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Introducción: el tratamiento de la malformación de Chiari I (MCI) y/o la siringomielia (SM) es controversial. La dinámica cuantitativa del LCR a nivel cráneo espinal es una alternativa que podría orientar la terapéutica. El objetivo de esta publicación es describir 5 casos en donde la utilización de la dinámica de LCR permitió guiar el tratamiento. Material y método: se revisaron las historias clínicas de 5 casos (edad media: 39 años / 3 mujeres y 2 varones). Todos fueron estudiados con RM en contraste de fase. El diagnóstico fue de MCI (1 caso) y SM (3 casos) o solo SM (1 caso). Sólo 2 casos con MCI+SM fueron intervenidos (descompresión + plástica dural). Todos fueron seguidos entre 1,5 y 6 años. Resultados: caso 1 (MCI) la velocidad del LCR fue normal por lo que su cefalea fue tratada médicamente con buenos resultados; caso 2 (MCI+SM) la velocidad estuvo aumentada por lo que fue intervenida controlándose los síntomas y la SM; caso 3 (MCI +SM) la velocidad fue normal siendo su diagnóstico compatible con síndrome post-siringomiélico; caso 4 (SM) la velocidad estuvo aumentada a nivel C5-C6 siendo su diagnóstico compatible con una SM espinal primaria; caso 5 (CMI + SM) luego de la intervención se observó que las velocidades y la SM tardaron 16 meses en normalizarse. Conclusión: en los casos descriptos la dinámica de LCR permitió realizar el diagnóstico correcto, determinar la conveniencia de realizar la cirugía, encontrar la causa y controlar la evolución postoperatoria(AU)
Background: the treatment of Chiari malformation I (CMI) and/or syringomyelia (SM) is controversial. The quantitative dynamics of CSF at the craniospinal level is an alternative that could guide therapy. The objective of this publication is to describe 5 cases in which the use of CSF dynamics allowed guiding the treatment. Methods: the medical records of 5 cases (mean age: 39 years / 3 women and 2 men) were reviewed. All were studied with MRI in phase contrast. The diagnosis was CMI (1 case) and SM (3 cases) or only SM (1 case). Only 2 cases with CMI+SM underwent surgery (decompression + duraplasty). All were followed between 1.5 and 6 years. Results: case 1 (CMI) the velocity of the CSF was normal, so his headache was treated medically with good results; case 2 (CMI+SM) the velocity was increased so it was intervened controlling the symptoms and the SM; case 3 (CMI +SM) the velocity was normal, its diagnosis being compatible with post-syringomyelic syndrome; case 4 (SM) the velocity was increased at the C5-C6 level, its diagnosis being compatible with a primary spinal SM; case 5 (CMI + SM) after the intervention it was observed that the velocities and the SM took 16 months to normalize. Conclusion: in the cases described, the CSF dynamics allowed the correct diagnosis to be made, to determine the advisability of performing surgery, to find the cause and to control the postoperative evolution(AU)
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Malformación de Arnold-Chiari , Cráneo , Siringomielia , Terapéutica , Espectroscopía de Resonancia MagnéticaRESUMEN
El neumoencéfalo es una patología que comúnmente se presenta después de cirugía neuroquirúrgica y ocasionalmente endonasal. Estos se suelen manejar de manera conservadora, sin embargo, se pueden asociar a distintas etiologías las cuales los hacen recurrir. En este reporte presentamos dos casos de neumoencéfalo tardío post quirúrgico asociado a fístulas de LCR de bajo flujo, donde se discute su clínica, etiología y manejo posterior.
Pneumocephalus is a pathology that commonly occurs after endonasal surgery, these are usually managed conservatively, however they can be associated with different etiologies which make them recur. In this report we present two cases of post-surgical late pneumocephalus associated with low-flow CSF fistulae, where its symptoms, etiology, and subsequent management are discussed.
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Humanos , Masculino , Persona de Mediana Edad , Neumocéfalo/cirugía , Fístula/líquido cefalorraquídeo , Neumocéfalo/diagnóstico por imagen , Complicaciones Posoperatorias , Imagen por Resonancia Magnética/métodos , Tomografía por Rayos X/métodosRESUMEN
Introduction:Post-dural puncture headache (PDPH) is defined as an orthostatic headache that develops within the first few days after performing a spinal tap and it is related to extravasation of cerebrospinal fluid (CSF) into the epidural space, resulting in CSF hypovolemia and hypotension. The risk factors for PDPH are not yet fully understood. Objective:To evaluate the risk of spontaneously reported PDPH according to the size and type of spinal tap needle. Methods:A total of 4589 patients undergoing outpatient lumbar puncture (LP) were included. All CSF collections were performed at Senne Liquor Diagnostico, a laboratory specialized in CSF collection and analysis. Patients were instructed to report by telephone if they had orthostatic headache during the first 7 days after LP to the medical team of the laboratory. Patients with previous headache were instructed to report any change in the headache pattern during the same period. Needle gauge was classified into two groups: 1) 25 G or less and 2) greater than 25 G. Two types of needles were used and compared: 1) Pencil point and 2) Quincke. Comparisons of the percentages of spontaneous reports of PDPH were made using the chi-square test. Results:141 patients (3.07%) reported PDPH to the laboratory's medical team. Needles of 25G gauge or less were used in 31.8% of cases. The percentage of patients reporting PHD in the group of 25G or less needles was 1.9% versus 3.6% in the group of larger than 25G needles (p=0.003). Pencil point needles were used in 10.6% of cases. The percentage of PHD among pencil point group was 1.4% versus 3.2% in Quincke group (p=0.026). Conclusion:25 G or finer gauge needles as well as pencil point type needles significantly reduced the risk of spontaneously reported PHD.
