Ivermectin reduces in vivo coronavirus infection in a mouse experimental model.

The objective of this study was to test the effectiveness of ivermectin for the treatment of mouse hepatitis virus (MHV), a type 2 family RNA coronavirus similar to SARS-CoV-2. Female BALB/cJ mice were infected with 6,000 PFU of MHV-A59 (group infected, n = 20) or infected and then immediately treated with a single dose of 500 µg/kg ivermectin (group infected + IVM, n = 20) or were not infected and treated with PBS (control group, n = 16). Five days after infection/treatment, the mice were euthanized and the tissues were sampled to assess their general health status and infection levels. Overall, the results demonstrated that viral infection induced typical MHV-caused disease, with the livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while mice treated with ivermectin showed a better health status with a lower viral load (23,192 AU; p < 0.05), with only a few having histopathological liver damage (p < 0.05). No significant differences were found between the group infected + IVM and control group mice (P = NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in the treated mice than in the infected animals. In conclusion, ivermectin diminished the MHV viral load and disease in the mice, being a useful model for further understanding this therapy against coronavirus diseases.

Hongos anamorfos biodegradan los libros del Área Histórica de la Universidad Central del Ecuador (UCE) / Anamorphous fungi biodegrade the books of the Historical Area from the Central University of Ecuador (CUE)

Determinamos los géneros de hongos anamorfos que contaminan los libros del área de cuarentena y limpieza, dentro del Área Histórica de la Universidad Central del Ecuador (UCE). Realizamos un hisopado aleatorio a una muestra representativa de 50 de estos libros de acuerdo a una Tabla militarizada estándar. También hisopamos como muestra preferencial a 21 libros gravemente contaminados con hongos. Los hisopados tuvieron una superficie de 5x5 cm, friccionando en la pasta, el borde y el interior de estos libros. Las 213 muestras tomadas fueron inoculadas en medio de cultivo Agar Malta. Los medios fueron incubados a una temperatura de 28°C durante 7 días. Realizamos observaciones por microscopía a 40 y 100x además de usar literatura especializada para la identificación hasta el nivel de género de hongos anamorfos. Los géneros más abundantes en este estudio fueron Penicillium (80,2%) y Mucor (8,1%). (AU)

We determined the genera of anamorphic fungi that contaminate the books in the quarantine and cleaning area, within the Historical Area of the Central University of Ecuador (CUE). We performed a random swab on a representative sample of 50 of these books according to a standard militarized Table. We also swabbed as a preferential sample 21 books seriously contaminated with fungi. The swabs had a surface area of 5x5 cm, rubbing on the paste, the edge and the interior of these books. The 213 samples taken were inoculated in Agar Malta culture medium. The media were incubated at a temperature of 28° C for 7 days. We made observations by microscopy at 40 and 100x in addition to using specialized literature for the identification down to the genus level of anamorphic fungi. The most abundant genus in this study were Penicillium(80,2%) and Mucor(8,1%). (AU)

Impacto de un programa educativo sobre epilepsia en los conocimientos generales de la comunidad: Experiencia de la Liga Chilena contra la Epilepsia (LICHE) entre los años 2018 y 2019 / Impact of an Epilepsy Educational Program on the General Knowledge of the Community: Experience of the Chilean League Against Epilepsy (LICHE) between 2018 and 2019

La epilepsia es una enfermedad neurológica crónica, no transmisible, que afecta en la actualidad a cerca de 50 millones de personas en el mundo. Un aspecto particular de esta patología se refiere al impacto psicosocial negativo que la acompaña, específicamente lo que se refiere a estigma y discriminación. Pese a los grandes avances en el conocimiento científico de esta patología dicho impacto psicosocial negativo se mantiene; estudios realizados en diferentes grupos y poblaciones así lo confirman. El objetivo del presente estudio es determinar si los programas educativos realizados por la Liga Chilena contra la Epilepsia que ha desarrollado desde hace varias décadas para toda la comunidad, con diferentes estrategias metodológicas, de manera de contribuir en la labor de mejorar la calidad de vida de las personas con epilepsia, sus familiares y cuidadores, aumentan los conocimientos sobre las Epilepsias en la población que participa. La capacitación mejoró significativamente los conocimientos en todos los ítems. El mayor impacto se produjo en las preguntas sobre las cuales había desconocimiento.

