Global intercomparison of polyurethane foam passive air samplers evaluating sources of variability in SVOC measurements.

Polyurethane foam passive air samplers (PUF-PAS) are the most common type of passive air sampler used for a range of semi-volatile organic compounds (SVOCs), including regulated persistent organic pollutants (POPs) and polycyclic aromatic hydrocarbons (PAHs), and emerging contaminants (e.g., novel flame retardants, phthalates, current-use pesticides). Data from PUF-PAS are key indicators of effectiveness of global regulatory actions on SVOCs, such as the Global Monitoring Plan of the Stockholm Convention on Persistent Organic Pollutants. While most PUF-PAS use similar double-dome metal shielding, there is no standardized dome size, shape, or deployment configuration, with many different PUF-PAS designs used in regional and global monitoring. Yet, no information is available on the comparability of data from studies using different PUF-PAS designs. We brought together 12 types of PUF-PAS used by different research groups around the world and deployed them in a multi-part intercomparison to evaluate the variability in reported concentrations introduced by different elements of PAS monitoring. PUF-PAS were deployed for 3 months in outdoor air in Kjeller, Norway in 2015-2016 in three phases to capture (1) the influence of sampler design on data comparability, (2) the influence of analytical variability when samplers are analyzed at different laboratories, and (3) the overall variability in global monitoring data introduced by differences in sampler configurations and analytical methods. Results indicate that while differences in sampler design (in particular, the spacing between the upper and lower sampler bowls) account for up to 50 % differences in masses collected by samplers, the variability introduced by analysis in different laboratories far exceeds this amount, resulting in differences spanning orders of magnitude for POPs and PAHs. The high level of variability due to analysis in different laboratories indicates that current SVOC air sampling data (i.e., not just for PUF-PAS but likely also for active air sampling) are not directly comparable between laboratories/monitoring programs. To support on-going efforts to mobilize more SVOC data to contribute to effectiveness evaluation, intercalibration exercises to account for uncertainties in air sampling, repeated at regular intervals, must be established to ensure analytical comparability and avoid biases in global-scale assessments of SVOCs in air caused by differences in laboratory performance.

Assessing polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans in air across Latin American countries using polyurethane foam disk passive air samplers.

A passive air sampling network has been established to investigate polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) at Global Atmospheric Passive Sampling (GAPS) sites and six additional sites in the Group of Latin American and Caribbean Countries (GRULAC) region. The air sampling network covers background, agricultural, rural, and urban sites. Samples have been collected over four consecutive periods of 6 months, which started in January 2011 [period 1 (January to June 2011), period 2 (July to December 2011), period 3 (January to June 2012), and period 4 (July 2012 to January 2013)]. Results show that (i) the GAPS passive samplers (PUF disk type) and analytical methodology are adequate for measuring PCDD/F burdens in air and (ii) PCDD/F concentrations in air across the GRULAC region are widely variable by almost 2 orders of magnitude. The highest concentrations in air of Σ4-8PCDD/Fs were found at the urban site São Luis (Brazil, UR) (i.e., 2560 fg/m3) followed by the sites in São Paulo (Brazil, UR), Mendoza (Argentina, RU), and Sonora (Mexico, AG) with values of 1690, 1660, and 1610 fg/m3, respectively. Very low concentrations of PCDD/Fs in air were observed at the background site Tapanti (Costa Rica, BA), 10.8 fg/m3. This variability is attributed to differences in site characteristics and potential local/regional sources as well as meteorological influences. The measurements of PCDD/Fs in air agree well with model-predicted concentrations performed using the Global EMEP Multimedia Modeling System (GLEMOS) and emission scenario constructed on the basis of the UNEP Stockholm Convention inventory of dioxin and furan emissions.

Submicroscopic infection of placenta by Plasmodium produces Th1/Th2 cytokine imbalance, inflammation and hypoxia in women from north-west Colombia.

BACKGROUND: A large-scale study was set up in order to study the epidemiology, clinical aspects, and immunopathology of gestational and placental malaria in north-west Colombia. In this region, recent reports using a qPCR technique, confirmed frequencies of infection, by Plasmodium falciparum or Plasmodium vivax, up to 45%. Given the high rates of infection observed both in mother and placenta, a first exploratory study was proposed in order to characterize the effect on the inflammation status, tissue damage and hypoxia in Plasmodium spp. infected placentas. METHODS: A descriptive, prospective, cross-sectional design was applied to pregnant women with (PM+) and without (PM-) placental malaria. Messenger RNA expression of Fas, FasL; COX-1, COX-2, HIF, VEGF, and the cytokines IL-2, IL-4, IL-10, IFN-γ and TNF, were measured in peripheral and placental blood using a quantitative PCR. The percentage of apoptotic cells was determined with a TUNEL assay. RESULTS: In total 50 placentas were studied: 25 were positive for submicroscopic infection and 25 were negative for Plasmodium infection. Expression of IL-4 and IL-10 was observed high in placental tissue of PM+, while IL-2 was high in peripheral blood of the same group. Expression of TNF and IFNγ in peripheral blood of the PM + group was high. Similarly, the apoptotic index and Fas expression were significantly high in PM+. However, FasL expression was observed low in PM + compared to PM-. Inflammation markers (HIF, VEGF) and hypoxia markers (COX-1, COX-2) were high in the PM + group. CONCLUSION: During placental malaria expression of some pro-inflammatory cytokines is up-regulated and markers of hypoxia and tissue damage are increased in cases of submicroscopic infection.

