bluuebunny/crossref_metadata_2025 huggingface dataset:
Interest Rate Surprises and Stock Prices
Authors: Lobo Bento J.
Published: March 2003

This paper examines the impact of unexpected changes in the federal funds target on stock prices from 1988 to 2001. Measures of interest rate surprises are constructed from survey data and changes in the 3‐month T‐bill yield. I find that surprises associated with decreases in the target cause stock prices to rise significantly. Surprises associated with increases in the target increase stock market volatility on the announcement day, with volatility reverting to pre‐surprise levels on the day after the announcement. This volatility pattern is only evident since 1994. An implication is that concerns about immediate disclosure causing persistent and heightened stock market volatility might be misplaced.
The Effect of the Common Bond and Membership Expansion on Credit Union Risk
Authors: Frame W. Scott , Karels Gordon V. , McClatchey Christine
Published: March 2003

This paper empirically examines differences in credit union risk profiles based on membership type and membership expansion via select employee groups (SEGs). We find that (1) occupational credit unions have a greater exposure to concentration risk, which they hedge by holding greater proportions of capital, (2) the presence of SEGs is negatively related to credit union capital ratios and positively related to loan–to–share ratios, and (3) the number of SEGs and the proportion of loan delinquencies are positively related. We conclude that credit union membership expansion results in reduced concentration risk and expanded investment opportunities, but also dilutes the informational advantages associated with tight common bonds.
CHALLENGES ANDAPPROACHES TOREDUCINGFOODBORNEILLNESS
Authors: Woteki Catherine E. , Kineman Brian D.
Published: March 2003

▪ Abstract  Microorganisms have successfully adapted to changes in food production, processing, and preservation techniques, resulting in a number of new and emerging foodborne pathogens and the re-emergence of organisms that have been problematic in the past. To protect public health, science must meet the challenges that result from the remarkable adaptability of foodborne pathogens. However, not all of the challenges of preventing foodborne illness reside in the realm of science. Food safety policy must evolve in reponse to new scientific understanding of hazards in the food supply and an ever-changing food processing industry. The laws, regulations, and organizations comprising the food safety system frequently lag behind current scientific knowledge of the risks posed by foodborne pathogens. Future systemic changes to enhance food safety will require better understanding of risks associated with specific pathogens occurring in the food supply and the costs and benefits of implementing mitigation strategies.
On the convergence properties of basic series representing Clifford valued functions
Authors: Abul-Ez M. A. , Constales D.
Published: March 2003

It is shown that certain classes of special monogenic functions cannot
be represented by the basic series in the whole space. New definitions
for the order of basis of special monogenic polynomials are given,
together with theorems on the representation of classes of special
monogenic functions in certain balls and at a point.
Examples of Friedrichs model operators with a cluster point ofeigenvalues
Authors: Iakovlev Serguei I.
Published: March 2003

A family of selfadjoint operators of the Friedrichs model is
considered. These symmetric type operators have one singular
point, zero of order m. For every m > 3/2, we construct a rank
1 perturbation from the class Lip 1 such that the corresponding
operator has a sequence of eigenvalues converging to zero. Thus,
near the singular point, there is no singular spectrum finiteness
condition in terms of a modulus of continuity of a perturbation
for these operators in case of m > 3/2.
Minimum distances of error‐correcting codes in incidence rings
Authors: Kelarev A. V.
Published: March 2003

The main theorem of this paper gives a formula for
the largest minimum distance of error‐correcting codes
considered as ideals in incidence rings defined by
directed graphs.
Thrombin and Vascular Development
Authors: Moser Martin , Patterson Cam
Published: March 2003

Formation of the vasculature is an essential step in embryogenesis. It was observed decades ago that the vasculature and the intravascular blood compartment, which uses the former as a means of transportation, develop in a close spatial and temporal relationship. In this review, we discuss the role of the blood coagulation system as a tool to coordinate angiogenesis. Several mouse models lacking coagulation factors result in impaired thrombin generation and display a phenotype of disturbed cardiovascular development. Similar phenotypes are observed in mouse models of impaired thrombin binding to its cellular receptor, protease-activated receptor-1, or of disrupted signaling via G proteins. Most interestingly, the available data provide evidence that thrombin signaling in vascular development cannot be explained by a model based only on the classic extrinsic and intrinsic coagulation pathways. Because angiogenesis in adults follows the same signaling patterns as angiogenesis in embryos, it is important to learn about these pathways, hoping that they may serve as therapeutic targets in cardiovascular disease.
Pharmacokinetics of alemtuzumab used for in vivo and in vitro T-cell depletion in allogeneic transplantations: relevance for early adoptive immunotherapy and infectious complications
Authors: Morris Emma C. , Rebello Peppy , Thomson Kirsty J. , Peggs Karl S. , Kyriakou Charalampia , Goldstone Anthony H. , Mackinnon Stephen , Hale Geoff
Published: March 2003

Persistence of alemtuzumab at lympholytic concentrations after reduced-intensity conditioning allogeneic stem cell transplantations (RITs) could impair immune reconstitution and reduce donor T-cell–mediated graft-versus-leukemia/lymphoma (GVL) effects, derived from the graft or subsequent adoptive immunotherapy. We have studied the pharmacokinetics of alemtuzumab in 2 different groups: RIT (100 mg alemtuzumab in vivo over 5 days) and myeloablative allografts (20 mg alemtuzumab added in vitro to the stem cells prior to return). Alemtuzumab concentrations in RIT patients were in excess of that required to kill infused donor CD52+ cells at the time of transplantation and remained at potentially lympholytic levels (> 0.1 μg/mL) for approximately 56 days after transplantation, 26 days longer than for the myeloablative group. Total lymphocyte counts were significantly lower in the RIT group persisting beyond 6 months after transplantation (P = .005), and median absolute CD4 counts higher than 200 × 106/L were delayed until 9 months after transplantation. (Blood. 2003;102:404-406)
A Novel Nonsense Mutation in the Pit-1 Gene: Evidence for a Gene Dosage Effect
Authors: Hashimoto Yukiko , Cisternino Mariangela , Cohen Laurie E.
Published: March 2003

