Associations of apolipoprotein E exon 4 and lipoprotein lipase S447X polymorphisms with acute ischemic stroke and myocardial infarction

Background: Because apolipoprotein E (apoE) and lipopoprotein lipase (LPL) polymorphisms interact with each other and with other factors to affect lipid metabolism, we sought to determine their separate and combined effects in association with ischemic vascular disease. Methods: We performed a case-control study of 816 subjects: 246 acute ischemic stroke patients, 234 acute myocardial infarction patients, and 336 controls. APOE exon 4 and LPL S447X genotypes were determined. Results: APOE ε2 and ε4 homozygotes were increased in stroke (4.5% vs. 1.0%, p = 0.008), while in myocardial infarction the ε4 allele was increased (12.6% vs. 9.5%, p = 0.006) but ε2 was decreased (3.7% vs. 12.1%, p = 0.000006). For subjects with either APOE ε2 or ε4 alleles, LPL X alleles were increased in vascular disease (OR = 2.2, p = 0.01). LPL X alleles displayed opposite tendencies toward association with disease when subjects were divided by sex, smoking, or APOE genotype. Meta-analysis and regression analysis of previous studies supported the sex and smoking dichotomies. Conclusion: This is the first report of an association of vascular disease with an interaction of APOE exon 4 and LPL S447X genotypes. Therefore, APOE genotypes and LPL S447X interactions with apoE, sex, and smoking may affect the risk of myocardial infarction and ischemic stroke. © 2006 by Walter de Gruyter.published_or_final_versio

Copy-Number Variants in Patients with a Strong Family History of Pancreatic Cancer

Copy-number variants such as germ-line deletions and amplifications are associated with inherited genetic disorders including familial cancer. The gene or genes responsible for the majority of familial clustering of pancreatic cancer have not been identified. We used representational oligonucleotide microarray analysis (ROMA) to characterize germ-line copy number variants in 60 cancer patients from 57 familial pancreatic cancer kindreds. Fifty-seven of the 60 patients had pancreatic cancer and three had nonpancreatic cancers (breast, ovary, ovary). A familial pancreatic cancer kindred was defined as a kindred in which at least two first-degree relatives have been diagnosed with pancreatic cancer. Copy-number variants identified in 607 individuals without pancreatic cancer were excluded from further analysis. A total of 56 unique genomic regions with copy-number variants not present in controls were identified, including 31 amplifications and 25 deletions. Two deleted regions were observed in two different patients, and one in three patients. The germ-line amplifications had a mean size of 662 Kb, a median size of 379 Kb (range 8.2 Kb to 2.5 Mb) and included 425 known genes. Examples of genes included in the germ-line amplifications include the MAFK, JunD and BIRC6 genes. The germ-line deletions had a mean size of 375Kb, a median size 151 Kb (range 0.4 Kb to 2.3 Mb) and included 81 known genes. In multivariate analysis controlling for region size, deletions were 90% less likely to involve a gene than were duplications (p < 0.01). Examples of genes included in the germ-line deletions include the FHIT, PDZRN3 and ANKRD3 genes. Selected deletions and amplifications were confirmed using real-time PCR, including a germ-line amplification on chromosome 19. These genetic copy-number variants define potential candidate loci for the familial pancreatic cancer gene

Prognostic and therapeutic significance of carbohydrate antigen 19-9 as tumor marker in patients with pancreatic cancer

In pancreatic cancer ( PC) accurate determination of treatment response by imaging often remains difficult. Various efforts have been undertaken to investigate new factors which may serve as more appropriate surrogate parameters of treatment efficacy. This review focuses on the role of carbohydrate antigen 19- 9 ( CA 19- 9) as a prognostic tumor marker in PC and summarizes its contribution to monitoring treatment efficacy. We undertook a Medline/ PubMed literature search to identify relevant trials that had analyzed the prognostic impact of CA 19- 9 in patients treated with surgery, chemoradiotherapy and chemotherapy for PC. Additionally, relevant abstract publications from scientific meetings were included. In advanced PC, pretreatment CA 19- 9 levels have a prognostic impact regarding overall survival. Also a CA 19- 9 decline under chemotherapy can provide prognostic information for median survival. A 20% reduction of CA 19- 9 baseline levels within the first 8 weeks of chemotherapy appears to be sufficient to define a prognostic relevant subgroup of patients ('CA 19- 9 responder'). It still remains to be defined whether the CA 19- 9 response is a more reliable method for evaluating treatment efficacy compared to conventional imaging. Copyright (c) 2006 S. Karger AG, Basel

Increased risk of second malignancies after in situ breast carcinoma in a population-based registry

