经皮冠状动脉自体骨髓单个核细胞移植对重症心力衰竭患者心功能的影响

目的:观察自体骨髓单个核细胞经皮冠状动脉移植治疗重症心力衰竭的效果,探讨其可行性、安全性和有效性。方法:选取2006-02/08承德北方医院收治的20例重症心力衰竭患者,男14例,女6例,平均年龄(54±13)岁,由家属签署手术同意书。①患者俯卧位局麻,双测髂后上嵴行多点穿刺,抽取骨髓血60～260mL,要求在60min内完成。将采集的骨髓血进行骨髓细胞分离、洗涤,用生理盐水稀释单个核细胞悬液至20～30mL。②用PTCA球囊以先后顺序放置在左前降支中段或右冠状动脉中段,以4～6个大气压扩张球囊临时阻断远端血流,从球囊导管尾端注入分离净化的骨髓单个核细胞,左冠状动脉注射总量2/3,右冠状动脉注射总量1/3。③分别于术后1,3个月进行随访,检测NYHA心功能分级与射血分数,以6min标准步行实验评估运动能力。结果:实验选取20例重症心力衰竭患者,3例于术前发生猝死而退出试验,最终17例成功进行自体骨髓细胞移植,均完成术后3个月随访。①自体骨髓单个核细胞移植过程中的不良反应:17例患者中,严重心律失常1例,急性左心室衰竭1例,心绞痛2例,头痛1例,术中呕吐2例,术后低热1例,穿刺点血肿1例。②自体骨髓单个核细胞移植后不同时间NYHA心功能分级的变化:与术前比较,自体骨髓单个核细胞移植术后1,3个月NYHA心功能分级均明显提高(t=9.294～10.102,P均<0.01)。③自体骨髓单个核细胞移植后不同时间心功能指标与运动能力的变化:与术前比较,自体骨髓单个核细胞移植术后1,3个月NYHA心功能分级、左心室射血分数、左心室舒张末期直径、6min行走距离均得到明显改善(t=3.034～5.064,P<0.05)。④NYHA心功能改善程度与其他心功能参数的相关性:细胞移植后3个月,NYHA心功能分级改善程度与左心室射血分数、左心室舒张末期直径呈明显正相关(r=0.461～0.494,P均<0.05)。结论:经皮冠状动脉移植自体骨髓单个核细胞,可明显改善重症心力衰竭患者心功能及运动能力,安全可行。     

Progress in fighting systemic fungal infections in haematological neoplasia

 Considering the limited data available, there is clearly a need for thorough, well-designed clinical research on the epidemiology, diagnosis, treatment and prevention of invasive fungal infection in patients who are treated for cancer. Our knowledge has increased, but the information obtained so far is patchy and not generally applicable, as it is influenced by local problems and circumstances. New diagnostic tools have become available, but they are still insufficient in many cases. Until the value of the presently available chemoprophylaxis has been established beyond doubt, the strategy should be one of wait-and-see for patients with a low or moderate risk of developing infection. In bone marrow transplant recipients fluconazole has shown favourable results in eliminating yeast infections, but in patients at high risk of mould infections early initiation of intravenous treatment with amphotericin B at a therapeutic dose remains the best approach. The question of the optimal time point to start empirical antifungal treatment remains and has even been extended by the dispute about what antifungal drugs should be used for this purpose. Amphotericin B is still the drug of choice for the treatment of disseminated fungal infection, but its lipid formulations seem to offer a safer, though far more expensive, alternative. Head-to-head comparisons between the different formulations are required before a final conclusion on their respective efficacies and toxicities can be drawn, and it is questionable whether a higher dose will produce better results. Fluconazole appears very useful against the majority of Candida infections, whereas itraconazole is effective against both yeast and moulds, providing that adequate resorption can be ensured. The results of the first clinical trial of voriconazole in pulmonary aspergillosis have proved very promising.     

