bluuebunny/crossref_metadata_2025 huggingface dataset:
Secondary Myeloid Leukemia and Myelodysplastic Syndromes in Patients Treated for Hodgkin’s Disease: A Report From the German Hodgkin’s Lymphoma Study Group
Authors: Josting Andreas , Wiedenmann Sabine , Franklin Jeremy , May Michael , Sieber Markus , Wolf Juergen , Engert Andreas , Diehl Volker
Published: March 2003

Purpose: To assess the incidence and outcome of secondary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in patients with Hodgkin’s disease (HD).

Patients and Methods: Between 1981 and 1998, the GHSG conducted three trial generations for early, intermediate, and advanced HD involving a total of 5,411 patients (called HD1 through HD9).

Results: A total of 46 patients with secondary AML/MDS were identified. The median age at diagnosis of leukemia was 47 years (range, 22 to 79 years). Primary therapy was as follows: radiotherapy alone (n = 4); doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD; n = 1); cyclophosphamide, vincristine, procarbazine, and prednisone (COPP)/ABVD or similar (n = 30); bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) baseline (n = 2); and BEACOPP escalated (n = 9). Twelve patients developed AML/MDS after salvage therapy, including four patients who developed AML/MDS after high-dose chemotherapy with autologous stem-cell transplantation. Thirty-six of the secondary malignancies were AML, and 10 malignancies were MDS. After a median observation time of 55 months, incidence of secondary AML/MDS was 1%. Treatment for secondary AML/MDS was as follows: cytarabine (Ara-C)–containing regimens (6-thioguanin, cytarabine, daunorubicin [TAD]/high-dose cytarabine, mitoxantrone [HAM], HAM, Ida-Ara-C (idarubicin + Ara-C), Ida-Flag (idarubicin, fludarabin, Ara-C, G-CSF), and idarubicin, cytarabine, etoposide [ICE]+HAM; n = 11), TAD-chemotherapy (n = 5), other regimens (n = 3), no treatment or supportive care (n = 24), palliative oral chemotherapy (n = 3), and allogeneic stem cell transplantation (n = 9). After 24 months of observation, no difference in freedom from treatment failure and overall survival (2% and 8%, respectively) was observed in patients who developed AML or MDS.

Conclusion: The prognosis of patients with secondary AML/MDS after primary HD is poor. Thus, emphasis should be made to improve initial treatment in an attempt to prevent this complication.
Age-Related Changes in Cortical Bone Content of Insulin-Like Growth Factor Binding Protein (IGFBP)-3, IGFBP-5, Osteoprotegerin, and Calcium in Postmenopausal Osteoporosis: A Cross-Sectional Study
Authors: Ueland Thor , Brixen Kim , Mosekilde Lis , Mosekilde Leif , Flyvbjerg Allan , Bollerslev Jens
Published: March 2003

Serum GH and IGF-I levels decline with increasing age, whereas osteoprotegerin (OPG) increases. IGFs as well as OPG are present in bone matrix and mediate the effects of many upstream hormones (e.g. estrogen). To evaluate whether changes in these proteins may to some extent explain the decrease in bone mass in postmenopausal or senile osteoporosis, we measured bone contents of IGF-I, IGF-II, IGF binding protein (IGFBP)-3, IGFBP-5, and OPG in combined extracts obtained after EDTA and guanidine hydrochloride extraction in 60 postmenopausal women aged 47–74 (mean, 63) yr with a previous distal forearm fracture and a hip or spine Z-score less than 0. We found age-related increases in IGFBP-3 (r = 0.35; P < 0.01), IGFBP-5 (r = 0.59; P < 0.001), and OPG (r = 0.36; P < 0.01) in cortical bone, significantly inversely correlated with femoral neck and lumbar spine BMD. A correlation between age and OPG was also detected in trabecular bone (r = 0.27; P < 0.05). A pronounced age-related decrease in cortical calcium contents (r = −0.60; P < 0.001), positively correlated with femoral neck and lumbar spine BMD, was also found. No age-related changes were detected for IGF-I or IGF-II. The present study demonstrates age-related changes in cortical bone contents of IGFBPs, calcium, and OPG, possibly related to the pathophysiology of postmenopausal osteoporosis. As for OPG, our findings probably represent compensatory responses to increased osteoclastic resorption.
Postpartum Thyroiditis Is Associated with Fluctuations in Transforming Growth Factor-β1 Serum Levels
Authors: Olivieri A. , De Angelis S. , Vaccari V. , Valensise H. , Magnani F. , Stazi M. A. , Cotichini R. , Gilardi E. , Cordeddu V. , Sorcini M. , Boirivant M.
Published: March 2003

Postpartum thyroiditis (PPT) is characterized by a rapid evolution and recovery of euthyroidism. Therefore, it can represent a good model to study early cytokine fluctuations in autoimmune thyroid diseases. TGFβ1 is an immunosuppressive cytokine, as it inhibits T and B cell proliferation, natural killer cell cytotoxic activity, and the generation of T cell cytotoxicity.

