骨髓增生异常综合征患者染色体核型及两种治疗方案的比较分析

目的 探讨骨髓增生异常综合征(myelodysplastic syndromes,MDS)患者的细胞遗传学特点及其对预后的影响,观察地西他滨3 d和5 d方案治疗骨髓增生异常综合征(MDS)的临床疗效及安全性。方法 回顾性分析48例MDS患者的临床资料,探讨所有患者的染色体核型与预后的关系。观察比较两组方案各完成2个疗程治疗的MDS患者的疗效与不良反应。其中3 d方案患者20例,地西他滨每天45 mg·m-2,QD,静脉滴注,连用3 d,28 d为一个疗程。5 d方案患者28例,地西他滨每天20 mg·m-2,QD,静脉滴注,连用5 d,28 d为一个疗程。结果 48例患者中20例检出异常染色体核型,占所有患者的41.67%,其中难治性贫血伴原始细胞增多1型及2型异常染色体核型检出率较高。据IPSS-R积分系统分组,危险分层越高,异常染色体核型检出率越高(P<0.05),转化为急性白血病的概率越高。3 d方案组总反应率为30%,5 d方案组总反应率为46.43%,差异无统计学意义(P>0.05)。不良反应主要表现为骨髓抑制、感染、出血,其中3 d方案组和5 d方案组比较,差异有统计学意义(P＜0.05),前者均高于后者。结论 染色体核型分析对MDS的诊断及预后判断具有重要价值。5 d方案较3 d方案治疗MDS具有相似的有效率,但其具有明显较低的不良反应发生率,5 d方案更值得推广。     

急性白血病细胞遗传学改变与临床预后关系的探讨

目的应用细胞遗传学分析方法研究急性白血病(AL)染色体异常特征,结合临床评价细胞遗传学对AL诊治和判断预后的价值.方法采用直接法和短期培养法制备骨髓细胞染色体,并以R显带为主、G显带为辅对76例AL患者进行染色体核型分析,并观察疾病的诊治及转归情况.结果 76例急性白血病细胞核型异常检出率为 55%(42/ 76),初发病例异常核型31例,检出率61%(31/51),缓解病例异常核型5例,检出率31%(5/16);对52例患者随访中发现:核型正常16例,其中13例(81%)达缓解,2例(15%)复发;核型异常36例中22例(61%)达缓解,8例(36%)复发(P<0.05),核型正常组缓解率明显高于核型异常组,复发率明显低于核型异常组;核型正常、超二倍体及t(15;17)易位者疗效较好 ,而伴-7/7q-、t(9;22)、t(4;11)、t (9;11)、t(1;19)易位者疗效较差;缓解期染色体仍为异常核型者常复发,继发性染色体改变常预示病情恶化.结论半数以上AL患者可检出克隆性染色体异常且主要为特异性染色体重排,它们和特定的FAB亚型相关;细胞遗传学改变与预后的关系密切,是影响白血病预后的独立性因素.     

不同亚型骨髓增生异常综合征患者染色体核型异常研究

<正>骨髓增生异常综合征(myelodysplastic syndromes,MDS)是一类异质性的造血系统疾病,表现为骨髓衰竭、外周血细胞减少和易于向急性髓细胞白血病(AML)转化。大约有近50%的患者存在克隆性的细胞遗传学异常。本文收集2009年4月至11月23例原发性MDS的患者资料,根据不同亚型各组患者染色体核型异常的比例进行相关研究,综合评价不同亚型MDS患者染色体核型分布情况。     

14例骨髓增生异常综合征的染色体研究

目的 探讨骨髓增生异常综合征（MDS）染色体改变的临床意义。方法 采用骨髓细胞短期培养G显带染色。结果 14例MDS中，9例检出染色体异常核型，占64.2%，其中MDS-RA2例，占14.2%，MDS-RAEB和MDS-RAEB-t共7例，占50%，后者发现有复杂染色体核型变化。结论 MDS的细胞遗传学与诊断和鉴别诊断，分型、转白及预后密切相关。     

