An in vitro assay for evaluating chemosensitivity of leukaemia cells: preclinical studies

The present study was aimed at defining the standard conditions for predictive chemosensitivity testing of human leukaemias. The in vitro cytotoxic potential of 11 anticancer drugs against L1210 murine leukaemia was comparatively determined 3 and 48 h after in vitro exposure of leukaemia cells to these agents. In preliminary testing, drug-induced damage was estimated in terms of percent inhibition of: tumour cell proliferation, by microscopic determination of viable cell numbers; and DNA synthesis, by measuring the extent of incorporation of the labelled nucleoside 125IUdR. Since the two tests appeared to yield comparable results, all subsequent experiments on the various murine tumours were performed using the radiolabel incorporation technique. The results obtained pointed out that this metabolic assay performed 48 hours after drug exposure appears to be capable of predicting both "spontaneous" and "induced" in vivo resistance of murine leukaemias.     

Percutaneous transluminal renal angioplasty in patients with solitary kidney

We report our experience with percutaneous transluminal angioplasty of renal arteries (PTRA) in solitary kidney patients. Our series includes 31 patients (mean age: 52 years). 7 with solitary kidney following surgical nephrectomy and 24 with functioning solitary kidney. PTR indicated in presence of stenoses ranging from 60–95 % of vessel lumen. Procedure, with 29 patients were technically successful and mean values for stenosis dropped from 77 % to 33 %. In order to assess the results technically, changes in arterial blood pressure (according to Martin's classification) and creatinine levels were considered. Of 25 followed-up patients, 13 were cured (52%), 8 improved (32%),and 4 were unchanged (16%%). Complications were observed during procedures in five patients (16. 1 % ), superimposing that of nonsolitary kidney patients. Good revasculariiation, reduction of blood pressure, preservation or even improvement of renal function and low complications, make PTRA the best procedure with solitary kidney patients.     

Design and synthesis of modified quinolones as antitumoral acridones.

The bacterial topoisomerase II (DNA gyrase) and the mammalian topoisomerase II represent the cellular targets for quinolone antibacterials and a wide variety of anticancer drugs, respectively. In view of the mechanistic similarities and sequence homologies exhibited by the two enzymes, tentative efforts to selectively shift from an antibacterial to an antitumoral activity was made by synthesizing a series of modified tricyclic quinolones, in which the essential 3-carboxylic function is surrogated by phenolic OH and the classic C-6 fluorine atom is replaced by a NH2 group. The resulting 7-amino-9-acridone derivatives were assayed for their antibacterial as well as cytotoxic activities. No antibacterial activity was found. On the other hand, many derivatives showed significant cytotoxic activity against both HL-60 and P388 leukemias and a wide panel of human and rodent solid tumor cells, derivatives 25 and 26 displaying the best overall antiproliferative activity. Against the LoVo cell line, derivative 25 exhibited higher cytotoxic effects than etoposide.     

男性与女性糖尿病患者致死性冠心病的额外危险：37个前瞻性队列研究的汇总分析

目的：估计男性和女性糖尿病患者致死性冠心病的相对危险。设计：前瞻性队列研究的汇总分析。数据来源：自1966年至2005年3月间Embase和Medline确认并发表的研究，加上源自亚太队列研究协作组的研究，采用正文词组与MeSH主题词相结合的策略进行检索。综述方法：对入选研究的要求为报告有或无糖尿病的男性与女性致死性冠心病的相对危险比较的估计值。如果对估计值仅做年龄调整（而其它因素来经调整——泽者注），则将该研究排除在外。结果：总共纳入37项2型糖尿病和致死性冠心病的研究，涉及447064例患者。糖尿病患者的致死性冠心病发生率显著高于非糖尿病患者（5．4％比1．6％）。与无糖尿病者相比，糖尿病患者发生致死性冠心病的总的相对危险，女性为3．50，95％可信区间为2．70～4．53，显著高于男性患者（2．06，95％可信区间1．81～2．34）。在除外8项仅根据年龄调整的研究后，两性之间危险的差异大大减小，但仍然具有极显著统计学意义。汇集29项经多因素调整估计值的研究，总的相对危险比（女性比男性）为1．46（1．14～1．88）。结论：糖尿病相关的致死性冠心病相对危险，女性比男性高出50％。这种额外的冠心病危险可以通过女性糖尿病患者具有更多不利的心血管危险因素特点以及倾向于对男性患者更注重治疗的可能偏差来解释。     

Predictors of remission and relapse in idiopathic nephrotic syndrome: a prospective cohort study

Background

Although most children with idiopathic nephrotic syndrome will respond to corticosteroid therapy, 80–90 % suffer one or more relapses.

Methods

Using Cox proportional hazard models, we analyzed predictors of remission and relapse in 1-year follow-up data on children aged below 15 years with new-onset nephrotic syndrome.

