供体白细胞输注治疗急慢性白血病和多发性骨髓瘤

目的　观察供体白细胞输注 (DL I)治疗急慢性白血病和多发性骨髓瘤的疗效和安全性。方法　慢性髓性白血病 (CML ) 7例 ,慢性期 (CML - CP) 5例 ,加速期 (CML - AP)和急性变 (CML - BP)各 1例 ,急性髓性白血病 (AML - m2 ) ,急性淋巴细胞白血病 (A L L )和多发性骨髓瘤 (MM)各 2例。预处理方案用去髓性和非去髓性两种。供体白细胞采用 COBE,Spectra血细胞分离机 ,回输的细胞数 (CD3 +)细胞为 (0 .6～ 3.4)× 10 7/ kg,平均细胞数 1.7× 10 7/ kg,DL I前停用免疫抑制剂。非去髓性异基因干细胞移植 (NST)患者通常在移植后每月输注 1次 ,连续 1～ 4次。对移植后或化疗、放疗后复发的患者 ,在复发的早期每月输注 1次 ,也连续 1～ 4次。结果　 4例 NST后的 CML- CP患者 DL I2次后嵌合体逐渐形成 ,其中 1例发生全血细胞减少 ,骨髓增生不良 ,经对症治疗后获得CR。 1例异基因骨髓移植后 (allo- BMT)复发的 CML- CP患者在 DL I1次后发生严重再障 ,经抢救后恢复并获CR2 ,长期生存。 1例 CML- AP及 1例 CML- BP患者 NST后虽然联合 DL I2次 ,嵌合体也未出现。 2例 NST后的A ML 患者在 DL I1次后混合嵌合体出现 ,现仍在随访中。 2例 DL I各 1次的 AL L 复发患者 (allo- BMT1例 ) (化疗及交替半身照射后复发 1例 )分别?     

非清髓性造血干细胞移植及嵌合体检测

目的评价非清髓性造血干细胞移植(NMSCT)的疗效及供受者嵌合体的检测。方法用氟达拉宾25mg/m2,-5d~-1d、马法兰140mg/m2?1d、抗胸腺细胞球蛋白15mg/(kg.d)-4d~ 5d作为预处理方案,环胞霉素3mg/(kg.d),麦考芬酸脂15mg/(kg.d)用于GVHD的预防。为17例患者做了,并对嵌合体进行检测。结果17例患者达到了早期植入,中性粒细胞恢复至0.5×109/L,中位时间为13d,血小板恢复至30×109/L,中位时间为17d。全部供者粒细胞嵌合体形成中位时间为4周,全部供者T细胞形成中位时间为8周。结论应用氟达拉宾、马法兰、抗胸腺细胞球蛋白作为非清髓性造血干细胞移植预处理方案,可获得供者早期植入,不良反应少。     

异基因造血干细胞移植治疗儿童白血病疗效观察

目的观察异基因造血干细胞移植治疗儿童白血病的疗效。方法在3例行异基因造血干细胞移植的白血病患儿中,2例行无血缘相关人类白细胞相关抗原（HLA）不全相合脐血造血干细胞移植,1例行同胞HLA全相合骨髓造血干细胞与外周血造血干细胞联合移植。移植后进行对症治疗及相关并发症的预防。结果 3例患儿均获造血重建,其中病例1在＋37d全血恢复正常;病例2在＋90d外周血供体嵌合率（STR）97.8%,脐血造血干细胞完全稳定植入。病例3在＋80d外周血STR：99.4%,造血干细胞完全稳定植入。结论异基因造血干细胞移植是一种治疗儿童白血病的较好方法,可以提高白血病患儿的长期生存率。     

异基因造血干细胞-间充质干细胞协同移植治疗急性粒细胞白血病(附2例报道)

目的探讨急性粒细胞白血病异基因造血干细胞—间充质干细胞协同移植的效果。方法培养扩增供者骨髓间充质细胞,经形态学及细胞表面分子加以鉴定,并与外周血造血干细胞协同移植给患者。结果输注供者的MSC总数分别为2×106/kg和7.7×106/kg,中性粒细胞>0.5×109/L以及血小板>20×109/L的中位时间分别是12d和14d。例1出现了Ⅰ度aGVHD,Ⅱ度cGVHD,已存活11个月;例2未出现急、慢性GVHD,现已存活6个月余。结论异基因造血干细胞-间充质干细胞协同移植可加速造血功能恢复,对GVHD的发生及严重程度有一定抑制作用,但还需加大病例数进一步观察。     

异基因造血干细胞移植治疗成人B细胞性急性淋巴细胞白血病的疗效

目的 探讨异基因造血干细胞移植(Allo-HSCT)治疗B细胞性急性淋巴细胞白血病(B-ALL)的疗效.方法 外周血Allo-HSCT治疗B-ALL 15例.预处理方案:6例为改良马利兰(BU)联合环磷酰胺(CY),9例为环磷酰胺/全身照射(TBI).预防急性移植物抗宿主病(GVHD)采用环孢霉素A、短程甲氨喋呤及霉酚酸酯(骁悉).结果 输注单个核细胞5.36-12.30×108/kg,中性粒细胞大于0.5×109/L的为10-15 d.血小板大于20×109/L的为11-16 d.6例(40.0％)发生急性GVHD,6例(40.0％)发生慢性GVHD,皆为广泛性.中位随访时间14个月(2.5-65个月),9例患者无病生存.结论 Allo-HSCT可以作为治疗成人B-ALL的有效手段.     

