Distinctive patterns of placental lesions in pre-eclampsia vs small-for-gestational age and their association with fetoplacental Doppler.

OBJECTIVES: To describe placental histopathological findings in a large cohort of pregnancies complicated by pre-eclampsia (PE) and/or small-for-gestational age (SGA), and to investigate their association with fetoplacental Doppler parameters. METHODS: This was a prospective observational study of normotensive pregnancies with SGA (defined as birth weight < 10th centile) (n = 184), PE pregnancies with a normally grown fetus (n = 102), pregnancies with both PE and SGA (n = 120) and uncomplicated pregnancies (n = 202). Uterine (UtA), umbilical (UA) and fetal middle cerebral (MCA) artery pulsatility indices (PI) were assessed. The cerebroplacental ratio (CPR) was calculated by dividing MCA-PI by UA-PI. Doppler parameters were considered abnormal when UtA-PI or UA-PI was > 95th centile or MCA-PI or CPR was < 5th centile. Placental lesions were categorized as vascular (maternal or fetal side), immunoinflammatory or other, according to the 2014 Amsterdam Placental Workshop Group Consensus Statement. Comparison between the study groups was performed using univariate and multiple regression analysis, and logistic regression was used to determine the relationship between abnormal Doppler parameters and placental lesions. RESULTS: Maternal-side vascular lesions were significantly more common in PE pregnancies with SGA than in the other groups (PE + SGA, 73% vs PE, 46% vs SGA, 38% vs controls, 31%; P = 0.01) and included mainly two types of lesion: developmental (PE + SGA, 13% vs PE, 5% vs SGA, 3% vs controls, 1.5%; P < 0.001) and malperfusion (PE + SGA, 70% vs PE, 39% vs SGA, 32% vs controls, 25%; P = 0.001). In contrast, the incidence of fetal-side developmental lesions was significantly higher in normotensive SGA pregnancies than in controls and PE pregnancies (PE + SGA, 0% vs PE, 3% vs SGA, 8% vs controls, 2%; P = 0.001). All cases displayed a lower prevalence of infectious lesions than did controls, with the highest prevalence of immune lesions observed in pregnancies with both PE and SGA (PE + SGA, 18% vs PE, 8% vs SGA, 10% vs controls, 9%; P = 0.001). All fetoplacental Doppler parameters evaluated were associated with maternal-side vascular lesions, mainly malperfusion (mean UtA-PI: odds ratio (OR), 2.45 (95% CI, 1.51-3.97); UA-PI: OR, 2.05 (95% CI, 1.02-4.47); MCA-PI: OR, 2.75 (95% CI, 1.40-5.42); CPR: OR, 1.75 (95% CI, 1.04-2.95)). This association was evident mainly in the normotensive SGA group, being non-significant in controls or PE pregnancies without SGA. No significant associations were observed between fetoplacental Doppler parameters and other placental lesions in any of the study groups. CONCLUSIONS: PE and SGA are associated with different patterns of placental histopathological lesions in accordance with the clinical manifestation of the placental disorder (maternal vs fetal). Fetoplacental Doppler findings show an association with placental malperfusion lesions on the maternal side, supporting the use of abnormal Doppler as a surrogate for placental insufficiency. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Premature placental aging in term small-for-gestational-age and growth-restricted fetuses.