40例骨髓增生异常综合征染色体核型及凋亡

目的 探讨不同类型骨髓增生异常综合征(MDS)患者骨髓染色体核型和凋亡现象及其机制.方法 采用骨髓短期培养和G显带技术对40例MDS患者进行染色体核型分析,钙磷脂结合蛋白(Annexia-V)-FITC标记药物骨髓单个核细胞,了解其早期凋亡的情况,逆转录-PCR分析自杀相关因子(Fas)和凋亡抑制蛋白(survivin,生存素)mRNA表达变化.结果 20/40例MDS患者检出染色体异常,其中难治性贫血(RA)7/20例(35%),RA伴有环状铁幼粒细胞(RARS)1/2例(50%),RA伴多系发育异常(RCMD)5/8例(62.5%),RA伴原始细胞增多(RAEB)7/10例(70%);国际预后评分系统(IPSS)1年白血病转化率为低危组5%(1/20),中危1、2组25%(3/12),高危组75%(6/8),各组间差异有统计学意义(P＜0.05);骨髓单个核细胞凋亡MDS患者高于10例正常体检者(对照组),从低危组到高危组凋亡减少,生存素基因mRNA表达增加,Fas mRNA表达下降.结论 染色体核型分析在MDS的预后评估中有重要价值;MDS从低危组到高危组凋亡减少,可能与生存素、Fas基因表达有关.     

49例骨髓增生异常综合征的细胞形态学和细胞遗传学分析

目的分析骨髓增生异常综合征(MDS)的形态学和细胞遗传学特征。方法将2012年~2014年本院确诊的49例MDS临床和血液学特征进行回顾性分析。结果 MDS病例的血涂片及骨髓涂片中粒、红、巨三系均存在不同程度的病态造血,在可供细胞遗传学分析的31例患者中,染色体核型异常检出率为51.6%(15/31例),其中单一异常53.3%(8/31),两种异常33.3%(5/31),复杂异常13.3%(2/31),最常见的克隆性异常是+8,其余依次为-7/del(7q),5q-/del(5)(q13),5q-/del(5)(q22q35),5q-/del(5)(q11q15),del(20)(q11),del(18)(q21),+16(q24)),-6,-15,-17,+21(p11)。结论细胞形态学是MDS最重要、最基础的诊断手段,细胞遗传学是MDS的确诊条件之一,同时,也是判断预后以及制定治疗策略的主要依据。     

急性白血病患者的染色体核型分析及临床意义

目的结合细胞形态学、免疫学探讨染色体核型在急性白血病(AL)中的诊断、治疗价值。根据国内外细胞遗传学危险度划分标准,分析核型与完全缓解率(CR)的相关性。方法采用短期培养法处理骨髓样本,并以R显带为主,G显带为辅,对119例初诊的AL患者进行染色体核型分析,并观察患者CR与染色体核型分析之间的关系。结果患者核型率异常在急性髓细胞白血病(AML)、急性淋巴细胞白血病(ALL)中分别为58.11%、53.33%,平均异常率为56.30%,AML患者中最常见的平衡易位为46,XY,t(15;17)(q22;q21),占所分析患者的19.33%(23/119),且仅在M3中检测到,其次是t(8;21)(q22;q22),占10.08%(12/119)。在ALL患者中最常见的为t(9;22)(q34;q11),且多见于B-ALL,占6.72%。119例患者中首次化疗CR达71.43%,特异性染色体核型的患者CR较高。结论染色体检查技术结合细胞形态学、免疫表型分析对于白血病的准确诊断、靶向治疗、评估预后具有重要意义。     

