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61.
Persistent pain following common outpatient surgeries in children: A multicenter study in Italy 下载免费PDF全文
62.
Gender‐related differences in elderly patients with myocardial infarction in a European Centre 下载免费PDF全文
63.
Nicolina Cristina Sorrentino Veronica Maffia Sandra Strollo Vincenzo Cacace Noemi Romagnoli Anna Manfredi Domenico Ventrella Francesco Dondi Francesca Barone Massimo Giunti Anne-Renee Graham Yan Huang Susan L Kalled Alberto Auricchio Maria Laura Bacci Enrico Maria Surace Alessandro Fraldi 《Molecular therapy》2016,24(2):276-286
Cerebrospinal fluid administration of recombinant adeno-associated viral (rAAV) vectors has been demonstrated to be effective in delivering therapeutic genes to the central nervous system (CNS) in different disease animal models. However, a quantitative and qualitative analysis of transduction patterns of the most promising rAAV serotypes for brain targeting in large animal models is missing. Here, we characterize distribution, transduction efficiency, and cellular targeting of rAAV serotypes 1, 2, 5, 7, 9, rh.10, rh.39, and rh.43 delivered into the cisterna magna of wild-type pigs. rAAV9 showed the highest transduction efficiency and the widest distribution capability among the vectors tested. Moreover, rAAV9 robustly transduced both glia and neurons, including the motor neurons of the spinal cord. Relevant cell transduction specificity of the glia was observed after rAAV1 and rAAV7 delivery. rAAV7 also displayed a specific tropism to Purkinje cells. Evaluation of biochemical and hematological markers suggested that all rAAV serotypes tested were well tolerated. This study provides a comprehensive CNS transduction map in a useful preclinical large animal model enabling the selection of potentially clinically transferable rAAV serotypes based on disease specificity. Therefore, our data are instrumental for the clinical evaluation of these rAAV vectors in human neurodegenerative diseases. 相似文献
64.
Carr BI Carroll S Muszbek N Gondek K 《Journal of gastroenterology and hepatology》2010,25(11):1739-1746
Background and Aim: A double‐blind, randomized phase III trial of sorafenib in advanced hepatocellular carcinoma demonstrated that sorafenib significantly prolonged overall survival compared to placebo (median overall survival = 10.7 months vs 7.9 months, P < 0.001). Sorafenib is the first and only systemic agent demonstrating survival benefit in these patients. The aim of this study was to assess the cost‐effectiveness of sorafenib versus best supportive care in the treatment of advanced hepatocellular carcinoma in the USA. Methods: A Markov model was developed following time‐to‐progression and survival using phase III trial data. Health effects are expressed as life‐years gained. Resource utilization included drugs, physician visits, laboratory tests, scans, and hospitalizations. Unit costs, expressed in 2007 $US, came from diagnosis‐related groupings, fee schedules, and the Red Book. Costs and effects were evaluated over a patient's lifetime and discounted at 3%. Results: Results are presented as incremental cost/life‐year gained. Deterministic and probabilistic sensitivity analyses were conducted. Life‐years gained were increased for sorafenib compared to best supportive care (mean ± standard deviation: 1.58 ± 0.17 vs 1.05 ± 0.10 life‐years gained/sorafenib patient and best supportive care, respectively). Lifetime total costs were $US40 639 ± $US3052 for sorafenib and $US7 804 ± $US1349 for best supportive care. The incremental cost‐effectiveness ratio was $US62 473/life‐year gained. Conclusions: The economic evaluation indicates that sorafenib is cost‐effective compared to best supportive care, with a cost‐effectiveness ratio within the established threshold that US society is willing to pay (i.e. $US50 000–$US100 000) and significantly lower than alternative thresholds suggested in recent years ($US183 000–$US264 000/life‐year gained, or $US300 000/quality‐adjusted life‐year) in oncology. 相似文献
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Festini F Taccetti G Mannini C Campana S Mergni G Vignoli N Allegretti N Ravenni N Cocchi P Neri S Repetto T de Martino M 《Pediatric pulmonology》2007,42(9):779-784
Acquisition of respiratory pathogens such as Pseudomonas aeruginosa (PA) is associated with increased morbidity and mortality in cystic fibrosis (CF). Research on the prevalence of these pathogens on environmental surfaces of a CF Center is scanty, and so far no study has determined what risk CF patients have of coming in contact with them during their visits to the CF Center. This study is aimed at assessing the prevalence of some respiratory pathogens in samples taken systematically during a 4-year period from inanimate surfaces and sinks in a CF Outpatient Clinic, and to estimate the risk that a non-PA colonized CF patient has of contact with PA when visiting the CF Center. Microbiological samples were taken and cultured from the inanimate surfaces and sinks of the Outpatient clinic of a CF Center once a month from 2001 to 2005. Four hundred and sixty environmental specimens were collected: 36.3% were positive for respiratory pathogens (23% of rooms' inert surfaces, 49.5% of sinks). Achromobacter xylosoxidans was found in 0.8% of surface samples. PA was isolated in 22.8% samples. The estimated risk for each non-colonized patient of coming in contact with PA on the surfaces in the Clinic at each visit was 5.4 per thousand (CI95% 0.9-30.1). Genotyping of a sample of environmental PA strains revealed a genetic relation between environmental and clinical isolates in most cases. Micro-organisms relevant for CF patients can be found on inanimate surfaces of a CF Center, although the risk for patients of coming in contact with PA during their visits to the CF center seems low. 相似文献
69.
