bluuebunny/crossref_metadata_2025 huggingface dataset:
Disclosing special needs to parents. Have we got it right yet?
Authors: Pearson D. , Simms K. , Ainsworth C. , Hill S.
Published: March 2003

Parents’ perceptions of how they were told that their child has special needs were examined. Thirty‐nine families on the Isle of Wight completed a structured interview. Participants formed two groups. The first group comprised of 23 families who had a child aged from birth to 5 years with special needs. In the second group there were 16 families who had a child aged between 15 and 20 years with special needs. Parents were asked about their perceptions of how their child's special needs were disclosed, their satisfaction with how they were told and what improvements they would have liked. Differences between the two cohorts were examined, and changes in how services were perceived were investigated. Overall, parents in the group with younger children were more satisfied about the way in which they were told that their child had special needs than those with older children. Implications for service delivery and future research are considered.Keywords: special needs, disclosure
Evaluating child disability programmes: the role of commissioners
Authors: Davidson L. L.
Published: March 2003

The paper briefly reviews the role of a health care commissioner in planning and evaluating children's disability services, an area with a strong statutory framework but a paucity of guidance. It also explores how different aspects of evaluation apply to commissioning.
Co‐existence of lysosomal storage diseases in a consanguineous family
Authors: Guy R , Forsyth J M , Cooper A , Morton R E
Published: March 2003

Lysosomal storage diseases are rare and coexistence of more than one in a family can present a diagnostic challenge as illustrated by this study. The index case born to consanguineous Asian parents presented with developmental delay. Investigations led to an incidental finding of Fabry disease. After numerous additional investigations over a year, a second diagnosis of aspartylglucosaminuria (AGU) was made. A family history of renal disease and developmental delay was disclosed. The sister and first cousin of the index case were diagnosed as homozygous for AGU, but do not have Fabry disease. The younger brother has since been diagnosed with both Fabry disease and AGU. Another cousin has learning difficulties and fits, but is heterozygous for AGU, and possibly has another uncharacterised autosomal recessive disorder. In a family with consanguinity when the clinical picture in an individual is not fully explained by the presence of one rare metabolic disease, it is essential to investigate further for the presence of others.
Acknowledging the extra care parents give their disabled children
Authors: Roberts K , Lawton D
Published: March 2003

Around 150 000 families in the UK care for a severely disabled child under the age of 16. Many of these families receive assistance from the Family Fund Trust, which provides grants and information relating to the care of a severely disabled child. The aim of this study was to identify patterns of extra care needs among severely disabled children known to the Trust. Extra care needs are requirements for care not experienced by similarly aged non‐disabled children. The research comprised analysis of 40 000 records from the Trust database and qualitative exploration of the extra care needs of disabled children with parents and Trust staff. Although all children require parenting, the care parents give disabled children generally exceeds that given to a non‐disabled child. Quantitative analysis showed that the majority of children in the sample required extra assistance or supervision with multiple areas of daily life. With each of five activities (washing, dressing, meal times, during the night and keeping occupied), >70% of children needed extra help and, on average, each child needed extra help or supervision in six areas of daily life. Cluster analysis indicated distinctive combinations of extra care needs. Qualitative material indicated variety in extra care tasks undertaken (physical help, supervision, guidance) and causal factors (physical limitations, cognitive difficulties, behavioural problems). The findings confirm that severely disabled children have considerable extra care needs in many areas of daily life. Parents want professionals to recognize and offer explicit acknowledgement of the extra care they give their disabled children.
Technology‐dependent children in the community: definitions, numbers and costs1
Authors: Glendinning C , Kirk S , Guiffrida A , Lawton D
Published: March 2003

Summary Objectives To assess available data on the numbers of technology‐dependent children living at home in the UK and estimate the costs of caring for them.

Design Data were obtained from all known secondary sources, including surveys of children with specific conditions known to specialist paediatric departments and the database of applicants to the Family Fund Trust. The costs of all services received by three hypothetical exemplar ‘case study’ children were calculated.

Results All existing sources of data have some shortcomings. Taking these shortcomings into account, it is estimated that there may be up to 6000 technology‐dependent children living at home. They appear to be disproportionately young and may be distributed unevenly between different regions of the UK. The total service costs of caring for each child will vary according to the types of technologies involved and local patterns of services, but may be as high as £150 000 a year.

Conclusions Because of the very high costs of services, routine information on the numbers of technology‐dependent children discharged home is urgently needed. This should include details of the duration of technology dependence and the local area to which the child is discharged. New opportunities for joint service planning and purchasing should improve the co‐ordination of services for these children.
Measuring everyday visual discrimination in visually impaired children with the Sonksen Picture Guide to visual function
Authors: Vervloed M P J , Ormel E A , Schiphorst S A M
Published: March 2003

