http://hdl.handle.net/10171/18985 2013-05-21T18:08:42Z http://hdl.handle.net/10171/28278 Title: Neuropsychological evaluation of children with intracranial tumors: impact of treatment modalities Author(s) : Garcia-Perez, A. (A.); Sierrasesumaga, L. (Luis); Narbona, J. (Juan); Calvo-Manuel, F. (F.); Aguirre-Ventallo, M. (M.) Abstract: Antineoplastic treatment has a deleterious effect on intellectual functions, which is mainly attributable to radiotherapy. With the object of determining the neuropsychological disturbances associated with brain irradiation in the child, and to try to differentiate them from the effects caused by the other types of treatment (surgical and chemotherapy) as well as from the effects of the tumor itself, a cross-sectional study was carried out in 25 survivors of medial edge intracranial tumors. In order to monitor the effect of systemic chemotherapy on the cognitive functions, and the effect of prolonged absence from school, two control groups were formed, one made up of subjects treated with chemotherapy for extracranial tumors, and the other of patients with non-malignant chronic disease. Neuropsychological functions were measured using the Spanish version of the Wechsler scale, as well as the following tests: Spreen-Benton, ITPA and TALE scales, Yuste Memory Test, Thurstone Attention Test, and the Rey Complex Figure. In addition to a progressive decline found in the full scale intelligence quotient in children irradiated for intracranial tumors, variance analysis showed that these patients deteriorate mainly in visual attention and memory, but also significantly in verbal fluency and in the Performance Intelligence Quotient and all its subtests, when compared to the control groups. Visual attention and the Wechsler Picture Arrangement and Block Designs, were the tests whose decline correlated with the total radiation administered. The article relates this specific neuropsychological injury with the total brain irradiation dose but also with the structures located in the cone-down fields of irradiation to boost regions in the middle edge intracranial content. 1993-12-31T23:00:00Z http://hdl.handle.net/10171/28188 Title: Design and evaluation of a treatment programme for Spanish adolescents with overweight and obesity. The EVASYON Study Author(s) : Martinez-Gomez, D. (David); Gomez-Martinez, S. (Sonia); Puertollano, M.A. (M. Ángeles); Nova, E. (Esther); Wärnberg, J. (Julia); Veiga, O.L. (Oscar L.); Marti, A. (Amelia); Campoy, C. (Cristina); Garagorri, J.M. (Jesús M.); Azcona, C. (Cristina); Vaquero, M.P. (M. Pilar); Redondo-Figuero, C. (Carlos); Delgado, M. (Manuel); Martinez, J.A. (José Alfredo); Garcia-Fuentes, M. (Miguel); Moreno, L.A. (Luis A.); Marcos, A. (Ascensión); EVASYON Study Group Abstract: Background The prevalence of overweight and obesity (OW/OB) among adolescents worldwide has increased since the 60 s. Spain has reached one of the highest OW/OB prevalence rates among adolescents from European countries. The aim of this methodological paper is to describe the design and evaluation in the EVASYON study (Development, implementation and evaluation of the efficacy of a therapeutic programme for adolescents with OW/OB: integral education on nutrition and physical activity). Methods/Design The EVASYON was planned by a multidisciplinary team to treat OW/OB in Spanish adolescents. The EVASYON is a multi-centre study conducted in 5 hospitals in 5 Spanish cities (Granada, Madrid, Pamplona, Santander and Zaragoza) and two hundred and four OW/OB Spanish adolescents were recruited for this intervention. The treatment was implemented for approximately one-year follow-up. The adolescents were treated in groups of a maximum of 10 subjects; each group had 20 visits during the treatment period in two phases: intensive during the first 2 months (1st to 9th visits), and extensive during the last 11 months (10th to 20th visits). In order to assess the efficacy of the treatment, 8 dimensions were measured: diet; physical activity and fitness; eating behaviour; body composition; haematological profile; metabolic profile; minerals and vitamins; immuno-inflammatory markers. Moreover, genetic polymorphisms were also determined. Discussion The treatment programme developed in the EVASYON study was designed as a national pilot study to be implemented as an effective treatment for adolescents with OW/OB into the Spanish Health Care Service. 