牵张应力对人骨髓间充质干细胞增殖及细胞周期的影响

目的:观察周期性机械牵张应力对人骨髓间充质干细胞的增殖活性与细胞周期的影响。方法:实验于2006-02/06在同济医院矫形外科实验室完成。①建立体外细胞周期性机械牵张力学装置,并利用三维有限元的方法分析基膜的力学分布。②使用密度梯度离心法分离人骨髓间充质干细胞。③取第3～6代细胞接种于弹性硅胶膜培养板,分组:实验组细胞接受力学装置1.0Hz的频率,不同大小的应力(3%,6%,9%,12%,18%)、不同时间(12,24,36,48,60,72h)的机械信号刺激,对照组细胞不受力学信号刺激,其他培养条件与实验组一致。④细胞行力学干预后,用相差显微镜观察行细胞形态、排列,分别用细胞计数法、四甲基偶氮唑和流式细胞仪测量细胞增殖和细胞周期。结果:①自行建立的力学装置性能稳定,细胞接种硅胶6孔板后12～24h贴壁,贴壁良好,24h后细胞覆盖率约达70%,无细菌污染现象,可以用于应力刺激体外细胞效应的实验研究。②应力干预人骨髓间充质干细胞12h后,细胞形态稍变细长,轮廓鲜明,并沿受力环切线方向规则排列,干预24h变化更明显。③通过细胞计数、四甲基偶氮唑、流式细胞周期检测,发现适当大小的力学刺激对人骨髓间充质干细胞具促细胞增殖作用,增殖指数增大,其中12%的应力作用最明显,其增殖指数约为对照组的1.86倍;过强的机械应力(18%)对细胞不具有促增殖效应,并可能存在毒性作用;早期力学干预可以促进细胞增殖,干预时间过长(48h以后)反而表现为抑制生长趋势。结论:适当的周期性牵张应力可以提高人骨髓间充质干细胞的增殖能力。     

In vitro activities of new and conventional antifungal agents against clinical Scedosporium isolates.

The susceptibilities of 13 clinical isolates of Scedosporium apiospermum and 55 clinical isolates of S. prolificans to new and conventional drugs belonging to three different classes of antifungal agents, the azoles (miconazole, itraconazole, voriconazole, UR-9825, posaconazole), the polyenes (amphotericin B, nystatin and liposomal nystatin), and allylamines (terbinafine), were studied by use of proposed standard M38-P of NCCLS. Low growth-inhibitory antifungal activities were found in vitro for most of the drugs tested against S. prolificans isolates, with the MICs at which 90% of isolates are inhibited (MIC(90)s) being >8 microg/ml; the MIC(90)s of voriconazole and UR-9825, however, were 4 microg/ml. S. apiospermum isolates were more susceptible in vitro, with the highest activity exhibited by voriconazole (MIC(90)s, 0.5 microg/ml), followed by miconazole (MIC(90)s, 1 microg/ml), UR-9825 and posaconazole (MIC(90)s, 2 microg/ml), and itraconazole (MIC(90)s, 4 microg/ml). The MICs of terbinafine, amphotericin B, and the two formulations of nystatin (for which no statistically significant differences in antifungal activities were found for the two species) for S. apiospermum isolates were high. Cross-resistance was observed among all the azoles except posaconazole and among all the polyenes except the lipid formulation. A distribution analysis was performed with the MICs of each drug and for each species. Bimodal and skewed MIC distributions were obtained, and cutoffs indicating the borders of different MIC subpopulations of the distributions were determined on the basis of the normal plot technique. These cutoffs were in many cases reproducible between 48 and 72 h.     

