Twenty Years’ Experience in Allogeneic Hematopoietic Stem Cell Transplantation for Philadelphia Chromosome—Positive Acute Lymphoblastic Leukemia in the Nagoya Blood and Marrow Transplantation Group

Between October 1981 and December 2000, 46 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) underwent allogeneic hematopoietic stem cell transplantation (HSCT) in the Nagoya Blood and Marrow Transplantation Group. The median age was 28.5 years (range, 4-51 years). All but one patient achieved engraftment. Grade II-to-IV acute graft-versus-host disease (GVHD) developed in 32.5% of patients, and chronic GVHD developed in 40.5%. The incidences of relapse and treatment-related mortality (TRM) at 5 years were 65% and 26%, respectively. The estimated overall survival rate at 5 years was 23%. Univariate analysis showed that improved disease-free survival (DFS) was independently associated with complete remission (CR) at transplantation (39%), compared with non-CR (8%) (P = .023). Non-CR at transplantation was associated with a higher risk of relapse. Donor type, acute GVHD, and time from diagnosis to HSCT all had a significant effect on TRM. In a multivariate analysis, 9 months or more from diagnosis to HSCT was the only variable statistically significant for DFS (relative risk, 3.22; P = .01). This study demonstrates that allogeneic HSCT cures a significant population of patients with Ph+ ALL. Relapse is the major obstacle limiting the success of HSCT. Early transplantation during CR from donors, including unrelated persons or mismatched relatives, may offer improved long-term DFS.     

Captopril (SQ 14,225) (d-3-mercapto-2-methylpropanoyl-l-proline): A novel orally active inhibitor of angiotensin-converting enzyme and antihypertensive agent

Relatively potent and specific in vitro and in vivo (oral or intravenous) inhibition of angiotensin-converting enzyme by a nonpeptidic compound, captopril (SQ 14,225; d-3-mercapto-2-methylpropanoyl-l-poline), was demonstrated in excised guinea pig ileum and in rats, rabbits, cats, dogs, and monkeys. The design of captopril was based on a hypothetical model of the active site of the enzyme. Captopril, in vitro or in vivo, was about ten times as potent as teprotide. Inhibition of angiotensin-converting enzyme was evaluated in vitro and in vivo by inhibition of the contractile or vasopressor activity of angiotensin I or by augmentation of the contractile or vasodepressor activity of bradykinin. Acute of subacute dosage with captopril moderately to markedly lowered the blood pressure of the renin-dependent aorticligated and the conscious two-kidney Goldblatt hypertensive rat; in the latter, the effect was intensified by concomitant dosage with a thiazide diuretic. Furthermore, the life-prolonging effects of captopril in renal hypertensive rats were augmented by a thiazide diuretic. In the two-kidney Goldblatt rat, acute captopril (p.o.) was about ten times as potent as teprotide (s.c.) in lowering blood pressure. Acute or subacute oral doses of captopril moderately reduced the blood pressure of the spontaneously hypertensive Wistar-Kyoto rat; chronic dosage almost normalized blood pressure. Captopril produced little or no hypotension in the saltreplete normotensive Wistar-Kyoto rat. Bilateral nephrectomy virtually abolished the hypotensive activity of captopril in the spontaneous hypertensive rat. The results suggest that captopril acts in large part by inhibiting the renin-angiotensin-aldosterone system to reduce elevated blood pressure, especially in renindependent models of hypertension; the roles of the kallikrein-kinin-prostaglandin systems and sodium balance remain to be elucidated. Captopril also lowers blood pressure in apparently non-renin-dependent types of hypertension by mechanisms that are as yet undefined.     

