bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution of HCN1 and HCN2 in rat auditory brainstem nuclei
Authors: Koch Ursula , Braun Marianne , Kapfer Christoph , Grothe Benedikt
Published: July 2004

Auditory brainstem neurons that are involved in the precise analysis of the temporal pattern of sounds have ionic currents activated near the resting potential to shorten membrane time constants. One of these currents is the hyperpolarization‐activated current (Ih). Molecular cloning of the channels underlying Ih revealed four different isoforms (HCN1–4). HCN1 and HCN2, which are widely distributed in the brain, differ in their activation kinetics, voltage dependence and sensitivity to cAMP. We determined the distribution of the HCN1 and HCN2 isoform in the auditory brainstem and midbrain of young rats (P20–30), using standard immunohistochemical techniques. HCN1 antibodies gave rise to punctate staining on the somatic and dendritic membrane. Strong HCN1 staining was present on octopus and bushy cells of the ventral cochlear nucleus, principal neurons of the lateral and medial superior olive, and neurons of the ventral nucleus of the lateral lemniscus. No HCN1 staining was observed in the dorsal cochlear nucleus and the medial nucleus of the trapezoid body (MNTB). In contrast, HCN2 staining was strongest in the MNTB and the dorsal nucleus of the lateral lemniscus. Strong HCN2 antibody labelling was also observed in bushy cells of the ventral cochlear nucleus. In the central nucleus of the inferior colliculus only a subpopulation of neurons showed HCN1 or HCN2 immunolabelling. This differential distribution of HCN1 and HCN2 channels is in agreement with the physiologically observed Ih currents in corresponding neuronal populations and might represent the basis for functional heterogeneity and diverse sensitivity to neuromodulators.
Anti‐ganglioside antibodies in children with coeliac disease: correlation with gluten‐free diet and neurological complications
Authors: Briani C. , Ruggero S. , Zara G. , Toffanin E. , Ermani M. , Betterle C. , Guariso G.
Published: July 2004

Background : Emerging evidence points to humoural mechanisms in neurological complications of coeliac disease. Immunoglobulin G anti‐ganglioside antibodies have been reported in coeliac disease patients with neuropathy, suggesting an immune response to peripheral nerve antigens. No data are so far available on anti‐ganglioside antibodies in coeliac disease children or on antibody modifications after gluten‐free diet.

Aim : To evaluate the presence of antibodies to ganglioside antigens in children with coeliac disease, their modification after gluten‐free diet, and possible correlations with neurological manifestations.

Methods : Sera from 42 coeliac disease children, before and after gluten‐free diet, were tested by enzyme‐linked immunosorbent assay for the presence of antibodies (immunoglobulin M, immunoglobulin A, immunoglobulin G) to gangliosides. Thirty‐five sera of age‐matched children with dyspepsia were used as control.

Results : High anti‐ganglioside antibodies titres were present in two patients. In one patient, antibody titre reversed after gluten‐free diet, whereas in the other one the titre increased after diet. Neither one complained of neurological symptoms.

Conclusions : Anti‐ganglioside antibodies do not seem to correlate with gluten ingestion or with neurological manifestations in children with coeliac disease. Mechanisms different from gluten exposure may be implicated in the antibody production. An ongoing prospective study will help clarify the role, if any, of these antibodies in coeliac disease.
How effective are the usual treatments for Crohn's disease?
Authors: Bebb J. R. , Scott B. B.
Published: July 2004

Background: Details of the efficacy of the various drugs used in Crohn's disease are not readily available.

Methods: We have reviewed all placebo controlled trials of the commonly used drugs in Crohn's disease for both the induction and maintenance of remission to determine the efficacy and to calculate the numbers needed to treat (NNTs) to achieve a specified benefit for each drug.

Results: Both the drug response rates and the NNTs (with 95% confidence intervals) are tabulated for each drug.

Conclusion: Prednisolone/prednisone is the most effective drug to achieve remission with a remission rate of 60% and an NNT for remission of 3 (95% confidence interval: 2–6). Aminosalicylates are only moderately effective in achieving remission with an overall NNT of 10 (95% confidence interval: 6–75), but more effective in high‐dose (e.g. NNT for Pentasa 4 g daily = 4; 95% confidence interval: 2.6–9), and less effective in maintaining remission with an NNT of 14 (95% confidence interval: 9–29). Both azathioprine and infliximab are associated with remission induction and maintenance rates of 40–66% and NNTs of 3–5. Methotrexate intramuscularly has a remission induction rate of 39% and an NNT of 5 (95% confidence interval: 3–25).
Japanese cedar pollen‐specific interleukin‐4 production develops immediately after the first exposure to pollens in infants with atopic dermatitis
Authors: Kimura M. , Obi M. , Saito M.
Published: July 2004

Background
Japanese cedar pollens (JCPs) spread over most areas of Japan from February to April and cause pollenosis. While IgE synthesis against JCPs starts after age 1, it remains to be clarified when JCP‐specific T helper cells acquire the ability to produce IL‐4, a cytokine that induces IgE synthesis.

Objective
This study aimed to clarify when the sensitization of T cells to JCPs develops.

Methods

Peripheral blood mononuclear cells from 153 children with atopic dermatitis (AD) aged 0–15 years were stimulated with a standardized JCP allergen. As parameters of T cell responsiveness, lymphocyte proliferation and the production of IL‐4 and IFN‐γ were measured.

