bluuebunny/crossref_metadata_2025 huggingface dataset:
Allergic contact dermatitis from hair dye and development of lichen simplex chronicus
Authors: Chey Won Young , Kim Kyung Lok , Yoo Tae‐Yeon , Lee Ai‐Young
Published: August 2004

Those who dye their hair frequently manifest allergic contact dermatitis (ACD) from p‐phenylenediamine (PPD)‐containing hair dye. PPD is known to be the most frequent sensitizer in hair dye, but there has been no documentation of this sensitizer having a role in chronic dermatologic conditions. Our department experienced a case of a 62‐year‐old woman with lichen simplex chronicus (LSC), who complained of aggravation after hair dyeing and made such an association. We conducted a prospective and retrospective study to further evaluate the clinical associations between the two. In our prospective study, patch testing was performed in selected patients who regularly carried out hair dyeing and also had clinical manifestations of LSC. Also a retrospective examination was conducted in cases where patch testing had been performed with PPD in the past for suspected ACD and further selected cases with concurrent LSC and/or other neurodermatitis. 11 and 14 patients in our prospective and retrospective study, respectively, presented with both LSC and positive findings to PPD. 5 (45.5%) and 4 (28.6%) patients in our prospective and retrospective study showed clinical relevance from clinical improvement after stopping use and rechallenge. We report several cases of patients diagnosed as having LSC and/or prurigo nodularis who showed clinical improvement after discontinuing the use of hair dye. The suggestion can therefore be made that hair dye could be a possible aetiologic agent causing LSC in those using hair dyes.
The validity of the Mathias criteria for establishing occupational causation and aggravation of contact dermatitis
Authors: Ingber Arieh , Merims Sharon
Published: August 2004

Mathias proposed 7 criteria for establishing occupational causation and aggravation of contact dermatitis (Mathias, J Am Acad Dermatol 1989, 20, 842–848). 4 of the 7 criteria must be positive to conclude occupational dermatitis. In order to evaluate the validity of these criteria, we re‐examined 19 patients (17 male and 2 female) with contact dermatitis, who had given a positive answer to at least 4 of the criteria and had either exchanged their workplace or stopped working. We re‐evaluated them, 2–5 years later, for the presence of contact dermatitis. 14 of 19 patients (74%) reported that their dermatitis had cleared after they had left their previous workplace. Only 5 patients still suffered from dermatitis, 2–5 years later. 3 of these 5 patients could have been exposed to the causative allergens in their new workplace. We conclude that the Mathias criteria are useful to assess occupational contact dermatitis.
Allergic and non‐allergic periorbital dermatitis: patch test results of the Information Network of the Departments of Dermatology during a 5‐year period
Authors: Herbst R. A. , Uter W. , Pirker C. , Geier J. , Frosch P. J.
Published: August 2004

Periorbital dermatitis is common and can be due to the external use of ophthalmic drugs. We evaluated patch test results of the Information Network of the Departments of Dermatology. During a 5‐year period (1995–99), of a total 49 256 patch‐tested patients, 1053 (2.1%) were eventually diagnosed as allergic periorbital contact dermatitis (APD) and 588 (1.2%) as non‐allergic periorbital dermatitis (NAPD). Patient characteristics between APD, NAPD and other cases (OCs) differed with respect to sex (19.7% male in both periorbital groups versus 36.3% in OCs), atopic dermatitis (10.4% in APD versus 60.2% in NAPD versus 16.9% in OCs) and age, APD being substantially more often (68.2%) aged 40 and above than NAPD (52.6%). Several of the top allergens in OCs [such as fragrance mix, Myroxylon pereirae resin (balsam of Peru), lanolin alcohol and potassium dichromate] caused significantly fewer positive test reactions in both periorbital groups. In contrast, thimerosal, phenylmercuric acetate, sodium disulfite, gentamicin sulfate, phenylephrine hydrochloride and benzalkonium chloride tested positively significantly more often in APD but not in NAPD, verifying them as true ophthalmic allergens. Finally, in 42 cases (4%) of APD patients, additional allergens were identified by testing of the patients' own substances (mostly β‐blockers, oxybuprocaine and dexpanthenol), supporting the necessity of testing with ophthalmic drugs as is where individual substances are not readily available.
Intra‐individual variation of irritant threshold and relationship to transepidermal water loss measurement of skin irritation
Authors: Smith H. R. , Rowson M. , Basketter D. A. , McFadden J. P.
Published: August 2004

Irritant susceptibility studies have used either visual assessment or transepidermal water loss (TEWL) to determine subject response. We have developed a visual assessment method which determines subject irritant threshold. We examined the relationship between sodium lauryl sulfate (SLS) irritant threshold and TEWL measurements from normal skin and SLS patch tests. 19 subjects were recruited. The irritant threshold of each subject was measured and TEWL measurements made from the applied SLS patch tests. Individuals with a lower irritant threshold (easily irritated skin) had elevated TEWL levels compared to those with higher thresholds. The irritant threshold test had a low intraindividual variation. This study showed that the 2 methods grouped patients in a similar manner. The variation seen may reflect the different outcomes measured: irritant threshold visually assesses the skin inflammatory response while TEWL measures skin barrier modification.
Making sense of BSAE for linguistic democracy in South Africa
Authors: Makalela Leketi
Published: August 2004

