Evaluación de un cuestionario de conocimientos en insuficiencia cardíaca y su utilidad para guiar la intervención educativa / Evaluation of a heart failure knowledge questionnaire and its use in guiding the educational intervention

ntroducción y objetivo: La educación por enfermería es una pieza clave en todo programa de insuficiencia cardíaca (IC), pero existen modelos muy heterogéneos y faltan instrumentos de medida. Nuestro objetivo ha sido evaluar un cuestionario propio y su utilidad como guía de la educación.Métodos: Estudio de cohortes prospectivo de pacientes tras el diagnóstico de IC seguidos en una unidad especializada. El grupo expuesto recibió sesiones educativas guiadas por evaluación del conocimiento mediante el cuestionario, y se comparó con un grupo con educación estándar. Se evaluó la validez y la fiabilidad del cuestionario. La utilidad del modelo educativo se determinó por la variable combinada principal de muerte y/o ingreso hospitalario o atención en urgencias por IC.Resultados: Se incluyeron 152 pacientes, 88 con educación guiada y 64 estándar, con un seguimiento medio de 16±4 meses. En el grupo guiado, la puntuación del cuestionario de evaluación (pc) subió del 59 al 78,5% (p=0,018) y se asoció con un mayor autocuidado (28,5-0,6*pc; p=0,04) y una tendencia a mejor calidad de vida (51,1-1,1*pc; p=0,09) y adherencia (5,02+0,04*pc; p=0,06), con una fiabilidad aceptable (Alfa de Cronbach: 0,75). La variable combinada principal ocurrió en 12 pacientes (13,6%) con educación guiada frente a 19 (29,7%) con la estándar (hazard ratio: 0,46; intervalo de confianza del 95%: 0,24-0,88; p=0,019), aunque en el análisis multivariante, solo fueron predictores: el nivel educativo, la edad, NT-proBNP y la fibrilación auricular.Conclusión: El cuestionario de conocimientos en IC propuesto es una herramienta válida y fiable, y permite cuantificar el aprendizaje. Su utilidad para guiar la educación precisa de cierta habilidad del paciente que determina un grupo con mejor pronóstico. (AU)

Introduction and objective: Patient education by nurses is a cornerstone of any heart failure (HF) program, but the models are widely heterogeneous and few specific instruments exist. Our objective is to evaluate our own questionnaire and its utility as a guide for educational intervention.Methods: This work is a prospective cohort study of patients followed-up on in a specialized unit after diagnosis of HF. The intervention group received educational sessions guided according to their knowledge using the questionnaire and was compared to a group which received standard education. The validity and reliability of the questionnaire was evaluated. The utility of the educational model was determined by the primary composite endpoint of death and/or hospital admission or emergency care for HF.Results: A total of 152 patients were included, 88 which received guided education and 64 which received standard education, with a mean follow-up time of 16±4 months. In the guided education group, the evaluation questionnaire score (qs) rose from 59% to 78.5% (P=0.018), which was associated with greater self-care (28.5-0.6*qs, P=0.04), a tendency toward better quality of life (51.1-1.1*qs, P=0.09), and adherence (5.02+0.04*qs, P=0.06), with acceptable reliability (Cronbach's alpha 0.75). The primary composite endpoint was met in 12 patients (13.6%) in the intervention group compared to 19 (29.7%) in the control group (hazard ratio: 0.46; 95% confidence interval: 0.24-0.88; P=0.019). Only educational level, age, NT-proBNP, and atrial fibrillation were predictors in the multivariate analysis.Conclusion: The HF knowledge questionnaire proposed is a valid, reliable tool and allows for quantifying learning. Its utility in guiding education requires a certain degree of skill from the patient that determines a group with better prognosis. (AU)

Evaluation of a heart failure knowledge questionnaire and its use in guiding the educational intervention.

INTRODUCTION AND OBJECTIVE: Patient education by nurses is a cornerstone of any heart failure (HF) program, but the models are widely heterogeneous and few specific instruments exist. Our objective is to evaluate our own questionnaire and its utility as a guide for educational intervention. METHODS: This work is a prospective cohort study of patients followed-up on in a specialized unit after diagnosis of HF. The intervention group received educational sessions guided according to their knowledge using the questionnaire and was compared to a group which received standard education. The validity and reliability of the questionnaire was evaluated. The utility of the educational model was determined by the primary composite endpoint of death and/or hospital admission or emergency care for HF. RESULTS: A total of 152 patients were included, 88 which received guided education and 64 which received standard education, with a mean follow-up time of 16±4 months. In the guided education group, the evaluation questionnaire score (qs) rose from 59% to 78.5% (p=0.018), which was associated with greater self-care (28.5-0.6*qs, p=0.04), a tendency toward better quality of life (51.1-1.1*qs, p=0.09), and adherence (5.02+0.04*qs, p=0.06), with acceptable reliability (Cronbach's alpha 0.75). The primary composite endpoint was met in 12 patients (13.6%) in the intervention group compared to 19 (29.7%) in the control group (hazard ratio: 0.46; 95% confidence interval: 0.24-0.88; p=0.019). Only educational level, age, NT-proBNP, and atrial fibrillation were predictors in the multivariate analysis. CONCLUSION: The HF knowledge questionnaire proposed is a valid, reliable tool and allows for quantifying learning. Its utility in guiding education requires a certain degree of skill from the patient that determines a group with better prognosis.

