Evaluation of the melting temperature of TaqMan probes as a genotyping method for IDH1, IDH2, and H3F3A in pediatric astrocytomas / Evaluación del método de temperatura de disociación de sondas TaqMan para la genotipificación de IDH1, IDH2 y H3F3A en astrocitomas pediátricos

Abstract Background: Astrocytomas are cancer tumors of the central nervous system and represent the most common type of solid tumors during human childhood. In 2016, the World Health Organization established a molecular classification system to regroup tumor entities to achieve a more accurate diagnosis and a better clinical decision-making and selection of treatment in patients with these types of tumors. Methods: We evaluated a genotyping assay for rapid and cost-effective mutation detection in astrocytomas using TaqMan probes in an asymmetric polymerase chain reaction (PCR) assay. Results: Four diffuse astrocytomas (Grade II), three anaplastic astrocytomas (Grade III), and four glioblastomas (Grade IV) were sequenced, and all of them displayed the wild-type (WT) sequence. We tried to set up this melting analysis for the genotyping of pediatric astrocytomas by identifying the specific melting temperatures of the TaqMan probes due to the presence of the WT sequences in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) and H3.3 histone A genes (H3F3A). We used an IDH1-TaqMan probe to identify the WT status of IDH1 in two different WT deoxyribonucleic acid (DNA) templates (pilocytic and diffuse astrocytoma) and obtained four melting temperature values ranged from 65.6 to 92.2°C. Furthermore, only four out of 29 reactions displayed amplification of the DNA template. Sanger sequencing was faster and more reliable to detect the gene status in all the sequenced samples. Conclusions: We conclude that conventional Sanger sequencing remains the gold standard for the genotyping of pediatric astrocytomas.

Resumen Introducción: Los astrocitomas son un tipo de cáncer que afecta al sistema nervioso central y representan el tumor sólido más común durante la infancia. En el año 2016, la Organización Mundial de la Salud estableció un sistema de clasificación molecular para reagrupar tumores con identidades genéticas similares y lograr un diagnóstico más preciso, lo que lleva a tomar las decisiones clínicas idóneas al elegir el tratamiento de pacientes con este tipo de tumores. Métodos: Se evaluó un protocolo que involucra el uso de sondas TaqMan en un ensayo de reacción en cadena de la polimerasa asimétrica para la detección de mutaciones en astrocitomas. Se secuenciaron cuatro astrocitomas difusos (Grado II), tres astrocitomas anaplásicos (Grado III) y cuatro glioblastomas (Grado IV). Se intentó establecer las condiciones del análisis para la genotipificación de los astrocitomas pediátricos mediante la identificación de las temperaturas de disociación específicas de las sondas TaqMan producidas por la prescencia de las secuancias WT en los genes isocitrato deshidrogenasa 1 y 2 (IDH1, IDH2) y H3.3 histona A (H3F3A). Resultados: Los astrocitomas mostraron la secuencia wild type (WT) (silvestre) de los genes. Se utilizó una sonda TaqMan IDH1 para identificar el estado de este gen en dos templados WT de DNA (astrocitoma pilocítico y difuso) y se obtuvieron cuatro valores de temperatura de disociación (65.6-92.2 °C). Solo cuatro de las 29 reacciones mostraron amplificación de DNA. La secuenciación de Sanger fue más rápida y confiable para detectar el estado de los genes en todas las muestras. Conclusiones: La secuenciación de Sanger sigue siendo la técnica más práctica para la genotipificación de astrocitomas pediátricos.

Craneoestenosis. II. Análisis de las craneoestenosis sindromáticas y diferentes tipos de tratamiento / Craneosynostosis. II. Analysis of syndromatic craniosynostosis and different types of treatment

En esta segunda parte del trabajo de revisión de las craneoestenosis se analizan los diferentes tipos de craneoestenosis sindromáticas, sus características clínicas, imagenológicas y, en los casos que se conocen, las alteraciones genéticas. También se describen los diferentes tipos de tratamientos para las craneoestenosis, tanto sindromáticas como no sindrómaticas, desde los tratamientos quirúrgicos clásicos para lograr la descompresión cerebral, la restauración de la anatomía y proporcionar el mayor grado de estética al menor. Por último, se incluye información acerca de los tratamientos de vanguardia como son las técnicas en ingeniería de tejidos, la utilización de sistemas bioabsorbibles, de sistemas de distracción ósea e, incluso, la cirugía endoscópica. Se espera que pronto exista un mayor número de publicaciones que reporten el éxito de estas nuevas técnicas.

In this second part of the Review Article on craniosynostosis, different types of syndromatic craniosynostosis are analyzed along with clinical and imaging aspects and, in known cases, embryogenetic alterations. Different types of treatments are also described for both syndromic and nonsyndromic craniosynostosis. These range from the classic surgical treatments for achieving brain decompression, restoring the anatomy and providing the highest degree of aesthetics for the child. Last, but not least, information on cutting-edge treatments such as techniques in tissue engineering, use of bioabsorbable bone distractors and even endoscopic surgical systems are included. It is expected that in the near future there should be a greater number of publications that report the success of these new techniques.

