单次与两次自体造血干细胞移植治疗血液肿瘤的远期结局比较：150例资料回顾

目的:对没有与供者HLA配型相合的血液恶性肿瘤患者来说,自体造血干细胞移植不失为一种积极有效的治疗方法。评价比较单次与两次自体造血干细胞移植治疗血液肿瘤的效果。方法:①实验对象:选取1988～2001年解放军总医院血液科行自体造血干细胞移植的150例患者,对本实验均知情同意。其中两次自体移植25例(两次骨髓移植3例、两次外周血造血干细胞移植1例、1次骨髓移植 1次外周血造血干细胞移植21例),单次自体移植125例(骨髓移植44例、外周血造血干细胞移植81例);急性非淋巴细胞白血病75例,急性淋巴细胞白血病43例,非霍奇金淋巴瘤22例,霍奇金淋巴瘤10例。②实验方法:应用化疗使白血病患者在移植前达到完全缓解,淋巴瘤患者要求移植前至少骨髓中没有肿瘤累及。动员化疗方案原则上采用对相应肿瘤有效的联合化疗方案,并适当增加剂量。骨髓移植及外周血造血干细胞移植患者回输单核细胞中位数分别为2.68×108/kg,4.20×108/kg。115例患者采用环磷酰胺/全身放疗方案,35例患者采用不含全身放疗的高剂量化疗方案。③实验评估:自体造血干细胞移植5年后血液肿瘤患者的无病存活率。结果:①急性非淋巴细胞白血病:69例患者单次移植,5年无病存活率58.0%(40例),复发率29.0%(20例),移植相关死亡率13.0%(9例)。6例患者两次移植,其中1例M5患者复发死亡,5例无病存活。②急性淋巴细胞白血病:29例患者单次移植,5年无病存活率34.5%(10例),复发率34.5%(10例),移植相关死亡率31.0%(9例)。14例患者两次移植,5年无病存活率42.9%。③非霍奇金淋巴瘤:18例患者单次移植,5年无病存活率61.1%(11例),复发率16.7%(3例),移植相关死亡率22.2%(4例)。4例患者两次移植,其中1例CR1期患者在首次移植后21个月复发,化疗获得PR后行第2次自体造血干细胞移植,17个月后复发死亡;其余3例均无病存活。④霍奇金淋巴瘤:9例患者单次移植,5年无病存活率100%。1例患者行两次移植,首次移植前13个化疗疗程未缓解,行自体外周血造血干细胞移植后达到部分缓解,9个月后行自体骨髓移植后完全缓解,无病存活。结论:①自体造血干细胞移植是治疗血液肿瘤安全有效的方法。②自体造血干细胞两次移植5年无病存活率明显优于单次移植效果,可改善血液肿瘤患者预后。     

Absence of HIV-1 infection in antibody-negative sexual partners of HIV- 1 infected hemophiliacs

In order to confirm the presence and determine the frequency of human immunodeficiency virus, type 1 (HIV-1) infection prior to antibody production, 23 healthy women with histories of repeated unprotected sexual exposure to HIV-1 infected hemophiliacs were tested for evidence of HIV-1 infection. Female subjects were tested for HIV-1 antibody (enzyme immunoassay [EIA] and Western blot), HIV-1 serum antigen, HIV-1 DNA gag sequences by the polymerase chain reaction, and HIV-1 virus isolation from peripheral mononuclear cells. Twenty-two of 23 (96%) women were negative by all HIV-1 assays. One woman was positive by all the HIV-1 assays including an EIA screening test for HIV-1 antibody. These preliminary results suggest that the frequency of HIV-1 infection in antibody-negative sexual partners of HIV-1 infected individuals is probably very low.     

Idiopathic pulmonary ossification

Idiopathic pulmonary ossification is an uncommon and asymptomatic disorder of unknown etiology in which trabeculated bone is found in the lung. It is usually mistaken for more serious entities radiographically, most commonly appearing as branching linear shadows of calcific density involving a limited area of the lung and exhibiting very slow progression; however, the shadows may be round or irregular and bulky. Sometimes the trabeculae are recognizable, and occasionally the lungs demonstrate widespread involvement. The authors describe 8 proven cases, including one in which a bone scan revealed uptake by heterotopic bone in the lung.     

