bluuebunny/crossref_metadata_2025 huggingface dataset:
A double‐blind comparison of nasal budesonide and oral astemizole for the treatment of perennial rhinitis
Authors: Bunnag C. , Jareoncharsri P. , Wong E. C. K.
Published: May 2007

Sixty‐nine outpatients with symptomatic perennial rhinitis were recruited to this double‐blind, parallel‐group study to compare budesonide nasal spray with oral astemizole. Following a 1‐week run‐in on placebo, 67 patients achieved a mean daily total symptom score of at least 4 (scoring for each symptom was 0 = none, 1 = mild, 2 = moderate, 3 = severe), and were randomized to study treatments ‐ 33 to budesonide, 100 ug in each nostril morning and evening, and 34 to astemizole, one 10‐mg tablet each morning, for a period of 4 weeks. No antihistamine preparations other than eye drops and no corticosteroids were permitted during the active treatment period. Patients recorded symptoms of blocked nose, runny nose, sneezing, itchy nose, sore eyes or runny eyes in diary cards each evening before retiring. Diary card data showed that there was significantly greater improvement in blocked nose, runny nose and runny eyes during the first 2 weeks of budesonide treatment than during the same period on astemizole. A similar, although non‐significant, trend was observed for sneezing and itchy nose, but there was no apparent difference in the reporting of sore eyes. After 4 weeks, blocked nose and runny nose remained significantly less troublesome in the budesonide group. Both treatments were well‐tolerated and no major adverse effects were reported. Patient ratings for treatment efficacy were significantly higher for budesonide than astemizole at both 2 weeks and 4 weeks.
Human basophil histamine release is differently affected by inhibitors of calmodulin, diacylglycerol kinase and peptidyl prolyl cis‐trans isomerase in a secretagogue specific manner
Authors: Bergstrand H. , Lundquist B.
Published: May 2007

Bergstrand H, Lundquist B. Human basophil histamine release is differently affected by inhibitors of calmodulin, diacylglycerol kinase and peptidyl prolyl cis‐trans isomerase in a secretagogue specific manner.

To assess the role of calmodulin in human basophil histamine release, we triggered leukocytes with different secretagogues in the presence of putative inhibitors of calmodulin. Calcium ionophore‐induced histamine release was reduced or blocked by calmidazolium, CGS 9343B, felodipine, metofenazate, and Ro 22–4839. H 186/86, a felodipine‐related dihydropyridine derivative, blocked A23187‐but not ionomycin‐triggered histamine release, suggesting a difference in the mode of action of these ionophores. In contrast, leukocyte histamine release triggered by the purported protein kinase C (PKC) activator, l, 2‐isopropylidene‐3‐decanoyl‐sn‐glycerol (IpOCOC9), was enhanced by calmidazolium, CGS 9349B and metofenazate but not affected by felodipine or Ro 22‐4839, whereas the response triggered by 4β‐phorbol 12‐myristate 13‐aeetate (PMA) was reduced by metofenazate and Ro 22‐4839 but not consistently affected by calmidazolium, CGS 9343B or felodipine. The PMA‐induced histamine release was enhanced by H 186/86. Anti‐IgE‐ and Fmlp‐induced responses were either unaffected or slightly enhanced by the examined calmodulin antagonists. In comparison with the calmodulin antagonists, R 59022, an inhibitor of diacylglycerol kinase, failed to reduce calcium ionophore‐triggered histamine release, whereas FK506, an inhibitor of peptidyl prolyl cis‐trans isomerase (PPI), reduced both anti‐IgE‐ and ionophore‐triggered responses. These results indicate that calmodulin constitutes an obligate link in signal transduction pathways leading to human leukocyte histamine release if the trigger is a calcium ionophore but not when responses are induced by anti‐IgE, Fmlp or PMA; a calmodulin‐dependent component may rather balance responses induced by IpOCOC9. We also conclude that most employed stimuli, including IpOCOC9, trigger human basophil histamine release through partly distinet pathways.
The major allergen content of allergenic preparations reflects their biological activity
Authors: Dreborg S. , Einarsson R.
Published: May 2007

The content of major allergens in biologically standardized allergenic preparations of birch, mite (Der p), cat, Alternaria (Alt a) and ragweed (Amb e) was determined. It was found fairly constant between species, i.e. varied within a factor of 2, with the exception of Alt a 1 in Alternaria alternata extract. This variation is allowed by authorities between different batches prepared from the same species of allergen. The method for biological standardization (BS) prescribed in the Nordic Guidelines has, for common inhalant allergens, been shown to give reproducible results between regions of Europe. However, it is difficult to define patients suitable for BS of most food allergens as well as less common inhalant allergens. Therefore we propose that, in the future, BS is replaced by determination of well‐established major allergens and that 1 ng of major allergen is given the value of 1 Biological Unit.