OBJECTIVE: To perform a comprehensive assessment of the placental aging process in small term fetuses classified as being small-for-gestational age (SGA) or having fetal growth restriction (FGR) through analysis of senescence and apoptosis markers. METHODS: This was a prospective nested case-control study of singleton pregnancies delivered at term, including 21 control pregnancies with normally grown fetuses and 36 with a small fetus classified as SGA (birth weight between the 3rd and 9th percentiles and normal fetoplacental Doppler; n = 18) or FGR (birth weight < 3rd percentile and/or abnormal cerebroplacental ratio and/or uterine artery Doppler; n = 18). Telomerase activity, telomere length (quantified by comparing the amount of amplification product for the telomere sequence (T) to that of a single copy of the gene 36B4 (S)) and RNA expression of senescence (Sirtuins 1, 3 and 6) and apoptosis (p53, p21, BAX and Caspases 3 and 9) markers (analyzed using the 2-ΔΔCt method) were determined in placental samples collected at birth and compared between the three groups. RESULTS: Compared to pregnancies with a normally grown fetus, both SGA and FGR pregnancies presented signs of accelerated placental aging, including lower telomerase activity (mean ± SD, 12.8 ± 6.6% in controls vs 7.98 ± 4.2% in SGA vs 7.79 ± 4.6% in FGR; P = 0.008), shorter telomeres (mean ± SD T/S ratio, 1.20 ± 0.6 in controls vs 1.08 ± 0.9 in SGA vs 0.66 ± 0.5 in FGR; P = 0.047) and reduced Sirtuin-1 RNA expression (mean ± SD 2-ΔΔCt , 1.55 ± 0.8 in controls vs 0.91 ± 0.8 in SGA vs 0.63 ± 0.5 in FGR; P = 0.001) together with increased p53 RNA expression (median (interquartile range) 2-ΔΔCt , 1.07 (0.3-3.3) in controls vs 5.39 (0.6-15) in SGA vs 3.75 (0.9-7.8) in FGR; P = 0.040). FGR cases presented signs of apoptosis, with increased Caspase-3 RNA levels (median (interquartile range) 2-ΔΔCt , 0.94 (0.7-1.7) in controls vs 3.98 (0.9-31) in FGR; P = 0.031) and Caspase-9 RNA levels (median (interquartile range) 2-ΔΔCt , 1.21 (0.6-4.0) in controls vs 3.87 (1.5-9.0) in FGR; P = 0.037) compared with controls. In addition, Sirtuin-1 RNA expression, telomerase activity, telomere length and Caspase-3 activity showed significant linear trends across groups as severity of the condition increased. CONCLUSIONS: Accelerated placental aging was observed in both clinical forms of late-onset fetal smallness (SGA and FGR), supporting a common pathophysiology and challenging the concept of SGA fetuses being constitutionally small. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Envejecimiento prematuro de la placenta en fetos pequeños para la edad gestacional y con restricción del crecimiento OBJETIVO: Realizar una evaluación integral del proceso de envejecimiento de la placenta en fetos a término clasificados como pequeños para la edad gestacional (PEG) o con restricción del crecimiento fetal (RCF) mediante el análisis de los marcadores de senescencia y apoptosis. MÉTODOS: Este fue un estudio prospectivo de casos y controles anidados de embarazos únicos a término, que incluyó 21 embarazos de control con fetos de crecimiento normal y 36 con un feto clasificado como PEG (peso al nacer entre los percentiles 3o y 9o y Doppler fetoplacentario normal; n=18) o con RCF (peso al nacer menor del percentil 3o y/o relación cerebroplacentaria anómala y/o Doppler de la arteria uterina; n=18). La actividad de la telomerasa, la longitud de los telómeros (cuantificada comparando la cantidad de producto de amplificación para la secuencia de telómeros (T) con la de una sola copia del gen 36B4 (S)) y la expresión del ARN de la senescencia (Sirtuinas 1, 3 y 6) y los marcadores de apoptosis (p53, p21, BAX y Caspasas 3 y 9) (analizados usando el método 2-∆∆Ct ) se determinaron en muestras de placenta obtenidas en el momento del nacimiento y se compararon entre los tres grupos. RESULTADOS: En comparación con los embarazos con un feto de crecimiento normal, tanto los embarazos PEG y con RCF presentaron signos de envejecimiento placentario acelerado, como una menor actividad de la telomerasa (media ± SD, 12,8 ± 6,6% en los controles frente a 7,98 ± 4,2% en PEG frente a 7,79 ± 4,6% en RCF; P=0,008), telómeros más cortos (media ± SD razón T/S, 1,20 ± 0,6 en los controles frente a 1,08 ± 0,9 en PEG frente a 0,66 ± 0,5 en RCF; P=0,047) y expresión reducida de la Sirtuina 1 en el ARN (media ± SD 2-∆∆Ct , 1,55 ± 0,8 en los controles frente a 0,91 ± 0,8 en PEG frente a 0,63 ± 0,5 en RCF; P=0,001), junto con una mayor expresión del p53 en el ARN (mediana (rango intercuartil) 2-∆∆Ct , 1,07 (0,3-3,3) en los controles frente a 5,39 (0,6-15) en PEG frente a 3,75 (0,9-7,8) en RCF; P=0,040). Los casos de RCF presentaron signos de apoptosis, con un aumento de los niveles en ARN de la Caspasa 3 (mediana (rango intercuartil) 2-∆∆Ct , 0,94 (0,7-1,7) en los controles frente a 3,98 (0,9-31) en RCF; P=0,031) y Caspasa 9 (mediana (rango intercuartil) 2-∆∆Ct , 1,21 (0,6-4,0) en los controles frente a 3,87 (1,5-9,0) en RCF; P=0,037) en comparación con los controles. Además, la expresión de la Sirtuina 1 en el ARN, la actividad de la telomerasa, la longitud de los telómeros y la actividad de la Caspasa 3 mostraron tendencias lineales significativas entre los grupos en función del aumento de la severidad de la anomalía. CONCLUSIONES: Se observó un envejecimiento acelerado de la placenta en ambas formas clínicas de tamaño pequeño del feto de inicio tardío (PEG y RCF), lo que apoya una fisiopatología común y pone en tela de juicio el concepto de que los fetos PEG son en pequeños por su propia condición.

