bluuebunny/crossref_metadata_2025 huggingface dataset:
Polyethylene glycol 4000 vs. lactulose for the treatment of neurogenic constipation in myelomeningocele children: a randomized‐controlled clinical trial
Authors: RENDELI C. , AUSILI E. , TABACCO F. , FOCARELLI B. , PANTANELLA A. , DI ROCCO C. , GENOVESE O. , FUNDARÒ C.
Published: March 2006

Aim  To compare the therapeutic effectiveness and tolerability of low daily doses of polyethylene glycol 4000 vs. lactulose in the treatment of neurogenic constipation in children with myelomeningocele.

Methods  Sixty‐seven children with chronic neurogenic constipation were randomized allocated to receive either polyethylene glycol 4000 (0.50 g/kg) or lactulose (1.5 g/kg) for 6 months. Patients or their parents reported frequency and modality of evacuation and side effects on a diary card. Primary outcome was bowel frequency ≥3/week, and the second one was side effects at the end of treatment.

Results  Complete remission of constipation was reported by a significantly (P < 0.01) higher number of patients treated with polyethylene glycol compared with lactulose. At the end of the study, 46% patients of polyethylene glycol group and 22% of the lactulose group were asymptomatic. Compared with lactulose, patients treated with polyethylene glycol reported higher bowel frequency (5.1 vs. 2.9 bowel movements/week, P < 0.01) and reduction of encopresis. Neither lactulose nor polyethylene glycol caused clinically‐significant serious side effects and palatability was similar.

Conclusions  Polyethylene glycol 4000 compared with lactulose provided a higher success rate, without significant side effects, for the treatment of constipation in myelomeningocele children.
Meta‐analysis: the dialysis mode and immunological response to hepatitis B virus vaccine in dialysis population
Authors: FABRIZI F. , DIXIT V. , BUNNAPRADIST S. , MARTIN P.
Published: March 2006

Background  Patients on maintenance dialysis typically show a suboptimal immune response to hepatitis B virus vaccine compared with the non‐uraemic population. Some authors have claimed that dialysis mode has an impact on the immune response to hepatitis B virus vaccine but consistent information is lacking on this issue.

Aim  To evaluate the relationship between dialysis mode and immune response to hepatitis B vaccine in dialysis population by performing a systematic review with a meta‐analysis of clinical trials.

Method  We used the random effects model of DerSimonian and Laird; sources of heterogeneity in effect estimates were explored by performing sensitivity analyses.

Results  The relative risk of failure to respond to hepatitis B vaccine among patients who underwent maintenance haemodialysis vs. peritoneal dialysis was the end point of interest. We identified 14 clinical trials involving 1211 unique patients on maintenance dialysis. Pooling of study results did not show a significant decreased risk of response to hepatitis B vaccine among haemodialysis patients (overall risk ratio: 1.0, 95% confidence intervals: 0.92–1.1). The P‐value was 0.13 for our test of study heterogeneity.

Conclusion  There is no significant link between dialysis mode and seroresponse to hepatitis B virus vaccine in dialysis population.
Antibiotic treatment of Crohn's disease: results of a multicentre, double blind, randomized, placebo‐controlled trial with rifaximin
Authors: PRANTERA C. , LOCHS H. , CAMPIERI M. , SCRIBANO M. L. , STURNIOLO G. C. , CASTIGLIONE F. , COTTONE M.
Published: March 2006

Background  Clinicians often employ antibiotics in Crohn's disease. Rifaximin is active against bacteria frequently found in the intestinal mucosa of Crohn's disease patients.

Aim  To evaluate the difference in efficacy between once and twice/daily oral administration of rifaximin and placebo in the treatment of active Crohn's disease.

Methods  We enrolled 83 patients with mild‐to‐moderate Crohn's disease and randomized to three treatments for 12 weeks: Group A (rifaximin 800 mg o.d. + placebo), Group B (rifaximin 800 mg b.d.) and Group C (placebo b.d.).

Results  Clinical remission was achieved by 52% of Group B, 32% (A) and 33% (C). Clinical response was seen in 67% (B), 48% (A) and 41% (C), without reaching a statistically significant difference. Treatment failures were: 4% (B), 12% (A) and 33% (C), (P = 0.010). Remission and response rates of rifaximin 800 mg b.d. were significantly higher than those of placebo and rifaximin 800 mg o.d. in patients with elevated C reactive protein values (P < 0.05).

Conclusions  Rifaximin 800 mg b.d. was superior to placebo in inducing clinical remission of active Crohn's disease. Although this difference was not statistically significant, the number of the failures in the placebo group was significantly higher than those who received rifaximin 800 mg b.d.
Assessing patients’ understanding of hepatitis C virus infection and its impact on their lifestyle
Authors: FABRIS P. , TOSITTI G. , GIORDANI M. T. , BALDO V. , GRASSO A. , PIGNATTARI E. , CANTON S. , ROSSATO S. , FLOREANI A.
Published: March 2006

Aims  To assess how much patients with hepatitis C virus infection know about their condition and what impact it has on their lifestyle.

Materials and methods  A multiple‐choice questionnaire was administered anonymously to 364 hepatitis C virus‐infected subjects just before their first specialist visit.

Results  Even before hepatitis C virus infection was diagnosed, 257 subjects (70.6%) already knew something about this infection. Overall, 36% of patients had changed the way they behaved within the family, 25.5% had changed their sexual habits, 46.9% had changed their diet, and 69% reported having stopped or limited their alcohol intake after being told they were hepatitis C virus positive. Hepatitis C virus infection had a negative impact on the psychological status in 44.2% of patients. This effect was significantly greater among women and was independent of either the duration of their infection or any counselling received from the general practitioner. The need for specific treatment was reported by 59.8%. A demand for more detailed information about hepatitis C virus was expressed by 89.9% of patients.

