CDKN2A promoter methylation is related to the tumor location and histological subtype and associated with Helicobacter pylori flaA(+) strains in gastric adenocarcinomas

Alves MKS, Lima VP, Ferrasi AC, Rodrigues MA, de Moura Campos Pardini MI, Rabenhorst SHB. CDKN2A promoter methylation is related to the tumor location and histological subtype and associated with Helicobacter pylori flaA(+) strains in gastric adenocarcinomas. APMIS 2010; 118: 297–307. Promoter hypermethylation of CDKN2A (p16^INK4A protein) is the main mechanism of gene inactivation. However, its association with Helicobacter pylori infection is a controversial issue. Therefore, we examined a series of gastric adenocarcinomas to assess the association between p16^INK4A inactivation and H. pylori genotype (vacA, cagA, cagE, virB11 and flaA) according to the location and histological subtype of the tumors. p16^INK4A expression and CDKN2A promoter methylation were found in 77 gastric adenocarcinoma samples by immunohistochemistry and methylation‐specific PCR, respectively. Helicobacter pylori infection and genotype were determined by PCR. A strong negative correlation between immunostaining and CDKN2A promoter region methylation was found. In diffuse subtype tumors, the inactivation of p16^INK4A by promoter methylation was unique in noncardia tumors (p = 0.022). In addition, H. pylori‐bearing flaA was associated with non‐methylation tumors (p = 0.008) and H. pylori strain bearing cagA or vacAs1m1 genes but without flaA was associated with methylated tumors (p = 0.022 and 0.003, respectively). Inactivation of p16^INK4A in intestinal and diffuse subtypes showed distinct carcinogenic pathways, depending on the tumor location. Moreover, the process of methylation of the CDKN2A promoter seems to depend on the H. pylori genotype. The present data suggest that there is a differential influence and relevance of H. pylori genotype in gastric cancer development.     

The prognostic significance of post-infarction angina pectoris and the effect of verapamil on the incidence of angina pectoris and prognosis

The prognostic sign of angina pectoris and the effect of interventionwith verapamil on the incidence of angina pectoris were studiedin patients recovering from myocardial infarction and includedin the Danish Verapamil Infarction Trial II. During the secondweek after admission patients were double-blindly randomizedto treatment with verapamil 360 mg. day^–1 or placebo.Treatment was continued for up to 18 months. At discharge anginapectoris was reported in 11% of 869 patients randomized to verapamiland in 12% of 888 randomized to placebo (ns). One month afterdischarge a significantly increase in the prevalance of anginapectoris was reported in both the verapamil (33%) (P<0·001)and the placebo groups (39%) (P <0·001). The one monthprevalence of angina pectoris (P=0·03) and the 18 monthsoverall incidence of angina pectoris (P= 0·002) wereboth .sigificant lower in the verapamil group compared withplacebo. Stable angina pectoris during the first month of follow-upwas a significant predictor of major events (i.e. death or reinfarction)(hazard ratio = 1·45; 95% confidence limits: 1·101·89). As verapamil significantly reduced the incidenceof angina pectoris during daily activities, and thereby thenumber of patients at high risk, the beneficial effect of verapamilin reducing major events in patients recovering from myocardialinfarction is likely to be due to abolishing myocardial ischaemia.     

Prevalence and risk factors of non-alcoholic fatty liver disease among Korean adults

Background and Aim: Differences in the prevalence of non‐alcoholic fatty liver disease (NAFLD) between Eastern and Western populations are primarily attributable to differences in definitions and biased population selection. Thus, the aim of the present study was to accurately determine the actual prevalence of NAFLD by sonography and to characterize the risk factors for NAFLD. Methods: The present cross‐sectional study was performed with data obtained from 6648 subjects, all of whom were older than 20 years of age (3530 men and 3118 women). The term ‘non‐drinker’ was applied to men who consumed less than 30 g alcohol/day and to women who consumed less than 20 g alcohol/day. Non‐alcoholic fatty liver disease was defined as a sonographically detected fatty liver in the absence of viral hepatitis in a non‐drinker. Results: Of the 1613 subjects who were diagnosed with sonographic fatty liver, 1240 were non‐drinkers and had no viral hepatitis. Overall, the unadjusted and age‐adjusted prevalences of NAFLD were 18.7% (23% in men, 13.7% in women) and 16.1% (21.6% in men, 11.2% in women), respectively. Multivariate analysis revealed that several risk factors were profoundly associated with the prevalence of NAFLD, including obesity, insulin resistance, hyperlipidemia and hyperglycemia in both genders, as well as age, menopausal status and estrogen medication in women only. Conclusions: These results demonstrate that the prevalence of NAFLD in Korean adults, according to sonographic surveys, is comparable to that seen in more developed countries. From the perspective of increasing obesity, the high prevalence rates noted in the study may herald an increased burden of chronic liver disease in the Korean population.     

