Treatment, outcomes and costs of asthma exacerbations in Chilean children: a prospective multicenter observational study.

OBJECTIVE: To describe potential regional variations in therapies for severe asthma exacerbations in Chilean children and estimate the associated health expenditures. METHODS: Observational prospective cohort study in 14 hospitals over a one-year period. Children five years of age or older were eligible for inclusion. Days with oxygen supply and pharmacological treatments received were recorded from the clinical chart. A basic asthma hospitalization basket was defined in order to estimate the average hospitalization cost for a single patient. Six months after discharge, new visits to the Emergency Room (ER), use of systemic corticosteroids and adherence to the controller treatment were evaluated. RESULTS: 396 patients were enrolled. Patients from the public health system and from the north zone received significantly more days of oxygen, systemic corticosteroids and antibiotics. Great heterogeneity in antibiotic use among the participating hospitals was found, from 0 to 92.3% (ICC 0.34, 95% CI 0.16-0.52). The use of aminophylline, magnesium sulfate and ketamine varied from 0 to 36.4% between the different Pediatric Intensive Care Units (ICC 0.353, 95% CI 0.010-0.608). The average cost per inpatient was of $1910 USD. 290 patients (73.2%) completed the follow-up six months after discharge. 76 patients (26.2%) were not receiving any controller treatment and nearly a fourth had new ER visits and use of systemic corticosteroids due to new asthma exacerbations. CONCLUSIONS: Considerable practice variation in asthma exacerbations treatment was found among the participating hospitals, highlighting the poor outcome of many patients after hospital discharge, with an important health cost.

Hospitalizations for asthma exacerbation in Chilean children: A multicenter observational study.

BACKGROUND: Asthma hospitalization rates in Chilean children have increased in the last 14 years, but little is known about the factors associated with this. OBJECTIVE: Describe clinical characteristics of children hospitalized for asthma exacerbation. METHODS: Observational prospective cohort study in 14 hospitals. Over a one-year period, children five years of age or older hospitalized with asthma exacerbation were eligible for inclusion. Parents completed an online questionnaire with questions on demographic information, about asthma, indoor environmental contaminant exposure, comorbidities and beliefs about disease and treatment. Disease control was assessed by the Asthma Control Test. Inhalation technique was observed using a checklist. RESULTS: 396 patients were enrolled. 168 children did not have an established diagnosis of asthma. Only 188 used at least one controller treatment at the time of hospitalization. 208 parents said they believed their child had asthma only when they had an exacerbation and 97 correctly identified inhaled corticosteroids as anti-inflammatory treatment. 342 patients used the wrong spacer and 73 correctly performed all steps of the checklist. CONCLUSIONS: Almost half of the patients were not diagnosed with asthma at the time of hospitalization despite having a medical history suggestive of the disease. In the remaining patients with an established diagnosis of asthma potentially modifiable factors like bad adherence to treatment and poor inhalation technique were found. Implementing a nationwide asthma program including continued medical education for the correct diagnosis and follow up of these patients and asthma education for patients and caregivers is needed to reduce asthma hospitalization rates in Chilean children.

Simulation of risk of tuberculosis infection in healthcare workers in hospitals of an intermediate incidence country.

We simulated the frequency of tuberculosis infection in healthcare workers in order to classify the risk of TB transmission for nine hospitals in Medellín, Colombia. We used a risk assessment approach to estimate the average number of infections in three risk groups of a cohort of 1082 workers exposed to potentially infectious patients over 10- and 20-day periods. The risk level of the hospitals was classified according to TB prevalence: two of the hospitals were ranked as being of very high priority, six as high priority and one as low priority. Consistent results were obtained when the simulation was validated in two hospitals by studying 408 healthcare workers using interferon gamma release assays and tuberculin skin testing. The latent infection prevalence using laboratory tests was 41% [95% confidence interval (CI) 34·3-47·7] and 44% (95% CI 36·4-51·0) in those hospitals, and in the simulation, it was 40·7% (95% CI 32·3-49·0) and 36% (95% CI 27·9-44·0), respectively. Simulation of risk may be useful as a tool to classify local and regional hospitals according to their risk of nosocomial TB transmission, and to facilitate the design of hospital infection control plans.

