Favorable prognosis of hyperdiploid common acute lymphoblastic leukemia may be explained by sensitivity to antimetabolites and other drugs: results of an in vitro study

DNA hyperdiploidy is a favorable prognostic factor in childhood acute lymphoblastic leukemia (ALL). The explanation for this prognostic significance is largely unknown. We have studied whether DNA ploidy was related to cellular resistance to 12 drugs, assessed with the methyl- thiazol-tetrazolium assay, in samples of 74 children with common (CD10+ precursor B-cell) ALL. Sixteen patients had hyperdiploid ALL cells and 58 patients had nonhyperdiploid ALL cells. Hyperdiploid ALL cells were more sensitive to mercaptopurine (median, 9.0-fold; P = .000003), to thioguanine (1.4-fold; P = .023), to cytarabine (1.8-fold; P = .016), and to I-asparaginase (19.5-fold; P = .022) than were nonhyperdiploid ALL cells. In contrast, these two ploidy groups did not differ significantly in resistance to prednisolone, dexamethasone, vincristine, vindesine, daunorubicin, doxorubicin, mitoxantrone, and teniposide. The percentage of S-phase cells was higher (P = .05) in the hyperdiploid ALL samples (median, 8.5%) than in the nonhyperdiploid ALL samples (median, 5.7%). However, the percentage of cells in S-phase was not significantly related to in vitro drug resistance. We conclude that the favorable prognosis associated with DNA hyperdiploidy in childhood common ALL may be explained by a relative sensitivity of hyperdiploid common ALL cells to antimetabolites, especially to mercaptopurine and to I-asparaginase.     

聚乙二醇干扰素α-2b单药或聚乙二醇干扰素α-2b联合拉米夫定治疗HBeAg阳性慢性乙型肝炎的多中心、随机、双盲、对照试验

与干扰素非应答者相比,应答的慢性乙型肝炎(乙肝)患者发生肝硬化、肝衰竭及肝细胞癌的可能性明显下降[1,2].然而,大部分慢性乙肝患者不能获得应答.在已经获得批准治疗慢性乙肝的药物中,最常用的是干扰素和核苷类似物,如拉米夫定或阿德福韦.     

Seven years of regional malaria control collaboration--Mozambique, South Africa, and Swaziland

The Lubombo Spatial Development Initiative is a joint development program between the governments of Mozambique, Swaziland, and South Africa, which includes malaria control as a core component of the initiative. Vector control through indoor residual spraying (IRS) was incrementally introduced in southern Mozambique between November 2000 and February 2004. Surveillance to monitor its impact was conducted by annual cross-sectional surveys to assess the prevalence of Plasmodium falciparum infection, entomologic monitoring, and malaria case notification in neighboring South Africa and Swaziland. In southern Mozambique, there was a significant reduction in P. falciparum prevalence after the implementation of IRS, with an overall relative risk of 0.74 for each intervention year (P < 0.001), ranging from 0.66 after the first year to 0.93 after the fifth intervention year. Substantial reductions in notified malaria cases were reported in South Africa and Swaziland over the same period. The success of the program in reducing malaria transmission throughout the target area provides a strong argument for investment in regional malaria control.     

2007年青海省碘缺乏病高危地区育龄妇女尿碘调查

Objective To investigate the iodine nourishment in women of child-beating age in high risk region of iodine deficiency disorders (IDD) in Qinghai Province. Methods According to The Notice to Launch a Reinforced Survey on IDD in High Risk Region issued by The Ministry of Public Health, 17 counties in 6 districts were selected as investigated area in Qinghai Province in 2007, using two stage cluster sampling and combining The National IDD Preliminary Surveillance Scheme, 30 women aged from 18 to 40 years were selected in each village, 1 or 2 villages in each town, 3 to 5 towns in each county, who were divided into newly wedding, pregnant, lactation and other women of child-bearing age. Iodine concentration in urine was detected by the method of As3+-Ce4+catalytic spectrophotometry. Results One thousand six hundreds and four urine iodine samples were analyzed. The median was 93.3 μg/L,52.1%(836/1604),31.8%(510/1604) and 12.4%(199/1604) was lower than 100,50 and 20 μg/L, respectively. It was 70.5%(527/747) and 43.0%(128/298) of women in Yushu and Haixi that had urinary iodine lower than 100 μg/L, respectively, while it was 50% of women in the 6 districts, to be specific, 88.3%(91/103) in Nangqian, 83.8% (62/74) in Zaduo and 70.7%(118/167) in Zhiduo Counties respectively. The median of urinary iodine in women who were not lactating and not pregnant was only 88.6 μg/L, of whom 53.9% (763/1415) lower than 100 μg/L. Conclusions The women of reproductive age in high risk region of IDD are deficient of iodine in Qinghai Province.     

