维生素D_3对报告载体荧光素酶表达的作用

目的：　研究１,２５－二羟维生素Ｄ３ 对结肠癌细胞系Ｃａｃｏ－２ 细胞中报告基因表达的作用,并探讨在报告载体ｐＧＬ２ 序列中存在潜在的抑制性维生素Ｄ应答元件（ＶＤＲＥ）的可能性。方法：　采用磷酸钙沉淀法将报告载体转染入Ｃａｃｏ－２ 细胞。Ｃａｃｏ－２细胞经不同浓度１,２５－二羟维生素Ｄ３ 处理后测定细胞裂解液中表达的荧光素酶活性。结果：　应用ｐＧＬ２ 报告载体时,当用ｐＳＧ５－ＶＤＲ表达载体共转染后,１,２５－二羟维生素Ｄ３显著地抑制Ｃａｃｏ－２ 细胞荧光素酶的表达（Ｐ＜ ０．０５）;而未使用该表达载体共转染则无抑制作用（Ｐ＞ ０．０５）。应用ｐＧＬ３ 报告载体时,不同浓度的１,２５－二羟维生素Ｄ３ 对ｐＬＧ３转染后Ｃａｃｏ－２ 细胞表达的荧光素酶活性均无显著抑制作用（Ｐ＞ ０．０５）,该作用不依赖是否存在有ｐＳＧ５－ＶＤＲ表达载体共转染。结论：１,２５－二羟维生素Ｄ３ 对报告载体ＰＧＬ２ 荧光素酶表达具有抑制作用,而对ｐＧＬ３ 则否;类似人类ＰＴＨ基因中的潜在抑制性ＶＤＲＥ存在于报告载体ｐＧＬ２,在ｐＧＬ３ 中该ＶＤＲＥ业已改变。     

Measuring health-related quality of life in patients with venous leg ulcers

Introduction: The effect on quality of life by healing leg ulcers is not known and no validated disease-specific tool is available for measuring health-related quality of life (HRQoL) for people with venous leg ulcers. The objective of this paper was to compare four generic instruments [MOS 36-Item Short-Form Health Survey (SF-36); EuroQol (EQ); McGill Short Form Pain Questionnaire (SF-MPQ) and the Frenchay Activities Index (FAI)] used for measuring HRQoL in people with venous leg ulcers, and to offer guidance on the most appropriate tool for researchers. Methods: Two hundred and thirty-three patients with venous leg ulcers were recruited as part of a randomised controlled trial of the cost-effectiveness of community leg ulcer clinics. Subjects completed questionnaires containing the four instruments on three occasions (initial assessment, 3 and 12 months). The discriminative and evaluative properties of the four instruments were compared. Results: All four instruments were acceptable to patients, taking a mean of 19.3 (SD 6.3) min to complete. At initial assessment, the SF-MPQ had poorer discriminative properties than the other three instruments and was not able to distinguish between the different patient groups in relation to age and ulcer duration. The FAI was good at discriminating between the different patient groups (at initial assessment) in relation to age, mobility and ulcer size. At the three-month follow-up, the SF-MPQ was more responsive than the other measures and detected changes in HRQoL, whereas the EQ and SF-36 did not. At 12 months, the SF-MPQ still identified differences and the SF-36 and EQ also did at this stage. Conclusion: In the absence of a validated condition-specific tool for measuring changes in general health status for patients with venous leg ulcers, we make the following recommendations. For evaluating the outcome of interventions with a short-term follow-up (three months) in a clinical study we recommend the SF-MPQ and for 12-month follow-up in a clinical study the SF-36, with or without the SF-MPQ.     

Salmeterol tachyphylaxis in steroid treated asthmatic subjects.

BACKGROUND: Tachyphylaxis to the protection afforded by salmeterol to broncho-constrictor stimuli after regular use has been described in patients with mild asthma not receiving inhaled corticosteroids. The present study was performed to investigate whether airway tachyphylaxis occurs in symptomatic asthmatic subjects receiving inhaled corticosteroids, the group for whom salmeterol is recommended in clinical practice. METHODS: Thirty one adult patients with symptomatic chronic asthma who were receiving inhaled corticosteroids were randomised in a double blind manner and on a 2:1 basis to receive salmeterol 50 micrograms (n = 22) or placebo (n = 9) twice daily. Baseline forced expiratory volume in one second (FEV1) was measured during the run-in period, on day 0, and after four and eight weeks of regular treatment (following a 36 hour test drug washout period). Airway responsiveness to methacholine was measured one hour after administration of the test drug on these occasions. Diary cards were kept throughout the study and for a two week follow up period. RESULTS: Baseline FEV1 was not significantly different between the treatment groups or between visits. There was significant bronchodilatation one hour after salmeterol administration at 0, four, and eight weeks. No significant tachyphylaxis of the bronchodilator action of salmeterol was seen. Protection against methacholine induced bronchoconstriction reduced from 3.3 doubling dilutions after the first dose of salmeterol to two doubling dilutions after four and eight weeks of regular treatment. Symptom scores and "rescue" salbutamol use were significantly reduced during salmeterol treatment and daytime improvements were maintained into the follow up period. CONCLUSIONS: Inhaled corticosteroids did not prevent tachyphylaxis to the protection afforded by salmeterol to methacholine induced bronchoconstriction. The clinical significance, if any, of these findings remains to be defined.     

