COUP-TFII in pancreatic adenocarcinoma: clinical implication for patient survival and tumor progression.

Despite the accumulating knowledge of alterations in pancreatic cancer molecular pathways, no substantial improvements in the clinical prognosis have been made and this malignancy continues to be a leading cause of cancer death in the Western World. The orphan nuclear receptor COUP-TFII is a regulator of a wide range of biological processes and it may exert a pro-oncogenic role in cancer cells; interestingly, indirect evidences suggest that the receptor could be involved in pancreatic cancer. The aim of this study was to evaluate the expression of COUP-TFII in human pancreatic tumors and to unveil its role in the regulation of pancreatic tumor growth. We evaluated COUP-TFII expression by immunohistochemistry on primary samples. We analyzed the effect of the nuclear receptor silencing in human pancreatic cancer cells by means of shRNA expressing cell lines. We finally confirmed the in vitro results by in vivo experiments on nude mice. COUP-TFII is expressed in 69% of tested primary samples and correlates with the N1 and M1 status and clinical stage; Kaplan-Meier and Cox regression analysis show that it may be an independent prognostic factor of worst outcome. In vitro silencing of COUP-TFII reduces the cell growth and invasiveness and it strongly inhibits angiogenesis, an effect mediated by the regulation of VEGF-C. In nude mice, COUP-TFII silencing reduces tumor growth by 40%. Our results suggest that COUP-TFII might be an important regulator of the behavior of pancreatic adenocarcinoma, thus representing a possible new target for pancreatic cancer therapy.

Apple consumption is related to better sexual quality of life in young women.

INTRODUCTION: Even if some evidence exists of a positive correlation between regular intake of phytoestrogens, polyphenols, antioxidants and women's sexual health, there is not a study addressing the potential correlation between daily apple consumption and women's sexual function. We aim to assess whether there is a tie between daily apple intake and sexual function in a sample of healthy young sexually active Italian women, not complaining of any sexual disorders. MATERIALS AND METHODS: Seven hundred and thirty-one women (mean age 31.9, range 18-43) were enrolled in this cross-sectional study (from September 2011 to April 2012). All participants completed anonymously the Female Sexual Function Index (FSFI) and were asked to report on their amount of daily apple consumption and their eating habits. On the basis of apple consumption all women were split into two groups: Group A--regular daily apple consumption, Group B--no regular apple consumption (<1 apple/day). The main outcome measure was the FSFI questionnaire result. RESULTS: Three hundred and forty-three women reported a regular daily apple intake and were classified in Group A, while 388 were included in Group B. Group A had a significantly higher total (p = 0.001; Cohen's d = 3.39) and lubrication domain (p = 0.001; Cohen's d = 3.02) FSFI scores than participants in Group B. Multivariate analysis demonstrated that daily apple intake must be considered as an independent parameter (p = 0.002) in predicting a better score at questionnaire examination. DISCUSSION: This study suggests a potential relationship between regular daily apple consumption and better sexuality in our young women population.

The role of asymptomatic bacteriuria in young women with recurrent urinary tract infections: to treat or not to treat?

BACKGROUND: Little is known about the role of asymptomatic bacteriuria (AB) treatment in young women affected by recurrent urinary tract infection (UTI). We aimed to evaluate the impact of AB treatment on the recurrence rate among young women affected by recurrent UTI. METHODS: A total of 673 consecutive asymptomatic young women with demonstrated bacteriuria from January 2005 to December 2009 were prospectively enrolled. Patients were split into 2 groups: not treated (group A, n = 312) and treated (group B, n = 361). Microbiological and clinical evaluations were performed at 3, 6, and 12 months. Quality of life was also measured. Recurrence-free rate at the end of the entire study period was the main outcome measure. RESULTS: At baseline, the 2 most commonly isolated pathogens were Escherichia coli (group A, 38.4%; group B, 39.3%) and Enterococcus faecalis (group A, 32.7%; group B, 33.2%). At the first follow-up visit, there was no difference between the 2 groups (relative risk [RR], 1.05; 95% confidence interval [CI], 1.01-1.10), whereas after 6 months, 23 (7.6%) in group A and 98 (29.7%) in group B showed recurrence with a statistically significant difference (RR, 1.31; 95% CI, 1.21-1.42; P < .0001). At the last follow-up, 41 (13.1%) in group A and 169 (46.8%) in group B showed recurrence (RR, 3.17; 95% CI, 2.55-3.90; P < .0001). One patient in group A and 2 patients in group B were found to have pyelonephritis. CONCLUSIONS: This study shows that AB should not be treated in young women affected by UTI, suggesting it may play a protective role in preventing symptomatic recurrence.

