Drug-induced liver injury: Relation between the R ratio and histopathology.

INTRODUCTION AND AIM: Drug-induced liver injury (DILI) is a diagnosis based on the ruling out of potential liver diseases and consolidated by establishing causality through the temporal relation between a potentially hepatotoxic substance and altered liver biochemistry. Incidence fluctuates greatly worldwide, with very few reports of causal agents of DILI in Colombia. A retrospective study on patients treated at the Centro de Estudios en Salud (CES), within the time frame of January 2015 and June 2020, was conducted to document the causal substances of DILI in patients with liver biopsy and to correlate the types of histologic patterns with the biochemical pattern of liver injury (R ratio). RESULTS: Of the 254 adult patients with liver biopsy and no tumor etiology, 20 patients were identified as cases of DILI (7.87%). The two most frequently found causal substances were efavirenz, in three HIV-positive patients, and Moringa oleifera (moringa), in two patients. There was a statistically significant association between cholestatic patterns (p = 0.037) and mixed patterns (p = 0.031), in the comparison of the histopathologic categories and the R ratio. CONCLUSION: To the best of our knowledge, there are no reports on DILI secondary to Moringa oleifera (moringa). The R ratio could be a useful tool, in relation to the histologic pattern of injury, in cases of mixed and cholestatic patterns.

The sensory innervation of the human nipple.

Nipples represent a highly specialized skin with capital importance in mammals for breastfeeding and additionally in humans due to sexuality. The histological studies regarding this region are scarce, so 42 human nipples were studied to describe the morphology of the nipple innervation. Our results exclude the presence of a rich innervation on nipple's skin or superficial dermis, thus definitely excluding nipple skin from the concept glabrous skin. The presence of mechanoreceptors is limited to scarce Merkel cells on the epidermis and some corpuscular capsulated and non-capsulated structures in the dermis; Merkel cells progressively decrease with ageing. No Meissner corpuscles were found and the rare Pacinian corpuscles identified were close to vascular structures and embroidered in the mammary fatty tissue. The great sensitivity observed functionally on the breast and especially in the nipple can be morphologically explained by two elements; on the one hand there is a rich smooth muscle innervation present in the deep dermis; on the other hand the mammary gland demonstrate Piezo2 expression in many glandular cells, with two differentiated patterns in the ductal and in the acinar tissue of the breast. The role of Piezo2 in the normal mammary gland is discussed.

Análisis electroencefalográfico de la conectividad funcional en habituación por teoría de gráficas / Electroencephalographic analysis of the functional conectivity in habituation by graphics theory

Resumen Se ha propuesto, en la literatura de neurociencias, la hipótesis de que el cerebro funciona con base en redes glioneuronales, responsables de los procesos sensoriales, motores y cognitivos. La teoría de gráficas ofrece modelos matemáticos para describir estas redes complejas a partir de simples abstracciones: nodos y aristas. En este trabajo se plantea el uso de técnicas de procesamiento de señales para el análisis de la conectividad funcional entre ensambles neuronales a partir de medidas derivadas del EEG a través de la teoría de gráficas. Se describen los procedimientos para el análisis de la conectividad, desde el procesamiento y acondicionamiento de los registros, el cálculo de la densidad espectral en el EEG en banda ancha, la determinación de medidas de conectividad entre electrodos, y la estimación de parámetros de las redes complejas resultantes. Se analizó el EEG de 50 sujetos en intervalos de antes (Pre) y durante la fotoestimulación repetida (Rph). Con base en la significancia estadística de la respuesta durante Rph de desincronización/sincronización (D/S) en la banda alfa, y su extensión en las regiones corticales, los participantes se separaron en tres grupos: G1, G2 y G3. La pendiente de la regresión lineal D/S vs repetición en banda alfa, fue significativa en 16 de 16 regiones en G1, 12 de 16 en G2 y 5 de 16 en G3. La conectividad funcional siguió estos cambios mientras que en las bandas delta, theta y beta no se registraron modificaciones. D se relaciona con activación y la S con inhibición lo que apoya la hipótesis de la participación de alfa en el proceso cognitivo de habituación a la fotoestimulación.