Results
T cell responses against JCPs were negative before March in infants with AD who had never been exposed to JCPs or who were exposed for less than a month (nine, seven and nine subjects for lymphocyte proliferation, cytokine production and IgE synthesis, respectively). Lymphocyte proliferation distinctly increased in 67.6% (23/34) of infants with AD examined between March and June. JCP‐specific IL‐4 production was observed in 56.0% (14/25) of infants with AD examined between March and June. Correspondingly, a slight increase in the level of serum JCP‐specific IgE antibody was seen in 17.2% (five of 29) of infants with AD examined between April and June.

Conclusion
These results demonstrate that the sensitization of T cells to JCPs is effectively completed within a few months after the first exposure to JCPs.
Acoustic rhinometry in nasal allergen challenge study: which dimensional measures are meaningful?
Authors: Wang D. Y. , Raza M. T. , Goh D. Y. T. , Lee B. W. , Chan Y. H.
Published: July 2004

Background
Acoustic rhinometry (AR) is commonly used as a quantitative assessment of nasal response to nasal allergen challenge (NAC). However, sources of error and physical limitations of various AR area–distance measurements have not been adequately evaluated.

Objective
To investigate the clinical value of AR measurements, and the relationship between subjective sensation and objective AR measurements in the NAC study.

Methods
Nasal challenge using increasing concentrations of crude Blomia tropicalis (Bt) extracts (0.6, 6, and 60 μg/mL) was performed in 15 adult patients (eight males and seven females) with ongoing persistent allergic rhinitis. Subjective symptom scores of nasal obstruction were recorded together with the objective AR measurements of the minimum cross‐sectional area (MCA), distance to MCA and cross‐sectional area (CSA) at 3.3, 4.0 and 6.4 cm from the nostril, during the 7 h after the last challenge.

Results
The dose–response increase in nasal obstruction score was significantly (P<0.001 for all) associated with decreases in mean MCA (r=0.75), mean CSA3.3 (r=0.54), mean CSA4.0 (r=0.53) and mean CSA6.4 (r=0.20). The mean MCA (±SD) for each subjective symptom score 0, 1, 2 and 3 was found to be 0.73 (±0.22) cm2, 0.63 (±0.29) cm2, 0.33 (±0.17) cm2 and 0.21 (±0.14) cm2, respectively. When the MCA (left and right separately) reached an area <0.2 cm2, measurements of CSA3.3 and CSA4.0 were significantly reduced by 60–70%.

Conclusion
This study demonstrates that AR is a useful and objective investigational tool, which correlates well with the sensation of nasal obstruction. MCA, CSA3.3 and CSA4.0 are more reliable measurements than CSA6.4 due to physical limitations. It is important to note that when the MCA is smaller than 0.2 cm2, a common condition in the early‐phase reaction, area–distance measurements beyond this point can be misinterpreted and should be considered with caution.
In vitro diagnosis of chronic nasal inflammation
Authors: Kramer M. F. , Burow G. , Pfrogner E. , Rasp G.
Published: July 2004

Background
Differential diagnosis of chronic nasal inflammation is insufficient when based solely on clinical examination and radiography of paranasal sinuses. Patients complain about more or less similar symptoms. Activation of mast cells and eosinophils is pivotal in nasal inflammation.

Objective
To compare tryptase and eosinophilic cationic protein (ECP) in nasal secretions in different forms of chronic nasal inflammation and to establish norm values.

Methods
The study included 1710 patients presenting with nasal complaints. Nasal secretions were gained by the cotton wool method and analysed for tryptase, as a marker of mast cell activation, and for ECP, as a marker of tissue eosinophilia and activation. Patients were grouped according to their diagnosis: chronic, non‐allergic rhinosinusitis (sinusitis, n=194), non‐allergic nasal polyposis (polyposis, n=138), non‐allergic rhinitis with eosinophilia syndrome (NARES, n=198), isolated perennial allergic rhinitis (AR) (n=126), isolated seasonal AR (n=132), and patients allergic to both, seasonal and perennial allergens (n=193). Seven hundred and twenty‐nine patients with nasal complaints due to a deviated septum and without any nasal inflammation served as controls.

Results
Nasal tryptase was highly significantly (P<0.001) elevated in polyposis, NARES, and in AR. ECP was highly significantly (P<0.001) elevated in all groups of patients suffering from chronic nasal inflammation. Based on our data and method we established norm values (95% confidence interval of mean value) for nasal tryptase in healthy adults, ranging from 12.0 to 18.7 ng/mL and for ECP ranging from 84.4 to 102.6 ng/mL.

Conclusion
Mast cells and eosinophils are involved in non‐allergic and allergic forms of chronic nasal inflammation. We established an in vitro assay for tryptase and ECP in nasal secretions and defined norm values based on our data and method. In vitro measurement of biological markers in nasal secretions provides important information for differential diagnosis and therapeutic strategies of chronic nasal inflammation.
Phenotypic alteration of neuropeptide‐containing nerve fibres in seasonal intermittent allergic rhinitis
Authors: Heppt W. , Thai Dinh Q. , Cryer A. , Zweng M. , Noga O. , Peiser C. , Melvan M. , Witt C. , Fischer A. , Groneberg D.A.
Published: July 2004

Background
Allergic rhinitis (AR) is the most common allergic disease affecting the respiratory tract. Next to inflammatory changes, the airway innervation plays an important modulatory role in the pathogenesis of the disease.

Objective
To examine the participation of different neuropeptides in the human nasal mucosa of intermittent (seasonal) AR tissues in the allergic season.