Introdução: A cefaleia pós-punção dural (CPPD) é definida como uma cefaleia ortostática que se desenvolve nos primeiros dias após a realização de uma punção lombar e está relacionada ao extravasamento de líquido cefalorraquidiano (LCR) para o espaço peridural, resultando em hipovolemia do LCR e hipotensão. Os fatores de risco para CPPD ainda não são totalmente compreendidos. Objetivo:Avaliar o risco de CPPD relatada espontaneamente de acordo com o tamanho e tipo de agulha de punção lombar. Métodos: Foram incluídos 4.589 pacientes submetidos à punção lombar (PL) ambulatorial. Todas as coletas de LCR foram realizadas no Senne Liquor Diagnostico, laboratório especializado em coleta e análise de LCR. Os pacientes foram orientados a relatar por telefone à equipe médica do laboratório se apresentassem cefaleia ortostática nos primeiros 7 dias após a PL. Pacientes com cefaleia prévia foram orientados a relatar qualquer alteração no padrão de cefaleia durante o mesmo período. O calibre da agulha foi classificado em dois grupos: 1) 25 G ou menos e 2) maior que 25 G. Dois tipos de agulhas foram utilizados e comparados: 1) ponta de lápis e 2) Quincke. As comparações dos percentuais de notificações espontâneas de CPPD foram feitas por meio do teste do qui-quadrado. Resultados:141 pacientes (3,07%) relataram CPPD à equipe médica do laboratório. Agulhas de calibre 25G ou menos foram utilizadas em 31,8% dos casos. A porcentagem de pacientes que relataram HDP no grupo de agulhas 25G ou menos foi de 1,9% versus 3,6% no grupo de agulhas maiores que 25G (p=0,003). Agulhas com ponta de lápis foram utilizadas em 10,6% dos casos. O percentual de DPH no grupo ponta de lápis foi de 1,4% versus 3,2% no grupo Quincke (p=0,026). Conclusão: Agulhas de calibre 25 G ou mais fino, bem como agulhas tipo ponta de lápis reduziram significativamente o risco de HP relatado espontaneamente.
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Background The unintentional ingestion of oropharyngeal or gastric contents into the respiratory tract is known as aspiration. Rhinorrhea can cause aspiration pneumonia (cerebrospinal fluid leakage). Objective There are only a few reports in the literature about pneumonia as a complication of rhinorrhea. There are no reports on how to handle such cases if they present to the clinic at the peak of COVID-19 disease and distinguish between these two conditions. Methods We reviewed the literature and retrospectively analyzed the clinical information and treatment protocols used to treat the two clinical cases. Results By screening the COVID-19 PCR and antibodies more than twice, surgery was postponed for 1014 days in both cases to rule out COVID-19-induced pneumonia. Chest CT scans still revealed ground glass opacities. In both cases, the skull base defect was repaired. In both cases, radiological signs of rhinorrhea-induced pneumonia had completely resolved at the 24- and 30-day follow-ups. Conclusion CSF aspiration causes radiological changes in the lungs in rhinnorhea. This is a short-term local decrease in lung tissue airness (partial filling of alveoli with fluids), which is visible radiographically (ground-glass opacities). To rule out COVID-19 infection, surgery should be postponed for 1014 days, and PCR and antibodies (IgG, IgM) should be performed at least twice. If the COVID-19 screening test is negative, repair surgery can be scheduled.
Introdução A ingestão não intencional de conteúdo orofaríngeo ou gástrico no trato respiratório é conhecida como aspiração. A rinorréia pode causar pneumonia por aspiração (vazamento de líquido cefalorraquidiano). Objetivo Existem poucos relatos na literatura sobre pneumonia como complicação da rinorréia. Não há relatos sobre como lidar com esses casos se eles se apresentarem à clínica no pico da doença COVID-19 e distinguirem entre essas duas condições. Métodos Revisamos a literatura e analisamos retrospectivamente as informações clínicas e os protocolos de tratamento utilizados para tratar os dois casos clínicos. Resultados Ao rastrear a PCR e os anticorpos da COVID-19 mais de duas vezes, a cirurgia foi adiada por 10 a 14 dias em ambos os casos para descartar pneumonia induzida pela COVID-19. A tomografia computadorizada de tórax ainda revelou opacidades em vidro fosco. Em ambos os casos, o defeito na base do crânio foi reparado. Em ambos os casos, os sinais radiológicos de pneumonia induzida por rinorréia foram completamente resolvidos nos acompanhamentos de 24 e 30 dias. Conclusão A aspiração do LCR causa alterações radiológicas nos pulmões na rinorreia. Esta é uma diminuição local de curto prazo na leveza do tecido pulmonar (preenchimento parcial dos alvéolos com fluidos), que é visível radiograficamente (opacidades em vidro fosco). Para descartar infecção por COVID-19, a cirurgia deve ser adiada por 10 a 14 dias e a PCR e anticorpos (IgG, IgM) devem ser realizados pelo menos duas vezes. Se o teste de rastreio da COVID-19 for negativo, pode ser agendada uma cirurgia reparadora.
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Information regarding resistance and virulence traits of meningitis-causing enterobacteria in hospital environment remains scarce. The aim of this study was to characterize virulence and acquired resistance genes of carbapenem-resistant and/or 3rd to 4th generation cephalosporin-resistant Klebsiella pneumoniae isolated from the cerebrospinal fluid of inpatients. Antimicrobial susceptibility testing was performed by disk diffusion. The string test was performed to identify hypermucoviscous phenotype. Galleria mellonella infection model was used to evaluate the virulence profile of the isolates. Screening for virulence determinants and acquired resistance genes were performed by PCR. The blaCTX-M and/or blaKPC and/or rmtG were detected in all the isolates. Genetic virulence determinants, including mrkD, entB, iroD, fecIRA, uge, wabG, fimH, ureA, ybtS, and clb were detected in the majority of multidrug-resistant K. pneumoniae isolates. One isolate presented hypermucoviscous phenotype, and several isolates showed enhanced virulence in G. mellonella infection model. The combination of the virulence genes found here seems to support not only the known virulence genetic context among nosocomial infections-causing K. pneumoniae but also the role that clb and ybtS may play in K. pneumoniae virulence.
