Score Statistic to Test for Genetic Correlation for Proband-Family Design

In genetic epidemiological studies informative families are often oversampled to increase the power of a study. For a proband‐family design, where relatives of probands are sampled, we derive the score statistic to test for clustering of binary and quantitative traits within families due to genetic factors. The derived score statistic is robust to ascertainment scheme. We considered correlation due to unspecified genetic effects and/or due to sharing alleles identical by descent (IBD) at observed marker locations in a candidate region. A simulation study was carried out to study the distribution of the statistic under the null hypothesis in small data‐sets. To illustrate the score statistic, data from 33 families with type 2 diabetes mellitus (DM2) were analyzed. In addition to the binary outcome DM2 we also analyzed the quantitative outcome, body mass index (BMI). For both traits familial aggregation was highly significant. For DM2, also including IBD sharing at marker D3S3681 as a cause of correlation gave an even more significant result, which suggests the presence of a trait gene linked to this marker. We conclude that for the proband‐family design the score statistic is a powerful and robust tool for detecting clustering of outcomes.     

中药安迪对HL-60细胞分化的诱导作用

目的　探讨安迪粉针剂 (Andi)对 HL- 60细胞分化的诱导作用 .方法　采用人早幼粒白血病细胞株 (HL - 60 )为靶细胞 ,分为不加任何药物的对照组 (C组 )、安迪粉针剂 (Andi)组、阳性对照药维甲酸 (RA)组和苦参 (KS)组 ,进行体外培养和诱导分化 ,观测细胞生长曲线、细胞形态、硝基蓝四氮唑(NBT)还原和吞噬能力等指标 .结果　 2 mg· L-1 Andi可显著地抑制 HL - 60细胞增殖 ,使原始细胞分化为中幼以下的成熟细胞 ,分化后的细胞具有 NBT还原能力和吞噬功能 ;Andi为 68.0 % ,RA为 61 .5% ,KS为 59.0 % ,C组还原能力仅6.0 % (P<0 .0 1 vs C) .其形态的改变和吞噬能力与阳性对照药维甲酸 (RA)和苦参 (KS)相似 ,分别为 52 .0 % ,45.5%和56.5% (P>0 .0 5) ;均明显高于空白对照组 .C组吞噬功能仅7.5% (P <0 .0 1 vs C)其 NBT还原能力与 KS相当 (P >0 .0 5) .结论　 Andi对 HL - 60细胞具有显著的诱导分化作用     

Systemic effects of two nasally administered glucocorticosteroids

Two topical corticosteroids, budesonide (BUD) and beclomethasone dipropionate (BDP), both administered as suspensions in water, were investigated in healthy volunteers regarding influence on cortisol in plasma and urine (U-cortisol) after nasal application. In the first study, single doses of 200, 400, and 800 μg of BDP and BUD were given at 10:00 pm. In the second study, 100, 200, and 400 μg were given mornings and evenings for 4 days. In the single-dose study, none of the drugs or doses showed any significant influence on cortisol in plasma. However, U-cortisol decreased significantly after BUD 400 and 800 μg. In the multidose study, U-cortisol values were significantly reduced after all doses of BUD and the highest dose of BDP. The compounds tested showed different ability to cause measurable systemic effects after nasal application. The clinical implication is that the prescriber, when choosing a compound, should take the application site into consideration and should also be encouraged to find the lowest effective dose.     

化学染发剂和冷烫精的毒性及对人体健康影响的调查研究

本文通过化学染发剂和冷烫精对大白鼠骨髓多染红细胞，毛囊细胞的微核实验及人群健康影响调查，结果表明化学染发剂，冷烫清具有较强致突变作用，两者同时使用致突变明显增强，并提出研制高效无毒染发剂和加强防护的重要性。     

Super-reactivity to amphetamine toxicity induced by schedule of reinforcement

The chronic exposure of rats to a schedule of operant water reinforcement coupled with chronically restricted access to water sensitized the animals to intermittentd-amphetamine injections (0.31–2.5 mg/kg with intervals of 12–23 days between any two injections) in such a way that this drug came to produce catastrophic losses of body weight (32.4% of control levels). In the sessions whend-amphetamine was administered, the rats were also given a total of 12 brief electric shocks. Loss of body weight was unaccompanied by parallel changes in operant behavior performance, or in food or water intake. Remarkably, in other studies with the same interventions (sham schedule sessions, water deprivation, and foot shocks), with the exception that reinforcers were never delivered,d-amphetamine did not produce catastrophic falls in body weight. This super-reactivity tod-amphetamine toxicity may be mediated by a possible stressor action of the schedule of reinforcement. Its mechanism might be analogous to the known sensitization produced by classical experimental stressor stimuli to the repeated administration ofd-amphetamine.     

Effect of dietary fat content on the bioavailability of a sustained release quinidine gluconate tablet

Quinidine gluconate 324 mg sustained release tablets (Quinaglute) was administered as a single dose to 15 healthy male subjects following an overnight fast, immediately following a high fat (HF) breakfast or immediately following a low fat (LF) breakfast. Serum samples were obtained over a 48 h period and analyzed for quinidine content using a high performance liquid chromatographic assay. Under the conditions of the study, both the rate and extent of quinidine bioavailability was significantly affected by food. The extent of bioavailability was statistically significantly greater (p less than 0.05) following both the HF and LF meals as compared to that in the fasted state. Rate of bioavailability was significantly enhanced following the LF meal as compared to that of the other two treatment groups. Although peak concentrations were greater and time to peak concentrations somewhat later following the HF meal versus those under fasting conditions, these differences were not statistically significant. In addition, the characteristics of the serum concentration-time profile (as defined by the number, magnitude, and time of occurrence of the multiple absorption maxima) was unique for each of the three treatment groups. Possible mechanisms underlying these results are explored.     

Comparative effects of enoximone and theophylline on plasma catecholamines and haemodynamics in cardiosurgical patients

Summary The release of endogenous catecholamines in aorto-coronary bypass graft patients receiving either 0.5 mg/kg enoximone (n=10), 4.0 mg/kg theophylline (n=10) or saline solution (control,n=10) has been studied, as well as certain haemodynamic parameters. Adrenaline (A) and noradrenaline (NA) concentrations were not significantly changed by the administration of enoximone. Theophylline caused a small increase in NA (+ 40% in the 1st min) and a marked increase in A (approximately + 7000% in the 1st min), which still remained elevated at the end of the investigation period (+ 220% in the 30th min). The major haemodynamic effects of enoximone were a significant increase in cardiac index (CI; + 35%) and a decrease in pulmonary capillary wedge pressure (PCWP; −27%), pulmonary artery pressure (PAP; −21%), RVEDV and RVESV, while the heart rate (HR) remained almost unchanged. The dominant haemodynamic effects of theophylline were an increase in HR (+ 26%; arrhythmia in 3 patients), PAP (+ 22%), and RVEDV (+ 19%), while REVESV (+ 26%), MAP (−16%), CI (−14%), and RVEF (−15%) fell significantly. It is concluded that the haemodynamic actions of enoximone are not mediated by catecholamine release, whereas the adverse cardiovascular effects of theophylline might partly be explained by the significant increase in plasma adrenaline.     

Guidelines and recommendations for MR imaging safety and patient management III. Questionnaire for screening patients before MR procedures

The authors present the third installment of the guidelines and recommendations from the Safety Committee of the Society for Magnetic Resonance Imaging (now the Society of Magnetic Resonance) concerning various issues related to the safety and management of patients undergoing magnetic resonance (MR) procedures. This document was developed to provide standardized and consistent information for use by health practitioners involved in screening patients or other individuals for MR procedures.