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Objetivo: Evaluar la efectividad de los enjuagues de ketamina asociados o no a fentanilo transmucoso en una serie de diversos dolores orofaciales de etiología neoplásica de difícil control analgésico. Material y métodos: Estudio prospectivo de 20 pacientes, con 8 pacientes que recibieron enjuagues de ketamina (40 mg = 4 ml), 8 pacientes que recibieron ketamina asociada a citrato de fentanilo por vía transmucosa oral a dosis de 200 mcg y 4 pacientes con opiáceos sistémicos para el dolor orofacial y mucositis refractaria. Resultados: Un total de16 de los 20 pacientes tenían dolor orofacial o mucositis refractaria al tratamiento con lidocaína y opiáceos. La tasa de éxito del empleo de enjuagues de ketamina fue del 50% (8/16 pacientes). La asociación ketamina y fentanilo transmucoso obtuvo una tasa de éxito del 94,1% (15/16 pacientes). Los efectos adversos se asocian al uso de la ketamina; todos los efectos secundarios fueron transitorios y desaparecieron cuando se suspendieron los enjuagues con ketamina. Conclusión: Los enjuagues de ketamina son una opción eficaz para el tratamiento del dolor orofacial secundario al cáncer. En caso de presencia de episodios de dolor irruptivo recurrente, la asociación de ketamina en enjuague bucal y citrato de fentanilo oral transmucoso puede ser una opción viable en dolor refractario a otros tratamientos.

Water quality criteria regulating silver discharge to the environment have been heavily scrutinized by both the photographic industry and the regulatory community over the last decade. In the United States, there is now a general consensus that the present regulatory framework, which is based on work done in the 1970's, fails to appropriately assess the impact of silver in the environment. Nonetheless, other countries have begun developing water quality criteria for silver which are in many cases based on this same old toxicological information. The present thesis addresses the need for new information, and specifically characterizes the toxicological, physiological and biochemical responses of freshwater fish to waterborne and dietary exposures of silver. This thesis provides concrete evidence that acute waterborne toxicity in juvenile rainbow trout is produced by the free Ag+ ion, yielding 4 to 7-day LC50 values ranging from 3.1 to 5.5 μg/L Ag+ . In comparison, LC50 values varied by as much as 30-fold during toxicity tests in which complexing agents such as chloride and dissolved organic carbon were manipulated. Using these data, together with other recently published results from physiologically-based studies, a new acute toxicity model has been developed within a Biotic Ligand Modeling (BLM) framework where the geochemistry of the receiving water is taken into account. This new acute toxicity model is unique in that it relates toxicity to a prediction of the binding of Ag+ to toxic sites on the gill, rather than to a prediction of total gill silver load. This distinction is important because the total bioaccumulated silver load appears to be unrelated to the acute toxic response. Silver accumulated in the liver is shown to bind to metallothionein within the cell, possibly explaining why silver can accumulate to high levels in the liver during waterborne silver exposure with no apparent toxicity to the fish. Chronic exposure to low levels of silver results in a significant disturbance to plasma Na+ and Cl- at levels from 0.1 to 0.5 μg/L total silver. The ionoregulatory disturbance is mild in comparison to acute waterborne exposure to LC50 levels of silver, and requires longer to be fully manifested. Interestingly, fish show physiological acclimation to silver-induced perturbations in ion balance after only 7 to 16 days, and toxicological acclimation to 3.0 μg/L total silver exposure after 23 days. Acclimation appears to be associated with enhanced branchial Na+ influx and Na/K-ATPase activity (the target of Ag+ ), despite the continued presence of metal in the water. Considering the level of silver required to elicit toxicological acclimation, it is unlikely that acclimation will significantly impact the predictive capability of the acute toxicity model. Finally dietary exposures to silver sulfide up to 3,000 μg/g and a biologically incorporated silver up to 3.1 μg/g produced no physiological impairment in juvenile rainbow trout during long-term studies. Interestingly, the biologically incorporated form of silver was accumulated in the livers of fish over four orders of magnitude better than dietary silver sulfide. The fact that the bioavailability of dietary silver is influenced by speciation suggests that a Biotic Ligand Modeling approach may be plausible for dietary silver exposure. Doctor of Philosophy (PhD)