Epilepsy is a chronic, non-communicable neurological disease that currently affects nearly 50 million people worldwide. A particular aspect of this pathology refers to the negative psychosocial impact that accompanies it, specifically regarding stigma and discrimination. Despite great advances in scientific knowledge of this pathology this negative psychosocial impact remains; studies in different groups and populations confirm this. The objective of this study is to determine whether the educational programs carried out by the Chilean League against Epilepsy which it has developed for several decades for the whole community, with different methodological strategies, in order to contribute to the work of improving the quality of life of people with epilepsy, their families and caregivers, increase knowledge about epilepsy in the people that participate in them. The training significantly improved the knowledge in all items. The greatest impact occurred on questions about which there was no prior knowledge.

Satisfacción de los usuarios con las intervenciones educativas realizadas por la Liga Chilena contra la Epilepsia (LICHE) entre los años 2017 a 2019 / User Satisfaction with Educational Interventions carried out by the Chilean League against Epilepsy (LICHE) between 2017 and 2019

La epilepsia es una enfermedad neurológica crónica frecuente, que afecta aproximadamente a 50 millones de personas en el mundo. Puede ser definida, desde un punto de vista biológico, como una enfermedad caracterizada por una tendencia sostenida en el tiempo a presentar crisis epilépticas. Pero para comprender el impacto que conlleva para las personas afectadas y su grupo familiar, además del componente biológico, es necesario también prestar atención a las consecuencias psicosociales de la enfermedad: discriminación y estigma. La Liga Chilena contra la Epilepsia, integrante de Anliche (Asociación Nacional de Ligas Chilena contra la Epilepsia), capítulo chileno del IBE, cuenta con una larga experiencia de más de 20 años en lo que se refiere a educación en Epilepsia. El objetivo del presente trabajo es describir el nivel de satisfacción de los participantes sobre las actividades de capacitación realizadas por LICHE, comparando diferentes grupos de usuarios y la evolución temporal entre 2017 y 2019. El 79,3% de los participantes está completamente de acuerdo en que la intervención educativa cumplió satisfactoriamente sus expectativas. Los ítems con mayor porcentaje de nota óptima fueron: Objetivos 88,9%; Aplicabilidad 85,6% y Contenidos 85,5%.

Epilepsy is a common chronic neurological disease, affecting approximately 50 million people worldwide. It can be defined, from a biological point of view, as a disease characterized by a sustained tendency over time to develop epileptic seizures. But to understand the impact it has on people afflicted by it and their family group, in addition to the biological component, it is also necessary to pay attention to the psychosocial consequences of the disease: discrimination and stigma. The Chilean League against Epilepsy, a member of Anliche (Chilean National Association of Leagues against Epilepsy), Chilean chapter of the IBE, has a long experience of more than 20 years in terms of education in Epilepsy. The objective of this work is to describe the level of satisfaction of the participants on the training activities carried out by LICHE, comparing different user groups between 2017 and 2019. 79.3% of participants fully agree that the educational intervention satisfactorily met their expectations. Items with the highest optimal grade percentage were: Objectives 88.9%; Applicability 85.6% and Contents 85.5%.

Development, behaviour and sensory processing in Marshall-Smith syndrome and Malan syndrome: phenotype comparison in two related syndromes.

BACKGROUND: Ultrarare Marshall-Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross-sectional study, and results are presented with genetic findings. METHODS: Behavioural phenotypes are compared of eight individuals with Marshall-Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long-term follow-up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall-Smith syndrome. RESULTS: Marshall-Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow-up measurement of cognition and adaptive behaviour in Marshall-Smith syndrome shows different individual learning curves over time. CONCLUSIONS: Results show significant between and within syndrome variability. Different NFIX variants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person-environment fit.

Role of inflammasome activation in tumor immunity triggered by immune checkpoint blockers.

