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While suction cups prevail as common gripping tools for a wide range of real-world parts and surfaces, they often fail to seal the contact interface when engaging with irregular shapes and textured surfaces. In this work, the authors propose a suction-based soft robotic gripper where suction is created inside a self-sealing, highly conformable and thin flat elastic membrane contacting a given part surface. Such soft gripper can self-adapt the size of its effective suction area with respect to the applied load. The elastomeric membrane covering edge of the soft gripper can develop an air-tight self-sealing with parts even smaller than the gripper diameter. Such gripper shows 4 times higher adhesion than the one without the membrane on various textured surfaces. The two major advantages, underactuated self-adaptability and enhanced suction performance, allow the membrane-based suction mechanism to grip various three-dimensional (3D) geometries and delicate parts, such as egg, lime, apple, and even hydrogels without noticeable damage, which can have not been gripped with the previous adhesive microstructures-based and active suction-based soft grippers. The structural and material simplicity of the proposed soft gripper design can have a broad use in diverse fields, such as digital manufacturing, robotic manipulation, transfer printing, and medical gripping., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Hierarchical surfaces that aid in the droplet nucleation, growth, and removal is highly desirable for fog and moisture harvesting applications. Taking inspiration from the unique architecture of leaf skeletons, we present a multiscale surface capable of rapidly nucleating, growing, and directional transport of the water droplets. Copper oxide microtufts were fabricated onto the Ficus religiosa leaf skeletons via electroplating and chemical oxidation techniques. The fabricated surfaces with microtufts had high wettability and very good fog harvesting ability. CuO surfaces tend to become hydrophobic over time because of the adsorption of the airborne species. The surfaces were efficient in fog harvesting even when the hydrophobic coating is present. The overall water collection efficiencies were determined, and the role of the microtufts, fractal structures, and the orientation of leaf veins was investigated. Compared to the planar control surfaces, the noncoated and hydrophobic layer-coated copper oxide microtufts on the leaf skeletons displayed a significant increase in the fog harvesting efficiency. For superhydrophilic skeleton surfaces, the water collection rate was also observed to slightly vary with the vein orientation. The CuO microtufts along with high surface area fractals allowed an effective and sustainable way to capture and transport water. The study is expected to provide valuable insights into the design and fabrication of sustainable and efficient fog harvesting systems.

Grasping is one of the key tasks for robots. Gripping fragile and complex three-dimensional (3D) objects without applying excessive contact forces has been a challenge for traditional rigid robot grippers. To solve this challenge, soft robotic grippers have been recently proposed for applying small forces and for conforming to complex 3D object shapes passively and easily. However, rigid grippers are still able to exert larger forces, necessary for picking heavy objects. Therefore, in this study, we propose a magnetically switchable soft suction gripper (diameter: 20 mm) to be able to apply both small and large forces. The suction gripper is in its soft state during approach and attachment while it is switched to its rigid state during picking. Such stiffness switching is enabled by filling the soft suction cup with a magnetorheological fluid (MR fluid), which is switched between low-viscosity (soft) and high-viscosity (rigid) states using a strong magnetic field. We characterized the gripper by measuring the force required to pull the gripper from a smooth glass surface. The force was up to 90% larger when the magnetic field was applied (7.1 N vs. 3.8 N). We also demonstrated picking of curved, rough, and wet 3D objects, and thin and delicate films. The proposed stiffness-switchable gripper can also carry heavy objects and still be delicate while handling fragile objects, which is very beneficial for future potential industrial part pick-and-place applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: 3-year subcutaneous specific immunotherapy (SIT) in children with seasonal allergic rhinoconjunctivitis reduced the risk of developing asthma during treatment and 2 years after discontinuation of SIT (5-year follow-up) indicating long-term preventive effect of SIT., Objective: We evaluated the long-term clinical effect and the preventive effect of developing asthma 7-years after termination of SIT., Methods: One hundred and forty-seven subjects, aged 16-25 years with grass and/or birch pollen allergy was investigated 10 years after initiation of a 3-year course of SIT with standardized allergen extracts of grass and/or birch or no SIT respectively. Conjunctival provocations were performed outside the season and methacholine bronchial provocations were performed during the season and winter. Asthma was assessed by clinical evaluation., Results: The significant improvements in rhinoconjunctivitis and conjunctival sensitivity persisted at the 10-year follow-up. Significantly less actively treated subjects had developed asthma at 10-year follow-up as evaluated by clinical symptoms [odds ratio 2.5 (1.1-5.9)]. Patients who developed asthma among controls were 24/53 and in the SIT group 16/64. The longitudinal treatment effect when adjusted for bronchial hyper-responsiveness and asthma status at baseline including all observations at 3, 5 and 10 years follow-up (children with or without asthma at baseline, n = 189; 511 observations) was statistically significant (P = 0.0075). The odds ratio for no-asthma was 4.6 95% CI (1.5-13.7) in favor of SIT., Conclusion: A 3-year course of SIT with standardized allergen extracts has shown long-term clinical effects and the potential of preventing development of asthma in children with allergic rhinoconjunctivitis up to 7 years after treatment., Clinical Implication: Specific immunotherapy has long-term clinical effects and the potential of preventing development of asthma in children with allergic rhino conjunctivitis up to 7 years after treatment termination.

