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Honorato-Cia C.,University of Navarra | Martinez-Simon A.,University of Navarra | Alegre M.,University of Navarra | Alegre M.,IDISNA Navarras Health Research Institute | And 7 more authors.
Stereotactic and Functional Neurosurgery | Year: 2015

Introduction: Dexmedetomidine is an α2-agonist recently proposed as a potentially ideal drug for sedation during the surgical treatment of Parkinson's disease (PD). This report documents the incidence of changes in motor symptoms (especially tremor) in PD patients sedated with dexmedetomidine for deep brain stimulation or ablation procedures. Methods: We reviewed a retrospective cohort of 22 patients who underwent surgery for PD with dexmedetomidine sedation at a single institution from 2010 to 2014. A logistic regression analysis was performed to analyze possible confounding factors. Results: 14 cases of tremor reduction or suppression were recorded (cumulative incidence: 63.6%; 95% CI: 40.7-82.8). No association could be identified between loading dose, β-blocker use and preoperative total Unified Parkinson's Disease Rating Scale III, with tremor changes. The maintenance dose of dexmedetomidine was higher in patients who did not experience changes [median and range for patients with and without tremor alteration 0.75 (0.2-1.0) and 1.0 μg × kg-1 × h-1 (0.7-1.4), respectively; p = 0.021]. Conclusion: Dexmedetomidine provides adequate sedation during surgery for PD, but it might affect motor signs making intraoperative testing difficult or even impossible. Dosage appears not to be the determining factor in motor changes, whose cause remains unclear. © 2015 S. Karger AG, Basel. All rights reserved.

Ciaurriz M.,IDISNA Navarras Health Research Institute | Zabalza A.,IDISNA Navarras Health Research Institute | Beloki L.,IDISNA Navarras Health Research Institute | Mansilla C.,IDISNA Navarras Health Research Institute | And 7 more authors.
Cellular and Molecular Life Sciences | Year: 2015

Approximately, up to 70 % of the human population is infected with cytomegalovirus (CMV) that persists for life in a latent state. In healthy people, CMV reactivation induces the expansion of CMV-specific T cells up to 10 % of the entire T cell repertoire. On the contrary, CMV infection is a major opportunistic viral pathogen that remains a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Due to the delayed CMV-specific immune recovery, the incidence of CMV reactivation during post-transplant period is very high. Several methods are currently available for the monitoring of CMV-specific responses that help in clinical monitoring. In this review, essential aspects in the immune recovery against CMV are discussed to improve the better understanding of the immune system relying on CMV infection and, thereby, helping the avoidance of CMV disease or reactivation following hematopoietic stem cell transplantation with severe consequences for the transplanted patients. © 2015 Springer Basel.

Beloki L.,IDISNA Navarras Health Research Institute | Ciaurriz M.,IDISNA Navarras Health Research Institute | Mansilla C.,IDISNA Navarras Health Research Institute | Zabalza A.,IDISNA Navarras Health Research Institute | And 5 more authors.
Journal of Translational Medicine | Year: 2015

Background: Adoptive transfer of CMV-specific T cells has shown promising results in preventing pathological effects caused by opportunistic CMV infection in immunocompromised patients following allogeneic hematopoietic stem cell transplantation. The majority of studies have used steady-state leukapheresis for CMV-reactive product manufacture, a collection obtained prior to or months after G-CSF mobilization, but the procurement of this additional sample is often not available in the unrelated donor setting. If the cellular product for adoptive immunotherapy could be generated from the same G-CSF mobilized collection, the problems associated with the additional harvest could be overcome. Despite the tolerogenic effects associated with G-CSF mobilization, recent studies described that CMV-primed T cells generated from mobilized donors remain functional. Methods: MHC-multimers are potent tools that allow the rapid production of antigen-specific CTLs. Therefore, in the present study we have assessed the feasibility and efficacy of CMV-specific CTL manufacture from G-CSF mobilized apheresis using MHC-multimers. Results: CMV-specific CTLs can be efficiently isolated from G-CSF mobilized samples with Streptamers and are able to express activation markers and produce cytokines in response to antigenic stimulation. However, this anti-viral functionality is moderately reduced when compared to non-mobilized products. Conclusions: The translation of Streptamer technology for the isolation of anti-viral CTLs from G-CSF mobilized PBMCs into clinical practice would widen the number of patients that could benefit from this therapeutic strategy, although our results need to be taken into consideration before the infusion of antigen-specific T cells obtained from G-CSF mobilized samples. © 2015 Beloki et al.

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