Abstract:  This paper re‐examines the debate over the emergence of Black South African English (BSAE) as a variety of English that is institutionalized with distinct properties. It focuses on the tense logic in Bantu languages and discourse markers that chiefly account for uniquely BSAE features. Through an in‐depth analysis of these linguistic properties, the paper presents fresh angles of reconceptualizing the status of BSAE, which might move the debate to a level that makes sense to the policy‐makers and language planners. In the end, I argue for English harmonization in South Africa as a necessary path to empowering the local masses that are otherwise excluded through the orthodox tradition of upholding British Standard English in African classrooms.
Evolving naming patterns: anthroponymics within a theory of the dynamics of non‐Anglo Englishes
Authors: Tan Peter K. W.
Published: August 2004

Abstract:  English place names show vestiges of the original languages spoken (e.g. Kent is Celtic): this is seen as characterising the early stages of dialect birth. In contrast to place names, little attention has been given to personal names. This paper attempts to explore ways in which this can be done by examining ethnic‐Chinese names in Singapore with a view to understanding how this could be related to the spread of non‐Anglo Englishes. To illustrate my point, I examine graduation lists as data; these are from Singaporean universities and span 40 years and characterise the patterns of change. One significant change is the rise of the proportion of the population with English‐based given names, although there are other patterns of change too: these are indicative of some of the tensions within Singaporean society. I also suggest that some aspects of anthroponymics can be incorporated into the theory of dialect birth.
Linguistic hybridization in K‐Pop: discourse of self‐assertion and resistance
Authors: Lee Jamie Shinhee
Published: August 2004

Abstract:  English mixing in Korean popular music (K‐Pop) is prevalent and heterogeneous in its forms and functions. The size of a mixed English constituent in K‐Pop lyrics varies from a single word to an entire song. The manifestation of linguistic sophistication differs from Koreanized English only intelligible to the Korean public to American English with African American Vernacular English (AAVE) features. Functions of English mixing are also varied from a simple attention‐getter for stylistic purposes to assertion of liberated self and exercising freedom of speech. K‐Pop is a sociolinguistic breathing space for young South Koreans to construct identity and socially connect with others. The findings of the study show that K‐Pop provides discursive space for South Korean youth to assert their self‐identity, to create new meanings, to challenge dominant representations of authority, to resist mainstream norms and values, and to reject older generations’ conservatism. English is used as discourse of resistance. Young South Korean artists are empowered by tactical English switches into Korean. Appropriations between global and local dialogues yield resultant linguistic hybrids. Mixing two language codes epitomizes South Korean youth's battle with their unsettling identities in dealing with the tension between global and local dialogues to which they are simultaneously exposed.
Fatal miscommunication: English in aviation safety
Authors: Tajima Atsushi
Published: August 2004

Abstract:  This paper critically analyzes the use of English in the field of aviation. International air traffic has played an increasingly important role in recent globalization, which stresses the massive movement of people. Many pilots and air‐traffic controllers having a variety of Englishes, in terms of proficiency and local influence, share this communicative context. Proper use of phraseologic English is a crucial prerequisite for them to participate in the field. However, fatal accidents due to miscommunication where insufficient and improper English were contributing factors have still occurred. With particular focus on communication in air‐traffic control (ATC), this paper reexamines some salient aviation accidents in order to critically analyze how communication breakdowns occurred and how various usages of Englishes account for them. It then introduces some attempts to avoid such communication breakdowns as well as analyzes limitations of those attempts. Finally, the paper proposes a few suggestions that may help aviation personnel to cooperatively achieve a better communicative context in aviation.
Human leukaemic stem cells: a novel target of therapy
Authors: Sperr W. R. , Hauswirth A. W. , Florian S. , Öhler L. , Geissler K. , Valent P.
Published: August 2004

Acute myeloid leukaemia (AML) is a life‐threatening haematopoietic disease that is characterized by clonal growth and the accumulation of myelopoietic progenitor cells. Although AML cells only have a limited potential to undergo differentiation and maturation, each AML clone is organized in a hierarchical manner similar to normal haematopoiesis. Recent data have shown that each AML clone consists of leukaemic stem cells and their progeny, and that AML stem cells differ from more mature cells in several aspects, including survival and target antigen profiles. Most importantly, AML stem cells, but not their progeny, have the capacity to repopulate haematopoietic tissues with leukaemias in NOD/SCID mice. Furthermore, AML stem cells are thought to be responsible for the infinite growth of leukaemias in patients with AML. The phenotypic properties of AML stem cells have also been described. In most cases, these cells are detectable within the CD34+, CD38–, Lin–, CD123+ subpopulation of AML cells. Because of their AML‐initiating and ‐renewing capacity and their unique phenotype, which includes several molecular targets of drug therapy, AML stem cells have recently been proposed as novel important target cell populations in the context of curative therapies. The present article gives an overview of our knowledge about AML stem cells, their phenotype, and their role as a ‘therapy‐target’ in new concepts to treat and to cure patients with AML.
On the way to targeted therapy of mast cell neoplasms: identification of molecular targets in neoplastic mast cells and evaluation of arising treatment concepts
Authors: Valent P. , Ghannadan M. , Akin C. , Krauth M.‐T. , Selzer E. , Mayerhofer M. , Sperr W. R. , Arock M. , Samorapoompichit P. , Horny H.‐P. , Metcalfe D. D.
Published: August 2004