Genital Chlamydia trachomatis infection is related to poor sexual quality of life in young sexually active women.

INTRODUCTION: Chlamydia trachomatis (Ct) genital infection has been related to several diseases in young sexually active women. It could be related to their sexual quality of life. AIM: To assess whether genital Ct infection can induce sexual function alterations in women. METHODS: Nine hundred ninety-eight women (mean age 29.4, range 18-43) attending our Sexually Transmitted Disease Centre were enrolled in this observational case-control study. All participants were clinically and microbiologically investigated due to their sexual relationships with a subject affected by chronic bacterial prostatitis. All participants underwent microbiological cultures, DNA and antibodies evaluation for common bacteria and Ct on vaginal swab and urine samples. They completed the Female Sexual Function Index [FSFI] questionnaire. On the basis of microbiological investigation results, all patients were split into three groups: Group A-genital Ct infection, Group B-genital common bacteria/yeast infection, and Group C-negative for Ct and bacteria/yeast infection. MAIN OUTCOME MEASURES: FSFI questionnaire. RESULTS: Two hundred ninety-one women were classified in Group A, 276 in Group B, and 431 in Group C. Group A patients were statistically, significantly different from Group B and Group C patients in terms of pain during sexual intercourse and sexual satisfaction. Group C patients had significantly higher FSFI scores (27.1 ± 1.3) (P < 0.001) for both desire (4.9 ± 1.0) and lubrication domain (3.8 ± 1.1) (P < 0.001, P < 0.003, respectively) when compared with Group A patients. Multivariate analysis demonstrated that negative Ct infection marker in female patients must be considered as an independent prognostic factor in predicting a subsequent optimal FSFI questionnaire score (P = 0.002). CONCLUSIONS: Positive values of Ct infection markers are associated with lower FSFI scores for sexual desire, lubrication, and overall sexual function. Genital Ct infection could induce pain during sexual intercourse, reducing sexual satisfaction and sexual quality of life in young sexually active women.

Acute viral hepatitis increases liver stiffness values measured by transient elastography.

Liver tissue alterations other than fibrosis may have an impact on liver stiffness measurement. In this study we evaluated 18 patients without a previous clinical history of liver disease, consecutively admitted for acute viral hepatitis. In each patient, aminotransferase determination and liver stiffness measurement were performed on the same study day, at 3 different points: (1) peak increase in aminotransferase; (2) aminotransferase 50% or less of the peak; (3) aminotransferase levels

Regular moderate intake of red wine is linked to a better women's sexual health.

INTRODUCTION: While some evidence does exist for a positive correlation between moderate wine intake and men's sexual health, there is no study addressing the potential correlation between red wine intake and women's sexual function. AIM: The aim of our study was to assess whether there is a tie between daily red wine intake and sexual function in a sample of healthy Italian women, living in the Chianti area (Tuscany) not complaining of any sexual disorders. METHODS: We recruited 798 women (age 18-50), living in the Chianti area (Tuscany), not complaining of any sexual disorders. We divided the participants into three groups: daily moderate (one to two glasses) red wine intake (group 1); teetotallers (group 2); and daily intake of more than two glasses of red wine and/or other types of alcoholic drinks (including white wine), as well as of those reporting occasional drinking (group 3). MAIN OUTCOME MEASURES: All participants completed anonymously the Female Sexual Function Index (FSFI) questionnaire and were asked to report on their amount and type of alcohol consumption. RESULTS: Group 1 had significantly higher total (P = 0.001), as well as desire and lubrication domain (P = 0.001 and P = 0.001, respectively) FSFI scores than participants in groups 2 and 3. No significant differences between the groups were observed concerning sexual arousal, satisfaction, pain, and orgasm. Univariate analysis showed a significant correlation between age, alcohol consumption (P = 0.009), and a better score at questionnaire examination. During multivariate analysis, alcohol consumption was identified as an independent prognostic parameter (P = 0.002) in predicting the better score at questionnaire examination. CONCLUSIONS: The finding that regular moderate intake of red wine is associated with higher FSFI scores for both sexual desire, lubrication, and overall sexual function as compared to the teetotaller status is intriguing. While this finding needs to be interpreted with some caution, because of the small sample size, self-reported data, and the lack of support from laboratory exams, it nevertheless suggests a potential relationship between red wine consumption and better sexuality.

