Study of socio-economic characteristics, diagnosis and outcome of women participating or not participating in mammogram screening.

BACKGROUND: Breast cancer is the most common cancer and the leading cause of cancer death in women. Early detection is essential to reduce cancer mortality. Studying participation in an organised breast cancer screening program is important in order to evaluate the program effectiveness. Breast screening both enables minimally invasive breast surgery and reduces cause-specific mortality. METHODS: The main objective of this study was to evaluate, through the use of a questionnaire, the influence of socio-economic characteristics (age, education, occupational status, participation in other screening programs etc.) on participation in a mammography screening program organized by the local health units (LHU) of Novara and Verbano-Cusio-Ossola, located in the Italian region of Piedmont. A sample of 500 women was identified. Eligible participants included women aged 50-69 years, resident in the area of the LHUs of Novara and Verbano-Cusio-Ossola who had been invited to participate in the screening program 2006-2007. Twenty six women were excluded, leaving 474 women in the final analysis: 23 women were unable to be contacted due to incorrect contact details and 3 women were unable to complete the questionnaire due to neurodegenerative diseases. A postal questionnaire was sent by post during 2008-2009. Two postal reminders were sent to non-responders, followed by a phone call. One group of women received an additional copy of the questionnaire with the first postal reminder and another group received only the reminder letter. The socio-personal profiles and their influence in women's participation in the screening program were evaluated. RESULTS: Among the responders, 93% of the women (348/374) received a mammogram at least once following LHU invitation for check-up. 74.1% of women got a mammogram at least once using the organized screening program, an additional 17.8% got a mammogram in a private clinic, and the type of prevention was unknown for 8.1% of the women. 25.3% began having mammogram for prevention before the age of 45. CONCLUSIONS: A screening program is a sanitary intervention of secondary prevention and the identification of the attitude towards this kind of prevention is quite complex. Some causes of non-participation in this screening program were the belief that mammogram is not necessary, fear of pain, and presence of family problems. This study obtained a higher response than expected and the data also allowed an assessment of the degree of participation of women in the prevention services, identifying that most of them carried out a mammogram using an organized screening program.

XRCC1 and ERCC1 variants modify malignant mesothelioma risk: a case-control study.

Malignant pleural mesothelioma (MPM) is a rare aggressive tumor associated with asbestos exposure. The possible role of genetic factors has also been suggested and MPM has been associated with single nucleotide polymorphisms (SNPs) of xenobiotic and oxidative metabolism enzymes. We have identified an association of the DNA repair gene XRCC1 with MPM in the population of Casale Monferrato, a town exposed to high asbestos pollution. To extend this observation we examined 35 SNPs in 15 genes that could be involved in MPM carcinogenicity in 220 MPM patients and 296 controls from two case-control studies conducted in Casale (151 patients, 252 controls) and Turin (69 patients, 44 controls), respectively. Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Two DNA repair genes were associated with MPM, i.e. XRCC1 and ERCC1. Considering asbestos-exposed only, the risk increased with the increasing number of XRCC1-399Q alleles (Casale: OR=1.44, 95%CI 1.02-2.03; Casale+Turin: OR=1.34, 95%CI 0.98-1.84) or XRCC1 -77T alleles (Casale+Turin: OR=1.33, 95%CI 0.97-1.81). The XRCC1-TGGGGGAACAGA haplotype was significantly associated with MPM (Casale: OR=1.76, 95%CI 1.04-2.96). Patients heterozygotes for ERCC1 N118N showed an increased OR in all subjects (OR=1.66, 95%CI 1.06-2.60) and in asbestos-exposed only (OR=1.59, 95%CI 1.01-2.50). When the dominant model was considered (i.e. ERCC1 heterozygotes CT plus homozygotes CC versus homozygotes TT) the risk was statistically significant both in all subjects (OR=1.61, 95%CI 1.06-2.47) and in asbestos-exposed only (OR=1.56, 95%CI 1.02-2.40). The combination of ERCC1 N118N and XRCC1 R399Q was statistically significant (Casale: OR=2.02, 95%CI 1.01-4.05; Casale+Turin: OR=2.39, 95%CI 1.29-4.43). The association of MPM with DNA repair genes support the hypothesis that an increased susceptibility to DNA damage may favour asbestos carcinogenicity.

