Relationship between respiratory and food allergy and evaluation of preventive measures

Food allergy and respiratory allergy are two frequently associated diseases and with an increasing prevalence. Several reports show the presence of respiratory symptoms in patients with food allergy, while certain foods may be related to the development or exacerbation of allergic rhinitis and asthma. The present update focuses on this relationship, revealing a pathogenic and clinical association between food and respiratory allergy. This association is even more intense when the food hypersensitivity is persistent or starts in the early years of life. Food allergy usually precedes respiratory allergy and may be a risk factor for allergic rhinitis and asthma, becoming a relevant clinical marker for severe atopic asthma. Furthermore, the presence of co-existing asthma may enhance life-threatening symptoms occurring during a food allergic reaction. Recommendations for dietary restrictions during pregnancy and breastfeeding to prevent the development of respiratory allergy are controversial and not supported by consistent scientific data. Current recommendations from medical societies propose exclusive breastfeeding during the first four months of life, with the introduction of solid food in the fourth to the seventh month period of life. A delayed introduction of solid food after this period may increase the risk of developing subsequent allergic conditions. Further studies are encouraged to avoid unjustified recommendations involving useless dietary restrictions

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Relationship between respiratory and food allergy and evaluation of preventive measures.

Food allergy and respiratory allergy are two frequently associated diseases and with an increasing prevalence. Several reports show the presence of respiratory symptoms in patients with food allergy, while certain foods may be related to the development or exacerbation of allergic rhinitis and asthma. The present update focuses on this relationship, revealing a pathogenic and clinical association between food and respiratory allergy. This association is even more intense when the food hypersensitivity is persistent or starts in the early years of life. Food allergy usually precedes respiratory allergy and may be a risk factor for allergic rhinitis and asthma, becoming a relevant clinical marker for severe atopic asthma. Furthermore, the presence of co-existing asthma may enhance life-threatening symptoms occurring during a food allergic reaction. Recommendations for dietary restrictions during pregnancy and breastfeeding to prevent the development of respiratory allergy are controversial and not supported by consistent scientific data. Current recommendations from medical societies propose exclusive breastfeeding during the first four months of life, with the introduction of solid food in the fourth to the seventh month period of life. A delayed introduction of solid food after this period may increase the risk of developing subsequent allergic conditions. Further studies are encouraged to avoid unjustified recommendations involving useless dietary restrictions.

Obinutuzumab in follicular lymphoma.

The CD20 marker continues to be exploited as a therapeutic target for non-Hodgkin's lymphoma. Obinutuzumab is part of a new generation of anti-CD20 monoclonal antibodies, which are synthesized using molecular engineering technology, resulting in novel target epitopes and unprecedented optimization of antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. Rituximab is the current gold standard for anti-CD20 therapy, yet despite outstanding results published over the past decade, many patients continue to relapse after anti-CD20 regimens. Obinutuzumab is slowly positioning itself in the treatment of CD20+ B-cell neoplasms. On the basis of favorable results from the phase III GADOLIN trial, obinutuzumab was recently approved by the U.S. Food and Drug Administration in combination with bendamustine followed by obinutuzumab maintenance, for the treatment of follicular lymphoma (FL) patients who relapsed or are refractory to a rituximab-containing regimen. Additional phase III trials are underway to test obinutuzumab as a first-line anti-CD20 agent in FL with good preliminary results (GALLIUM trial); thus, it is likely that obinutuzumab will soon achieve a first-line indication. It is plausible that obinutuzumab will replace rituximab as the gold standard for chemoimmunotherapy in FL, although some safety concerns still need to be resolved. This review will address the preclinical pharmacology and the main aspects of the clinical development of obinutuzumab for the treatment of FL.

Consensus document on allergic conjunctivitis (DECA).