Several emerging treatment concepts for myeloid neoplasms are based on novel drugs targeting cell surface antigens, signalling pathways, or critical effector molecules. Systemic mastocytosis is a haematopoietic neoplasm that behaves as an indolent myeloproliferative disease in most patients, but can also present as aggressive disease or even as an acute leukaemia. In patients with aggressive disease or mast cell leukaemia, the response to conventional therapy is poor in most cases, and the prognosis is grave. Therefore, a number of attempts have been made to define novel treatment strategies for these patients. One promising approach may be to identify novel targets and to develop targeted drug therapies. In this article, we support the notion that neoplastic mast cells indeed express a number of potential molecular targets including immunoreactive CD antigens, the microphthalmia transcription factor (MITF), and members of the Bcl‐2 family. In addition, the tyrosine kinase receptor KIT and downstream signalling pathways have been proposed as targets of a specific pharmacological intervention. A particular challenge is the disease‐related D816V‐mutated variant of KIT, which is resistant against diverse tyrosine kinase inhibitors including STI571, but may be sensitive to more recently developed targeted compounds. The therapeutic potential of target‐specific approaches in malignant mast cell disorders should be evaluated in forthcoming clinical trials in the near future.
Determinants of the Timing of Interim and Majority of Audit Work
Authors: Makkawi Bilal , Abdolmohammadi Mohammad J.
Published: August 2004

This study investigates the effect of the risk of material misstatement at the financial statement level on audit program planning. Using an inventory‐production cycle case study, we engaged forty‐eight auditors to assess the risk of material misstatement at the financial statement level. The auditors incorporated their assessments in planning the total number of audit hours and the timing of performance of interim tests and the majority of audit work. To further investigate the sources of variation, we classified auditors by their level of audit experience and tolerance‐for‐ambiguity, and analyzed the effects of these variables on the audit program planning.

The results indicate that the risk of material misstatement is statistically significant in explaining changes in the total number of audit hours and the timing of the majority of audit work. Moreover, experience and tolerance‐for‐ambiguity were significant in explaining changes in the timing of interim tests and majority of work. Interaction between experience and tolerance‐for‐ambiguity was also significant in explaining the variation in the total number of hours planned for the overall audit work. This result indicated that inexperienced auditors with a low tolerance‐for‐ambiguity planned more audit procedures than the more experienced auditors with a high tolerance‐for‐ambiguity. Implications for audit practice and research are discussed.
Histological aspects and role of mast cells in Helicobacter pylori‐infected gastritis
Authors: Nakajima S. , Bamba N. , Hattori T.
Published: August 2004

Background : Mast cells are one of the main pro‐inflammatory cells, while their knowledge in Helicobacter pylori infection has not been summarized.

Methods : We reviewed studies on mast cells in H. pylori infection, and summarized the histological aspects and roles.

Results : The density of mast cells is greater in H. pylori‐infected than in non‐infected subjects. Increased mast cell density in infected gastritis significantly decreases after eradication. On electron microscopy, mast cells in infected gastric mucosa show degranulation. Some experimental studies demonstrate that mast cells are degranulated with H. pylori‐derived products.

Conclusions : Mast cells are actively involved in the pathogenesis of H. pylori‐infected gastritis. The possible roles are to initiate and promote the formation of oedema through degranulated and secreted mediators, and to release multiple chemotactic factors, which induce inflammatory cells to infiltrate to the site of oedema, showing acute inflammatory changes. Mast cells also stimulate the degradation of pericellular matrices and the growth of cells in their vicinity, and thereby promote tissue turnover. In chronic H. pylori infection, these reactions continue until the bacteria are eradicated. Mast cells may act both to maintain gastritis and to repair tissue damage in H. pylori‐infected chronic gastritis.
Oesophageal hypersensitivity in Japanese patients with non‐erosive gastro‐oesophageal reflux diseases
Authors: Miwa H. , Minoo T. , Hojo M. , Yaginuma R. , Nagahara A. , Kawabe M. , Ohkawa A. , Asaoka D. , Kurosawa A. , Ohkusa T. , Sato N.
Published: August 2004

Background : Visceral hypersensitivity plays a major role in the pathogenesis of non‐erosive oesophageal reflux disease (NERD). Prevalence of NERD differs according to the population and geographical region. Oesophageal hypersensitivity in NERD has not been well studied, especially in Japanese patients.

Aim : To investigate oesophageal hypersensitivity in Japanese NERD patients.

Patients and methods:  We performed upper GI endoscopy and the modified acid perfusion test on 14 control subjects and 68 GERD patients, including 26 with NERD, 34 with erosive GERD, and six with Barrett's oesophagus. The stimulus‐response function to acid was quantified by three parameters (lag time, intensity rating and the acid perfusion sensory score) and compared among four groups.

Results : The mean value of the lag time, intensity rating, and acid perfusion scores in NERD patients (4.6 ± 3.4, 4.4 ± 3.4, 27.8 ± 26.7, respectively) were higher than in erosive GERD (3.2 ± 3.3, 3.0 ± 3.2, 18.2 ± 24.8) and Barrett patients (2.5 ± 4.0, 1.8 ± 3.3, 15.0 ± 28.8), and significantly higher than in the control group (1.7 ± 2.7, 1.1 ± 2.0, 5.4 ± 11.8). The ratio of patients with higher sensory scores was also greater in the NERD group (57.7%) than in erosive GERD (32.3%) and Barrett group (16.7%), and significantly greater than in control group (6.7%).

