Impact of hepatitis B virus infection on the progression of AIDS and mortality in HIV-infected individuals: a cohort study and meta-analysis.

BACKGROUND: The effect of hepatitis B virus (HBV) infection on the natural history of human immunodeficiency virus (HIV) disease remains uncertain. Therefore, a retrospective cohort study was conducted to examine the influence of HIV-HBV coinfection on AIDS development and overall mortality. Moreover, our results were added to those of previous studies in a literature-based meta-analysis. METHODS: Serum samples obtained from HIV-seropositive patients from 1984 through 2003 were retrospectively tested for hepatitis B surface antigen. Multivariable analyses were performed using Poisson and logistic regression models. For meta-analytic purposes, eligible articles were identified and relevant data were abstracted. Pooled estimates of effect were calculated applying fixed and random effects models. RESULTS: The prevalence of chronic HBV infection (documented hepatitis B surface antigen seropositivity for >6 months) among 1729 HIV-positive patients was approximately 6%. The multivariable analyses in our primary study revealed no significant impact of concomitant HIV-HBV infection on progression to AIDS and all-cause mortality. However, a meta-analysis performed on data from 12,382 patients enrolled in 11 studies revealed a significant effect of HIV-HBV coinfection on overall mortality (pooled effect estimate, 1.36; 95% confidence interval, 1.12-1.64). The increased rate of death among coinfected individuals was observed in the meta-analyses of studies conducted both before (pooled effect estimate, 1.60; 95% confidence interval, 1.07-2.39) and after (pooled effect estimate, 1.28; 95% confidence interval, 1.03-1.60) commencement of highly active antiretroviral therapy. CONCLUSIONS: HIV-HBV coinfection seems to affect all-cause mortality, and strategies to reduce liver damage in patients coinfected with HIV and HBV are justified.

Estrogen alpha and progesterone receptor expression in the normal mammary epithelium in relation to breast cancer risk.

Estrogens play a central role in the etiology of breast cancer, and results from observational studies and randomized trials have also implicated progestins. The effects of these hormones in the mammary tissue are exerted through binding with specific receptor proteins in the cell nucleus. It has been proposed that higher estrogen receptor alpha expression in the normal breast epithelium may increase breast cancer risk. In a study in Greece, we determined estrogen alpha and progesterone receptor expression in normal mammary tissue adjacent to the pathological tissue from 267 women with breast cancer and 299 women with benign breast disease. Mouse monoclonal antibodies specific for estrogen receptor alpha and progesterone receptor were applied. The H-index, which incorporates frequency and intensity of staining of the cells, and can range from 0 to 300, was deemed positive when it exceeded 9. Among premenopausal women, there was no evidence for an association with breast cancer risk for expression of either type of receptors. Among postmenopausal women, breast cancer risk was inversely associated with expression of both estrogen alpha (odds ratio (OR)=0.39; p=0.015) and progesterone (OR=0.40; p=0.008) receptors. The hypothesis that overexpression of estrogen receptors alpha or progesterone receptors in normal breast epithelium may increase the risk of breast cancer was not supported by our data. Instead, we found evidence that overexpression of these receptors may be associated with reduced risk for breast cancer in line with the well-known association of expression of these receptors in the malignant tissue and better breast cancer prognosis.

Anthropometric characteristics and non-Hodgkin's lymphoma and multiple myeloma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).

BACKGROUND: The incidences of non-Hodgkin's lymphoma and multiple myeloma are increasing steadily. It has been hypothesized that this may be due, in part, to the parallel rising prevalence of obesity. It is biologically plausible that anthropometric characteristics can infuence the risk of non-Hodgkin's lymphoma and multiple myeloma. DESIGN AND METHODS: In the context of the European Prospective Investigation into Cancer and Nutrition (EPIC), anthropometric characteristics were assessed in 371,983 cancer-free individuals at baseline. During the 8.5 years of follow-up, 1,219 histologically confirmed incident cases of non-Hodgkin's lymphoma and multiple myeloma occurred in 609 men and 610 women. Gender-specific proportional hazards models were used to estimate relative risks and 95% confidence intervals (95% CI) of development of non-Hodgkin's lymphoma and multiple myeloma in relation to the anthropometric characteristics. RESULTS: Height was associated with overall non-Hodgkin's lymphoma and multiple myeloma in women (RR 1.50, 95% CI 1.14-1.98) for highest versus lowest quartile; p-trend < 0.01) but not in men. Neither obesity (weight and body mass index) nor abdominal fat (waist-to-hip ratio, waist or hip circumference) measures were positively associated with overall non-Hodgkin's lymphoma and multiple myeloma. Relative risks for highest versus lowest body mass index quartile were 1.09 (95% CI 0.85-1.38) and 0.92 (95% CI 0.71-1.19) for men and women, respectively. Women in the upper body mass index quartile were at greater risk of diffuse large B-cell lymphoma (RR 2.18, 95% CI 1.05-4.53) and taller women had an elevated risk of follicular lymphoma (RR 1.25, 95% CI 0.59-2.62). Among men, height and body mass index were non-significantly, positively related to follicular lymphoma. Multiple myeloma risk alone was elevated for taller women (RR 2.34, 95% CI 1.29-4.21) and heavier men (RR 1.77, 95% CI 1.02-3.05). CONCLUSIONS: The EPIC analyses support an association between height and overall non-Hodgkin's lymphoma and multiple myeloma among women and suggest heterogeneous subtype associations. This is one of the first prospective studies focusing on central adiposity and non-Hodgkin's lymphoma subtypes.

