Non-functional alternative splicing caused by a Latino pathogenic variant in a case of PMM2-CDG.

We report on a Mexican mestizo with a multisystemic syndrome including neurological involvement and a type I serum transferrin isoelectric focusing (Tf IEF) pattern. Diagnosis of PMM2-CDG was obtained by clinical exome sequencing (CES) that revealed compound heterozygous variants in PMM2, the encoding gene for the phosphomannomutase 2 (PMM2). This enzyme catalyzes the conversion of mannose-6-P to mannose-1-P required for the synthesis of GDP-Man and Dol-P-Man, donor substrates for glycosylation reactions. The identified variants were c.422G>A (R141H) and c.178G>T, the former being the most frequent PMM2 pathogenic mutation and the latter a previously uncharacterized variant restricted to the Latino population with conflicting interpretations of pathogenicity and that we here report causes leaky non-functional alternative splicing (p.V60Cfs*3).

[Hypersensitivity reactions associated with the use of asparaginase in children with acute lymphoblastic leukemia]. / Reacciones de hipersensibilidad asociadas al uso de asparaginasa en niños con leucemia linfoblástica aguda.

INTRODUCTION: The treatment of acute lymphoblastic leukemia (ALL) includes the use of asparaginase (ASP), a drug associated with hypersensitivity reactions (HSR) that requires discontinuing its use. OBJECTIVE: To determine the incidence of HSR associated with ASP that require discontinuation of its use and des cribe them, and to verify if there is a relationship between HSR incidence and protocols or survival. PATIENTS AND METHOD: Retrospective study. Clinical records of all patients (1-15 years) diagnosed with ALL between January 2010 and December 2015 at the Hospital Luis Calvo Mackenna were reviewed. The incidence of HSR to ASP was determined and classified according to the CTCAE v5.0 severity score. We analyzed the relative risk of HSR using Fisher's test and the survival with the Kaplan-Meier estimator. RESULTS: 110 patients were collected. During the first treatment (ALL-IC- BFM), the incidence of HSR to L-ASP was 55%, therefore it was changed to PEG-ASP as second-line treatment, and 44% of them had HSR, and ASP should discontinued in 25% of patients. Of all the HSR to ASP, 77% were anaphylactic (CTCAE 3-5). Patients treated with augmented IB protocol were at higher risk of not completing ASP treatment due to HSR, RR 3.81 (95% CI, 1.98-7.31, p = 0.0001). Patients without HSR in ALL-IC-BFM were at lower risk of relapse, HR 0.29 (95% CI, 0.14-0.62, p = 0.0013). Considering all treatments (ALL-IC-BFM and relapse), patients who completed the ASP treatment had higher overall survival, HR 0.20 (95% CI, 0.07-0.57, p = 0.0026). CONCLUSIONS: HSR to ASP that require discontinuation of treatment are frequent in children with ALL, most of them were severe anaphylactic reactions. This study suggests a better prognosis in patients without HSR to ASP.

UPD(14)mat and UPD(14)mat in concomitance with mosaic small supernumerary marker chromosome 14 in two new patients with Temple syndrome.

Temple syndrome (TS14) can be originated by maternal uniparental disomy (UPD(14)mat), paternal deletion, or epimutation, leading to disturbances in 14q32.2 imprinted region. The most frequent phenotypic manifestations are prenatal and postnatal growth failure, hypotonia, developmental delay, small hands/feet, precocious puberty, and truncal obesity. However, the diagnosis can be challenging due to the clinical overlap with other imprinting disorders such as Silver-Russell or Prader-Willi syndromes. Although rare, TS14 has been also reported in patients with concomitant UPD(14)mat and mosaic trisomy 14. In the present report, the clinical and genetic profiles of two new patients with TS14 are described. SNParray and MS-MLPA, allowed the determination of segmental UPD(14)mat and the hypomethylation of MEG3 gene. Additionally, in one of our patients we also observed by cytogenetics a small supernumerary marker chromosome that led to partial trisomy 14 in mosaic. Only few patients with concomitant UPD(14)mat and mosaic partial trisomy 14 have been reported. Our patients share cardinal TS14 phenotypic features that are associated to the genetic abnormalities detected; however, we also observed some clinical features such as fatty liver disease that had not previously been reported as part of this syndrome. The detailed clinical, cytogenetical and molecular description of these two new patients, contributes to a more accurately delineation of this syndrome.

