bluuebunny/crossref_metadata_2025 huggingface dataset:
A model of evidence production and optimal standard of proof and penalty in criminal trials
Authors: Yilankaya Okan
Published: March 2003

The defendant is either innocent or guilty, which she, not the court or prosecutor, knows. The court convicts the defendant whenever its posterior probability of her guilt – which depends on the evidence presented – is greater than the standard of proof. Evidence production by litigating parties is a costly stochastic process. Subsequently, the optimal choice of standard of proof and penalty is analysed. The optimal standard of proof is increasing in the cost of convicting an innocent defendant and decreasing in the cost of acquitting a guilty defendant. Higher penalties may increase probabilities of both false conviction and false acquittal.

Un modèle de production de la preuve et la norme optimale de la preuve et de la punition dans les procès criminels. On développe un modèle de production de la preuve par les parties en litige dans un contexte criminel. L’accusé peut être de deux types – innocent ou coupable – et il sait de quel type il est. Mais ni le tribunal ni le procureur n’ont cette information. Le tribunal ne va condamner l’accusé que si la probabilité a posteriori de culpabilité de l’accusé est plus grande qu’une certaine valeur seuil – la norme de la preuve. Cette probabilité dépend des preuves présentées par les parties au tribunal. La production de la preuve est un processus stochastique coûteux. Ce modèle de production de la preuve est utilisé pour analyser le choix optimal de la preuve et de la punition. Comme on pouvait s’y attendre, on peut montrer que la norme optimale de la preuve s’accroît à proportion que s’accroît le coût de condamner un innocent et décroît à proportion que s’accroît le coût de l’acquittement d’un coupable. Ce qui est plus surprenant, on peut montrer que l’accroissement de la punition infligée à un accusé trouvé coupable peut accroître les probabilités à la fois de condamnation et d’acquittement non fondés.
On the domain of selfadjoint extension of the product of Sturm‐Liouville differential operators
Authors: Ibrahim Sobhy El-Sayed
Published: March 2003

The second‐order symmetric Sturm‐Liouville differential
expressions τ1, τ2, …, τn with real
coefficients are considered on the interval I = (a, b), −∞ ≤ a < b ≤ ∞. It is shown that the characterization
of singular selfadjoint boundary conditions involves the
sesquilinear form associated with the product of Sturm‐Liouville
differential expressions and elements of the maximal domain of
the product operators, and it is an exact parallel of the regular
case. This characterization is an extension of those obtained by
Everitt and Zettl (1977), Hinton, Krall, and Shaw (1987),
Ibrahim (1999), Krall and Zettl (1988), Lee (1975/1976), and
Naimark (1968).
Generalized join‐hemimorphisms on Boolean algebras
Authors: Celani Sergio
Published: March 2003

We introduce the notions of generalized join‐hemimorphism and
generalized Boolean relation as an extension of the notions of
join‐hemimorphism and Boolean relation, respectively. We prove a
duality between these two notions. We will also define a
generalization of the notion of Boolean algebra with operators by
considering a finite family of Boolean algebras endowed with a
generalized join‐hemimorphism. Finally, we define suitable
notions of subalgebra, congruences, Boolean equivalence, and open
filters.
Plasma Adiponectin Concentrations in Relation to Endometrial Cancer: A Case-Control Study in Greece
Authors: Petridou Eleni , Mantzoros Christos , Dessypris Nick , Koukoulomatis Panagiotis , Addy Carol , Voulgaris Zannis , Chrousos George , Trichopoulos Dimitrios
Published: March 2003

Adiponectin is a hormone secreted exclusively by adipocytes, and obesity is an established risk factor for endometrial cancer. We have, thus, evaluated the association of adiponectin with the occurrence of endometrial cancer. Questionnaire information and blood samples were taken before treatment from 84 women with newly diagnosed, histologically confirmed endometrial cancer and 84 control women who were admitted for minor gynecologic problems, mainly pelvic prolapse. Adiponectin levels were measured by immunoassay. The results were analyzed through multiple logistic regression and controlled for known risk factors for endometrial cancer, leptin, as well as major components of the IGF system (IGF-I, IGF-II, and IGF-binding protein 3). Among control women, there was no significant association of adiponectin with age or parity. Although there was no association of adiponectin with endometrial cancer among women 65 yr or older, there was an inverse, fairly strong, and statistically significant inverse association among younger women. Among women younger than 65 yr, an increase of adiponectin by 1 sd was associated with a more than 50% reduction of the risk for endometrial cancer [odds ratio (OR) 0.44; 95% confidence interval (CI) 0.24–0.81], even after controlling for body mass index and other potential confounders. Among all women, the adjusted OR for a 1 sd increase in adiponectin was not significant (OR, 0.78; 95% CI, 0.56–1.10) but was significant for a one quintile increase in adiponectin (OR, 0.74; 95% CI, 0.56–0.97). In women younger than 65 yr, among whom obesity represents a powerful risk factor for endometrial cancer, adiponectin is inversely and significantly related to the risk of this disease. This association is independent of possible effects of major components of the IGF system, leptin, body mass index, sociodemographic variables, and known endometrial cancer risk factors. Future studies are needed to prove causality and provide insight on both the mechanism of action of this hormone and its potential role in endometrial cancer.
Effects of Recombinant Human Insulin-Like Growth Factor (IGF)-I and Estrogen Administration on IGF-I, IGF Binding Protein (IGFBP)-2, and IGFBP-3 in Anorexia Nervosa: A Randomized-Controlled Study
Authors: Grinspoon Steven , Miller Karen , Herzog David , Clemmons David , Klibanski Anne
Published: March 2003