Ferritin levels in children with juvenile idiopathic arthritis of systemic onset and children with other causes of fever of unknown origin: A multicenter study of diagnostic tests / Niveles de ferritina en artritis idiopática juvenil de inicio sistémico comparada con otras fiebres de origen desconocido: estudio multicéntrico de pruebas diagnósticas

Introduction: There are no sensitive or specific tests available to diagnose systemic juvenile idiopathic arthritis (sJIA). Objective: To assess the utility as diagnostic tests of total ferritin (TF) levels greater than 5 times the normal value (TF>5N) and the decreased percentage (less than or equal to 20% of TF) of glycosylated ferritin (GF≤20%) for the diagnosis of sJIA in patients with fever of unknown origin evaluated by pediatric rheumatology. Materials and methods: We conducted an observational, cross-sectional study of diagnostic tests in children under 16 years of age hospitalized between 2010 and 2014. The reference diagnostic standard was the fulfillment of the classification criteria or confirmed diagnosis at follow-up. We determined the measures of utility of the tests. Results: We included 40 patients with fever of unknown origin, 11 with sJIA, and 29 with other diagnoses. The median TF was higher in sAIJ (3992 ng/ml) versus other causes of fever of unknown origin (155 ng/ml) (p=0.0027), as well as TF>5N (90.91% versus 51.72%) (p=0.023). The percentage of GF≤20% was higher in patients with other causes of fever of unknown origin (96.5%) compared to sJIA (81.8%) (p=0.178). TF>5N had a sensitivity of 91%, specificity of 48%, positive likelihood ratio (LR) of 1.76, and negative LR of 0.19 demonstrating greater utility for the diagnosis of sJIA than the combination of FT> 5N with GFR <20%, with a sensitivity of 81.8%, specificity of 48.3%, positive LR of 1.58, and negative LR of 0.38. Conclusion: In patients with FUO evaluated by pediatric rheumatology, TF> 5N proved useful as a screening test for the diagnosis of sJIA.

Introducción. No se dispone de pruebas sensibles ni específicas para diagnosticar la artritis idiopática juvenil sistémica. Objetivo. Evaluar la utilidad diagnóstica de niveles de ferritina total cinco veces por encima del valor normal (ferritina total>5N) y el porcentaje disminuido (menor de o igual a 20 % de la ferritina total) de la ferritina glucosilada (ferritina glucosilada<20 %) para el diagnóstico de artritis idiopática juvenil sistémica en pacientes con fiebre de origen desconocido evaluados por reumatología pediátrica. Materiales y métodos. Se hizo un estudio observacional de pruebas diagnósticas de corte transversal en menores de 16 años hospitalizados entre el 2010 y el 2014. El patrón diagnóstico de referencia fue el cumplimiento de los criterios de clasificación o diagnóstico confirmado en el seguimiento. Se determinaron las medidas de utilidad de las pruebas. Resultados. Se incluyeron 40 pacientes con fiebre de origen desconocido: 11 con artritis idiopática juvenil sistémica y 29 con otros diagnósticos. La mediana de la ferritina total fue mayor en la artritis idiopática juvenil sistémica (3.992 ng/ml) comparada con otras causas de fiebre de origen desconocido (155 ng/ml) (p=0,0027), así como la ferritina total>5N (90,91 % Vs. 51,72 %) (p=0,023). El porcentaje de ferritina glucosilada≤20 % fue de 96,5 % en otras fiebres de origen desconocido en comparación con la artritis idiopática juvenil sistémica (81,8 %) (p=0,178). La ferritina total>5N tuvo una sensibilidad del 91 %, una especificidad del 48 %; un cociente de probabilidades (Likelihood Ratio, LR) positivo de 1,76 y uno negativo de 0,19, demostrando mayor utilidad para el diagnóstico que la combinación de la ferritina total>5N y ferritina glucosilada≤20 %, cuya sensibilidad fue del 81,8 %, la especificidad del 48,3 %, un cociente de probabilidades LR positivo de 1,58 y un LR negativo de 0,38. Conclusión. En pacientes con fiebre de origen desconocido evaluados por reumatología pediátrica, la ferritina total>5N demostró ser útil como prueba de tamización para el diagnóstico de artritis idiopática juvenil sistémica.

Impact of polycyclic aromatic hydrocarbons in mangroves from the Colombian pacific coast: Evaluation in sediments and bivalves.

Bivalves and sediments were sampled from mangroves in the Pacific Coast of Colombia to evaluate the concentrations of the 16 polycyclic aromatic hydrocarbons (PAHs) prioritized by U.S.EPA. Mangroves are highly vulnerable to anthropogenic activities, such as oil spills, which affect sediments and the organisms that depend on that ecosystem. Twelve samples of mangrove and non-mangrove (sandy) sediments and 20 samples of Anadara tuberculosa from mangrove were collected in marine and estuarine areas. In sediments and A. tuberculosa, the highest concentration of Æ©16PAHs was found in estuarine mangroves close to the Rosario River mouth, ranging from 171.4 to 564.0 ng g-1 and 31.0 to 169.0 ng g-1, respectively. For the bivalve, the concentrations showed less variability than sediment, with 25% and 20% of bivalve samples exceeding the limits established by the European Regulatory Commission and Ministry of Health and Social Protection of Colombia, respectively, which can cause effects on people's health. The PAHs isomeric ratios determined in sediments indicated that these compounds were originated mainly from petrogenic sources. The PAHs profile reveals the dominance of 3 and 4 rings PAHs in sediments and dominance of 4 rings PAHs in bivalves.

Gene expression analysis of Paracoccidioides brasiliensis transition from conidium to yeast cell.