2008-12-31T23:00:00Z http://hdl.handle.net/10171/28052 Title: Partial splenic embolization in a child with hereditary spherocytosis Author(s) : Jimenez, M. (M.); Azcona, C. (Cristina); Castro, L. (L.); Bilbao, J.I. (José Ignacio); Leon, P. (P.); Sierrasesumaga, L. (Luis) 1994-12-31T23:00:00Z http://hdl.handle.net/10171/28051 Title: Use of recombinant human granulocyte-macrophage colony stimulating factor in an infant with reticular dysgenesis Author(s) : Azcona, C. (Cristina); Alzina, V. (Valentín); Barona, P. (Pascual); Sierrasesumaga, L. (Luis); Villa-Elizaga, I. (Ignacio) Abstract: We present the case of a 2-month-old infant with reticular dysgenesis who was treated with recombinant granulocyte-macrophage colony stimulating factor with the aim of stimulating granulopoiesis while awaiting bone marrow transplant. 1994-12-31T23:00:00Z http://hdl.handle.net/10171/27425 Title: Hallazgos neurorradiológicos de la Acidosis Glutárica tipo I Author(s) : Luis, E. (Esther) de; Larrache, J. (Javier); Garcia-de-Eulate, R. (Reyes); Narbona, J. (Juan); Zubieta, J.L. (José L.) Abstract: Glutaric aciduria type I is a rare disorder of organic acid metabolism caused by deficiency of glutaryl-CoA dehydrogenase, a mitochondrial enzyme. Improper degeneration of amino acids: tryptophan, lysine, and hydroxylysine, results in increased levels of glutaric acid, which typically becomes clinically manifest as an acute dystonic crisis in young children. Accumulation of glutaric acid causes neurotoxicity in the basal ganglia and fronto-temporal cortex which can lead to progressive dystonia, hypotonia, permanently impaired speech and seizures. Because dietary and drug therapy may alter the natural history of the disease, early diagnosis of such patients is critical. We report the magnetic resonance (MR) imaging findings in a 16 year-old girl with this disorder who presented with a chronic dystonic syndrome and previously diagnosed of brain paralysis. MR imaging demonstrated bilateral involvement of the putamina and periventricular white matter, and bilateral temporal atrophy and widened Silvian fissures 2006-12-31T23:00:00Z http://hdl.handle.net/10171/23778 Title: Transient Posterior Encephalopathy Induced by Chemotherapy in Children Author(s) : Sanchez-Carpintero, R. (Rocío); Narbona, J. (Juan); Lopez-de-la-Mesa, R. (R.); Arbizu, J. (J.); Sierrasesumaga, L. (Luis) Abstract: The cases of three children, 16, 12, and 12 years of age, who suffered sudden confusional state and cortical blindness lasting 12 to 30 minutes while under treatment with high-dose methotrexate, cyclophosphamide, and dactinomycin for a lower limb osteosarcoma are reported. Transient neuropsychologic deficits arose after the acute phase of treatment: left hemispatial neglect and constructive apraxia (Patient 1); constructive apraxia (Patient 2); and constructive apraxia and alexia without aphasia (Patient 3). The three patients recovered completely from all their deficits within the time frame of 3 hours to 2 weeks. Arterial hypertension and hypomagnesemia were found during the acute phase in all patients. In Patients 2 and 3, magnetic resonance imaging revealed increased parieto-occipital T(2) signal involving gray and white matter. In Patients 1 and 2, HmPAO-SPECT revealed parieto-occipital hypoperfusion that resolved a few days later. The alterations detected by neuroimaging were concurrent with the appearance and disappearance of the clinical symptoms. Such transient acute episodes have been named occipital-parietal encephalopathy. On the basis of our clinical, laboratory, and neuroimaging findings, an explanation for the origin of this syndrome, a migrainelike mechanism, triggered by chemotherapy-induced hypomagnesemia, is proposed. 