Improved estimates of discordance ratios in twin studies

In the study of monozygotic twins relative to disease and risk factors, particular interest focuses on the subset who are discordant for some suspected risk factor (for example, smoking), since such twins constitute a natural case-control pair. In such studies, questionnaires designed to identify the status of all twin pairs are sometimes error prone and can yield misleading estimates of the concordance-discordance ratios. Greater efforts to verify the characteristics of apparently discordant pairs than to verify those of apparently concordant pairs can result in the 'unequal ascertainment' fallacy. Using the results of a questionnaire with known error rates and the 'apparent' frequencies yielded, we present unbiased, maximum likelihood estimates of the 'true' proportions of concordant and discordant pairs. concordant and discordant pairs. We also present approximate covariances among these estimates.     

荧光染料在视神经脊髓鞘形成期从轴突至少突胶质细胞的扩散

将真蓝(true blue)混悬液注入出生后7、14、28d大鼠眼球内,经过一定时间后,视神经内的轴突和少突胶质细胞被荧光标记。荧光强度在视神经眼球端强于视神经交叉端;出生后14～28d的幼鼠荧光标记明显强于出生后7d的幼鼠;不同年龄组的动物荧光标记普遍在注射荧光染料后的第5d显著增强。本研究表明,荧光染料可被视网膜的节细胞吸收,经轴突输送,然后,横向扩散到少突胶质细胞,扩散的通路可能是朗氏结旁区的轴胶连接。     

人体液中喷布洛尔及其代谢物的GC/MS分析

用气相色谱一质谱联用(GC-MSD)系统分析方法检出了人尿中喷布洛尔的6个羟化代谢物,用Scp-Pak柱提取的方法检出了人血浆中的原型药物。并从分子结构上对此药物的代谢途径进行了研究。尿中提取和血中提取的回收率分别为90.83.%和85.88%,Gc-MSD的检测限为5pg。本方法适用于运动员兴奋剂的系统检查。     

The relationship between maternal needs and priorities in a neonatal intensive care environment

AIM: The aim of this study was to investigate the nature and organization of maternal needs and priorities in a neonatal unit. BACKGROUND: The relationship between maternal needs and priorities appears to be an under studied area in neonatal nursing. METHODS: A quantitative survey was carried out based on 209 mothers with premature infants. Two self-assessment schedules were used: critical care maternal needs inventory (J. Leske, Heart and Lung 15, 27-42) and a ranking scale. The data were analysed with multivariate analysis. FINDINGS: Data analysis revealed clear priorities in maternal needs. In particular the need for accurate infant related information was a priority for 93% of the mothers. Good communication practices with professionals were also valued. The mothers displayed altruistic behaviour, and self-related needs took second place. It is proposed that maternal needs demonstrate a hierarchical organization. CONCLUSION: It is important for nurses to consider the individual needs of the mothers, simply because the satisfaction of these needs is essential for maternal well-being.     

Steroid trials in the assessment of reversibility of air flow limitation: a survey of current clinical practice of chest physicians

To evaluate how steroid trials are currently used in the assessment of reversibility of air flow limitation, a postal questionnaire was sent to 355 consultant members of the British Thoracic Society working in England and Wales; 253 questionnaires were returned (71% response rate). Two respondents did not undertake steroid trials; of the remaining 251, 75% prescribed 30-40 mg oral prednisolone, with the commonest treatment period being 2 weeks. A high dose steroid inhaler was sometimes used as an alternative by 31% of respondents. Although 71% of respondents made lung function measurements on several occasions before starting steroids and 76% made measurements during treatment, 78% assessed patients on only one occasion at the end of the trials to ascertain its outcome. Weight, blood pressure and glycosuria were measured less frequently after the steroid treatment compared to the pre-trial period. Blood glucose and serum electrolytes were infrequently measured both before and after treatment. Wide variations exist in steroid trial regimens and current practice may neither provide definitive evidence of treatment benefit nor an adequate safeguard for patients against potential side-effects.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Five year study of prenatal testing for Huntington''s disease: demand, attitudes, and psychological assessment.

Adult predictive and prenatal testing programmes for Huntington's disease (HD) in Canada have been available since 1986. However, the demand for prenatal testing and the reasons why some people choose not to have the prenatal test for this late onset disorder have not been well documented. In addition, the knowledge and attitudes of adult predictive testing candidates and their partners about prenatal testing are not well known nor are the psychological effects of prenatal testing well understood. As of September 1991, 425 subjects had entered the Canadian Collaborative Study of Predictive Testing and, of these, 47 subjects or their partners had become pregnant. Of this group, 14 (30%) couples requested prenatal testing, 24 (51%) couples did not want prenatal testing, and nine (19%) at risk subjects had already received a decreased risk through adult predictive testing and, therefore, were not eligible for the prenatal test. Of the 14 couples who initially requested prenatal testing, seven withdrew. Thus, demand for the prenatal test by eligible candidates was 7/38 or 18%, which is much lower than the 32 to 65% expected based on early survey data. The most frequently cited reason for declining prenatal testing was the hope that a cure would be found in time for their children. While the majority of adult predictive testing candidates (71%) in our study had accurate information about definitive prenatal testing, many (63%) did not have a correct understanding of exclusion prenatal testing. Although no serious adverse events such as suicide planning or admission to psychiatric hospital have occurred, a particular need for careful counselling was identified for those at risk candidates and their partners who have one prenatal test and feel compelled to use the test again in future pregnancies. Even though prenatal testing for HD is not requested as often originally expected, it still remains a desired option for some at risk persons and their partners.     

Surface modification of poly(ether urethane urea) with modified dehydroepiandrosterone for improved in vivo biostability

In this study, a fatty acid urethane derivative of dehydroepiandrosterone (DHEA) was synthesized and evaluated as a polyurethane additive to increase long-term biostability. The modification was hypothesized to reduce the water solubility of the DHEA and physically anchor the additive in the polyurethane during implantation. Polyurethane film weight loss in water as a function of time was studied to determine the polymer retention of the modified DHEA. The polyurethane film with unmodified DHEA had significant weight loss in the first day (10%) that was previously correlated to rapid leaching of the additive. The polyurethane film with modified DHEA had significantly less weight loss at all time points indicating improved polymer retention. The effect of the modified DHEA additive on the biostability of a poly(ether urethane urea) was examined after 5 weeks of subcutaneous implantation in Sprague-Dawley rats. Optical micrographs and infrared analysis of the specimens indicated that the modified DHEA bloomed to the surface of the film forming a crystalline surface layer approximately 10-15 microns thick. After explantation, this surface layer was intact without measurable differences in surface chemistry as monitored by attenuated total reflectance-Fourier transform infrared spectroscopy. There was no evidence of degradation of the polyurethane underneath the modified DHEA surface layer as compared with the polyurethane control. We have concluded that the modified DHEA self-assembled into a protective surface coating that inhibited degradation of the polyurethane. The roughness of the modified DHEA surface layer prevented adherent cell analysis to determine if the additive retained the ability to down-regulate macrophage activity. Subsequent studies will investigate the ability of surface-modifying additives to modulate cellular respiratory bursts in addition to the formation of an impermeable barrier. This bimodal approach to improving biostability holds great promise in the field of polyurethane biomaterials.