Conclusion : Our findings suggest that oesophageal sensitivity is likely to be enhanced especially in NERD patients also in Japanese population in comparison with erosive GERD, Barrett's oesophagus and controls.
Farming exposure in childhood, exposure to markers of infections and the development of atopy in rural subjects
Authors: Radon K. , Windstetter D. , Eckart J. , Dressel H. , Leitritz L. , Reichert J. , Schmid M. , Praml G. , Schosser M. , Von Mutius E. , Nowak D.
Published: August 2004

Background
Within the context of the hygiene hypothesis, we aimed to study the potential association between farming‐related risk factors and Toxoplasma gondii (T. gondii) as well as Helicobacter pylori (H. pylori) seropositivity.

Methods
The study included questionnaire data and serum samples of 321 young adults living in a rural environment. Serum samples were analysed for specific IgE to a common panel of aeroallergens (SX1) as well as IgG against T. gondii and H. pylori.

Results
Regular contact with animal stables before the age of 3 years (odds ratio (OR) (95% confidence interval): 2.0 [1.0; 4.0]) and unpasteurized milk consumption at age 6 years (1.8 [1.0; 3.3]) were the strongest risk factors for T. gondii infection. None of the farming‐related factors were significantly associated with H. pylori infection. Current consumption of raw farm milk was not significantly associated with H. pylori infection (2.1 [0.8; 5.3]). Regular contact with animal houses before the age of 7 years was the strongest predictor for atopy (0.49 [0.26–0.96]). The reduction in risk could not be further decreased by any other factor under consideration. After adjustment for animal house contact, the OR for atopy was decreased by raw milk consumption and H. pylori infection in an additive manner.

Conclusion
Exposure to farming environments in childhood might predict T. gondii seropositivity in rural subjects. Nevertheless, the strongest predictor for atopy in rural subjects seems to be regular contact with farm animals. Whether T. gondii infection is an intermediate factor in the association between farm contact and atopy needs to be confirmed in larger studies.
Induction of T ‘regulatory’ cells by standardized house dust mite immunotherapy: an increase in CD4+CD25+ interleukin‐10+ T cells expressing peripheral tissue trafficking markers
Authors: Gardner L. M. , Thien F. C. , Douglass J. A. , Rolland J. M. , O'Hehir R. E.
Published: August 2004

Background
Clinically effective subcutaneous allergen‐specific immunotherapy (SIT) is associated with altered circulating T cell cytokine production and altered local cytokine responses with increased IL‐10 following allergen challenge in target organs.

Objective
This study aimed to elucidate mechanisms for these T cell changes, by examining surface expression of markers for peripheral tissue trafficking on circulating cytokine‐positive T cells following standardized house dust mite‐ (HDM‐) SIT.

Methods
A randomized conventional HDM immunotherapy study was performed on a panel of 12 HDM‐allergic subjects. Nine subjects received treatment with conventional HDM immunotherapy using a standardized extract and three subjects were treated by standard pharmacotherapy alone. Symptom and medication scores and allergen‐induced cutaneous late‐phase responses were assessed before and 9 months after institution of therapy. Before and at 3 and 9 months of SIT, peripheral blood mononuclear cells were cultured for 14 days with HDM extract and CD4+ and CD8+ T cell expression of CD62L, CD49d and CCR5 and production of IL‐10, IFN‐γ and IL‐4 were analysed by flow cytometry. Allergen‐specific T cell proliferation was assessed by 3H‐thymidine incorporation.

Results
At 9 months, all SIT‐treated patients showed reduced symptom scores and late‐phase cutaneous responses to HDM compared with baseline levels. The proportions of CD4+ T cells which were IL‐10+ were increased (P<0.01), and the proportions of CD4+ and CD8+ T cells which were IL‐4+ decreased (P<0.05) compared with baseline. CD4+ and CD8+ T cell IFN‐γ production, expression of surface markers for peripheral tissue trafficking and allergen‐specific proliferation remained unchanged during SIT treatment. However, increased proportions of CD4+CD62L−, CD4+CD49dhi, CD4+CCR5+ T cells expressing IL‐10 were detected at 9 months of SIT compared with baseline (P<0.05). IL‐10 staining co‐localized with CD4+CD25+ T cells.

Conclusion
Clinically effective subcutaneous immunotherapy with a standardized HDM Dermatophagoides pteronyssinus preparation results in decreased numbers of IL‐4+ T cells and expansion of CD4+IL‐10+ T cells expressing a peripheral tissue trafficking phenotype. The co‐localization of IL‐10+ staining to CD4+CD25+ T cells is consistent with the induction of a T regulatory cell population by SIT.
Interactions between eotaxin, histamine and mast cells in early microvascular events associated with eosinophil recruitment to the site of allergic skin reactions in humans
Authors: Menzies‐Gow A. , Ying S. , Phipps S. , Kay A. B.
Published: August 2004

Background
The mechanism whereby allergen induces eotaxin expression at the site of allergic inflammation is incompletely understood. Structural cells, including endothelial cells, are a major source of eotaxin.

Objective
We have investigated, in vivo and in vitro, the relationship between mast cell activation and the expression of eotaxin (eotaxin 1) by endothelial cells.

Methods
The effects of intradermal allergen challenge and histamine injection on eotaxin mRNA and protein generation were studied in atopic subjects using immunofluorescence, immunohistochemistry and in situ hybridization. Histamine‐induced expression of eotaxin mRNA and protein by endothelial cells was also measured, as was histamine‐induced eosinophil adhesion to cultured endothelial cells.

