Polymorphisms in manganese superoxide dismutase and catalase genes: functional study in Hong Kong Chinese asthma patients

BACKGROUND: Reactive oxygen species may contribute to the pathogenesis of asthma. Functional genetic polymorphisms of antioxidant enzymes, superoxide dismutase (SOD) and catalase are good candidates for asthma susceptibility. OBJECTIVE: To investigate the association of the manganese-containing form of SOD (MnSOD) gene at amino acid position 16 (Val16Ala) and catalase gene in the promoter at A-21T and C-262T polymorphisms and asthma in a Hong Kong Chinese population. METHODS: The association study was conducted in a case-control design in asthma patients (n=251) and healthy controls (n=316) by genotyping. The functional significance was assessed by determining erythrocyte SOD and catalase activity. RESULTS: The Val allele of MnSOD at Val16Ala and the A allele of catalase gene at A-21T were not different between patients and controls, while the C allele of catalase gene at C-262T was found to be significantly different between patients and controls (P=0.033). The less frequent variant of catalase gene (-262T) was found to be protective from the development of asthma in a Hong Kong Chinese non-smoking population (adjusted odds ratio=0.35, 0.15-0.85; P=0.017). Asthma patients had elevated erythrocyte SOD and catalase activities in comparison with healthy controls (P<0.01). However, their activities were not associated with different genotypes within healthy controls or asthma patients. CONCLUSION: This is the first report showing that SOD and catalase functional activities are not associated with their respective genetic polymorphisms but related to the presence of asthma in a Hong Kong Chinese population.     

阳城县居民吸烟状况调查分析

对阳城县3646名15岁以上人群吸烟状况分析表明,男性吸烟率63.71％,女性吸烟率0.64％,男女合计吸烟率31.49％,并对不同年龄、职业、文化程度与吸烟率的关系进行了分析。吸烟心理动机:“烟草成瘾”占32.06％,“消遣”占28.48％,“解除疲劳”占16.90％,“交际”占22.56％。吸烟人群的4周患病率和慢性病患病率均高于不吸烟人群,两组差别有显著性(P<0.05,P<0.001)。     

A longitudinal study of age-associated memory impairment

An 8-year longitudinal study of elderly people has provided data concerning age-associated impairment (AAMI). In 1985 a random sample of 146 persons aged 65 years or more, living in their own homes, were assessed using the Guild Memory Test the Mini–Mental State Examination (MMSE) and other ratings. After excluding 21% of the sample because they scored less than 24 on the MMSE, and another 34% who fulfilled other exclusion criteria, some 48% of the remainder (22% of the total sample) clearly fulfilled NIMH criteria for AAMI and a further 36% (16% of the total sample) were recorded as forgetful. The NIMH criteria are appropriate for certain research purposes but not in assessing prevalence of memory disorders. Follow–up interviews were conducted after 2, 4, 6 and 8 years. The mortality rate and development of dementia among those fulfilling criteria for AAMI appeared similar to the other non-demented groups of subjects; the mortality rate of those with MMSE scores below 24 was significantly higher. Guild test results at 2-yearly intervals showed considerable changes; half of those scoring least well who were retested showed improvement.     

Sampling Patients Within and Across Health Care Providers: Multi-Stage Non-Nested Samples in Health Services Research

In order to better inform study design decisions when sampling patients within and across health care providers we develop a simulation-based approach for designing complex multi-stage samples. The approach explores the tradeoff between competing design goals such as precision of estimates, coverage of the target population and cost.We elicit a number of sensible candidate designs, evaluate these designs with respect to multiple sampling goals, investigate their tradeoffs, and identify the design that is the best compromise among all goals. This approach recognizes that, in the practice of sampling, precision of the estimates is not the only important goal, and that there are tradeoffs with coverage and cost that should be explicitly considered. One can easily add other goals. We construct a sample frame with all phase III clinical cancer treatment trials that are conducted by cooperative oncology groups of the National Cancer Institute from October 1, 1998 through December 31, 1999. Simulation results for our study suggest sampling a different number of trials and institutions than initially considered.Simulations of different study designs can uncover efficiency gains both in terms of improved precision of the estimates and in terms of improved coverage of the target population. Simulations enable us to explore the tradeoffs between competing sampling goals and to quantify these efficiency gains. This is true even for complex designs where the stages are not strictly nested in one another.     

Is there a ‘Basque’ profile regarding autosomal recessive deficiencies of coagulation factors?*

When excluding haemophilia and von Willebrand disease, coagulation factors deficiencies constitute rare autosomal recessive disorders (<1 in 500,000) of less precisely defined epidemiology. We have reported herein the distribution of these entities in the French Basque Country, a genetic isolate of very old individualization with peculiar biological specificities. The prevalence of these disorders was markedly high, especially, as already shown, factor XI deficiency. This unusual profile needs to be discussed in the view of population genetics.     