Immune checkpoint blockers improve the overall survival of a limited number of patients among different cancers. Identifying pathways that influence the immunological and clinical response to treatment is critical to improve the therapeutic efficacy and predict clinical responses. Recently, a key role has been assigned to innate immune mechanisms in checkpoint blockade-driven anti-tumor responses. However, inflammatory pathways can both improve and impair anti-tumor immunity. In this review, we discuss how different inflammatory pathways, particularly inflammasome activation, can influence the clinical outcome of immune checkpoint blockers. Inflammasome activation may reinforce anti-tumor immunity by boosting CD8+ T cell priming as well as by enhancing T helper type 17 (Th17) responses. In particular, we focus on the modulation of the cation channel transmembrane protein 176B (TMEM176B) and the ectonucleotidase CD39 as potential targets to unleash inflammasome activation leading to reinforced anti-tumor immunity and improved efficacy of immune checkpoint blockers. Future studies should be aimed at investigating the mechanisms and cell subsets involved in inflammasome-driven anti-tumor responses.

Use of Everolimus After Multivisceral Transplantation: A Report of Two Cases.

Inhibitors of mechanistic target of rapamycin are used in solid organ transplant procedures to avoid calcineurin inhibitor complications, including nephrotoxicity and malignancy. We present 2 cases of multivisceral transplantation for neuroendocrine tumor (NET) for which everolimus was implemented for its potential to prevent NET recurrence as well as preserve renal function. The first case was complicated by NET recurrence in the liver before initiation of everolimus. After initiation of everolimus, the patient developed a ventral hernia and elevated aminotransferase levels with nonspecific biopsy findings. The second case was complicated by cytomegalovirus infection with elevated everolimus trough levels as well as acute cellular rejection. Everolimus was reinitiated in both cases in addition to decreasing the dosage of tacrolimus, and there were no further complications. Everolimus was beneficial in stabilizing renal function in both patients and has the theoretical potential to prevent recurrence of NET.

A Case Report of Acute Cellular Rejection Following Intestinal Transplantation Managed With Adalimumab.

There is a higher incidence of acute cellular rejection (ACR) in small bowel transplantation (SBT) compared with transplantation of other solid organs. Although there are reports on the use of infliximab to successfully treat ACR refractory to other treatments, there are no reports, to our knowledge, regarding the use of adalimumab. We present a case of a female patient with a history of Crohn's disease who underwent an isolated SBT and developed an episode of severe ACR. She was initially treated with methylprednisolone, thymoglobulin, basiliximab, and a dosage adjustment of tacrolimus. Results of repeat endoscopies and biopsies revealed no significant improvement. The patient initiated treatment with adalimumab every 2 weeks for a total of 6 months, in addition to maintenance treatment with prednisone and tacrolimus. Subsequent evaluations showed gradual improvement to normal mucosa and villi without ulceration. A regimen that incorporates adalimumab can thus be used to treat ACR after intestinal transplantation. Larger multicenter studies are needed to show the full efficacy of this therapeutic regimen.

Experiencia del uso de terapia biológica en pacientes con enfermedad inflamatoria intestinal en un hospital público / Experience in the use of biological therapy in IBD patients in a public hospital

Biological therapy plays an important role in the treatment of inflammatory bowel disease (IBD). However, the use of these drugs is limited due to fears about their side effects. Aim: To report the experience with the use of infliximab/adalimumab in IBD patients in a public hospital. Material and Methods: Descriptive study of a historical cohort of IBD patients treated with infliximab and adalimumab between April 2012 and July 2014. The clinical response was considered favourable when general, intestinal and extra intestinal symptoms subsided after the induction therapy. In addition, endoscopic and/or imaging response was evaluated at three and six months of treatment. Results: Fifteen out of 162 patients, aged 17 to 52 years (7 women) were included. Seven had Crohn´s Disease, 7 had ulcerative colitis and one had non-classifiable IBD. Biological therapy was indicated due to conventional refractory disease in all patients. All patients received combined treatment with immunosuppressive medications. A favorable clinical response was observed in 93 percent after induction therapy and 73 percent showed endoscopic/imagining remission after 3-6 months. Only one patient experienced side effects associated to the biological therapy, which did not result in discontinuation or treatment interruption. Conclusions: In this cohort of IBD patients treated in a public hospital, the use of infliximab/adalimumab was associated with favorable clinical and endoscopic evolution, post induction therapy with no major side effects.

