Quality Standards for Allergen Immunotherapy Clinics in Spain: Consensus Document.

BACKGROUND AND OBJECTIVE: Allergen immunotherapy clinics (AITCs) in Spain differ widely in terms of structure, organization, resources, and portfolio of services. Therefore, it is essential to unify treatment criteria and define quality standards for the most complex AITCs. Objective: To establish a series of recommendations that make it possible to guarantee quality and safety in the administration of immunotherapy and define quality standards for the most complex AITCs. METHODS: This project began with an online survey of 65 allergy departments/units throughout Spain in 2013. Next, a 2-phase consensus process was carried out. In the first phase, 10 experts defined and agreed on the standards using the RAND/UCLA Appropriateness method; in the second, the agreements were validated by means of a 2-round Delphi consultation with 84 experts. RESULTS: Consensus was reached on minimum safety and quality criteria in the administration of allergen immunotherapy, and 2 levels of highly complex AITCs were defined: accredited AITCs and accredited AITCs with excellence. Consensus was also reached on quality standards and accreditation criteria for both levels. CONCLUSIONS: This project is pioneering in terms of its purpose (the definition of quality standards for AITCs) and of the use of structured participation techniques (combination of the RAND/UCLA and Delphi methods). It enabled the design of minimum standards for quality and safety in administering AIT, as well as quality criteria for accreditation of AITCs supported by a broad panel of experts from the Spanish Society of Allergology and Clinical Immunology.

Consensus document on dog and cat allergy.

The prevalence of sensitization to dogs and cats varies by country, exposure time and predisposition to atopy. It is estimated that 26% of European adults coming to the clinic for suspected allergy to inhalant allergens are sensitized to cats and 27% to dogs. This document is intended to be a useful tool for clinicians involved in the management of people with dog or cat allergy. It was prepared from a consensus process based on the RAND/UCLA method. Following a literature review, it proposes various recommendations concerning the diagnosis and treatment of these patients, grounded in evidence and clinical experience. The diagnosis of dog and cat allergy is based on a medical history and physical examination that are consistent with each other and is confirmed with positive results on specific IgE skin tests. Sometimes, especially in polysensitized patients, molecular diagnosis is strongly recommended. Although the most advisable measure would be to avoid the animal, this is often impossible and associated with a major emotional impact. Furthermore, indirect exposure to allergens occurs in environments in which animals are not present. Immunotherapy is emerging as a potential solution to this problem, although further supporting studies are needed.

Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer.

BACKGROUND: We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose. METHODS: Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using (99)Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry. RESULTS: Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1 ± 8.9 vs 31.3 ± 12.9 mg (P = 0.01). Both, AUC24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P < 0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P = 0.03) in tumour specimens. CONCLUSION: Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.

Kidney allograft survival of African American and Caucasian American recipients with lupus.

BACKGROUND: African Americans with lupus who receive kidney transplants have high prevalence of predictors of allograft failure, which can explain their poor outcomes. METHODS: Of 1223 African Americans and 1029 Caucasian Americans with lupus who received kidney transplants from deceased donors between 1987 and 2006 with complete records in the UNOS program, 741 pairs were matched in 16 predictors employing a predicted probability of group membership. The primary outcome was allograft failure. Main secondary outcomes were rejection, allograft failure due to rejection, and mortality. RESULTS: Matched pairs were predominantly women (82%) with a mean age of 39 years. Twenty-four percent of recipients received kidneys from expanded criteria donors. African Americans and Caucasian Americans matched well (p ≥ 0.05): donor age, gender and race; recipient age, gender, education and insurance; dialysis prior to transplant, kidneys from expanded criteria donors, cold ischemia time, history of prior kidney transplant, panel reactive antibodies, human leukocyte antigens mismatch, blood type compatibility, transplant Era, and follow-up time. Contrary to the unmatched cohort with significantly higher allograft failure rate (events per 100 patient-years) in African Americans compared to Caucasian Americans (10.49 vs 6.18, p<0.001), matched pairs had similar allograft failure rates (8.41 vs 7.81, p=0.418). Matched pairs also had similar rates of rejections (9.82 vs 9.39, p=0.602), allograft failure due to rejection (6.19 vs 5.71, p=0.453), and mortality (2.79 vs 3.52, p=0.097). CONCLUSION: In lupus recipients of kidney transplants from deceased donors, African American and Caucasian Americans have similar allograft failure rates when predictors are matched between groups.

The growing family of photoactive yellow proteins and their presumed functional roles.

