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Today, allogeneic stem cell transplantation (allo-SCT) can be offered to patients up to age 70 to 72 years and represents one of the most effective curative treatments for many hematologic malignancies. The primary objective of the study was to collect data from the allo-SCTs performed in Italy between 2000 and 2017 in patients aged ≥60 years to evaluate the changes in safety and efficacy outcomes, as well as their distribution and characteristics over time. The Italian Group for Bone Marrow Transplantation, Hematopoietic Stem Cells and Cell Therapy (GITMO) AlloEld study (ClinicalTrials.gov identifier NCT04469985) is a retrospective analysis of allo-SCTs performed at 30 Italian transplantation centers in older patients (age ≥60 years) between 2000 and 2017 (n = 1996). For the purpose of this analysis, patients were grouped into 3 time periods: time A, 2000 to 2005 (n = 256; 12%); time B, 2006 to 2011 (n = 584; 29%); and time C, 2012 to 2017 (n = 1156; 59%). After a median follow-up of 5.6 years, the 5-year nonrelapse mortality (NRM) remained stable (time A, 32.8%; time B, 36.2%; and time C, 35.0%; P = .5), overall survival improved (time A, 28.4%; time B, 31.8%; and time C, 37.3%; P = .012), and the cumulative incidence of relapse was reduced (time A, 45.3%; time B, 38.2%; time C, 30.0%; P < .0001). The 2-year incidence of extensive chronic graft-versus-host disease was reduced significantly (time A, 17.2%; time B, 15.8%; time C, 12.2%; P = .004). Considering times A and B together (2000 to 2011), the 2-year NRM was positively correlated with the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score; NRM was 25.2% in patients with an HCT-CI score of 0, 33.9% in those with a score of 1 or 2, and 36.1% in those with a score of 3 (P < .001). However, after 2012, the HCT-CI score was not significantly predictive of NRM. This study shows that the transplantation procedure in elderly patients became more effective over time. Relapse incidence remains the major problem, and strategies to prevent it are currently under investigation (eg, post-transplantation maintenance). The selection of patients aged ≥60 could be improved by combining HCT-CI and frailty assessment to better predict NRM.

The paper describes an approach to model soot formation/oxidation in non premixed turbulent flames, which in particular accounts for the effect of gas-phase carbon depletion due to sooting. The effect is relevant to combustion chambers fed with oxygen (rather than air), operating at high pressure and overall rich, such as rocket chambers. A scaled gas-phase elemental carbon mass fraction is introduced to this end and, in the framework of a laminar flamelet approach, a library is developed for use in turbulent combustion models. Due to the lack of reference data for rocket chambers conditions, the library is limited for the time being to nonpremixed methane/air flames at two values of pressure, 1 atm and 3 atm, for which experimental data are available. Results indicate a signicant effect of carbon depletion on the concentration of soot precursor acetylene in particular, and on the ensuing soot nucleation rate. The model is shown to correctly capture the decrease of the latter rate with gas-phase carbon depletion, thereby potentially enabling to extend the range of applicability of semi-empirical soot prediction models for nonpremixed turbulent combustion.

The LHCb experiment at CERN will have an on-line trigger farm composed of up to 2000 PCs. In order to monitor and control each PC and to supervise the overall status of the farm, a farm monitoring and control system (FMC) was developed. The FMC is based on distributed information management (DIM) system as network communication layer, it is accessible both through a command line interface and through the Prozeszligvisualisierungs und Steuerungssystem (PVSS) graphical interface, and it is interfaced to the finite state machine (FSM) of the LHCb experiment control system (ECS) in order to manage anomalous farm conditions. The FMC is an integral part of the ECS, which is in charge of monitoring and controlling all on-line components; it uses the same tools (DIM, PVSS, FSM, etc.) to guarantee its complete integration and a coherent look and feel throughout the whole control system.

Autologous stem cell transplantation is still a valid option in good- and intermediate-risk AML: a GITMO survey on 809 patients autografted in first complete remission

In this contribution we propose a numerical and experimental verification of a high power amplifier operating in the V-UHF (Very-Ultra High Frequency) regime. The designed amplifier has a push-pull configuration without negative feedback network in order to have low-distortion using high-level of AM (Amplitude Modulation). It is shown from the numerical and experimental results that the amplifier exhibits an output power of more than 100W CW (Continuous Waveform) and 200W PEP (Peak Envelope Power) over the entire frequency band from 30 to 512MHz. The amplifier can find application in military communication systems.

Background: diagnosis and onset prediction of Graft-versus-host disease (GvHD) after hematopoietic stem cell transplantation (HSCT) as well as therapy monitoring is still an open issue. Aim: to evaluate the role of FDG PET for the assessment of GvHD in patients after HSCT. Methods: we retrospectively studied patients with malignant lymphoma and multiple myeloma who underwent FDG PET between 2004 and 2009. We included patients who underwent HSCT and performed PET scan before transplant and at least three follow up PET scans. Overall 36 patients (8 non-Hodgkin lymphoma, 20 Hodgkin's disease, 8 multiple myeloma) were included. GvHD diagnosis was based on clinical data and, when available, on biopsy results. PET scans were evaluated by two experienced nuclear medicine physicians unaware of clinical data: findings of scans acquired at the time of GvHD clinical manifestation were compared with scans obtained before transplant and with scans during clinical remission, as well as with PET scans carried out in patients without GvHD. Results: overall 25/36 patients developed GvHD (22 acute, 9 chronic) while 11 remained GvHD clinically-free during the time of follow up. In 8/25 patients one or more PET scans were performed during clinical GvHD, and PET was positive in 8/8 cases. Pathological FDG uptake was evident at intestinal and/or liver and/or mouth level. Intestinal GvHD was clinically observed in 6/8 patients. PET corresponding images showed intense uptake in the bowel in comparison to the scans obtained in the same patients in the GvHD clinically-free period. A strong decrease in bowel FDG uptake was observed in patients responding to therapy. In 2 cases in which liver GvHD was pathologically confirmed, PET was positive in one case. Among 6 patients with mouth GvHD, only 1 showed intense FDG uptake as compared to scans obtained in the GvHD clinically-free group. Among the 11 patients who did not develop GvHD clinical manifestation, only one showed a faint intestinal FDG uptake. Overall considering sites of documented GvHD, PET was true positive in all cases presenting intestinal GvHD (6), false negative at liver in 1/2 cases, false negative at mouth in 5/6 cases and false positive in 1 patient not presenting GvHD. Conclusion: our preliminary data show that together with clinical findings, FDG PET could be useful in diagnosing and monitoring GvHD, especially at bowel level.

