bluuebunny/crossref_metadata_2025_split huggingface dataset:
Childhood atopy and allergic disease and skin test responses to environmental mycobacteria in rural Crete: a cross‐sectional survey
Authors: Bibakis I. , Zekveld C. , Dimitroulis I. , Pedioti A. , Gerakianaki T. , Fanourgiaki S. , Kokiadi I. , Iliakou‐Bibakis V. , Newman Taylor A. J. , Stanford C. A. , Stanford J. L. , Cullinan P. 
Published: May 2005

SummaryBackground
Through its powerful immunoregulatory effects, infection with atypical mycobacteria may exert a protective effect on the development of childhood allergic disease.Objective
To examine the relationship between childhood atopy or allergic disease and previous infection with four species of atypical mycobacteria.Methods
Eight hundred and six children aged 8–18 years and living in rural Crete – most of whom had had previous BCG immunization – underwent skin prick testing with 10 aeroallergens; their parents completed a standardized questionnaire relating to allergic disease. No less than 8 weeks later each child underwent intradermal skin tests with 0.1 mL solutions of four selected mycobacterial reagents (Aviumin C, Gordonin, Chelonin and Ranin I).Results
Twenty‐three percent of children were atopic on skin prick testing; far fewer had symptoms of asthma (5%) or hayfever in conjunction with a positive prick test to pollens (2%). Eighty percent of children had positive skin responses to one or more mycobacterial species. Among all children – and those with a BCG scar – there was no association between atopy or allergic symptoms and mycobacterial skin responses; among the few children without a BCG scar however those with positive mycobacterial responses were less likely to be atopic or to report allergic symptoms; these differences were not statistically significant.Conclusions
Our findings, in a population of BCG‐immunized children, do not lend support to the suggestion that infection with atypical mycobacteria is protective against childhood allergic disease.
Rational design of hypoallergens applied to the major cat allergen Fel d 1
Authors: Saarne T. , Kaiser L. , Grönlund H. , Rasool O. , Gafvelin G. , Van Hage‐Hamsten M. 
Published: May 2005

SummaryBackground
Allergen‐specific immunotherapy is the only treatment for allergic disease providing long‐lasting symptom relief. Currently, it is mainly based on the use of crude allergen extracts. The treatment may be improved by the use of genetically engineered allergens, hypoallergens, aiming at a more effective and safer therapy.Objective
The aim of this study was to provide a rational design of hypoallergen candidates for immunotherapy by using structural information and knowledge of B and T cell epitopes of an allergen.Methods
The three‐dimensional structure of the major cat allergen Fel d 1 was systematically altered by duplication of selected T cell epitopes and disruption of disulphide bonds. Seven Fel d 1 derivatives were generated and screened for allergenic reactivity in comparison with recombinant Fel d 1 in competition‐ELISA. The allergenicity was further evaluated in basophil activation experiments and T cell reactivity was assessed in a lymphoproliferation assay.Results
Three out of seven Fel d 1 derivatives, with two duplicated T cell epitopes and one or two disulphide bonds disrupted, were carefully evaluated. The three derivatives displayed a strong reduction in allergenicity with 400–900 times lower IgE‐binding capacity than recombinant Fel d 1. In addition, they induced a lower degree of basophil activation and similar or stronger T cell proliferation than recombinant Fel d 1.Conclusion
By a rational approach, we have constructed three Fel d 1 hypoallergens with reduced IgE‐binding capacities and retained T cell reactivities. This strategy may be applied to any well‐characterized allergen to improve immunotherapy for allergic patients.
Variability of total serum immunoglobulin E levels from birth to the age of 10 years. A prospective evaluation in a large birth cohort (German Multicenter Allergy Study)
Authors: Nickel R. , Illi S. , Lau S. , Sommerfeld C. , Bergmann R. , Kamin W. , Forster J. , Schuster A. , Niggemann B. , Wahn U. ,   the German Multicenter Allergy Study Group (MAS‐90)
Published: May 2005