For several years following the discovery and characterization of the first PYP, from Halorhodospira halophila, it was thought that this photoactive protein was quite unique, notwithstanding the isolation of two additional examples in rapid succession. Mainly because of genomic and metagenomic analyses, we have now learned that more than 140 PYP genes occur in a wide variety of bacteria and metabolic niches although the protein has not been isolated in most cases. The amino acid sequences and physical properties permit their organization into at least seven groups that are also likely to be functionally distinct. Based upon action spectra and the wavelength of maximum absorbance, it was speculated nearly 20 years ago but never proven that Hr. halophila PYP was involved in phototaxis. Nevertheless, in only one instance has the functional role and interaction partner for a PYP been experimentally proven, in Rs. centenum Ppr. Genetic context is one of several types of evidence indicating that PYP is potentially involved in a number of diverse functional roles. The interaction with other sensors to modulate their activity stands out as the single most prominent role for PYP. In this review, we have attempted to summarize the evidence for the functional roles and interaction partners for some 26 of the 35 named species of PYP, which should be considered the basis for further focused molecular and biochemical research.

Lamotrigine induced subacute cutaneous lupus erythematous.

A 48-year-old woman developed drug-induced subacute lupus erythematosus while taking lamotrigine. The eruption resolved after discontinuance of lamotrigine, suggesting this drug as the cause.

[Optic neuritis: aetiopathogenesis, diagnosis, prognosis and management]. / Neuritis óptica: etiopatogenia, diagnóstico, pronóstico y manejo.

The main causes of optic neuritis (ON) are multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease, also known as MOGAD. When all screening is negative, we can speak of idiopathic ON, although this diagnosis should be provisional. ON can be diagnosed clinically and paraclinical tests are not routinely required to confirm it. However, tests such as magnetic resonance imaging (MRI), visual evoked potentials (VEP) and optical coherence tomography (OCT) can lend support to the diagnosis if the clinical presentation is atypical. The use of new MRI sequences, OCT, multifocal VEPs and the determination of neurofilaments has allowed ON to be used as a model for remyelination and neuroprotection, leading to phase II clinical trials. Some of these drugs, such as opicinumab, clemastine, phenytoin or simvastatin, have shown positive results; however, their clinical effect remains to be defined. It is accepted that corticosteroids do not improve the long-term prognosis of ON, although some retrospective studies suggest that there is a therapeutic window from the onset of symptoms. Plasmapheresis has also been shown to be effective in patients with ON. In this review we will address basic aspects of the management of ON, in the fundamental context of MS, NMOSD and MOGAD, with emphasis on etiopathogenic, diagnostic, prognostic and therapeutic developments.

TITLE: Neuritis óptica: etiopatogenia, diagnóstico, pronóstico y manejo.La neuritis óptica (NO) tiene como principales causas la esclerosis múltiple (EM), las enfermedades dentro del espectro de la neuromielitis óptica (NMOSD) y la enfermedad asociada a anticuerpos contra la proteína de la mielina del oligodendrocito, también conocida como MOGAD. Cuando todo el cribado es negativo, podemos hablar de NO idiopática, aunque este diagnóstico deberá ser provisional. La NO se puede diagnosticar clínicamente y no se requieren de forma rutinaria pruebas paraclínicas para confirmarla. Sin embargo, pruebas como la resonancia magnética (RM), los potenciales evocados visuales (PEV) y la tomografía de coherencia óptica (OCT) pueden dar soporte al diagnóstico si la presentación clínica es atípica. El uso de nuevas secuencias de RM, la OCT, los PEV multifocales y la determinación de neurofilamentos han posibilitado el uso de la NO como modelo de remielinización y neuroprotección, propiciando la realización de ensayos clínicos de fase II. Algunos de estos fármacos, como el opicinumab, la clemastina, la fenitoína o la simvastatina, han obtenido resultados positivos; no obstante, su efecto clínico está por definir. Se acepta que los corticoides no mejoran el pronóstico a largo plazo de la NO, aunque algunos estudios retrospectivos sugieren que existe una ventana terapéutica desde el inicio de los síntomas. La plasmaféresis también ha demostrado eficacia en pacientes con NO. En esta revisión abordaremos aspectos básicos del manejo de la NO, en el contexto fundamental de la EM, la NMOSD y la MOGAD, haciendo hincapié en las novedades etiopatogénicas, diagnósticas, pronósticas y terapéuticas.

Urticaria caused by antihistamines: report of 5 cases.