The POU transcription factor Pit-1 functions in the development of somatotrophs, lactotrophs, and thyrotrophs of the anterior pituitary gland. It also plays a role in cell-specific gene expression and regulation of the gene products from these cell types, GH, prolactin, and TSH, respectively. In the present report we studied a patient with severe growth failure. Provocative studies revealed undetectable GH, prolactin, and TSH levels, and her pituitary gland was hypoplastic on magnetic resonance imaging. She had a novel homozygous nonsense mutation in the 3′ end of the first α-helix of the POU-specific domain of the Pit-1 gene. This mutation results in a truncated protein with loss of most of the Pit-1 DNA-binding domains. Interestingly, her parents, who each have one mutant allele, have evidence of mild endocrine dysfunction. Thus, two normal copies of the Pit-1 gene appear necessary for full Pit-1 gene function.
Different pattern of risk factors for atopic and nonatopic asthma among children – report from the Obstructive Lung Disease in Northern Sweden Study
Authors: Rönmark E. , Lundbäck B. , Jönsson E. , Rönmark E , Lundbäck B , Platts‐mills T
Published: March 2003

Background: A cross‐sectional study was performed among 7–8‐year‐old schoolchildren during the winter of 1996 in three municipalities in the most northern province of Sweden, Norrbotten. The study was the starting point of a longitudinal study of asthma, rhinitis, eczema, and type‐1 allergy, and provided data on prevalence and risk factors for these conditions. The aim of the present study was to validate the classification of asthma based on a parental questionnaire, and to examine risk factors for atopic and nonatopic asthma.

Methods: The ISAAC questionnaire with additional questions was distributed by the schools to the parents. The response rate was 97%, and 3431 completed questionnaires were returned. The children in Kiruna and Luleå were also invited to be skin tested, and 2149 (88%) were tested with 10 common airborne allergens. A structured interview was administered by pediatricians in stratified samples of the children to test the validity of the diagnosis of asthma based on the questionnaire.

Results: After the validation study, the prevalence of “ever asthma” was estimated to be 8.0%. The specificity of the question, “Has your child been diagnosed as having asthma by a physician?”, was high, >99%, while the sensitivity was around 70%. The strongest risk factor for “ever asthma” was a positive skin test (OR 3.9). Risk factors for asthma in the asthmatics who were not sensitized were family history of asthma, OR 3.6; breast‐feeding less than 3 months, OR 1.8; past or present dampness at home, OR 1.8; smoking mother, OR 1.7; and male sex, OR 1.6. Among the sensitized asthmatics, only a family history of asthma was a significant risk factor (OR 3.0), while breast‐feeding less than 3 months was not associated with an increased risk (OR 1.0). A synergistic effect between genetic and environmental factors was found especially in the nonatopic asthmatics; the children with a family history of asthma who had a smoking mother and past or present dampness at home had an OR for “ever asthma” of 13.

Conclusions: Different risk‐factor patterns were found for asthma and type‐1 allergy. In addition, the risk factors for atopic or allergic asthma diverged from those for nonatopic asthma.
Allergic contact gingivostomatitis from a temporary crown made of methacrylates and epoxy diacrylates
Authors: Kanerva L. , Alanko K. , Estlander T.
Published: March 2003

Occupational allergic contact dermatitis caused by (meth)acrylates is common in dental personnel, whereas dental acrylic fillings and crowns have rarely been reported to cause problems in dental patients. Here we report on a 48‐year‐old woman who developed gingivitis, stomatitis, and perioral dermatitis after a temporary crown made of restorative, two‐component material had been inserted. The manufacturer stated that the temporary crown base paste and catalyst contained three (meth)acrylates, namely, a proacrylate, which is a modification of 2,2‐bis[4‐(2‐hydroxy‐3‐methacryloxypropoxy)phenyl]propane (BIS‐GMA); a tricyclate, which is a saturated, aliphatic, tricyclic methacrylate; and urethane methacrylate. The manufacturer refused to give more exact information on the (meth)acrylates. Patch testing revealed that the patient was highly allergic to BIS‐GMA, other epoxy diacrylates, and (meth)acrylates, as well as to the base paste and catalyst of the temporary crown. Accordingly, it was concluded that the allergic reaction was caused by BIS‐GMA, or a cross‐reacting (meth)acrylate, or other (meth)acrylates in the temporary crown.
Mast‐cell growth and differentiation
Authors: Li L , Krilis SA
Published: March 2003

Abbreviations. MC: mast cell; T: tryptase; C: chymase; CPA: carboxypeptidase A; Bsp‐1: basophil specific antibody 1.
A double‐blind, placebo‐controlled comparison of treatment with fluticasone propionate and levocabastine in patients with seasonal allergic rhinitis
Authors: Ortolani C. , Mirone C. , Foresi A. , Leone C. , Di Lorenzo G. , Bagnato G. , Bonifazi F. , Crimi N. , Emmi L. , Prandini M. , Senna G.E. , Tursi A. , Fina P. , Testi R. ,   FLNC02 Italian Study Group*
Published: March 2003