高危骨髓增生异常综合征PTEN基因异常表达的临床意义

目的观察高危骨髓增生异常综合征（MDS）患者骨髓细胞中PTEN表达情况,探讨其在高危MDS患者临床病理意义以及与疾病转归的关系（相关性）,初步评价其对高危MDS的临床意义和判断预后的指导作用。方法采用免疫组化方法（S-P法）检测高危MDS 25例、良性血液病24例（对照组）患者的骨髓（病理石蜡切片）细胞中PTEN表达情况,并对25例高危MDS的治疗反应及疾病转归进行随访。结果高危MDS的PTEN阳性表达率为56.00%;对照组为90%;两者间差异有非常显著性（P〈0.01）。以PTEN表达水平标本积分判定≥3分为标准,设高表达组和低表达组：高表达组8例,低表达组17例。高表达组治疗反应率（有效率）62.50%（5/8例）;低表达组治疗反应率（有效率）47.06%（8/17例）,两者之间差异有显著性（P〈0.05）。25例高危MDS均行染色体核型分析,其中异常9例;正常16例;PTEN的表达水平与染色体核型异常无相关性。转急性白血病（MDS-AL）高表达组3/8例（37.50%）;低表达组11/17例（64.71%）。结论高危MDS存在PTEN基因表达的异常,PTEN表达与治疗反应有相关性,PTEN对于高危MDS的预后判断有一定的意义。     

慢性粒细胞白血病染色体核型分析及临床意义

目的:探讨细胞遗传学分析方法研究慢性粒细胞白血病(CML)染色体异常特征及其临床意义.方法:对70例骨髓或外周血细胞采用短期培养法(24～48小时)制备染色体,以G显带进行核型分析,并观察接受治疗后患者的临床转归.结果:70例CML患者中,66例检出典型Ph染色体(94.29%),6例伴有染色体数目异常(8.57%),其中6例出现复杂易位(8.57%),4例出现附加染色体异常(5.71%).染色体数目异常预后较差.结论:CML患者进行染色体分析对于疾病的诊断、临床治疗、判断预后具有重要意义.     

男性不育的细胞遗传学分析

目的探讨男性不育与染色体异常的关系。方法对108例男性不育患者进行外周血染色体核型分析。结果细胞遗传学分析染色体异常占24.1%,其中性染色体异常19例,占染色体异常核型73.1%;常染色体异常7例,占染色体异常核型26.9%。结论染色体异常是男性不育的重要原因之一。对男性不育患者进行遗传咨询及遗传检测十分必要。     

急性骨细胞白血病CD11b表达的临床意义

目的　研究急性髓细胞白血病（AML）CD11b表达的临床意义。方法　采用碱性磷酸酶抗碱性磷酸酶复合物法（APAAP）,测定80例AML患者细胞膜表面CD11b的阳性表达。结果　CD11b     

代谢综合征多元医学参考值标准的应用

目的 探讨多指标组合指标法制定的代谢综合征(MS)多元医学参考值标准的应用.方法 以2008年6月至12月在汕头大学医学院第一附属医院行健康体检的居民为研究对象,收集体检相关数据,随机抽取资料完备的1204例,分别采用多元医学参考值标准、2007年<中国成人血脂异常防治指南>(防治指南)以及2005年美国国家胆固醇教育计划成人治疗组第三次报告修订版(ATP III)制定的MS诊断标准计算该人群MS的患病率,分析各定义下诊断MS的差异和一致性.结果 应用多元参考值、防治指南和ATPⅢ三种标准计算人群MS的标化患病率分别为9.9%、9.3%和14.8%(P<0.01);男性患病率(分别为10.5%、11.0%和15.1%)高于女性(分别为8.7%、5.8%和13.1%,P<0.01).多元参考值标准下该人群血压异常率为32.6%,低于防治指南和ATPⅢ标准的检出率(均为45.1%);在诊断为MS的人群中,多元参考值对肥胖的检出率最高(78.7%).多元参考值与防治指南以及ATPⅢ的检出结果一致性较好,Kappa系数分别为0.759和0.715(P<0.01).结论 多元参考值标准分别提出了适合男性和女性MS的诊断标准,对MS各指标检出率有其特点,适用于该地区人群MS的诊断.