Clinical aspects

Clinicians have had difficulties in understanding differences and similarities between units used by manufacturers for labelling of allergenic extracts. Biological standardization is time‐consuming and expensive. Probably therefore, and to avoid comparison with extracts prepared by other manufacturers, most manufacturers have used their own units and few of them have used the biological units as defined by the Nordic Guidelines or FDA. Determination of the amount of major allergen by ELISA is simple and cheap. However, the biological relevance of major allergen content has not been established. Our results clearly indicate the possibility of replacing biological units by major allergen content, provided the composition of allergens is adequate. The major allergen content can easily be declared by all manufacturers. In the future, manufacturers should be forced to declare the major allergen content, thus making it easier for clinicians to compare extracts from different suppliers.
Role of carbohydrate moieties in cross‐reactivity between different components of Parietaria Judaica pollen extract
Authors: Mucci N. , Liberatore P. , Federico R. , Forlani F. , Di Felice G. , Afferni C. , Tinghino R. , De Cesare F. , Pini C.
Published: May 2007

Cross‐reactivity between the different components in Parietaria judaica pollen extract has been investigated by polyclonal as well as monoclonal antibodies before and after chemical deglycosylation obtained by trifluoromethanesulphonic acid (TFMS) treatment of the extract. In western blotting a polyclonal rabbit antiseruni, obtained by injecting purified Par j I, was able to recognise many components of the native extract. However, its reactivity was restricted, after chemical deglycosylation of the extract, to the major allergen alone, indicating that its cross‐reactivity was due to sugar moieties. Moreover, out of several monoclonal antibodies raised by injecting the whole Parietaria judaica extract, one (1A4/2F8) was also able in western blotting to recognise an epitope shared by many components of the extract except the major allergen Par j I. However, in this case the broad reactivity of the antibody was not affected by the deglycosylating procedure. When the reactivity of Parietaria Judaica extract was tested before and after sugar removal, against specific IgE from a pool of patient sera, no differences could be demonstrated, thus indicating that carbohydrates are not strongly involved in the binding of Parietaria judaica‐specific IgE. The results indicate that both proteic and carbohydratic cross‐reactive epitopes are shared by many components of Parietaria judaica pollen extract.
Delayed hypersensitivity to 6‐methyl‐prednisolone in Henoch Schoenlein syndrome
Authors: Astone A. , Romano A. , Pietrantonio F. , Garcovich A. , Venuti A. , Barone C.
Published: May 2007

We report a case of allergic reaction to oral 6‐methyl‐prednisolone in a patient with Henoch Schoenlein syndrome. When this syndrome was first diagnosed the patient was started on 6‐methyl‐prednisolone orally and after 4 days he developed a pruriginous generalized maculo‐papular eruption. The rash disappeared 1 week after withdrawal of 6‐methyl‐prednisolone. The skin tests performed 1 month after with main food allergens were negative. Patch test with 0.10 ml of solution containing 6‐methyl‐prednisolone 40 mg/ml was positive after 48 and 72 h. The cutaneous biopsy on the patch tested skin revealed a perivaseular infiltrate of lymphocytes, histiocytes and eosinophils.
Basophil histamine release in patients with birch pollen hypersensitivity with and without allergic symptoms to fruits
Authors: Kleine‐Tebbe J. , Galleani M. , Jeep S. , Pilz B. , Baisch A. , Kunkel G.
Published: May 2007

Histamine release (HR) studies were performed in 40 birch pollen‐allergic patients (positive case history, positive SPT, positive birch pollen‐specific serum IgE: RAST ≤ 3) with (n= 20, A) and without (n= 20, B) fruit hypersensitivity, and 10 nonatopic volunteers (C). Several fruit allergens were used and characterized by protein determination and immunoblot techniques. Dose‐dependent HR (apple peel = apple pulp> peach = cherry) was demonstrated in both allergic groups, but to a higher extent in patients with fruit allergy (P < 0.01). Increased basophil sensitivity to birch pollen was found in the group with fruit allergy (P < 0.001). Strong correlations between the mediator response induced by several fruits indicate common allergens within the extracts. We conclude that fruit‐related symptoms require not only high specific serum IgE, but a strong cellular sensitization to birch pollen allergens together with an increased cellular reactivity to fruit allergens.
Elevated levels of peripheral‐blood, naturally occurring aliphatic polyamines in bronchial asthmatic patients with active symptoms
Authors: Kurosawa M. , Shimizu Y. , Tsukagoshi H. , Ueki M.
Published: May 2007

The levels of peripheral‐blood, naturally occurring aliphatic polyamines, such as putrescine, spermidine, and spermine, from 21 bronchial asthmatic patients (11 atopics and 10 nonatopics) were measured by postcolumn derivatization high‐performance liquid chromatography analysis. None of the patients, except the 44‐year‐old woman in the case report below, were given prednisolone, and they were instructed to take only regular medication during the tests. Blood was drawn from the patients in a fasting state, and the polyamine levels were compared between the times when they were free of asthmatic symptoms and when they had mild spontaneous attacks. Nine (5 atopics and 4 nonatopics), 6 (3 atopics and 3 nonatopics), and 4 (3 atopics and 1 nonatopic) out of 20 patients, when they had relatively mild asthmatic attacks, showed higher putrescine, spermidine, and spermine levels, respectively, than those of normal healthy control subjects. The levels of peripheral blood polyamines from a 44–year‐old atopic bronchial asthmatic woman, who was admitted to the hospital with severe asthmatic attacks, were measured serially, and the putrescine and spermidine levels were found to be elevated during the asthmatic attacks, returning to normal levels in parallel with the clinical course. These data may suggest a role for naturally occurring aliphatic polyamines in bronchial asthma.
Tryptase in nasal fluid is a useful marker of allergic rhinitis
Authors: Rasp G. , Hochstrasser K.
Published: May 2007

