慢性苯中毒致继发性骨髓增生异常综合征2例

慢性苯中毒致继发性骨髓增生异常综合征２例郝凤桐，赵培青，朱桂珍，黄敏，李继梅慢性苯中毒可以导致再生障碍性贫血、白血病或骨髓增生异常综合征（ＭＤＳ）。国内已有苯中毒引起难治性贫血（ＲＡ）和慢性粒－单核细胞白血病（ＣＭＭＬ）的报道［１～３］。我们曾收治２...     

37例慢性苯中毒患者骨髓象分析

目的：对慢性苯中毒患者骨髓象进行分析，探讨骨髓象分类及形态特点，以便提高苯中毒诊断的准确率。方法：对患者进行骨髓穿刺，选取材、涂片、染色好的骨髓片计数有核细胞200个，对其进行分类并观察细胞形态，最后按诊断标准进行分组。结果：随着轻、中、重分组变化，骨髓增生度及粒红比值减低的比例逐渐增加，骨髓异常改变的比例也逐渐增加。结论：长期接触苯及化合物可导致骨髓造血异常，骨髓象检查是苯中毒诊断的必要项目。     

慢性苯中毒100例骨髓检查报告

100例慢性苯中毒的骨髓象中,轻度增生减低81例,中度增生减低4例,轻度增生明显活跃15例;其中41例有轻重不等的细胞成熟障碍以及中毒性形态异常如毒性颗粒与空泡等。各例如骨髓细胞分类都见到中性分叶粒细胞增加,从正常的10%增加到20～30%;结合周围血液中中性粒细胞计数长期减少,表明慢性苯中毒的骨髓除了造血功能异常外,还有释放障碍。这些情况与一般再生障碍性贫血相似,但慢性苯中毒的骨髓变化较轻。     

慢性苯中毒与脾功亢进患者的骨髓象比较

本文集收确诊为慢性轻度苯中毒患者33例及经同位素检查确诊的脾功亢进患者23例的完整骨髓象资料进行分析比较。结果发现慢性苯中毒患者的骨髓增生程度较脾亢者低,并有增生受抑的表现。脾亢者红系统增生最为显著,粒系增生相对减低,粒红比例显著低于苯中毒者,苯中毒者粒系受损更重,骨髓象可见细胞老化及中毒颗粒等形态异常,脾亢患者则表现为红系统形态异常。     

骨髓增生异常综合征骨髓涂片和活检切片联合形态学分型的研究

本文于国内首次报道４４例骨髓增生异常综合征（ＭＤＳ）患者骨髓涂片结合活检切片联合形态学分型的研究结果，证明两种标本的联检较之单项检查更能可靠而正确地诊断ＭＤＳ。文章介绍了以红系受累为主的亚型（铁粒幼细胞型和类巨幼细胞型）．以髓系细胞受累为主的亚型（增殖型、原始细胞型和粒一单核细胞型）以及以基质受累为主的亚型（增生减退型、纤维增生型和炎症型）判断的形态指标及分型依据，并对这一联合分型法的优点进行了讨论。     

骨髓增生异常综合征的细胞形态学及分类诊断问题

骨髓增生异常综合征的细胞形态学及分类诊断问题河北医科大学第二医院（石家庄０５００００）姚尔固骨髓增生异常综合征（ＭＤＳ）为多能造血干细胞白血病前期克隆性疾病，血细胞生成有量与质的异常，临床表现为难治性不同系列或三系血细胞减少，骨髓有核细胞增生、有形态...     

慢性轻度苯中毒骨髓象探讨

慢性轻度苯中毒骨髓象探讨单宝荣吴学霖赵学文本文对４５例确诊为职业性慢性轻度苯中毒（下称苯中毒）患者作了骨髓穿刺检查，对骨髓细胞进行认真分析，以探讨苯中毒的骨髓分类及形态的特点，有助于提高苯中毒诊断的准确率。１材料与方法４５例确诊为苯中毒患者，从事苯作...     