Allergic conjunctivitis (AC) is an inflammatory disease of the conjunctiva caused mainly by an IgE-mediated mechanism. It is the most common type of ocular allergy. Despite being the most benign form of conjunctivitis, AC has a considerable effect on patient quality of life, reduces work productivity, and increases health care costs. No consensus has been reached on its classification, diagnosis, or treatment. Consequently, the literature provides little information on its natural history, epidemiological data are scarce, and it is often difficult to ascertain its true morbidity. The main objective of the Consensus Document on Allergic Conjunctivitis (Documento dE Consenso sobre Conjuntivitis Alérgica [DECA]), which was drafted by an expert panel from the Spanish Society of Allergology and Spanish Society of Ophthalmology, was to reach agreement on basic criteria that could prove useful for both specialists and primary care physicians and facilitate the diagnosis, classification, and treatment of AC. This document is the first of its kind to describe and analyze aspects of AC that could make it possible to control symptoms.

Nasal Hyperreactivity: Nonspecific Nasal Provocation Tests. Review by the Rhinoconjunctivitis Committee of the Spanish Society of Allergy and Clinical Immunology.

Nasal hyperreactivity is the abnormal reaction of nasal tissue to a stimulus that is innocuous to most people. This response is caused by dysregulation of the autonomic nervous system at various levels of the nasal autonomic reflex arc. Various stimuli (methacholine, histamine, adenosine 5'-monophosphate, cold air, mannitol, rapsaicin, phentolamine, and distilled water) have been used in an attempt to find the test that most reliably differentiates between healthy individuals and patients and also between different types of rhinitis. Despite the small number of publications available, in the present review, we provide an update on current nonspecific nasal provocation techniques. The studies published to date are not comparable: the stimuli applied act through different mechanisms and are used to assess different pathways, and the methodologies differ in terms of selection of participants, concentrations used, and assessment of response (criteria for positivity). Given the limited use of nonspecific nasal provocation tests in routine clinical practice, we believe that more studies are warranted to address the research issues we present at the end of the present review, for example, the need to standardize the methodology for each test or even the clinical benefits of knowing whether or not a patient has nasal hyperreactivity.

Consensus document on allergic conjunctivitis (DECA)

Allergic conjunctivitis (AC) is an inflammatory disease of the conjunctiva caused mainly by an IgE-mediated mechanism. It is the most common type of ocular allergy. Despite being the most benign form of conjunctivitis, AC has a considerable effect on patient quality of life, reduces work productivity, and increases health care costs. No consensus has been reached on its classification, diagnosis, or treatment. Consequently, the literature provides little information on its natural history, epidemiological data are scarce, and it is often difficult to ascertain its true morbidity. The main objective of the Consensus Document on Allergic Conjunctivitis (Documento dE Consenso sobre Conjuntivitis Alérgica [DECA]), which was drafted by an expert panel from the Spanish Society of Allergology and Spanish Society of Ophthalmology, was to reach agreement on basic criteria that could prove useful for both specialists and primary care physicians and facilitate the diagnosis, classification, and treatment of AC. This document is the first of its kind to describe and analyze aspects of AC that could make it possible to control symptoms (AU)

La conjuntivitis alérgica (CA), es una enfermedad inflamatoria que se produce en la conjuntiva ocular mediada predominantemente, por un mecanismo IgE. En la alergia ocular, la CA se considera la entidad más frecuente y, a pesar de ser la forma más benigna, supone para los pacientes una importante afectación en su calidad de vida, una disminución de su productividad laboral y un elevado gasto sanitario. En la actualidad, no existen criterios consensuados acerca de su clasificación, diagnóstico y tratamiento de tal manera que por los trabajos publicados es difícil conocer su historia natural, existen escasos datos sobre su epidemiologia y, a veces es complejo identificar su morbilidad real. El objetivo principal del Documento de Consenso sobre Conjuntivitis Alérgica (DECA) realizado por un grupo de expertos de las Sociedades Españolas de Alergología y Oftalmología, ha sido establecer de forma consensuada unos criterios básicos que puedan ser útiles tanto para los especialistas, como para los médicos de atención primaria y que faciliten el diagnóstico, la clasificación y el tratamiento de los pacientes con CA. Por primera vez se describen y analizan distintos aspectos que pueden servir de herramientas para establecer el control de los síntomas de la CA (AU)