Administration of recombinant human (rh) IGF-I has been shown to have positive effects on bone density in anorexia nervosa, but the effects of rhIGF-I and estrogen on IGF binding protein (IGFBP)-2 and IGFBP-3 in anorexia nervosa are not known. Sixty-five osteopenic women with anorexia nervosa were randomized to rhIGF-I (30 μg/kg sc twice daily) alone (n = 15), daily ethinyl estradiol (Ovcon 35) with rhIGF-I (n = 15), estradiol and placebo (n = 15), or placebo (n = 14) for 9 months. Subjects were 25.6 ± 0.8 yr of age, low weight (body mass index 16.6 ± 0.2 kg/m2) and osteopenic (T scores −2.06 ± 0.09 for spine and −1.76 ± 0.13 for hip). IGFBP-3 correlated with total hip bone density (r = 0.47, P = 0.0002) and was a significant predictor of hip bone density (P = 0.010) independent of IGF-I and body mass index in a multivariate regression model. During therapy, IGFBP-2 increased by 48 ± 19 ng/ml in response to rhIGF-I and decreased by −38 ± 22 ng/ml in response to placebo (P = 0.011). IGFBP-3 decreased (−895 ± 120 ng/ml) in response to rhIGF-I but showed a minimal change (−53 ± 99 ng/ml) in response to placebo (P < 0.0001). In contrast, no significant effect of estrogen was seen on IGF-I, IGFBP-2 or IGFBP-3. Among patients receiving rhIGF-I, the change in IGFBP-2 was inversely associated with the change in total hip bone density (R = −0.47, P = 0.013). In conclusion, our data suggest that chronic rhIGF-I administration increases IGF-I and IGFBP-2 and decreases IGFBP-3 in women with anorexia nervosa. IGFBP-2 and IGFBP-3 may be important determinants of bone density in this population.
Occupational asthma caused by champignon flies
Authors: Cimarra M , Martínez‐Cócera C , Chamorro M , Cabrera M , Robledo T , Alonso A , Castellano A , Bartolome JM , Lombardero M
Published: March 2003

Background: Occupational bronchial asthma in mushroom (champignon) workers is unusual, although reports on it appeared in 1938 and 1951; we have not found any others since those dates. Here we report the case of a 52‐year‐old man who works as a champignon cultivator. He suffered rhinoconjunctivitis and asthma attacks whenever he entered the champignon culture caves. We studied flies as a possible antigen source. We collected these insects from the growing sites in order to identify them, and then prepare an extract; the samples turned out to be of two families of insects of the order Diptera, 98% from the Phoridae family (Brachycera suborder) and 2% from the Sciaridae (Nematocera suborder).

Methods: Skin prick tests, conjunctival provocation tests, serum specific IgE, specific IgE‐binding fractions in immunoblotting, and monitoring of PEFR (at work and off work) were performed.

Results: IgE‐mediated hypersensitivity to these flies was demonstrated by skin prick test, conjunctival provocation test, serum specific IgE, and IgE‐binding fractions in immunoblotting. Monitoring of PEFR both at work and off work showed a clear relationship between symptoms, or fall in PEFR, and the workplace.

Conclusions: We report the case of a patient suffering from asthma and rhinoconjunctivitis caused by hypersensitivity to fly proteins.
Fluticasone and budesonide inhibit cytokine release in human lung epithelial cells and alveolar macrophages
Authors: Ek A , Larsson K , Siljerud S , Palmberg L
Published: March 2003

Glucocorticoids are potent anti‐inflammatory agents capable of influencing cytokine release in a number of cell types. The aim of the present study was to investigate whether glucocorticoids, frequently used in the treatment of asthma, interfere with cytokine secretion by lung epithelial cells and alveolar macrophages in vitro. Inhalation of swine dust induces airway inflammation with influx of inflammatory cells and release of proinflammatory cytokines in the lungs. Therefore, human lung epithelial cells (A549) and human alveolar macrophages were stimulated with swine dust or lipopolysaccharide (LPS), and the inhibitory effect of budesonide and fluticasone propionate on cytokine release was studied in a dose‐response (10−13–10−8 M) manner. The time course for the steroid effect was also investigated. Both steroids caused a dose‐dependent, almost total, inhibition of swine dust‐induced IL‐6 and IL‐8 release from epithelial cells and LPS‐induced IL‐6 and TNF‐α from alveolar macrophages. The steroids only partially inhibited IL‐8 release from alveolar macrophages. Budesonide was approximately 10 times less potent than fluticasone propionate. Preincubation with the steroids did not inhibit cytokine release more than simultaneous incubation with stimulus and steroid. In conclusion, budesonide and fluticasone propionate, in concentrations that probably occur in the airway lining fluid during inhalational therapy, inhibited cytokine release from human lung epithelial cells (IL‐6, IL‐8) and alveolar macrophages (TNF‐α, IL‐6, IL‐8). In vitro, the onset of this effect was rapid.
Serum eosinophil cationic protein (ECP): reference values in healthy nonatopic children
Authors: Fitch P.S. , Brown V. , Schock B.C. , Ennis M. , Shields M.D. , Taylor R.
Published: March 2003

Background: Although serum ECP concentrations have been reported in normal children, there are currently no published upper cutoff reference limits for serum ECP in normal, nonatopic, nonasthmatic children aged 1–15 years.

Methods: We recruited 123 nonatopic, nonasthmatic normal children attending the Royal Belfast Hospital for Sick Children for elective surgery and measured serum ECP concentrations. The effects of age and exposure to environmental tobacco smoke (ETS) on the upper reference limits were studied by multiple regression and fractional polynomials.