Kinetics of HTT lowering in brain of YAC 128 mice following single and repetitive intranasal dosing of siRNA packaged in chitosan-based nanoparticle.

This report describes the kinetics of Huntington's Disease (HD) gene (HTT) lowering in brains of YAC 128 mice. Lowering (or "knock-down") of HTT mRNA expression was achieved by intranasal administration of specially designed siRNA loaded into chitosan nanoparticles. Kinetic patterns of HTT lowering observed in different brain regions allowed calculation of cumulative lowering effects that result from multiple consecutive administrations. Mathematical modeling generated dosing schedules for approaching a steady knock-down effect and for prediction of magnitude and duration of HTT lowering. Kinetic modeling of HTT lowering with our algorithm will be useful in determining intranasal dosing schedules to produce chronic, therapeutically significant lowering effect of gene expression.

The expression of the transcription factor TAF1 is modified by the HPV16 E2 protein.

High-risk human papillomaviruses (e.g., HPV16 and 18) are associated with cervical cancer occurrence and development. The early viral gene E2 encodes a protein involved in several key processes in HPV biology, such as replication, genome segregation, and viral gene transcription. E2's presence also affects the expression of a variety of cellular genes involved in a wide range of biological processes, including cell cycle regulation and apoptosis, which are mediated by E2's interaction with cellular proteins. In this report, a lentiviral system was used to express the HPV16 E2 gene in the HPV-negative C-33A cell line for several weeks. E2 expression was measured by RT-qPCR and its biological activity was evaluated using a reporter gene. In HPV16 E2-positive cells, we observed a statistically significant increase in mRNA and protein levels of TAF1 and p27, a basal transcription factor and one of its target genes, respectively. To our knowledge, this is the first study showing that the viral protein HPV16 E2 upregulates TAF1 expression. This suggests that E2's expression promotes a transcriptionally-favorable cellular environment that allows HPV to successfully complete its replication cycle. Keywords: HPV16; E2 protein; transcription; TAF1 regulation.

Correlation of transforming growth factor ß-1 vitreous levels with clinical severity of proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment. / Correlación de niveles del factor de crecimiento transformante ß-1 con severidad de vitreorretinopatía proliferativa en pacientes con desprendimiento de retina regmatógeno.

OBJECTIVE: To correlate the vitreous concentration of transforming growth factor ß-1 (TGF ß-1) with the degree of clinical severity of proliferative vitreoretinopathy (PVR). DESIGN: A prospective, observational, cross-sectional study carried out on cases and controls. PARTICIPANTS: The study included 40 patients with a diagnosis of PVR secondary to rhegmatogenous retinal detachment. METHODS: Vitreous was obtained in patients undergoing pars plana vitrectomy by rhegmatogenous retinal detachment, who were treated during the period from August 2015 to June 2016, in a national reference centre for ophthalmological care in Mexico City, Mexico. The levels of TGFß-1 were quantified by ELISA technique. An ANOVA test was performed for the comparison of the different groups, together with a post-hoc Dunns test. A statistically significant difference was considered when obtaining P <.05. RESULTS: The levels of TGFß-1 were quantified, and the following means were found for each group: In the group with PVR grade A, 1150.6 ± 452.08 pg / ml, PVR grade B: 1129.6 ± 365.54 pg / ml, and PVR grade C: 1146.4 ± 330.21 pg / ml. The statistical analysis did not find significant differences when comparing the different PVR groups. (P=.53). However, when performing the differential analysis for each level of severity, a statistically significant increase in the expression of TGFß-1 was observed in the group of patients with PVR-A at a greater number of days of evolution of the detachment. (P=.03). There were no statistically significant differences for PVR-B and PVR-C (P=.16 and P=.16, respectively). CONCLUSION: Although the levels of TGFß-1 are not directly related to the clinical severity grade, suggesting that there must be other factors involved in the advanced stages of PVR, TGFß-1 may have greater relevance during the initial stages of the clinical course by promoting the epithelial-mesenchymal transition due to its greater expression in PVR-A. Thus, it can be concluded that each isoform plays a very particular role in the complex process of PVR.

Study of the metabolomic relationship between lung cancer and chronic obstructive pulmonary disease based on direct infusion mass spectrometry.

