ABSTRACT
Objetivo: Evaluar cual de las 3 estrategias ensayadas es más efectiva para detectar nuevos casos de infección por virus de la hepatitis C (VHC) en atención primaria. Métodos: Estudio observacional, prospectivo y multicéntrico. Se evaluaron 3 estrategias: Estrategia 1: carta explicativa dirigida a personas adultas adscritas a 2 equipos de atención primaria (EAP), invitándoles a realizar un examen serológico. Estrategia 2: colocación en los EAP de pósteres y dípticos explicativos, ofreciendo la posibilidad de realizar un examen analítico. Estrategia 3: revisar el resultado de anti-VHC en los pacientes con hipertransaminasemia detectada en los últimos 2 años mediante la historia electrónica y efectuar determinación del anti-VHC en los casos en quienes no se había determinado. Resultados: Participaron 598 personas (51% mujeres con una media de edad de 50,6±13 años). Con la estrategia 1 se captaron 238 personas (4,1% de participación), con la estrategia 2, 69 personas (0,3%) y con la estrategia 3, 291 pacientes (100%). La detección de VHC oculto fue de un caso en las estrategias 1 y 2, representando una prevalencia del 0,4 y 1,4%, respectivamente, y de 2 casos en la estrategia 3 lo que representa una prevalencia de 0,7%. Conclusiones La búsqueda activa de casos ocultos de infección por VHC ha sido poco efectiva con los métodos ensayados, atendiendo al coste y esfuerzo que comportan (AU)
Objective: To evaluate which of the three studied strategies is the most effective to detect new cases of Hepatitis C virus (HCV) infections in primary care. Methods: This is an observational, prospective, and multicentre study evaluating three strategies. Strategy 1: provide an explanatory letter to adults assigned to two primary care teams (PCTs), inviting them to have a blood test. Strategy 2: place posters and leaflets in PCTs advertising the possibility of laboratory tests. Strategy 3: reexamine HCV antibody test results in patients with hypertransaminasemia diagnosed within the last two years through electronic records, and determine anti-HCV status in undiagnosed cases. Results: There were a total 598 participants (51% female with an average age of 50.6±13 years). There were 238 people (4.1% of letters sent) in Strategy 1, 69 people (0.3% of potential participation) in Strategy 2, and 291 people (100% participation) from Strategy 3. One new case of HCV was found in both Strategy 1 and Strategy 2, representing a prevalence of 0.4 and 1.4%, respectively. Two new cases of HCV were found in Strategy 3, representing a prevalence of 0.7%. Conclusions: The three studied strategies for detecting new cases of HCV infection are ineffective, especially in regards to their cost and effort (AU)
Subject(s)
Humans , Hepacivirus/isolation & purification , Hepatitis C Antibodies/isolation & purification , Hepatitis C, Chronic/epidemiology , Mass Screening/methods , Strategic Planning , Primary Health Care/methods , Transaminases/analysisABSTRACT
OBJECTIVE: To evaluate which of the three studied strategies is the most effective to detect new cases of Hepatitis C virus (HCV) infections in primary care. METHODS: This is an observational, prospective, and multicentre study evaluating three strategies. Strategy 1: provide an explanatory letter to adults assigned to two primary care teams (PCTs), inviting them to have a blood test. Strategy 2: place posters and leaflets in PCTs advertising the possibility of laboratory tests. Strategy 3: reexamine HCV antibody test results in patients with hypertransaminasemia diagnosed within the last two years through electronic records, and determine anti-HCV status in undiagnosed cases. RESULTS: There were a total 598 participants (51% female with an average age of 50.6 ± 13 years). There were 238 people (4.1% of letters sent) in Strategy 1, 69 people (0.3% of potential participation) in Strategy 2, and 291 people (100% participation) from Strategy 3. One new case of HCV was found in both Strategy 1 and Strategy 2, representing a prevalence of 0.4 and 1.4%, respectively. Two new cases of HCV were found in Strategy 3, representing a prevalence of 0.7%. CONCLUSIONS: The three studied strategies for detecting new cases of HCV infection are ineffective, especially in regards to their cost and effort.