Summary Background Allergic rhinitis and asthma comorbidity is supported by both the similar underlying pathogenesis and immunologic mechanisms. The aim of this study was to verify whether the characteristics of rhinitis classified according to the new Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines correlate with the prevalence of asthma. Methods From 1 March to 30 June 2002, a multi-centre cross-sectional study was conducted by 154 allergists chosen from throughout Italy. Duration, severity of rhinitis (according to the ARIA classification) and the type of allergic sensitizations were compared with the prevalence of asthma. Results One thousand three hundred and twenty-one consecutive rhinitis-allergic patients aged 18 years or older were enrolled for the study. The majority of patients, 1060 (80.24%), were on medication at the time of their specialist visit. Mild intermittent rhinitis was diagnosed in 7.7% of patients, moderate/severe intermittent in 17.1%, mild persistent in 11.6%, and moderate/severe persistent in 63.6%. The prevalence of asthma was 48% in patients with mild intermittent rhinitis, 49.6% in moderate–severe intermittent rhinitis, 36.6% in mild persistent rhinitis and 47.5% in moderate severe persistent patients. No correlation between the ARIA categories of rhinitis and the prevalence of asthma was found. A multivariate analysis, after adjustment for age, sex, type of sensitization, level of severity and duration of rhinitis classified according to the ARIA guidelines, demonstrated that age, over 41 years [risk ratio (RR) 1.260, 95% confidence interval (CI) 1.072–1.482] and especially over 51 years (RR 1.460, 95% CI 1.237–1.723), sensitization to indoor allergens (mite and cat), (RR 1.203, 95% CI 1.060–1.366), and polysensitization (RR 1.178, 95% CI 1.004–1.383) are significant risk factors for asthma. Conclusion In allergic rhinitis (AR) patients referred to a specialist, the features of AR as defined by the ARIA classification are not able to predict the presence of asthma, therefore all such patients should be assessed for asthma.

Based on the knowledge of the living conditions and habitat of social Aculeatae a series of recommendations have been formulated which can potentially greatly minimize the risk of field re-sting. After a systemic sting reaction, patients should be referred to an allergy specialist for evaluation of their allergy, and if necessary venom immunotherapy (VIT). An emergency medical kit should be supplied, its use clearly demonstrated and repeatedly practised until perfected. This should be done under the supervision of a doctor or a trained nurse. Epinephrine by intramuscular injection is regarded as the treatment of choice for acute anaphylaxis. H1-antihistamines alone or in combination with corticosteroids may be effective in mild to moderate reactions confined to the skin and may support the value of treatment with epinephrine in full-blown anaphylaxis. Up to 75% of the patients with a history of systemic anaphylactic sting reaction develop systemic symptoms once again when re-stung. Venom immunotherapy is a highly effective treatment for individuals with a history of systemic reaction and who have specific IgE to venom allergens. The efficacy of VIT in yellow jacket venom allergic patients has been demonstrated also by assessing health-related quality of life. If both skin tests and serum venom specific IgE turn negative, VIT may be stopped after 3 years. After VIT lasting 3-5 years, most patients with mild to moderate anaphylactic symptoms remain protected following discontinuation of VIT even with positive skin tests. Longer term or lifelong treatment should be considered in high-risk patients. Because of the small but relevant risk of re-sting reactions, in these patients, emergency kits, including epinephrine auto-injectors, should be discussed with every patient when stopping VIT.

The purpose of diagnostic procedure is to classify a sting reaction by history, identify the underlying pathogenetic mechanism, and identify the offending insect. Diagnosis of Hymenoptera venom allergy thus forms the basis for the treatment. In the central and northern Europe vespid (mainly Vespula spp.) and honeybee stings are the most prevalent, whereas in the Mediterranean area stings from Polistes and Vespula are more frequent than honeybee stings; bumblebee stings are rare throughout Europe and more of an occupational hazard. Several major allergens, usually glycoproteins with a molecular weight of 10-50 kDa, have been identified in venoms of bees, vespids. and ants. The sequences and structures of the majority of venom allergens have been determined and several have been expressed in recombinant form. A particular problem in the field of cross-reactivity are specific immunoglobulin E (IgE) antibodies directed against carbohydrate epitopes, which may induce multiple positive test results (skin test, in vitro tests) of still unknown clinical significance. Venom hypersensitivity may be mediated by immunologic mechanisms (IgE-mediated or non-IgE-mediated venom allergy) but also by nonimmunologic mechanisms. Reactions to Hymenoptera stings are classified into normal local reactions, large local reactions, systemic toxic reactions, systemic anaphylactic reactions, and unusual reactions. For most venom-allergic patients an anaphylactic reaction after a sting is very traumatic event, resulting in an altered health-related quality of life. Risk factors influencing the outcome of an anaphylactic reaction include the time interval between stings, the number of stings, the severity of the preceding reaction, age, cardiovascular diseases and drug intake, insect type, elevated serum tryptase, and mastocytosis. Diagnostic tests should be carried out in all patients with a history of a systemic sting reaction to detect sensitization. They are not recommended in subjects with a history of large local reaction or no history of a systemic reaction. Testing comprises skin tests with Hymenoptera venoms and analysis of the serum for Hymenoptera venom-specific IgE. Stepwise skin testing with incremental venom concentrations is recommended. If diagnostic tests are negative they should be repeated several weeks later. Serum tryptase should be analyzed in patients with a history of a severe sting reaction.

