and FO approaches can produce biased results. It is therefore of interest to determine any design consequences between the various methods and approximations. As optimal design for nonlinear mixed effects models is dependent upon initial parameter estimates and an approximation to the expected Fisher information matrix, it is necessary to incorporate any influence of nonlinearity (or parameter-effects curvature) into our exploration. Hence, sequential versus simultaneous design with FO and FOCE considerations are compared under low, typical and high degrees of nonlinearity. Additionally, predicted standard errors of parameters are also compared to empirical estimates formed via a simulation/estimation study in NONMEM. Initially, design theory for nested multiple response models is developed and approaches mentioned above are investigated by considering a pharmacokinetic–pharmacodynamic model found in the literature. We consider design for situations where all responses are continuous and extend this methodology to the case where a response may be a discrete random variable. In particular, for a binary response pharmacodynamic model, it is conjectured that such responses will offer little information about all parameters and hence a sequential optimization, in the form of product design optimality, may yield near optimal designs.     

多发性骨髓瘤患者血浆尿激酶型纤溶酶原激活物及其可溶性受体的检测与临床意义

目的 :研究多发性骨髓瘤 ( MM)患者血浆尿激酶型纤溶酶原激活物 ( u- PA )及其可溶性受体 ( su PAR )的水平变化 ,并探讨其临床意义。方法 :用 ELISA法检测 34例 MM患者血浆 u- PA及 su PA R的浓度 ,同时观察其中6例 MM患者化疗前后血浆 u- PA及 su PAR的浓度变化。结果 :MM患者血浆 u- PA及 su PA R水平均明显高于正常对照组 ,其中进展期 MM患者血浆 u- PA及 su PAR水平明显高于正常对照组和稳定期 MM患者 ( P <0 .0 1) ,而稳定期 MM患者血浆 u- PA及 su PA R水平与正常对照组无显著性差异 ( P>0 .0 5)。 6例 MM患者化疗后血浆 u- PA及 su PA R水平 ,明显低于化疗前血浆 u- PA及 su PAR水平 ( P<0 .0 5)。骨髓涂片瘤细胞比例 >2 0 %的 MM患者血浆 u- PA及 su PA R水平 ,明显高于瘤细胞比例≤ 2 0 % M M患者 ( P<0 .0 5;P<0 .0 1)。M M患者血浆 u- PA及su PA R水平均与骨髓瘤细胞百分比及血清球蛋白呈正相关 ,而与血清白蛋白呈负相关。结论 :血浆 u- PA及 su PA R水平升高可能与多发性骨髓瘤的发生、发展有密切关系 ;其水平可作为临床分期、判断疗效、了解疾病进展情况及预后的一个重要指标。     

内镜下鼻胆管引流治疗急性梗阻性化脓性胆管炎(附25例报告)

目的探讨急性梗阻性化脓性胆管炎伴多器官衰竭的治疗方法。方法对25例急性梗阻性化脓性胆管炎伴多器官衰竭的患者采取以内镜下鼻胆管引流术、经鼻胆管冲洗及灌注抗生素为主的非手术综合治疗,观察患者治疗前后的血清总胆红素水平、B超下胆总管内径变化,并对患者临床资料进行回顾性分析。结果本组25例患者除2例需转外科急诊手术治疗外,其余23例内镜下胰胆管造影、内镜下鼻胆管引流术成功,胆汁引流通畅,多器官衰竭得以纠正,急性梗阻性化脓性胆管炎伴多器官衰竭治愈率为92.0%。结论对急性梗阻性化脓性胆管炎伴多器官衰竭患者采取内镜下鼻胆管引流术、静脉应用和经鼻胆管冲洗及灌注抗生素为主的综合治疗是有效、安全的。     

掌背动脉逆行岛状筋膜瓣修复手部皮肤缺损

目的:介绍掌背动脉逆行筋膜瓣修复手部皮肤缺损的临床应用。方法:采用第二、第三掌背动脉逆行岛状筋膜瓣分别修复手部皮肤缺损10例。皮肤缺损面积2.0cm×3.0cm-3.0cm×5.0cm。结果:10例筋膜瓣移位均成活,效果满意。结论:应用第二、三掌背动脉逆行岛状筋膜瓣移植是治疗手部皮肤缺损一种简单有效的手术方法。     

Fisher information matrix for nonlinear mixed effects multiple response models: Evaluation of the appropriateness of the first order linearization using a pharmacokinetic/pharmacodynamic model

We focus on the Fisher information matrix used for design evaluation and optimization in nonlinear mixed effects multiple response models. We evaluate the appropriateness of its expression computed by linearization as proposed for a single response model. Using a pharmacokinetic–pharmacodynamic (PKPD) example, we first compare the computation of the Fisher information matrix with approximation to one derived from the observed matrix on a large simulation using the stochastic approximation expectation–maximization algorithm (SAEM). The expression of the Fisher information matrix for multiple responses is also evaluated by comparison with the empirical information obtained through a replicated simulation study using the first‐order linearization estimation methods implemented in the NONMEM software (first‐order (FO), first‐order conditional estimate (FOCE)) and the SAEM algorithm in the MONOLIX software. The predicted errors given by the approximated information matrix are close to those given by the information matrix obtained without linearization using SAEM and to the empirical ones obtained with FOCE and SAEM. The simulation study also illustrates the accuracy of both FOCE and SAEM estimation algorithms when jointly modelling multiple responses and the major limitations of the FO method. This study highlights the appropriateness of the approximated Fisher information matrix for multiple responses, which is implemented in PFIM 3.0, an extension of the R function PFIM dedicated to design evaluation and optimization. It also emphasizes the use of this computing tool for designing population multiple response studies, as for instance in PKPD studies or in PK studies including the modelling of the PK of a drug and its active metabolite. Copyright © 2009 John Wiley & Sons, Ltd.     

Genetics in multiple sclerosis: past and future perspectives

The enormous development in the field of molecular genetics during the last decades has lead to optimism concerning the possibilities for identifying the causes of multiple sclerosis (MS) through genetic studies. However, we have learned that dense mapping of large sample sets is needed, which only can be achieved through large collaborative studies. The contribution from each yet unidentified gene is probably weaker than that of the well established human leukocyte antigen association. The ultimate goal of the search for susceptibility genes in MS is to develop diagnostic tools and better treatments that can prevent or reduce the development of symptoms of this often devastating disease.     

益气复智颗粒对多发脑梗死性痴呆模型大鼠脑组织细胞凋亡的影响

目的 观察益气复智颗粒对多发脑梗死性痴呆模型大鼠脑皮质形态学、细胞凋亡的影响。方法 采用颈内动脉注射血栓的方法，复制多发梗死性痴呆大鼠模型，观察益气复智颗粒12．42g/kg分别于手术前、手术前后、手术后灌胃对实验动物脑皮质形态学、细胞凋亡的影响。结果 益气复智颗粒能使脑缺血后脑内神经细胞凋亡数目下降。结论 益气复智颗粒具有较好的保护脑神经元，阻断脑缺血致神经细胞死亡病理过程的作用。