Anal canal duplication and triplication: a rare entity with different presentations.

Anal canal duplication (ACD) is the rarest of gastrointestinal duplications. Few cases have been reported. Most cases present as an opening in the midline, posterior to the normal anus. The aim of our revision is to contribute with eight new cases, some of them with unusual presentations: five presented as the typical form, one with a perianal nodule, and two presented as two separate orifices (anal canal triplication). Complete excision was performed in all patients with no complications. ACD is the most distal and the least frequent digestive duplication. Its treatment should be surgical excision, to avoid complications such as abscess, fistulization, or malignization. Anal canal triplication has never been described before.

Infratentorial congenital glioblastoma multiforme. A rare tumour with a still unknown biology. / Glioblastoma multiforme congenito infratentorial. Un tumor excepcional con una biologia aun desconocida.

INTRODUCTION: Congenital glioblastoma multiforme represents only 3% of congenital central nervous system tumours and an infratentorial location is unusual. CASE REPORT: A newborn with congenital glioblastoma multiforme with no mutation in the TP53 gene or p53 nuclear immunoreactivity that infiltrated practically the whole brainstem and also invaded supratentorial structures. CONCLUSIONS: As far as we know, only four cases with an infratentorial location have been reported previously, three in the cerebellum and one in the brainstem. The biology of congenital glioblastoma multiforme is not well known and, unlike glioblastoma multiforme in adults and children, mutations in the TP53 gene are uncommon. However, this is not associated with a more favourable prognosis. These observations suggest that specific biological processes underlie fetal glioblastoma multiforme development.

TITLE: Glioblastoma multiforme congenito infratentorial. Un tumor excepcional con una biologia aun desconocida.Introduccion. El glioblastoma multiforme congenito representa solo el 3% de los tumores congenitos del sistema nervioso central, y su ubicacion infrantentorial es excepcional. Caso clinico. Recien nacido con un glioblastoma multiforme congenito sin mutacion en el gen TP53 ni inmunorreactividad nuclear p53, que infiltraba practicamente todo el tronco cerebral e invadia tambien estructuras supratentoriales. Conclusiones. Hasta donde sabemos, solo se han referido previamente cuatro casos de localizacion infratentorial, tres en el cerebelo y uno en el tronco del encefalo. La biologia del glioblastoma multiforme congenito no se conoce bien y, a diferencia del glioblastoma multiforme en la edad adulta, las mutaciones en el gen TP53 son poco frecuentes, sin que eso parezca implicar un mejor pronostico. Estas observaciones sugieren que el glioblastoma multiforme con origen en la vida fetal tiene una biologia diferente del que se presenta en otras etapas de la vida.

Enzymatic Cleavage of Glycosidic Bonds: Strategies on How to Set Up and Control a QM/MM Metadynamics Simulation.

Carbohydrates play crucial roles in many biological processes, from cell-cell adhesion to chemical signaling. Their complexity and diversity, related to α/ß anomeric configuration, ring substituents, and conformational variations, require a diverse set of enzymes for their processing. Among them, glycoside hydrolases (GHs) are responsible for the hydrolysis of one of the strongest bonds in nature: the glycosidic bond. These highly specialized biological catalysts select particular conformations their carbohydrate substrates to enhance catalysis. The evolution of this conformation during the reaction of glycosidic bond cleavage, known as the conformational catalytic itinerary, is of fundamental interest in glycobiology, with impact on inhibitor and drug design. Here we review some of the aspects and the main strategies one needs to take into account when simulating a reaction in a GH enzyme using QM/MM metadynamics. Several specific aspects are highlighted, from the importance of the distortion of the substrate at the Michaelis complex to the variable control during the metadynamics simulation or the analysis of the reaction mechanism and conformational itinerary. The increasing speed of computer power and methodological advances have added a vital tool to the study of GH mechanisms, as shown here and recent reviews. It is hoped that this chapter will serve as a first guide for those attempting to perform a metadynamics simulation of these relevant and fascinating enzymes.