The high prevalence of lung cancer (LC) has triggered the search of biomarkers for early diagnosis of this disease. For this purpose the study of metabolic changes related to the development of lung cancer could provide interesting information about its early diagnosis. In this sense, chronic obstructive pulmonary disease (COPD), a disease associated with tumor development, is a comorbidity that increases the risk of onset and progression of lung neoplasia and has also to be considered in the study of pathology related to lung cancer. This work develop a metabolomic approach based on direct infusion mass spectrometry using a hybrid triple quadrupole-time of flight mass spectrometer (DI-ESI-QqQ-TOF-MS) in order to identify altered metabolites from serum of LC and COPD patients and evaluate its relationship and implication in the progression of LC. This methodology has been applied to 30 serum samples from LC, 30 healthy patients used as controls (HC) and 30 serum samples from COPD to found altered metabolites from both LC and COPD diseases. In addition, some metabolic differences and similarities were found in Pulmonary Emphysema and Chronic Bronchitis patients. On the other hand, altered metabolites were studied in different stages of LC (II, III and IV) to evaluate the perturbation of them throughout the progression of disease. The sample treatment consisted of the extraction of polar and non-polar metabolites from serum that was later infused into the mass spectrometer using an electrospray ionization source in positive and negative mode. Partial least squares discriminant analysis (PLS-DA) allowed a classification between LC, HC and COPD groups in all acquisition modes. A total of 35 altered and common metabolites between LC and COPD, including amino acids, fatty acids, lysophospholipids, phospholipids and triacylglycerides were identified, being alanine, aspartate and glutamate metabolism the most altered. Finally, ROC curves were applied to the dataset and metabolites with AUC value higher than 0.70 were considered as relevant in the progression of LC.

Clinical markers of asthma and IgE assessed in parents before conception predict asthma and hayfever in the offspring.

BACKGROUND: Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans. OBJECTIVE: We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever. METHODS: The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972-2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions. RESULTS: Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11-22 years with information on parental disease activity both before and after birth. CONCLUSION & CLINICAL RELEVANCE: Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.

Analgesic effect of a single-dose of perineural dexamethasone on ultrasound-guided femoral nerve block after total knee replacement. / Eficacia analgésica de una dosis única de dexametasona perineural en el bloqueo ecoguiado del nervio femoral en cirugía de prótesis total de rodilla.

INTRODUCTION: Total knee replacement is usually a very painful procedure. A single-dose of femoral nerve block has been shown to provide similar analgesia to an epidural, with fewer side effects, but limited in time. OBJECTIVE: To compare the analgesia provided by dexamethasone used at perineural level in the femoral nerve block after total knee replacement with the one used at intravenous level, and with that of a control group. MATERIAL AND METHODS: A prospective, randomised, double-blind controlled trial was conducted on 81 patients randomly assigned to one of three groups: 1)IV dexamethasone (8mg); 2)perineural dexamethasone (8mg), and 3)placebo. All patients received 20ml of ropivacaine 0.5% for femoral nerve block. The primary outcome was the duration of the sensory-analgesic block of the femoral nerve block. The secondary outcomes included pain intensity measurements, patient satisfaction, and incidence of complications. RESULTS: Randomisation was effective. Analgesia duration was significantly higher (P<.0001) in the perineural dexamethasone group (mean 1152.2min, 95% confidence interval [95% CI]: 756.9-1547.6) in comparison with the control group (mean 186min, 95%CI: 81.2-292) and dexamethasone IV group (mean 159.4min, 95%CI: 109.8-209). Postoperative pain, complications and side effects were also lower in this group. CONCLUSIONS: Dexamethasone prolongs sensory block of single dose of femoral nerve block using ropivacaine. It also provides better analgesia and patient satisfaction, with fewer side effects.

Estudio epidemiológico de seguimiento de asma en adolescentes de la ciudad de huelva / Epidemiological study of the follow up of asthma in adolescents of Huelva city