2000-12-31T23:00:00Z http://hdl.handle.net/10171/23777 Title: Bone Mineral Density and Bone Metabolism In Children Treated for Bone Sarcomas Author(s) : Ruza, E. (Elena); Sierrasesumaga, L. (Luis); Azcona, C. (Cristina); Patiño, A. (Ana) Abstract: In adolescent bone sarcoma patients, bone mass acquisition is potentially compromised at a time in which it should be at a maximum. To evaluate the problem we measured bone mineral density (BMD) and serum markers of bone formation and resorption in a series of pediatric patients with bone tumors. BMD was measured by dual-energy x-ray absorptiometry, at clinical remission, for lumbar spine and the neck of the femur in 38 osteosarcoma and 25 Ewing's sarcoma patients. Mean age was 20.65 and 19.13 y respectively. Serum markers of bone metabolism were: OC, PICP, ICTP, 25-OH vit D and 1,25-(OH)(2) vit D, IGF-I, IGFBP-3 and intact PTH. Serum was sampled throughout anti-tumoral treatments and follow-up. We analyzed 85 samples from 59 osteosarcoma patients and 54 samples from 36 Ewing's sarcoma patients. Patients had decreased lumbar and femoral BMD. The decrease was more pronounced in pubertal patients compared with those who had completed pubertal development at the time of disease diagnosis. Multivariate analysis indicated that sex, age, weight and BMI were significant in lumbar BMD depletion. Weight and BMI were significant in femoral BMD depletion. Serum markers of bone formation (PICP and OC) and resorption (ICTP) were, throughout, lower than reference values. Significant alterations in other markers were also observed. Up to a third of osteosarcoma and Ewing's sarcoma patients in clinical remission had some degree of BMD deficit. The corresponding increased risk of pathologic bone fractures constitutes a reduction in future quality of 2005-12-31T23:00:00Z http://hdl.handle.net/10171/23776 Title: Methotrexate Pharmacokinetics and Survival in Osteosarcomat Author(s) : Aquerreta, I. (Irene); Aldaz, A. (Azucena); Giraldez, J. (J.); Sierrasesumaga, L. (Luis) Abstract: The aim of this study was to analyze the relationship between exposure to high-dose methotrexate (HDMTX) and tumor response in terms of survival in children with osteosarcoma. PROCEDURE: This study included 44 patients (479 courses) who received a median dose of 5.92 g/m2 of MTX (interquartile range (IQR) 2.37 g/m2) in a 4-hr infusion. The mean area under the concentration-time curve (AUC) estimated by parametric methods (non-parametric expectation maximization, NPEM), and the mean concentration at the end of the infusion were considered to be the exposure parameters. Tumor response was recorded as disease-free survival (DFS), overall survival (OS), and histologic tumor response. The relationship between MTX exposure and survival parameters was analyzed by Cox regression. RESULTS: The group of 11 patients who were the least exposed to MTX (AUC <2,400 micromol/L hr) presented a high DFS, probably due to the shorter interval of time between MTX courses that led to a higher dose density. In patients with AUC >2,400 micromol/L hr, an increase in the AUC was related to an increase in the DFS. Significant differences were observed in the DFS between patients whose mean AUC was below or above 4,000 micromol/L hr (P=0.024), such that 4,000 micromol/L hr was considered as the minimum AUC to be aimed at for future patients. CONCLUSIONS: Dose density seems to be an important factor in osteosarcoma response, but this must be confirmed in further studies. In order to improve the response to osteosarcoma in children, it is recommended that the dose of MTX to be increased such as to obtain an AUC higher than 4,000 micromol/L hr. 2003-12-31T23:00:00Z http://hdl.handle.net/10171/23775 Title: Screening of the human tumor necrosis factor-alpha (TNF-α) gene promoter polymorphisms by PCR–DGGE analysis Author(s) : Patiño, A.