Paracoccidioides brasiliensis infectious process relies on the initial expression of virulence factors that are assumed to be controlled by molecular mechanisms through which the conidia and/or mycelial fragments convert to yeast cells. In order to analyze the profile of the thermally-induced dimorphic gene expression, 48 h C-L transition cultures which had been incubated at 36 degrees C were studied. By this time approximately 50% of the conidial population had already reverted to yeast form cells. At this transition time, an EST-Orestes library was constructed and characterized. As a result, 79 sequences were obtained, of which 39 (49.4%) had not been described previously in other libraries of this fungus and which could represent novel exclusive C-Y transition genes. Two of these sequences are, among others, cholestanol delta-isomerase, and electron transfer flavoprotein-ubiquinoneoxidoreductase (ETF-QO). The other 40/79 (50.6%) sequences were shared with Mycelia (M), Yeast (Y) or Mycelia to yest transition (M-Y) libraries. An important component of this group of sequences is a putative response regulator receiver SKN7, a protein of high importance in stress adaptation and a regulator of virulence in some bacteria and fungi. This is the first report identifying genes expressed during the C-Y transition process, the initial step required to understand the natural history of P. brasiliensis conidia induced infection.

Involvement of extracellular matrix proteins in the course of experimental paracoccidioidomycosis.

We aimed at determining involvement of extracellular matrix proteins (ECMp) and an ECM-binding adhesin (32-kDa protein) from Paracoccidioides brasiliensis, in the course of experimental paracoccidioidomycosis. BALB/c mice were infected with P. brasiliensis conidia previously incubated with soluble laminin, fibronectin and fibrinogen or a mAb against the fungal adhesin. Inflammatory response, chitin levels and cytokine production at different postinfection periods were determined. Chitin was significantly decreased in lungs of mice infected with ECMp-treated conidia when compared with controls at week 8, especially with laminin and fibrinogen. Contrariwise, when animals were infected with mAb-treated conidia no differences in chitin content were found. The observed inflammatory reaction in lungs was equivalent in all cases. IFN-gamma increased significantly in lungs from mice infected with soluble ECMp - (at day 4 and week 12) or mAb-treated conidia (at week 12) when compared with animals infected with untreated conidia. Significant increased levels of tumour necrosis factor-alpha were observed at 8 weeks in animals infected with ECMp-treated conidia while no differences were observed during the remaining periods. These findings point toward an inhibitory effect of ECMp on P. brasiliensis conidia infectivity and suggest that these proteins may interfere with conidia initial adhesion to host tissues probably modulating the immune response in paracoccidioidomycosis.

Lysozyme plays a dual role against the dimorphic fungus Paracoccidioides brasiliensis.

In order to determine the role of lysozyme, an antimicrobial peptide belonging to the innate immune system, against the dimorphic fungus Paracoccidioides brasiliensis, co-cultures of the MH-S murine alveolar macrophages cell line with P. brasiliensis conidia were done; assays to evaluate the effect of physiological and inflammatory concentrations of lysozyme directly on the fungus life cycle were also undertaken. We observed that TNF-alpha-activated macrophages significantly inhibited the conidia to yeast transition (p = 0.0043) and exerted an important fungicidal effect (p = 0.0044), killing 27% more fungal propagules in comparison with controls. Nonetheless, after adding a selective inhibitor of lysozyme, the fungicidal effect was reverted. When P. brasiliensis propagules were exposed directly to different concentrations of lysozyme, a dual effect was observed. Physiologic concentrations of the enzyme facilitated the conidia-to-yeast transition process (p < 0.05). On the contrary, inflammatory concentrations impaired the normal temperature-dependent fungal transition (p < 0.0001). When yeast cells were exposed to lysozyme, irrespective of concentration, the multiple-budding ability was badly impaired (p < 0.0001). In addition, ultra-structural changes such as subcellular degradation, fusion of lipid vacuoles, lamellar structures and interruption of the fibrillar layer were observed in lysozyme exposed conidia. These results suggest that lysozyme appears to exert a dual role as part of the anti-P. brasiliensis defense mechanisms.

Efficacy of Different Primaquine Regimens to Control Plasmodium falciparum Gametocytemia in Colombia.

Treatment against Plasmodium falciparum malaria includes blood schizonticides to clear asexual parasites responsible for disease. The addition of gametocytocidal drugs can eliminate infectious sexual stages with potential for transmission and the World Health Organization recommends a single dose (SD) of primaquine (PQ) to this end. The efficacy of PQ at 0.75 mg/kg to suppress gametocytemia when administered in single or fractionated doses was evaluated. A clinical controlled study with an open-label design was executed; three groups of 20 subjects were studied sequentially. All subjects were treated with the standard dose of artemether-lumefantrine plus the total dose of 0.75 mg/kg of PQ administered (without previous G6PD testing) in three different ways: Group "0.75d-3" received 0.75 mg/kg on day 3; Group "0.50d-1 + 0.25d-3" received 0.50 mg/kg on day 1 and 0.25 mg/kg on day 3; Group "0.25d-1,2,3" received 0.25 mg/kg on days 1, 2, and 3. Subjects were evaluated on days 1, 4, and 7 by thick smear microscopy and quantitative polymerase chain reaction to determine the carriage of immature and mature gametocytes. There were no adverse events. The three schemes caused a marked reduction (75-85%) in prevalence of gametocytes on day 4 compared with day 1, but only the group that received 0.75 mg/kg on day 3 maintained the reduced gametocyte burden until day 7. None of the three treatments were able to clear gametocyte carriage on days 4 or 7, but the group that received the SD had the lowest prevalence of gametocytes (15%). Further studies are needed to establish a PQ regimen with complete efficacy against gametocytes.