Subject(s)
Hepatitis C/diagnosis , Primary Health Care , Serologic Tests/methods , Transaminases/blood , Adult , Aged , Aged, 80 and over , Female , Hepatitis C/epidemiology , Humans , Male , Middle Aged , Prevalence , Prospective Studies , Young AdultABSTRACT
Host factors seem to be crucial for the spontaneous clearance of hepatitis C virus (HCV). Monocytes play a pivotal role in innate immunity and help regulate adaptive responses. This study assesses the characteristics of monocytes from patients with self-limiting HCV infections. We studied 35 consecutive patients [11 with a self-limiting HCV infection, 16 chronically infected with HCV and sustained virological responders (SVR) following antiviral therapy, and eight chronically infected HCV but untreated] and eight healthy donors (HD). The production of interleukin (IL)-10, tumour necrosis factor-alpha (TNF-alpha) and IL-12p40 by monocytes stimulated with lipopolysaccharides(LPS) or HCV Core protein was measured by enzyme-linked immunoassay. Monocyte surface markers were analysed by flow cytometry. LPS and Core protein triggered IL-10 and TNF-alpha production, but monocytes from self-limiting infection patients produced significantly less IL-10 and TNF-alpha than those of SVR, chronically infected or HD (P < 0.05), while IL-12p40 production was unchanged. This cytokine production profile did not appear to be due to expansion of the CD14(+) CD16(+) monocyte subset or to a classical or alternative activation monocyte profile. Monocytes from self-limiting infection patients had more CCR7 than those from SVR or chronically infected patients (P < 0.05). Monocytes of self-limiting infection patients appear to produce little IL-10 and TNF-alpha in response to viral or unspecific stimulation and to have a higher CCR7 expression. This profile seems to be independent to a particular monocyte subset or activation state. Low IL-10 production may help establish an effective immune response and spontaneous HCV clearance.
Subject(s)
Hepatitis C/immunology , Interleukin-10/metabolism , Monocytes/immunology , Adult , Aged , Enzyme-Linked Immunosorbent Assay/methods , Female , Flow Cytometry , Humans , Interleukin-12 Subunit p40/metabolism , Male , Middle Aged , Monocytes/chemistry , Receptors, CCR7/analysis , Tumor Necrosis Factor-alpha/metabolismABSTRACT
BACKGROUND: Peritoneal carcinomatosis from pancreatic cancer has a poor prognosis with a median survival of 3.1 months. This is mainly due to lack of effective treatment. Interleukin 12 (IL12) is a proinflammatory cytokine that has a potent antitumoral effect by stimulating innate and adoptive immunity. AIM: To examine the antitumoral effect and toxicity of intraperitoneal delivery of IL12 using an ex vivo gene therapy approach in a murine model of pancreatic peritoneal carcinomatosis. METHODS: Peritoneal carcinomatosis was generated by direct intraperitoneal inoculation of the pancreatic cancer cell line Capan-1 in athymic mice. Syngenic fibroblasts were genetically modified in vitro to secrete IL12 using a polycistronic TFG murine IL12 retroviral vector coding for both p35 and p40 murine IL12 subunits. Ex vivo gene therapy involved injection of the genetically modified fibroblasts intraperitoneally twice a week for 4 weeks. RESULTS: Treatment of pre-established peritoneal carcinomatosis with fibroblasts genetically modified to express IL12 induced a marked inhibition of tumour growth as measured by comparison of the weights of the intraperitoneal tumour nodules in the treated and control animals (3.52 (SD 0.47) v 0.93 (SD 0.21) g, p<0.05) and improved survival. This effect was associated with infiltration of the peritoneal tumour nodules with macrophages. Peritoneal lavage confirmed enhancement of the innate peritoneal inflammatory activity, with an increased number of activated macrophages and natural killer cells. Moreover, macrophages harvested from animals with peritoneal carcinomatosis and treated with IL12-expressing fibroblasts expressed an activated proinflammatory antitumoral M1 phenotype that included strongly enhanced reactive oxygen species and nitric oxide production. There was no treatment-related toxicity. CONCLUSION: Multiple injections of genetically modified fibroblasts to express IL12 is an effective and well-tolerated treatment for experimental murine pancreatic peritoneal carcinomatosis via activated innate immunity and in particular activated M1 macrophages.