Methods
Immunohistochemistry for substance P (SP), calcitonin gene‐related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and neuropeptide tyrosine (NPY) was related to the characterization of inflammatory cells in tissues of patients with seasonal AR (n=18).

Results
While there was a significant increase in the number of eosinophils present if compared with a control group, no changes occurred in mast cell numbers. Immunostaining was abundantly found in different nerve fibre populations of both groups. SP expression was significantly increased in mucosal nerve fibres of patients with intermittent (seasonal) AR. Also, significantly increased numbers of VIP‐ and NPY‐immunoreactive nerve fibres were found in biopsies of rhinitis patients in comparison with sections of normal human nasal mucosa. In contrast, CGRP expression did not change significantly.

Conclusion
The increase of neuropeptide expression in mucosal nerve fibres indicates a major role of the autonomous mucosal innervation in the pathophysiology of intermittent (seasonal) AR.
Compliance of asthmatic families with a primary prevention programme of asthma and effectiveness of measures to reduce inhalant allergens – a randomized trial
Authors: Schönberger H. J. A. M. , Maas T. , Dompeling E. , Knottnerus J. A. , Van Weel C. , Van Schayck C. P.
Published: July 2004

Background
Compliance to and the effect of pre‐ and post‐natal exposure reduction measures to prevent asthma in high‐risk children from asthmatic families were studied.

Method
Families were randomized to a special care group (n=222) and a control group (n=221). Educational advice on measures to reduce their newborn's exposure to allergens and smoke was provided to the special care group during three visits (two pre‐natal and one post‐natal). The control group (n=221) received usual care.

Result
After the intervention, the special care group differed significantly (P<0.01) from the usual care group in: use of anti‐mite encasings (parental: 88% vs. 14%; baby: 98% vs. 10%); keeping pets outside (51% vs. 19%); combined breast‐ and hypoallergenic formula feeding (55% vs. 22%); first solids postponement until after the sixth month (71% vs. 28%); maternal post‐natal smoking (52% vs. 28%). Little or no compliance was found for other sanitary measures (cleaning habits, providing a smooth floor covering, ventilation/airing, pet removal), exclusive breastfeeding, pre‐natal smoking and partner smoking. In spite of pre‐existent low allergen levels in both groups, there was a significant reduction of mite, cat, and dog allergens on the mattresses and mite and cat allergens in the living room in the special care group and were significantly lower compared with the usual care group after 1 year.

Conclusion
High compliance was found for the use of anti‐mite encasings; substantial compliance for using hypoallergenic formula, solid food postponement, keeping pets outside and reported post‐natal maternal smoking. There was no compliance for sanitary measures and the reduction of maternal pre‐natal passive smoking. Mite and pet allergens on mattresses were strongly reduced by anti‐mite encasings.
Anaphylaxis after hamster bites – identification of a novel allergen
Authors: Lim D. L. , Chan R. M. E. , Wen H. , Van Bever H. P. S. , Chua K. Y.
Published: July 2004

Background
Hamsters are popular household pets and anaphylaxis after their bites have described. However, the putative allergen has not been identified.

Objective
This study was conducted to identify the allergen causing dwarf hamster (Phodopus sungoris) bite‐induced anaphylaxis.

Methods
Two children with hamster bite‐induced anaphylaxis were enrolled. They both had negative results to skin testing and specific IgE to hamster epithelium. However, they were both allergic to Dermatophagoides pteronyssinus (Der p). Identification of the putative IgE‐binding allergens from the hamster saliva was performed using immunoblot analysis.

Results
A specific IgE‐binding component at 21 kD in the hamster saliva was identified. ELISA inhibition tests showed partial inhibition with Der p.

Conclusions
The putative allergen from the hamster saliva causing dwarf hamster‐induced anaphylaxis was identified. Possible cross‐reactivity with Der p was demonstrated. Further studies will be needed to identify the exact nature and function of this allergen.
Association study of 15 novel single‐nucleotide polymorphisms of the T‐bet locus among Finnish asthma families
Authors: Ylikoski E. , Kinos R. , Sirkkanen N. , Pykäläinen M. , Savolainen J. , Laitinen L. A. , Kere J. , Laitinen T. , Lahesmaa R.
Published: July 2004

Objective
T‐box expressed in T cells (T‐bet) is a transcription factor regulating the commitment of T helper (Th) cells by driving the cells into the Th1 direction. Abnormal Th1/Th2 balance may lead to complex disorders like asthma or autoimmune diseases. Recent studies have suggested that T‐bet might be a candidate gene for asthma. This led us to screen 23 Finnish individuals for single‐nucleotide polymorphisms (SNPs) in the T‐bet locus and study the association between the SNPs and high serum IgE level and asthma.

Methods
We screened all six exons, adjacent intronic areas and 2 kb of the 5′‐flanking region from 23 individuals utilizing WAVE™ technology. To explore whether T‐bet is associated in serum IgE regulation or asthma we genotyped the SNPs in a Finnish asthmatic founder population. The association analyses were made using haplotype pattern mining.

Results
Fifteen novel SNPs were found in the T‐bet gene. Within the Finnish asthmatic founder population, there was no association between T‐bet SNPs and high serum IgE level or asthma.

Conclusions

The genetic variability in the T‐bet gene does not play a role in the pathogenesis of human asthma. Our results provide a novel panel of SNPs in T‐bet and will help determine whether the SNPs have a functional role in other T cell‐mediated diseases.
Nasal conditioning in perennial allergic rhinitis after nasal allergen challenge
Authors: Rozsasi A. , Leiacker R. , Keck T.
Published: July 2004

Background
Antigen challenge in seasonal allergic rhinitis is considered to be associated with an increased ability of the nose to condition inspired air. In contrast, little is known about air conditioning after antigen challenge in perennial allergic rhinitis (PAR).