Significant decrease in the prevalence of Wuchereria bancrofti infection in anopheline mosquitoes following the addition of albendazole to annual, ivermectin-based, mass treatments in Nigeria

A prospective entomological survey was conducted in four sentinel villages in central Nigeria from 1999-2002, to assess the impact of annual, single-dose, mass drug administrations (MDA), with a combination of ivermectin and albendazole, on the transmission of Wuchereria bancrofti. As they were also endemic for human onchocerciasis, the four villages had received annual MDA based on ivermectin alone for 7 years prior to the addition of albendazole. Resting Anophelines gambiae s. l., An. funestus and Culex species were collected from 92 sequentially sampled households and dissected. Mosquitoes harbouring any larval stage of W. bancrofti were classified as 'infected', and those containing the third-stage larvae of the parasite were classified as 'infective'. Over the 41-month observation period, 4407 mosquitoes were captured and dissected, of which 64% were An. gambiae s. l., 34% An. funestus, and 1% Culex species. The baseline data, from dissections performed before the addition of albendazole to the MDA, showed high prevalences of mosquito infection (8.9%) and infectivity (2.9%), despite apparently good treatment coverages during the years of annual ivermectin monotherapy. Only the anopheline mosquitoes were found to harbour W. bancrofti larvae. After the third round of MDA with the ivermectin-albendazole combination, statistically significant decreases in the prevalences of mosquito infection (down to 0.6%) and infectivity (down to 0.4%) were observed (P<0.0001 for each). The combination of albendazole and ivermectin appears to be superior to ivermectin alone for reducing the frequency of W. bancrofti infection in mosquitoes.     

慢性重型乙型肝炎Th1／Th2平衡状态与预后关系的研究

目的研究慢性重型乙型肝炎Th1／Th2类细胞因子的水平及其对预后的影响。方法采集112例慢性重型乙型肝炎患者外周血,以30例慢性乙型肝炎（CHB）患者和30名健康体检者作为对照,应用ELISA法检测IL-4和IFN-γ水平,荧光PCR法检测HBVDNA载量,分析重型肝炎患者不同分期细胞因子水平以及与HBVDNA载量及短期预后的关系。结果慢性重型乙型肝炎患者外周血IL-4、IFN-γ水平和Th1／Th2比值明显高于CHB患者和健康体检者（z值分别为8．968,10．004和26．067,P值分别为0．009,0．007和0．000）;晚期重型肝炎患者的IL-4水平明显高于早、中期患者（z值分别为3．672和3．158,P值分别为0．000和0．002）,但Th1／Th2比值低于早、中期患者（Z值分别为3．161和2．166,P值分别为0．002和0．030）;不同HBVDNA复制水平的重型肝炎患者IL4、IFN-γ及Th1／Th2比值差异无统计学意义（z值分别为4．431,2．626和0．140,P值分别为0．219,0．403和0．987）;但患者外周血IL4浓度越高,12周的病死率越高。结论Th1／Th2失衡导致重型肝炎的发生,随着病情加重,Th1／Th2比值下降,提示短期预后不良。     

Surveillance of HIV and syphilis infections among antenatal clinic attendees in Tanzania-2003/2004

Background

SPARCLE is a nine-centre European epidemiological research study examining the relationship of participation and quality of life to impairment and environment (physical, social and attitudinal) in 8–12 year old children with cerebral palsy. Concepts are adopted from the International Classification of Functioning, Disability and Health which bridges the medical and social models of disability.

Methods/Design

A cross sectional study of children with cerebral palsy sampled from total population databases in 9 European regions. Children were visited by research associates in each country who had been trained together. The main instruments used were KIDSCREEN, Life-H, Strength and Difficulties Questionnaire, Parenting Stress Index. A measure of environment was developed within the study. All instruments were translated according to international guidelines. The potential for bias due to non response and missing data will be examined. After initial analysis using multivariate regression of how the data captured by each instrument relate to impairment and socio-economic characteristics, relationships between the latent traits captured by the instruments will then be analysed using structural equation modelling.

Discussion

This study is original in its methods by directly engaging children themselves, ensuring those with learning or communication difficulty are not excluded, and by studying in quantitative terms the crucial outcomes of participation and quality of life. Specification and publication of this protocol prior to analysis, which is not common in epidemiology but well established for randomised controlled trials and systematic reviews, should avoid the pitfalls of data dredging and post hoc analyses.     

Triple simultaneous primary gynecological malignancies in a 56-year-old patient

The occurrence of double simultaneous primary cancers is common. However, the occurrence of synchronous primary triple gynecological malignancies is an extremely rare event. In this report, the clinical and pathologic findings of a 56-year-old female patient with synchronous triple primary gynecological cancers including well-differentiated ovarian mucinous cystadenocarcinoma, well-differentiated endometrial endometrioid adenocarcinoma, and uterine leiomyosarcoma were presented. Synchronous primary, well-differentiated endometrial endometrioid adenocarcinoma and leiomyosarcoma of uterus without any ovarian neoplasm has only been once described in the English literature. To our knowledge, the presented patient is the first case in aspect of accompanying ovarian mucinous adenocarcinoma to endometrial endometrioid adenocarcinoma and leiomyosarcoma of uterus.