Subject(s)
Antineoplastic Agents/immunology , Fibroblasts/immunology , Genetic Therapy/methods , Interleukin-12/immunology , Peritoneal Neoplasms/therapy , Animals , Cell Division/immunology , Cell Line, Tumor , Disease Models, Animal , Female , Flow Cytometry/methods , Immunity, Innate/immunology , Immunohistochemistry/methods , Injections, Intraperitoneal , Interleukin-12/administration & dosage , Interleukin-12/genetics , Macrophages/immunology , Mice , Mice, Inbred BALB C , Mice, Nude , Nitric Oxide/biosynthesis , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/immunology , Peritoneal Neoplasms/genetics , Peritoneal Neoplasms/immunology , Reactive Oxygen Species/metabolismABSTRACT
Severe malaria is associated with the failure of host defenses to control parasite replication, with the excessive secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), and with the sequestration of parasitized erythrocytes (PEs) in the microcirculation of vital organs. The scavenger receptor CD36, known as a major sequestration receptor, has also been identified as an important factor in mediating nonopsonic phagocytosis of PEs by monocytes and macrophages. The specific consequence of this phagocytosis is a decrease in parasite-induced TNF-alpha secretion. We evaluated the variations in CD36 level and in lipopolysaccharide (LPS)-induced TNF-alpha production in monocytes from Plasmodium falciparum-infected patients and in vitro in the presence of PEs. Both the monocytes from infected patients and from in vitro culture showed a decrease of CD36 expression and a reduced production of TNF-alpha induced by LPS. Using incubation assays with no contact between monocytes and PEs, or in the presence of a soluble supernatant obtained from the incubation of monocytes and PEs, this study shows that decreased CD36 expression was posttranscriptional and not directly related to PEs phagocytosis. In addition, these culture models suggest that the reduced capacity of TNF-alpha production occurred in 2 phases. The early phase (24 hr) appeared to be CD36 dependent and the second phase (48 hr) was due to a soluble factor produced by PEs. These observations suggest that the control of the TNF-alpha production in malaria by monocytes was not entirely dependent on the phagocytosis of PEs by CD36 and that soluble factors produced by PEs could play a role in this process.