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Infecciones por Klebsiella , Klebsiella pneumoniae , Antibacterianos/farmacología , Carbapenémicos , Cefalosporinas , Humanos , Infecciones por Klebsiella/microbiología , Pruebas de Sensibilidad Microbiana , Urea , Virulencia/genética , Factores de Virulencia/genética , beta-Lactamasas/genéticaRESUMEN
El cáncer de cuello uterino es el cuarto cáncer más frecuente en mujeres en el mundo y a nivel mundial, el VPH 16 se encuentra presente en aproximadamente el 60% de los casos. A la fecha, las variantes de VPH 16 se clasifican en 4 linajes y 16 sublinajes asociándose algunas variantes con severidad de lesión. La secuenciación de la región LCR y del gen E6 es utilizada para la clasificación de variantes. Por ello, el objetivo fue optimizar 2 PCRs convencionales para detectar la región LCR y una PCR para el gen E6. Para ello, se utilizaron muestras positivas para VPH 16, cebadores específicos para la región LCR y el gen E6. Se probaron las reacciones a diferentes temperaturas de anillamientos. La concentración de MgCl2, dNTP y cebadores fueron determinadas siguiendo las recomendaciones del fabricante de la enzima ADN polimerasa utilizada. Para la amplificación de la región LCR y el gen E6 del VPH 16, se observaron mejores resultados a una temperatura de anillamiento de 57°C y 50°C, respectivamente. La concentración de MgCl2 utilizada en ambas reacciones fue de 1,5mM, la de dNTP 0,2mM y la de cebadores 0,2uM. La optimización de la reacción de PCR permitirá obtener amplicones aptos para secuenciación, a fin de determinar las variantes génicas y posteriormente evaluar funcionalidad y actividad transcripcional que puedan estar relacionadas con la patogénesis cervical.
Cervical cancer is the fourth most common cancer in women in the world and worldwide HPV 16 is present in approximately 60% of cases. To date, HPV 16 variants are classified into 4 lineages and 16 sublineages, with some variants being associated with lesion severity. Sequencing of the LCR region and the E6 gene is used for variant classification. Therefore, the objective was to optimize two conventional PCRs to detect the LCR region and one PCR for the E6 gene. For this purpose, HPV 16 positive samples, specific primers for the LCR region and the E6 gene were used. The reactions were tested at different alignment temperatures. The concentration of MgCl2, dNTP, and primers was determined following the recommendations of the manufacturer of the DNA polymerase enzyme used. For amplification of the LCR region and the HPV 16 E6 gene, the best results were observed at an annealing temperature of 57°C and 50°C, respectively. The concentration of MgCl2 used in both reactions was 1.5mM, dNTP 0.2mM and primers 0.2uM. The present optimization will be used to sequence the amplified products to determine the variants and subsequently evaluate the functionality and transcriptional activity in order to relate it to cervical pathogenesis.
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Persistent infections with some types of human papillomavirus (HPV) constitute the major etiological factor for cervical cancer development. Nanog, a stem cell transcription factor has been shown to increase during cancer progression. We wanted to determine whether Nanog could modulate transcription of E6 and E7 oncogenes. We used luciferase reporters under the regulation of the long control region (LCR) of HPV types 16 and 18 (HPV16/18) and performed RT-qPCR. We found that Nanog increases activity of both viral regulatory regions and elevates endogenous E6/E7 mRNA levels in cervical cancer-derived cells. We demonstrated by in vitro mutagenesis that changes at Nanog-binding sites found in the HPV18 LCR significantly inhibit transcriptional activation. Chromatin immunoprecipitation (ChIP) assays showed that Nanog binds in vivo to the HPV18 LCR, and its overexpression increases its binding as well as that of c-Jun. Surprisingly, we observed that mutation of AP1-binding sites also affect Nanog's ability to activate transcription, suggesting cooperation between the two factors. We searched for putative Nanog-binding sites in the LCR of several HPVs and surprisingly found them only in those types associated with cancer development. Our study shows, for the first time, a role for Nanog in the regulation of E6/E7 transcription of HPV16/18.