Tryptase is a mast cell‐specific marker of degranulation. To investigate the possible diagnostic value of tryptase in allergic rhinitis, we measured the levels in both serum and native nasal fluid with a sandwich RIA‐assay (Pharmacia). Twenty‐three allergic patients and five patients with chronic ethmoidal sinusitis were included. Eighteen of the 23 allergic patients were tested within the pollen season or had perennial rhinitis; the remainder were tested at least 1 month out of the pollen season. None of the patients had detectable serum tryptase (>0.1 ng/ml). Also patients with chronic ethmoidal sinusitis showed no tryptase in nasal fluid. One of seven allergic patients tested out of season had slightly increased nasal tryptase of 1.8 ng/ml. In patients with active nasal allergy, the tryptase in nasal fluid ranged from 6.4 ng/ml to 640 ng/ml with a mean of 101 ng/ml and SD 173. These results show a clear distinction between active and non‐active nasal allergy and other non‐mast‐cell‐related nasal disease. Further, nasal tryptase release by natural allergen exposure is even higher than that observed in allergen challenge tests.
A new method of counting airborne Japanese cedar (Cryptomeria japonica) pollen allergens by immunoblotting
Authors: Takahashi Y. , Nagoya T. , Watanabe M. , Inouye S. , Sakaguchi M. , Katagiri S.
Published: May 2007

We have devised a new method of counting pollen allergen particles, modified from the fluorescent immunoblotting technique of Schumacher et al. Airborne Japanese cedar pollen allergens collected on Burkard's sampling tape were transferred onto a nitrocellulose membrane. The membrane was then treated with antiallergen mouse monoclonal antibody conjugated with alkaline phosphatase. Pollen allergens were detected as purple spots on the nitrocellulose membrane after phosphate substrate staining was performed. Pollen allergen particles were visible under a stereoscopic microscope or to the naked eye and could thus be counted easily. This new counting method takes less time than previous methods and requires no special skill.
Heterogeneity of atopy. I. Clinical and immunologic characteristics of patients allergic to cypress pollen
Authors: Bousquet J. , Knani J. , Hejjaoui A. , Ferrando R. , Cour P. , Dhivert H. , Michel F.‐B.
Published: May 2007

The heterogeneity of pollen‐allergic persons is well known but poorly characterized. Cypress is one of the major pollen‐producing plants of the Mediterranean area. A study was undertaken to characterize the symptoms presented by patients allergic to cypress pollen and the heterogeneity of the IgE immune response between patients allergic only to cypress pollen and those who are polysensitized. Eighty‐nine patients allergic to cypress pollen were studied, 26 being allergic only to cypress pollen. The IgE response was assessed by skin prick tests and the titration of serum total IgE and cypress‐specific IgE by RAST. Clinical reactivity was assessed by symptom scores during the cypress pollen season and skin tests. Pollen counts were obtained. The clinical reactivity was similar in both patient groups. Rhinitis was present in all patients, conjunctivitis in 73.7–88.5%, and asthma in only 7.4–19.2%. The age of onset of symptoms caused by cypress pollen allergy was significantly greater in patients allergic to cypress pollen only. Total serum IgE was within the normal range in the cypress pollen group and significantly lower than in the polysensitized groups. Cypress pollen RAST was higher in the polysensitized group. We concluded that conjunctivitis is particularly common in cypress pollen allergy. Patients allergic only to cypress pollen may be unique in their way of expressing serum total IgE levels.
Comparison of the effects on bronchial hyperresponsiveness of antiallergic agents and beclomethasone dipropionate in long‐term bronchial asthma
Authors: Hoshino K. , Kawasaki A. , Mizushima Y. , Oosaki R. , Yano S. , Kobayashi M.
Published: May 2007

The effect of antiallergic agents (DSCG (disodium cromoglycate), ketotifen, and ibudilast) and beclomethasone dipropionate inhaler (BDI) on bronchial hyperresponsiveness to histamine inhalation was retrospectively assessed in 72 asthmatic patients with more than a year's duration of the disease. Decrease in bronchial hyperresponsiveness to histamine was observed in 10 out of the 33 (30%) antiallergic‐agents‐treated patients (group A, mean duration = 7.8 months), in 12 of 19 (63.2%) BDI‐treated patients (group B, 6.2 months), but only 2 of the 20 (10%) control patients (group C, 7.8 months). Improvement of histamine PC20 was from 310 to 597 μg/ml (P<0.01) in group A, from 308 to 1622 μg/ml (P<0.0005) in group B, and from 575 to 525 μg/ml (NS) in group C. A significant decrease in the peripheral eosinophil count was observed only in group B. The improvement in bronchial hyperresponsiveness was parallel with that of asthmatic symptoms; the percentage of patients becoming symptom‐free rose from 12 to 42%, 5 to 89%, and 5 to 20% in groups A, B, and C, respectively. Out of 11 unimproved patients in group A, 7 showed a significant improvement in their histamine PC20 by BDI treatment (mean PC20: 311 → 1828 μg/ml). These results suggest that BDI might be more effective than antiallergic agents in the treatment of patients with long‐standing bronchial asthma.
Effects of H1‐receptor antagonists on nasal obstruction in atopic patients
Authors: Horak F. , Toth J. , Jäger S. , Berger U.
Published: May 2007

The aim of this study is to investigate whether H1‐receptor antagonists, besides their effect on nasal itching and sneezing, also have a measurable effect on nasal obstruction caused by allergen challenge. The antihistamine used was astemizole (10 mg) versus placebo, in a double‐blind, cross‐over, randomized study of two groups. Between the two sessions there was a wash‐out period of at least 4 weeks. Seven patients of both sexes, with proven allergy to grass pollen, underwent a specific long‐term provocation with grass pollen in the Vienna challenge chamber. Using a physiological method of challenge and a sensitive method for evaluating nasal function, we were able to prove H1‐receptor antagonist influence on nasal airway obstruction. The main parameters obtained arc nasal flow and nasal resistance at 75, 150 and 300 Pa, evaluated by active anterior rhinomanometry. We also investigated subjective symptom scores (0–3) of nasal, eye. and lung symptoms. It can be shown that the nasal flow under astemizole treatment is statistically significantly higher than the nasal flow under placebo treatment (P= 0.034). This is in accordance with the findings in subjective nasal itching and sneezing.
Occupational asthma and contact urticaria from dried flowers of Limonium tataricum
Authors: Quirce S. , García‐Figueroa B. , Olaguíbel J. M. , Muro M. D. , Tabar A. I.
Published: May 2007