The dendritic cell receptor for endocytosis, DEC-205, can recycle and enhance antigen presentation via major histocompatibility complex class II-positive lysosomal compartments.

Many receptors for endocytosis recycle into and out of cells through early endosomes. We now find in dendritic cells that the DEC-205 multilectin receptor targets late endosomes or lysosomes rich in major histocompatibility complex class II (MHC II) products, whereas the homologous macrophage mannose receptor (MMR), as expected, is found in more peripheral endosomes. To analyze this finding, the cytosolic tails of DEC-205 and MMR were fused to the external domain of the CD16 Fcgamma receptor and studied in stable L cell transfectants. The two cytosolic domains each mediated rapid uptake of human immunoglobulin (Ig)G followed by recycling of intact CD16 to the cell surface. However, the DEC-205 tail recycled the CD16 through MHC II-positive late endosomal/lysosomal vacuoles and also mediated a 100-fold increase in antigen presentation. The mechanism of late endosomal targeting, which occurred in the absence of human IgG, involved two functional regions: a membrane-proximal region with a coated pit sequence for uptake, and a distal region with an EDE triad for the unusual deeper targeting. Therefore, the DEC-205 cytosolic domain mediates a new pathway of receptor-mediated endocytosis that entails efficient recycling through late endosomes and a greatly enhanced efficiency of antigen presentation to CD4(+) T cells.

TCR-Mediated internalization of peptide-MHC complexes acquired by T cells.

Peptide-major histocompatibility complex protein complexes (pMHCs) on antigen-presenting cells (APCs) are central to T cell activation. Within minutes of peptide-specific T cells interacting with APCs, pMHCs on APCs formed clusters at the site of T cell contact. Thereafter, these clusters were acquired by T cells and internalized through T cell receptor-mediated endocytosis. During this process, T cells became sensitive to peptide-specific lysis by neighboring T cells (fratricide). This form of immunoregulation could explain the "exhaustion" of T cell responses that is induced by high viral loads and may serve to down-regulate immune responses.

Conducta fumadora en estudiantes de kinesiología y su asociación con actitudes y conocimientos sobre tabaquismo: estudio de corte transversal / Smoking behavior in Chilean physical therapist students and their association with attitudes and knowledge on cigarette smoking: a cross sectional study

INTRODUCCIÓN: El tabaquismo continúa siendo un problema sanitario en población universitaria y profesionales de la salud. Los kinesiólogos participan en la implementación de programas orientados a la prevención y cese del tabaquismo en la comunidad. El objetivo de este estudio fue explorar la prevalencia de tabaquismo y actitudes sobre consumo de tabaco en estudiantes de kinesiología. MÉTODOS: Estudio de corte transversal realizado en estudiantes de Kinesiología de Concepción (Chile), durante los años 2017 y 2018. Se determinó la conducta y actitudes sobre tabaquismo. Mediante regresión logística se determinó la asociación entre la conducta fumadora y las actitudes sobre tabaquismo. Se consideró un valor de p < 0,05 como estadísticamente significativo. RESULTADOS: Se contestaron 554 cuestionarios. El 57,8% de los estudiantes encuestados declaró no haber fumado nunca, 13 % no haber fumado los últimos 6 meses y 29,4% declaró ser fumador actual. Por su parte, el 99,5% expresó algún grado de acuerdo con que fumar es perjudicial para la salud, lo cual se relacionó con la conducta fumadora (p < 0,0002). En relación a actitudes sobre tabaquismo, comparado a los no fumadores, los fumadores actuales presentan mayor probabilidad de mostrar desacuerdo o indiferencia respecto a actitudes positivas sobre tabaquismo. Principalmente en aquellas acciones que restringen su consumo, venta y divulgación (OR ponderado = 2,43; 95%IC 2,02 - 2,92). CONCLUSIONES: La prevalencia de tabaquismo en estudiantes de Kinesiología de Concepción es del 29,2%. Los estudiantes fumadores expresan una menor aprobación relacionada a intervenciones, actitudes y consecuencias del tabaquismo para la salud comparada con los no fumadores.