Niveles de ferritina en artritis idiopática juvenil de inicio sistémico comparada con otras fiebres de origen desconocido: estudio multicéntrico de pruebas diagnósticas / Ferritin levels in children with juvenile idiopathic arthritis of systemic onset and children with other causes of fever of unknown origin: A multicenter study of diagnostic tests

Resumen | Introducción. No se dispone de pruebas sensibles ni específicas para diagnosticar la artritis idiopática juvenil sistémica. Objetivo. Evaluar la utilidad diagnóstica de niveles de ferritina total cinco veces por encima del valor normal (ferritina total>5N) y el porcentaje disminuido (menor de o igual a 20 % de la ferritina total) de la ferritina glucosilada (ferritina glucosilada<20 %) para el diagnóstico de artritis idiopática juvenil sistémica en pacientes con fiebre de origen desconocido evaluados por reumatología pediátrica. Materiales y métodos. Se hizo un estudio observacional de pruebas diagnósticas de corte transversal en menores de 16 años hospitalizados entre el 2010 y el 2014. El patrón diagnóstico de referencia fue el cumplimiento de los criterios de clasificación o diagnóstico confirmado en el seguimiento. Se determinaron las medidas de utilidad de las pruebas. Resultados. Se incluyeron 40 pacientes con fiebre de origen desconocido: 11 con artritis idiopática juvenil sistémica y 29 con otros diagnósticos. La mediana de la ferritina total fue mayor en la artritis idiopática juvenil sistémica (3.992 ng/ml) comparada con otras causas de fiebre de origen desconocido (155 ng/ml) (p=0,0027), así como la ferritina total>5N (90,91 % Vs. 51,72 %) (p=0,023). El porcentaje de ferritina glucosilada≤20 % fue de 96,5 % en otras fiebres de origen desconocido en comparación con la artritis idiopática juvenil sistémica (81,8 %) (p=0,178). La ferritina total>5N tuvo una sensibilidad del 91 %, una especificidad del 48 %; un cociente de probabilidades (Likelihood Ratio, LR) positivo de 1,76 y uno negativo de 0,19, demostrando mayor utilidad para el diagnóstico que la combinación de la ferritina total>5N y ferritina glucosilada≤20 %, cuya sensibilidad fue del 81,8 %, la especificidad del 48,3 %, un cociente de probabilidades LR positivo de 1,58 y un LR negativo de 0,38. Conclusión. En pacientes con fiebre de origen desconocido evaluados por reumatología pediátrica, la ferritina total>5N demostró ser útil como prueba de tamización para el diagnóstico de artritis idiopática juvenil sistémica.

Abstract | Introduction: There are no sensitive or specific tests available to diagnose systemic juvenile idiopathic arthritis (sJIA). Objective: To assess the utility as diagnostic tests of total ferritin (TF) levels greater than 5 times the normal value (TF>5N) and the decreased percentage (less than or equal to 20% of TF) of glycosylated ferritin (GF≤20%) for the diagnosis of sJIA in patients with fever of unknown origin evaluated by pediatric rheumatology. Materials and methods: We conducted an observational, cross-sectional study of diagnostic tests in children under 16 years of age hospitalized between 2010 and 2014. The reference diagnostic standard was the fulfillment of the classification criteria or confirmed diagnosis at follow-up. We determined the measures of utility of the tests. Results: We included 40 patients with fever of unknown origin, 11 with sJIA, and 29 with other diagnoses. The median TF was higher in sAIJ (3992 ng/ml) versus other causes of fever of unknown origin (155 ng/ml) (p=0.0027), as well as TF>5N (90.91% versus 51.72%) (p=0.023). The percentage of GF≤20% was higher in patients with other causes of fever of unknown origin (96.5%) compared to sJIA (81.8%) (p=0.178). TF>5N had a sensitivity of 91%, specificity of 48%, positive likelihood ratio (LR) of 1.76, and negative LR of 0.19 demonstrating greater utility for the diagnosis of sJIA than the combination of FT> 5N with GFR <20%, with a sensitivity of 81.8%, specificity of 48.3%, positive LR of 1.58, and negative LR of 0.38. Conclusion: In patients with FUO evaluated by pediatric rheumatology, TF> 5N proved useful as a screening test for the diagnosis of sJIA.

Short report: Inhibition by tumor necrosis factor-alpha-activated macrophages of the transition of Paracoccidioides brasiliensis conidia to yeast cells through a mechanism independent of nitric oxide.

It is known that peritoneal murine macrophages activated with interferon-gamma exert a fungicidal effect against Paracoccidioides brasiliensis conidia by a nitric oxide (NO)-mediated mechanism. This NO-mediated effect can also be induced by other cytokines such as tumor necrosis factor-alpha (TNF-alpha). The aim of this study was to determine if TNF-alpha-activated peritoneal murine macrophages infected with P. brasiliensis were able to show fungistatic/fungicidal effects mediated by NO. The results indicated that although macrophage activation with TNF-alpha did not result in NO production, these cells played an important role in inhibiting the conidia from becoming yeast cells. In vivo, the NO-independent inhibitory effect would prove of importance for the establishment of P. brasiliensis in host tissues.

[Frequency of HLA alleles class I and II in a cohort of northwestern Colombian patients with spondyloarthritis]. / Frecuencia de alelos HLA de clase I y II en una cohorte de pacientes con espondiloartritis provenientes del noroccidente colombiano.