Results

Of 129 children, 107 achieved remission with corticosteroid therapy and 86 subsequently relapsed. Boys achieved remission more often than girls (adjusted hazard ratio [AHR] 1.52, 95 % confidence interval (CI) 1.02–2.3). Boys relapsed significantly more frequently than girls (AHR 1.77, 95 % CI 1.11–2.83) and were more likely to have frequently relapsing disease (AHR 3.3, 95 % CI 1.18–9.23). The risk of first relapse increased with the number of days to first remission (AHR 1.02, 95 % CI 1.01–1.04). The risk for a frequently relapsing course increased with a shorter time from remission to first relapse (AHR 0.92, 95 % CI 0.87–0.97).

Conclusions

In idiopathic nephrotic syndrome, boys are more likely to respond initially, more likely to relapse, and to be classified as having frequently relapsing nephrotic syndrome. A decrease in time from remission to first relapse predicts for a frequently relapsing course.     

Blood glucose and risk of cardiovascular disease in the Asia Pacific region

OBJECTIVE: To assess the shape and strength of the association between usual blood glucose and cardiovascular disease (CVD) in Asian and Australasian cohorts and to determine the impact of adjusting for other determinants of CVD risk and excluding people with diabetes. RESEARCH DESIGN AND METHODS: Relative risk estimates and 95% CIs were calculated from Cox models, stratified by sex and cohort, and adjusted for age at risk on individual participant data from 17 cohort studies. Repeat measurements of blood glucose were used to adjust for regression dilution bias. RESULTS: Fasting blood glucose data were available for 237,468 participants, and during approximately 1.2 million person-years of follow-up, there were 1,661 stroke and 816 ischemic heart disease (IHD) events. Data were also available on 27,996 participants with nonfasting glucose measurements. Continuous positive associations were demonstrated between usual fasting glucose and the risks of CVD down to at least 4.9 mmol/l. Overall, each 1 mmol/l lower usual fasting glucose was associated with a 21% (95% CI 18-24%) lower risk of total stroke and a 23% (19-27%) lower risk of total IHD. The associations were similar in men and women, across age-groups, and in Asian compared with Australasian (Australia and New Zealand) populations. Adjusting for potential confounders or removing those with diabetes as baseline did not substantially affect the associations. Associations for nonfasting glucose were weaker than those with fasting glucose. CONCLUSIONS: Fasting blood glucose is an important determinant of CVD burden, with considerable potential benefit of usual blood glucose lowering down to levels of at least 4.9 mmol/l.     

In vitro synergistic activity of PDN-IFN alpha and NM + IFN alpha combinations on fresh bone-marrow samples from multiple myeloma patients

The differential staining cytotoxicity (DiSC) assay was used to evaluate the in vitro sensitivity of tumour and normal bone-marrow cells from 21 multiple myeloma (MM) patients to antitumour agents methylprednisolone (PDN), nitrogen mustard (NM) and recombinant interferon alpha-2b (IFN alpha) tested singly and in the combinations PDN + IFN alpha and NM + IFN alpha. Both the PDN-IFN alpha and NM-IFN alpha associations were more efficacious than any agents used singly in reducing the percentage of myeloma cell survival. However, whereas NM, alone and in combination with IFN alpha, provoked a severe reduction in normal bone-marrow population, PDN and PDN + IFN alpha induced an increase percentage survival of normal bone-marrow cells. These findings indicate that, at least in vitro, the PDN-IFN alpha combination exerts a great antitumor effect which is not associated with a relevant cytotoxic activity on normal myeloid cells.     

The discrimination of dyslipidaemia using anthropometric measures in ethnically diverse populations of the Asia–Pacific Region: The Obesity in Asia Collaboration

Dyslipidaemia is a major risk factor for cardiovascular disease and is only detectable through blood testing, which may not be feasible in resource‐poor settings. As dyslipidaemia is commonly associated with excess weight, it may be possible to identify individuals with adverse lipid profiles using simple anthropometric measures. A total of 222 975 individuals from 18 studies were included as part of the Obesity in Asia Collaboration. Linear and logistic regression models were used to assess the association between measures of body size and dyslipidaemia. Body mass index, waist circumference, waist : hip ratio (WHR) and waist : height ratio were continuously associated with the lipid variables studied, but the relationships were consistently stronger for triglycerides and high‐density lipoprotein cholesterol. The associations were similar between Asians and non‐Asians, and no single anthropometric measure was superior at discriminating those individuals at increased risk of dyslipidaemia. WHR cut‐points of 0.8 in women and 0.9 in men were applicable across both Asians and non‐Asians for the discrimination of individuals with any form of dyslipidaemia. Measurement of central obesity may help to identify those individuals at increased risk of dyslipidaemia. WHR cut‐points of 0.8 for women and 0.9 for men are optimal for discriminating those individuals likely to have adverse lipid profiles and in need of further clinical assessment.