Objetivo: Analizar y comparar la incidencia de asma en adolescentes y adultos de Huelva. Determinar los cambios (aparición, persistencia y remisión) de sibilancias, hiperreactividad bronquial (HB) y asma, así como esclarecer los posibles factores de riesgo de asma incidente. Metodología: Seguimiento de 9 años de la cohorte original tras el estudio transversal inicial. Se realizó una segunda evaluación de los 2 grupos analizados, 401 niños del Estudio de Enfermedades Respiratorias y 204 adultos del Estudio Europeo de Enfermedades Respiratorias. Ambos realizaron un cuestionario sobre síntomas respiratorios, una espirometría y una prueba de metacolina. Resultados: La incidencia anual acumulada de asma en los niños (15,69/1000 personas-año) fue tres veces superior a la de los adultos (4,76/1000 personas-año). En los niños hubo un 24,2% de apariciones y un 4,3% de remisiones de sibilancias en los últimos 12 meses. De esta forma, las apariciones superaban a las remisiones (p < 0.001). También se produjeron más apariciones que remisiones en HB (13,9% vs 5,4%;p = 0,02) y asma (9,3% vs 3%; p = 0,004). En los adultos se encontraron más apariciones que remisiones (15,7%vs6,9%;p= 0,011)de sibilancias e HB (10,1% vs3% ; p =0,017) no se hallaron cambios significativos en el seguimiento de asma. Los factores de riesgo más importantes relacionados con asma incidente fueron: tener sibilancias (RR: 8,12) y opresión torácica(RR: 9,17) al estar cerca de un animal. Conclusiones: La incidencia de asma en adolescentes es tres veces superior a la de los adulto (AU)

Objective: To analyse and to compare the incidence of asth main adolescents and adults of Huelva. To determine the changes (appearance, persistence and remission) of wheezing, bronchialhyper-responsiveness(BH) and asthma, as well as to clarify the potential risk factors for incidence of asthma. Methodology: Nine year follow-up of the original cohort after the initial cross-sectional study. A second evaluation was made of the 2 analysed groups, 401 children of the Respiratory Diseases Study and 204 adults of the European Respiratory Diseases Study. Both groups completed a questionnaire on respiratory symptoms, spirometry and methacholine challenge test. Results: The accumulated annual incidence of asthma in children(15.69/1000 persons / year) was three times higher than in adults (4.76/1000 persons / year). In children there were24.2% of occurrences and 4.3% of remissions of wheezing in the last 12 months. Thus, the occurrences exceeded remissions(p < 0.001). There were also more occurrences than remissions in BH (13.9% vs. 5.4%; p = 0.02) and asthma (9.3%vs. 3%; p = 0.004). In adults, there were more occurrences than remissions (15.7% vs. 6.9%; p= 0.011) of wheezing and BH (10.1% vs. 3%; p =0,017) with no significant changes found in the asthma follow-up. The most important risk factors associated with incident asthma were presence of wheezing (RR: 8.12) and thoracic oppression (RR: 9.17) when being near an animal. Conclusions: The incidence of asthma in adolescents is three times higher than in adults (AU)

Premenstrual asthma and leukotriene variations in the menstrual cycle.

BACKGROUND: Several authors have reported an increase in leukotriene C4 in the premenstrual phase in women with severe premenstrual asthma, indicating that antileukotrienes could be used in treatment. OBJECTIVE: To analyse the role of leukotrienes in premenstrual asthma. METHODS: A questionnaire on respiratory symptoms and peak flow during one complete menstrual cycle was given to women of fertile age to define them as asthmatics who suffered from premenstrual asthma or not. Premenstrual asthma (PMA) was defined as a clinical or functional deterioration (≥20%) in the premenstrual phase compared with the preovulatory phase. Blood samples to measure leukotriene C4 were taken during the preovulatory and premenstrual phases. RESULTS: Blood samples were taken in 62 asthmatic women, 34 of whom (54.3%) presented PMA criteria, all with a premenstrual deterioration of between 20 and 40%. There was no difference in leukotriene C4 levels between the preovulatory and premenstrual phases in the women who suffered from PMA (1.50ng/mL vs. 1.31ng/mL; p=0.32) and those who did not (1.40ng/mL vs. 1.29ng/mL; p=0.62). Neither were there any differences in leukotriene levels between women with or without PMA. The results were similar for each category of asthma severity. CONCLUSIONS: Our data show that leukotriene C4 does not appear to be involved in the pathogenesis of premenstrual asthma, or support the use of anti-leukotrienes in the specific treatment of premenstrual asthma, at least in women with a moderate premenstrual deterioration. No differences appeared in any of the categories of asthma severity.

Clinical vignettes in Parkinson's disease: a collection of unusual medication-induced hallucinations, delusions, and compulsive behaviours.

Hallucinations, delusions, and compulsive behaviors are frequent iatrogenic complications of the treatment of motor dysfunction in Parkinson's disease (PD). Although these have been studied, and the phenomenology described, there are few detailed descriptions of the various psychiatric problems our treated PD patients live with that allow physicians who do not have a great deal of experience with PD patients to appreciate the extent of their altered lives. This report is a compilation of vignettes describing these behavioral problems that the treating neurologist or psychiatrist attributed to the medications used for treating PD.

Variability in the prevalence of premenstrual asthma.