The Sonksen Picture Guide to Visual Function (SPGVF) assesses a person's ability to discriminate pictures of everyday objects. Sonksen added the SPGVF to tests of visual acuity, because real objects, miniatures, and pictures are the main learning medium for young children. In earlier studies correlations have been found between visual acuity and responses to the SPGVF. However, to date no studies have used visually impaired children. In the study reported here, the associations between performance on the SPGVF task, visual acuity and contrast sensitivity were investigated. Participants were 17 visually impaired and 29 children without disabilities, 4–6 years of age. The results showed that visual acuity was more important for picture recognition than contrast sensitivity. Contrast thresholds < 3.33% implied that not all SPGVF‐pictures could be recognized. The visually impaired children in the current study showed shorter mean identification distances than the normally sighted children in the original Sonksen and Macrae study.
Severity of hyperactivity and the comorbidity of hyperactivity with clumsiness in three sample sources: school, support group and hospital
Authors: Miyahara M , Möbs I , Doll‐Tepper G
Published: March 2003

The aim of this study was to examine whether or not there were any differences in the severity of hyperactivity and the comorbidity of hyperactivity with clumsiness due to the sampling sources of hyperactive children. It was hypothesized that hyperactivity would be more severe and the comorbidity higher in the hospital sample than in the community support group and the school sample. A total of 47 hyperactive children were assessed with the German version of the Conners Teacher Rating Scale (CTRS) and the Movement Assessment Battery for Children (Movement ABC). The hypotheses were not supported by the results. Although the school sample demonstrated the least prevalence rate of comorbid clumsiness, their conduct problems were rated higher than were the hospital and the support group samples. The possible difference in teachers' perception was discussed in terms of their understanding and communication with parents and professionals. The need to determine the effect of inattention on manual performance is addressed with a research strategy.
Social adjustment of children with a severe craniofacial anomaly (Apert syndrome)
Authors: Sarimski K
Published: March 2003

Objective Children with a severe craniofacial anomaly are at risk for emotional and behavioural problems. Do children with Apert syndrome present with a special psychological profile?

Method Parent reports (Child Behaviour Checklist) were obtained from 25 children with Apert syndrome.

Results Fourteen children were characterized by clinically significant social problems, 10 by attentional problems, nine by social withdrawal. Total CBCL‐scores were in the clinical range for eight children.

Conclusion Information on psychosocial state should be included in regular check‐ups of children with a severe craniofacial anomaly in order to identify children who are in need of psychological interventions.
Quantitative neuropathological analysis of Sudden Infant Death Syndrome
Authors: Ansari T. , Sibbons P. D. , Parsons A. , Rossi M. L.
Published: March 2003

Detailed stereological analyses of specific regions of brains of children who had died from Sudden Infant Death Syndrome (SIDS) was undertaken to determine whether global evidence of an underlying pathology exists, contributing to an increased susceptibility to SIDS. A significant reduction in the total number of neocortical neurones and neurone volume was observed in SIDS normal birth weight (NBW) infants in comparison to controls. A significant reduction in both volume and total neurone number were also noted in the dorsal motor nucleus of the vagus in SIDS NBW group when compared with controls. Anomalies in regions of the brain involved with cardiorespiratory control (brainstem) and arousal (brainstem and neocortex) may play a crucial role in the chain of events resulting in a SIDS event.
Coping of parents with physically and/or intellectually disabled children
Authors: Taanila A. , Syrjälä L. , Kokkonen J. , Järvelin M.‐R.
Published: March 2003

Objective
The aim was to clarify how families with physically and/or intellectually disabled children cope, what kind of coping strategies they use and how the families with good and poor coping capacities differ.

Methods
The parents of eight children (aged 8–10 years) with physical and/or intellectual disability were interviewed twice, and the data elicited in these interviews were analysed qualitatively using the grounded theory method.

Results
Information and acceptance, good family co‐operation and social support were related to the coping strategies most frequently used. Half of the families seemed to have found successful ways of coping, whereas another half had major problems. There were five main domains in which the high‐ and low‐coping families differed most from each other: (1) parents’ initial experiences; (2) personal characteristics; (3) effects of the child’s disability on family life; (4) acting in everyday life; and (5) social support.

Conclusion
The findings can be utilized in developing supportive activities for families with disabled children. By recognizing the coping strategies used by the family, professionals and service providers can find the right ways to support their adaptation. As the role of physicians, nursing staff and other professionals in this process is very important, more attention should be attached to the collaboration between these groups, to enable them to view the situation from the perspective of the whole family.
Oscillating between hope and despair — a qualitative study
Authors: Sällfors C. , Fasth A. , Hallberg L. R.‐M.
Published: March 2003

Objective The aim of this qualitative study was to elucidate the life situation and psychosocial processes of living with chronic pain in children suffering from juvenile chronic arthritis (JCA).

Methods Taped open qualitative interviews with 22 children (aged 6–17 years) were transcribed verbatim and analysed using the comparative method for grounded theory.

Results A core category, labelled oscillating between hope and despair, was identified and related to four additional categories labelled disturbed order, dependency, ambivalence and uncertainty about the future. There were relationships between the children's subjective experience of pain and their experiences of disturbed order in daily life, dependency on treatment, health care and significant others, ambivalence related to environmental reactions and uncertainty about the future. Chronic pain and disease control the children's lives and lead to restricted participation in social life.