Among 1276 primary breast carcinoma in situ (BCIS) patients diagnosed in 1972–2002 in the Southern Netherlands, 11% developed a second cancer. Breast carcinoma in situ patients exhibited a two-fold increased risk of second cancer (standardised incidence ratios (SIR): 2.1, 95% confidence interval (CI): 1.7–2.5). The risk was highest for a second breast cancer (SIR: 3.4, 95% CI: 2.6–4.3; AER: 66 patients per 10 000 per year) followed by skin cancer (SIR: 1.7, 95% CI: 1.1–2.6; AER: 17 patients per 10 000 per year). The increased risk of second breast cancer was similar for the ipsilateral (SIR: 1.9, 95% CI: 1.3–2.7) and contralateral (SIR: 2.0, 95% CI: 1.4–2.8) breast. Risk of second cancer was independent of age at diagnosis, type of initial therapy, histologic type of BCIS and period of diagnosis. Standardised incidence ratios of second cancer after BCIS (SIR: 2.3, 95% CI: 1.8–2.8) resembled that after invasive breast cancer (SIR: 2.2, 95% CI: 2.1–2.4). Surveillance should be directed towards second (ipsi- and contra-lateral) breast cancer

Human-centred automation to simplify the path to social and economic sustainability

Musculoskeletal Disorders (MSDs) pose a serious threat to sustainability in manufacturing. In particular, this phenomenon impacts the sustainability indicators of worker health and safety and the Gross Domestic Product (GDP). Effective MSD prevention measures would therefore constitute a remarkable contribution to social and economic sustainability. This chapter provides first an outline of existing methods to prevent MSD at the workplace. Analysis of the approaches yields that effective solutions require earmarked finances as well as qualified personnel, both of which are not affordable for many companies. In pursuit of solutions, Human-centred Automation (HCA), a recent paradigm in manufacturing, proposes the design of manufacturing systems using intelligent technology to support the worker instead of replacing him/her. HCA has the unique potential of reducing the effort needed to implement MSD prevention strategies by simplifying the path to social and economic sustainability. This chapter demonstrates this process with the example of the “Working Posture Controller” (WPC), which illustrates how the HCA concept can be applied. Finally, the lessons learned from the case are outlined, providing a vision of how future workplaces can benefit from HCA

Establishment and characterisation of six human biliary tract cancer cell lines

Human cell lines established from biliary tract cancers are rare, and only five have been reported previously. We report the characterisation of six new six biliary tract cancer cell lines (designated SNU-245, SNU-308, SNU-478, SNU-869, SNU-1079 and SNU-1196) established from primary tumour samples of Korean patients. The cell lines were isolated from two extrahepatic bile duct cancers (one adenocarcinoma of common bile duct, one hilar bile duct cancer), two adenocarcinomas of ampulla of Vater, one intrahepatic bile duct cancer (cholangiocarcinoma), and one adenocarcinoma of the gall bladder. The cell phenotypes, including the histopathology of the primary tumours and in vitro growth characteristics, were determined. We also performed molecular characterisation, including DNA fingerprinting analysis and abnormalities of K-ras, p15, p16, p53, hMLH1, hMSH2, DPC4, β-catenin, E-cadherin, hOGG1, STK11, and TGF-βRII genes by PCR–SSCP and sequencing analysis. In addition, we compared the genetic alterations in tumour cell lines and their corresponding tumour tissues. All lines grew as adherent cells. Population doubling times varied from 48–72 h. The culture success rate was 20% (six out of 30 attempts). All cell lines showed (i) relatively high viability; (ii) absence of mycoplasma or bacteria contamination; and (iii) genetic heterogeneity by DNA fingerprinting analysis. Among the lines, three lines had p53 mutations; and homozygous deletions in both p16 and p15 genes were found three and three lines, respectively; one line had a heterozygous missense mutation in hMLH1; E-cadherin gene was hypermethylated in two lines. Since the establishment of biliary tract cancer cell lines has been rarely reported in the literature, these newly established and well characterised biliary tract cancer cell lines would be very useful for studying the biology of biliary tract cancers, particularly those related to hypermethylation of E-cadherin gene in biliary tract cancer