Results: The median serum ECP concentration was 6.5 μg/l and the 95th and 97.5th percentiles were 18.8 and 19.9 μg/l. The median and 95th percentile did not vary with age. Exposure to ETS was not associated with altered serum ECP concentrations (P=0.14).

Conclusions: The 95th and 97.5th percentiles for serum ECP for normal, nonatopic, nonasthmatic children (aged 1–15 years) were 19 and 20 μg/l, respectively. Age and exposure to parental ETS did not significantly alter serum ECP concentrations or the normal upper reference limits. Our data provide cutoff upper reference limits for normal children for use of serum ECP in a clinical or research setting.
Integrin expression on neutrophils and mononuclear cells in blood and induced sputum in stable asthma
Authors: Maestrelli P. , De Fina O. , Bertin T. , Papiris S. , Saetta M. , Mapp C.E. , Ruggieri M.P. , Fabbri L.M.
Published: March 2003

Background: We speculated that the expression of integrins in the airway lumen of asthmatic subjects might be altered compared with normal subjects during cell recruitment from circulation.

Methods: To test this hypothesis, we investigated the expression of integrin α‐chains (CD11a, CD11b, and CD11c) in hypertonic saline‐induced sputum and peripheral blood leukocytes in mild to moderate stable asthmatic and control subjects. Immunoreactivity for integrin α‐chains was assessed by immunocytology on cytospin preparations of sputum and blood.

Results: In comparison of the percentages of CD11a+, CD11b+ and CD11c+ mononuclear cells in sputum with their blood counterparts, no significant differences were observed in control subjects, whereas CD11a and CD11b in asthmatic subjects were less expressed on sputum cells. In both control and asthmatic subjects, sputum neutrophils tended to decrease their expression of integrin α‐chains compared with circulating neutrophils.

Conclusions: We showed that the sputum of asthmatics, unlike normal subjects, is characterized by decreased expression of integrins on mononuclear cells compared with their blood counterparts. The results suggest that downregulation of integrins occurs in asthmatic airways after cell recruitment from circulation.
Interleukin‐8 inhalation directly provokes bronchoconstriction in guinea pigs
Authors: Fujimura M , Myou S , Nomura M , Mizuguchi M , Matsuda T , Harada A , Mukaida N , Matsushima K , Harada A , Nonomura A
Published: March 2003

Background: Although it has been reported that the concentration of interleukin (IL)‐8 in nasal lavage fluid and sputum and its production in bronchial epithelium were increased in asthmatic subjects, the direct effects of IL‐8 on the airways in vivo is unclear.

Methods: We examined bronchoconstriction in response to IL‐8 inhalation through an endotracheal cannula in anesthetized, artifically ventilated guinea pigs.

Results: Inhalation of IL‐8 at concentrations of 1 and 10 μg/ml caused significant bronchoconstriction, as revealed by the elevation of pressure at the airway opening. Moreover, the bronchoconstriction induced by IL‐8 was significantly inhibited by the antihistamines diphenhydramine and terfenadine, suggesting the involvement of histamine release in the IL‐8‐induced bronchoconstriction. No significant leukocyte infiltration was observed in the bronchoalveolar lavage fluid or histologic findings 25 min after the first IL‐8 inhalation.

Conclusions: IL‐8 provokes bronchoconstriction without leukocyte accumulation in the airways, mediated in part by histamine release, in guinea pigs.
A study on severe food reactions in Sweden – is soy protein an underestimated cause of food anaphylaxis?
Authors: Foucard T , Malmheden Yman I
Published: March 2003

Background and methods: Because of a fatal case of soy anaphylaxis occurring in Sweden in 1992, a study was started the following year in which all physicians were asked to report fatal and life‐threatening reactions caused by food. The results of the first 3 years of the study are reported here, including results from another ongoing study on deaths from asthma during the same period.

Results: In 1993–6, 61 cases of severe reactions to food were reported, five of them fatal. Peanut, soy, and tree nuts seemed to have caused 45 of the 61 reactions, and four of them were fatal. If two cases occurring less than a year before our study started are included, we are aware of two deaths caused by peanuts and four deaths caused by soy. All four youngsters who died from soy anaphylaxis with asthma were severely allergic to peanuts but had no previously known allergy to soy. In most cases, there was a rather symptom‐free period for 30–90 min between early mild symptoms and severe and rapidly deteriorating asthma.

Conclusions: Soy has probably been underestimated as a cause of food anaphylaxis. Those at risk seem to be young people with asthma and peanut allergy so severe that they notice symptoms after indirect contact.
Quantitative flow cytometric analysis of the effects of cetirizine on the expression of ICAM‐1/CD54 on primary cultured nasal cells
Authors: Mincarini M. , Cagnoni F. , Canonica G. W. , Cordone G. , Sismondini A. , Semino C. , Pietra G. , Melioli G.
Published: March 2003

An in vitro flow cytometric model has been developed to evaluate the effects of antiallergic drugs such as cetirizine (CTZ) on the expression of surface molecules on primary cultured normal cells. Quantitative analysis demonstrated that HLA class I and ICAM‐1/CD54 molecules are present on both epithelial and stromal cells, and that their expression is strongly enhanced by treatment with interferon‐gamma (IFN‐γ). Nevertheless, the IFN‐γ‐mediated upregulation of ICAM‐1/CD54 was inhibited by treatment with CTZ, demonstrating a direct effect on both cell types. This finding is particularly interesting because ICAM‐1/CD54 is the main rhinovirus receptor, and rhinoviruses are the principal cause of asthma exacerbation in children. Thus, according to data derived from this in vitro model, CTZ should have an important role in the reduction of infectious exacerbation of asthma in atopic patients.
Mustard allergy in children
Authors: Rancé F. , Dutau G. , Abbal M M.
Published: March 2003

Background: Mustard allergy is not well known. This study aimed to assess its clinical features and other associated allergies, and to define skin prick tests (SPT), specific IgE, and dose response by oral food challenge.