INTRODUCTION: Spondyloarthritis is a chronic rheumatic disease that affect the axial skeleton and peripheral joints, along with several extra-articular manifestations. The association with HLA-B27 remains one of the strongest known links between these entities and the major histocompatibility complex. However, the global distribution of HLA-B27 varies considerably and furthermore, associations with non-HLA-B27 genes have been described. OBJECTIVE: The frequency of HLA class I and II was determined in a population of patients with spondyloarthritis with respect to detection in the clinical setting and by radiology. MATERIALS AND METHODS: A descriptive, observational, cross-sectional, retrospective and prospective study was conducted in 56 patients from northwestern Colombia. Each was diagnosed with spondyloarthritis between 2005 and 2008. In each case, alleles were identified for the loci HLA class I and II (HLA-B; HLADQB1 and HLADRB). The frequency of these alleles in the axial, peripheral, extraarticular and radiological manifestations. RESULTS: The frequency of HLA-B27 was 50% overall, and it was the most frequent allele. The two other alleles were HLA.DRB4*01 at 35.7% and HLA-DQB1*0501 at 28.6%, as detected in each of the clinical and radiological manifestations. A high frequency of HLA-B27 and HLA-DRB4*01 (64.3%) was noted in patients with dactylitis. CONCLUSION: The alleles HLA-B27, HLA-DRB4*01 and HLA-DQB1*0501 were common in the different subtypes of spondyloarthritis and were frequent in the specific clinical axial, peripheral and extraarticular clinical manifestations, as well as radiological sacroiliitis.

Methodology for Anti-Gene Anti-IGF-I Therapy of Malignant Tumours.

The aim of this study was to establish the criteria for methodology of cellular "anti-IGF-I" therapy of malignant tumours and particularly for glioblastoma multiforme. The treatment of primary glioblastoma patients using surgery, radiotherapy, and chemotherapy was followed by subcutaneous injection of autologous cancer cells transfected by IGF-I antisense/triple helix expression vectors. The prepared cell "vaccines" should it be in the case of glioblastomas or other tumours, have shown a change of phenotype, the absence of IGF-I protein, and expression of MHC-I and B7. The peripheral blood lymphocytes, PBL cells, removed after each of two successive vaccinations, have demonstrated for all the types of tumour tested an increasing level of CD8(+) and CD8(+)28(+) molecules and a switch from CD8(+)11b(+) to CD8(+)11. All cancer patients were supervised for up to 19 months, the period corresponding to minimum survival of glioblastoma patients. The obtained results have permitted to specify the common criteria for "anti-IGF-I" strategy: characteristics sine qua non of injected "vaccines" (cloned cells IGF-I(-) and MHC-I(+)) and of PBL cells (CD8(+) increased level).

Seguimiento con carga viral para virus Epstein- Barr en pacientes pediátricos con trasplante hepático / Follow up with viral load monitoring for Epstein-Barr virus in pediatric pacients with hepatic transplant

INTRODUCCIÓN: Los pacientes trasplantados son un reto desde todo punto de vista. La infección por el virus de Epstein-Barr es frecuente y su manejo suele ser difícil por la falta de medicamentos efectivos. Los pacientes con trasplante hepático tienen una alta incidencia de infección/reactivación por virus Epstein-Barr por el riesgo de primoinfección durante este periodo o la reactivación por inmunosupresión. OBJETIVOS: Describir los hallazgos obtenidos con el uso de la carga viral para el virus de Epstein-Barr en el seguimiento de los pacientes pediátricos sometidos a trasplante hepático en una institución de cuarto nivel en Medellín, Colombia. SELECCIÓN DE PACIENTES: Se revisaron siete historias clínicas de pacientes con trasplante hepáticos escogidos al azar, obteniendo de ellas los datos demográficos, motivo de trasplante, momento de la aparición de la de la carga viral positiva por el virus de Epstein-Barr, evolución de la carga viral, efectos de los medicamentos inmunosupresores y antivirales, y el desenlace de los pacientes. DESCRIPCIÓN DE CASOS: La edad promedio de los pacientes al momento del trasplante fue de 28,4 meses, el efecto de los medicamentos antivirales como gangiclovir, valganciclovir, inmunoglobulina contra citomegalovirus, no parece ejercer una disminución adecuada y sostenida de la carga viral. CONCLUSIONES: A pesar de las opciones terapéuticas disponibles para el herpes virus, según lo encontrado en la literatura actual y lo visto los pacientes evaluados, el grado de inmunosupresión parece ser el principal factor para el control de la replicación del virus de Epstein-Barr

INTRODUCTION: Transplant patients are a challenge from every point of view. Infection with Epstein- Barr virus is common and management is often hampered by the lack of effective medicaments available. Liver transplant patients have a high incidence of Epstein-Barr virus infection / reactivation because of the the risk of primary infection during this period or immunosuppression associated reactivation. OBJECTIVES: Describe the findings when using EBV viral load monitoring in liver transplant patients in an institution of the fourth level in Medellin, Colombia. SELECTION OF PATIENTS: Seven medical records from liver transplant patients were randomly chosen obtaining from them demographic data, cause of transplantation, time of the Epstein-Barr virus detection, viral load evolution, effects of immunosuppressive medications over them and the patient's outcome. DESCRIPTION OF PATIENTS: Average patient age at transplant was 28,4 months, the effect of antiviral drugs (gangiclovir, valganciclovir, cytomegalovirus immunoglobulin) seems not to be adequate and sustained in decreasing viral load. CONCLUSIONS: Although the therapeutic options available for Herpes virus , as found in current literature and seen in our patients, immunosupression degree seems to be the main factor for controlling EBV replication

[Identification of genes associated with germination of conidia to form mycelia in the fungus Paracoccidioides brasiliensis]. / Identificación de algunos genes asociados al proceso de germinación de la conidia al micelio en Paracoccidioides brasiliensis.