Association of COMT Val158Met Polymorphism with Psychopathological Symptoms in Patients with Eating Disorders.

BACKGROUND: Dopamine physiological functions make dopaminergic genes suitable candidates for association studies in eating disorders (ED). A Val158Met polymorphism in the catechol-O-methyltransferase (COMT) gene, which is involved in dopamine degradation, has been studied in relation to ED. OBJECTIVE: We aimed to analyze the association between this polymorphism and general psychopathological symptoms that are often coupled to these disorders. METHOD: A total of 303 ED patients, diagnosed according to DSM-5 criteria, completed the SCL-90R questionnaire and were genotyped for the Val158Met polymorphism. RESULTS: There were significant differences in the global indices of the SCL-90R inventory between the three ED groups (Anorexia Nervosa (AN), Bulimia Nervosa (BN) and binge-eating disorder; ANOVA-p < 0.05). Females with BN showed the highest scores (worse symptomatology) of all participants. In this group, a gene-dose effect was observed on the psychometric evaluation of the patients, as Val/Val carriers displayed the highest scores for all the SCL-90R scales, followed by Val/Met and then Met/Met carriers. Significant differences between genotypes were observed in the Obsessive- Compulsive (p = 0.018), Paranoid Ideation (p = 0.0005) and Psychoticism (p = 0.039) scales, as well as in the PSDI (p = 0.014) general index. CONCLUSION: The results taken together suggest that COMT genetic variability may contribute to general psychopathological symptoms in patients with BN.

[Impact of an educational program for parents of children with cancer on the increased knowledge of their children's disease and the decrease in anxiety]. / Impacto de un programa educativo a los padres de niños con cáncer en el aumento del conocimiento de la enfermedad de sus hijos y la disminución de la ansiedad.

PURPOSE: To determine the impact of an educational program provided by a nurse to parents of children with cancer to improve the level of knowledge of the disease and to decrease the levels of anxiety. PATIENTS AND METHODS: A prospective randomized study was conducted on parents of children recently diagnosed with cancer and treated in the Hospital Luis Calvo Mackenna. After informed consent, parents were randomized in two groups: one receiving the educational program and another without intervention. Both groups completed a questionnaire on social risk, and three tests to assess the levels of knowledge and anxiety. RESULTS: A total of 96 parents were enrolled (July 2010-November 2011). When comparing the number of correct responses on day 10, and day 90 after the intervention, a significant increase was observed in the level of parental knowledge in the group that received the educational program (P<.0001). No significant differences were observed in the levels of anxiety (P=.06) between both groups. CONCLUSIONS: An educational program provided by nurses to parents of children recently diagnosed with cancer, increased the knowledge of their children's disease. However there was no effect on the levels of anxiety. A feasible educational intervention is proposed that could be implemented at other cancer centers for children.

Impacto de un programa educativo a los padres de niños con cáncer en el aumento del conocimiento de la enfermedad de sus hijos y la disminución de la ansiedad / Impact of an educational program for parents of children with cancer on the increased knowledge of their children's disease and the decrease in anxiety

Propósito: Determinar el impacto de un programa de educación entregado por la enfermera a los padres de niños con cáncer en el aumento del conocimiento de la enfermedad de sus hijos y disminución de la ansiedad. Pacientes y métodos: Estudio prospectivo y aleatorio. Incluyó a los padres de niños con diagnóstico reciente de cáncer, atendidos en el Hospital Dr. Luis Calvo Mackenna. Tras la firma de consentimiento informado se aleatorizó a los padres en 2 grupos, uno que recibió el programa educativo y otro sin intervención. Ambos grupos contestaron una encuesta de riesgo social y 3 evaluaciones de conocimiento y de ansiedad. Resultados: Un total de 96 padres fueron incluidos (julio 2010-noviembre 2011). Al comparar el número de respuestas correctas al día 10 y 90 posterior a la intervención entre ambos grupos, se encontró un aumento significativo en el nivel de conocimiento de los padres del grupo que recibió el programa educativo (p < 0,0001). Al comparar los resultados obtenidos en las evaluaciones de ansiedad entre ambos grupos, no se obtuvo una diferencia significativa (p = 0,06). Conclusiones: El estudio mostró que la realización de un programa educativo, entregado a los padres de niños con diagnóstico reciente de cáncer, aumentó el conocimiento de estos en mayor grado que aquellos que no la recibieron. Sin embargo, no hubo efectos en los grados de ansiedad de dichos padres en el período evaluado. Esta es una intervención factible que se podría implementar en los centros oncológicos infantiles del país.