SummaryBackground
Many environmental factors influence the concentration of total serum IgE (tIgE); however, tIgE synthesis is believed to be under strong genetic influence. Multiple genetic studies on tIgE regulation have been performed. For these population‐based studies tIgE was commonly determined at one time‐point, assuming that tIgE phenotypes (adjusted for age and gender) are stable over time.Objective
We assessed correlations of tIgE levels from birth to the age of 10 years in the birth cohort MAS (Multicenter Allergy Study; n=1314).Materials and methods
We determined cord‐blood IgE levels, total and specific IgE at the age of 1, 2, 3, 5, 6, 7, and 10 years. Spearman correlation coefficients were calculated for tIgE at different time‐points. All analyses were performed in the entire cohort, adjusted for gender, as well as in non‐atopic children only.Results
tIgE percentiles increased steadily from birth to the age of 10 years with higher values for boys than for girls at each time‐point. tIgE values from birth to 3 years of age correlated poorly with tIgE levels at 10 years (r<0.5). However, good correlations (r>0.8) were observed for tIgE concentrations at 6, 7 and 10 years. The same results were observed when the analyses were limited to non‐atopic children.Conclusion
In childhood, tIgE levels underlie remarkable variation over time even in the absence of atopy. For cross‐sectional population‐based genetic and epidemiologic studies, tIgE values of children <5 years should be interpreted with caution since these values correlate poorly with tIgE levels later in life.
Intragastric administration of Mycobacterium vaccae inhibits severe pulmonary allergic inflammation in a mouse model
Authors: Hunt J. R. F. , Martinelli R. , Adams V. C. , Rook G. A. W. , Brunet L. Rosa 
Published: May 2005

SummaryBackground
Coexistence with harmless microorganisms such as lactobacilli, saprophytic mycobacteria and some helminths, throughout evolution, may have shaped the host immune system. Exposure to such organisms may have therapeutic benefits by triggering immunoregulatory mechanisms that control inappropriate immune responses to self, gut contents or allergens.Objective
We determined whether treatment with Mycobacterium vaccae by gavage influences the host immune response both locally and systemically. We also investigated whether delivery by this route prevents severe symptoms of disease in a murine model of pulmonary allergic inflammation.Results
A single intragastric administration of M. vaccae induced a transient increase in the production of IL‐10 and IFN‐γ by mesenteric lymph nodes cells and splenocytes. In addition, in a mouse model of pulmonary allergic inflammation, a single treatment with M. vaccae by gavage not only diminished the total cellular infiltrate and the eosinophilic component induced by subsequent intratracheal allergen challenge, but also biased local and systemic cytokine production towards IL‐10. Delivery of M. vaccae by gavage was as effective as subcutaneous treatment.Conclusion
This is the first report to suggest that heat‐killed mycobacteria can down‐regulate symptoms of allergic inflammation by the intragastric route. These data suggest an alternative route of treatment with M. vaccae for patients with allergic conditions.
The safety of sublingual‐swallow immunotherapy: an analysis of published studies
Authors: Gidaro G. B. , Marcucci F. , Sensi L. , Incorvaia C. , Frati F. , Ciprandi G. 
Published: May 2005

SummaryBackground
As the main target of sublingual immunotherapy (SLIT) is to reduce at most the occurrence of adverse events (AE), safety represents a critical issue. This aspect deserves particular mention when a higher dose of allergen extract than traditional subcutaneous immunotherapy (SCIT) is required to be effective: that may be up to 500 times that employed for SCIT.Objective
All published controlled studies concerning SLIT‐swallow were analysed to evaluate AE rates.Methods
Studies were subdivided in two groups: (i) studies using low allergen dose (LAD), i.e. ranging from 1 to 50 times the dose commonly administered with SCIT, and (ii) studies with high allergen dose (HAD), i.e. ranging from 50 to 500 times the dose administered with SCIT.Results
Twenty‐five studies were altogether analysed: 13 studies belonged to the low‐dose group, 12 belonged to the high‐dose group. We considered all patients with at least one AE. Local reactions were significantly more frequent in the LAD group than in the HAD group (P<0.0001), while there was no difference in the rate of systemic reactions. Severe systemic reactions were never reported.Conclusion
This study represents the first analysis of the safety of SLIT concerning the allergen dose employed in the treatment. There is evidence that AE occurrence is substantially not dose‐dependent. This fact highlights two main clinical aspects: the elevated tolerability of SLIT in general and the safety of HAD regimen.
The pro‐fibrogenic effect of nerve growth factor on conjunctival fibroblasts is mediated by transforming growth factor‐β
Authors: Micera A. , Puxeddu I. , Lambiase A. , Antonelli A. , Bonini S. , Bonini S. , Aloe L. , Pe'er J. , Levi‐Schaffer F. 
Published: May 2005