The aim of this study was to assess serum concentrations of TGFβ1 during pregnancy and to study possible serum fluctuations of this cytokine during the different phases of PPT. Thyroid biochemical pattern, antithyroid autoantibodies (ATA), and total and active TGFβ1 (aTGFβ1) serum concentrations were evaluated in 63 pregnant women. Thirty-four of them were ATA+, and 29 were ATA−. Twenty of the 34 ATA+ women were followed in the postpartum year. Nine of these 20 women developed PPT; 11 remained euthyroid. All of the PPT women became euthyroid during the follow-up. Our results showed 1) detectable serum levels of aTGFβ1 in 50% of ATA+ pregnant women, suggesting that the presence of autoantibodies may characterize a favorable condition for TGFβ1 activation; and 2) decreased total TGFβ1 and increased aTGFβ1 serum levels during the active phase of PPT in ATA+ women. This seems to suggest that inflammation may be responsible for TGFβ1 activation and autoantibody increase because of antigen release. Although further studies of women with persistent hypothyroidism after the postpartum year are needed, the possibility that the enhanced activation of TGFβ1 may contribute to resolution of thyroid inflammation postpartum cannot be excluded.
Prospective Study of Thymic Carcinoids in Patients with Multiple Endocrine Neoplasia Type 1
Authors: Gibril Fathia , Chen Yuan-Jia , Schrump David S. , Vortmeyer Alexander , Zhuang Zhengping , Lubensky Irina A. , Reynolds James C. , Louie Adeline , Entsuah Laurence K. , Huang Kane , Asgharian Behnam , Jensen Robert T.
Published: March 2003

Little is known of the natural history of thymic carcinoids in multiple endocrine neoplasia type 1 (MEN1). This is important because in 1993 they were identified as a frequent cause of death, yet only small retrospective studies and case reports exist. We report results of a prospective study of 85 patients with MEN1 evaluated for pancreatic endocrine tumors and followed over a mean of 8 yr with serial chest computed tomography, magnetic resonance imaging (MRI), chest x-ray, and, since 1994, octreoscans [somatostatin receptor scintigraphy (SRS)]. Seven patients (8%) developed thymic carcinoids. Patients with and without carcinoids did not differ in clinical, laboratory, or MEN1 tumor features, except for male gender and the presence of a gastric carcinoid. All thymic tumors were hormonally inactive. Four thymic carcinoids lacked 11q loss of heterozygosity, although it was found in three pancreatic endocrine tumors. Computed tomography and/or MRI were more sensitive than SRS or chest x-ray in detecting tumors initially or with recurrence. All patients underwent resection of the thymic carcinoid, and in all patients followed more than 1 yr, the tumor recurred. Bone metastases developed in two patients and were detected early only on MRI, not SRS. This study provides information on early thymic carcinoids and allows modifications of existing guidelines to be recommended for their diagnosis, surveillance, and treatment.
Identification of a 36‐kDa olive‐pollen allergen by in vitro and in vivo studies
Authors: Martínez A , Asturias JA , Palacios R , Martínez J , Sanz Ml , Sánchez G , Oehling A
Published: March 2003

Background: Ole e 1 has been considered the major allergen of olive (Olea europaea) pollen. Some other relevant allergens (Ole e 2, 3, 4, and 6) have been recently described. This work aimed to study the IgE‐binding frequency of a 36‐kDa protein from O. europaea pollen in a large population of olive‐allergic patients, its allergenic reactivity in vivo, and its presence in olive pollens of different origin, as well as in other relevant allergenic pollens.

Methods: Identification of IgE‐binding components from O. europaea pollen extracts was elucidated by inhibition of SDS–PAGE immunoblotting using recombinant profilin (Ole e 2) and Ole e 1 molecules. The IgE‐binding frequency of the 36‐kDa protein was estimated by Western blot in a sample of 120 sera from olive‐allergic patients. The cutaneous test with the 36‐kDa protein was performed by intradermoreaction in allergic patients and control subjects.

Results: Exactly 83% of the sera from O. europaea‐allergic patients recognized a protein with an apparent molecular weight of 36 kDa, under reducing conditions. It was detected by sera from monosensitized and polysensitized patients, showing a higher IgE frequency than the major allergen Ole e 1 (59%) and the minor profilin (Ole e 2) allergen (27%). Similar reactivity rates (79%) was found by intradermal test. Extracts from olive pollens collected in California presented a much higher amount (around 16‐fold on average) of the 36‐kDa protein than those from pollens of Spanish origin. The presence of similar allergens was detected only in closely related species (Syringa, Fraxinus, Ligustrum), and not in other common allergenic pollens.

Conclusions: The 36‐kDa protein constitutes a major allergen for olive‐sensitized patients, but it is not equally represented in O. europaea pollens of different origins.

Abbreviations: BSA: bovine serum albumin; PVDF: polyvinylidene difluoride; SDS–PAGE: sodium dodecyl sulfate‐polyacrylamide gel electrophoresis; TBS: Tris borate saline buffer.
The role of immunoglobulin therapy in allergic diseases
Authors: Rabinovitch N , Gelfand Ew , Leung Dym
Published: March 2003

Intravenous immunoglobulin (IVIG) has been used for many years to treat patients with primary immunodeficiencies. More recently, IVIG has been shown to have anti‐inflammatory activity when used at substantially higher concentrations. A number of studies have examined the efficacy of IVIG in allergic diseases. For patients with severe refractory asthma, sinusitis, atopic dermatitis, and urticaria, IVIG offers an alternative therapy with relatively few side‐effects. Although the mechanism by which IVIG may attenuate the allergic response is still undetermined, clinical studies have shown that immunoglobulin therapy can decrease serum IgE levels and increase glucocorticoid binding affinity, while in vitro studies have shown that IVIG can decrease T‐cell secretion of TH2 cytokines. Further studies are needed to confirm the initial encouraging results seen in allergic patients with severe, resistant disease.
Allergens in house‐dust samples in Germany: results of an East–West German comparison
Authors: Fahlbusch B. , Jäger L. , Heinrich J. , Groβ I. , Wichmann H.‐E. , Richter K.
Published: March 2003