A standard procedure for creating a frailty index

<p>Abstract</p> <p>Background</p> <p>Frailty can be measured in relation to the accumulation of deficits using a frailty index. A frailty index can be developed from most ageing databases. Our objective is to systematically describe a standard procedure for constructing a frailty index.</p> <p>Methods</p> <p>This is a secondary analysis of the Yale Precipitating Events Project cohort study, based in New Haven CT. Non-disabled people aged 70 years or older (n = 754) were enrolled and re-contacted every 18 months. The database includes variables on function, cognition, co-morbidity, health attitudes and practices and physical performance measures. Data came from the baseline cohort and those available at the first 18-month follow-up assessment.</p> <p>Results</p> <p>Procedures for selecting health variables as candidate deficits were applied to yield 40 deficits. Recoding procedures were applied for categorical, ordinal and interval variables such that they could be mapped to the interval 0–1, where 0 = absence of a deficit, and 1= full expression of the deficit. These individual deficit scores were combined in an index, where 0= no deficit present, and 1= all 40 deficits present. The values of the index were well fit by a gamma distribution. Between the baseline and follow-up cohorts, the age-related slope of deficit accumulation increased from 0.020 (95% confidence interval, 0.014–0.026) to 0.026 (0.020–0.032). The 99% limit to deficit accumulation was 0.6 in the baseline cohort and 0.7 in the follow-up cohort. Multivariate Cox analysis showed the frailty index, age and sex to be significant predictors of mortality.</p> <p>Conclusion</p> <p>A systematic process for creating a frailty index, which relates deficit accumulation to the individual risk of death, showed reproducible properties in the Yale Precipitating Events Project cohort study. This method of quantifying frailty can aid our understanding of frailty-related health characteristics in older adults.</p

Effect Modification of the Association between Short-term Meteorological Factors and Mortality by Urban Heat Islands in Hong Kong

Background Prior studies from around the world have indicated that very high temperatures tend to increase summertime mortality. However possible effect modification by urban micro heat islands has only been examined by a few studies in North America and Europe. This study examined whether daily mortality in micro heat island areas of Hong Kong was more sensitive to short term changes in meteorological conditions than in other areas. Method An urban heat island index (UHII) was calculated for each of Hong Kong’s 248 geographical tertiary planning units (TPU). Daily counts of all natural deaths among Hong Kong residents were stratified according to whether the place of residence of the decedent was in a TPU with high (above the median) or low UHII. Poisson Generalized Additive Models (GAMs) were used to estimate the association between meteorological variables and mortality while adjusting for trend, seasonality, pollutants and flu epidemics. Analyses were restricted to the hot season (June-September). Results Mean temperatures (lags 0–4) above 29°C and low mean wind speeds (lags 0–4) were significantly associated with higher daily mortality and these associations were stronger in areas with high UHII. A 1°C rise above 29°C was associated with a 4.1% (95% confidence interval (CI): 0.7%, 7.6%) increase in natural mortality in areas with high UHII but only a 0.7% (95% CI: −2.4%, 3.9%) increase in low UHII areas. Lower mean wind speeds (5th percentile vs. 95th percentile) were associated with a 5.7% (95% CI: 2.7, 8.9) mortality increase in high UHII areas vs. a −0.3% (95% CI: −3.2%, 2.6%) change in low UHII areas. Conclusion The results suggest that urban micro heat islands exacerbate the negative health consequences of high temperatures and low wind speeds. Urban planning measures designed to mitigate heat island effects may lessen the health effects of unfavorable summertime meteorological conditions

Help-Seeking Behavior during Elevated Temperature in Chinese Population

The negative impact of extreme temperatures on health is well-established. Individual help-seeking behavior, however, may mitigate the extent of morbidity and mortality during elevated temperatures. This study examines individual help-seeking behavior during periods of elevated temperatures among a Chinese population. Help-seeking patterns and factors that influence behavior will be identified so that vulnerable subgroups may be targeted for health protection during heat crises. A retrospective time-series Poisson generalized additive model analysis, using meteorological data of Hong Kong Observatory and routine emergency help call data from The Hong Kong Senior Citizen Home Safety Association during warm seasons (June–September) 1998–2007, was conducted. A “U”-shaped association was found between daily emergency calls and daily temperature. About 49% of calls were for explicit health-related reasons including dizziness, shortness of breath, and general pain. The associate with maximum temperature was statistically significant (p = 0.034) with the threshold temperature at which the frequency of health-related calls started to increase being around 30–32°C. Mean daily relative humidity (RH) also had a significant U-shaped association with daily emergency health-related calls with call frequency beginning to increase with RH greater than 70–74% (10–25% of the RH distribution). Call frequency among females appeared to be more sensitive to high temperatures, with a threshold between 28.5°C and 30.5°C while calls among males were more sensitive to cold temperatures (threshold 31.5–33.5°C). Results indicate differences in community help-seeking behavior at elevated temperatures. Potential programs or community outreach services might be developed to protect vulnerable subgroups from the adverse impact of elevated temperatures