The most recent clinical trials on adult acute lymphoid leukaemia (ALL) have shown complete remission and disease-free survival (DFS) rates of 80-85% and 30-40%, respectively (Annino, et al, Durrant, et al, Kantarjian, et al, Larson, et al, Ribera, et al, Rowe). Intensified consolidation, particularly with high-dose methotrexate and high-dose cytarabine, may be one of the reasons for the improved outcome in recent series (Bassan and Hoelzer, Hoelzer and Gokbuget, Kebriaei and Larson). In addition, risk-adapted and subtype-oriented therapy may have contributed to this better outcome. However, the long term outcome of adult patients is still dismal, with approximately one third of the cases only being cured. At present, therapeutic options include conventional chemotherapy (CHT), high dose therapy with autologous and, especially, allogeneic stem cells transplantation (SCT) and, for certain subsets, such as BCR-ABL1+ ALL, specific targeted therapy (Piccaluga, et al). Although SCT has been used in adult ALL for more than 20 years, its role remains controversial as demonstrated by conflicting results in various studies. Previous casecontrolled studies did not show that allogeneic SCT (alloSCT) provided any advantage over CHT (Horowitz, et al, Zhang, et al) while in some studies there was an advantage, but restricted to young adults (Oh, et al). The number of controlled published or ongoing trials is remarkably small and some of them did not include both standard-risk and high-risk patients. Thus, it is difficult to draw definitive conclusions from their results. In fact, while some authors did not report any differences between alloSCT and chemotherapy or autologous SCT (ASCT)(Gupta, et al, Labar, et al), others only found differences favouring allogeneic SCT in standard risk (Goldstone, et al) or high-risk ALL patients (Sebban, et al, Thiebaut, et al, Thomas, et al). In this chapter, the Authors reviewed data concerning alloSCT in adult ALL and discuss current controversial and possible perspectives.

The development of component-resolved diagnostics constitutes a potential breakthrough in food allergy testing, as detection of specific IgE (sIgE) to individual allergens may make it possible to establish the risk of a mild versus severe reaction.To compare allergists' risk assessment based on the current decision making process with that of virtual allergen-oriented risk assessment through microarray-based immunoassay.An observational, real-life study was performed on 86 adults with food allergy. The prescription of epinephrine was the surrogate marker of a severe reaction. In the same patients, the prescription of epinephrine based on the current decision making of the allergist and the independently established allergen-oriented risk assessment determined by microarray-based immunoassay were compared.Fair degree of agreement between the specialists' risk assessment and that of the microarray-based immunoassay (k index 0.372 (95% CI: 0.185- 0.559) p0.001) was documented. Three causes of discrepancy emerged: the poor sensitivity of the allergen microarray-immunoassay (51.9%), the differences in risk assessment established by the specialist and the microarray-immunoassay (33.3%), the non-inclusion of the causative allergen in the microarray-immunoassay platform (14.8%).Improvement of the diagnostic accuracy of microarray-immunoassay, combined with marrying its results to clinical information, could one day soon lead to changes in clinical practice in food allergy.

Database replication is a key topic in the framework of the LHC Computing Grid to allow processing of data in a distributed environment. In particular, the LHCb computing model relies on the LHC File Catalog, i.e. a database which stores information about files spread across the GRID, their logical names and the physical locations of all the replicas. The LHCb computing model requires the LFC to be replicated at Tier-1s. The LCG 3D project deals with the database replication issue and provides a replication service based on Oracle Streams technology. This paper describes the deployment of the LHC File Catalog replication to the INFN National Center for Telematics and Informatics (CNAF) and to other LHCb Tier-1 sites. We performed stress tests designed to evaluate any delay in the propagation of the streams and the scalability of the system. The tests show the robustness of the replica implementation with performance going much beyond the LHCb requirements.

Fluticasone propionate aqueous nasal spray (FPANS) is a topically active glucocorticoid which has been successfully used for the treatment of seasonal allergic rhinitis (SAR). Topical levocabastine is a highly selective H1 antagonist which has been proposed as an alternative treatment of SAR. The purpose of this study was to compare the clinical efficacy of two topical nasal treatments, FPANS and levocabastine, in the treatment of SAR. Additionally, the effect of treatments on nasal inflammation was examined during natural pollen exposure. A group of 288 adolescent and adult patients with at least a 2-year history of SAR to seasonal pollens participated in a multicenter, doubleblind, double-dummy, and placebo-controlled study. Patients were treated with either FPANS 200 microg, once daily (n = 97), or topical levocabastine, 200 microg, given twice daily (n = 96), or matched placebo (n = 95) for a period of 6 weeks, starting from the expected beginning of the pollen season. Clinically relevant pollens included Parietaria, olive, and grass. Assessment of efficacy was based on scores of daily nasal symptoms and on nasal cytology of nasal lavage. Nasal lavage was performed immediately before, during, and at the end of treatment in 39 patients. FPANS significantly increased the percentage of symptom-free days for nasal obstruction on waking and during the day, rhinorrhea, sneezing, and itching. FPANS provided a better control for night and day nasal obstruction (P

The prevalence of sensitization to cockroach (CR) was evaluated by skin prick test (SPT) in 1299 patients consecutively referred for rhinitis and asthma to five allergy centers in northern, central, and southern Italy. In patients with positive SPT to CR, an SPT with D. pteronyssinus extract was made. RAST inhibition was performed with pooled sera of subjects with positive SPT and RAST of at least Class 3 for CR and D. Pteronyssinus, to assess the cross-reactivity between these two allergenic sources. The protein content of allergen extracts was assayed by isoelectric focusing (IEF). A total of 170 patients (13%) had a positive SPT with CR extract, and 133 of them (78.2%) were also positive for D. pteronyssinus. RAST inhibition showed a cross-reactivity between CR and D. pteronyssinus, and IEF detected in the extracts employed a series of bands focusing at the same pI of CR and D. pteronyssinus relevant allergens. Therefore, the prevalence of sensitization to CR in the population studied, corresponding to 13%, suggests that CR extract might be added to standard SPT panels for respiratory allergy. However, the cross-reactivity with D. pteronyssinus calls for careful evaluation of the clinical importance of this sensitization.