艾灸神阙穴对不同程度力竭运动大鼠海马区单胺类神经递质的影响

目的:探讨艾灸神阙穴对不同程度力竭运动大鼠海马区单胺类神经递质的影响。方法:将72只SD雄性大鼠按随机数字表法分为正常组8只、模型组和艾灸组各32只,根据造模或治疗时间将模型组和艾灸组随机分为1、4、7、10次亚组,每亚组8只,采用游泳实验建立力竭模型。艾灸各亚组大鼠造模后即刻温和灸神阙穴15min,隔日1次,各亚组大鼠完成相应力竭运动后24 h检测海马组织5-HT、DA、NE的含量。结果:与正常组比较,模型各亚组5-HT含量均明显升高,模型1、4、7次亚组NE含量均明显升高,模型1次亚组DA含量明显升高,模型10次亚组却明显降低。与相应模型亚组比较,艾灸4次亚组NE含量明显升高,艾灸7、10次亚组5-HT含量显著降低,DA、NE含量明显升高。结论:艾灸神阙穴可以通过调节反复力竭运动大鼠海马区神经递质,促进神经细胞的功能恢复,改善机体疲劳状态,为今后临床应用提供一定的实验基础。     

Allergenicity of various peanut products as determined by RAST inhibition

Extracts of 19 different peanut products and peanut oil were tested for their allergenicity by the radioallergosorbent test inhibition assay using a crude peanut extract from raw peanuts as the standard for comparison. Seventeen of the extracts were able to competitively inhibit the binding of serum IgE from peanut-sensitive patients with the solid-phase raw peanut extract. Peanut oil and the extract from hydrolyzed peanut protein did not inhibit binding, which suggests that these products are not allergenic. The peanut hull flour extract showed a slight ability to inhibit binding, suggesting that this product contains minor amounts of the peanut allergen.     

9例Ph染色体阳性成人急性淋巴细胞白血病的临床和实验研究

报道９例Ｐｈ染色体阳性的急性淋巴细胞白血病（Ｐｂ￣－ＡＬＬ）的临床和实验研究结果。Ｐｈ￣－ＡＬＬ占同期研究的３１例成人ＡＬＬ的２９％。其中４例Ｐｈ染色体与正常核型嵌合，３例合并＋１７。病情完全缓解后２例Ｐｈ染色体消失，１例其百分比显著降低。免疫表型检测８例为Ｂ系列ＡＬＬ。以、为主要表型，同时有ＣＤ＿２和ＣＤ＿（３４）的高表达。１例病程中转变为杂合性急性白血病。上述免疫表型特点反映Ｐｈ￣＋ＡＬＬ的恶性细胞起源于早期定向或多能干细胞。该组患者白细胞计数较高，治疗反应差，提示Ｐｈ￣＋ＡＬＬ为一预后不良的特殊亚型，治疗上应有别于ＰｈＡＬＬ。     

Nosocomial pseudoepidemics and pseudoinfections: an increasing problem.

The infection control practitioner often relies on microbiologic data in order to conduct nosocomial infection surveillance and control activities. On the basis of a review of the medical literature, false positive culture and stained smear results representing pseudoinfection are being reported with greater frequency. Documented cases and clusters of pseudoinfectons are reviewed, and the epidemiologic characteristics and methods for detection and prevention of this increasingly recognized problem are discussed.     

Out of the boxes,out of the silos: The need of interdisciplinary collaboration to reduce poor-quality medical products in the supply chain

In this paper, we argue that understanding and addressing the problem of poor-quality medical products requires a more interdisciplinary approach than has been evident to date. While prospective studies based on rigorous standardized methodologies are the gold standard for measuring the prevalence of poor-quality medical products and understanding their distribution nationally and internationally, they should be complemented by social science research to unpack the complex set of social, economic, and governance factors that underlie these patterns. In the following sections, we discuss specific examples of prospective quality surveys and of social science studies, highlighting the value of cross-sector partnerships in driving high-quality, policy-relevant research in this area.     