Exchange Coupling Inversion in a High-Spin Organic Triradical Molecule.

The magnetic properties of a nanoscale system are inextricably linked to its local environment. In adatoms on surfaces and inorganic layered structures, the exchange interactions result from the relative lattice positions, layer thicknesses, and other environmental parameters. Here, we report on a sample-dependent sign inversion of the magnetic exchange coupling between the three unpaired spins of an organic triradical molecule embedded in a three-terminal device. This ferro-to-antiferromagnetic transition is due to structural distortions and results in a high-to-low spin ground-state change in a molecule traditionally considered to be a robust high-spin quartet. Moreover, the flexibility of the molecule yields an in situ electric tunability of the exchange coupling via the gate electrode. These findings open a route to the controlled reversal of the magnetic states in organic molecule-based nanodevices by mechanical means, electrical gating, or chemical tailoring.

Are French general practitioners consulted before travel to developing countries? A cross-sectional study conducted in a French airport.

BACKGROUND: General practitioners (GPs) could play a central role in preventing travel-related health issues. The aim of this study was to assess, in travellers departing to developing countries from a French airport, the proportion of individuals having sought GP counseling before departure and to identify determinants for having consulted a GP. METHODS: Cross-sectional study conducted between November 2012 and July 2013, in all adults living in France. Sociodemographic, health characteristics, type of travel and resources consulted before departure were collected. A descriptive analysis was performed. Determinants for having consulted a GP before departure were investigated using a logistic regression analysis. RESULTS: Of the 360 travellers included, 230 (64%) sought health counseling before departure. GPs were the main source of information for 134 (58%) travellers having sought health information and the only one for 49 (21%). Almost half of the travellers (48%) departing to sub-Saharan countries did not seek health counseling from a medical doctor (GP, non-GP specialist, specialist consulted in an international vaccination center or occupational physician). Individuals significantly more likely to travel without having consulted a GP were young and male, held foreign nationality, had travelled more than five times before, rarely consulted their GP and were travelling to a non-malarious area. CONCLUSION: GPs were the main but not the only source of information and counseling before traveling to a developing country. This study helps identify the characteristics of individuals likely to travel without having consulted a GP before departure.

[Surgical treatment of giant congenital melanocytic nevi: a change of aim]. / Tratamiento quirúrgico del nevus melanocítico gigante: un cambio de objetivo.

OBJECTIVE: To review the surgical experience in Giant Congenital Melanocytic Nevi (GCMN). MATERIAL AND METHODS: Review of GCMN cases consulting at the Department of Pediatric Surgery since 1994. Data registered were: year and age at 1st consultation, type of treatment, number of surgical procedures and complications, histology, central nervous system MRI and follow-up. RESULTS: Eleven patients with GCMN > 10% of body surface consulted at ages ranging from newborn to 8 years. All of them had multiple surgical procedures (2-19), from nevus removal to only biopsies. Eight patients had tissue expansion, completed in 3 of them with skin grafts on dermal substitute. Six patients had complications: 4 expander extrusions, 5 infections, 3 flap necrosis and 1 dehiscence. In 6 children a total or subtotal resection of the nevus was achieved; in 2 the treatment was interrupted, remaining 20% and 50% of the initial nevus; three patients had not had nevus treatment. None of the patients presented cutaneous melanoma; one died from intracranial melanoma; another one has leptomeningeal melanosis. The first 4 patients underwent an average of 16 surgical procedures each, the last 7 patients only 5. CONCLUSIONS: The aim of GCNM management has changed: GCNM treatment is now surgically conservative. Complete excision is now not the aim when technically unfeasible in few procedures; multiple surgical procedures with poor cosmetical results are not acceptable. The gravity is determined by CNS involvement.