INTRODUCTION: Notwithstanding control policies, smoking continues to be a health problem in university students and health professionals, who are responsible for implementing programs oriented to prevention and cessation of smoking in the community. The objective of this study was to explore the prevalence of smoking and attitudes about smoking in physical therapy students. METHODS: Cross-sectional study carried out in students of physical therapy from three universities of Concepción city (Chile), during the years 2017 and 2018. Behavior and attitudes about smoking were evaluated. Association between smoking behavior and attitudes about smoking was determined by logistic regression. A p value < 0.05 was considered statistically significant. RESULTS: 554 questionnaires were answered. 57.8% of respondents had never smoked, 13.0% had not smoked in the last 6 months and 29.4% were current smokers. Moreover 99.5% of respondents stated some degree of agreement that smoking is harmful to health, which was related to smoking behavior (p < 0.0002). In relation to attitudes about smoking, compared to non-smokers, current smokers have a greater chance of showing disagreement or indifference regarding positive attitudes about smoking. Mainly in those actions that restrict tobacco consumption, sale and disclosure (weighted OR = 2.43, 95% CI 2.02 - 2.92). CONCLUSIONS: The prevalence of current smoking in physical therapy students from Concepcion city is 29.2%. Smoking students express lower approval related to interventions, attitudes and consequences of smoking for health compared with non-smokers.

Manejo del cáncer de mama en tiempos de pandemia COVID-19: experiencia local / Management of breast cancer in COVID-19 pandemic: a local experience

La pandemia por COVID-19 ha generado un estancamiento mundial en la atención y resolución de todas las patologías graves y crónicas, debido al colapso de los sistemas de salud, a la dificultad de consulta, dada por la disminución de movilidad de las personas, por las cuarentenas establecidas y también por el temor de los pacientes al contagio en los centros de salud. Los enfermos oncológicos han visto canceladas sus atenciones, suspendidos o postergado sus tratamientos y diferidas sus cirugías. Esto no ha sido ajeno a las pacientes con cáncer de mama. En el presente trabajo, se reporta la experiencia de una Unidad de Patología Mamaria de un hospital público de Santiago de Chile y de las acciones realizadas para mantener la continuidad de atención en una comuna con una alta tasa de infección por SARS-CoV-2.

The COVID-19 pandemic has generated a global stagnation in the care and medical treatment of serious and chronic illnesses due to the collapse of the health systems, the difficulty of consulting due to decreased mobility caused by forced quarantines and also because of the fear of infection when attending a health center. Cancer patients have had their medical appointments canceled, their treatments suspended or postponed, and their surgeries delayed. Breast cancer patients have not been the exception. We report the experience of a Breast Pathology Unit of a public hospital in Santiago of Chile, and the actions carried out to maintain continuity of care in a community with a high infection rate of SARS-CoV-2.

Toma de impresiones en prótesis fija. Implicaciones periodontales / Impression making in fixed prosthesis. Periodontal approach

Uno de los principales éxitos en prostodoncia es la exactitud de la restauración final que garantice la sobrevida de las prótesis, la reproducción precisa de márgenes de la preparación en una impresión es un requisito necesario para lograr una buena calidad marginal. Es por eso que la técnica y material de impresión, así como el manejo de los tejidos periodontales resultan claves en la consecución del éxito. Entender las propiedades década uno de los materiales utilizados durante el proceso de toma de impresión así como el diagnóstico oportuno de la condición periodontal previa (salud, enfermedad, biotipo periodontal) y las técnicas disponibles para la retracción o desplazamiento de los tejidos gingivales, proporcionan al clínico las herramientas necesarias para la toma de decisiones y la consecución de los mejores resultados estéticos y funcionales en prótesis fija. El propósito de esta revisión de tema es proponer una serie de recomendaciones para el clínico restaurador desde el punto de vista periodontal, que le permita establecer protocolos en el diagnóstico, planificación y ejecución de sus casos clínicos, conociendo las actuales técnicas de desplazamiento o retracción gingival y toma de impresión y sus efectos sobre el periodonto (AU)