INTRODUCTION: Paracoccidioides brasiliensis is a thermo-dimorphic fungus. At room temperature it grows as a mold that produces conidia, whereas in the vertebrate host it grows as a multiple-budding yeast. The molecular mechanisms involved in the germination from the conidia to the mycelia process remain unknown. OBJECTIVE: The kinetics of conidia to mycelia germination process were studied in the dimorphic fungus P. brasiliensis. Gene expression during this process was evaluated by construction and analysis of an EST library. MATERIALS AND METHODS: For the germination kinetics study, P. brasiliensis conidia were isolated as single cell units. Then, they were cultured at 18 degrees C in BHI (brain-heart infusion) broth for 24, 48, 72 and 96 hr. After each perion, they were examined by light microscopy. From conidia harvested at 96 hr, an EST library was constructed; at this stage the gene expression was presumed to be maximal for the germination process. RESULTS: During the conidia to the mycelia developmental process, the following germination rates were observed: at 24 hr, 11.7+/-1.2%; at 48 hr, 30+/-0.6%; at 72 hr, 43+/-1.3%; and at 96 hr, 66+/-2.4%. At the 96 hour stage, an EST library was constructed. It consisted of 129 sequences grouped in 4 contigs and 7 singlets for a total of 11 possible genes. Eight of the sequences had not been described previously in other EST libraries of this fungus. CONCLUSIONS: New genes were identified that were expressed during the conidia to the mycelia germination process and may represent genes specific to the germination process.

Consenso médico de biopsia por aspiración con aguja fina de tiroides. reporte de citología tiroidea basado en el sistema de bethesda / Medical consensus of fine-needle aspiration biopsy of the thyroid. bethesda system for reporting thyroid cytopathology

En este artículo se presenta un consenso médico basado en el sistema de Bethesda del Instituto Nacionalde Cáncer (Estados Unidos) para el uso de la biopsia por aspiración con aguja fina en el manejo de nódulos tiroideos, realizado en conjunto con patólogos, radiólogos, endocrinólogos y otras especialidades médicas de Colombia, España, Chile, Venezuela, Estados Unidos y Panamá. En este trabajo se describen las indicaciones de la biopsia por aspiración con aguja fina de tiroides, requisitos previos, entrenamiento, acreditación, técnicas, terminología diagnóstica, pruebas complementarias y opciones de tratamiento. El objetivo del actual artículo es presentar ante la comunidad médica la clasificación de los reportes citológicos, el reporte de ecografía que propone usar el sistema de datos y el reporte de imágenes tiroideas (TIRADS, del inglés The Thyroid Imaging Reporting and Data System), el uso de la medición de tiroglobulina en biopsia por aspiración con aguja fina y técnicas de citología líquida;...

This article presents a medical consensus based on the Bethesda system of the National Cancer Institute (USA) for the use of fine needle aspiration biopsy in the management of thyroid nodules. This consensus was performed in conjunction with pathologists, radiologists, endocrinologists, and other medical specialties of Colombia, Spain, Chile, Venezuela, United States, and Panama. In this work was described the indications for fine needle aspiration biopsy of thyroid, prerequisites, training, accreditation, techniques, diagnostic terminology, additional tests and treatment options. The aim of this article is present to the medical community the classification of cytological report, ultrasound report using the data system, and the thyroid imaging reporting and data system (TIRADS); as well as, the use of thyroglobulin measurement in fine needle aspiration biopsy, and liquid-based cytology techniques...

Frecuencia de alelos HLA de clase I y II en una cohorte de pacientes con espondiloartritis provenientes del noroccidente colombiano / Frequency of HLA alleles class I and II in a cohort of northwestern Colombian patients with spondyloarthritis

Introducción. Las espondiloartritis son enfermedades reumatológicas crónicas que afectan el esqueleto axial y las articulaciones periféricas, con varias manifestaciones extraarticulares. La asociación con el HLA-B27 sigue siendo uno de los vínculos más fuertes conocidos entre estas entidades y el complejo mayor de histocompatibilidad; sin embargo, la distribución mundial del HLA-B27 varía considerablemente y se han descrito asociaciones con genes no HLA-B27. Objetivo. Conocer la frecuencia de alelos HLA de clase I y II en pacientes con espondiloartritis provenientes del noroccidente colombiano y su frecuencia en las manifestaciones clínicas y radiológicas específicas. Materiales y métodos. Se condujo un estudio descriptivo, observacional, de corte transversal, retrospectivo y prospectivo entre 2005 y 2008 de 56 pacientes colombianos con espondiloartritis. Se identificaron los alelos correspondientes a los loci HLA de clase I y II (HLA-B, HLADQB1 y HLADRB). Se analizó su frecuencia con las manifestaciones clínicas axiales, periféricas, extraarticulares y radiológicas. Resultados. Se encontró una baja frecuencia de HLA-B27 en la población total (50 %), aunque fue el alelo más frecuente, junto con HLA-DRB4*01 (35,7 %) y HLA-DQB1*0501 (28,6 %), en todos los pacientes en general y en cada una de las manifestaciones clínicas y radiológicas. Se resalta la alta frecuencia de HLA-B27 y HLA-DRB4*01 (64,3 %) en pacientes con dactilitis, hallazgo novedoso sin previa descripción. Conclusión. Los alelos HLA-B27, HLA-DRB4*01 y HLA-DQB1*0501 fueron frecuentes en los diferentes subtipos de espondiloartritis y en las manifestaciones clínicas axiales, periféricas y extraarticulares específicas, además de la sacroiliítis radiológica.