Conclusions  Hepatitis C virus changes all aspects of lifestyle and psychological status. The patients’ strong demand for more information suggests that counselling and educational programmes must be an integral part of the activities of both the general practitioner and the specialist.
Effect of anti‐viral therapy for occult hepatitis C virus infection
Authors: PARDO M. , LÓPEZ‐ALCOROCHO J. M. , CASTILLO I. , RODRÍGUEZ‐IÑIGO E. , PEREZ‐MOTA A. , CARREÑO V.
Published: March 2006

Background  Occult hepatitis C virus infection is defined by the presence of hepatitis C virus‐RNA in liver but with undetectable anti‐hepatitis C virus and serum viral RNA.

Aim  To study the response to anti‐viral therapy in occult hepatitis C virus infection to assess the pathogenic effect of occult hepatitis C virus.

Methods  Ten patients with occult hepatitis C virus infection were treated with pegylated‐interferon plus ribavirin for 24 weeks and were followed‐up 24 weeks after therapy. All patients had abnormal alanine aminotransferase, hepatitis C virus‐RNA positive in peripheral blood mononuclear cells and liver necroinflammation.

Results  At the end of treatment and follow‐up, the percentage of patients with normal alanine aminotransferase was 80% (95% CI: 48–96%) and 60% (95% CI: 31–84%) respectively, and hepatitis C virus‐RNA in peripheral blood mononuclear cells was negative in 80% (95% CI: 48–96%) and 70% (95% CI: 40–90%) cases. At the end of follow‐up sustained response was observed in 30% (95% CI: 11–61%) of cases. Five patients underwent a second liver biopsy. In all cases, liver hepatitis C virus‐RNA persisted, although hepatitis C virus‐RNA load was significantly lower (3.2 × 104 ± 5.1 × 104 copies/μg RNA) than in the basal biopsy (2.4 × 105 ± 3.8 × 105 copies/μg RNA); (P = 0.043). Necroinflammation and fibrosis decreased in three cases.

Conclusion  The biochemical, virological and histological response to therapy achieved in patients with occult hepatitis C virus infection demonstrates the pathologic effects of occult hepatitis C virus.
Evaluating upwelling estimates off the west coasts of North and South America
Authors: PICKETT MARK H. , SCHWING FRANKLIN B.
Published: March 2006

Both low‐ and high‐resolution studies of wind and upwelling were conducted off the west coasts of North and South America between August 1999 and December 2001. For the low‐resolution study, done at 25 regional sites spanning both coasts, weekly mean winds were calculated from satellite measurements, from geostrophic estimates, and from an operational 100‐km‐resolution global atmospheric model. The satellite‐measured winds, used as the reference, showed that the coastal regions of both North and South America were divided into fairly uniform climatic domains located at higher, mid, and lower latitudes. All three weekly‐mean wind data sets were compared at each of the 25 sites, and then used to estimate upwelling based on the method employed by NOAA's Pacific Fisheries Environmental Laboratory. Within each of the wind domains, model‐derived wind and upwelling estimates agreed with satellite‐derived values better than those from geostrophic‐derived estimates. To investigate variability between the regional sites, a 9‐km‐resolution atmospheric model was run for an area off California which spanned four of the regional sites. This high‐resolution model, verified with satellite measurements, revealed jets of wind curving and intensifying around coastal promontories. These near‐shore wind jets, undetected in the global model, resulted in strong upwelling bands on the order of 50 km alongshore by 20 km offshore. These bands are critical for calculating local upwelling. Our results indicate that regional upwelling estimates for fisheries research can be improved by replacing geostrophic estimates of winds with those from a global atmospheric model. For localized coastal upwelling estimates, however, models with resolution an order of magnitude higher are required.
Antibodies targeting p63 react specifically in the cytoplasm of breast epithelial cells exhibiting secretory differentiation
Authors: Bratthauer G L , Saenger J S , Strauss B L
Published: March 2006

Aims : The nuclear detection of p63 in myoepithelial cells of the breast has been useful in identifying possibly invasive carcinomas. While examining myoepithelial cells for p63 a very strong cytoplasmic reaction product was noted in secretory cells. The aim was to determine whether this reaction is specific for p63 and indicative of all breast secretory cells.

Methods : Thirty breast specimens were tested immunohistochemically for p63 protein. These included seven with benign secretory changes, 10 secretory carcinomas (nine invasive), one microglandular adenosis, three lobular neoplasias, four invasive ductal carcinomas, three clear cell carcinomas, one squamous cell carcinoma and one mucinous carcinoma.

Results : Only cells exhibiting secretory changes or secretory carcinoma were cytoplasmically reactive for p63. The positive reaction was also present as an intraluminal secretory product. This reaction was not seen in cells undergoing apocrine differentiation or in other cells containing secretory vacuoles.

Conclusions : Cells with secretory changes contain p63 protein or an antigenic equivalent. The detection of p63 protein continues to have considerable value for the identification of myoepithelial cells and thus the determination of invasion, but will also have value in the determination of secretory carcinomas of the breast and in understanding their development.
Angiogenic potential of ductal carcinoma in situ (DCIS) of human breast
Authors: Vogl G , Dietze O , Hauser‐Kronberger C
Published: March 2006

Aims : Comedo carcinoma is generally regarded as the subtype of ductal carcinoma in situ (DCIS) most likely to progress to invasive carcinoma. Increased angiogenesis could be associated with an enhanced risk of progression and might therefore be a marker of poor prognosis, as can be demonstrated for invasive breast tumours. Therefore, the present study investigates the correlations between the expression of oncoproteins (HER2, HER1/EGFR), angiogenic growth factors (VEGF and PD‐ECGF/TP) and microvessel density (MVD) in DCIS.