Can early single dose instillation of epirubicin improve bacillus Calmette-Guerin efficacy in patients with nonmuscle invasive high risk bladder cancer? Results from a prospective, randomized, double-blind controlled study.

PURPOSE: We evaluated the impact of epirubicin perioperative instillation in improving subsequent bacillus Calmette-Guerin instillation efficacy in high risk patients with nonmuscle invasive bladder cancer. MATERIALS AND METHODS: Between January 2005 and June 2007, 161 patients affected by high risk nonmuscle invasive bladder cancer were enrolled in this prospective, randomized, controlled, double-blind study. A total of 80 patients were assigned to group A (perioperative epirubicin 80 mg/50 ml normal saline) plus delayed bacillus Calmette-Guerin instillations (5 x 108 colony-forming units in 50 ml saline) and 81 to group B (delayed bacillus Calmette-Guerin alone). The main outcome measures were time to first recurrence and recurrence rate. All data obtained from a median followup of 15.3 months in group A and 14.8 months in group B, were analyzed. RESULTS: At the end of followup 46 of 80 patients in group A (57.5%) had no evidence of disease, just like 41 of 81 in group B (50.6%). No statistical difference was observed between the 2 groups in terms of recurrence rate (p = 0.82) or time to first recurrence (p = 0.095). Kaplan-Meier analysis of recurrence showed no significant differences between group A and group B (p = 0.0952). On multivariate analysis the early single dose instillation of epirubicin was not indicated as an independent prognostic factor (HR 0.50, 95% CI 0.32-1.18). CONCLUSIONS: The present study showed no statistically significant differences in terms of disease-free time and recurrence rate between high risk patients with nonmuscle invasive bladder cancer who had undergone perioperative epirubicin instillation plus delayed bacillus Calmette-Guerin and those who had undergone delayed bacillus Calmette-Guerin alone.

Prevalence, incidence estimation, risk factors and characterization of chronic prostatitis/chronic pelvic pain syndrome in urological hospital outpatients in Italy: results of a multicenter case-control observational study.

PURPOSE: We evaluated the prevalence and estimated the incidence and risk factors of chronic prostatitis/chronic pelvic pain syndrome in urological hospital outpatients in Italy. MATERIALS AND METHODS: From January to June 2006 patients from 28 Italian urological centers who were between 25 and 50 years old with symptoms of chronic prostatitis/chronic pelvic pain syndrome were consecutively enrolled in this prospective epidemiological case-control study. A total of 152 subjects of similar age, race and area of origin who were investigated for infertile couples but were otherwise healthy served as controls. All subjects provided a medical history and underwent different symptom scorings, clinical evaluation and microbiological tests. RESULTS: Of 5,540 male urological outpatients 764 with chronic prostatitis/chronic pelvic pain syndrome were enrolled, including 225 (29.4%) at the first presentation and 539 (70.6%) who underwent previous treatment. Thus, the prevalence of the syndrome was 13.8%, while the estimated incidence was 4.5%. Cigarette smoking, a high caloric diet with low fruit and vegetable consumption, constipation, meteorism, slow digestion, a sexual relationship with more than 1 partner and coitus interruptus were more likely in patients with chronic prostatitis/chronic pelvic pain syndrome than in controls (each p <0.001). The syndrome had a negative influence on sexual desire, erectile dysfunction and premature ejaculation (p <0.001). The Meares and Stamey test was positive in 13.3% of patients and in 2.9% of controls. Urethral swabs in patients with a negative Meares and Stamey test were positive for sexually transmitted pathogens in 6%. CONCLUSIONS: The prevalence and estimated incidence of chronic prostatitis/chronic pelvic pain syndrome in urological hospital outpatients in Italy are high. The syndrome is closely related to lifestyle, diet, smoking, gastrointestinal or anorectal disease and impaired sexual function.