Evaluation of hypothesis testing for comparing two populations using NONMEM analysis

In a simulation study of inference on population pharmacokinetic parameters, two methods of performing tests of hypotheses comparing two populations using NONMEM were evaluated. These two methods are the test based upon 95% confidence intervals and the likelihood ratio test. Data were simulated according to a monoexponential model and, in that context, power curves for each test were generated for (i)the ratio of mean clearance and (ii)the ratio of the population standard deviations of clearance. To generate the power curves, a range of these parameters was employed; other pharmacokinetic parameters were selected to reflect the variability typically present in a Phase II clinical trial. For tests comparing the means, the confidence interval tests had approximately the same power as the likelihood ratio tests and were consistently more faithful to the nominal level of significance. For comparison of the standard deviations, and when the volume of information available was relatively small, however, the likelihood ratio test was more able to detect differences between the two groups. These results were then compared to results on parameter estimation in order to gain insight into the question of power. As an example, the nonnormality of estimates of the ratio of standard deviations plays an important role in explaining the low power for the confidence interval tests. We conclude that, except for the situation of modeling standard deviations with only sparse information, NONMEM produces tests of significance that are effective at detecting clinically significant differences between two populations.Partial support from the Upjohn Company, NIH-BRSG SO RR 07066, and the Burroughs Wellcome Foundation.     

Appendizitissonographie durch chirurgen — Erfahrungssache? Eine prospektive studie

A number of studies have shown that ultrasound has an advantage over physical examination in the diagnosis of acute appendicitis. Most of these studies were conducted by experts in the field of ultrasonography. In this study the influence of experience on the results of the sonography of actue appendicitis were evaluated. All 203 patients admitted to our unit between December 1990 and December 1992 were examined physically and sonographically by a team of surgeons consisting of one experienced sonographer and six inexperienced surgical trainees. Laparotomy was performed in 136 patients (46%). Appendicitis was demonstrated histologically in 119 cases (39.4%). Initial clinical findings were positive in 87 (28.8%). Sonography was positive in 119 patients (39.4%). The 163 patients not operated on demonstrated other pathology on ultrasound in 60 cases (19.9%). The rate of negative laparotomies amounted to 7.2% in our study. Sensitivity and specificity for the sonographic diagnosis were 92% and 95%, respectively. They were only 81% and 80% for physical examination. Overall accuracy was 92% for sonography. Sensitivity and specificity for the inexperienced surgeons were 87% and 93%, respectively, while the experienced surgeon reached values of 97% and 98%, respectively. The results of both groups are comparable with values in the literature, suggesting that ultrasound evaluation of appendicitis is not a diagnostic tool limited to a few experienced sonographers.     

精神发育迟滞儿童特殊教育三年随访

采用Ｈ－ＮＴＬＡ量表及婴儿～初中学生社会生活能力量表对太原市一个培智学校４４例精神发育迟滞患儿从１９８９～１９９２年连续４次测查智力，２次测查适应行为。结果显示３年间ＩＱ值变化无显著统计学意义，但视觉联想、概念关系、注意力及视觉识知能力有明显提高。患儿适应行为明显提高。经多元逐步回归分析显示，精神发育迟滞儿童智商的提高和母亲文化程度较高、患儿智力低下程度较轻、母亲职业为科技或行政管理人员、患儿初始教育年龄早呈正相关。     

Association and linkage with quantitative traits

This paper examines two approaches for the analysis of quantitative traits: (1) association studies and (2) linkage studies. The trait studied was Q1 from simulated Problem 2 data set in Genetic Analysis Workshop 9. Our purpose was to evaluate associations present in the data, to identify nongenetic and genetic predictors of the trait, and to explore the simulated genome for linkage. Through the association study, we found evidence for the primary major gene associated with this trait. The linkage study found evidence of residual genetic effect acting through other traits. Adjustments of Q1 for Q2 and Q3 led to a failure to find significant effects of MG2 and MG3. This supports the suggestion that adjustment for genetically influenced traits for effects of other genetic traits can reduce the power to detect major gene effects. In summary, we detected the major gene directly associated with the trait of interest through association studies. Linkage analysis detected evidence for two other genes associated to a lesser degree with the trait. © 1995 Wiley-Liss, Inc.     

Mammographic screening: case-control studies.

BACKGROUND: The case-control design can be used to evaluate the benefit of cancer screening programmes. MATERIALS AND METHODS: This paper outlines the main methodological features of the case-control design in this context, and indicates some potential biases. It also reviews the existing case-control literature on mammographic screening. RESULTS: Case-control studies consistently indicate a reduction of approximately 50% in breast cancer mortality associated with mammography. This result indicates greater benefit than shown in randomised trials; however, one should recognise that trials indicate effectiveness whereas case-control studies indicate efficacy. The two types of evidence are broadly compatible when one allows for screening non-compliance and contamination in the randomised trials. CONCLUSIONS: The case-control evidence supports and is consistent with the findings of randomised trials of mammography. Effectiveness estimates from trials indicate the benefit of screening to the population as a whole, and are pertinent to the public policy debate as to the value of offering screening. In contrast, case-control studies indicate benefit to actual screening participants. As such, case-control estimates of efficacy are appropriate for individual decision-making by women about their use of mammography when it is potentially available to them.