重点中学中学生6307人的抑郁障碍现况调查

目的:了解中学生抑郁障碍的患病情况。方法:在北京、辽宁、安徽3省市各随机取1所重点中学,在同1个月内分别对该校全体非毕业班的在校中学生6307人采用抑郁自评量表进行抑郁障碍的筛查。对筛查结果异常及由班主任提供的筛查结果虽正常但怀疑有情绪问题的学生进行精神科检查,根据ICD-10中F32抑郁发作、抑郁复发和F34.1恶劣心境的诊断标准筛选出抑郁障碍的学生。其中北京市某校参加学生(北京组)3727人;辽宁省某校学生(辽宁组)1637人;安徽省某校高一年级学生943人(安徽组)。结果:发放问卷6307份,收回合格问卷6307份,有效率100%。①在6307人,抑郁自评量表筛查的阳性率为23.50%;诊断为抑郁障碍的学生184例,患病率2.92%(184/6307)。其中北京组89例,辽宁组45例,安徽组50例。男女学生抑郁障碍的发病情况接近,差异无显著性意义(85/3016,99/3291,χ2=0.392,P=0.531)。三所中学高一学生的总检出率以安徽最高(50/943),辽宁次之(32/870),北京最低(25/668),差异无显著性意义(χ2=5.423,P=0.066)。北京组高中学生抑郁障碍患病率与辽宁组接近,差异无显著性意义[3.11%(42/1349),2.75%(45/1647),χ2=0.344,P=0.558]。②北京组中学学生抑郁障碍的总患病率为2.39%。初一学生的总患病率明显低于初二、高一、高二学生,且差异有显著性意义(P=0.001,0.011,0.037)。但各年级中学生抑郁障碍男女性别之间差异均无显著性。③辽宁组中学学生抑郁障碍总检出率为2.75%。高一学生抑郁障碍患病率明显高于高二学生(3.68%,1.84%,χ2=6.016,P=0.0146);各年级男女学生抑郁障碍患病率差异无显著性。④安徽组高一学生抑郁障碍总患病率为5.31%(50/943),男女学生差异无显著性意义(5.20%,5.44%,χ2=0.027,P=0.870)。结论:所调查的重点中学学生中抑郁障碍比较常见,从初二年级开始出现有较明显的增加趋势,男女学生抑郁障碍的患病情况无明显差别。     

In vitro susceptibilities of zygomycetes to conventional and new antifungals

In vitro susceptibilities of 36 zygomycete isolates, belonging to six genera, to itraconazole, posaconazole, voriconazole, terbinafine, amphotericin B and 5-fluorocytosine were determined by using a broth microdilution adaptation of the National Committee for Clinical Laboratory Standards M-38P reference method. The influence of incubation time on MIC values, and the performance of a spectrophotometric method for MIC determination in comparison with the visual reference method, were also evaluated. Amphotericin B was active against most of the isolates. All the isolates were highly resistant to 5-fluorocytosine (MICs > 256 mg/L). Voriconazole was significantly less active than the other drugs with an overall MIC(90) (MIC at which 90% of the isolates were inhibited) of 32 mg/L. In contrast, posaconazole showed good activity (MIC(90) 1 mg/L). A wide range of MICs, from 0.03 to > or =32 mg/L, was obtained for itraconazole and terbinafine. Differences in susceptibility between and within genera were noted. Rhizopus spp. were significantly less susceptible to itraconazole, posaconazole, terbinafine and amphotericin B than Absidia spp., and less susceptible than Mucor spp. to amphotericin B. Terbinafine appeared to be more active against Rhizopus microsporus than against Rhizopus oryzae (geometric mean MIC of 0.15 and 64 mg/L, respectively). The activity of the drugs was dependent on the incubation period. A significant increase in MICs was noted between 24 and 48 h of incubation. On the other hand, the two methods used for MIC determination (visual and spectrophotometric readings) showed good agreement. These results suggest that the zygomycetes are a heterogeneous group for antifungal susceptibility. Some of the conventional and new antifungals are effective in vitro; their efficacies in vivo remain to be determined. The spectrophotometric method appears to be a valuable alternative to the visual method for MIC determination for zygomycetes.     

Factors influencing 20-hour increments after platelet transfusion

The 20-hour posttransfusion platelet count determines transfusion policy for patients requiring platelet support, and yet factors influencing the 20-hour count have been poorly defined. The clinical factors influencing both the 1- and 20-hour corrected count increment (CCI), were studied in 623 human leukocyte antigen (HLA)-unmatched platelet transfusions in 108 patients. The 1- and 20-hour CCIs were highly correlated (r = 0.67, p less than 0.001). On average, the 20-hour CCI was 64 percent of the 1-hour CCI. Multiple linear regression analyses identified splenectomy, bone marrow transplantation, disseminated intravascular coagulation, administration of amphotericin B, palpable spleen, and HLA antibody grade as the major factors influencing the 20-hour posttransfusion CCI. Platelet-specific antibodies, number of concurrent antibiotics, clinical bleeding, and temperature did not significantly influence the 20-hour posttransfusion CCI. The 1-hour CCI was the only significant factor influencing the 20-hour CCI in a regression model containing the 1-hour CCI and the above factors. Thus, the same clinical factors exert a major influence on the CCI at both 1 and 20 hours after platelet transfusion, with no evidence that any factor has more influence at 20 hours after transfusion than at 1 hour.     