慢性苯中毒和几种血液病的骨髓细胞形态学比较研究

目的 探讨慢性苯中毒患者骨髓细胞的一些形态特征。方法 采用病例对照研究，将9例慢性苯中毒患者的骨髓细胞分别和原发性骨髓增生异常综合征（MDS），慢性再生障碍性贫血（CAA）和白细胞减少症三个对照组的骨髓细胞作对比，观察在病态造血方面的差异性。结果 慢性苯中毒与MDS在红系，粒－单核系，巨核系病态造血方面的差异均无显著性（P＞0．05），无鉴别诊断价值，但较CAA，白细胞减少症在三系病态造血方面明显严重（P＜0．05），具有鉴别诊断意义。结论 慢性苯中毒在发病过程中可表现和原发性MDS相类似的骨髓病态造血，其机制有待进一步确定。     

32例慢性粒细胞性白血病骨髓象分析

目的 分析慢性粒细胞性白血病骨髓象表现,加深对该病的了解和骨髓象特点的认识.方法 观察32例慢性白血病骨髓象,对患者的骨髓增生度进行分析.结果 32例慢性粒细胞白血病患者中,29例（90.6％）外周血NAP染色积分显著下降;骨髓象27例（84.4％）核象极度活跃,5例（15.6％）活跃;29例（90.6％）粒红细胞比值升高,3例（9.4％）粒红细胞比值无特异性;而24例（75.0％）巨核细胞升高,5例（15.6％）正常,3例（9.4％）下降.结论 骨髓象总结分析是慢性粒细胞性白血病的一项基本检查,熟练掌握其特征,能为该病的早期诊断提供可靠依据.     

苯中毒患者骨髓象56例临床分析

目的 通过对56例苯中毒患者骨髓象进行分析,探讨苯对造血系统损害的骨髓象的特点.方法 按GBZ 68-2008<职业性苯中毒诊断标准>将苯中毒患者分为轻度中毒组、中度中毒组、再生障碍性贫血及全血细胞减少症组(再障组)、白血病组,均进行骨穿、涂片、以瑞氏-姬姆萨染色的骨髓片计数100个有核细胞,进行分类并观察细胞形态.结果 骨髓增生程度和巨核细胞增殖按轻度中毒、中度中毒、再障依次递减.轻度、中度中毒患者的原始和幼稚细胞增殖有受抑制的趋势,出现中毒相关的细胞形态异常.与其余各组及正常参考值比较,再障组的骨髓细胞占有核细胞百分率(早幼粒0.17%、中幼粒3.11%,早幼红0.06%、中幼红3.16%)降低,差异有统计学意义(P＜0.01,P＜0.05).白血病表现为粒系、红系幼稚细胞单克隆性增殖伴成熟障碍,巨核细胞增殖分化受明显抑制,与其余各组及正常参考值比较,白血病组的骨髓细胞占有核细胞百分率(原幼粒21.25%、早幼粒4.88%)升高、差异有统计学意义(P＜0.01).再障组、白血病组的粒细胞、红细胞出现细胞形态异常和核畸形比例增高,以白血病组尤为明显.结论 慢性苯中毒轻度、中度病例的骨髓象可见骨髓原始和幼稚细胞增殖已出现受抑制的趋势,且出现部分细胞形态异常.重度中毒骨髓象表现出与临床分型相对应的异常改变.

Abstract：

Objective To explore the bone marrow feature of hemopoietic system injured by benzene through analyzing 56 benzolism cases. Methods The 56 benzolism cases were divided into mild poisoning group, midrange poisoning group, aplastic anemia group, pancytopenia group and leukemia group. All cases progressed bone marrow aspiration and smear, and counted hundred karyocytes by Wright-Giemsa tinct bone marrow smear to classification and observe the cells' feature. Results The megakaryocytes and the extent of bone marrow hyperplasia were decreased by turns of mild poisoning group, midrange poisoning group and aplastic anemia group. The archaeocytes and juvenile cells proliferation in mild poisoning group and midrange poisoning group were inhibited and occured cell paramorphia which related to intoxication. Comparing with the other groups and mormal reference value, the pancytopenia group' s percentage of bone marrow cells in karyotes was significantly decreased (P＜0.01. P＜0.05) and the leukemia group's pecentage of bone marrow cells in karyotes was significantly increased (P＜0.01). The proportion of cell paramorphia and nucleus malformation of granulocytes and red blood cells in pancytopenia group and leukemia group were increased, expecially in leukemia group. Conclusion We saw the inhibition of archaeocytes and juvenile cells proliferation and somecell paramorphia appearances in mild poisoning and midrange poisoning cases of chronic benzolism. The abnormality changes which can be seen in bone marrow of severe benzolism cases were corresponding with the clinical classification.     