Abstract The hypothesis that the brain works using glial-neuronal networks that are responsible for sensory, motor and cognitive processes has been proposed in the neuroscience literature. Graph theory offers mathematical models to describe these complex networks from simple abstractions such as nodes and connecting edges. In this work, usign signal processing techniques to the analysis of functional connectivity between neuronal emsembles derived from EEG measurements through theory graph. Procedures for the analysis of connectivity are described, from multichannel record processing and conditioning, computation of wideband power spectral density, determination of connectivity measures between electrodes, and parameter estimation of the resulting complex networks. EEG recordings from fifty subjects were analyzed in intervals before (pre) and during repeated photostimulation (Rph). Based on the statistical significance of the response during Rph, desynchronization/synchronization (D/S) in alfa band, and its wide distribution in corticals areas, the participants were divided into three groups: G1 , G2 and G3. The slope D/S in alfa band was significant in 16 of 16 regions (G1), 12 of 16 (G2) and 5 of 16 (G3). The functional connectivity depicted the same trend as these changes, whereas in the delta, theta and beta bands occurred no modifications. D is related to activation and S with inhibition, supporting the hypothesis of alfa-band's participation in the cognitive process of habituation to photostimulation.

Coevolución genética Homo sapiens-Helicobacter pylori y sus implicaciones en el desarrollo del cáncer gástrico: una revisión sistemática / A Systematic Review of Genetic Coevolution of Homo Sapiens and Helicobacter Pylori: Implications for Development of Gastric Cancer

Helicobacter pylori (H. pylori), clasificada como carcinógeno tipo I para cáncer gástrico (CG), ha acompañado al hombre al menos desde hace 116 000 años. Los conocimientos de las fuerzas evolutivas que modulan el rol de esta bacteria en el desarrollo del espectro de enfermedades gástricas son aún escasos. Esta revisión sistemática recopila artículos que reportan un proceso de coevolución, relacionan los componentes ancestrales huésped-hospedero y describen mecanismos adaptativos de H. pylori al entorno gástrico humano, con el fin de comprender si el proceso de coevolución modula la patogenicidad de la bacteria y el desarrollo de enfermedades gástricas. Se realizó una búsqueda sistemática en las bases de datos electrónicas: MEDLINE (OvidSP), Scopus (ScienceDirect), Scielo y Tree of Science (ToS); términos de búsqueda: "stomach", "cancer", "neoplasms", "ethinicity", "evolution", "genetics", "ancestry" y "Helicobacter pylori". Idiomas: inglés y español. Los datos fueron filtrados por un revisor utilizando un formulario estándar de extracción y ulteriormente revisados por otro. El riesgo de sesgo y la calidad metodológica de los estudios fueron evaluadas con el programa: Critical Appraisal Skills Programme (CASP). Del total de 1584 estudios, 36 cumplieron los criterios de inclusión. Los factores más relevantes en el desarrollo del espectro de enfermedades asociadas con la infección por H. pylori son: la disrupción en el proceso de coevolución entre la bacteria y su huésped humano -por la transferencia horizontal de segmentos de genes que no han evolucionado con sus anfitriones-; las sustituciones de aminoácidos; la fijación y la selección positiva principalmente en las regiones hipervariables.

Helicobacter pylori (H. pylori) is classified as carcinogen type I for gastric cancer (GC). Although it has accompanied man for at least 116,000 years, knowledge of the evolutionary forces that modulate the role of this bacterium within the development of the spectrum of gastric diseases is still scarce. This systematic review compiles articles that report a process of coevolution process, relate host-host ancestral components, and describe H. pylori’s mechanisms of adaptation to the human gastric environment in order to understand if coevolution has modulated the pathogenicity of these bacteria and the development of gastric diseases. A systematic search was carried out in MEDLINE (OvidSP), Scopus (ScienceDirect), Scielo and Tree of Science (ToS). The following search terms were used: "Stomach", "Cancer", "Neoplasms", "Ethinicity", "Evolution", "Genetics", "Ancestry" and "Helicobacter pylori", and searches were conducted in both English and Spanish. The data were filtered by one reviewer using a standard extraction form and then reviewed by another. The risk of bias and the methodological quality of the studies were evaluated using the Critical Appraisal Skills Program (CASP). Thirty-six of the total 1,584 studies found met the inclusion criteria. The most relevant factors in the development of the spectrum of diseases associated with H. pylori infection are amino acid substitutions, binding and positive selection mainly in the hypervariable regions, and disruption of the coevolution process between the bacteria and their human hosts as the result of horizontal transfer of gene segments that did not evolve with their host.

BK Virus Nephropathy in Kidney Transplantation: An Approach Proposal and Update on Risk Factors, Diagnosis, and Treatment.

BK virus belongs to Polyomaviridae family; it causes 95% of nephropathy cases related to polyomavirus, with the other 5% caused by JC virus. Nephropathy jeopardizes graft function, causing a premature failure of the graft in 1%-10% of patients with kidney transplants. Nowadays, antiviral effective treatment is unknown, which is why blood and urine screening of renal transplantation patients has become the most important recommendation to guide the decrease of immunosuppression, and the only proven method to decrease poor outcomes. Different interventions, such as cidofovir, leflunomide, fluoroquinolones, and intravenous immunoglobulin, have been attempted with no improvement at all. This review aims to summarize the most relevant features of BK virus, historical issues, transmission mechanisms, risk factors, and therapeutic interventions.