Background: Subcutaneous immunotherapy has been the principal approach of immunotherapy in the treatment of allergic diseases. Several clinical studies with birch, alder or hazel pollen extract conducted as subcutaneous immunotherapy have been published suggesting a well-tolerated and clinically effective treatment. Only a few clinical studies of sublingual immunotherapy (SLIT) with these allergens have been published. This study investigated the clinical efficacy, safety and dose-response relationship of SLIT in children suffering from rhinoconjunctivitis with/without asthma., Methods: Eighty-eight children (5-15 years) with a history of tree pollen-induced allergic rhinoconjunctivitis with/without seasonal asthma for >or=2 years were included. Allergy to tree pollen was confirmed by positive skin-prick test, positive specific IgE and positive conjunctival provocation test. The extract used was a glycerinated mixture of Betula verrucosa, Corylus avellana and Alnus glutinosa 100,000 SQ-U/ml. Children were randomized into three groups receiving SLIT 5 days a week for up to 18 months; dose group 1: accumulated weekly dose of 24,000 SQ-U; dose group 2: accumulated weekly dose of 200,000 SQ-U; and placebo., Results: In the birch pollen season, dose group 2 showed a significant reduction of symptom (P = 0.01) and medication scores (P = 0.04) compared with placebo. Dose group 1 showed a significant reduction of symptom scores (P = 0.03). There were no statistical differences between dose groups 1 and 2. All children tolerated the treatment well., Conclusion: SLIT with tree pollen extract provided dose-dependent benefits in tree pollen-allergic children in terms of significantly reduced symptoms and medication use. The treatment was well tolerated.

Background: A 3-year course of specific immunotherapy (SIT) in children with hay fever to grass and/or birch pollen significantly reduced the risk of developing asthma. To investigate the long-term preventive effect, we performed a follow up--2 years after termination of immunotherapy., Methods: A total of 183 children, aged 6-14 years with grass and/or birch pollen allergy could be investigated 2 years after discontinuation of SIT or no treatment. Conjunctival provocation tests (CPTs) and methacholine bronchial provocation tests were carried out during the season and winter after 5 years. The development of asthma was assessed by clinical evaluation., Results: The significant improvement in hay fever and CPT results observed after 3 years of SIT persisted at the 5-year follow-up. No difference in bronchial responsiveness to methacholine was found after 5 years because of spontaneous improvement during the follow-up period in the control patients. The immunotherapy-treated children had significantly less asthma after 5 years as evaluated by clinical symptoms [odds ratio 2.68 (1.3-5.7)] in favor of SIT for prevention of development of asthma and significantly less patients reported an increase in asthma scores (P < 0.01)., Conclusion: Immunotherapy for 3 years with standardized allergen extracts of grass and/or birch shows long-term clinical effect and preventive effect on development of asthma in children with seasonal rhinoconjunctivitis.

Asthma is the most common chronic disorder among Finnish children, however, the economic burden of paediatric asthma in Finland has not yet been comprehensively evaluated. The objective of this study was to compare inpatient resource utilisation between younger (2-5 yrs) and older children (6-14 yrs) with asthma in Finland. A national database of inpatient resource utilisation was applied to determine use of hospital services among children with asthma in 1999. Regional estimates of charges were combined with hospitalisation episodes to determine total inpatient cost. The results indicate that younger asthmatic children consume 3-times more inpatient resources per capita. Incidence of first admissions because of asthma was 3-times higher in younger children. Hospitalisation and rehospitalisation rates were also 3- and 4-times higher, respectively. The total annual inpatient cost of asthma in children aged 2-5 and 6-14 yrs was Euro 1.98 million with each group accounting for Euro 1.12 million and Euro 0.86 million, respectively. Regional and age-related differences in hospitalisation rates and costs were likely related to variable clinical practice on the primary level, difficulties with diagnosis and compliance among younger children.

Background: Children with allergic rhinitis are likely to develop asthma., Objective: The purpose of this investigation was to determine whether specific immunotherapy can prevent the development of asthma and reduce bronchial hyperresponsiveness in children with seasonal allergic rhinoconjunctivitis., Methods: From 6 pediatric allergy centers, 205 children aged 6 to 14 years (mean age, 10.7 years) with grass and/or birch pollen allergy but without any other clinically important allergy were randomized either to receive specific immunotherapy for 3 years or to an open control group. All subjects had moderate to severe hay fever symptoms, but at inclusion none reported asthma with need of daily treatment. Symptomatic treatment was limited to loratadine, levocabastine, sodium cromoglycate, and nasal budesonide. Asthma was evaluated clinically and by peak flow. Methacholine bronchial provocation tests were carried out during the season(s) and during the winter., Results: Before the start of immunotherapy, 20% of the children had mild asthma symptoms during the pollen season(s). Among those without asthma, the actively treated children had significantly fewer asthma symptoms after 3 years as evaluated by clinical diagnosis (odds ratio, 2.52; P <.05). Methacholine bronchial provocation test results improved significant in the active group (P <.05)., Conclusion: Immunotherapy can reduce the development of asthma in children with seasonal rhinoconjunctivitis.