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Proteínas de Unión al ADN/genética , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Proteína Homeótica Nanog/metabolismo , Proteínas Oncogénicas Virales/genética , Proteínas E7 de Papillomavirus/genética , Infecciones por Papillomavirus/metabolismo , Proteínas Represoras/genética , Línea Celular Tumoral , Proteínas de Unión al ADN/metabolismo , Femenino , Regulación Viral de la Expresión Génica , Interacciones Huésped-Patógeno , Papillomavirus Humano 16/metabolismo , Papillomavirus Humano 18/metabolismo , Humanos , Proteína Homeótica Nanog/genética , Proteínas Oncogénicas Virales/metabolismo , Proteínas E7 de Papillomavirus/metabolismo , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/virología , Regiones Promotoras Genéticas , Proteínas Represoras/metabolismo , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/metabolismo , Activación Transcripcional , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/virologíaRESUMEN
ABSTRACT Background: Increased concentrations of serum proteins in cerebrospinal fluid (CSF) are interpreted as blood-CSF barrier dysfunction. Frequently used interpretations such as barrier leakage, disruption or breakdown contradict CSF protein data, which suggest a reduced CSF flow rate as the cause. Results: Even the severest barrier dysfunctions do not change the molecular size-dependent selectivity or the interindividual variation of the protein transfer across barriers. Serum protein concentrations in lumbar CSF increase with hyperbolic functions, but the levels of proteins that do not pass the barrier remain constant (brain proteins) or increase linearly (leptomeningal proteins). All CSF protein dynamics above and below a lumbar blockade can also be explained, independent of their barrier passage, by a reduced caudally directed flow. Local accumulation of gadolinium in multiple sclerosis (MS) is now understood as due to reduced bulk flow elimination by interstitial fluid (ISF). Nonlinear change of the steady state in barrier dysfunction and along normal rostro-caudal gradients supports the diffusion/flow model and contradicts obstructions of diffusion pathways. Regardless of the cause of the disease, pathophysiological flow blockages are found in bacterial meningitis, leukemia, meningeal carcinomatosis, Guillain-Barré syndrome, MS and experimental allergic encephalomyelitis. In humans, the fortyfold higher albumin concentrations in early fetal development decrease later with maturation of the arachnoid villi, i.e., with beginning CSF outflow, which contradicts a relevant outflow to the lymphatic system. Respiration- and heartbeat-dependent oscillations do not disturb net direction of CSF flow. Conclusion: Blood-CSF and blood-brain barrier dysfunctions are an expression of reduced CSF or ISF flow rate.
RESUMO Introdução: Concentrações aumentadas de proteínas séricas no líquido cefalorraquidiano são interpretadas como disfunção da barreira (hemato-liquórica) sanguínea do LCR. Interpretações frequentemente usadas, como vazamento de barreira (quebra ou rompimento de barreira), rompimento ou quebra, contradiz os dados de proteína do LCR, que sugerem uma taxa de fluxo reduzida do LCR como a causa. Resultados: Mesmo as disfunções de barreira mais graves não alteram a seletividade dependente do tamanho molecular nem a variação interindividual da transferência de proteína através de barreiras. As concentrações de proteínas séricas no LCR lombar aumentam com as funções hiperbólicas, mas as proteínas que não passam a barreira permanecem constantes (proteínas do cérebro) ou aumentam linearmente (proteínas leptomeningeais). Toda a dinâmica das proteínas do LCR acima e abaixo de um bloqueio lombar também pode ser explicada, independente de sua passagem pela barreira, por um fluxo caudal reduzido. O acúmulo local de gadolínio na esclerose múltipla (EM) é agora entendido como decorrente da redução da eliminação do bulk flow pelo fluido intersticial (FIS). A mudança não linear do estado estacionário na disfunção da barreira e ao longo dos gradientes rostro-caudais normais apoia o modelo de difusão/fluxo e contradiz as obstruções das vias de difusão. Independentemente da causa da doença, os bloqueios fisiopatológicos do fluxo são encontrados na meningite bacteriana, leucemia, carcinomatose meníngea, síndrome de Guillain-Barré, EM e encefalomielite alérgica experimental. Em humanos, as concentrações de albumina quarenta vezes mais altas no desenvolvimento fetal inicial diminuem tarde com a maturação das vilosidades aracnoides, isto é, com o início do fluxo de LCR, o que contradiz um fluxo relevante para o sistema linfático. As oscilações dependentes da respiração e do batimento cardíaco não perturbam a direção do fluxo do LCR. Conclusão: As disfunções das barreiras hemato-liquórica e hemato-encefálica são uma expressão da redução da taxa de fluxo do LCR ou FIS.
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Humanos , Encéfalo/metabolismo , Barrera Hematoencefálica/metabolismo , Proteínas Sanguíneas/metabolismo , Líquido Cefalorraquídeo/metabolismoRESUMEN
Persistent infections by high-risk human papillomavirus (HR-HPV) are a necessary condition, but not sufficient for cervical cancer development. Genetic variants of HR-HPV appear to be related to the risk of persistent infections. The study performed a functional evaluation of variants of the HPV-31 promoter region (LCR). For this, cloning and subcloning of variants HPV-31/UFPE-21 HPV-31/UFPE-89, HPV-31/UFPE-66, E2 gene and prototype HPV-31 were performed. Transfection with different concentrations of E2 was done and the concentration of 25 ng was determined to be ideal for LCR activation. HPV-31/UFPE-21 and HPV-31/UFPE-89 have a greater ability to alter Nluc reporter gene expression levels and HPV-31/UFPE-66 showed decreased levels of gene expression of Nluc reporter gene compared to control. Statistical analysis showed a significant difference between the polymorphic LCR regions and the control (p < 0.0001). A more refined profile of variants of HPV-31 and its importance for the prognosis of cervical lesions begins to be drawn.