Fluticasone propionate aqueous nasal spray (FPANS) is a topically active glucocorticoid which has been successfully used for the treatment of seasonal allergic rhinitis (SAR). Topical levocabastine is a highly selective H1 antagonist which has been proposed as an alternative treatment of SAR. The purpose of this study was to compare the clinical efficacy of two topical nasal treatments, FPANS and levocabastine, in the treatment of SAR. Additionally, the effect of treatments on nasal inflammation was examined during natural pollen exposure. A group of 288 adolescent and adult patients with at least a 2‐year history of SAR to seasonal pollens participated in a multicenter, double‐blind, double‐dummy, and placebo‐controlled study. Patients were treated with either FPANS 200 μg, once daily (n=97), or topical levocabastine, 200 μg, given twice daily (n=96), or matched placebo (n=95) for a period of 6 weeks, starting from the expected beginning of the pollen season. Clinically relevant pollens included Parietaria, olive, and grass. Assessment of efficacy was based on scores of daily nasal symptoms and on nasal cytology of nasal lavage. Nasal lavage was performed immediately before, during, and at the end of treatment in 39 patients. FPANS significantly increased the percentage of symptom‐free days for nasal obstruction on waking and during the day, rhinorrhea, sneezing, and itching. FPANS provided a better control for night and day nasal obstruction (P<0.02 and P<0.01) and rhinorrhea (P<0.01) than levocabastine. In addition, fewer patients treated with FPANS used rescue medication (P<0.025). The percentage of eosinophils in nasal lavage was reduced only during treatment with FPANS. The results of this study indicate that FPANS 200 μg, once daily, provides a better clinical effect than levocabastine 200 μg, twice daily, in patients with SAR. Unlike levocabastine, FPANS significantly attenuates nasal eosinophilia during pollen exposure, a feature which may explain its therapeutic efficacy.
Biologic activity of Dermatophagoides siboney and Blomia tropicalis allergens in exposed and unexposed mite‐allergic individuals. Effect of patient selection on the biologic standardization of mite extracts
Authors: Casas R , Ferrándiz R , Wihl J.‐A , Fernández B , Dreborg S
Published: March 2003

Background: This study aimed to investigate the influence of patient selection criteria, i.e., mite‐allergic individuals exposed and not exposed to Dermatophagoides siboney and Blomia tropicalis, on the biologic activity of mite extracts. Determination of the potency of mite extracts in vivo requires selection of patients with a clinical history of mite allergy. In Scandinavia, there are some anamnestic criteria for mite allergy, whereas in the tropics, where patients are continuously exposed to high levels of mites, selection of patients with mite allergy by clinical history is difficult.

Methods: A total of 210 Cuban asthmatics with continuous symptoms, and 43 Swedes with a clinical history of mite allergy were investigated. Skin prick tests were performed with D. siboney, D. pteronyssinus, D. farinae, B. tropicalis, Acarus siro, Lepidoglyphus destructor, and Tyrophagus putrescentiae extracts. For analysis of the biologic activity of mite extracts, Cuban patients were divided into four groups:

1)all patients skin‐test‐positive to mites

2)patients positive to mites, but not to other inhalant allergens

3)patients reacting most to the mite species analyzed

4)patients reactive only to mites and reacting most to the mite species analyzed.

The biologic potency was calculated according to the Nordic Guidelines.

Results: Due to cross‐reactivity between mites, Swedish mite‐sensitive patients, with a clear clinical history of mite allergy, but not exposed to D. siboney and B. tropicalis, were more skin reactive to these mites than were Cubans. The estimated potency increased gradually to >200% in group 4. In group 1 Cubans, the reactivity to all mites but B. tropicalis was lower than that in mite‐sensitive Swedes.

Conclusions: According to the influence of patient selection criteria on the estimation of the potency of mite extracts, the determination of the biologic activity of allergenic extracts in subjects without a clear‐cut clinical history should be replaced by new methods when available.
Basophil histamine release, IgE, eosinophil counts, ECP, and EPX are related to the severity of symptoms in seasonal allergic rhinitis
Authors: Winther L , Reimert CM , Skov PS , Kærgaard Poulsen L , Moseholm L
Published: March 2003

Background: Serum specific IgE, basophil histamine release, and blood eosinophil parameters are associated with allergic rhinitis, but investigations of the relationship to the severity of allergic symptoms are few and conflicting. Our study aimed to investigate the seasonal changes in the following laboratory tests: specific IgE, basophil histamine release, eosinophil counts, and serum and plasma eosinophil cationic protein (ECP) and eosinophil protein X (EPX), and to analyze, in detail, the relationship of each individual test to the severity of symptoms in rhinitis patients allergic to both birch and grass pollen.

Methods: The above tests were performed on blood samples obtained from 49 allergic rhinitis patients during the birch‐pollen season, during the grass‐pollen season, and after the seasons. Symptom‐medication diaries were filled in during both pollen seasons. We used partial least square (PLS) analysis to establish an optimal statistical link between the symptom score and medication and the laboratory tests, in an investigator‐independent way.

