Cardiovascular and thrombophilic risk factors for idiopathic sudden sensorineural hearing loss

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Electromotive instillation of mitomycin immediately before transurethral resection for patients with primary urothelial non-muscle invasive bladder cancer: a randomised controlled trial.

BACKGROUND: The clinical effect of intravesical instillation of chemotherapy immediately after transurethral resection of bladder tumours (TURBT) has recently been questioned, despite its recommendation in guidelines. Our aim was to compare TURBT alone with immediate post-TURBT intravesical passive diffusion (PD) of mitomycin and immediate pre-TURBT intravesical electromotive drug administration (EMDA) of mitomycin in non-muscle invasive bladder cancer. METHODS: We did a multicentre, randomised, parallel-group study in patients with primary non-muscle invasive bladder cancer in three centres in Italy between Jan 1, 1994, and Dec 31, 2003. Patients were randomly assigned to receive treatment by means of stratified blocked randomisation across six strata. Patients and physicians giving the interventions were aware of assignment, but it was masked from outcome assessors and data analysts. Patients were randomly assigned to receive TURBT alone, immediate post-TURBT instillation of 40 mg PD mitomycin dissolved in 50 mL sterile water infused over 60 min, or immediate pre-TURBT instillation of 40 mg EMDA mitomycin dissolved in 100 mL sterile water with intravesical 20 mA pulsed electric current for 30 min. Our primary endpoints were recurrence rate and disease-free interval. Analyses were done by intention to treat. Follow-up for our trial is complete. This study is registered with ClinicalTrials.gov, number NCT01149174. FINDINGS: 124 patients were randomly assigned to receive TURBT alone, 126 to receive immediate post-TURBT PD mitomycin, and 124 to receive immediate pre-TURBT EMDA mitomycin. 22 patients were excluded from our analyses because they did meet our eligibility criteria after TURBT: 11 had stage pT2 disease and 11 had carcinoma in situ. Median follow-up was 86 months (IQR 57-125). Patients assigned to receive EMDA mitomycin before TURBT had a lower rate of recurrence (44 [38%] of 117) than those assigned to receive PD mitomycin after TURBT (70 [59%] of 119) and TURBT alone (74 [64%] of 116; log-rank p<0·0001). Patients assigned to receive EMDA mitomycin before TURBT also had a higher disease-free interval (52 months, IQR 32-184) than those assigned to receive PD mitomycin after TURBT (16 months, 12-168) and TURBT alone (12 months, 12-37; log-rank p<0·0001). We recorded persistent bladder symptoms after TURBT in 18 (16%) of 116 patients in the TURBT-alone group (duration 3-7 days), 37 (31%) of 119 in the PD mitomycin post-TURBT group (duration 20-30 days), and 24 (21%) of 117 in the EMDA mitomycin pre-TURBT group (duration 7-12 days); haematuria after TURBT in eight (7%) of 116 patients in the TURBT-alone group, 16 (13%) of 119 in the PD mitomycin post-TURBT group, and 11 (9%) of 117 in the EMDA mitomycin pre-TURBT group; and bladder perforation after TURBT in five (4%) of 116 patients in the TURBT-alone group, nine (8%) of 119 in the PD mitomycin post-TURBT group, and seven (6%) of 117 in the EMDA mitomycin pre-TURBT group. INTERPRETATION: Intravesical EMDA mitomycin before TURBT is feasible and safe; moreover, it reduces recurrence rates and enhances the disease-free interval compared with intravesical PD mitomycin after TURBT and TURBT alone