Human herpesvirus 8 (HHV-8) infection in healthy urban employees from Greece: seroprevalence and associated factors.

A cross-sectional study was carried out in healthy company employees from Greece with the aim of assessing the prevalence of human herpesvirus 8 (HHV-8) and identifying risk factors for this herpesviral infection. Serum samples obtained from 955 subjects were tested for antibodies to HHV-8 by the K8.1 enzyme-linked immunosorbent assay (ELISA). Associations between HHV-8 serostatus and potential risk factors were examined using t-test, chi square test, and multivariate logistic regression analysis. HHV-8 prevalence was 7.6% (95% confidence interval (CI): 6.0%, 9.5%) and it increased with age from 6.5% among <30 years old to 13.8% among > or =50 years old subjects (P = 0.006). HHV-8 seropositivity was independently associated with endoscopic examination (odds ratio (OR): 2.01; 95% CI: 1.09, 3.70; P = 0.026), HBsAg positivity (OR: 5.16; 95% CI: 2.02, 13.20; P = 0.001) and age (OR > or =50 years old vs. <50 years old: 2.09; 95% CI: 1.23, 3.52; P = 0.006). No statistically significant associations between HHV-8 positive status and gender, occupational status, surgery, transfusion, tattoos/body piercing, multiple sex partners, weakness/fatigue, HCV status were observed. HHV-8 is prevalent in Greece. The strong association between HBV infection and HHV-8 positive status supports the hypothesis of an association between these two viral infections. The association between HHV-8 seropositivity and endoscopic examination requires further investigation.

Physical activity and lung cancer risk in the European Prospective Investigation into Cancer and Nutrition Cohort.

Research conducted predominantly in male populations on physical activity and lung cancer has yielded inconsistent results. We examined this relationship among 416,277 men and women from the European Prospective Investigation into Cancer and Nutrition (EPIC). Detailed information on recent recreational, household and occupational physical activity, smoking habits and diet was assessed at baseline between 1992 and 2000. Relative risks (RR) were estimated using Cox regression. During 6.3 years of follow-up we identified 607 men and 476 women with incident lung cancer. We did not observe an inverse association between recent occupational, recreational or household physical activity and lung cancer risk in either males or females. However, we found some reduction in lung cancer risk associated with sports in males (adjusted RR = 0.71; 95% confidence interval 0.50-0.98; highest tertile vs. inactive group), cycling (RR = 0.73; 0.54-0.99) in females and non-occupational vigorous physical activity. For occupational physical activity, lung cancer risk was increased for unemployed men (adjusted RR = 1.57; 1.20-2.05) and men with standing occupations (RR = 1.35; 1.02-1.79) compared with sitting professions. There was no evidence of heterogeneity of physical activity associations across countries, or across any of the considered cofactors. For some histologic subtypes suggestive sex-specific reductions, limited by subgroup sizes, were observed, especially with vigorous physical activity. In total, our study shows no consistent protective associations of physical activity with lung cancer risk. It can be assumed that the elevated risks found for occupational physical activity are not produced mechanistically by physical activity itself but rather reflect exposure to occupation-related lung cancer risk factors.

Breast cancer risk in relation to abortion: Results from the EPIC study.

The role of spontaneous and induced abortion on breast cancer risk is examined among 267,361 women recruited into the European Prospective Investigation into Cancer and nutrition between 1992 and 2000. The data were collected from 20 centers, across 9 countries, and included information on a total of 4,805 women with breast cancer, of whom 1,657 reported having ever had any type of abortion. Overall, the relative risk of breast cancer in women who reported ever having had a spontaneous abortion was not significantly elevated when compared with women who reported never having had such an abortion (RR = 1.07, 95% CI = 0.99-1.14). However, there was some evidence of a slight increase in the risk of breast cancer among women who reported having had 2 or more spontaneous abortions (1.20, 1.07-1.35). The relative risk of breast cancer among women who reported ever having had an induced abortion when compared to women who reported never having had an induced abortion was 0.95 (0.87-1.03). Overall, the findings provide further unbiased evidence of the lack of an adverse effect of induced abortion on breast cancer risk.