恶性血液病非清髓性造血干细胞移植后供者淋巴细胞输注的观察及护理

目的：探讨非清髓性移植后供淋巴细胞输注(DLI)的并发症的观察及护理，以确保DLI的安全性及疗效。方法：对5例恶性血液病非清髓性移植后形成混合性嵌合体(MC)状态后。逐渐增加输注供的T细胞剂量方案进行DLI。首次于移植后4—5周进行第1次DLI，此后在无aGTHD情况下，每隔3—4周进行1次，分离血量4000—10000ml，观察输注时尿常规，患的反应情况，输注后血象、骨髓象，嵌合体情况及GVHD发生情况。结果：输注过程仅有轻微血红蛋白尿;出现急慢性移植物抗宿主病(GVHD)和骨髓抑制。结论：无论血型相合与否，供淋巴细胞输注过程安全，GVHD和骨髓抑制为其主要两大并发症。     

成人急性淋巴细胞白血病患者异基因造血干细胞移植预后相关因素探讨

目的:回顾性分析影响成人急性淋巴细胞白血病(ALL)异基因造血干细胞移植(allo-HSCT)后疗效的相关因素。方法:选择1995年—2011年于南方医科大学南方医院血液科接受allo-HSCT的200例ALL患者,分析影响移植疗效的因素,包括年龄、免疫分型、BCR/ABL融合基因、移植前疾病状态、HLA配型、预处理方案、移植物抗宿主病(GVHD)及CsA减免和供体淋巴细胞输注(DLI)等。结果:中位随访时间为891d(367⁶ 212d),复发55例,总复发率为27.5%。死亡82例,总病死率为41.0%。单因素及Cox回归模型分析均显示具有BCR/ABL融合基因及移植时非CR状态是复发与死亡的危险因素。结论:ALL患者预后较差,allo-HSCT后复发率及病死率较高,复发与死亡的危险因素有Ph染色体和移植时非CR状态。     

自体造血干细胞移植急性髓系白血病患者的药学监护与实践1例

急性髓系白血病属于血液系统肿瘤,由于疾病本身特点或治疗相关操作,患者发生不良反应或院内感染的风险极高。笔者以1例自体造血干细胞移植急性髓系白血病患者为例,对治疗方案进行分析,为患者开展全程药学监护及相关药学服务工作,保证患者用药安全及治疗方案顺利进行。     

非T细胞去除单倍体造血干细胞移植治疗难治性白血病

目的探讨非T细胞去除(TCD)单倍体造血干细胞移植(HSCT)治疗难治性白血病的疗效及毒性反应。方法4例难治性急性髓系白血病(AML)、4例慢性粒细胞白血病(CML，伴骨髓纤维化1例、加速期2例、急单变1例)、2例难治性急性淋巴细胞性白血病(ALL)。母亲或同胞供粒细胞集落刺激因子(G-CSF)动员5d后采集骨髓或／和外周造血干细胞(HSC)，患输注CD34^ 细胞、单个核细胞(MNC)，预处理方案为司莫司汀(MeCCNC)、阿糖胞苷(Ara-C)、马利兰[Bu，ALL以全身放疗(TIB)代替]、环磷酰胺(CTX)、抗人体胸腺细胞球蛋白(ATG)。以环胞霉素A(CsA)、骁悉(MMF)和氨甲喋呤(MTX)预防移植物抗宿主病(GVHD)。结果均顺利完成预处理，出现Ⅰ～Ⅲ度黏膜炎4例，血清病样表现1例，肝功能损害5例。移植后发生急性GVHD(aGVHD)7例，达Ⅳ度3例，慢性GVHD(cGVHD)4例；并发出血性膀胱炎2例，肝静脉闭塞病(VOD)、巨细胞病毒(CMV)间质性肺炎、白质脑病各1例。均在移植后9～12d获造血重建。存活7例(6例母亲供，1例同胞供)。结论非TCD单倍体HSCT治疗难治性白血病有效，GVHD发生率高，母亲供可能更好。     

异基因造血干细胞移植治疗急性白血病

异基因造血干细胞移植治疗急性白血病杨凌李惠民杨绵本李维佳魏彩霞陈卫建梁瑞琼何争春刘青杨弘肖敏吕娅同种异基因造血干细胞移植是目前可望治愈白血病的最佳手段。我们于１９９７年初为１例急性白血病患者成功地进行了我省首例异基因骨髓移植（...     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.