Methods: Our study investigated 36 children with positive mustard SPT. The diagnosis of mustard allergy was based on open or single‐blind, placebo‐controlled food challenge (SBPCFC). We compared the subjects to 22 controls.

Results: The initial clinical features were atopic dermatitis (51.8%), and urticaria and/or angioedema (37%). Fifteen children were allergic (positive SBPCFC) and 21 children were nonallergic (negative SBPCFC). Symptoms after mustard ingestion started under 3 years of age in 53.3% of the subjects. There was no significant difference in the food allergies and associated inhalant allergen sensitizations between the two groups. In the allergic group, the mean wheal diameter for mustard SPT was 8.8 mm and the median concentration of mustard serum (s) IgE 14.8 kU/l. The mean cumulative reactive dose were 153 mg.

Conclusions: Allergic reactions to mustard started early in life. Clinical symptoms were not severe in children. Mustard should be included in screening tests of food allergy in children.
Trends in hospital admissions for childhood asthma in Oslo, Norway, 1980–95
Authors: Jónasson G. , Lødrup Carlsen K. C. , Leegaard J. , Carlsen K.‐H. , Mowinckel P. , Halvorsen K. S.
Published: March 2003

Background: Prevalence of asthma and quality of asthma care both influence hospital admission rates for childhood asthma. Therefore, we aimed to assess possible changes in hospital admission rate for acute asthma in Oslo, Norway, from 1980 to 1995, as well as evaluate the possible effect of changes in asthma treatment upon hospitalization for acute asthma in this period.

Methods: All pediatric patient records from the two municipal hospitals in Oslo from 1980 through 1995 with the discharge diagnosis (ICD‐9) acute asthma, acute bronchitis/bronchiolitis, pneumonia, and/or atelectasis were thoroughly reviewed.

Results: Of the 3538 children admitted for acute asthma, 66% were boys and 75% were younger than 4 years, and the admittance rate increased significantly among children aged 0–3 years. First admissions increased throughout the study, whereas readmissions, as well as the mean duration of hospital stay, decreased significantly. Prophylactic treatment with inhaled steroids prior to admission increased over 1980–89, but stabilized thereafter. The use of a short course of systemic steroids during admission increased markedly from 1991.

Conclusions: The findings of increasing first admission rate as well as overall admission rate for acute asthma in children under 4 years of age, but decreasing readmissions as well as number of treatment days in hospital, probably reflect changes in the management of the disease, as well as an increasing prevalence of childhood asthma.
Glucocorticosteroids rapidly inhibit allergen‐induced expression of E‐selectin in vitro in a mucosal model of allergic rhinitis
Authors: Rudack C. , Bachert C.
Published: March 2003

Background: Transendothelial migration of cells to sites of inflammation is a hallmark of the allergic reaction. The adhesion cascade involves the initial expression of the adhesion molecule E‐selectin on endothelial cells. The aim of the study was to determine the efficacy of a 30‐min preincubation of the glucocorticosteroids (GCS) fluticasone, prednisolone, and fluocortin butyl on allergen‐ and interleukin (IL)‐1β‐induced E‐selectin expression in allergic rhinitis.

Methods: Freshly taken nasal inferior turbinate mucosa of 19 subjects with allergic rhinitis was cut into small cubes and preincubated for 30 min with prednisolone (n=6), fluticasone (n=5), and fluocortin butyl (n=3) in different concentrations, followed by allergen exposure at a concentration of 1000 BU/ml for 1 and 2 h. Additionally, fluticasone‐preincubated tissues were exposed to recombinant human rhIL‐1β (n=5) at a concentration of 2 pg/ml. The expression of E‐selectin was assessed by immunohistochemistry (APAAP technique) and computerized image evaluation.

Results: In this model, E‐selectin expression was significantly upregulated by allergen and rhIL‐1β within 1 and 2 h. After 30‐min preincubation with prednisolone and fluocortin butyl at drug concentrations of 10−8 mol/l, we found a significant (≥50%) reduction of the E‐selectin expression after 1 and 2 h. Allergen‐induced E‐selectin expression was nearly abolished at concentrations of 10−5 (prednisolone) and 10−4 mol/l (fluocortin butyl). Fluticasone significantly inhibited E‐selectin expression by ≥50% at concentrations of 10−14 and 10−12 mol/l after 1 and 2 h, and abolished E‐selectin induction at concentrations of 10−12 and 10−10 mol/l, respectively. Exposure of mucosal cubes to rhIL‐1β (n=5) also induced rapid upregulation of E‐selectin expression, an effect which could be only partially suppressed by fluticasone preincubation at concentrations of 10−10 mol/l.

Conclusions: Allergen‐induced E‐selectin expression is significantly and rapidly inhibited by GCS preincubation, fluticasone being more potent than prednisolone and fluocortin butyl. We suggest that this rapid effect is mainly indirect, possibly by inhibition of allergen‐induced cytokine release.
House‐dust‐mite sublingual‐swallow immunotherapy (SLIT) in perennial rhinitis: a double‐blind, placebo‐controlled study
Authors: Guez S. , Vatrinet C. , Fadel R. , André C.
Published: March 2003

Background: The safety and efficacy of sublingual‐swallow immunotherapy (SLIT) in rhinitis caused by house‐dust mite were evaluated in a double‐blind, placebo‐controlled study including 75 patients for 24 months.