Soil functionality assessment in degraded plots of vineyards

Land transformation to adapt fields to mechanization in perennial crop farming is a common practice which includes land levelling, deep ploughing, stone-breakage and clearing, application of fertilizers and amendments. Manipulation of the natural soil profile along its entire depth can severely disturb the naturally existing chemical physical,biological and hydrological equilibrium (Costantini and Barbetti, 2008; Costantini et al., 2013). The most common effects of the land transformation are mixing of soil horizons and soil truncation, which result in reduction of soil depth and available water, organic matter depletion, enrichment of calcium carbonate content in the topsoil,imbalance of some element ratio, and decline in the activity and diversity of soil biological communities involved in nutrient cycles. A decline in the capacity of soil to accommodate the soil-dwelling organisms causes a strong impact on several ecosystem services, in particular, the growth of the vine, the quality and quantity of the grapes,the production costs and the risk of erosion. These negative effects of a pre-planting mismanagement can occur simultaneously and interact to decrease soil fertility and grapevine performance (Lanyon et al., 2004; Tagliavini and Rombolà, 2001; Martínez-Casasnovas and Ramos, 2009).Since soil spatial variability is usually high, soil manipulations frequently result into reduced soil functionality and decline of soil ecosystem services in defined plots of the vineyards. Sometimes soil degradation in these areas is very high and compromises not only vine performance and crop yield, but also disease resistance of plants to diseases and their survival. The impact of improper soil manipulations in vineyards may be of particular concern, because vineyards are frequently located on marginal hillsides, which are sensitive to soil erosion and characterized by shallow soil depth (Ramos, 2006). This paper wants to show the assessment of soil functionality in degraded areas within two farms in Tuscany. This work reports the results of the first activities in Italian sites of the ReSolVe Core-organic+ project, aimed at restoring optimal Soil functionality in degraded areas within organic European vineyards

Assessment and restoring soil functionality in degraded areas of organic vineyards. The preliminary results of the ReSolVe project in Italy

In both conventional and organic Italian vineyards, it is quite common to have areas characterized by problems in vine health, grape production and quality, often caused by improper land preparation before vine plantation and/or management. Causes for soil malfunctioning can include: reduced contribution of the soil fauna to the ecosystem services (i.e. nutrient cycles), poor organic matter content, imbalance of some element ratio, altered pH, water deficiency, soil compaction and/or scarce oxygenation. ReSolVe is a transnational and interdisciplinary 3-years research project aimed at testing the effects of selected organic strategies for restoring optimal soil functionality in degraded areas within vineyard. The different restoring strategies implemented in each plot will be: i) compost produced on farm by manure + pruning residue + grass, ii) faba bean and barley green manure, iii) sowing and dry mulching with Trifolium squarrosum L. During two years of such treatments, the trend of the soil features and the grapevine status will be monitored in detail, to reveal the positive and negative effects of such treatments. The project involves 8 research groups in 6 different EU countries (Italy, France, Spain, Sweden, Slovenia, and Turkey), with experts from several disciplines, including soil science, ecology, microbiology, grapevine physiology, viticulture, and biometry. The experimental vineyards are situated in Italy (Chianti hills and Maremma plain, Tuscany), France (Bordeaux and Languedoc), Spain (La Rioja) and Slovenia (Primorska) for winegrape, and in Turkey (Adana and Mersin) for table grape. Soil features before implementing restoring strategies showed lower content of soil organic matter and enzyme activities, and higher carbonates in degraded areas than in the non-degraded areas. The Biological Soil Quality values of microarthropods were always high, in comparison with data registered in similarly managed vineyards or stable ecosystems, and the data showed homogeneous patterns within the experimental plots. Nematode abundance, taxa richness and maturity (MI) and plant parasitic (PPI) indices were higher in nondegraded than degraded areas, but differences were not significant. Grapevines in degraded areas of both farms showed less vegetative vigour and significantly lower values in the SPAD colour index. The yield and the weight of the grape bunches and berries were greater in the not degraded. The grapes of degraded areas at harvest had instead a sugar content significantly higher (on average +2.5�Brix). The restoration techniques and the monitoring methodologies developed and tested during the ReSolVe project will be described in specific final guidelines. The restoration techniques will be accessible for all the European farmers and will be low cost and environmental-friendly. A protocol of analyses and measurements between the all partners will allow an effective and comparable monitoring of vineyard ecosystemic functioning in European countries

[Pancreatic passenger leukocytes in organs obtained from cadaver donors for allotransplantation].

In previous studies we have demonstrated that human normal pancreata were populated by interstitial mononuclear cells constituted by dendritic cells (70\%), macrophages (30\%) and few B cells (less than 1\%). Furthermore, the endocrine parenchyma and the centroacinar cells appeared negative for the detection of HLA-A,B,C molecules. In the present report, 15 pancreata from cadaver donors were studied by means of immunohistochemical methods. 5 out of 15 organs were found to contain a larger amount of interstitial hematic cells that were constituted mainly by macrophages and B cells, together with a small percentage of granulocytes and T cells. In such "infiltrated" pancreata both endocrine parenchyma and centroacinar cells displayed a positivity for HLA-A,B,C antigens. As HLA-class I antigens have importance in allo-recognition and rejection responses, our data suggest that pre-transplant biopsies may be useful for a better evaluation of the pancreatic tissue immunogenicity