Lack of association of HLA class I genes and TNF alpha-308 polymorphism in toluene diisocyanate-induced asthma.

BACKGROUND: Toluene diisocyanate (TDI)-induced asthma is a common cause of occupational asthma and it affects 5-15% of the exposed population suggesting an underlying genetic susceptibility. METHODS: To investigate the role of genetic factors in the development of TDI-induced asthma, we analyzed the distribution of human leukocyte antigen (HLA) class I genes and of tumor necrosis factor (TNF)-alpha A-308G polymorphism in 142 patients with TDI-induced asthma and in 50 asymptomatic exposed subjects. RESULTS: Neither the distribution of HLA class I antigens nor the distribution of TNF-alpha A-308G polymorphism was different between patients with TDI-induced asthma and asymptomatic exposed subjects. CONCLUSIONS: These results suggest that HLA class I antigens and TNF-alpha A-308G are not associated with susceptibility or resistance to the development of TDI-induced asthma.

Long-term follow-up of toluene diisocyanate-induced asthma.

Eighty-seven cases of occupational asthma induced by toluene diisocyanate (TDI) were diagnosed by an inhalation challenge with TDI and methacholine. After an average follow-up interval of 11 yrs, all subjects were re-examined. Of the 87 subjects examined, 13 (15%) had remained in the same job, 44 (50.5%) had been removed from exposure for <10 yrs and 30 (34.5%) had been removed for >10 yrs. The proportion of subjects who experienced symptoms of asthma and those who were hyperresponsive to methacholine was significantly lower. Of the patients, 59% used short-acting bronchodilators, 8% long-acting bronchodilators and 18% were on regular inhaled glucocorticoids. Thus, multiple regression analysis showed a positive correlation between forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) at follow-up and FVC and FEV1 at diagnosis, and a negative correlation with smoking and with therapy with bronchodilators. Stepwise logistic regression showed that the follow-up provocative dose causing a 20% fall in the FEV1 (PD20) could be predicted from baseline PD20. These results indicate that respiratory symptoms and airway hyperresponsiveness to methacholine persist in subjects removed from exposure to TDI for >10 yrs. A more favourable prognosis was associated with a better lung function and a lower degree of airway hyperresponsiveness to methacholine at diagnosis.

Extracellular NAD(+) induces calcium signaling and apoptosis in human osteoblastic cells.

ADP-ribosyl cyclase/CD38 is a bifunctional enzyme that catalyzes at its ectocellular domain the synthesis from NAD(+) (cyclase) and the hydrolysis (hydrolase) of the calcium-mobilizing second messenger cyclic ADP ribose (cADPR). Furthermore, CD38 mediates cADPR influx inside a number of cells, thereby inducing Ca(2+) mobilization. Intracellularly, cADPR releases Ca(2+) from ryanodine-sensitive pools, thus activating several Ca(2+)-dependent functions. Among these, the inhibition of osteoclastic-mediated bone resorption has been demonstrated. We found that HOBIT human osteoblastic cells display ADP-ribosyl cyclase activity and we examined the effects of CD38 stimulation on osteoblasts function. Extracellular NAD(+) induced elevation of cytosolic calcium due to both Ca(2+) influx from the extracellular medium and Ca(2+) release from ryanodine-sensitive intracellular stores. Culturing these cells in the presence of NAD(+) caused a complete growth arrest with a time-dependent decrease of cell number and the appearance of apoptotic nuclei. The first changes could be observed after 24 h of treatment and became fully evident after 72-96 h. We propose a role of extracellular NAD(+) in bone homeostatic control.

Association between HLA genes and susceptibility to toluene diisocyanate-induced asthma.