Methods and results : Forty‐six breast cancer specimens of DCIS were tested immunohistochemically for the expression of angiogenic factors and oncoproteins. Different vascular distribution patterns of DCIS were examined semiquantitatively. Our results showed a significantly inverse correlation between HER1/EGFR and comedo‐type DCIS (P = 0.048), but HER1/EGFR expression seemed to be independent of HER2 overexpression. VEGF expression was significantly associated with endoglin expression (P = 0.031) and the cuffing phenomenon (P = 0.017).

Conclusions : The significantly inverse correlation between HER1/EGFR and comedo‐type DCIS and the observation that VEGF and the other angiogenic factors tested are independent of HER2 overexpression, suggest that progression of comedo‐type DCIS and angiogenesis in breast carcinoma are not regulated via the HER1/EGFR or HER2 pathway.
Decreased annexin I expression in prostatic adenocarcinoma and in high‐grade prostatic intraepithelial neoplasia
Authors: Patton K T , Chen H M , Joseph L , Yang X J
Published: March 2006

Aims : To analyse annexin I expression in prostatic carcinoma. Annexin I belongs to a family of structurally related calcium and phospholipid‐binding proteins implicated in signal transduction, DNA replication, cell proliferation and apoptosis. The decreased expression of annexin I, II and VII proteins has been reported in different types of cancer.

Methods and results : Using immunohistochemistry, we analysed annexin I expression in 77 cases of prostatic adenocarcinoma (Gleason score 6, N = 40; Gleason scores 7–8, N = 27; and Gleason scores 9–10, N = 10) and high‐grade prostatic intraepithelial neoplasia (PIN, N = 50). Immunoreactivity of annexin I in tumour cells was evaluated as negative (< 5% of cells), focally positive (5–25% of cells) or positive (> 25% of cells). In contrast to positive staining in adjacent benign prostatic epithelium, annexin I expression was decreased (focally positive) in 76% of cases of high‐grade PIN (P < 0.0001) and was decreased or absent in 81% of prostatic adenocarcinomas (P < 0.0001). Annexin I expression in all higher grade tumours (Gleason scores 7–10) was only focally positive or absent.

Conclusions : Expression of annexin I inversely correlates with the increasing histological grade of prostatic adenocarcinoma. By showing a progressive loss of annexin I expression in high‐grade PIN, intermediate‐grade and high‐grade cancer, our findings suggest that the loss of annexin I expression occurs early in prostatic tumorigenesis and becomes more prominent throughout tumour progression. The loss of expression of annexin I may serve as a useful marker of prostate cancer development and progression.
Seasonal life‐history models for the integrated management of the invasive weed nodding thistle Carduus nutans in Australia
Authors: SHEA KATRIONA , SHEPPARD ANDY , WOODBURN TIM
Published: March 2006

It is widely accepted that combining several control options into integrated pest management strategies is the most effective way to provide long‐term suppression of pest populations. However, full factorial field trials of all single and integrated control options for a pest species would be prohibitively expensive and time consuming. Methods to allow triage of the huge array of management options would be of great value in streamlining the decision‐making process.

We present a seasonally structured, individual‐based model, specifically designed to compare and rank detailed management strategies for a noxious pasture weed. The model structure is determined in part by the demographic data available, and in part by the management options under consideration. The case study is for nodding thistle Carduus nutans in Australia. Eight years of demographic data, for more than 8000 mapped plants, were used to parameterize the model, which is age‐, size‐ and density‐dependent and incorporates individual variation. Management options for this plant include three biocontrol agents, as well as conventional herbicide and grazing management strategies, which can be used alone or in a variety of combinations. Data on management impacts were drawn from multiple studies.

The model predicts that the root‐crown weevil Trichosirocalus mortadelo will more effectively suppress weed populations than either of the two flowerhead‐feeding insect agents Urophora solstitialis and Rhinocyllus conicus. Crash grazing (up to four times the regular grazing pressure) in any single season, or when most effectively applied across spring and summer, is less effective than T. mortadelo, while combinations of crash grazing and biocontrol agents strongly decrease weed population persistence. However, lethal herbicide is the best single strategy, while spring spray–grazing (a combination of non‐lethal herbicide and grazing) is the best integrated weed management strategy.

Synthesis and applications. The model is structured by, and serves to integrate, available information on demography and management from multiple sources. The subset of strategies that performed well forms the focus for fewer, more thorough, field trials. The decision‐making approach illustrated here is also applicable to any species and any array of management options.
Genetic and karyotypic structure in the shrews of the Sorex araneus group: are they independent?
Authors: BASSET P. , YANNIC G. , HAUSSER J.
Published: March 2006