Conclusions Chronic pain is a substantial problem for children with JCA, which must be considered in health care. The pain affected and disturbed the children's ordinary way of life. It blocked a number of goals. Psychological and physiological processes interact in the phenomenological experience of pain, and the response of the environment elicits, maintains or decreases the experience of pain. Hopefully, the findings contribute to a deeper understanding of the life situation of children suffering from JCA and can be of importance in developing rehabilitation programmes for these children.
Cognitive and psychosocial outcome of infants dialysed in infancy
Authors: Madden S.J. , Ledermann S.E. , Guerrero‐Blanco M. , Bruce M. , Trompeter R.S.
Published: March 2003

Objective   To contribute further to the understanding of cognitive and psychosocial outcome of children with end‐stage renal disease undergoing long‐term peritoneal dialysis.

Methods   In total, 16 surviving infants at a single centre beginning peritoneal dialysis in the first year of life were studied. The age range of the children at assessment was 1.6–12.1 years. Children were assessed using the Griffiths Mental Development Scales, the Wechsler Intelligence Scale for Children – Third Edition UK, and the Strengths and Difficulties Questionnaire. Information regarding the child's hospital stay and family background was also collated. A Pearson's Product Moment correlation was used to analyse the results.

Results   Although 67% of the children's scores fell within the average range, 87% were within at least two SDs of the norms (mean IQ = 86.6). Psychosocial adjustment measures revealed that 50% of scores fell within the borderline to abnormal category, suggesting that the frequency of psychological difficulties was above that of the normal population.

Conclusions   These findings lend support to recent studies indicating that, developmentally, children undergoing long‐term peritoneal dialysis are faring better than in the past. This may indeed be a reflection of improvements in renal treatment and diet. The behavioural results suggest the need to monitor psychological adjustment in this group of children.
Children's representation of family mealtime in the context of maternal eating disorders
Authors: Park R. J. , Lee A. , Woolley H. , Murray L. , Stein A.
Published: March 2003

Background  Recent research provides evidence for specific disturbance in feeding and growth in children of mothers with eating disorders.

Aim  To investigate the impact of maternal eating disorders during the post‐natal year on the internal world of children, as expressed in children's representations of self and their mother in pretend mealtime play at 5 years of age.

Methods  Children of mothers with eating disorders (n = 33) and a comparison group (n = 24) were videotaped enacting a family mealtime in pretend play. Specific classes of children's play representations were coded blind to group membership. Univariate analyses compared the groups on representations of mother and self. Logistic regression explored factors predicting pretend play representations.

Results  Positive representations of the mother expressed as feeding, eating or body shape themes were more frequent in the index group. There were no other significant group differences in representations. In a logistic regression analysis, current maternal eating psychopathology was the principal predictor of these positive maternal representations. Marital criticism was associated with negative representations of the mother.

Conclusions  These findings suggest that maternal eating disorders may influence the development of a child's internal world, such that they are more preoccupied with maternal eating concerns. However, more extensive research on larger samples is required to replicate these preliminary findings.
Expression of the house dust mite allergen Der p 2 in the baker's yeast Saccharomyces cerevisiae
Authors: Hakkaart  , Harmsen  , Chua  , Thomas  , Aalberse  , Van Ree
Published: March 2003

Background and Results

The major house dust mite allergen Der p 2 was expressed as a recombinant mature protein in the baker's yeast Saccharomyces cerevisiae. The yeast produces the protein fused to the invertase signal peptide, leading to the secretion of Der p 2 as a soluble protein into the culture medium. The signal peptide is hereby cleaved off, resulting in a mature allergen. In this system Der p 2 was produced in 7.6 (± 2.9) mg/L growth culture. Purification of the recombinant allergen was achieved by a single gel filtration step, resulting in a purity ≥ 95%. The yeast‐derived Der p 2 was almost indistinguishable from natural Der p 2 with respect to IgE‐reactivity and binding to the majority of Der p 2 specific MoAbs — as was shown in RAST analysis (n = 168) and a sandwich ELISA and RIA analysis, respectively. Recombinant and natural Der p 2 also showed similar biological activity in histamine release assays (n = 4).

Conclusion

An expression system for Der p 2 was developed that enables the production of a soluble allergen in the culture supernatant with immunological characteristics similar to the natural allergen. In addition, yeast offers the advantage of the absence of endotoxin in comparison to E. coli. This might facilitate acceptance of recombinant allergens for in vivo applications as immunotherapy or skin‐prick testing.
Changes in IgE‐mediated allergy to ubiquitous inhalants after removal from or diminution of exposure to the agent causing occupational asthma
Authors: Perfetti  , HÉbert  , Lapalme  , Ghezzo  , Gautrin  , Malo
Published: March 2003

Background

One possibility, among others, for explaining the persistence of asthma symptoms in occupational asthma (OA) after the cessation of exposure to the causal agents may be that subjects become sensitized to ubiquitous inhalants.

Objective

The aim of this study was to evaluate the development or increase of IgE‐mediated sensitization to ubiquitous allergens, both to high‐ and low‐molecular‐weight agents, in 100 subjects with OA after cessation of exposure.