Dried flowers of Limonium tataricum (LT) are widely used for semipermanent floral arrangements. We report a case of a floral industry worker in whom exposure to LT precipitated rhinoconjunctivitis, asthma, and contact urticaria. Studies revealed the presence of immediate skin test reactivity and positive leukocyte histamine release in response to LT extract. Specific anti‐LT antibodies were detected in the patient's serum by direct RAST. Bronchial challenge with LT extract also resulted in an isolated immediate asthmatic response. Both the positive methacholine inhalation test and the significant changes observed in PEFR measurements when the patient handled LT supported the diagnosis of occupational asthma. These findings strongly suggest that an IgE‐mediated immunologic mechanism is responsible for the patient's respiratory and cutaneous symptoms.
Allergens of Pityrosporum ovale and Candida albicans
Authors: Doekes G. , Kaal M. J. H. , van Ieperen‐van Dijk A. G.
Published: May 2007

Pityrosporum ovale has recently been recognized as a source of allergens to which many patients with atopic dermatitis (AD) show type I skin reactions and specific IgE antibodies. In this study the IgE‐binding components and/or epitopes in P. ovale extract were shown to be partially sensitive to pronase or trypsin treatment, whereas periodate oxidation resulted in a complete loss of IgE‐binding capacity, thus suggesting the involvement of carbohydrate structures. In Con A affinity chromatography most of the IgE‐binding capacity of crude P. ovale extract bound to the column, and could be eluted with mannoside. Gel filtration on Sephacryl S‐400 revealed a marked heterogeneity with respect to molecular mass, with most of the IgE‐binding activity associated with high‐mol.‐mass fractions (from 5 × 104 up to 2 × 106 Da). A similar heterogeneity was found after chromatofocusing, with IgE‐binding in the whole pI‐range from 7.0 to 4.0. Essentially identical results were obtained with extracts of Candida albicans, in agreement with the previously shown cross‐reactivity of IgE‐binding components in the two yeast extracts. In inhibition ELISA, gel filtration and chromatofocusing fractions containing components with widely different mol. mass or pi showed complete reciprocal cross‐inhibition, and were all capable of inhibiting the binding of IgE to unfractionated extracts. We therefore conclude that the cross‐reacting anti‐P. ovale/anti‐C. albicans IgE antibodies in the sera of AD patients are mainly directed at a restricted number of carbohydrate epitope that are expressed on a heterodisperse range of high‐mol‐mass components, probably mannans or mannoproteins.
A prospective safety‐monitoring study of immunotherapy with biologically standardized extracts
Authors: Tabar A. I. , García B. E. , Rodríguez A. , Olaguibel J. M. , Muro M. D. , Quirce S.
Published: May 2007

We evaluated the safety of immunotherapy in 419 patients who attended our allergy department for treatment. They were suffering from rhinitis and asthma caused by sensitization to grass pollen or Dermatophagoides pteronyssinus. Immunotherapy was given by biologically standardized aluminum hydroxide adsorbed extracts according to a conventional schedule. Local reactions were recorded in 10.5% of the patients and systemic reactions in 4.8%. Only 0.37% of the doses administered were associated with systemic side‐effects. We found that 84% of the patients who showed systemic reactions were asthmatic subjects (P<0.01), and most of them were sensitized to D. pteronyssinus (71%). Side‐effects occurred more frequently during the dose‐increase period (P<0.05). After 9482 doses had been administered, no anaphylactic shock or life‐threatening reactions were registered. We believe the risk associated with immunotherapy to be drastically reduced when treatment is carefully monitored by skilled personnel. In such conditions, as shown by our study, immunotherapy is safe.
The effect of immunotherapy on T‐cell subsets in peripheral blood and bronchoalveolar lavage fluid in pollen‐allergic patients
Authors: Rak S. , Hallden G. , Sörenson S. , Margari V. , Scheynius A.
Published: May 2007

The effect of immunotherapy (IT) on T‐cell subsets in peripheral blood and bronchoalveolar lavage fluid (BAL) was examined in 15 patients with rhinoconjunctivitis and asthma caused by sensitivity to birch pollen. They were treated with IT for 3 years. Seven patients were treated with highly standardized birch‐pollen extract (Pharmacia, Sweden). Eight untreated patients served as controls. Histamine challenge, blood sampling, and BAL were performed before (January, February), and at the peak of, the birch‐pollen season (May). The subpopulations of T cells in peripheral blood and BAL fluid were investigated by immunocytochemistry and flow cytometry. During the birch‐pollen season, the percentage of CD3+ and CD4+ cells of blood mononuclear cells in the IT patients increased significantly (P<0.03 and P<0.02, respectively). The percentage of CD8 + cells remained unaltered. In control patients, no changes of T‐cell subsets in the peripheral blood were observed. T‐cell subsets in BAL did not change during the season in relation to preseasonal values for either IT‐treated or non‐IT‐treated patients.
Inhibitory effect of levocabastine on allergen‐induced increase of nasal reactivity to histamine and cell influx
Authors: Pazdrak K. , Górski P. , Ruta U.
Published: May 2007