The species of the common shrew (Sorex araneus) group are morphologically very similar but exhibit high levels of karyotypic variation. Here we used genetic variation at 10 microsatellite markers in a data set of 212 individuals mostly sampled in the western Alps and composed of five karyotypic taxa (Sorex coronatus, Sorex antinorii and the S. araneus chromosome races Cordon, Bretolet and Vaud) to investigate the concordance between genetic and karyotypic structure. Bayesian analysis confirmed the taxonomic status of the three sampled species since individuals consistently grouped according to their taxonomical status. However, introgression can still be detected between S. antinorii and the race Cordon of S. araneus. This observation is consistent with the expected low karyotypic complexity of hybrids between these two taxa. Geographically based cryptic substructure was discovered within S. antinorii, a pattern consistent with the different postglaciation recolonization routes of this species. Additionally, we detected two genetic groups within S. araneus notwithstanding the presence of three chromosome races. This pattern can be explained by the probable hybrid status of the Bretolet race but also suggests a relatively low impact of chromosomal differences on genetic structure compared to historical factors. Finally, we propose that the current data set (available at http://www.unil.ch/dee/page7010_en.html#1) could be used as a reference by those wanting to identify Sorex individuals sampled in the western Alps.
Virulence spectrum of Puccinia hordei in barley production systems in Ethiopia
Authors: Woldeab G. , Fininsa C. , Singh H. , Yuen J.
Published: March 2006

Barley leaf rust caused by Puccinia hordei is an important disease of barley in Ethiopia. In the 2003 and 2004 cropping seasons, surveys of P. hordei were conducted on fields in the main rainy, residual moisture and short rainy season‐barley production systems. A total of 381 isolates were analysed on 12 barley differential hosts carrying different Rph resistance genes (Rph1–Rph12). Based on infection phenotypes on leaf rust (Rph) resistance genes, seven pathotypes were identified, namely ETPh7611, ETPh7631, ETPh6611, ETPh7651, ETPh7671, ETPh7653 and ETPh7633, with frequencies of 63·0, 21·5, 6·8, 2·9, 2·6, 2·1 and 1·2%, respectively. ETPh7611 and ETPh7631 were the most common pathotypes found in all the surveyed areas of the three production systems. ETPh7653 was found in the small rainy season production system only. ETPh7671, ETPh7653 and ETPh7633 were the most virulent, but the least frequent, pathotypes. All isolates were virulent on resistance genes Rph1, Rph4, Rph8, Rph9, Rph11 and Rph12. Virulence against Rph3 and Rph7 was absent. Genes Rph2, Rph6+2, Rph5 and Rph10 were effective against 96·3, 88·9, 65 and 2·4% of the rust isolates tested, respectively.
Diversity of pathogenic Fusarium populations associated with asparagus roots in decline soils in Spain and the UK
Authors: Wong J. Y. , Jeffries P.
Published: March 2006

Asparagus decline is a disease associated with several species of Fusarium. In order to assess the relative significance of causative species, single‐stranded conformational polymorphism (SSCP) analysis of the ITS2 (internal transcribed sequence) region of the ribosomal DNA was used to rapidly and objectively identify the fusarial populations associated with the roots of two intensively sampled asparagus crops, one in the UK and the other in Spain. Over 360 fusarial isolates were obtained from fields showing symptoms of asparagus decline, and most were easily differentiated by SSCP into four principal species, F. oxysporum f. sp. asparagi, F. proliferatum, F. redolens and F. solani. Fusarium oxysporum f. sp. asparagi (Foa) was most frequently isolated from the UK site (69%), whilst Foa and F. proliferatum were found in similar proportions overall (40 and 39%, respectively) from the Spanish site, although individual fields showed considerable intraregional variation. Other minor populations, such as F. culmorum, were also found. Most isolates were highly pathogenic to asparagus in vitro, although F. solani isolates comprised both pathogenic and nonpathogenic populations. Two populations of Foa were distinguished by a single ITS2 base transition, and the dominance of these two populations differed between Europe and the USA. Fusarium proliferatum was more abundant in Spain than in the UK. Phylogenetic analysis using EF1α sequences indicated that isolates of F. oxysporum pathogenic to asparagus are spread across a number of clades within the species complex, supporting the hypothesis that pathogenicity to asparagus in this species is a relatively unspecialized trait.
Histological investigation of stripe rust (Puccinia striiformis f.sp. tritici) development in resistant and susceptible wheat cultivars
Authors: Moldenhauer J. , Moerschbacher B. M. , Van Der Westhuizen A. J.
Published: March 2006

The wheat cultivar Kariega expresses complete adult plant resistance against stripe rust, whereas cv. Avocet S is susceptible. Using confocal laser scanning microscopy, initial fungal penetration into flag leaves was identical in both cultivars, with directional germ‐tube growth towards stomata that were penetrated without the formation of an appressorium, followed by differentiation of a substomatal vesicle, infection hyphae, haustorial mother cells and haustoria. During the following 4 days, further fungal development occurred more quickly in the resistant than in the susceptible cultivar. However, by 7 days postinoculation (dpi) the situation changed, with exponential growth of the pathogen occurring only in the susceptible line. Induced cellular lignification, a typical defence reaction of cereals, was observed at 4 dpi in the resistant cultivar, and 2 days later lignified tissue completely surrounded the fungal colonies. In the susceptible cultivar, isolated lignified host cells occurred at 6 dpi, and long, unbranched fungal hyphae outgrowing the resistance reaction were observed.
Recombinant factor VIIa reduces transfusion requirements in liver transplant patients with high MELD scores
Authors: Niemann C. U. , Behrends M. , Quan D. , Eilers H. , Gropper M. A. , Roberts J. P. , Hirose R.
Published: March 2006

summary.  Patients undergoing orthotopic liver transplantation (OLT) often experience significant coagulopathy and remain at risk for excessive blood loss and massive transfusion. The ability of recombinant factor VIIa (rFVIIa) to reduce transfusion requirements during OLT has not been well established.