Purpose: To determine the impact of an educational program provided by a nurse to parents of children with cancer to improve the level of knowledge of the disease and to decrease the levels of anxiety. Patients and methods: A prospective randomized study was conducted on parents of children recently diagnosed with cancer and treated in the Hospital Luis Calvo Mackenna. After informed consent, parents were randomized in two groups: one receiving the educational program and another without intervention. Both groups completed a questionnaire on social risk, and three tests to assess the levels of knowledge and anxiety. Results: A total of 96 parents were enrolled (July 2010-November 2011). When comparing the number of correct responses on day 10, and day 90 after the intervention, a significant increase was observed in the level of parental knowledge in the group that received the educational program (P < .0001). No significant differences were observed in the levels of anxiety (P = .06) between both groups. Conclusions: An educational program provided by nurses to parents of children recently diagnosed with cancer, increased the knowledge of their children's disease. However there was no effect on the levels of anxiety. A feasible educational intervention is proposed that could be implemented at other cancer centers for children.

Tumores raros en niños y adolescentes / Rare tumors in children and adolescents

Los tumores infrecuentes están definidos como cánceres pediátricos con una incidencia anual <2 casos por millón. Aunque son percibidos como raros, constituyen el 15% de todos los cánceres en menores de 20 años y 30% de todos los tumores de pacientes entre 15 y 19 años. Se han desarrollado proyectos cooperativos nacionales e internacionales pediátricos con el fin de mejorar el manejo clínico y la investigación básica en estos tumores. Revisamos los procesos desarrollados y las dificultades que se han enfrentado, como bajas tasas de registro y participación en bancos de tumores y estudios clínicos. Esta experiencia inicial ha permitido desarrollar estrategias alternativas que permitirían implementar una iniciativa similar para América Latina. La experiencia demuestra la factibilidad de cooperación multidisciplinaria a nivel nacional y sugiere que se pueden realizar estudios internacionales, que aumenten nuestro entendimiento de la biología de estos tumores, mejorando los resultados de tratamiento de niños y adolescentes con cánceres infrecuentes.

Although perceived as rare, infrequent tumors, defined as childhood solid malignancies with an annual incidence < 2/million and not considered in other clinical trials, account for 15% of all cancers in patients younger than age 20 and for 30% of all tumors in patients ages 15 to 19. National and international cooperative projects on rare paediatric tumours have been developed to improve the clinical management and basic research on these tumors. We reviewed the process developed and the problems it had to face, as low rates of registration, low levels of participation in tumor banking, and clinical trials. This initial experience has allowed to develop alternative strategies that could help to launch a latinamerican initiative. Experience demonstrates the feasibility of a national multidisciplinary cooperation and suggests that international studies can be performed, increasing our knowledge to understand the biology and improving the treatment results of young patients with rare cancers.

Mechanisms and ecological consequences of plant defence induction and suppression in herbivore communities.