Subject(s)
CD36 Antigens/biosynthesis , Erythrocytes/parasitology , Malaria, Falciparum/immunology , Monocytes/immunology , Plasmodium falciparum/immunology , Tumor Necrosis Factor-alpha/biosynthesis , Animals , CD36 Antigens/genetics , Case-Control Studies , Cells, Cultured , Erythrocytes/immunology , Flow Cytometry , Gene Expression , Humans , Malaria, Falciparum/blood , Phagocytosis , Polymerase Chain Reaction , RNA, Messenger/analysisABSTRACT
Introducción: El término anafilaxia hace referencia a una reacción alérgica generalizada, casi siempre como resultado de un mecanismo de hipersensibilidad tipo I, dependiente de IgE. Dentro de las causas más frecuentes de anafilaxia recurrente se encuentran entre otras el ejercicio, con o sin asociación a determinados alimentos. Se presenta el caso de una reacción anafiláctica en una paciente que realizaba ejercicio físico en un pinar. Método: se estudió, mediante prueba cutánea de prick y detección de IgE específica por immunoblotting frente a la procesionaria del pino, una vez que se sospechó que podía ser el alergeno implicado y una vez descartado el ejercicio y los alimentos como sospechosos de la reacción alérgica. Resultados: la prueba cutánea y la detección de IgE fue positiva para el extracto de oruga. En el immunoblotting se detectaron bandas reactivas entre 70-22 kDa. Conclusiones: se trataba de una reacción anafiláctica, mediada por IgE frente a la procesionaria del pino (AU)
Subject(s)
Adult , Female , Humans , Exercise , Hypersensitivity/immunology , Anaphylaxis/etiology , Immunoblotting , LarvaABSTRACT
La alergia a lo alimento es el cuarto motivo de consulta en los servicios de alergia en España, detrás de la rinoconjuntivitis, el asma bronquial y la reacciones alérgica a los medicamento. Este análisis bibliométrico intenta valorar la cantidad y la calidad de la información sobre la alergia alimentaria en las distintas bases de datos. Su objetivo es conocer lo que se publica desde 1998 sobre la alergia a los alimentos centrándose en lo publicado en España. Las bases de datos que e van a utilizar son: Pubmed, EMBASE, BIOSIS e IME. Las bases de datos que nos ofrecen más resultados son Pubmed y EMBASE. Las publicaciones más utilizadas por los autores españoles son Allergy (publicación danesa), J Allergy Clin Inmunol (publicación norteamericana) y Clin Exp Allergy (publicación británica). Los autores españoles publican más en inglés. La comunidad autónoma que más publica e Madrid, la institución que más publica es La Paz, seguida de la Fundación Jiménez Díaz y La Escuela Superior de Ingenieros Agrónomos. Al comparar el resultado obtenidos por autores españoles con los de otros países de nuestro entorno podemos apreciar que el número de trabajos publicados por los españoles es bastante elevado (AU)
Background: The fourth consultation reason to the allergy departments in Spain is the food allergy after hay fever, bronchial asthma and adverse drug reaction .This work is intended to asses the quantity and the quality of information related with food allergy in different databases. The objective is to know what has been published from 1998 about food allergy, compared with what is published in Spain. The databases used are Pubmed. EMBASE. BIOSIS, and IME. The data- bases wich offer us more results are Pubmed and EMBASE. The publications more used by the Spanish autor are Allergy (Danish publication), J Allergy Clin Immunol (American publication) and Clin Exp Allergy (British publication). Spanish authors usually publish in English language. Madrid i the Spanish Community wich publishes more articles and Hospital La Paz as institution, followed by Fundación Jiménez Díaz and Escuela Superior de Ingenieros Agrónomo. Comparing the results obtained for Spanish authors with other countries, we can appreciate the number of papers published is quite large (AU)
Subject(s)
Humans , Food Hypersensitivity , Access to Information , Databases, Bibliographic/trends , Social Networking , Webcasts as Topic , Publications/statistics & numerical data , 50088ABSTRACT
It has been shown that oxidative stress occurs in chronic hepatitis C. Release of reactive oxygen species (ROS) from sequestered phagocytes and activated resident macrophages represents the predominant component of oxidative stress in the liver. However, little is known about the ability of the monocyte to produce ROS in response to protein of hepatitis C virus. In this study, we investigated the ROS production in human monocytes stimulated by several viral proteins of hepatitis C virus. Human monocytes from healthy blood donors were incubated with recombinant viral protein: Core, NS3, NS4, and NS5. ROS production was measured by chemiluminescence. Only NS3 triggered ROS production in human monocytes. Generated ROS were mainly the anion superoxide. NS3 also induced a rapid and transient increase in intracellular calcium concentration measured by a video digital microscopy technique. By using different metabolic inhibitors, we showed that ROS production requires calcium influx, tyrosine kinases, and the stress-activated protein kinase, p38. The study of p47(PHOX) phosphorylation and translocation showed that NADPH oxidase was activated and involved in ROS production induced by NS3. In a second experiment, NS3 inhibited the oxidative burst induced by phorbol 12-myristate 13-acetate. These results indicate that NS3 activates NADPH oxidase and modulates ROS production, which may be involved in the natural history of hepatitis C infection.