This retrospective study investigates whether rFVIIa reduces transfusion requirements in liver transplant patients with a significantly prolonged prothrombin time (PT) and a model of end‐stage liver disease (MELD) score of >20. Eleven patients received a single dose of rFVIIa (58 ± 18 μg kg−1) at the time of incision. This group was matched with a selected control group that fulfilled all of the inclusion/exclusion criteria.

Patient characteristics, pre‐operative PT, HCT, PLT and MELD were identical between groups. Prophylactic application of rFVIIA reduced packed red blood cells (3·9 ± 2·6 versus 6·9 ± 2·3 U, P = 0·01) and fresh‐frozen plasma (FFP) (12·6 ± 6 versus 19·8 ± 7 U, P = 0·018) transfusion requirements when compared with the control group. FFP administration in the first 24 h after surgery was also significantly less in the rVIIa group when compared with the control group (388 ± 385 versus 1225 ± 701 mL, P = 0·003). Hospital stay following transplantation tended to be shorter in the rFVIIa group, albeit statistical significance was not achieved (11 ± 7·3 versus 7·9 ± 2·7, P = 0·2). All but one patient in the control group survived for 30 days after transplantation.

In a selected group of patients with prolonged PT and high MELD score, the prophylactic application of rFVIIa at the start of the OLT may reduce perioperative transfusion requirements.
Asthma during the primary school ages – prevalence, remission and the impact of allergic sensitization
Authors: Bäcklund A. B. , Perzanowski M. S. , Platts‐Mills T. , Sandström T. , Lundbäck B. , Rönmark E.
Published: March 2006

Background:  Childhood is the most important time for asthma development. The aims of this study were to study changes in prevalence of asthma and wheeze, remission of asthma and changes in risk factor pattern from age 7–8 to age 11–12 in a cohort of school children.

Methods:  In 1996, 3525 children aged 7–8 years in northern Sweden were invited to participate in a parental expanded ISAAC questionnaire survey. The cohort has been followed prospectively with yearly follow‐ups to age 11–12, with a 97% yearly response rate. Skin prick tests were conducted at age 7–8 and 11–12.

Results:  The prevalence of physician‐diagnosed asthma increased from 5.7% at age 7–8 to 7.7% at age 11–12. Life‐time prevalence of wheeze was 34.7% at age 11–12. The remission of asthma was 10% yearly and inversely related to allergic sensitization. Relapses were common, and remission persisting throughout the observation period was 5% yearly. Allergic sensitization was associated with current asthma at age 7–8 [adjusted odds ratio (OR) 4.9 (95% confidence interval (CI) 3.3–7.3)] and when the children were 4 years older [OR 5.6 (3.9–8.2)]. A family history of asthma was associated with current asthma at age 7–8 [OR 3.0 (2.1–4.5)] and 11–12 (OR 2.8 [2.0–3.9]). Ever having lived with a cat was significantly negatively associated with current asthma.

Conclusions:  The prevalence of asthma increased continuously during the primary school ages. Among several significant risk factors, allergic sensitization and a family history of asthma were the most important. With increasing age many known risk factors lost significance. Remission was inversely related to allergic sensitization.
Type‐IV sensitization profile of individuals with atopic eczema: results from the Information Network of Departments of Dermatology (IVDK) and the German Contact Dermatitis Research Group (DKG)
Authors: Heine G. , Schnuch A. , Uter W. , Worm M.
Published: March 2006

The role of atopic eczema (AE) as risk factor for the development of allergic contact dermatitis is discussed controversially, as well as its influence on patch test results due to increased irritability. In this study, we analysed the pattern of positive patch test results to most frequent contact allergens in patients with AE (n = 9020) and age matched nonatopic (n = 15 263) individuals. The pattern and the frequencies of the observed sensitizations did not differ greatly from nonatopic individuals. Bufexamac is an exception: in AE patients sensitization is observed three times more often. For the other substances tested only minor differences were detected. Moreover, the frequencies of single, double or polyvalent sensitizations were nearly identical between the two groups. The analysis of the anatomical sites of dermatitis shows differences between the groups: in AE patients, the face (7.2%) and hand dermatitis (6.6%) was more common, and leg dermatitis (4.0%) less common. Analysis of occupation, suspected allergen source, and accompanying factors revealed no major differences between the both groups. Conclusion: The chronic and long‐term exposure to external drugs and emollients presumably carries a risk for sensitization against specific contact allergens in AE patients. However, the sensitization of contact allergens differs surprisingly little between patients with or without AE.
Gas cooking, kitchen ventilation, and asthma, allergic symptoms and sensitization in young children – the PIAMA study
Authors: Willers S. M. , Brunekreef B. , Oldenwening M. , Smit H. A. , Kerkhof M. , De Vries H. , Gerritsen J. , De Jongste J. C.
Published: March 2006

Background:  Several studies reported inconsistent associations between using gas for cooking and respiratory symptoms or lung function in children. Kitchen ventilation characteristics may modify the relationship between gas cooking and respiratory health. The aim of this study was to investigate the effect of kitchen ventilation (while cooking) on the relationship between gas cooking, combustion product dispersal, and respiratory and allergic outcomes in children.

Methods:  Data on respiratory and allergic symptoms and diagnoses were collected by yearly questionnaires in a population of over 3000 children participating in a birth cohort study on development of allergy and asthma. At 4 years of age, a sub‐sample of 647 children provided blood samples for antibody testing. Data on gas cooking and kitchen ventilation were collected when the children were 5 years old. Based on these data a model was constructed to determine the chance of accumulation of combustion products (CACP) in the kitchen.

