From expert-based to quantitative retrospective exposure assessment at a Soderberg aluminum smelter

OBJECTIVES: Expert judgement of exposure levels is often only poorly or moderately correlated with directly measured levels. For a follow-up of a historical cohort study at a S?derberg aluminum smelter we updated an expert-based semiquantitative job exposure matrix of coal tar pitch volatiles (CTPV) to quantitative estimates of CTPV and benzo(a)pyrene (BaP). METHODS: Mixed effects models to predict exposure for potroom operation and maintenance jobs were constructed from personal CTPV and BaP measurements. Mean exposures of jobs in non-potroom locations were directly calculated when measurements were available. Exposure estimates for jobs/time periods with no measurements were based on proportion of time spent in exposed areas compared to jobs where exposure was modeled or measured. For pre-1977, the original expert exposure assignments were calibrated using the updated 1977 estimates. RESULTS: The rate of change in exposure levels varied by time period and was accounted for in mixed models with a linear spline time trend. Other variables significant in the models were job, potroom group and season as fixed effects, and worker as a random effect. The models for potroom operations explained 45 and 27% of the variability in the CTPV and BaP measurements, respectively. The models for maintenance jobs explained 40 and 19% of the variability in the CTPV and BaP measurements, respectively. For 1977-2000 model estimates, direct calculation of means and extrapolation from modeled/measured exposures accounted for 57, 6 and 37% of the exposed person-years, respectively. CONCLUSIONS: The above methodology maximized the use of exposure measurements and largely replaced the original expert-based estimates. Finer discrimination between exposure levels was possible with the updated exposure assessment. The new estimates are expected to reduce exposure misclassification and help better assess the exposure-response relationships.     

Medroxyprogesterone acetate with Zoladex for long-term treatment of fibroids: effects on bone density and patient acceptability

A randomized trial was carried out to investigate the effect of 12 months administration of the gonadotrophin-releasing hormone agonist (GnRHa) Zoladex in combination with either placebo or medroxyprogesterone acetate (MPA) from the third month. Bone density, markers of bone resorption, symptoms and uterine volume were monitored in 24 women with symptomatic fibroids or menstrual problems. A total of 21 women were recruited to act as controls for the assessment of bone parameters. Vasomotor side-effects were reduced significantly in the MPA-treated group. The reduction in uterine volume in women with fibroids was not impaired by the addition of MPA. The bone markers osteocalcin and alkaline phosphatase were assessed in plasma, and the cross-links pyridinoline and deoxypyridinoline measured in urine. Changes in these markers are reported which suggest increases in bone resorption during the period of observation. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry at the spine and forearm. The net reduction in BMD at the spine in the treated groups was 4.30 +/- 0.59% at 6 months and 7.50 +/- 0.78% at 1 year, with no change in the control group. No change was seen in forearm BMD. No protective effect was observed when MPA was added. At 1 year after the completion of treatment, BMD remained significantly below baseline, and this has implications for the prolonged use of GnRHa.      

基于简易反向滤波跟踪算法分析松质骨的微结构特征

平均散射元间距（MSS）已被众多研究者用于分析准规则组织的微结构特征，平均骨小梁间距（MTBS）是诊断骨质疏松症的重要参数之一。本研究提出一种基于简易反向滤波跟踪（SIFT）的算法，用于估计平均骨小梁间距。对计算机仿真信号和离体牛胫骨松质骨的超声背散射信号分别进行分析处理。实验结果表明，SIFT算法能简单而有效地减小测量系统和传播介质特性的干扰，并且在较强噪声存在的情况下，SIFT算法比AR倒谱法的估计结果更为精确。因此，SIFT算法可用于估计平均骨小梁间距，从而反映松质骨的微结构特征。     

S-100B、NSE和MBP对急性脑出血预后的临床评估

目的:研究脑出血后血清S-100B蛋白、神经特异性烯醇化酶(NSE)和碱性髓鞘蛋白 (MBP)浓度在预后评估中的价值。方法:对40例急性脑出血住院病人在病后72 h内进行血清S- 100B、NSE和MBP浓度检测,并结合格拉斯哥昏迷量表(GOS)评分进行比较分析。结果:本组40例病人脑出血后血清S-100B、NSE和MBP浓度均显著高于正常对照组,而且病人中不同预后组之间S- 100B、NSE和MBP浓度存在显著差异。分别以脑出血后72 h血清S-100B浓度2．0μg／L,NSE浓度 30μg／ml和MBP浓度10 μg／ml为临界标准评估顶后,S-100B的特异度为91％,敏感度为72％;NSE 特异度为77％,敏感度为67％;MBP特异度为63％,敏感度为61％。结论:脑出血后血清S-100B蛋白、NSE和MBP浓度对评估脑出血病人预后具有较高的特异性和敏感性。     

The efflux of 86Rb and [3H]5-HT from human platelets during continuous perfusion: effects of potassium-induced membrane depolarization and thrombin stimulation