Methods

Subjects were evaluated on a first visit, at the time of diagnosis of OA, coinciding with the cessation or diminution of exposure to the causal agent, and on a second visit, 5.8 ± 3.3 years afterwards. At each visit, a history of ocular, nasal and asthmatic symptoms related to exposure to common allergens was obtained together with spirometry and assessment of bronchial responsiveness to methacholine. We analysed total IgE and specific IgE to Dermatophagoides farinae, D. pteronyssinus, birch, ragweed and timothy grass pollens, cat and dog danders, and Alternaria, using enzyme allergosorbent test (EAST) from blood samples taken on each visit.

Results

Total IgE levels showed a tendency to diminish. No changes were found in the number of positive EAST (presence of detectable levels of specific IgE) or in the levels of specific IgE. Although significantly more symptoms of rhinoconjunctivitis and asthma in contact with house dust (P < 0.05) and pets (P < 0.01) were reported on the second visit than on the first, no significant changes in the frequency of symptomatic sensitized subjects were found.

Conclusion

Subjects with OA are unlikely to develop IgE‐dependent sensitization to common inhalants after removal from exposure to occupational agents.
Peanut allergic subjects' peripheral blood mononuclear cell proliferative responses to crude peanut protein
Authors: Hourihane J. O'B , Dean T. P. , Warner J. O.
Published: March 2003

Background

Peanut allergy is characterized by a high frequency of severe and occasionally fatal reactions.

Objective

To determine if there are features of the in vitro cellular response that may account for the observed severity of peanut allergy.

Methods

Skin‐prick testing (SPT), RAST assay of serum peanut‐specific and total IgE and mixed peripheral blood mononuclear cells (PBMC) proliferative responses to crude peanut protein were measured in 44 peanut allergics with varying severity of clinical reactions. PBMC responses of 13 non‐peanut allergic controls (six atopic) were also studied.

Results

Subjects' PBMCs proliferated more than controls', even without stimulation. Subjects' PBMC proliferative responses did not correlate with clinical severity, SPT weal size or peanut‐specific IgE levels. Controls’ PBMCs did not respond to peanut. There was no correlation between PBMC response and time since last reaction to peanut. Subjects' PBMCs responded more than controls, to mitogen as well as allergen. Proliferation increased with increasing concentration of peanut protein (P < 0.0001).

Conclusion

PBMCs of peanut allergics demonstrate a dose‐dependent response to peanut which does not correlate with clinical severity, SPT reaction or levels of peanut specific IgE. The response is antigen‐specific. Peanut protein is not mitogenic and is not acting as a superantigen. While there are non‐specific differences in the PBMC responses of peanut allergic individuals compared with atopic and non‐atopic controls, these differences do not explain the unique severity of peanut allergy.
Expression and localization of the inducible isoform of nitric oxide synthase in nasal polyp epithelium
Authors: Watkins D. N. , Lewis R. H. , Basclain K. A. , Fisher P. H. , Peroni D. J. , Garlepp M. J. , Thompson P. J.
Published: March 2003

Background

The pathogenesis of nasal polyp disease is poorly understood. Recent evidence has suggested that nitric oxide (NO), an endogenous soluble gas vasodilator and inflammatory mediator, may be synthesised within the nasal cavity. Three nitric oxide synthase isoforms have been identified in humans, with the inducible isoform (iNOS) generally expressed in the setting of inflammation.

Objective

The aim of this study was to detect and localize iNOS expression in nasal polyp tissue, and compare these findings with normal nasal turbinate tissue.

Methods

We examined the expression and localisation of inducible nitric oxide synthase (iNOS) in human nasal airway specimens from patients undergoing elective nasal turbinectomy (n = 5) or nasal polypectomy (n = 5). iNOS mRNA expression was determined by semi‐quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) followed by Southern blot analysis and localised by in situ hybridization. Densitometric data were analysed using Student's unpaired t‐test. Adjacent sections were also examined for iNOS protein expression by immunohistochemistry.

Results

Semi‐quantitative RT‐PCR/Southern analysis of RNA obtained from the 10 surgical specimens demonstrated that iNOS mRNA expression was significantly increased in the five nasal polyps (P < 0.05). In situ hybridization studies revealed strong iNOS mRNA signal localized to the respiratory epithelium of nasal polyps, but not nasal turbinates. This pattern was confirmed by immunohistochemistry. Localization to inflammatory cells or other subepithelial structures was not seen.

Conclusions

We conclude that iNOS expression is upregulated in nasal polyp disease, and is localized to the polyp epithelial layer. These data reinforce the concept that the epithelial layer may be important in the pathogenesis of nasal disease, and suggest a potential role for NO in the formation of nasal polyps.
Association study of asthma and atopy traits and chromosome 5q cytokine cluster markers
Authors: Mansur A. H. , Bishop D. T. , Markham A. F. , Britton J. , Morrison J. F. J.
Published: March 2003

Background

Linkage studies have provided evidence for the presence of gene(s) in the 5q cytokine cluster region which control total serum immunoglobulin E (IgE) concentration, and bronchial hyperreactivity (BHR). However, the identification of the gene(s) involved has been confounded by the lack of power of the published linkage studies and the presence of multiple candidate genes mapped to the region.

Objective

To define the important loci on 5q31‐33 which are implicated in the control of total serum IgE and BHR through a case/control study of association.