BACKGROUND: Plants are hotbeds for parasites such as arthropod herbivores, which acquire nutrients and energy from their hosts in order to grow and reproduce. Hence plants are selected to evolve resistance, which in turn selects for herbivores that can cope with this resistance. To preserve their fitness when attacked by herbivores, plants can employ complex strategies that include reallocation of resources and the production of defensive metabolites and structures. Plant defences can be either prefabricated or be produced only upon attack. Those that are ready-made are referred to as constitutive defences. Some constitutive defences are operational at any time while others require activation. Defences produced only when herbivores are present are referred to as induced defences. These can be established via de novo biosynthesis of defensive substances or via modifications of prefabricated substances and consequently these are active only when needed. Inducibility of defence may serve to save energy and to prevent self-intoxication but also implies that there is a delay in these defences becoming operational. Induced defences can be characterized by alterations in plant morphology and molecular chemistry and are associated with a decrease in herbivore performance. These alterations are set in motion by signals generated by herbivores. Finally, a subset of induced metabolites are released into the air as volatiles and function as a beacon for foraging natural enemies searching for prey, and this is referred to as induced indirect defence. SCOPE: The objective of this review is to evaluate (1) which strategies plants have evolved to cope with herbivores and (2) which traits herbivores have evolved that enable them to counter these defences. The primary focus is on the induction and suppression of plant defences and the review outlines how the palette of traits that determine induction/suppression of, and resistance/susceptibility of herbivores to, plant defences can give rise to exploitative competition and facilitation within ecological communities "inhabiting" a plant. CONCLUSIONS: Herbivores have evolved diverse strategies, which are not mutually exclusive, to decrease the negative effects of plant defences in order to maximize the conversion of plant material into offspring. Numerous adaptations have been found in herbivores, enabling them to dismantle or bypass defensive barriers, to avoid tissues with relatively high levels of defensive chemicals or to metabolize these chemicals once ingested. In addition, some herbivores interfere with the onset or completion of induced plant defences, resulting in the plant's resistance being partly or fully suppressed. The ability to suppress induced plant defences appears to occur across plant parasites from different kingdoms, including herbivorous arthropods, and there is remarkable diversity in suppression mechanisms. Suppression may strongly affect the structure of the food web, because the ability to suppress the activation of defences of a communal host may facilitate competitors, whereas the ability of a herbivore to cope with activated plant defences will not. Further characterization of the mechanisms and traits that give rise to suppression of plant defences will enable us to determine their role in shaping direct and indirect interactions in food webs and the extent to which these determine the coexistence and persistence of species.

Impact of NEGR1 genetic variability on psychological traits of patients with eating disorders.

Genetics variants in the NEGR1 gene, strongly expressed in the brain, have been reported to affect the neuronal control of food intake therefore inducing obesity. With the same rationale, we hypothesized that this genetic variability may be associated with psychological traits commonly displayed by eating disorder (ED) patients and/or with the risk for the disorder. We analyzed 21 tag-single-nucleotide polymorphisms (SNPs) in the coding sequence and adjacent regions of the NEGR1 gene. A total of 169 ED patients (106 with anorexia nervosa (AN) and 63 with bulimia nervosa (BN)) and 312 healthy subjects were genotyped. Personality traits and general psychopathological symptoms were assessed by the Eating Disorders Inventory Test-2 (EDI-2) and Symptom Checklist 90 Revised inventories. None of the SNPs or haplotypes analyzed were associated with a greater risk of ED or correlated with anthropometric parameters. However, in patients with BN, four SNPs (rs12740031, rs10789322, rs6659202 and rs591540) correlated with the scores in Drive for Thinness (DT), Ineffectiveness (I) and Interoceptive Awareness (IA) (Bonferroni-P<0.05 in all instances). The first two SNPs along with rs954299 and rs2422021 formed a haplotype block, which showed a consistent association with the EDI-2 score in BN patients (Bonferroni-P=0.01). A subsequent three-SNP sliding-window approach identified a central area, encompassing both the haplotype block and the individually relevant SNPs that strongly correlated with the scores of BN patients in DT, I, IA and Bulimia. No associations were identified in the AN group. These preliminary results indicate that NEGR1 could be an important locus influencing certain personality dimensions in BN patients.

Polycystic ovarian morphology in adolescents with regular menstrual cycles is associated with elevated anti-Mullerian hormone.