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Papillomavirus Humano 31/genética , Regiones Promotoras Genéticas , Proteínas de Unión al ADN/metabolismo , Células HeLa , Humanos , Polimorfismo Genético , Transactivadores/metabolismo , Activación Transcripcional , Proteínas Virales/metabolismoRESUMEN
Although progress has been made, the cognitive, biological and, particularly, the genetic underpinnings of math learning difficulties (MD) remain largely unknown. This difficulty stems from the heterogeneity of MD and from the large contribution of environmental factors to its etiology. Understanding endophenotypes, e.g., the role of the Approximate Number System (ANS), may help understanding the nature of MD. MD associated with ANS impairments has been described in some genetic conditions, e.g., 22q11.2 deletion syndrome (22q11.2DS or Velocardiofacial syndrome, VCFS). Recently, a girl with MD was identified in a school population screening. She has a new syndrome resulting from a microdeletion in 22q11.2 (LCR22-4 to LCR22-5), a region adjacent to but not overlapping with region 22q11.2 (LCR22-2 to LCR22-4), typically deleted in VCFS. Here, we describe her cognitive-neuropsychological and numerical-cognitive profiles. The girl was assessed twice, at 8 and 11 years. Her numerical-cognitive performance at both times was compared to demographically similar girls with normal intelligence in a single-case, quasi-experimental study. Neuropsychological assessment was normal, except for relatively minor impairments in executive functions. She presented severe and persistent difficulties in the simplest single-digit calculations. Difficulties in commutative operations improved from the first to the second assessment. Difficulties in subtraction persisted and were severe. No difficulties were observed in Arabic number writing. Difficulties in single-digit calculation co-occurred with basic numerical processing impairments in symbolic and non-symbolic (single-digit comparison, dot sets size comparison and estimation) tasks. Her difficulties suggest ANS impairment. No difficulties were detected in visuospatial/visuoconstructional and in phonological processing tasks. The main contributions of the present study are: (a) this is the first characterization of the neuropsychological phenotype in 22q11.2DS (LCR22-4 to LCR22.5) with normal intelligence; (b) mild forms of specific genetic conditions contribute to persistent MD in otherwise typical persons; (c) heterogeneity of neurogenetic underpinnings of MD is suggested by poor performance in non-symbolic numerical processing, dissociated from visuospatial/visuoconstructional and phonological impairments; (d) similar to what happens in 22q11.2DS (LCR22-2 to LCR22-4), ANS impairments may also characterize 22q11.2DS (LCR22-4 to LCR22-5).
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La proteína beta trace (PBT), también llamada Prostaglandina D2 Sintasa de tipo lipocalina, es una glicoproteína de peso molecular entre 23 y 29 kDa que convierte la prostaglandina H2 en prostaglandina D2. La misma está asociada a diferentes entidades clínicas. Por sus características moleculares puede ser un indicador útil de la alteración precoz en la filtración glomerular; por el aumento de su síntesis y su concomitante elevación en suero, un predictor de riesgo cardiovascular; y por su alta concentración en líquido cefalorraquídeo (LCR), un biomarcador de fístula de LCR. Puede medirse en distintos líquidos biológicos, como suero, orina y LCR. El objetivo de esta revisión fue actualizar los conocimientos de esta proteína para evaluar su utilidad en distintas áreas de la Medicina. La trascendencia de PBT en el campo de la bioquímica como posible biomarcador dependerá de la patología de base del paciente.
The beta trace protein (BTP), also called Prostaglandin D2 Synthase lipocalin type PGDS, is a glycoprotein between 23 and 29 kDa of low molecular weight that converts prostaglandin H2 in prostaglandin D2. BTP is a protein that has multiple clinical associations. Due to the characteristics of the molecule, it may indicate an early alteration in glomerular filtration; by the serum increase of its synthesis, it is a predictor of cardiovascular risk, and for its high concentration in cerebrospinal fluid (CSF), it is a marker of leakage. This protein can be measured in different biological fluids such as serum, urine, and CSF. The objective of this review is to update the knowledge about this protein as a biomarker. The significance of BTP in the field of biochemistry as a possible biomarker will depend on the patient's underlying pathology.
A proteína beta trace (PBT), também chamada de Prostaglandina D2, sintase de lipocalina é uma glicoproteína de peso molecular entre 23 e 29 kDa, que converte prostaglandina H2 em prostaglandina D2. PBT é uma proteína que está associada a várias entidades clínicas. Devido às características moleculares, pode ser uma indicação útil da alteração precoce na filtração glomerular, devido ao aumento de sua síntese e sua concomitante elevação em soro, um preditor de risco cardiovascular e, devido à sua alta concentração no líquido cefalorraquidiano (LCR), é um biomarcador da fístula LCR. É uma proteína que pode ser medida em diferentes fluidos biológicos, como soro, urina e LCR, e o objetivo desta revisão foi atualizar os conhecimentos desta proteína para avaliar sua utilidade em diversas áreas da medicina. A importância de PBT no campo da bioquímica como possível biomarcador dependerá da patologia subjacente do paciente.
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Abstract Objective: To assess the performance of cerebrospinal fluid (CSF) lactate as a biomarker to differentiate bacterial meningitis from viral meningitis in children, and to define an optimal CSF lactate concentration that can be called significant for the differentiation. Methods: Children with clinical findings compatible with meningitis were studied. CSF lactate and other conventional CSF parameters were recorded. Results: At a cut-off value of 3 mmol/L, CSF lactate had a sensitivity of 0.90, specificity of 1.0, positive predictive value of 1.0, and negative predictive value of 0.963, with an accuracy of 0.972. The positive and negative likelihood ratios were 23.6 and 0.1, respectively. When comparing between bacterial and viral meningitis, the area under the curve for CSF lactate was 0.979. Conclusions: The authors concluded that CSF lactate has high sensitivity and specificity in differentiating bacterial from viral meningitis. While at a cut-off value of 3 mmol/L, CSF lactate has high diagnostic accuracy for bacterial meningitis, mean levels in viral meningitis remain essentially below 2 mmol/L.
Resumo Objetivo: Estudar o desempenho do lactato no líquido cefalorraquidiano como biomarcador para diferenciar a meningite bacteriana da meningite viral em crianças, e definir uma concentração de lactato ótima no líquido cefalorraquidiano que possa ser significativa para a diferenciação. Métodos: Foram estudadas crianças com achados clínicos compatíveis com meningite. O nível de lactato no líquido cefalorraquidiano e outros parâmetros convencionais do líquido cefalorraquidiano foram registrados. Resultados: Em um valor de corte de 3 mmol/L, o lactato no líquido cefalorraquidiano apresentou uma sensibilidade de 0,90, especificidade de 1,0, valor preditivo positivo de 1,0, valor preditivo negativo de 0,963, com uma precisão de 0,972. Os índices de probabilidade positivo e negativo foram 23,6 e 0,1, respectivamente. Para comparação entre a meningite bacteriana e viral, a área abaixo da curva do lactato no líquido cefalorraquidiano foi 0,979. Conclusões: Concluímos que o lactato no líquido cefalorraquidiano possui alta sensibilidade e especificidade na diferenciação da meningite bacteriana da meningite viral. Embora em um valor de corte de 3 mmol/L o lactato no líquido cefalorraquidiano possua alta precisão de diagnóstico da meningite bacteriana, os níveis médios na meningite viral permanecem basicamente abaixo de 2 mmol/L.