A group of 28 patients from Italy was studied who had asthma after consumption of snail. All patients also had asthma and/or rhinitis caused by house-dust mite. RAST analyses confirmed the combined sensitization to snail and mite. In a few sera, IgE antibodies reactive with other foods of invertebrate origin (mussel and shrimp) were detected. RAST inhibition showed that most IgE antibodies against snail were cross-reactive with house-dust mite. In contrast, the mite RAST was not significantly inhibited by snail. This indicates that house-dust mite was the sensitizing agent. Immunoblot analyses revealed multiple bands in snail extract recognized by IgE. In contrast to what has been described for cross-reactivity between shrimp and mite, tropomyosin played only a minor role as a cross-reactive allergen in these patients. The observations in this study indicate that snail consumption can cause severe asthmatic symptoms in house-dust-mite-allergic patients. It might, therefore, be advisable to screen mite-allergic asthma patients for allergy to snail and other invertebrate animal foods.

Sera of 17 patients receiving immunotherapy for house-dust mite allergy were tested for IgE antibodies against snail and shrimp. Serum samples were taken at the start of immunotherapy and 14-20 months later. While the average IgE response to mite, Der p 1, and Der p 2 did not alter significantly, the average response to snail showed a significant increase. This included two conversions from negative to strongly positive. These novel IgE antibodies against snail were shown to be cross-reactive with mite. Three patients had a positive RAST for shrimp. For one of them, a strong increase of IgE against shrimp (and snail) was observed. In 2/3 snail/shrimp-positive sera, IgE antibodies against the cross-reactive allergen tropomyosin from mite, snail, and shrimp were demonstrated. A clear IgE response to snail (> 10% binding in a snail RAST) was confirmed by a positive skin prick test (SPT) for 6/10 patients. The two patients with antitropomyosin IgE also had a positive SPT for shrimp, and demonstrated the oral allergy syndrome (OAS) after eating shrimp. The observations in this study indicate that house-dust mite immunotherapy is accompanied by the induction of IgE against foods, including tropomyosin-reactive IgE. Food allergy (OAS) was observed in patients that had IgE antibodies against this cross-reactive allergen. In conclusion, induction of IgE during mite immunotherapy might occasionally cause allergy to foods of invertebrate animal origin.

The paper describes an approach to model soot formation/oxidation in non premixed turbulent flames, which in particular accounts for the effect of gas-phase carbon depletion due to sooting. The effect is relevant to combustion chambers fed with oxygen (rather than air), operating at high pressure and overall rich, such as rocket chambers. A scaled gas-phase elemental carbon mass fraction is introduced to this end and, in the framework of a laminar flamelet approach, a library is developed for use in turbulent combustion models. Due to the lack of reference data for rocket chambers conditions, the library is limited for the time being to nonpremixed methane/air flames at two values of pressure, 1 atm and 3 atm, for which experimental data are available. Results indicate a signicant effect of carbon depletion on the concentration of soot precursor acetylene in particular, and on the ensuing soot nucleation rate. The model is shown to correctly capture the decrease of the latter rate with gas-phase carbon depletion, thereby potentially enabling to extend the range of applicability of semi-empirical soot prediction models for nonpremixed turbulent combustion.

The aim of this review article is to provide greater insight into the relationship between allergic rhinitis and the three most frequently diagnosed conditions of exacerbating viral infections, chronic rhinosinusitis with polyps and obstructive sleep apnoea syndrome. The alleged physiopathological effects of steroids are also investigated within the scope of this paper. Regarding the exacerbating viral infections, seems to establish a dynamic and counter relationship between the load and nature of the viral infection on one hand and widespread and pre-existing allergic inflammation on the other. If chronic rhinosinusitis with polyps and allergic rhinitis present overlapping picture of inflammatory cell and cytokine, the etyiological relationship between the two conditions appears to be influenced by the type of antigenic stimulus. Allergic rhinitis can influence the presence of OSAS through both obstructive and inflammatory mechanical factors. Topical corticosteroid therapy is a promising candidate as a new therapeutic tool able to improve symptoms and quality of life in patient with chronic rhinosinusitis with polyps and obstructive sleep apnoea syndrome. Other study are necessary to elucidate relationship between corticosteroids therapy and hypothetical benefit effect on viral infection when concomitant atopy inpatient.

Hymenoptera stings can cause severe systemic allergic reactions and occasionally fatal anaphylaxis, which contribute significantly to morbidity and deterioration in health-related quality of life. The latest epidemiological data confirm the importance of insect sting allergy as a cause of anaphylaxis. Despite the high prevalence of asymptomatic sensitization, the prevalence of sting-induced systemic reactions (SRs) is low. However, to date, no parameter has been identified that can predict who will have a future reaction and whether it will be a large local reaction or anaphylactic. The combination of several concomitant factors, which include environmental, genetics and individual factors, may account for the occurrence of a system reaction in individual patients. Several not completely known factors may be associated with the severity of systemic re-stings. As about 50% of subjects with fatal sting reactions had no documented history of a previous SR, greater insight of the natural history and risk factors is required, especially in asymptomatic sensitized subjects. For patients with SRs, prevention of future severe allergic reactions starts with referral to an emergency department, correct administration of epinephrine by medical staff, referral to an allergist and coaching for the self-administration of epinephrine. However, most insect sting victims failed to seek medical advice and hospital attendance does not always correlate with the severity of the allergic reaction. Moreover, only about one-third of patients received a prescription for self-injectable epinephrine and were officially referred to an allergist after being discharged, causing the non- or delayed prescription of specific immunotherapy. Significantly, this means that at least half of the sting fatalities in patients with a positive history could have been avoided through the timely administration of specific immunotherapy. These findings indicate the urgent need to educate the general population and doctors on the management of venom-allergic patients.