Aim: It has been suggested that living on a farm decreases the risk of childhood allergy, especially if farming involves livestock. The aim of this study was to examine the association between farming and allergy in children, and the influence of atopic heredity in this association., Methods: The cross-sectional data of the 7981 children aged 13-14 y who participated in the Finnish ISAAC study between the years 1994 and 1995 were used to evaluate the association between farming and allergy., Results: Living on a farm was associated with a decreased risk of current symptoms of allergic rhinoconjunctivitis among all children (aOR 0.79; 95% CI 0.63, 0.99), and with a decreased risk of hay fever, especially among those children with a parental history of hayfever (aOR 0.60; 95% CI 0.40-0.89, p = 0.072 for interaction). The children of farmers with a history of hay fever also had a decreased risk of current wheeze (aOR 0.38; 95% CI 0.12-1.24, p = 0.040 for interaction). No significant association was found between farming and either asthma or eczema. Children living on a farm with livestock had the lowest risk of allergic rhinoconjunctivitis (aOR 0.69), followed by those living on a farm without livestock (aOR 0.89) compared with the non-farming children (p-value for trend 0.024)., Conclusion: Our results support the recent findings on a decreased risk of allergy among the children living on farms. A possible differential effect of parental history of hay fever on the relation of farming environment and the risk of allergic symptoms warrant further investigation.

Food-related symptoms are common in the first years of life, and food allergy should be diagnosed using an elimination challenge test. We surveyed Finnish hospital-based pediatricians using a self-completion questionnaire to ascertain the current clinical practice: 24 of the 25 pediatricians (representing 24 of 25 hospitals) so approached gave evaluable responses. Food allergies were diagnosed using a clinical elimination challenge test in patients with suspected allergy to cow's milk or cereals (wheat, rye, barley, oats). Of the 24 departments, four reported that they performed challenge in all patients before diagnosis was confirmed, and 14 performed challenge in most patients before diagnosis was confirmed. The duration of the challenge varied from 0.5 to 7 days (median 4 days). A 1-week challenge was used in eight hospitals. The double-blind placebo-controlled challenge was used in seven of the hospitals, and in none routinely. Altogether, 16 of the respondents agreed that there is a need to establish clinical guidelines for the diagnosis of food allergy. In conclusion, despite a long tradition of medical education on the subject of food allergy, practices vary for its diagnosis. There is therefore a requirement for appropriate clinical guidelines.

The primary aim of the study was to evaluate the prevalences of allergic rhinitis and atopic dermatitis and their regional differences among Finnish children. The secondary objective was to determine whether the responses to the questions used are affected by the pollen season if asked during such a season. In 1994-5, the self-reported prevalence of allergic symptoms in four regions of Finland was studied among 11,607 schoolchildren aged 13-14 years, as part of the International Study of Asthma and Allergies in Childhood (ISAAC). The prevalence of rhinoconjunctivitis during the preceding year was 16% in eastern Finland (Kuopio County, n=2821), 23% in southern Finland (Helsinki area, n=2771), 15% in southwestern Finland (Turku and Pori County, n=2983), and 16% in northern Finland (Lapland, n=3032). The respective prevalences of flexural dermatitis were 15%, 19%, 16%, and 18%. The surveys were performed in winter, except in the Helsinki area where the survey was carried out mainly in the spring pollen season. Among the children studied in autumn in Helsinki, the prevalence of rhinoconjunctivitis was 19% and that of flexural dermatitis 17%. In multivariate analysis, flexural dermatitis was slightly more common in Lapland than in all other areas. In contrast, no significant differences were found in rhinoconjunctivitis. The prevalences of both disorders were twice as high in girls as in boys. In conclusion, regional differences in the prevalence of allergic rhinitis and atopic dermatitis were small in our country, and the prevalence figures were rather similar to those reported from other European countries. Almost half of the children had suffered from at least one atopic disorder, and over one-third had had symptoms in the past year. A clear season-of-response effect was observed; the prevalence of rhinoconjunctivitis was 25% when studied during the pollen seasons in the Helsinki area.

