格列卫治疗加速期急变期慢性粒细胞白血病27例临床报道

目的初步评价格列卫治疗慢性粒细胞白血病加速期急变期疗效及毒性反应。方法27例慢性粒细胞白血病患者口服格列卫300~800mg/d,并记录服药前及服药后各时间点血常规指标变化。结果加速期患者血液学缓解率37.0%;急性变期患者血液学缓解率22.2%。血液学总有效率59.3%。血液学不良反应以白细胞,血小板减少多见,非血液学不良反应以恶心、呕吐、水肿多见,其为骨骼肌酸痛、乏力、头昏常见;而胸腔积液、头痛、皮疹等少见。结论格列卫治疗慢性粒细胞白血病加速期急变期患者疗效好,不良反应少,可耐受且加速期疗效优于急变期。     

格列卫治疗慢性粒细胞自血病进展期的临床疗效观察

目的探讨甲磺酸伊马替尼（STI571,格列卫）治疗慢性粒细胞白血病进展期（即加速期、急变期）患者的临床疗效。方法所选22例均为慢性粒细胞白血病进展期患者,将11例服用格列卫的病人设为治疗组,口服格列卫400mg／d或600mg/d,11例传统化疗的病人设为对照组,持续治疗6-9个月后观察疗效。结果治疗组的总有效率为72．7％,主要遗传学缓解率为45．5％,而对照组总有效率为18．2％,主要遗传学缓解率为0（两组比较均P〈0．05）。血液学不良反应以白细胞、血小板减少多见,非血液学不良反应以水肿及恶心呕吐等多见。结论格列卫对慢性粒细胞白血病进展期病人有较好疗效,不良副作用发生率低,但治疗期间,需加强支持治疗。     

实时定量PCR监测慢性粒细胞白血病患者BCR——ABL融合基因转录本水平

目的 探讨实时定量聚合酶链反应(RQ-PCR)在监测慢性粒细胞白血病(CML)患者微小残留病变、考核疗效以及预测疾病预后方面的应用.方法 应用实时RQ-PCR对84例不同病期患者之间的BCR-ABL转录本水平进行比较,并对5例慢粒患者治疗前后BCR-ABL转录本水平的变化进行监测.结果 加速期和急变期患者的转录本水平明显高于慢性期患者.对于慢性期患者,造血干细胞移植后其BCR-ABL转录本水平明显下降,甚至检测不到,格列卫治疗可获得类似结果.结论 RQ-PCR方法准确可靠,对于监测慢粒患者的微小残留病变、考核疗效以及预测慢粒急变具有重要的临床应用价值.     

慢性白血病治疗动态

慢性白血病是指临床过程较长,发展较慢的一组血液系统恶性肿瘤。包括慢性粒细胞性白血病(慢粒)及慢性淋巴细胞性白血病(慢淋)。发病机制可能与癌基因活化有关,但机制还不清楚。慢性粒细胞性白血病的治疗: 近来慢粒的生物学、分子生物学及细胞遗传学的研究颇多,并与预后发生联系,现就有关问题,综述如下。     

格列卫治疗加速期、急变期慢性粒细胞白血病18例临床疗效观察

目的 探讨格列卫治疗慢性粒细胞白血病(CML)加速期、急变期的临床疗效.方法 18例CML加速期、急变期应用格列卫患者为治疗组,口服格列卫600～800 mg/d,同期住院18例CML加速期、急变期接受传统化疗的患者设为对照组,两组均持续治疗7～9个月后观察疗效及不良反应.结果 治疗组CHR 5例(27.8％),PHR 8例(44.4％),血液学总有效率72.2％.对照组CHR 1例(5.6％),PHR3例(16.7％),血液学总有效率22.2％.两组疗效比较差异有统计学意义(P＜0.01);治疗组遗传学总有效率33.3％,对照组遗传学总有效率为5.6％,两组疗效比较差异有统计学意义(P＜0.05).治疗组血液学不良反应主要为白细胞、血小板减少,非血液学不良反应最常见为恶心、呕吐(611％),其次为水肿(44.4％)及肌肉疼痛等,不良反应的发生及程度均较化疗组轻,给予对症处理后,均能耐受.结论 格列卫治疗加速期、急变期CML安全有效,但获得遗传学缓解后仍需坚持服药,一旦出现耐药可考虑改用第二代TKI或行造血干细胞移植.     