Our aim is to analyse the differences in the prevalence of premenstrual asthma (PMA) according to a set of criteria, the relationship between them and the influence of asthma severity. The answer "Yes" to "Does your asthma get worse before menstruation?" was considered subjective PMA. A daily respiratory symptoms register of fertile asthmatic females was taken during two consecutive menstrual cycles. For the semi-objective diagnosis, an exacerbation of > or =20% was required in the symptoms register. Objective diagnosis was a premenstrual worsening of > or =20% of peak flow. We selected 103 patients. Subjective premenstrual deterioration was perceived in 43.7%. The semi-objective deterioration of symptoms in the first cycle occurred in 44.7%, and in 22.3% in both cycles. A total of 54.3% of females with semi-objective criteria in the first cycle perceived a subjective deterioration of symptoms, versus 35.1% of those without semi-objective criteria (p = 0.05). PMA was present at all levels of asthma severity, with no clear link to the degree of severity. The detection of PMA prevalence, the subjective perception of this deterioration and its presence at all levels of asthma severity lead us to urge research into possible premenstrual deterioration in all fertile asthmatic females.

Granulocyte colony stimulating factor decreases brain amyloid burden and reverses cognitive impairment in Alzheimer's mice.

Granulocyte colony stimulating factor (G-CSF) is a multi-modal hematopoietic growth factor, which also has profound effects on the diseased CNS. G-CSF has been shown to enhance recovery from neurologic deficits in rodent models of ischemia. G-CSF appears to facilitate neuroplastic changes by both mobilization of bone marrow-derived cells and by its direct actions on CNS cells. The overall objective of the study was to determine if G-CSF administration in a mouse model of Alzheimer's disease (AD) (Tg APP/PS1) would impact hippocampal-dependent learning by modifying the underlying disease pathology. A course of s.c. administration of G-CSF for a period of less than three weeks significantly improved cognitive performance, decreased beta-amyloid deposition in hippocampus and entorhinal cortex and augmented total microglial activity. Additionally, G-CSF reduced systemic inflammation indicated by suppression of the production or activity of major pro-inflammatory cytokines in plasma. Improved cognition in AD mice was associated with increased synaptophysin immunostaining in hippocampal CA1 and CA3 regions and augmented neurogenesis, evidenced by increased numbers of calretinin-expressing cells in dentate gyrus. Given that G-CSF is already utilized clinically to safely stimulate hematopoietic stem cell production, these basic research findings will be readily translated into clinical trials to reverse or forestall the progression of dementia in AD. The primary objective of the present study was to determine whether a short course of G-CSF administration would have an impact on the pathological hallmark of AD, the age-dependent accumulation of A beta deposits, in a transgenic mouse model of AD (APP+ PS1; Tg). A second objective was to determine whether such treatment would impact cognitive performance in a hippocampal-dependent memory paradigm. To explain the G-CSF triggered amyloid reduction and associated reversal of cognitive impairment, several mechanisms of action were explored. (1) G-CSF was hypothesized to increase activation of resident microglia and to increase mobilization of marrow-derived microglia. The effect of G-CSF on microglial activation was examined by quantitative measurements of total microglial burden. To determine if G-CSF increased trafficking of marrow-derived microglia into brain, bone marrow-derived green fluorescent protein-expressing (GFP+) microglia were visualized in the brains of chimeric AD mice. (2) To assess the role of immune-modulation in mediating G-CSF effects, a panel of cytokines was measured in both plasma and brain. (3) To test the hypothesis that reduction of A beta deposits can affect synaptic area, quantitative measurement of synaptophysin immunoreactivity in hippocampal CA1 and CA3 sectors was undertaken. (4) To learn whether enhanced hippocampal neurogenesis was induced by G-CSF treatment, numbers of calretinin-expressing cells were determined in dentate gyrus.

Asma premenstrual, relación con la severidad del asma y su apreciación subjetiva / Premenstrual Asthma, relation between the severity of the asthma and its subjective appreciation

Introducción: diversos estudios, aunque con resultados dispares, han relacionado el asma premenstrual (AP) con la severidad delasma. Por otra parte, no existe uniformidad respecto al hecho de que las pacientes con AP manifiesten una percepción subjetiva de empeoramiento de su asma en el periodo premenstrual. Objetivo: estudiar en mujeres asmáticas, con o sin criterios de AP, la relación con la clasificación del asma (GINA 2005) y el hecho de manifestar un empeoramiento de su asma en el periodo premenstrual. Material y método: se ha realizado un estudio observacional trasversal sobre una población de mujeres asmáticas en edad fértil en las que se realizó un cuestionario en el que se recogía, entre otros aspectos, la clasificación del asma (GINA 2005) y el hecho de manifestar un empeoramiento de los síntomas asmáticos en el periodo premenstrual. Por otra parte, se recogía diariamente durante un ciclo menstrual completo un cuestionario de síntomas respiratorios–SR– (tos, disnea, sibilancias y opresión torácica) y los valores depeak flow (PF) matutino y vespertino durante dicho ciclo. Se considera AP al empeoramiento > 20% en el PF y/o en los síntomas asmáticos (>20%) en el periodo premenstrual. Resultados: hasta el momento, han completado la recogida de los cuestionarios y los valores de PF, en los distintos hospitales participantes,82 pacientes. (6 graves, 29 moderados, 26 persistentes leves y 21 intermitentes leves). De ellas, 35 (42,7%; IC 95%: 31,96-53,41) presentaban criterios clínicos de asma premenstrual. Presentaban criterios funcionales 3 de las mujeres (3,7%), cumpliendo todas ellas también criterios clínicos. El asma premenstrual se distribuyó con frecuencia similar en los distintos grupos de gravedad(p=0,98). Las mujeres con AP reconocían con mayor frecuencia(61,8% frente a 40,4%) el empeoramiento premenstrual de sus síntomas (p=0,06).(..) (AU)