重度苯中毒骨髓检查及其临床诊断价值的研究

目的探讨骨髓涂片及活检对重度苯中毒的诊断和鉴别诊断意义.方法对46例重度苯中毒进行骨髓穿刺,取骨髓液及活体组织进行研究.结果 46例有23例骨髓像符合再生障碍性贫血(AA)的典型表现,11例为可疑AA.苯中毒患者的骨髓涂片中粒红比值、巨核细胞数量随着骨髓增生程度降低而降低.结论骨髓活检结合涂片检查对苯中毒的病情及诊断可作较为全面的综合评价.     

苯中毒性再生障碍性贫血患者外周血网织血小板水平观察

目的探讨苯中毒性再生障碍性贫血(BPAA)患者外周血网织血小板(RPs)的变化规律.方法采用流式细胞仪技术测定47例BPAA患者外周血RPs的比例和绝对值,观察RPs在BPAA中的变化规律,并与30例健康对照组进行比较.结果苯中毒性急性再生障碍性贫血(ABPAA)患者外周血中RPs百分率及绝对计数均低于正常对照组(P＜0.05);苯中毒性慢性再生障碍性贫血(CBPAA)患者外周血中RPs百分率与正常对照组差异无显著性(P＞0.05),而RPs绝对计数低于正常对照组,差异有显著意义(P＜0.05).CBPAA和ABPAA组之间RPs百分率及绝对计数差异有显著性(P＜0.05).RPs绝对计数与BPC计数间呈正相关(r＝0.74).治疗有效的患者在外周血象开始好转前,首先出现RPs%上升.22例ABPAA患者按疗效分成治疗有效组和治疗无效组,治疗有效组患者的RPs%及RPs绝对计数均明显高于治疗无效组,差异有显著意义(P＜0.05).结论在BPAA患者中,RPs%及RPs绝对计数的水平间接地反映了苯对骨髓的损害程度,并可作为预测其疗效的有用指标.     

苯中毒再生障碍性贫血患者骨髓细胞免疫功能和Fas、CD34抗原变化

目的　探讨细胞免疫功能、Fas和CD3 4抗原与苯中毒再生障碍性贫血发生、发展及转归的关系。方法　用流式细胞仪检测2 4例苯中毒再障(BPAA)和16例无苯制剂接触史的再障(AA)患者治疗前后骨髓单个核细胞Fas、CD3 4的表达率和T细胞亚群变化。结果　苯中毒再生障碍性贫血和再障患者骨髓单个核细胞Fas表达率显著增高(P <0 . 0 0 1) ,CD3 4阳性率明显降低(P <0 . 0 0 1) ;CD3 + CD8+ T淋巴细胞明显升高(P <0 . 0 5 ) ,CD4+ /CD8+ 比值明显降低(P <0 . 0 0 1) ;治疗缓解后Fas、CD3 4阳性率、CD3 + CD8+ T淋巴细胞和CD4+ /CD8+ 比值趋于正常(P >0 . 0 5 )。但在AA组Fas、CD3 4阳性率和CD4+ /CD8+ 比值较正常对照组差异仍有显著性。两组再障患者之间比较差异无显著性。结论　细胞免疫功能紊乱、Fas抗原的异常表达和CD3 4+ 干/祖细胞损伤,可能与苯中毒再生障碍性贫血病理发病机制有关,用环孢霉素A治疗可能有效。     