BACKGROUND: The significance of polycystic ovarian morphology (PCOM) during adolescence is not clear. The aim of this study was to determine the relationship between PCOM and anti-Müllerian hormone (AMH), inhibin B, testosterone and insulin levels in healthy girls during the second decade of life. We also determined whether AMH could be used as a surrogate marker of PCOM during adolescence. METHODS: Seventy-four non-obese adolescents (age range: 13.5-19.75 years old) with regular menstrual cycles participated in this study. Transabdominal ultrasound and blood samples were obtained during the follicular phase. RESULTS: PCOM was present in 33.8% of the subjects. Girls with PCOM had higher AMH levels than girls without PCOM (72.5 ± 6.1 versus 33.4 ± 2.6 pmol/l; P < 0.0001) and lower FSH levels (5.4 ± 0.3 versus 6.2 ± 0.2 mUI/ml; P < 0.036). Similar levels of inhibin B, androgens and LH were observed in girls with and without PCOM. PCOM prevalence and AMH levels were not associated with age (P = 0.745 and 0.2, respectively) or BMI-SDS (P = 0.951 and 0.096, respectively). AMH levels positively correlated with the of 2-5 mm follicle number. AMH levels ≥ 60.15 pmol/l had a sensitivity and specificity of 64.0 and 89.8%, respectively, to diagnose PCOM (area under the curve = 0.873). CONCLUSIONS: These data confirm that PCOM in healthy non-hyperandrogenic girls with regular menstrual cycles is prevalent and is not associated with hyperandrogenism. The elevated AMH and lower FSH levels observed in healthy girls with regular menses and PCOM suggest that this ovarian pattern is secondary to a larger number of 2-5 mm follicles. An elevated AMH level is suggestive of the presence of PCOM during adolescence.

Hipercalcemia tumoral: a propósito de tres casos: [revisión] / Tumor related hypercalcemia: a review of three cases: [review]

Hypercalcemia is an infrecuent complication in pediatric oncology, with an incidence between 0,5 and 3 percent. It can occur at diagnosis, during the disease course or at relapse, and it is resolved by treating the underlying pathology, requiring in some cases the use of specific therapy such as calcitonin and biphosphonates. This article presents 3 cases of children with cancer and hypercalcemia during their illness, analyzing its clinical presentation, pathophysiology and treatment.

La hipercalcemia es una complicación infrecuente en niños con cáncer, con una incidencia que oscila entre 0,5 y 3 por ciento. Se puede presentar al diagnóstico, durante el tratamiento o en la recaída de una neoplasia, se resuelve al tratar la enfermedad de base, pudiendo además, requerir el uso de terapia específica como calcitonina y bifosfonatos. En el presente artículo se revisan 3 casos clínicos de niños con cáncer que presentaron hipercalcemia en algún momento de su enfermedad, se discute su forma de presentación, fisiopatología y manejo.

Retinoblastoma en pediatría, experiencia en un hospital pediátrico / Retinoblastoma in children, experience at a pediatric hospital

Methods: Retrospective analysis of clinical charts of 41 children (59 eyes) diagnosed with retinoblastoma and treated by a multidisciplinary team at Hospital Luis Calvo Mackenna in Santiago-Chile, between 1999 and 2007. The information included gender, laterality, diagnosis age, presenting signs, tumor spread, treatment modality and survival rate. Results: A total of 23 cases (56 percent) were unilateral and 18 cases (44 percent) were bilateral. The mean age at diagnosis was 21.6 months (range 2 - 84) and 27 children (65.9 percent) were male. The most common presenting signs were leucokoria (51.2 percent), strabismus (24.4 percent) and proptosis (4.9 percent). Enucleation was performed in 48 eyes (81.3 percent), being the only required treatment in 17 children (41.5 percent). The remaining 24 patients received systemic and/or local therapy with chemotherapy, focal therapy and external beam radiation. 5 children died during the follow - up study period, due to extraocular extension to the orbit, central nervous system and bone marrow. Conclusion: In spite of high enucleation rate as initial therapy for retinoblastoma, the survival rate with this current treatment protocol is similar to those from developed countries.

