异基因造血干细胞移植联合伊马替尼治疗Ph~+急性淋巴细胞白血病

为了探讨异基因造血干细胞移植(allo-HSCT)联合伊马替尼治疗Ph+急性淋巴细胞白血病(Philadelphiachromosome positive acute lymphoblastic leukemia,Ph+ALL)的疗效。对我院2007-2008年Ph+ALL患者3例所进行的allo-HSCT联合伊马替尼治疗效果进行了小结。3例Ph+ALL中1例接受同胞全相合移植,另2例为单倍体相合移植,移植前均处于完全缓解状态。3例患者在移植前后不同时间接受不同疗程的伊马替尼治疗,同时应用RT-PCR方法监测bcr/abl融合基因转录水平。随访日期至2009年10月21日。结果表明:3例患者均成功植入,未出现严重移植相关并发症;移植后bcr/abl融合基因处于低转录水平并逐渐转阴。结论:异基因造血干细胞移植联合伊马替尼是Ph+ALL有效的治疗方法。     

135例非单纯Ph染色体的慢性髓系白血病细胞遗传学分析

本研究探讨135例非单纯Ph染色体慢性髓系白血病（CML）的染色体检查结果并进行细胞遗传学分析：135例CML染色体均采用骨髓细胞直接法和／或短期培养法制备，应用R显带技术对其进行显带分析。结果表明：经染色体检测的1210例的CML中135例有非单纯Ph染色体异常。本组135例非单纯Ph染色体CML中，慢性期87例、加速期21例、急变期27例.87例慢性期患者中，14例伴简单变异易位，22例伴复杂变异易位，其余的伴其他染色体异常，其中伴8号染色体三体4例，伴双Ph4例，伴i（17）5例；在21例加速期患者中，伴8号染色体三体4例，伴双Ph4例，伴i（17）3例；在27例急变期患者中，2例伴简单变异易位，3例伴复杂变异易位，其余的伴其他染色体异常，其中伴8号染色体三体5例，伴双Ph5例，伴i（17）2例。本组常见额外染色体异常检出率高低依次为＋Ph、＋8、i（17）、-Y、＋19和＋21。本组有16例伴简单变异易位，25例伴复杂变异易位。结论：CML是起源于多能干细胞的恶性血液病．染色体核型分析对CML的诊断、预后、发病机制的探讨和治疗方案的选择都具有重要的价值。     

Roux-en-Y gastric bypass for nonobese patients with uncontrolled type 2 diabetes: a long-term evaluation

BackgroundThere is growing evidence that the impact of Roux-en-Y gastric bypass (RYGB) on type 2 diabetes (T2D) occurs regardless of the amount of weight loss. Taking this background into consideration, it is plausible to study this procedure in individuals with lower body mass index (BMI) under clinical treatment failure for uncontrolled T2D.ObjectivesTo elucidate the long-term impact of RYGB on T2D regression in a non-obese population.SettingHospital das Clínicas, Federal University of Pernambuco, Brazil.MethodsTwelve patients with BMI 25 to 30 kg/m² and inadequately controlled T2D underwent RYGB and were followed up for 6 years. Fasting plasma glucose, glycated hemoglobin, BMI, and the use of insulin and/or oral hypoglycemic agents were assessed. Each variable was analyzed in 3 distinct moments: preoperative evaluation, 2-year postoperative follow-up (2-PO), and 6-year postoperative follow-up (6-PO).ResultsThere were no cases of early or late mortality. Mean BMI at preoperative evaluation, 2-PO, and 6-PO were 28.1 ± 1.2; 23.2 ± 2.4; and 24.7 ± 3.1, respectively. The lowest BMI at 6-PO was 19.1 kg/m². Complete remission of T2D was achieved in 16.7%, partial remission in another 16.7%, glycemic control in 25%, and glycemic improvement in 25% of the sample at 6-PO; 16.7% did not present positive glycemic outcomes. Only 1 patient needed to resume insulin administration between 2-PO and 6-PO.ConclusionsRYGB was found to be safe and effective in treating uncontrolled T2D in non-obese patients, providing improvements in the glycemic patterns in 83.4% of our sample.     

Cigarette smoking, manifest anxiety and somatic symptoms

Fifty smokers and fifty non-smokers were administered the MMPI's Manifest Anxiety Scale (MAS). Mean MAS scores for smokers were significantly higher than those of non-smokers. Item analysis revealed that smokers obtained higher scores than non-smokers on significantly more items in which anxiety is manifested by a physical symptom rather than a psychological symptom. It is possible that physical stimulation by nicotine may contribute to a more ready arousal to anxiety in smokers.     

B-ALL患者PTEN表达及其启动子甲基化状态研究

目的:探讨抑癌基因PTEN在急性B淋巴细胞白血病(B-ALL)患者外周血单个核细胞中的表达及其与启动子甲基化状态之间的关系.方法:收集24例初发B-ALL患者和25例正常人外周血单个核细胞,通过Kolmogorov-Smirnov(KS)分析,利用定量流式细胞术检测PTEN表达.提取基因组DNA后,采用MSP方法检测PTEN启动子甲基化状态,进而在体外培养过程中,以DNA甲基化转移酶抑制剂5-氮-2'脱氧胞嘧啶进行处理,观察其对B-ALL单个核细胞PTEN表达的影响.结果:25例正常人外周血单个核细胞均表达PTEN,KS分析时D值为0.941±0.017,而24例B-ALL患者中22例(91.6%)外周血单个核细胞PTEN表达明显缺失,D值仅为0.546±0.115,两者差异具有显著性意义(P＜0.01);正常人和PTEN高表达的B-ALL患者外周血单个核细胞中未发现PTEN启动子发生甲基化修饰,而PTEN表达缺失的B-ALL患者中有5例(22.7%)出现PTEN启动子甲基化,将其单个核细胞培养时以5-氮-2'脱氧胞嘧啶处理4d,PTEN表达明显升高.结论:PTEN的表达缺失在B-ALL患者中很常见,其启动子甲基化导致的PTEN表达缺失在B-ALL的发生中可能起重要作用.     

