bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic evaluation of a large group of patients with immediate allergy to penicillins: the role of skin testing
Authors: Torres J. , Romano A. , Mayorga C. , Carmen M. , Guzman A. E. , Reche M. , Juarez C. , Blanca M. 
Published: March 2003

Background: Penicillin is no longer the most commonly prescribed β‐lactam, and the pattern of reactions has changed. We studied the diagnostic value of skin testing in penicillin‐allergic subjects from a population where benzylpenicillin is not now the most frequently used β‐lactam. Methods: Patients with a history of immediate allergic reactions to penicillins were studied with: skin tests with major and minor determinants of benzylpenicillin (BPO/MDM), amoxicillin, and ampicillin; in vitro determination of specific IgE; and controlled administration for those with a positive history but negative skin and in vitro tests. A reaction was considered immediate when symptoms appeared within a maximum of 1 h after drug intake. Results: After testing, 290 patients (71% having anaphylaxis and 29% having urticaria) proved to be allergic. Amoxicillin was involved in 64.8% and benzylpenicillin in 2.8% of the patients. Skin test positivity to at least one determinant appeared in 70% of cases, amoxicillin being the most frequent. The overall sensitivity decreased markedly when only BPO and MDM were considered. In 13.1% of patients, the diagnosis was established by in vitro test and in 16.9% by controlled administration. Of the 290 patients, 42.1% were positive to determinants generated from benzylpenicillin and 57.9% were selective responders. Conclusions: Sensitivity of skin tests to BPO was lower than reported, being partly replaced by minor determinants, mostly amoxicillin. The incorporation of additional reagents and the development of new tests are required, and these will probably change as the patterns of consumption vary.
The potential role of orbicules as a vector of allergens
Authors: Vinckier S. , Smets E. 
Published: March 2003

Background:In the locules of anthers of flowering plants, tiny (1.5‐2 µm) granules of sporopollenin may occur next to the pollen grains. Those granules, called orbicules, mostly occur on the radial and innermost tangential wall of secretory tapetum cells.Methods:We have investigated the presence of orbicules in 15 important European allergenic species with scanning electron microscopy (SEM).Results:Orbicules were present in all species investigated of the families Betulaceae, Chenopodiaceae, Fagaceae, Poaceae, Polygonaceae, and Urticaceae. However, in the Asteraceae and Oleaceae species studied, orbicules were lacking. In all Chenopodiaceae, Poaceae, and Urticaceae species, orbicules were attached to the pollen exine. These observations indicate the possibility of the dispersal of orbicules into the atmosphere during anthesis.Conclusions:The hypothesis of the potential role of orbicules as possible important vectors of allergens is put forward, based on the comparison of our results with recent literature about the evidence of allergenic activity in the smaller micronic atmospheric aerosol fraction. Our results provide evidence that an in‐depth investigation of the sites of allergens across the whole anther is required. We suggest that allergen researchers apply immunoelectron microscopy on whole anthers to determine whether orbicules possess allergens.
Safety of sublingual immunotherapy with monomeric all_ergoid in adults: multicenter post‐marketing surveillance study
Authors: Lombardi C. , Gargioni S. , Melchiorre A. , Tiri A. , Falagiani P. , Walter Canonica G. , Passalacqua G. 
Published: March 2003

Background: Sublingual immunotherapy (SLIT) appears to be acceptably safe in clinical trials, but post‐marketing data are needed to provide essential information. This study specificall_y evaluated the safety of commercial SLIT in adult patients in a post‐marketing phase. Methods: A total of 198 patients (83 male, 115 female, mean age 24.4 years) receiving SLIT for respiratory all_ergy were followed up for 3 years by a specific questionnaire for side‐effects. SLIT (LAIS, Lofarma SpA, Milan, Italy), a monomeric all_ergoid in tablets, was administered, in association with drug therapy, pre‐ or pre‐coseasonall_y for pollen and continuously for mites. The average duration was 12–36 months, and the total of doses was about 32 800. Side‐effects were grouped as ocular, gastrointestinal, rhinitis, asthma, urticaria, edema of tongue/lips, and anaphylaxis. The severity was graded as low (no need for treatment or dose adjusting, no interference with activities), moderate (interference with activities/need for drugs/SLIT discontinuation), and severe (life‐threatening/hospitalization/emergency care). Results: Seventeen events corresponding to 7.5% of patients and 0.52 per 1000 doses were reported. Seven episodes of rhinitis (two in two patients), three of oral itching, and one of abdominal pain were self‐limiting. Two cases of urticaria and two of abdominal pain/nausea were controlled by a temporary dose‐adjustment, and one case of urticaria and conjunctivitis required oral antihistamines. Medical intervention was needed in six patients only during a 3‐year period. Conclusions: The results of this study, performed in a real situation of clinical practice, confirm the satisfactory safety profile of SLIT.
Specific immunotherapy prevents increased levels of allergen‐specific IL‐4‐ and IL‐13‐producing cells during pollen season
Authors: Gabrielsson S. , Söderlund A. , Paulie S. , Van Der Pouw Kraan T.C.T.M. , Troye‐Blomberg M. , Rak S. 
Published: March 2003