Objective
The aims of this study were to investigate whether antigen challenge in PAR changes nasal air conditioning and to assess the relationship between nasal conditioning and nasal patency and geometry.

Methods
Nineteen subjects with PAR were enrolled into this study. Measurement of nasal conditioning, active anterior rhinomanometry (AAR), acoustic rhinometry (AR), and clinical symptom evaluation were performed before and after nasal allergen challenge with allergen extracts from house dust mites.

Results
Ten and 20 min after nasal allergen challenge, the total water content of the air measured in the nasopharynx and the water gradient across the nose were significantly higher in the nasal cavity in which the allergen extract was sprayed. The temperature on both sides of the nose increased non‐significantly after nasal allergen challenge. No correlation to data obtained by AAR, AR, and clinical symptom evaluation after nasal allergen challenge was found.

Conclusion
We suggest that an increase in mucosal humidity due to the allergic provocation might be responsible for the increase in nasal conditioning capacity because no correlation to changes in nasal perimeter and patency was found.
The allergy epidemic extends beyond the past few decades
Authors: Isolauri E. , Huurre A. , Salminen S. , Impivaara O.
Published: July 2004

Background
Increased prevalence of allergic diseases in western societies has been described as an epidemic. The precise turning point for the epidemic and the antigens responsible for it remain obscure.

Objective
To evaluate how the prevalence of atopic disease has changed in terms of detectable sensitization to aeroallergens and dietary allergens in a cross‐sectional comparison of subjects from birth cohorts more than 60 years apart.

Methods
We studied four groups of 100 subjects each (at ages 7, 27, 47 and 67 years), representing those born in 1990, 1963–66, 1943–46 and in 1923–26, respectively. Serum total and specific IgE concentrations against aeroallergens and dietary allergens were determined. A questionnaire elicited information on symptoms, allergic diseases and medication.

Results
The proportion of subjects with detectable IgE antibodies against aeroallergens increased consistently from the oldest to the youngest birth cohorts; χ2 trend=56.809, P<0.0001. Similar progression was not seen in sensitization to dietary allergens. The proportion of those with diagnosed asthma differed significantly (χ2=13.45, P=0.004) across the birth cohorts. The lowest prevalence of asthma and sensitization to dietary allergens was detected in those born in 1943–46, i.e. during or immediately after World War II.

Conclusion
Prevalence of sensitization to airborne allergens, unlike that to dietary allergens, has increased over a long period of time. Our results support the concept of the immune function being programmed by external factors early in life. They also call for caution when interpretations of the pace and possible causes of the allergy epidemic are made on the basis of short‐term studies.
Polymorphism of the mast cell chymase gene (CMA1) promoter region: lack of association with asthma but association with serum total immunoglobulin E levels in adult atopic dermatitis
Authors: Iwanaga T. , McEuen A. , Walls A. F. , Clough J. B. , Keith T. P. , Rorke S. , Barton S. J. , Holgate S. T. , Holloway J. W.
Published: July 2004

Background
Mast cell chymase has the potential to be an important mediator of inflammation and remodelling in the asthmatic lung. Previous studies have examined association between promoter polymorphism of the chymase gene (CMA1) and allergic phenotypes but the significance of this polymorphism is unclear. We have examined association of a CMA1 variant in relation to asthma in a large UK Caucasian family cohort.

Methods
A polymorphism of the CMA1 gene promoter (−1903G/A) was genotyped in 341 asthmatic families and in 184 non‐asthmatic adults recruited from the UK PCR‐RFLP based genotyping. Association with asthma diagnosis, atopy, specific and total IgE, and atopy and asthma severity was examined.

Results
Case–control studies did not reveal a significant difference in allele frequency between asthmatics and controls. A significant association was found between CMA1 genotypes and total IgE levels in subjects with self‐reported eczema that remained significant after correction for multiple testing (median total serum IgE GG 297 kU/L, GA 144 kU/L, AA 48.4 kU/L, Pc=0.0032).

Conclusion
These data suggest that CMA1 promoter polymorphism does not contribute to asthma susceptibility or severity but may be involved in regulating IgE levels in patients with eczema.
Increased prevalence of asthma and allied diseases among active adolescent tobacco smokers after controlling for passive smoking exposure. A cause for concern?
Authors: Annesi‐Maesano I. , Oryszczyn M. P. , Raherison C. , Kopferschmitt C. , Pauli G. , Taytard A. , Tunon de Lara M. , Vervloet D. , Charpin D.
Published: July 2004

Background
Whereas effects on allergic and respiratory health have been established for passive tobacco smoking, contradictory results still exist for active tobacco smoking.

Objective
Whether adolescents with asthma and allied diseases have higher rates of active smoking compared with adolescents without asthma was assessed after controlling for environmental tobacco smoking exposure.

Methods
A population‐based sample of 14 578 adolescents was enrolled in an epidemiological survey on allergies in France.