Introduction: A number of studies, although with incongruent results, have related premenstrual asthma (PA) to the severity of the asthma. On the other hand, there is no uniformity regarding the fact that patients with PA express a subjective perception of a worsening of their asthma during the premenstrual period. Objective: To study asthmatic women with/without PA criteria, the relationship between the classification of the asthma (GINA2005) and whether there is a worsening of their asthma during the premenstrual period. Materials and method: A transverse observational study was carried out on a population of fertile, asthmatic women, who completed a questionnaire in which included, amongst other aspects, the asthma classification (GINA 2005) and whether there was a manifest worsening of the asthmatic symptoms during the premenstrual period. On the other hand, a questionnaire of respiratory symptoms (RS), including cough, dyspnea, sibilance and thoracic oppression, was completed daily, during a complete menstrual cycle, plus the Peak Flow values in the morning and evening during this cycle. PA is consider edif there is a worsening >20% during the PF and/or in the asthmatic symptoms (>20%) during the premenstrual period. Results: Up to now, the completed questionnaires have been collected and the values of the Peak Flow (PF), at the different participating hospitals, 82 patients (6 serious, 29 moderate, 26 persistent light and21 intermittent light). Of these, 35 (42.7%; IC95%: 31.96-53.41) presented clinical criteria of Premenstrual Asthma. Three of the women presented functional criteria (3.7%), all them also fulfilling clinical criteria. Premenstrual asthma was distributed with a similar frequently in the different groups of seriousness (p=0.98). The women with PA recognized with more frequency (61.8% as against 40.4%) the premenstrual worsening of their symptoms (p=0.06). (..) (AU)

[Inter-observer variability in the diagnosis and classification of diabetic retinopathy through biomicroscopy]. / Variabilidad interobservador en el diagnóstico y clasificación de la retinopatía diabética mediante biomicroscopía.

OBJECTIVE: Analysis of the inter-observer variability of biomicroscopy used for the diagnosis of Diabetic Retinopathy. METHODS: This was a descriptive study. Parallel observer-blind evaluations of the degree of retinopathy in type 2 diabetic patients, as defined on biomicroscopic photographs, were performed by two ophthalmologists. The sample size required for the Kappa index among ophthalmologists with a disagreement ratio of 15%, precision ratio of 5% and confidence level of 95% is n=196 (<> being the number of eyes). The only variable measured was the degree of Diabetic Retinopathy, according to the modified Early Treatment Diabetic Research Study (ETDRS) classification. RESULTS: The average age of the 217 patients photographed was of 65.42 years (SE= 9.91). In 191 instances there was total agreement between the 2 ophthalmologists. In 24 instances the discrepancy was only of one degree of the classification of the ETDRS, and in 2 the discrepancy was of two degrees. In no case was it greater than this. (Quadratic weighed Kappa = 0.876, IC95%: 0.655-0.952 and linear weighed Kappa = 0.804, IC95%: 0.729-0.878). CONCLUSIONS: The Weighed Kappa index demonstrated a <> agreement of the degree of diabetic retinopathy. The discrepancies were slight, were of no clinical importance, and would not have affected treatment decisions. The results indicate that this examination, performed by a single ophthalmologist, can be utilised as a reference standard in Diabetic Retinopathy diagnosis.