A screening algorithm for HIV‐associated neurocognitive disorders

Background

HIV physicians have limited time for cognitive screening. Here we developed an extra‐brief, clinically based tool for predicting HIV‐associated neurocognitive impairment (HAND) in order to determine which HIV‐positive individuals require a more comprehensive neurological/neuropsychological (NP) assessment.

Methods

Ninety‐seven HIV‐positive individuals with advanced disease recruited in an HIV out‐patient clinic received standard NP testing. A screening algorithm was developed using support vector machines, an optimized prediction procedure for classifying individuals into two groups (here NP‐impaired and NP‐normal) based on a set of predictors.

Results

The final algorithm utilized age, current CD4 cell count, past central nervous system HIV‐related diseases and current treatment duration and required approximately 3 min to complete, with a good overall prediction accuracy of 78% (against the gold standard; NP‐impairment status derived from standard NP testing) and a good specificity of 70%.

Conclusion

This noncognitive‐based algorithm should prove useful to identify HIV‐infected patients with advanced disease at high risk of HAND who require more formal assessment. We propose staged guidelines, using the algorithm, for improved HAND therapeutic management. Future larger, international studies are planned to test the predictive effect of nadir CD4 cell count, hepatitis C virus infection, gender, ethnicity and HIV viral clade. We recommend the use of this first version for HIV‐infected Caucasian men with advanced disease.     

四川省凉山州艾滋病病毒感染者配偶感染状况调查

目的了解以吸毒感染为主的艾滋病高流行地区感染者配偶的HIV感染状况及危险因素,提出防治建议。方法 2008年1-3月通过入户调查,对凉山州布拖县和昭觉县226名HIV感染者的配偶开展艾滋病知识、态度和行为学调查,同时进行HIV血清学检测。结果感染者配偶HIV阳性检出率达到25.7%,调查对象按国家督导评估方案计算的知识知晓率为50.9%,71.7%的调查对象最近1个月与配偶发生过性行为,最近1次性行为安全套使用率仅为9.1%(11/121)。结论凉山地区HIV感染者的配偶感染状况严重,配偶间无保护性行为发生比例高,针对配偶间危险性行为的干预工作不足,应扩大检测,加强随访干预,提供适宜的预防技术。     

Induction of bone formation in biphasic calcium phosphate scaffolds by bone morphogenetic protein‐2 and primary osteoblasts

Bone tissue engineering strategies mainly depend on porous scaffold materials. In this study, novel biphasic calcium phosphate (BCP) matrices were generated by 3D‐printing. High porosity was achieved by starch consolidation. This study aimed to characterise the porous BCP‐scaffold properties and interactions of osteogenic cells and growth factors under in vivo conditions. Five differently treated constructs were implanted subcutaneously in syngeneic rats: plain BCP constructs (group A), constructs pre‐treated with BMP‐2 (group B; 1.6 µg BMP‐2 per scaffold), seeded with primary osteoblasts (OB) (group C), seeded with OB and BMP‐2 (group D) and constructs seeded with OB and pre‐cultivated in a flow bioreactor for 6 weeks (group E). After 2, 4 and 6 weeks, specimens were explanted and subjected to histological and molecular biological analyses. Explanted scaffolds were invaded by fibrovascular tissue without significant foreign body reactions. Morphometric analysis demonstrated significantly increased bone formation in samples from group D (OB + BMP‐2) compared to all other groups. Samples from groups B‐E displayed significant mRNA expression of bone‐specific genes after 6 weeks. Pre‐cultivation in the flow bioreactor (group E) induced bone formation comparable with group B. In this study, differences in bone distribution between samples with BMP‐2 or osteoblasts could be observed. In conclusion, combination of osteoblasts and BMP‐2 synergistically enhanced bone formation in novel ceramic scaffolds. These results provide the basis for further experiments in orthotopic defect models with a focus on future applications in orthopaedic and reconstructive surgery. Copyright © 2012 John Wiley & Sons, Ltd.     

改良皮内注射法在新生儿卡介苗接种中的应用

目的探讨改良皮内注射法提高新生儿卡介苗接种成功率的效果。方法将136例符合接种条件的新生儿随机分成2组，实验组66例采用改良皮内注射手法接种卡介苗，对照组70例采用常规皮内注射法接种卡介苗，比较2组的接种效果。结果实验组接种一次成功率，新生儿卡介苗接种后12周卡痕率、结核菌素纯蛋白衍化物（PPD）试验阳性率，均高于对照组，2组比较差异有统计学意义，P〈0．01。结论改良皮内注射法应用于新生儿卡介苗接种，具有不漏液，皮丘大小符合接种要求，接种成功率高的优点。