2007全球医药市场增长趋势：新药动态（二）

抗肿瘤药：靶向给药是关键 慢性粒细胞白血病：诺华公司2001年推出的Gleevee（格列卫，imatinib）具有很好的疗效。该药是通过攻击慢性粒细胞白血病癌症细胞中的异常蛋白质BcxAbl来完成的。但格列卫还有改进的空间，目前该公司正致力于研发其更新产品——Tasgina（Nilotinib），更有效针对诱发癌症的BerAbl基因及其变异基因将是研究的重点方向。Ⅱ期临床研究表明，Tasgina对46％的具有格列卫抗药性的病人有效，且副作用更小，通常不会出现使用格列卫治疗时常见的毒性反应（例如液体潴留、体表水肿、体重增加）。据预测，Tasigna将达到10亿美元的销售潜能。另一个同样作用机制的药物是百时美施贵宝的Spryeel，该药于2006年6月获得FDA批准，上市后第一季度的销售额就达到了1100万美元。     

实时定量逆转录-聚合酶链反应监测慢性粒细胞白血病患者融合基因转录本水平及其变化

目的探讨实时定量逆转录-聚合酶链反应(RT—PCR)在监测慢性粒细胞白血病(慢粒)患者微小残留病变、考核疗效以及预测疾病预后方面的应用。方法应用实时定量RT—PCR对11例慢粒患者治疗前后融合基因(BCR—ABL)转录本水平的变化进行监测,对55例不同病期患者之间的转录本水平进行比较。结果对于慢性期患者,造血干细胞移植后其BCR—ABL转录本水平明显下降,甚至检测不到,甲磺酸伊马替尼(格列卫)治疗可获得类似结果,而羟基脲、干扰素α或三尖杉酯碱治疗后,其BCR—ABL转录本水平虽有下降但仍维持在较高水平;患者发生急变时,其BCR—ABL转录本水平升高约10倍;急变期患者的转录本水平明显高于慢性期或加速期患者。结论实时定量RT—PCR方法准确可靠,对于监测慢粒患者的微小残留病变、考核疗效以及预测慢粒急变具有重要的临床应用价值。     

伊马替尼治疗慢性粒细胞白血病加速期致尿崩症1例及文献复习

目的 通过观察伊马替尼治疗慢性粒细胞白血病过程中出现罕见毒副反应,探讨甲磺酸伊马替尼在治疗慢性粒细胞白血病中的安全性.方法 对1例伊马替尼治疗晚期慢性粒细胞白血病加速期的过程中出现罕见毒副反应的临床资料进行分析,并结合文献复习.结果 1例确诊为慢性粒细胞白血病的患者接受甲磺酸伊马替尼治疗后,出现尿崩症、窦性心动过速伴肌肉损坏,停药70多天再次减量服用后又出现类似症状.结论 伊马替尼治疗慢性粒细胞白血病加速期可能出现罕见的严重不良反应.     

免疫学分型在慢性粒细胞白血病不同期中的应用价值

<正> 运用免疫学分型对白血病的诊断和治疗具有很重要的价值,可以弥补形态学诊断的不足.我们对慢性粒细胞白血病(慢粒)慢性期、急变期、加速期的患者进行了形态学(FAB)诊断和免疫学分型,并进行二者的比较分析,以探讨免疫学分型的临床应用价值.1 资料与方法1.1 一般资料 测定者为1996年3月～1997年4月我院住院病人.根据形态学诊断为慢粒慢性期10例,慢粒急变期10例,慢粒加速期4例.男14例,女10例,年龄20～60岁.1.2 标本处理 慢粒急变期用骨髓直接涂片,慢粒加速期和慢粒慢性期用肝素抗凝骨髓液0.5ml或静脉血4ml按常规分离单个核细胞制片.     