Detección de virus entéricos en un sistema piloto de tratamiento de aguas residuales municipales / Detection of Enteric Viruses in a Pilot System for Municipal Wastewater Treatment

Se evaluó un sistema piloto de tratamiento de aguas residuales municipales para verificar su capacidad de remoción de patógenos virales. La presencia de Adenovirus, Calicivirus, Enterovirus, Virus de Hepatitis A y Virus de Hepatitis E. Se determinó mediante RT-PCR (Reacción en Cadena de la Polimerasa con Transcriptasa Reversa). Además se examinó la eficacia de los colifagos como indicadores y se verificó la presencia de indicadores bacterianos clásicos. Se obtuvo un 100% de positividad para la presencia de todos los virus en la entrada y salida del sistema, por lo que el sistema no es capaz de eliminarlos. Los colifagos no fueron removidos por este sistema, pero sirvieron como indicadores para la presencia de virus entéricos en el mismo. Los indicadores bacterianos redujeron su número a su paso por el sistema, pero aún al final del sistema, los coliformes se encontraban en números por encima de los límites establecidos por las leyes venezolanas. Por lo tanto, sería necesario agregar otros pasos al sistema, para poder obtener un efluente que cumpla las leyes y que garantice la ausencia de virus entéricos.

A pilot system for treating municipal waste was evaluated to verify its ability to remove viral pathogens. The presence of Adenovirus, Calicivirus, Enterovirus and Hepatitis A and E was determined using RT-PCR. The efficiency of coliphages as indicators and the presence of classic bacterial indicators were also investigated. A 100% positivity was obtained for the presence of all viruses at the entrance and exit of the system; therefore, the system was not able to remove them. Coliphages weren’t removed by the system, but they were effective as indicators of enteric viral presence in it. Bacterial indicators reduced their number going through the system, but even at the end of the system, coliforms had numbers above the limits dictated by Venezuelan law. Therefore, it would be necessary to add additional steps to the system in order to obtain an effluent that meets the laws and to ensure the absence of enteric viruses.

Calcium-activated potassium channel SK1 is widely expressed in the peripheral nervous system and sensory organs of adult zebrafish.

Sensory cells contain ion channels involved in the organ-specific transduction mechanisms that convert different types of stimuli into electric energy. Here we focus on small-conductance calcium-activated potassium channel 1 (SK1) which plays an important role in all excitable cells acting as feedback regulators in after-hyperpolarization. This study was undertaken to analyze the pattern of expression of SK1 in the zebrafish peripheral nervous system and sensory organs using RT-PRC, Westernblot and immunohistochemistry. Expression of SK1 mRNA was observed at all developmental stages analyzed (from 10 to 100 days post fertilization, dpf), and the antibody used identified a protein with a molecular weight of 70kDa, at 100dpf (regarded to be adult). Cell expressing SK1 in adult animals were neurons of dorsal root and cranial nerve sensory ganglia, sympathetic neurons, sensory cells in neuromasts of the lateral line system and taste buds, crypt olfactory neurons and photoreceptors. Present results report for the first time the expression and the distribution of SK1 in the peripheral nervous system and sensory organs of adult zebrafish, and may contribute to set zebrafish as an interesting experimental model for calcium-activated potassium channels research. Moreover these findings are of potential interest because the potential role of SK as targets for the treatment of neurological diseases and sensory disorders.

Análisis de los proyectos del sector agropecuario financiados por Colciencias durante el año 2010 / Analysis of agricultural projects funded by Colciencias during 2010

Objetivo. Analizar los proyectos del sector agropecuario financiados por Colciencias durante el año 2010. Materiales y métodos. Se utilizó la base de datos de registro de proyectos correspondientes al Programa Nacional de Ciencia, Tecnología e Innovación Agropecuarias para identificar las propuestas presentadas, elegibles y financiadas de las convocatorias del año 2010. Los proyectos se clasificaron con base en la nomenclatura Internacional de la UNESCO para los campos de la ciencia y la tecnología. Se identificó la convocatoria, campos, disciplinas, rama productiva, entidades participantes, departamento de ejecución y montos financiados. Resultados. Durante el año 2010 Colciencias recibió un total de 4.725 propuestas para financiación, de éstas, 790 correspondieron al Programa Nacional de Ciencia, Tecnología e Innovación Agropecuaria. Las disciplinas de los proyectos financiados, fueron en su mayoría pertenecientes al subsector agrícola, seguido por el pecuario y el agroindustrial. Las universidades públicas fueron el tipo de entidad ejecutora al que se le financió un mayor número de proyectos. Los departamentos en los cuales se ejecutó la mayoría de las propuestas financiadas fueron Antioquia, Cundinamarca, Boyacá y Tolima. Conclusiones. El Programa Nacional de Ciencia Tecnología e Innovación Agropecuaria recibió el 16.7% del total de proyectos recibidos por Colciencias en sus convocatorias del año 2010. El mayor número de proyectos recibidos, elegibles y financiables fueron del subsector agrícola y estuvieron presentados y ejecutados por universidades públicas. La inversión total de Colciencias en proyectos del sector agropecuario fue de $32.923.594.000 con un aporte de contrapartida de $33.225.740.000.

