Sensitization to Gibberellin-Regulated Protein (Peamaclein) Among Italian Cypress Pollen-Sensitized Patients.

BACKGROUND AND OBJECTIVES: Peach gibberellin-regulated protein (peamaclein) has recently emerged as a relevant food allergen in cypress pollen-hypersensitive patients. Objective: We investigated monosensitization to peamaclein among Italian cypress pollen-allergic patients. MATERIAL AND METHODS: A total of 835 cypress pollen-hypersensitive patients from 28 Italian allergy centers underwent a thorough work-up to determine food-allergic reactions and performed skin prick testing with a commercial peach extract containing peamaclein. IgE to rPru p 3 was measured in peach reactors, and those with negative results were enrolled as potentially monosensitized to peamaclein. IgE reactivity to rPru p 7 was evaluated using immunoblot and an experimental ImmunoCAP with rPru p 7. RESULTS: Skin prick tests were positive to peach in 163 patients (19.5%); however, 127 (77.9%) were excluded because they reacted to Pru p 3. Twenty-four patients (14.7%) corresponding to 2.8% of the entire study population) were considered potentially monosensitized to peamaclein. No geographic preference was observed. Seventeen of the 24 patients (70.8%) had a history of food allergy, mainly to peach (n=15). Additional offending foods included other Rosaceae, citrus fruits, fig, melon, tree nuts, and kiwi. On peach immunoblot, only 3 of 18 putative peamaclein-allergic patients reacted to a band at about 7 kDa; an additional 4 patients reacted at about 50-60 kDa. Ten of 18 patients (56%) had a positive result for Pru p 7 on ImmunoCAP. CONCLUSION: Allergy and sensitization to peamaclein seem rare in Italy. Most patients react to peach, although other Rosaceae fruits and several citrus fruits may also be offending foods. Peach and cypress pollen probably also share cross-reacting allergens other than peamaclein.

Evaluation of two commercial peach extracts for skin prick testing in the diagnosis of hypersensitivity to lipid transfer protein. A multicenter study.

Summary: The clinical usefulness of two commercial peach extracts for SPT (by Lofarma SpA and ALK-Abellò, respectively) was compared in a multicenter study carried out in Italy. Peach allergic patients were tested with the two extracts in parallel and underwent the detection of IgE specific for all three peach allergens currently available (Pru p1, Pru p3, and Pru p4, respectively). The two extracts were almost identical in terms of sensitivity and specificity, being able to detect virtually all patients sensitized to stable peach allergens (lipid transfer protein (LTP) and, presumably, peamaclein) but scoring negative in patients exclusively sensitive to labile allergens (either PR-10 and/or profilin). Thus, the two extracts represent an excellent tool to carry out a preliminary component-resolved diagnosis of peach allergy at the first patient visit.

Systemic nickel allergy syndrome: epidemiological data from four Italian allergy units.

The prevalence of nickel hyper-sensitivity varies widely in different countries, nevertheless it is the leading cause of contact dermatitis. The presence of nickel in the diet (mainly plant foods) in some nickel-sensitive subjects can provoke/aggravate eczema and systemic contact dermatitis as well as cause extra-cutaneous symptoms (respiratory, gastrointestinal, neurological). These symptoms, correlated to the ingestion of nickel-containing foods and beverages, in nickel patch test positive individuals, defines the so called Systemic Nickel Allergy Syndrome (SNAS), a condition successfully treated by oral desensitization. Although numerous studies have investigated the prevalence of contact nickel allergy or addressed the relationship between nickel intake and onset of systemic symptoms, to our knowledge no epidemiological studies have attempted to estimate the prevalence of SNAS. Therefore, we decided to evaluate consecutive patients (1,696), afferent to four allergy units in Sicily, a region of southern Italy, from October 2010 to March 2011. SNAS was confirmed in 98 patients (5.78 percent) of the 1,696 studied, suggesting that this clinical entity may be an emergent allergological condition rather than an occasional finding. The most common symptoms complained of in our population were cutaneous (51 patients), gastrointestinal (87 patients) and other systemic clinical manifestations (37 patients). Furthermore, 16 out of the 98 SNAS patients (16.3 percent) presented IgE-mediated food allergy with a statistically significant association (X2=16.950; P<0.0001), therefore suggesting underlying cross-facilitating pathways. These findings need confirmation on wider populations but may help allergists to suspect, during common clinical practice, that cutaneous and extra-cutaneous symptoms may be referred to nickel intake and deserve specific in-depth investigation.