Results
A rapid increase in degranulating cutaneous mast cells, together with a concomitant increase in eosinophils, was observed 60 min after allergen challenge. This was accompanied by the appearance of immunoreactive eotaxin that peaked at 1 h around blood vessels and at 3 h within the tissue. Intradermal histamine injection produced an increase in the number of eotaxin+ cells in the tissues, which was maximal at the 3‐h time‐point. In vitro, endothelial cells produced eotaxin mRNA and protein product in a dose‐ and time‐dependent fashion following incubation with histamine, an effect that was blocked by levocetirizine. Pre‐incubation of endothelial cells with histamine also induced a significant increase in eosinophil adherence, an effect that was inhibited with an anti‐eotaxin blocking monoclonal antibody.

Conclusion
The antigen‐induced expression of eotaxin by endothelial cells and the adherence and subsequent migration of eosinophils from the microvasculature to the tissues are rapid events partially under the control of histamine released from degranulating mast cells.
Gene–gene interaction between interleukin‐4 and interleukin‐4 receptor α in Korean children with asthma
Authors: Lee S.‐G. , Kim B.‐S. , Kim J.‐H. , Lee S.‐Y. , Choi S.‐O. , Shim J.‐Y. , Hong T.‐J. , Hong S.‐J.
Published: August 2004

Background
Interleukin‐4 receptor α (IL‐4Rα), which binds IL‐4 and IL‐13, is involved in signal transduction of those cytokines that lead to IgE production, and is also a key functional component of the Th2 lymphocyte phenotype.

Objective
To determine whether IL‐4 and IL‐4Rα polymorphisms are associated with susceptibility to asthma and whether there are gene–gene interactions between IL‐4 and IL‐4Rα polymorphisms.

Methods
We genotyped three groups of Korean children, consisting of 196 atopic asthmatics, 60 non‐atopic asthmatics, and 100 healthy children, for an IL‐4 promoter polymorphism (C‐590T) and three IL‐4Rα polymorphisms (Ile50Val, Pro478Ser, and Arg551Gln) using PCR‐RFLP (restriction fragment length polymorphism) assays.

Results
The allele frequencies of the IL‐4 (C/T) polymorphism and the Ile50Val and Pro478Ser polymorphisms of IL‐4Rα did not differ statistically among the three groups of children. For the Arg551Gln polymorphism, the combined genotype frequency of the Arg/Gln heterozygote and the Arg/Arg homozygote was significantly higher in atopic asthmatics (27.6%) than in healthy children (16.0%) (odds ratio (OR)=1.97, 95% CI (confidence interval)=1.07–3.71). The eosinophil fraction (%) and bronchial responsiveness were higher in children with the Arg/Gln and Arg/Arg genotype than in those with the Gln/Gln genotype (P=0.036 and 0.024, respectively). In asthmatic children, combinations of the IL‐4 CT/TT genotype and the IL‐4Rα Arg/Gln and Arg/Arg genotypes were associated with significantly increased risk for development of asthma (OR=3.70, 95% CI=1.07–12.78, P=0.038).

Conclusions
In Korean children, the IL‐4Rα Arg551 allele may play a role in susceptibility to atopic asthma and correlate with markers of asthma pathogenesis, including increased eosinophil fraction and enhanced bronchial hyper‐responsiveness. In addition, a significant gene–gene interaction between the IL‐4‐590C and the IL‐4Rα Arg551 allele significantly increases an individual's susceptibility to asthma.
Bronchial hyper‐responsiveness to hypertonic saline and blood eosinophilic markers in 8–13‐year‐old schoolchildren
Authors: De Meer G. , Postma D. S. , Janssen N. A. H. , De Jongste J. C. , Brunekreef B.
Published: August 2004

Background
In adult asthma, bronchial hyper‐responsiveness (BHR) to indirect stimuli reflects eosinophilic activation more closely than BHR to stimuli that directly cause smooth muscle contraction.

Aim
To assess the relationship between BHR to the indirect stimulus hypertonic saline (HS), blood eosinophil numbers, and serum eosinophilic cationic protein (ECP) in children with and without current wheeze.

Methods
A cross‐sectional survey among 8–13‐year‐old schoolchildren, using the International Study of Asthma and Allergic disease in Childhood questionnaire, bronchial challenge with HS, skin prick tests, serum IgE, blood eosinophil counts and ECP (in a subset). Based upon the presence of current wheeze (WHE) and BHR, we defined three case groups (WHE+BHR+, WHE−BHR+, WHE+BHR−) and the reference group (WHE−BHR−). By regression analyses, each case group was compared with the reference group for differences in atopic sensitization, blood eosinophil counts and serum ECP.

Results
Complete data were obtained for 470 children. BHR was present in 103 children (22%), 66 being asymptomatic and 37 symptomatic. Children of all three case groups were more often atopic. Sensitization to indoor allergens particularly occurred in children with BHR, irrespective of symptoms (P<0.05).

Children with WHE+BHR+ had highest values for blood eosinophils and serum ECP (P<0.05). Children with WHE−BHR+ had less severe responsiveness. In atopic children with WHE−BHR+, serum ECP was higher than in children with WHE‐BHR‐(P<0.05).