The background of this study is the finding of several studies that the frequency of respiratory allergies was significantly higher in the former West Germany than the former East Germany. The present study investigated the levels of allergens of house‐dust mite (Der p 1 and Der f 1), cat (Fel d 1), and cockroach (Bla g 2) in the household dust of 201 homes in Hamburg (West Germany) and 204 homes in Erfurt (East Germany), and examined the factors that affect these levels. The characteristics of homes were assessed by a questionnaire. The allergen levels were studied in dust from living rooms (LR), bedrooms (BR), and mattresses (MA). We detected in samples from Hamburg significantly higher allergen concentrations than in Erfurt: three times higher Der p 1, five times higher Der f 1, and three times higher Fel d 1. For Bla g 2, no comparison was possible because the concentrations were below the detection limit in 93% of the samples. Most of the differences could be explained by differences in housing and living characteristics between both cities. The mean ratio of Der p 1 levels in mattress dust between Hamburg and Erfurt decreased from 4.1 to 1.54 (NS) after adjustment for season, building material, age of the house, story of the dwelling, type of heating, age of carpet/mattress, presence of dogs, and indoor climate (temperature, humidity). The mean ratio of Der f 1 levels decreased from 6.9 to 2.78 (P<0.05) after adjustment for these factors. The mean ratio for Fel d 1 in mattress dust decreased fom 4.03 to 1.65 (P<0.05) after adjustment for season, building material, story of dwelling, size of dwelling, ventilation, cleaning routines, and pets. A similar reduction was seen for floor dust (LR plus BR). Our results indicate that the differences between the concentrations of mite and cat allergens found in Hamburg and Erfurt are explicable mainly, but not completely, by different building characteristics (age of houses, building material, story, and size of the dwelling) which affected the indoor climate, as well as by differences in other individual living habits (keeping of pets, age of carpets or mattresses, and cleaning routines).
Sublingual immunotherapy: a double‐blind, placebo‐controlled trial with Parietaria judaica extract standardized in mass units in patients with rhinoconjunctivitis, asthma, or both
Authors: Purello‐D'Ambrosio F. , Gangemi S. , Isola S. , La Motta N. , Ricciardi L. , Puccinelli P. , Parmiani S. , Savi E.
Published: March 2003

Background: New routes of administering immunotherapy in respiratory allergy are being studied as an alternative to conventional injective immunotherapy. We carried out a study to evaluate the clinical efficacy and effects of sublingual immunotherapy in patients with Parietaria judaica‐induced respiratory allergy.

Methods: A double‐blind, placebo‐controlled design was followed. Thirty patients with P. judaica rhinoconjunctivitis, mild asthma, or both were randomly chosen for sublingual immuno‐therapy (14 patients) or placebo treatment (16 patients). The patients underwent preseasonal rush induction treatment followed by coseasonal maintenance treatment during the Parietaria pollen season. Symptom and drug scores, as well as specific IgE and specific IgG4, were recorded.

Results: Significantly lower symptom and drug scores were found (P=0.04), especially during the Parietaria pollination period, in the immunotherapy group. No significant difference in specific IgE and specific IgG4 was detected between the active and placebo groups; a statistically significant increase of specific IgE was detected in both groups (P=0.05). No patient undergoing active sublingual immunotherapy reported local or systemic side‐effects.

Conclusions: Our data suggest that sublingual immunotherapy is both clinically effective and safe in treating patients with Parietaria‐induced rhinoconjunctivitis and mild asthma.
p38 MAP kinase regulates RANTES production byTNF‐α‐stimulated human pulmonary vascular endothelial cells
Authors: Hashimoto S. , Gon Y. , Asai Y. , Asai Y. , Machino T. , Jibiki I. , Takeshita I. , Anazawa H. , Horie T.
Published: March 2003

Background: RANTES plays an important role in the production of allergic inflammation of the airway through its chemotactic activity for eosinophils. However, the intracellular signal regulating RANTES expression in human pulmonary vascular endothelial cells has not been determined. In the present study, therefore, we examined the role of p38 mitogen‐activated protein (MAP) kinase in RANTES production by tumor necrosis factor (TNF)‐α‐stimulated pulmonary vascular endothelial cells in order to clarify the signal transduction pathway regulating RANTES production by pulmonary vascular endothelial cells.

Methods: We examined p38 MAP kinase activation, and the effect of SB 203580, as the specific inhibitor for p38 MAP kinase, on p38 MAP kinase activity and RANTES production by TNF‐α‐stimulated human pulmonary vascular endothelial cells.

Results: The results showed that TNF‐α induced RANTES production and p38 MAP kinase activity in human pulmonary vascular endothelial cells. Abrogation of p38 MAP kinase activity by SB 203580 repressed TNF‐α‐induced p38 MAP kinase activity and RANTES production.

Conclusions: These results indicate that p38 MAP kinase plays an important role in the TNF‐α‐activated signaling pathway which regulates RANTES production by human pulmonary vascular endothelial cells.
Anaphylactic reaction to young garlic
Authors: Pérez‐pimiento Aj , Santaolalla M , De Paz S , Fernández‐parra B , Domínguez‐lázaro A. R , Moneo I
Published: March 2003

Background: Garlic is well known to cause contact dermatitis and asthma. However, it is a very rare cause of food allergy. We present the case of a 23‐year‐old woman with previous history of allergy to pollen and dried fruit, and food‐dependent, exercise‐induced anaphylaxis for which no specific food could be identified as responsible, who experienced an anaphylactic reaction after eating young garlic.

Methods: Skin prick tests and specific IgE immunoassay with several pollens and foods were performed, as well as the prick‐prick test with young garlic and SDS–PAGE followed by immunoblotting IgE to young garlic and other Liliaceae species, mustard, sesame, parsley, celery, hazelnut, almond, and pollen of birch and mugwort.