Antihistamines are widely used drugs. Hypersensitivity reactions with these drugs are rare and a challenge for the physician. We describe 5 outpatients who experienced urticaria after taking antihistamines. All 5 were treated at our outpatient clinic over a period of 15 years. The allergy workup included a clinical history, skin prick testing, patch testing with antihistamines, and single-blind placebo-controlled oral challenge tests. Biopsy samples were taken and serum tryptase levels were determined in 1 patient. The results of the skin prick tests and patch tests were negative in all patients but 1, in whom the prick test result was positive to some antihistamines. We confirmed all diagnoses using a single-blind challenge test. The biopsy obtained from 1 patient strongly supported urticaria. We present 5 cases of antihistamine-induced urticaria where the immunologic mechanism remains unclear. Hypersensitivity reactions should be taken into account in patients receiving antihistamines, especially in those who experience urticaria.

Enhanced covalent p-phenylenediamine crosslinked graphene oxide membranes: Towards superior contaminant removal from wastewaters and improved membrane reusability.

The increasing depletion of freshwater necessitates the re-use and purification of wastewaters. Among the existing separation membrane materials, graphene oxide (GO) is a promising candidate, owing to its tunable physicochemical properties. However, the widening of GO membranes pore gap in aqueous environments is a major limitation. Crosslinking agents can be incorporated to alleviate this problem. This study describes a comparative analysis of uncrosslinked and p-Phenylenediamine (PPD) crosslinked GO membranes' water purification performance. Dip-coating and dip-assisted layer-by-layer methods were used to fabricate the uncrosslinked and crosslinked membranes respectively. The covalent interaction between GO and PPD was confirmed by Fourier Transform Infra-Red and X-ray Photoelectron Spectroscopy. The excellent membrane topographical continuity and intactness was assessed by means of Scanning Electron Microscopy, while water contact angle measurements were undertaken to evaluate and confirm membrane hydrophilicity. The improvement impact of the crosslinker was manifested on the enhancement of the stability and performance of the membranes during nanofiltration tests of aqueous solutions of methylene blue in a homemade nanofiltration cell operated at 1 bar.

Thermoluminescence of single wall carbon nanotubes synthesized by hydrogen-arc-discharge method.

Single Wall Carbon Nanotubes (SWNT) synthesized by the hydrogen-arc-discharge method were tested as thermoluminescent (TL) material and found to be highly resistant to gamma radiation. Gamma irradiation of the as-prepared material with doses between 1 and 20 kGy induced changes on the morphology of the SWNT, such as nanoloops, as observed by Scanning Electron Microscopy. From X-ray diffraction, the as-prepared material shows content of various forms of carbon, including nanotubes, hexagonal carbon (graphite), and rhombohedral carbon too. The full width at half maximum (FWHM) of diffraction peaks remain practically unchanged after irradiation. The glow curves show a single TL peak centered at about 449 K. Because the complex structure of the glow curves, it seems that the TL signal could be produced by a trap distribution instead of a single level of traps. To dilucidate the mechanism responsible of glow curves and the value of activation energy of traps, kinetic parameters like Eeff, ΔE, and s of experimental the glow curves have been analyzed using computerized glow curve deconvolution (CGCD) considering a continuous distribution of trapping levels, peak shape and initial rise methods, as well as heuristic equations. The measured TL dosimetric properties may be summarized as follows: (a) moderate reproducibility of the TL signal (coefficient of variation 24.87%); (b) main peak activation energy of 1.206 eV; (c) threshold dose of ~1 kGy; (d) TL-sensitivity of ~7.0 × 10-4; (e) human bone equivalence, i.e., high-Z material, Zeff = 15 and, (f) wide linear range of TL dose-response in the range 0.170-2.5 kGy.

[Intermittent theta-burst transcranial magnetic stimulation for the treatment of spasticity in patients with recurring multiple sclerosis: the results of a double-blind randomised clinical trial]. / Estimulacion magnetica transcraneal theta-burst intermitente para el tratamiento de la espasticidad en pacientes con esclerosis multiple recurrente: resultados de un ensayo clinico aleatorizado doble ciego.

AIM: It has been suggested that the repetitive transcranial magnetic stimulation could be useful as a non-pharmacological treatment for spasticity. The aim of this study was to evaluate the clinical and neurophysiological effects of high-frequency intermittent theta burst stimulation (iTBS) on lower limb spasticity in patients with relapsing multiple sclerosis in a randomized, double-blind placebo controlled trial. PATIENTS AND METHODS: Seventeen patients in the remitting phase of the disease were randomly allocated to sham or magnetic therapy group and underwent iTBS over contralateral motor cortex of the most affected leg once a day for two weeks. Each session consisted of 10 bursts containing three pulses at 50 Hz repeated at 200 ms intervals (5 Hz) every 10 s for a total of 600 stimuli. The iTBS effect was assessed by using clinical (such as the Modified Ashworth Scale) and neuro-physiological (H/M amplitude ratio and cortical silent period duration) parameters. RESULTS: Two-week iTBS over motor cortex of the most affected leg did not produce any significant clinical effect on spasticity. However, it decreases the H/M amplitude ratio and increases duration of cortical silent period but not significantly, in patients with relapsing multiple sclerosis. CONCLUSION: The stimulation protocol used in this study does not have significant therapeutic effect. Therefore, we do recommend further studies as neurophysiological changes were evident.