Methods

We performed an association study between 11 polymorphic markers (spanning the region 5q31.1‐33.1) and total serum IgE and BHR traits. A case/control sample of 181 individuals was drawn from a larger set of 2415 adults, sampled at random from a district in Nottingham, UK. Half of the subjects in this case/control sample were hyperreactive to methacholine and asthmatic (cases), while the other half were non‐reactive and non‐asthmatic (controls). Association analysis was performed using the non‐parametric chi‐squared and Mann–Whitney U‐tests.

Results

We observed no evidence of strong allelic association between any of the above markers and the studied traits. Markers D5S404, interferon regulatory factor 1 (IRF‐1) and D5S210 showed evidence of borderline association with BHR (P = 0.04, 0.03 and 0.04 respectively), and D5S404 showed borderline significance with IgE levels (P = 0.029).

Conclusions

This study presents evidence against the presence of a strong association between markers mapped to 5q31‐33 and either BHR or total serum IgE. The significance of the weaker associations observed with markers D4S404, IRF‐1 and D5S210 is not clear. Whether this represents a type I error secondary to multiple hypothesis testing or a true association is uncertain.
Intranasal fluticasone propionate reduces ICAM‐1 on nasal epithelial cells both during early and late phase after allergen challenge
Authors: Ciprandi  , Ricca  , Passalacqua  , Fasolo  , Canonica
Published: March 2003

Background

Allergen specific nasal challenge (ASNC) is an optimal method to study the pathophysiological mechanisms sustaining the allergic inflammation and in particular the adhesion molecule system, which is involved in cellular infiltration of nasal mucosa. Topical steroids have been accepted as a highly effective anti‐inflammatory therapy for allergic rhinitis.

Objective

The aim of this double‐blind placebo‐ controlled study was the evaluation of clinical and cytological parameters, including ICAM‐1 expression on nasal epithelial cells, after a 4 week treatment with nasal fluticasone propionate (200 μg/daily) or placebo, using the model of ASNC.

Methods

Twenty allergic rhinitics underwent nasal challenge before and after treatment. The following parameters were evaluated: (i) nasal symptoms (rhinorrhoea, itching, sneezing, obstruction), (ii) inflammatory cells (eosinophils and neutrophils), (iii) ICAM‐1 expression on nasal epihelial cells at baseline, 30 min (early phase) and 6 h (late phase) after ASNC.

Results

Fluticasone propionate was capable of reducing: (i) clinical symptoms during both early (P < 0.001) and late phase (P < 0.04), (ii) eosinophil (P < 0.002) and neutrophil (P < 0.001) infiltrate during late phase, and (iii) ICAM‐1 expression on nasal epithelial cells during both early (P < 0.01) and late phase (P < 0.03).

Conclusions

The present results demonstrate that fluticasone propionate exerts a significant action on early and late phase clinical events following specific nasal challenge, reducing also the cellular influx during the late phase. This event is likely due to the modulation of ICAM‐1 expression on epithelial cells.
Acoustic rhinometry, rhinomanometry and the amount of nasal secretion in the clinical monitoring of the nasal provocation test
Authors: PirilÄ  , Nuutinen
Published: March 2003

Backround

The reliable interpretation of the nasal provocation test in allergy diagnosis requires objective and measurable monitoring parameters for clinical practice. The clinical usefulness of the nasal provocation test has been limited by scanty knowledge of the specificity and sensitivity of the test and a lack of reference values.

Objective

To test and compare three objective monitoring parameters of a nasal provocation test in occupational allergic rhinitis. To evaluate the magnitude of the nasonasal effects in a unilateral allergen challenge.

Methods

The monitoring parameters of the nasal reaction were derived from the minimum cross‐sectional area on acoustic rhinometry, the nasal resistance on active anterior rhinomanometry and the amount of nasal secretion measured at 15 min intervals for 60 min. Twenty‐three bovine‐allergic dairy and beef cattle farmers and 19 exposed, non‐allergic control subjects were challenged first with a control solution and then with the cow allergen.

Results

All the three monitoring parameters showed high specificity and sensitivity in finding allergic and non‐allergic subjects. The secretion parameter was found to be slightly superior to the acoustic rhinometry and rhinomanometry parameters. The side difference in the nasal response between the allergen‐challenged and the contralateral diluent‐challenged cavity was significant for all the parameters among the allergic subjects. The contralateral secretion amount was 1/3 of the ipsilateral secretion, indicating the magnitude of the contralateral nasonasal reflex. A nasonasal reflex was also noted in the nasal patency monitoring. The coefficient of variation was significantly lower for the acoustic rhinometry than for the rhinomanometry (P = 0.0001). The optimal threshold values for a positive test were a secretion amount of 100 mg, a 15% decrease in the minimum cross‐sectional area and a 50% increase in the resistance for the observation period of 30 min and correspondingly 210 mg, 30% and 100% for 60 min.