Liquid-based endometrial cytology in the management of sonographically thickened endometrium.

Liquid-based cytology represents an opportunity to re-evaluate endometrial cytology. We evaluated the accuracy of liquid-based endometrial cytology as compared to biopsy in 670 women scheduled for histeroscopy because of thickened endometrium (>4 mm), as evaluated by transvaginal sonography. Endometrial biopsy detected pathology in 41 (6%) of cases (21 of which were adenocarcinomas). Cytologic study found pathology in 62 (9%) cases (19 of which were adenocarcinomas). Two hundred ninety-one biopsies (43%) and 28 (4%) cytologies were inadequate. The sensitivity and the specificity were estimated, respectively, at 95% and 98%; the positive and negative predictive values were estimated, respectively, at 83% and 99%. Cytology provided sufficient material more often than biopsy (P < 0.01). We consider endometrial cytology an efficacious diagnostic opportunity. It could be usefully applied in association with transvaginal sonography. The combination of these procedures might reduce more invasive and expensive diagnostic procedures.

Prognostic role of the tumor-associated tissue inflammatory reaction in transitional bladder cell carcinoma.

Many authors have indicated that the presence of an inflammatory response within the tumor may predict not only recurrence and progression but also survival in several tumors, including transitional cell carcinoma (TCC) of the urinary bladder. Several studies have been performed with a mean follow-up period that is often too limited for predicting patient outcome. The aim of the present study was to define the influence of inflammatory cell infiltrate on recurrence, progression and survival in TCC of the bladder over a long follow-up period. Between January and December 1995, 410 consecutive patients, who had undergone transurethral or open surgery for bladder tumors at the same urologic center, were selected for the study. All cases were reviewed to assess histotype, stage and grade of the tumor and presence or absence of tumor-associated inflammatory reaction. To better evaluate the prognostic role of each single factor in TCC, a follow-up of 10 years after surgery was performed. Pathologic evaluation showed superficial TCC in 312 patients, while 98 had an invasive bladder tumor. Three among 410 bladder tumors were squamous cell carcinomas. Out of 407 TCCs, 119 (29.23%) presented inflammation within the tumor or the lamina propria. At 10 years follow-up, a statistically significant association was shown between the presence of inflammation within the tumor or lamina propria and the number of recurrences (p<0.0001). Moreover, the absence of inflammatory infiltrate in the tumor established the relative risk of suffering more than one recurrence at 2.287 (95% CI 1.180-3.346). The Mann-Whitney test confirmed a statistically significant difference between superficial bladder tumors with inflammation and those without (26.3 vs 11.5 months, p<0.001). In terms of survival rate, a statistically significant difference was reported between carcinomas with and without inflammation (p=0.0261). On multivariate analysis, the presence of inflammation within the tumor was found to be an independent predictor of survival in patients with TCC of the bladder (p=0.027). Survival analysis by means of the Kaplan-Meier curves showed a statistically significant difference between patients with tumor-associated inflammatory reaction and those without (p=0.0098). These results confirm that the presence of inflammatory reaction has a good prognostic value in transitional bladder cell carcinoma. However, to better define its prognostic significance, the characterization of inflammatory cells in tumor-associated tissue reaction must be accomplished.

Seasonal variations of DNA damage in human lymphocytes: correlation with different environmental variables.