In order to study the ionic efflux or granule release from human platelets following pulse exposure to various stimuli, a method for continuous perfusion of platelets was developed. The method was applied to compare the effects of membrane depolarization and thrombin stimulation on the release of 86Rb and [3H]5-HT. Washed and preloaded human platelets were placed on a membrane filter in a temperature controlled polypropylene chamber, and subsequently perfused with buffer. After an initial washout period the efflux of 86Rb or [3H]5-HT reached steady, low levels. K+ induced concentration dependent increases in 86Rb efflux, corresponding to a depolarization of the membrane potential, whereas the efflux of [3H]5-HT was unaltered. Thrombin induced concentration dependent increases in the efflux of both 86Rb and [3H]5-HT. Pretreatment with K+ 12 or 30 mM did not alter the [3H]5-HT efflux induced by thrombin 0.1 U ml-1. Scanning electron micrographs of platelets on the filter showed that the unstimulated platelets had regular shape, whereas after addition of thrombin there was formation of pseudopods and minor aggregates. The effect of potassium-induced membrane depolarization on platelet aggregation was also studied. High concentration of K+ did not induce aggregation or shape change during 2 or 10 minutes of incubation. K+ had little or no effect on aggregation induced by ADP 2 microM or thrombin 0.4 U ml-1. The results from release experiments and aggregation tests argue against an immediate coupling between membrane potential and platelet reactivity.     

Methylprednisolone differentially regulates IL-10 and tumour necrosis factor (TNF) production during murine endotoxaemia

IL-10 is an endogenous antiinflammatory cytokine that inhibits TNF biosynthesis and protects mice from lipopolysaccharide (LPS)-induced lethality. As synthetic glucocorticoids are widely used as antiinflammatory agents, we analysed the effects of methylprednisolone administration on IL-10 biosynthesis during murine endotoxaemia. We found that low doses of methylprednisolone (2–10 mg/kg) markedly inhibited TNF production but did not affect serum levels of IL-10, while a high methylprednisolone dose (50 mg/kg) increased LPS-induced IL-10 levels. In parallel, we observed that LPS-induced IL-10 production is TNF-independent in this experimental setting. Experiments conducted in vitro indicated that methylprednisolone (from 0·01 to 100 μg/ml) also increased the biosynthesis of IL-10 by LPS-activated mouse peritoneal macrophages. We conclude that methylprednisolone differentially regulates IL-10 and TNF production induced by LPS both in vivo and in vitro at the macrophage level.     

雌激素受体β基因Rsa I和A／uI多态性与原因不明月经过少的关系

目的探讨西南地区雌激素受体β（estrogen receptor β，ERβ）基因多态性与原因不明月经过少的关系。方法用聚合酶链反应-限制性片段长度多态性方法，对西南地区100例原因不明月经过少患者和100名月经正常者ERβ基因RsaI和AluI多态性进行分析。结果R等位基因频率患者组为37．5％，正常对照组为48．5％（比值比值：0．64，95％CI：0．42～0．97，P=0．026）。患者组A等位基因频率为18．0％，正常对照组为11．5％（比值比值：1．69，95％CI：0．93～3．09，P=0．07）；RsaI和A／uI限制性片段长度多态性在两组中均呈多态性分布。结论ERβ基因多态性与原因不明月经过少有关，R等位基因可能是其保护因素，A等位基因可能是其危险因素。     

Isotypic analysis of maternally transmitted Plasmodium falciparum-specific antibodies in Cameroon, and relationship with risk of P. falciparum infection

In malaria-endemic areas, infants are relatively protected against malaria infection. Such protection is though to be related principally to the transplacental transfer of maternal antibodies. We measured total and Plasmodium falciparum-specific IgG (including subclasses), IgM, and IgE antibodies in 154 paired maternal-cord serum samples from an area of meso- to hyperendemic malaria in South Cameroon. Among peripheral mother blood samples, total IgG and IgM were detected in all samples, IgE in all but two. Plasmodium falciparum-specific IgG were detected in all serum samples, IgM and IgE in < 75% of samples. The prevalence rates of anti-P. falciparum IgG subclasses varied from 75% to 97%. With the exception of P. falciparum-sptcifxc IgG, all antibody class and subclass levels were lower in cord blood than in peripheral mother blood. Plasmodium falciparum-spccific IgGl and IgG3 isotypes were transferred to the offspring more often and more efficiently than IgG2 and IgG4. The detection of total and P. falciparum-specific IgM and IgE in some cord serum samples demonstrated that fetuses can mount humoral response against malaria parasites. We also determined whether transplacentally acquired antibodies protect against malaria infection by relating the antibody levels at birth to the risk of acquiring P. falciparum infection during the first 6 months of life. Among various classes and subclasses of P. falciparum-spccific antibodies, only IgG2 were related to a decrease in the risk of acquiring a P. falciparum peripheral blood infection from birth to 6 months of age.