Correlation between Soluble Triggering Receptor Expressed on Myeloid Cells-1 and Endoscopic Activity in Intestinal Behcet's Disease

PURPOSE: The serum levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) have recently been shown to be correlated highly with disease activity in patients with intestinal Behcet's disease (BD). However, it remains unclear whether sTREM-1 levels reflect endoscopic activity in intestinal BD. This study aimed to evaluate the correlation of sTREM-1 levels with endoscopic activity in intestinal BD. MATERIALS AND METHODS: A total of 84 patients with intestinal BD were enrolled. Endoscopic activity was compared with sTREM-1 levels as well as other laboratory findings, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). RESULTS: sTREM-1 levels were significantly increased in intestinal BD patients compared with controls (37.98+/-27.09 pg/mL vs. 16.65+/-7.76 pg/mL, p=0.002), however, there was no difference between endoscopically quiescent and active diseases (43.53+/-24.95 pg/mL vs. 42.22+/-32.68 pg/mL, p=0.819). Moreover, serum sTREM-1 levels did not differ in terms of number, shape, depth, size, margin, or type of ulcer in patients with intestinal BD. However, mean ESR and CRP levels in patients with active disease were significantly higher than those in patients with quiescent disease (p=0.001, p<0.001, respectively). In addition, endoscopic activity scores for intestinal BD were correlated significantly with both CRP levels (gamma=0.329) and ESR (gamma=0.298), but not with sTREM-1 levels (gamma=0.166). CONCLUSION: Unlike CRP levels and ESR, serum sTREM-1 levels were not correlated with endoscopic activity in patients with intestinal BD.

Characterization of nCD64 expression in neutrophils and levels of s-TREM-1 and HMGB-1 in patients with suspected infection admitted in an emergency department / Caracterización de la expresión de nCD64 en neutrófilos y de los niveles de s-TREM-1 y HMGB-1 en pacientes con sospecha de infección admitidos en el departamento de emergencias

Introduction: The nCD64 receptor, the soluble triggering receptor expressed in myeloid cells (s-TREM-1), and the high mobility group-box 1 protein (HMGB-1) have been proposed as significant mediators in sepsis. Objective: To evaluate the prognostic value of these markers in patients with suspected infection recently admitted in an emergency department (ED). Materials and methods: All patients who presented to the ED with suspected infection were eligible for enrollment in this study. Baseline clinical data, Sequential Organ Failure Assessment score (SOFA) score, APACHE II score, HMGB-1 levels, s-TREM-1 levels, and nCD64 levels were analyzed. The HMGB-1 and sTREM-1 serum concentrations were determined using commercially available ELISA kits, and CD64 on the surface of neutrophils was measured by flow cytometry. Results:. A total of 579 patients with suspected infection as their admission diagnosis were enrolled in this study. The median patient age was 50 years (IQR = 35-68). Morbidity during the 28-day followup period was 11.1% (n=64). The most frequent diagnosis at the time of admission was communityacquired pneumonia (CAP) in 23% (n=133) patients, followed by soft tissue infection in 16.6% (n=96), and urinary tract infection in 15% (n=87). After multivariable analysis, no significant association was identified between any biomarker and 28-day mortality. Conclusion: In the context of a tertiary care hospital emergency department in a Latin-American city, the nCD64 receptor, s-TREM-1, and HMGB-1 biomarkers do not demonstrate prognostic utility in the management of patients with infection. The search continues for more reliable prognostic markers in the early stages of infection.

Introducción. El receptor CD64, receptor soluble ´desencadenador´ expresado en células mieloides (sTREM-1) y la proteína del grupo Box-1 de alta movilidad (HMGB-1), se han propuesto como mediadores en la sepsis. Objetivo. Evaluar el valor pronóstico de estos marcadores en pacientes con sospecha de infección, recientemente admitidos en un departamento de emergencias. Materiales y métodos. Se incluyeron en el estudio pacientes que consultaron al hospital con sospecha de infección. Se analizó la base de datos clínica, el puntaje SOFA, el puntaje APACHE II, los niveles de HMGB-1, los niveles de sTREM-1 y los niveles de nCD64. Se determinaron las concentraciones en suero de HMGB-1 y sTREM-1, usando kits de ELISA disponibles comercialmente, y la de CD64 se midió por citometría de flujo. Resultados. Se analizaron 579 pacientes con sospecha de infección al ingreso. La edad media fue de 50 años (rango intercuartílico=35-68), y 11,1 % (n=64) murieron durante el seguimiento de 28 días. El diagnóstico más frecuente en el momento del ingreso fue neumonía adquirida en la comunidad, en 23 % (n=133) de los pacientes, seguida de infección de tejidos blandos, en 16,6 % (n=96), e infección urinaria, en 15 % (n=87). Después de un análisis multivariado, no hubo asociación significativa entre ningún biomarcador y la mortalidad a los 28 días. Conclusión. Los resultados sugieren que en el contexto de un departamento de emergencias de tercer nivel de una ciudad latinoamericana típica, los tres marcadores evaluados no ofrecieron ninguna ventaja en el pronóstico de infección. La búsqueda de marcadores pronósticos más confiables en estadios tempranos de la infección aún continúa abierta.