Subject(s)
Hepacivirus/physiology , Monocytes/metabolism , NADPH Oxidases/metabolism , Respiratory Burst , Viral Nonstructural Proteins/physiology , Calcium/metabolism , Enzyme Activation , Humans , Mitogen-Activated Protein Kinases/metabolism , Monocytes/virology , Phosphorylation , Protein-Tyrosine Kinases/metabolism , Reactive Oxygen Species , p38 Mitogen-Activated Protein KinasesABSTRACT
Objetivo: Evaluar la problemática de las tentativas de suicidio en el Hospital General "Miguel Servet" de Zaragoza. Diseño: Estudio retrospectivo Pacientes: Fueron estudiados 206 casos durante los años 1992 a 1995. Resultados: Fueron más frecuentes las tentativas de suicidio en solteros. parados o jubilados. Permanecieron ingresados una media de 11,25 días. La media de intentos previos era de 0,93. El 39.80 por ciento presento un riesgo somático grave, el resto fue leve o moderado. Los diagnósticos más frecuentes fueron: trastornos de personalidad, trastornos en relación con sustancias psicoactivas, distimia y depresión mayor. Los métodos más frecuentes de parasuicidio fueron: intoxicación medicamentosa (71,36 por ciento), heridas (11.65 por ciento) y precipitación (5,34 por ciento). El 50,83 por ciento habrá realizado alguna visita médica en las 3 semanas previas a la tentativa de suicidio. Las mujeres realizaron intentos más leves. Los pacientes mayores de 65 años presentaron más trastornos depresivos mayores y trastornos mentales orgánicos y aumentó la letalidad de los métodos. En las esquizofrenias y otras psicosis, depresión mayor y trastornos relacionados con sustancias psicoactivas la gravedad somática fue mayor. Una tentativa de suicidio pasada es, quizás, el mayor indicador de riesgo para un suicidio futuro (AU)
Subject(s)
Adult , Aged , Female , Male , Middle Aged , Humans , Suicide, Attempted/psychology , Hospitals, General/trends , Hospitals, General , Dysthymic Disorder/psychology , Dysthymic Disorder/therapy , Antipsychotic Agents/administration & dosage , Anti-Anxiety Agents/therapeutic use , Retrospective Studies , Depressive Disorder/psychology , Depressive Disorder/therapy , Psychotherapy/methodsABSTRACT
The present study investigates phenotypic and functional differentiation of peritoneal macrophages during ovalbumin-induced subcutaneous immunization of mice. For the first time we show that, in mouse peritoneal macrophages, ovalbumin immunization induces an increase in cyclooxygenase-2 (COX-2) and 5-lipoxygenase activating protein (FLAP) expression whereas it inhibits cytosolic phospholipase A(2) (cPLA2) expression. The study of arachidonic acid (AA) metabolism in peritoneal macrophages from control (cPM) and ovalbumin-immunized (iPM) mice shows that the reduced cPLA2 expression is correlated to a reduced basal AA metabolism, but is not a limiting factor for the opsonized zymosan-, PMA-, or A23187-triggered AA metabolism. We also show that in vitro ovalbumin challenge induces, only in iPM, cPLA2 activation through phosphorylation of serine residues, via a mechanism involving MAP kinases, and through increased intracellular calcium concentrations, leading to eicosanoid production. In parallel, we report that, in peritoneal macrophages, ovalbumin immunization induces the expression of CD23, the low affinity receptor for IgEs known for its involvement in allergic diseases. Thus, the modified expression of the enzymes involved in AA metabolism and the difference of response of cPM and iPM toward the antigen are important elements to understand the underlying mechanisms of ovalbumin-induced allergic responses.