Objective. Identify and analyze the science, technology and innovation projects of the agriculturaland livestock sector, funded by Colciencias during 2010. Materials and methods. The registrationdatabase of Colciencias was used to identify eligible and funded project proposals by the NationalProgram of Agricultural Science, Technology and Innovation among 2010 calls. The projects wereclassified based on the UNESCO International nomenclature for the fields of science and technology.The variables identified for each project were: number of the call, field, discipline, subdiscipline,productive chain, participating institutions and execution department. Results. In 2010 Colcienciasreceived a total of 4,725 research proposals for funding, of these the National Program of AgriculturalScience, Technology and Innovation received 790 projects. The disciplines of the projects financedwere mostly from the agricultural subsector, followed by livestock and agribusiness. Public universitieswere the type of entity that received most of the funding for research projects. The departments thatreceived most of the funding from Colciencias were Antioquia, Cundinamarca, Boyaca and Tolima.Conclusions. The National Program of Agricultural Science, Technology and Innovation received16.7% of all projects received by Colciencias calls in 2010. Most of the projects submitted, eligible andfunded were from the agricultural subsector. Most of these projects were presented and implementedby public universities. Total investment of Colciencias to fund the agricultural sector was $32,923,594with a matching contribution of $33.225.740, 50.2% of total project value.

Optimized Detection of the Infrequent Response in P300-Based Brain-Computer Interfaces / Detección optimizada de la respuesta infrecuente en interfaces cerebro-computadora

This paper presents an application developed on the BCI2000 platform which reduces the average spelling time per symbol on the Donchin speller. The motivation was to reduce the compromise between spelling rate and spelling accuracy due to the large amount of responses required in order to perform coherent average techniques. The methodology was made under a Bayesian approach which allows calculation of each target's class posterior probability. This result indicates the probability of each response of belonging to the infrequent class. When there is enough evidence to make a decision the system stops the stimulation process and moves on with the next symbol, otherwise it continues stimulating the user until it finds the selected letter. The average spelling rate, after using the proposed methodology with 14 healthy users and a maximum number of 5 stimulation sequences, was of 6.1 ± 0.63 char/min, compared to a constant rate of 3.93 char/min with the standard system.

Este trabajo presenta una aplicación desarrollada sobre la plataforma BCI2000 que disminuye el tiempo promedio de selección de los símbolos del deletreador de Donchin. La motivación consistió en reducir el compromiso entre la taza de deletreo y la precisión correspondiente, la cual surge como consecuencia de la gran cantidad de respuestas necesarias para realizar técnicas de promediación coherente. La metodología propuesta se basa en un enfoque Bayesiano que permite calcular la probabilidad posterior asociada con la clasificación de cada objetivo, resultado que indica la evidencia que presentan las respuestas de pertenecer a la clase infrecuente. Cuando existe evidencia suficiente para tomar una decisión, el sistema detiene el proceso de estimulación y continúa con el siguiente símbolo, de lo contrario permanece estimulando al usuario hasta conseguir identificar la letra seleccionada. Después de utilizar la metodología propuesta sobre los registros de 14 usuarios sanos con un número máximo de 5 series de estimulación, el tiempo promedio de deletreo reportado es de 6.1 ± 0.63 letras/min, el cual es comparado con una taza constante de 3.93 letras/min obtenido con un sistema convencional.

[Atypical vascular tumors of the gastrointestinal tract: four uncommon cases]. / Tumores vasculares atípicos del tracto gastrointestinal: cuatro casos poco frecuentes.