Background: Specific allergen immunotherapy (SIT) is effective for treatment of IgE‐mediated diseases; however, the mechanisms of action still remain unclear. Earlier, we showed that IL‐4 and IL‐13 are produced in response to specific allergens. The aim of this study was to investigate whether these cytokine responses were affected by allergen SIT, and, furthermore, to evaluate the effect of SIT on allergen‐specific IgE and IgG4 levels. Methods: Blood samples from pollen‐sensitized individuals were collected before the pollen season (before treatment) and during the pollen season (after SIT or placebo treatment). Peripheral blood mononuclear cells were activated in vitro with allergens and the numbers of IL‐4‐, IL‐13‐, IL‐10‐, and IFN‐γ‐producing cells were determined by ELISPOT. Serum levels of allergen‐specific IgE and IgG4 were measured by RAST and ELISA, respectively. Results: The numbers of IL‐4‐ and IL‐13‐producing cells were shown to be increased in the placebo group during the pollen season, an increment which was absent in patients receiving allergen SIT. We found an increase in allergen‐specific IgG4 in the SIT‐treated individuals, but not in the placebo group. Both groups displayed elevated specific IgE levels during the pollen season. Conclusions: Taken together, our data show a downregulation of IL‐4‐ and IL‐13‐producing cells in peripheral blood after SIT, suggesting induction of nonresponsiveness/tolerance or a redistribution of these cells. Furthermore, we demonstrate that SIT acts on antibody production by increasing the specific IgG4 levels.
Retrospective study on fluticasone propionate aqueous nasal spray efficacy in patients with allergic rhinitis: evaluation of clinical and laboratory parameters
Authors: Ventura M. , Piccinni T. , Matino M. G. , Giuliano G. , Di Corato R. , Di Napoli P. , Tursi A. 
Published: March 2003

Background: In allergic rhinitis, allergenic stimulation causes the release of various mediators that induce symptoms and the development of chronic inflammation, which, in turn, is caused by cells involved in the late phase of inflammation, such as eosinophils. The eosinophils also cause damage at the mucosal level through the secretion of eosinophil cationic protein and other preformed factors contained in their granules. The objective was to verify the efficacy of fluticasone propionate aqueous nasal spray in patients with allergic rhinitis; in a retrospective study, we have evaluated mediators of inflammation, making correlations with the clinical symptoms score during and outside the pollen season. Methods: Forty patients with allergic rhinitis and 15 normal controls were included in our study. Eosinophil cationic protein, eosinophil chemotactic activity, and blood and nasal lavage eosinophil count were evaluated as laboratory parameters. Results: We found a significant increase in nasal lavage levels of eosinophil cationic protein in allergic patients, and this was strictly correlated with the clinical symptoms score. No differences were found in the eosinophil count of allergic patients and in the serum eosinophil cationic protein of patients sensitized to seasonal allergens in comparison with normal subjects. By contrast, an increase in serum eosinophil cationic protein level was found in patients sensitized to perennial allergens. After topical administration of fluticasone propionate aqueous nasal spray, a reduction in nasal lavage eosinophil cationic protein secretion was obtained with a reduction of eosinophil chemotactic activity at the local level. This reduction correlated with an improvement of clinical symptoms. Conclusions: The clinical improvement and reduction in nasal lavage eosinophil cationic protein and eosinophil chemotactic activity after administration of fluticasone propionate aqueous nasal spray further confirms the role of this treatment in allergic rhinitis.
Interleukin‐4‐positive mast cells are highly associated with the extent of immediate allergic wheal reaction in the skin
Authors: Saarinen J. V. , Harvima R. J. , Horsmanheimo M. , Harvima I. T. , Naukkarinen A. 
Published: March 2003