Abstract：

Objecttve To investigate the application of the reference value criterion for metabolic syndrome (MS)established by the multivariate combination indicatrixes method.Methods The data of participants was collected In the chronic disease monitoring site built by the First Afflicted Hospital of Shantou University Medical College from June to December in 2008.One thousand two hundred and four people were randomly selected to calculate the preValence rates of MS and its components according to these three criterions proposed by the multivariate combination indicatrixes method,guidelines of dyslipidemia of Chinese adult in 2007,and the Third Report of National Cholesterol Education Program-Adult Treatment Panel III(NCEP-ATP III2005)in 2005,and to compare the differences and agreement rates between these criterions. Results According to multivariate reference value,guidelines and ATP III,the age-adjusted MS prevalence rates were 9.9%,9.3%and 14.8% respectively(P<0.01),and the prevalence rate in male was more than that in female(P<0.01).The prevalence rate of abnormal blood pressure according to multivariate reference value was 32.6%,which was less than the value of guideline and ATP III (45.1%).Among the MS patients,the detection ratio of obesity diagnosticed by multivariate reference value was 78.7%,which was the highest.The diagnostic agreement rate between multivariate and guidelines.multivariate and ATP Ⅲ(2005)was high and the Kappa value was 0.759 and 0.715 respectively(P<0.01).Condusions,The multivariate reference criterion for MS about male and female has been set up.The multivariate reference value criterion for MS is adaptable for enrolled population.     

New drugs in acute myelogenous leukemia: a review.

Numerous clinical trials in adult patients with newly diagnosed acute myelogenous leukemia indicate that the survival rate is approximately 20%. A limited number of favorable prognostic features have been identified; patients who present with specific cytogenetic abnormalities such as t(15;17), t(8;21) and inv (16) tend to have survival rates approaching 40%. However, such patients constitute only a small proportion of the total denominator and it has therefore been a major focus of scientific endeavor to develop new drugs for the treatment of this disease. A wide variety of agents have undergone preliminary testing in this regard and include both natural substances such as homoherringtonine, a drug that has demonstrated modest complete remission rates in this disease and all-trans retinoic acid, a compound that has revolutionized the treatment of acute promyelocytic leukemia. This review will put in perspective some of the newer drugs for the treatment of acute myelogenous leukemia and allow for some conclusions to be drawn as to their impact in the treatment of this disease.     

代谢综合征对青年女性冠心病的影响

目的 探讨代谢综合征对年龄＜ 45岁的青年女性冠心病患者的发病及病变特点的影响.方法 收集2005年1月至2011年12月在北京安贞医院行冠状动脉造影的20 ～ 45岁女性患者的病历资料进行回顾性分析.共302例患者入选,其中冠心病患者188例,无冠心病患者114例.对2组中代谢综合征以及其他冠心病易患因素分布进行对比研究.比较伴代谢综合征及不伴代谢综合征冠心病患者的临床特点、冠状动脉造影结果及治疗方式等.结果 冠心病组代谢综合征比例明显高于非冠心病组[40.4％(76/188)比22.8％(26/114),P＜0.01].伴代谢综合征冠心病患者急性ST段抬高心肌梗死患者的比例明显高于不伴代谢综合征者[30.2％ (23/76)比17.0％(20/112),P＜0.05].Logistic回归分析显示HDL水平[比值比(OR)为0.47,95％置信区间(CI)为0.123 ～0.813),P＜0.05]及入院时SBP(OR为1.018,95％ CI为1.003 ～1.034,P=0.013)为冠心病发生的独立预测因子.结论 代谢综合征是青年女性冠心病的危险因素,应早期发现,并且予以控制.     

Significance of Genome-Wide Analysis of Copy Number Alterations and UPD in Myelodysplastic Syndromes using Combined CGH - SNP Arrays

Genetic information is an extremely valuable data source in characterizing the personal nature of cancer. Chromosome instability is a hallmark of most cancer cells. Chromosomal abnormalities are correlated with poor prognosis, disease classification, risk stratification, and treatment selection. Copy number alterations (CNAs) are an important molecular signature in cancer initiation, development, and progression. Recent application of whole-genome tools to characterize normal and cancer genomes provides the powerful molecular cytogenetic means to enumerate the multiple somatic, genetic and epigenetic alterations that occur in cancer. Combined array comparative genomic hybridization (aCGH) with single nucleotide polymorphism (SNP) array is a useful technique allowing detection of CNAs and loss of heterozygosity (LOH) or uni-parental disomy (UPD) together in a single experiment. It also provides allelic information on deletions, duplications, and amplifications. UPD can result in an abnormal phenotype when the chromosomes involved are imprinted. Myelodysplastic syndromes (MDS) are the most common clonal stem cell hematologic malignancy characterized by ineffective hematopoiesis, which leads to rapid progression into acute myeloid leukemia. UPD that occurs without concurrent changes in the gene copy number is a common chromosomal defect in hematologic malignancies, especially in MDS. Approximately 40-50% of MDS patients do not have karyotypic abnormalities that are detectable using classical metaphase cytogenetic techniques (MC) because of inherent limitations of MC, low resolution and the requirement of having dividing cells. In this review, we highlight advances in the clinical application of microarray technology in MDS and discuss the clinical potential of microarray.     