AIM: A small but significant percentage of vascular tumors may develop at extracutaneous location. They are difficult to detect on the physical exam and usually they require immediate intervention. Pediatric surgeons must have acknowledge of its prognostic and therapeutic implications. PATIENTS AND RESULTS: We report 4 of these patients. Patient 1 was a healthy newborn who presented in the second week of life, recurrent severe gastrointestinal bleeding, thrombocytopenia and anemia. Diagnosis of multifocal linfangioendoteliomatosis with thrombocytopenia was established. Patient 2 had prenatal diagnosis of ascites and presented at birth sepsis, anemia, thrombocytopenia and hypoproteinemia. Upon laparotomy hemorrhagic ascites and thickening of rectum-sigmoid wall and mesentery were found. Pathologic diagnosis was Kaposiform hemangioendothelioma and the clinical course was consistent with Kassabach-Merrit phenomenon. Patient 3 had at birth, multifocal hepatic GLUT1- hemangiomatosis with severe cardiac insufficiency and coagulopathy. She died while waiting for a liver transplantation. Patient 4 is a girl who presented in the newborn period with vomiting and hematochezia. She required several transfusions and endoscopic biopsies showed a vascular tumor that infiltrated duodenum, jejunum and mesentery. Imaging studies and histologic findings on biopsy led to the diagnostic of juvenile hemangioma GLUT-1+. CONCLUSIONS: Vascular tumors of the digestive tract may be difficult to diagnosis and their classification is still incomplete. Pediatric surgeons must be acquainted with these varieties of tumors because they are always involved in diagnosis and therapeutic decision making.

Micobacteriosis sistémica por mycobacterium avium en paciente con SIDA / Systemic mycobacteriosis for Mycobacterium avium in a AIDS patient

Se analizaron repetidas muestras procedentes de un paciente cubano con SIDA, para descartar la presencia de bacilos ácido alcohol resistente (BAAR), pasadas 2-3 semana en las muestras de esputo, líquido cefalorraquídeo y de hemocultivo que habían sido procesadas y cultivadas se detecta la presencia de algunas colonias, como resultado se obtuvo el aislamiento de una cepa micobacteriana no pigmentada, de crecimiento lento perteneciente al Grupo III de Runyon, esta cepas fueron clasificadas como Mycobacterium avium por los métodos convencionales establecidos para la identificación de cepas micobacterianas, como técnica confirmativa diagnóstica se utilizó el análisis de las fracciones de ácido micólicos por la técnica de cromatografía en capa delgada bidimensional. El objetivo fundamental de este estudio ha sido reportar el primer caso de micobacteriosis sistémica en un paciente cubano con SIDA

Several sputum and blood culture simples from a Cuban HIV/AIDS patient were analyzed to discard the presence of alcohol acid resistant bacillus. After 2-3 weeks the culture revealed in both kinds of samples some colonies from non-pigmented mycobacterium strain with slow growth and belonging to III Runyon Group. This strain was classified as Mycobacterium avium by conventional methods established for mycobacterium identification. To diagnostic confirmative method was used the analysis of fraction mycolic acid by bi-dimensional thin layer chromatography. The main objective of this study was to report the first case of systemic mycobacteriosis in a Cuban HIV/AIDS patient

TrkB is necessary for the normal development of the lung.

Normal development of the lung requires coordinated activation of cascades of signaling pathways initiated by growth factors signaling through their receptors. TrkB and its ligands, brain-derived neurotrophic factor (BDNF) and neurotrophin-4, belong to the neurotrophin family of growth factors, which are expressed in a large variety of non-neuronal tissues including the lung. Aberrant neurotrophin signaling underlies the pathogenesis of several lung-related pathologies, including asthma and lung cancer, however, little is known about the role of neurotrophins in the embryonic development of the lung. To fill this gap in knowledge, we analyzed the pattern of TrkB expression in the murine lung and we observed that TrkB is expressed in alveolar macrophages, type II pneumocytes, neuroepithelial bodies and nerves. Analysis of the structure of lung from mice deficient in TrkB revealed that absence of TrkB signaling results in thinner bronchial epithelium and apparent larger air space, and, more importantly, lack of neuroepithelial bodies, an important reduction in the density of nerve fibres in the bronchial smooth muscle, submucous plexus in bronchioles, and pulmonary artery walls. These findings suggest TrkB is essential for the normal development of the lung and the nervous system in the lung.

Rehabilitación temprana de los maxilares en pacientes con labio y paladar hendido bilateral utilizando un dispositivo ortopédico dinámico intraoral, cinta adhesiva labial y gingivoperiosteoplastia: estudio piloto experimental / Early maxillary rehabilitation of bilateral cleft lip and palate patients using an intraoral dynamic orthopedic appliance, lip tape adhesion and gingivoperiosteoplasty: experimental pilot study