Results
After controlling for age, sex, geographic region, familial allergy and passive smoking, current (in the past year) wheezing (12.4%), current asthma (5.6%), lifetime asthma (12.3%), current rhinoconjunctivitis (13.9%), lifetime hayfever (14.4%) and current eczema (9.3%) but not lifetime eczema (22.5%) were all significantly related to active smoking (>1 cigarette/day) (9.3%). A higher risk of current wheezing, current and lifetime asthma or current eczema was seen in smokers exposed to passive smoking compared with smokers not exposed to it using a polychotomous logistic regression model, in which the different modalities of exposure to active and passive smoking constituted the response variable. Passive smoking was significantly associated only with current diseases. Active smoking was also highly related to both severe asthma (OR=4.02; 95% confidence interval: 1.37, 11.79) and severe rhinoconjunctivitis (OR=2.95; 1.58, 5.49). The highest rate of adolescents suffering from the co‐morbidity of lifetime asthma and hayfever (3.6%) was also seen in active smokers compared with passive and non‐smokers (5.5% vs. 3.6% and 3.1%, respectively; P=0.001).

Conclusions
Being asthmatic or allergic does not seem to act as a deterrent towards starting active smoking or continuing to smoke in adolescence. Results suggest the need for considering individual allergic status in programming health educational activities aimed at reducing smoking among adolescents.
Allergen activates peripheral blood eosinophil nuclear factor‐κB to generate granulocyte macrophage‐colony stimulating factor, tumour necrosis factor‐α and interleukin‐8
Authors: Coward W. R. , Sagara H. , Wilson S. J. , Holgate S. T. , Church M. K.
Published: July 2004

Background
Allergic inflammation is characterized by the influx and activation of eosinophils. Cytokines generated by both resident and infiltrating cells are responsible for the initiation and maintenance of this pathogenesis. This study focuses on allergen‐induced activation of eosinophil NF‐κB and generation of granulocyte macrophage‐colony stimulating factor (GM‐CSF), TNF‐α, and IL‐8.

Methods
Peripheral blood eosinophils were enriched to >99.9% by Percoll gradient sedimentation and negative magnetic affinity chromatography. NF‐κB activation by 10 μg/mL house dust mite (HDM) extract was demonstrated immunocytochemically using a monoclonal antibody against the active form of NF‐κB (NF‐κBa). The authenticity of NF‐κB was confirmed by Western blot. Cytokine production was assessed both by immuno‐staining of eosinophils and by assay of cytokines in the cell supernatant.

Results
Activation of peripheral blood eosinophils from atopic, but not non‐atopic, donors induced activation of NF‐κB, which peaked at 4 h and was accompanied by a decline in IκB‐α. The activation of authentic NF‐κB was confirmed in gel shift assays. Supershift assays showed p65 to be the major subunit of eosinophil NF‐κB. Immunofluorescent confocal microscopy demonstrated localization of NF‐κBa to the nucleus. Following activation, cytokine immunoreactivity was seen in a fraction of the eosinophils and cytokines were released into the supernatant. The NF‐κB inhibitors, calpain inhibitor 1 (10 μm), pentoxifylline (0.5 mm), pyrrolidine dithiocarbamate (PDTC, 10 μm) or gliotoxin (1 pg/mL) reduced the generation of GM‐CSF, TNF‐α and IL‐8 in parallel with their inhibition of NF‐κB.

Conclusions
HDM allergen activates human eosinophil NF‐κB leading to the production of the cytokines GM‐CSF, TNF‐α and IL‐8. We speculate that a role for eosinophil NF‐κB‐dependent cytokines is to act as an autocrine loop augmenting the survival of eosinophils in vivo.
Nerve growth factor enhances cholinergic innervation and contractile response to electric field stimulation in a murine in vitro model of chronic asthma
Authors: Bachar O. , Adner M. , Uddman R. , Cardell L.‐O.
Published: July 2004

Background
Asthma is a chronic inflammatory disease characterized by airway hyper‐responsiveness. Alterations in the neurogenic control are believed to contribute to the pathogenesis. Yet, the long‐term interaction between nerves and inflammatory mediators, such as the neurotrophin nerve growth factor (NGF), are not fully understood much due to the absence of appropriate experimental assays.

Objective
To develop an ex vivo mouse organ culture assay and to investigate the effects of NGF on nerve‐mediated airway contractions.

Method
Mouse tracheal segments were cultured in periods of up to 16 days. Their contractile responses to electric field stimulation (EFS) were investigated. In addition, the effect of 4 days of NGF treatment was analysed using EFS and immunohistochemistry.

Results
EFS (0.2–25.6 Hz) induced reproducible and frequency‐dependent cholinergic contractions of both fresh and cultured tracheal segments. The main part of the EFS response was blocked by tetrodotoxin or atropine. After 4 days in culture, regional differences appeared, with stronger EFS responses in distal than in proximal segments. More nerve fibres were seen in distal segments than in proximal segments. Treatment with NGF during 4 days of culture increased the innervation of the proximal segments, at the same time as the cholinergic contractile responses to EFS were enhanced dose‐dependently.

Conclusion
Culture of tracheal segments appears to be a suitable assay for the examination of long‐term effects induced by inflammatory mediators on neurally mediated airway contractions. NGF treatment enhanced the cholinergic, nerve‐dependent contractions and increased the amount of nerve fibres seen in the murine tracheal segments, suggesting a role for NGF in the development of airway hyper‐responsiveness.
The effects of diet, breast‐feeding and weaning on caries risk for pre‐term and low birth weight children
Authors: DAVENPORT E. S. , LITENAS C. , BARBAYIANNIS P. , WILLIAMS C. E. S.
Published: July 2004

Objectives. The aims of this study were to determine the prevalence of dental disease in 3–4‐year‐old children born pre‐term and low birth weight (PLBW) in East London, UK, to make comparisons with normal birth weight children (NBW), and to investigate the impact of dietary habits on the development of dental caries in primary teeth.