For evaluation of the effect of levocabastine pretreatment on allergen‐induced rhinitis symptoms, changes in nasal washings, and nasal responsiveness to histamine, 12 asymptomatic patients with documented allergic rhinitis participated in a single‐blind, placebo‐controlled study. Eight‐day treatment with levocabastine (twice in each nostril, four times a day) caused significant reduction in nasal symptoms and inflammatory cell influx after allergen challenge, as compared with placebo administration. Levocabastine inhibited increased nasal reactivity to histamine induced by allergen provocation, as controlled by rhinitis symptoms and albumin level in nasal washings. These data reveal a high effectiveness of levocabastine in the prevention of allergen‐induced rhinitis symptoms. Moreover, its inhibitory effect on inflammatory cell influx and hyperresponsiveness to histamine suggest that levocabastine is more than a simple H1‐receptor antagonist.
Nucleotide sequence of cDNA encoding the group II allergen of cocksfoot/orchard grass (Dactylis glomerata), Dac g II
Authors: Roberts A. M. , Bevan L. J. , Flora P. S. , Jepson I. , Walker M. R.
Published: May 2007

Cocksfoot/orchard grass (Dactylis glomerata) anther cDNA clones encoding the group II allergen Dac g II were previously isolated on the basis of immunoreactivity of human, rabbit, and murine antibodies with a 24–kDa protein expressed as a fusion protein with β‐galactosidase. Nucleotide sequencing reveals an open reading frame predicting expression of a 98–amino‐acid (11–kDa) polypeptide exhibiting > 90% homology with the group II allergen of Lolium perenne, Lol p II. In vitro translation of different sized clone fragments generated by polymerase chain amplification confirms eukaryotic expression of a 10–12–kDa polypeptide by SDS‐PAGE and the position of a translational stop apparently unrecognized during expression of λgt 11 in E. coli. The unusual characteristics of the prokaryote‐expressed fusion proteins may be exerting conformational alterations in Dac g II, as reflected by previous demonstrations of differences in human IgE immunoreactivity. Northern blot analysis using PCR‐generated partial and full‐length probes suggests that group II allergens may be encoded by a different family or families of temporally expressed genes from those encoding group I major allergens, although a group I gene may have been the progenitor.
The role of eosinophils in the pathogenesis of atopic dermatitis ‐ eosinophil granule proteins as markers of disease activity
Authors: Kapp A.
Published: May 2007

Currently, there is a large body of evidence that atopic dermatitis (AD) has an Immunologic basis. Atopy‐specific helper T cells (Th2‐like T cells) may play a pathogenetic role by producing and releasing cytokines relevant for the allergic inflammation, such as IL‐4, IL‐5, and other growth factors. Eosinophils are believed to be of major importance as effector cells mediating the pathogenetically relevant late‐phase reaction which is associated with a significant destruction of the surrounding tissue. Accordingly, a significant preactivation of peripheral blood eosinophils was detected in AD patients, leading to an enhanced susceptibility of these cells to distinct stimuli such as IL‐5. Toxic proteins, such as eosinophil cationic protein (ECP), contained in the matrix and the core of secondary granules of eosinophils, may play an important role by propagating the allergic inflammatory process and by modulating the immune response. The pathogenetic role of eosinophils in AD is further supported by the detection of these proteins in the eczematous skin of patients. Furthermore, recent data point to a significant correlation between disease activity and deposition of eosinophil granule content: ECP serum levels were significantly increased in AD patients. In addition, ECP levels correlated with the disease activity. Moreover, clinical improvement was associated with a decrease of both the clinical score and serum ECP levels. These data clearly indicate that activated eosinophils may play a major role in the allergic inflammatory process of AD. Therefore, modulation of eosinophil activation could prove to be an important pharmacologic modality for the treatment of AD.
Pharmacodynamic and pharmacokinetic studies with azelastine in the guinea pig: evidence for preferential distribution into the lung
Authors: Chand N. , Adusumalli V. E. , Nolan K. , Diamantis W. , Wichmann J. K. , Pivonka J. , Langevin C. N. , Wong K. K. , Kucharczyk N. , Sofia R. D.
Published: May 2007

The correlation between the antiasthma activity of azelastine and the concentrations of azelastine and its major metabolite, desmethylazelastine, in the blood and lung were investigated in guinea pigs. Blood and lung tissue samples collected at 15 min after aeroallergen (ovalbumin, 0.5 mg/ml, 30 s, 15 psi) challenge, i.e., 2–1/4 h after oral administration of the drug, were analyzed for azelastine and its desmethyl metabolite by specific HPLC assay. Azelastine afforded protection against immediate allergic responses (IAR, characterized by gasping and bronchospasmic convulsions). Based on the reduction of the severity of IAR, the ID50 was 0.04 mg/kg. It also delayed the onset of IAR and prevented mortalities. A positive correlation (r2= 0.944) between the antiallergic activity and the sum concentrations of azelastine and desmethylazelastine in the lung was observed. Preferential uptake of azelastine and desmethylazelastine by the lung was demonstrated by the mean lung/blood ratio of about 22 and 146, respectively. The selective uptake of azelastine and its active metabolite by the lungs could contribute to its antiasthmatic/antiallergic activity in guinea pigs.
T‐cell and antibody response to Parietaria Judaica allergenic fractions in atopic and nonatopic individuals
Authors: Sallusto F. , Quintieri F. , Pugliese O. , Reale G. , Pini C. , Di Felice G.
Published: May 2007