TITLE: Estimulacion magnetica transcraneal theta-burst intermitente para el tratamiento de la espasticidad en pacientes con esclerosis multiple recurrente: resultados de un ensayo clinico aleatorizado doble ciego.Objetivo. La estimulacion magnetica transcraneal repetitiva podria ser util como tratamiento no farmacologico para la espasticidad. El objetivo de este estudio es reevaluar el efecto clinico y los cambios neurofisiologicos que produce la estimulacion theta-burst intermitente (ETBi) sobre la espasticidad de las extremidades inferiores en pacientes con esclerosis multiple recurrente en un ensayo aleatorizado, doble ciego, controlado con placebo. Pacientes y metodos. Diecisiete pacientes en la fase remitente de la enfermedad fueron aleatoriamente asignados al grupo placebo o al grupo de tratamiento activo mediante estimulacion magnetica transcraneal repetitiva con protocolo ETBi sobre la corteza motora contralateral de la pierna mas afectada. El procedimiento consistio en 10 sesiones diarias durante dos semanas. Cada sesion consistio en 10 rafagas que contenian tres pulsos a 50 Hz repetidos a intervalos de 200 ms (5 Hz) cada 10 s para un total de 600 estimulos. El efecto de ETBi se evaluo mediante el uso de parametros clinicos (como la escala de Ashworth modificada) y neurofisiologicos (ratio de amplitud H/M y duracion del periodo cortical silente). Resultados. Dos semanas de ETBi sobre la corteza motora de la pierna mas afectada no produjeron ningun efecto clinico significativo sobre la espasticidad en pacientes con esclerosis multiple recurrente. Sin embargo, aunque de forma no significativa, se observo disminucion de la ratio de amplitud H/M y un aumento de la duracion del periodo cortical silente. Conclusion. El protocolo de estimulacion utilizado en este estudio no parece tener un efecto terapeutico significativo. Sin embargo, recomendamos estudios adicionales, ya que los cambios neurofisiologicos fueron evidentes.

An innovative sandwich ELISA system based on an antibody cocktail for gluten analysis.

A cocktail sandwich ELISA based on the employ of two monoclonal antibodies (MAbs) as coating antibodies and a third MAb conjugated to horseradish peroxidase has been developed for the analysis of gluten in foods. Given that each MAb displays a wide specificity spectrum for wheat, barley, rye and oats prolamins, their combination for ELISA ensures a high crossreactivity with most of the potentially toxic gliadin, hordein, secalin and avenin protein family. One of the unprecedented features of the cocktail sandwich ELISA is that it permits for the first time analysis of barley hordeins in foods, which is unattainable using conventional or commercial ELISA kits. Besides, gliadins, hordeins and secalins are recognised to the same extent. The system provides a high detection sensitivity for gliadins, hordeins, secalins and avenins (1.5, 0.05, 0.15 and 12 ng/ml, respectively). The working linear range comprises 3-100 ng/ml with a gliadin detection limit of 1.5 ppm. This limit of detection is even better than that demanded in the latest Codex recommendation, 10 ppm. Cocktail ELISA data were contrasted with those of commercial ELISA kits and confirmed by mass spectrometry, a non-immunological technique which provides evidence for the occurrence of false positive results with the commercial kits.

Monoclonal antibodies against the major coat protein of filamentous phage as a useful analytical tool for bacteriophage peptide/protein display.

Four mouse monoclonal antibodies (MAbs) that react with filamentous M13KO7 and R408 phage were obtained. Three of these MAbs (two IgG2a and one IgG3) recognize linear sequences of the p8 main structural coat protein, and one (IgG2a) identifies a putatively conformational epitope, as suggested by Western blot. These MAbs also react with recombinant phage expressing peptide antigens fused to p8, and are though useful reagents for peptide/protein phage display screening based methods. The latter was shown in an enzyme-linked immunoadsorbent assay (ELISA) and a visual immunoassay where one of the anti-p8 MAbs was used to capture recombinant phages displaying a peptide characteristic of the Hepatitis B virus surface antigen or a Dengue virus-related peptide antigen.