Methods: Patients received either placebo or SLIT with a standardized Dermatophagoides pteronyssinus (D.pt.) –D. farinae (D.f.) 50/50 extract. The mean cumulative dose was 90 000 IR, equivalent to 2.2 mg of Der p 1 and 1.7 mg of Der f I. Symptom and medication scores were assessed throughout the study. Exposure to house‐dust mite, skin sensitivity, and serum specific IgE and IgG4 were assessed before starting treatment and after 12 and 24 months.

Results: Seventy‐two patients (36 active–36 placebo) were eligible for intent‐to‐treat analysis. Thirty‐six patients dropped out of the study. The number of patients who dropped out due to lack of efficacy was eight out of 37 (21.6%) in the active treatment group compared to 15 out of 38 (39.5%) in the placebo group (chi‐square=2.81, P=0.09). Total symptom and medication scores decreased significantly after 12 and 24 months (P<0.05) of treatment in both groups, but no significant difference was observed between the active and placebo groups. After 24 months, the number of patients with high levels of indoor allergenic load decreased significantly in both groups compared to baseline data (P=0.01). Specific IgE (D.pt. and D.f.) increased significantly in the active treatment group after 12 and 24 months, while no change was observed in the placebo group. Specific IgG4 levels were not significantly modified in either group. Two patients in each group reported mild adverse effects. No severe adverse effects were reported.

Conclusions: We conclude that SLIT in rhinitis caused by house‐dust mite was safe, but there was a lack of consistent clinical benefit compared to placebo, probably due to the impact of the allergen avoidance measures that lowered the allergen burden.
Relationships between natural T cells, atopy, IgE levels, and IL‐4 production
Authors: Magnan A. , Mély L. , Prato S. , Vervloet D. , Romagné F. , Camilla C. , Necker A. , Casano B. , Montero‐Jullian F. , Malissen B. , Bongrand P. , Fert V.
Published: March 2003

Background: Th2 cells govern allergic disorders. Mechanisms leading to the Th2 commitment are dominated by the requirement of IL‐4. A potential source of this triggering IL‐4 could be the CD4+ subset of a small population of T cells, natural T (NT) cells. Indeed, this subset is involved in IgE responses in mice and produces promptly high amounts of IL‐4 in both mice and man.

Methods: NT cells were identified in peripheral blood by flow cytometry with antibodies against Vα24 and Vβ11, recognizing the T‐cell receptor specific for NT cells. Simultaneous staining with anti‐CD3, anti‐CD4, or anti‐CD8 antibodies was performed. The frequency of NT cells in man was studied according to the presence of atopy defined by the positivity of skin tests, according to total IgE levels in serum, and according to IL‐4 concentration of whole‐blood culture supernatants determined by a flow cytometer microsphere‐based assay.

Results: Seventy subjects were included, of whom 30 were atopic. The number of CD4+ NT cells was higher in atopics than in nonatopics (P=0.009). This number was correlated to the total IgE levels (r=0.34, P=0.03). In addition, the number of CD4+ NT cells, but also of CD8+ NT cells, was correlated to the levels of IL‐4 (r=0.71, P=0.01, and r=0.6, P=0.03, respectively).

Conclusions: These results show that the number of NT cells, particularly the CD4+ subset, is related to atopy, IL‐4 production, and IgE levels. Therefore, this population of T cells is likely to play a role in the Th2 commitment initiating atopic diseases.
IgE‐binding activity to enzyme‐digested ovomucoid distinguishes between patients with contact urticaria to egg with and without overt symptoms on ingestion
Authors: Yamada K. , Urisu A. , Koyama H. , Tokuda R. , Wada E. , Kondo Y. , Ando H. , Morita Y. , Torii S.
Published: March 2003

Background: We occasionally see egg‐allergic children who develop contact urticaria to hen's egg despite the absence of the overt symptoms on ingestion. The mechanisms remain to be elucidated.

Methods: Twenty‐one subjects with positive reactions to 20‐min patch tests for egg‐white antigens were divided into subgroups with positive (n=10) and negative (n=11) results to oral challenge tests by the same antigens. We measured IgE antibody for egg white and its components, and IgE‐binding activities to digestive enzyme‐treated ovomucoid by RAST inhibition.

Results: There were no significant differences in IgE antibody titers to egg white (positive vs negative: 30.3%vs 15.3%, P=0.130), ovomucoid (21.5%vs 10.2%, P=0.078), ovotransferrin (9.9%vs 3.7%, P=0.105), and lysozyme (3.4%vs 2.9%, P=0.944), except ovalbumin (16.8%vs 5.6%, P=0.024), between the positive and negative subjects in the provocation tests. In contrast, the concentration (1.93 μg/ml) of pepsin‐treated ovomucoid needed for 50% RAST inhibition in the challenge‐positive subjects was significantly (P=0.0003) lower than that(114.9 μg/ml) of negative subjects. Similar but less significant differences were obtained when ovomucoid fragments treated with chymotrypsin (0.91 μg/ml vs 6.86 μg/ml, P=0.014) and trypsin (0.75 μg/ml vs 4.67 μg/ml, P=0.041) were used as inhibitors.

Conclusions: We suggest that IgE antibodies from subjects showing contact urticaria despite the absence of reactions to the ingestion of egg white recognize the epitope(s) unstable to digestive enzymes.
Antigliadin IgE – indicator of wheat allergy in atopic dermatitis
Authors: Varjonen E. , Vainio E. , Kalimo K.
Published: March 2003

Background: Cereal grains are recognized as the cause of adverse reactions in some patients exposed to grain or flour by either inhalation or ingestion. Cereal‐related diseases, such as celiac disease and baker's asthma, have been well studied and the causative cereal proteins have been characterized. Although cereals form an essential part of daily nutrition, the allergenic proteins causing symptoms on ingestion in atopic dermatitis (AD) have remained obscure. In this study, we have investigated the allergenic fraction of wheat in AD.