Conclusion

The low‐pressure aspiration of the nasal secretion from the anterior part of the nasal cavity was found to be a reliable and practical monitoring parameter to be used together with acoustic rhinometry or rhinomanometry in the nasal provocation test for clinical purposes. Although significant nasonasal effects took place in the unilateral allergen challenge, the response was more prominent in the allergen‐challenged than in the contralateral diluent‐challenged nasal cavity in most allergic subjects.
PDE4 inhibition and a corticosteroid in chronically antigen exposed conscious guinea‐pigs
Authors: Danahay  , Broadley
Published: March 2003

Background

The physiological and pharmacological consequences of repeated aero‐allergen challenge have not been previously characterized in conscious, sensitized guinea‐pigs.

Objectives

This study was undertaken to compare the effects of two anti‐inflammatory compounds, dexamethasone and Ro 20–1724, on an acute and chronic airway inflammation, in terms of airway function, reactivity and leucocyte infiltration.

Methods

Sensitized guinea‐pigs received eight saline or ovalbumin (OvA) inhalation exposures over 4 weeks and either vehicle, the type 4 PDE inhibitor, Ro 20–1724 (3 mgkg−1), or dexamethasone (1.5 mg/kg−1), 30 min before and 6 h after each challenge. Airway function of the conscious animal (sGaw) was monitored over the duration of the first and final OvA challenge. Airway reactivity to the thromboxane mimetic, U46619, was also determined following the final OvA exposure as was the leucocyte infiltration.

Results

The first antigen challenge induced a large early (0–3 h) and smaller late (17–24 h) bronchoconstrictor response. Neither phase was affected by the drug treatments. The final OvA challenge induced early and late phase bronchoconstrictor responses but of similar magnitude. The late phase was also significantly prolonged. Ro 20–1724 and dexamethasone significantly attenuated both phases. Airway reactivity to the inhaled thromboxane‐mimetic, U46619, was also significantly enhanced at 120 h after the final OvA exposure in contrast to the saline challenged group. This hyperreactivity was attenuated by Ro 20–1724 and dexamethasone. Bronchoalveolar lavage after repeated OvA exposures revealed eosinophilia which was attenuated by Ro 20–1724 and dexamethasone.

Conclusions

This model demonstrates differential airway responses to acute and chronic antigen challenge. Repeated administration of dexamethasone and Ro 20–1724 with each OvA exposure attenuted all of the chronic inflammatory responses: early and late phase responses, hyperreactivity and eosinophilia.
Inhibition of substance P‐induced histamine release from rat peritoneal mast cells by low doses of protoporphyrin plus long‐wave ultraviolet light irradiation: decreased intracellular calcium as a possible mechanism
Authors: Amano  , Kurosawa  , Miyachi
Published: March 2003

Background

A considerable amount of recent interest has been devoted to the down‐regulatory effects of photosensitizers plus long‐wave ultraviolet light (UVA) irradiation on multiple biologic systems. However, these effects on mast cells are controversial.

Objective

We have investigated the effect of low doses of protoporphyrin (PP) plus UVA irradiation (PP/UVA) on substance P (SP)‐induced histamine release from rat mast cells.

Methods

Rat peritoneal mast cells purified on a Percoll gradient were treated with 3 ng/mL PP and/or UVA, and challenged with SP. In some experiments, IgE‐sensitized mast cells were stimulated by antirat IgE in the presence of phosphatidylserine. Histamine released from mast cells and intracellular calcium concentrations ([Ca2+]i) were measured, respectively.

Results

SP at a concentration of 10−5 mol/L caused a significant histamine release with the increase in [Ca2+]i. PP or UVA irradiation alone at doses used in the present study induced no histamine release from mast cells and had no significant effects on SP‐induced histamine release from the cells. On the other hand, PP/UVA inhibited SP‐induced histamine release in a dose‐dependent manner of UVA with the reduction of SP‐induced maximal increases in [Ca2+]i. Comparing with the inhibitory effects of PP/UVA on anti‐IgE‐induced histamine release from IgE‐sensitized mast cells and maximal increases in [Ca2+]i in the cells, the inhibitory effects of PP/UVA on the findings in SP‐stimulated mast cells were less.

Conclusion

These data suggest that low doses of PP/UVA inhibits histamine release from SP‐activated rat peritoneal mast cells through the suppression of [Ca2+]i.
Impaired NK1.1+ T cells do not prevent the development of an IgE‐dependent allergic phenotype
Authors: Daser  , Gerstner  , Hansen  , Bulfone‐Paus  , Renz
Published: March 2003

Background

The induction of TH2 immune responses is critically dependent on initial IL‐4. Although crucial, the source of this early IL‐4 has not been identified. One candidate is a CD1 restricted NK1.1+ T cell subpopulation which is known to produce such early IL‐4.

Objectives and methods

The necessity of NK1.1+ T cells for the expression of an IgE‐dependent phenotype was investigated in a NK1.1+ T cell deficient mouse model. The allergic phenotype was defined as immediate cutaneous hypersensitivity. It was induced by immunization of mice with ovalbumin. Mouse strains used were C57BL/6 mice and C57BL/6 mice homozygous for a targeted mutation of the β2 microglobulin gene with consecutive loss of CD1 expression, which leads to a drastic reduction of NK1.1+ T cells. Manifestation of an allergic sensitization was assessed by intradermal allergen challenge after i.v. injection of Evans blue solution. The blue stained weal formations were quantified with the Bonitur method. In addition, the Th2 response was confirmed by the measurement of cytokines and serum immunoglobulins. The capability to produce early IL‐4 was tested through the assessment of IL‐4 mRNA shortly after a single challenge.