Comparison of DNA adduct formation by aristolochic acids in various in vitro activation systems by 32P-post-labelling: evidence for reductive activation by peroxidases

Aristolochic acid I (AAI) and aristolochic acid II (AAII), the two major components of the carcinogenic plant extract aristolochic acid (AA), are known to be mutagenic and to form DNA adducts in vivo. According to the structures of the major DNA adducts identified in animals and humans, nitroreduction is the crucial pathway in the metabolic activation of these naturally occurring nitroarenes to their ultimate carcinogenic species. Using the nuclease P1-enhanced version of the 32P-post-labelling assay we investigated the formation of DNA adducts by AAI and AAII in different in vitro activation systems in order to determine the most suitable in vitro system mimicking target tissue activation. Although DNA adducts resulting from oxidative activation of AAs have not yet been identified both reductive and oxidative in vitro systems were employed. In vitro incubations were conducted under standardized conditions (0.3 mM AAs; 4 mM dNp as calf thymus DNA) using rat liver microsomes, xanthine oxidase (a mammalian nitroreductase), horseradish peroxidase, lactoperoxidase and chemical reduction by zinc. Enzymatic incubations were performed under aerobic and anaerobic conditions. A combination of two independent chromatographic systems (ion-exchange chromatography and reversed-phase HPLC) with reference compounds was used for the identification of DNA adducts detected by the 32P-post-labelling assay. The two known major adducts of AAI or AAII found in vivo were generated by all in vitro systems except for incubations with AAII and horseradish peroxidase where two unknown adducts predominated. Irrespective of the in vitro activation system used, the majority of adduct spots obtained were identified as the previously characterized four AA-DNA adducts: dA-AAI, dA-AAII, dG-AAI and dG-AAII. This indicates that both reductive and peroxidative activation of AAI or AAII resulted in chromatographically indistinguishable DNA adducts. Thus, peroxidase mediated activation of AAs led to the formation of the same adducts that had been observed in vivo and upon reductive activation in several in vitro systems. Quantitative analyses of individual adducts formed in the various in vitro systems revealed relative adduct labelling (RAL) values over a 100,000-fold range from 4 in 10(3) for activation of AAII to deoxyadenosine adducts by zinc to only 3 in 10(8) for activation of AAII by lactoperoxidase. The extent of DNA modification by AAI was higher than by AAII in all enzymatic in vitro systems. Only activation by zinc resulted in higher total binding to exogenous DNA by AAII than by AAI. Aerobic incubations with rat liver microsomes generated AAI- and AAII-DNA adduct profiles reproducing profiles in target tissue (forestomach) of rats, thus providing the most appropriate activation among the in vitro systems tested.      

Tumor markers in patients with advanced breast cancer as prognosticators: A preliminary study

Summary A retrospective study was performed on 69 breast cancer patients (stage II, N=18; advanced disease, N=51) in order to assess the prognostic value of circulating prolactin (PRL), CEA, CA 15-3, insulin-like growth factor-1 (IGF-1), and epidermal growth factor (EGF) by RIA/IRMA. These markers were compared with short-term prognosis (two years). Significant difference was observed only for PRL (<20.0 ng/ml vs. >20.0 ng/ml), which provide an independent predictor of short-term prognosis in advanced breast cancer.     

兔骨髓间充质干细胞构建组织工程化海绵体尿道的可行性

目的:探索以骨髓间充质干细胞为种子细胞构建组织工程化海绵体尿道的可行性。方法:实验于2004-11/2006-03在中山大学第二附属医院医学科研中心完成。①参照张金明等报道的方法,制备脱细胞尿道海绵体-尿道基质,并行组织学检查观察脱细胞效果。②分离兔骨髓间充质干细胞,鉴定其表型,体外培养增殖后种植于兔脱细胞尿道海绵体-尿道基质上。③48只兔随机均分为实验组、对照组,每组24只。实验组用种植有干细胞的脱细胞基质即组织工程尿道修复部分切除的兔海绵体尿道,对照组组仅用脱细胞基质修复。④术后观察动物排尿情况,并于术后1,2,4,8,12,24周切取标本,看有无狭窄及腔面一般性状并行组织学检查,比较两者差异。结果:两组共48只兔全部进入结果分析。①自行制备的组织工程支架和种子细胞鉴定结果:所制备脱细胞基质质地柔软,镜下未见细胞成份;分离培养的细胞表型为CD45阴性,CD166,CD29,CD105阳性,符合骨髓间充质干细胞特征。②术后动物及标本一般观察:实验组术后2周时发现1例尿瘘;对照组2周时发现1例尿瘘,8,12,24周时分别发现各1例尿道狭窄。其余实验动物在拔除导尿管后排尿通畅。③两组兔再造尿道组织学检查结果:实验组自术后2周开始,组织学检查见血管和平滑肌逐渐增多;24周时,尿道腔面光滑,可见和正常尿道海绵体类似的组织结构。对照组自2周起可见血管,4周起可见平滑肌再生,24周时血管和平滑肌形成仍较少,较多纤维瘢痕,且无窦样组织形成,再造尿道腔面不如实验组光滑。结论:以骨髓间充质干细胞为种子细胞,脱细胞尿道海绵体为基质,构建组织工程化尿道海绵体,移植修复兔海绵体尿道缺损,可形成类似于正常尿道海绵体的组织结构。     