Nasal hyperreactivity: nonspecific nasal provocation tests. Review by the rhinoconjunctivitis committee of the Spanish Society of Allergy and Clinical Immunology

Nasal hyperreactivity is the abnormal reaction of nasal tissue to a stimulus that is innocuous to most people. This response is caused by dysregulation of the autonomic nervous system at various levels of the nasal autonomic reflex arc. Various stimuli (methacholine, histamine, adenosine 5´-monophosphate, cold air, mannitol, capsaicin, phentolamine, and distilled water) have been used in an attempt to find the test that most reliably differentiates between healthy individuals and patients and also between different types of rhinitis. Despite the small number of publications available, in the present review, we provide an update on current nonspecific nasal provocation techniques. The studies published to date are not comparable: the stimuli applied act through different mechanisms and are used to assess different pathways, and the methodologies differ in terms of selection of participants, concentrations used, and assessment of response (criteria for positivity). Given the limited use of nonspecific nasal provocation tests in routine clinical practice, we believe that more studies are warranted to address the research issues we present at the end of the present review, for example, the need to standardize the methodology for each test or even the clinical benefits of knowing whether or not a patient has nasal hyperreactivity (AU)

La hiperreactividad nasal es la reacción anormal del tejido nasal frente a un estímulo inocuo en la mayoría de las personas. La respuesta nasal es un mecanismo de defensa fisiológico que puede verse híper-regulado cuando existe inflamación, como en la rinitis alérgica, pero también en ausencia de ésta. Mecanismos inmunes inflamatorios y neurogénicos se interrelacionan generando cambios inflamatorios y diferentes tipos clínicos. Metacolina, histamina, manitol, AMP, capsaicina, fentolamina así como aire frío o agua destilada, se han usado para medir la hiperreactividad nasal. Los estudios publicados hasta la fecha no son comparables; difieren en la selección de pacientes, las concentraciones usadas para la provocación y la valoración de la respuesta en cuanto a métodos y criterios de positividad. La falta de estandarización de estas pruebas, y la dificultad que han mostrado en discriminar entre sujetos con rinitis de sujetos sanos, y entre los diferentes tipos de rinitis, hacen escasa su utilidad en la práctica clínica diaria y actualmente su uso está limitado al campo de la investigación. En esta revisión hacemos una puesta al día de las técnicas de provocación nasal no específica de que disponemos en la actualidad (AU)

Bendamustine as salvage treatment for patients with relapsed or refractory mantle cell lymphoma patients: a retrospective study of the Spanish experience.

Patients with mantle cell lymphoma (MCL) have an adverse outcome after relapse. Bendamustine has demonstrated a good efficacy and toxicity profile in previously reported trials. In this study, we present a retrospective analysis of the Spanish experience in relapsed/refractory MCL treated with bendamustine in combination or alone with the objective of knowing the efficacy and toxicity profile of this treatment in our current clinical practice. Fifty eight patients were registered: 67 % male with median age of 71 years, and 2 is the median number of previous lines. The most frequent bendamustine regimen was bendamustine plus rituximab (83 %). The median number of cycles was 5 (range 1-8). The overall response rate was 84 % with 53 % of complete response/unconfirmed complete response (CR/uCR). Median progression-free survival (PFS) was 16 months (95 % confidence interval (CI) 13.3-18.8), and for patients who achieved CR/uCR, it was 33 months (95 % CI 11.1-54.2). Median overall survival (OS) was 30 months (95 % CI 25.6-34.9). For PFS, only blastoid histology and not achieving CR after bendamustine had a significant negative impact on the univariate and multivariate analyses (p < 0.05). Nevertheless, for OS, only an elevated lactate dehydrogenase (LDH) had negative impact on both, univariate and multivariate analyses (p < 0.05). Only one case of treatment-related mortality in a 79-year-old patient with very bad performance status was reported. In 280 cycles, 12 (4 %) hospitalizations for febrile neutropenia were reported. In our population, bendamustine has been a good salvage treatment with a favorable toxicity profile in a non selected and heavily pretreated population of patients with MCL.