Methods: Skin prick tests (SPT) with a NaCl wheat suspension and the ethanol‐soluble wheat gliadin were performed on 18 wheat‐challenge‐positive or ‐negative children with AD, six adult AD patients with suspected cereal allergy, and one adult with wheat‐dependent exercise‐induced urticaria/anaphylaxis. Serum total IgE and specific IgE‐antibody levels to wheat and gluten were measured with the radioallergosorbent test (RAST) simultaneously. In addition serum samples of all 25 patients were analyzed by IgE immunoblotting with the ethanol‐soluble wheat‐protein extract.

Results: Thirteen of the AD children were wheat‐challenge‐positive, 11/12 of them appeared to be positive with gliadin SPT, and all had an elevated gluten RAST value. Those challenge‐negative were negative with both gliadin SPT and gluten RAST. Positive wheat SPT and RAST alone were not associated with positive challenges. Four of the adult patients responded to a cereal‐free diet, although only two of them appeared to be positive with gliadin SPT and gluten RAST. A broad and intensive staining of gliadin peptides in IgE‐immunoblotting studies was seen in challenge‐positive children with positive gliadin SPT and/or gluten RAST. Besides staining of peptides in the main gliadin area of 30–46 kDa, a characteristic finding was the staining of small, <14‐kDa proteins with sera of challenge‐ and gliadin‐SPT‐positive patients.

Conclusions: We found that wheat‐allergic AD patients have IgE antibodies against gliadin that can be detected by both SPT and the sensitive immunoblotting method. This suggests that gliadin peptides are important allergens, and ingestion of wheat causes symptoms of AD. A broad and intensive IgE staining was seen of gliadin peptides against both the previously characterized peptides in the main gliadin area and small, previously uncharacterized peptides of less than 14 kDa. The gliadin SPT and gluten RAST are good screening methods. Further characterization of the IgE‐stained gliadin proteins is needed.
The atopy patch test (APT) – a useful tool for the diagnosis of food allergy in children with atopic dermatitis
Authors: Niggemann B. , Reibel S. , Wahn U.
Published: March 2003

Background: While immediate‐type clinical reactions to food can quite easily be identified by history or measurement of specific IgE in combination with positive oral food challenges, the evaluation of food allergy in the absence of immediate clinical reactions still presents diagnostic difficulties – particularly in children with atopic dermatitis. The objective of this study was to evaluate the diagnostic value of the atopy patch test (APT) with regard to late‐phase reactions observed in double‐blind, placebo‐controlled food challenges with cow's milk, hen's egg, wheat, and soybean.

Methods: We investigated 75 children (median age 2.1 years) with suspected food allergy by double‐blind, placebo‐controlled food challenges, specific IgE in serum, skin prick test, and APT. Of the subjects, 69/75 suffered from atopic dermatitis.

Results: Of 209 oral challenges, 133 were performed with allergen and 76 with placebo. We assessed 77/133 allergen and 2/76 placebo challenges as positive. In 66 of 77 (86%) positive oral challenges, specific IgE in serum to the corresponding allergen was positive; in 64/77 (83%) the skin prick test, and in 42/77 (55%) the APT was positive. While immediate‐type reactions were associated with positive skin prick test and proof of specific IgE in serum, late‐phase clinical reactions were associated with a positive APT (sensitivity 76%, specificity 95%).

Conclusions: The APT seems to be a valuable additional tool in the diagnostic work‐up of food allergy in children with atopic dermatitis – especially with regard to late‐phase clinical reactions. The APT may help to prevent unnecessary restrictive diets which may be the consequence of misjudging late reactions by clinical assessment alone.
Respiratory infections and asthma
Authors: Errico M. , Andrea B. , D'auria D. , Gennaro M.
Published: March 2003

Clinical and experimental evidence suggests an important role for respiratory infections in the development of asthma attacks. Viral upper respiratory infections have been associated with 80% of asthma exacerbations in children and 50% of all asthma episodes in adults. Human rhinovirus has been implicated as the principal virus associated with asthma episodes. Separate studies indicate that atypical bacteria such as Chlamydia pneumoniae and Mycoplasma pneumoniae may precipitate asthma symptoms. Although not completely clarified, the intricate pathogenetic mechanisms by which viral infections promote asthma attacks have been extensively investigated in recent years. By contrast, it has not yet been established whether atypical bacterial infections are an epiphenomenon or a pathogenic event in asthma.
Immediate contact allergy from hydrolyzed wheat in a cosmetic cream
Authors: Varjonen E. , Petman L. , Mäkinen‐Kiljunen S.
Published: March 2003

Immediate contact allergy to cosmetics seems to be rare, since only a few case reports on it have been published. We report on a case of IgE‐mediated allergic contact urticaria caused by hydrolyzed wheat in a body cream.
Reduction of side‐effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine:a double‐blind, placebo‐controlled trial
Authors: Reimers A. , Hari Y. , Müller U.
Published: March 2003

Background:Immunotherapy with Hymenoptera venoms is highly effective but causes allergic side‐effects frequently, especially when honeybee venom is used. Therefore, our objective was to investigate the effect of pretreatment with the antihistamine fexofenadine on the incidence of allergic side‐effects during ultrarush immunotherapy with bee venom.

Methods:In a double‐blind, placebo‐controlled trial, 57 patients with a history of systemic allergic reactions to honeybee stings and positive diagnostic tests (skin tests, serum specific IgE to honeybee venom) were investigated. Bee venom immunotherapy was started with an ultrarush protocol and patients were randomized to pretreatment with either fexofenadine 180 mg or placebo on days 1, 8, 22, and 50 of the protocol. Local and systemic allergic side‐effects were registered.