SummaryBackground
Nerve growth factor (NGF) and nerve growth factor receptor (NGFR) expressions have been found to be increased in sub‐conjunctival scarring.Objective
The aim of this study was to investigate the in vitro effects of NGF on some pro‐fibrogenic properties of human conjunctival fibroblasts.Methods
Expression of NGF, trkANGFR and p75NTR on human fibroblasts grown from conjunctival biopsies and incubated for 2 or 6 days with NGF were evaluated by immunofluorescence, RT‐PCR, flow cytometry and ELISA. The fibrogenic effect of NGF on conjunctival fibroblasts was investigated by evaluating their migration (wound model), proliferation ([3H]‐thymidine incorporation), collagen production (3H]‐proline incorporation), expression of alpha‐smooth muscle actin (α‐SMA) (cell surface ELISA) and contraction of 3D collagen gels.Results
NGF induced the expression of p75NTR in the fibroblasts that constitutively expressed only trkANGF and increased the migration of wounded fibroblasts, but not their proliferation and collagen production. NGF induced the conversion of fibroblasts into myofibroblasts expressing α‐SMA, and enhanced their contraction of a collagen matrix. Interestingly, chronic NGF treatment induced transforming growth factor‐β1 (TGF‐β1) production by fibroblasts, and following specific TGF‐β neutralization, all the NGF‐induced effects were completely abrogated.Conclusion
Our findings indicate that NGF, via TGF‐β induction, is likely to be involved in the healing or fibrotic processes occurring in conjunctiva during some pathological conditions.
Persistence of rhinovirus RNA after asthma exacerbation in children
Authors: Kling S. , Donninger H. , Williams Z. , Vermeulen J. , Weinberg E. , Latiff K. , Ghildyal R. , Bardin P. 
Published: May 2005

SummaryBackground
Rhinoviruses (RVs) are believed to cause most asthma exacerbations but their role in the severity of acute asthma and subsequent recovery of airway function is not defined. The importance of atopy in virus‐host interactions is also not clear.Objective
We postulated that RV infection and atopic skin prick responses influence the severity of asthma exacerbations as measured by peak expiratory flow (PEF).Methods
Patients aged 4–12 years admitted with acute severe asthma to a hospital emergency room (ER) were recruited. PEF measurements were obtained and nasal aspirates (NA) were taken. Atopy was diagnosed by skin prick responses to allergen and the presence of RV RNA and respiratory syncytial virus (RSV) RNA in NAs was detected using validated PCR assays. Patients were restudied after 6 weeks and after 6 months.Results
Fifty children with acute asthma (mean age±SD, 7.4±2.7) were enrolled; atopy was present in 37 (74%). RV RNA was detected in 41 (82%) and RSV RNA in six (12%) subjects. After 6 weeks 41 patients were restudied and RV RNA was again detected in 18 (44%). RV RNA was detected after 6 months in four of 16 patients restudied (25%; P=0.008 vs. ER) and in two of nine children from a control group with stable asthma (22%; P=0.009 vs. ER). Overall PEF measurements were reduced in asthmatics admitted to ER (% predicted, 63.4±16.4%) but did not differ between patients with RV RNA, RSV RNA or neither virus present. In subjects with RV RNA detectable in ER and after 6 weeks, measurements of PEF in ER were significantly lower than in patients in whom RV RNA was present in ER but absent after 6 weeks (P=0.009). Regression analysis linked persistence of RV RNA, but not skin prick responses to allergen, to severity of PEF reductions in ER.Conclusion
RV RNA was detectable in >40% of asthmatic children 6 weeks after an acute exacerbation. Asthma exacerbations were more severe in patients with persistence of RV RNA suggesting that the severity of acute asthma may be linked to prolonged and possibly more severe RV infections.
Immunotherapy with depigmented glutaraldehyde‐polymerized extracts: changes in quality of life
Authors: Alvarez‐Cuesta E. , Aragoneses‐Gilsanz E. , Martín‐Garcia C. , Berges‐Gimeno P. , Gonzalez‐Mancebo E. , Cuesta‐Herranz J. 
Published: May 2005