The role of genetic and environmental factors, as well as their interaction, in the natural history of asthma, allergic rhinitis and chronic obstructive pulmonary disease (COPD) is largely unknown. This is mainly due to the lack of large-scale analytical epidemiological/genetic studies aimed at investigating these 3 respiratory conditions simultaneously. The GEIRD project is a collaborative initiative designed to collect information on biomarkers of inflammation and oxidative stress, individual and ecological exposures, diet, early-life factors, smoking habits, genetic traits and medication use in large and accurately defined series of asthma, allergic rhinitis and COPD phenotypes. It is a population-based multicase-control design, where cases and controls are identified through a 2-stage screening process (postal questionnaire and clinical examination) in pre-existing cohorts or new samples of subjects. It is aimed at elucidating the role that modifiable and genetic factors play in the occurrence, persistence, severity and control of inflammatory airway diseases, by way of the establishment of a historical multicentre standardized databank of phenotypes, contributed by and openly available to international epidemiologists. Researchers conducting population-based surveys with standardized methods may contribute to the public-domain case-control database, and use the resulting increased power to answer their own scientific questions.

In medical endoscopy, quantifying anatomical dimensions would be of great help, but the appropriate tools are not yet available. We present a novel method for the calibration and size measurement of endoscopic images. We realized an optical sensor, based on Fiber Optic Low Coherence Interferometry (FOLCI), capable of measuring the absolute distance between the tip of an endoscopic probe and an anatomical object under inspection. We showed that this sensor provides very sensitive and accurate (error lower than 0.1 mm) measurements of biological samples. The sensing fiber of the sensor was introduced in the operative channel of an Olympus rhinoscope. After calibrating the endoscope magnification system as a function of the distance, our system was capable of providing the size of any object included in the field of view of the endoscope. Tests performed on planar targets and pig trachea showed the accuracy of the system to be adequate for allowing quantitative dimensional information.

Introduction: The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines provide a stepwise treatment to rhinitis, which classifies the disease according to its duration and severity. Objectives: The aim of the study was to verify whether these variables influence drug prescriptions for rhinitis and asthma. Methods: A multi-centre cross-sectional pharmaco-epidemiological survey was carried out on 1610 allergic rhinitis patients and the relationship between the clinical features of rhinitis and drug therapy for rhinitis and asthma was evaluated. Results: A total of 1321 adult patients were enrolled. Mild intermittent rhinitis was diagnosed in 7.7%of the patients, moderate/severe intermittent in 17.1%, mild persistent in 11.6%, and moderate/severe persistent in 63.6%. A high level of rhinitis-asthma comorbidity (616/1321 = 46.6%) was found. The majority of patients [1060 (80.24%)] were treated. Significant associations between the severity of rhinitis and the presence of therapy (P = 0.008), the use of oral antihistamines (P

The LHCb experiment at CERN will have an on-line trigger farm composed of up to 2000 PCs. In order to monitor and control each PC and to supervise the overall status of the farm, a Farm Monitoring and Control (FMC) application was developped. The FMC is based on DIM(*) and is accessible both through a command line interface and through a PVSS graphical interface. The FMC consists of a Logger, to collect the application messages (which can work either in no-drop or in congestion-proof mode, with filter and duplicate suppression capability), an IPMI Power Manager to switch on/off the farm nodes and monitor physical parameters, a Task Manager to start/stop processes (able to manage real-time schedulers, to real-time notify a process termination and to redirect application stdout/stderr to the FMC logger), a Process Controller to manage automatic process respawn and a detailed but light-weight Monitoring system. The FMC is an integral part of LHCb's Experiment Control System, in charge of monitoring and controlling all online components: it uses the same tools (DIM, PVSS, FSM, etc.) to guarantee its complete integration and a coherent look and feel throughout the control system.

The loss of sensitization over time, the involvement of a different pathogenetic mechanism and the poor sensitivity of diagnostic tests have been included among the causes of a non IgE-mediated anaphylaxis triggered by an insect sting. To provide further insight into this topic we describe the case of a patient suffering from urticaria pigmentosa, anaphylactic shock due to a Vespid sting and monosensitive to Polistes dominulus venom, who was previous diagnosed with non-IgE mediated insect sting anaphylaxis in subjects with urticaria pigmentosa. Therefore ultra-rush specific immunotherapy using an acqueous Polistes dominulus venom extract was performed over two mornings until a total dose of 100mcg was reached without any side effects. Presently the patient is undergoing maintenance therapy with a depot Polistes dominulus venom extract at 4-weekly intervals and is free of side effects. In conclusion, despite the high cross-reactivity among the venoms of the various species of Polistes, recent evidence of a selective specificity unique to European Polistes allergens raises the problem of the need to make the American Polistes venom as well as that of Polistes dominulus (a very common insect in Europe) available both for diagnostic and therapeutic purposes. Besides the fact that the presence of urticaria pigmentosa alone could have explained the anaphylactic reaction to the aspecific stimulation triggered by the venom, this case history also demonstrates that omitting to perform skin tests for Polistes dominulus venom would have led to the same misdiagnosis of non IgE-mediated anaphylaxis and served only to further delay commencing specific immunotherapy.