Tratamiento quirúrgico del nevus melanocítico gigante: un cambio de objetivo / Surgical treatment of giant congenital melanocytic nevi: a change of aim

Objetivo. Revisión de la experiencia quirúrgica en Nevus Melanocítico Gigante Congénito (NMGC).Material y métodos. Revisión de los casos de NMGC que consultarona cirugía pediátrica desde 1994, recogiendo: año y edad en la 1ªconsulta, tipo de tratamiento, número de intervenciones, complicaciones, histología, RM de SNC y evolución. Resultados. Once pacientes con NMGC >10% de la superficie corporal consultaron entre el nacimiento y los 8 años y fueron sometidos a alguna intervención (2 a 19), desde exéresis hasta sólo biopsias. En 8 niños se utilizaron expansores y plastias, y en 3 de ellos injertos de piel sobre sustituto dérmico; en 6 hubo complicaciones: 4 extrusiones, 5 infecciones,3 necrosis de colgajo y 1 dehiscencia. En 6 niños se consiguió la exéresis total o subtotal del nevus, en 2 se ha interrumpido el tratamiento, quedando 20% y 50% del nevus; tres niños no se trataron del NMGC. Ningún paciente ha presentado melanoma cutáneo; uno falleció de melanoma intracraneal y otro presenta melanosis leptomeníngea. La media de intervenciones de los 4 primeros pacientes fue de 16 y en los 7 últimos fue de 5.Conclusiones. Los objetivos del tratamiento han variado: el tratamiento del NMGC es quirúrgicamente más conservador; las exéresis completas ya no se indican si no son técnicamente posibles en pocos pasos; no es aceptable un resultado cosmético inadecuado tras una infancia lastrada por múltiples intervenciones. La gravedad la confiere la afectación del SNC

Objective. To review the surgical experience in Giant Congenital Melanocytic Nevi (GCMN).Material and Methods. Review of GCMN cases consulting at the Department of Pediatric Surgery since 1994. Data registered were: year and age at 1st consultation, type of treatment, number of surgical procedures and complications, histology, central nervous system MRI and follow-up. Results. Eleven patients with GCMN >10% of body surface consulted at ages ranging from newborn to 8 years. All of them had multiple surgical procedures (2-19), from nevus removal to only biopsies. Eight patients had tissue expansion, completed in 3 of them with skin grafts on dermal substitute. Six patients had complications: 4 expander extrusions, 5 infections, 3 flap necrosis and 1 dehiscence. In 6 children a total or subtotal resection of the nevus was achieved; in 2 the treatment was interrupted, remaining 20% and 50% of the initial nevus; three patients had not had nevus treatment. None of the patients presented cutaneous melanoma; one died from intracranial melanoma; another one has leptomeningeal melanosis. The first 4 patients underwent an average of 16 surgical procedures each, the last 7 patients only 5. Conclusions. The aim of GCNM management has changed: GCNM treatment is now surgically conservative. Complete excision is now not the aim when technically unfeasible in few procedures; multiple surgical procedures with poor cosmetical results are not acceptable. The gravity is determined by CNS involvement

Surface-confined electroactive molecules for multistate charge storage information.

Bi-stable molecular systems with potential for applications in binary memory devices are raising great interest for device miniaturization. Particular appealing are those systems that operate with electrical inputs since they are compatible with existing electronic technologies. The processing of higher memory densities in these devices could be accomplished by increasing the number of memory states in each cell, although this strategy has not been much explored yet. Here we highlight the recent advances devoted to the fabrication of charge-storage molecular surface-confined devices exhibiting multiple states. Mainly, this goal has been realized immobilizing a variety (or a combination) of electroactive molecules on a surface, although alternative approaches employing non-electroactive systems have also been described. Undoubtedly, the use of molecules with chemically tunable properties and nanoscale dimensions are raising great hopes for the devices of the future in which molecules can bring new perspectives such as multistability.

An analysis of a stochastic model for bacteriophage systems.

In this article, we analyze a system modeling bacteriophage treatments for infections in a noisy context. In the small noise regime, we show that after a reasonable amount of time the system is close to a bacteria free equilibrium (which is a relevant biologic information) with high probability. Mathematically speaking, our study hinges on concentration techniques for delayed stochastic differential equations.

Facial telangiectasia: an unusual manifestation of neonatal lupus erythematosus.