异基因外周血干细胞移植治疗苯中毒性再生障碍性贫血

目的　研究异基因外周血造血干细胞移植治疗苯中毒致重型再生障碍性贫血 (SAA)。方法　用HLA配型全相合的女性供者异基因外周血造血干细胞移植 (Allo PBSCT)治疗 1例苯中毒致SAA男性患者。输入单个核细胞数为 9.4 1× 10 8 kg、CD34 阳性细胞为 12 .4 9× 10 6 kg、粒 -巨噬细胞系祖细胞集落数为 8.2× 10 5 kg。预处理方案由环磷酰胺加全身照射和抗淋巴细胞球蛋白组成 (环磷酰胺总量 12 0mg kg ,全身照射为 8Gy ,抗淋巴细胞球蛋白总量 6 0mg kg)。为防止植入失败 ,移植后第 18天再次输入供者白细胞层 ,其中单个核细胞数为 9.0 2× 10 8 kg、CD34 阳性细胞为 10 .6 2× 10 6 kg、粒 -巨噬细胞系祖细胞集落数为 6 .3× 10 5 kg,并用环孢菌素A和甲氨蝶呤预防移植物抗宿主病。结果　输入单个核细胞后白细胞最低值为 0 ,血小板最低值为 3× 10 9 L ;中性粒细胞于移植后第 2 1天开始大于0 .5× 10 9 L ,血小板于移植后第 2 8天开始大于 5 0× 10 9 L。移植后第 4个月出现皮肤局限性慢性移植物抗宿主病。受者染色体转为 4 6 ,XX ;ABO血型由B型转为O型。结论　此例为国内首例采用Allo PBSCT治疗苯中毒致SAA并获得成功 ,为苯中毒治疗开辟了新的途径。     

cDNA微阵列结合聚类分析探讨苯中毒免疫相关基因表达谱的改变

目的通过基因表达谱研究寻找苯中毒发病机制中参与苯中毒免疫调控通路的苯中毒免疫相关基因。方法应用含2779条免疫相关基因的cDNA芯片检测7例苯中毒患者和7例正常人的外周血白细胞基因表达谱，观察其在基因表达谱上的差异。进行了基因表达谱聚类分析和比较；筛选有统计学意义的差异表达的免疫相关基因。结果存在差异表达的基因共有38条。在2张以上芯片结果中表达上调的基因10个，主要包括有CD59、TRA@、MCP等。在2张以上芯片结果中表达下调的基因14个，有HLA—DMB、HLA—DQA1、HLA—DPB1、ITGB2、PFC等基因。聚类分析揭示38条基因的基因表达谱特征存在关联。结论通过有统计学意义的差异表达的苯中毒免疫相关基因，推测免疫调控通路在苯中毒发病中可能扮演重要角色。基因芯片技术是分析不同研究对象之间基因差异表达的有效手段。     

Hematopoietic stem-cell transplantation in aplastic anemia

Severe aplastic anemia is a rare syndrome characterized by bone marrow failure with cytopenias and hypocellular bone marrow biopsy (usually 10-15%), without blasts or myelodysplasia. The first choice treatment for these patients is allogeneic bone marrow transplantation from a sibling matched for HLA-A, HLA-B and HLA-DR. Unfortunately only 30% of patients have an HLA-matched sibling (a 25% chance per sibling). The alternative treatment for severe aplastic anemia for the rest of the patients (70%) is immunosuppression with antithymocyte globuline and cyclosporine. The evolution of bone marrow transplantation since 1970's has been positive in terms of survival and transplant success (initial overall survival 43% vs. 90% lately, and graft rejection of 29% vs. 4%). The favorable outcome of bone marrow transplantation for severe or very severe aplastic anemia is due to: the use of conditioning with antithymocyte globuline and cyclophosphamide, the use of graft-vs.-host disease prophylaxis with short curse methotrexate and cyclosporine and the use of filtrated and irradiated blood products. For those patients without an HLA-matched related donor the first treatment to use is the immunosuppression with antithymocyte globuline and cyclosporine. Another option emerged in the late 80's is the unrelated bone marrow transplantation, with survival hardly half of the HLA-identical related bone marrow transplants. In our country, the first allogeneic bone marrow transplant was done in the Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, in a patient with aplastic anemia, making possible to perform this procedure safely in our country.     