Design. This was a cross‐sectional study.

Subjects and methods. The subjects were 100 children (54 boys and 46 girls) with a mean age (± SD) of 41·70 ± 5·11 months. The children were resident within walking distance of the dental hospital and were invited to attend with their parents. Demographic data and information about feeding practices from infancy to the present were ascertained by structured questionnaire. Dental caries status was determined, and height, weight and head circumference were also measured.

Results. Sixty children had experienced dental caries with a mean (± SD) dmft of 2·98 ± 3·93, 25 of whom had a dmft greater than 5. Normal birth weight children (3·00 ± 4·18) and boys (3·55 ± 4·48) had a significantly increased dmft over PLBW children (2·95 ± 3·35) and girls (2·29 ± 3·04). The PLBW children were more likely to have used a bottle from birth and one in four children were still using a bottle at the time of the dental examination. The PLBW children were significantly more likely to eat sugar than NBW children, scoring 5·53 ± 2·10 and 4·61 ± 1·94, respectively.

Conclusions. A clear relationship exists between poor diet and PLBW in a group of children resident in the East End of London. Targeted infant feeding programmes, education and support for families with regard to dental care is of importance to avoid an unnecessary amount of dental disease in young children.
Fluid for thought: availability of drinks in primary and secondary schools in Cardiff, UK
Authors: HUNTER M. L. , CHESTNUTT I. G. , EVANS S. M. , WITHECOMBE A. C.
Published: July 2004

Objective. While adequate hydration is undoubtedly essential for health, well‐being, performance and learning, it is important to recognize that drinks may also have significant detrimental effects on both general and dental health. Since, on weekdays, at least half of a child's recommended daily fluid intake must be imbibed at school, this study sought to examine the provision of drinks in that setting.

Subjects and methods. A self‐administered postal questionnaire study was sent to the head teachers of all 107 state primary and all 20 state secondary schools in Cardiff, South Wales, UK.

Results. A response rate of 81·9% was achieved. Children had access to fresh drinking water from at least one drinking fountain in 69 (66·4%) of the 104 schools who responded to the questionnaire. Milk was available in 69 (80·2%) of the 86 responding primary schools. Sixteen (88·9%) of the 18 responding secondary schools had drink vending machines selling a variety of drinks.

Conclusions. While primary schools appear largely to restrict the availability of drinks to those conducive to the maintenance of good general and dental health, secondary schools appear to foster the use of vending machines. Guidelines should be developed on the use and content of vending machines in schools in order to both meet school objectives and promote healthy choices.
Defective enamel ultrastructure in diabetic rodents
Authors: ATAR M. , ATAR‐ZWILLENBERG D. R. , VERRY P. , SPORNITZ U. M.
Published: July 2004

We investigated six different types of diabetic rodents. Four expressed a genetic obesity resulting in diabetes. One developed diabetes induced by a diet‐dependent obesity, and one with genetic diabetes received anti‐diabetic medication. The tooth samples were examined under a scanning electron microscope and with an energy dispersive microanalysis (EDX). The electron micrographs showed severe, varying degrees of damage within the six different diabetic animal types, such as irregular crystallite deposition and prism perforations in genetically obese animals compared to less‐disordered prism structures in diet‐dependent obesity. Anti‐diabetic medication resulted in normal enamel ultrastructure. The EDX analysis revealed a reduction in the amount of calcium and phosphorus in all regions affected by diabetes. Based on these animal studies, we suggest that both juvenile diabetes type I (in infants) and adult diabetes type II (in pregnant mothers, affecting the developing foetus) may affect the normal development of teeth in humans.
Fluoride content in bottled waters, juices and carbonated soft drinks in Mexico City, Mexico
Authors: JIMÉNEZ‐FARFÁN M. D. , HERNÁNDEZ‐GUERRERO J. C. , LOYOLA‐RODRÍGUEZ J. P. , LEDESMA‐MONTES C.
Published: July 2004

Objective. The objective of this study was to analyse 283 samples of soft drinks available in the metropolitan market of Mexico City, Mexico: 105 juices, 101 nectars, 57 carbonated drinks and 20 bottled waters.

Materials and methods. Samples of the beverages were analysed using an Orion 720A potentiometer and an Orion 9609BN F ion‐specific electrode.

Results. Fluoride concentration in the above‐mentioned products ranged from 0·07 to 1·42 p.p.m. It was found that fluoride concentrations varied according to the brand, flavour and presentation of the product. The highest mean concentration of fluoride was found in the juices and cola drinks (0·67 ± 0·38 and 0·49 ± 0·41 p.p.m., respectively). The mean fluoride concentration for carbonated drinks was 0·43 ± 0·36 p.p.m. Bottled waters had a fluoride concentration of 0·21 ± 0·08 p.p.m.