Craneoestenosis. I. Bases biológicas y análisis de las craneoestenosis no sindromáticas / Craniosynostosis. I. Biological basis and analysis of nonsyndromic craniosynostosis

Las craneoestenosis, definidas como el cierre, la osificación y la esclerosis de una o más suturas del cráneo, ocasionan diferentes grados de compresión cerebral, hipertensión intracraneana y deterioro del cociente intelectual y la visión del niño. En esta primera parte de la revisión se presenta un panorama histórico de este padecimiento desde la época prehistórica, atravesando por diferentes siglos y culminando con la experiencia francesa y mexicana. Se presenta el informe de la serie del Hospital Infantil de México Federico Gómez. Se presentan sucintamente las bases biológicas, abordando aspectos embriogénicos, epidemiológicos, etiológicos, así como fisiopatológicos, clínicos e imagenológicos. Finalmente, se analizan siete diferentes tipo de craneoestenosis simples o no sindromáticas, ya sea de una o más suturas.

Craniosynostoses are defined as closure, ossification and sclerosis of one or more cranial sutures. This condition causes different grades of brain compression, intracranial hypertension and detriment of intellectual coefficient and vision. In the first part of this review article, an overview of the history of craniosynostosis is presented from prehistorical times through the subsequent centuries, culminating with the French and Mexican experience. The Hospital Infantil de México Federico Gómez series are also presented. Following this, the biological bases are summarized including embryogenetic, epidemiological and etiological features, as well as pathophysiological, clinical and imaging aspects. Finally, seven different types of nonsyndromatic craniosynostoses are analyzed including those with one or more sutures.

Cerebral Anatomy of the Spider Monkey Ateles Geoffroyi Studied Using Magnetic Resonance Imaging. First Report: a Comparative Study with the Human Brain Homo Sapiens / Anatomía Cerebral del mono araña Ateles geoffroyi estudiada utilizando imágenes de resonancia magnética. Primer reporte: estudio comparativo con el cerebro humano Homo Sapiens

The objective of the present qualitative study was to analyze the morphological aspects of the inner cerebral anatomy of two species of primates, using magnetic resonance images (MRI): spider monkey (A. geoffroyi) and human (H. sapiens), on the basis of a comparative study of the cerebral structures of the two species, focusing upon the brain of the spider monkey and, primarily, its limbic system. In spite of being an endemic Western hemisphere species, a fact which is by its own right interesting for research due to this animal’s social organization and motor functions, the spider monkey (A. geoffroyi) has hardly been studied in regard to its neuroanatomy. MRI was carried out, in one spider monkey, employing a General Electric Signa 1.5 T scanner. This investigation was carried in accordance to international regulations for the protection of animals in captivity, taking into account all protective means utilized in experimental handling, and not leaving behind any residual effects, either physiological or behavioral. From a qualitative point of view, the brains of the spider monkey and the human were found to have similar structures. In reference to shape, the most similar structures were found in the limbic system; proportionally, however, cervi cal curvature, amygdala, hippocampus, anterior commissure and the colliculi, were larger in the spider monkey than in the human.

El objetivo del presente estudio cualitativo fue analizar los aspectos morfológicos de la anatomía cerebral interna utilizando imágenes de resonancia magnética (IRM) en dos especies de primates, El mono Araña (A. geoffroyi) y el humano (H. sapiens), tomando como base un estudio comparativo de las estructuras cerebrales de las dos especies, concentrándose primordialmente en el sistema límbico del cerebro del mono araña. Aunque es una especie común en el hemisferio occidental, es interesante para estudiar dada su organización social y funciones motoras, el mono araña (A. geoffroyi) ha sido poco estudiado en cuanto a su neuroanatomía. Las IRM fueron hechas a un mono araña utilizando un resonador General Electrics Signa 1.5 T. Esta investigación se llevo a cabo conforme a las leyes internacionales para la protección de animales en cautiverio y teniendo en cuenta todas las medidas de protección para el manejo experimental para evitar cualquier efecto residual de índole comportamental o fisiológico. Desde un punto de vista cualitativo, los cerebros del mono araña y el humano tenían estructuras similares. Con respecto a la forma, las estructuras más parecidas fueron encontradas en el sistema límbico, sin embargo la curvatura cervical, la amígdala, el hipocampo, la comisura anterior y el colículo fueron más grandes proporcionalmente en el mono araña que en el humano.