研究环孢菌素A对再障病患骨髓细胞Fas表达及凋亡率的影响

目的：研究环孢菌素A（CsA）对再生障碍病患骨髓细胞Fas表达及凋亡率的影响。方法：从2010年2月-2013年2月,本院共计48例病患被确诊为再障。以数字法随机分成观察组24例和对照组24例,对照组以注射用丹参治疗,观察组在此基础上另以CsA治疗。对比两组疗效,分析CsA对于再障病患骨髓Fas表达情况和对MNC有关凋亡率影响。结果：观察组总有效率为83.33%（20/24）,显著高于对照组的37.50%（9/24）,比较差异有统计学意义（P〈0.05）。两组在治疗前后CD34＋Fas＋的细胞百分率相比,差异无统计学意义。观察组病患骨髓CD34-细胞的Fas表达和对照组相比,差异无统计学意义。观察组治疗后MNC有关凋亡率为（2.27±0.74）%,显著低于治疗前的（6.58±2.33）%,以及对照组治疗后的（2.92±1.20）%,比较差异均有统计学意义（P〈0.05）。结论：细胞Fas异常表达和再障发病情况有一定联系,以CsA治疗再障病患,可明显降低其骨髓MNC凋亡率,疗效显著,值得临床推荐。     

基因芯片检测与苯中毒相关的信号传导通路中基因的差异表达

目的检测苯中毒信号转导相关基因的表达，探讨苯引起的血液系统损害的发病机理。方法应用含4265条信号转导基因的cDNA芯片检测7例苯中毒患者和7例无苯接触的正常人的外周血白细胞基因表达谱，观察其在基因表达谱上的差异。进行了基因表达谱聚类分析。结果在4265条基因中，存在明显差异表达的基因176条。至少在六张芯片结果中有显著性表达上调的基因35个，主要包括有PTPRC、STAT4、IFITM1等。至少在5张芯片结果中有显著性表达下调的基因45个，主要包括有ARHB、PPP3CB、CDC37等。结论微矩阵基因芯片在检测苯中毒信号转导相关基因的改变时．具有快速、高通量、高灵敏度等特点．细胞信号转导的障碍在苯中毒发病中起一定的作用。     

Chemical of current interest--benzene

Benzene is one of the world's major commodity chemicals. It is derived from petroleum and coal and is used both as a solvent and as a starting material in chemical syntheses. The numerous industrial uses of benzene over the last century need not be recounted here, but the most recent addition to the list of uses of benzene is as a component in a mixture of aromatic compounds added to gasoline for the purpose of replacing lead compounds as anti-knock ingredients. The best known and longest recognized toxic effect of benzene is the depression of bone marrow function seen in occupationally exposed individuals. These people have been found to display anemia, leucopenia, and/or thrombocytopenia. When pancytopenia, i.e., the simultaneous depression of all three cell types, occurs and is accompanied by bone marrow necrosis, the syndrome is called aplastic anemia. In addition to observing this decrease in humans and relating it to benzene exposure, it has been possible to establish animal models which mimic the human disease. The result has been considerable scientific investigation into the mechanism of benzene toxicity. Although the association between benzene exposure and aplastic anemia has been recognized and accepted throughout most of this century, it is only recently that leukemia, particularly of the acute myelogenous type, has been related to benzene. The acceptance of benzene as an etiological agent in aplastic anemia in large measure derives from our ability to reproduce the disease in most animals treated with sufficiently high doses of benzene over the necessary time period. Unfortunately, despite extensive efforts in several laboratories, it has not been possible to establish a reproducible, reliable model for the study of benzene-induced leukemia. The recent demonstration that several animals exposed to benzene either by inhalation or in the drinking water during studies by Drs. B. Goldstein and C. Maltoni suggests that such a model may be forthcoming. Nevertheless, at this time it is not clear whether bone marrow damage of the type that leads to aplastic anemia is required for the development of leukemia. Most studies of benzene toxicity have involved dosing animals with benzene either by inhalation or by injection, using high doses to ensure a toxic response. Very few studies have concentrated on the oral route of administration and none have concentrated on administering benzene by mouth at the low doses occasionally detected in drinking water.(ABSTRACT TRUNCATED AT 400 WORDS)