Serum- free culture of dendritic cells from patients with chronic myeloid leukemia in vitro and estimation of their cytotoxicity

Objective To establish a serum- free culture system of dendritic cells (DCs) from chronic myeloid leukemia (CML) cells so that DCs vaccine may be applied to the adoptive immunotherapy of CML in the near future.Methods Fetal calf serum, serum- free medium and autologous serum were used for culture of DCs. The usage of cytokines was classified into two groups: group A (stem cell factor, granulocyte/macrophage colony- stimulating- factor, tumor necrosis factor- α and interleukin- 4) and group B (granulocyte/macrophage colony- stimulating- factor, tumor necrosis factor- α and interleukin- 4). The phenotypes of DCs were analyzed by using indirect immunofluorescence and flow cytometry. Mixed leukocyte responses were performed by methyl thiazolyl tetrazolium (MTT) assay. Chromosome analysis of DCs can be achieved by displaying G banding. T cells from CML patients were stimulated with autologous DCs and T- cell cytotoxicity was measured by (MTT) assay. Results CD34(+) cells or mononuclear cells were obtained from peripheral blood or bone marrow samples of eight patients of chronic- phase CML. Group A of serum- free medium was better than group B in expansion of total cell numbers and the rate of DCs. These results of serum- free medium were not significantly different from those of fetal calf serum medium, but the results of autologous serum medium were inferior to two groups above. The expression of major histocompatibility complex class Ⅱ antigen on the surface of DCs was notable (＞50%), but the expression of CD83 and the costimulatory molecules CD86 was not noticeable (10%-50%). Although CD1a+/CD14- DCs were potent stimulators of allogeneic lymphocytes, expansion of T cells from normal volunteers were not significant (average 27. 2 fold at DCs∶T cells ratio of 1∶10). At day 12, CD1a+ cells from three patients were studied by displaying G banding and Ph+ cells in these populations were 100%, 98% and 60%, respectively. At an effector∶target ratio of 40∶1, 32% to 45% cytotoxicity was noted with DC- stimulated T cells against autologous leukemia cells. Conclusions A stable serum- free culture system of CML- DCs was established. The expression of CD83 and CD86 on the surface of CML- DCs and DCs’ potent stimulation of allogeneic lymphocytes were not notable. DCs in CML patients can be derived from the malignant clone and these malignant DCs could induce anti- leukemic reactivity in autologous T lymphocytes without the necessity for additional exogenous antigens.     

The effects of exercise on the amplitude of the first heart sound in normal subjects

The cardiovascular responses to isometric and dynamic exercise have been studied in six normal subjects, before and after intravenous propranolol, using the amplitude of the first heart sound (S1), measured from an ultra-low frequency phonocardiogram, as an index of left ventricular mechanical performance. Dynamic exercise caused significant increases in heart rate and S1 amplitude which were largely inhibited by beta-adrenergic blockade. Isometric exercise also produced increases in heart rate and blood pressure, but a decrease in S1 amplitude. Propranolol had no significant effect on the cardiovascular response to isometric exercise. These results confirm previous suggestions that, in contrast to dynamic exercise, the normal cardiovascular responses to isometric exercise are relatively independent of the beta-adrenergic nervous system. Possible reasons why the improvement in left ventricular performance, which has previously been shown to occur during isometric handgrip, was not reflected in the phonocardiogram, are also discussed.     

Failure of sulfites to produce clinical responses in patients with systemic mastocytosis or recurrent anaphylaxis: Results of a single-blind study

Although sulfite sensitivity can precipitate asthma in a subpopulation of subjects with asthma, its role in precipitating anaphylaxis or as a nonspecific mast cell degranulator in systemic mastocytosis has not been examined. To evaluate critically the importance of sulfites in these diseases, eight patients with systemic mastocytosis and 25 patients with unexplained, recurrent anaphylaxis were challenged in a single-blind fashion; sodium bisulfite in capsules was administered in increasing doses of 1, 5, 10, 25, 50, 100, and 200 mg every 30 minutes. On separate occasions a liquid suspension of 200 mg of sodium bisulfite was administered to one patient with systemic mastocytosis and nine patients with anaphylaxis. Vital signs, pulmonary function tests, plasma histamine levels, and clinical reactions were monitored. There were no observable responses in either the mastocytosis group or in 23 of 25 patients in the anaphylaxis group. Two patients in the anaphylaxis group with initial positive challenges had similar symptoms on subsequent placebo challenge. One subject with asthma and with a history suggestive of sulfite sensitivity responded to oral challenge with 5 mg of sodium bisulfite and 100 micrograms of sodium bisulfite intradermally with a dramatic reduction in FEV, requiring treatment with bronchodilators. A comparison of baseline plasma histamine levels with those obtained after the sulfite challenge procedure in each category demonstrated a significant rise (p less than 0.05) in the systemic mastocytosis group. The overall level of significance determined by applying paired sample t tests to the histamine data from all subjects was p less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)