Results: Skin prick tests and specific IgE were mainly positive for grass, plane tree, and mugwort pollen; peanut; hazelnut; walnut; almond; and mustard. Prick‐prick tests with young garlic and garlic were positive. Total IgE was 113 U/ml. SDS–PAGE immunoblotting showed IgE‐binding bands at 12 kDa to young garlic, garlic, onion, and leek extracts. Similar bands could also be detected with mugwort pollen and hazelnut extract.

Conclusions: We describe IgE‐mediated reaction to young garlic in a patient sensitized to pollen and dried fruit.
Intractable pruritus in HIV infection: immunologic characterization
Authors: Milazzo F , Piconi S , Trabattoni D , Magni C , Coen M , Capetti A , Fusi ML , Parravicini C , Clerici M
Published: March 2003

Background: Severe, intractable pruritus, often associated with erythematopapular skin lesions and hypereosinophilia, is a condition observed in some nonatopic, HIV‐infected patients. We performed immunovirologic analyses of this condition.

Methods: Immunologic (mitogen‐stimulated production of cytokines, tumor necrosis factor‐alpha [TNF‐α], and soluble CD23; serum levels of soluble CD23, ICAM‐1, TNF‐α, IgG, IgE, and IgA) and virologic (HIV viral load) parameters were analyzed in six patients with therapy‐resistant pruritus. Hypereosinophilia was present in all these patients. Results were compared to those of seven HIV‐seropositive individuals similar to the first one in terms of CD4 counts and clinical staging, but without pruritus.

Results: Hypereosinophilia; hyper‐IgE and hyper‐IgA; augmented interleukin (IL)‐4, IL‐5, and sCD23; and reduced interferon‐gamma production by mitogen‐stimulated peripheral blood mononuclear cells (PBMC) were detected when patients with pruritus were compared to HIV controls. HIV viral load was also augmented in patients in whom pruritus was present.

Conclusions: The results suggest that therapy‐resistant, intractable pruritus accompanied by hypereosinophilia may be used to define a subset of HIV‐seropositive individuals showing prototypic hyperactivation of humoral immunity, and in whom augmented HIV viral load is present.
Cellular infiltration and cytokine mRNA expression in perennial allergic rhinitis
Authors: Varga EM , Jacobson MR , Till SJ , Masuyama K , O'Brien F , Durham SR , Rak S , Lund V , Scadding GK , Hamid QA
Published: March 2003

Background: Allergen challenge in allergic rhinitis patients leads to local eosinophilia and Th2‐type cytokine expression. Natural exposure to grass pollen is additionally characterized by epithelial mast‐cell infiltration. We hypothesized that perennial allergic rhinitis is also associated with T‐cell and eosinophil infiltration of the nasal mucosa, local Th2‐type cytokine expression, and increased numbers of nasal epithelial mast cells.

Methods: Nasal biopsies from perennial allergic rhinitis patients and controls were analysed by immunocytochemistry for different cell populations and in situ hybridization for cytokine mRNA‐expressing cells.

Results: Perennial allergic rhinitis was associated with increased numbers of submucosal CD3+ T cells (P=0.05), EG2+ activated eosinophils (P=0.01), and CD68+ macrophages (P=0.01) compared to controls. Epithelial, but not submucosal, tryptase‐positive mast cells were also elevated in rhinitics compared to controls (P=0.01). The numbers of cells expressing interleukin (IL)‐5 were higher (P=0.01) and the numbers of cells expressing IL‐2 were lower (P=0.04) in rhinitic patients than controls. There were no significant differences for either IL‐4 or interferon‐gamma between the groups.

Conclusions: Perennial allergic rhinitis is characterized by mast‐cell migration into the epithelium; submucosal infiltration by T cells, eosinophils, and macrophages; and an imbalance in local T‐cell cytokine production in favour of enhanced IL‐5 and reduced IL‐2 expression.
Nonatopic wheezy children have reduced interferon‐gamma
Authors: Leech S.C. , Price J.F. , Holmes B.J. , Kemeny D.M.
Published: March 2003

Viruses cause asthmatic exacerbations in schoolchildren. We tested the hypothesis that children who wheezed with viral respiratory tract infections secrete higher levels of the type 1 cytokine interferon‐gamma (IFN‐γ) in the peripheral circulation than children who had never wheezed. Blood was taken from 13 children (eight atopic) with episodic wheeze and 11 controls. CD4 and CD8 cells were separated from peripheral blood mononuclear cells and stimulated with phorbol 12‐myrisate 13‐acetate (PMA) and ionomycin for 24 h. IFN‐γ, IL‐4, and IL‐5 were measured in the supernatant by ELISA. IFN‐γ production by CD4 and CD8 cells was lower in children with a history of wheeze (CD4, P=0.046; CD8, P=0.037). These children were then analysed according to atopic status. CD4 and CD8 IFN‐γ production in nonatopic wheezy children was reduced (CD4, P=0.009; CD8, P=0.003). IFN‐γ production by atopic wheezy children was lower than by controls, but the differences were not significant (CD4, P=0.2831; CD8, P=0.1372). CD8 IL‐5 was lower in children who wheezed (P=0.012). Release of IL‐4 and IL‐5 by CD4 cells did not differ between the three groups. We propose that defective IFN‐γ secretion by CD4 and CD8 cells may contribute to viral‐induced wheeze in nonatopic children.
Effects of maternal allergen‐specific IgG in cord blood on early postnatal development of allergen‐specific T‐cell immunity
Authors: Prescott S. L. , Holt P. G. , Jenmalm M. , Björkstén B.
Published: March 2003

Background:A wide body of epidemiologic evidence indicates that as yet unknown maternal factor(s) can influence susceptibility to allergic disease in the offspring. It is also well established that the induction of allergen‐specific T‐cell memory is frequently initiated in utero, and it is likely that maternal factors exert their influence during this period.