One of the major successes in prosthodontics is the accuracy of the final restoration to ensure the survival of the prosthesis, the precise reproduction of the preparation margins in impressions is a need for good quality marginal requirement. That’s why the technique and impression materials, as well as the management of periodontal tissues are key in achieving success. Understanding the properties of each of the materials used for the impression making process and the timely diagnosis of previous periodontal condition (health, disease, periodontal biotype), and techniques available to the retraction or displacement of the gingival tissues, provide clinicians the tools necessary for making decisions and achieving the best aesthetic and functional results infixed prosthesis. The purpose of this topic review is to propose a series of recommendations for clinical restorative from the periodontal approach, which to establish protocols for the diagnosis, planning and execution of their clinical cases, knowing the current techniques of gingival displacement and takes impression and its effects on the periodontium (AU)

Treatment, outcomes and costs of asthma exacerbations in Chilean children: a prospective multicenter observational study

Objective: To describe potential regional variations in therapies for severe asthma exacerbations in Chilean children and estimate the associated health expenditures. Methods: Observational prospective cohort study in 14 hospitals over a one-year period. Children five years of age or older were eligible for inclusion. Days with oxygen supply and pharmacological treatments received were recorded from the clinical chart. A basic asthma hospitalization basket was defined in order to estimate the average hospitalization cost for a single patient. Six months after discharge, new visits to the Emergency Room (ER), use of systemic corticosteroids and adherence to the controller treatment were evaluated. Results: 396 patients were enrolled. Patients from the public health system and from the north zone received significantly more days of oxygen, systemic corticosteroids and antibiotics. Great heterogeneity in antibiotic use among the participating hospitals was found, from 0 to 92.3% (ICC 0.34, 95% CI 0.16-0.52). The use of aminophylline, magnesium sulfate and ketamine varied from 0 to 36.4% between the different Pediatric Intensive Care Units (ICC 0.353, 95% CI 0.010-0.608). The average cost per inpatient was of $1910 USD. 290 patients (73.2%) completed the follow-up six months after discharge. 76 patients (26.2%) were not receiving any controller treatment and nearly a fourth had new ER visits and use of systemic corticosteroids due to new asthma exacerbations. Conclusions: Considerable practice variation in asthma exacerbations treatment was found among the participating hospitals, highlighting the poor outcome of many patients after hospital discharge, with an important health cost

No disponible

Hospitalizations for asthma exacerbation in Chilean children: A multicenter observational study

BACKGROUND: Asthma hospitalization rates in Chilean children have increased in the last 14 years, but little is known about the factors associated with this. OBJECTIVE: Describe clinical characteristics of children hospitalized for asthma exacerbation. METHODS: Observational prospective cohort study in 14 hospitals. Over a one-year period, children five years of age or older hospitalized with asthma exacerbation were eligible for inclusion. Parents completed an online questionnaire with questions on demographic information, about asthma, indoor environmental contaminant exposure, comorbidities and beliefs about disease and treatment. Disease control was assessed by the Asthma Control Test. Inhalation technique was observed using a checklist. RESULTS: 396 patients were enrolled. 168 children did not have an established diagnosis of asthma. Only 188 used at least one controller treatment at the time of hospitalization. 208 parents said they believed their child had asthma only when they had an exacerbation and 97 correctly identified inhaled corticosteroids as anti-inflammatory treatment. 342 patients used the wrong spacer and 73 correctly performed all steps of the checklist. CONCLUSIONS: Almost half of the patients were not diagnosed with asthma at the time of hospitalization despite having a medical history suggestive of the disease. In the remaining patients with an established diagnosis of asthma potentially modifiable factors like bad adherence to treatment and poor inhalation technique were found. Implementing a nationwide asthma program including continued medical education for the correct diagnosis and follow up of these patients and asthma education for patients and caregivers is needed to reduce asthma hospitalization rates in Chilean children

