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101.
Jacopo Morini Antonio Vella Simone Cesaro Claudio Sorio Andrea Biondi Cesare Danesino Piero Farruggia Baroukh Maurice Assael Marco Cipolli 《American journal of hematology》2018,93(4):527-536
Shwachman‐Diamond syndrome (SDS) is a rare inherited recessive disease mainly caused by mutations in the Shwachman‐Bodian‐Diamond syndrome (SBDS) gene, which encodes for the homonymous protein SBDS, whose function still remains to be fully established. SDS affects several organs causing bone marrow failure, exocrine pancreatic insufficiency, skeletal malformations, and cognitive disorders. About 15% of SDS patients develop myelodysplastic syndrome (MDS) and are at higher risk of developing acute myeloid leukemia (AML). Deficiency in SBDS expression has been associated with increased apoptosis and lack of myeloid differentiation in bone marrow hematopoietic progenitors. Importantly, most SDS patients carry nonsense mutations in SBDS. Since ataluren is a well‐characterized small molecule inhibitor that can suppress nonsense mutations, here, we have assessed the efficacy of this drug in restoring SBDS expression in hematopoietic cells obtained from a cohort of SDS patients. Remarkably, we show that ataluren treatment readily restores SBDS protein expression in different cell types, particularly bone marrow stem cells. Furthermore, ataluren promotes myeloid differentiation in hematopoietic progenitors, reduces apoptotic rate in primary PBMCs, and brings mammalian target of rapamycin phosphorylation levels back to normal in both lymphoblasts and bone marrow mesenchymal stromal cells (BM‐MSCs). Since a specific therapy against SDS is currently lacking, these results provide the rationale for ataluren repurposing clinical trials. 相似文献
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Osborn TM Assael LA Bell RB 《Oral and maxillofacial surgery clinics of North America》2008,20(3):353-365
Knowledge of the management of infections of the deep spaces of the neck is essential to the daily practice of oral and maxillofacial surgery. Timely decisions must be made through the acute course of the disease. Interventions must be performed with the appropriate surgical skill. The surgeon must decide on medical and surgical management, including antibiotic selection, how to employ supportive resuscitative care, when to operate, what procedures to perform, and how to secure the airway. To make these decisions the surgeon must understand the anatomy of the region and the etiology of infection, appropriate diagnostic workup, and medical and surgical management. This article provides a review of these pertinent topics. 相似文献
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J. A. Ziemniak B. M. Assael R. Padoan J. J. Schentag 《European journal of clinical pharmacology》1984,26(2):183-189
Summary The pharmacokinetics and metabolism of cimetidine were studied in five cystic fibrosis patients (mean age 12.6 years) after oral and intravenous administration. As compared to healthy adult volunteers, cystic fibrosis children had an elevated cimetidine total body clearance (474 vs 300 ml/min/m2) as well as renal clearance (293 vs 232 ml/min/m2) whether normalized for body weight or surface area differences. Cimetidine elimination was elevated in juvenile cystic fibrosis patients as compared to adult volunteers, however, it did not differ significantly from that previously seen in age matched children. There were no appreciable differences in cimetidine metabolism after either route of administration. Differences between adults and cystic fibrosis children were attributed to developmental and age related differences between the two groups. The recommended pediatric dose of 15 to 20 mg/kg, although four-fold greater than that used in adults, produces serum concentrations similar to those seen in adults, and is adequate for most juvenile cystic fibrosis patients. 相似文献
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Dibenzapine (720 mg, Noveril) was infused intravenously to 16 depressed patients during a period of 3 h. Serum prolactin levels were determined by radioimmunoassay and changes in clinical condition were evaluated according to the Hamilton Equation. The two variables were correlated to each other. In most of the patients Noveril caused a dramatic but short-lived improvement in depressive symptoms. There was much variability in the prolactin response to the drug. Serum prolactin levels showed a great elevation in 9 patients. In all patients the hormonal levels returned to their former normal levels after termination of the infusions. The treatment was then continued with Noveril per os. There was no significant correlation between serum prolactin levels and clinical condition or its change. The elevation of serum prolactin levels as a reaction to Noveril treatment may be explained by the prominent serotonergic action of Noveril. A time lag between serotonergic and dopaminergic actions of the drug when given in higher doses may be an additional explanation. Other possible hypotheses are discussed. 相似文献
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Crucial to the proper care of a child sustaining electric trauma to the oral cavity are both a complete understanding of the possible systemic sequelae of this injury and knowledge of the management of the particular lesion. The physical properties of electricity, the systemic and regional effects of electric injuries, and the associated complications are reviewed. The methods of treatment are discussed and the benefit of delaying surgical intervention is emphasized. 相似文献