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Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Meningitis Bacterianas/diagnóstico , Ácido Láctico/líquido cefalorraquídeo , Meningitis Viral/diagnóstico , Valores de Referencia , Biomarcadores/líquido cefalorraquídeo , Estudios Prospectivos , Sensibilidad y Especificidad , Meningitis Bacterianas/líquido cefalorraquídeo , Diagnóstico Diferencial , Meningitis Viral/líquido cefalorraquídeoRESUMEN
Three areas are highlighted in Gran La Plata, Argentina: industrial, urban, and residential. In this work, the levels of volatile organic compounds (VOCs) in indoor air of homes and schools in those areas were analyzed, through the use of passive monitors. The study period is between 2007 and 2010. Higher levels of VOCs were found in homes and schools in the industrial zone, higher than the levels corresponding to urban and residential. Taking into account the relationship between indoor and outdoor levels of VOCs, they have ratios (I/O) between 1.5 and 10 are evidenced contributions of emission sources of VOCs both indoor and outdoor. Complementarily, we estimated the life time cancer risk (LCR) for benzene, styrene, trichloroethylene, and tetrachloroethylene in children who spend their time mostly in such indoor environments. The results show high LCR values for benzene, which exceed acceptable values for the US EPA.
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Contaminantes Atmosféricos/toxicidad , Contaminación del Aire Interior , Neoplasias/inducido químicamente , Compuestos Orgánicos Volátiles/toxicidad , Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Argentina , Benceno/análisis , Niño , Monitoreo del Ambiente/métodos , Vivienda , Humanos , Industrias , Medición de Riesgo , Instituciones Académicas , Compuestos Orgánicos Volátiles/análisisRESUMEN
OBJECTIVE: To assess the performance of cerebrospinal fluid (CSF) lactate as a biomarker to differentiate bacterial meningitis from viral meningitis in children, and to define an optimal CSF lactate concentration that can be called significant for the differentiation. METHODS: Children with clinical findings compatible with meningitis were studied. CSF lactate and other conventional CSF parameters were recorded. RESULTS: At a cut-off value of 3mmol/L, CSF lactate had a sensitivity of 0.90, specificity of 1.0, positive predictive value of 1.0, and negative predictive value of 0.963, with an accuracy of 0.972. The positive and negative likelihood ratios were 23.6 and 0.1, respectively. When comparing between bacterial and viral meningitis, the area under the curve for CSF lactate was 0.979. CONCLUSIONS: The authors concluded that CSF lactate has high sensitivity and specificity in differentiating bacterial from viral meningitis. While at a cut-off value of 3mmol/L, CSF lactate has high diagnostic accuracy for bacterial meningitis, mean levels in viral meningitis remain essentially below 2mmol/L.
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Ácido Láctico/líquido cefalorraquídeo , Meningitis Bacterianas/diagnóstico , Meningitis Viral/diagnóstico , Biomarcadores/líquido cefalorraquídeo , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Humanos , Lactante , Masculino , Meningitis Bacterianas/líquido cefalorraquídeo , Meningitis Viral/líquido cefalorraquídeo , Estudios Prospectivos , Valores de Referencia , Sensibilidad y EspecificidadRESUMEN
Introducción: Cryptococcus neoformans es un hongo levaduriforme encapsulado, de distribución mundial, principalmente en regiones tropicales, causando infecciones en individuos inmunocomprometidos, sobre todo en los infectados con el virus de la inmunodeficiencia humana (HIV). La capacidad de infección de este hongo es variable, pudiendo citar la facultativa patogenicidad, cápsula con actividad fagocitaria y producción de melanina como antioxidante. El objetivo de este trabajo fue evaluar el uso de la PCR/ RFLP para la detección e identificación de C. neoformans directamente del líquido cefalorraquídeo (LCR) de pacientes ingresados en un hospital público de la ciudad de Lages, Estado de Santa Catarina, sur de Brasil, comparando el resultado con la tinción específica para el hongo y el crecimiento en medio de cultivo. Métodos: Las muestras fueran directamente teñidas con tinta china para observar la cápsula, bien como después sembladas en medio de cultivo (agar dextrosa Sabouraud y agar de Níger) para crecimiento fúngico; también se hizo la extracción del ADN con fenol-cloroformo. La técnica fue utilizada para amplificación del gen URA5 mediante reacción en cadena de la polimerasa (PCR) y después con las enzimas de restricción HhaI y Sau96I para genotipaje mediante la PCR-RFLP. Resultados: En dos muestras fueran aislados C. neoformans con la tinción china y amplificados en la PCR, en las cuales fueran identificados como var. grubii. Conclusión: El serotipo A var. grubii es lo más aislado en la criptococosis humana, principalmente en pacientes HIV, pero se desconoce la preferencia de este serotipo por este grupo de enfermos. (AU)