SummaryBackground
Immunotherapy (IT) with modified allergens reduces allergic rhinitis (AR) symptoms and medications requirements. Improvement of quality of life (QOL) is a key point in the treatment of AR. The aim of this study was to provide evidence of changes related to the patient's QOL (well‐being) induced by a modified (depigmented glutaraldehyde‐polymerized) therapeutic vaccine and of its safety.Material and Methods
Fifty‐three patients with a well‐documented clinical history of seasonal AR sensitized to Dactylis glomerata and Olea europaea pollens were included in a randomized clinical trial. Twenty‐five patients (Group‐A) received a mixture of D. glomerata and O. europaea pollen extracts and 28 patients received placebo (group‐C). Any adverse event was recorded and graded in accordance with EAACI guidelines. RQLQ was recorded before the treatment (pollen season 2000) and after 1 year of treatment (pollen season 2001). Dose–response skin prick test with each allergen extract was conducted at baseline and at the end of the study.Results
Each patient received 17 injections during this period. All patients completed the trial and no systemic adverse reactions were recorded. Symptom scores (P<0.001) and medication requirements (P<0.001) were significantly reduced in the IT group during the pollen season. This patient group also experienced greater and statistically significant improvement in overall RQLQ score and in five of the seven domains, all of them surpassing the threshold of ‘minimal important difference’ of 0.5 points.Conclusions
Results of this study provided evidence that IT with depigmented, glutaraldehyde‐modified allergen extracts was well‐tolerated and added beneficial effects to AR treatment in pollen allergic patients eliciting an improvement in QOL enough to justify a change in the patient's treatment.
The Ossicle Bank of the University Medical Centre (UMCU), the Netherlands
Authors: Meeuwsen F. , Veldman J.E. , Hordijk G.J. 
Published: May 2005

Keypoints• Long term results show high extrusion rates of porous and ceramic ossicle prosthesis.• For this reason, allogenic ossicular bone remains the first choice for many Otolaryngologists.• The combination of adequate tissue preservation and definite donor selection criteria guarantees the safe use of allogenic ossicles for ossiculoplasty.
Extended high‐frequency audiometry in patients with acoustic trauma
Authors: Balatsouras D.G. , Homsioglou E. , Danielidis V. 
Published: May 2005

Objectives:  The aim of this study was to examine extended high‐frequency (EHF) hearing in patients with acoustic trauma.Design:  A prospective, case–control study in a group of soldiers with acoustic trauma caused by shooting practice during basic training.Setting:  Tertiary referral centre.Participants:  A total of 39 young soldiers hospitalized for hearing loss and tinnitus following exposure to weapon impulse noise were studied. Conventional audiometry in the frequency range 0.25–8 kHz and EHF audiometry in the frequency range 9–20 kHz were performed, both on admittance and before discharge. Thirty healthy recruits of similar age and sex were used as controls.Main outcome measures:  Pure‐tone threshold changes documented by conventional and EHF audiometry.Results:  The most significant differences in pure‐tone thresholds on initial testing were found in the frequency range 0.25–11.2 kHz, and especially in the 4–8 kHz region. Reduction in thresholds across most frequencies was observed after treatment, although recovery was partial in most cases.Conclusions:  The EHF audiometry adds no significant additional information to conventional pure‐tone audiometry in assessing and monitoring noise‐induced hearing loss.
How we do it: Head and neck cancer waiting times
Authors: Tandon S. , Machin D. , Jones T.M. , Lancaster J. , Roland N.J. 
Published: May 2005

KeypointsAfter instigation of rapid access referrals from GPs and the Calman‐Hine 2‐week rule, the times taken from initial presentation to the GP, until the start of definitive treatment for patients with head and neck cancer managed was audited and compared with national guidelines.• An improvement in time from GP referral to first outpatient clinic (2.1 weeks), time to fine needle aspiration cytology (FNAC; 2.9 days), time to endoscopic examination (2.3 weeks) and to staging scans (3.3 weeks) was seen, these fell just outside the standards set. Time to histological report was within the standards set (0.4 weeks).• As a result of the improvement in preoperative work up of cancer patients, there has been an increased delay to primary surgery (7.7 weeks) and a continued delay to primary radiotherapy (10.2 weeks).• Delays because of poor patient education about head and neck cancer are still very apparent and need to be addressed, as well as further improvement in GP education about early referral to ENT services.• The shortfalls seen need to be addressed by an increase in infrastructure as well as medical and paramedical staffing to ensure patients are managed within given time standards. Although patient throughput can be enhanced by improvements in system efficiency, it is unlikely that targets will be met consistently without an increase in resources to fund greater capacity and more personnel.
Micropapillary pattern: a distinct pathological marker to subclassify tumours with a significantly poor prognosis within small peripheral lung adenocarcinoma (≤20 mm) with mixed bronchioloalveolar and invasive subtypes (Noguchi's type C tumours)
Authors: Makimoto Y , Nabeshima K , Iwasaki H , Miyoshi T , Enatsu S , Shiraishi T , Iwasaki A , Shirakusa T , Kikuchi M 
Published: May 2005

