Images of alcohol among Italian adolescents. Understanding their point of view

Aims: This study aims to plug the gap about how young people understand their direct and indirect experience with alcohol by investigating the prevalent images of alcohol among 15-year-olds. The study also aims to clarify the position of young Italians towards traditional Italian drinking culture.

Methods: Twenty-two focus groups were organized in two Italian towns, Torino and Cosenza. The focus groups (FGs) used the Reception Analytical Group Interview (RAGI) method, wherein respondents are invited to discuss after seeing video clips used as a stimulus. The material thus collected was analysed through an approach that takes both the participants’ interpretative processes and their socio-cultural environment into consideration.

Findings: Using ‘drinking situations’ as an analytical tool, it was found that young people's images about drinking are still in line with tradition, as are the importance assigned to social drinking and the stigma attached to intoxication. Young people also appear to be aware of the negative consequences of drinking, even if the risks related to pharmaceutical use seem to be underestimated.

Conclusions: Results cast doubt on the supposed convergence of drinking patterns within Europe and provide useful insights for the development of alcohol use and abuse policies and prevention.     

Loco-regional treatment of hepatocellular carcinoma: Role of contrast-enhanced ultrasonography

Hepatocellular carcinoma (HCC) is one of the few cancers for which locoregional treatments (LRTs) are included in international guidelines and are considered as a valid alternative to conventional surgery. According to Barcelona Clinic Liver Cancer classification, percutaneous treatments such as percutaneous ethanol injection, radiofrequency ablation and microwave ablation are the therapy of choice among curative treatments in patients categorized as very early and early stage, while transcatheter arterial chemoembolization is considered the better option for intermediate stage HCC. A precise assessment of treatment efficacy and surveillance is essential to optimize survival rate, whereas residual tumor requires additional treatment. Imaging modalities play a key role in this task. Currently, contrast-enhanced computed tomography/magnetic resonance imaging are considered the standard imaging modalities for this purpose. Contrast enhanced ultrasound (CEUS), using second generation contrast agents, plays an increasingly important role in detecting residual disease after LRTs. CEUS is a straightforward to perform, repeatable and cost-effective imaging modality for patients with renal failure or iodine allergies. Due to the ability to focus on single regions, CEUS can also provide high temporal resolution. Moreover, several studies have reported the same or better diagnostic accuracy as contrast-enhanced computed tomography for assessing tumor vascularity 1 mo after LRTs, and recently three-dimensional (3D)-CEUS has been reported as a promising technique to improve the evaluation of tumor response to therapy. Furthermore, CEUS could be used early after procedures in monitoring HCC treatments, but nowadays this indication is still debated, and data from literature are conflicting, especially after transcatheter arterial chemoembolization procedure.     

Factors influencing outcome and incidence of long-term complications in children who underwent autologous stem cell transplantation for acute myeloid leukemia in first complete remission

To evaluate factors influencing outcome and incidence of long-term complications, we analyzed, in a retrospective, multicenter study, 387 children who underwent autologous hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) in first complete remission (CR). Median follow-up time from transplantation was 60 months. Transplantation of bone marrow cells was performed in 318 children, whereas in 60 patients peripheral blood progenitor cells (PBPCs) were used. In multivariate analysis, we investigated the variables influencing probability of hematopoietic recovery, transplantation-related mortality (TRM), relapse, and leukemia-free survival (LFS). We found that use of PBPCs as stem cell sources and use of BCNU (N,N-bis[2-chloroethyl]-N-nitrosourea), amsacrine, VP-16, and cytosine arabinoside (BAVC) as a preparative regimen were associated with faster neutrophil recovery. Infusion of PBPCs, young age of patients, use of BAVCs, and absence of marrow purging predicted an accelerated platelet reconstitution. The 5-year Kaplan-Meier estimates of TRM, relapse, and LFS were 3% +/- 1%, 39% +/- 3% and 60% +/- 3%, respectively. Relapse probability was increased in children given the BAVC regimen, and it was decreased after in vitro purging of hematopoietic progenitors and in children with a French-American-British classification of M3 and a time interval of 170 days or more between CR and HSCT. These 2 latter variables favorably influenced the probability of LFS, which was, by contrast, reduced with the BAVC regimen. Thirty-three percent of patients surviving more than 18 months experienced at least one late sequela; use of total body irradiation was the only predictive factor. The results obtained in this analysis can be of help in designing prospective studies of autologous HSCT in children with AML in first CR.     

Effect of oral contraceptives on endothelial function in the peripheral microcirculation of healthy women

OBJECTIVES: We assessed whether third-generation oral contraceptive (OC) treatment (30 microg ethinylestradiol + 75 microg gestodene daily) could affect the endothelial function of healthy women. METHODS: In 20 young healthy women (HW) and 10 hypercholesterolemic women (CW) we assessed forearm blood flow (strain-gauge plethysmography) changes induced by the intrabrachial infusion of acetylcholine (ACH) (0.15-15 microg/100 ml forearm tissue/min) and sodium nitroprusside (SNP) (1-4 microg/100 ml forearm tissue/min). ACH was repeated during the nitric oxide synthase inhibitor intra-arterial NG-monomethyl-L-arginine (L-NMMA) (100 microg/100 ml forearm tissue/min) or the antioxidant vitamin C (8 mg/100 ml forearm tissue/min). HW repeated the protocol after 6-month OC (n = 10) or placebo (n = 10) treatment. RESULTS: In HW the maximal vasodilation to ACH, similar between placebo and OC subgroups, was significantly reduced in CW (P < 0.01). Vasodilation to ACH was blunted (P < 0.01) by L-NMMA and unaffected by vitamin C, in both OC and placebo groups. In CW the vasodilation to ACH, not modified by L-NMMA, was improved by vitamin C (P < 0.01). OC treatment raised (P < 0.01) plasma total and low-density lipoprotein cholesterol, and values were similar to those shown by CW. Both OC and placebo intake did not change the response to ACH and the modulation induced by L-NMMA or vitamin C. Vasodilation to SNP was similar in all groups. CONCLUSIONS: In HW 6-month treatment with third-generation OC, although associated with an abnormal lipid profile, does not adversely affect endothelium-dependent vasodilation. This neutral effect could be the balance between a deleterious effect of hypercholesterolemia and a protective effect of OC on endothelial function.     