Background: In addition to histamine, mast cells contain other potent mediators which can contribute to the allergic wheal reaction in the skin. Methods: To study the association of tryptase‐, chymase‐, and interleukin‐4 (IL‐4)‐positive mast cells with the size of the prick‐test wheal reaction, 50 sensitive atopic subjects were prick‐tested with the cow‐dander allergen on the forearm skin, and the wheal area was measured. A corresponding site of intact healthy‐looking skin was biopsied and examined enzyme‐histochemically for tryptase and chymase. A double‐staining method was used to demonstrate the immunoreactivity of IL‐4 and chymase inhibitors (α1‐proteinase inhibitor and α1‐antichymotrypsin) in mast cells. The levels of total and cow‐specific immunoglobulin E (IgE) were measured in serum. Results: The number of tryptase‐ and chymase‐positive mast cells or those containing chymase inhibitors revealed no correlation with the wheal reaction. In contrast, both the percentage and the number of IL‐4‐positive mast cells showed significant positive correlation with the wheal size per se (P<0.0001), as well as with the ratio of the wheal size by cow allergen to that by histamine control (P<0.003). In addition, tryptase‐, chymase‐, and IL‐4‐positive mast cells correlated with total IgE, but not with specific IgE, levels, and they showed no relation to the clinical manifestation of atopic disease, asthma or atopic dermatitis. Conclusions: The novel finding was that IL‐4‐positive, but not tryptase‐ and chymase‐positive, mast cells are intimately associated with the extent of the prick‐test wheal.
The mechanisms of serum‐treated zymosan (STZ)‐induced oxidative metabolism by human eosinophils and the effects of IL‐5 priming
Authors: Woschnagg C. , Garcia R. C. , Venge P. 
Published: March 2003

Background: The aim of this work was to study the mechanisms of action of IL‐5 on the subsequent stimulation of the oxidative metabolism of blood eosinophils by serum‐treated zymosan (STZ), in terms of signal transduction characteristics, and by comparing the response of cells from healthy and allergic subjects during environmental exposure to birch pollen. Methods: Eosinophils from healthy controls and allergic patients were purified to over 95% by Percoll gradients and the MACS system. Oxidative metabolism was measured by a lucigenin‐enhanced chemiluminescence (CL) assay. Eosinophils were primed with IL‐5 and subsequently stimulated with STZ. The signal transduction mechanisms of IL‐5 priming were studied with the MEK inhibitor PD 98059,the PkC inhibitors staurosporine and Ro 318220, and the PI3 kinase inhibitor wortmannin. Results: IL‐5 increased the maximum radical production (P=0.0079) and reduced the t½ rise (0.000018) of the CL reactions. The t½ rise was PkC dependent and MEK independent, while the maximum radical production was PkC, MEK, and PI3 kinase dependent. During the pollen season, IL‐5 reduced the total STZ‐induced CL response in the patients' cells (P=0.016), but not in the control cells, whereas it primed the response to STZ of both cell populations in terms of the t½ rise (P=0.012 and 0.00066, respectively). Conclusions: STZ‐induced oxidative metabolism consists of different stages. The initial stage (t½ rises of the curves) is PkC dependent and MEK independent, while the end stage (maximum radical production) is PkC, MEK, and PI3 kinase dependent. IL‐5 shortened the initial stage, and increased the end stage. During allergen exposure, however, the end stage was reduced by IL‐5. This could be due to increased amounts of hypodense eosinophils and/or some abnormality in cell responses.
Increased prevalence of atopy among children exposed to mold in a school building
Authors: Savilahti R. , Uitti J. , Roto P. , Laippala P. , Husman T. 
Published: March 2003