Rituximab en dermatología / Rituximab in dermatology

El Rituximab se ha introducido en Medicina como un agente terapéutico con un futuro muy prometedor. Después de su empleo en casos de linfomas B y artritis reumatoide son numerosas las indicaciones que se han establecido dentro de las enfermedades autoinmunes, muchas de ellas dermatológicas. Es por ello que los dermatólogos debemos familiarizarnos con las características de los anticuerpos anti-CD20, así como con el papel de las células B en muchas enfermedades cutáneas. Estos 2 hechos permitirán que pueda utilizarse este fármaco cada vez más y mejor en nuestros pacientes, y a su vez puedan establecerse guías consensuadas de su uso basadas en series amplias de pacientes; es decir, podremos establecer en qué circunstancias y situaciones rituximab estará indicado, acortando de esta manera la enfermedad y disminuyendo la morbilidad en los enfermos por el empleo de fármacos más específicos (AU)

Rituximab was introduced into clinical practice as a medication with considerable potential. Its use in patients with B-cell lymphoma and rheumatoid arthritis revealed numerous indications in autoimmune diseases, many of which involve the skin, thus requiring dermatologists to become familiar with both the characteristics of anti-CD20 antibodies and the role of B cells in multiple skin diseases. Thanks to these developments, we will be able to use rituximab more frequently and appropriately in our patients and draw up consensus guidelines based on large case series. In other words, establishing the indications for rituximab will make it possible to shorten disease course and reduce morbidity due to more specific drugs (AU)

Rituximab in dermatology.

Rituximab was introduced into clinical practice as a medication with considerable potential. Its use in patients with B-cell lymphoma and rheumatoid arthritis revealed numerous indications in autoimmune diseases, many of which involve the skin, thus requiring dermatologists to become familiar with both the characteristics of anti-CD20 antibodies and the role of B cells in multiple skin diseases. Thanks to these developments, we will be able to use rituximab more frequently and appropriately in our patients and draw up consensus guidelines based on large case series. In other words, establishing the indications for rituximab will make it possible to shorten disease course and reduce morbidity due to more specific drugs.

Estudio cuantitativo y socioeconómico de los espectáculos taurinos populares en la Región de Murcia / Quantitative and socioeconomic study of the bullfighting traditional in the Region Murcia (Spain)

En este trabajo se han abordado determinados aspectos relacionados con la gran tradición, así como la importancia cuantitativa y socio-económica que presentan los espectáculos taurinos populares (ETP) en diferentes pueblos de la Región de Murcia. Para ello se han contabilizado todos los espectáculos taurinos celebrados incluidos los ETP, desglosados por municipios, que han sido comunicados al Colegio Oficial de Veterinarios en los últimos 8 años (2004-2011). Para realizar el estudio socioeconómico hemos dividió los ETP en dos tipos; encierros previos a la lidia y encierros o suelta de reses sin lidia posterior. Se han realizado encuesta a asistentes, 150 en el primer tipo de ETP en los municipios de Calasparra y Blanca, 200 participantes en el segundo tipo de ETP en los municipios de Moratalla, Caravaca de la Cruz y Cehegín. Igualmente se han realizado 28 encuestas a peñas de las localidades del Noroeste, donde se celebran ETP. Los festejos taurinos se celebran prácticamente en la totalidad de los municipios, en los últimos 8 años en 42 de ellos, lo que representa el 95%. Se ha producido un aumento de los ETP respecto al total de espectáculos taurinos que pasa del 35% al 53% en 2010, aunque nos encontramos por debajo de la media, ya que en España los ETP fueron el 81% del total de festejos taurinos. Respecto a las características de los asistentes a este tipo de espectáculos, son en su mayoría de fuera de la localidad, suelen ser varones en torno a los 40 años, y casados por lo que pueden acudir con la familia, situación que permite una gran actividad en la localidad y favorece el nivel de gasto en la misma. En relación a la afición de los participantes a los asistentes a los encierros previos a la lidia, les interesa en mayor proporción otro tipo de espectáculos taurinos. Otro dato a resaltar es el alto % de la gente que se queda a dormir en el caso de los encierros con toreo un 40% se queda a dormir, frente al 14% en el caso de los encierros y sueltas sin lidia. El nivel de gasto medio por asistente a un encierro con lidia posterior es de 50€/día, el doble del asistente a un encierro y suelta sin lidia que es de 25€/día y fundamentalmente en restauración en ambos casos. Podemos concluir que en la Región de Murcia en los últimos 8 años se han celebrado ETP el 71,1% del total de municipios, lo que avala la tradición de estos festejos. El número de ETP ha ido en aumento hasta 2009, llegando a celebrarse 98 ETP, lo que supuso el 48% del total de espectáculos taurinos. Los asistentes a los ETP son mayoritariamente de fuera de la localidad, varones y en torno a los 40 años, casados que pueden venir con la familia, situación que permite una gran actividad en la localidad y favorece el nivel de gasto en la misma, que es mayor en el caso de haber lidia posterior al encierro (AU)