Results:Fifty‐four patients completed the study, 28 on fexofenadine and 26 on placebo pretreatment. On day 1, large local reactions were significantly reduced in both extension and duration by fexofenadine pretreatment (P<0.025). Systemic allergic side‐effects on the whole were not reduced. However, the symptoms pruritus, urticaria, and angioedema occurred less frequently with fexofenadine (P<0.05).

Conclusions:Pretreatment with fexofenadine during venom immunotherapy reduces local allergic reactions and generalized symptoms of the urticaria and angioedema type.
Combining a β2‐agonist with a face mask to prevent exercise‐induced bronchoconstriction
Authors: Millqvist E. , Bengtsson U. , Löwhagen O.
Published: March 2003

Background: In this study, we aimed to test the effect of combining a β2‐agonist with a heat‐ and moisture‐exchanging cellulose face mask in patients with bronchoconstriction induced by exercise in cold air.

Methods: Nine allergic, asthmatic patients with a history of adverse reaction to exercise were tested on an ergometric bicycle at a temperature of approximately −10°C. They were in turn given no treatment, given premedication with a β2‐agonist, allowed to breathe through a heat‐ and moisture‐exchanging cellulose face mask, and given both premedication and the face mask. After each treatment regimen, they were subjected to provocation with exercise and cold air.

Results: The decrease in FEV1was greatest with no therapy (mean maximal change: 27%), and this diminished when the face mask was used (mean maximal change: 12%) or premedication with a β2‐agonist was given (mean maximal change: 7%); no decrease in FEV1 occurred with the combination of agonist and face mask.

Conclusions: The results suggest that different mechanisms are involved in the pathophysiology of exercise‐induced bronchoconstriction (EIB). This finding may be of importance for asthmatic athletes who train and compete in a cold climate and are affected by small changes in their lung function.
Intolerance of osteosynthesis material: evidence of dichromate contact allergy with concomitant oligoclonal T‐cell infiltrate and TH1‐type cytokine expression in the peri‐implantar tissue
Authors: Thomas P. , Summer B. , Sander C. A. , Przybilla B. , Thomas M. , Naumann T.
Published: March 2003

Background: We report on a 37‐year‐old man without history of previous allergic disease who developed an aseptic intolerance reaction to a chromium‐cobalt alloy, with local discomfort, loosening, and absence of fracture healing. Both in vivo and in vitro allergoimmunologic diagnostic tests were performed.

Methods: Patch testing was done with a European standard series. Specific serum IgE was measured by CAP‐FEIA. In addition to immunohistology (APAAP method), peri‐implantar tissue was further analyzed by PCR to determine T‐cell‐receptor‐γ rearrangement and thus the potential clonal (antigen‐driven) T‐cell repertoire. The actual tissue mRNA expression for IL‐4, IL‐6, and IFN‐γ was visualized by RT‐PCR.

Results: Skin testing gave a delayed‐type reaction to dichromate. Specific serum IgE to natural rubber latex and grass pollen was found – but without clinical symptoms. Immunohistology revealed a monocytic and dense T‐cell infiltrate. The latter, instead of being random, showed an oligoclonal T‐cell receptor rearrangement. In addition, there was TH1‐type mediator expression (IL‐6 and IFN‐γ, but not IL‐4).

Conclusions: Skin test, examination of peri‐implantar tissue, and the prompt healing after replacement of the osteosynthesis material suggest an allergic reaction. PCR analysis of peri‐implantar tissue can further help to identify and understand allergy‐mediated implant intolerance reactions.
Low‐dose inhaled budesonide once or twice daily for 27 months in children with mild asthma
Authors: Jónasson G. , Carlsen K‐H. , Jonasson C. , Mowinckel P.
Published: March 2003

This study is an extended follow‐up for 24 months of a 12‐week trial to study the long‐term clinical efficacy of low‐dose inhaled budesonide (BUD) once or twice daily in children with mild asthma. A total of 122 children (mean age 9.7 years, girls/boys; 42/80) with mild asthma (FEV1 103.7% of predicted, reversibility in FEV1 3.5%, and fall in FEV1 afterexercise 12.2%), not previously treated with inhaled steroids, were included in a double‐blind, randomized, parallel‐group study. The children were treated with inhaled BUD 100 or 200 µg administered via Turbuhaler® once daily in the morning, 100 µg twice daily, or placebo for 27 months. Exercise and methacholine challenges were performed at 3‐month intervals the first year and at 6‐month intervals the second year, in a total of seven visits. A significant dose‐response effect favoring BUD 200 µg daily (vs 100 µg daily) was found when comparing changes in FEV1, FEF25%, and FEV50%; the fall in FEV1 after an exercise test; and the effect on blood eosinophils. Bronchial hyperreactivity to methacholine decreased significantly on three visits in patients treated with BUD 200 µg daily compared to placebo. Growth rate was not significantly affected except in children aged 7–11 years at baseline after 12 months of treatment. In conclusion, 100 or 200 µg daily of inhaled BUD for 27 months is safe and effective in protecting against exercise‐induced asthma and achieving nearly normal lung function. Baseline lung function was not significantly affected in this group of children with mild asthma.
Atopic dermatitis in 5–6‐year‐old Swedish children: cumulative incidence, point prevalence, and severity scoring
Authors: Broberg A. , Svensson Å , Borres M. P. , Berg R.
Published: March 2003

Background: This study aimed to evaluate the cumulative incidence, point prevalence, and severity of atopic dermatitis (AD) in a pediatric population. We also aimed to identify differential diagnoses relevant to AD in this population.

