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Potential Option (potential + option)
Selected AbstractsTranscatheter Aortic Valve Replacement: A Potential Option for the Nonsurgical PatientCLINICAL CARDIOLOGY, Issue 6 2009Jigar H. Patel MD With improved life expectancy, the incidence of aortic stenosis is rising. However, up to one-third of patients who require lifesaving surgical aortic valve replacement are denied surgery due to a high operative mortality rate. Such patients can only be treated with medical therapy or percutaneous aortic valvuloplasty, neither of which has been shown to improve mortality. With advances in interventional cardiology, transcatheter methods have been developed for aortic valve replacement. Clinical trials are investigating these devices in patients with severe aortic stenosis that have been denied surgery. Preliminary results from these trials suggest that transcatheter aortic valve replacement (TAVR) is not only feasible, but an effective way to improve symptoms. In this review, we describe the current technology and display available outcome data. Though technical challenges and operator learning curve limit optimal use of the current technology, continued experience and advancements in technology may one day make TAVR a viable alternative to traditional surgical aortic valve replacement. Copyright © 2009 Wiley Periodicals, Inc. [source] Validity and ethics of the human 4-h patch test as an alternative method to assess acute skin irritation potentialCONTACT DERMATITIS, Issue 1 2001Michael K. Robinson For more than 50 years, the Draize rabbit skin irritation test has reigned supreme as the regulatory method of choice for the identification of skin irritant chemicals. To date no in vitro alternative test has been validated as an adequate replacement. However, one potential option, to test the endpoint of concern (skin irritation) in the species of concern (man) has been overlooked. The advent of predictive in vitro tools for the identification of substances corrosive to the skin has opened up the practical possibility of carrying out safe and ethical studies on small panels of humans. The human 4-h patch test has been developed to meet the needs of identifying chemical skin irritation potential, providing data which is inherently superior to that given by a surrogate model, such as the rabbit. This paper reviews in detail the present state of the human 4-h patch test, highlighting its advantages and noting its utility as the ,gold standard' on which to build future in vitro models. [source] Clofarabine in the treatment of poor risk acute myeloid leukaemiaHEMATOLOGICAL ONCOLOGY, Issue 3 2010Janusz Krawczyk Abstract Clofarabine is a second generation nucleoside analogue. It inhibits DNA repair and activates the mitochondrial apoptotic pathway leading to cell death. In vitro clofarabine has demonstrated synergy with daunorubicin and Ara-C and in phase II clinical trials has shown promising activity in poor risk Acute myeloid leukaemia (AML) patients. In our institution over a 24 month period 22 AML patients (11 M, 11 F) with poor risk features, deemed unsuitable for standard therapy, were treated with clofarabine, alone (eight patients) or in combination (14 patients) for up to three cycles of treatment. The median age was 67.5 years (24,76) with 16 patients > 60 years. At the time of treatment 18 patients had active AML. Four patients intolerant of standard induction received clofarabine as consolidation. The overall response rate (ORR) for the 18 patients with active AML was 61%, nine patients (50%) achieving a complete response (CR). Induction and consolidation were well tolerated with no unexpected toxicities. Predictably, all patients developed grade 4 neutropenia but the median duration was only 20 days (17,120). Induction mortality was acceptable at 17%. In conclusion, clofarabine (alone or in combination) is active in poor risk AML with an acceptable safety profile and should be considered a potential option in poor risk AML patients. Copyright © 2009 John Wiley & Sons, Ltd. [source] Towards evolution-proof malaria control with insecticidesEVOLUTIONARY APPLICATIONS (ELECTRONIC), Issue 4 2009Jacob C. Koella Abstract As many strategies to control malaria use insecticides against adult mosquitoes, control is undermined by the continual evolution of resistant mosquitoes. Here we suggest that using alternative insecticides, or conventional insecticides in alternative ways might enable effective control, but delay considerably or prevent the evolution of resistance. Our reasoning relies on an epidemiological and an evolutionary principle: (i) the epidemiology of malaria is strongly influenced by the life-span of mosquitoes, as most infected mosquitoes die before the malaria parasite has completed its development; and (ii) evolutionary pressure is strongest in young individuals, for selection on individuals that have completed most of their reproduction has little evolutionary effect. It follows from these principles, first, that insecticides that kill mosquitoes several days after exposure can delay considerably the evolution of resistance and, second, that the evolution of resistance against larvicides can actually benefit control, if it is associated with shorter life-span or reduced biting in adults. If a late-acting insecticide and a larvicide are combined, the evolution of resistance against larvicides can in some circumstances prevent the evolution of resistance against the more effective, late-acting insecticide, leading to sustainable, effective control. We discuss several potential options to create such insecticides, focussing on biopesticides. [source] Cystic fibrosis lung disease starts in the small airways: Can we treat it more effectively?PEDIATRIC PULMONOLOGY, Issue 2 2010Harm A.W.M. Tiddens MD Abstract The aims of this article are to summarize existing knowledge regarding the pathophysiology of small airways disease in cystic fibrosis (CF), to speculate about additional mechanisms that might play a role, and to consider the available or potential options to treat it. In the first section, we review the evidence provided by pathologic, physiologic, and imaging studies suggesting that obstruction of small airways begins early in life and is progressive. In the second section we discuss how the relationships between CF transmembrane conductance regulator (CFTR), ion transport, the volume of the periciliary liquid layer and airway mucus might lead to defective mucociliary clearance in small airways. In addition, we discuss how chronic endobronchial bacterial infection and a chronic neutrophilic inflammatory response increase the viscosity of CF secretions and exacerbate the clearance problem. Next, we discuss how the mechanical properties of small airways could be altered early in the disease process and how remodeling can contribute to small airways disease. In the final section, we discuss how established therapies impact small airways disease and new directions that may lead to improvement in the treatment of small airways disease. We conclude that there are many reasons to believe that small airways play an important role in the pathophysiology of (early) CF lung disease. Therapy should be aimed to target the small airways more efficiently, especially with drugs that can correct the basic defect at an early stage of disease. Pediatr Pulmonol. 2010; 45:107,117. © 2010 Wiley-Liss, Inc. [source] |