Several types of DNA damage, including DNA breaks and DNA base oxidation, display a seasonal trend. In the present work, a sample of 79 healthy subjects living in the city of Florence, Italy, was used to analyse this effect. Three possible causative agents were taken into consideration: solar radiation, air temperature and air ozone level. DNA damage was measured in isolated human lymphocytes at different times during the year and the observed damage was correlated with the levels of these three agents in the days preceding blood sampling. Three time windows were chosen: 3, 7 and 30 days before blood sampling. DNA strand breaks and the oxidized purinic bases cleaved by the formamidopyrimidine glycosylase (FPG sites) were measured by means of the comet assay. The results of multivariate regression analysis showed a positive correlation between lymphocyte DNA damage and air temperature, and a less strong correlation with global solar radiation and air ozone levels.

Long-term albumin infusion improves survival in patients with cirrhosis and ascites: an unblinded randomized trial.

AIM: To investigate the effects of long-term albumin administration on survival, recurrence of ascites and onset of other complications. METHODS: One hundred consecutive patients admitted for first-onset ascites were randomized to receive diuretics plus human albumin 25 g/wk in the first year and 25 g every two wk thereafter (group 1) or diuretics alone (group 2). The primary endpoint was survival without liver transplantation. Secondary endpoints were recurrence of ascites and occurrence of other complications. RESULTS: Median follow-up was 84 (2-120) mo. Albumin-treated patients had significantly greater cumulative survival rate (Breslow test=7.05, P=0.0078) and lower probability of ascites recurrence (51% versus 94%, P<0.0001). Chronic albumin infusion resulted in a mean increase in survival of 16 mo. CONCLUSION: Long-term albumin administration after first-onset ascites significantly improves patients' survival and decreases the risk of ascites recurrence.

Prolonged treatment interruption in chronic HIV infection: a new strategy?

The introduction of highly active antiretroviral therapy in 1995 dramatically decreased AIDS-related events and deaths rates; however, the enthusiasm among the medical and social community was soon limited by the growing incidence of various side-effects that often greatly limited patients' quality of life. The second problem caused by such a complex treatment consisted of sub-optimal adherence, with a consequent higher risk of the development of drug resistance.

Active and passive smoking and lifestyle determinants of 8-oxo-7,8-dihydro-2'-deoxyguanosine levels in human leukocyte DNA.

We investigated the effects of smoking and exposure to environmental tobacco smoke (ETS) on oxidative DNA damage by measuring 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) levels in DNA of leukocytes of healthy donors (30 smokers, 29 nonsmokers, and 28 ETS-exposed subjects). Nonsmokers had lower 8-oxodGuo levels compared with smokers (5.94 +/- 0.87 x 10(-6) and 19.85 +/- 4.75 x 10(-6) 2-deoxyguanosine, respectively, means +/- SE, P = 0.00007). Subjects exposed to ETS had higher mean value of 8-oxodGuo compared with nonsmokers (9.18 +/- 1.53 x 10(-6) 2-deoxyguanosine, mean +/- SE), nonsignificant by univariate analysis (P = 0.074). Multiregression analysis indicated that the increase of 8-oxodGuo levels induced by ETS was significant (P = 0.045) and that coffee and tea consumption reduced DNA oxidation (P = 0.0053). Oxidative leukocyte DNA damage was positively correlated with plasma cotinine levels in ETS-exposed subjects (r = 0.47, P < 0.01, n = 28) and was increased by age in nonsmokers and ETS-exposed subjects (P = 0.049). The results seem to confirm that ETS exposure is capable of inducing some oxidative DNA damage in circulating leukocytes and that coffee and tea consumption might partially protect against smoking-induced oxidation damage.

Relationships between promoter polymorphisms in the thymidylate synthase gene and mRNA levels in colorectal cancers.