Se presenta un estudio retrospectivo de las fichas clínicas de 41 niños (59 ojos) con diagnóstico de retinoblastoma tratados por un equipo multidisciplinario en el Hospital Luis Calvo Mackenna, Santiago, Chile, entre los a±os 1999-2007. Se recolectó información respecto al género, edad al diagnóstico, signos de presentación, lateralidad, diseminación del tumor, tipos de tratamiento y sobrevida. Veintitrés casos (56 por ciento) fueron unilaterales y 18 (44 por ciento) bilaterales. La edad promedio al momento del diagnóstico fue de 21,6 meses (rango 2-84) y 27 niños (65,9 por ciento) fueron hombres. Los signos de presentación más frecuentes fueron leucocoria (51,2 por ciento), estrabismo (24,4 por ciento) y proptosis (4,9 por ciento). Se realizó enucleación en 48 ojos afectados (81,3 por ciento), siendo el único tratamiento necesario en 17 niños (41,5 por ciento). Los 24 pacientes restantes recibieron tratamientos complementarios locales y/o sistémicos en la modalidad de quimioterapia, terapia focal y radioterapia externa. Durante el período de seguimiento del estudio fallecieron 5 niños, todos ellos con extensión extraocular de la enfermedad hacia la órbita, sistema nervioso central o médula ósea. Conclusiones: No obstante el alto porcentaje de pacientes con retinoblastoma que requieren enucleación como terapia inicial, la tasa de sobrevida con el protocolo actual de tratamiento es comparable a la de países desarrollados.

Tratamiento antimicrobiano en niños con neutropenia febril de alto riesgo / Antibiotic treatment in children with high risk febrile neutropenia

Background: In children with cancer and high risk febrile neutropenia (HRFN), the initial empirical treatment used in our hospital for 5 years includes the association of Cloxacillin + Ceftazidime + Amikacin. There is no chilean literature that reviews the effectiveness of this therapy. Objective: Evalúate the clinical and microbiological effectiveness of this associated therapy in children with HRFN. Method: A prospective-descriptive study evaluating children with HRFN admitted at Hospital Luis Calvo Mackenna between January 2005-August 2006. Results: 100 HRFN episodes were evaluated. In 48 percent of cases, the antimicrobial treatment was considered effective, whereas in 52 percent of episodes the therapy required modifications (15 percent cases within the first 72 hours). The most frequent diagnoses were fever without clinical focus (51 percent) and sepsis (13 percent). 36 percent had microbiological identification and the most frequently isolated bacteria were Escherichia coli (9 percent) and Staphylococcus aureus (9 percent). Conclusions: A favorable answer with the initial empirical therapy was obtained for 48 percent of cases; meanwhile in the remaining episodes, 28 percent required antibiotics modifications without justification. This fact remarks the importance of following the established guidelines for antimicrobial treatment modification in these patients.

Introducción: En los niños con cáncer y netropenia febril (NF) de alto riesgo, se utiliza en nuestro centro hace 5 años, como esquema empírico inicial, la asociación de ceftazidima-amikacina-cloxacilina. No hay literatura nacional que analice la eficacia de este esquema. Objetivo: Evaluar la eficacia clínica y microbiológica de la asociación de ceftazidima, amikacina y cloxacilina en niños con NF de alto riesgo. Método: Protocolo descriptivo, prospectivo. Evaluar niños con NF de alto riesgo hospitalizados en el HLCM entre enero 2005 y agosto 2006. Resultados: 100 episodios de NF de alto riesgo. El tratamiento antimicrobiano fue considerado eficaz en 48 por ciento de los casos, y requirió ajustes en 52 por ciento de los casos. En 13 por ciento se cambia tratamiento sin justificación y en 15 por ciento se realiza antes de 72 horas de iniciado el tratamiento antimicrobiano. Foco mßs frecuente fue: ausencia de foco clínico 51 por ciento, presentando sepsis 13 por ciento de los niños. Hubo identificación microbiológica en 36 por ciento, microorganismos mßs frecuentemente aislados Echerichia coli (9 por ciento) y Staphylococcus aureus (9 por ciento). Conclusiones: Se obtuvo una respuesta favorable de 48 por ciento con el esquema antimicrobiano empírico inicial, de el 52 por ciento restante, en un 28 por ciento se efectúan cambios de antibióticos no justificados, esto recalca la importancia de seguir las pautas ya establecidas para cambio de esquema antimicrobiano en estos pacientes.