Results

Wild type and mutated mice did not differ in any of the immunological parameters measured.

Conclusion

A single exposure to antigen with or without adjuvant induces early IL‐4 production in C57BL/6 β2 m−/− mice. This early IL‐4 is therefore independent of the presence of NK1.1+ T cells and functional MHC class I molecules and leads to IgE production and immediate cutaneous hypersensitivity.
Analysis of induced sputum for studying allergen‐specific IgE antibodies in airway secretion from asthmatic patients
Authors: Nahm  , Park
Published: March 2003

Background

Allergen‐specific IgE antibodies have been considered to play an important role in the pathogenesis of atopic asthma. However, studies on allergen‐specific IgE antibodies in airway secretion from asthmatic patients are very rare compared with those in serum.

Objectives

The present study was undertaken to determine whether induced sputum might provide a useful method for analysing allergen‐specific IgE antibodies in airway secretions from asthmatic patients.

Methods

Specific IgE antibodies to house dust mite (HDM) antigen were measured in induced sputum from 10 HDM‐sensitive asthmatic patients and 12 non‐allergic controls by enzyme‐linked immunosorbent assay. HDM‐specific IgE was regarded as positive when the absorbance value was higher than mean + 2 SD of controls. Their antigen‐binding characteristics were determined by immunoblot analysis.

Results

HDM‐specific IgE was positive in induced sputum from seven of 10 HDM‐sensitive asthmatics. The IgE binding to HDM antigen could be inhibited by fluid phase HDM antigen in a dose‐dependent manner, not by mugwort antigen. Treatment of induced sputum with dithiothreitol decreased the antigen‐specific bindings, and increased the non‐specific bindings on the measurement of HDM‐specific IgE. These effects were significant in a concentration of dithiothreitol greater than 0.05%. Immunoblot analysis revealed that HDM‐specific IgE antibodies in induced sputum recognized the HDM antigens with molecular weights of 42, 34, 32, 25 and 14 kDa. These antigen binding characteristics were similar to those in serum.

Conclusion

We conclude that analysis of induced sputum is a useful non‐invasive method for studying allergen‐specific IgE antibodies in airway secretion from asthmatic patients.
Enzymatic activity of soluble phospholipase A2 does not affect the specific IgE, IgG4 and cytokine responses in bee sting allergy
Authors: Wymann  , Akdis  , Blesken  , Akdis  , Crameri  , Blaser
Published: March 2003

Background

The soluble bee venom phospholipase A2 (PLA) represents the major allergen/antigen for allergic and hyperimmune individuals following bee sting. A number of studies implicate enzymes, and PLA in particular, as potent allergens. We have studied specific activation of T cells by enzymatically active and inactive mutants of PLA, and secretion of cytokines regulating IgE and IgG4 antibody formation.

Methods

Recombinant (r) wild type PLA (rPLA‐WT) and an enzymatically inactive rPLA (rPLA‐H34Q) were produced in Escherichia coli. Eleven bee venom allergic patients and three hyperimmune, healthy individuals were included in the study. After specific stimulation of PBMC with the rPLA variants, proliferative response, IFNγ, IL‐2, IL‐4, IL‐5, and IL‐13 production, as well as total and PLA‐specific IgE and IgG4 production, were analysed.

Results

Similar levels of specific B cell recognition, proliferative and cytokine responses were observed after stimulation with either enzymatically active or inactive rPLA. In addition, equal amounts of antigen‐specific and total IgE and IgG4 antibodies were produced by stimulation with both forms of rPLA.

Conclusions

The enzymatic activity of PLA does not influence the specific activation and cytokine production by T cells from bee venom‐sensitized or hyperimmune individuals, or the IgE/IgG4 antibodies synthesis by B cells in vitro.
Direct measurements of temperature and humidity in dust mite microhabitats
Authors: Cunningham
Published: March 2003

Background

Up to 70% of atopic asthmatics have a positive skin test to the dust mite allergen Der p 1. Reduction of dust mite numbers by lowering room humidity control is one suggested technique for reducing dust mite allergen levels to clinically acceptable levels. Trials of this technique in temperate climates have reported mixed results. It has been speculated that one reason for this is that humidity changes in room ambient air are not tightly linked to humidity changes in the dust mite microenvironment (in the base of carpets, bedding, furniture etc.).

Objective

To directly measure humidities and temperatures in dust mite microenvironments and compare these to ambient conditions, and so gather data on how the microclimates are influenced by room conditions and moisture and heat sources, such as an occupant in a bed.

Methods

A special small humidity device has been developed which can discriminate humidity changes over distances of millimetres. With these devices microclimates have been measured in the base of carpets, in layers through bedding, and in furniture.

Results

Measured base‐of‐carpet humidities were significantly higher than room humidities. Bedding relative humidities show complex behaviour according to the distance separation between the measuring point and the occupant. Immediately below the occupant, bed relative humidities fall when the person enters the bed. Similar behaviour is observed in a sofa.