Factors influencing the prescription of allergen immunotherapy: the allergen immunotherapy decision analysis (AIDA) study.

The evidence of efficacy of allergen immunotherapy (AIT) for respiratory allergy has been demonstrated by a number of meta-analyses. However, the daily practice of AIT is quite different from controlled trials, facing challenges in terms of selection of patients, practical performance, and, of particular importance, use of allergen extracts of inadequate quality. We here performed a survey, named the Allergen Immunotherapy Decision Analysis (AIDA), to evaluate which criteria are used by specialists to choose a product for sublingual immunotherapy (SLIT) in patients with respiratory allergy. A questionnaire composed of 14 items to be ranked by each participant according to the importance attributed when choosing SLIT products was submitted to 444 Italian specialists. The responses of the 169 (38.1%) physicians, who answered all questions, were analysed. Most of the respondents were allergists (79%), followed by pulmonologists (10.8%), both allergists and pulmonologists (4.8%), and otorhinolaryngologists (3%); 59.8% of the respondents were males and 40.2% were females. The age distribution showed that 89.9% of the respondents were aged between 35 and 64 years. All respondents usually prescribed AIT products in their clinical practice: 31.4% used only SLIT, whereas 69.2% used both subcutaneous and sublingual administration. The rankings, expressed as means, attributed by physicians for each of the 14 items were as follows: level of evidence-based medicine (EBM ) validation of efficacy (3.44), level of EBM validation of safety (4.30), standardization of the product (5.37), efficacy based on personal experience (5.82), defined content(s) of the major allergen(s) in micrograms (5.96), scientific evidence for each single allergen (6.17), safety based on personal experience (6.32), ease of administration protocol (8.08), cost and terms of payment (e.g. instalments) (9.17), dose personalization (9.24), patient preference (9.25), ease of product storage (9.93), reimbursement (10.12), and availability of a helpline or on-line assistance from the manufacturer (11.89). These attitudes need to be taken into consideration by regulatory agencies as well as by producers.

Neuropathological and genetic characteristics of a post-mortem series of cases with dementia with Lewy bodies clinically suspected of Creutzfeldt-Jakob's disease.

INTRODUCTION: The disease course of dementia with Lewy bodies (DLB) can be rapidly progressive, clinically resembling Creutzfeldt-Jakob's disease (CJD). To better understand factors contributing to this rapidly progressive disease course, we describe load and distribution of neuropathology, and the presence of possible disease-associated genetic defects in a post-mortem series of DLB cases clinically suspected of CJD. METHODS: We included pathologically confirmed DLB cases with a disease duration of 3.5 years or less from the Dutch Surveillance Center for Prion Diseases, collected between 1998 and 2014. Lewy body disease (LBD) and Alzheimer's disease (AD)-related pathology were staged and semi-quantitatively scored in selected brain regions. Whole exome sequencing analysis of known disease-associated genes, copy number analysis, APOE ε genotyping and C9orf72 repeat expansion analysis were performed to identify defects in genes with a well-established involvement in Parkinson's disease or AD. RESULTS: Diffuse LBD was present in nine cases, transitional LBD in six cases and brainstem-predominant LBD in one case. Neocortical alpha-synuclein load was significantly higher in cases with intermediate-to-high than in cases with low-to-none AD-related pathology (p = 0.007). We found two GBA variants (p.D140H and p.E326K) in one patient and two heterozygous rare variants of unknown significance in SORL1 in two patients. CONCLUSION: A high load of neocortical alpha-synuclein pathology was present in most, but not all DLB cases. Additional burden from presence of concomitant pathologies, synergistic effects and specific genetic defects in the known disease-associated genes may have contributed to the rapid disease progression.

Soluble interleukin-2 receptor release defect in vitro in elderly subjects.

The evidence from several studies indicates that as individuals age, they may display immune dysfunctions, mostly T cell dysfunctions. Recently, a soluble form of the receptor for interleukin-2 (IL-2) (sIL-2R) has been demonstrated in human sera and in vitro stimulated culture supernatants from human T lymphocytes. In the present paper, we report in vitro sIL-2R production from peripheral blood mononuclear cells in elderly subjects. The results show that no difference exists for unstimulated cultures, whereas after mitogen stimulation the elderly subjects showed the lowest values compared with young ones. These findings suggest that sIL-2R may provide a new tool for the study of T lymphocyte dysfunctions in old age.

The effect of age on mitogen responsive T cell precursors in human beings is completely restored by interleukin-2.