Methods:This study examines the relationship between maternally derived allergen‐specific IgG subclass antibodies and cellular immune responses (lymphoproliferation and cytokine production) against the same allergens in 49 subjects tested at birth and at 2 years of age. Polyclonal production of the Th1 cytokine IFN‐γ was also examined in the cord‐blood samples.

Results:At birth, there were positive correlations between both house‐dust mite (HDM)‐ and ovalbumin (OVA)‐specific IgG subclass levels in cord blood, maternal atopy, and the magnitude of perinatal lymphoproliferative responses to respective allergens. Inverse relationships were also observed between cord‐blood IgG antibody titres and allergen‐specific production of some Th2 cytokines. However, there were no consistent relationships between cord‐blood allergen‐specific IgG antibodies and subsequent immune responses to allergens when the same subjects were retested at 2 years of age. An inverse relationship was observed between maternal history of atopy and perinatal IFN‐γ production capacity.

Conclusions:Our results suggest that transplacental transfer of allergen‐specific IgG antibody is unlikely to be a major mechanism for maternal regulation of allergen‐specific immunity in infancy. An alternative possibility is that maternal effects may operate by influencing IFN‐γ production by T cells in the offspring.
Allergenic cross‐reactivity of olive pollen
Authors: González E. M. , Villalba M. , Rodríguez R.
Published: March 2003

Background: Sera of patients allergic to olive (Olea europaea) pollen were used to analyze the IgE cross‐reactivity between olive‐pollen extract and other pollens obtained from phylogenetically unrelated species.

Methods: We used IgE immunostaining of pollen extracts blotted to nitrocellulose membranes after SDS–PAGE and inhibition analysis of this binding.

Results: A high inhibition of the IgE binding on olive‐pollen extract was exhibited by birch, mugwort, pine, and cypress pollens, suggesting that these extracts contain proteins which share common epitopes and thus can be recognized by olive‐allergic sera. IgE binding to Gramineae pollen extracts was not inhibited by olive‐pollen extract, indicating a primary sensitization of the patients to these species. From the inhibition assays, the presence of an allergen of 45 kDa in the olive pollen, which has no homologous counterparts in other allergenic species, has been inferred.

Conclusions: Olive pollen contains allergens which cross‐react with pollens from unrelated species, a fact that could simplify the diagnosis and treatment of pollinosis.
Th1/Th2 lymphocyte polarization in asthma
Authors: Mazzarella G. , Bianco A. , Catena E. , De Palma R. , Abbate G. F.
Published: March 2003

Asthma is a complex inflammatory disease of the lung characterized by variable airflow obstruction, bronchial hyperresponsiveness, and airway inflammation. Inflammation in asthma consists of airway infiltration by mast cells, lymphocytes, and eosinophils. There is accumulating evidence that CD4+ lymphocytes with a Th2‐cytokine pattern play a pivotal role in the pathogenesis of asthma. These cells orchestrate the recruitment and activation of the primary effector cells of the allergic response (mast cells and eosinophils), through the release of cytokines such as IL‐4, IL‐5, and IL‐13. Allergic inflammation is also implicated in airway epithelium changes, although the mechanisms by which inflammatory cells and, in particular, T cells interact with the epithelium are not completely clarified. This paper explores the role of T cells in the allergic inflammation of asthma.
Marker antigens to assess exposure to molds and their allergens.II. Alternaria alternata
Authors: Wijnands L. M. , Deisz W. D. C. , Van Leusden F. M.
Published: March 2003

The estimation of exposure to molds and their products in the indoor environment, which may lead to the occurrence of allergies or respiratory complaints, by means of enumeration of viable parts is inadequate. Therefore, other methods must be developed. When grown under various circumstances (22°C and 30°C, high and low water activity) under laboratory conditions, Alternaria alternata produces one antigen that can be found under all studied growth conditions in extracts of the water‐soluble portion of the mycelium. This common antigen may serve as marker antigen for exposure to A. alternata and its allergens. In extracts of the culture filtrate, three antigens, designated index antigens, have been identified that together may have the function of marker for the exposure to allergens of A. alternata.
Levels of house‐dust‐mite allergen in homes of nonallergic people in Pavia, Italy
Authors: Moscato G. , Perfetti L. , Galdi E. , Pozzi V. , Minoia C.
Published: March 2003

Background: HDM distribution varies between geographic areas and may be affected by housing characteristics. We quantified Der p 1 and Der f 1 and assessed the relationships between their levels and housing characteristics in homes of nonallergic subjects.

Methods: Der f 1 and Der p 1 were measured by ELISA in dust samples from living‐room floors and mattresses of 44 homes of nonallergic subjects in Pavia. Information about household characteristics was obtained by questionnaire.

Results: Der p 1 and Der f 1 concentrations (μg/g dust, median) were 0.34 and 7.8 on mattresses, and 0.15 and 0.83 on living‐room floors. Higher Der f 1 levels on mattresses were associated with synthetic pillows (P<0.05), and (only when expressed as μg/m2) with bedding washing temperature of ≤60°C (P<0.05). Der f 1 levels were higher on the living‐room floors of homes located on lower (≤first) floors (P<0.05). Good correlations were found between Der p 1 and Der f 1 expressed as μg/g dust and μg/m2 on both mattresses and living‐room floors.