Percepciones, actitudes y conductas de médicos gineco-obstetras, respecto al uso actual de terapia de reemlazo hormonal / Perceptions, attitudes, and behavior of obstetrician-gynecologists for the use of hormonal replacement therapy

Resultados de una encuesta con preguntas específicas contestadas por el 97,6 por ciento de los gineco-obstetras del Departamento de Obstetricia y Ginecología de Clínica Alemana de Santiago, para establecer un diagnóstico de situación sobre el uso de terapia de reemplazo hormonal (TRH). Se enfatizan preguntas sobre la aceptabilidad de las futuras usuarias tanto de TRH como de terapias alternativas; sobre la percepción de los eventuales beneficios desde un punto de vista general, o específicamente cardiovascular; así como las preferencias de hormonas a usar y predilecciones por las vías de administración; las asociaciones del uso y cáncer mamario; las variaciones sobre el uso de TRH pos publicación del Women Health Iniciative Study; los factores que inciden en la discontinuación del tratamiento; la importancia de edad para el uso, factores relacionados con los costos de las terapias y la preferencia o no de productos originales de investigación. Conclusión: Es necesaria una mayor capacitación sobre el uso de TRH en la actualidad tanto de los ginecólogos especialistas en climaterio y menopausia, como de los que no lo son. A falta de información concluyente sobre esta temática en el momento actual se sugiere que el manejo de este tipo de pacientes sea efectuado por los equipos médicos especializados.

In order to set a diagnosis about the use of hormonal replacement therapy (HRT) in peri and postmenopausal women by the obstetricians and gynecologists members of our staff, we did a survey that was answered by 97.6 percent of them. Questions about the future patients desire related to use of HRT or use of natural or alternative medicines were included. There were also questions related to the "risk-benefit" relationship on the use of HRT from an overall point of view as well as from a cardiovascular point of view. The preference of medical doctors (MD) on choice of hormone type in HRT use, in respect to the administration, were also asked. Among others, questions were asked in order to know MD opinions on the relationship with breast cancer, the changes on acceptability use after the WHI study, reasons for the treatment discontinuation, the importance of women's age and the cost of pharmaceuticals produces on HRT use. Conclusions: Are focused on a need of a solid educational program on use of HRT addressed to gynecologists, as well as to general practitioners, cardiologists, oncologists and others related. Educational programs are also quite beneficial to future users as well as women that are currently under treatment. In the absence of conclusive information available at the present moment, we advise that patients considering HRT should seek the counsel of medical teams whose specialties include menopause.

Levonorgestrel pharmacokinetics in plasma and milk of lactating women who take 1.5 mg for emergency contraception.

BACKGROUND: Progestin-only methods are among the contraceptive options available for breastfeeding women, however the doses of progestin used in emergency contraception (EC) have not been evaluated in nursing mothers. We therefore investigated the pharmacokinetics of 1.5 mg levonorgestrel (LNG) in lactating women. METHODS: Twelve healthy exclusively breastfeeding volunteers received 1.5 mg LNG. Women refrained from nursing for 72 h after dosing and fed their infants with milk frozen beforehand. Serial blood and milk samples were collected for 120 h and assayed for LNG and sex hormone binding globulin. RESULTS: LNG concentrations peaked in plasma and in milk 1-4 h and 2-4 h after dosing, respectively. Concentrations in milk (M) paralleled those in plasma (P) but were consistently lower (mean M:P ratio 0.28). Estimated infant exposure to LNG is 1.6 microg on the day of dosing (1 microg in the first 8 h), 0.3 microg on the second day and 0.2 microg on the third day. CONCLUSIONS: Nursing mothers may need EC. These results suggest that to limit infant exposure to the period of maximum LNG excretion in milk, mothers should discontinue nursing for at least 8 h, but not more than 24 h, after EC.

Diagnóstico precoz del cáncer infantil / Early diagnosis of infant neoplasms

El cáncer es una enfermedad rara en pediatría. Para Chile, se estiman 500 casos nuevos por año. A pesar de su baja frecuencia, esta patología tiene gran impacto, ya que es la segunda causa de muerte en el grupo entre los cinco a 15 años, precedida sólo por accidentes. Con los protocolos actuales de tratamiento, aproximadamente el 65 por ciento de los niños en nuestro país se cura de cáncer según última revisión de octubre 2004. Para mejorar estas cifras y tener menos secuelas es fundamental el diagnóstico precoz. Esto es difícil por la baja frecuencia de esta patología, lo que incide en un bajo índice de sospecha por parte del médico, y porque el 85 por ciento de los cánceres infantiles se presentan con signos y síntomas inespecíficos. Ante la sospecha de cáncer en un niño se debe realizar anamnesis y examen físico completo, consignando hechos destacados. No se debe demorar la derivación realizando exámenes sofisticados.