Lack of protective effect of autotransplanted splenic tissue to pneumococcal challenge

Studies in animals and clinical experience in patients have demonstrated that splenectomy may lead to an increased susceptibility to infection. The infections are usually caused by encapsulated bacteria such as penumococcus. It has been shown in a variety of experimental animals that autotransplanted splenic tissue is capable of regenerating into implants that are microscopically indistinguishable from normal spleen and of restoring a number of normal splenic functions. The response to intravenous challenge with Streptococcus pneumoniae, type 25, was therefore studied in control, asplenic, and autotransplanted Sprague-Dawley rats. Despite previous observations that a number of immune functions can be restored in this animal model by autotransplanted splenic tissue, the present study indicates that splenic tissue autotransplants do not restore the ability to resist intravenous pneumococcal challenge.     

Hemin does not cause commitment of murine erythroleukemia (MEL) cells to terminal differentiation

The effect of hemin on the differentiation program of murine erythroleukemia (MEL) cells has been investigated. While hemin treatment does induce increased levels of globin mRNA and hemoglobin, it fails to lead to other biochemical changes associated with MEL cell differentiation induced by DMSO and thioguanine. These include increased levels of the nuclear protein IP25 and of the enzyme cytidine deaminase. Clonal analysis of hemin-treated cells revealed that unlike other inducers, hemin does not cause a reprogramming of MEL cells to a specific limitation of proliferative capacity. These observations suggest that hemin differs from DMSO and thioguanine in that it exerts specific effects on globin expression in MEL cells without triggering commitment to the terminal differentiation program.     

KRDS--a tetrapeptide derived from lactotransferrin--inhibits binding of monoclonal antibody against glycoprotein IIb-IIIa on ADP-stimulated platelets and megakaryocytes

Short peptides isolated from fibrinogen and K-casein have been shown to inhibit platelet aggregation and fibrinogen binding to stimulated platelets. We studied the effects of synthetic peptides occurring in milk proteins (bovine K-casein, KNQDK, and human lactotransferrin, KRDS) and in fibrinogen (RGDS and L10) on subsequent binding of monoclonal antibodies (MoAb) against the glycoprotein (GP) IIb-IIIa complex (AP2 and P2) on adenosine diphosphate (ADP)-stimulated and unstimulated human platelets and megakaryocytes (MKs) by using an immunoperoxidase method to visualize antibody binding. Only KRDS (900 mumol/L) inhibited the binding of AP2 and P2 on ADP (5 mumol/L)- stimulated platelets, but not on unstimulated platelets. However, the binding of P2 was considerably more inhibited than that of AP2 as judged by immunoperoxidase intensity. Radiolabeled AP2 binding was inhibited by 30% with KRDS on ADP-stimulated platelets as compared with platelets incubated in the absence of ADP. KRDS did not inhibit the binding of MoAbs against GP IIIa (SZ 21), GP IIb (SZ 22), and GP Ib (SZ 2) on ADP-stimulated human platelets. Inhibition of P2 binding by KRDS was also observed in a section of MKs isolated from human bone marrow and stimulated by 15 or 20 micron ADP. A lower concentration of ADP (5 or 10 mumol/L) failed to produce any inhibition of binding. This indicates that MKs may not be equally responsive to agonists as platelets. Moreover, P2 binding inhibition was observed in a larger (P less than .001) percentage of mature MKs (29%) as compared with younger, maturing MKs (11%). The observations suggested that a functional ability possessed by platelets, namely, agonist-induced exposure of the site of interaction of KRDS, may occur at a late stage of MK development.