慢性髓细胞白血病和Ph~+急性淋巴细胞白血病口服治疗药Ponatinib

Ponatinib(又名AP-24534)是由ARIAD制药公司开发用于治疗慢性髓细胞白血病(CML)和Ph染色体阳性急性淋巴细胞白血病(Ph+ALL)的口服药物,为一种多靶向酪氨酸激酶抑制剂,其主要靶点是CML和Ph+ALL特有的标志性异常酪氨酸激酶BCR-ABL。CML的病理特征是,由于异常基因表达而产生BCR-ABL蛋白,导致骨髓过度和无节制地产     

33例慢性白血病骨髓涂片的观察分析

目的探讨慢性白血病的骨髓象特点和骨髓涂片检查的临床应用价值。方法总结分析23例慢性粒细胞白血病(CML)和10例慢性淋巴细胞白血病(CLL)的骨髓涂片检查结果。结果 CML的骨髓增生度比CLL高,CML和CLL的红系细胞比率相近,CML的巨核细胞数比CLL高。CML和CLL之间的同类白血病细胞、正常细胞相比较,存在着形态大小不一,核凹陷、卷曲以及核浆发育不平衡等差异。除了嗜酸性粒细胞和嗜碱性粒细胞增多以外,CML还可见戈谢氏样细胞。结论骨髓涂片检查能为慢性白血病的诊断提供可靠依据,对于掌握病情、制订有效合理的治疗方案具有重要作用。     

世界药物新闻(六十二)

1　美国批准 Gleevec作为一线用药美国已批准诺华公司的抗癌药物 Gleevec(译注 :亦称Glivec) (通用名 :伊马替尼 ,imatinib)用作治疗早期慢性髓细胞样白血病 ( chronic myeloid leukaemia,CML)的一线药物 ,这是该药的新适应证。美国 FDA于 8月份优先审查了该药治疗早期 CML(慢性期 )适应证。Gleevec现已成为晚期 CML ,即加速期和未成熟细胞危象期的一线治疗药物 ,并可用于 α-干扰素治疗失败后的早期CML 治疗。公司说 ,Gleevec作为治疗早期 CML 的一线药物 ,在瑞士首先上市 ,该药的这一适应证在欧洲的其他国家即将获准上市。美国 …     

慢性粒细胞白血病的血象及骨髓象的观察分析

目的通过血象及骨髓象的观察分析,了解其在诊断慢性粒细胞白血病(CML)的作用及价值,不断提高对CML的诊断水平。方法对已经确诊的20例CML患者的血象及骨髓象检查资料进行回顾性总结分析。结果 20例患者血象白细胞均异常增多(47.4~663.7×109/L),占100%;轻度贫血5例(占25%),中度贫血7例(占35%),重度贫血3例(占15%);血小板增多者10例(占50%),2例为减少(占10%)。外周血涂片白细胞明显增多,以中性中幼粒及以下阶段细胞增多为主。骨髓细胞涂片增生明显活跃4例(占20%),极度活跃16例(占80%),粒系各阶段细胞均明显异常增多,以中性中幼粒及以下阶段细胞增多为主,且多伴有形态异常,嗜酸性粒细胞和嗜碱性细胞也明显增多。20例NAP染色均为阴性。结论血象及骨髓象检查是诊断CML的主要手段,当发现血常规结果异常时,不能仅依赖仪器检测,应涂片观察细胞形态,并及时做骨髓穿刺检查,为CML的诊断和治疗提供可靠的依据。     

伊马替尼对慢性髓系白血病骨髓细胞VEGF表达的影响

目的 研究伊马替尼对慢性髓系白血病(CML)患者骨髓细胞及白血病细胞系K562血管内皮生长因子(VEGF)表达的影响.方法 采用ELISA检测伊马替尼作用前后CML骨髓细胞和K562细胞VEGF蛋白表达水平,实时荧光定量PCR检测伊马替尼对K562细胞VEGF mRNA表达的影响.结果 CML患者骨髓单个核细胞在伊马替尼作用后VEGF蛋白表达量为(130.66±100.58)pg/ml,明显低于未加药组(269.11±176.79)pg/ml(P＜0.01).K562细胞VEGF mRNA和蛋白表达水平于伊马替尼作用后亦呈剂量依赖性下降.结论 伊马替尼对CML患者VEGF的表达有明显抑制作用,提示该药对CML可能具有抗血管新生作用.     