Conclusions: In homes of nonallergic subjects in northern Italy, Der f 1 exceeded the threshold for sensitization in a high proportion of mattress samples.
Imbalanced switch of the IGHG (immunoglobulin constant heavy G chain) Gm(bfn) genes in atopic childhood asthma
Authors: Oxelius V‐A.
Published: March 2003

Background: The IGHG genes on chromosome 14q32, 5′μδγ3 γ1α1 γ2 γ4 εα2 3′, as studied by Gm allotypes, are involved in the inheritance of atopy. The 5′μδ b f α1 n γ4 εα2 3′, Gm(bfn) haplotype of the genetic B1‐cell variant has been found to be associated with the atopic phenotype of children with bronchial asthma.

Methods: An indirect competitive enzyme‐linked immunosorbent assay for quantitation in serum of the alternative serum Gm allotypes from the γ3‐, γ1‐, and γ2 loci and radial immunodiffusion for quantitation of IgG subclasses were used. Children with the genetic B1‐cell variants B1/B1 (=Gm[bfn/bfn]), B1/B2 (=Gm[bfn/bf‐n]), and B1/B4 (=Gm[bfn/ga‐n]) and bronchial asthma were investigated and compared to healthy children of the same age and B‐cell type.

Results: The three groups with B1/B1, B1/B2, and B1/B4 cells exhibited increased IgE. In both homozygous and heterozygous B1 or Gm(bfn), the serum G1m(f) levels from γ1 loci were significantly downregulated to 75% of normal, while G2m(n) from γ2 loci were significantly upregulated to about double the normal level. In heterozygous patients with additional B2 or B4 cells, the G2m(‐n) levels from γ2 loci were instead downregulated. G1m(a) from γ1 of B4 cells was also downregulated.

Conclusions: Children with atopic bronchial asthma demonstrated an imbalanced class switch in rearrangement of the genes for IgG. The activity of G1m(f) from the γ1 locus was downregulated, but G2m(n) from γ2 was upregulated together with the closely situated ε locus downstream of the IGH genes. Low levels of G1m(f), G1m(a), and G2m(‐n) indicated a low pressure of infections. The imbalanced activation of the IGH genes in more hygienic environments might be one explanation of the increased prevalence of atopy in children in recent decades.
Clinical advantages of dual activity in urticaria
Authors: Kontou‐Fili K.
Published: March 2003

Urticaria is a common disorder that adversely affects quality of life; work‐related and recreational activities are restricted, while rest, sleep, and emotions are seriously disturbed in a significant proportion of patients. The pathogenic mechanisms vary, but cutaneous mast‐cell activation with release of histamine and other vasoactive or proinflammatory mediators is thought to be the final common pathway for lesion induction in most cases. A subsequent, but incompletely understood, late‐phase allergic reaction seems to prolong the inflammatory process, particularly in certain chronic forms of the disorder. Although histamine is considered an important mediator of urticaria, additional substances, including the cysteinyl leukotrienes (LTs), are putative mediators of the immediate urticarial responses and the inflammatory events that follow in some types of urticaria. A second‐generation antihistamine, mizolastine, which exhibits dual activity with selective H1‐receptor antagonism and, as shown in animal studies, anti‐5‐lipoxygenase activity, represents an advance in the treatment of urticaria. It has rapid, potent and sustained action. At the recommended 10‐mg dose, mizolastine suppresses the histamine‐induced wheal reaction as early as 1 h after oral administration. Compared to placebo, mizolastine significantly reduces overall patient discomfort and pruritus in patients with chronic idiopathic urticaria. Double‐blind, placebo‐controlled studies have also shown mizolastine to be at least as effective as other second‐generation antihistamines. Furthermore, with long‐term use of mizolastine over 1 year, a reduction in pruritus and the number of urticarial episodes was maintained with no evidence of tachyphylaxis or tolerance. Mizolastine has also been shown to be an effective treatment for cold‐induced urticaria, causing significant delay in the whealing response to the ice‐cube test and also reducing the wheal diameter.
Generic or disease‐specific quality of life scales to characterize health status in all_ergic rhinitis?
Authors: Kremer B. , Klimek L. , Bullinger M. , Mösges R.
Published: March 2003

Background:  In patients with all_ergic rhinitis (AR), various instruments have been validated for the measurement of quality of life (QOL), which may be greatly reduced. However, it is not clear which QOL instruments should be used for the different types of AR and whether they are sensitive to treatment.

Methods:  The QOL of patients suffering from symptomatic seasonal AR (sSAR) (before and during treatment with a topical or systemic antihistamine), symptomatic perennial AR (sPAR), and asymptomatic seasonal AR (aSAR) was determined with the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) as disease specific and with the Munich Life Dimension List (MLDL) and the Visual Analogue Scale for Quality of Life (VAS‐QOL) as generic QOL instruments.

Results:  The different forms of AR were associated with typical QOL patterns. In sSAR, we found severe limitation of the global QOL, reduced global life satisfaction, high ranking of practical problems, high limitation of activity, and a high degree of disturbance in all_ subscales of the RQLQ. In sPAR, there were moderate limitation of the global QOL, normal global life satisfaction, high ranking of practical problems, moderate limitation of activity, and a high degree of disturbance by common symptoms. Under antihistamine treatment, both systemic and nasal, a significant improvement of QOL parameters was found, reaching the levels of patients with aSAR after 2 weeks.

Conclusions:  QOL instruments can distinguish the impairment resulting from sSAR from that of sPAR and are sensitive to treatment with topical and systemic antihistamines. However, as the RQLQ was not designed to measure the short‐term variations of disease status that appear in SAR, it may not demonstrate the rapid improvement of QOL under antihistamine treatment.
Clinical evaluation of Pharmacia CAP System™ RAST FEIA amoxicilloyl and benzylpenicilloyl in patients with penicillin allergy
Authors: Blanca M. , Mayorga C. , Torres M. J. , Reche M. , Moya C. , Rodriguez J. L. , Romano A. , Juarez C.
Published: March 2003

Background: The diagnosis of IgE‐mediated immediate reactions to penicillins can be supported by in vivo or in vitro tests using classical benzylpenicillin determinants. The wide variety of β‐lactams and the description of new specificities requires a re‐evaluation of the different tests available. The objective was to evaluate the diagnostic capacity of Pharmacia CAP System™ RAST FEIA amoxicilloyl c6 (AXO) and benzylpenicilloyl c1 (BPO) in patients with a documented IgE‐mediated penicillin allergy.