Comparison of the immunomodulatory effects of the plant sterol β-sitosterol to simvastatin in peripheral blood cells from multiple sclerosis patients

Statins as hypocholesterolimic drugs have recently shown to have ant-inflammatory properties and thus are being assessed for the treatment of multiple sclerosis (MS). Dietary phytosterols such as β-sitosterol (SIT) are also hypocholesterolemic compounds and from preliminary studies they appear to have also anti-inflammatory properties. In this communication, we report on studies to investigate the immunomodulatory effects of SIT on proliferation and release of key cytokines from peripheral blood mononuclear cells (PBMC) of MS patients. In PBMC of MS patients, 16 μM SIT had no effect on cell proliferation; however simvastatin (SV) at 10 and 20 μM reduced cell proliferation by as much as 60%. SIT (4 μM) reduced TNF-α release by 24% in PBMC of MS patients whereas 10 μM SV reduced TNF-α release by 94%. SIT reduced IL-12 release in MS patients at 4 and 16 μM by 27% and 30%, respectively. In healthy subjects, 16 μM SIT increased the anti-inflammatory cytokine IL-10 by 47% whereas 10 μM SV decreased IL-10 by 30%. In PBMC of MS patients, SIT had no effect on IL-10 release whereas 10 μM SV reduced IL-10 by 62%. SIT (4 μM) reduced IL-5 release by 47% in MS patients while 10 μM SV reduced IL-5 by 89%. The results show that SIT is effective in modulating the secretion of pro/anti-inflammatory cytokines and suggest a potential beneficial effect of SIT in MS management without the side effects associated with statin therapy.     

Haematological effects of interferon-beta-1a (Rebif) therapy in multiple sclerosis.

INTRODUCTION: Interferon-beta-1a (Rebif) is an established treatment for relapsing-remitting multiple sclerosis (MS) and haematological changes are commonly reported in clinical trials of this agent. The combined clinical trial and postmarketing safety database for subcutaneous interferon-beta-1a (Rebif) allows a comprehensive, retrospective assessment of both common and infrequent haematological effects associated with interferon-beta therapy. METHODS: Haematological laboratory abnormalities were analysed from six randomised, controlled clinical trials of subcutaneous interferon-beta-1a in MS, five of which were placebo-controlled. Treatment data were collected from 2482 patients for up to 6 months, 1178 patients for up to 2 years and 786 patients for up to 6 years. Total interferon-beta-1a doses ranged from 22 microg once weekly to 44 microg three times weekly. Postmarketing surveillance data were also analysed. RESULTS: Treatment with interferon-beta-1a led to asymptomatic dose-related reductions in all cell lineages under investigation, predominantly white blood cells. The greatest differences between interferon-beta-1a therapy and placebo were seen for total leucocyte and neutrophil counts. At least two-thirds of patients affected by cytopenia experienced the onset of cytopenia within the first 6 months of therapy. The majority of events were mild and generally resolved within 3--4 months, while continuing therapy. Dose reductions were uncommon and only a small proportion (6 of 727; 0.8%) of patients stopped treatment over 2 years because of haematological abnormalities when receiving the highest dose of interferon-beta-1a, 44 microg three times weekly. Postmarketing safety reports were similarly related to asymptomatic cytopenias, although one case of potentially related autoimmune haemolytic anaemia was reported. CONCLUSION: Although haematological abnormalities are common and dose-related in patients with MS receiving interferon-beta-1a, the events are mainly mild and transient, with little impact on adherence to therapy. Haematological events are rarely of clinical significance and do not adversely affect the benefit-to-risk ratio that favours high-dose interferon-beta-1a therapy.     