This study was undertaken to analyze the differences in exposure and sensitization to five common environmental yeasts. The responses of IgG, IgA, and IgE to Candida albicans, C. utilis, Cryptococcus albidus, Rhodotorula rubra, and Saccharomyces cerevisiae and purified S. cerevisiae enolase were analyzed by immunoblotting (IgE-IB), and the cross-reactivity of their IgE-binding components by IgE-IB inhibition. Twenty atopic subjects, with asthma, allergic rhinitis, or atopic dermatitis were included. In skin prick tests (SPT), 12 of the patients showed simultaneous reactivity to at least two of the five yeasts, four reacted to one of the yeasts, and four had no responses. Antigens run in SDS-PAGE and transferred to nitrocellulose were probed with enzyme-labeled IgA-, IgG-, and IgE-specific antibodies. The IgE immunoblotting revealed most IgE-binding bands in C. albicans (11 bands) followed by C. utilis (eight bands), S. cerevisiae (five bands), R. rubra (five bands), and Cr. albidus (four bands). Six of the IgE-binding bands of C. albicans and C. utilis shared molecular weight, and only two bands shared molecular weight with other yeasts. These were the 46-kDa band, shared by all five yeasts, and a 13-kDa band shared by four yeasts. Prominent IgE binding was seen to a 46-kDa band of C. albicans (seven patients), C. utilis (five patients), and S. cerevisiae (one patient) and to corresponding weak bands of Cr. albidus and R. rubra (one patient). The possible cross-reactivity of the 46-kDa band was analyzed by IgE-IB inhibition and densitometry, revealing clear C. albicans inhibition of C. utilis (80%) and enolase (98%) (autoinhibition 100%). The strongest IgG responses were seen against S. cerevisiae and C. albicans. The responses were mainly against mannans of C. albicans and S. cerevisiae, suggesting that most of the exposure is to these yeasts. Yeasts with different types of exposure, from saprophytic growth on human mucous membranes to exposure by air and food, were shown to cross-react at the allergenic level. Atopic patients primarily sensitized by C. albicans and S. cerevisiae may develop allergic symptoms by exposure to other environmental yeasts due to cross-reacting IgE antibodies.

A standardized, controlled procedure for preparation of an in-house reference (IHR) preparation of an allergen extract of Candida albicans is described. The procedure, based on previous studies of allergens of C. albicans, is designed to yield a maximum of allergens in optimum extraction conditions and to provide a reference preparation for further extract production. The SDS-PAGE, IgE-immunoblotting, and crossed radioimmunoelectrophoresis (CRIE) analyses showed that the procedure is reproducible with acceptable batch-to-batch variation. The variation in the content of the most important allergens, namely, proteins with molecular weights of 46, 29, and 27 kDa in the pooled final batches, is acceptable (coeff. of variation < 15%), although in the intermediate batches of different strains, the coefficient of variation may occasionally exceed 20%. A comparison with other C. albicans allergen preparations used in our previous studies is also presented. The resulting extract can be used as a reference in further extract production and also in experimental in vitro and in vivo studies.

The aim of this study was to determine whether there are regional differences in the prevalence of childhood asthma in Finland. A secondary objective was to assess the concordance between a written and a video questionnaire on asthma symptoms. In 1994-1995, the self-reported prevalence of asthma symptoms in four regions of Finland was studied among 11,607 schoolchildren aged 13-14 yrs, as part of the International Study of Asthma and Allergies in Childhood (ISAAC). The ISAAC written and video (AVQ 3,0) questionnaires were administered in the school setting. The prevalences of any wheezing during the previous 12 months in the ISAAC video questionnaire were 10% in East Finland (Kuopio County, n=2,821), 12% in South Finland (Helsinki area, n=2,771), 12% in Southwest Finland (Turku and Pori County, n=2,983), and 11% in North Finland (Lapland, n=3,032). The prevalences in the ISAAC written questionnaire were 13, 20, 15, and 16%, respectively. The surveys were performed during winter, except in Helsinki where the survey was carried out mainly during the spring pollen season. During autumn, the prevalence in the written questionnaire in Helsinki was 16%. In multivariate analysis, boys had a lower prevalence than girls, and smokers a threefold higher prevalence than nonsmokers. In conclusion, the prevalence of childhood asthma is lower in Finland than in other European countries, and may be even lower in the eastern part of the country. In contrast to the results from some other European countries, prevalences were lower in the video than in the written questionnaire, which suggests that translating the word "wheezing" into other languages, including Finnish, may produce results that cannot be compared. The strong association of smoking with wheeze both in the video and written questionnaires should be considered in further analysis of the ISAAC study.

The objective of the study was to investigate the features of cardiovascular and respiratory autonomic nervous regulation in asthmatic and control children. Cardiorespiratory reactivity was studied by continuous and non-invasive recording of the electrocardiogram, finger systolic arterial pressure (SAP) and flow-volume spirometry in supine and upright positions and during a deep breathing test in 19 children with bronchial asthma and 10 healthy control children (age 8-11 years). The periodic variability components of R-R intervals (the time between successive heart beats) and SAP in relation to respiration were assessed using spectral analysis techniques. Nine asthmatic children without beta2-agonist medication had a lower respiratory rate and larger high frequency (HF) variability of SAP than the controls, and 10 asthmatic children with beta2-agonist medication had greater low-frequency (LF) variability of SAP and LF/HF ratio of R-R intervals, but their respiratory rate did not differ from the controls. No intergroup differences were found in the postural change of variables. Stable bronchial asthma appears to increase respiratory-induced alterations in systolic blood pressure in children. Beta2-agonist medication, on the other hand, increases sympathetic cardiovascular activity in children with asthma.

