Valoración de las técnicas esterotáxicas actuales en psicocirugía y utilidad de la tractografía cerebral

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid. Facultad de Medicina, Departamento de Cirugía. Fecha de lectura: 1 de Julio de 201

Intrathecal cell therapy with autologous stromal cells increases cerebral glucose metabolism and can offer a new approach to the treatment of Alzheimer's type dementia

After recent observations that intrathecal administration of autologous bone marrow mesenchymal stromal cells (MSCs) increases cerebral metabolism in patients with severe traumatic brain injury (TBI), we examined this type of cell therapy in Alzheimer's type dementia. Three patients with clinical diagnosis of Alzheimer's disease received every 3 months 100million autologous MSCs by intrathecal route, until a total dose of 300million. During cell therapy the patients showed arrest in neurological deterioration and two of them manifested clear improvement of previous symptoms. A global increase in cerebral glucose metabolism, measured using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET), was observed after every administration of cell therapy. Our present findings suggest that intrathecal administrations of autologous MSCs can be a new strategy for the treatment of Alzheimer's dementiaWe thank the institutions supporting the development of our cell therapy program, in particular Mapfre and Rafael del Pino Foundation

Gigantism: microsurgical treatment by transsphenoidal approach and prognostic factors

Purpose: We present the results of transsphenoidal microsurgical treatment in 14 patients with gigantism. The influence on the prognosis of factors such as the tumor size and preoperative levels of GH and IGF-1 is also quantified. Materials and methods: The patients, operated between 1982 and 2004, were reviewed retrospectively in June 2022. All patients had complete endocrinological studies in the preoperative period and a postoperative control between 6 days and 3 weeks. Follow-up has been supported with annual check-ups between 3 and 31 years. We have compared the preoperative levels of GH and IGF-1 of these patients with the levels of a series of acromegalic patients operated on in the same Center. Results: In this series there were 4 women and 10 men. The age ranged between 14 and 21 years. In 6 patients, postoperative hormone levels achieved the disease control criteria (42.8%). The CT/MRI studies revealed the existence of invasive tumors in 10 of the patients (71.4%). Postoperative CT/MRI showed no tumor tissue in 3 patients but in 7 patients there were tumor remains. The remaining 4 patients had abnormal images although not considered as tumor. A statistical comparison of preoperative serum GH and IGF-1 levels in patients with gigantism and patients with acromegaly showed a significant elevation in the former. Conclusion: Pituitary adenomas that cause gigantism are generally large and invasive, which makes them difficult to cure. High preoperative levels of GH and IGF-1 are also factors that decrease remission

Fundamento y diseño de un proyecto de evaluación de la integración educativa de los niños con necesidades especiales por su deficiencia visual

Este artículo pretende dar a conocer una investigación de evaluación de la educación integrada con niños ciegos y deficientes visuales en España que se está realizando por la O.N.C.E. con un grupo de profesores de la Universidad Autónoma de Madrid. En él se hace un resumen de los objetivos y naturaleza de la investigación evaluativa emprendida, valorativa, iluminativa y formativa, y un análisis del diseño, variables y metodología usada en la investigaciónThis article feports a research work on the evaluation of educational integration with blind and visually handicapped children in Spain. The research is being conducted by the O.N.C.E. in collaboration with a group o teachers of the Universidad Autónoma de Madrid. It outlines the objectives and nature of the evaluative study undertaken (valuative, instructive and formative) and analyzes the design, thé variables and the methodology used in the stud

Immediate effects of dasatinib on the migration and redistribution of naïve and memory lymphocytes associated with lymphocytosis in chronic myeloid leukemia patients

Introduction: Dasatinib is a dual SRC/ABL tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML) that is known to have unique immunomodulatory effects. In particular, dasatinib intake typically causes lymphocytosis, which has been linked to better clinical response. Since the underlying mechanisms are unknown and SRC family kinases are involved in many cell motility processes, we hypothesized that the movement and migration of lymphocytes is modulated by dasatinib. Patients, Materials and Methods: Peripheral blood samples from CML patients treated with second-line dasatinib were collected before and 2 h after the first dasatinib intake, and follow-up samples from the same patients 3 and 6 months after the start of therapy. The migratory capacity and phenotype of lymphocytes and differential blood counts before and after drug intake were compared for all study time-points. Results: We report here for the first time that dasatinib intake is associated with inhibition of peripheral blood T-cell migration toward the homeostatic chemokines CCL19 and CCL21, which control the trafficking toward secondary lymphoid organs, mainly the lymph nodes. Accordingly, the proportion of lymphocytes in blood expressing CCR7, the chemokine receptor for both CCL19 and CCL21, decreased after the intake including both naïve CD45RA+ and central memory CD45RO+ T-cells. Similarly, naïve B-cells diminished with dasatinib. Finally, such changes in the migratory patterns did not occur in those patients whose lymphocyte counts remained unchanged after taking the drug. Discussion: We, therefore, conclude that lymphocytosis induced by dasatinib reflects a pronounced redistribution of naïve and memory populations of all lymphocyte subsets including CD4+ and CD8+ T-cells and B-cells

Gigantism: microsurgical treatment by transsphenoidal approach and prognostic factors