We describe a case of intraoperative gelatine-induced anaphylaxis whose diagnosis was delayed as the use of gelatine during surgical procedures was omitted for two times in patient's medical records. The subject is a 66-year old woman, with a negative medical history of atopy, food and drug allergy, with arterial hypertension on a course of beta-blockers and with bladder carcinoma requiring surgery. The patient had tolerated both general and local anaesthesia on several previous occasions. On the first occasion she experienced arterial fibrillation secondary to a severe episode of hypotension following local anaesthesia, while on a course of beta-blockers. On the second occasion she developed a very severe episode of hypotension followed by the outbreak of a generalised rash during general anaesthesia. The tryptase sera level was 109 mg/L one hour after the reaction had subsided, while the basal values were normal. On the third occasion the patient redeveloped severe hypotension and a generalised rash during general anaesthesia. The allergological work-up was negative, except for intradermal test with gelatine. A study of the intra-cellular cytokines in blood lymphocytes showed a production of IL4 from CD4+ lymphocytes after stimulation by gelatine. The patient underwent a successive surgical procedure without any adverse event.

Background: The presence of anti-FceRI and anti-IgE autoantibodies in a subset of patients with chronic urticaria suggests their aetiopathogenetic role. In clinical practice, the presence of these antibodies is usually considered when the autologous serum skin test (ASST) is positive. Aims: To evaluate if the positive ASST follows up the activity of chronic urticaria. Methods: Autologous serum skin test and thyroid autoantibody detection were performed in 82 patients with chronic urticaria and repeated 1 year later, when the vast majority of patients were symptom-free. Twenty patients with Hashimoto thyroiditis (HT), who had never suffered from urticaria, represented the control group. Results: At the start of the study, the prevalence of positive ASST was 46.6%. The association of HT–urticaria was 29.3%. ASST was positive in 62 and 39% of patients with and without HT, respectively (P > 0.05 ns). One year later, 28 of 34 patients with a positive ASST were symptom-free, but 50% of them were positive for ASST. The ASST was positive in 86.7 and 8% of patients with and without HT, respectively (P

Ninety ET patients diagnosed according to the PVSG criteria entered a phase II study designed to identify a treatment with PEG Interferon α-2b (PEG Intron, Schering-Plough Corp) safe and able to obtain and to maintain for a long time the Hematological Response (HR, PLTs < 500x 109/L). The patients, 30 Males and 60 Females, median age 45 years (18–72), judged at risk and in the majority of cases pre-treated with cytoreductive drugs (60%), at study entry showed a mean PLT count of 1093 ± 357 x 109/L (>1000 in 49% of cases). During the first year (part 1 of the study) the PEG Intron starting dose of 25 μg/week was gradually increased if necessary at week 13, 26 and 39 till a maximum of 100 μg/week to reach the HR. The HR at the end of the 1st year (primary endpoint) was registered in 64 patients who represented the 71% of the 90 enrolled subjects (analysis on Intent-to-Treat, ITT) and the 79% of the 81 patients still receiving PEG Intron. The PEG Intron effective dose had a mean value of 50 ± 22 μg/week resulting very low (25μg/week) in 33% of cases. The primary endpoint was reached independently by sex, age, cytoreductive pre-treatment and baseline PLT count. Nevertheless, the HR was more frequent in the patients with true ET respect those with false ET (WHO criteria, HR 93% vs. 68%). In the 64 responder patients admitted to the part 2 of the study according to the protocol, the HR at the end of the 2nd year was registered in 75% of cases on ITT and in 87% of the 55 patients still on treatment, with a PEG Intron maintenance dose gradually reduced to a mean level of 27 μg/week. No thrombotic or hemorrhagic events occurred during the study and, moreover, a decrease of splenomegaly (from 22% to 6%) and of disease related symptoms (from 42% to 2%) was registered. The unmaintained HR, in 29 valuable patients who discontinued the PEG Intron treatment after two years, had a median duration of 11 weeks (4–52). Eighteen patients discontinued PEG Intron treatment (9 during the 1st year and 9 during the 2nd year) as consequence of PEG Intron toxicity and side effects (n 7), loss of compliance (n 5) and drug unrelated reasons (n 6). Toxicity and side effects (WHO grading) were never of grade 4, in very few cases of grade 3 and in the majority of patients of grade 1 or 2 (mainly flu-like syndrome, leukopenia, hypertransaminasemia). The ECOG Performance status (PS) was of grade 0 in all but few patients who showed a transitory grade 1 PS. In conclusion, PEG Intron treatment performed at relatively low dose seems safe and able to induce and to maintain the HR for a long time in the majority of at risk ET patients.

This paper examines the main features of the deliberate sting challenge with regard to the type of insect, the advantages and disadvantages of its use in untreated and treated patients and after discontinuation of specific immunotherapy.

Asthma represents a growing public health problem and the cost of asthma has been rising in many countries. The aim of this study was to estimate the direct and indirect cost of asthma among adult patients in Italy, and to assess the relationship between healthcare resource use and asthma severity according to the Global Initiative for Asthma (GINA) classification system. A multicentre cross-sectional study was conducted in 16 Italian hospital-based specialised asthma clinics. Data collection was based on self-administered questionnaires and took place during the period May 1–November 30, 1999, and 500 consecutive patients with asthma, aged 18–55 yrs, were enrolled during regularly scheduled visits. Direct costs (drugs, physician visits, emergency service use and hospitalisation), indirect costs (loss of paid workdays) and total costs were determined in euros () for 1999. Patients with more severe disease, as classified by the GINA guideline, exhibited more night-time and daytime symptoms and were more limited in performing normal daily activities. The mean total cost of asthma per patient per year was estimated to be 1,260; drug costs accounted for 16%, physician costs 12%, emergency service and hospitalisation costs 20% and indirect costs 52% of the mean cost. Stratified by severity, the total annual cost per patient amounted to 720, 1,046, 1,535 and 3,328 for patients with intermittent, mild persistent, moderate persistent and severe persistent asthma, respectively. Asthma severity, as determined by the Global Initiative for Asthma classification, is significantly associated with symptoms, limitations in normal daily activities, asthma-related medical resource utilisation and both direct and indirect costs. Asthma control is not only a clinical but also an economic imperative. This study was supported by a grant from Merck & Co., Inc., Whitehouse Station, NJ, USA.