Interobserver variation in the assessment of pelvic organ prolapse

The aim of this study was to determine the interobserver agreement of two grading systems for pelvic organ prolapse: the vaginal profile and the International Continence Society (ICS) draft proposal. Forty-nine consecutive women referred for evaluation of urinary incontinence and/or pelvic organ prolapse were studied. Patients were first examined by a physician and a nurse clinician using the vaginal profile, followed by an examination according to the technique described in the ICS draft proposal for standardization of terminology (1994). statistic and Pearson's correlation coefficient were used to determine interobserver variability for the ICS system by overall stage, by stage-specific comparison, and by specific anatomic location. The vaginal profile was evaluated by obtaining a for overall degree of prolapse, stage-specific comparison and by anatomic area. The for the ICS stage was 0.79 (P<0.001), and the for the vaginal profile by area of greatest prolapse was 0.68 (P<0.001), indicating substantial interobserver agreement for both systems. The ICS system was noted to have substantial interobserver agreement by a stage-specific comparison. All anatomic locations of the ICS staging system were found to correlate significantly, and a high degree of interobserver precision was found. The vaginal profile also showed significant interobserver agreement by overall degree of prolapse, by specific degree of prolapse, and by anatomic area. It was concluded that both the proposed ICS staging system and the traditional vaginal profile show significant interobserver agreement both by overall stage, stage-specific analysis and specific location. The registered nurse examination correlated well with the physican examination, indicating that the most important factor in obtaining reproducible results may be definition and close attention to examination technique.EDITORIAL COMMENT: There has recently been a great deal of interest in the anatomy and physiology of the pelvic floor and the various investigative techniques to define its function. The lack of a standardized and reproducible system to describe pelvic organ prolapse through the hiatus of the pelvic floor has hampered research into its pathophysiology and treatment. The authors applied a validated statistic and Pearson's correlation coefficient to convincingly measure interobserver reliability for the ICS system and indicated an index of trend between points on the ICS scale as well.     

State mediation of conflicts over work refusals: the role of the Ontario Labour Relations Board.

A key feature of occupational health and safety legislation is that it has sought to compartmentalize health and safety issues by creating structures and processes that depart from "typical" social relations of production. The Ontario Labour Relations Board, in adjudicating disputes concerning work refusals, faces the difficult, if not impossible, task of defining and maintaining a sphere in which workers have an uncommon latitude and power. Analysis of cases before the Board during the 1980s shows how it errs on the side of caution and uses criteria related to "typical" social relations of production to define convincing testimony and assess workers' entitlement to redress. Similarly, employers' interests and the requirements of the labor process are a reference point in the Board's definition of the scope of workers' rights and what constitute legitimate penalties for the "abuse" of these. Yet decisions are not wholly biased toward employers; dissenting opinions reveal important differences and progressive rulings establish precedents that could be a basis for future decisions.     

Income differences in persons seeking outpatient treatment for mental disorders: a comparison of the United States with Ontario and The Netherlands

BACKGROUND: Variations in the relationships among income, use of mental health services, and sector of care are examined by comparing data from 3 countries that differ in the organization and financing of mental health services. METHODS: Data come from the 1990-1992 National Comorbidity Survey (n = 5,384), the 1990-1991 Mental Health Supplement to the Ontario Health Survey (n = 6,321), and the 1996 Netherlands Mental Health Survey and Incidence Study (n = 6031). Analysis of the association between income and use of mental health services was carried out for the population that was between ages 18 and 54 years. Differential use of mental health treatment was examined in 3 sectors: the general medical sector, the specialty sector, and the human services sector. RESULTS: No significant association between income and probability of any mental health treatment was observed for persons with psychiatric disorders in any of the 3 countries. However, there were significant differences among countries in the association between income and sector of mental health care treatment. In the United States, income is positively related to treatment being received in the specialty sector and negatively related to treatment being received in the human services sector. In the Netherlands, patients in the middle-income bracket are less likely to receive specialty care, while those in the high-income bracket are less likely to be seen in the human service sector. Income is unrelated to the sector of care for patients in Ontario. CONCLUSIONS: Future research should examine whether differential access to the specialty sector for low-income people in the United States is associated with worse mental health outcomes.