Results: Increases in specific IgE, basophil histamine release, eosinophil counts, serum ECP and EPX, and plasma EPX were observed from the birch‐pollen season to the grass‐pollen season, followed by a decrease from the grass‐pollen season to after the pollen seasons, except for the specific IgE. No seasonal changes in plasma ECP and total IgE were seen. The PLS analysis found a relationship between symptom score and medication and the aggregate laboratory tests (F‐test value 40.2, correlation 0.34 for the cumulative relation). However, the variation in laboratory tests could explain only half of the total variation in symptoms and less than a quarter of the total variation in medication. The symptom score and, to a minor degree, medication were especially correlated with the basophil histamine‐release results, with a decreasing relevance of specific IgE, eosinophil counts, total IgE, serum and plasma EPX, and serum ECP. Plasma ECP was not related to the symptom score and medication.

Conclusions: A significant relationship between the severity of allergic rhinitis and various allergic inflammatory markers was found but could account for only a minor part of the variation in the patients' evaluation of their disease.

Abbreviations: ACRI: mean daily capsules of acrivastine; ANTA: mean daily antazoline‐naphazoline eye‐drops; CAP: specific IgE measured by Pharmacia CAP System; ECP: eosinophil cationic protein; EOS: eosinophil counts; EPX: eosinophil protein X; HR: histamine release; HR15: lowest concentration of extract giving ≥15 ng histamine/ml blood in histamine‐release test; LEU: leukocyte counts; MAX: maximum histamine released (ng/ml) at any concentration of extract in histamine‐release test; NAL: nasal lavage; PLS: partial least square analysis; PRED: mean daily mg of prednisolone; SYMP: mean daily value of total symptom score.
Sublingual‐swallow immunotherapy (SLIT) in patients with asthma due to house‐dust mites: a double‐blind, placebo‐controlled study
Authors: Bousquet J , Scheinmann P , Guinnepain MT , Perrin‐Fayolle M , Sauvaget J , Tonnel AB , Pauli G , Caillaud D , Dubost R , Leynadier F , Vervloet D , Herman D , Galvain S , Andre C
Published: March 2003

A double‐blind, placebo‐controlled study was carried out in 85 patients with a well‐documented history of perennial asthma caused by house‐dust mites. Patients received either placebo or sublingual immunotherapy (SLIT) with a standardized Dermatophagoides pteronyssinus (DP)–D. farinae (DF) 50/50 extract. After a run‐in period, patients received increasing doses up to 300 IR every day for 4 weeks and then three times a week for the following 24 months. The cumulative dose was about 104 000 IR, equivalent to 4.2 mg Der p 1 and 7.3 mg Der f 1. Symptom and medication scores and respiratory function were assessed throughout the trial. Serum specific IgE and IgG4 were determined before SLIT (t0) and after 6 (t1), 11 (t2), 17 (t3), and 25 months (t4) of SLIT. Mite exposure was evaluated at t0, t2, and t4 by semiquantitative guanine determinations. Patients aged 15 years and older were asked to assess their quality of life (QoL) by completing the SF20 (Short Form Health Status Survey) plus two items at t0, t2, and t4. Use of inhaled corticosteroids and β2‐agonists was significantly decreased after 25 months of treatment in both groups (P<0.03). SLIT patients showed significant improvements in respiratory function at t4 (% predicted FEV1 (P=0.01), VC (P=0.002), morning (P=0.01) and evening (P=0.03) PEFR), and reduction in daytime asthma score (P=0.02). In the SLIT group, the post‐treatment PD20 was 1.75 times higher than the baseline value. There was no change in PD20 in the placebo group. Compared to the placebo group, the SLIT group showed a significant increase in specific IgE DP (P=0.05), IgE DF (P=0.02), IgG4 DP (P=0.001), and IgG4 DF (P=0.001) levels after SLIT. QoL scores were similar in both groups at t0 and t2. At t4, all scores were better in the SLIT group than in the placebo group, with the differences being most marked for the general perception of health (P=0.01) and physical pain (P=0.02). Adverse events were similar in the two groups. This study shows that SLIT in house‐dust‐mite‐related asthma has a good safety profile and improves respiratory function, bronchial hyperreactivity, and QoL.
Asthma in the desert: spectrum of the sensitizing aeroallergens
Authors: Ezeamuzie C. I. , Thomson M. S. , Al‐Ali S. , Dowaisan A. , Khan M. , Hijazi Z.
Published: March 2003

Background: Bronchial asthma is common in Kuwait, a desert country, but the sensitizing allergens are uncertain. This study investigated the sensitizing allergens in Kuwaiti patients with extrinsic asthma.

Methods: A total of 553 asthmatics (male:female ratio: 1.4; mean age: 31.7 years [range 3–76 years]) and 112 matched controls were studied. Sera from all patients/subjects were tested by the CAP‐RAST method for specific IgE to 14 locally relevant inhalant allergens.

Results: Specific IgE to at least one allergen was detected in 87.2% of the patients compared with 24.1% in controls. Among the confirmed extrinsic asthmatics, the sensitization rates for the allergen groups were as follows: pollens (87.1%), house dust (76.1%), and molds (30.3%). The three most prevalent sensitizing pollens were from Chenopodium (70.7%), Bermuda grass (62.9%), and Prosopis (62.7%), all of which are horticultural plants imported for the purpose of “greening” the desert. For all allergens, except the molds, the prevalence rate was higher in males than females, but age had only a weak effect. Severe asthma occurred significantly more frequently among mold‐sensitized patients.

Conclusions: These results show that even in a desert environment, pollens and house dust allergens may be important sensitizing allergens. They also illustrate how practices that “green” the desert can affect public health.
Development of allergies and asthma in infants and young children with atopic dermatitis – a prospective follow‐up to 7 years of age
Authors: Gustafsson D. , Sjöberg O. , Foucard T.
Published: March 2003

Background: The prognosis of atopic dermatitis is usually good, but the risk of developing asthma and allergic rhinitis is very high. The aim of this study was to follow children with atopic eczema up to school age to chart the course of sensitization and development of clinical allergy, as well as to study risk factors of sensitization.