It is well known that the function of T lymphocytes is significantly impaired by advancing age. In the present study, attempts have been made to further characterize the T cell impairment of elderly subjects. Thus, we have performed limiting dilution microculture analysis to evaluate the precursor frequency of T lymphocytes responding to a mitogenic stimulus in old and young subjects. Furthermore we have evaluated the activity of recombinant interleukin-2 (rIL-2) on these cells. The results demonstrate that in older subjects the frequency of these precursors is significantly decreased. The in vitro treatment with rIL-2 increased the frequency of mitogen responsive T lymphocyte precursors in both groups so that the difference between the two groups was not significant. Thus present results extend the findings demonstrating that older subjects display an impairment of T cell functions and that IL-2 treatment may correct these alterations. In particular, they confirm the hypothesis that age-associated functional changes are more likely due to diminished numbers of reactive cells, than to a decline in the activity of all cells.

Effects of intravenous erythromycin lactobionate in respiratory infections.

The antibiotic erythromycin lactobionate given intravenously acts almost exclusively on Gram-positive bacteria. Even at high plasma and tissue concentrations there is an almost total absence of side-effects. It could be considered, therefore, as first choice in the treatment of patients with infectious respiratory diseases. Most of the 40 patients admitted to the present study were elderly and all had either acute or chronic and becoming acute respiratory disease. Their clinical symptoms and levels of phlogosis improved on treatment with erythromycin lactobionate without any interruption of therapy due to side-effects and toxicity. The absence of unfavourable pharmacological interactions further enhances the usefulness of the drug. In view of the excellent response to monotherapy with erythromycin lactobionate and the few groups of resistant bacteria found in those cases when it was possible to check, it was not considered necessary to investigate any synergistic association with other antibiotics. It can be concluded, therefore, that therapy with erythromycin lactobionate in patients with infective respiratory disease is favourable and patients show excellent tolerability.

[Superficial bladder neoplasia unresponsive to endocavitary treatment: when should the treatment approach be changed?]. / Neoplasie vescicali superficiali non responsive al trattamento endocavitario: quando cambiare approccio terapeutico?

PURPOSE: The appropriate treatment of superficial bladder neoplasm is still debated. The urologist must weigh the risk of tumor recurrence and progression against the possible side effects of conservative treatment (transurethral resection, intravesical therapy). Furthermore it is difficult to decide exactly when to abandon the conservative therapy and proceed with radical cystectomy and urinary diversion in order to prevent the potentially lethal sequelae of invasive bladder cancer. There are no certain scientific data on the appropriate therapeutic approach of recurrences of superficial bladder cancer after intravesical therapy and often the urologist takes a decision based on his personal experience ("art rather than science"). Based on these considerations, our aim was to evaluate applicable criteria to predict the risks of tumor recurrence and progression and so decide the best treatment for each patient. METHODS: 148 patients with multifocal, multirecurrent or persistent superficial bladder cancer (stage Ta-T1-Tis, G1-3) were treated with transurethral resection and/or two or more administration of intravesical chemo- (Mitomycin C, Doxorubicin, Epirubicin, Mitoxantron) or immuno-therapy (BCG) using common treatment schedule. Our first end point was the disease-free survival (DFS) evaluated by three different criteria: 1) "dynamic" stage (stage T1 diagnosed at the beginning, or during the follow-up or never); 2) "dynamic" grade (G3 tumor diagnosed at the beginning or during the follow-up or never); 3) "number of positive cystoscopies at the 3-year follow-up". Data were evaluated by a univariate statistical analysis (log-rank test) and a multivariate ones (MPLR stepwise procedure and L-ratio Cox's test). RESULTS: "Dynamic" stage: patients who never developed a T1 stage tumor have a better DFS than patients who developed a T1 stage tumor and even more than patients in which T1 was diagnosed from the beginning (p < 0.0001). "Dynamic" grade: patients who never developed a G3 tumor have a better DFS than patients who developed a G3 tumor and patients in which G3 tumor was diagnosed from the beginning (p < 0.0017). "Number of positive cystoscopies at the 3-year follow-up": patients with less than 3 positive cystoscopies have a better prognosis than patients with 3 or more positive cystoscopies at the three-year follow-up (p < 0.0380). DISCUSSION: We have found three independent predictive prognostic factors: "dynamic" stage, "dynamic" grade and number of positive cystoscopies at the 3-year follow-up. The statistical univariate and multivariate analyses allow us to define three risk categories for tumor progression (> or = T2): low, moderate, high.

[Significance of health education in schools. Strategy for the prevention of cardiovascular diseases]. / L'importanza dell'educazione sanitaria nelle scuole. Una strategia per la prevenzione delle malattie cardiovascolari.

