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.

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.

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 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.

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.

Validation of a commercially available human immunoturbidimetric assay for haptoglobin determination in canine serum samples.

Haptoglobin is a positive acute-phase protein with a valuable role as a marker of inflammation in both human and veterinary medicine. The aim of this study was to validate a commercially available immunoturbidimetric method designed for human haptoglobin determination (Izasa SA, Barcelona, Spain) for its use in canine samples. Cross-reactivity between anti-human haptoglobin antiserum and canine haptoglobin was found when agarose gel immunodiffusion and ELISA tests were performed. The use of canine pooled serum with haptoglobin concentration of 6.3 g/L as standard provided higher analytical range than commercially available standards. Intra-assay and inter-assay coefficients of variation were 2.49% and 4.60%, respectively. A linear regression model between immunoturbidimetric results and a previously validated spectrophotometric method (Tridelta Development Limited, Ireland) yielded a slope at 95% confidence interval of 0.94 (0.86, 1.02) and y-intercept at 95% confidence interval of 0.11 (-0.59, 0.82). No significant differences were produced by anticoagulants, lipaemia and bilirubinaemia, although haemolysis significantly decreased haptoglobin. A significant increase of haptoglobin concentration was detected in inflammatory conditions such as pyometra and leishmaniasis, in neoplastic conditions, and after glucocorticoid administration. Canine serum haptoglobin concentration can be reliably measured using the commercially available Izasa immunoturbidimetric method developed for human haptoglobin determination. This method is precise and accurate, provides a wider analytical range than previous reported methods, and can be easily automated and used for routine haptoglobin determination in canine samples.

[Anemia in chronic lymphatic leukemia: is erythropoietin the solution?]. / La anemia en la leucemia linfática crónica: Es la eritropoyetina la solución del problema?

Anemia is a common complication in the clinical course of chronic lymphocytic leukemia. Low hemoglobin levels both correlate with an adverse prognosis and adversely affect the quality of life of chronic lymphocytic leukemia patients. Different physiopathological phenomena may lead to anemia: marrow infiltration, hypersplenism, immune hemolysis or toxicity of chemotherapy. Treatment with human recombinant erythropoietic agents has been shown to be effective for anemia associated with different lymphoproliferative syndromes. This paper analyses the available evidence on erythropoietic agent treatment for chronic lymphocytic leukemia associated anemia. The comparative effect of different dosage schemes, the role of possible response-prediction factors such as the endogenous erythropoietin level and the results achieved using darbopoietin alpha are reviewed.

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.

The normal electrocardiogram of the unanesthetized peregrine falcon (Falco peregrinus brookei).

The mean duration and amplitudes of the lead II electrocardiogram were determined in the peregrine falcon (Falco peregrinus brookei) using 10 birds ranging in age from 1 to 5 yr. Electrocardiograms were performed on unanesthetized falcons in order to avoid the anesthesia effect on the electrocardiogram, by a method which seems to induce a tonic immobility-like reaction. All the falcons had a normal sinus rhythm, with a mean heart rate of 268 beats per minute. Mean durations of PR, ST, QT, and RR intervals were higher (but not statistically significant) in females than in males, except for the ST segment, with similar values in both sexes. P-wave deflections were positive in I, II, III, aVL, and aVF and negative in aVR. The normal patterns of wave forms of the QRS complexes in all leads were of QS and rS types, except for aVR and aVL, which presented an R configuration. The mean electrical axis was negative, with an average of -99.9 degrees. T-wave deflections were positive in I, II, III, and aVF leads II and negative in aVR and aVL. The data collected in this study may serve as a guide for electrocardiographic monitoring of peregrine falcons.

[Usefulness of sectorization of pediatric hospital emergency units in the community of Madrid]. / Utilidad de la sectorización de las urgencias hospitalarias pediátricas en la comunidad de Madrid.

We have studied the procedence of the children that came to the Emergency Department of the Niño Jesús Hospital, analyzing if they belonged to the pediatric emergency area corresponding to this hospital, the procedence from the different postal districts of Madrid, from other localities of the Madrid Community, or from the Health Areas of this Community. We found that only 12.42% of the children came from the corresponding area of the emergency care sectorization, and that they came from very disperse zones, having no clear relation with any of the Health Care Areas. We conclude that current sectorization of the pediatric emergencies in hospitals is not being usefull, and we suggest alternative solutions.

Electrocardiographic changes in the growing Mastín Español.

Serial electrocardiograms were recorded from 70 Mastín Español dogs in right lateral recumbency, aged between one day and three years, in order to observe the changes in the waveform and intervals, QRS morphology, cardiac rhythm and heart rate caused by their growth. Age and bodyweight caused a gradual increase in the duration and amplitude of the P wave, duration of the PR, QT and RR intervals, amplitude of the R wave and duration of the QRS complex and ST segment. Q wave was observed in nearly all the recordings with different amplitudes. The S wave was only significant in one-day-old animals and QRS morphology showed significant important changes from qrS and rS to qR and qRs morphologies during the first two weeks of life. The T wave increased its amplitude until the age of two months and changed its polarity (from negative to positive) from five months of age onwards. The heart rate decreased until the age of seven months, reaching stabilised values of 110 +/- 7.3 beats per minute. Sinus tachycardia was commonplace in animals under one month old and respiratory sinus arrhythmia was found from six months of age. Sex only influenced the duration and amplitude of the T wave. Males had higher mean values than females.

[Past, present and future of anti-idiotype vaccination]. / Pasado, presente y futuro de la vacunación anti-idiotipo.

Cancer vaccines are conceived as therapeutic tools, in contrast to the prophylactic vaccines used to fight against infectious diseases. Among the most potent therapeutic vaccines, anti-idiotype vaccination is directed against the tumor idiotype, the only well-characterized tumor antigen displayed in neoplastic B-cells. Anti-idiotype vaccines have demonstrated clinical benefit against follicular lymphoma and are currently being evaluated in two different phase III clinical trials. Additional emerging strategies, which include the use of dendritic cells and the production of vaccines via molecular means will surely allow us to draw important conclusions concerning the treatment of cancer patients.

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)

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)