Severity of a previous reaction, adult age, male gender and honeybee sting are risk factors for severe systemic reactions after hymenoptera stings. The aim of the study was to assess the association between the Vespa crabro sting and severe systemic reactions.One hundred fifty seven hymenoptera allergic patients with a positive case history for systemic reactions were selected on the basis of unequivocal identification of the stinging insect. In 97 patients the culprit insect was Vespula spp., in 35 was Vespa crabro in the remaining 25 patients was Apis mellifera. The relative risk for a life-threatening reactions after a sting was evaluated for each hymenoptera species.While the percentage of life-threatening reactions was similar both in Apis mellifera (24%) and in Vespula spp. Allergic patients groups (27.8%), a very high prevalence (81.2%) was documented in Vespa crabro allergic patients group. The relative risk for life-threatening reactions after a Vespa crabro sting was about three times higher (RR = 2.74--CI 95% 1.93-3.89--R0.0001) than it was for a honeybee or yellow jacket sting. The increase of the risk for life-threatening reactions after a Vespa crabro sting was independent from the age of patients.Vespa crabro sting seems to be a new risk factor for life-threatening reactions after hymenoptera sting.

The aim of the study was to determine whether a short interval (< 2 months) between two consecutive stings influences the development of Hymenoptera venom allergy. The study compared the sting-interval distribution in 120 allergic patients who experienced a first-time systemic reaction to a Hymenoptera sting, and in 100 healthy controls. A significant difference in sting-interval distribution between the two groups was found (P = 0.0001). In 71 of 120 allergic patients, the sting that provoked the systemic reaction had been preceded by another, completely tolerated sting not more than 2 months before. However, in the control group only four subjects out of 100 had received two consecutive stings within less than 2 months. In conclusion, a short interval between two consecutive stings seems to be a risk factor for the onset of Hymenoptera venom allergy.

Latex allergy continues to be a feature of allergy practice worldwide. In adults, the major exposure is the occupational setting, especially in relation to natural rubber latex (NRL) gloves use by health care workers (HCWs). The most concerning issue of latex allergy in HCWs is the development of occupational asthma in up to 25% or more of the affected subjects, which may not remit with personal avoidance of latex. Multiple investigators, using a variety of methodologies, have succeeded in identifying major immunoglobulin (Ig)E binding allergens; consequently, there has been an improvement in the diagnostic accuracy of NRL sensitization and allergy over the past years. Future development in this area may lead to possible therapeutic agents for sensitized patients. Preliminary studies of primary preventive strategies suggest that avoidance of high-protein, powdered gloves in health care settings can be cost-effective and is associated with a decline in sensitized workers and prevention of new sensitivities.

Understanding the relationship between upper and lower airways has greatly increased through epidemiological and pharmacological studies. Scientific evidence supports the concept that rhinosinusitis and asthma may be the expression of an inflammatory process which appears in different sites of the respiratory tract at different times. The implications are not only academic but are important for diagnostic and therapeutic purposes.

As it has been shown that alpha-interferon (alphaIFN) treatment modifies the survival of chronic myeloid leukaemia (CML) patients in comparison with conventional chemotherapy, a new prognostic score was devised with the aim of providing a treatment-adapted risk evaluation. We have tested the new prognostic score (the Euro score) in an independent series of 272 patients less than 56 years old with previously untreated, chronic phase, Philadelphia (Ph)-positive CML who had been assigned prospectively to alphaIFN treatment between 1989 and 1991. The Sokal score system was used as a reference. The new Euro score predicted the response to alphaIFN as the Sokal score. The median survival of low-risk, intermediate-risk and high-risk patients was similar using the Euro score (105, 65 and 45 months) and Sokal score (105, 76 and 45 months) but, by multivariate analysis, the Euro was more potent than Sokal for predicting survival time. The new Euro score identified more low-risk cases (59% vs. 48%) and fewer high-risk cases (9% vs. 23%) than the Sokal score. The main differences between the Euro and Sokal scores concerned age (it is more important in the Euro than in Sokal), spleen size and the percentage of myeloblasts in peripheral blood (more important in Sokal than in Euro). We conclude that the new Euro score marks an improvement in the prognostic evaluation of CML treated with alphaIFN. By comparison with the Sokal score, the Euro was more potent and identified more low-risk patients but left only a small number of cases in the high-risk group.

Fluticasone propionate aqueous nasal spray (FPANS) is a topically active glucocorticoid which has been successfully used for the treatment of seasonal allergic rhinitis (SAR). Topical levocabastine is a highly selective H1 antagonist which has been proposed as an alternative treatment of SAR. The purpose of this study was to compare the clinical efficacy of two topical nasal treatments, FPANS and levocabastine, in the treatment of SAR. Additionally, the effect of treatments on nasal inflammation was examined during natural pollen exposure. A group of 288 adolescent and adult patients with at least a 2-year history of SAR to seasonal pollens participated in a multicenter, doubleblind, double-dummy, and placebo-controlled study. Patients were treated with either FPANS 200 microg, once daily (n = 97), or topical levocabastine, 200 microg, given twice daily (n = 96), or matched placebo (n = 95) for a period of 6 weeks, starting from the expected beginning of the pollen season. Clinically relevant pollens included Parietaria, olive, and grass. Assessment of efficacy was based on scores of daily nasal symptoms and on nasal cytology of nasal lavage. Nasal lavage was performed immediately before, during, and at the end of treatment in 39 patients. FPANS significantly increased the percentage of symptom-free days for nasal obstruction on waking and during the day, rhinorrhea, sneezing, and itching. FPANS provided a better control for night and day nasal obstruction (P0.02 and P0.01) and rhinorrhea (P0.01) than levocabas tine. In addition, fewer patients treated with FPANS used rescue medication (P0.025). The percentage of eosinophils in nasal lavage was reduced only during treatment with FPANS. The results of this study indicate that FPANS 200 microg, once daily, provides a better clinical effect than levocabastine 200 microg, twice daily, in patients with SAR. Unlike levocabastine, FPANS significantly attenuates nasal eosinophilia during pollen exposure, a feature which may explain its therapeutic efficacy.