The in vitro proliferative response to separated immunologically relevant components of Parietaria judaica pollen extract (PjE) was investigated by proliferation assay and limiting dilution analysis, in peripheral blood mononuclear cells from Parietaria‐allergic subjects and nonallergic controls. In the same subjects, the profile of the antibody response to the PjE fractions was also studied by immunoblotting to evaluate the functional significance of allergen‐induced T‐cell activation in the two groups. The estimated frequency of PjE‐reactive T cells in peripheral‐blood mononuclear cells was low in both groups. No difference was found between the Parietaria‐allergic subjects and nonallergic controls. To assess the overall contribution to the cellular response of PjE components of different molecular weights, we separated the extract by the SDS‐PAGE technique, and the fractions were blotted onto nitrocellulose and solubilized. Almost all the 14 fractions tested induced T‐cell proliferation, at different degrees of magnitude. Responses were similar in the allergic subjects and nonallergic controls. Immunoblotting demonstrated specific IgG antibodies to the 14 PjE fractions not only in the allergic subjects, but also in the healthy controls, whereas IgE antibodies were found, as expected, only in the sera from atopic subjects. These findings indicate that PjE fractions elicit similar T‐cell activation and IgG production in allergic and normal subjects.
Occupational protein contact dermatitis from herring
Authors: Alonso M. D. , Dávila I. , Salazar L. Conde , Cuevas M. , Martin J. A. , Guimaraens M. D. , Losada E.
Published: May 2007

We present a case of occupational protein contact dermatitis caused by herring in a dolphinarium worker. The in vivo and in vitro tests results indicated a type I allergic mechanism. In vivo cross‐reactivity among fish belonging to the Clupeiformes order was observed.
Regional distribution of asthma‐related hospital treatment periods in Finland in 1972–86
Authors: Tuuponen T. , Keistinen T. , Kivelä S.‐L.
Published: May 2007

We examined the use of asthma‐related hospital services in geographically different areas of Finland in 1972–86, using data obtained from hospital discharge registers. A total of 254402 cases diagnosed as asthma was identified (diagnosis 493, International Classification of Diseases, 8th Revision), information on the patient's place of residence enabling comparison of the southern, western, eastern, and northern parts of the country. Annual hospitalizations and the occurrence of new cases were calculated relative to the population, the former being found to increase throughout the country during the period studied, the most marked rise being 8.8% in Northern Finland (95% confidence interval 6.4–11.3%), and the smallest, 1.1%, in Western Finland (−0.2 to +2.5). A corresponding trend was also noted in the annual occurrence of new cases, which increased most in Northern Finland, i.e. by 4.8% (3.0–6.6), and decreased in Western Finland by 2.9% (– 3.6 to –2.1). The change in asthma and the organization of treatment and factors related to the cold environment may, in combination, contribute to difficulties in the treatment of asthma in Northern Finland.
IgA antiendomysium antibodies have a high positive predictive value for celiac disease in asymptomatic patients
Authors: Grodzinsky E. , Hed J. , Skogh T.
Published: May 2007

Many attempts have been made to find screening tests for celiac disease to reduce the need for biopsy, or to achieve better selection criteria before intestinal biopsy. We have recently analyzed apparently healthy blood donors for antigliadin antibodies (AGA) to select subjects for further gastrointestinal investigation. A prevalence of gluten enteropathy of at least 1/256 was found in this population. The positive predictive value (+ PV), however, was only 20%. In the present study we have analyzed IgA antiendomysium antibodies (IgA‐EmA) to estimate the sensitivity and specificity of the test, and determine whether or not the + PV of the assay increases when screening for adult celiac disease in an asymptomatic population. We found that asymptomatic persons with celiac disease may have IgA‐EmA. We found a 100% specificity of IgA‐EmA in the tested population of blood donors, whereas the sensitivity was about the same as that of IgA‐AGA. This result of a + PV of 100% indicates that a positive IgA‐EmA could replace biopsy in diagnosing celiac disease. However, further extended studies are needed to determine whether this is applicable in other populations. To screen patients for celiac disease, we recommend the easy and cheap IgA‐AGA assay as a preliminary test and the IgA‐EmA to verify the diagnosis and avoid unnecessary biopsies.
Detection of at least one high‐molecular‐mass, IgE‐binding component of the dust mite Lepidoglyphus destructor
Authors: Olsson S. , Härfast B. , Johansson S. G. O. , van Hage‐Hamsten M.
Published: May 2007

We studied the allergen composition in an extract of the storage mite Lepidoglyphus destructor. Monoclonal antibodies (mAbs) were raised against L. destructor by a standard hybridoma technique. In the subsequent screening, we concentrated on mAbs fulfilling three criteria. First, in ELISA, mAbs were assessed against a panel of various mite species, and only those reacting exclusively with L. destructor extract were selected for further analyses. Secondly, mAbs were selected in immunoblotting according to whether or not a novel pattern of reactivity emerged in comparison with earlier results. Thirdly, by radioimmunoassay (RIA), we selected mAbs that recognized components which were also recognized by human IgE from sera RAST positive to L. destructor. This yielded an L. destructor‐specific mAb (117F9) reacting with two previously unknown components of approximately 79 and 93 kDa, respectively. We also analyzed 80 sera for the presence of IgE binding to these components. These sera were divided into three groups according to their RAST specificity. Eighteen of the 30 sera (60%) that were RAST positive to L. destructor were also positive in RIA. Correlation was moderate between kU/1 for L. destructor and the counts per minute values for the two components in RIA. The group of control sera lacking IgE antibodies against L. destructor displayed no positive results in RIA. However, 4/20 sera RAST positive to Dermatophagoides pteronyssinus but negative to L. destructor were scored as positive in RIA. We conclude that at least one of the high‐mol.‐mass components of L. destructor causes IgE‐mediated sensitization.
Prevalence of IgE antibodies specific for food allergens in patients with chronic urticaria of unexplained etiology
Authors: Kaeser P. , Revelly M. L. , Frei P. C.
Published: May 2007