In this work some aspects related with the great tradition and the quantitative and socioeconomic importance of the bullfighting traditional shows in different towns of the Murcia Region have been treated. To do this have been posted all the bullfights held including the ETP, disaggregated by municipalities, which have been communicated to the official College of veterinarians in the last 8 years (2004-2011). For the socio-economic study, we have divided the ETP into two types; running bulls previous to the bullfighting and running or release of cattle without bullfighting. Survey to 150 attendees in the first type of ETP in Calasparra and Blanca and 200 attendees in the second type of ETP in Caravaca de la Cruz, Moratalla, Cehegín were realized. Also there have been 28 surveys to sentences of the towns in the Northwest, where they are held ETP. Bullfighting practically takes place in all the towns, in the last eight years in 42 of them, which represents the 95% of the towns. The increase of the percentage of bullfighting traditional shows with respect to the total of bullfighting shows from the 35% to the 53% in 2010, although is minor that average because for Spain bullfighting traditional shows represents the 81% of all bullfighting shows. With regard to the characteristics of the audience to this type of shows, are mainly people from other different towns, about 40 years old, and married so they can come with the family that increase the activity in the town and favor the level of expenses there. In connection with the preferences of the audience to running of bulls previous to the bullfighting, they prefer others types of bullfighting. Another datum to take into account is the high percentage of people that stay overnight, in the case of running of bulls previous to the bullfighting is of 40% against the 14% in the case of loosing and running of bulls without subsequent bullfighting. The average level of expenses by attending person to running of bulls previous to the bullfighting is of 50 €/day, the double that an attending person to loosing and running of bulls without subsequent bullfighting that is 25 €/day, mainly in catering in both cases. In conclusion, the 71,1 % of the total of towns in the Murcia Region has been bullfighting traditional in the last eight years. The number of bullfighting traditional increasing until 2009, when took place 98 shows and represent the 48% of total. The audience bullfighting traditional are mainly people from other different towns, male, about 40 years old, and married so they can come with the family that increase the activity in the town and favor the level of expenses there, that is greater in shows with subsequent bullfighting (AU)

Effect of addition of rituximab to salvage chemotherapy on outcome of patients with diffuse large B-cell lymphoma relapsing after an autologous stem-cell transplantation.

