Update in atherothrombotic disease

Crucial advances in our understanding of the pathogenesis of atherothrombosis, defined as atherosclerosis and its thrombotic complications, have been achieved during the past two decades. The historical hypothesis of pathogenesis ("lipid accumulation") has evolved to integrate several factors contributing to the initiation and evolution of this complex disease. Endothelial dysfunction is considered to be the earliest event in atherogenesis. Inflammation and apoptosis play critical roles in its progression and onset. Tissue factor is postulated to be a central actor in determining plaque thrombogenicity. A hyperreactive state of the blood ("vulnerable blood") may be responsible for one-third of all the acute coronary syndromes. This review will discuss emerging concepts in the pathogenesis of and therapeutic approaches to atherothrombotic disease.     

Public perception of risk concerning celltowers and mobile phones

Summary Objective: The controversy about health risks of electromagnetic fields (EMF) has contributed in raising fears concerning emissions from celltowers. The study was to examine whether or not neighbours of celltowers are particularly concerned about adverse health effects of mobile phones and their base stations.Methods: Prior to information delivered by medical doctors of the Institute of Environmental Health at public hearings a questionnaire was handed out to participants asking for their personal rating of several environmental health risks including those of mobile telecommunication (n=123, response rate approx. 48%). Medical students (n=366) served as a contrast group.Results: Participants rated health risk for both, mobile phones and celltowers higher as students. A trend for higher ratings was also seen with older subjects and female sex. The risk ratings of both exposures correlated well with each other. The magnitude of the perceived risks, however, resembled that of other ubiquitous exposures like traffic noise and air pollution.Conclusion: Contrary to the claims of the telecommunication industry, opponents of celltowers generally do not express unusual fears concerning electromagnetic field exposure. The outcome of our study indicates that the risk rating is comparable with other perceived common hazards of the civilised world. It is hypothesised that offering information and participation to the concerned population will be efficient in reducing exaggerated fears.     

Prediction of the shelf life of cellulose acetate hemodialyzers by Monte Carlo simulation

A previous investigation by our laboratory linked cellulose acetate degradation with adverse health effects in hemodialysis patients. To establish the accumulation of degradation products with time, a Monte Carlo model of degradation kinetics was developed. The model tracks changes in a population of molecules representative of the dialyzer membrane during the degradation process. The degradation calculation is a two step process: First, the model uses a random number to select an individual polymer molecule out of the population, and then a second random number is used to identify a site on the selected molecule for the degradation reaction to occur. After the reaction calculation, the resulting degraded molecules are redistributed into the population. The course of the reaction is determined by recalculating the molecular weight averages in the changing population as the calculations proceed. The model was validated using gel permeation chromatography molecular weight results and total acetyl content measurements on dialyzers stored up to 13.3 years after manufacture. It was found that the degradation reactions can be accurately modeled as random events and that the chain scissions and deacetylation events occur at constant rates. The shelf life of these devices was estimated using the model predictions and animal test results.     

甲硝唑葡萄糖注射液细菌内毒素检查法的研究

目的;以细菌内毒素检查法对甲硝唑葡萄糖注射液进行试验研究。方法;采用抑制或增强试验,并将细菌内毒素检查法与家兔法检测结果作对比。结果：该注射液经一定稀释后对测定无干扰。结论：细菌内毒素检查法适用于检测该注射液。     

N-acetyltransferase 2 influences cancer prevalence in hMLH1/hMSH2 mutation carriers.

Hereditary nonpolyposis colorectal cancer (HNPCC), an inherited cancer predisposition syndrome, has been associated with germline mutations in DNA mismatch repair (MMR) genes. Because a deficiency in MMR does not predict a specific cancer phenotype, modifying genes may account in part for the variation in disease expression. We determined the N-acetyltransferase 2 (NAT2) genotype in 26 unaffected and 52 cancer-affected hMLH1/hMSH2 mutation carriers coming from 21 Swiss HNPCC families. Slow acetylators were found to be significantly (P < 0.03) more prevalent in the group of affected mutation carriers. Our results suggest a protective effect of the NAT2 rapid acetylator phenotype, an observation that could have implications for genetic counseling and management of MMR gene mutation carriers.     

A polymorphism in the ATM gene modulates the penetrance of hereditary non-polyposis colorectal cancer

Germ-line mutations in MLH1 and MSH2 genes predispose to hereditary non-polyposis colorectal cancer (HNPCC) syndrome, but they do not predict a specific phenotype of the disease. We speculated that the ataxia-telangiectasia mutated gene (ATM) was a candidate gene to modulate the phenotypic expression of HNPCC, as heterozygous individuals for germ-line ATM mutations have been considered at higher risk of developing epithelial malignancies. The frequency of the ATM D1853N polymorphism was evaluated in 167 individuals from 20 HNPCC families in which MLH1 or MSH2 germ-line mutations co-segregated with the disease. Among the 67 MLH1 or MSH2 mutation carriers, the ATM 1853N variant was associated with a significantly higher incidence of colorectal and other HNPCC-related cancers, when compared with individuals carrying the ATM 1853D variant [12/13 (92%) vs. 31/54 (57.5%); p = 0.02]. MLH1 and MSH2 mutation carriers who concomitantly carried the ATM 1853N variant, had an 8 times increased risk of developing colorectal and other HNPCC-related cancers (OR: 8.9; p = 0.02), when compared with MLH1 or MSH2 mutation carriers with the ATM 1853D variant. Our results suggest that the ATM D1853N polymorphism modulates the penetrance of MLH1 and MSH2 germ-line mutations.     

SELECTIVE IgA DEFICIENCY PRESENTING WITH HYPERSPLENISM

SUMMARY A young patient presenting with splenomegaly and hypersplenism was inadvertently found to have selective IgA deficiency. There were no symptoms of immunodeficiency and the patient responded well to splenectomy, with return of blood counts to normal without adverse effects. No other cause for the hypersplenism was found. We postulate selective IgA deficiency as a cause of splenomegaly and hypersplenism.     

Genetic causes of monogenic heterozygous familial hypercholesterolemia: a HuGE prevalence review

The clinical phenotype of heterozygous familial hypercholesterolemia (FH) is characterized by increased plasma levels of total cholesterol and low density lipoprotein cholesterol, tendinous xanthomata, and premature symptoms of coronary heart disease. It is inherited as an autosomal dominant disorder with homozygotes having a more severe phenotype than do heterozygotes. FH can result from mutations in the low density lipoprotein receptor gene (LDLR), the apolipoprotein B-100 gene (APOB), and the recently identified proprotein convertase subtilisin/kexin type 9 gene (PCSK9). To date, over 700 variants have been identified in the LDLR gene. With the exception of a small number of founder populations where one or two mutations predominate, most geographically based surveys of FH subjects show a large number of mutations segregating in a given population. Studies of the prevalence of FH would be improved by the use of a consistent and uniformly applied clinical definition. Because FH responds well to drug treatment, early diagnosis to reduce atherosclerosis risk is beneficial. Cascade testing of FH family members is cost effective and merits further research. For screening to be successful, public health and general practitioners need to be aware of the signs and diagnosis of FH and the benefits of early treatment.