Conclusions. The findings suggest that fluoride ingested through bottled drinks represents an important part of the total fluoride ingested by the population. In view of the wide variation of fluoride concentration in the tested products, it is necessary to implement regulatory guidelines for controlling its concentration in order to prevent dental fluorosis.
Phylogeographical structure, distribution and genetic variation of the green algaeUlva intestinalisandU. compressa(Chlorophyta) in the Baltic Sea area
Authors: LESKINEN E. , ALSTRÖM‐RAPAPORT C. , PAMILO P.
Published: July 2004

The marine algaeUlva intestinalisandU. compressaare morphologically plastic with many overlapping characters and are therefore difficult to distinguish from each other. The present distribution ofU. intestinalisandU. compressais investigated along the salinity gradient in the Baltic Sea area through analyses of internal transcribed spacer (ITS) sequence data. Also, the amount and distribution of intraspecific genetic polymorphism in the ITS region is studied allowing inferences on the phylogeographical pattern and postglacial recolonization of the Baltic Sea area. The data show that of the two species onlyU. intestinalisoccurs in the Baltic Sea. The distribution ofU. compressais more restricted than previously reported, and it was not found in salinities lower than 15 ppt. All of Scandinavia and the Baltic Sea were covered with ice during the last ice age and the organisms in the Baltic Sea must have colonized the area after the ice had started to melt. The genetic diversity ofU. intestinalisandU. compressain the Baltic Sea and the neighbouring area was found to be reduced compared to that in the British Isles. This reduction may be the result of either a historical reduction of diversity or an adaptation of specific clones to the northern environmental conditions.
Camouflaged invasion of Lake Malawi by an Oriental gastropod
Authors: GENNER MARTIN J. , MICHEL ELLINOR , ERPENBECK DIRK , DE VOOGD NICOLE , WITTE FRANS , POINTIER JEAN‐PIERRE
Published: July 2004

In this study we report the first animal invasion, to our knowledge, into Lake Malawi. The colonizer is a non‐native morph of the gastropod Melanoides tuberculata that differs substantially in external shell characters from co‐occurring indigenous forms. However, because the species possesses extensive within‐Africa geographical variation in shell morphology, it was unclear whether the invasion was range expansion of a native African morph, or a colonization from elsewhere. Mitochondrial DNA sequences indicate a southeast Asian origin for the invader, suggesting that shell variation found among indigenous allopatric populations camouflaged an intercontinental invasion.
Natural selection of the major histocompatibility complex (Mhc) in Hawaiian honeycreepers (Drepanidinae)
Authors: JARVI SUSAN I. , TARR CHERYL L. , MCINTOSH CARL E. , ATKINSON CARTER T. , FLEISCHER ROBERT C.
Published: July 2004

The native Hawaiian honeycreepers represent a classic example of adaptive radiation and speciation, but currently face one the highest extinction rates in the world. Although multiple factors have likely influenced the fate of Hawaiian birds, the relatively recent introduction of avian malaria is thought to be a major factor limiting honeycreeper distribution and abundance. We have initiated genetic analyses of class II β chain Mhc genes in four species of honeycreepers using methods that eliminate the possibility of sequencing mosaic variants formed by cloning heteroduplexed polymerase chain reaction products. Phylogenetic analyses group the honeycreeper Mhc sequences into two distinct clusters. Variation within one cluster is high, with dN > dS and levels of diversity similar to other studies of Mhc (B system) genes in birds. The second cluster is nearly invariant and includes sequences from honeycreepers (Fringillidae), a sparrow (Emberizidae) and a blackbird (Emberizidae). This highly conserved cluster appears reminiscent of the independently segregating Rfp‐Y system of genes defined in chickens. The notion that balancing selection operates at the Mhc in the honeycreepers is supported by transpecies polymorphism and strikingly high dN/dS ratios at codons putatively involved in peptide interaction. Mitochondrial DNA control region sequences were invariant in the i’iwi, but were highly variable in the ‘amakihi. By contrast, levels of variability of class II β chain Mhc sequence codons that are hypothesized to be directly involved in peptide interactions appear comparable between i’iwi and ‘amakihi. In the i’iwi, natural selection may have maintained variation within the Mhc, even in the face of what appears to a genetic bottleneck.
Breast‐feeding and atopic eczema dermatitis syndrome: protective or harmful?
Authors: Eigenmann P. A.
Published: July 2004

Numerous studies have addressed the potential of breast‐feeding to protect for the development of allergic diseases, and in particular of atopic eczema dermatitis syndrome (AEDS). Although the majority of studies, as well as several meta‐analyses, are strongly in favour of breast‐feeding, there are some conflicting results and open issues. Furthermore, breast‐feeding might be detrimental in a subgroup of young infants with severe early manifestations of AEDS and immunoglobulin E sensitizations to common foods. The aim of this review is not to analyse systematically the current literature, but to suggest a scientifically and clinically based analysis of the benefits of breast‐feeding in atopic infants.
Immunoglobulin E‐ (IgE) and non‐IgE‐mediated reactions in the pathogenesis of atopic eczema/dermatitis syndrome (AEDS)
Authors: Bardana E. J.
Published: July 2004

AEDS is a chronic, relapsing, highly pruritic inflammatory skin disease that commonly begins in childhood. Two forms of this disorder exist, i.e. an allergic (extrinsic) form and a nonallergic (intrinsic) form. There are clear genetic, humoral and cellular differences between the allergic and nonallergic forms of AEDS. The allergic variants express local IgE production in affected tissue and both allergic and nonallergic triggers play a major role in the expression of disease. The role of allergens is very important in the immunopathogenesis of AEDS. Nonimmunological triggers play a secondary modulatory role often hampering treatment effort and optimal response to therapeutic efforts.
The utility of specific immunoglobulin E measurements in primary care
Authors: Duran‐Tauleria E. , Vignati G. , Guedan M. J. A. , Petersson C. J.
Published: July 2004

Background:  The identification of atopic patients may not be considered a necessary step in the diagnosis process in primary care. This study investigated the impact of the addition of a specific immunoglobulin E (IgE) antibody test on the current management by primary‐care physicians of patients with respiratory and skin symptoms.