经椎弓根人工骨植入并后路椎弓根钉内固定材料置入治疗胸腰椎爆裂骨折

目的:加用后路植骨融合减少并发症是国内外学者均认可的有效方法,使用中大多数为横突间植骨或椎间植骨,其植骨融合率不高,术后仍然存在丢失矫正角度的问题。拟验证采用椎弓根钉系统内固定材料置入配合人工骨经椎弓根植入在预防无神经损伤的胸腰椎爆裂性骨折术后并发症中的作用和应用价值。方法:①实验对象:于2004-03/2007-02吉林医药学院附属医院骨科采用后路椎弓根钉系统撑开复位内固定材料置入并用经椎弓根植入人工骨治疗无神经症状的胸腰椎爆裂性骨折患者26例。男15例,女11例,年龄22～岁,平均45岁。合并有骨质疏松688例。CT示椎体后壁不完整并有碎骨块压迫硬膜囊,椎管变窄20%～50%。经X射线片判定均有脊柱后凸畸形;术前Cobb角6°～30°,平均26°。术前伤椎前缘压缩率50%～70%,平均60%;后缘压缩10%～15%,平均11.5%。26例均为单一椎体损伤,损伤椎体:T1210例,L112例,L24例。②实验材料:椎弓根钉系统使用国产创伤钉系列,人工骨使用美国生物材料公司生产的Nova Bone,商品名固骼生,具有良好的组织相容性,可完全生物降解,机械强度高等优点;其成骨速度快,应用在骨缺损上能即刻增加骨强度,短时间内可产生大量新生骨,促进骨愈合,是一种较好的植骨材料。③实验评估:CT与X射线片评估Cobb角和椎体压缩率改善状况,是否存在矫正角度丢失及Nova Bone吸收降解状况,有无不良反应。VAS评分标准评估脊柱活动度,腰背痛及下肢痛情况。结果:26例患者术后疼痛均明显缓解,椎体高度和形态得到明显恢复,Cobb角平均改善11.5°,椎体压缩率改善50%。Nova Bone比较均匀分布于伤椎骨缺损间隙中,无泄漏现象发生。经平均20.5个月随访,疼痛均消失,骨折均达到满意复位并骨性愈合,Nova Bone均完全降解,无Cobb角明显加大,未发现明显并发症。结论:后路椎弓根钉系统固定材料置入加经椎弓根植入人工骨能即时增加椎体的骨容量和脊柱前柱的抗压稳定性,减少内固定因应力过大造成的断钉、断杆、椎体再压缩等并发症,是一种治疗胸腰椎爆裂性骨折预防矫正丢失的有效方法。     

Thyrotoxic periodic paralysis in a Chinese population

We retrospectively evaluated the characteristics of adult patients admitted with thyrotoxic hypokalaemic periodic paralysis in Hong Kong. From 1984 to 1993, 45 Chinese adult patients were admitted with acute limb weakness, plasma potassium &les;3.5 mmol/l and thyrotoxicosis confirmed by laboratory investigations. All but one were male. Seventy-five percent of attacks occurred between 9pm and 9am. Half of the attacks occurred between July and October (49.1%), most commonly in August (20%). Mean (+SEM) plasma potassium on admission was 2.17 &plusmn; 0.08 mmol/l (range 1.1-3.5). In 15 episodes (27.3%), plasma potassium on recovery exceeded 5.0 mmol/l, while in three episodes (5.5%), potassium exceeded 6.0 mmol/l. No patient had a positive family history of thyrotoxic periodic paralysis. Only 28.9% had a known history of thyrotoxicosis before their first presentation with periodic paralysis. Twenty-seven (60%) had clinical evidence of thyrotoxicosis. Although all were biochemically thyrotoxic, 11.4% had only a mild degree of thyrotoxicosis (suppressed thyroid-stimulating hormone, high free thyroxine, but normal free triiodothyronine). One quarter of the patients had a normal erythrocyte zinc concentration, indicating either a short history of thyrotoxicosis or transient thyrotoxicosis. The diagnosis of thyrotoxic hypokalaemic paralysis should always be considered in Chinese patients with acute muscle weakness, especially in young males. Absence of clinical thyrotoxicosis does not exclude the diagnosis. Plasma potassium should be monitored carefully during treatment to prevent rebound hyperkalaemia.