La terapia biológica tiene un papel fundamental en el tratamiento de la enfermedad inflamatoria intestinal (EII). Sin embargo, el uso de estos fármacos es escaso debido a los costos y los temores sobre los efectos secundarios. Objetivo: Dar a conocer la experiencia en el uso de infliximab/adalimumab en pacientes con EII atendidos en un hospital público de nuestro país. Material y Métodos: Estudio descriptivo de una cohorte histórica de pacientes con EII tratados con infliximab y adalimumab entre abril de 2012 y julio de 2014. La respuesta clínica fue considerada favorable cuando los síntomas generales, intestinales y extra-intestinales desaparecieron después de la terapia de inducción. Además se evaluó la respuesta endoscópica/radiológica a los 3 y 6 meses de tratamiento. Resultados: De un total de 162 pacientes con EII, 15 fueron tratados con terapia biológica, con edad entre 17-52 años (7 mujeres). Siete presentaban el diagnóstico de enfermedad de Crohn, siete colitis ulcerosa y uno EII no clasificable. En todos se inició terapia biológica debido a la presencia de refractariedad a la terapia convencional. Todos recibieron terapia combinada con inmunosupresores. Se observó una respuesta clínica favorable en 93 por ciento después de la terapia de inducción y 73 por ciento tuvo una mejoría endoscópica después de 3-6 meses. Sólo un paciente presentó un evento adverso a terapia biológica, el cual no motivó la interrupción del tratamiento. Conclusiones: En esta cohorte de pacientes con EII tratados en un hospital público, el uso de infliximab/adalimumab se asoció con mejoría clínica y endoscópica post terapia de inducción, sin mayores efectos secundarios.

Frecuencia y factores asociados a daño hepático inducido por medicamentos en tratamiento antituberculosis / Frequency and factors associated with DILI in antituberculosis treatment

Introduction: Potentially hepatotoxic drugs are used in tuberculosis treatment. The incidence range of drug-induced liver injury (DILI) varies from 0.6 to 33 percent. Adverse reactions can be asymptomatic; therefore periodical liver tests are required. Multiple risk factors are described, such as age and HIV infection, among others. Objective: To determine risk factors associated to DILI and secondary lethality in patients receiving anti-tuberculosis drugs. Materials and Methods: The database from the Servicio de Salud Metropolitano Central de Chile was used. 1,249 patients were analyzed from 2003 to 2008 to determine DILI’s frequency and time of appearance. Multivariate binominal regression was used to study possible risks associated to hepatotoxicity. Results: 2,8 percent of our patients presented DILI (n = 35), three of them died from this cause (8.5 percent). Association between DILI and HIV infection and extrapulmonary tuberculosis was observed (p < 0.01). DILI was present in 50 percent of our patients before the 23rd day. Conclusions: We propose a more exhaustive control of the liver function in patients with DILI risk factors, including HIV carriers and extrapulmonary tuberculosis.

Introducción: El tratamiento antituberculosis incluye drogas hepatotóxicas, estimándose una incidencia de daño hepático inducido por medicamentos (DHIM) entre 0,6 y 33 por ciento. Puede ser asintomático, debiendo evaluarse periódicamente con perfil hepático. Se han descrito múltiples factores de riesgo, como mayor edad e infección por VIH, entre otros. Objetivo: Determinar factores asociados al desarrollo de DHIM y letalidad secundaria a tratamiento antituberculosis. Materiales y Métodos: Base de datos del Programa de Tratamiento antituberculosis del Servicio de Salud Metropolitano Central de Chile. Se analizaron 1.249 pacientes entre 2003 y 2008. Se determinó frecuencia y tiempo de aparición de DHIM. Se estudiaron posibles factores asociados a hepatotoxicidad mediante regresión binomial. Resultados: se diagnosticó DHIM en 2,8 por ciento de los pacientes (n = 35), falleciendo 3 de ellos por esta causa (8,5 por ciento). Se observó asociación entre DHIM con ser portador de VIH (+) y tuberculosis extrapulmonar (p < 0,01). Aparición de DHIM antes del día 23 en 50 por ciento de los casos. Conclusión: Sugerimos un control más exhaustivo del perfil hepático en pacientes con factores de riesgo, entre los cuales deben considerarse los portadores de VIH y tuberculosis extrapulmonar.