Neurotransmisores del sistema límbico. Hipocampo. GABA y memoria. Segunda parte

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Summary: Action of GABA agonists and antagonists on memory. The θ rhythm. Muscimol may directly alter memory. Recently, a modified matching to position (MTP) paradigm was employed aimed at influencing the type of associations a rat may use to solve the task. The main behavioral manipulation was the application of a differential outcomes procedure (DOP). DOP implies correlating each event to be remembered with a different reward condition. This procedure will result in the development of specific reward expectations which will in turn increase and guide choice behavior. Such different reward expectations will not be present when the reward assignation used is either common or random (non-differential outcomes procedure, NOP). Intraventricular infusion of muscimol or CSF in rats carrying out a delayed MTP using either a MOP or an NOP protocol will affect both groups of rats, but the nature of the deficit will differ depending on the reinforcement contingencies. Rats trained in DOP will show general non-mnemonic damage independent of delay, i.e., performance will be affected at all delay intervals employed. On the contrary, rats trained in NOP will show delay-dependent damage. This appears to demonstrate that muscimol may also have untoward memory effects, which further indicates that activation of GABA receptors will affect a set of memory associations and functions. Difficulties experienced in the past regarding LTP induction at the level of the CA3-CA1 synapse using time-based spike presentation protocols have been disconcerting given the preeminence of these synapses as a model system for the study of synaptic plasticity. Results previously discussed in experiments using picrotoxin as a GABA inhibitor have suggested that such difficulties arise from the requirement that, for LTP to be induced, CA1 dendrites must be persistently and totally activated. Doublets used in this case represent a minimal burst, or level of post-synaptic stimulation for LTP induction that subsumes greater depolarizations. In vitro, synaptically induced bursts would correspond to regenerative electrical events in apical dendrites of pyramidal neurons. The same requirements for dendritic activation would be satisfied in vivo during the θ rhythm, which is present during active exploration. Therefore, GABA might serve as an engram modulator through the activation of the hippocampal θ rhythm. Effect of μ-opioid receptors on hippocampal memory activity. Hippocampal μ-opioid receptors (MOR) have been involved in the formation of memory associated with the abuse of opioid drugs. When chronically activated, and during programmed drug abstinence, MORs acutely modulate hippocampal synaptic plasticity At the level of neuronal networks, MORs increase excitability of area CA1 by means of a disinhibition of pyramidal cells. The specific inhibitory interneuronal subtypes which become affected by activation of MORs are not known. Nevertheless, not all subtypes are inhibited and some subtypes preferentially express these receptors. In one study, the effect of activation of MORs on inhibitory patterns and propagation of excitatory activity in CA1 of rat hippocampus was investigated through cortical images created using voltage-sensitive dyes. MOR activation increased excitatory activity originated by the increased stimulating input to stratum oriens (i.e., Schäffer collateral and commissural [SCC] fibers, as well as the retrograde pathway), to stratum radiatum (i.e., SCC fibers) and to stratum lacunosum-moleculare (i.e., the perforant pathway and the thalamus). Increased excitatory activity was additionally facilitated by propagation through the neural network of area CA1. This was observed as a proportionally greater increment of amplitudes of excitatory activity in sites distant from the originally evoked activity. Such facilitation was noted in excitatory activity propagating from three sites of stimulation. The increment and facilitation were prevented with GABAA receptor antagonists (bicuculline, 30 μM), but not with GABAB receptor antagonists (CGP, 10 μM). Besides, MOR activation inhibited inhibitory post-synaptic potentials (IPSPs) in every layer of area CA1. These findings suggest that MOR-originated suppression of GABA release to GABAA receptors increases every type of input to pyramidal CA1 neurons and facilitates propagation of excitatory activity through the neural network of area CA1. Cannabis indica and memory. Cannabinoids (derived from Cannabis indica, or marihuana) disturb memory processes in mammalians. In spite of the fact that the neuronal cannabinoid CB1 receptor was identified several years ago, the neuronal network mechanisms mediating these effects are still controversial. Tritium-labeled GABA-releasing experiments have been used to test for the localization of this receptor at a cellular and subcellular level in the human hippocampus. CB1 expression detected with this technique is limited to hippocampal interneurons, most of which, it could be determined, are cholecystokinin-containing basket neurons. The CB1-positive neuronal somata show immune staining of their cytoplasm, but not of their somatodendritic plasma membrane. CB1-immunoreactive axonic terminals densely cover the entire hippocampus and form symmetrical synapses, characteristic of GABAergic neuronal boutons. It could thus be observed that WIN 55,212-2, a CB1-receptor agonist, considerably reduces the release of tritium-labeled GABA, and that this effect is preventable using the receptor antagonist, SR 141716A. This single pattern of expression and pre-synaptic modulation of GABA release suggests the existence of a preserved role of CB1 receptors in the control of inhibitory hippocampal networks responsible for the generation and maintenance of fast and slow oscillation patterns. Therefore, a probable mechanism whereby cannabinoids could affect associational processes in memory might be a disturbance of synchrony of rhythmical events in distinct neuronal populations. GABA effects against aging. Certain components which stimulate GABAergic neurotransmission might prevent the hippocampal and striatal degeneration which typically appears with old age and causes memory deterioration. On using a 4-vessel occlusion model in animals to study the effect of ischemia on expression of GABAA receptor subunits, which are vulnerable in region CA1 and resistant in region CA3 of Amnion's horn, an increment in expression of GABAA2, GABA B2, GABA G2 units and a decrement in expression of GABA A1 and GABA A3 subunits in region CA3 were obtained. On the contrary, there was no change in region CA1 or the dentate gyrus under the same conditions. These data speak in favor of the stimulation of type 2 receptor GABAergic subunits which might protect certain hippocampal areas against a harmful neurodegenerative effect, for example, of memory activities during old age.