Neonatal lupus erythematosus (NLE) is an uncommon condition usually associated with maternal anti-Ro autoantibodies. The cutaneous lesions of NLE are usually transient, disappearing about six months after birth, but telangiectasia is a rare complication of NLE which persists. Telangiectasias are small focal red macules and papules created by abnormally prominent capillaries, venules, and arterioles and are a characteristic marker of connective tissue diseases. We report the case of an infant diagnosed with NLE presenting typical annular lesions, positive ANA and positive anti-Ro antibodies. By five months of age, both ANA and anti-Ro antibodies were negative and the annular cutaneous lesions had gradually faded, but small scattered focal red macules appeared on the face, especially in the peri-orbital area and scalp. The cutaneous lupus disappeared but the telangiectasia persisted. We would like to suggest that the diagnosis of NLE should be considered when cutaneous telangiectasias are observed in infants.

Proton transfer drives protein radical formation in Helicobacter pylori catalase but not in Penicillium vitale catalase.

Heme catalases prevent cells from oxidative damage by decomposing hydrogen peroxide into water and molecular oxygen. Here we investigate the factors that give rise to an undesirable side reaction competing with normal catalase activity, the migration of a radical from the heme active site to the protein in the principal reaction intermediate compound I (Cpd I). Recently, it has been proposed that this electron transfer reaction takes place in Cpd I of Helicobacter pylori catalase (HPC), but not in Cpd I of Penicillium vitale catalase (PVC), where the oxidation equivalent remains located on the heme active site. Unraveling the factors determining the different radical locations could help engineer enzymes with enhanced catalase activity for detection or removal of hydrogen peroxide. Using quantum mechanics/molecular mechanics metadynamics simulations, we show that radical migration in HPC is facilitated by the large driving force (-0.65 eV) of the subsequent proton transfer from a histidine residue to the ferryl oxygen atom of reduced Cpd I. The corresponding free energy in PVC is significantly smaller (-0.19 eV) and, as we argue, not sufficiently high to support radical migration. Our results suggest that the energetics of oxoferryl protonation is a key factor regulating radical migration in catalases and possibly also in hydroperoxidases.

Early detection of age-related memory deficits in individual mice.

To date, no consensus has been reached concerning the age of the earliest onset of age-related cognitive deficits in rodents. Our aim was to develop a behavioral model allowing early and individual detection of age-related cognitive impairments. We tested young (3 months), middle-aged (10 months) and aged (17 months) C57Bl/6 mice in the starmaze, a task allowing precise analysis of the search pattern of mice via standardized calculation of two navigation indices. We performed mouse-per-mouse analyses and compared each mouse's performance to a threshold based on young mice's performances. Using this method we identified impaired mice from the age of 10 months old. Their deficits were independent of any sensorimotor dysfunctions and were associated with an alteration of the maintenance of the hippocampal CA1 late-LTP. This study develops reliable methodology for early detection of age-related memory disorders and provides evidence that memory can decline in some individuals as early as from the age of 10 months.

Niveles séricos de factor de necrosis tumoral-α e interferón-γ en pacientes con dengue febril / Serum levels of tumor necrosis factor-α and interferon-γ in patients with dengue

Los monocitos/macrófagos constituyen las células diana para el virus dengue, activando linfocitos T, liberando citoquinas proinflamatorias como el Factor de Necrosis Tumoral alfa e Interferón gamma. El objetivo del estudio fue determinar TNF-α e IFN-γ en suero de pacientes dengue IgM positivo e IgM negativo, que concurrieron al Instituto de Investigaciones en Ciencias de la Salud, de febrero a abril 2007. Se realizó un estudio analítico en 163 sueros de pacientes con dengue, 143 IgM positivo y 20 IgM negativo, de ambos sexos con edad promedio de 30 y rango entre 18 a 70 años. El anticuerpo IgM para dengue y las citoquinas fueron determinados por ELISA de captura. En los 143 sueros dengue IgM positivo, el IFN-γ se detectó en 73% (104/143) con valores entre 558 y superiores a 2000 pg/ml y en el 27% (39/143) valores por debajo del punto de corte. Se encontró una diferencia estadísticamente significativa comparado con sueros dengue IgM negativo (p = < 0.005). El TNF-α se detectó en 24% (35/143) sueros IgM positivo, de los cuales 33 presentaron valores entre 45 a 176 pg/ml y 2 con valores superiores a 2000 pg/ml. No hubo significancia estadística comparando con sueros dengue IgM negativo (p = 0.26). Niveles elevados de IFN-γ y TNF-α podrían ser considerados marcadores de pronóstico para la progresión al dengue hemorrágico. Se debería tener en cuenta la potencial significancia terapéutica de estas citoquinas que podrían ayudar en las estrategias de inhibir o inducir perfiles de citoquinas adecuadas en respuesta al dengue.