Introducción: el objetivo fue corroborar la respuesta ortopédica de los componentes alveolares al dispositivo ortopédico dinámico intraoral propuesto en el estudio piloto realizado por el mismo grupo investigador, combinado con la utilización de una cinta adhesiva sobre el labio y la gingivoperiosteoplastia (GPP) en una población colombiana. Métodos: denueve pacientes con LPHB entre los cinco y diez meses de edad, se seleccionaron seis pacientes, cuatro hombres y dos mujeres. Se les implantó el dispositivo dinámico y la cinta adhesiva durante un promedio de 3,5 semanas. Después de obtener el resultado ortopédico se les realizó la GPP y la rinoqueiloplastia primaria. Se obtuvieron modelos maxilares antes y después del tratamiento ortopédico, donde se tomaron medidas directamente con un calibrador digital y se compararon entre sí. Se evaluó la formación ósea cualitativamente con tomografías computarizadas, seis meses después de realizada la GPP. Se les hizo análisis estadístico descriptivo. Resultados: en todos los pacientes se logró retracción óptima de la premaxila. Cuatro de los seis pacientes requirieron expansión anterior. Hubo neoformación ósea en los ocho sitios donde se realizó la GPP. Conclusiones: el uso del dispositivo ortopédico dinámico y la cinta adhesiva sobre el labio permite disminuir las discrepancias entre los segmentos maxilares enpacientes con LPHB. La gingivoperiosteoplastia hecha en este esquema de tratamiento actúa como un procedimiento osteoinductor que propicia la neoformación ósea. Se corroboraron los hallazgos del estudio piloto realizado por el mismo grupo investigador y representa una opción terapéutica para pacientes con LPHB en nuestra comunidad.

Introduction: the purpose of this study was to corroborate the orthopaedic alveolar results of dynamic orthopaedic devices used in the pilot study by the same research group, combined with the use of an adhesive tape over the lip and gingivoperiostioplasty in a Colombian population. Methods: 6 patients with complete bilateral cleft lip and palate, 4 males and 2 females were selected out of 9 patients between five and ten months of age. The dynamic orthopaedic device and the adhesive tape were used during an average time of 3.5 weeks. After obtaining the orthopaedic result, the gingivoperiostioplasty and rhinoplasty were performed. Comparisons between before and after treatment casts were analyzed with an electronic digital calliper. The boneformation was evaluated with a dental CT scan after a period of 6 months. Descriptive statistical analysis was used. Results: every patient after orthopaedic treatment retracted the premaxilla, four of the six patients studied required anterior alveolar expansion. There was bone formation in the 8 sites where the gingivoperiostioplasty was performed. Conclusion: the use of the dynamic orthopaedic device and the adhesive tape over the lip decreased the discrepancies in maxillary segments of bilateral cleft lip and palate patients. The gingivoperiosteoplasty performed in this protocol serves as an osteo-inductor suitable for bone formation. This study corroborates the pilot study by the same research group and represents a practical option for the treatment in cases with protrusion of the premaxilar in our community.

[Morbility and mortality associated with prosthetic patch in congenital diaphragmatic hernia]. / Morbimortalidad en pacientes con parche protésico para el cierre de la hernia diafragmática congénita.

AIM: To analyze morbility, mortality and neonatal intensive care management in CDH patients who required a prosthetic patch to close the diaphragmatic defects, and to compare these results with those who were made a primary closure. MATERIAL AND METHODS: We reviewed the clinical charts of CDH patients managed at our institution between January 1994 and December 2006, including demographic data, clinical management, treatment options, complications and mortality. Appropriate statistical tests were used to evaluate the data: mortality, need of high frequency oscillatory ventilation (HFOV), days of intubation, days of total parenteral nutrition (TPN), days of admission, reherniation, need of Nissen funduplication and intestinal obstruction; a p value less than 0.05 was considered statistically significant. RESULTS: Eighty-seven CDH patients were reviewed, 68 right, 17 left and 2 bilateral defects. Seventeen died before surgery (19.5%). Among the 70 operated patients, 21 (24.1%) required a prosthetic patch, 18 in the left and 3 in the right side. Overall mortality, need of HFOV, intubation days, need of TPN, days of admission, reherniation rate and need of Nissen funduplication were all significantly worse in the group who required a patch. Rate of intestinal obstruction was similar in both groups. CONCLUSIONS: Patients who required a prosthetic patch to close the diaphragmatic defect suffered from higher morbidity and presented a higher mortality than those who did not required the patch.

[Reoperations in gastroesophageal reflux disease]. / Reoperaciones en reflujo gastroesofágico.