Neurotransmisores del sistema límbico. Hipocampo, GABA y memoria. Primera parte

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Summary: Introduction. The entire hippocampus is derived from the telencephalon. Embryologically, it is made up of the most archaic cortices. Through special phylogenetic and ontogenetic telencephalization processes, it will arrive at its particular mesial basal position. This structure has three components: a) Retrocommisural hippocampus, or hippocampus proper (RH). b) Supracommisural hippocampus (SH). c) Precommisural hippocampus (PH). The RH is situated in the most medial part of the 5th temporal gyrus (5 TG). The outer/upper face of the RH is to be found in the temporal recess of the lateral ventricle. It is called pes hippocampi or albeus. Inwards, it is limited by the choroid fissure, outwards and downwards by the parenchyma of the 5th TG, forwards, by the amygdala of the striatal body and, backwards, by the isthmus. The fornix is a continuation of efferent pathways from CA3, CA1 and the subiculum. By means of a circular course, it ascends over the thalamus and, descending in front of Monro's foramina and traversing the hypothalamus, reaches the mammillary bodies. It consists of fimbria, posterior pillars and a body and anterior pillars. The latter pass behind the anterior white commisure (AWC), and make up the anterior portion of Monro's foramina. The SH originates in the RH. At the level of the splenium of the corpus callosum (CC), the fornix produces two striae, medial and lateral, and the dentate gyrus turns from fasciola cineria into induceum griseum. These structures are to be found in both hemispheres and, traveling over the CC, will reach the preoptic and hypothalamic septal areas, as well as the PH. The PH is a small fiber contingent which stems from the fornix at the level and in front of the AWC. Memory. General aspects. There is general agreement that the main role of the hippocampus is that of creating new memories relative to experienced events (episodic or autobiographic memory). Some researchers, however, prefer to think of the hippocampus as part of a major medial temporal lobe memory system responsible for declarative memory. This memory would include, besides episodic memory, memory of events. Another very important hippocampal function would relate to storage of semantic (conceptual) memories. Engrams. Memory and synaptic plasticity. Engrams are hypothetical means whereby memory traces are stored as physical or chemical changes in the brain in response to external stimuli. The existence of engrams has been proposed by diverse scientific theories which try to explain the persistence of memory and how some memories are stored in the brain. The term engram was coined by Sermon and explored by Pavlov Lashley tried to locate the engram and failed in finding a sole biological locus for the same which made him think that memories were not localized in any particular part of the brain, but distributed throughout the cerebral cortex. Afterwards, in 1949, Hebb, a student of Lashley's, published his empiricist theories in The Organization of Behavior. Hebb referred to Lorente de Nó's reverberating circuits to propose a mechanism for maintaining activity in the cerebral cortex after the external stimulus had ceased: the so called central autonomous process. This led him to consider the cellular assembly, a complex reverberating circuit which could be assembled by experience. Changes in synaptic resistance with experience were eventually named Hebb's, or the Hebbian, synapse. Hebbian theory describes a basic mechanism for synaptic plasticity by means of which an increment in synaptic efficacy stems from repetitive and persistent stimulation of the post-synaptic cell. This theory receives the name of Hebb's rule. The fact that memory is persistent stresses the relevance of understanding those factors which maintain synaptic strength and prevent undesired synaptic changes. There is evidence that recurrent inhibitory connections in region CA1 of Ammon's horn of the hippocampus might contribute in this sense by modulating the ability to induce long-term potentiation (LTP) or long-term depression (LTD) of synaptic activity, given by a sequence of high-or low-frequency stimulations, respectively. The hippocampus seems to be able to select the most relevant from the least relevant aspects of a definite experience in order to transform them into long-term memory. According to the concept of Emotional Tagging, for example, through the activation of the amygdala by emotionally suggestive events, the experience will be tagged as important and synaptic plasticity promoted in other cerebral regions, such as the hippocampus. Recently, it has been shown that activation of the amygdala transforms transient plasticity into long-term plasticity. This finding directly relates to the afore mentioned hypothesis of emotional tagging, since activation of this organ could trigger neuromodulatory systems, further reduce the activation threshold of the synaptic marker and facilitate transformation of early into late memory at the level of the hippocampus via direct amygdalar action on the latter organ. γ-aminobutyric acid. γ-aminobutyric acid (GABA), together with its different receptor subunits, functions as an inhibitor neurotrans-mitter in hippocampus and memory activities. GABA and memory. LTP has been a widely studied mechanism of synaptic plasticity and, as we have mentioned, it is intimately related to diverse memory and learning processes in mammals. It has been observed in pyramidal cells of area CA1 of the hippocampus of young C57BL/6 mice that the pairing of pre-synaptic stimulation with just one post-synaptic action potential will be sufficient to induce LTP, whereas in the adult animal this stimulation must be paired with several post-synaptic action potentials to achieve such induction. This change might result from a modification during maturation of GABAergic inhibitory processes. A bath of muscimol, a GABAA agonist, given to sections of hippocampal area CA1 will increase the range of frequencies inducing LTD, while in the presence of picrotoxin, a GABAA antagonist, LTD will be induced only at very low stimulation frequencies. The resulting recurrent inhibition appears to stem from GABAergic input to pyramidal neurons of CA1. In this way, post-synaptic spike activity could increase GABAergic feedback inhibition, and thus favor LTD. However, in experiments in which the pairing of stimulating action potentials is set apart in time, LTD, LTP or no plasticity may be observed. An explanation for these results could be that, in the presence of picrotoxin, and therefore GABA inhibition, the first action potential may have a greater tendency to "back propagate", so that only one spike would be enough to cause LTP instead of LTD, and affect memory processes differently.