No disponible

Exclusión social y calidad de vida relacionada con la salud en personas entre 25 y 60 años de la zona nororiental de Medellín - Colombia, 2009 / Social exclusion and quality of life related to health in people from 25 to 60 years old living in the northeast zone, Medellín, 2009

OBJETIVO: identificar la percepción de exclusión social y sus dimensiones demográfica, económica, de participación social y política y su asociación con la calidad de vida relacionada con la salud en las personas de 25 a 60 años de la zona nororiental de Medellín - Colombia, 2009. METODOLOGIA: se condujo un estudio transversal de asociación. El tamaño muestral se calculó con un nivel de confianza de 95%, un error de 4,5% y una proporción de 0,28 derivada de la investigación sobre exclusión social realizada en Medellín en el año 2008, para un total de 404 sujetos. La muestra fue obtenida mediante un muestreo probabilístico, por conglomerados, polietápico, proporcional por sexo sin reemplazo. Los datos se analizaron en el software SPSS v.15.0 y StataSE 10. RESULTADOS: el 22,8% de la población se percibió en situación de exclusión social. En la evaluación de la Calidad de vida relacionada con la salud (CVRS) se encontraron altos puntajes en todos los dominios del cuestionario SF-36, presentándose diferencias significativas en los puntajes del Desempeño Físico (p = 0,000), Desempeño Emocional (p = 0,000) y Salud Mental (p = 0,023), teniendo mayores puntajes en estos dominios las personas no excluidas. Conclusiones: los resultados sugieren que la percepción de exclusión social afecta la CVRS y las condiciones individuales de salud pueden incidir en la percepción de exclusión social. Esto puede deberse a que la salud (enfermedad) en sí es un generador de exclusión social o que la prestación de los servicios de salud en el sistema de salud colombiano, haga que las personas enfermas se sientan excluidas.

OBJECTIVE: to identify the perception of social exclusion and its demographic, economic, and sociopolitical participation dimensions as well as its association with the Health-Related Quality of Life (HRQOL) of people aged 25 to 60 living in the northeastern area of Medellin - Colombia, 2009. METHODOLOGY: a cross-sectional study of association was conducted. The sample size was calculated with a confidence level of 95%, an error of 4.5%, and a ratio of 0.28 derived from a study on social exclusion conducted in Medellín in 2008. The study was conducted with a total of 404 subjects. The sample was obtained through a probability, cluster, and multistage sampling that was proportional by sex and had no replacement. The data was analyzed using the SPSS v.15.0 and Stata 10 software. RESULTS: 22.8% of the population was perceived to be in a situation of social exclusion. The assessment of the Health-Related Quality of Life (hrqol) showed high scores in all the domains of the SF-36 questionnaire. Significant differences were observed in role physical (p = 0.000), role emotional (p = 0.000), and Mental Health (p = 0.023) scores. Non-excluded individuals showed higher scores in these domains. CONCLUSIONS: the results suggest that the perception of social exclusion affects HRQOL and individual health conditions may affect the perception of social exclusion. This may be due to the fact that health (disease) in itself generates social exclusion or that the healthcare services in the Colombian health system cause sick people to feel excluded.

[Infant pneumonia at periodic check-ups. Characteristics and associated factors]. / Neumonía en lactantes en control periódico de salud. Características y factores asociados.