Results:  No relationship was found between gas cooking and any of the respiratory or allergy outcomes except nasal symptoms. The overall results did not change when the ‘CACP’ was used as exposure variable instead, while the association for nasal symptoms decreased to borderline significance.

Conclusion:  Our results suggest that gas cooking per se is associated with nasal symptoms in young children and not with the other respiratory symptoms that were investigated. Taking kitchen ventilation characteristics into account did not lead to different conclusions in this population where, according to the classification system, the majority of households using gas for cooking have insufficient kitchen ventilation.
Attenuation of human lung mast cell degranulation by bronchial epithelium
Authors: Yang W. , Wardlaw A. J. , Bradding P.
Published: March 2006

Background:  Human lung mast cells (HLMC) lie in close proximity to the bronchial epithelium in asthma and adhere with high affinity to bronchial epithelial monolayers in vitro. We investigated the consequences of this adhesive interaction on HLMC activation in response to FcɛRI cross‐linking.

Methods:  Human lung mast cells were cultured with the bronchial epithelial cell line BEAS‐2B or plastic control for either 30 min or 16 h and then activated with anti‐IgE. Histamine was measured by radioenzymatic assay.

Results:  After co‐culture for 30 min, IgE‐dependent histamine release from HLMC was identical on both BEAS‐2B and plastic. After 16 h of co‐culture, there was a marked decrease in constitutive and IgE‐dependent histamine release from HLMC cultured on BEAS‐2B compared with those cultured on plastic or fibronectin. In contrast, the Ca2+/ATPase inhibitor thapsigargin produced concentration‐dependent histamine release that was significantly increased on BEAS‐2B compared with plastic. IgE‐dependent degranulation was not significantly affected by BEAS‐2B‐conditioned medium.

Conclusions:  BEAS‐2B bronchial epithelial cells attenuate IgE‐dependent but not thapsigargin‐induced histamine release from HLMC. The differential effect with anti‐IgE compared with thapsigargin suggests that the mechanism includes interference with the proximal FcɛRI signalling pathway.
Diesel exhaust particles enhance T‐cell activation in severe asthmatics
Authors: Mamessier E. , Nieves A. , Vervloet D. , Magnan A.
Published: March 2006

Prevalence of asthma is increasing in westernized countries. Epidemiological studies showed the impact of traffic pollution on the triggering of asthma symptoms and exacerbations, and this effect is mainly attributed to the polycyclic aromatic hydrocarbon core of diesel exhaust particles (DEP). However, although DEP induce IgE synthesis, little is known of their role on T‐cell activation, the main cells orchestrating asthma inflammation. We assessed the effect of DEP on T‐cell activation in severe uncontrolled asthmatics during (n = 13) and outside (n = 19) exacerbations. Results were compared with data obtained in healthy controls (n = 14). Peripheral blood mononuclear cells were cultured in the presence of low‐dose DEP. T‐cell activation markers, CD69 and CD25, interleukin‐4 (IL‐4) and interferon (IFN)‐γ production and T‐cell proliferation were assessed by flow cytometry. DEP exposure increased the proportion of CD3+CD69+ T cells in all subjects. The proportion of CD25+ T cells increased under DEP stimulation in the exacerbation group only. IFN‐γ‐ and IL‐4‐producing T cells increased in both asthmatic groups, especially during exacerbations, but not in controls. This effect was more pronounced for IL‐4. In response to DEP stimulation, T‐cell proliferation increased in higher proportion in asthmatics compared with controls. These results show that DEP activate T cells in asthmatics only, with a higher effect during exacerbations. This is in keeping with epidemiological data which demonstrated that DEP trigger respiratory symptoms in asthmatics but not in controls. The higher effect of DEP in exacerbated asthmatics suggests that uncontrolled asthma is a risk factor for aggravation under exposure to traffic pollutants.
Confirmation of association ofIL‐15with pediatric asthma and comparison of different controls
Authors: Bierbaum S. , Nickel R. , Zitnik S. , Ahlert I. , Lau S. , Deichmann K. A. , Wahn U. , Heinzmann A.
Published: March 2006

Background: Interleukin (IL)‐15 is an important mediator in chronic inflammatory diseases. Recently, we have described the association ofIL‐15haplotypes with bronchial asthma. Asthma genetics is highly complex – about every second candidate gene is not confirmed in consecutive studies. We were interested in whether association of asthma withIL‐15holds in a second population. Furthermore, we sought to investigate the effect of different controls.

Methods: FiveIL‐15polymorphisms were genotyped on the German Multicenter Allergy Study (MAS) cohort consisting of 886 children who were followed up from birth to 10 years of age. At 10 years of age, 96 were found to be asthmatic. MAS children who never had any wheezing symptoms (n = 576), who were never diagnosed with asthma (n = 790) and 129 super controls who had never had any atopic disorder were used as controls. Finally, 270 randomly chosen adults served as controls.

Results: Association was confirmed with single polymorphism and haplotypes. The super controls showed the highest difference to the asthmatics regarding haplotype frequencies. However, the effect escaped statistical significance, most likely because of the small sample size.

Conclusion: Association ofIL‐15with asthma was confirmed. Although super controls might be the most suitable, more numbers are needed. This might hamper the value of these controls especially when investigating common diseases.
Anti‐inflammatory effects of once daily low dose inhaled ciclesonide in mild to moderate asthmatic patients
Authors: Wilson A. M. , Duong M. , Pratt B. , Dolovich M. , O'Byrne P. M.
Published: March 2006

Background:  Ciclesonide exhibits clinical efficacy at 160 μg (ex‐actuator) once daily but the anti‐inflammatory effects at this dose are not known. We wished to know whether 4 weeks therapy with ciclesonide pMDI 160 μg once daily in the morning exhibited significant anti‐inflammatory effects.