Perfiles criminológicos: el arte de Sherlock Holmes en el siglo XXI

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Summary Within the frame of an international interest to explain and reduce violent behavior, criminological profiles provide relevant knowledge on the characteristics and circumstances concerning violent events, their authors and victims. In this review the main lines of investigation on this subject are addressed, as well as some of the most important findings and inquiries yet to be solved. Finally, some challenges and perspectives of this type of research and the application of criminological profiles are discussed. Our conclusions include the necessity of developing a line of research to generate an insight into this subject in general, as well as to assess its applicability in specific contexts in Spanish speaking countries. Even though criminological profiles have been simultaneously supported and criticized, the findings in this research area evince the possibility of creating useful criminological profiles with accuracies above the random level. However, the outcomes of studies related to this subject suggest a precautionary approach with respect to its achievements. This manuscript reviews the research on criminological profiles from five study areas: a) crime and delinquent typologies; b) behavioral patterns and the theory of facets; c) spatial patterns and geographical profiles; d) temporal patterns and chrono-ecological rhythms, and e) reliability and validity. Studies in crime and delinquent typologies are marked within a clinical focus, in which deductive logic, experience of the profiler and analysis of previous cases are the keys to tackle cases of unknown aggressors. One of the representative models in this line is that of the FBI, which proposes a classification of murder scenes that are related with two different types of delinquents: unorganized (probably with mental disorder) and organized (probably psychopaths). This model also propounds the existence of a third type called "mixed" category, which includes characteristics from both previously mentioned types. The main contribution of clinical methodology has been the identification of socio-demographic characteristics common in persons committing crimes such as homicide, rape, robbery, pyromania and even terrorist acts; the selection of a victim type; characteristics of their modus operandi, and motivations referred to by perpetrators for justifying the deed. Recent research goes beyond mere descriptive studies by means of co-occurrence analysis of variables. From this viewpoint, hypotheses are posed and demonstrated based upon the study of large samples, this resulting knowledge is then applied to the analysis of new cases, casuistics (statistical methodology). This perspective originates the identification of behavioral patterns that initially give no support to previous classifications but propound more specific categories. Results from different type of offenses consistently indicate the existence of some useful behavioral patterns for the identification of the various ways of perpetrating a crime and its relation to distinct types of criminals. Among the main identified patterns are: violence used, level of planning and aggressor-victim relationship. Besides, the evidence supports the idea of a relation between the characteristics in the commission of a crime (information from the crime scene and the victims) and the characteristics of those persons responsible of the crime (in terms of the useful information leading to their identification and capture). The results of an investigation from a statistical viewpoint suggest that typologies can not be seen as static or rigid and that it is necessary to review the evidence backing up those typologies before using it in crimes committed by unknown aggressors and in contexts differents from the ones initially proposed. The theory of facets is the most representative model along this line. One of the most crucial findings so far is the existence of spatial patterns and their applicability in the elaboration of geographical profiles. In this sense, the relations between the zones in which crimes occur and the possible characteristics of the criminals have been studied. Results indicate that offenders tend to perpetrate their offenses in familiar places and near the areas in which their everyday life takes place. This knowledge has been useful for the development of computer programs that can predict the area where a criminal may live in or in which he may remain most of the time, based on the information available from the case investigation (for example, the place where the victims disappeared or where the bodies were found). Studies in this area indicate that the choice of places and victims is not at random, even in crimes that may be classified as impulsive. With respect to chrono-ecological patterns, there is evidence pointing to a relation between the commission of a crime and certain biological rhythms associated with annual, seasonal and lunar rhythms; though the information relating the lunar cycle and homicides is still controversial. In relation to the validity and reliability of profiles, research indicates that profiles depend on the type of offense, quality and quantity of available information, as well as the abilities of the persons performing the profile. Valid and reliable profiles are associated with both a large amount of available information and with the fact that persons trained in doing profiles are endowed with abilities of logical thinking and insight into human behavior. However, it is not quite clear if the main ability for producing accurate profiles is that of analysis and level of general intelligence on the part of the profile designer or a specific type of knowledge or training. In spite of the achievements in the study of profiles at international level, Latin America has experienced a slow development in this area. Mexico in particular, is not an exception. Publications on this subject in Spanish are really scarce. The development in the research on profiles and the questions pending an answer lead us to propose, as well as to discuss, the necessity for the development of a research line in criminological profiles in countries like Mexico with the aim of making a contribution at international level to the identification of behavioral, cognitive, criminological, spatial and chrono-ecological patterns. Besides, there is a need to corroborate whether if the international findings are valid in our contexts, and to what extent they can be introduced into our practice. Finally, we propound that this research line be permanent and independent of immediate reactions in the face of crimes creating great impact. This line must be constituted upon the basis of theoretical models empirically demonstrated, the search of relations between available information in crime cases of unknown aggressors and data that may be useful for the identification and capture of offenders. Among the challenges and perspectives of criminological profiles we must go beyond deductive tools to approach a science based on scientific evidence.

Hernia diafragmática: primer caso informado en México por el doctor Agustín Arellano en 1839 / First case report in Mexico of a diaphragmatic hernia, by Agustín Arellano in 1839

Desde mediados del siglo XVII, ya se habían informado casos de hernia diafragmática congénita por ausencia parcial del diafragma. La publicación de Agustín Arellano de 1839, en México, sería de las primeras ha informar sobre este tipo de fenómenos en el mundo, 9 años antes de la publicación de Bochdalek. Contando las referencias primeras de los siglos XVII, XVIII y XIX, la de Arellano ese posicionaría en el quinto o en el sexto lugar. No se han encontrado otras referencias de esta patología antes de 1839 en América entera. Si no se demuestra lo contrario, la publicación del doctor Arrellano sería la primera en América para este tipo de padecimiento. En esta época, la presencia de los investigadores mexicanos no iba a la zaga de los países más adelantados del mundo en el estudio de estos problemas. La holoprosencefalia que la acompaña es también uno de los primeros informes mundiales, el cuarto en línea de aparición. Recalcamos que la revista en donde se publicó, el Periódico de la Academia de Medicina de Mégico (sic), fundado y dirigido por el doctor Manuel Carpio en 1836, es la antecesora directa de de la actual Gaceta Médica de México, la revista de medicina en circulación más antigua de América.