P210bcr/abl融合蛋白的形成机制及作用的研究进展

慢性粒细胞白血病(CML)是以费城染色体(Ph)为特征的多潜能干细胞异常的骨髓恶性增殖性疾病。Ph染色体是由9号染色体c-abl癌基因易位到22号染色体的bcr基因处,形成bcr／abl融合基因,该基因经转录后,编码8．5kb的嵌合体mRNA,翻译成分子量为210kD的蛋白质,即P210^bcr/abl融合蛋白(P210^bcr/abl),该蛋白具有异常活跃的酪氨酸激酶活性(PTK),并活化细胞内相关的信号转导通路从而调控细胞的分裂与增殖,抑制细胞的凋亡。P210^bcr/abl是CML的特征性标志。因此,研究P210^bcr/abl对研究与治疗CML具有重要的意义．有关P210^bcr/abl的形成机制及作用已部分阐明．现做综速如下．     

细胞原位检测36例慢性粒细胞性白血病BCR／ABL融合基因方法的探讨

目的：探索一种新的细胞原位检测BCR/ABL融合基因方法，用于慢性粒细胞性白血病(CML)的早期诊断及鉴别诊断。方法：在试管内对固定和消化后的细胞直接进行原位逆转录并扩增，反应结束后在显微镜下原位检测CML患者的BCR／ABL融合基因。结果：36例CML病例阳性检出率达94．4％。其中5例Ph-CML有3例检出BCR/ABL融合基因表达。急变期和加速期CML患者的基因表达水平明显高于慢性期。结论：细胞原位检测方法简便快速，灵敏度高，特异性强。不仅可以定性检测BCR／ABL融合基因表达，而且可以量化基因表连水平及其变化。为慢粒的诊断，鉴别诊断以及预测病程的进展提供了直观精确的依据。     

髓系白血病患者骨髓单个核细胞β-连环蛋白mRNA的表达

目的观察急慢性髓系白血病患者骨髓单个核细胞β-连环蛋白的表达及其意义。方法 41例髓系白血病患者,其中25例急性髓系白血病（AML）,16例慢性髓系白血病（CML）。同时选择18例非恶性血液病患者作为对照。肝素抗凝骨髓2 ml,Ficoll液分离骨髓单个核细胞,荧光定量逆转录聚合酶链反应法检测β-连环蛋白的表达。结果β-连环蛋白在AML组表达量明显高于CML组及对照组（P〈0.01）;CML组表达量高于对照组表达量,差异有统计学意义（P〈0.05）;CML组4例急变患者的β-连环蛋白表达量也较高。β-连环蛋白表达量与患者年龄、性别无关;与骨髓原始细胞含量有关,含量≥30%的患者β-连环蛋白表达量较高。结论β-连环蛋白在AML和CML急变的患者骨髓单个核细胞中异常高表达,Wnt/β-连环蛋白通路在AML和CML急变病例中异常激活可能与白血病细胞的异常增殖有关。     

慢性粒细胞性白血病抗原负载树突状细胞激发抗白血病作用

目的研究慢性粒细胞性白血病(CML)细胞冻融抗原(CLA)负载的树突状细胞(DC)对特异性抗白血病T细胞的作用.方法将CML患者外周血单个核细胞(PBMNC)来源的DC在体外用CLA负载,再与CML患者的经细胞因子诱导的杀伤细胞(CIK)共同培养,应用乳酸脱氢酶(LDH)释放法观察其对自身CML细胞杀伤活性(A组),与未负载的DC+CIK(B组)、CIK(C组)及CIK+CLA(D组)进行比较.结果效靶比为10∶1条件下,A、B、C、D4组的杀伤活性分别为(63.69±8.35)%、(45.02±5.49)%、(27.28±4.64)%、(29.63±5.71)%.A组比B组杀伤活性强(P＜0.01);C组与D组比无显著性差异.结论CLA负载的DC可进一步提高DC介导的特异性抗白血病T细胞对CML细胞的杀伤活性.     