Subject(s)
Arachidonate 5-Lipoxygenase/metabolism , Carrier Proteins/biosynthesis , Isoenzymes/metabolism , Macrophages, Peritoneal/metabolism , Membrane Proteins/biosynthesis , Ovalbumin/administration & dosage , Phospholipases A/metabolism , Prostaglandin-Endoperoxide Synthases/metabolism , 5-Lipoxygenase-Activating Proteins , Animals , Arachidonic Acid/metabolism , Calcium/metabolism , Cyclooxygenase 2 , Cytosol/enzymology , Enzyme Activation , Female , Flow Cytometry , Gene Expression , Immunization , Injections, Subcutaneous , Macrophages, Peritoneal/enzymology , Mice , Ovalbumin/immunology , Phosphorylation , Receptors, IgE/biosynthesis , TritiumABSTRACT
Using purified B95-8 Epstein-Barr virus (EBV), a MAb designated H667 was produced. We demonstrated by indirect membrane immunofluorescence (IF) on six EBV producer cell lines and by immunoelectron microscopy that H667 reacted with a membrane antigen. H667 recognized a 43-kDa EBV protein (p43) as determined by immunoblotting using purified EBV from the six producer cell lines. Phosphonoacetic acid treatment of B95-8 cells was associated with the disappearance of p43, indicating that it was a late antigen. This antigen was shown to be a glycoprotein by incorporation of [14C]glucosamine and was shown to contain an N-asparagine-linked glycosyl group by its sensitivity to tunicamycin. It was named gp43. The H667 MAb inhibited B95-8 EBV cord blood lymphocyte transformation only when a low inoculum was used but failed to inhibit EA induction in Raji cells by P3HR1 EBV. Human sera reactivity against the gp43 antigen was studied. By the immunoblotting method, using H667 immunoaffinity chromatography-purified gp43, we showed that 70.9% of the human sera tested had antibodies directed against gp43. By IF blocking tests, we found that only 12.5% of the sera tested were reactive, indicating that the epitope corresponding to the H667 MAb was not the most immunogenic gp43 epitope.
Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Viral/immunology , Herpesvirus 4, Human/immunology , Viral Proteins/immunology , Animals , Antibodies, Monoclonal/biosynthesis , Antibodies, Viral/blood , Antibodies, Viral/isolation & purification , Antigens, Viral/immunology , Cell Line , Cross Reactions/immunology , Fetal Blood/immunology , Fluorescent Antibody Technique , Herpesvirus 4, Human/isolation & purification , Herpesvirus 4, Human/ultrastructure , Humans , Immunoblotting , Lymphocyte Activation/immunology , Mice , Mice, Inbred BALB C , Neutralization Tests , Viral Proteins/isolation & purificationABSTRACT
A monoclonal antibody (mAb) designated H250, directed against an Epstein-Barr virus (EBV) capsid antigen, was obtained following immunization of BALB/c mice with naked particles from the producer cell line B95.8. This antigen was present in the producer lines B95.8, P3HR1, M81, RI and CA, and absent from the non-producer lines BJAB, Raji and 1022. H250 did not inhibit the transformation of cord blood lymphocytes by the B95.8 virus, nor did it inhibit EA induction on Raji cells by the P3HR1 virus. In addition, H250 showed no fluorescence on living B95.8 cells. This indicates that H250 does not recognize a membrane antigen. By indirect immunofluorescence, no fluorescence was observed on induced Raji cells or on PAA-treated B95.8 cells. Thus, H250 recognized a late antigen of the EBV virus replication cycle. Agglutination of naked virus by H250 showed it was directed against a capsid antigen. Positive fluorescence was observed on cells treated with tunicamycin, indicating that H250 recognized a protein. The molecular weight of this protein was obtained by Western blot and was approximately 75 kDa. The blocking tests carried out with H250 seemed to indicate that this Ab appeared late in patient sera during primary infection.