Thymidylate synthase (TS) intratumoural expression may be a prognostic marker and predict outcome of 5-fluorouracil (5-FU)-based chemotherapy in colorectal cancer patients. The TS gene promoter enhancer region contains two different polymorphisms which can influence TS mRNA transcriptional and translational efficiency: a polymorphic tandem repeat sequence (2 or 3 repeats; 2R and 3R) and a single nucleotide polymorphism (SNP), G > C, within the second repeat of the 3R alleles. We studied the relationship between tumoural TS mRNA expression levels and TS gene polymorphisms in the colonic mucosa of 48 colorectal cancer patients. The 3R/3R genotype was characterised by higher TS mRNA levels in the tumour than the 2R/2R-2R/3R genotypes (P = 0.071). Regarding the relationship with the SNP polymorphism, a statistically significant difference in TS gene expression between the 3RG/3RG genotype and 2R/2R-2R/3RC-2R/3RG genotype subset was observed (P = 0.017). No statistically significant correlation was observed between experimental data and baseline clinical-pathological characteristics as well as clinical outcome in the relatively small patient series investigated. This is the first study reporting an association between the TS intra-repeat SNP and gene expression levels in colorectal cancer patients. These results suggest that in 3R/3R patients, the G > C polymorphism may be an important factor in determining TS mRNA expression levels, and warrant further investigation of the role of TS promoter polymorphisms as predictors of sensitivity to 5-FU-based chemotherapy in larger case series.

Moon orientation in adult and young sandhoppers under artificial light.

Our experiments, carried out at night and during the day on adults and laboratory-born young of the sandhopper Talitrus saltator, deal with the identification and use of the moon as an orientating factor. Sandhoppers were released in an apparatus (a Plexiglas dome) that produced a scenario similar to the natural one (with artificial sky, moon or sun illuminated at different intensities). When tested at night, the adult and young sandhoppers used the artificial moon like the natural one, independently of the intensity of illumination of the artificial sky and moon. In other words, sandhoppers tested at night always identified the artificial moon as the moon and never as the sun. In daytime releases, the seaward orientation failed at low intensities of artificial sky and sun illumination (3.07 and 1.55 microW cm2, respectively), whereas the sun compass was used effectively at higher levels of artificial sun and sky illumination. The innate ability of moon compass orientation in inexpert young sandhoppers was demonstrated even under artificial light.

Comparison of the usefulness of Doppler-derived deceleration time versus plasma brain natriuretic peptide to predict left ventricular remodeling after mechanical revascularization in patients with ST-elevation acute myocardial infarction and left ventricular systolic dysfunction.

The correlation between Doppler deceleration time (DT) and brain natriuretic peptide (BNP) and their predictive value for detecting left ventricular (LV) remodeling in patients who are treated with primary percutaneous intervention for infarction and LV dysfunction are unknown. Fifty-six patients (64 +/- 12 years of age; 11 women) who had a first ST-segment elevation myocardial infarction and systolic dysfunction that was successfully treated with direct primary coronary intervention underwent 2-dimensional Doppler echocardiographic and plasma BNP evaluation at days 1 and 3 and 1 and 6 months after the index infarction. Repeat coronary angiograms were obtained at 1 and 6 months. Because of previous consistent evidence, 3 days after the index infarction was the time point of comparison between BNP and DT values. Echocardiographic LV remodeling was defined as an increase in end-diastolic volume index above baseline values of 2 x SD. Ventricular remodeling occurred in 20 patients (36%). Multivariate analyses that included BNP level, Doppler DT, echocardiographic measurements of systolic function, peak creatine kinase, and anterior infarct location showed Doppler DT to be the only predictor of LV remodeling (odds ratio 0.963, 95% confidence interval 0.936 to 0.990, p = 0.008). The optimal cutoff for DT in the prediction of 6-month LV remodeling was <136 ms (sensitivity 75%, specificity 97%, accuracy 81%, area under receiver-operating characteristic curve 0.90). Thus, in patients who have a first ST-segment elevation myocardial infarction and LV systolic dysfunction that is successfully treated with primary percutaneous coronary intervention, Doppler-derived DT 3 days after index infarction is more effective than BNP level in detecting patients who are at higher risk for 6-month LV remodeling.

Correlation of epidermal growth factor receptor expression with tumor microdensity vessels and with vascular endothelial growth factor expression in ovarian carcinoma.