Two particle samplers for ambient air, situated together: a static size-selective bio-aerosol sampler (SSBAS) and a Burkard pollen and spore trap were compared in sampling intact birch pollen grains through one flowering period of Betula (a total of 44 days). The SSBAS trapped pollen grains three times more efficiently than the Burkard trap, but the variations in pollen counts were significantly correlated. In contrast, birch pollen antigenic activity and the pollen count in the Burkard samples were not closely correlated. The antigenic concentration was occasionally high both before and after the pollination period. There was a high birch pollen antigenic activity in particle size classes where intact pollen grains were absent, even on days when the pollen count was very low. Correspondingly, on days with high birch pollen counts in the air, pollen antigenic activity was on several occasions low, indicating that pollen grains were empty of antigenic material. The small particle size classes are especially important to allergic patients because they are able to penetrate immediately into the alveoli and provoke asthmatic reactions. Therefore, aerobiological information systems based on pollen and spore counts should be supplemented with information concerning antigenic activities in the air.

Stability of Candida albicans allergens was studied under various storage conditions. Lyophilized extract was reconstituted with human serum albumin (NSA) diluent, glycerol-free and in the presence of 10% or 50% glycerol and stored at various temperatures for different time periods. All extracts were tested at the same time with immunoblotting using C. albicans allergic patient sera and galactosidase-labelled anti-IgE. The highest number of detected allergens in the immunoblotting pattern was found in the presence of 50% glycerol at +6 degrees C. The most important allergen of C. albicans, the 46 kD protein allergen was stable up to 10 weeks at +6 degrees C in the presence of 50% glycerol but thereafter began to lose its IgE-binding capacity. After 30 weeks more than 50% of the IgE binding had disappeared. The 27 kD protein, another important allergen, was also labile but retained the allergenicity better than the 46 kD one. The 29 kD protein allergen was stable at all storage conditions, except +37 degrees C tested even after one year. More than 6 months storage at +6 degrees C or higher temperature is, however, unacceptable even in the presence of the 50% glycerol. These findings have particular importance in the diagnosis and treatment of allergic diseases.

The clinical significance of mould allergens in Phadebas RAST panel was investigated in 121 asthmatic children. They were selected from a total population of 1649 patients. The patients were distributed into four groups, based on the combination of positive or negative skin prick tests (SPT) together with symptoms suggestive or not of mould sensitivity. Mould-specific IgE antibodies were investigated using the original RAST panel (Alternaria, Aspergillus, Candida, Cladosporium, Mucor and Penicillium) and a set of 10 additional mould-allergen discs (Aureobasidium, Botrytis, Curvularia, Epicoccum, Fusarium, Helminthosporium, Phoma, Rhizopus, Stemphylium and Trichoderma). The set of additional RAST discs revealed patients with mould-reaginic antibodies not found with the original RAST panel. This occurred in four of 49 (8.2%) RAST positive (class greater than or equal to 2) patients. The allergens most frequently positive were Cladosporium (in 28% of the patients), Candida (28%) and Helminthosporium (26%). A remarkable degree of simultaneous reactivity to almost all moulds tested was observed. Patients with multiple (greater than or equal to 7) mould sensitization were effectively pinpointed using any duplicate combination of Aureobasidium, Botrytis, Candida, Cladosporium, Helminthosporium, Penicillium and Stemphylium.

Pollen and spore counts from Burkard traps for routine pollen and spore sampling placed at 15 m above ground and at ground level were compared. Daily counts of most pollen types were higher on the ground than at roof level, but the counts were significantly correlated. The ratios of pollen frequencies at high and low levels varied between 1.0 and 11.5. The most prominent differences were recorded for herbaceous pollen (e.g. Artemisia counts 11.5 and Poaccae counts 4.4 times higher at ground level) and in Botrytis and Ustilaginales spores. Tree pollen grains and basidiomycetous spores were more equally distributed. Wind speed did not affect the variation of pollen frequencies at either height. Large spores are not so unevenly distributed as previously supposed. Artemisia and grass pollen was detected 1 to 2 weeks earlier at ground level than on the roof. It is therefore concluded that especially the beginning of flowering should be monitored at a low level.

Fifty four patients aged from 1 to 6 years who had had recurrent attacks of wheezy bronchitis were prospectively followed up for three months to find out if there was an association between different viral respiratory infections and episodes of wheezing. Of the 115 episodes of upper or lower respiratory tract symptoms, virus or Mycoplasma pneumoniae infection were diagnosed in 52 (45%). Thirty four of rhinoviruses. The patients had an average of 2.1 episodes of respiratory tract symptoms the total mean (SD) duration of which was 30 (2) days of the 92 days that followed. Wheezing occurred during 76 (66%) of the 115 episodes and during a third of these the patient was admitted to hospital because of severe dyspnoea. Wheezing started a mean (SD) of 43 (7) hours after the first symptoms of respiratory infection and persisted for 3.8 (4.2) days in patients in whom virus infection was diagnosed. The incidence of wheezing was not associated with IgE mediated atopy, with positive virological tests, or with fever during virus infection, but was associated with parental smoking and more than one sibling.

