The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant.However,despite the long use of tacrolimus in clinical practice,the best way to use this agent is still a matter...The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant.However,despite the long use of tacrolimus in clinical practice,the best way to use this agent is still a matter of intense debate.The start of the genomic era has generated new research areas,such as pharmacogenetics,which studies the variability of drug response in relation to the genetic factors involved in the processes responsible for the pharmacokinetics and/or the action mechanism of a drug in the body.This variability seems to be correlated with the presence of genetic polymorphisms.Genotyping is an attractive option especially for the initiation of the dosing of tacrolimus;also,unlike phenotypic tests,the genotype is a stable characteristic that needs to be determined only once for any given gene.However,prospective clinical studies must show that genotype determination before transplantation allows for better use of a given drug and improves the safety and clinical efficacy of that medication.At present,research has been able to reliably show that the CYP3A5 genotype,but not the CYP3A4 or ABCB1 ones,can modify the pharmacokinetics of tacrolimus.However,it has not been possible to incontrovertibly show that the corresponding changes in the pharmacokinetic profile are linked with different patient outcomes regarding tacrolimus efficacy and toxicity.For these reasons,pharmacogenetics and individualized medicine remain a fascinating area for further study and may ultimately become the face of future medical practice and drug dosing.展开更多
AIM:To evaluate radiofrequency thermal ablation (RTA) for treatment of cystic echinococcosis in animal models (explanted organs).METHODS:Infected livers and lungs from slaughtered animals,10 bovine and two ovine,were ...AIM:To evaluate radiofrequency thermal ablation (RTA) for treatment of cystic echinococcosis in animal models (explanted organs).METHODS:Infected livers and lungs from slaughtered animals,10 bovine and two ovine,were collected.Cysts were photographed,and their volume,cyst content,germinal layer adhesion status,wall calcification and presence of daughter or adjacent cysts were evaluated by ultrasound.Some cysts were treated with RTA at 150 W,80℃,7 min.Temperature was monitored inside and outside the cyst.A second needle was placed inside the cyst for pressure stabilization.After treatment,all cysts were sectioned and examined by histology.Cysts were defined as alive if a preserved germinal layer at histology was evident,and as successfully treated if the germinal layer was necrotic.RESULTS:The subjects of the study were 17 cysts (nine hepatic and eight pulmonary),who were treated with RTA.Pathology showed 100% success rate in both hepatic (9/9) and lung cysts (8/8);immediate volume reduction of at least 65%;layer of host tissue necrosis outside the cyst,with average extension of 0.64 cm for liver and 1.57 cm for lung;and endocyst attached to the pericystium both in hepatic and lung cysts with small and focal de novo endocyst detachment in just 3/9 hepatic cysts.CONCLUSION:RTA appears to be very effective in killing hydatid cysts of explanted liver and lung.Bile duct and bronchial wall necrosis,persistence of endocyst attached to pericystium,should help avoid or greatly decrease in vivo post-treatment fistula occurrence and consequent overlapping complications that are common after surgery or percutaneous aspiration,injection and reaspiration.In vivo studies are required to confirm and validate this new therapeutic approach.展开更多
文摘The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant.However,despite the long use of tacrolimus in clinical practice,the best way to use this agent is still a matter of intense debate.The start of the genomic era has generated new research areas,such as pharmacogenetics,which studies the variability of drug response in relation to the genetic factors involved in the processes responsible for the pharmacokinetics and/or the action mechanism of a drug in the body.This variability seems to be correlated with the presence of genetic polymorphisms.Genotyping is an attractive option especially for the initiation of the dosing of tacrolimus;also,unlike phenotypic tests,the genotype is a stable characteristic that needs to be determined only once for any given gene.However,prospective clinical studies must show that genotype determination before transplantation allows for better use of a given drug and improves the safety and clinical efficacy of that medication.At present,research has been able to reliably show that the CYP3A5 genotype,but not the CYP3A4 or ABCB1 ones,can modify the pharmacokinetics of tacrolimus.However,it has not been possible to incontrovertibly show that the corresponding changes in the pharmacokinetic profile are linked with different patient outcomes regarding tacrolimus efficacy and toxicity.For these reasons,pharmacogenetics and individualized medicine remain a fascinating area for further study and may ultimately become the face of future medical practice and drug dosing.
文摘AIM:To evaluate radiofrequency thermal ablation (RTA) for treatment of cystic echinococcosis in animal models (explanted organs).METHODS:Infected livers and lungs from slaughtered animals,10 bovine and two ovine,were collected.Cysts were photographed,and their volume,cyst content,germinal layer adhesion status,wall calcification and presence of daughter or adjacent cysts were evaluated by ultrasound.Some cysts were treated with RTA at 150 W,80℃,7 min.Temperature was monitored inside and outside the cyst.A second needle was placed inside the cyst for pressure stabilization.After treatment,all cysts were sectioned and examined by histology.Cysts were defined as alive if a preserved germinal layer at histology was evident,and as successfully treated if the germinal layer was necrotic.RESULTS:The subjects of the study were 17 cysts (nine hepatic and eight pulmonary),who were treated with RTA.Pathology showed 100% success rate in both hepatic (9/9) and lung cysts (8/8);immediate volume reduction of at least 65%;layer of host tissue necrosis outside the cyst,with average extension of 0.64 cm for liver and 1.57 cm for lung;and endocyst attached to the pericystium both in hepatic and lung cysts with small and focal de novo endocyst detachment in just 3/9 hepatic cysts.CONCLUSION:RTA appears to be very effective in killing hydatid cysts of explanted liver and lung.Bile duct and bronchial wall necrosis,persistence of endocyst attached to pericystium,should help avoid or greatly decrease in vivo post-treatment fistula occurrence and consequent overlapping complications that are common after surgery or percutaneous aspiration,injection and reaspiration.In vivo studies are required to confirm and validate this new therapeutic approach.