Methods:  Seventeen patients with mild persistent asthma (FEV1 3.35 l) were recruited into a double‐blind placebo‐controlled randomized crossover study. Measurements were made after ciclesonide and placebo treatment as well as after run‐in and washout periods, for adenosine monophosphate (AMP) bronchial challenge (primary variable), exhaled nitric oxide (NO) and induced sputum (in a subgroup).

Results:  The mean (SEM) AMP bronchial challenge PC20 following ciclesonide (140 (63) mg/ml) was significantly (P < 0.001) increased compared with placebo (17 (8) mg/ml), run‐in (13 (5) mg/ml) and washout (9 (3) mg/ml) periods. This amounted to an eightfold (CI: 5.3–12.0) for ciclesonide vs placebo. Likewise, there were significant improvements in exhaled NO levels and a significant reduction in induced sputum eosinophil cell counts.

Conclusion:  We have shown that inhaled ciclesonide given at 160 μg once daily in the morning exhibits significant anti‐inflammatory effects that are in keeping with the previously described clinical effects.
Surfactant protein levels in bronchoalveolar lavage after segmental allergen challenge in patients with asthma
Authors: Erpenbeck V. J. , Schmidt R. , Günther A. , Krug N. , Hohlfeld J. M.
Published: March 2006

Background:  Allergic asthma is associated with airway inflammation and dysfunction of pulmonary surfactant. Because surfactant proteins (SP) account for immunomodulatory functions as well as biophysical functions, we hypothesized that the allergic response in asthma might be accompanied by a dysregulation of SPs.

Methods:  We measured levels of SP‐A, SP‐B, SP‐C and SP‐D by enzyme‐linked immunosorbent assay in bronchoalveolar lavage (BAL) fluid of 23 asthma patients and 10 healthy control subjects under well‐controlled conditions before and 24 h after segmental allergen provocation. These data were related to surfactant function, Th2 cytokine levels in BAL fluid and to the degree of eosinophilic inflammation.

Results:  In patients with asthma, allergen challenge increased BAL levels of SP‐B, SP‐C and SP‐D while SP‐A was decreased. For SP‐B and SP‐D, a moderate increase was also observed after saline challenge. In contrast, no alterations were observed in healthy control subjects. Levels of SP‐B and SP‐C in asthmatics correlated with the ratio of small to large surfactant aggregates (SA/LA ratio) and correlated negatively with BAL surface activity. Furthermore, increased SP‐C but not SP‐B levels after allergen challenge correlated with eosinophil numbers, interleukin (IL)‐5, and IL‐13 in BAL while increased SP‐D levels only correlated with eosinophil numbers.

Conclusions:  This study demonstrates significant alterations of all SPs in BAL fluid after allergen challenge of which SP‐C was most closely related to surfactant dysfunction and the degree of the allergic inflammation.
Susceptibility loci for atopic dermatitis on chromosome 21 in a Swedish population
Authors: Bu L. M. , Bradley M. , Söderhäll C. , Wahlgren C. F. , Kockum I. , Nordenskjold M.
Published: March 2006

Background:  Atopic dermatitis (AD) is a hereditary, pruritic, chronic, relapsing, inflammatory skin disease resulting from multiplex interactions between genes and environmental factors. We have previously found several loci showing suggestive linkage on chromosomes 3q14, 13q14, 15q14‐15 and 17q21, and weaker linkage to chromosomes 1p32, 4q24‐26 and 21q21 in 109 Swedish families.

Methods:  In order to confirm the linkage to chromosome 21, we carried out a replication linkage analysis with additional microsatellite markers on chromosome 21 in another set of 295 families.

Results:  In the extended material, the Z‐score was 2.40 (P < 7.4 × 10−4) in the region 21q21 for a semi‐quantitative variable measurement; the severity of AD. When combining the two data sets into 404 families and stratifying according to asthma status, suggestive linkage was found only in the group of AD patients who also had asthma (Z‐score 2.45, P < 7.4 × 10−4 and 2.69, P < 7.4 × 10−4) in two different regions.

Conclusions:  Our results suggest that 21q21 could contain a susceptibility gene modulating the severity of AD especially in combination with asthma.
Modulation of the atopy patch test: tacrolimus 0.1% compared with triamcinolone acetonide 0.1%
Authors: Oldhoff J. M. , Knol E. F. , Laaper‐Ertmann M. , Bruijnzeel‐Koomen C. A. F. M. , de Bruin‐Weller M. S.
Published: March 2006

Background:  The atopy patch test (APT) is an in vivo model to study the induction of eczema by inhalant allergens in atopic dermatitis patients. We studied the effect of pretreatment with topical tacrolimus 0.1% on APT in nonlesional skin of patients with atopic dermatitis.

Methods:  Nonlesional skin of the back of patients with atopic dermatitis (n = 8) was treated once daily for 3 weeks with tacrolimus 0.1% ointment. Cetomacrogol ointment (placebo) was used as a negative control and triamcinolone acetonide 0.1% ointment as positive control. Twenty‐four hours after the last APT application, samples were taken from the three treated areas (t = 0 and 24 h) for immunohistochemical analysis.