Methods: Ninety‐four children with atopic dermatitis were followed up to 8 years of age. The children were examined twice a year up to 3 years of age, and thereafter once yearly. At each visit, a clinical examination was performed, and a blood sample was taken. After 3 years of age, skin prick tests (SPTs) with inhalation allergens were performed at each visit. Information was obtained about atopy in the family, feeding patterns during infancy, symptoms of atopic disease, infections, and environmental factors.

Results: During the follow‐up, the eczema improved in 82 of the 94 children, but 43% developed asthma and 45% allergic rhinitis. The risk of developing asthma was higher in children with a heredity of eczema. Presence of severe eczema at the time of inclusion in the study was associated with an increased tendency to produce food‐specific IgE. An early onset of eczema was associated with an increased risk of sensitization to inhalant allergens, and development of urticaria. Early allergic reactions to food were associated with later reactions to food, allergic rhinitis, urticaria, and sensitization to both food and inhalant allergens. Early feeding patterns, time of weaning, and introduction of solid food, did not influence the risk of development of allergic symptoms. A large number of periods or days with fever during the follow‐up was associated with an increased risk of developing allergic rhinitis and urticaria.

Conclusions: Our results confirm the good prognosis for dermatitis and the increased risk of developing asthma and allergic rhinitis. Development of otherallergic symptoms or sensitization was associated withthe following factors: a family history of eczema, age at onset of eczema and its severity, early adverse reactions to foods, and proneness to infections.
A double‐blind, placebo‐controlled oral challenge study with lyophilized larvae and antigen of the fish parasite, Anisakis simplex
Authors: Sastre J. , Lluch‐Bernal M. , Quirce S. , Arrieta I. , Lahoz C. , Del Amo A. , Fernández‐Caldas E. , Marañón F.
Published: March 2003

Background: The third‐stage larvae of Anisakis simplex may be a hidden source of allergens in fish. The objective was to determine whether the ingestion of lyophilized A. simplex larvae, or antigen, induces clinical symptoms in a group of A. simplex‐sensitized patients.

Methods: Double‐blind, placebo‐controlled oral challenges were conducted in 11 individuals who had experienced allergic reactions after eating fish. Another patient had chronic urticaria unrelated to the ingestion of fish. All patients had positive skin tests and specific IgE determinations for A. simplex and negative skin tests to a battery of fish species. Conjunctival tests with A. simplex extracts were conducted in all patients and in five controls. The 12 patients received capsules containing either lactose or one, five, or 25 lyophilized larvae of A. simplex at 2‐h intervals in a double‐blind fashion. The highest single dose was 100 larvae. ECP and tryptase levels in serum were measured before and after the last oral challenge. Lyophilized antigen was also given to five patients.

Results: None of the 12 patients experienced a positive reaction after the ingestion of the placebo, the lyophilized larvae, or the antigen. Tryptase and ECP levels before and after challenges did not change significantly. Conjunctival provocation tests were positive in 11 out of the 12 patients and in none of the controls.

Conclusions: The ingestion of 100 lyophilized A. simplex larvae, or its equivalent in antigen, does not induce clinical symptoms in individuals with a clinical history and laboratory findings of hypersensitivity to A. simplex. The data suggest that only the ingestion of live larvae may be capable of inducing allergic manifestations.
Eotaxin in induced sputum of asthmatics: relationship with eosinophils and eosinophil cationic protein in sputum
Authors: Yamada H. , Yamaguchi M. , Yamamoto K. , Nakajima T. , Hirai K. , Morita Y. , Sano Y. , Yamada H.
Published: March 2003

Background: Eosinophilic inflammation is a crucial aspect of allergic diseases such as bronchial asthma. An eosinophil‐active chemokine, eotaxin, may play a role in the pathogenesis of the tissue eosinophilia accompanying asthma.

Methods: Induced sputa were obtained from 53 patients with atopic asthma and six healthy subjects, and the concentration of eotaxin in the sputum was measured by ELISA. We investigated whether the sputum content of eotaxin is related to 1) asthma status or corticosteroid therapy, and 2) other sputum indices, including percentage of eosinophils and concentration of eosinophil cationic protein (ECP).

Results: The patients with stable or unstable asthma showed significantly higher concentrations of sputum eotaxin than the normal controls. The level of sputum eotaxin demonstrated a positive correlation with the percentage of eosinophils in stable asthmatics not receiving corticosteroid therapy, but not in stable patients treated with corticosteroids, or in unstable patients. Sputum eotaxin demonstrated a positive correlation with ECP in asthmatic patients who were either in a stable state or not receiving steroid therapy.

Conclusions: The elevated level of eotaxin detected in association with increased eosinophils and ECP in the sputum of asthmatics suggests that eotaxin is involved in the pathogenesis of eosinophilic airway inflammation. The relationship of eotaxin to airway eosinophilia may be modified by the stability status of asthma and corticosteroid therapy.
Occupational IgE‐mediated allergy to Tribolium confusum (confused flour beetle)
Authors: Alanko K. , Tuomi T. , Vanhanen M. , Pajari‐Backas M. , Kanerva L. , Havu K. , Saarinen K. , Bruynzeel D. P.
Published: March 2003

Background: We report on IgE‐mediated allergy in a worker caused by Tribolium confusum (confused flour beetle). These beetles lived in the “old” flour to which he was exposed in his work.