Multiple sclerosis-induced neuropathic pain: pharmacological management and pathophysiological insights from rodent EAE models

In patients with multiple sclerosis (MS), pain is a frequent and disabling symptom. The prevalence is in the range 29–86 % depending upon the assessment protocols utilised and the definition of pain applied. Neuropathic pain that develops secondary to demyelination, neuroinflammation and axonal damage in the central nervous system is the most distressing and difficult type of pain to treat. Although dysaesthetic extremity pain, L’hermitte’s sign and trigeminal neuralgia are the most common neuropathic pain conditions reported by patients with MS, research directed at gaining insight into the complex mechanisms underpinning the pathobiology of MS-associated neuropathic pain is in its relative infancy. By contrast, there is a wealth of knowledge on the neurobiology of neuropathic pain induced by peripheral nerve injury. To date, the majority of research in the MS field has used rodent models of experimental autoimmune encephalomyelitis (EAE) as these models have many clinical and neuropathological features in common with those observed in patients with MS. However, it is only relatively recently that EAE-rodents have been utilised to investigate the mechanisms contributing to the development and maintenance of MS-associated central neuropathic pain. Importantly, EAE-rodent models exhibit pro-nociceptive behaviours predominantly in the lower extremities (tail and hindlimbs) as seen clinically in patients with MS-neuropathic pain. Herein, we review research to date on the pathophysiological mechanisms underpinning MS-associated neuropathic pain as well as the pharmacological management of this condition. We also identify knowledge gaps to guide future research in this important field.     

骨髓增生异常综合征异常克隆分布及与外周血细胞变化的关系

目的探讨不同染色体异常的骨髓增生异常综合征（MDS）患者异常克隆在骨髓各细胞系列中的分布及其与外周血细胞变化的关系。方法对del（20q）,8号染色体三体和含有5q-复杂核型的MDS患者和核型正常者的骨髓涂片进行Wright-Giemsa染色,并行荧光原位杂交检测,统计其红系、粒系、淋巴系细胞的荧光信号后与临床指标相比较。结果异常克隆在MDS患者红系中的比例分别为92.4%、56.4%、57.6%、63.2%、60.2%;粒系中的比例分别为71.2%、68.1%、72.4%、44.4%和49.3%,均高于对照组;异常克隆在淋巴系中的比例除在病例2三体8的患者中高于对照组,其余均低于对照组。异常克隆分布在红系和粒系的患者,外周血细胞水平可表现为正常或降低（Hb48～132g/L,ANC0.38×109/L～2.60×109/L）。病例2三体8的患者外周血淋巴细胞比例较高。结论 MDS异常克隆主要分布于骨髓粒系和红系细胞,个别患者分布于淋巴细胞。异常克隆在骨髓细胞系列中的分布与外周血细胞变化无明显相关性。     

伊马替尼治疗Ph染色体阳性慢性粒细胞白血病的临床观察

目的:评价酪氨酸激酶抑制剂伊马替尼治疗Ph染色体阳性慢性粒细胞白血病的有效性及安全性。方法:90例慢性粒细胞白血病患者,其中慢性期67例,非慢性期23例(加速期14例,急变期9例),每天应用剂量分别为400,600mg。每周复查血常规,每3个月进行骨髓象及细胞遗传学检查,根据血象和骨髓象调整剂量。结果:观察截止时,84例(93.3%)获得血液学完全缓解;68例可评价遗传学效应,35例(51.5%)发生主要遗传学效应(慢性期30例,加速期3例,急变期2例),其中31例(88.6%)为遗传学完全缓解(慢性期27例,加速期2例,急变期2例)。11例(12.2%)患者发生严重白细胞和/或血小板减少,但可通过调整剂量控制。严重非血液学不良反应发生较少。结论:伊马替尼治疗Ph染色体阳性慢性粒细胞白血病患者疗效较好,可获得较高的完全血液学缓解率和主要细胞遗传学缓解率,起效迅速,且不良反应较少,可耐受或自行消失。