Fish consumption and breast cancer risk. The European Prospective Investigation into Cancer and Nutrition (EPIC).

There is current interest in fish consumption and marine omega-3 (n-3) fatty acids and breast cancer risk. Some in vitro and animal studies have suggested an inhibitory effect of marine n-3 fatty acids on breast cancer growth, but the results from epidemiological studies that have examined the association between fish consumption and breast cancer risk in humans are inconsistent. We examined fish consumption and breast cancer risk in 310,671 women aged between 25 and 70 yr at recruitment into the European Prospective Investigation Into Cancer and Nutrition (EPIC). The participants completed a dietary questionnaire between 1992-98 and were followed up for incidence of breast cancer for a median of 6.4 yr. Hazard ratio for breast cancer by intake of total and lean and fatty fish were estimated, stratified by study centre and adjusted for established breast cancer risk factors. During follow-up, 4,776 invasive incident breast cancers were reported. No significant associations between intake of total fish and breast cancer risk were observed, hazard ratio (HR) 1.01 (95% confidence interval [CI] 0.99-1.02; p = 0.28 per 10 g fish/day). When examining lean and fatty fish separately, we found a positive significant association only in the highest quintile for fatty fish (HR 1.13, 95% CI 1.01-1.26), but test for trend was not significant (p = 0.10). No associations with breast cancer risk were observed when the study participants were subdivided by menopausal status. Although the period of follow-up is relatively short, the results provide no evidence for an association between fish intake and breast cancer risk.

Human herpesvirus 8 infection in hemodialysis patients.

BACKGROUND: The aim of the present study was to evaluate human herpesvirus 8 (HHV-8) seroprevalence in Greek hemodialysis patients. Patterns of change in HHV-8 serostatus (seroconversions and seroreversions) over time were also evaluated. METHODS: Serum samples obtained from a cohort of 485 Greek hemodialysis patients were tested for antibodies to HHV-8 by whole virus lysate enzyme-linked immunosorbent assay, and reactive samples were confirmed by means of the orf-73 enzyme-linked immunosorbent assay. HHV-8 seroprevalence at study entry and the incidence of seroreversions and seroconversions per 100 person-years were estimated. RESULTS: The prevalence of HHV-8 antibodies in Greek hemodialysis patients at enrollment was 7.2%. No univariate associations were established between HHV-8 serostatus and patients' characteristics. Incidences of seroreversions and seroconversions were 16.4/100 person-years (95% confidence interval, 7.1 to 32.3) and 0.28/100 person-years (95% confidence interval, 0.03 to 1.02), respectively. Patients 50 years and younger had an increased probability for seroreversion to HHV-8 antibodies than patients older than 50 years (log-rank test, P = 0.018). CONCLUSION: We observed a fair number of seroreversions and a low incidence of seroconversion to HHV-8 infection in hemodialysis patients in Greece. Our data provide indirect evidence that HHV-8 transmission in the hemodialysis setting is uncommon.

Fruit and vegetable consumption and risk of epithelial ovarian cancer: the European Prospective Investigation into Cancer and Nutrition.

OBJECTIVE: The association between consumption of fruit and vegetables and risk of ovarian cancer is still unclear from a prospective point of view. METHODS: Female participants (n = 325,640) of the European Prospective Investigation into Cancer and Nutrition study, free of any cancer at baseline, were followed on average for 6.3 years to develop ovarian cancer. During 2,049,346 person-years, 581 verified cases of primary, invasive epithelial ovarian cancer were accrued. Consumption of fruits and vegetables as well as subgroups of vegetables, estimated from validated dietary questionnaires and calibrated thereafter, was related to ovarian cancer incidence in multivariable hazard regression models. Histologic subtype specific analyses were done. RESULTS: Total intake of fruit and vegetables, separately or combined, as well as subgroups of vegetables (fruiting, root, leafy vegetables, cabbages) was unrelated to risk of ovarian cancer. A high intake of garlic/onion vegetables was associated with a borderline significant reduced risk of this cancer. The examination by histologic subtype indicated some differential effects of fruit and vegetable intake on ovarian cancer risk. CONCLUSION: Overall, a high intake of fruits and vegetables did not seem to protect from ovarian cancer. Garlic/onion vegetables may exert a beneficial effect. The study of the histologic subtype of the tumor warrants further investigation.

Dehydroepiandrosterone relations to dietary and lifestyle variables in a general population sample.