Introduction. Spondyloarthritis is a chronic rheumatic disease that affect the axial skeleton and peripheral joints, along with several extra-articular manifestations. The association with HLA-B27 remains one of the strongest known links between these entities and the major histocompatibility complex. However, the global distribution of HLA-B27 varies considerably and furthermore, associations with non-HLA-B27 genes have been described. Objective. The frequency of HLA class I and II was determined in a population of patients with spondyloarthritis with respect to detection in the clinical setting and by radiology. Materials and methods. A descriptive, observational, cross-sectional, retrospective and prospective study was conducted in 56 patients from northwestern Colombia. Each was diagnosed with spondyloarthritis between 2005 and 2008. In each case, alleles were identified for the loci HLA class I and II (HLA-B; HLADQB1 and HLADRB). The frequency of these alleles in the axial, peripheral, extraarticular and radiological manifestations. Results.The frequency of HLA-B27 was 50% overall, and it was the most frequent allele. The two other alleles were HLA.DRB4*01 at 35.7% and HLA-DQB1*0501 at 28.6%, as detected in each of the clinical and radiological manifestations. A high frequency of HLA-B27 and HLA-DRB4*01 (64.3%) was noted in patients with dactylitis. Conclusion. The alleles HLA-B27, HLA-DRB4*01 and HLA-DQB1*0501 were common in the different subtypes of spondyloarthritis and were frequent in the specific clinical axial, peripheral and extraarticular clinical manifestations, as well as radiological sacroiliitis.

Concordancia entre la determinación de anticuerpos antinucleares por inmunofluorescencia e inmunoensayo lineal / Concordance between antinuclear antibody determination by immunofluorescence and line immunoassay

Introducción: La inmunofluorescencia indirecta (IFI)sobre células Hep-2 es la prueba usada para la tamización deautoanticuerpos en enfermedades del tejido conectivo, en tanto queel perfil de anticuerpos específicos se puede detectar por métodosinmunométricos como el inmunoensayo lineal en soporte sólido (LIA).Objetivos: 1) evaluar el desempeño de un LIA comercial en el suerode pacientes, y compararlo con la determinación de anticuerposantinucleares por IFI; 2) describir el perfil de los autoanticuerposdetectados por las dos pruebas; y 3) conocer la frecuencia de losdiferentes autoanticuerpos en los pacientes evaluados. Materialesy métodos: se incluyeron 72 pacientes consecutivos, con sospechade enfermedad autoinmune, que consultaron en el HospitalPablo Tobón Uribe en Medellín, Colombia. Las muestras fueronprocesadas por IFI y por LIA. Resultados: el patrón homogéneoy el moteado fueron los más frecuentes en estos pacientes. Losanticuerpos específicos que prevalecieron fueron los anti-histonas,anti-nucleosomas y anti-dsDNA; estos hallazgos eran esperablespues son los anticuerpos que se asocian al patrón homogéneo, quefue el más prevalente. Se encontró una concordancia del 68,05%entre los resultados por ambos métodos. Conclusiones: la bajaconcordancia entre las dos pruebas, menor que la reportada enla literatura (90%), pudo ser el resultado de la baja probabilidadpre-test de los pacientes incluidos en el estudio. Entre las ventajasdel LIA se encuentra que acorta el tiempo del diagnóstico y delinicio del tratamiento, su mayor sensibilidad y especificidad, y laposibilidad de identificar los anticuerpos específicos de maneraindividual, además de detectar anticuerpos extraíbles que no sonidentificados por IFI.

Abstract: Introduction:Indirect immunofluorescence (IFI) on Hep-2 cells is the test used for screening autoantibodies in connective tissue diseases, while the profile of specific antibodies can be detected by immunometric methods such as solid support line immunoassay (LIA). Objectives: 1) To evaluate the performance of a commercial LIA on serum of patients, and compare it with the determination of antinuclear antibodies by IFI, 2) to describe the profile of the autoantibodies detected by both tests, and 3) to determine the frequency of the different autoantibodies in the evaluated patients. Materials and methods: We included 72 consecutive patients with suspected autoimmune disease that consulted the Pablo Tobón Uribe Hospital in Medellín, Colombia. The samples were processed by IFI and LIA. Results:The homogeneous and speckled patterns were more common in these patients. The most prevalent specific antibodies were the anti-histone, anti-nucleosome and anti-dsDNA; these findings were expected because these are the antibodies associated with the homogeneous pattern, which was the most prevalent. There was a 68,05% concordance between the results by both methods. Conclusions:The low concordance between the two tests, lower than that reported in the literature (90%), could be the result of low pre-test probability of the patients included in the study. The advantages of LIA include that it allows shortening the time of diagnosis and initiation of treatment, its highest sensitivity and specificity, and the ability to individually identify specific antibodies, as well as to detect extractable antibodies that are not identified by IFI.

Espondiloartritis en el Hospital Pablo Tobón Uribe. Descripción de una cohorte / Hospital Pablo Tobón Uribe-Spondyloarthropathies. A cohort description