Case report: A 35‐year‐old, nonatopic mechanic in a rye crispbread factory developed rhinitis, conjunctivitis, and asthmatic symptoms, as well as urticaria on his wrists, lower arms, hands, neck, and face, during the maintenance and repair of machines contaminated by flour. This flour had been in and on the machines for a long time, and it contained small beetles. The patient did not suffer any symptoms when handling fresh, clean flour.

Results: Skin prick tests with standard environmental allergens, storage mites, enzymes, flours, and molds were negative. A prick test with flour from the machines gave a 10‐mm reaction. An open application of the same flour caused urticarial whealing on the exposed skin. Prick tests with fresh flour from the factory were negative. A prick test with minced T. confusum from the flour in the machines gave a 7‐mm reaction. Histamine hydrochloride 10 mg/ml gave a 7‐mm reaction. Specific serum IgE antibodies to T. confusum were elevated at 17.2 kU/l. Prick tests with the flour from the machines were negative in five control patients.

Conclusions: The patient had occupational contact urticaria, rhinitis, conjunctivitis, and asthmatic symptoms from exposure to flour. His symptoms were caused by immediate allergy to the beetle T. confusum. Immediate allergy to this beetle has rarely been reported in connection with respiratory symptoms, but it may be more common. Contact urticaria from this source has not been reported before.
The relevance of skin prick tests for Pityrosporum ovale in patients with head and neck dermatitis
Authors: Devos S. A. , Van Der Valk P. G. M.
Published: March 2003

Background: Patients with atopic dermatitis often develop immunoglobulin E antibodies against the yeast Pityrosporum ovale. This organism may produce positive skin prick reactions in a higher rate in patients with atopic dermatitis of the head, scalp, and neck region.

Methods: We investigated whether positive prick tests to P. ovale were associated with a specific localization in the head and neck region. A total of 589 consecutive patients were prick tested with a P. ovale extract from ALK Abelló.

Results: Thirty‐seven patients (6.3%) showed a positive reaction to the P. ovale extract. We could not find significant differences in the localizations of the dermatitis and the pattern of reaction to the tested intracutaneous allergens between the 37 patients positive to P. ovale and the control group of 55 subjects with negative reactions. In a subgroup, we found an elevated level of P. ovale‐specific IgE in 100.0% of the patients with head and neck dermatitis, compared with 13.6% in the atopic dermatitis patients with lesions in any other localization.

Conclusions: Our results clearly show that P. ovale‐specific IgE is strongly related to the head and neck localization of atopic dermatitis, but RAST seems more sensitive than a prick test with the extract we used.
Mizolastine in the treatment of seasonal allergic rhinoconjunctivitis: a European clinical experience with 5408 patients managed in daily practice (PANEOS SAR Study)
Authors: Bachert C. , Vovolis V. , Margari P. , Murrieta‐Aguttes M. , Santoni J. P.
Published: March 2003

Background: Mizolastine, a potent H1 antihistamine with additional antiallergic properties, is marketed for the treatment of allergic rhinoconjunctivitis and urticaria. The objective was to investigate the safety and effectiveness of mizolastine under conditions of daily practice in patients with seasonal allergic rhinoconjunctivitis (SAR).

Methods: In an open multicenter study, mizolastine 10 mg daily was administered for 14 days during the pollen season. Nasal and ocular symptoms, time to onset of symptom relief, and effect of the drug on diurnal alertness were evaluated. Safety was evaluated on the basis of self‐reported adverse events (AE).

Results: A total of 5408 patients (36±14 years of age, females=57%) with a history of SAR for 8±9 years were treated for a mean of 17.1±5.0 days. SAR symptoms improved in 93% and decreased by at least 50% in 86% of patients; 78% reported improvement after the first drug intake and 51% from the first hour. Sixty‐nine percent considered mizolastine more effective than other antihistamines taken previously. The incidence of AE was low (3.8%).

Conclusions: The high responder rate, the rapid onset of action, and the low incidence of AE observed in this large multicenter study confirm the previously reported beneficial efficacy and safety of mizolastine in the management of SAR.
Double‐blind, placebo‐controlled food challenge with apple
Authors: Skamstrup Hansen K. , Vestergaard H. , Stahl Skov P. , Khinchi M. Søndergaard , Vieths S. , Poulsen L. K. , Bindslev‐Jensen C.
Published: March 2003

The aim of the study was to develop and evaluate different methods of double‐blind, placebo‐controlled food challenge (DBPCFC) with apple. Three different DBPCFC models were evaluated: fresh apple juice, freshly grated apple, and freeze‐dried apple powder. All challenges were performed outside the pollen season and took place from 1997 to 1999. The freeze‐dried apple material was characterized by means of leukocyte histamine release (HR), skin prick test (SPT), and immunoblotting experiments. The study population consisted of birch pollen‐allergic patients with a history of rhinitis in the birch‐pollen season and positive specific IgE to birch. For comparison of the DBPCFC models, 65 patients with a positive open oral challenge with apple were selected. In the characterization of the freeze‐dried apple material, 46 birch pollen‐allergic patients were included. The IgE reactivity to apple was evaluated by measurement of specific IgE, HR, and SPT. Golden Delicious apples were used in all experiments. The results of this study showed that it was possible to perform DBPCFC with apple in birch pollen‐allergic individuals. The model with freshly squeezed apple juice had a low sensitivity and displayed a high frequency of reactions to placebo, probably due to the ingredients used for blinding. The sensitivity of the models with freshly grated apple and freeze‐dried apple powder was 0.74/0.60. An increase in sensitivity is desirable. The freeze‐dried apple powder proved to be useful for SPT, HR, and oral challenges, but further investigation of the stability and the allergenic profile of the material is needed.
IgE‐mediated downregulation of L‐selectin (CD62L) on lymphocytes from asthmatic patients
Authors: Monteseirín J. , Llamas E. , Sánchez‐Monteseirín H. , Bonilla I. , Camacho M. J. , Conde J. , Sobrino F. , Sobrino F.
Published: March 2003