Uso de expansores cutáneos en Cirugía Plástica Pediátrica / Use of cutaneous expanders in Pediatric Plastic Surgery

Los expansores cutáneos son una valiosa herramienta terapéutica en Cirugía Plástica. Esta técnica permite obtener una cobertura cutánea de color y textura similar a la piel adyacente, con baja morbilidad del área donante, en comparación con otras alternativas. Sin embargo, es un procedimiento por etapas y no está exento de complicaciones que pueden minimizarse mediante una meticulosa planificación y ejecución, única forma en la que la calidad de los resultados justifica su empleo. La mayor parte de las publicaciones hacen referencia a su uso en adultos, por lo que se consideró de interés presentar la experiencia la de la Unidad de Cirugía Plástica del Hospital Clínico de Niños Dr Roberto del Río (Chile), con 32 pacientes pediátricos en los que se realizaron un total de 48 expansiones cutáneas. Se analizan las indicaciones, resultados y complicaciones de la técnica, comparando los resultados con otros descritos en la literatura al respecto (AU)

The cutaneous expansion is a valuable therapeutic tool in Plastic Surgery. In comparison with other alternative, this technique allows to obtain a cutaneous covering of similar color and texture to the adjacent skin, with low donor site morbidity. However, it is a procedure in stages and don’t exempt of complications. These could minimize by means of a meticulous planning and execution, only way in which the quality of the results justifies their employment. Most of the publications make reference to their use in adults, for these reason we considered of interest present the experience of the Unit of Plastic Surgery of the Hospital Clínico de Niños Dr Roberto del Río (Chile), with 32 patients in which was carried out a total of 48 cutaneous expansions. Indications, results and complications of the technique are analysed, comparing with literature (AU)

Inyección de sustancias esclerosantes vasculares en el manejo de lesiones vasculares orbitarias / Injection of vascular sclerosing agent in the treatment of orbital vascular lesions

Objetivo: Evaluar el efecto de la inyección de espuma de polidocanol como sustancia esclerosante vascular en la reducción del tamaño de hemangiomas y linfangiomas orbitarios. Material y Métodos: Estudios prospectivo intervencional de 2 casos con diagnóstico de hemangioma capilar, 7 casos de linfangioma de la región orbitaria y 1 malformación vascular superficial preseptal, que recibieron una o más inyecciones de polidocanol intralesional. Se evaluaron el tipo de tumor, disminución de su tamaño, variación de ptosis palpebral, proptosis y presencia de complicaciones con el procedimiento. Resultados: Se realizaron 4,5 inyecciones promedio con una dosificación final de 0,6 cc al 0,5 por ciento de polidocanol. El seguimiento promedio fue 16,2 meses. Todos los pacientes redujeron el tamaño de la lesión significativamente. La principal complicación fue dolor postinyección. Conclusiones: El uso de inyecciones de polidocanol en el tratamiento de hemangiomas capilares y linfangiomas orbitarios sería una alternativa novedosa y efectiva para reducir el tamaño de las lesiones sin mayores complicaciones.

Curación de mucormicosis rinocerebral en un paciente pediátrico con leucemia activa / Rhinocerebral mucormycosis healing in a pediatric patient with active leukemia

Un paciente de 14 años, portador de leucemia linfoblástica aguda desarrolló una sinusitis subaguda con manifestaciones neurológicas. Mediante biopsia de mucosa nasal y resonancia magnética cerebral se diagnosticó una mucormicosis rinocerebral y basado en un teórico mal pronóstico se decidió efectuar tratamiento conservador: cirugía funcional de la sinusitis y terapia prolongada con anfotericina B deoxicolato completando tras 8,8 meses, 7.700 mg del fármaco. La quimioterapia de la leucemia fue reanudada durante el tratamiento antifúngico alcanzando la remisión oncológica. Tras 31 meses de seguimiento, el paciente está asintomático pero recayó de la leucemia.