An efficient design for verifying disease outcome status in large cohorts with rare exposures and low disease rates.

Cohort studies require the use of large samples when the risk of the event is very low. Databases that are large and population-based, such as Medicaid files, are frequently used for cohort studies, since they provide access to the large samples required for adequate statistical power at a relatively affordable cost. Epidemiologic studies using these databases typically require verification of reported diagnoses, however, because of the potential for errors in disease reporting. When exposure prevalence is also low, as in many pharmacoepidemiologic investigations of drug toxicity, there are few exposed cases compared to the number of unexposed cases. Verification of all unexposed presumptive cases through medical records is costly. We investigate the statistical efficiency of a design in which all exposed cases but only a subsample of the unexposed cases are verified. We show that good efficiency can usually be achieved with a small subsample of unexposed cases. Published in 1999 by John Wiley & Sons, Ltd.     

(-)-Epigallocatechin-3-gallate inhibition of ultraviolet B-induced AP-1 activity

Green tea polyphenols have been shown to inhibit cancer in a variety of tumor models, including ultraviolet B (UVB)-induced non-melanoma skin cancer. In green tea extracts, the major dry mass constituent is the family of catechins, of which (-)-epigallocatechin-(3)-gallate (EGCG) is considered to be important for the chemopreventive activity. EGCG has been shown to have antioxidant properties, but there has been little progress toward identifying the specific targets and mechanisms of its action. Using cultured human keratinocytes, we show that UVB- induced AP-1 activity is inhibited by EGCG in a dose range of 5.45 nM to 54.5 microM. EGCG is effective at inhibiting AP-1 activity when applied before, after or both before and after UVB irradiation. EGCG also inhibits AP-1 activity in the epidermis of a transgenic mouse model. This work begins to define a mechanism by which EGCG could be acting to inhibit UVB-induced tumor formation.      

Flexible sigmoidoscopy training and its impact on colorectal cancer screening by primary care physicians

BACKGROUND: Colorectal cancer is an ideal disease for prevention with screening programs. Efforts to increase compliance with screening recommendations have included training primary care physicians to perform flexible sigmoidoscopy. OBJECTIVE: To assess the impact of flexible sigmoidoscopy training on compliance with current screening recommendations. METHODS: We performed a cross-sectional study of 232 patients cared for by physicians in a primary care network. MAIN OUTCOME MEASURES: Rates of screening for colorectal cancer and rates of undergoing flexible sigmoidoscopy were compared across patient groups according to the physician's training and whether the physician performs flexible sigmoidoscopy in his or her practice. RESULTS: Among 217 patients included in the analysis, 122 (56%) were cared for by physicians who were trained in flexible sigmoidoscopy, of whom 79 (36%) were cared for by physicians who perform flexible sigmoidoscopy in their practice. Patients cared for by physicians trained in flexible sigmoidoscopy were not significantly more likely to receive any colorectal cancer screening than were patients cared for by physicians not trained in flexible sigmoidoscopy (odds ratio, 1.16; 95% confidence interval, 0.67-2.01). However, patients cared for by physicians who perform flexible sigmoidoscopy in their practice were more likely to have undergone any colorectal cancer screening (odds ratio, 1.73; 95% confidence interval, 1.02-2.95) and flexible sigmoidoscopy (odds ratio, 2.69; 95% confidence interval, 1.14-6.36). CONCLUSION: Performance of flexible sigmoidoscopy by primary care physicians has the potential to increase the rate of colorectal cancer screening with flexible sigmoidoscopy.     

Neuropsychological deficits among patients with late-onset minor and major depression.

Cognitive ability of minor depressed patients (N=28), major depressed patients (N=26) and healthy elderly (N=38) was examined cross-sectionally to determine if cognitive abilities of patients with late-onset depression decrease with increasing severity of disease and if cognitive scores for minor depressed patients fall between those of healthy elderly and major depressed patients. A pooled within-group principal component analysis of cognitive test scores identified five components, three of which showed significant group differences. Verbal Recall and Maintenance of Set separated controls from major depressed patients and minor from major depressed patients. Executive Functioning separated controls from minor depressed patients, and Working Memory was borderline for separating controls from major depressed patients. The component representing Nonverbal Recognition was not statistically significant. Partial correlations controlling for age and education indicate that cognitive performance does decrease as severity of depression increases, and the magnitude of the change varies from a trend to a significant deficit depending on the cognitive domain. This decline in cognitive performance parallels a similar trend observed in neuroanatomical studies in which the volume of the frontal and temporal lobes decrease with increasing severity of depression.     