Methods:  The study had a prospective before–after design. It was conducted in two geographic areas of Italy and Spain and consisted of two parts, Part I and Part II. In each part patients were recruited according to inclusion and exclusion criteria. After the clinical examination, the patients were classified into one of the following categories using a physician's classification: allergic, nonallergic or uncertain. A blood sample was taken from each included patient for specific IgE antibody determination using a Pharmacia CAP SystemTM, including either Phadiatop Infant (0–5 years of age) or Phadiatop and food mix (fx5e) (>5 years of age). If a positive result was found, an additional 6–26 specific IgE tests were performed. In Part I the result of the specific IgE antibody determinations was not available before the physician's classification was made. In contrast, in Part II, the result of the IgE test was available at the time when the physician's classification was made. Between Part I and Part II an educational intervention for physicians to improve their knowledge of blood testing for IgE‐mediated allergy was carried out.

Results:  A total of 721 patients were included in the study. The agreement between classifications based on clinical data and IgE antibody results changed from a kappa coefficient of 0.13 in Part I to 0.86 in Part II. With regard to the allergic status the proportion of uncertain cases was reduced from 26.3% in Part I to 4.1% in Part II. The proportion of patients that were advised to avoid allergens increased from 18% in Part I to 62% in Part II in the group of patients classified both by the clinician and the IgE test.

Conclusions:  The use of specific IgE antibody determinations improves the clinical management of patients with allergy related symptoms in primary care, allowing advice to be given on specific allergen avoidance. However, the applicability of this diagnostic tool in different areas and countries should be further assessed in cost‐effectiveness studies.
Consensus guidelines in diagnosis and treatment of atopic dermatitis
Authors: Eichenfield L. F.
Published: July 2004

Atopic dermatitis is a common condition of great health significance. Consensus‐driven guidelines of care or specific practice parameters may be useful, as are treatment algorithms based upon disease severity. Development of consensus guidelines on diagnosis and treatment of atopic dermatitis are discussed, and disease‐severity‐based guidelines of care proposed.
Role of oral food challenges in the diagnostic work‐up of food allergy in atopic eczema dermatitis syndrome
Authors: Niggemann B.
Published: July 2004

The diagnosis of food allergy in infants and children is still a challenging task for the pediatrician. While immediate‐type allergic reactions to foods can be diagnosed quite easily, late‐phase reactions, e.g. in atopic dermatitis, often represent a diagnostic challenge. Once classical diagnostic procedures such as history, skin prick tests, atopy patch test, and specific immunoglobulin E in serum have been exhausted, double‐blind, placebo‐controlled food challenges represent the state of the art. After an oligo‐allergenic diet, suspected foods or placebo are given in a titrated manner until a clear clinical reaction or the highest dose. The observation period should be 48 h in the case of atopic dermatitis. Constant clinical monitoring is mandatory. Dietetic recommendations are given for 12 months. The effort involved in such a procedure is justified because it can help to avoid clinically relevant food allergens in some cases and in others can prevent children from being exposed unnecessarily to diets that may be harmful to them.
Hypoallergenic formulas – when, to whom and how long: after more than 15 years we know the right indication!
Authors: Høst A. , Halken S.
Published: July 2004

Hypoallergenic formulas are processed by enzymatic hydrolysis of different protein sources such as bovine casein/whey and soy followed by further processing such as heat treatment and/or ultrafiltration, or they are based on amino acid mixtures. The products have been classified according to the degree of protein hydrolysis as ‘extensively’ or ‘partially’ hydrolysed protein products. Product properties may be characterized by biochemical techniques, and reduction of allergenicity may be assessed in vitro with various immunological methods, and in vivo with skin prick tests, patch tests and challenge tests. In vitro tests do not predict the allergenic effects in humans, and at present there is no evidence of a specific threshold of immunogenic protein. Only pure amino acid mixtures are considered to be nonallergenic. Other ‘hypoallergenic’ products contain residual allergenicity. At present, the potential of a product for treatment and prevention of food allergy can only be determined by clinical trials using scientifically appropriate standards. It has been recommended that dietary products for treatment of cow's milk protein allergy in infants should be tolerated by at least 90% (with 95% confidence) of infants with documented cow's milk protein allergy. Some extensively hydrolysed products and amino‐acid‐based products have met these criteria. Formulas intended for prevention should have a very low, if any, allergenic activity until otherwise proven. So far there are no firm criteria available for the design of hypoallergenic foods for prevention. Newborns included in prevention studies should be from high‐risk families; they should be randomized at birth and fed the formula when supplements are needed for at least the first 4–6 months of life. Follow‐up should be at least 18 months, and children should be investigated when symptoms appear. Validated clinical criteria, including controlled food challenges, should be used for diagnosis. Infants fed formulas that claim to prevent or delay allergy should have a statistically significant lower prevalence of allergy when compared with infants fed a standard cow's milk formula. Feeding high‐risk infants a documented hypoallergenic formula combined with avoidance of solid foods during the first 4–6 months reduces the cumulative incidence of cow's milk protein allergy and atopic dermatitis as compared with a standard cow's‐milk‐based formula. Partially hydrolysed formulas may have an effect, though it seems to be less than that of extensively hydrolysed formulas at present. Thus, if exclusive breast‐feeding for 4–6 months is not possible in high‐risk infants, a documented hypoallergenic formula and avoidance of solid foods are recommended for the first 4 months of life.