Monocytes/macrophages are target cells for dengue virus, taking part in the activation of T lymphocytes, releasing proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). The objective of this study was to determine TNF-α and IFN-γ in sera of dengue patients with IgM positive and negative who attended the Instituto de Investigaciones en Ciencias de la Salud from February to April 2007. An analytical study was performed in 163 sera of dengue patients, 143 IgM positive and 20 IgM negative, men and women with an mean age of 30 years and a range from 18 to 70 years. The IgM antibody for dengue and the serum levels of cytokines were performed by capture ELISA. Serum levels of IFN-γ were detected in 73% (104/143) of the patients with dengue IgM positive, with values between 558 and higher than 2000 pg/ml, and in 27% (39/143) were below the cut-off value. A statistically significative difference was found when they were compared with dengue IgM negative sera (p=<0.005). TNF-α serum levels were detected in 24% (35/143) of the dengue IgM positive patients, 33 patients presented values between 45 and 176 pg/ml and 2 had values above 2000 pg/ml. No statistical significance was found when these values were compared with those of dengue IgM negative sera (p=0.26). IFN-γ and TNF-α high levels could be considered prognostic markers for progression to hemorrhagic dengue. The potential therapeutic significance of these cytokines should be considered as they could help in the strategies to inhibit or induce appropriate cytokine profiles in response to dengue virus.

Frecuencia de los patrones de anticuerpos anti-nucleares en pacientes con sospecha clínica de LES / Frequency of antinuclear antibody patterns in patients with SLE clinical suspicion

Las enfermedades autoinmunes son alteraciones de los mecanismos de tolerancia inmunológica, con producción de anticuerpos contra antígenos propios, como los anticuerpos antinucleares (ANA), que detectados por inmunofluorescencia indirecta,permiten reconocer varios patrones nucleares y citoplasmáticos, como en el Lupus Eritematoso Sistémico (LES). El objetivo del estudio fue describir los patrones de tinciónde ANA en sueros de pacientes con sospecha clínica de LES, que concurrieron al Instituto de Investigaciones en Ciencias de la Salud, durante el año 2008. En este estudio observacional descriptivo, se analizaron 150 sueros positivos para ANA, codificados,respetando la confidencialidad de los mismos. Para la determinación de ANA se utilizaron láminas con células HEp-2 (BIO-RAD-USA), y el conjugado fue anti human IgG de Sigma(USA); la técnica fue inmunofluorescencia indirecta. Del total de 150 pacientes estudiados, 134 (89%) fueron mujeres y 16 (11%) hombres, cuyas edades estaban comprendidas entre 11 y 87 años. De los sueros positivos analizados para ANA, 44 (29%)correspondieron al patrón periférico, 18(12%) puntillado grueso, 39(26%) puntillado fino,42(28%) homogéneo, 5(3%) nucleolar y 2(1.3%) citoplásmico puntillado fino. En este estudio se encontró en mayor porcentaje el patrón periférico, seguido del homogéneo y puntillado fino, los cuales se hallan asociados a pacientes con LES, indicando un pronóstico poco favorable para estos pacientes.

Autoimmune diseases are alterations of the immunological tolerance mechanisms, with production of antibodies against self-antigens, such as antinuclear antibodies (ANA), which are detected by indirect immunofluorescence, and allow the recognition of several nuclear and cytoplasmic patterns, as shown in the systemic lupus erythematosus (SLE).The objective of this study was to describe the ANA staining patterns in sera of patients with clinical suspicion of SLE that attended the Instituto de Investigaciones en Ciencias de la Salud during 2008. In this descriptive observational study, 150 coded positive ANA sera were analyzed, respecting the confidentiality of patients. ANA determination was made by indirect immunofluorescence using slides with HEp-2 cells (BIO-RAD-USA) and aantihuman-IgG-fluorescein conjugate from Sigma (USA). Of the 150 studied patients, 134 (89%) were females and 16 (11%) males with ages between 11 and 87 years. Of the ANA positive sera analyzed, 44 (29%) showed peripheral patterns, 18 (12%) coarse speckled patterns, 39 (26%) fine speckled patterns, 42 (28%) homogeneous patterns, 5 (3%) nucleolar patterns and 2 (1.3%) fine speckled cytoplasmic patterns. In this study, the peripheral pattern was found in greater percentage, followed by homogeneous and fine speckled patterns, which are associated to patients with SLE, indicating an unfavorable prognosis for these patients.