Methods: Children scheduled for a health visit at 5.5 years of age were selected consecutively during the period October 1997–March 1998 from two cities in southern Sweden (Göteborg and Kristianstad). Schultz Larsen's questionnaire was used to evaluate the cumulative incidence of AD. Clinical examination was performed by dermatologists (A.B. and Å.S.) for those children with active eczema. The UK working party's criteria were used for the clinical diagnosis of AD. The SCORAD index was used to evaluate the severity of eczema. This index includes evaluation of extent, intensity, and subjective symptoms to a maximum score of 103 points.

Results: In Göteborg 1219 and in Kristianstad 742 questionnaires were answered regarding 1961 children, 1004 boys and 957 girls. The response rate was 89%. According to the answers to Schultz Larsen's questionnaire, the cumulative incidence of AD in the whole material was 20.7% (406/1961) (CI 95% 18.9–22.5). In Göteborg, 104 of the examined children fulfilled the UK working party's criteria, equivalent to a point prevalence of 8.5% (CI 95% 7.0–10.1). In Kristianstad, the corresponding point prevalence was 11.5% (CI 95% 9.2–13.8). The severity of AD was evaluated in all children with visible eczema. SCORAD evaluation was performed in 155 of the 157 children with visible eczema. The majority of children had mild or moderate eczema; mean value 20.5 (CI 95% 18.7–22.3), median 19.6. Of the 96 children who did not fulfil the criteria of AD, other skin disorders were diagnosed in 51 at the clinical examination. Dry skin was by far the most common differential diagnosis.

Conclusions: We have used validated protocols to evaluate the cumulative incidence, point prevalence, and severity of AD in a population‐based study in southern Sweden The present study, involving a rural and urban pediatric population, shows that AD is common, usually classified as mild or moderate, and seems to increase over time.
Ash (Fraxinus excelsior)‐pollen allergy in central Europe:specific role of pollen panallergens and the major allergen of ash pollen, Fra e 1
Authors: Hemmer W. , Focke M. , Wantke F. , Götz M. , Jarisch R. , Jäger S. , Götz M.
Published: March 2003

Background: The role of ash (Fraxinus excelsior) pollen as a cause of spring pollinosis in central Europe has received little attention. It is not clear whether ash pollen is a primary cause of sensitization or whether it is implicated through cross‐sensitization to other pollens.

Methods: Over a 22‐month period, ash pollen was included in a screening series for inhalant allergies. Pollen data were documented from 1976 through 1999. The frequency of IgE‐binding to the ash‐specific allergen Fra e 1 and pollen panallergens, respectively, was compared by Western blot between mono‐ (n=6), oligo‐ (n=16), and polysensitized (n=25) patients.

Results: Of 5416 consecutive patients sensitized to any pollen, 920 (17.6%) had a positive skin prick test to ash. Total pollen counts varied extensively between years (229–5351) as did peak concentrations (23–837 grains/m3/24 h). Western blotting revealed Fra e 1 sensitization in 100% of monosensitized, 93% of oligosensitized, but only 44% of polysensitized patients. IgE against profilins (Fra e 2), Ca‐binding proteins (Fra e 3), and carbohydrate epitopes in the three groups was found in 0/0/17%, 0/19/31%, and 32/72/60%, respectively. At least 50% of sera from patients with Fra e 1 sensitization did not bind with the protein in Western blots under reducing conditions.

Conclusions: Ash pollen should be considered a relevant factor and distinct entity in spring pollinosis. In all, only 20% of positive skin tests to ash appear to result from cross‐sensitization to pollen panallergens.
Identification and characterization of the major allergens of buckwheat
Authors: Park J. W. , Kang D. B. , Kim C. W. , Ko S. H. , Yum H. Y. , Kim K. E. , Hong C‐S. , Lee K. Y.
Published: March 2003

Background: Buckwheat (BW) has been recognized as a common food allergen in Korea, Japan, and other countries. Until now, serologic findings of BW food‐allergic patients and its major allergenic components have not been clarified. In this study, we analyzed the serologic findings of BW food allergy and characterized its major allergenic components.

Methods: Nineteen BW‐allergic subjects with symptoms after BW ingestion and 15 asymptomatic control subjects with positive skin prick test to BW were recruited. BW‐specific IgE was measured with the Pharmacia CAP kit. Allergenic components of BW were analyzed by IgE immunoblotting, periodate oxidation, two‐dimensonal PAGE, and sequencing of N‐terminal amino acids.

Results: From the BW‐allergic patients and asymptomatic controls, the sensitivity (100%), specificity (53%), and negative (100%) and positive predictive values (73%) of Pharmacia CAP specific IgE for diagnosis were estimated. The prevalence of IgE binding to 24‐kDa (pI 8.3), 16‐kDa (pI 5.6), and 9‐kDa (pI 5.0/6.0) allergens was higher than 50% in BW‐allergic and asymptomatic subjects. However, the specific IgE to split 19‐kDa (pI 6.5/7.0) allergens were more specifically found in BW‐allergic patients than in asymptomatic subjects (78%vs 7%). N‐terminal amino‐acid sequences of 19‐kDa and 16‐kDa allergens showed moderate and weak homology to the 19‐kDa globulin protein of rice and α‐amylase/trypsin inhibitor of millet, respectively. The N‐terminus of the 9‐kDa isoallergens were not different from each other and were identified as the reported trypsin inhibitors of BW. Attenuation of the IgE binding to the 9‐kDa allergen was found with periodate oxidation.

Conclusions: The allergens of 24, 19, 16, and 9 kDa are strong candidates to be major allergens, and the 19‐kDa allergen was relatively specific for BW‐allergic patients. Moreover, measurement of BW‐specific IgE and the features of immunoblotting should be very useful tools in the diagnosis of BW allergy.