Immunoblotting and RAST were used to analyse IgE, IgA and IgG responses to antigens of Candida albicans. These were compared with the delayed skin response and C. albicans carriage in 40 atopic subjects. The majority of the atopic patients showed a strong IgG and IgA antibody response towards mannan, a carbohydrate, but only occasionally to proteins. Altogether 22 of the 40 patients showed specific IgE towards C. albicans by immunoblotting. The IgE response was mainly towards proteins, particularly to ones with molecular weights of 29 kD and 46 kD, and only in eight out of 22 IgE-positive subjects towards mannan. The IgG and IgA responses to mannan and the total IgE response towards C. albicans assessed by RAST showed an association with C. albicans carriage, whereas the delayed skin response showed an inverse relationship. The immunological parameters characteristic of C. albicans carriage were found to be C. albicans-specific depressed delayed skin response and elevated IgE, IgA and IgG responses. This situation in the atopics presenting such parameters may favour simultaneous sensitization and exposure by colonization. The degree of sensitization may be sufficiently high to produce symptomatic allergy, such as asthma, in some individuals during occasional overgrowth of C. albicans, e.g. due to antibiotic therapy.

Analysis of IgE, IgA and IgG antibodies directed against Candida albicans antigens in 28 asthmatic children was performed with immunoblotting after SDS-PAGE. Analysis with the purified cytoplasmic protein fraction revealed a major protein allergen with an MW of 46 kD. In addition to the major allergen, 15 other antigenic bands with molecular weights between 16 and 135 kD bound IgE. Ten of 13 anti-C. albicans IgE-positive children had IgE towards the 46 kD major allergen. None of the subjects in the study group or in the non-atopic controls had IgA or IgG antibodies towards this protein. Analysis of the crude surface extract showed that mannan, a carbohydrate, was an intermediate allergen contrary to being the major antigen in IgA and IgG antibody responses.

Watersoluble antigens of Candida albicans were sequentially extracted from intact and disrupted yeast cells grown on protein-free agar, and analysed on immunoblots after SDS-PAGE. Washing of the cells in saline before proper extraction resulted in loss of 47.2% of the total carbohydrate and 1.5% of the total protein. The protein fraction contained 14 antigenic bands when analysed with hyperimmune rabbit antisera. Four of these bound IgE when probed with a RAST-positive serum pool and beta-galactosidase-labelled anti-IgE. Extraction of the disrupted cells resulted in 15% of the total carbohydrate and 94% of the total protein. The cytoplasmic protein fraction showed 69 antigenic bands, 13 of which bound IgE. The carbohydrate fraction contained mannan, which was found in the washing solutions and in the surface extract as well as in the cytoplasmic extract. Allergens found in washing solutions were also present in cytoplasmic fraction. This study suggests that the rapid release of allergens from saprophytic C. albicans cells on mucous membranes of the body may cause continuous exposure and result in sensitization.

The carbohydrate-containing fraction of Candida albicans was isolated from the crude extract with ConA Sepharose affinity chromatography and studied by IgE-immunoblotting with individual and pooled sera from C. albicans-allergic subjects. In the ConA-bound fraction there was a diffuse IgE binding in the high molecular weight area which also gave a carbohydrate stain (PAS). A distinct band corresponding to a molecular weight of 70 kD bound specific IgE antibodies. This glycoprotein, presumably a mannoprotein, gave a weak carbohydrate staining and a strong protein staining. Further biochemical studies are needed to reveal the exact nature of the epitopes in the ConA-bound mannose-containing fraction of C. albicans.

Skin prick tests (SPT) were carried out on 164 asthmatic children using dog dander allergen preparations (A, B1, B2 and D) from three manufacturers. Bronchial and/or conjunctival provocation tests with allergen A were performed on all patients, as well as the Phadebas RAST (allergen e5). There was a close agreement between the clinical history and the SPT with allergens A and D. The provocation tests and RAST gave results in good agreement with the SPT reactions to all allergens except B1. The overall agreement between the SPT reactions to the different allergens was good. However, significant differences were observed in the allergenic activity of the different preparations and between different batches from the same manufacturer (allergens B1 and B2).

Dog dander and hair (DDH) specific IgA and IgG antibodies from serum samples of 202 asthmatic children aged from 4 to 15 years were measured by enzyme-linked immunosorbent assay. The results were compared with clinical history, and with allergy tests (skin prick test, provocation test and RAST) using the same DDH extract. A blood sample for the in vitro lymphocyte stimulation test was obtained from 40 children, and a nasal secretion sample for analysis of the local DDH-specific IgA, IgG and IgE antibody levels was collected from 35 of them. In children of dog-keeping families, higher serum levels of DDH-specific antibodies, especially IgE antibodies, were observed if the dog had been in the home already during the first years of the child's life. The serum levels of DDH-specific antibodies, however, did not correlate with the degree of the present exposure to dogs. The serum levels of DDH-specific IgA and IgG antibodies did not correlate with each other, with the levels of specific or total IgE, or with the results of skin prick or provocation test. The serum levels of DDH-specific IgA were highest in children who were subjectively most sensitive to dogs. Nasal levels of DDH-specific IgE correlated positively with serum specific IgE levels. The correlation was weaker between nasal and serum titers of specific IgG, and not significant between nasal and serum IgA antibody levels. Specific IgE antibody levels were higher, while specific IgA and IgG antibody levels were lower, in nasal secretion from subjects with nasal symptoms on contact with dogs, when compared with subjects with other complaints (asthma, conjunctival or skin reactions). DDH-specific IgG levels correlated negatively with specific IgE level in the nasal secretion from subjects with a positive provocation test result, while the correlation was positive in subjects with a negative provocation test. The in vitro lymphocyte responses to DDH did not correlate with the results of allergy tests, or with the levels of DDH-specific antibodies in serum or in nasal secretion.