Conclusion

Some dust mite microclimates have been shown to be very different from room conditions. Consequently, reduction of dust mite numbers and allergen levels cannot be guaranteed by the controlling of room humidities.
Correlation among urinary eosinophil protein X, leukotriene E4, and 11‐dehydrothromboxane B2 in patients with spontaneous asthmatic attack
Authors: Oosaki  , Mizushima  , Kawasaki  , Mita  , Akiyama  , Kobayashi
Published: March 2003

Various kinds of cells and their mediators are thought to be involved in the pathogenesis of bronchial asthma. However, changes in each mediator or relationship among mediators during an asthmatic attack have not been well documented. In this study, to clarify whether eosinophil protein X (EPX) is a marker which is distinct from leukotriene E4 (LTE4), or 11‐dehydrothromboxane B2 (11DTXB2), we measured the urinary excretion of EPX, LTE4, and 11DTXB2 in 14 asthmatics who were admitted to the hospital with either an acute asthmatic attack or status asthmaticus. These patients included eight atopic and six non‐atopic types of bronchial asthma, with a median age of 34.0 years. Urinary excretion of EPX was significantly high on admission with the asthmatic attack, and returned to control levels 175 [122 –384] μg/day when the patients were in the improved state (1036–317 μg/day, P < 0.01). Similar findings were observed in LTE4 (155–59 ng/day, P < 0.01) and 11DTXB2 (991–442 ng/day, P < 0.01). No significant differences in values were observed between atopic and non‐atopic types of asthma in all three substances. When the individual data during the attack state were analysed, a significant correlation was observed between changes (%) in urinary EPX and those in urinary LTE4, but no such relationship was observed between changes (%) in urinary EPX and those in urinary 11DTXB2. These results suggest that measuring urinary EPX levels may be a useful marker for the understanding and management of the disease.
Unreliability of IgE/IgG4 antibody testing as a diagnostic tool in food intolerance
Authors: Jenkins  , Vickers
Published: March 2003

Background

Some clinicians link chronic disease in certain patients to ‘food intolerance’. This is currently diagnosed by exclusion dieting, a time‐consuming and tedious technique. It has been claimed that IgE/IgG4 antibody testing is a rapid and valid method of determining food intolerance.

Objective

To determine the test/retest reliability of IgE/IgG4 antibody testing as a diagnostic tool.

Methods

Blinded testing of duplicate blood samples from nine patients with suspected food intolerance was undertaken by tertiary referral centre using the services of a commercial laboratory. The proportions of consistent and inconsistent results for tests of 95 different foods were analysed.

Results

Test/retest reliability was low. Even though the study method systematically over‐estimated kappa, this value never exceeded 0.51, regardless of the statistical model used. All but one patient had a greater number of inconsistent results than had been prespecified as an unacceptable level of disagreement. In one case, 50 out of 95 test results were inconsistent on retest.

Conclusions

We found no evidence that IgE/IgG4 antibody testing as performed by this laboratory is a reliable diagnostic tool.
Urinary excretion of inflammatory mediators during allergen‐induced early and late phase asthmatic reactions
Authors: O'sullivan  , Roquet  , DahlÉN  , DahlÉN  , Kumlin
Published: March 2003

Background

It is generally accepted that the early asthmatic response to inhaled allergen is a result of IgE‐mediated mast cell activation. In contrast, the underlying mechanism of the late asthmatic response is much less clear.

Objective

In order to investigate the pattern of mediator release during the early and late asthmatic responses to allergen, measurements of the urinary excretion of the mast cell markers 9α,11β‐PGF2 and Nτ‐methylhistamine were made. In addition, urinary levels of eosinophil protein X (EPX) and leukotriene E4 (LTE4) were measured.

Methods

Twelve mild atopic asthmatics participated in the study. On the study day, pulmonary function was recorded at baseline and for 12 h after inhalation of allergen. Urine was collected prior to challenge and thereafter at 1 h intervals. Measurements of 9α,11β‐PGF2 and LTE4 were made with enzyme‐immunoassay, and levels of Nτ‐methylhistamine and EPX were analysed with radioimmunoassay.

Results

All subjects developed both an early and late phase airway response. Within 1 h of the early peak airway response, there was a significant increase in the urinary concentrations (AUC/h) of 9α,11β‐PGF2 (49.3 ± 9.2 to 142.5 ± 49.2; P < 0.001) Nτ‐methylhistamine (10.4 ± 1.4 to 19.5 ± 1.4; P < 0.001) and LTE4 (43.7 ± 5.9 to 105.9 ± 21.3; P < 0.001). Levels of all three mediators were also significantly increased above baseline during the LAR to 79.4 ± 9.5 (P < 0.01), 19.8 ± 1.9 (P < 0.001) and 85.6 ± 10.4 (P < 0.001), respectively. Levels of EPX remained unchanged during the early and late responses (39.2 ± 10.2 to 37.5 ± 18.5, 33.9 ± 6.8).

Conclusions

These results indicate that mast cell activation is a feature not only of the early but also the late asthmatic response. Finally, increased LTE4 supports the contribution of the leukotrienes to airway obstruction during both phases of the asthmatic response to allergen.