Contribution of sex steroids and prolactin to the modulation of T and B cells during autoimmunity

VERSIÓN FINAL DE AUTORES ACEPTADA PARA PUBLICACIÓN (PRE-PRINT). In this review we discuss how sex steroids and prolactin affect regulation and responsiveness of B and T cells. Sex hormones exert profound effects on several physiological processes of nonreproductive tissues. In the immune system, several studies with experimental models for SLE have shown a noticeable pro-inflammatory role for ERα, contributing to disease development reflected in proteinuria and renal pathology. On the other hand, ERβ appears to have an antiinflammatory and immunosuppressive effect. Estrogen/ERα signaling induced an increase of Th17 cells in lymph nodes as well as the expression of its correspondent chemokine receptor CCR6 during collagen induced arthritis acute phase. High levels of anti- DNA antibodies and increased mortality was observed when given high E and prolactin doses to NZB/NZW mice, as compared with mice receiving low E and prolactin doses, or high E and low prolactin doses. Intracellular progesterone receptors have been detected in TCD4+ cells but in contrast as observed with ERs, it suppresses T cell dependent responses. Progestagen administration on female NZB/NZW mice decreased anti DNA IgG, improved survival, decreased glomerulonephritis and proteinuria

La adaptación al castellano de la Children’s Communication Checklist permite detectar las dificultades en el uso pragmático del lenguaje y diferenciar subtipos clínicos

Introducción. La Children’s Communication Checklist (CCC) de Bishop es una prueba útil para la valoración de la pragmática verbal en los escolares. El objetivo del trabajo es comprobar la fiabilidad y la validez de esta escala en castellano. Sujetos y métodos. Se analiza la CCC contestada por los padres de 360 niños/as de 4-12 años, con inteligencia normal, 160 controles y 200 de cuatro grupos clínicos: trastorno por déficit de atención/hiperactividad (n = 68), trastorno de aprendizaje no verbal procedimental (n = 77), trastorno de la comunicación social (n = 25) y trastornos del espectro autista de nivel 1 (n = 30). Se realizan análisis: factorial para agrupar los ítems del cuestionario, de fiabilidad de las nuevas escalas y discriminante para comprobar si clasifica bien a los afectos de dificultades en el uso del lenguaje. Resultados. Se obtienen siete factores (Kaiser-Meyer-Olkin: 0,852) con moderada similitud a las de la CCC original: relaciones sociales, intereses y otros cinco que constituyen pragmática (habilidades conversacionales, coherencia-comprensión, compenetración, comunicación no verbal y pertinencia). La correlación es significativa entre todos ellos, en el grupo control, y entre los cinco que configuran pragmática, en los grupos clínicos (r de Pearson). La fiabilidad de las escalas es buena (alfa de Cronbach: 0,914). El cuestionario clasifica bien al 98,9% de los casos agrupados con y sin trastorno pragmático; y al 78% de los participantes en sus correspondientes grupos clínicos. Además, permite diferenciar las patologías según la presencia e intensidad de los síntomas. Conclusiones. Esta versión española de la CCC es altamente válida y fiable. Los estadísticos aportados pueden utilizarse como valores de referencia

Efecto positivo de la suplementación con isoflavonas derivadas de la soya sobre síntomas menopáusicos

Antecedente: En los últimos años han aumentado los tratamientos alternativos para el manejo de los síntomas de la menopausia, sobre todo en poblaciones de alto riesgo que tienen contraindicaciones para el uso de estrógenos. Objetivo: Evaluar el efecto de la suplementación con isoflavonas derivadas de la soya sobre síntomas climatéricos en mujeres postmenopáusicas. Método: Sesenta y seis mujeres postmenopáusicas entre 40 y 65 años de edad participaron en este estudio para recibir 50 mg/día de isoflavonas derivadas de soya durante 3 meses. Se evaluaron los síntomas de la menopausia al inicio del estudio y a los 45 y 90 días mediante la Escala de Puntuación de la Menopausia (MRS: Menopause Rating Scale). Resultados: La suplementación con isoflavonas derivadas de la soya tuvo un efecto positivo sobre síntomas de la menopausia. Así, los puntaje totales de la MRS disminuyeron significativamente de 23.0±8.7 (al basal) a 12.8±7 y 4.3±4.5 (45 y 90 días, respectivamente, ambos p<0.05). Se observó la misma tendencia para los puntajes de las sub-escalas del MRS (somática, psicológica y urogenital) y de cada uno de los síntomas componentes de las subescalas. Conclusión: En esta muestra de mujeres postmenopáusicas, la suplementación con isoflavonas derivadas de la soya ejerció un efecto positivo sobre los síntomas de la menopausia