Purpose: We present the results of transsphenoidal microsurgical treatment in 14 patients with gigantism. The influence on the prognosis of factors such as the tumor size and preoperative levels of GH and IGF-1 is also quantified. Materials and methods: The patients, operated between 1982 and 2004, were reviewed retrospectively in June 2022. All patients had complete endocrinological studies in the preoperative period and a postoperative control between 6 days and 3 weeks. Follow-up has been supported with annual check-ups between 3 and 31 years. We have compared the preoperative levels of GH and IGF-1 of these patients with the levels of a series of acromegalic patients operated on in the same Center. Results: In this series there were 4 women and 10 men. The age ranged between 14 and 21 years. In 6 patients, postoperative hormone levels achieved the disease control criteria (42.8%). The CT/MRI studies revealed the existence of invasive tumors in 10 of the patients (71.4%). Postoperative CT/MRI showed no tumor tissue in 3 patients but in 7 patients there were tumor remains. The remaining 4 patients had abnormal images although not considered as tumor. A statistical comparison of preoperative serum GH and IGF-1 levels in patients with gigantism and patients with acromegaly showed a significant elevation in the former. Conclusion: Pituitary adenomas that cause gigantism are generally large and invasive, which makes them difficult to cure. High preoperative levels of GH and IGF-1 are also factors that decrease remission

Intrathecal Cell Therapy with Autologous Bone Marrow Stromal Cells as a New Tool for Neurologic Sequels after Spinal Cord Surgery: A Report of Two Cases

Background aims: The possibility of permanent neurological sequels after surgery of benign lesions affecting the spinal cord is well known. Frequently, they are irreversible, with no effective treatment other than rehabilitation. However, in recent years, intrathecal cell therapy with autologous bone marrow stromal cells (MSCs) in patients with incomplete paraplegia has shown benefits for diverse sequels of spinal cord injury (SCI). Methods: We present two patients with chronic spinal cord sequels after a surgery, who underwent cell therapy treatment with NC1 medicament (repeated intrathecal administrations of MSCs). Results: In both cases, cell therapy achieved a clear improvement in neurological sequels, such as recovery of gait disturbances, bowel dysfunction, or neuropathic pain. Conclusion: Intrathecal cell therapy with autologous MSCs offers a new approach for neurological sequels after spinal cord surgery

Intrathecal Cell Therapy with Autologous Bone Marrow Stromal Cells as a New Tool for Neurologic Sequels after Spinal Cord Surgery: A Report of Two Cases

Background aims: The possibility of permanent neurological sequels after surgery of benign lesions affecting the spinal cord is well known. Frequently, they are irreversible, with no effective treatment other than rehabilitation. However, in recent years, intrathecal cell therapy with autologous bone marrow stromal cells (MSCs) in patients with incomplete paraplegia has shown benefits for diverse sequels of spinal cord injury (SCI). Methods: We present two patients with chronic spinal cord sequels after a surgery, who underwent cell therapy treatment with NC1 medicament (repeated intrathecal administrations of MSCs). Results: In both cases, cell therapy achieved a clear improvement in neurological sequels, such as recovery of gait disturbances, bowel dysfunction, or neuropathic pain. Conclusion: Intrathecal cell therapy with autologous MSCs offers a new approach for neurological sequels after spinal cord surgery

Anti-CCR7 therapy exerts a potent anti-tumor activity in a xenograft model of human mantle cell lymphoma

[Background]: The chemokine receptor CCR7 mediates lymphoid dissemination of many cancers, including lymphomas and epithelial carcinomas, thus representing an attractive therapeutic target. Previous results have highlighted the potential of the anti-CCR7 monoclonal antibodies to inhibit migration in transwell assays. The present study aimed to evaluate the in vivo therapeutic efficacy of an anti-CCR7 antibody in a xenografted human mantle cell lymphoma model. [Methods]: NOD/SCID mice were either subcutaneously or intravenously inoculated with Granta-519 cells, a human cell line derived from a leukemic mantle cell lymphoma. The anti-CCR7 mAb treatment (3 × 200 μg) was started on day 2 or 7 to target lymphoma cells in either a peri-implantation or a post-implantation stage, respectively. [Results]: The anti-CCR7 therapy significantly delayed the tumor appearance and also reduced the volumes of tumors in the subcutaneous model. Moreover, an increased number of apoptotic tumor cells was detected in mice treated with the anti-CCR7 mAb compared to the untreated animals. In addition, significantly reduced number of Granta-519 cells migrated from subcutaneous tumors to distant lymphoid organs, such as bone marrow and spleen in the anti-CCR7 treated mice. In the intravenous models, the anti-CCR7 mAb drastically increased survival of the mice. Accordingly, dissemination and infiltration of tumor cells in lymphoid and non-lymphoid organs, including lungs and central nervous system, was almost abrogated. [Conclusions]: The anti-CCR7 mAb exerts a potent anti-tumor activity and might represent an interesting therapeutic alternative to conventional therapies.BSC is supported by the Fundación Leucemia Linfoma and Fundación Vistare. Grants from the Fondo de Investigaciones Sanitarias to CMC (PI09/01336 and PI12/00494), JMZ (PI12/01135) and EFR (PI11/00128) and from IMMED to CMC supported this work.Peer Reviewe