Differential cation regulation of the alpha 5 beta 1 integrin-mediated adhesion of leukemic cells to the central cell-binding domain of fibronectin

Normal and neoplastic leukocytes interact with the central cell-binding and carboxyl-terminal regions of fibronectin (FN) primarily via the alpha(4) beta(1) and alpha(5) beta(1) integrins. By using a unique centrifugation-based cell adhesion assay and affinity chromatography of the cell surface-labeled integrins, we show in this study that the constitutive alpha(5) beta(1)-dependent attachment of three leukemic cell lines, BV-173, K562, and Nalm-6, to FN or to a 110-kDa central cell-binding fragment of FN was totally inhibited at 37 degrees C by preincubation of the substrate with either antibodies to the arginine-glycine-aspartic acid-containing region (3Fn-9 module) or to the synergistic region (3Fn-9 module) of FN. Similar results were obtained when assays were carried out at 4 degrees C, suggesting that energy-dependent events were not involved. On the other hand, only the antibody against the 3Fn-10 module was able to detach most firmly adherent cells. Constitutive cell attachment to the 110-kDa fragment was cation dependent, with the order of efficacy of the cation being Mn2+ > Mg2+ > Ca2+, and Ca2+ was only effective for BV-173 cells. Antibodies against the alpha(5) beta(1) integrin or the alpha(5) subunit completely impaired cell attachment of all cell lines, whereas several blocking anti-beta(1) subunit antibodies, including 4B4, P4C10, and AIIB2, differentially perturbed cell adhesion of BV-173, depending on which cation was present. These anti-beta(1) blocking antibodies, whose epitopes map to a region distant from the one expected to contain the beta(1) putative cation binding sites, seemed to lock the higher activation state of this integrin attained in the presence of Mg2+ and to preserve it during the subsequent adhesion events irrespectively of the presence of the low avidity state-inducing Ca2+ ion. Because the higher binding avidity displayed by BV-173 could not be explained by a higher degree of preclustering of alpha(5) beta(1) integrin in this cell line compared to K562, these findings suggest that cations might act as allosteric activators of integrin function. Whether this novel cation-dependent parameter of alpha(5) beta(1) integrin-FN interaction might contribute to the growth control and/or tissue dissemination of leukemic cells remains to be determined

Betahistine dihydrochloride in the treatment of peripheral vestibular vertigo

The present study compares the efficacy and safety of betahistine dihydrochloride to that of a placebo in recurrent vertigo resulting from Meniere\u2019s disease (MD) or in paroxysmal positional vertigo (PPV) of probable vascular origin. The design was double-blind, multicentre and parallel-group randomised. Eleven Italian centres enrolled 144 patients: 75 of the patients were treated with betahistine (41 MD/34 PPV) and 69 with placebos (40 MD/29 PPV). The betahistine dosage was 16 mg twice per day for 3 months. Compared to the placebo, betahistine had a significant effect on the frequency, intensity and duration of vertigo attacks. Associated symptoms and the quality of life also were significantly improved by betahistine. Both the physician\u2019s judgement and the patient\u2019s opinion on the efficacy and acceptability of the treatment were in agreement as to the superiority of betahistine. The effective and safe profile of betahistine in the treatment of vertigo due to peripheral vestibular disorders was confirmed

Betahistine dihydrochloride in the treatment of peripheral vestibular vertigo.

The present study compares the efficacy and safety of betahistine dihydrochloride to that of a placebo in recurrent vertigo resulting from Meniere's disease (MD) or in paroxysmal positional vertigo (PPV) of probable vascular origin. The design was double-blind, multicentre and parallel-group randomised. Eleven Italian centres enrolled 144 patients: 75 of the patients were treated with betahistine (41 MD/34 PPV) and 69 with placebos (40 MD/29 PPV). The betahistine dosage was 16 mg twice per day for 3 months. Compared to the placebo, betahistine had a significant effect on the frequency, intensity and duration of vertigo attacks. Associated symptoms and the quality of life also were significantly improved by betahistine. Both the physician's judgement and the patient's opinion on the efficacy and acceptability of the treatment were in agreement as to the superiority of betahistine. The effective and safe profile of betahistine in the treatment of vertigo due to peripheral vestibular disorders was confirmed