Background: L‐selectin (CD62L) mediates the binding of lymphocytes to high endothelial venules of peripheral lymph nodes and is also involved in leukocyte attachment to the endothelium at sites of inflammation. Although it has been demonstrated that L‐selectin is shed after lymphocyte activation, it is unknown whether the expression of L‐selectin on the surface of lymphocytes can be modulated by an IgE‐dependent mechanism or whether immunotherapy (IT) might affect this mechanism.

Methods: One group of adult allergic asthmatic patients had received IT for the previous 3 years. Another similar group was not treated with IT. We challenged peripheral blood lymphocytes from both groups of asthmatic patients in vitro with an anti‐IgE antibody (Ab). Expression of L‐selectin on the lymphocyte surface was analyzed by flow cytometry, and the levels of soluble L‐selectin (sL‐selectin) on culture supernatant by ELISA.

Results: L‐selectin was downregulated from the surface of lymphocytes in a time‐ and anti‐IgE antibody dose‐dependent manner (with a concomitant upregulation of shed L‐selectin in the supernatant). When lymphocytes from non‐IT asthmatic patients were cultivated with anti‐IgE Ab, a statistically significantly greater CD62L downmodulation on the lymphocyte surface was observed compared with lymphocytes from the healthy group (P<0.002) and from the IT‐asthmatic group (P<0.001). When lymphocytes from non‐IT asthmatic patients were cultivated with anti‐IgE Ab, a significantly greater sL‐selectin level in the culture supernatant was observed compared with lymphocytes from the healthy group (P<0.001) and with lymphocytes from IT‐asthmatic group (P<0.001).

Conclusions: We present evidence that the expression of L‐selectin on the surface of lymphocytes can be modulated by an IgE‐dependent mechanism. This mechanism can be affected by IT.
Duration of the antihistaminic effect after discontinuation of ebastine
Authors: Frossard N. , Vital‐Durand D. , Mounedji N. , Valleteau A.
Published: March 2003

Background: The inhibitory effect of antihistamines on allergen‐induced skin reactions can impair the results of allergen skin testing, which are necessary for the diagnosis of atopic diseases. This study was designed to determine the time period required for the inhibitory effect of ebastine on allergen‐induced skin reactivity to disappear completely.

Methods: This was a double‐blind, placebo‐controlled, parallel‐group study including 23 out of 27 randomized patients. They received either ebastine 20 mg or placebo once daily for 7 days. At the end of treatment, allergen challenge was performed daily for 7 days. Histamine challenge was performed on day 1 (6 and 24 h) and day 5 after treatment. The wheal and flare surface areas were measured and analyzed.

Results: Highly significant inhibition of the wheal and flare response induced by allergen was observed after ebastine treatment on days 1 and 2 as compared with placebo (P<0.01 for both). The inhibition was reduced, although still significant, by day 3 (P<0.05). No significant difference was observed by day 4 between the ebastine and the placebo groups. The effects of histamine challenge were significantly reduced in the ebastine compared with the placebo group at day 1 (6 and 24 h), and were similar at day 5 after treatment.

Conclusions: Our results show that the wheal and flare response to allergen after ebastine discontinuation returns to placebo values after 4 days. Therefore, patients using ebastine need to be antihistamine‐free for 4 days before the skin prick test. This is valuable information for the allergologist seeking to diagnose allergen sensitivity.
Skin reactions to histamine of healthy subjects after hypnotically induced emotions of sadness, anger, and happiness
Authors: Zachariae R. , Jørgensen M. M. , Egekvist H. , Bjerring P.
Published: March 2003

Background: The severity of symptoms in asthma and other hypersensitivity‐related disorders has been associated with changes in mood but little is known about the mechanisms possibly mediating such a relationship. The purpose of this study was to examine the influence of mood on skin reactivity to histamine by comparing the effects of hypnotically induced emotions on flare and wheal reactions to cutaneous histamine prick tests.

Methods: Fifteen highly hypnotically susceptible volunteers had their cutaneous reactivity to histamine measured before hypnosis at 1, 2, 3, 4, 5, 10, and 15 min after the histamine prick. These measurements were repeated under three hypnotically induced emotions of sadness, anger, and happiness presented in a counterbalanced order. Skin reactions were measured as change in histamine flare and wheal area in mm2 per minute.

Results: The increase in flare reaction in the time interval from 1 to 3 min during happiness and anger was significantly smaller than flare reactions during sadness (P<0.05). No effect of emotion was found for wheal reactions. Hypnotic susceptibility scores were associated with increased flare reactions at baseline (r=0.56; P<0.05) and during the condition of happiness (r=0.56; P<0.05).

