Incidence and characteristics of non-Hodgkin lymphomas in a multicenter case file of patients with hepatitis C virus-related symptomatic mixed cryoglobulinemias

BACKGROUND: Some patients with cryoglobulinemic syndrome (CS) develop frank non-Hodgkin lymphoma (NHL), but the incidence and timing of this event are still poorly defined. METHODS: A retrospective multicenter study was performed of hepatitis C virus-positive patients with CS observed in 11 Italian centers belonging to the Italian Group for the Study of Cryoglobulinemia. RESULTS: The inclusion criteria were satisfied by 1,255 patients. During a cumulative follow-up of 8,928 patient-years, 59 cases of NHL were diagnosed, for an estimated rate of 660.8 new cases per 100,000 patient-years with 224.1 new cases of aggressive NHL subtypes per 100,000 patient-years. More than 90% of the patients developing NHLs had type II cryoglobulins. The NHLs were classified as nonaggressive in 31 cases (53%), aggressive in 20 (34%), and mucosa-associated lymphoid tissue lymphomas in 6 (10%); 2 cases were unclassifiable. The median time from the diagnosis of CS to the clinical onset of NHL was 6.26 years (range, 0.81-24 years). The clinical course and response to chemotherapy in the patients with CS who had NHL were similar to those usually described in patients with NHL without CS; the course of the CS only marginally benefited from chemotherapy. CONCLUSIONS: The overall risk of NHL in patients with CS is about 35 times higher than in the general population (12 times higher if nonaggressive lymphomas are excluded). The presence of CS did not significantly affect the treatment of newly diagnosed lymphomas.     

Expression and function of α2,3-sialyl- and α,3/l,4-fucosyltransferases in colon adenocarcinoma cell lines: Role in synthesis of E-selectin counter-receptors

We show here that colon-carcinoma cell lines adhere to E-selectin via sialyl Lewis x and sialyl Lewis a (sLex and sLea) oligosaccharides and that this adhesion can be enhanced by TNF stimulation. To study in greater detail this endothelial binding, we analysed the mRNA expression and function of the enzymes participating in the generation of sLex and sLea on cancer cells. These oligosaccharides are synthesized by sequential action of α2,3 sialyl (α2,3-ST) and α1,3/1,4 fucosyltransferases (α1,3/1,4-FT) on existing (poly)N-acetyllactosamine chains. We report here that mRNAs of 2 recently cloned α2,3-STs and 4 α1,3/l,4-FTs are expressed in adenocarcinoma cells. In functional assays α2,3-ST and α1,3- or 1,4-FT activities were observed in adenocarcinoma cell lysates to exogenous N-acetyllactosamine and lacto-N-biose acceptors and to their sialytated derivatives, leading to the synthesis of the sialyl-N-acetyllactosamine and sLex or the sialyllacto-N-biose and sLea, respectively. Furthermore, the inflammatory cytokine TNF could enhance some α2,3-ST and α1,3/1,4-FT activities capable of generating E-selectin counter-receptors. Taken together, these data show that COLO 205 and HT-29 adenocarcinoma cell lines adhere to E-selectin in a TNF-inducible manner via their cell-surface sLex and sLea. These cells also express mRNA as well as inducible enzyme activities of several α2,3-STs and α,3/1,4-FTs responsible for the final steps in the synthesis of sLex and sLea. We show here that the TNF-induced adhesion to E-selectin might be due to the increased synthesis of sLex and sLea in colon-carcinoma cells.     

Risk indicators for varicose veins in forty- to sixty-year-olds in the Tampere varicose vein study

The objectives of the study were to discover the main determinants for the prevalence of varicose veins in a general population, and to assess the possibilities for prevention of this common surgical disease. Varicose veins were evaluated in three defined cohorts of 3284 men and 3590 women aged 40, 50, and 60 years by using a validated questionnaire. The response rate was 75% among men and 86% among women, and varicose veins were determined by self-assessment. Increasing age, female sex, childbirths, standing posture at work, higher weight or height, and positive family history were significantly associated with varicose veins in a univariate analysis. These factors were further taken into a multivariate logistic regression analysis, and female gender (adjusted odds ratio, OR 2.2), increasing age (OR 2.2-2.8), a reported positive family history for varicose veins (OR 4.9), increasing number of births (OR 1.2-2.8), standing posture at work (OR 1.6), and higher weight (OR 1.2) and height (OR 1.4) were found to independent and significant risk indicators of varicose veins. Increasing age, positive family history of varicose veins, and child-births in women were the most important factors in terms of population etiologic fractions. Familial predisposition and pregnancy-related factors bear important associations with varicose veins. Thus prevention of varicose veins appears to be difficult. Varicose veins are nonlethal and, therefore, higher age is related to higher prevalence.     