Recurrent Catecholamine-Induced Cardiomyopathy in a Patient With a Pheochromocytoma

Pheochromocytomas presents with variable clinical manifestations. Cardiomyopathy caused by a pheochromocytoma is well known. We report the case of a 62-year-old woman with recurrent left ventricular dysfunction, who was subsequently found to have a pheochromocytoma. The patient had two different patterns of cardiomyopathy. Patients with a cardiomyopathy, of non-specific origin, should have a pheochromocytoma ruled out

A Case of Intra- and Extra-Mural Hematomas During Recanalization for Chronic Total Occlusion

An intramural hematoma is an accumulation of blood between the internal and external elastic membranes within the medial space, whereas an extramural hematoma is a dilution and/or dissemination of blood throughout the adventitia. Intra- and extra-hematomas are observed by intravascular ultrasound during percutaneous coronary intervention (PCI). The patient described herein presented with angina pectoris. Her coronary angiogram showed diffuse narrowing of the mid-left anterior descending artery and total occlusion of the distal right coronary artery (RCA). Intra- and extra-mural hematomas developed during PCI of the RCA; however, the lesions were covered successfully using long drug-eluting stents

Drug-eluting stents appear superior to bare metal stents for vein-graft PCI in vessels up to a stent diameter of 4 mm.

BACKGROUND: Research trials have shown improved short-term outcome with drug-eluting stents (DES) over bare metal stents (BMS) in saphenous vein graft (SVG) percutaneous coronary intervention (PCI), primarily by reducing target vessel revascularization (TVR) for in-stent restenosis. We compared the outcomes in patients undergoing SVG stent implantation treated with DES or BMS. In exploratory analyses we investigated the influence of stent generation and diameter. METHODS: Data were obtained from a prospective database of 657 patients who underwent PCI for SVG lesions between 2003 and 2011. A total of 344 patients had PCI with BMS and 313 with DES. Propensity scores were developed based on 15 observed baseline covariates in a logistic regression model with stent type as the dependent variable. The nearest-neighbour-matching algorithm with Greedy 5-1 Digit Matching was used to produce two patient cohorts of 313 patients each. We assessed major adverse cardiac events (MACE) out to a median of 3.3 years (interquartile range: 2.1-4.1). MACE was defined as all-cause mortality, myocardial infarction (MI), TVR and stroke. RESULTS: There was a significant difference in MACE between the two groups in favour of DES (17.9% DES vs. 31.2% BMS group; p = 0.0017) over the 5-year follow-up period. MACE was driven by increased TVR in the BMS group. There was no difference in death, MI or stroke. Adjusted Cox analysis confirmed a decreased risk of MACE for DES compared with BMS 0.75 (95% confidence interval (CI) 0.52-0.94), with no difference in the hazard of all-cause mortality (hazard ratio: 1.08; 95% CI: 0.77-1.68). However, when looking at stent diameters greater than 4 mm, no difference was seen in MACE rates between BMS and DES. CONCLUSIONS: Overall in our cohort of patients who had PCI for SVG disease, DES use resulted in lower MACE rates compared with BMS over a 5-year follow-up period; however, for stent diameters over 4 mm no difference in MACE rates was seen

A survey of the clinicopathological and molecular characteristics of patients with suspected Lynch syndrome in Latin America