A double-blind histamine placebo controlled immunotherapy trial was performed to investigate the clinical effect of a purified and standardized Cladosporium herbarum allergen preparation. Thirty children with a clinical history suggesting mould-induced asthma and/or rhinoconjunctivitis were included. The diagnosis was confirmed by positive skin prick test and Phadebas RAST as well as positive bronchial and/or conjunctival provocation test to Cladosporium herbarum. Immunotherapy was given for 10 months in a double-blind manner to randomized groups with either Pharmalgen/Cladosporium herbarum preparation or histamine placebo. Allergic side effects to injections were common, especially during the peak of the mould season (July-September in Scandinavia). In the active group, 13/16 patients experienced general reactions during the first 10 months of treatment. After 6 months of treatment, eye, nose and bronchial symptom scores and peak expiratory flow rates were similar for the groups, maybe because most of the children were also sensitive to many other allergens, including Alternaria alternata. However, medication scores were significantly lower in the treated group (P less than 0.01). Bronchial (P less than 0.01) and conjunctival sensitivity (P = 0.01) were significantly reduced in the Cladosporium-treated group but not in the placebo group after 10 months of treatment. This is the first double-blind clinical trial showing the clinical efficacy of immunotherapy in children with mould-induced asthma.

This double-blind immunotherapy trial in children, using a purified and standardized Cladosporium herbarum allergen preparation, has shown that children with mould asthma and/or rhinoconjunctivitis, responded to immunotherapy with a decrease in specific IgE and a significant increase in specific IgG. There was a marked increase in the ratio specific IgG/specific IgE as a result of active treatment. IgE-CRIE radiostaining patterns showed no pronounced changes after 10 months' active treatment and no "new sensitivities" could be detected in the studied patients. IgG-CRIE radiostaining, primarily directed towards the important allergens, was significantly increased in the active group and particularly towards Ag-12 (partially identical to a previously described major allergen in Cladosporium herbarum, Ag-54). Children treated with histamine placebo showed no change in antibody patterns during 10 months of treatment.

543 children were followed up from birth to 5 years of age. Children with a positive history of parents' atopy had a 51% occurrence of respiratory or dermal symptoms of atopy vs. a 19% occurrence among children with no family history of atopy. There was an association between asthma and allergic rhinitis while atopic dermatitis occurred equally in children with or without respiratory symptoms. The clinical course of atopic symptoms could not be correlated to the family history of atopy. The significance of date of birth, nasal eosinophilia and serum IgE levels seemed to be relatively low in atopic dermatitis while these parameters had a correlation to the development of respiratory atopies.

The commercial cat and dog allergen extracts are traditionally prepared from pelt, fur or dander. However, there is increased evidence of the allergenicity of saliva and urine of the animals. We have investigated 25 asthmatic children with a positive cat and/or dog RAST result. All 20 subjects with a positive cat RAST gave a positive skin prick test result to cat saliva, cat urine and cat hair. Analogously, all 20 subjects with a positive dog RAST had a positive skin reaction to dog saliva, urine and dander. In RAST inhibition experiments with dog and cat allergen discs, dog saliva appeared to be at least as potent as a commercial dog dander and hair extract, while cat saliva was less potent than the respective commercial extract. Both dog and cat salivas were clearly more potent than the respective urine. Significant cross-reactivity was observed between cat hair and dog dander in the RAST inhibition, whereas saliva and urine were shown to be more species-specific. An experimental dog dander preparation had about the same specificity as, and even higher allergenic activity than, that of dog saliva or urine. Our results suggest that saliva actually may be the best source of cat and dog allergen preparations. The importance of urine warrants further investigation.

The incidence of asthma, hay fever and atopic dermatitis was assessed in three generations in 2820 families by a questionnaire. 35% of the families were atopic when the histories of parents and grandparents were included. 64% of atopic children had atopy in probands and the corresponding figure for non-atopic individuals was 31%. The highest prevalence of atopy was found in the parents' generation (13.5%) but it did not differ significantly from that of children (10.8%) when compared with grandparents (7.6%). The results suggested an increasing prevalence of children's atopic dermatitis in Finland since the 1950s. The influence of heredity was apparent. Few geographical differences were observed.