Cardiovascular diseases are the first cause of death in our Country. They mainly manifests in adult age but it is the result of initiated lesions since the young age and imputable often to errors of behaviours and to non appropriate styles of life. The knowledges related to the prevention of some illnesses, allows a reduction of the incidence of these, a reduction of the mortality, with consequent reduction of the health and social costs related to the care and to the rehabilitation. In our educational system, unlike what happens in the most greater part of the other European countries, these themes are only partially present and however treated in sporadic and insufficient way. For these raisons Pronto Cuore onlus Association has decided to start, in collaboration with the Regione Lazio, a project of health education to the high schools students considering that a more informed population has a longer expectancy of life and a better life quality. This job wants to underline the necessity to undertake a health education program to teach and inform students and teachers: to recognize some factors of risk as principal causes of cardiovascular diseases; to change life style; to recognize critical situations and behaviours to be adopted.

Isolation of a trans-acting factor involved in localization of Paracentrotus lividus maternal mRNAs.

Localization of Paracentrotus lividus bep maternal mRNAs at the animal pole occurs by association with the cytoskeleton and involves a 54-kDa protein, called LP54, that is able to bind to the 3' untranslated regions (UTRs) of bep mRNAs. We describe here the isolation and purification of this protein. Antibodies raised against purified LP54 allowed us to establish its localization in P. lividus eggs and embryos. This localization coincides with the mRNAs with which it is associated, that is, the animal pole in the egg, and, after fertilization, the regions derived from this part of the egg, and finally the oral ectoderm of the pluteus. Association with the cytoskeleton was shown by the copurification of LP54 in a microtubule preparation. Involvement in bep mRNA localization was demonstrated by microinjection of anti-LP54 antibodies in P. lividus eggs, which caused alteration of spatial distribution of bep3 mRNA.

Muscle tone: objective evaluation of the static component at the wrist.

A device measuring the flexion of the hand from an extended position was evaluated as a technique for assessing the passive component of muscle tone. Wrist measurements of 23 individuals, ten able-bodied, eight with spastic and five with flaccid wrists, were collected for three days of each week for three weeks, to determine the interrater, test-retest reliability, and construct validity of the device. Findings demonstrated high interrater reliability, inadequate test-retest reliability for single daily score comparisons, but an acceptable level of test-retest reliability for composite weekly score comparisons. Construct validity was supported since measurements of the involved limbs of individuals with spastic and flaccid wrists and the able-bodied group were significantly different from each other. This technique may provide useful objective information for therapists.

Blood antiphospholipid antibody levels are influenced by age, sex and HLA-B8,DR3 phenotype.

Antiphospholipid antibodies (APA) are known to be associated with a number of seemingly heterogeneous pathological conditions that are part of the antiphospholipid syndrome, formerly called anticardiolipin syndrome. Recent studies on the mechanism of action of these autoantibodies suggest that we are dealing with a new autoimmune syndrome which may occur either in a primary form or in the context of other autoimmune diseases, mainly systemic lupus erythematosus (SLE). Moreover, increased levels of APA have been found in elderly subjects, who are known to display increased frequency of autoimmune phenomena. It is well known that many autoimmune diseases, including SLE, are associated with HLA antigens, particularly with HLA-B8,DR3 phenotype. In our study, APA serum levels were analyzed in 26 old subjects and in 56 young ones. The results demonstrate that HLA-B8,DR3-positive young females display significantly higher levels of APA than HLA-B8,DR3-negative ones. Interestingly, the same is true for elderly subjects on the whole with respect to young individuals. These data are consistent with previous findings demonstrating that HLA-B8,DR3-positive subjects (mainly female) as well as old subjects display (also in the absence of any clinical manifestation), multiple immune dysfunctions that may underlie the predisposition to autoimmunity.

Intracavitary therapy of noninvasive transitional cell carcinomas of the upper urinary tract. A review of the literature.

Noninvasive (stages Ta, T1, Tis) transitional cell carcinomas of the upper urinary tract are suitable for a conservative therapeutic approach. Intracavitary therapy (alone or as adjuvant treatment) has recently been proposed and successfully used by some authors. Even though bacillus Calmette-Guérin is the most frequent agent employed, chemotherapeutic drugs, such as mitomycin C and thiotepa, have also been successfully used. The current information available in the literature is therefore reviewed. According to the data available, intracavitary therapy is a worthwhile conservative therapeutic option for noninvasive upper urinary tract urotheliomas with acceptable side effects. For this reason it may be included in the routine urological armamentarium.