Modelling Germline Mosaicism and Different New Mutation Rates Simultaneously for Appropriate Risk Calculations in Families with Duchenne Muscular Dystrophy

For several genetic diseases two biological phenomena have been recognised as important: germline mosaicism; and different new mutation rates in males and females depending on mutation type. Both principles have been investigated separately and their influence on risk estimation in families has been exemplified in the literature. The aim of this paper is to present a general model that includes mosaicism and different new mutation rates. Mosaicism is introduced by defining additional alleles at the disease locus in combination with adapted segregation rules. Taking Duchenne muscular dystrophy as an example, we derive the conditions which have to be fulfilled for a population in mutation selection equilibrium. Our approach describes the model at the population level and not in individual subjects. This has the advantage of being able to use well known algorithms for the calculation of likelihoods in pedigrees, and to include additional diagnostic information such as marker genotypes and carrier deletion test results. We demonstrate the impact of the new model on a typical pedigree. In families where the patient is not available, the distinction between point mutations and deletions is important, since often molecular diagnostic tests for females can only screen for deletions. Negative deletion test results can now be included in the risk calculations.     

肥胖类型与脑卒中亚型的相关性研究

目的探讨肥胖类型与脑卒中亚型的相关性。方法将573例急性脑卒中患者分为脑出血组126例,脑梗死组447例,脑梗死组再分为脑血栓形成组(215例)和腔隙性脑梗死组(232例),另外选择277例无脑卒中者为对照组。测量腰围、臀围和体重,计算体重指数和腰臀比(WHR),分析肥胖参数与脑卒中各亚组的关系。结果脑卒中各亚组与对照组肥胖发生率差异无显著性意义(P>0.05);各组WHR明显大于对照组(P<0.05)。WHR增大明显增加脑卒中各亚组的危险性(P<0.05);女性腹围增大患腔隙性脑梗死危险性升高(P<0.05);男性体重增加患脑出血的危险性升高(P<0.01)。结论腹型肥胖是脑出血、脑血栓形成和腔隙性脑梗死的危险因素之一。     

Non-alcoholic fatty liver disease, the metabolic syndrome and the risk of cardiovascular disease: the plot thickens.

Non-alcoholic fatty liver disease (NAFLD) affects a substantial proportion of the general population and is frequently associated with many features of the metabolic syndrome (MetS). Currently, the importance of NAFLD and its relationship with the MetS is being increasingly recognized, and this has stimulated an interest in the possible role of NAFLD in the development of atherosclerosis. Recent studies have reported the association of NAFLD with multiple classical and non-classical risk factors for cardiovascular disease (CVD). Moreover, there is a strong association between the severity of liver histopathology in NAFLD patients and greater carotid artery intima-media thickness and plaque, and lower endothelial flow-mediated vasodilation (as markers of subclinical atherosclerosis) independent of obesity and other MetS components. Finally, it has recently been demonstrated that NAFLD is associated with an increased risk of all-cause death and predicts future CVD events independently of other prognostic factors, including MetS components. Overall, therefore, the evidence from these recent studies strongly emphasizes the importance of assessing the global CVD risk in patients with NAFLD. Moreover, these novel findings suggest a more complex picture and raise the possibility that NAFLD, as a component of the MetS, might not only be a marker but also an early mediator of CVD.     

Abdominal aortic aneurysm repair and colonic infarction: a risk factor appraisal

OBJECTIVE: Colonic infarction is a recognized complication of abdominal aortic aneurysm (AAA) surgery. The clinical difficulty in establishing the diagnosis combined with the patient's poor physiological status is usually associated with a fatal outcome. We assessed our experience with this problem to identify a possible risk factor profile for these patients. METHOD: Patients records were identified from the operative logs, intensive care unit, Hospital Inpatient Enquiry system and vascular unit databases over a 6-year period. RESULTS: A total of 405 patients underwent AAA repair during this period; 140 as emergency ruptures. Nine patients were identified from the databases with known colonic infarction (2.2%). One was a woman. The mean age was 70 years. Seven patients had emergency ruptures (5%). Twenty independent risk factors were analysed using univariate and multivariate logistic regression models. Significant risk factors identified by using a multivariate analysis included the nature of the presenting patient, preoperative hypotension, prolonged cross-clamp time, intra-operative ischaemia and postoperative acidosis. Confirmatory diagnosis was made by colonoscopy in eight patients. One patient survived following the salvage surgery. The mean duration of survival was 10.5 days. The overall mortality was 89% of patients. CONCLUSION: In our unit infrarenal AAA repair has a 2.2% rate of colonic infarction. A definitive diagnosis is best made by colonoscopy. A risk factor profile for the development of colonic infarction may be constructed on the basis of specific clinical parameters. Earlier intervention on the basis of this profile may ultimately reduce the current excessive mortality.     

Peritoneal dialysis patient survival: a comparison between a Swedish and a Korean centre.