甲磺酸伊马替尼诱发剥脱性皮炎1例

报道1例服用甲磺酸伊马替尼(格列卫)诱发剥脱性皮炎的病例.患者70岁,3年多前经骨髓检查诊断为慢性粒细胞性白血病,长期予羟基脲及干扰素治疗,白细胞控制在(4～15)×109/L之间.此次人院诊断为慢粒急变,给予伊马替尼200mg,bid治疗.     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

目的：评价使用安心颗粒对急诊经皮冠状动脉介入术（PPCI）术后生活质量的影响.方法：将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组（术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次）和对照组（仅接受基础药物治疗）.所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表（MIDAS）、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果：入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异（P＞0.05）;出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低（P＜0.05）;组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低（P＜0.05）.两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血（P＞0.05）.两组发生轻度血小板减少症的患者数比较无差异（P＞0.05）.结论：PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.     

The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function, atrio-ventricular node function and hemodynamics

Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P＜0.01);the MAP decreased(P＜0.01)and the HR increased drastically(P＜0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.     

Expression of OPGmRNA and ODFmRNA in the patients of hip fracture due to osteoporosis

Objective：To investigate the gene expression of osteoprotegerin（OPG） and osteoclast differentiation factor（ODF） in the bone tissue of patients with hip fracture due to osteoporosis. Methods：OPGmRNA and ODFmRNA in the bone tissue in 50 cases of osteoporosis sufferers（over 50 years old） with hip fracture（Observer Group） and 30 cases of hip facture sufferers with no osteoporosis（Control group） were analyzed with the Semi-Quantitative RT-PCR method. Results：The mRNA expressed of ODF, OPG were both high in the patients with hip fracture. In the control group, the expression of OPG mRNA was observed, while the expression of ODF mRNA was very slight. Conclusion：Aged patients contained all signals including OPG, ODF that are essential for inducing osteoclastogenesis and promoting bone resorption.     

The clinicopathological and immuohistochemical analysis of solid-pseudopapillary tumor of the pancreas： report of 9 cases

Objective：To investigate the clinical features, pathological characteristics and immunophenotype of solid-pseudopapillary tumor of the pancreas（SPTP）. Methods：Nine surgically treated cases of SPTP were retrospectively reviewed. Hematoxylin and Eosin（HE） staining and immunohistochemical staining were used to analyze all cases, and the general clinical data was collected. Results：Six patients were asymptomatic except for a palpable mass. Two patients complained of vague-epigastric pain. One patient appeared jaundice. The tumor was encapsulated and solid tissues alternately with cystic tissues. Histologically, the histological structure of solid portion was pseudopapillary with a fibrovascular core. Tumor cells were uniform and medium-sized which were arranged in sheets ets or nests or pseudopapillary patterns. Immunohistochemical studies demonstrated that SPTP proved positive in vimentin（9/9 cases）, AAT（9/9 cases）, NSE（9/9 cases）, ACT（7/9 cases）, CK20（2/9 cases）, CgA（1/9 cases）, S-100（3/gcases）, PR（4/gcases）, Syn（3/9 cases） and CD56（5/9cases）, negative in CEA and ER. Conclusion：SPTP is a tumor predominantly occurring in young women frequently without special symptoms. This tumor has various characteristical histological patterns with different immunophenotype.     

Dynamic Changes in Serum Estradiol and Progesterone levels in Patients of Premenstrual Syndrome with Adverse Flow of Liver-qi

Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.     

Real-time Three-dimensional Echocardiography in Assessment of Left Ventricular and Right Ventricular Volumes

Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.     

SCREENING FOR A 21-CHROMOSOME ABNORMALITY IN PREIMPLANTED EMBRYOS OF ELDERLY WOMEN

Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.