自体外周血纯化CD34+细胞移植治疗进展型多发性硬化

目的 评价自体外周血纯化CD34+细胞移植治疗进展型多发性硬化(PMS)的安全性和疗效.方法 2002-09―2006-03期间15例PMS患者在首都医科大学宣武医院接受了自体外周血纯化CD34+细胞移植.单独使用粒细胞集落刺激因子(G-CSF)动员造血干细胞,全部回输采集物进行CD34+细胞纯化.预处理采用BEAM(卡氮芥、依托泊甙、阿糖胞苷、马法兰)方案.中位随访期为21(3～45)个月,移植前后应用扩充神经功能残疾量表(EDSS)、年平均发病次数进行疗效评价. 结果分选后中位CD34+细胞纯度为93.2 (78.6～97.7)%,中位回收率为67.0(22.4～79.8)%,相当于减少了4个对数级的T细胞.无移植相关死亡,造血重建时间与其自体外周造血干细胞移植(APBSCT)相当,未出现严重的毒性反应及并发症.患者移植后12个月EDSS评分(3.95±2.55)较移植前(5.64±0.71)降低(P＜0.05),年平均发病次数移植后(0.45±0.82)较移植前(1.31±0.71)减少(P＜0.05).移植后45个月疾病无活动者生存率为(47.01±17.87)%,EDSS评分无进展者(包括稳定和改善)生存率为(57.69±20.24)%. 结论自体外周血纯化CD34+细胞移植治疗PMS安全有效.     

复合维生素E,C,B组合物面膜治疗寻常痤疮117例的疗效和安全性(英文)

目的:了解维生素E,C,B组合物面膜治疗寻常痤疮的疗效及安全性。方法:117例13a以上、痤疮严重程度分级在2级以上且主要表现于脸部的病人,予维生素E,C,B组合物面膜治疗,每日1次,共8wk。观察治疗前后痤疮数量及性质,包括粉刺、丘疹、脓疱及囊肿之数目,并评估整体疗效。结果:治疗后,粉刺、丘疹、脓疱及囊肿数目下降了13±s13,10±12,5±7及3±3,均P<0.01。7例(6.0%)病人症状完全改善,44例(37.6%)中度改善,56例(47.9%)轻度改善,10例(8.6%)无改善。59例(50.4%)病人无红肿、搔痒、灼热及脱皮等现象发生。结论:维生素E,C,B组合物面膜治疗痤疮有效,超过半数的受试者无不良反应发生,可作为传统治疗寻常痤疮药物的替代。     

Axonal damage in the spinal cord of multiple sclerosis patients detected by magnetic resonance spectroscopy.

Axonal damage is a major factor contributing to permanent disability in patients with multiple sclerosis (MS); it has been extensively investigated in the brain using magnetic resonance spectroscopy (MRS). In this study, MRS was used to investigate the degree of neuronal damage in the cervical spinal cord in MS. Spectra were acquired from spinal cord and brain in 11 patients with MS (expanded disability status score [EDSS], range 2.5-7.0) and 11 controls. Brain lesion volume and spinal cord cross-sectional area were measured. Concentration of the neuronal metabolite N-acetyl-aspartate ([NAA]) was reduced in the spinal cord in MS patients relative to controls (reduced by 32%, P < 0.05), indicating significant neuronal damage. Additionally, the spinal cord was significantly atrophied in MS patients (15%, P < 0.001). No significant reduction in brain [NAA] was seen in the MS group. There were no correlations between clinical measures and cord atrophy or brain lesion volume on MRI; however, spinal cord [NAA] correlated with the cerebellar subscore of the neurological assessment (P < 0.005), while brain [NAA] correlated with disease duration (P < 0.05). MRS demonstrated cellular damage within the cord over and above the tissue atrophy seen by MRI. Combining MRI and MRS may therefore give a more complete picture of neurodegeneration in the spinal cord.     

Serial in vivo MR tracking of magnetically labeled neural spheres transplanted in chronic EAE mice.

Neural stem cell (NSC) transplantation has been shown to attenuate the severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Central to the future success of NSC transplantation in MS is the ability of transplanted cells to migrate from the site of transplantation to relevant foci of disease. Using magnetically labeled mouse neurospheres and human embryonic stem cell (hESC)-derived neurospheres, we applied serial magnetic resonance imaging (MRI) to assess the biodynamics of transplanted cell migration in a chronic mouse EAE model. Magnetic labeling did not affect the in vitro and in vivo characteristics of cells as multipotential precursors. Cell migration occurred along white matter (WM) tracts (especially the corpus callosum (CC), fimbria, and internal capsule), predominantly early in the acute phase of disease, and in an asymmetric manner. The distance of cell migration correlated well with clinical severity of disease and the number of microglia in the WM tracts, supporting the notion that inflammatory signals promote transplanted cell migration. This study shows for the first time that hESC-derived neural precursors also respond to tissue signals in an MS model, similarly to rodent cells. The results are directly relevant for designing and optimizing cell therapies for MS, and achieving a better understanding of in vivo cell dynamics and cell-tissue interactions.     