Reports on partial lacking of the diaphragm and diaphragmatic hernia date to seventeenth century reports. In 1939 Arellano published in Mexico, a necropsy case of diaphragmatic hernia with holoprosencephaly and cyclocephaly. Agustín Arellano's was the the fifth or sixth report ever published worldwide and his manuscript was reported nine years before Bochdalek's publication. Before 1839, in the Americas, there is no other existing report describing this type of pathology, and we can safely assume Arellano's work was the first of its kind in the Western hemisphere. It is well known that, at the time, the quality ofscientific publications of this Mexican medical researcher could be compared to the level of any medical publication in the developed world. It is worth noting that the Journal were Arellano's work was published, named "Periodico de la Academia de Médicina de Mégico (sic)," founded and directed by Dr. Manuel Carpio in 1836, is the direct precursor of the present-day "Gaceta Médica de México" the oldest current medical journal in the Americas.

Tumores intracraneanos del niño / Pediatric intracranial tumors

Introducción. Los tumores intracraneanos (TIC) pediátricos son las neoplasias sólidas más frecuentes en niños. Se presenta la experiencia del Hospital Infantil de México Federico Gómez (HIMFG) de los últimos 36 años. Material y métodos. Se utilizaron los siguientes archivos del HIMFG: Clínico, de los Departamentos de Neurocirugía y de Patología. Los resultados se compararon con los datos del Hospital for Sick Children de Toronto y del Instituto Nacional de Pediatría de México, D. F. Resultados. En el HIMFG, 55% de los pacientes eran del sexo masculino. Predominaron desde lactantes mayores hasta escolares, con más de 50%. Los tumores fueron: 397 supratentoriales y 413 infratentoriales. Los más frecuentes fueron: astrocitomas (32%), meduloblastomas (19%), craneofaringiomas (11%) y ependimomas (10%); en el quinto lugar quedaron los germinomas (4%). Los gliomas mixtos, los meningiomas, los tumores neuroectodérmicos primitivos y los ependimoblastomas representaron de 1 a 3%. Conclusiones. En el HIMFG, los 4 tipos más frecuentes de tumor fueron: astrocitomas, meduloblastomas, craneofaringiomas y ependimomas. El trabajo de campo del HIMFG ha tenido un desarrollo exponencial desde la mitad de los años setenta. Actualmente, el volumen de pacientes manejado por el HIMFG es semejante a, o rebasa discretamente, al de otras instituciones.

Introduction. Pediatric intracranial tumors (PIC) make up the most frequent solid neoplastic pathology in children. We present an analysis of the experience of Hospital Infantil de Mexico Federico Gomez (HIMFG), in Mexico City, over the course of 36 years in this regard. Material and methods. Cases from the archives of the Department of Clinical Records, Department of Neurosurgery and Department of Pathology at HIMFG were used for this analysis. Results were compared to data published by the Hospital for Sick Children of Toronto (HSCT) and by Instituto Nacional de Pediatria (INP) in Mexico City. Results. Of 810 cases reviewed at HIMFG, 55% belonged to the male gender. By age, older-infant and grade-school-children cases predominated (> 50%). Of those, 397 cases were supratentorial and 413 infratentorial. Most frequent tumors were: astrocytomas (23%), medulloblastomas , craniopharyngiomas (11%) and ependymomas (10%). Fifth place was occupied by germinomas (4%). Mixed gliomas, meningiomas, primitive neuroectodermal tumors and ependymoblastomas were the last (1 to 3%). Conclusions. At HIMFG, the most frequent tumour types were: astrocytomas, medulloblastomas, craniopharyngiomas and ependymomas. Since the 70s, on the number of patients presenting with intracranial tumors at HIMFG has grown exponentially, and the amount carried out till now at this hospital parallels, or slightly exceeds, that carried out at similar institutions in Mexico and abroad.

Neurotransmisores del sistema límbico. Amígdala. Segunda parte

Resumen: Los neurotransmisores de la amígdala en el sistema límbico comprenden, entre otros, a las monoaminas (noradrenalina [NA]), la acetilcolina (ACh), los corticoides y la histamina. Ciertas drogas infundidas a la amígdala podrían modular la consolidación en la memoria de la inhibición del entrenamiento dirigido a evitar situaciones de estrés. La administración de anta gonistas de los receptores de la β NA en la amígdala afecta la retención en la memoria por un lapso de un día cuando se administra inmediatamente después del entrenamiento, pero no surte ningún efecto cuando se administra a las seis horas. Infusiones intraamigdalinas de NA acompañadas de antagonistas de aquellos receptores atenuarán el trastorno mnemónico. De manera importante, se ha podido determinar que la NA produce un incremento de la consolidación de la memoria, que depende tanto del tiempo como de la dosis de aplicación cuando el fármaco se infunde a la amígdala inmediatamente después de la inhibición de este tipo de entrenamiento. La amígdala, la neocorteza y el hipocampo son regiones meta del sistema cerebral frontal basal colinérgico, que se relaciona estrechamente con diversas funciones del aprendizaje y la memo ria. Cualquier neurotransmisor con actividad fosforiladora o desfosforiladora podrá regular el estado de sensibilidad a la ACh, así como las propiedades funcionales de las neuronas amigdalinas. Es posible, entonces, que exista una modulación entre los estados de aprendizaje y de recuerdo de lo aprendido en la amígdala, la neocorteza y el hipocampo que esté regida por receptores muscarínicos acetilcolinérgicos. Por medio de receptores presinápticos de la histamina 3 (H3) y un mecanismo por el momento aún desconocido, la histamina disminuye o aumenta la transmisión sináptica excitadora en el BLA. Tal modulación histaminérgica de la actividad neuronal cumple un papel importante en los procesos fisiológicos y patofisiológicos del miedo, el aprendizaje y la memoria de la emo ción y los trastornos afectivos.