Introduction: Cryptococcus neoformans is an encapsulated yeast with worldwide circulation, predominantly in tropical regions, causing infections in immunocompromised individuals, particularly those infected with human immunodeficiency virus (HIV). The virulence of this fungus is variable, and it should be mentioned the facultative pathogenicity, capsule with anti-phagocytic activity, and antioxidant melanin production. The aim of this study was to evaluate the use of polymerase chain reaction (PCR)/ restriction fragment length polymorphism (RFLP) for detection and identification of C. neoformans directly from the cerebrospinal fluid (CSF) of patients admitted to a public hospital with suspected meningitis and/or meningoencephalitis in the city of Lages, Santa Catarina, southern Brazil. Results were compared using Chinese ink and growth media. Methods: The samples were submitted to direct examination with Chinese ink for capsule observation, then to growth on culture media (Sabouraud Agar and Niger), with subsequent DNA extraction with phenol-chloroform. PCR was the technique used for amplification of URA5 gene, and then restriction enzymes HhaI and Sau96I were used for genotyping by PCR-RFLP. Results: In two samples, C. neoformans were isolated by Chinese ink and amplified by PCR. They were identified as serotype var. grubii. Conclusion: C. neoformans var. grubii is the most commonly isolated in human cryptococcosis, mainly in HIV patients. However, the preference of this serotype for this group of patients is unknown. (AU)
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Humanos , Animales , Masculino , Femenino , Adulto , Criptococosis/líquido cefalorraquídeo , Cryptococcus neoformans/patogenicidad , Criptococosis/diagnóstico , Criptococosis/microbiologíaRESUMEN
Introducción: En los últimos años se han desarrollado múltiples escalas con el fin de establecer parámetros objetivos, basados en las características del líquido cefalorraquídeo que faciliten el diagnóstico diferencial entre meningitis bacteriana (MB) y aseptica (MA) y la consecuente decisión de iniciar o no antibióticos. Objetivos: Validar una escala predictiva para el diagnóstico de MA y MB en los pacientes pediátricos mayores de 30 días de vida y menores de 12 años. Métodos: Se revisaron de forma retrospectiva los estudios de líquido cefalorraquídeo de 69 historias de pacientes pediátricos, los cuales cumplieron con las definiciones establecidas, criterios de inclusión y ningún criterio de exclusión. Se asignó el puntaje según la Escala de Valgado, y se manejaron los datos usando EpiInfo SPSS y Epidat. Resultados: Los parámetros de la escala, mostraron una sensibilidad de 100 % (IC 95 %: 95,8-100 %); especificidad de 94,7 % (IC 95 %: 88,1-100 %). Se obtuvo un valor predictivo positivo de 80 % (IC 95 %: 56,4-100 %) y un valor predictivo negativo de 100 % (IC 95 %: 99,1-100 %). La razón de verosimilitud positiva fue de 19 (I.C 95 %: 6,3-57,2 %) y la negativa fue de 0; el test de KAPPA obtuvo un valor de 0,86. Conclusión: La escala clínica predictiva de Valgado resultó ser una herramienta válida, en vista de sus altos niveles de sensibilidad y especificidad; segura, por sus elevados valores de predictividad; eficiente, en vista de sus aceptables índices de eficiencia pronóstica; y reproducible en vista de los niveles de concordancia mostrados.
Introduction: In recent years, multiple scales have been developed in order to establish objective parameters, based on the characteristics of the cerebrospinal fluid that facilitate the differential diagnosis between bacterial meningitis (BM) and aseptic (AM) and the consequent decision to initiate or not antibiotics. Objectives: Validate a predictive scale for the diagnosis of am and bm in pediatric patients older than 30 days of age and younger than 12 years. Methods: The cerebrospinal fluid caractheristics of 69 pediatric patients were retrospectively reviewed by using their medical records. all of them, met the established definitions, inclusion criteria and no exclusion criteria. the score was assigned according to the valgado scale, and the data were handled using epiinfo spss and epidat. Results: Scale parameters showed a sensitivity of 100 % (95 % ci: 95.8-100 %); specificity of 94.7 % (95 % ci: 88.1-100 %). a positive predictive value of 80 % (95 % ci: 56.4-100 %) and a negative predictive value of 100 % (95 % ci: 99.1-100 %) were obtained. the positive likelihood ratio was 19 (95 % ci: 6.3-57.2 %) and negative was 0. kappa test obtained a value of 0.86. Conclusion: The predictive clinical valgado scale proved to be a valid tool in view of its high levels of sensitivity and specificity; safe, because of its high values of predictivity; efficient, in view of its acceptable predictive efficiency indices; and reproducible in view of the levels of concordance shown.
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Persistent infections with high-risk human papillomavirus (HPV) constitute the main risk factor for cervical cancer development. HPV16 is the most frequent type associated to squamous cell carcinomas (SCC), followed by HPV18. The long control region (LCR) in the HPV genome contains the replication origin and sequences recognized by cellular transcription factors (TFs) controlling viral transcription. Altered expression of E6 and E7 viral oncogenes, modulated by the LCR, causes modifications in cellular pathways such as proliferation, leading to malignant transformation. The aim of this study was to identify specific TFs that could contribute to the modulation of high-risk HPV transcriptional activity, related to the cellular histological origin. We identified sex determining region Y (SRY)-box 2 (SOX2) response elements present in HPV16-LCR. SOX2 binding to the LCR was demonstrated by in vivo and in vitro assays. The overexpression of this TF repressed HPV16-LCR transcriptional activity, as shown through reporter plasmid assays and by the down-regulation of endogenous HPV oncogenes. Site-directed mutagenesis revealed that three putative SOX2 binding sites are involved in the repression of the LCR activity. We propose that SOX2 acts as a transcriptional repressor of HPV16-LCR, decreasing the expression of E6 and E7 oncogenes in a SCC context.