BACKGROUND: Each year, pneumonia is the cause of death of forty thousand children under four years of age in America. AIM: To follow children from birth until two years of age and record episodes of pneumonia, their features and associated factors. PATIENTS AND METHODS: Four hundred thirty seven healthy newborns were followed in a public out patient clinic of Northern Santiago until two years of age. Pneumonia was diagnosed using clinical or radiological criteria. The mothers of each child were interviewed in each follow up visit. RESULTS: Two hundred ten episodes of pneumonia were detected during the study, 0.6 episodes per child and 1.8 episodes per affected child. Sixty six percent of episodes occurred during the first year of age. Total prevalence was 22.4 and 14.3% during the first and second year of age respectively. Semi annual incidence was 13.8 and 5.5% during the first and fourth semester respectively. Children that had pneumonia, were male in a higher proportion, had a lower birth weight, had higher number of brothers, mothers with less that 8 years of school courses and a lower socioeconomic level. During the first year of life, breast feeding during less than four months and a birth date during spring and summer were associated with a higher incidence of pneumonia. Seventy seven episodes, that occurred in 48 children, required hospitalization. The hospitalization rate for the whole cohort was 13.4% percent and 41.2% for affected children. Mean hospital stay was 5.8 days. Risk factors for hospitalization were male sex, less than four months of breast feeding, low birth weight, to have brothers, a lower mother education and lower socioeconomic level. Two children died. CONCLUSIONS: One out of three healthy newborns had pneumonia during the first year of life and a low socioeconomic level was an important risk factor.

Acute respiratory illnesses in the first 18 months of life.

To help assess the causes and frequency of acute respiratory illnesses (ARI) during the first 18 months of life in Chile, a cohort of 437 children born in good health between May 1991 and April 1992 was followed at an urban health clinic in northern Santiago. Information was obtained from medical checkups performed at the clinic, from emergency health care services, from private physicians, and from interviews with each child's mother when the child was enrolled in the study and when it was 6, 12, and 18 months old. Followup was completed for 379 (87%) of the children. ARI accounted for 67% of all 3762 episodes of illness recorded for these children in the 18-month study period, 1384 (55%) of the ARI episodes affecting the upper respiratory tract and the remaining 1144 (45%) affecting the lower. The overall rate of ARI observed was 33 episodes per 100 child-months of observation. The incidences of upper, lower, and total ARI episodes decreased significantly in the third six months of life. A statistically significant association was found between upper ARI (> or = 2 episodes) and maternal smoking (> or = 5 cigarettes per day), but no significant associations were found with any of the other risk factors studied. However, lower ARI (> or 2 episodes) was significantly associated with maternal schooling (< 8 years), a family history of atopic allergy, and substandard housing conditions; and lower ARI (> or = 4 episodes) was significantly associated with these factors and also with the existence of one or more siblings, birth in a cold season, limited breast-feeding (< 4 months), and low socioeconomic status. Significant associations were found between obstructive bronchitis episodes and most of the risk factors studied (gender, siblings, season of birth, duration of breast-feeding, maternal schooling, smoking, use of polluting fuels in the home, and a family history of atopic allergy); similarly, significant associations were found between the occurrence of pneumonia and many risk factors (including siblings, season of birth, duration of breast-feeding, maternal schooling, smoking, and socioeconomic level). Overall, 42 of the study children were hospitalized during the study period for lower tract ARI, and two children died of pneumonia at home during their first 6 months of life. The rate of hospitalization fell significantly with increasing age.

[Treatment of typhoid fever with chloramphenicol or ampicillin combined with oxyphenbutazone]. / Tratamiento de las fiebres tíficas con cloranfenicol o ampicilina asociados a oxifenbutazona.

Ninety-four patients with typhoid fever were treated, at random, with three therapeutic regimens: chloramphenicol alone, chloramphenicol plus oxyphenbutazone, and ampicillin plus oxyphenbutazone. The results are evaluated analyzing the body temperature graph and by serial blood had bone marrow cultures taken at intervals until they became negative. Bacteriologic diagnosis was confirmed by blood culture (39.3%) and/or bone marrow culture (77%). The mean duration of fever was 3.3 days for the group treated with chloramphenicol-oxyphenbutazone, 4.3 for those with chloramphenicol alone and 5 days for the group ampicillin-oxyphenbutazone; at the same time, blood cultures became negative at 4.4, 5.5 and 4.4 days respectively. Negativization of bone marrow cultures was not influenced by the addition of oxyphenbutazone. It is concluded that the influence of oxyphenbutazone in shortening the febrile period or in the negativization of blood cultures is not significant. It is considered that oxyphenbutazone is not an important therapeutic tool in this group of diseases.