Abstract: Neurotransmitters of the amygdala in the limbic system include monoamines (noradrenaline [NA]) acetylcholine (ACh), corticoids and histamine. Drugs infused into the amygdala may modulate consolidation in memory of inhibition of training directed to avoid stressful situations. Administration of antagonists of β NA receptors to the amygdala will affect retention in memory for a whole day when given immediately after training, but will have no effect when given six hours after training a test animal. Intra-amygdalar infusions of NA which may be accompanied by antagonists of those receptors will attenuate the memory disturbance. It is worth mentioning that later studies have been able to show that NA will produce an increment of memory consolidation, which will depend on the time as well as on the dose of application, when the drug is infused to the amygdala shortly after inhibition of training directed to avoid stressful situations. The amygdala, the neocortex and the hippocampus are target regions of the frontal basal cholinergic brain system, which has different effects on cognitive functions, such as memory and learning. Any neurotransmitter with phosphorylating or dephosphorylating activity may regulate the sensitive state of ACh, as well as the functional properties of amygdalar neurons. It is possible, then, that modulation mechanisms may exist between learning and recall states in the amygdala, the neocortex and the hippocampus, which could be controlled by muscarinic acetylcholinergic receptors. Through pre-synaptic receptors of histamine 3 (H3) and a currently unknown mechanism, histamine will decrease or increase excitatory synaptic transmission in BLA. Such histaminergic modulation of neuronal activity will play an important role in fear-related physiological and patho-physiological processes, learning and memory of emotion, and affective disturbances.

Neurotransmisores del sistema límbico. I. Amígdala. Primera parte

Resumen Los neurotransmisores de la amígdala en el sistema límbico comprenden, entre otros, al ácido γ-aminobutírico (GABAA,B,G), el ácido glutámico (GLU) y el N-metil-D-aspartato (NMDA), así como a las monoaminas [dopamina (DA) e hidroxitriptamina (5-HT)]. El GABA es el principal neurotransmisor inhibidor. Su actividad inhibidora se bloquea, por ejemplo, por los efectos ansiolíticos de las benzodiacepinas, tanto en la amígdala como en otros centros del sistema límbico (tálamo, corteza prefrontal, hipocampo, etc.) conectados con esta estructura. Igualmente, la corteza prefrontal cerebral regula los procesos de memoria en los que esté involucrado un componente afectivo a través de conexiones inhibidoras GABAérgicas sobre el núcleo lateral (LA) de la amígdala. Al estimularse las vías córtico-amigdalinas y tálamo-amigdalinas, se produce una excitación seguida de una inhibición mediadas por receptores del GABA en el LA. Una reducción de la inhibición puede obtenerse ya sea al estimular conjuntamente ambas vías, o al estimular primero una y luego la otra vía. Ambos tipos de depresión se regulan por inhibidores presinápticos del GABAB en interneuronas del LA que conectan con el núcleo central (CE) de la amígdala, y que aparentemente llegan por una u otra vía. Este dato apoya la existencia de un ingreso monosináptico convergente de información al LA, ingreso que interviene en la respuesta a diferentes condiciones estresantes y que limita una actividad neuronal excesiva. El GLU es el principal neurotransmisor excitador. Al estimularse la amígdala durante la aversión condicionada contra ciertos sabores por este neurotransmisor, se produce una inhibición de la actividad hipotalámica procedente de vías GABAérgicas amigdalinas que van al hipotálamo. El LA es parte del circuito neural que subyace al condicionamiento pavloviano al miedo. En este circuito, el bloqueo de los receptores de NMDA glutámicos en el LA antes del entrenamiento altera el aprendizaje del condicionamiento al miedo, pero el bloqueo previo a la prueba también altera dicha expresión. Se ha visto que un bloqueo específico causa una disrupción del circuito que interviene en el aprendizaje de este condicionamiento, mas no de la consolidación en la memoria del proceso en un momento posterior al aprendizaje. La estimulación de los colículos inferiores (CI) causa un aumento significativo de los niveles de DA en la corteza prefrontal (PFC). Asimismo, el complejo basolateral de la amígdala (BLA) sirve como filtro de la información con carga negativa que promueve el escape y que asciende a estructuras más elevadas del tallo cerebral. Se ha observado que la desactivación del BLA interfiere con la activación de los egresos dopaminérgicos corticales producidos por una estimulación con carga negativa de los CI. Se ha podido demostrar que la información con carga negativa que asciende desde los CI cursa con una modulación opuesta dada por mecanismos de DA/5-HT que descienden desde la PFC. Estos procesos parecen regularse por filtros localizados en el BLA. Existe la posibilidad de que la DA proveniente del BLA module las respuestas de la DA del nucleus accumbens durante el estrés indirectamente por medio de conexiones de la primera con la corteza prefrontal medial, la cual inhibirá, por medio de la DA, la transmisión dopaminérgica de este núcleo.