We analyzed in advanced ovarian serous G3 carcinoma the correlation between epidermal growth factor receptor (EGFR) overexpression and tumor angiogenesis and their relation with clinical outcome. Microvessel density (MVD) and vascular endothelial growth factor (VEGF) were statistically correlated with disease-free interval and death from disease both in univariate and multivariate analyses while EGFR expression was not correlated with clinical outcome. MVD was significantly associated with progression of disease during chemotherapy while VEGF and EGFR expression were not correlated with responsiveness to chemotherapy (Fisher's exact test). VEGF expression was correlated with MVD (Fisher's exact test). EGFR showed a trend to correlation with MVD. Further studies focusing on the use of angiogenesis inhibitors in addition to EGFR inhibitors on ovarian carcinoma cells may produce therapeutic strategies in the selection of tailored therapies in ovarian cancer patients.

Benzo(a)pyrene diolepoxide (BPDE)-DNA adduct levels in leukocytes of smokers in relation to polymorphism of CYP1A1, GSTM1, GSTP1, GSTT1, and mEH.

Benzo(a)pyrene [B(a)P] diolepoxide (BPDE)-DNA adducts were measured in the leukocytes of 41 healthy smokers using high-performance liquid chromatography coupled with a fluorimetric detector. The correlation between exposure to B(a)P through smoking and BPDE-DNA adduct levels was poor (r = 0.31), although subjects in the high exposure group [B(a)P > 50 ng/d] had a slightly higher level of adducts compared with the less exposed group (mean +/- SE, 1.70 +/- 0.3 versus 1.09 +/- 0.1; P = 0.057). We studied the effect on BPDE-DNA adducts of individual variations in genes controlling B(a)P metabolism, classifying subjects in "low-risk" and "high-risk" genotypes for smoking-related B(a)P DNA damage. The high-risk group included subjects characterized by a combination of increased B(a)P activation [cytochrome P450 1A1 (CYP1A1) MspI and/or exon 7 Ile462Val allele variants and microsomal epoxide hydrolase (mEH) fast activity] and decreased deactivation ability [presence of glutathione S-transferase M1 (GSTM1) null allele and wild-type glutathione S-transferase P1 (GSTP1)]. The low-risk group included smokers with lower B(a)P activation (wild-type CYP1A1, low or intermediate mEH activity) and higher deactivation capacity (active GSTM1, GSTP1 Ile105Val allele). Subjects in the low-risk group had lower levels of BPDE-DNA adducts compared with subjects in the high-risk genotype group; this difference was significant using two markers (CYP1A1 and GSTM1, median +/- SD, 0.77 +/- 1.16 versus 1.89 +/- 0.39; P = 0.03) or three markers (CYP1A1, GSTM1, and GSTP1, median +/- SD, 0.66 +/- 0.93 versus 1.43 +/- 1.17; P = 0.013). The discrimination between groups was reduced when including mEH as an additional marker (P = 0.085). In conclusion, CYP1A1, GSTM1, and GSTP1 genotyping seems to be a risk predictor of BPDE-DNA adduct formation in leukocytes.

Prognostic value of 6-minute walk corridor test in patients with mild to moderate heart failure: comparison with other methods of functional evaluation.

AIM: The study was designed to evaluate the prognostic value of the 6-min walk test (6MWT) in patients with mild to moderate congestive heart failure (CHF). METHODS AND RESULTS: Two hundred and fourteen patients (119 men and 95 women, mean age 64 years) were followed for a mean period of 34 months to assess event-free survival (death, heart transplantation). Sixty-six patients (34%) died (63 cardiovascular causes, 2 cancer and 1 stroke) and five patients underwent heart transplantation. For patients who walked <300 m during the 6MWT, survival was 62% compared with 82% in patients who walked 300-450 m or>450 m. With univariate analysis, NYHA class was the strongest predictor of death. LVEF (P<0.0001), aetiology of heart failure (P<0.001), LV filling pattern (P=0.002) and 6MWT distance (P<0.01) were all significantly related to survival. No significant relationship was found between survival, peak oxygen consumption or anaerobic threshold. Multivariate analysis using the Cox-stepwise regression model showed that LV fractional shortening (P<0.009) and 6MWT distance (P<0.0005) were the strongest prognostic markers. CONCLUSION: A 6MWT distance of <300 m is a simple and useful prognostic marker of subsequent cardiac death in unselected patients with mild to moderate CHF.