Monoclonal antibody that distinguishes between a phosphorylated, beta 2-microglobulin-associated, and a free, nonphosphorylated, chain of MHC class I.

We have shown that a mAb, 7.2.14, recognizes a conserved sequence in exon 7 of a number of murine MHC class I molecules. 7.2.14 binding is abolished when the molecule is phosphorylated, presumably at a serine residue in exon 7, whereas treatment of material in cell lysates with alkaline phosphatase increases the intensity of the binding. A genomic construct containing Dd was transfected into human fibroblasts and a clonal cell line expressing high levels of surface MHC was selected. Cell lysates were prepared from surface-iodinated cells and analyzed by using a panel of antibodies. An apparent size heterogeneity was detected in the MHC class I gene product precipitated by different anti-class I MHC antibodies, suggesting that more than one conformational species of Dd was present. This was further investigated regarding the molecules precipitated by antibodies 34-2-12, M1/42, and 7.2.14. After preclearing of surface-iodinated cell lysates by using one antibody, challenge with the others still precipitated a Dd molecule, confirming that there were three independent conformations of the Dd gene product. A similar complexity could be observed in the lysates of surface-labeled spleen cells from C57BL/6 mice. A major polypeptide at approximately 48 to 50 kDa, representing the MHC H chain, was seen, and one or two as yet unidentified but strongly associated polypeptides at 41 kDa and 56 kDa were also visible. Sequential clearing of surface-iodinated material with one antibody followed by precipitation with the other confirmed that the 7.2.14-reactive material was distinct from that which reacted with M1/42. We propose that the 7.2.14-reactive 50-kDa band is the nonphosphorylated form of class I MHC, which exists in a conformation different from that of the conventional 48-kDa, phosphorylated, beta 2-microglobulin-associated entity.

CD28, IL-2-independent costimulatory pathways for CD8 T lymphocyte activation.

We investigate, here, the mechanism of the costimulatory signals for CD8 T cell activation and confirm that costimulation signals via CD28 do not appear to be required to initiate proliferation, but provide survival signals for CD8 T cells activated by TCR ligation. We show also that IL-6 and TNF-alpha can provide alternative costimulatory survival signals. IL-6 and TNF-alpha costimulate naive CD8 T cells cultured on plate-bound anti-CD3 in the absence of CD28 ligation. They act directly on sorted CD8-positive T cells. They also costimulate naive CD8 T cells from Rag-2-deficient mice, bearing transgenic TCRs for HY, which lack memory cells, a potential source of IL-2 secretion upon activation. IL-6 and TNF-alpha provide costimulation to naive CD8 T cells from CD28, IL-2, or IL-2Ralpha-deficient mice, and thus function in the absence of the B7-CD28 and IL-2 costimulatory pathways. The CD8 T cell generated via the anti-CD3 plus IL-6 and TNF-alpha pathway have effector function in that they express strong cytolytic activity on Ag-specific targets. They secrete only very small amounts of any of the cytokines tested upon restimulation with peptide-loaded APC. The ability of the naive CD8 T cells to respond to TCR ligation and costimulatory signals from IL-6 and TNF-alpha provides a novel pathway that can substitute for signals from CD4 helper cells or professional APC. This may be significant in the response to viral Ags, which can be potentially expressed on the surface of any class I MHC-expressing cell.

Restricted IgH V gene usage in the response to the ese epitope on "Hi" sheep red blood cells.