Conclusions
BHR to HS is associated with blood markers of eosinophilic activation, particularly in atopic children.
Differential modulation of human basophil functions through prostaglandin D2 receptors DP and chemoattractant receptor‐homologous molecule expressed on Th2 cells/DP2
Authors: Yoshimura‐Uchiyama C. , Iikura M. , Yamaguchi M. , Nagase H. , Ishii A. , Matsushima K. , Yamamoto K. , Shichijo M. , Bacon K. B. , Hirai K.
Published: August 2004

Background
Both prostaglandin (PG) D receptor (DP) and CRTH2 (chemoattractant receptor‐homologous molecule expressed on Th2 cells)/DP2 are high‐affinity receptors for PGD2. Previous studies have demonstrated that PGD2 enhances releasability and induces CRTH2/DP2‐mediated migration in human basophils, but the precise effects of PGD2 on basophils as well as receptor usage have not been fully clarified.

Objective
We comprehensively explored the roles of DP and CRTH2/DP2 in basophil functions by using selective agonists and antagonists for each receptor.

Methods
DP and CRTH2/DP2 transcripts were quantified by real‐time PCR. We studied the effects of selective agonists (DP: BW245C; CRTH2/DP2: 13,14‐dihydro‐15‐keto (DK)‐PGD2) and/or antagonists (DP: BWA868C; CRTH2/DP2: ramatroban) on Ca2+ mobilization, migration, degranulation, CD11b expression and survival of human basophils.

Results
Basophils expressed transcripts of both DP and CRTH2/DP2, but the levels of CRTH2/DP2 transcripts were ca. 100‐fold higher compared with DP transcripts. Ca2+ influx was induced in basophils by either PGD2 or DK‐PGD2/CRTH2 agonist but not by BW245C/DP agonist. Basophils treated with PGD2 were completely desensitized to subsequent stimulation with DK‐PGD2, but not vice versa. DK‐PGD2 as well as PGD2 up‐regulated CD11b expression, induced migration and enhanced degranulation, and those effects were completely antagonized by ramatroban/CRTH2 antagonist. In contrast, BW245C/DP agonist exhibited an inhibitory effect on basophil migration and IgE‐mediated degranulation, and the migration inhibitory effect was effectively antagonized by BWA868C/DP antagonist. On the other hand, while PGD2 significantly shortened the basophil life‐span, neither DK‐PGD2/CRTH2 agonist nor BW245C/DP agonist did.

Conclusion
CRTH2/DP2 is primarily responsible for the pro‐inflammatory effects of PGD2 on human basophils, while DP introduces negative signals capable of antagonizing the effects of CRTH2/DP2 in these cells. The effects of PGD2 on longevity imply a mechanism(s) other than via DP or CRTH2/DP2. CRTH2/DP2 on basophils may afford opportunities for therapeutic targeting in allergic inflammation.
The effect of supplementation with fish oil during pregnancy on breast milk immunoglobulin A, soluble CD14, cytokine levels and fatty acid composition
Authors: Dunstan J. A. , Roper J. , Mitoulas L. , Hartmann P. E. , Simmer K. , Prescott S. L.
Published: August 2004

Background
Breast milk contains many immunomodulatory factors (soluble CD14 (sCD14), IgA and cytokines) with the potential to influence infant immune development.

Objective
To determine if changes in breast milk ω‐3 polyunsaturated fatty acid (n‐3 PUFA) composition as a result of maternal dietary fish oil supplementation during pregnancy can modify levels of these immunological parameters in breast milk.

Method
In a randomized controlled trial, 83 atopic women received either 4 g fish oil capsules (containing 3.7 g n‐3 PUFA) (n=40) or 4 g olive oil capsules (n=43) from 20 weeks gestation until delivery. Breast milk was collected 3 days post‐partum and fatty acids were analysed by gas liquid chromatography and IgA, sCD14 and cytokines (IL‐5, IL‐6, IL‐10, TNF‐α and IFN‐γ) were quantitated by ELISA or time resolved fluorescence (TRF).

Results
ω‐3 docosahexaenoic acid (DHA; 22:6n‐3) and eicosapentaenoic acid (EPA; 20:5n‐3) levels were significantly higher (P<0.001) in breast milk from women supplemented with fish oil (n=33, DHA mean 1.15%, SD 0.47% and EPA mean 0.16%, SD 0.07%) than in samples from the control group (n=40, DHA mean 0.50%, SD 0.17% and EPA mean 0.05%, SD 0.02%). Breast milk arachidonic acid (AA; 20:4n‐6) levels were significantly lower (P=0.045) in the fish oil group (mean 0.55%, SD 0.12%) compared with the control group (mean 0.61%, SD 0.14%). Breast milk IgA was positively correlated with DHA (P=0.046) and 22:5n‐3 (P=0.003), but inversely correlated with linoleic acid (LA; 18:2n‐6) (P=0.034). Levels of sCD14 were also positively correlated with 22:5n‐3 (P=0.009). Cytokines involved in IgA synthesis (IL‐10 and IL‐6) were also significantly correlated with both IgA and n‐3 PUFA levels, although there were no differences in the levels of breast milk IgA, sCD14 or cytokines between study groups.