‘Mate’ Intake,Hormone-Based Risk Factors and Breast Cancer: a Case-Control Study

Previous reports on the inverse association between ‘mate’ intake (infusion of Ilex Paraguariensis herb) and breastcancer (BC) risk led us to consider two main roles for the infusion: as a substantial antioxidant contributor and asa hormone regulator, particularly through anti-aromatase capacities. Since menstrual-reproductive risk factors forBC reflect women’s estrogenic exposure during the reproductive lifespan, and considering that ‘mate’ intake exertsputative stronger protection among high antioxidant contributors, we attempted to analyze interactions among theinfusion, hormon-linked reproductive factors and BC risk, which have hitherto remained unexplored. We analyzed adatabase of 572 BC incident cases and 889 controls. Women were interviewed with a specific questionnaire featuringsocio-demographic, lifestyle and reproductive variables (age at menarche, 1st live birth and menopause; number of livebirths; breastfeeding months), and a food frequency questionnaire, focusing on ‘mate’ intake (consumer status, dailyintake, age at start, age at quit, duration of habit). Odds ratios (OR) and their 95% confidence Intervals were calculatedthrough unconditional logistic regression, adjusting for relevant potential confounders. ‘Mate’ intake showed stronginverse associations with some high-risk hormone-related factors: early menarche, nulliparity, low breastfeeding, longreproductive years and high number of ovulatory cycles. Moreover, all subsets of high dietary energy demonstratedeven stronger associations. In conclusion, regarding exposure to known hormone risk factors, we found strong inverseassociations between high ‘mate’ intake and BC, which were greater among those consuming higher calorific diets.Our analyses support possible combined antioxidant and antiestrogenic effects for ‘mate’ infusions.     

异基因造血干细胞移植后伊马替尼维持治疗对Ph＋ALL疗效的Meta分析

目的：系统评价异基因造血干细胞移植（Allo-HSCT）后伊马替尼（IM）维持治疗对费城染色体急性淋巴细胞白血病（Ph＋ALL）的疗效。方法计算机检索 Cochrane Library及临床试验注册中心、PubMed、Embase、中国知网、中国生物医学文献数据库、中国万方和中国维普数据库等,并辅以手工检索和文献追溯,获取 Allo-HSCT后 IM维持治疗对 Ph＋ALL疗效的随机对照研究及观察性研究。检索时限均从建库至2014年4月3日。筛选文献并提取资料和评价质量后,采用 Cochrane协作网RevMan5．2软件进行 Meta分析。共纳入7篇研究文献,共计366例 Allo-HSCT后Ph＋ALL患者。分别比较移植后 Ph＋ALL不同 IM治疗起点的疗效差异,及移植后Ph＋ALL是否使用 IM的疗效差异。结果 Allo-HSCT后 IM维持治疗对患者总体生存率、无病生存率、非复发死亡率方面的影响差异有统计学意义（P＜0．05）,其效应统计量风险比（HR）及其95％CI 分别为0．22（0．17～0．27）、0．84（0．80～0．89）、0．41（0．20～0．82）;IM维持治疗对移植后白细胞植入时间及血小板植入时间影响差异无统计学意义（P＞0．05）,其效应统计量均数差（MD）及其95％CI分别为－0．92（－4．35～2．50）、0．78（－1．59～3．16）;对复发率的影响尚存在争议。预防性应用 IM与检测到微小残留病变后应用相比,可降低移植后的分子学复发率,并延长 BCR／ABL持续阴性的时间。但对于缓解持续时间、无病生存期、总生存率及无事件生存率等方面均无明显影响。结论 Allo-HSCT后应用 IM维持治疗可提高Ph＋ALL患者总体生存率,改善无病生存率并降低非复发死亡率,对白细胞、血小板植入时间无明显影响,对复发率的影响尚存在争议。移植后早期检测到BCR／ABL阳性与不良预后相关,而移植后 IM最佳治疗起点尚无定论。     

Effect of Carbon Dioxide on Cochlear Blood Flow in Guinea Pigs

The influence of carbon dioxide (CO2) on cochlear blood flow (CBF), blood pressure (SBP) and skin blood flow (SBF) was studied in anaesthetized guinea pigs. A transient acute respiratory acidosis was produced by inhalation of CO2 and oxygen (O2) gas mixtures. The blood flows were measured by laser Doppler flowmetry (LDF). High CO2 increased CBF and SBP, and decreased SBF in a dose-dependent manner. The responses of CBF, SBP and SBF to high CO2 were reversible. Our results indicate that high CO2 (and low pH) dilates the smooth muscle of the blood vessels, resulting in an increase in CBF. CO2 also activates the sympathetic nervous system in the whole body, producing an increase in SBP. The distribution of alpha-adrenergic fibres/receptors is abundant in skin and scarce in the cochlea. The constrictive effect on blood vessels is much greater in the skin than in the cochlea, thus our results showed a decrease in SBF during stimulation with higher CO2.