Methods: We studied 129 patients in five groups. Groups 1, 2, and 3 had developed an immediate reaction after penicillin treatment. Group 1 (n=19) were skin test positive to amoxicillin (AX) and/or BPO and/or minor determinant mixture (MDM); group 2 (n=29) were skin test positive to AX but negative to BPO and MDM; and group 3 (n=26) were skin test negative to all determinants, the diagnosis being confirmed by a previous repetitive history or controlled administration. Two control groups, one with nonimmediate reactions – group 4 (n=25) – and one with good tolerance to penicillin – group 5 (n=30) – were included. All samples were analyzed in vitro for AXO and BPO, and the results compared to the in vivo diagnosis.

Results: AX was the drug most often involved. In group 1, 53% were in vitro positive for AXO and 68% for BPO, but 74% had at least one positive test result. In group 2, only 10% had a positive in vitro test to BPO compared to 41% to AXO. In group 3, 42% had positive BPO and/or AXO in vitro tests. In the control groups 4 and 5, the negative in vitro results for AXO were 96% and 100%, and for BPO 100% and 97%, respectively. A positive correlation between specific IgE levels and the time interval from the reaction to the evaluation was found only for group 3.

Conclusions: This in vitro assay is beneficial for evaluating subjects allergic to β‐lactams. It is necessary to test for specific IgE to AXO in addition to BPO in patients with immediate allergic reactions after AX. The combination of in vivo and in vitro tests for estimating IgE antibodies to penicillins is important because of the existence of patients with a positive history but negative skin test.
Eosinophilia, interleukin‐5, and tumour necrosis factor‐alpha in asthmatic children
Authors: Hughes J.M. , Rimmer S.J. , Salome C.M. , Hodge L. , Liu‐Brennan D. , Woolcock A.J. , Armour C.L.
Published: March 2003

Background: There are few paediatric studies of the interrelationships between inflammatory markers and asthma severity. We therefore assessed the relationships between eosinophil‐associated markers, cytokines, and asthma severity in asthmatic children aged 8–12 years.

Methods: Forty‐five children were tested twice, 2 weeks apart. Asthma severity was measured in terms of symptoms, lung function, medication needs, and histamine responsiveness. Peripheral inflammatory markers measured included eosinophil numbers, serum ECP, IL‐5, and TNF‐α and mononuclear cell IL‐5, and TNF‐α production.

Results: Histamine responsiveness was correlated with circulating eosinophils (r=0.56, P=0.0001) and serum ECP (r=0.54, P=0.003). Eosinophilia was increased in children with severe as opposed to mild airway hyperresponsiveness (P=0.02) and those who lost days at school as opposed to those who did not (P=0.01). There were no other associations between markers of asthma severity and inflammation. Children taking inhaled corticosteroids had lower serum IL‐5 levels than those on β‐agonists±cromolyn (mean and 95% CI: 20.5 [11.7–35.7] pg/ml vs 64.3 [26.6–155.4] pg/ml; P=0.04). Cellular IL‐5 production correlated with serum TNF‐α (r=0.63, P=0.0062) and IL‐5 (r=−0.59, P=0.005).

Conclusions: Serum levels of TNF‐α and IL‐5 were not related to peripheral eosinophilia and asthma severity in these children but were related to their own cellular production ex vivo. This study confirms that eosinophilia is the index of inflammation that is most closely related to the clinical severity of childhood asthma.
Double‐blind, randomized, placebo‐controlled trial of effect of nedocromil sodium on clinical and inflammatory parameters of asthma in children allergic to dust mite
Authors: Stelmach I. , Jerzynska J. , Brzozowska A. , Kuna P.
Published: March 2003

Background: The purpose of this study was to determine the clinical effect of nedocromil sodium and its relationship with serum levels of inflammatory mediators by monitoring lung function and noninvasive markers of airway inflammation, such as eosinophil blood counts; serum ECP, sIL‐2R, IL‐4 and sICAM; and total IgE. Anti‐inflammatory medications cause a reduction in the markers of airway inflammation, decrease the intensity of airway hyperresponsiveness, and improve clinical symptoms of asthma. Among the available choices is nedocromil sodium, which is favored in the treatment of asthmatic children due to its very mild side‐effects. It has been previously shown to improve the clinical parameters of asthma, but there are limited data on its effect on inflammatory mediators in the serum of asthmatic children.

Methods: In this double‐blind, randomized, placebo‐controlled 8‐week trial, 39 children, aged 9–16 years, with moderate atopic asthma were randomly allocated to receive either nedocromil sodium, two puffs twice daily, 0.002 g/puff, or placebo, two puffs twice daily. The primary end points were the clinical parameters of asthma measured by asthma symptom score, FEV1, and PC20H. Other end points included the serum levels of various inflammatory markers – ECP, sIL‐2R, IL‐4, sICAM, and IgE.

Results: Clinical and inflammatory parameters improved with the use of nedocromil sodium, compared with placebo. Nedocromil significantly decreased serum levels of inflammatory markers, as shown in the following table. No correlation was found between any of the measured parameters.