慢性粒细胞性白血病尿酸及乳酸脱氢酶水平分析

目的观察慢性粒细胞性白血病(CML)患者血清尿酸与乳酸脱氢酶浓度变化及与正常人浓度的对比分析。方法按病例对照研究方法,设试验组6例CML患者,对照组20例健康体检者,分别测定两组尿酸及乳酸脱氢酶水平,进行统计学分析。结果 CML患者尿酸及乳酸脱氢酶水平明显高于正常者。结论 CML患者血清尿酸与乳酸脱氢酶明显高于正常者,反映了患者体内白血病细胞的负荷,可用于CML的诊断依据。     

Self-evaluation of single test doses and objective indices of ladasten vs. placebo efficacy in neurasthenic patients

Self-evaluation of the effect of single-dose (15 mg) ladasten administration versus placebo has been studied in patients with neurasthenia diagnosis. Relationships between self-evaluation parameters and personal features, psychopathological and psychophysiological parameters of patients, drug action characteristics, and course treatment effectiveness have been analyzed. Results suggest that the self-rated high tolerability of ladasten treatment is comparable with that of placebo. No relationships are found between the self-evaluated single-dose effects of ladasten and personal features of patients. Correlations of the self-estimations and some psychopathological and psychophysiological parameters before treatment, main drug effects, and overall course treatment effectiveness are revealed, whereas the self-evaluation of placebo effect was related to personal features.     

Toxicity and Local Irritation Action of the Biomedical Cell Product Anti-HER2-CAR-T-NK Upon Multiply Repeated Administration

Pharmaceutical Chemistry Journal - CAR-cell therapy is a promising new method of cancer treatment. The biomedical cell product Anti-HER2-CAR-T-NK cells has been found safe in a course of...     

糖皮质激素在急性呼吸窘迫综合征患者中的应用

急性呼吸窘迫综合征(Acute respiratory distress syndrome,ARDS)是由多种原因引起的急性进行性呼吸衰竭,虽然目前对其发病机制以及治疗手段的研究已经取得了一些进展,但是发病率和病死率仍较高。糖皮质激素因其强大的抗炎作用早已应用于ARDS,但由于临床给药时机、给药剂量及疗程不同,糖皮质激素对ARDS的治疗作用一直存在争议。本文就糖皮质激素在ARDS患者中的应用作一综述。     

Aversion therapy of cannabis dependence in Nigeria

Cannabis dependence is fast becoming a public health problem in Nigeria. Prevalent studies indicate that up to 9% of secondary school students and 33% of University undergraduates (i.e., one in every three students) abuse cannabis. Cases of cannabis dependence seen in hospital practise in Nigeria are usually associated with psychotic illness and there is a strong feeling among psychiatrists in the country that the cannabis abuse is contributory to the precipitation of the psychosis. If this is true, then abstinence from cannabis abuse is necessary in order to reduce the possibility of relapse of the psychotic illness when this has been treated.The paper to be presented describes a method of treatment which has been developed and tried in an Ife University Teaching Hospital, Ile-Ife, Nigeria. This treatment is a form of behaviour therapy and its cost has been estimated at about US$12, which was found to be within reach of most patients. Patients who have undergone a course of this treatment (one course of 3 treatments) have abstained from cannabis for an average period of 9 months. A single treatment administered within this period further prolongs the period of abstinence.Further work is recommended to explore the range of application of this method of treatment, for example, the personality types for whom it is most suitable and those in whom it would contraindicated.     

Time course of response to antidepressants in late-life major depression: therapeutic implications

In the treatment of depression, there is considerable interest in the time course of response and, in particular, the speed with which individuals recover from depressive episodes. Examination of the time course and speed of response is critical for assessing the usefulness of specific treatments. However, while this issue has received attention in mid-life adult populations, it has received little consideration in the context of late-life major depression. The synthesis of empirical reports indicates that, while older adults with depression seem to respond with the same speed as mid-life adults, several factors have consistently been associated with reduced speed of response to antidepressant treatment, including greater severity of depressive symptoms and co-occurring anxiety symptoms. Limited evidence suggests that sleep impairment and genetic factors (e.g. presence of the s allele of the serotonin transporter gene promoter region) may also be associated with reduced speed of response. Some factors have consistently been found to be unrelated to speed of response (demographic characteristics, nonpsychiatric physical illnesses) whereas other factors have only mixed evidence supporting any effect (psychosocial and other clinical factors). While there is little work available to date, some evidence suggests that time course and speed of response affect longer-term outcomes of depression pharmacotherapy; thus, older adults with more rapid versus slower patterns of response may differ in the types of maintenance treatment needed to avert additional depressive episodes. None of potential strategies for accelerating speed of response have been clearly shown to be effective in late-life depression. Future treatment studies for late-life depression should routinely consider not only overall efficacy of a given pharmacotherapy (i.e. total rate of response), but time course and speed of response. To this end, new investigations must be designed to overcome the methodological limitations of prior studies that have examined time course and they should include a range of potential covariates and outcomes of between-patient differences in speed of response. Better understanding of factors related to such differences may suggest new intervention strategies to accelerate response.     