We investigated whether some cases of chronic urticaria of unexplained cause might be related to food allergy which had remained undetected during routine examination. This investigation was undertaken as the consequence of the availability of a new in vitro assay for specific IgE with increased sensitivity. The following three groups of subjects were studied: 1) a control group of 60 nonatopic subjects, 2) 60 patients with allergy to perennial aeroallergens without skin involvement, and 3) 60 patients suffering from chronic urticaria with no evidence of any triggering factor despite careful clinical investigation. Specific IgE against 19 food allergens frequently involved in urticaria were investigated in all subjects with the new CAP System (Pharmacia). Positive results (CAP > 0.70 kU/1) for one or more food allergens were found in none of the nonatopic controls, in six of the subjects with respiratory allergy, and in 16 of the urticaria patients. The use of an in vitro test with an increased sensitivity allowed us to detect a significant prevalence of IgE specific for food allergens in patients with chronic urticaria of unknown origin. This suggests that, in several of those patients, chronic urticaria might be triggered by a food allergy undetected by the usual methods.
Comparison between sodium cromoglycate (MDI: metered‐dose inhaler) and beclomethasone dipropionate (MDI) in treatment of adult patients with mild to moderate bronchial asthma A double‐blind, double‐dummy randomized, parallel‐group study
Authors: Faurschou P. , Bing J. , Edman G. , Engel A.‐M.
Published: May 2007

This study compared the efficacy and tolerability of sodium cromoglycate (SC) and beclomethasone dipropionate (BDP) in adult patients with bronchial asthma inadequately treated with bronchodilators alone. The study was a double‐blind, randomized, double‐dummy, parallel‐group study. Patients with mild to moderate symptomatic asthma, inadequately treated with bronchodilators only, were, after a 2–week run‐in (base‐line) period, randomized to 8 weeks of treatment with either SC 10 mg four times daily or BDP 100 μg four times daily. Salbutamol metered‐dose inhaler was given as relief medication. A total of 37 patients were randomized for treatment, 19 patients in the SC group and 18 patients in the BD group. Efficacy and safety were determined by daily record card data: morning and evening peak‐expiratory‐flow rates (PEER), daytime and nighttime asthma symptom scores, and rescue salbutamol use. At clinic visits, FEV1 and FVC were measured, as were the physician's and the patient's assessment of the medication at the end of the study. The safety and tolerability of the trial medication were assessed by monitoring adverse events throughout the study. A clinically and statistically significant improvement of the asthma in FEV1, symptom scores, rescue medication, and global opinion of efficacy was observed, and both groups provided equivalent efficacy. The morning PEFR as well as the evening PEFR for both groups improved, but was statistically significant only for the BDP group (M‐PEFR). Both drugs were well tolerated with only a few minor adverse events. This trial shows that SC and BDP are equally effective anti‐inflammatory treatments for mild to moderate bronchial asthma in adults.
Therapeutic effect of loratadine on pruritus in patients with atopic dermatitis
Authors: Langeland T. , Fagertun H. E. , Larsen S.
Published: May 2007

The aim of the study was to assess the therapeutic efficacy of loratadine on pruritus in patients with atopic dermatitis, considering the patients’ sensation of itch. Sixteen patients, mean age 24.8 years, with moderate or severe atopic dermatitis were included in a double‐blind and placebo‐controlled study with a six‐period, multi‐crossover design. The patients were given 10 mg loratadine or placebo every day, alternating between loratadine and placebo every 2 weeks. The degree of pruritus during the day and during the night was recorded by the patients every morning and every evening, respectively, on a 10‐cm visual analog scale. The study detected a significant effect of loratadine, as compared with placebo, on pruritus during the day, pruritus during the night, and severity of rash. At least nine of the 16 patients included were classified as responders and only one as a nonresponder to loratadine treatment. It is concluded that loratadine may be tried as an adjuvant therapy in the management of severe and moderate atopic dermatitis, in patients complaining of pruritus.
Plasma acetylsalicylic acid and salicylic acid levels during aspirin provocation in aspirin‐sensitive subjects
Authors: Dahlén B. , Boréus L. O. , Anderson P. , Andersson R. , Zetterström O.
Published: May 2007