BACKGROUND: Dialysis patient mortality remains high, and this high mortality may be due to many factors. In peritoneal dialysis (PD) patients, old age, co-morbid diseases, malnutrition, low residual renal function (RRF) and a high peritoneal transport rate have been shown to influence survival, but the relative importance of these factors may differ between different patient populations. Besides, centre practice patterns may differ between centres and may influence patient survival. In addition, the literature suggests that dialysis patient survival may be better in Asian than in Caucasian patients. METHODS: The influence of centre and patient characteristics on patient survival was investigated in 132 Korean and 106 Swedish incident PD patients, who underwent initial biochemical measurements and assessment of adequacy of dialysis, nutritional status, RRF and peritoneal transport characteristics. RESULTS: At the start of PD, Korean patients had a higher prevalence of diabetes, peritoneal Kt/V(urea), peritoneal creatinine clearance and peritoneal fluid removal, and lower body mass index, RRF and dialysate to plasma creatinine concentration ratio (D/P Cr) compared with Swedish patients. Significantly more patients from Korea were placed on temporary haemodialysis before PD (100 out of 132) when compared with Swedish patients (21 out of 106). During the follow-up, there was a significantly higher rate of transfer to other units in Korea and a significantly higher rate of kidney transplantation in Sweden. On Kaplan-Meier analysis, overall patient survival did not differ and relative risk for death was also not different between the two centres even after adjustment for age, diabetes, cardiovascular disease, RRF and D/P Cr. On Cox proportional hazards multivariate analysis, age, diabetes, RRF and D/P Cr were found to be independent predictors of mortality in the combined cohort of patients. While age, diabetes and D/P Cr were independent predictors of mortality in Korean patients, age and RRF independently predicted mortality in Swedish patients. CONCLUSION: Although there were significant differences in centre and patient characteristics, we were unable to confirm a survival advantage for Korean over Swedish PD patients. The results of this study suggest that the reported difference in survival between Asian and Caucasian dialysis patients may have been due, in part, to differences in centre and patient characteristics rather than to race as such. The genetic influence on patient characteristics remains, however, to be elucidated.     

社区人群痛风危险因素的病例对照研究

目的 探讨社区人群(20岁以上)痛风的危险因素。方法 采用1：3病例对照研究方法，进行单因素与多因素与多因素logistic回归分析。结果 经单因素筛选和多因素分析，在P=0．05水平，高尿酸(OR=8．601)、肥胖(OR=2．910)、伴有高血压病史(OR=2．330)是痛风的独立危险因素。结论 痛风是一种在遗传基础上的与环境和生活方式有关的疾病，改变生活方式、控制相关疾病可能预防或减少高尿酸血症的发生，进而减少痛风的发生。     

Critical trust: understanding lay perceptions of health and safety risk regulation

The binary opposition of trusting or not trusting is inadequate to understand the often ambiguous and contradictory ideas people possess about risk regulators, particularly when knowledge and experience of such institutions is limited. The paper reports qualitative and quantitative data from a major study of public perceptions (n?=?30 focus groups) of UK risk regulators. We compare the complex and widely different ‘trust profiles’ of two regulatory organisations which are institutionally related (the Health and Safety Executive and the Railways Inspectorate) but very separate in the minds of our participants. The paper develops the notion of critical trust to interrogate the various ways in which people make sense of such organisations, as well as discussing the modes of reasoning that people deploy. The paper argues that views of participants are the outcome of a reconciliation of diverse perceptions concerning the role of the organisation, structural factors and the nature of the regulated risk.     

检测MEGX判定肝储备功能评估手术风险

目的 通过检测肝癌病人利多卡因代谢产物(MEGX)的量,判定肝储备功能,评估手术风险.方法 对准备手术治疗的肝癌病人术前静注利多卡因1 mg/kg体重,15 min后抽血,用HPLC法检测MEGX,与常用肝生化检查、Child-Pugh分级方法比较.结果 根据MEGX检测结果将55例准备手术的肝癌病人分成手术耐受组和手术非耐受组.耐受组均经受了手术打击,无术后严重肝衰发生,而非耐受组有两例手术治疗,术后均出现了严重的肝衰,其中一例死亡.结论 MEGX试验较Child-Pubh分级方法更能准确判定肝储备功能,对评估手术风险有较高的特异性.     

Soluble CD14 at 2 yr of age: Gender-related effects of tobacco smoke exposure, recurrent infections and atopic diseases

The endotoxin receptor soluble CD14 (sCD14) has been implicated in the 'hygiene hypothesis' suggesting reduced allergic sensitization with bacterial stimulation. However, the relationship between early life sCD14 and allergic diseases is conflicting. We aimed to investigate whether possible risk factors for allergic diseases were associated with sCD14 levels at 2 yr of age. In the nested case-control study of the birth cohort studies 'Environment and Childhood Asthma study in Oslo' 411 children selected with recurrent bronchial obstruction (rBO) (n=241) and no bronchial obstruction (n=170) by 2 yr were investigated with skin prick test and structured parental interview at age 2 yr. Exposure to tobacco smoke, pets and infections was recorded semi-annually by questionnaires (0-2 yr). The sCD14 was analysed from frozen, stored serum by ELISA technique. Regression analyses were performed in all subjects with complete data (n=406, 180 girls), and in girls and in boys separately. Mean sCD14 (ng/ml) was significantly higher among girls 2035 (1973-2096) vs. 1947 (1890-2004) (boys). The sCD14 was significantly reduced among girls exposed to antenatal maternal smoking and with parental asthma, after adjusting for age, parental rhino-conjunctivitis, pet keeping and childhood infections. Recurrent otitis media (OM) increased and common colds significantly decreased sCD14 levels in girls. Boys with atopic dermatitis and rBO had reduced sCD14. Pet exposure was not significantly associated with sCD14. We report novel gender-related effects of sCD14 in early life and suggest that gender, tobacco smoke exposure, age and middle ear disease in particular should be accounted for when assessing the role of sCD14 in childhood allergic diseases.