BACKGROUND/AIMS: Dehydroepiandrosterone (DHEA) is generally considered to have beneficial effects in humans. There is, however, limited information concerning the role of lifestyle variables, including diet, on blood DHEA levels. We have undertaken a study of DHEA determinants in a general population sample of adult Greeks. METHODS: The sample consisted of 620 apparently healthy men and women aged 35-65 years, from all over Greece, participating in the EPIC study. Plasma DHEA was determined by radioimmunoassay. Nutritional intakes were ascertained through an interviewer-administered validated food frequency questionnaire, which also contained information on lifestyle variables. Statistical analyses were undertaken through simple cross-tabulations and by modelling the data through multiple regression. RESULTS: DHEA declines sharply with age and there is some evidence that the decline may be sharper in men than in women. Protein intake was significantly inversely associated with plasma levels of DHEA, whereas other dietary factors, energy expenditure and anthropometric variables were unrelated to this hormone. Alcohol intake and tobacco smoking tended to be positively related to DHEA, but the respective associations were not statistically significant. CONCLUSION: There has been a growing interest in replacement of DHEA in ageing adults. If confirmed, our results would indicate that a reduction in protein intake could have qualitatively similar effects.

Epidemiology of multiresistant Enterococcus avium isolates in a Greek tertiary care hospital.

A retrospective survey of the isolation rate of Enterococcus avium during the period March 1994-February 2000 conducted in Laikon General Hospital using the WHONET software, revealed a peak in the isolation rates of this species during March 1995-February 1996. The ten strains isolated during this time were studied further. No glycopeptide resistance was detected but resistance to ampicillin, ciprofloxacin, erythromycin, gentamicin (high-level) and streptomycin (high-level) was present in nine, ten, nine, three and seven of the isolates, respectively. The genes aac(6')-Ie+aph(2")-Ia and ant(6)-I, encoding for high-level gentamicin and streptomycin resistance, respectively, were detected only in the isolates with the corresponding phenotypes. Beta-lactamase production and haemolysis were not detected. There was evidence of ward-, floor- and building-specific distribution among the different aminoglycoside resistance phenotypes. DNA fingerprinting by PFGE grouped six of the ten isolates in a single cluster with 83% similarity, even though they expressed various resistance phenotypes. These results suggest dissemination of resistance genes among both genetically related and unrelated strains.

Molecular analysis of ampicillin-resistant sporadic Salmonella typhi and Salmonella paratyphi B clinical isolates.

OBJECTIVE: To study the mechanisms of antibiotic resistance in Salmonella typhi and Salmonella paratyphi B clinical isolates, and the clonality of resistant strains. METHODS: Antibiotic susceptibility was tested by disk-agar diffusion. Conjugation experiments and plasmid analysis by agarose gel electrophoresis after EcoRI digestion were followed by hybridization to a digoxigenin-labeled TEM-type beta-lactamase probe. DNA fingerprints were obtained by pulsed-field gel electrophoresis of Xbal-digested chromosomal DNA. RESULTS: Three S. typhi isolates (7% of the isolates studied), of which one was ampicillin resistant and the other two multiresistant (ampicillin, chloramphenicol, tetracycline, sulfamethoxazole/trimethoprim and streptomycin), and two ampicillin-resistant S. paratyphi B isolates (25% of the isolates studied) were further evaluated. A 34-MDa conjugative plasmid, previously isolated from Salmonella enteritidis, conferred ampicillin resistance. A 100-MDa conjugative plasmid encoded resistance to chloramphenicol, tetracycline and sulfamethoxazole/trimethoprim, as well as ampicillin. Chromosomal fingerprinting revealed two distinct resistant strains for each serovar which were different from a matched set of sensitive S. typhi strains. CONCLUSIONS: Two conjugative, TEM-type beta-lactamase-encoding plasmids conferred ampicillin resistance to S. typhi and S. paratyphi B. The 34-MDa plasmid was identical to that previously characterized from S. enteritidis, while the 100-MDa plasmid also encoded resistance to chloramphenicol, tetracycline and sulfamethoxazole/trimethoprim. Resistant isolates did not belong to a single clone but rather represented distinct strains.

Isolation of Salmonella from Fluid Milk with the Use of Rappaport-Vassiliadis Medium.

The performances of Rappaport-Vassiliadis (RV) medium and tetrathionate brilliant green broth (TT) for the detection of salmonellae in pasteurized fluid whole milk, artificially contaminated, were compared. The RV medium was found to be more sensitive and more selective than the TT medium, as far as Salmonella typhimurium was concerned. From the 100 samples contaminated with S. typhimurium only, 97 were found positive witb RV medium, while 86 were found positive with TT medium (P<0.001). From the 100 samples contaminated with S. typhimurium plus gram-negative competing organisms, 79 were found positive with RV medium, while only 41 with TT medium (P<10-6). The mean values of growth of competing organisms in RV medium after 24 and 48 h of incubation at 43°C were 0.81 and 0.92, respectively, while the corresponding values in TT medium were 1.81 and 1.87.