¿Beneficio o riesgo del uso de ácido ursodeoxicólico en prevención de cáncer colorrectal en pacientes con colangitis esclerosante primaria/colitis ulcerosa? / Benefit or risk from the use of ursodeoxycholic acid in prevention of colorectal

cancer in patients with primary sclerosing cholangitis/ulcerative colitis? Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of intra-and extrahepatic bile ducts. About 70 percent of patients with CEP have idiopathic ulcerative colitis (IUC). PSC is considered a premalignant condition with an increased risk of colorectal cancer (CC). Individuals with PSC and IUC have higher risk of developing CC than IUC patients. There are different positions between American and European experts in the fields of hepatology and inflammatory bowel disease regarding the use of ursodeoxycholic acid (UDCA) in PSC and IUC as a chemo preventive. Studies have shown mixed results about the use of UDCA in preventing CC. The following is an update on the role of UDCA as a chemo preventive in this group of patients.

La colangitis esclerosante primaria (CEP) es una enfermedad crónica hepática colestásica caracterizada por inflamación y fibrosis de ductos biliares intra y extrahepáticos. Alrededor de 70 por ciento de los pacientes con CEP presenta colitis ulcerosa idiopática (CUI). La CEP es considerada una condición premaligna con un incremento del riesgo de cáncer colorrectal (CCR). Individuos con CEP más CUI tienen mayor riesgo de desarrollar CCR que pacientes con sólo CUI. Existen distintas posturas a nivel mundial entre expertos americanos y europeos tanto en el área de la hepatología como en el área de las EII (enfermedades inflamatorias intestinales) frente al uso de ácido ursodeoxicólico (AUDOC) en CEP y CUI como quimioprotector. Estudios han mostrado resultados contradictorios para el uso de AUDOC en la prevención de CCR. Se expone una revisión actualizada sobre el rol de AUDOC como quimioprotector en este grupo de pacientes.

Enfermedad inflamatoria intestinal y trasplante de órgano sólido: ¿Qué factores hay que considerar en el manejo? Revisión de la literatura a partir de un caso clínico / Inflammatory bowel disease and solid organ transplant. What factors must be considered for management?: case report and review of the literature

Inflammatory bowel disease (IBD), is a chronic condition, nevertheless its association with solid organ transplantation (SOT) is rare. Its presence stresses decisions on best options dealing with IBD management, immunosuppressive therapy and colorectal cancer (CRC) risks in this group of patients. Literature focused on this topic is scarce. Most of the literature corresponds to retrospective or case series of IBD patients submitted to hepatic orthotropic transplant, due to primary sclerosing cholangitis. The aim of this review is, from an individual clinical case, to tackle the different issues that could be of interest in patients requiring SOT, with or without previous IBD. The interest is focused on IBD evolution, de novo- active IBD and CRC risk. In conclusion, the most important point is that the need to perform a proctocolectomy is more related to the IBD severity than to the transplant itself. The recommendation is that these patients should be managed by a multidisciplinary team on a case by case analysis.

Aunque la enfermedad inflamatoria intestinal (EII) es una condición crónica, la asociación de pacientes con EII y trasplante de órgano sólido (TOS) ocurre de manera muy infrecuente. Sin embargo, su presencia sin duda estresa las decisiones sobre cuáles son las mejores opciones en el manejo de la EII, la terapia inmunosupresora y el riesgo de cáncer colorectal (CCR) en este grupo de pacientes. Hasta la fecha, existe escasa literatura sobre este tema y la mayoría se basa en series retrospectivas y casos clínicos de pacientes con EII que han sufrido un trasplante hepático por colangitis esclerosante primaria. El objetivo de esta revisión es mencionar a partir de un caso clínico, los diferentes aspectos relacionados con pacientes que requieren un TOS con o sin EII previa, destacando la evolución de la EII, el desarrollo de una EII-de novo y el riesgo de CCR. Sin duda, el punto más importante es que la decisión de realizar una colectomía está determinada por la gravedad de la EII y no por el TOS en sí. Es recomendable que estos pacientes sean abordados por un equipo multidisciplinario experto, y analizados caso a caso.