Determinación de péptidos solubles relacionados a mesotelina para la detección precoz del mesotelioma maligno / Soluble mesothelin-related protein for malignant pleural mesothelioma screening

Introduction: Malignant Pleural Mesothelioma (MPM) is a tumor of the mesothelial cells related to asbestos exposure. This malignancy is extremely aggressive, with poor response to different treatment modalities, and it has a mean survival of 8 months since diagnosis. With the introduction of new chemotherapeutic agents and trimodality protocols, five-year survival of 40 percent in initial stages has been reported. Serum detection of Soluble Mesothelin-related Protein (SMRP) could be used for screening of MPM. Using the MESOMARK® test, 53 percent of MPM patients had levels greater than 1,5 nM, while 99 percent of control patients had lower concentrations. The aim of this study is to evaluate the use of this test in Chile and determine its utility for screening ofMPM. Methods: Quantitative blind measurement of serum SMRP by MESOMARK® test. We studied 3 groups: 8 workers exposed to asbestos, 5 patients with diagnosed MPM and 14 age matched workers without known exposure to asbestos. Participants were informed of the study. Results: Mean +/- standard deviation SMRP levels in the control group was 0,53 +/- 0,4 nM, 0,89 +/- 0,46 nM in patients exposed to asbestos and 10,68 +/- 10,28 nM in MPMpatients. Differences between the groups were statistically significant (p = 0,02). In the MPM group, 3 patients were found to have SMRP levels greater than 1,5 nM (17,27 nM; SD 6,95) and 2 patients normal values (0,79 nM; SD 0,32). Using a cut-off value of 1,5 nM, sensitivity of the test was 60 percent and specificity was 100 percent. Conclusions: Detection of SMRP levels allowed to identify patients with MPM, three of whom had very high concentrations. The sensitivity and specificity found is similar to that previously reported. If our results are confirmed in greater studies, SMRP detection could be used for screening of MPM.

Resumen Introducción: El Mesotelioma Maligno (MM) es un tumor de las células mesoteliales relacionado a la exposición a asbesto, altamente agresivo, con pobre respuesta al tratamiento y con una sobrevida promedio de 8 meses después del diagnóstico. Sin embargo, nuevos agentes quimioterapéuticos y protocolos de terapia trimodal han logrado sobrevidas de hasta 40 por ciento en etapas iniciales. La detección en sangre periférica de Péptidos Solubles Relacionados a Mesotelina (SMRP) podría ser útil para el diagnóstico precoz de MM. Utilizando el test MESOMARK® para la determinación de SMRP, 53 por ciento de los pacientes con MM tenían valores mayores a 1,5 nM mientras que 99 por ciento de los controles mostraron valores inferiores. El objetivo del presente trabajo es evaluar la implementación de este test en Chile y determinar su utilidad para el diagnóstico precoz en MM. Métodos: Medición cuantitativa de SMRP en suero humano por test MESOMARK®. Se realizaron mediciones en forma ciega a 8 trabajadores con exposición a asbesto, a 5 pacientes con MMy a 14 voluntarios sin exposición. Todos los participantes fueron informados del estudio. Resultados: El promedio +/- desviación estándar de SMRP en el grupo control fue de 0,53 +/- 0,4 nM, de 0,89 +/- 0,46 nM en los expuestos sin MMy de 10,68 +/- 10,28 nM en el grupo con MM; encontrándose una diferencia estadísticamente significativa entre los valores de estos tres grupos (p = 0,02). En el grupo con MM, 3 pacientes tuvieron concentraciones mucho mayores a 1,5 nM (17,27 nM; DS 6,95) y 2 valores normales (0,79 nM; DS 0,32). Utilizando un valor de 1,5 nM como punto de corte, la sensibilidad fue de 60 por ciento y la especificidad de 100 por ciento. Conclusiones: La medición de SMRP permitió diferenciar a los pacientes con MM, presentando 3 de ellos concentraciones muy elevadas. La sensibilidad y especificidad encontrada es similar con datos previamente reportados. De confirmarse estos resultados en estudios con mayor ...

