Desarrollo y futuro de la salud pública veterinaria

En la presente comunicación se analizan diferentes instancias de la gestión de la salud pública veterinaria y su evolución en el país.Academia Nacional de Agronomía y Veterinari

Radioimmunotherapy for mantle cell lymphoma : 5-year follow-up of 90 patients from the international RIT registry

To assess the efficacy of radioimmunotherapy (RIT) wit

Chronic lymphocytic leukemia developing in a patient with chronic myeloid leukemia: Evidence of distinct lineage-associated genomic events

We describe the cytogenetic, fluorescence in situ hybridization (FISH), and molecular findings in a patient who developed a typical chronic lymphocytic leukemia (CLL) 20 months after the diagnosis of a Philadelphia (Ph)-positive chronic myeloid leukemia. Unstimulated bone marrow culture showed a 46,XX,t(9;22)(q34;q11) karyotype, and interphase FISH detected the presence of a BCR/ABL fusion signal in 13% of cells. On stimulated bone marrow culture, a normal karyotype and a 13q14 deletion by interphase FISH with D13S319 probe in 14% of the cells were found. Molecular studies detected the chimeric BCR/ABL messengers by nested reverse-transcriptase polymerase chain reaction. The B-cellular clone was documented by the presence of a clonal heavy chain inmunoglobulin rearrangement. The coexistence of these two hematologic malignancies leads to questions about their cell(s) of origin. We provide evidence that CLL arose in a Ph-negative clone. The implications of these findings are discussed. © 2005 Elsevier Inc. All rights reserved.Fil: Gargallo, Patricia Martha. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Cacchione, Roberto. Centro de Estudios Médicos e Investigaciones Clínicas; ArgentinaFil: Chena, Christian. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Dupont, Juan. Centro de Estudios Médicos e Investigaciones Clínicas; ArgentinaFil: Garay, Guy. Centro de Estudios Médicos e Investigaciones Clínicas; ArgentinaFil: Riveros, Dardo Alberto. Centro de Estudios Médicos e Investigaciones Clínicas; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentin

Forjadores del INTA. Tomo 4

Biografías, historias y experiencias de las personalidades del INTA de los Institutos de Investigación de INTA Castelar y de las Estaciones Experimentales Balcarce, Bariloche, Pergamino y Sáenz PeñaFil: Cacchione, Roberto Antonio. Instituto Nacional de Tecnología Agropecuaria (INTA). Centro de Investigación en Ciencias Veterinarias y Agronómicas; ArgentinaFil: Favret, Ewald Alfredo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; ArgentinaFil: Franchelli, Rómulo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Ingeniería Rural; ArgentinaFil: Kugler, Walter Federico. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino; ArgentinaFil: López Saubidet, Carlos Alfredo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Grenville Manhouse Morris, Arthur. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche; ArgentinaFil: Ragonese, Arturo Enrique. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Recursos Biológicos; ArgentinaFil: Ricciardi, Aldo Angel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Sáenz Peña; Argentin

Consolidation with Radioimmunotherapy May Prolong Survival in First Remission of Mantle Cell Lymphoma Patients Uneligible for Stem Cell Transplantation, An Analysis of the International RIT-Network

Background: Mantle cell lymphoma (MCL) is a rare subtype (3-9%) of Non Hodgkin Lymphoma (NHL) with a relatively poor prognosis (5-year survival < 40%). Although consolidation of first remission with autologous stem cell transplantation (ASCT) is regarded as "golden standard", less than half of the patients may be subjected to this intensive treatment due to advanced age and co-morbidities. Standard-dose non-myeloablative radioimmunotherapy (RIT) seems to be a very efficient approach for treatment of certain NHL. However, there are almost no data available on the efficacy and safety of RIT in MCL. Methods and Patients: In the RIT-Network, a web-based international registry collecting real observational data from RIT-treated patients, 115 MCL patients treated with ibritumomab tiuxetan were recorded. Most of the patients were elderly males with advanced stage of the disease: median age - 63 (range 31-78); males - 70.4%, stage III/IV - 92%. RIT (i.e. application of ibritumomab tiuxetan) was a part of the first line therapy in 48 pts. (43%). Further 38 pts. (33%) received ibritumomab tiuxetan after two previous chemotherapy regimens, and 33 pts. (24%) after completing 3-8 lines. In 75 cases RIT was applied as a consolidation of chemotherapy induced response; the rest of the patients received ibritumomab tiuxetan because of relapse/refractory disease. At the moment follow up data are available for 74 MCL patients. Results: After RIT the patients achieved high response rate: CR 60.8%, PR 25.7%, and SD 2.7%. Only 10.8% of the patients progressed. For survival analysis many data had to be censored since the documentation had not been completed yet. The projected 3-year overall survival (OAS, fig.1 - image 001.gif) after radioimmunotherapy was 72% for pts. subjected to RIT consolidation versus 29% for those treated in relapse/refractory disease (p=0.03). RIT was feasible for almost all patients; only 3 procedure-related deaths were reported in the whole group. The main adverse event was hematological toxicity (grade III/IV cytopenias) showing a median time of recovery of Hb, WBC and Plt of 45, 40 and 38 days respectively. Conclusion: Standard-dose non-myeloablative RIT is a feasible and safe treatment modality, even for elderly MCL pts. Consolidation radioimmunotherapy with ibritumomab tiuxetan may prolong survival of patients who achieved clinical response after chemotherapy. Therefore, this consolidation approach should be considered as a treatment strategy for those, who are not eligible for ASCT. RIT also has a potential role as a palliation therapy in relapsing/resistant cases