BACKGROUND: We have investigated if rituximab-based salvage regimens improve response rates and survival of patients with diffuse large B-cell lymphoma (DLBCL) relapsing after an autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: We have retrospectively analyzed 82 patients with DLBCL who received salvage therapy for relapse or progression after ASCT. Patients were divided into two groups, according to whether rituximab-based salvage regimens were given (n = 42, 'R-' group) or not (n = 40, 'R+' group) after ASCT. RESULTS: Patients in the R+ group had better complete remission (CR) (55% versus 21.4%, P = 0.006) and overall response (OR) (75% versus 40.4%, P = 0.001) rates, and better 3-year event-free survival (EFS) (37% versus 9%, P = 0.002) and overall survival (OS) (50% versus 20%, P = 0.005) than patients in the R- group. Patients retreated with rituximab had better CR (42.9% versus 21.4%, P = 0.032) and OR (66.7% versus 40.4%, P = 0.019) rates, and better OS (36.2% versus 20% at 3 years, P = 0.05) and EFS (36.2% versus 9% at 3 years, P = 0.05) than patients who received chemotherapy alone at relapse after ASCT. CONCLUSIONS: The addition of rituximab to salvage chemotherapy improves response rates and EFS in patients with relapsed DLBCL after ASCT. These patients may benefit from rituximab retreatment, although larger prospective studies are needed to confirm these results.

In vivo and in vitro immunological changes induced by a short course of grass allergy immunotherapy tablets.

BACKGROUND: The fast-dissolving grass allergy immunotherapy tablet (grass AIT), Grazax, has proven effective in grass pollen-induced rhinoconjunctivitis. OBJECTIVE: To investigate the immunological and cutaneous changes induced after a short course with grass AIT. METHODS: We performed a randomized, double-blind placebo-controlled trial with 78 patients randomly assigned to receive either grass AIT or placebo in a 2:1 ratio. Treatment lasted at least 8 weeks before the grass pollen season (GPS), and continued until the season finished. Specific immunoglobulin (Ig) G4, IgE, and IgE-blocking factor to Phleum pratense were measured at the beginning of the trial and at different intervals during treatment. Immediate and delayed skin tests with P pratense were also performed. Safety endpoints were defined in terms of adverse events reported. RESULTS: A total of 75 patients completed the trial (50 active and 25 placebo). P pratense IgG4, IgE, and IgE-blocking factor in actively treated patients increased significantly from baseline to the start of the GPS compared to placebo (P > .001, P = .017, and P = .005, respectively). The immediate cutaneous response was reduced during therapy in actively treated subjects, whereas placebo-treated subjects showed a decrease only after the start of the GPS. The delayed response to the intradermal test in grass AIT-treated subjects diminished, although not in a significantly different way from the placebo-treated subjects. CONCLUSION: Treatment with grass AIT for grass pollen allergic rhinoconjunctivitis induces immunological changes after only 1 month of treatment.

[Prolonged complete clinical remission in patients with severe pemphigus vulgaris after cycles of intravenous cyclophosphamide]. / Remisión clínica completa prolongada en pacientes con pénfigo vulgar grave después del tratamiento con ciclos intravenosos de ciclofosfamida.

BACKGROUND: Corticosteroids are the systemic treatment of choice in patients with pemphigus vulgaris, but chronic administration is associated with side effects. Intravenous treatment with cyclophosphamide can improve the clinical signs of pemphigus vulgaris. MATERIAL AND METHODS: We prospectively studied 8 patients diagnosed with pemphigus vulgaris. Six of these had mucocutaneous pemphigus vulgaris and 2 had mucosal pemphigus vulgaris. Treatment consisted of 10 cycles of cyclophosphamide at a dose of 10-15 mg/kg separated by 15 days, while maintaining the initial corticosteroid and immunosuppressant dose. Clinical efficacy was assessed and the anti-epidermal intercellular substance (EIS) and anti-desmoglein (DSG) 3 and 1 antibody titers were monitored (by indirect immunofluorescence and enzyme-linked immunosorbent assay, respectively). RESULTS: All patients with pemphigus vulgaris responded excellently to treatment. Five of the 8 patients achieved complete remission of pemphigus lesions after 10 cycles of cyclophosphamide. In the other 3 patients, the skin lesions disappeared a few weeks after the last cycle of cyclophosphamide. A substantial reduction in immuno suppressant dose was possible in all patients. Furthermore, an improved immunologic response was observed in all cases after cyclophosphamide treatment, with decreased anti-DSG1 and anti-DSG3 antibody titers and well as decreased circulating anti-EIS antibody titers. During the mean 15.1 month follow-up (range, 1-25 months), no new lesions appeared and no side effects of cyclophosphamide therapy were reported. CONCLUSIONS: Fortnightly cycles of intravenous cyclophosphamide may be a useful therapeutic option in patients with severe pemphigus vulgaris. A reduction of corticosteroid dose was possible with this therapeutic approach and the cumulative cyclophosphamide dose was lower than with daily oral administration. Our findings also show that the therapeutic approach induces clinical and immunologic remission in most patients.