Rhinitis is defined as nasal congestion, sneezing, itching and rhinorrhoea, recently classified as allergic, infective, structural or "other". The increasing employment of flexible rhynolaringoscopy may represent one of the most useful diagnostic tools in the complex differential diagnosis between allergic and nonallergic rhinitis. Furthermore, chronic allergic rhinitis, with secondary impairment of mucociliary clearance and the plethora of frequent anatomical variations, especially in the ostiomeatal complex, appear to predispose the patient to recurrent rhinosinusitis. In the last two decades, a better understanding of mucociliary clearance of nasal cavity and paranasal sinuses has shifted the attention from the maxillary sinuses to the area of the antherior ethmoid sinuses. Plain film radiographic examination, the historical standard, due to its inability to individualize ethmoid and sphenoid disease, is being rapidly supplanted by computed tomography and magnetic resonance imaging in the diagnosis of rhinosinusitis. In allergic and non-allergic rhinitis the diagnostic role of magnetic resonance imaging and computed tomography is still under debate. Computed tomography and magnetic resonance imaging are more efficient in demonstrating the bone wall, mucosal layer and sinus content than classical and computerized radiology; they have a higher diagnostic performance index in spite of a higher cost and, for computed tomography, a higher radiation dose.

This study was designed primarily to assess the safety and tolerability of fluticasone propionate (FP) 1 mg day-1 by comparison with beclomethasone dipropionate (BDP) 2 mg day-1 over a 12-month study period. Lung function data were also recorded and used to determine whether the potency ratio between the two inhaled corticosteroids observed in previous studies was maintained in the long-term. Two hundred and thirteen patients with an established clinical history of severe chronic asthma and who were currently receiving between 1000 micrograms and 2000 micrograms day-1 of inhaled steroids were randomized to treatment in a ratio of 3:1 for FP:BDP (159 patients FP; 54 patients BDP), both via metered dose inhalers. Both treatments were well tolerated with a similar adverse event profile. No unexpected adverse events were recorded. Most adverse events were related to the patients' asthma, an intercurrent infection or underlying atopy. The incidence of pharmacologically predictable adverse events was equally low in both treatment groups as was the incidence of events suggestive of systemic steroid effect. Mean serum cortisol levels remained within the normal range at all visits for both treatments. At 12 months, however, the mean cortisol levels for the FP group had risen 4% above the baseline value but had dropped 15% below for the BDP group, giving a ratio of FP:BDP of 1.22; P = 0.01; 95% confidence limits (CL) 1.05-1.43. Fluticasone propionate 1 mg day-1 was at least as effective as BDP 2 mg day-1 in improving lung function (PEF, FEV1 and FVC) over this period. Moreover, the difference in FEV1 values at 6 months was significantly greater for the FP group than for the BDP group (P = 0.04; difference = 0.12 1; 95% CL = 0.01, 0.24 1). The difference between treatments in the amount of FEV1 reversibility was also significantly greater for FP at 12 months (difference in treatments = -3%; 95% CL = - 7-0%; P = 0.044). This study supports previous studies and suggests that FP is likely to be of benefit in the long-term treatment of chronic severe asthma.

The authors describe a case of paradoxical bronchospasm with laryngospasm and cutaneous rash occurring in an asthmatic woman after the use, via metered-dose inhaler, of different bronchodilators containing soy-derived excipients. It is noteworthy that the patient was not affected by soy allergy. After a short review of the relevant literature, the authors consider the possible aetiopathogenetic factors and outline the importance of this rare adverse reaction in the care of asthmatic patients.

A group of 28 patients from Italy was studied who had asthma after consumption of snail. All patients also had asthma and/or rhinitis caused by house-dust mite. RAST analyses confirmed the combined sensitization to snail and mite. In a few sera, IgE antibodies reactive with other foods of invertebrate origin (mussel and shrimp) were detected. RAST inhibition showed that most IgE antibodies against snail were cross-reactive with house-dust mite. In contrast, the mite RAST was not significantly inhibited by snail. This indicates that house-dust mite was the sensitizing agent. Immunoblot analyses revealed multiple bands in snail extract recognized by IgE. In contrast to what has been described for cross-reactivity between shrimp and mite, tropomyosin played only a minor role as a cross-reactive allergen in these patients. The observations in this study indicate that snail consumption can cause severe asthmatic symptoms in house-dust-mite-allergic patients. It might, therefore, be advisable to screen mite-allergic asthma patients for allergy to snail and other invertebrate animal foods.

Sera of 17 patients receiving immunotherapy for house-dust mite allergy were tested for IgE antibodies against snail and shrimp. Serum samples were taken at the start of immunotherapy and 14-20 months later. While the average IgE response to mite, Der p 1, and Der p 2 did not alter significantly, the average response to snail showed a significant increase. This included two conversions from negative to strongly positive. These novel IgE antibodies against snail were shown to be cross-reactive with mite. Three patients had a positive RAST for shrimp. For one of them, a strong increase of IgE against shrimp (and snail) was observed. In 2/3 snail/shrimp-positive sera, IgE antibodies against the cross-reactive allergen tropomyosin from mite, snail, and shrimp were demonstrated. A clear IgE response to snail (10% binding in a snail RAST) was confirmed by a positive skin prick test (SPT) for 6/10 patients. The two patients with antitropomyosin IgE also had a positive SPT for shrimp, and demonstrated the oral allergy syndrome (OAS) after eating shrimp. The observations in this study indicate that house-dust mite immunotherapy is accompanied by the induction of IgE against foods, including tropomyosin-reactive IgE. Food allergy (OAS) was observed in patients that had IgE antibodies against this cross-reactive allergen. In conclusion, induction of IgE during mite immunotherapy might occasionally cause allergy to foods of invertebrate animal origin.