Conclusion
Supplementation with fish oil during pregnancy significantly alters early post‐partum breast milk fatty acid composition. ω‐3 PUFA levels were positively associated with IgA and sCD14 levels, suggesting a relationship between fatty acid status and mucosal immune function.
Urinary leukotriene E4 in Henoch–Schonlein purpura
Authors: Tsuji Y. , Abe Y. , Hisano M. , Sakai T.
Published: August 2004

Background
Children with Henoch–Schonlein purpura (HSP) occasionally have allergic disease. We have previously shown that pranlukast hydrate was effective for purpura in HSP. Pranlukast hydrate is a leukotriene (LT) receptor antagonist; therefore, it is likely that LTs take part in the cause of HSP. Urinary leukotriene E4 (LTE4u) levels are a useful index of whole‐body cysteinyl LT production in vivo. In this study, LTE4u was examined in children with HSP.

Objective
The purpose of this study was to examine the relation between the level of LTE4u and the cause of HSP.

Methods
Eighteen HSP children (six boys and 12 girls) and six healthy children were enrolled.

Results
LTE4u levels in patients with HSP were significantly higher (P<0.05) at the onset than those in healthy children. Four weeks therapy with pranlukast hydrate lowers LTE4u levels in patients with HSP (P<0.05). There were no differences in LTE4u between the group of HSP patients with purpura nephritis and the group of HSP patients without purpura nephritis.

Conclusion
These results indicate that csyteinyl LTs may play a role in the pathophysiology of purpura in HSP.
Interleukin‐4 increases murine airway response to kinins, via up‐regulation of bradykinin B1‐receptors and altered signalling along mitogen‐activated protein kinase pathways
Authors: Bryborn M. , Adner M. , Cardell L.‐O.
Published: August 2004

Background
IL‐4 is believed to play a role in asthma and chronic obstructive pulmonary disease through promotion of eosinophilic inflammation and mucus hypersecretion. Whether IL‐4 can induce a direct effect on airway smooth muscle remains unknown.

Objective
To investigate the effect of IL‐4 on airway smooth muscle, focusing on the contractile response to des‐Arg9‐bradykinin and bradykinin.

Methods
Tracheal segments from murine airways were cultured for 1–8 days in the absence and presence of IL‐4. The smooth muscle response induced by des‐Arg9‐bradykinin and bradykinin was investigated in myographs. Expression levels for the IL‐4‐, bradykinin B1‐ and B2‐receptors were characterized using RT‐PCR. Specific inhibitors were used to study signal changes along the IL‐4 receptor‐ (IL‐4R‐) coupled mitogen‐activated protein (MAP) kinase (MAPK) pathways.

Results
IL‐4 treatment increased the contractile response to des‐Arg9‐bradykinin and bradykinin in a concentration‐ and time‐dependent manner. Dexamethasone and the transcriptional inhibitor actinomycin D blocked this effect. c‐Jun N‐terminal kinase inhibitor SP600125 also blocked the effect of both des‐Arg9‐bradykinin and bradykinin, whereas p38 inhibitor SB203580 blocked only the former and the MAPKK inhibitor PD098059, only the latter agonist responses. IL‐4 treatment increased the mRNA levels representing bradykinin B1‐ but not B2‐receptors. Levels of IL‐4R were not altered during culture.

Conclusion
Long‐term exposure to IL‐4 increases the contractile response induced by des‐Arg9‐bradykinin and bradykinin in cultured murine airways. This effect appears to be mediated via an up‐regulation of B1‐receptors and altered signalling along the MAPK pathways.
Sensitization to Ficus benjamina: relationship to natural rubber latex allergy and identification of foods implicated in the Ficus‐fruit syndrome
Authors: Hemmer W. , Focke M. , Götz M. , Jarisch R.
Published: August 2004

Background
Ornamental Ficus benjamina (FB) has been recognized as a new indoor allergen. Little is known about the prevalence in moderately exposed subjects and the proposed association with fruit and Hevea latex hypersensitivity.

Objective
To study the prevalence of FB sensitization and the relationship with Hevea latex allergy, to identify cross‐reacting fruits, and to characterize the responsible allergens.

Methods
A skin prick test solution prepared from FB latex (200 μg/mL) was included in our routine screening programme for suspect inhalant allergy. Patients reacting with the FB extract were further skin tested with exotic fruits by the prick‐to‐prick method. Inhibition of fig and FB CAP by FB latex, fig (Ficus carica), kiwi, the thiolproteases ficin and papain, Hevea latex and rHev b 6.02 (hevein) was performed in selected patients.

Results
Of 2662 patients with a positive skin test to any aeroallergen, 66 (2.5%) reacted with FB. Ten patients showed isolated sensitization to FB. Although FB‐positive subjects were more often co‐sensitized to Hevea latex than FB‐negative (10.6% vs 3.8%, P<0.01), nearly 90% tested negative for Hevea latex. Sensitization to FB was specifically associated with positive skin tests to fresh fig (83%), dried fig (37%), kiwi fruit (28%), papaya (22%), avocado (19%), banana (15%), and pineapple (10%) (n=54). Clinical reactions were reported mainly from fresh and dried fig and kiwi (47%, 60%, and 64%, respectively, of skin test‐positive patients), including seven patients with systemic reactions (urticaria, angiooedema, asthma). CAP to fig in 11 patients with clinical fruit allergy was inhibited on average by 87% by FB latex, 89% by fresh fig, 80% by dried fig, 38% by kiwi (100 μg/mL each), and by 59% and 44% by ficin and papain (50 μg/mL), respectively. No inhibition was obtained with Hevea latex and rHev b 6.02. CAP to FB was inhibited on average by 95% by FB, 60% by fresh fig, 41% by ficin, 29% by papain, and less than 7% by rubber latex allergens.