PURPOSE: The purpose was to determinate the indications in which the failure of the surgical treatment of the gastroesophageal reflux disease (GERD) is more frequent and to analyze the results of the reinterventions. PATIENTS AND METHOD: We made a restrospective review of the patients who underwent reoperation at our Institution during 1992-2006. RESULTS: 19 of 252 Nissen underwent reoperation. In one case was the fourth fundoplication, in another was the third and the second in the rest of them. The reflux was confirmed by upper gastrointestinal contrast study, endoscopy, pH monitoring and, in some cases, manometry. 5 cases have surgical comorbidity (3 Esophageal Atresia (EA), 2 Congenital diaphragmatic hernia (CDH), 4 patients was neurologically impaired, 1 had caustic stenosis (CS), and 9 only symptoms of GERD. 8.7% of the patients with GERD, 5.8% of the neurologically impaired children, 10% of the EA, 20% of the CDH and 50% of the CS underwent redo Nissen. The mean time between first and second fundoplication was 1.6 years (range = 1 m-5.5 y). It was 11.2 in neurologically impaired patients, 5 m in CS, 11.5 m in CDH, 2.4 y in EA and 2.8 y in the rest. In patients with respiratory disease, the mean was 1.1 y and 1.9 y in the rest. The mechanism of failure was herniation of the fundoplication through the hiatus in 8 cases, wrap incompetence in 4 and wrap dehiscence in 2. In 5 patients it couldn't be determined. There were 2 postoperative complications. The mean follow-up was 5.3 years (range = 6-151.5 m). There was no cases of mortality. 17 of the 19 patients (89.4%) are free of symptoms and don't need more treatments. The child with CS continuous periodic esophageal dilatations and 1 of the patients with EA has dysphagia to solid foods.

[Aplasia cutis congenita: surgical treatment and results in 36 cases]. / Revisión de 36 casos de aplasia cutis congénita. Protocolo quirúrgico y resultados.

INTRODUCTION: Aplasia cutis congenita is a rare congenital absence of skin most commonly affecting the scalp. Although most defects are small and superficial, approximately 20% of cases involve absence of the skull. Such defects expose the brain and sagital sinus, with concomitant risk of fatal hemorrage, infection, or both. This anomaly most commonly presents as a solitary defect, but sometimes it may occur as multiple lesions. The lesions are noninflammatory and well demarcated, and range is variable from 0.5 cm to 10 cm or more. Although the majority of these scalp defects occurs sporadically, many family cases have been reported. Multiple causes have been suggested for aplasia cutis: genetic causes, syndromes and teratogens, intrauterine infection -varicella zoster virus, herpes simplex virus-, fetal exposure to cocaine, heroin, alcohol or antithyroid drugs. MATERIALS AND METHODS: A retrospective study of children with Aplasia Cutis Congenita who received treatment in Hospital La Paz, in Madrid between 1995 and 2005 was undertaken. We checked location, moment of the surgery, type of surgery and aesthetic results. RESULTS: In the 20 year period between 1985-2005, we treated 36 patients with Aplasia Cutis. 33 of them have the scalp affected and only in 3 cases the trunk was involved. In 4 cases there was an absence of the skull, two slight and two severe. 3 patients had Adams-Oliver and one Cutis Marmorata Telangiectasica syndrome. Fifteen patients were operated in neonatal period with direct closure or advancement or rotational flaps, and in 17 cases the late treatment included use of tissue expanders to cover definitely the defect. One of the patients died for bleeding of the sagital sinus while was waiting for the secondary closure of the wound, and other patient required complex skull reconstruction to achieve a complete coverage. CONCLUSIONS: In view of our experience and results, we believe that early surgery prevents vital risks, reduces local complications and makes easier the final reconstruction.

[Pediatric patient in adult age. Long-terms results of esophageal replacement]. / El paciente pediátrico en la edad adulta: revisión a largo plazo de los resultados de la sustitución esofágica.

BACKGROUND: Esophagocoloplasty is one of the most used procedures for esophageal replacement in children. Considering high life expectancy in these patients, long-term results must be considered when evaluating this technique. The aim of our study is to evaluate quality of life of adult patients who underwent surgery at pediatric age. PATIENTS AND METHODS: We report a retrospective study of 99 patients who underwent esophageal replacement in our institution between 1966 and 2006. Eight of them have died and 63 out of the remaining 91 are over 18 years now and represent our study serie. Long-term results and actual situation of those patients, considering psychological, physic and social aspects, were evaluated through clinical review and telephonic interview. Karnofsky index was applied to mesure functional ability from 0-100% (bad, medium, good-excellent) according to the answers the patients gave to our questions. We also recorded their health personal experience and subjective evaluation of their quality of life. RESULTS: Sixty-three patients were reviewed (43 males and 20 females) with a mean age of 4.3 +/- 3.4 D.S. Mean follow-up time was 29.6 +/-7.7 years. Indications for esophageal replacement were as follows: caustication (n = 32), type III esophageal atresia (n = 15), type I AE (n = 13) and others (n = 3). In 48 patients the graft was placed in retroestenal position and in 15 cases retromediastic location was used. Postoperative period was uneventful in 44% of the patients, being the most frequent early complications in the remaining, cervical leakage and stenosis. Long-term, 56,8% did not have any sequelae, 28.5% required further surgery and the remaining 43.13% presented the following complications: symptomatic graft reflux (22), scoliosis and thoracic asymmetry (12), colonic redundancy or cervical diverticulum (7), food impaction (6) and failure to thrive (5). Only one 38 year old patient does not have intestinal tract continuity nowadays. Thirty-one patients have a Karnofsky index > or = 80-100%, being considered healthy and able to have a normal activity. Eighteen patients are included between 40-80%, being the most frequent limitation the need of medication to avoid reflux, backache and occasional episodes of food impact. Only 2 patients have Karnofsky index inferior to 40%. None of them are under 20%. CONCLUSIONS: Esophagocoloplasty allows restoration of intestinal tract continuity in almost all cases and the mortality of this procedure has decreased over time. Even though some risks are still remarkable, it offers long-term good results with little repercussion on functional ability in adult age. Most of the patients consider themselves healthy and enjoy an acceptable quality of life.