No support for a truncated interferon-α17 allele as risk factor for MS

Cytokines have a central role in multiple sclerosis (MS) pathogenesis and may contribute to the aetiology of MS. A polymorphism in the IFNA17 gene with an allele carrying a pre-mature stop codon has been suggested to convey a 26-fold increased risk for MS. We investigated the possible association between this polymorphism and MS using population-based samples from a genetically well-characterized population. The IFNA17 gene variant was found in 2.8% of 327 MS cases and 3.3% of 698 referents ( P  = 0.64). Thus, our study does not support an association between the IFNA17 allele and risk for MS.     

Clinical and demographical characteristics of primary progressive multiple sclerosis in Isfahan, Iran

Primary progressive multiple sclerosis (PPMS) is an uncommon form of multiple sclerosis (MS) in which the course of disease is progressive from onset. In a retrospective study amongst 1606 MS patients registered in Isfahan MS Society (IMSS) from April 2003 to 31 December 2005, 92 PPMS cases were identified. That means, the frequency of PPMS amongst all included MS patients would be 5.7% (95% CI: 6.7% and 4.7%). The mean expanded disability status scale (EDSS) for the group was 5.09 ± 1.3. The commonest mode of presentation was motor disturbance in 55 (59.8%), other modes of presentation were, vertigo in 15 (16.3%), visual problems in 12 (13%), sensory disturbances in six (6.5%), and diplopia in four (4.3%). The current existing symptoms were motor problems in all 92 (100%), cerebellar symptoms in 46 (50%), and cognitive impairment in only six (6.5%). Interestingly, two (2%) were affected by poliomyelitis during childhood and presenting symptom in both was limb weakness. Primary progressive form of MS is less common in Persian population and some of the rates observed in PPMS patients differ from those in other regions, these differences may be due to different ethnicity of Persian patients or to geographical differences.     

急性脑梗死诱发全身炎症反应综合征致多器官功能障碍综合征的临床研究

目的　探讨急性脑梗死 (ACI)诱发全身炎症反应综合征 (SIRS)致多器官功能障碍综合征(MODS)的发病机制 ,以及血清肿瘤坏死因子 (TNF α)、白细胞介素 (IL 1) β含量变化在ACI诱发SIRS发生、发展并向MODS转化的临床意义。方法　 6 8例ACI患者根据病情变化分为 3组 ,其中单纯性ACI(SACI组 ) 36例 ,ACI致SIRS(SIRS组 ) 32例 ,ACI致SIRS后发展为MODS(MODS组 ) 2 4例 ;应用酶联免疫吸附法 (ELISA法 )分别测定患者不同病程中血清TNF α、IL 1β值 ,并与对照组 (为 2 8名同期健康体检者 )比较。 结果　 (1) 6 8例ACI中 4 7.0 6 %发生SIRS;SIRS时 75 %发生MODS。 (2 )血清TNF α、IL 1β的含量MODS 组 >SIRS组 >SACI组 >对照组 ,各组间比较 ,差异具有极显著性 (均P <0 0 1)。MODS重症者 (积分≥ 9分 )血清TNF α、IL 1β含量高于轻症者 (积分 <9分 ) (均P <0 0 1) ;MODS死亡者血清TNF α、IL 1β含量高于存活者 (均 P <0 0 1)。结论　 (1)ACI后出现SIRS可导致MODS的发生。 (2 )患者血清TNF α、IL 1β水平异常变化可作为判断ACI致SIRS、MODS病情进展、预后及转归的一项指标     

Physiological pharmacokinetics of solutes in the isolated perfused rat hindlimb: Characterization of the physiology with changing perfusate flow,protein content,and temperature using statistical moment analysis

Distribution of Evans Blue (EB), sucrose, and water into the isolated perfused rat hindlimb was studied under various conditions using the multiple indicator dilution (MID) technique. Statistical moment analyses of the outflow profiles for the EB, sucrose, and water were used to define the vascular, extravascular, and total water spaces, respectively. The varied perfusion conditions included albumin content (2, 4.7, and 7%), temperature (25, 37, and 42 C), perfusate flow rate (2, 4, 8, and 12 ml/min) and the presence/absence of red blood cells. The range of studies undertaken were chosen to represent the variety of conditions used in the preparation of both isolated animal and human limbs, the latter being particularly important in cytotoxic therapy for recurrent malignant melanoma. The distribution volumes of EB, sucrose, and water were dependent on the flow rate and the albumin content of perfusate. The normalized variances (CV ² ) of the markers were of the following order: sucrose (2.18) > water (1.58) > EB (0.68), indicating that some disequilibrium occurs during the capillary exchange of water and sucrose. It is suggested that a Krebs-Henseleit buffer containing 2% BSA is a suitable perfusate for most studies of the isolated rat hindlimb perfusion. The effect of albumin concentration manifests itself only at higher flows.We acknowledge the support of the National Heart Foundation (Queensland) and the Mayne Bequest Foundation. This study was conducted while the investigator (Z.Y. Wu) was in receipt of a WHO Research Training Grant. Professor M. S. Roberts also acknowledges the support of the Queensland and Northern New South Wales Lions Kidney & Medical Research Foundation.