Background: Genetic counselling and testing for Lynch syndrome (LS) have recently been introduced in several Latin America countries. We aimed to characterize the clinical, molecular and mismatch repair (MMR) variants spectrum of patients with suspected LS in Latin America. Methods: Eleven LS hereditary cancer registries and 34 published LS databases were used to identify unrelated families that fulfilled the Amsterdam II (AMSII) criteria and/or the Bethesda guidelines or suggestive of a dominant colorectal (CRC) inheritance syndrome. Results: We performed a thorough investigation of 15 countries and identified 6 countries where germline genetic testing for LS is available and 3 countries where tumor testing is used in the LS diagnosis. The spectrum of pathogenic MMR variants included MLH1 up to 54%, MSH2 up to 43%, MSH6 up to 10%, PMS2 up to 3% and EPCAM up to 0.8%. The Latin America MMR spectrum is broad with a total of 220 different variants which 80% were private and 20% were recurrent. Frequent regions included exons 11 of MLH1 (15%), exon 3 and 7 of MSH2 (17 and 15%, respectively), exon 4 of MSH6 (65%), exons 11 and 13 of PMS2 (31% and 23%, respectively). Sixteen international founder variants in MLH1, MSH2 and MSH6 were identified and 41 (19%) variants have not previously been reported, thus representing novel genetic variants in the MMR genes. The AMSII criteria was the most used clinical criteria to identify pathogenic MMR carriers although microsatellite instability, immunohistochemistry and family history are still the primary methods in several countries where no genetic testing for LS is available yet. Conclusion: The Latin America LS pathogenic MMR variants spectrum included new variants, frequently altered genetic regions and potential founder effects, emphasizing the relevance implementing Lynch syndrome genetic testing and counseling in all of Latin America countries.Radium Hospital Foundation (Oslo, Norway) in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript, Helse Sør-Øst (Norway) in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript, the French Association Recherche contre le Cancer (ARC) in the analysis, and interpretation of data, the Groupement des Entreprises Françaises dans la Lutte contre le Cancer (Gefluc) in the analysis, and interpretation of data, the Association Nationale de la Recherche et de la Technologie (ANRT, CIFRE PhD fellowship to H.T.) in the analysis, and interpretation of data and by the OpenHealth Institute in the analysis, and interpretation of data. Barretos Cancer Hospital received financial support by FINEP-CT-INFRA (02/2010)info:eu-repo/semantics/publishedVersio

Mucormycosis: an emerging disease?

ABSTRACTMucormycosis is the third invasive mycosis in order of importance after candidiasis and aspergillosis and is caused by fungi of the class Zygomycetes. The most important species in order of frequency is Rhizopus arrhizus (oryzae). Identification of the agents responsible for mucormycosis is based on macroscopic and microscopic morphological criteria, carbohydrate assimilation and the maximum temperature compatible with its growth. The incidence of mucormycosis is approximately 1.7 cases per 1000 000 inhabitants per year, and the main risk-factors for the development of mucormycosis are ketoacidosis (diabetic or other), iatrogenic immunosuppression, use of corticosteroids or deferoxamine, disruption of mucocutaneous barriers by catheters and other devices, and exposure to bandages contaminated by these fungi. Mucorales invade deep tissues via inhalation of airborne spores, percutaneous inoculation or ingestion. They colonise a high number of patients but do not cause invasion. Mucormycosis most commonly manifests in the sinuses (39%), lungs (24%), skin (19%), brain (9%), and gastrointestinal tract (7%), in the form of disseminated disease (6%), and in other sites (6%). Clinical diagnosis of mucormycosis is difficult, and is often made at a late stage of the disease or post-mortem. Confirmation of the clinical form requires the combination of symptoms compatible with histological invasion of tissues. The probable diagnosis of mucormycosis requires the combination of various clinical data and the isolation in culture of the fungus from clinical samples. Treatment of mucormycosis requires a rapid diagnosis, correction of predisposing factors, surgical resection, debridement and appropriate antifungal therapy. Liposomal amphotericin B is the therapy of choice for this condition. Itraconazole is considered to be inappropriate and there is evidence of its failure in patients suffering from mucormycosis. Voriconazole is not active in vitro against Mucorales, and failed when used in vivo. Posaconazole and ravuconazole have good activity in vitro. The overall rate of mortality of mucormycosis is approximately 40%