[Early surgical treatment in nasal tip hemangiomas: 36 cases review]. / Tratamiento quirúrgico precoz de los hemangiomas nasales: revisión de 36 casos.

BACKGROUND: Hemangiomas are the most common benign tumours in infancy. Its trophoblastic origin is now confirmed and it would explain their increasing incidence that runs parallel to the more frequent use of fertilization in vitro techniques and the high rates of prematurity and twinning. It is not a coincidence that they appear more often in the face and its location is related to the merging lines of the facial embryonal buds. Nose tip, upper-eyelid and orbital regions are special areas that need a different approach in each case. Over the last years we changed our therapy protocol for these tumours, in an attempt to decrease the psychological, social and scholar impact in children. PATIENTS AND METHODS: During the last 20 years, 36 patients with nasal tip hemangiomas underwent surgical treatment in our institution. We divided them into two groups, those treated between 1985 and 1992 (n=l1) and those treated between 1992 and 2005 (n=25). Traditionally, conservative management including close observation, corticosteroid therapy and finally surgical treatment of the sequelae, was proposed. Late surgical treatment was reserved for incompletely regressed or unsuccessfully treated facial tumours. Our more recent approach involves early surgical excision, in order to avoid psychological distress and cosmetics defects. Age at diagnosis, appearance at that moment, sort of treatment and time of surgical procedure were recorded to evaluate long-term results. RESULTS: In this paper we report our series of 36 patients, consisting of 26 females and 10 males, with a mean age of 5 +/- 2 months at the first visit. In 11 patients from the first period (1985-1992), corticosteroid therapy was applied waiting the spontaneous regression and they finally underwent delayed surgical treatment at a mean age of 8 years. In the remaining 25 patients treated in the second period, early surgical excision was carried out with a mean age of 3 years and before school age. Indications for corticosteroid therapy include uncontrolled growth and complications (ulceration). CONCLUSIONS: The approach to management of nasal tip hemangiomas should be individualized and must take into account their depth, location, rate of involution and functional disturbance. Children age as well as psychological problems arising from the presence of proliferative hemangioma must be considered when deciding a surgical approach. Upon the high rates of scholar failure in children with deforming hemangiomas, the lack of response to medical therapy and the need of surgical treatment in all cases, our policy now it is to attempt surgical excision and reconstruction before school age. Based on data reported and on our own experience, we consider that very early surgical treatment improves quality of life of our patients and their families.

Human DESC1 serine protease confers tumorigenic properties to MDCK cells and it is upregulated in tumours of different origin.

Proteolysis of the extracellular matrix components plays a crucial role in the regulation of the cellular and physiological processes, and different pathologies have been associated with the loss or gain of function of proteolytic enzymes. DESC1 (differentially expressed in squamous cell carcinoma gene 1), a member of the TTSP (type II transmembrane serine protease) family of serine proteases, is an epithelial-specific enzyme that has been found downregulated in squamous cell carcinoma of the head and neck region. We describe new properties of DESC1 suggesting that this protease may be involved in the progression of some type of tumours. Thus, this enzyme hydrolyses some extracellular matrix components, such as fibronectin, gelatin or fibrinogen. Moreover, Madin-Darby canine kidney (MDCK) cells expressing exogenous human DESC1 acquire properties associated with tumour growth such as enhanced motility and an increase of tubular forms in a 3D collagen lattice following HGF treatment. Finally, we generated polyclonal anti-DESC1 antibodies and immunohistochemical analysis in tissues different from head and neck region indicated that this protease was overexpressed in tumours of diverse origins. Taken together, our results suggest that DESC1 could be considered as a potential therapeutic target in some type of tumours.