In order to screen for mould allergy, extracts of five common atmospheric moulds (Cladosporium, Alternaria, Penicillium, Aspergillus and Mucor) from various manufacturers were investigated in 130 patients (5-60 years old) with clinical symptoms indicating possible mould allergy. The patients were screened by skin prick test (SPT) and radioallergosorbent test (RAST). SPT seemed to be more sensitive than RAST as a diagnostic screening procedure (80% positive reactions to one or more species compared to 50%). With a partially purified, standardized preparation of Cladosporium herbarum more positive reactions were obtained than with crude extracts without evidence of any unspecific reactions. The difference between commercial and standardized extracts is most probably a result of a variation of both the biological potency of allergenic determinants and the allergenic composition. A considerable number of negative RAST reactions with standard discs were found in patients with positive skin reactions to partially purified Cladosporium, but RAST seemed to be more sensitive than SPT with the other commercial mould extracts. Based on the screening, a very convincing tendency to IgE-reactivity to other moulds was found in patients reacting to Cladosporium, the most common cause of mould allergy. The results confirm the inadequacy of most mould extracts used in diagnostic procedures and strengthen the value of using standardized extracts.

Occurrence of airborne pollen in Finland has been studied for 10 years in Turku (southern Finland), 8 years in Oulu, 4 years in Kuopio (central Finland) and 7 years at Kevo (northern Lapland). Observations on the pollen seasons of alder, birch, grasses and mugwort are presented. All these pollens occur in south and mid- Finland in quantities capable of causing allergy symptoms. Except for birch pollen, allergenic pollens occur in far lower concentrations than in central Europe. In northern Lapland only birch and pine pollen concentrations are high. Pollens may occur without signs of local flowering when there are southerly winds. This finding suggests that long-distance transport is an essential contributing factor to the occurrence of pollens. There are wide year-to-year variations in the start of pollen seasons and the quantities of pollens. The variations in the start of birch and grass pollen seasons could very much depend on the mean temperature in April. However, a forecasting model based on this and other spring-time temperature parameters often fails to give sufficiently accurate forecasts.

A case of hepatotoxicity and encephalopathy (Reye's syndrome?) associated with salicylate therapy is presented and the aetiology of this syndrome is discussed. Hepatotoxicity developed with salicylate serum concentrations not exceeding therapeutic serum levels. The importance of controlling serum salicylate concentration and transaminase activity particularly during the first fourteen days of therapy is emphasized.

An asthma data register which collects annually certain data from all known local asthmatic children has been presented. The data register is utilized to make a two-page print-out for every patient, and statistics of the whole material. These data make the continuous surveillance and guidance of the patients possible. The easy-to-use and accurate data material has contributed to rationalization of routine work in an asthma clinic. Team work has also improved because the uniform data material enables various workers to quickly pick out a specific problem from the whole material. The cost, $ 2 to 3 per patient per year, is low compared with the immediate benefit. Indirect benefit is to be expected because the system helps to investigate the problems of asthmatic children.

One hundred and forty-four ears (72 patients), forming part of the computer controlled respiratory allergy group of the University of Turku, were analyzed with tympanometry and audiometry to diagnose secretory otitis media. Effusion was found in 3 ears (2 patients) and a pathological tympanogram in a total of 15 ears (10 patients). The incidence of secretory otitis media was 3% and of pathological tympanograms 14%. This study supports the opinion that immediate allergy is not an aetiological factor in secretory otitis media.

Two children with rotavirus gastroenteritis are presented. The first case developed a fatal Reye's syndrome and the other one encephalitis with slow recovery. The rotavirus diagnosis was made in both cases by electron microscopy and a significant rise in antibody titres to Nebraska calf diarrhea virus was seen in one of the two patients.

The growth of C. albicans yeast in the nasopharynx and in the anus as well as allergy symptoms were followed up for 8 months in 67 patients with bronchial asthma, allergic rhinitis and/or atopic eczema. 38 of the patients were skin prick test positive and 29 negative to C. albicans allergen extract. 32 of the patients had positive and 19 negative delayed skin reactions. The nasal, bronchial and skin symptoms of the yeast-sensitive allergic patients were not associated with the nasopharyngeal nor anal occurrence of C. albicans or other yeasts. The use of nasal or inhaled steroids had no effect on the occurrence of Candida in the nasopharynx. It was observed that immediate skin sensitivity had a positive correlation and the delayed sensitivity a negative correlation with the occurrence of C. albicans growth in nasopharynx and anus. These findings are in agreement with the concept that impaired cell-mediated immunity to C. albicans may lead to increased IgE response. This may explain the increased liability towards C. albicans nasopharyngeal and gastrointestinal "saprophytic" growth.

A 2 year prospective study of thirty-eight birch pollen-sensitive hay fever patients under specific immunotherapy and of nineteen untreated control patients showed a significant correlation between the total seasonal symptom scores of the patients and their clinical sensitivities assessed by the RAST and a graded nasal test. The agreement between a positive nasal test and a positive RAST was 74%. In the early season with low pollen counts the onset of symptoms was significantly associated with high sensitivity of the patients, while many patients showed symptoms in the late season irrespective of their nasal and RAST sensitivity. About 90% of both the treated and the untreated patients reported mild symptoms when the pollen count exceeded 80/m(3) in the early season. 80% of them still had symptoms when the count was below 30/m(3) in the late pollen season. Although hyposensitization therapy had no effect on the occurrence of the mild symptoms, the treated patinets had severe symptoms significantly less often than the untreated ones on days with high pollen counts.