André Gustavo Tempone Noemi Nosomi Taniwaki Juliana Quero Reim?o 《Parasitology research》2009,105(2):499-505
In a search for novel antileishmanial drugs, we investigated the activity of the calcium channel blocker nimodipine against
Leishmania spp. and explored the ultrastructural damages of parasites induced by nimodipine after a short period of incubation. Nimodipine
was highly effective against promastigotes and intracellular amastigotes of Leishmania (L.) chagasi, with 50% inhibitory concentration values of 81.2 and 21.5 μM, respectively. Nimodipine was about fourfold more effective
than the standard pentavalent antimony against amastigotes and showed a Selectivity Index of 4.4 considering its mammalian
cells toxicity. Leishmania (L.) amazonensis and Leishmania (L.) major promastigotes were also susceptible to nimodipine in a range concentration between 31 and 128 μM. Ultrastructural studies
of L. (L.) chagasi revealed intense mitochondria damage and plasma membrane blebbing, resulting in a leishmanicidal effect as demonstrated by
the lack of mitochondrial oxidative metabolism. The amastigote-killing effect suggests other mechanism than macrophage activation,
as no upregulation of nitric oxide was seen. This calcium channel blocker is an effective in vitro antileishmanial compound
and if adequately studied could be used as a novel drug candidate or as a novel drug lead compound for drug design studies
against leishmaniasis. 相似文献
70.
Maria Teresa Sandri Daniela Riggio Michela Salvatici Rita Passerini Laura Zorzino Sara Boveri Davide Radice Noemi Spolti Mario Sideri 《Journal of medical virology》2009,81(2):271-277
Human papillomavirus (HPV) are distributed widely and persistent infection with high‐risk (HR) HPV is recognized as a necessary cause of cervical cancer. The aim of this study was to evaluate the distribution of different HR‐HPV genotypes in 199 women with cervical pre‐invasive lesions undergoing conservative treatment. A Linear Array HPV Genotyping Test was used to identify individual HPV genotypes in cervical samples. It was observed that the most prevalent HPV genotypes were HPV 16 (52.6%), HPV 51 (13.5%), and HPV 31 (10.9%); HPV 18 was found in 7.3% of the patients. Stratifying the different HPV genotypes according to the severity of the cervical lesion, a strong association between the increasing severity of the histological diagnosis and the detection of more carcinogenic HR‐HPV type was found, and in all but one cervical intraepithelial neoplasia of grade 3 the presence of at least one HR‐HPV could be detected, with more than 70% of cervical intraepithelial neoplasia of grade 3 patients bearing HPV 16. Multiple infections, comprising between 2 and 6 HPV types, were found in 43% of patients; however, the presence of more than 1 HR‐HPV type was not associated with an increased risk of high grade lesions. In conclusion, this data show that HPV 16, 51, 31, 52, and 18 were the prevalent types found in patients with cervical lesion undergoing conservative treatment, with a high prevalence of HPV 16 in cervical intraepithelial neoplasia of grade 3 patients. No association between multiple infection and severity of the lesion could be found. J. Med. Virol. 81:271–277, 2009. © 2008 Wiley‐Liss, Inc. 相似文献