We had previously shown that the in vitro antibody response to a single epitope (ese; extra sheep E Ag) present on some sheep E but absent from others could be monitored by assay of the plaque-forming cell response on both Lo3 and Hi SRBC. We had shown also that the response was seen only in certain strains of mice and that the gene(s) controlling the response mapped to the IgH V region of the IgH chain complex. An additional feature of the response is that it is only seen in vitro and is absent and, we hypothesize, is suppressed in vivo. The strain distribution of the response to the ese determinant suggested that the response may only use one V gene (or a small set of closely related V genes) that would be present in the responder strains and absent from the nonresponder strains. To test this hypothesis, we made hybridomas with specificity for the ese determinant and for the shared determinants. cDNA from these hybridomas were sequenced. All four anti-ese hybridomas were almost identical in V region sequence, but varied considerably in D and J segment usage, thus confirming the hypothesis that the ese response would be limited at the V segment. The four anti-ese hybridomas used two Vh J558 genes that differed only by one, or possibly two, nucleotide(s). Importantly, these genes are quite different from most other published J558 sequences. The sequence is very similar to an unexpressed sequence from a C57Bl/6 perinatal mouse and slightly less similar to two other Vhb sequences. It was quite similar to two sequences from autoantibodies, one an anti-DNA hybridoma antibody, BXW-14, isolated from an NZB x NZWF1 mouse, and the other, an NZB hybridoma, G8, with specificity for a mouse E Ag. We speculate that the Ig encoded by the V ese gene react with an autoantigen, that the B cells persist in the animal, but that the secretion of Ig is somehow suppressed.

[Glucose overload test. Screening of gestational diabetes in population of pregnant women with risk factors for diabetes. Clinical experience]. / Prueba de sobrecarga a la glucosa. Screening de diabetes gestacional en población de embarazadas con factores de riesgo de diabetes. Experiencia clínica.

UNLABELLED: Clinical utility of the Overload Test with 50 g. of Oral Glucose (PSG) is evaluated, in 513 pregnancies with risk factors for diabetes. Of the 933 PSG which were made, 13.7% were positive (limit value: plasma glucose of much less than 150 mg/dl at 1 hour); the test were made after 20 weeks of gestation in 82.8% of the cases. Of the 128 positive PSG, 73 positive Oral Glucose Tolerance Test were obtained (O'Sullivan criteria). The prevalence of gestational diabetes found in this group was 15.2%. There was no difference on the most frequent risk factors (family history, obesity and macrosomia) between the general population in the study and the group of Gestational diabetes. CONCLUSION: PSG, because of its easy application, low cost and excellent tolerance is a test which should be included among the prenatal routine test as screening for gestational diabetes in our media.

Rapid simultaneous measurement of multiple cytokines using 100 microl sample volumes--association with neonatal sepsis.

Early diagnosis of neonatal infection has proved problematic due to the inadequacy of currently available laboratory tests. Neonatal sepsis is associated with an increase in plasma-derived cytokine levels, but an increase of a single cytokine cannot identify neonatal sepsis specifically and multiple cytokine levels are required. The time constraints and relatively large volume of plasma required to measure multiple cytokines from newborn infants by conventional enzyme-linked immunosorbent assay (ELISA) techniques is prohibitive. We therefore applied cytometric bead array (CBA) technology for simultaneous measurement of multiple cytokines from a group of 18 term neonates with infection confirmed by culture and a control group. 'Normal' ranges were established for each cytokine from 1-7-, 8-14- and 15-21-day-old newborns. There was no significant change in the levels of cytokines from infants in different control age groups, suggesting that basal cytokine levels are unchanged in the first 3 weeks of life. In the patient groups, however, there was a significant difference in several cytokines between the different age groups. Interleukin (IL)-6, IL-10 and IL-12 were increased significantly in the 1-7-day-old patient group compared to either the 8-14 and 15-21 age group, suggesting that infection in utero is associated with increased levels of these cytokines compared to infection acquired following birth. When individual patient cytokine levels were compared to normal control reference ranges, two patients failed to show significant elevation of any cytokine tested. All other patients showed elevated levels of between one and nine cytokines tested (mean of 4.6). There was no correlation between elevated cytokine levels and types of infective organism or patient age. In conclusion, neonatal sepsis is associated with the elevation of multiple plasma cytokines. The use of CBA kits is a rapid, easy, low sample volume and sensitive method to measure multiple plasma cytokines.