Remisión clínica completa prolongada en pacientes con pénfigo vulgar grave después del tratamiento con ciclos intravenosos de ciclofosfamida / Prolonged Complete Clinical Remission in Patients With Severe Pemphigus Vulgaris After Cycles of Intravenous Cyclophosphamide

Introducción: Los corticosteroides son el tratamiento sistémico de elección en los pacientes con pénfigo vulgar (PV). Su administración crónica produce efectos secundarios. La administración de ciclofosfamida (CF) intravenosa puede mejorar las manifestaciones clínicas del PV. Material y método: Estudiamos prospectivamente 8 pacientes diagnosticados de PV. Seis de los pacientes presentaban PV cutáneo-mucoso (PVCM) y 2 casos PV mucoso (PVM). El tratamiento consistió en 10 ciclos quincenales de CF en dosis de 10-15 mg/kg, manteniendo la dosis inicial de corticosteroides y de inmunosupresor. Se evaluó la eficacia clínica y la evolución del título de anticuerpos anti-sustancia intercelular epidérmica (SIE) (inmunofluorescencia indirecta) y específicamente anti-desmogleína (Dsg) 1 y 3 (ELISA). Resultados: Todos los pacientes con PV presentaron una excelente respuesta al tratamiento. Cinco de los 8 pacientes presentaron una remisión completa de las lesiones de PV después de los 10 ciclos de CF. En los otros 3 pacientes las lesiones cutáneas desparecieron unas semanas después del último ciclo de CF. En todos los pacientes se redujo de forma importante la dosis de inmunosupresores. Además, en todos los casos se observó una mejoría en la respuesta inmunológica después del tratamiento con CF, con disminución en el título de anticuerpos frente a las Dsg 1 y 3, así como del título de anticuerpos circulantes frente a la SIE. Tras un seguimiento medio de 15,1 meses (1-25 meses) ningún paciente ha presentado nuevas lesiones de PV. A su vez, no se han observado efectos secundarios por la CF. Conclusiones: La administración de pulsos quincenales de CF intravenosa puede ser una opción terapéutica útil en pacientes con PV grave. Este esquema terapéutico permite disminuir la dosis de corticosteroides con una menor dosis acumulada de CF que en la administración oral diaria. Además, nuestros resultados muestran que este esquema terapéutico se acompaña de una remisión clínica e inmunológica en la mayoría de los pacientes (AU)