The ability of aspirin and other nonsteroidal anti‐inflammatory drugs (NSAIDs) to inhibit the cyclo‐oxygenase which catalyzes formation of prostaglandins appears to be central to the mechanisms involved in aspirin sensitivity. We have investigated whether the plasma levels of acetylsalicylic acid (ASA) and its main metabolite salicylic acid (SA) at the time of intolerance reactions correspond with the concentrations required for enzyme inhibition in vitro. Twelve aspirin‐sensitive and 15 aspirin‐tolerant subjects were followed during provocation with aspirin. ASA and SA concentrations in plasma were determined by HPLC. After oral provocation (up to 460 mg cumulative dose), the levels of ASA and SA in plasma were equivalent in aspirin‐sensitive and aspirin‐tolerant subjects. For the aspirin‐sensitive subjects, at the time of adverse reaction, the concentration range was 2.9–33.3 μM for ASA and 18.1–245 μM for SA. Oral provocation with sodium salicylate yielding 10‐fold higher SA levels did not elicit intolerance reactions. Statistically significantly lower levels of ASA and SA (P>0.01) evoked airway obstruction, as compared with merely extrapulmonary symptoms. Bronchial absorption of aspirin was found after inhalation of lysine‐aspirin and was comparable in asthmatic and nonasthmatic subjects. In three aspirin‐sensitive subjects who developed airway obstruction, the plasma levels for ASA and SA were 0.9–2.6 μM and 0.0–6.7 μM, respectively. In conclusion, the plasma levels of ASA reached at the time of a positive reaction are of the magnitude known to inhibit cyclo‐oxygenases. Neither differences in bioavailability of ASA nor the formation of SA seems to contribute to the aspirin‐elicited reactions.
Positivity of patch tests in cutaneous reaction to diclofenac
Authors: Romano A. , Pietrantonio F. , Di Fonso M. , Garcovich A. , Chiarelli C. , Venuti A. , Barone C.
Published: May 2007

Immune‐mediated reactions to NSAIDs are unusual. We have observed two cases of maculopapular eruptions occurring 48–72 h after administration of diclofenac sodium. Patch tests performed with diclofenac were positive. The histopathologic findings resembled those of contact dermatitis with different degrees of dermal involvement. Clinical, allergologic, and histopathologic patterns strongly suggest a type IV mechanism of hypersensitivity. Patch tests play an important role in the assessment of possible immunologic mechanisms underlying cutaneous reactions to drugs.
Mechanisms of eosinophil and basophil migration
Authors: Wardlaw A. J. , Walsh G. M. , Symon F. A.
Published: May 2007

Wardlaw AJ, Walsh GM, Symon FA. Mechanisms of eosinophil and basophil migration.
Naturally occurring human IgA autoantibodies against IgE‐DES myeloma protein
Authors: Magnusson C. G. M.
Published: May 2007

The prevalence and specificity of naturally occurring human IgA anti‐IgE autoantibodies (a‐E Ab) were studied by ELISA with anti‐IgA monoclonal antibodies (mAb) and a purified myeloma IgE as solid‐phase protein, i.e., IgE‐DES(κ). Such detected IgA a‐E Ab were common among adults, and significantly increased geometric means (GM) were found in patients with atopy (P= 0.006; n= 41; GM = 79.3 arbitrary units (AU)/ml) and filariasis (P= 0.02; n= 41; GM = 75.9 AU/ml), as compared with nonatopic controls (n= 42; GM = 48.8 AU/ml). No such difference was observed between age‐matched nonatopic (n= 22; GM = 36.7 AU/ml) and atopic (n= 22; GM = 38.6 AU/ml) children. Children had significantly (P= 0.001) lower IgA a‐E Ab concentrations than adults, probably as a result of age, because IgA a‐E Ab concentrations and age of children were significantly correlated (n= 44; P<0.05; rs= 0.30). IgA a‐E Ab concentrations were very low in cord serum (n= 32; median <0.1 AU/ml). Sex did not influence IgA a‐E Ab concentrations in any study group. The specificity of IgA a‐E Ab in nine sera was studied by ELISA inhibition assay using IgE‐DES myeloma as solid‐phase protein and inhibitory proteins of the IgG, IgM, IgD, and IgE classes, including five different IgE myeloma proteins, as well as three enzymatic fragments of IgE‐DES. The inhibitions indicated that all IgA a‐E Ab tested reacted in a low‐affinity reaction with determinants restricted to IgE‐DES, i.e., the solid‐phase protein. These epitopes were heat‐resistant (2 h; 56°C) and located in the Fabɛ‐DES fragment. No isotype‐specific IgA a‐E Ab were found because none of the four other IgE proteins were inhibitory. Subclass typing indicated that most IgA a‐E Ab belonged to the IgA 1 subclass. It is unlikely, for reasons of restricted specificity, low affinity, and common prevalence, that such IgA 1 a‐E Ab are connected with IgE‐mediated disorders. The study also raises questions on the definition of anti‐IgE antibodies.
Salmeterol in two different doses in the treatment of nocturnal bronchial asthma poorly controlled by other therapies
Authors: Faurschou P. , Engel A.‐M. , Haanaes O. C.
Published: May 2007

This study compared the efficacy of inhaled salmeterol (SM) 50 μmg twice a day with SM 100 μmg once a day (at night) and placebo in patients with poorly controlled nocturnal asthma despite treatment with corticosteroids, oral long‐acting bronchodilators, or both. This was a two‐center, double‐blind, randomized, crossover study with three treatment periods, each of 3 weeks’ duration. The first treatment period was preceded by two 1‐week run‐in periods, and the last treatment period was followed by a 2‐week follow‐up period. In the three treatment periods, patients received either SM 50 μmg twice a day, SM 100 μmg nightly, or placebo, in randomized order. Salbutamol metered‐dose inhaler was given as relief medication. Of the 41 randomized patients, 38 were evaluable for more than one treatment period. Efficacy and safety were determined by daily record card data: morning and evening peak expiratory flow rates (PEFR), daytime and nighttime asthma symptom scores, and rescue salbutamol use. At clinic visits, FEV1 and FVC were measured, and the physicians’ and the patients’ respective assessments of the study mediation were noted. The study showed that the two doses, SM 50 μmg twice a day and SM 100 μmg nightly, were equally effective in controlling nocturnal asthma symptoms and were significantly better than placebo. SM was well tolerated, and no unexpected problems were revealed. The adverse events reported during this study were related either to the patient's underlying disease or to an intercurrent respiratory infection.