Cardiac safety of second-generation H1 -antihistamines when updosed in chronic spontaneous urticaria

The symptoms of chronic urticaria, be it chronic spontaneous urticaria (CSU) or chronic inducible urticaria (CindU), are mediated primarily by the actions of histamine on H1 receptors located on endothelial cells (the weal) and on sensory nerves (neurogenic flare and pruritus). Thus, second-generation H1 antihistamines (sgAHs) are the primary treatment of these conditions. However, many patients are poorly responsive to licensed doses of antihistamines. In these patients, the current EAACI/GA2 LEN/EDF/WAO guideline for urticaria suggests updosing of sgAHs up to fourfold. However, such updosing is off-label and the responsibility resides with the prescribing physician. Therefore, the safety of the drug when used above its licensed dose is of paramount importance. An important aspect of safety is potential cardiotoxicity. This problem was initially identified some 20 years ago with cardiotoxic deaths occurring with astemizole and terfenadine, two early sgAHs. In this review, we discuss the mechanisms and assessments of potential cardiotoxicity of H1 antihistamines when updosed to four times their licensed dose. In particular, we have focused on the potential of H1 antihistamines to block hERG (human Ether-a-go-go-Related Gene) voltage-gated K+ channels, also known as Kv11.1 channels according to the IUPHAR classification. Blockade of these channels causes QT prolongation leading to torsade de pointes that may possibly degenerate into ventricular fibrillation and sudden death. We considered in detail bilastine, cetirizine, levocetirizine, ebastine, fexofenadine, loratadine, desloratadine, mizolastine and rupatadine and concluded that all these drugs have an excellent safety profile with no evidence of cardiotoxicity even when updosed up to four times their standard licensed dose, provided that the prescribers carefully consider and rule out potential risk factors for cardiotoxicity, such as the presence of inherited long QT syndrome, older age, cardiovascular disorders, hypokalemia and hypomagnesemia, or the use of drugs that either have direct QT prolonging effects or inhibit sgAH metabolism

ATLAS RPC Quality Assurance results at INFN Lecce

The main results of the quality assurance tests performed on the Resistive Plate Chamber used by the ATLAS experiment at LHC as muon trigger chambers are reported and discussed. Since July 2004, about 270 RPC units has been certified at INFN Lecce site and delivered to CERN, for being integrated in the final muon station of the ATLAS barrel region. We show the key RPC characteristics which qualify the performance of this detector technology as muon trigger chamber in the harsh LHC enviroments. These are dark current, chamber efficiency, noise rate, gas volume tomography, and gas leakage.Comment: Comments: 6 pages, 1 table, 9 figures Proceedings of XXV Physics in Collision-Prague, Czech Republic, 6-9 July 200

Le Elezioni Politiche 2013

Le elezioni politiche del 24 e 25 febbraio 2013 hanno sancito un forte cambiamento della struttura del sistema partitico italiano. In un contesto di altissima volatilità elettorale e di accelerato declino della partecipazione al voto, il sistema è divenuto sostanzialmente tripolare, dopo vent’anni di strutturazione e tenuta del bipolarismo. A questo esito hanno concorso da un lato l’erosione dei principali schieramenti politici che a partire dal novembre 2011 avevano sostenuto l’esperienza del governo Monti (nonché la deludente prova elettorale dello stesso Presidente del Consiglio uscente), e dall’altro lo straordinario successo del Movimento 5 stelle. Quest’ultimo, al primo test elettorale di livello nazionale, ha raccolto un risultato sorprendente, giungendo ad oltre un quarto dei voti validi. Siamo di fronte ad una parentesi momentanea dovuta all’effetto combinato di crisi economica e crisi politica, oppure le contraddizioni interne alla Seconda Repubblica l’hanno condotta effettivamente al suo crepuscolo? Come uscirà il sistema partitico italiano da questa nuova fase di destabilizzazione? Questo quarto Dossier CISE, che raccoglie contributi apparsi sul sito web del Cise prima e dopo le elezioni, fornisce una prima analisi del voto, presentando elaborazioni su dati aggregati, stime dei flussi elettorali, alcune prime analisi su dati di sondaggio, nonché una panoramica dei nuovi eletti e un’appendice ricca di tabelle e mappe riassuntive del risultato elettorale. Come i precedenti Dossier, si tratta di uno strumento prodotto rapidamente all’indomani del voto, con l’intento di suggerire primi spunti di interpretazione da approfondire in seguito, cercando di contribuire alla lettura di un risultato elettorale cruciale, in una delicata fase di cambiamento del sistema partitico italiano

Assessment of body composition in health and disease using bioelectrical impedance analysis (bia) and dual energy x-ray absorptiometry (dxa): A critical overview