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Regulación Viral de la Expresión Génica , Interacciones Huésped-Patógeno , Papillomavirus Humano 16/fisiología , Proteínas Oncogénicas Virales/biosíntesis , Factores de Transcripción SOXB1/metabolismo , Transcripción Genética , Sitios de Unión , Línea Celular , Análisis Mutacional de ADN , Papillomavirus Humano 16/genética , Humanos , Mutagénesis Sitio-Dirigida , Unión ProteicaRESUMEN
Introducción: La tuberculosis es un problema de salud pública. La escala diagnóstica de Thwaites es una herramienta usada para diferenciar la meningitis tuberculosa de otros tipos de meningitis bacterianas. Materiales y métodos: Estudio retrospectivo en pacientes con sospecha de meningitis bacteriana realizado en el Hospital Carlos Anadrade Marín con la información de los registros médicos del sistema informático AS-400. Resultados: Estudiamos 41 casos de meningitis bacteriana no tuberculosa y 7 casos confirmados de tuberculosis. Los resultados del uso de la escala fueron: sensibilidad 88% y especificidad 88%. Razón de Verosimilitud positiva: 7.33 y Razón de Verosimilitud negativa: 0.14. Discusión: La escala de Thwaites podría ser útil para diferenciar la meningitis bacteriana piógena de la tuberculosa. Palabras clave: OMS-OPS; thwaites; LCR; Meningitis, Tuberculosis.
Introduction: tuberculous meningitis is one of the most common public health problems worldwide. Thwaites diagnostic scale is a tool used to differentiate tuberculous meningitis from other types of bacterial meningitis. Methods: This is a retrospective study carried out in patients diagnosed of bacterial meningitis developed at Carlos Andrade Marin Hospital. Information was taken from the medical records stored in the AS400 system. Results: Of 48 patients studied, 41 had bacterial meningitis and seven tuberculous meningitis. The sensitivity and the specificity of Thwaites' diagnostic score were 88%. The LR+ and LR- were 7.33 y 0.14 respectively. Discusion: Thwaites' diagnostic score was found to be a useful tool to differentiate bacterial from tuberculous meningitis.
Asunto(s)
Humanos , Tuberculosis , Líquido Cefalorraquídeo , Técnicas de Laboratorio Clínico , Diagnóstico , Meningitis , Tuberculosis Meníngea , Salud Pública , Meningitis BacterianasRESUMEN
La meningitis recurrente es una entidad rara que sugiere la presencia de una comunicación adquirida o congénita entre el liquido cefalorraquídeo y las áreas mucocutáneas adyacentes. Presentamos el caso de una paciente de 11 meses con historia de meningitis recurrente (4 episodios) asociadas a hipoacusia neurosensorial y otorrea intermitente en la que se diagnóstico fístula del LCR en oído interno así como una malformación secular cócleo-vestibular compatible con displasia de Mondini. Ante cuadros recurrentes de meningitis bacteriana en la edad pediátrica y más aún, si padece hipoacusia neurosensorial como en nuestro caso, es necesario agotar todas las posibilidades diagnósticas de forma precoz y oportuna en busca de malformaciones. En especial las fístulas congénitas que frecuentemente se les asocian y que con una temprana intervención quirúrgica puede evitar futuros episodios.
Recurrent meningitis is a rare but severe entity which suggests the presence of an acquired or congenital communication between of cerebrospinal fluid and adjacent mucocutaneous sites. We present the case of an 11 month patient with history of recurrent meningitis ( 4 episodes), associated to neurosensorial hipoacusia and intermittent otorrhea in which a diagnosis of cerebrospinal fluid fistula in the middle ear as well as a secular cochlea-vestibular malformation, compatible with Mondini dysplasia was made. In the presence of recurrent bacterial meningitis in the pediatric age, moreover if the patient suffers hearing impairment as in our case, it is necessary to exhaust all diagnostic possibilities early and timely in search of malformations, especially congenital fistulas, as they are associated and prompt surgical intervention may prevent futher episodes.
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ABSTRACT Lumbar puncture in neurologically asymptomatic HIV+ patients is still under debate. There are different criteria for detecting neurosyphilis through cerebrospinal fluid (CSF), especially in cases that are negative through the Venereal Disease Research Laboratory (VDRL), regarding cellularity and protein content. However, a diagnosis of neurosyphilis can still exist despite negative VDRL. Treponema pallidum hemagglutination assay (TPHA) titers and application of the TPHA index in albumin and IgG improve the sensitivity, with a high degree of specificity. Thirty-two patients were selected for this study. VDRL was positive in five of them. The number of diagnoses reached 14 when the other techniques were added. It was not determined whether cellularity and increased protein levels were auxiliary tools in the diagnosis. According to our investigation, CSF analysis using the abovementioned techniques may be useful in diagnosing neurosyphilis in these patients.
RESUMO La punción lumbar (PL) en pacientes VIH+ neurológicamente asintomáticos es controversial. Existen diferentes criterios para detectar en el líquido cefalorraquídeo (LCR) neurosífilis (NS): el examen Venereal Disease Research Laboratory (VDRL) en primer lugar, en caso de negatividad: la celularidad y el tenor de proteinas. Sin embargo el diagnóstico de NS puede ser sostenido a pesar de la negatividad de las técnicas mencionadas. La titulación del Treponema pallidum hemagglutination assay (TPHA) y la aplicación del índice de TPHA en Albúmina e Ig G mejoran la sensibilidad asociando elevado grado de especificidad. 32 pacientes fueron seleccionados para este estudio, el VDRL fue positivo en 5. El diagnóstico se elevó a 14 cuando se sumaron el resto de las técnicas. No se evidenció que la celularidad y el aumento de proteínas fueran herramientas auxiliares para el diagnóstico. De acuerdo a nuestro trabajo el estudio del LCR con las técnicas señaladas puede ser de utilidad en el diagnóstico de NS en estos pacientes.