Cancer Predisposition Syndromes and Medulloblastoma in the Molecular Era

Medulloblastoma is the most common malignant brain tumor in children. In addition to sporadic cases, medulloblastoma may occur in association with cancer predisposition syndromes. This review aims to provide a complete description of inherited cancer syndromes associated with medulloblastoma. We examine their epidemiological, clinical, genetic, and diagnostic features and therapeutic approaches, including their correlation with medulloblastoma. Furthermore, according to the most recent molecular advances, we describe the association between the various molecular subgroups of medulloblastoma and each cancer predisposition syndrome. Knowledge of the aforementioned conditions can guide pediatric oncologists in performing adequate cancer surveillance. This will allow clinicians to promptly diagnose and treat medulloblastoma in syndromic children, forming a team with all specialists necessary for the correct management of the other various manifestations/symptoms related to the inherited cancer syndromes

Posterior fossa ependymoma in neurodevelopmental syndrome caused by a de novo germline pathogenic Polr2a variant

Ependymoma is the third most common pediatric brain tumor. Predisposition to develop ependymomas has been reported in different hereditary diseases, but the pathogenic variants related to the familial syndromes have rarely been detected in sporadic ependymomas. De novo variants in POLR2A, the gene encoding the largest subunit of RNA polymerase II, cause a neurodevelopmental disorder with a wide range of clinical manifestations, characterized by severe infantile-onset hypotonia, developmental delay, feeding difficulties, palatal anomalies, and facial dysmorphisms. As somatic events, POLR2A mutations represent a recurrent somatic lesion in benign meningiomas. Here we describe a case of ependymoma in a 2-year-old male with a de novo pathogenic variant in POLR2A predicted to impair proper interaction of the subunit with transcription-elongation factor TFIIS, whose function is required for back-tracking of the enzyme due to elongation blocks or nucleotide misincorporation, and expected to result in an increased error and reduced elongation rates. To date, ependymoma has never been reported in patients harboring pathogenic POLR2A variants. Further information is required to explore the possibility of a differential clinical and functional impact of the pathogenic POLR2A variants and the eventual inclusion of the POLR2A neurodevelopmental disorder among the cancer predisposition syndromes with the possible development of ependymomas.s

Medulloblastoma Associated with Down Syndrome: From a Rare Event Leading to a Pathogenic Hypothesis

Down syndrome (DS) is the most common chromosome abnormality with a unique cancer predisposition syndrome pattern: a higher risk to develop acute leukemia and a lower incidence of solid tumors. In particular, brain tumors are rarely reported in the DS population, and biological behavior and natural history are not well described and identified. We report a case of a 10-year-old child with DS who presented with a medulloblastoma (MB). Histological examination revealed a classic MB with focal anaplasia and the molecular profile showed the presence of a CTNNB1 variant associated with the wingless (WNT) molecular subgroup with a good prognosis in contrast to our case report that has shown an early metastatic relapse. The nearly seven-fold decreased risk of MB in children with DS suggests the presence of protective biological mechanisms. The cerebellum hypoplasia and the reduced volume of cerebellar granule neuron progenitor cells seem to be a possible favorable condition to prevent MB development via inhibition of neuroectodermal differentiation. Moreover, the NOTCH/WNT dysregulation in DS, which is probably associated with an increased risk of leukemia, suggests a pivotal role of this pathway alteration in the pathogenesis of MB; therefore, this condition should be further investigated in future studies by molecular characterizations

Medulloblastoma Associated with Down Syndrome: From a Rare Event Leading to a Pathogenic Hypothesis

Down syndrome (DS) is the most common chromosome abnormality with a unique cancer predisposition syndrome pattern: a higher risk to develop acute leukemia and a lower incidence of solid tumors. In particular, brain tumors are rarely reported in the DS population, and biological behavior and natural history are not well described and identified. We report a case of a 10-year-old child with DS who presented with a medulloblastoma (MB). Histological examination revealed a classic MB with focal anaplasia and the molecular profile showed the presence of a CTNNB1 variant associated with the wingless (WNT) molecular subgroup with a good prognosis in contrast to our case report that has shown an early metastatic relapse. The nearly seven-fold decreased risk of MB in children with DS suggests the presence of protective biological mechanisms. The cerebellum hypoplasia and the reduced volume of cerebellar granule neuron progenitor cells seem to be a possible favorable condition to prevent MB development via inhibition of neuroectodermal differentiation. Moreover, the NOTCH/WNT dysregulation in DS, which is probably associated with an increased risk of leukemia, suggests a pivotal role of this pathway alteration in the pathogenesis of MB; therefore, this condition should be further investigated in future studies by molecular characterizations