非亲缘外周血造血干细胞移植治疗重型β-地中海贫血1例

患儿,女,4岁,体质量19kg。生后4个月开始进行性面色苍白伴巩膜黄染,血红蛋白65g/L,白细胞和血小板均正常,血红蛋白电泳血红蛋白A48.1%、血红蛋白A24.2%、抗碱血红蛋白47.7%,基因型为β地贫纯合子,诊断为重型β地中海贫血,以间断大量输血维持生命。于2005-12-09在厦门大学附属中山医院血液科接受非亲缘性外周血干细胞移植。预处理方案采用常规氟达拉滨、白消胺、环磷酰胺三药联合方案,以环孢菌素A、霉酚酸酯、抗胸腺淋巴细胞免疫球蛋白联合预防移植物抗宿主病,供受者人类白细胞抗原高分辨全相合,ABO血型次要不合(O-A),输入CD34 干细胞11.4×106/kg。植入成功,移植后12d中性粒细胞>0.5×109L-1,移植后37d血小板>50×109L-1,移植后35d患者血型检测转变为供者血型,患儿血红蛋白达到100g/L的时间是28d,移植后患儿未再输血,血红蛋白维持130g/L以上,整个移植过程顺利,未出现严重感染和移植物抗宿主反应,随访18个月,患儿生活正常,发育良好。     

Urate predicts subsequent cardiac death in stroke survivors.

AIMS: To test the hypothesis that urate predicts cardiac death after stroke independent of conventional risk factors of atherosclerosis, creatinine and diuretic use. METHODS AND RESULTS: Serum urate concentration was measured in an unselected cohort of 354 stroke survivors who were followed-up for a median of 2.8 years. Cardiac death was the primary end-point. Urate was associated with a statistically significant threefold increase in relative risk of cardiac death even after adjustment for other conventional risk factors. In the subgroup of patients who were not on diuretics, raised urate was associated with a 12-fold significant increase in relative risk of cardiac death after adjusting for renal function and other conventional risk factors. A urate concentration of greater than 0.31 mmol. l(-1) was 78% sensitive at predicting cardiac death within 5 years after stroke, but was only 54% specific. If urate exceeded 0.38 mmol. l(-1), specificity of predicting cardiac death within 5 years after stroke was 88%. CONCLUSIONS: Elevated serum urate concentration may be used to stratify risk of future cardiac death after stroke. This appeared to be true even in stroke survivors who were not on diuretic therapy.     

The influence of the polyphenols of cider on plasmin and plasminogen activators

Preliminary findings suggested that the inhibitory activity on fibrinolysis produced by most varieties of cider is due to their content of polyphenols. In particular, the inhibitory activity co-eluted with the brown coloration on gel filtration, was removed by adsorption with polyvinylpyrrolidine, and was greatly reduced in a type of cider with a low concentration of phenolic compounds. The individual polyphenols of apple juice and ciders were examined for their ability to inhibit tissue activator, urokinase and plasmin. Neither phloridzin nor chlorogenic acid had any inhibitory activity at concentrations of 500 micrograms/ml while epicatechin had only a slight inhibitory effect at this concentration. The procyanidin fractions were markedly inhibitory on urokinase-induced clot lysis, the amidolytic activity of plasmin and on the fibrinolytic activities of plasmin, urokinase and tissue activator on fibrin plates: inhibition was noted at concentrations as low as 0.25 micrograms/ml. The order of inhibition was polymer greater than oligomer greater than trimer greater than dimer.     

Characterization of the human neutrophil C1q receptor and functional effects of free ligand on activated neutrophils

The partial characterization and expression of the C1q receptor (C1q-R) in relation to other complement receptors present on the surface of neutrophils has been examined, as well as the effects of free C1q on cell function. A polyclonal anti-C1q-R antibody recognizes a 68-kD neutrophil surface protein. C1q-R expression was not upregulated upon warming, priming, or exposure to FMLP, but decreased after exposure to phorbol myristate acetate (PMA), because of shedding of the receptor into the extracellular medium, as detected by enzyme-linked immunosorbent assay. CR3 and CR1 expression was upregulated from intracellular pools after cell stimulation by PMA. No evidence of intracellular pools of C1q-R was found, as assessed by immunoblotting of subcellular fractions. But C1q-R appeared to be expressed early in cell differentiation, was detected on undifferentiated HL-60 cells, and like CR3 expression, increased upon 5 days differentiation towards a neutrophil lineage. However, C1q-R expression decreased upon additional culture, whereas CR3 expression continued to increase. A large variation in the percentage of peripheral cells expressing C1q receptors in donors was observed, ranging from 13% to 100%, contrasting with CR3 receptors that exhibited less variability. Interactions between free monomeric C1q and neutrophils were also studied. Incubation of stimulated neutrophils with 10 to 100 micrograms/mL C1q resulted in a further increase in CR3 expression and adherence to albumin-coated surfaces. Staphylococci opsonized with low quantities of C1q (0.1 to 1 microgram/mL) mediated a moderate and sustained respiratory burst in neutrophils, whereas a burst of similar magnitude was generated only with free C1q at concentrations 10- to 100-fold higher. Stimulation was only partially inhibited if cells were first treated with anti-C1q-R antibody, suggesting other C1q binding proteins may be present on the cell surface. In summary, neutrophil C1q receptor is approximately 68-kD, exhibits varying expression on different subjects, and is not upregulated from intracellular stores on exposure to soluble stimuli. Stimulated, but not resting, neutrophils selectively respond to raised levels of free C1q, resulting in altered cell function and enhanced CR3 receptor expression. These studies thus suggest complex roles for C1q in neutrophil function.     