Human erythrocyte pyrimidine 5-nucleotidase, PN-I, is identical to p36, a protein associated to lupus inclusion formation in response to alpha-interferon

Erythrocyte maturation is accompanied by RNA degradation and release of mononucleotides. We have previously purified PN-I, a pyrimidine nucleotidase whose deficiency is associated with hemolytic anemia. Computer-aided analysis of PN-I tryptic and CNBr peptide sequences revealed substantial identity with tryptic peptide sequences reported for p36, an alpha-interferon-induced protein. PN-I partial sequences were matched through the expressed sequence tag database with different human complementary DNA (cDNA) clones, whose sequences were exploited to screen a human placenta cDNA library. PN-I cDNA, coding for a 286-residue protein, was expressed in Escherichia coli, yielding a fully active recombinant enzyme. The recombinant protein sequence comprised the peptide sequences determined for PN-I and p36. Rabbit antisera raised against two peptides deriving from p36 and PN-I tryptic digestions, respectively, recognized both wild-type and recombinant PN-I. Molecular properties of the two proteins were essentially the same. We conclude that p36 and PN-I are identical proteins. (Blood. 2000;96:1596-1598)     

Pancreatic cancer mortality in Europe: the leveling of an epidemic

Mortality rates from pancreatic cancer have increased throughout Europe between the late 1950s and the 1980s. Trends in 22 European countries, the European Union (EU) and 6 selected eastern European countries have been updated using official death certification data for pancreatic cancer abstracted from the WHO database over the period 1980 to 1999. In EU men, a rise from 7.2 to 7.5/100,000 was observed between the early and the late 1980s, followed by a leveling off in the 1990s. For women, rates tended to rise up to the early 1990s, and to level off thereafter around 4.7/100,000. In eastern countries, rates for both sexes rose between the early 1980s and the mid-1990s, and leveled off thereafter around 8.5/100,000 men and 5/100,000 women. Thus, rates for men only were higher in Eastern Europe than in the EU. This analysis first documents a leveling of pancreatic cancer mortality in Europe, after decades of steady rises. This is partly or largely attributable to the decline in smoking, at least in men, but other factors, including mainly nutrition and diet, may also have played some role on these trends.     

A 20-year long term experience of the Italian Diamond-Blackfan Anaemia Registry: RPS and RPL genes,different faces of the same disease?

Diamond–Blackfan anaemia (DBA) is a rare and heterogeneous disease characterised by hypoplastic anaemia, congenital anomalies and a predisposition for malignancies. The aim of this paper is to report the findings from the Italian DBA Registry, and to discuss the Registry’s future challenges in tackling this disease. Our 20-year long work allowed the connection of 50 Italian Association of Paediatric Haematology and Oncology (AIEOP) centres and the recruitment of 283 cases. Almost all patients have been characterised at a molecular level (96%, 271/283), finding a causative mutation in 68% (184/271). We confirm the importance of determination of erythrocyte adenosine deaminase activity (eADA) and of ribosomal RNA assay in the diagnostic pipeline and characterisation of a remission state. Patients with mutations in large ribosomal subunit protein (RPL) genes had a significant correlation with the incidence of malformations, higher eADA levels and more severe outcomes, compared to patients with mutations in small ribosomal subunit protein (RPS) genes. Furthermore, as a consequence of our findings, particularly the incidence of malignancies and the high percentage of patients aged >18 years, we stress the importance of collaboration with adult clinicians to guarantee regular multi-specialist follow-up. In conclusion, this study highlights the importance of national registries to increase our understanding and improve management of this complex disease.     

Novel N-terminal domain mutation in prion protein detected in 2 patients diagnosed with frontotemporal lobar degeneration syndrome

Prion protein gene mutations have been associated with clinical pictures mimicking neurodegenerative diseases different from inherited prion diseases (IPD). We report a novel missense P39L mutation in the N-terminal domain of prion protein in 2 patients affected by frontotemporal lobar degeneration syndrome, negative for mutations in genes causative of dementia. Neither the first carrier, a 67-year-old male in which the onset was a progressive non-fluent aphasia, nor the second carrier, a 78-year-old male affected by frontotemporal dementia and parkinsonism, showed any clinical or instrumental findings suggestive of IPD. Genetic screening of healthy controls and in silico analysis provide support for the potential pathogenicity of this variant. Patient phenotypes, unclassifiable as prion disease, may depend on the location of the mutation in the N-terminal domain, outside the amyloid core of pathologic prion protein, although further functional studies are required to determine whether and how this mutation exerts its pathogenic effect. However, genetic screening of prion protein gene becomes relevant in familial degenerative dementia, particularly in geographical areas with high IPD prevalence.