Conclusions: Our results agree with previous studies showing mood to be a predictor of cutaneous immediate‐type hypersensitivity and histamine skin reactions. The results are also in concordance with earlier findings of an association between hypnotic susceptibility and increased reactivity to an allergen.
Similar T helper Th2‐like cytokine mRNA expression in vernal keratoconjunctivitis regardless of atopic constitution
Authors: Montan P. G. , Scheynius A. , Van Der Ploeg I.
Published: March 2003

Background: Many patients with vernal keratoconjunctivitis (VKC), a severe chronic allergic eye disease in children, exhibit IgE‐sensitization, but about 40% of cases lack this immunologic trait. As a disease factor in VKC, IgE is thus not fully understood. The aim of this study was to investigate whether there are any differences in the conjunctival cytokine messenger (m)RNA pattern related to IgE‐sensitization in children suffering from VKC.

Methods: Tissue samples were obtained from 16 symptomatic VKC subjects with sub‐tarsal disease and six control subjects. Expression of mRNA for interleukin (IL)‐4, IL‐5, IL‐13, and interferon (IFN)‐γ was investigated with a semiquantitative reverse‐transcriptase polymerase chain reaction (RT‐PCR) technique. The presence of T cells, IgE+ cells, mast cells, and eosinophils was analyzed with immunohistochemical methods. Allergen‐specific IgE antibodies were assessed in serum and with skin prick testing.

Results: Ten out of the 16 VKC subjects showed evidence of IgE‐sensitization. No differences were detected for any tissue variable between VKC subjects with and without IgE‐sensitization. Statistically significant increases over controls were found for both VKC groups with regard to all cell markers.

Conclusions: The amount of messenger RNA encoding cytokines and inflammatory cell markers in VKC did not correlate with IgE‐sensitization. Tissue changes in all patient samples were characterized by a prevalence of T cells, eosinophils, mast cells and cell‐bound IgE molecules. However, the role of cell‐bound IgE molecules in VKC patients lacking IgE‐sensitization remains to be determined.
Airway neutrophil inflammation in nonasthmatic patients with food allergy
Authors: Wallaert B. , Gosset P. , Lamblin C. , Garcia G. , Perez T. , Tonnel A. B.
Published: March 2003

Background: Patients with food allergy (FA) have been recently shown to develop bronchial hyperresponsiveness (BHR), despite the absence of any concomitant asthmatic manifestation. In order to explain this observation, we sought to examine the presence of a bronchial inflammation in induced sputum of nonasthmatic patients with FA.

Methods: Twelve nonasthmatic patients with FA (urticaria, digestive symptoms, anaphylaxis) were included in the study. Results were compared to these obtained from eight asthmatic patients without food allergy and eight healthy controls. Diagnosis of FA was based on double‐blind placebo‐controlled challenge. Sputum cells and fluid‐phase eosinophil cationic protein (ECP), myeloperoxidase (MPO) and interleukin‐8 (IL‐8) were measured in induced sputum. BHR was evaluated using methacholine inhalation.

Results: Sputum from asthmatics, in comparison with the sputum of healthy subjects and patients with FA contained a higher proportion of eosinophils and higher levels of ECP (< 0.001). In marked contrast, patients with FA exhibited an increased proportion of neutrophils and IL‐8 in comparison with asthmatics and controls (P < 0.05 for neutrophils and P < 0.001 for IL‐8). There was a significant correlation between sputum neutrophils and IL‐8 (r = 0.68, P < 0.001). MPO levels were not different between the groups. There was a trend toward higher levels of IL‐8 and ECP in food allergic patients with BHR in comparison with patients with FA without BHR.

Conclusion: Our results demonstrate that a subclinical neutrophil airway inflammation is present in patients with food allergy free of clinical respiratory symptoms and that IL‐8 may be an important mediator of this neutrophilia.
Alternative medicine in allergies – prevalence, patterns of use, and costs
Authors: Schäfer T. , Riehle A. , Wichmann H. –E. , Ring J.
Published: March 2003

Background:  There is evidence that the use of alternative medicine (AM) for allergies has increased. However, little is known from population‐based studies about what determines its use. The objective of this study was to evaluate the patterns of use of AM for allergies.

Methods:  A population‐based nested case‐control study was conducted in 2000–01 using computer‐assisted telephone interviews. Three hundred and fifty‐one adults participated (median age 46 years) with allergies including hay fever, asthma, atopic eczema, and food hypersensitivity. Information was obtained on demographics, prevalence, motivation, information, type of AM, provider, costs, willingness to pay, and subjective assessment of AM.

Results: 
26.5% of participants used AM because of their allergies. Compared to nonusers, this group of users was significantly younger (median age 43
vs
47;
p
=0.004) and better educated (school education > 8 year
vs
≤ 8 year; odds ratio (OR) 2.17, 1.28–3.67) and was mostly motivated by the assumption of few side‐effects (78.3%), by a wish to try everything (71.7%), and by unsatisfying results from conventional therapy (66.3%). Users also had more experience with conventional therapy than nonusers (94.6%
vs
63.6%; OR 10.10, 4.00–25.72). Four procedures accounted for almost the entire usage: homeopathy (35.3%), autologous blood injection (28.1%), acupuncture (16.6%), and bioresonance (10.0%). The AM were mostly promoted (40.2%) and provided (60.9%) by medical doctors, and produced median costs for single and entire treatment of 4 € (15–205) and 205 € (15–1278)e. Reimbursement from insurance companies was received by 52.3%, in full (37.8%) or partial (14.5%). Most subjects (55.4%) admitted that they would pay more (median 153e) for the achieved result. Users scored the efficacy of conventional therapy significantly lower (
p <0.001) than nonusers, and assessed the results of AM as very good (28.6%) or rather good (53.8%).

Conclusions:  AM is used widely for allergies by the general population and is associated with considerable costs. This has implications for the health care system and health policy.