Cell therapy with autologous tolerogenic dendritic cells induces allograft tolerance through interferon-gamma and epstein-barr virus-induced gene 3.

Innovative therapeutic strategies are needed to diminish the impact of harmful immunosuppression in transplantation. Dendritic cell (DC)-based therapy is a promising approach for induction of antigen-specific tolerance. Using a heart allograft model in rats, we analyzed the immunoregulatory mechanisms by which injection of autologous tolerogenic DCs (ATDCs) plus suboptimal immunosuppression promotes indefinite graft survival. Surprisingly, we determined that Interferon-gamma (IFNG), a cytokine expected to be propathogenic, was threefold increased in the spleen of tolerant rats. Importantly, its blockade led to allograft rejection [Mean Survival Time (MST) = 25.6 ± 4 days], showing that IFNG plays a critical role in immunoregulatory mechanisms triggered by ATDCs. IFNG was expressed by TCRαß(+) CD3(+) CD4(-) CD8(-) NKRP1(-) cells (double negative T cells, DNT), which accumulated in the spleen of tolerant rats. Interestingly, ATDCs specifically induced IFNG production by DNT cells. ATDCs expressed the cytokinic chain Epstein-Barr virus-induced gene 3 (EBI3), an IL-12 family member. EBI3 blockade or knock-down through siRNA completely abolished IFNG expression in DNT cells. Finally, EBI3 blockade in vivo led to allograft rejection (MST = 36.8 ± 19.7 days), demonstrating for the first time a role for EBI3 in transplantation tolerance. Taken together our results have important implications in the rationalization of DC-based therapy in transplantation as well as in the patient immunomonitoring follow-up.

Shunts portosistémicos espontáneos en pacientes con encefalopatía hepática / Spontaneous portal-systemic shunts in hepatic encephalopathy patients: preliminary experience

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome caused by hepatic dysfunction and portosystemic shunting of the intestinal blood. For HE patients nonresponsive to standard therapy, the presence of large spontaneous portal-systemic shunts can occasionally be the cause of the problem. Objective: To assess the prevalence of portal-systemic shunts in patients with cirrhosis and recurrent or persistent HE. Patients and Methods: Ten patients with liver cirrhosis were analyzed who repeatedly developed HE despite pharmacotherapy. Also, we studied seven control patients with cirrhosis and no HE, who were considered the control group. Results: Large spontaneous portal-systemic shunts were detected in all patients with HE and none in the control group (X2 13.1; P: 0.0003). If only splenorenal shunts are considered, the difference is also significant (X2 5.69; p: 0.017). Conclusion: Our study confirmed that the presence of large spontaneous portal-systemic shunts is frequent in patients with cirrhosis and recurrent or persistent HE.

La encefalopatía hepática (EH) es un síndrome neuropsiquiátrico causado por insuficiencia hepática o presencia de shunts portosistémicos (SPS) intra o extrahepáticos. En pacientes con EH refractaria a tratamiento médico habitual se ha planteado que la presencia de SPS podría ser la causa del problema. Objetivo: Evaluar la prevalencia de SPS espontáneos extrahepáticos en pacientes con cirrosis y EH recurrente o persistente. Pacientes y Métodos: Se evaluaron 10 pacientes con EH recurrentes o persistente. También, se estudiaron 7 pacientes con cirrosis y sin EH que se consideraron como grupo control. Resultados: Todos los pacientes con EH recurrente o persistente presentaron SPS; 7 presentaron shunts esplenorrenales espontáneos y 3 presentaron presencia de la vena umbilical recanalizada. Ningún paciente en el grupo control presentó SPS (X2 13,1; p: 0,0003). Si se considera sólo los shunts esplenorrenales, la diferencia también es significativa (X2 5,69; p: 0,017). Conclusión: En nuestros pacientes con cirrosis y EH recurrente o persistente fue frecuente la presencia de SPS espontáneos.