Cod liver oil (n-3 fatty acids) as an non-steroidal anti-inflammatory drug sparing agent in rheumatoid arthritis

Objectives. Dose-dependant gastrointestinal and cardiovascularside-effects limit the use of NSAIDs in the management of RA.The n-3 essential fatty acids (EFAs) have previously demonstratedsome anti-inflammatory and NSAID-sparing properties. The objectiveof this study was to determine whether cod liver oil supplementationhelps reduce daily NSAID requirement of patients with RA. Methods. Dual-centre, double-blind placebo-controlled randomizedstudy of 9 months’ duration. Ninety-seven patients withRA were randomized to take either 10 g of cod liver oil containing2.2 g of n-3 EFAs or air-filled identical placebo capsules.Documentation of NSAID daily requirement, clinical and laboratoryparameters of RA disease activity and safety checks were doneat 0, 4, 12, 24 and 36 weeks. At 12 weeks, patients were instructedto gradually reduce, and if possible, stop their NSAID intake.Relative reduction of daily NSAID requirement by >30% after9 months was the primary outcome measure. Results. Fifty-eight patients (60%) completed the study. Outof 49 patients 19 (39%) in the cod liver oil group and out of48 patients 5 (10%) in the placebo group were able to reducetheir daily NSAID requirement by >30% (P = 0.002, chi-squaredtest). No differences between the groups were observed in theclinical parameters of RA disease activity or in the side-effectsobserved. Conclusions. This study suggests that cod liver oil supplementscontaining n-3 fatty acids can be used as NSAID-sparing agentsin RA patients. KEY WORDS: RA, Fish oil, n-3 fatty acids, NSAIDs Submitted 15 August 2007; revised version accepted 10 January 2008.     

Death in Scotland and nineteen years of resource allocation.

The Scottish Health Authorities Revenue Equalisation (SHARE) programme has been operating since the late 1970s to allocate health services money on a more equitable basis between health boards. It is about to be replaced by a new method, however. The trends in per capita spending on healthcare services from the commencement of SHARE are examined here, as are changes in the relative experiences of mortality, in the 12 Scottish mainland health board regions. Every health board has committed increases in spending in real terms on services for their residents. Concurrently, the differential in boards' spending on their residents has reduced due to the effects of the SHARE process. Notwithstanding the global increase in expenditure on healthcare services, and the reduction in inequalities in resources between regions, inequality in the experience of mortality has increased within Scotland. The most important public health factors influencing mortality lie outside the control of healthcare providers.     

骨髓间充质干细胞移植后脑梗死大鼠脑电图的变化

目的:对比观察骨髓间充质干细胞移植前后脑梗死大鼠脑电图的变化。方法:实验于2002-09/12在解放军第三军医大学中心实验室及西南医院神经内科肌电图室完成。①实验分组:选取清洁级健康成年Wistar大鼠15只,随机数字表法分为干细胞移植组、模型对照组、假手术组,5只/组。②实验方法:另取2只健康幼年Wistar大鼠用于骨髓间充质干细胞的提取,联合采用密度梯度离心及贴壁法分离培养大鼠骨髓间充质干细胞,选取生长良好的1～3代细胞用于移植实验。干细胞移植组、模型对照组大鼠建立大脑中动脉栓塞模型。假手术组仅分离颈总动脉、颈外动脉和颈内动脉,不予结扎和放置线栓。造模后1周,干细胞移植组、假手术组大鼠行细胞移植,在立体定向仪定位下于脑梗死区(壳核)直接注射骨髓间充质干细胞悬液5μL,细胞浓度1×104μL-1,移植坐标为前囟前1.0mm,右旁开3.0mm,硬膜下5.0mm。模型对照组大鼠于相同部位注射等量不含细胞的磷酸盐缓冲液。③实验评估:采用脑电图机分别于造模前、造模后1周(移植前)、细胞移植后4周对各组大鼠进行脑电图检测。结果:15只大鼠均进入结果分析。①造模前基本节律为8～11Hz、15～30μV的α波,间或少量θ波,双侧对称。②造模后1周,假手术组异常率为0;模型对照组20%(1/5)轻度异常,80%(4/5)中度异常;干细胞移植组20%(1/5)轻度异常,60%(3/5)中度异常,20%(1/5)重度异常。③细胞移植后4周,假手术组脑电图恢复正常;模型对照组随术后时间的延长慢波有所减少,但仍可见到δ波、棘波、棘慢波的发放,至细胞移植后4周60%(3/5)轻度异常,40%(2/5)中度异常;干细胞移植组术后局限性慢波逐渐减少,基本节律全部恢复为α波,不对称的情况明显好转,至细胞移植后4周60%(3/5)轻度异常,以病灶侧局限性θ波较多为主,另外40%(2/5)基本正常。结论:动物实验显示骨髓间充质干细胞移植对脑梗死大鼠的脑电图背景节律有改善作用,一定程度上促进了神经系统功能的恢复。