Summary Neurotransmitters of the amygdala in the limbic system include, among others, γ-aminobutyric acid (GABAA,B.G), glutamic acid (GLU) and N-methyl-D-aspartate (NMDA), as well as the monoamines [dopamine (DA) and 5-hydroxytriptamine (5-HT)]. GABA is the main inhibitory neurotransmitter. Its inhibitory activity will be blocked, for example, by the anxiolytic effects of benzodiazepines both in the amygdala and in other nuclei of the limbic system (thalamus, prefrontal cortex, hippocampus, etc.) connected to this structure. Similarly, the cerebral prefrontal cortex will regulate memory and learning processes in which an affective component may be involved through GABAergic inhibitory connections reaching the lateral nucleus (LA) of the amygdala. On stimulating cortico- and thalamo-amygdalar pathways, an excitation will be produced followed by an inhibition, both of which are mediated by GABA receptors in LA. A reduction of the second inhibition may be obtained either by joint stimulation of both pathways or by stimulation of the first and then the other pathway. Both types of depression can be regulated by presynaptic inhibitors of GABAB in LA interneurons connecting with the central nucleus of the amygdala, and which apparently arrive via either the cortical or the thalamic pathway. These data support the existence of a convergent monosynaptic information input which will be active in response to different stressful conditions, and which will limit excessive neuronal activity. GLU is the main excitatory neurotransmitter. When the amygdala is excited in the course of aversive conditioning against certain flavors by this neurotransmitter, a further inhibition of hypothalamic activity will be produced arriving via GABAergic amygdalar pathways to the hypothalamus. LA is part of the neural circuit underlying pavlovian fear conditioning. In this circuit, blocking glutamate NMDA receptors in LA before training will alter acquisition of fear conditioning, but blocking this nucleus before testing will also alter such expression. Recent research has shown that blocking will cause specific disruption of the circuits participating in fear learning, and not of memory consolidation of this process some time after learning. Stimulation of the inferior colliculi (IC) will cause a significant increment of DA levels in prefrontal cortex (PFC). Likewise, the basolateral complex (BLA) of the amygdala will serve as a filter of aversive information ascending to upper structures of the brainstem. In this regard, it has been observed that deactivation of BLA will interfere with activation of cortical dopaminergic outputs produced by aversive stimulation arriving from the IC. Aversive information ascending from the IC has been shown to be modulated by DA/5-HT mechanisms descending from PFC. These processes appear to be regulated by filters located in BLA. In the same fashion, there is the possibility that DA from the basolateral amygdala may modulate responses of DA from the nucleus accumbens during stress indirectly via connections of the amygdala with the PFC, which will inhibit, again, via DA, dopaminergic transmission of the nucleus accumbens.

Características clínico-patológicas de los meningiomas del niño: experiencia de 30 años (1970-1999) en el Hospital Infantil de México Federico Gómez / Clinico-pathological characteristics of meningiomas in children: a 30 years experience of the Hospital Infantil de Mexico Federico Gomez

Introducción. Las neoplasias más comunes en la infancia son leucemias y linfomas seguidas por los tumores intracraneanos. De este grupo los meningiomas tienen una incidencia de 0.4 a 4.6 por ciento. En los adultos la incidencia es entre 13 y 27 por ciento. El tratamiento de elección es la resección quirúrgica con sobrevida, en las series recientes, de 100 por ciento para las variedades histológicas de bajo grado de malignidad (de acuerdo a la clasificación de la Organización Mundial de la Salud) y sobrevida de 1.5 años en promedio para las variantes de alto grado de malignidad. Material y métodos. Se analizaron 20 casos, con un método observacional y retrospectivo. Se revisaron los archivos clínicos y de patología de 1970 a 1999 del Hospital Infantil de México Federico Gómez, seleccionándose los casos con diagnóstico histopatológico de meningioma. Se hizo análisis estadístico descriptivo. Resultados. Se operaron 21 meningiomas en 20 pacientes. Once fueron del sexo masculino, 9 del femenino. El promedio de edad fue 8.6 años (10 meses-17 años). La sintomatología más frecuente fue cefalea y vómito. En relación a su localización 3 se encontraban en la convexidad, 3 en la base , 3 intraventriculares, 3 falciales, 3 intraparenquimatosos, 1 del valle silviano, 1 frontoparietal derecho y 1 múltiple, además de 3 casos raquídeos. Se observó predominio de la variedad transicional (7 casos); otros casos fueron meningoteliales(5), fibroblásticos (3), psamomatosos (3), papilar (1) y angioblástico (1). El grado de resección se calificó de acuerdo a la clasificación de Simpson. Nueve pacientes se encuentran en control, 5 fallecieron y 6 no tuvieron seguimiento suficiente. Conclusiones. El diagnóstico clínico, de imagen e histopatológico acertado llevará a la curación en 100 por ciento de los casos de meningiomas benignos y al tratamiento de elección en las variantes malignas. La serie que se presenta es la primera en niños mexicanos por lo que se considera de gran interés su difusión.

Meningioma papilar en una niña de 10 meses de edad / Papillary meningioma in a ten months infant

Introducción, El meningioma papilar es una variante histológica potencialmente agresiva con tendencia a presentar recurrencias locales y metástasis a distancia. Se presenta con mayor frecuencia a los 36 años, una década antes de la aparición usual de los meningiomas, con intervalo de sobrevida de 1 a 20 años. Caso clínico. Se describe el caso de una niña de 10 meses de edad con desarrollo psicomotor normal hasta los 9 meses cuando presentó abombamiento paulatino de la fontanela anterior, vómito postprandial, monoparesia de brazo izquierdo y pérdida de peso de 2 kg. En la tomografía axial se encontró un tumor frontoparietal derecho. El estudio histopatológico mostró una neoplasia maligna predominantemente papilar que correspondió a la variante papilar de meningioma. conclusión Hasta el momento hay menos de 50 casos de esta variedad histológica de meningioma maligno informados en la literatura, ninguno en individuos menores de 1 año