The long-term impact of in vitro drug sensitivity on risk stratification and treatment outcome in acute lymphoblastic leukemia of childhood (CoALL 06-97)

Background

In a study of childhood acute lymphoblastic leukemia (CoALL 06-97 study), the in vitro sensitivity of the patients’ cells to prednisolone, vincristine and asparaginase was introduced as a new additional risk parameter for treatment stratification. In parallel in vivo treatment response was assessed by determining the presence and extent of minimal residual disease in a subset of patients (n=224). Here we report the long-term impact of in vitro sensitivity-based risk stratification according to survival and compare the results of in vitro sensitivity with in vivo response.

Design and Methods

Patients with a sensitive in vitro profile were treated with a reduced intensity protocol (n=167) whereas patients defined as low risk according to conventional parameters but with a resistant in vitro profile were given intensified therapy (n=47).

Results

At a median follow-up of 6.8 years event-free survival was 0.80±0.03 for patients with a sensitive profile, 0.73±0.03 for those with an intermediate profile and 0.67±0.08 for those with a resistant profile (P=0.015). Overall, the treatment results of the cases stratified according to in vitro sensitivity were similar to those of the historical control group stratified based on conventional risk factors. Minimal residual disease at the end of induction was a strong predictor of outcome in B-precursor and T-cell acute lymphoblastic leukemia. There was no correlation between in vitro and in vivo treatment response in B-precursor leukemia (Spearman’s r=0.13; P=0.15) in contrast to T-cell acute lymphoblastic leukemia (Spearman’s r=0.63; P<0.001)

Conclusions

A moderate reduction in treatment intensity for patients with a sensitive in vitro profile was possible without jeopardizing treatment outcome. However, in vitro drug testing was affected by a decrease in risk predictive power over time and was not correlated with in vivo assessment of minimal residual disease in B-precursor acute lymphoblastic leukemia. It was, therefore, abandoned in favor of the assessment of in vivo response in subsequent CoALL trials.     

Percutaneous ethanol injection therapy of autonomous （toxic）thyroid nodules

Percutaneousethanolinjectiontherapy(PElT)hasbeenestablishedasaninterventionalmethodoftheablationofhepaticmalignancies ,especiallyhepatocellularcarcinoma(HCC) ,sincelong .Itseffectsarebasedoncellulardehydration ,toxicandcoagulationnecrosisandthrombosisofsmallvenuleswithinthetumour .Theresultisfibrosisofthedamagedtissue ,lossoffunctionandshrinkage .Hencethe“ablative”effectofabsolute(95 % )ethanol.Themoreconfinedallylesionthebettertheablativeeffectduetothehighconcentrationofthetoxicliquid .H…     

极低出生体重婴儿脐动脉导管血液采集量和速度对脑血容量和氧合度的影响

目的:从脐动脉导管采集血液可降低脑血容量和脑氧合度。本研究的目的是评价采集量和速度的影响。方法:对48名婴儿在常规从脐动脉采集血液时进行研究,其出生体重中位数为965g(480～1500g)、胎龄中位数为27周(23～34周)。采集步骤按照一个严格的方案进行:抽吸量(1.6m l)、采集量(1.7m l或0.2m l)、再注入量(1.6m l)和冲洗量(0.6m l),抽吸时间(40s或80s)、再注入时间(30s)和冲洗时间(6s)。每一婴儿的采集量和抽吸时间按照随机方式的顺序而不同(1.7m l/40s、1.7m l/80s、0.2m l/30s)。采用近红外光谱分析法测定脑氧合度和还原血红蛋白浓度的改变…     

Genetic amniocentesis: a risk factor for preterm delivery?

Objective: To determine whether genetic amniocentesis performed in the second trimester of pregnancy is associated with the risk of preterm delivery. Study design: Case–control study performed in several departments of obstetrics and gynaecology of nine European countries. Three thousand and ninety-one preterm births and 5298 controls randomly selected from singleton births born at term during 1994–1997 were analysed. Logistic regression models were used to compare preterm births altogether and, separately, spontaneous preterm delivery and induced preterm delivery. Results: An increased risk of preterm delivery was found in women having second trimester genetic amniocentesis after taking account of other risk factors and confounding variables (odds ratios (OR)=1.59, 95% confidence intervals (95% CI): 1.31–1.92). The association was statistically significant and similar for spontaneous preterm delivery and induced preterm delivery. Conclusion: The study shows an association between preterm delivery and genetic amniocentesis. In view of the wide use of amniocentesis, further research on the etiologic role of this prenatal diagnostic technique is needed.     

人胚胎及胎盘艾滋病毒(HIV)抗原的免疫组织化学检测

本文用免疫组织化学 ABC 法及 A-PAAP 桥联酶标技术,应用单克隆抗 HIV 抗体对临床确诊 HIV 阳性产妇的新生儿胎盘56例和 HIV阳性孕妇的流产胚胎19例,胎盘29例进行 HIV抗原的检测,并对 HIV抗原检出与胎儿官内 HIV感染的诊断,以及儿童期艾滋病的病因追踪等相互关系问题进行了讨论。     

导管消蚀无休止性室性心动过速

１９例无休止性室性心动过速（室速）采用导管消蚀治疗。１７例为冠心病，２例扩张性心肌病。平均年龄６４±８岁，平均左室射血分数３１％±９％。消蚀部位根据心内膜激动标测、隐匿性拖带和束支电位标测确定。消蚀能源为直流电９例，射频１０例。全部病例的心动过速均被导管消蚀终止。１例射频消蚀后发生心包填塞。电生理检查８例（４４％）有诱发性室速，７例消蚀后植入了心内转复除颤器。随访７例（３９％）有自发性室速，仅１例形态学与被消蚀的心动过速相同。本组结果表明，导管消蚀可作为一种选择性措施治疗无休止性室速，但消蚀后的心动过速复发率高     

Candesartan in heart failure

Candesartan cilexetil is a nonpeptide selective blocker of the angiotensin II receptor sub-type 1. It is a prodrug that is converted to its active metabolite during its variable absorption. It is highly protein bound with a small volume of distribution and a nine-hour half-life. Candesartan is one of two angiotensin receptor blockers approved for use in heart failure. MEDLINE was searched using OVID and PubMed to evaluate the evidence for using candesartan in patients with heart failure. Pharmacologic and pharmacokinetic evaluations, as well as clinical trials, were selected and are presented in this review. Clinical evidence supports the indication for use in systolic heart failure. Results for use in patients with diastolic heart failure were non-significant. Candesartan was well tolerated in the trials, with hyperkalemia, renal dysfunction, and hypotension being the most common adverse events. Use of angiotensin receptor blockers with angiotensin-converting enzyme inhibitors needs further study; however, candesartan appears to provide added benefit in this setting. Candesartan is a safe and effective option for patients with systolic heart failure. Data regarding other angiotensin receptor blockers is underway.