Evaluación del paciente asintomático con alteraciones en las pruebas hepáticas / Evaluation of asymptomatic patients with abnormalities in liver function tests

La cirrosis hepática (CH) es un trastorno frecuente y con complicaciones que presentan una alta morbimortalidad. Está caracterizada por una larga fase preclínica asintomática, que puede requerir de dos décadas o más para el desarrollo de las alteraciones en la arquitectura hepática que conforman el estado cirrótico. La presencia de alteración en las pruebas hepáticas, en ausencia de síntomas y signos de enfermedad hepática, constituye un evento frecuente en la práctica médica general. Requiere de una evaluación clínica completa, con anamnesis dirigida, examen físico y estudios de laboratorio e imagenológicos; si se realizan de manera sistemática cubriendo las causas más frecuentes, su diagnóstico etiológico puede ser adecuadamente efectuado, con las consecuentes implicancias terapéuticas en algunos casos. En esta revisión se evaluarán los estudios bioquímicos actualmente disponibles para realizar un estudio clínico hepático en un paciente asintomático, su capacidad de discriminación y el estudio etiológico de las enfermedades hepáticas crónicas. Se definen además las potenciales causas hepáticas y extrahepáticas que pueden generar esta alteración.

Chronic liver diseases are a frequent medical problem and its complications are an important cause of morbidity and mortality. It is characterized by a long preclinical phase and it may take more than two decades for a liver to gain a cirrhotic architecture. In an asymptomatic patient the abnormal liver-enzyme results is a common medical problem. A good clinical history and physical examination are mandatory. If a systematic approach is adopted covering the most frequent liver disease, the cause is often apparent. In this review we discuss the battery of liver enzyme tests available in daily clinical practice, their diagnostic accuracy for the detection of liver disease and suggest an approach to abnormal tests in asymptomatic patients. The clinician should be aware of non-hepatic diseases that can cause abnormal liver enzymes.

Avances sobre síndrome antifosfolípido / Advances in antiphospholipid syndrome

El Síndrome antifosfolípido (SAF) es una trombofilia adquirida, que se caracteriza por presentar eventos trombóticos recurrentes y complicaciones obstétricas en presencia de anticuerpos antifosfolípidos (aFL), los cuales son pesquisados por pruebas de laboratorio como anticoagulante lúpico y anticuerpos anticardiolipina. En esta revisión se muestran los aspectos más relevantes del SAF, destacando los avances en fisiopatología y criterios diagnósticos.

[Nitric oxide in malignant astrocytes]. / El monóxido de nitrógeno en los astrocitomas malignos.

INTRODUCTION: One of the different molecules involved in the development of astrocytomas is nitric oxide (NO), a gaseous radical that, depending on the cell type and the experimental paradigm selected in the pathology, can play either a cytotoxic or a cytoprotective role. DEVELOPMENT: During the development of an astrocytoma NO acts as a tumouricidal agent, although it can also alter vascular reactivity and lead to neovascularisation, thereby contributing to the invasive capacity (aggressiveness) of the tumour. One of the mechanisms of tumoural progression consists in the protein inactivation resulting from the NO nitration of tyrosine from proteins coded for by tumour-suppressing genes, such as p53. Furthermore, in malignant astrocytes, nitrosoglutathione, a natural NO-donor, has been seen to play a role in the chemoresistance displayed against nitrosourea derivatives. The NO excreted by irradiated astrocytoma cells also appears to be involved in the resistance to the radiotherapy shown by non-irradiated cells. CONCLUSIONS: The molecular mechanisms behind the complex and paradoxical activity of NO in glioblastoma multiforme have still not been fully explained and its implications in vivo are even further from being completely understood.

Fatal visceral leishmaniasis, with massive bone-marrow infection, in an immunosuppressed but HIV-negative Spanish patient, after the initiation of treatment with meglumine antimoniate.

Although visceral leishmaniasis is often fatal in the developing world, Leishmania-attributable deaths in Europe are relatively rare and nowadays almost always linked to HIV infection. In Spain, however, a HIV-negative man with a history of chronic obstructive pulmonary disease and prednisone treatment was recently hospitalized because of hypotension and asthenia. Although the patient was afebrile, a bone-marrow aspirate, collected after thrombo- and leuco-cytopenia had been observed, was found to contain huge numbers of amastigotes. A course of antileishmanial treatment with meglumine antimoniate was initiated but the patient went into refractory shock and died within 6 h. The significance of this case, in terms of the routine investigation and treatment of immunosuppressed patients who may have leishmaniasis, is discussed.