Glucocorticoid receptor and heat shock protein 90 in peripheral blood mononuclear cells from asthmatics

目的探讨糖皮质激素受体(GR)和热休克蛋白90(HSP90)mRNA在糖皮质激素敏感型(SS)、依赖型(SD) 和抵抗型(SR)哮喘中的表达及其在SR哮喘发病中的作用。 方法采用反转录-聚合酶链(RT-PCR)的方法分别测定正常人(10例)、SS哮喘(10例)、SD哮喘(5例)和 SR哮喘(6例)的外周血单个核细胞(PBMC)中GR mRNA和HSP90 mRNA的表达,并在体外用IL-2、IL-4分 别、联合刺激上述细胞观察其受刺激后GR mRNA和HSP90 mRNA表达的改变情况。 结果 SR哮喘的GR和HSP90 mRNA表达水平最高(分别为0.730±0.171和1.122±0.165),SS哮喘次之 (分别为0.359±0.350和0.885±0.250),SD哮喘最低(分别为0.017±0.008和0.078±0.039)。正常人有 一定表达(分别为0.052±0.013和0.362±0.101)。GR和HSP90 mRNA的表达各组间相比P＜0.05。正 常人、SS、SD和SR哮喘HSP90/GR的比值分别为7.15±1.84、8.39±7.95、5.51±3.30、1.57±0.18,SR哮喘 HSP90/GR比值明显低于前三组(P＜0.05)。IL-2和IL-4单独刺激对SS、SD和SR哮喘的GR、HSP90 mRNA表达无明显影响,二者联合刺激可使SS、SD和SR哮喘GR mRNA表达以及SS、SD哮喘HSP90 mRNA 表达增强,但不能使SR哮喘HSP90 mRNA表达增强。 结论 SR哮喘中HSP90 mRNA表达相对不足造成HSP90/GR比值降低可能是SR哮喘形成的原因之一, IL-2+IL-4对GR和HSP90 mRNA表达的不同调节作用可能是形成SR哮喘HSP90/GR比值降低的原因之一。     

Patient attitudes towards surgically implantable, long-term delivery of psychiatric medicine.

The introduction of surgically implantable medication delivery systems provides psychiatric patients with reversible, uninterrupted access to medication for up to 14 months. This study designed and administered a survey to assess patients' attitudes and beliefs towards illness, medication, and this potential new treatment method. The survey included questions about demographics, insight and attitudes towards illness, current and past medication adherence, attitudes towards psychiatric and nonpsychiatric medications, and understanding and attitudes towards surgical implants. The sample of 206 psychiatric patients was almost equally split between favorably and unfavorably considering implants. Patients favorable towards implants ascribed forgetting and failure to refill medication on time as the reasons for missing doses, recognized the benefits of medication in general, and understood that the implant would be inserted under the skin. Favorable consideration of implants was positively correlated with the desire to avoid adverse consequences of missing medicine, stay well, avoid the need for daily oral medications, and decrease family burden. Unfavorable consideration of implants was related to a preference to take medication orally, concern about feeling controlled, unwillingness to try something new, and not understanding that the implant would be placed under the skin. Demographic variables, past/current medications, specific diagnosis, and illness severity did not influence the decision. This survey elucidates patients' attitudes and beliefs towards illness, medication, and surgical implants. The results indicate that a significant proportion of patients recognize the difficulties of medication adherence and the need for better methods to attain therapeutic response. Thus, the study provides impetus for future work in this area.     

针刺疗法治疗功能性肠疾病的研究进展

针灸在中国已经经验性的应用了数千年,而且在全世界范围越来越广泛的被医生和患者所接受．功能性胃肠疾病是临床上常见疾病．依据罗马标准,普通人群中一种以上功能性胃肠病的患病率高达70％以上．由于其病因与发病机制仍不明确,所以治疗效果尚不能令人满意．在过去的几十年里,对于针灸对于功能性胃肠疾病的治疗及可能机制做了一些研究．对探求针刺疗法对功能性胃肠疾病的潜在治疗作用有着重要的临床意义．我们对已有的关于针刺疗法对于不同功能性肠疾病的治疗效果和机制研究作一综述．     

Children of alcoholics: Attention, information processing and event-related brain potentials

Recent studies on biological markers and risk factors for alcoholism have distinguished between nonalcoholic individuals with a family history of alcoholism and those without such a family history on measures of event-related brain potentials. The main finding of these "high-risk" studies is a smaller amplitude of the P300 component in males with a history of paternal alcoholism. This relationship between P300 amplitude and a family history of paternal alcoholism has been observed in adults and children. Consequently, several authors have suggested that a reduced P300 amplitude could serve as a vulnerability marker for alcoholism. We address several conceptual and methodological issues involved in the study of event-related potentials in children at high risk for alcoholism. Subsequently, the ongoing high-risk study of the Amsterdam Institute for Addiction Research is described briefly.     

Psychological mechanisms of enhanced risk of addiction in children of alcoholics: a dual pathway?

The background and rationale of a recently started project of the Amsterdam Institute for Addiction Research are outlined. This project is aimed at the psychological mechanisms underlying an enhanced risk of (later) addiction in children of alcoholics and the relationship with childhood psychopathology. A dual pathway mechanism is proposed, in which the type of alcoholism of the parent plays a major role. The child of a multigenerational primary alcoholic parent may suffer from an inherited mild dysfunction of the prefrontal cortex, expressed in neuropsychological and personality characteristics similar to those of the alcoholic parent. These are impulsive, aggressive and reward-seeking behaviour, response perseveration and, in some children, related psychopathology such as conduct disorders. For a child of a secondary alcoholic parent, another mechanism is proposed. In these children, stress and social learning may lead to negative affectivity and repressive coping style, with emotional problems at a later age, and the risk of falling into the "circle of secondary alcoholism". In both pathways, alcohol-related expectancies are suggested to constitute a "final common pathway" between different risk factors and later alcohol abuse. Specific expectancies might be related to different pathways and to gender differences in later drinking patterns.