Conclusions: Nedocromil sodium provided effective anti‐inflammatory treatment for children with moderate atopic asthma.
Trichophyton sensitivity in allergic and nonallergic asthma
Authors: Mungan D. , Bavbek S. , Peksari V. , Çelik G. , Gügey E. , Mısırlıgil Z.
Published: March 2003

Background: Although the role of inhaled fungi in inducing asthma has been repeatedly confirmed, there are few reports about the association of asthma with dermatophyte sensitivity and the causal role of Trichophyton allergy in asthma. The objective was to investigate the presence of Trichophyton sensitivity among patients with allergic and nonallergic asthma in combination with tinea, and to compare the situation with several control groups in order to evaluate the factors determining Trichophyton sensitivity.

Methods: A total of 86 subjects (55 female, 31 male) with a mean age of 38.6±11.1 years were included in the study. The patients were divided into five groups:

1) nonallergic asthma plus tinea (n=19)

2) allergic asthma plus tinea (n=15)

3) asthma without tinea (n=22)

4) tinea without asthma (n=17)

5) healthy controls (n=13).

Skin tests with standardized extracts of T. rubrum and specific IgE measurements were performed in all subjects. All patients were also subjected to microscopic evaluation and fungal culture for dermatophyte infection.

Results: The skin test positivity rate to Trichophyton extract of groups 1 (63.1%), 2 (46.7%), and 4 (47.1%) was higher than that in groups 3 (4.4%) and 5 (7.7%) (P<0.05). Although not significant, the rates of sensitivity to T. rubrum (63.1%) and of severe asthma (31.6%) were higher in the group with nonallergic asthma with tinea (group 1) than in other groups. Among 51 patients in whom direct microscopic evaluation revealed dermatophyte infection, 60.8% had positive fungal cultures for T. rubrum (58.1%), T. mentagrophytes (35.5%), and Candida (6.4%).

Conclusions: According to our data, the presence of fungal infection seems to be an important determinant in hypersensitivity to Trichophyton whether or not the subject is asthmatic and/or allergic. Since a greater proportion of patients with nonallergic asthma – in whom the rate of severe asthma was also higher – showed positive skin tests to Trichophyton extracts in this study, we believe that patients with severe, intrinsic asthma should be examined for signs of fungal infection and tested to determine immediate hypersensitivity to dermatophyte antigens.
Three cases of childhood nocturnal asthma due to buckwheat allergy
Authors: Lee S. Y. , Lee K. S. , Hong C. H. , Lee K. Y.
Published: March 2003

Background: Buckwheat flour (BF) is known as a potent food allergen. Sensitization to it usually occurs by ingestion but also by inhalation in occupational or domestic exposure. Buckwheat chaff‐stuffed pillows (BCP) can be contaminated with BF during the process of pilling, and many Korean children and adults use BCP for health reasons.

Methods and Results: We here present three cases of BF allergy in children using BCP, who had been treated as nonatopic asthmatics after undergoing the routine allergy skin tests and serologic tests. We took careful clinical histories, and performed skin prick tests (SPT), the radioimmunoassay (RIA) for specific IgE, the BCP‐elimination test, the BF bronchial provocation test, and IgE Western blot. All three children showed positive skin reactions to BF, but none of them had positive reactions to house‐dust mites. Nocturnal asthmatic symptoms were improved during 7 days of BCP elimination, and asthmatic responses were observed by bronchial provocation tests with homemade BF extract. Serum BF‐specific IgE antibodies and several IgE‐binding proteins were detected by RIA and Western blot analysis, respectively.

Conclusions: Thus, a small amount of BF attached to BCP can induce BF sensitization, and BCP should be considered a main cause of childhood nocturnal asthma in those asthmatics exposed to these pillows.
Olive allergen‐specific IgE responses in patients with Olea europaea pollinosis
Authors: Quiralte J. , Florido F. , Arias de Saavedra J. M. , Gómez A. , Sáenz de San Pedro B. , González E. , Rodríguez R.
Published: March 2003

Background Olive tree (Olea europaea) pollen is an important cause of pollinosis in the countries of the Mediterranean area.

Objective This work aimed to study the IgE‐binding frequency of Ole e 1, Ole e 2, Ole e 3, Ole e 6 and Ole e 7 from O. europaea pollen in a large population of olive pollen‐allergic patients.

Methods We studied: 119 consecutive patients with seasonal rhinitis and/or asthma and a positive skin prick test to O. europaea pollen extract; 10 atopic patients without history of pollinosis and a negative skin prick test to O. europaea; and 10 healthy controls. Allergens were purified from O. europaea pollen extract by reverse phase HPLC and characterized by N‐terminal amino acid sequencing, MALDI analysis, and specific IgE immunodetection. Skin prick tests and ELISA titration against above mentioned purified olive pollen allergens were performed in all pollinic patients and controls.

Results One‐hundred and seven (90.7%) patients had a positive skin response to Ole e 1; 88 (74.6%) reacted to Ole e 2; 57 (47.9%) reacted to both Ole e 6 and Ole e 7; and 43 (37.8%) reacted to Ole e 3. The allergenic activity determined by ELISA to Ole e 1 was found in 84%; to Ole e 2 in 61.3%; to Ole e 3 in 31.9%; to Ole e 6 in 39.4%; and to Ole e 7 in 41.2% of patients. All patients had positive skin responses to at least one of the allergens tested, However, a combination of Ole e 1 and Ole e 2 together with a minor allergen Ole e 6 or Ole e 7, disclosed the same diagnostic value that was obtained with the use of crude olive pollen extract. The nonatopic and atopic control subjects did not react to any purified allergens on the skin prick test.

Conclusions These results indicate that Ole e 1 and Ole e 2 are major allergens in patients with O. europaea pollinosis in our population. A combination of a few olive pollen allergens can substitute the crude extract for in vivo as well as in vitro diagnostic purposes.