(Ana); Sotillo, E. (Elena); Modesto, C. (C.); Sierrasesumaga, L. (Luis) Abstract: We have designed a new PCR-DGGE technique that enables detection of base changes in the TNF-alpha gene promoter. Screening of 130 samples from Spanish children has shown that this technique accurately detects the altered band patterns induced by the presence of the polymorphisms at positions -376, -308, -238 and -163 of the promoter sequence. Although further analysis are needed to fully characterise the alterations detected, we believe that this PCR-DGGE technique is a rapid and sensitive first approach to the genetic characterisation of the TNF-alpha promoter 1998-12-31T23:00:00Z http://hdl.handle.net/10171/23774 Title: Emergence of Secondary Acute Leukemia in a Patient Treated for Osteosarcoma: Implications of Germline TP53 Mutations Author(s) : Panizo, C. (Carlos); Patiño, A. (Ana); Calasanz, M.J. (María José); Rifon, J. (José); Sierrasesumaga, L. (Luis); Rocha, E. (Eduardo) Abstract: Secondary leukemia and myelodysplastic syndromes have been reported in patients following treatment for a wide range of neoplastic disorders. However second malignancies after chemotherapy and/or irradiation for osteosarcoma are unusual. PROCEDURE: We report the case of a 15-year-old girl who developed a myelodysplastic syndrome with evolution to acute nonlymphocytic leukemia after treatment for osteosarcoma. Therapy-related acute leukemia karyotype findings such as abnormalities of chromosomes 5, 7, and 17 were found in the cytogenetic analysis. Moreover, using denaturing gradient gel electrophoresis and DNA sequencing, we detected the presence of a double germline mutation in exon 7 of the TP53 gene. CONCLUSION: This observation supports the possibility of a causal relationship between germline TP53 mutations and the development of secondary leukemia and myelodysplasia 1997-12-31T23:00:00Z http://hdl.handle.net/10171/23773 Title: Recombinant Human Erythropoietin for the Treatment of Anemia in Children With Solid Malignant Tumors Author(s) : Leon, P. (Pedro); Jimenez, M. (Miguel); Barona, P. (Pascual); Sierrasesumaga, L. (Luis) Abstract: Cancer is often associated with chronic anemia which frequently requires blood transfusions. This study was performed to assess the efficacy and safety of r-HuEPO therapy in children with cancer. PATIENTS AND METHODS: Twenty-five patients under 18 years of age with solid malignant tumors were treated with 150 U/kg/day of r-HuEPO 5 times weekly for 12 weeks. Response was defined as an increase of the baseline hemoglobin level by at least 2 g/dl. r-HuEPO patients were compared to 25 matched historical controls. RESULTS: Response was achieved in 72% of r-HuEPO patients. Hemoglobin level increased from 9.8 +/- 0.6 g/dl at baseline to 12.4 +/- 1.7 g/dl at the end of treatment in the r-HuEPO group and increased from 9.5 +/- 0.7 g/dl to 9.6 +/- 1.4 g/dl in the control group (P < .001, Student's t-test). Only 16% of patients receiving r-HuEPO required blood transfusions vs 96% of control patients (P < .001, Student's t-test), with mean units of blood transfused per patient being 0.35 in the r-HuEPO group and 3.56 in controls (P < .001, Student's t-test). There was a statistically significance improvement in Karnofsky's index in r-HuEPO patients. No adverse reaction related to r-HuEPO therapy was observed. CONCLUSIONS: r-HuEPO is a safe and effective means of increasing hemoglobin level and reducing blood requirements in children with solid malignant tumors receiving chemotherapy. 1997-12-31T23:00:00Z http://hdl.handle.net/10171/23772 Title: Use of brachytherapy in children with cancer: the search for an uncomplicated cure Author(s) : Martinez-Monge, R. (Rafael); Cambeiro, M. (Mauricio); San-Julian, M. (Mikel); Sierrasesumaga, L. (Luis) Abstract: Brachytherapy is a sophisticated radiation method in which radioisotopes are placed inside or at a short distance from the tumour. The volume of tissue that receives the prescribed dose of radiotherapy is therefore fairly small compared with that used in standard radiotherapy techniques. In paediatric oncology, this method of radiation delivery can have a favourable effect on several undesirable long-term side-effects that sometimes develop in children who receive radiotherapy, such as growth retardation and development of second primary tumours. Here, we describe the rationale for use of brachytherapy in children with cancer, the methods of the different brachytherapy techniques available, and the results obtained with several brachytherapy regimens in expert institutions throughout the world. 