Results:  Pretreatment with tacrolimus ointment did not suppress nonlesional skin infiltrate, in contrast to triamcinolone acetonide. Furthermore, tacrolimus did not inhibit the induction of the APT macroscopically (t = 24 h). An equal influx of T cells, eosinophils, dendritic cells, CD64+ and FcɛRI‐positive cells was present compared with placebo. Only CD36+ and CD68‐positive cells were inhibited compared with placebo. All cell types were significantly inhibited in triamcinolone acetonide‐treated sites compared with placebo.

Conclusions:  Pretreatment with tacrolimus 0.1% ointment does not inhibit the APT reaction in patients with atopic dermatitis.
The performance of a component‐based allergen‐microarray in clinical practice
Authors: Wöhrl S. , Vigl K. , Zehetmayer S. , Hiller R. , Jarisch R. , Prinz M. , Stingl G. , Kopp T.
Published: March 2006

Background:  Currently, the diagnosis of IgE‐mediated allergy is based on allergen‐specific history and diagnostic procedures using natural allergen extracts for in vivo and in vitro tests.

Objective:  The aim of the study was to comparatively analyse a new component‐based allergen‐microarray and the ‘quasi‐standard’ ImmunoCAP® for their clinical relevance in patients with allergic rhinoconjunctivitis to five aeroallergens [house dust mite (HDM), cat dander, birch, grass and mugwort pollen] in a prospective, double‐centre study.

Methods:  We enrolled 120 subjects at the two study centres. Allergic patients were defined as having an allergen‐specific history plus a concomitant positive skin‐prick test (SPT) to natural allergen extracts and specific serum IgE was measured by both methods. Each allergen was analysed separately.

Results:  The microarray performed equally well in receiver‐operating characteristic curve (ROC) analyses when compared with the CAP in cat (23 allergic vs 97 non‐allergic, ROC area under the curve microarray 0.950 vs CAP 0.894, P = 0.211), birch (31/89, 0.908 vs 0.878, P = 0.483) and grass pollen (47/73, 0.923 vs 0.915, P = 0.770). It was slightly less sensitive in HDM‐allergic subjects (26 allergic vs 94 non‐allergic, ROC area microarray 0.808 vs CAP 0.911, P = 0.053) and displayed a reduced sensitivity in the mugwort pollen‐allergic patients (17/103, 0.723 vs 0.879, P = 0.032).

Conclusions:  Component‐based testing and the whole‐allergen CAP are equally relevant in the diagnosis of grass‐, birch‐ and cat‐allergic patients. Although slightly less sensitive, the microarray is sufficient for the diagnosis of HDM‐allergic patients, but needs alternative and/or additional components for detecting mugwort allergy.
Nonlinear relations between house dust mite allergen levels and mite sensitization in farm and nonfarm children
Authors: Schram‐Bijkerk D. , Doekes G. , Boeve M. , Douwes J. , Riedler J. , Üblagger E. , Von Mutius E. , Budde J. , Pershagen G. , Van Hage M. , Wickman M. , Braun‐Fahrländer C. , Waser M. , Brunekreef B. ,   the PARSIFAL study group
Published: March 2006

Background:  Low sensitization rates to common allergens have been observed in farm children, which might be due to high exposure to microbial agents. It is not known how microbial agents modify the association between specific allergen exposure and sensitization.

Objective:  To examine the relations between house dust mite allergen exposure and mite sensitization in farm and nonfarm children and to assess the effects of microbial agents levels on this association.

Methods:  Major mite allergens of Dermatophagoides pteronyssinus (Der p 1) and Dermatophagoides farinae (Der f 1), endotoxin, β(1,3)‐glucans and fungal extracellular polysaccharides were measured in mattress dust of 402 children participating in a cross‐sectional study in five European countries. Mite allergen (Der p 1 + Der f 1) levels were divided into tertiles with cut‐offs 1.4 and 10.4 μg/g. Sensitization was assessed by measurement of allergen‐specific immunoglobulin E against house dust mite.

Results:  Prevalence ratios of mite sensitization for medium and high when compared with low mite allergen levels were 3.1 [1.7–5.7] and 1.4 [0.7–2.8] respectively. Highest mite sensitization rates at intermediate exposure levels were consistently observed across country (except for Sweden) and in both farm and nonfarm children. The shape of the dose–response curve was similar for above and below median mattress microbial agent levels, but the ‘sensitization peak’ appeared to be lower for above median levels.

Conclusions:  Our data suggest a bell‐shaped dose–response relationship between mite allergen exposure and sensitization to mite allergens. In populations with high microbial agent levels and low sensitization rates, the curve is shifted down.
Local oropharyngeal side effects of inhaled corticosteroids in patients with asthma
Authors: Buhl R.
Published: March 2006

The widespread use of inhaled corticosteroids (ICS) for the treatment of persistent asthma, although highly effective, may be associated with both systemic and local side effects. Systemic side effects of ICS have been extensively studied. In contrast, relatively few studies have been performed to specifically evaluate local side effects of ICS. These local side effects – including oropharyngeal candidiasis, dysphonia, pharyngitis, and cough – are generally viewed as minor complications of therapy. However, they can be clinically significant, affect patient quality of life, hinder compliance with therapy, and mask symptoms of more serious disease. Local side effects result from deposition of an active ICS in the oropharynx during administration of the drug. Numerous factors can influence the proportion of an inhaled dose that is deposited in the oropharyngeal cavity, including the ICS formulation, type of delivery system, and patient compliance with administration instructions. Therefore, the incidence of local side effects can vary widely. The goal in developing a new ICS is to include key pharmacologic characteristics that reduce oropharyngeal exposure to active drug while maintaining efficacy comparable with currently available ICS.