Occupational class inequalities across key domains of health: results from the Helsinki Health Study

BACKGROUND: Studies comparing socioeconomic inequalities in health using several health indicators are scarce. Therefore, this study aims to compare the shape and magnitude of occupational class inequalities across key domains of health, i.e. the subjective, functional and medical domains. Additionally, we examine whether physical or mental workload will affect these inequalities, and whether these effects are specific to particular health indicators. METHODS: Cross-sectional survey data from the Helsinki Health Study in 2000 and 2001 were used. Each year employees of the City of Helsinki, reaching 40, 45, 50, 55 and 60 years received a mailed questionnaire. 6243 employees responded (80% women, response rate 68%). The socioeconomic indicator was occupational social class. Nine health indicators were included: self-rated health, pain or ache, GHQ-12 mental well-being, limiting long-standing illness, SF-36 physical and mental health functioning, Rose angina symptoms, circulatory diseases and mental problems. Prevalence percentages, odds ratios and inequality indices from logistic regression analysis were calculated. RESULTS: Occupational class inequalities were found for self-rated health, pain or ache, limiting long-standing illness, physical health functioning, angina symptoms, and circulatory diseases. Physical or mental workload did not account for these inequalities. Inequalities were non-existent or slightly reversed for GHQ-12 mental well-being, SF-36 mental health functioning and mental problems. CONCLUSION: Expected occupational class inequalities in health among both women and men were found for global and physical health but not for mental health. The observed inequalities could not be attributed to physical or mental workload.     

Associations of functional ability with health-related behavior and body mass index among the elderly

The main purpose of this study was to determine whether functional ability among the elderly associates with body mass index (BMI) and health-related behavior. The secondary aim was to examine whether health behavior and BMI can be seen as mechanisms explaining sociodemographic disparities in functional ability. Cross-sectional biennial surveys from 1985 to 2001 were used to study 11,793 Finnish people aged 65-79 years. Associations of activities of daily living (ADL) with BMI, health behaviors (smoking, alcohol consumption, diet, physical activity), time period, previous occupation, marital status and certain diseases were tested using an ordinal regression model. Current and ex-smoking, heavy and non-alcohol use, unhealthy diet, physical inactivity and obesity were associated with inferior ADL. Alcohol consumption among men showed a U-shaped relation to functional ability. Most of the differences in ADL by occupation and marital status vanished after adjustment of multiple factors. The results showed clear associations of ADL with health-related behaviors and BMI when adjusted for multiple factors. The findings suggesting a U-shaped relation between ADL and alcohol consumption among men and the association between diet and ADL add to our previous knowledge of factors related to functional ability.     

Working conditions and health behaviours among employed women and men: the Helsinki Health Study

BACKGROUND: Working conditions influence health, but previous studies on the associations between work-related factors and health behaviours are scarce. The aim of this study was to analyse whether unfavourable working conditions are associated with diet, physical activity, alcohol consumption, and smoking. METHODS: The data derive from postal questionnaires collected in 2000-2001 from 40- to 60-year-old employees of the City of Helsinki (n=6243, response rate: 68%). Logistic regression analysis was used to examine health behaviours as outcomes. Job demands and job control, physically and mentally strenuous work, work fatigue, working overtime and satisfaction with work-home interface were independent variables, adjusted for age, education, occupational social class and marital status. RESULTS: Most of the examined associations between working conditions and health behaviours were not statistically significant. Among women, mentally strenuous work and high job control were associated with a healthy diet. Work fatigue was associated with physical inactivity, whereas physically strenuous work and satisfaction with work-home interface were more often reported by physically active women. Work fatigue was associated with high drinking among men. Low job strain was reported by nonsmoking women, whereas working overtime was associated with nonsmoking among men. CONCLUSIONS: Working conditions were only weakly associated with health behaviours, and the associations varied for different health behaviours.     

Prognostic relevance of gene amplifications and coamplifications in breast cancer

Multiple different oncogenes have been described previously to be amplified in breast cancer including HER2, EGFR, MYC, CCND1, and MDM2. Gene amplification results in oncogene overexpression but may also serve as an indicator of genomic instability. As such, presence of one or several gene amplifications may have prognostic significance. To assess the prognostic importance of amplifications and coamplifications of HER2, EGFR, MYC, CCND1, and MDM2 in breast cancer, we analyzed a breast cancer tissue microarray containing samples from 2197 cancers with follow-up information. Fluorescence in situ hybridizations revealed amplifications of CCND1 in 20.1%, HER2 in 17.3%, MDM2 in 5.7%, MYC in 5.3%, and EGFR in 0.8% of the tumors. All gene amplifications were significantly associated with high grade. HER2 (P < 0.001) and MYC amplification (P < 0.001) were also linked to shortened survival. In case of HER2, this was independent of grade, pT, and pN categories. MYC amplification was almost 3 times more frequent in medullary cancer (15.9%), than in the histologic subtype with the second highest frequency (ductal; 5.6%; P = 0.0046). HER2 and MYC amplification were associated with estrogen receptor/progesterone receptor negativity (P < 0.001) whereas CCND1 amplification was linked to estrogen receptor/progesterone receptor positivity (P < 0.001). Coamplifications were more prevalent than expected based on the individual frequencies. Coamplifications of one or several other oncogenes occurred in 29.6% of CCND1, 43% of HER2, 55.7% of MDM2, 65% of MYC, and 72.8% of EGFR-amplified cancers. HER2/MYC-coamplified cancers had a worse prognosis than tumors with only one of these amplifications. Furthermore, a gradual decrease of survival was observed with increasing number of amplifications. In conclusion, these data support a major prognostic impact of genomic instability as determined by a broad gene amplification survey in breast cancer.