2005-12-31T23:00:00Z http://hdl.handle.net/10171/23771 Title: Pediatric Meningosarcoma: Clinical Evolution and Genetic Instability Author(s) : Lopez-de-la-Mesa, R. (R.); Sierrasesumaga, L. (Luis); Lopez-de-Cerain, A. (Adela); Calasanz, M.J. (Maria José); Patiño, A. (Ana) Abstract: This report presents a female diagnosed with a frontoparietal interhemispheric meningosarcoma who, parallel to the clinical worsening, revealed an increase in the genetic instability (in bleomycin cultures) and the complexity of the karyotypes, with the acquisition of a clonal deletion of 17p13 (the locus for the TP53 tumor suppressor gene). The genetic findings of this patient suggest that the increased genetic instability could contribute to tumor progression as well as to treatment resistance, possibly in the background of the clonal deletion of TP53. 2004-12-31T23:00:00Z http://hdl.handle.net/10171/23770 Title: Methotrexate in Pediatric Osteosarcoma: Response and Toxicity in Relation to Genetic Polymorphisms and Dihydrofolate Reductase and Reduced Folate Carrier 1 Expression Author(s) : Patiño, A. (Ana); Zalacain, M. (Marta); Marrodan, L. (Lucía); San-Julian, M. (Mikel); Sierrasesumaga, L. (Luis) Abstract: To determine the influence of the genotype and the level of expression of different enzymes involved in folate metabolism on the response to and toxicity of high-dose methotrexate treatment in pediatric osteosarcomas. STUDY DESIGN: DHFR and Reduced folate carrier 1 (RFC1) semiquantitative expression was analyzed in 34 primary and metastatic osteosarcoma tissues by real-time polymerase chain reaction. The following polymorphisms were also analyzed in peripheral blood from 96 children with osteosarcoma and 110 control subjects: C677T, A1298C (MTHFR), G80A (RFC1), A2756G (MTR), C1420T (SHMT), the 28bp-repeat polymorphism, and 1494del6 of the TYMS gene. Treatment toxicity was scored after each cycle according to criteria from the World Health Organization. RESULTS: DHFR and RFC1 expression was lower in initial osteosarcoma biopsy specimens than in metastases (P = .024 and P = .041, respectively). RFC1 expression was moderately decreased in samples with poor histologic response to preoperative treatment (P = .053). Patients with osteosarcoma with G3/G4 hematologic toxicity were more frequently TT than CT/CC for C677T/MTHFR (P = .023) and GG for A2756G/MTR (P = .048 and P = .057 for gastrointestinal and hematologic toxicity, respectively). CONCLUSIONS: The role of C677T/MTHFR and A2756G/MTR on chemotherapy-induced toxicity should be further investigated in pediatric osteosarcomas receiving high-dose methotrexate. Altered expression of DHFR and RFC1 is a feasible mechanism by which osteosarcoma cells become resistant to methotrexate. 2008-12-31T23:00:00Z http://hdl.handle.net/10171/23769 Title: Sistemas de acceso venoso central (SAVC) en pacientes pediátricos. Experiencia de seis años Author(s) : Torramade, J. (J.); Hernandez-Lizoain, J.L. (José Luis); Benito, C. (C.); Gonzalez-Fernandez, J. (J.); Balen, E. (Enrique); Martinez-Regueira, F. (Fernando); Pardo, F. (Fernando); Cienfuegos, J.A. (Javier A.) Abstract: The need for an access to the venous system, in order to infuse chemotherapeutic treatments or parenteral nutrition, has increased the number of central venous access systems (CVAS) implanted in the past years. Between February 1985 and December 1990, 87 devices were implanted in 76 patients (from 11 months to 15 years of age), with a median function time of 349 days (range: 7 to 1887 days). The overall incidence of complications was 0.10 per 10 days of catheterization, with complication rates for infection and thrombosis of 0.02 and 0.03, respectively. Nineteen systems were removed because of complications and 11 because of completion of the treatment. Of the cases, 97.7% included a follow-up period. The present study confirms the advantages of these devices, with a long working life and a low complication rate, being a good alternative for chronically ill children requiring long-term and/or cyclic intravenous therapy. 1992-12-31T23:00:00Z