Background: The purpose of this study was to assess the occurrence of immunoglobulin E sensitization to common environmental allergens (atopy) and new allergic diseases among schoolchildren after starting school in a water‐damaged school building. The staff and pupils of a Finnish elementary school with visible water damage and mold complained of respiratory and skin symptoms. The school building was examined and widespread moisture damage was found. A control school with no visible water damage was also examined. No indication of exceptional microbial growth was found in the samples taken from this school. Methods: History of allergic diseases and the year of diagnosis were established by a questionnaire. IgE antibodies to the common environmental allergens were determined from randomly selcted groups from both schools. Results: Elevated IgE values were significantly more common among the exposed children, as was the occurrence of new allergic diseases after the children started at the school. Conclusions: The odds ratios for the IgE values of the study groups indicated a possible relationship between exposure to microorganisms and IgE sensitization. Exposure to spores, toxins, and other metabolites of molds may have complex results with unknown immunogenic effects that may act as a nonspecific trigger for allergic sensitization leading to the development of atopy.
An Internet‐based survey of anaphylactic reactions to foods
Authors: Eigenmann P. A. , Pastore F. D. , Zamora S. A. 
Published: March 2003

Background: A favorable outcome of anaphylaxis depends on the rapidity of adequate initial management and epinephrine injection. However, few data on the management of anaphylactic reactions are available. The aim of this study was to investigate the management and awareness of anaphylaxis to foods by mean of an Internet‐based survey. Methods: Visitors to a website with information on food allergy were invited to join the survey. Items in the survey included the management of anaphylactic reactions, investigations done by the diagnosing physician, and information given to the responder in anticipation of a new anaphylactic reaction. Results: Almost all of the 264 responders were from North America, Europe, Australia, or New Zealand (263/264). The most recent reaction was treated by epinephrine injection in 68.7% (180/262) of cases, or by antihistamines in 14.1% (37/262). Epinephrine was the first treatment for the most severe reaction in only 43.9% (101/230), while antihistamines were given first in 43.5% (100/230). One‐third (62/210=29.5%) of the responders diagnosed by a physician received neither a diagnostic blood test nor a skin test. Responders diagnosed by an allergist were more often investigated (91/105=86.7%) than those diagnosed by a pediatrician or an internist (29/44=65.9%), a general practitioner (22/45=48.9%), or another physician (6/16=37.5%) (P<0.001). Most responders had received instructions on how to deal with a new episode of anaphylaxis (244/263=92.8%). Responders instructed by an allergist were most frequently satisfied with the instructions (115/131=87.8%). Conclusions: A large number of responders did not receive epinephrine for treatment of their most severe, or most recent anaphylactic reaction, and did not undergo allergy tests. The conventional management of anaphylaxis might still be improved.
Allergenic diversity of the olive pollen
Authors: Rodríguez R. , Villalba M. , Batanero E. , González E. M. , Monsalve R. I. , Huecas S. , Tejera M. L. , Ledesma A. 
Published: March 2003

A great number of allergenic proteins have been detected in olive pollen extracts. To date, nine allergens have been isolated and characterized, which have been called Ole e 1 to Ole e 9. The most prevalent olive allergen is Ole e 1, which affects more than 70% of patients hypersensitive to olive pollen, but others, such as Ole e 2, Ole e 8, and Ole e 9, have been demonstrated to be major allergens, and Ole e 6 or Ole e 7 reach high values of clinical incidence. Many of these allergens, such as Ole e 2 (profilin) and Ole e 3 (polcalcin), are involved in cross‐reactivities, which agrees with their adscription to panallergenic families. Among the many olive allergens of high molecular mass, only Ole e 9 (46 kDa) has been characterized. The allergen is a polymorphic and glycosylated β‐1,3‐glucanase, which belongs to a pathogenesis‐related (PR‐2) protein family. In addition to the polypeptide epitopes, Ole e 1 also exhibits IgE‐binding determinants in the carbohydrate, which are recognized by more than 60% of the sera from patients sensitive to the whole allergen, although the level of such glycan‐specific IgE seems not to be clinically relevant in the overall content of the sera. Recent advances in the elucidation of the structure of the Ole e 1‐oligosaccharide component allows us to explain the antigenicity of the molecule. Finally, the recombinant production of several allergens from olive pollen in both bacterial and eukaryotic cells has allowed us to resolve problems derived from the polymorphism and scarcity of the natural forms of these allergens. The biological equivalence between the natural and recombinant forms lets us initiate studies on the design of mixtures for clinical purposes, in which hypoallergenic derivatives of these allergens could play a definitive role.
Characterization of specific IgE response in vitro against protein and drug allergens using atopic and normal donors
Authors: Åkesson A. , Ingvarsson S. , Karlsson F. , Leyva L. , Blanca M. , Cuerden S. A. , Smith J. A. , Coleman J. W. , Borrebaeck C. A. K. 
Published: March 2003