The measurement of body composition (BC) represents a valuable tool to assess nutritional status in health and disease. The most used methods to evaluate BC in the clinical practice are based on bicompartment models and measure, directly or indirectly, fat mass (FM) and fat-free mass (FFM). Bioelectrical impedance analysis (BIA) and dual energy X-ray absorptiometry (DXA) (nowadays considered as the reference technique in clinical practice) are extensively used in epidemiological (mainly BIA) and clinical (mainly DXA) settings to evaluate BC. DXA is primarily used for the measurements of bone mineral content (BMC) and density to assess bone health and diagnose osteoporosis in defined anatomical regions (femur and spine). However, total body DXA scans are used to derive a three-compartment BC model, including BMC, FM, and FFM. Both these methods feature some limitations: the accuracy of BIA measurements is reduced when specific predictive equations and standardized measurement protocols are not utilized whereas the limitations of DXA are the safety of repeated measurements (no more than two body scans per year are currently advised), cost, and technical expertise. This review aims to provide useful insights mostly into the use of BC methods in prevention and clinical practice (ambulatory or bedridden patients). We believe that it will stimulate a discussion on the topic and reinvigorate the crucial role of BC evaluation in diagnostic and clinical investigation protocols

Ageing test of the ATLAS RPCs at X5-GIF

An ageing test of three ATLAS production RPC stations is in course at X5-GIF, the CERN irradiation facility. The chamber efficiencies are monitored using cosmic rays triggered by a scintillator hodoscope. Higher statistics measurements are made when the X5 muon beam is available. We report here the measurements of the efficiency versus operating voltage at different source intensities, up to a maximum counting rate of about 700Hz/cm^2. We describe the performance of the chambers during the test up to an overall ageing of 4 ATLAS equivalent years corresponding to an integrated charge of 0.12C/cm^2, including a safety factor of 5.Comment: 4 pages. Presented at the VII Workshop on Resistive Plate Chambers and Related Detectors; Clermont-Ferrand October 20th-22nd, 200

ATLAS RPC Cosmic Ray Teststand at INFN Lecce

We describe the design and functionality of the cosmic ray teststand built at INFN Lecce for ATLAS RPC quality control assurance.Comment: XXIV Physics in Collisions Conference (PIC04), Boston, USA, June 2004, 3 pages, LaTex, 2 eps figures. MONP0

The Air Microwave Yield (AMY) experiment - A laboratory measurement of the microwave emission from extensive air showers

The AMY experiment aims to measure the microwave bremsstrahlung radiation (MBR) emitted by air-showers secondary electrons accelerating in collisions with neutral molecules of the atmosphere. The measurements are performed using a beam of 510 MeV electrons at the Beam Test Facility (BTF) of Frascati INFN National Laboratories. The goal of the AMY experiment is to measure in laboratory conditions the yield and the spectrum of the GHz emission in the frequency range between 1 and 20 GHz. The final purpose is to characterise the process to be used in a next generation detectors of ultra-high energy cosmic rays. A description of the experimental setup and the first results are presented.Comment: 3 pages -- EPS-HEP'13 European Physical Society Conference on High Energy Physics (July, 18-24, 2013) at Stockholm, Swede

Effect of a Short-Course Treatment with Synbiotics on Plasma p-Cresol Concentration in Kidney Transplant Recipients.

We evaluated whether a short-term course with synbiotics may lower plasma p-Cresol concentrations in kidney transplant patients (KTRs) who accumulate this uremic toxin both because of increased production by their dysbiotic gut microbiome and because of reduced elimination by the transplanted kidneys. METHODS: Thirty-six KTRs (29 males, mean age 49.6 ± 9.1 years) with transplant vintage > 12 months, stable graft function, and no episode of acute rejection or infection in the last 3 months were enrolled in this single-center, parallel-group, double-blinded, randomized (2:1 synbiotic to placebo) study. Synbiotic (Probinul Neutro, CadiGroup, Rome, Italy) or placebo was taken at home for 30 days, as 5 g powder packets dissolved in water three times a day far from meals. The main outcome measure was the decrease in total plasma p-Cresol measured by high-performance liquid chromatography at baseline and after 15 and 30 days of placebo or synbiotic treatment. RESULTS: After 15 and 30 days of treatment, plasma p-Cresol decreased by 40% and 33% from baseline (both p < 0.05), respectively, in the synbiotic group, whereas it remained stable in the placebo group. After 30 days of treatment, no significant change was observed in either group in renal function, glycemia, plasma lipids, or albumin concentration. Treatment was well tolerated and did not induce any change in stool characteristics. CONCLUSION: The results of this pilot study suggest that treatment with synbiotics may be effective to lower plasma p-Cresol concentrations in KTRs. Prospective larger scale, longer term studies are needed to establish whether cardiovascular prognosis could also be improved with this nutritional intervention