Cambios en la prevalencia de síntomas de asma e hiperreactividad bronquial en el seguimiento de dos cohortes poblacionales de la ciudad de Huelva / Changes in the prevalence of asthma symptoms and bronchial hyper-reactivity in the follow-up of two population groups of the Huelva city

Objetivo: Analizar los cambios en la prevalencia de síntomas asmáticos e hiperreactividad bronquial (HB) que ocurren con la edad en dos cohortes de adolescentes y adultos jóvenes de la ciudad de Huelva. Material y métodos: Se ha realizado una segunda evaluación en el seguimiento de las dos poblaciones estudiadas entre 1991 y1993: jóvenes adolescentes de 11 a 16 años (n= 714), incluidos en el Estudio de Enfermedades Respiratorias de Huelva (EERH-I), y adultos jóvenes de 20-44 años (n=271), incluida en el Estudio Europeo de Enfermedades Respiratorias (ECRHS-I) de la ciudad de Huelva, a las que se realizaron cuestionario de síntomas respiratorios(SR) y prueba de hiperreactividad bronquial inespecífica con metacolina (MT). En la segunda evaluación, realizada con un seguimiento promedio de 9 años, se consiguió estudiar a 401 de los “niños - adolescentes” y 204 de los “adultos jóvenes”. Al igual que en la fase previa, se ha realizado en ambas población es el mismo cuestionario sobre síntomas respiratorios, una espirometría y una prueba de provocación bronquial inespecífica con metacolina. Se comparan las prevalencias de sibilancias (Sib), HB y asma encontradas en la misma población (niños o adultos), en ambos cortes trasversales (1991 y 2.001). Se comparan los resultados obtenidos entre ambas poblaciones. Resultados: Entre los años 1991 a 2001, tanto en jóvenes como en adultos, se incrementan los síntomas respiratorios, especialmente las sibilancias y la disnea, en reposo y al ejercicio. La hiperreactividad bronquial se incrementa claramente en los jóvenes(p<0.001) y sólo ligeramente en los adultos (NS). Como consecuencia de lo anterior, el diagnóstico epidemiológico de asma (sibilancias+ HB) se incrementó de forma significativa sólo en los jóvenes. Otro dato destacable en los niños era que recibían tratamiento para el asma sólo la mitad de los que estaban diagnosticados de asma por un médico y que éstos eran menos que los que referían haber tenido sibilancias en los últimos 12 meses. La discrepancia entre sibilancias y diagnóstico de asma era más evidente en adultos. Conclusiones: En la década de los 90 y en la ciudad de Huelva, una ciudad con elevada prevalencia de sibilancias (Sib) y nivel medio-bajo de hiperreactividad bronquial (HB) y asma, los SR y la HB se van incrementando durante la adolescencia y se estabilizan en la edad adulta. Esto podría explicarse tanto por la historia natural de la enfermedad como por la diferente influencia de las condiciones ambientales en las diferentes edades

Objective: To analyze the changes in the prevalence of asthmatic symptoms and bronchial hyper-reactive (BHR) conditions, which occur with age, in two groups of adolescents and young adults from the city of Huelva. Material and Methods: A second follow-up evaluation was performed on the two populations studied between 1991 and 1993:adolescents between 11 and 16 years of age (n = 714), included in the Study of Breathing Illnesses of Huelva (EERH-I), and young adults 20-44 years old (n=271), included in the European Study of Breathing Illnesses (ECRHS-I) of the city of Huelva. A questionnaire about breathing symptoms (BS) and a non-specific test of bronchial hyper-reactivity with methacholine (MT) were administered. In the second evaluation, carried out with an average follow up of 9 years, it was possible to study 401 of those “child-adolescents” and 204 of those “young adults.” The same as in the previous phase, both populations were administered the same questionnaire about breathing symptoms, aspirometry and a non-specific bronchial provocation test with methacholine was performed. The prevalence of wheezing, BHR and asthma found in the same population (children or adults) was compared in both cross samples (1991 and 2001). The results obtained were compared between both populations. Results: Between the years 1991 and 2001, both in adolescents and adults, the breathing symptoms increased, especially wheezing and dyspnea, at rest and at exercise. Bronchial hyper-reactivity had a clear increase in the adolescents (p < 0.001) and only a slight increase in the adults (NS). As a consequence of the above, the epidemiologic diagnosis of asthma (wheezing + BHR) increased significantly in adolescents. Another outstanding fact in the children was that only half of those medically diagnosed with asthma received treatment for their asthma, and amongst these, there were fewer that said they had experienced wheezing in the last 12 months. The discrepancy between wheezing and the diagnosis of asthma was more evident in adults. Conclusions: In the 90s and in the city of Huelva, a city with a high prevalence of wheezing and medium-low level of bronchial hyper-reactivity (BHR) and asthma, BS and the HR have increased during adolescence and stabilized in adulthood. This could be explained both by the natural evolution of the disease and by the different influences of the environmental conditions at the different ages

Can low level exposure to ochratoxin-A cause parkinsonism?