Background: As the incidence of allergy to different compounds increases in society, the need to understand and characterize specific IgE responses becomes obvious. Different cell culture systems have been evaluated for their ability to support such IgE secretion. Methods: One system employed human peripheral lymphocytes (PBL) from normal donors stimulated with anti‐CD3 activated T cells with or without the presence of allergens like benzylpenicillin (BP) and Phlenum pratense (PP). Secretion of IgE was analyzed in ELISA and compared to the IgG response to the nonallergenic antigen tetanus toxoid (TT). Another system employed stimulation of T and B cells with a heterotope, consisting of a T helper cell epitope derived from TT, and a B cell allergen epitope derived from BP. The specific IgE secretion was compared, using lymphocytes from normal as well as BP‐allergic donors. Results: Anti‐CD3 stimulated T cells supported BP‐specific IgE secretion in six of 11 normal donors. This response was inhibited in four donors and enhanced in two donors by the addition of the BP‐allergen to the culture. In contrast, addition of the protein allergen (PP) or antigen (TT) to the same culture system inhibited both IgE and IgG synthesis in all experiments. Cells from the majority (10/16) of the BP‐allergic donors failed to produce BP‐specific IgE in vitro, when cultured in the presence of allergen. Conclusions: An allergen specific immune response is readily generated in vitro. The differential response against benzylpenicillin between different donor categories most probably reflects the level of pre‐exposure to this allergen in vivo.
Cellular immune responses to ovalbumin and house dust mite in egg‐allergic children
Authors: Ng T.‐W. , Holt P. G. , Prescott S. L. 
Published: March 2003

Background: Although IgE‐mediated food (egg) allergy is typically lost with age the underlying immune mechanisms are not understood, particularly in relation to the development of persistent IgE‐mediated aeroallergen sensitivity. Methods: Lymphoproliferation and cytokine responses (IL‐5, IL‐10, IL‐13 and IFN‐γ) to house dust mite (HDM) allergen and egg ovalbumin (OVA) were assessed using peripheral blood mononuclear cells (PBMC) from children aged 6 months to 5 years (n = 59) with acute IgE‐mediated egg allergy (urticaria and angiedema or anaphylaxis), as confirmed by positive skin prick testing (SPT). Of these 46 had positive SPT on the day of blood collection and 13 had outgrown egg allergy (negative SPT and successful egg challenge). Where possible, responses were compared with previous data from nonallergic children of similar ages (n = 107). Results: Transient lymphoproliferative responses to OVA were seen in both egg‐allergic and nonallergic children, but were more marked and more prolonged in egg‐allergic children. Younger egg‐allergic children (< 18 months) showed a mixed Th0 cytokine response to OVA, with readily detectable IFN‐γ, IL‐5, IL‐13 IL‐10. Although IL‐13 and IL‐5 responses (OVA) correlated in younger egg‐allergic children, there was a dissociation of these Th2 responses with age. Loss of clinical reactivity to egg was associated with almost complete loss of IL‐5 responses and OVA‐specific lymphoproliferation. Although IL‐13 levels tended to be lower with age, this was not significant. Strong IFN‐γ and IL‐10 responses to OVA persisted in older children after loss of OVA‐specific lymphoproliferation. Lymphoproliferative responses to HDM also developed earlier in egg‐allergic children compared with nonallergic children. Th1 (IFN‐γ) responses to HDM were largely below detection prior to 18 months of age, but increased significantly with age. In egg‐allergic children Th2 (IL‐5, IL‐13) HDM responses also progressively increased with age. At 3 years of age almost all egg‐allergic children had positive SPT to HDM and positive lymphoproliferative responses to HDM, with strong Th1 and Th2 (Th0) cytokine production. Conclusions: IL‐5 responses (rather than IL‐13) responses most closely reflected clinical food allergy, with dissociation of IL‐5 and IL‐13 responses in older and egg‐tolerant children. In this population, food and aeroallergen sensitivity was not associated with inability to produce IFN‐γ, but rather with mixed Th2 and Th1 (Th0) responses. Strong IL‐10 and IFN‐γ responses where associated with the development of tolerance, suggesting persistent ‘regulatory’ populations of OVA‐specific T cells, rather than clonal deletion of OVA responsive T‐cells.