Las espondiloartritis comparten un contexto ambiental, genético y clínico. Objetivo. Conocer y describir el comportamiento demográfico, clínico y radiológico de pacientes con espondiloartritis en el Hospital Pablo Tobón desde el 1 de enero de 2005 hasta el 31 de diciembre de 2008. Materiales y métodos. Este es un estudio descriptivo, observacional, de corte transversal. Se empleó estadística descriptiva para las variables demográficas, clínicas, radiológicas y los diversos tipos de tratamiento. Resultados. 71 pacientes fueron identificados. Las características clínicas más importantes fueron: dolor lumbar inflamatorio en el 84% de los pacientes, entesopatía, 67%; artritis periférica, 64% y dolor glúteo alternante, 57%. Las articulaciones comprometidas con mayor frecuencia fueron: sacroilíacas, 62%; tobillos, 32%; rodillas, 30%; tarso, 14%. El 64% presentó sacroilitis radiológica. Las manifestaciones extraarticulares más frecuentes fueron: dactilitis, 22%; uveítis, 19%; compromiso renal, 5% y fibrosis pulmonar, 1%. Los índices de actividad (BASDAI) fueron de 4.82 y la función (BASFI) de 4. 54% y 34% de los pacientes tenían eritrosedimentación y PCR elevada, respectivamente. El HLA B27 + en el 52%. Los DMARDs (sulfasalazina y metotrexate) fueron los medicamentos más usados en el 68% de los casos. Le siguieron los AINES en el 52% y los medicamentos anti-TNF en el 42% de los pacientes (Infliximab 20%, adalimumab 16% y etanercept 6%). Conclusión. Nuestros pacientes tenían una enfermedad activa y con limitación funcional. Se encontró un alto porcentaje de pacientes con espondiloartritis indiferenciada. La dactilitis fue la manifestación extraarticular más frecuente y el compromiso radiológico fue similar al descrito en la literatura. Palabras clave: espondiloartritis, índices de actividad, dactilitis, entesitis.

Spondyloartropahties share a genetic, clinical and environmental context. Objective. To describe demographic, clinical and radiological characteristics of spondyloarthropathies in a tertiary hospital. Methods. Descriptive analysis of a 71 patients. Demographics, clinical, radiological and treatment modalities are shown. Results. A total of 71 patients were identified. Low back pain 84%, entesopathye 67%, peripheral arthritis 64% and alternant buttock pain were often seen. The most common joint involved were sacroiliac joints 62%, ankles 32%, knees 30%, tarsal joints 14%. Radiological sacroiliacs involvement 64%. Dactilytis 22%, uveitis 19%, renal and pulmonary involvement were seen 5% and 1% respectively. Activity and functional indexes were (BASDAI) 4.82 and (BASFI) 4. High ESR and PCR were seen 54% and 34%, while HLA B27+52%. DMARDs (sulfasalazine and methotrexate) were used 68%. NSAIDs 52%. Anti-TNF blockers 42% (Infliximab 20%, adalimumab 16% and etanercept 6%). Conclusion. Our patients shown an active disease. A high incidence of undifferentiated spondyloarthropahies was found. Dactylitis was the most common extraarticular manifestation and radiological findings were similar to previously reported in the literature.

Identificación de algunos genes asociados al proceso de germinación de la conidia al micelio en Paracoccidioides brasiliensis / Identification of genes associated with germination of conidia to form mycelia in the fungus Paracoccidioides brasiliensis

Introducción. Paracoccidioides brasiliensis es un hongo dimórfico térmico, que a temperatura ambiente se presenta como un moho productor de conidias, mientras que en el huésped se comporta como una levadura de gemación múltiple. Los mecanismos moleculares que rigen la germinación de conidia a micelio aún se desconocen. Objetivo. Estudiar en P. brasiliensis la cinética del proceso de germinación de conidia a micelio y determinar los genes expresados durante este proceso mediante la construcción y el análisis de una librería EST (Expressed Sequence Tag). Materiales y métodos. Para el estudio de la cinética de germinación, se produjeron y aislaron conidias de P. brasiliensis. Estas fueron incubadas en cultivos líquidos a 18°C por 24, 48, 72 y 96 horas, y se examinaron por microscopía de luz. A partir de conidias cultivadas por 96 horas, se construyó y caracterizó una librería EST, la cual representaría los genes expresados durante el proceso de germinación. Resultados. Durante el proceso de germinación de conidia a micelio, se observó 11,7±1,2%, 30±0,6%, 43±1,3% y 66±2,4% de germinación a las 24, 48, 72 y 96 horas de incubación, respectivamente. Además, se obtuvo una librería del proceso de germinación consistente en 129 secuencias agrupadas en cuatro secuencias contiguas y siete secuencias únicas, para un total de 11 posibles genes. Ocho secuencias (72,7%) no habían sido descritas anteriormente en otras librerías informadas para este hongo y podrían representar genes específicos de la germinación de conidia a micelio. Conclusiones. Éste es el primer reporte en el que se identifican genes no descritos anteriormente, que son expresados durante la germinación de conidia a micelio, proceso de gran importancia en la biología de P. brasiliensis.

Introduction. Paracoccidioides brasiliensis is a thermo-dimorphic fungus. At room temperature it grows as a mold that produces conidia, whereas in the vertebrate host it grows as a multiple-budding yeast. The molecular mechanisms involved in the germination from the conidia to the mycelia process remain unknown. Objective. The kinetics of conidia to mycelia germination process were studied in the dimorphic fungus P. brasiliensis. Gene expression during this process was evaluated by construction and analysis of an EST library. Materials and methods. For the germination kinetics study, P. brasiliensis conidia were isolated as single cell units. Then, they were cultured at 18° C in BHI (brain-heart infusion) broth for 24, 48, 72 and 96 hr. After each perion, they were examined by light microscopy. From conidia harvested at 96 hr, an EST library was constructed; at this stage the gene expression was presumed to be maximal for the germination process. Results. During the conidia to the mycelia developmental process, the following germination rates were observed: at 24 hr, 11.7±1.2%; at 48 hr, 30±0.6%; at 72 hr, 43±1.3%; and at 96 hr, 66±2.4%. At the 96 hour stage, an EST library was constructed. It consisted of 129 sequences grouped in 4 contigs and 7 singlets for a total of 11 possible genes. Eight of the sequences had not been described previously in other EST libraries of this fungus. Conclusions. New genes were identified that were expressed during the conidia to the mycelia germination process and may represent genes specific to the germination process.