幽门螺杆菌根除治疗及合理用药

临床上要求根除幽门螺杆菌感染的患者越来越多，但耐药等问题却给治疗带来了不少困难。为此，医生可以采用调整治疗方案、延长疗程等措施。本文对根除幽门螺杆菌感染治疗中的常用药物及其合理应用作一综述。     

Azo reduction of sulphasalazine in healthy volunteers.

1 A comparison of total sulphapyridine saliva concentrations resulting from administration of sulphapyridine and sulphasalazine at equimolar doses has been carried out. It is concluded that the extent of azo reduction of sulphasalazine to release sulphapyridine is complete in healthy volunteers. 2 An ampicillin course of treatment alters the azo reduction of sulphasalazine. The extent of cleavage is reduced by one third on average. There is no change in the rate of absorption of the release sulphapyridine. 3 An ampicillin course of treatment does not alter the disposition of sulphapyridine. The changes noted in acetyl conjugate plasma concentrations are entirely consistent with reduced availability of sulphapyridine.     

肝癌2009年临床研究进展与展望

原发性肝癌（primary hepatocellular carcinoma,PLC）是世界上常见的恶性肿瘤之一,居于恶性肿瘤的第5位,全球发病率已超过100万／年。我国一直是世界范围内的PLC高发区,目前的发病人数约34．7万人,约占全球总发病人数的55％;死亡约32．3万人,约占全球总死亡人数的45％。在全球,PLC在恶性肿瘤死亡中仅次于胃癌和食管癌,而在我国仅次于肺癌,位居第二（ParMaDM,BrayF,Ferlay J,etal．2005）。     

Pharmacokinetic studies of the hypoglycemic effects of insulin in the treatment of diabetic ketoacidosis

A recently developed pharmacokinetic model of the insulin-glucose system has been used to investigate the contribution of insulin-induced suppression of endogenous glucose production (EGP) to the hypoglycemic effect of insulin in the treatment of diabetic ketoacidosis and to determine the influence of the initial degree of hyperglycemia on the course of insulin treatment. Simulations of the time course of glucose concentration in the plasma following low-dose insulin therapy indicate that the hypoglycemic action of insulin is largely due to insulin-dependent glucose utilization and that suppression of EGP, if it occurs at all, contributes little to the overall effect. Nevertheless, a particularly useful characteristic of the pharmacokinetic model of the insulin-glucose system that assumes little or no suppression of EGP is its ability to predict glucose rebound when insulin has been effectively depleted. Other simulations reveal that the initial degree of hyperglycemia has little influence on the clinical outcome of low-dose insulin treatment of diabetic ketoacidosis. According to the simulation, 0.1 (U/kg)/hr intravenous infusion of insulin will produce satisfactory control of plasma glucose concentrations within 5–8 hr, assuming initial glucose concentrations ranging from 500 to 1500 mg/dl.     

The use of povidone-iodine ('Betadine') pessaries in the treatment of candidal and trichomonal vaginitis.

One hundred and thirty-five women suffering from trichomonal, candidal, or both infections simultameously, were treated with povidone-iodine pessaries, 2 pessaries being inserted nightly. Ninety-nine women were given a 7-day course of treatment, but the results obtained were disappointing, and the authors do not recommend such a regime for routine treatment. Better results were obtained with the recommended 14-day course. A further 36 women suffering from chronic trichomonal and/or canidal infections which had previously resisted orthodox treatment were given a prolonged 28-day course of pessary treatment. The results obtained were very encouraging, 92% of the trichomonal and 96% of the canidal infections being cured. Furthermore, although povidone-iodine is slightly less effective in trichomoniasis, most patients suffering from a chronic infection (candidal, as well as trichomonal) were cured by the one preparation. Side-effects did occur, but were significant in only 3 patients. Subjective symptoms, especially any offensive odour, disappeared within 3 days of the start of the treatment. The authors recommend that the 28-day course of povidone-iodine pessaries is used in those cases where trichomoniasis or candidosis has been a therapeutic problem in the past, particularly if the patient is currently on the oral contraceptive pill.