Background: Corticosteroids are the systemic treatment of choice in patients with pemphigus vulgaris, but chronic administration is associated with side effects. Intravenous treatment with cyclophosphamide can improve the clinical signs of pemphigus vulgaris. Material and methods: We prospectively studied 8 patients diagnosed with pemphigus vulgaris. Six of these had mucocutaneous pemphigus vulgaris and 2 had mucosal pemphigus vulgaris. Treatment consisted of 10 cycles of cyclophosphamide at a dose of 10-15 mg/kg separated by 15 days, while maintaining the initial corticosteroid and immunosuppressant dose. Clinical efficacy was assessed and the anti-epidermal intercellular substance (EIS) and anti-desmoglein (DSG) 3 and 1 antibody titers were monitored (by indirect immunofluorescence and enzyme-linked immunosorbent assay, respectively). Results: All patients with pemphigus vulgaris responded excellently to treatment. Five of the 8 patients achieved complete remission of pemphigus lesions after 10 cycles of cyclophosphamide. In the other 3 patients, the skin lesions disappeared a few weeks after the last cycle of cyclophosphamide. A substantial reduction in immunosuppressant dose was possible in all patients. Furthermore, an improved immunologic response was observed in all cases after cyclophosphamide treatment, with decreased anti-DSG1 and anti-DSG3 antibody titers and well as decreased circulating anti-EIS antibody titers. During the mean 15.1 month follow-up (range, 1-25 months), no new lesions appeared and no side effects of cyclophosphamide therapy were reported. Conclusions: Fortnightly cycles of intravenous cyclophosphamide may be a useful therapeutic option in patients with severe pemphigus vulgaris. A reduction of corticosteroid dose was possible with this therapeutic approach and the cumulative cyclophosphamide dose was lower than with daily oral administration. Our findings also show that the therapeutic approach induces clinical and immunologic remission in most patients (AU)

Modelos animales experimentales de enfermedad de hígado graso y síndrome metabólico / Experimental animal models of fatty liver disease and metabolic syndrome

Los estudios en modelos animales constituyen una valiosa herramienta para comprender los procesos fisiopatológicos asociados a la enfermedad del hígado graso, sus características histológicas y ensayo de nuevas terapias. Una gran parte de los trabajos se desarrollan en roedores (ratones y ratas principalmente), dada su similitud biológica con el hombre y el gran conocimiento que se tiene a todos los niveles (genético, molecular, enzimático…) de estas especies. Por su facilidad de desarrollar los procesos de esteatosis hepática también destacan las aves. En este trabajo se describen los principales modelos de enfermedad del hígado graso en diversas especies animales, y las formas de inducción de enfermedad. Básicamente, el excesivo acúmulo de grasa en hígado puede ser consecuencia de aporte elevado de grasa, aumento de la síntesis grasa, oxidación reducida, y/o reducción de su salida en forma de VLDL. Así, se describen modelos basados en alteraciones genéticas (animales transgénicos o bien mutaciones naturales) que incrementan la lipogénesis, otros que dificultan la eliminación de grasa hepática (genes que regulan la oxidación de ácidos grasos), inducción mediante dietas que dan lugar a obesidad (ricas en fructosa, sacarosa, grasas, dietas aterogénicas) o bien sin producir obesidad (dietas deficientes en arginina o ricas en fructosa y grasas), tóxicos que incrementan la lipogénesis hepática, o factores que disminuyen la oxidación de ácidos grasos (como dietas deficientes en colina o metionina, administración de estrógenos, glucocorticoides o ciertos tóxicos). Se describen por último modelos aviares inducidos por la dieta (AU)

Animal models are important tools for the study of fatty liver disease, mainly related to physiopathology, pathology and therapeutical trials. Most studies have been developed in rodents (usually in mice and rats), because of biological similarities with humans, and also because of the deep knowledge (genetics, molecular, enzymatic…) of these species. Hepatic steatosis is also easily developed in avian species. We describe the most used animal models of fatty liver disease, and the several means of disease induction. Basically, excessive fat accumulation in the liver can occur as a result of increased fat delivery, increased fat synthesis, reduced fat oxidation, and/or reduced fat export in the form of VLDL. Several animal models of hepatic steatosis are described: genetically engineered animals or spontaneous mutations, which increase lipogenesis; others show reduced fatty acid oxidation, and therefore interfere fat elimination; induction by diets producing obesity: high content in fructose, sacarose, fat, and atherogenic diets; induction by diets which don’t produce obesity (arginine deficient diets), toxic agents which increase hepatic lipogenesis, or factors inducing a decrease of fatty acid oxidation such as choline / methionine deficient diets, strogens and glucocorticoids administration, or toxic agents. Diet-induced avian models are also described (AU)