Distribuição e freqüência de alelos e haplotipos HLA em brasileiros com diabetes melito tipo 1 / Distribution and frequency of HLA alleles and haplotypes in brazilians with type 1 diabetes mellitus

A predisposição genética ao diabetes melito tipo 1 (DM1) é associada a múltiplos genes do sistema de histocompatibilidade humano (HLA) de classe II. Em caucasianos, os antígenos HLA-DR3 e -DR4 são associados à susceptibilidade e o -DR2, à proteção. No Brasil, um país constituído por grande miscigenação entre caucasianos europeus, índios nativos e negros africanos, a base genética do DM1 tem sido pouco estudada. O objetivo desse trabalho foi apresentar uma revisão crítica dos artigos indexados nos bancos de dados MEDLINE e LILACS-BIREME sobre a associação do HLA com DM1 em brasileiros. Todos os oito estudos encontrados foram realizados no sudeste do país. A susceptibilidade imunogenética para o DM1 em brasileiros foi associada com os alelos HLA-DRB1*03, -DRB1*04, -DQB1*0201, -DQB1*0302 e a proteção com os alelos -DQB1*0602 e -DQB1*0301 e os antígenos -DR2 e -DR7. Por ser o Brasil constituído por grande miscigenação, não se pode extrapolar para todo o país estudos realizados em apenas uma região. Faz-se necessário pesquisar populações de várias regiões, analisando sua diversidade alélica para identificar novas associações ou reforçar aquelas já existentes. Esse conhecimento contribuirá para futuras intervenções profiláticas e terapêuticas nos grupos de brasileiros com maior risco de desenvolver DM1.

Pilot neonatal screening program for lysosomal storage disorders, using lamp-1.

We have demonstrated that the lysosome associated membrane protein (LAMP-1) is elevated in plasma from approximately 70% of lysosomal storage disorder patients. As part of the development of a newborn screening program for lysosomal storage disorders we have developed a first tier screening assay based upon the level of LAMP-I in blood spots taken from newborn Guthrie cards. To determine the effectiveness of the first-tier marker a prospective pilot Guthrie neonatal screening program for the identification of LSD was commenced in April 1998. Prior to commencement of the pilot program ethical approval was obtained and information leaflets regarding the neonatal screening of LSD were distributed to parents at the time of their infant's Guthrie collection. The LAMP-1 assay utilizes a chicken polyclonal and a mouse monoclonal in a sandwich time resolved fluorescent immunoassay. LAMP-1 blood-spot calibrators and quality control specimens were developed and shown to be stable and reproducible. To date 11,183 infants have been screened using LAMP-1. The population distribution is described with a median and 98th percentile of 220pg/l whole blood and 483microg/l whole blood respectively. Acceptable CV% for intra and inter assay of 8.9% and 10% respectively were obtained.

Newborn screening for lysosomal storage disorders.

Lysosomal storage disorders (LSD) represent a group of over 40 distinct genetic diseases with a total incidence of approximately 1:7,000 births. Bone marrow transplantation and enzyme replacement therapy are currently in use for the treatment of some disorders and new forms of enzyme and gene replacement therapy are actively being researched. The effectiveness of these therapies, particularly for the LSD involving the central nervous system and bone pathology, will rely heavily upon the early diagnosis and treatment of the disorder, before the onset of irreversible pathology. In the absence of a family history the only practical way to detect these disorders will be by a newborn screening program. One common feature of these disorders is an increase in the number and size of lysosomes within the cell from approximately 1% to as much as 50% of total cellular volume. Associated with this, is a corresponding increase in some lysosomal proteins. We propose that the measurement of one or more of these proteins in blood spots taken from Guthrie cards, will form the basis of a newborn screening program, for the detection of all LSD. We have identified a number of lysosomal proteins as potential markers for LSD. The level of these proteins has been determined in blood spots taken from Guthrie cards and in plasma samples from over 300 LSD affected individuals representing 25 disorders. Based on these results we have proposed a strategy for a newborn screening program involving a two tier system, utilizing time resolved fluorescence immunoquantification of the protein markers in the first tier, followed by tandem mass spectrometry for the determination of stored substrates in the second tier assays.

An anorectic proteoglycan of membrane origin.

The endogenous substance(s) involved in the regulation of food intake has been isolated from serum, urine and feces. In the present study, a similar type of anorexigenic proteoglycan was isolated from human rat erythrocyte membranes and rat liver membranes. Membranes were suspended in 2.0% deoxycholate and allowed to stand at 25 degrees C for 30 min. The suspension was treated with 5% TCA, supernatant was collected, dialyzed and concentrated. TCA-soluble proteins were fractionated on Sephadex G-150. The active second peak fractions were further purified on DEAE-Sephadex A-25. Biologically active substance reduced the appetite in rats significantly when given intraperitoneally. The proteoglycan (50 kDa) consisted of 70-85% carbohydrate. Similar properties of plasma and membrane anorectic substance further indicated its membrane origin. We believe that this anorectic proteoglycan is anchored to cell membranes and released into the blood circulation to regulate the food intake.