Granulosa cell tumor and endometrial cancer: a case report and review of the literature.

Granulosa cell tumors (GCTs) of the ovary are an uncommon type of ovarian cancer, representing only 2-5%. Frequently, their tumoral cells present some features of normal granulosa cells, like hormonal production. As a consequence, this neoplasia can be diagnosed either by common ovarian cancer symptoms or endometrial pathologies due to an estrogenic effect. Symptoms caused by estrogen production can also give rise to different clinical manifestations depending on whether they appear in postmenopausal or young women. In the case we present below, a patient was referred for presenting postmenopausal bleeding of one year's duration. Once endometrial cancer was diagnosed and subsequently staged, an ovarian mass was detected. We report an atypical case of ovarian cancer with the aim of reviewing the clinical features of GCT, as well as its prognosis, treatment and follow-up recommendations, according to the available literature.

Niveles séricos de inmunoglobulinas en niños con infecciones a repetición / Serum immunoglobulin levels in children with recurrent infections

Las infecciones a repetición en niños, se deben generalmente a trastornos en la inmunidad humoral. El objetivo del trabajo fue evaluar los niveles séricos de inmunoglobulinas en niños con infecciones a repetición. Se incluyeron 17 niños (6 mujeres y 11 varones), con una edad promedio de 5 años (0 a 14 años), en el periodo comprendido de marzo de 2006 a julio de 2007. Previo consentimiento de los padres, se recolectaron los datos en una ficha y se tomaron las muestras de sangre. La determinación del nivel de inmunoglobulina se realizó por los métodos de Inmunodifusión radial y quimioluminiscencia. Las neumonías fueron las infecciones referidas más frecuentes. Se encontraron niveles de IgA < 5 mg/dl en 2 pacientes (12 %); IgG < 400 mg/dl en 2 pacientes (12 %); IgM > 250 mg/dl en 11 pacientes (64,7 %) y niveles de IgE > 91 mg/dl en 13 pacientes (77 %). En esta serie de 17 pacientes con infecciones a repetición se ha encontrado dos pacientes (12%), con diagnóstico de Inmunodeficiencia primaria con déficit de IgG. La evaluación del estado inmunológico de los pacientes con infecciones a repetición es de gran importancia, porque contribuye al diagnóstico precoz que mejora el pronóstico y previene de posibles complicaciones a los pacientes.

Recurrent infections in children are usually due to humoral immunity disorders. Our objective was to determine serum immunoglobulin levels in children with recurrent infections. We included 17 children (six females and 11 males) with an average age of 5 years (0-14 years) during the period of March 2006 to July 2007. After parental consent, we recorded their data on a chart and took blood samples. Determination of immunoglobulin levels was done by radial immunodiffusion and chemiluminescence. Pneumonia was the most frequently reported type of infection. IgA levels found were <5 mg/dl in 2 patients (12%); IgG <400 mg/dl in 2 patients (12%); IgM >250 mg/dl in 11 patients (64.7%), and IgE levels >91 mg/dl in 13 patients (77%).In this series of 17 patients with recurrent infections we found two patients (12%) diagnosed with primary immunodeficiency involving IgG deficiency. Immunological assessment of patients with recurrent infections is of great importance because it helps reach early diagnosis that improves prognosis and helps avoids complications for patients.

Porokeratotic eccrine ostial and dermal duct naevus: report of 10 cases.

BACKGROUND: Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is a congenital hamartoma that has rarely been documented. OBJECTIVES: To describe the clinical and histological features of 10 patients with PEODDN. METHODS: A retrospective study of 10 patients with PEODDN attended in our paediatric hospital between 1999 and 2009 was performed. The clinical and histopathological features were reviewed. RESULTS: Nine children and one adult were included in the study. In 6 cases the lesion was present at birth and they were unique in 5 cases and systematized in the other 5 cases. Two cases in the same family are reported. The lesions were most commonly found on the extremities, although the palms or soles were involved in 9 cases and only in one case there was not affection of this area. The lesions were mostly asymptomatic but there was moderate itching in two cases. Clinical examination revealed no extracutaneous involvement. CONCLUSIONS: PEODDN is a rare disorder that usually appears at birth or early childhood. It has a linear distribution following the Blaschko lines. To our knowledge this is the largest series reported in English literature and we also describe the first family case.