Aims:  A micropapillary pattern (MPP) in lung adenocarcinoma, characterized by papillary structures with epithelial tufts lacking a central fibrovascular core, has been reported to be a new pathological marker of poor prognosis. However, its clinicopathological and prognostic significance in small lung adenocarcinomas (≤20 mm) remains undetermined. A new histological classification of small lung adenocarcinoma proposed by Noguchi et al. has been found to be useful since it has defined surgically curable bronchioloalveolar carcinoma (BAC)‐type tumours (Noguchi's type A and B) based on the absence of active fibroblastic proliferation. However, BAC‐type tumours with active fibroblastic proliferation (Noguchi's type C), which is adenocarcinoma with mixed subtypes including BAC and invasive carcinoma in the new World Health Organization (WHO) classification, account for most of the small adenocarcinomas and represent a heterogeneous group ranging from minimal to overtly invasive cancer with variable prognoses. Therefore, in this study the aim was to investigate whether MPP can be an additional histological marker(s) to subclassify this heterogeneous group in small lung adenocarcinoma.Methods and results:  One hundred and twenty‐two cases of small lung adenocarcinomas (≤20 mm in maximum dimension) classified according to the new WHO classification and Noguchi's proposal were analysed with reference to the presence of MPP. Of the 122 cases, 67 (55%) were MPP‐positive and 55 (45%) were MPP‐negative. Lymph node metastasis and pleural invasion were significantly more frequent in the MPP‐positive group: 74% and 66% in the positive group versus 26% and 34% in the negative group, respectively. The 5‐year survival of the MPP‐positive group was 54%, whereas that of the MPP‐negative group was 81% (P = 0.024). The 5‐year survival rates of BAC (Noguchi's type A and B) (n =14), mixed BAC and invasive adenocarcinoma (Noguchi's type C) (n = 85) and invasive adenocarcinoma (Noguchi's type D and F) (n = 23) were 100%, 68% and 36%, respectively. In patients with mixed BAC and invasive adenocarcinoma (Noguchi's type C tumours), the 5‐year survival of the MPP‐positive group (n = 51) was 54%, significantly lower than that of the MPP‐negative group (n = 23) of 100% (P = 0.02).Conclusions:  MPP is a simple and distinct pathological marker to subclassify tumours with a significantly poor prognosis within small (≤20 mm) mixed BAC and invasive adenocarcinoma (Noguchi's type C tumours).
Ki67 and p53 immunohistochemistry reduces interobserver variation in assessment of Barrett's oesophagus
Authors: Lörinc E , Jakobsson B , Landberg G , Veress B 
Published: May 2005

Aims:  To devise clinically applicable methods for assessing p53 and Ki67 immunohistochemical (IHC) reactivity in Barrett's oesophagus (BE) and to compare the interobserver agreement between these methods and routine haematoxylin and eosin (H&E) evaluation.Methods and results:  One hundred and fifteen biopsies diagnosed as BE, selected from the files of the University Hospital MAS, Malmö, were re‐evaluated for dysplasia by three pathologists. For IHC analysis areas with the most prominent positivity were evaluated. The mean of p53+ epithelial nuclei/high‐power field (HPF) was obtained by counting between 1 and 5 HPFs/biopsy. A proliferation quotient (PQ) was obtained by dividing the number of Ki67+ epithelial nuclei in the upper half by the lower half of the mucosa, using two HPFs. Mean κ values were 0.24, 0.71 and 0.52 for H&E, p53 and Ki67 evaluations, respectively. There was a correlation between increasing severity of dysplasia, IHC measurable overexpression of p53 and shift of the mucosal proliferation zone towards the surface, measured as PQ.Conclusions:  The described methods for p53 and Ki67 evaluation are more reproducible than routine H&E evaluation of BE. Furthermore, the IHC methods correlate with the severity of dysplasia and are useful supplementary prognostic markers.