BACKGROUND: Only a small proportion of subjects exposed to isocyanates develop occupational asthma, suggesting individual predisposition. The human leucocyte antigen (HLA) class II molecules may play a crucial role in the development of the immune response to isocyanates. OBJECTIVES: To investigate the role of HLA class II molecules in the development of toluene diisocyanate (TDI)-induced asthma. SUBJECTS: Sixty-seven asthmatic subjects and 27 asymptomatic exposed subjects (controls) were typed at the HLA class II DQA1, DQB1 and DRB1 loci by polymerase chain reaction (PCR)-based techniques. RESULTS: The frequencies of DQA1*0104 and DQB1*0503 were significantly increased in asthmatics compared with asymptomatic exposed subjects, while DQA1*0101 and DQB1*0501 were significantly increased in asymptomatic exposed subjects. No significant difference was found in the distribution of DRB1 alleles between asthmatics and controls. CONCLUSIONS: The results of this study indicate that HLA-regulated immune mechanisms are involved in TDI-induced asthma and that, in exposed subjects, specific factors may increase or decrease the risk of developing disease.

Influence of length of time on dialysis before grafting on kidney transplant results.

The outcome of kidney transplantation was evaluated in 246 nondiabetic, CsA-treated recipients of primary cadaver transplant, divided into 4 groups according to length of time on dialysis: group < or = 2, 0-24 months; group 2-5, 25-60 months; group 5-15, 61-180 months; group > 15, over 180 months. The 4 groups did not differ in graft survival, proteinuria (g/die), or estimated GFR values at 1, 2, 3, 4, and 5 years after grafting. They did not differ in the frequency of cataract, hip osteonecrosis, tumors, or posttransplant diabetes mellitus at 3 years after grafting. Ocular hypertone (p < 0.02), tendon ruptures (p < 0.001), arterial occlusive disease of lower limbs (p < 0.01), cholelithiasis (p < 0.05), and chronic hepatitis--which occurred only in anti-HCV and/or HBs Ag-positive patients--(p < 0.001), were more frequent in group > 15, and in all these cases but ocular hypertone a linear trend of increasing frequencies with increasing dialytic age was statistically significant. Group 5-15 had the lowest patient survival (p < 0.02). Moreover, a progressive decline of patient survival with increasing dialytic age was noted in groups < or = 2, 2-5, and 5-15. Unexpectedly, group > 15 had remarkably good survival, and this finding denies the hypothesis of a purely linear decline of patient survival after transplantation with increasing dialytic age.

Plasma steroid responses to circadian-stage-specified injection of different doses of the ACTH analogue alsactide (ACTH 1-17) in healthy adult human males.

Plasma cortisol, progesterone, testosterone and aldosterone levels were measured on serial blood samples drawn in 10 healthy adult human males up to 6h after single administration at about 07 of increasing amounts of the short-chain analogue ACTH-agonist alsactide (Synchrodyn 1-17). The following doses were employed: 2, 4, 8, 10 and 20 micrograms subcutaneously (s.c.), as well as 2, 4 and 8 micrograms intravenously (i.v.). Data were compared with those obtained by placebo (isotonic saline) injections. The s.c. injections of 2 and 4 micrograms resulted to be ineffective in changing the hormonal pattern. A significant rise of cortisol and progesterone, but not of aldosterone and testosterone, followed the s.c. injections of 8 and 10 micrograms. The differential pattern of the glucocorticoid vs. the mineralocorticoid response was also apparent after the s.c. injection of 20 micrograms alsactide; when compared with placebo, this dose was able to elicit a significant increase of all examined hormones except testosterone. All i.v. injections of 2, 4 and 8 micrograms alsactide were effective; the highest dose did cause a sustained rise of plasma cortisol, progesterone and aldosterone, but also the other doses were able to change significantly the mineralocorticoid levels. These results provide evidence that circadian-stage-specified s.c. or i.v. administration of the analogue can be employed in the clinical practice for enhancing selectively and transiently the morning glucocorticoid secretion.