Mycotoxins are fungal metabolites with pharmacological activities that have been utilized in the production of antibiotics, growth promoters, and other classes of drugs. Some mycotoxins have been developed as biological and chemical warfare agents. Bombs and ballistic missiles loaded with aflatoxin were stockpiled and may have been deployed by Iraq during the first Gulf War. In light of the excess incidence of amyotrophic lateral sclerosis (ALS) in veterans from Operation Desert Storm, the potential for delayed neurotoxic effects of low doses of mycotoxins should not be overlooked. Ochratoxin-A (OTA) is a common mycotoxin with complex mechanisms of action, similar to that of the aflatoxins. Acute administration of OTA at non-lethal doses (10% of the LD(50)) have been shown to increase oxidative DNA damage in brain up to 72 h, with peak effects noted at 24 h in midbrain (MB), caudate/putamen (CP) and hippocampus (HP). Levels of dopamine (DA) and its metabolites in the striatum (e.g., CP) were shown to be decreased in a dose-dependent manner. The present study focused on the effects of chronic low dose OTA exposure on regional brain oxidative stress and striatal DA metabolism. Continuous administration of low doses of OTA with implanted subcutaneous Alzet minipumps caused a small but significant decrease in striatal DA levels and an upregulation of anti-oxidative systems and DNA repair. It is possible that low dose exposure to OTA will result in an earlier onset of parkinsonism when normal age-dependent decline in striatal DA levels are superimposed on the mycotoxin-induced lesion.

Neuroanatomical mapping of DNA repair and antioxidative responses in mouse brain: Effects of a single dose of MPTP.

The primary objective of this study was to map the normal distribution of the base excision enzyme oxyguanosine glycosylase (OGG1) across mouse-brain regions as a prelude to assessing the effects of various neurotoxicants, ranging from highly selective molecules like MPTP to more global toxic agents. This research is based on the hypothesis that regional brain vulnerability to a toxicant is determined, in part, by variation in the intrinsic capacity of cellular populations to successfully repair oxidative DNA damage. After mapping the normal distributions of OGG1 and superoxide dismutase (SOD) across 44 loci dissected from mouse brain, MPTP, a mitochondrial toxicant with selective dopamine (DA) neuron cytotoxicity was used to elicit focal oxidative stress and DNA repair responses. A single dose of MPTP (20mg/kg, i.p.) elicited time- and region-dependent changes in both SOD and OGG1, with early increases in DNA repair and anti-oxidant activities throughout all regions of brain. In some sampled loci, notably the substantia nigra (SN) and hippocampus, the heightened DNA repair and antioxidant responses were not maintained beyond 48h. Other loci from cerebellum, cerebral cortex and pons maintained high levels of activity up to 72h. Levels of dopamine (DA) were decreased significantly at all time points and remained below control levels in nigro-striatal and mesolimbic systems (ventral tegmental area and nucleus accumbens). Assessment of apoptosis by TUNEL staining revealed a significant increase in number of apoptotic nuclei in the substantia nigra at 72h and not in other loci. The marked degree of apoptosis that became evident in SN at 72h was associated with large decreases in SOD and DNA repair activity at that locus. In conclusion, MPTP elicited global effects on DNA repair and antioxidant activity in all regions of brain, but the most vulnerable loci were unable to maintain elevated DNA repair and antioxidant responses.

Acute neurotoxic effects of the fungal metabolite ochratoxin-A.

Ochratoxin-A (OTA) is a fungal metabolite with potential toxic effects on the central nervous system that have not yet been fully characterized. OTA has complex mechanisms of action that include evocation of oxidative stress, bioenergetic compromise, inhibition of protein synthesis, production of DNA single-strand breaks and formation of OTA-DNA adducts. The time course of acute effects of OTA were investigated in the context of DNA damage, DNA repair and global oxidative stress across six brain regions. Oxidative DNA damage, as measured with the "comet assay", was significantly increased in the six brain regions at all time points up to 72 h, with peak effects noted at 24 h in midbrain (MB), CP (caudate/putamen) and HP (hippocampus). Oxidative DNA repair activity (oxyguanosine glycosylase or OGG1) was inhibited in all regions at 6 h, but recovered to control levels in cerebellum (CB) by 72 h, and showed a trend to recovery in other regions of brain. Other indices of oxidative stress were also elevated. Lipid peroxidation and superoxide dismutase (SOD) increased over time throughout the brain. In light of the known vulnerability of the nigro-striatal dopaminergic neurons to oxidative stress, levels of striatal dopamine (DA) and its metabolites were also measured. Administration of OTA (0-6 mg/kg i.p.) to mice resulted in a dose-dependent decrease in striatal DA content and turnover with an ED50 of 3.2 mg/kg. A single dose of 3.5 mg/kg decreased the intensity of tyrosine hydroxylase immunoreactivity (TH(+)) in fibers of striatum, TH(+) cells in substantia nigra (SN) and TH(+) cells of the locus ceruleus. TUNEL staining did not reveal apoptotic profiles in MB, CP or in other brain regions and did not alter DARPP32 immunoreactivity in striatum. In conclusion, OTA caused acute depletion of striatal DA on a background of globally increased oxidative stress and transient inhibition of oxidative DNA repair.