Conclusions
Sensitization to FB latex is found in 2.5% of atopic individuals and mostly occurs independently of Hevea latex allergy. Sensitization is commonly associated with allergic reactions to figs and other tropical fruits (‘Ficus‐fruit syndrome’). This cross‐reactivity is mediated at least in part by thiolproteases.
Specific immunoglobulin E for staphylococcal enterotoxins in nasal polyps from patients with aspirin‐intolerant asthma
Authors: Suh Y. J. , Yoon S. H. , Sampson A. P. , Kim H. J. , Kim S. H. , Nahm D. H. , Suh C. H. , Park H. S.
Published: August 2004

Background
Nasal polyps infiltrated with eosinophils are commonly found in chronic asthmatic patients, more frequently in those with aspirin‐intolerant asthma (AIA) than aspirin‐tolerant asthma (ATA). Some studies have suggested a contribution of superantigens derived from Staphylococcus sp to nasal polyposis and eosinophilia, but their relative importance in AIA and ATA subjects is unknown.

Objective
We investigated whether local production of specific IgE to staphylococcal enterotoxins A and B (SEA and SEB) and relationships with markers of eosinophilic inflammation differ in the nasal polyps of AIA and ATA subjects.

Methods
Fifteen AIA subjects with positive responses to lysine–aspirin bronchoprovocation and 15 ATA subjects underwent polypectomy. Immunoassays were used to quantify eosinophil cationic protein (ECP), IL‐5, mast cell tryptase, soluble IL‐2 recepters (sIL‐2R), total IgE, and specific IgE for SEA and SEB.

Results
ECP levels in nasal polyp homogenates were higher in AIA subjects than in ATA subjects (P<0.02), with no significant differences in tryptase, IL‐5 or sIL‐2R. Total IgE, and specific IgE to both SEA and SEB, were detectable in some nasal polyps from both subject groups, but median levels were markedly higher in AIA subjects than in ATA subjects (P=0.04, 0.01, 0.05, respectively). Levels of specific IgE to SEA and SEB correlated significantly with levels of ECP and IL‐5, but not those of tryptase or sIL‐2R.

Conclusion
These findings suggest that staphylococcal superantigens may drive local eosinophilic inflammation in nasal polyp tissue, and that this is exacerbated in subjects with AIA.
Introducing the Learning Practice – II. Becoming a Learning Practice
Authors: Rushmer Rosemary , Kelly Diane , Lough Murray , Wilkinson Joyce E. , Davies Huw T. O.
Published: August 2004

Rationale, aims and objectives  This paper is the second of three related papers exploring the ways in which the principles of Learning Organizations (LOs) could be applied in Primary Care settings at the point of service delivery.

Methods  Based on a theoretical and empirical review of available evidence, here we introduce the process by which a Practice can start to become a Learning Practice (LP).

Results and conclusions  Steps taken to enhance both individual and organizational learning begin the process of moving towards a learning culture. Attention is given to the routines that can be established within the practice to make learning systematically an integral part of what the practice does. This involves focusing on all three of single‐, double‐ and triple‐loop learning. Within the paper, a distinction is made between individual, collective and organizational learning. We argue that individual and collective learning may be easier to achieve than organizational learning as processes and systems already exist within the Health Service to facilitate personal learning and development with some opportunities for collective and integrated learning and working. However, although organizational learning needs to spread beyond the LP to the wider Health Service to inform future training courses, policy and decision‐making, there currently seem to be few processes by which this might be achieved. This paper contributes to the wider quality improvement debate in three main ways. First, by reviewing existing theoretical and empirical material on LOs in health care settings it provides both an informed vision and a set of practical guidelines on the ways in which a Practice could start to effect its own regime of learning, innovation and change. Second, it highlights the paucity of opportunities individual general practitioner practices have to share their learning more widely. Thirdly, it adds to the evidence base on how to apply LO theory and activate learning cultures in health care settings.
The impact of economic information on medical decision making in primary care
Authors: Wu Olivia , Knill‐Jones Robin , Wilson Philip , Craig Neil
Published: August 2004

Background  Many general practitioners (GPs) are concerned about the increasing dominance of economic issues in major decisions about clinical care, and feel their opinions on economic matters have not been heard. It is unclear whether this information has any impact on everyday clinical practice in a primary care setting.

Aim  To investigate GPs’ perspectives on the use of economic information in medical decision making.

Design of study  Cross‐sectional survey.

Setting  GP members of the West of Scotland Primary Care Research and Development Network (WestNet).

Methods  Questionnaire survey sent to GPs by post and by email.

Results  The overall response rate was 44%, favouring postal over email responses. All respondents indicated that economic information has previously influenced them and should be incorporated into their medical decision making. The most common source of this information was generated by local authorities such as health boards, primary care groups and local prescribing advisors – used by 80% of the respondents. However, publications, such as the British Journal of General Practice, locally produced newsletters and prescribing formularies, and feedback from the General Practice Administration System for Scotland, were used as sources of economic information by 20%, 27% and 33%, respectively. Published materials – in particular, locally specific information and summarized information in leaflet format – were favoured (54%) in comparison to verbally presented material.

Conclusions  GPs believe that economic information should be incorporated in medical decision making. The need for precise and summarized information, produced locally, has been highlighted. Better understanding towards the type of economic evidence GPs find useful and comprehensible is required.
How information retrieval technology may impact on physician practice: an organizational case study in family medicine
Authors: Pluye P. , Grad R. M.
Published: August 2004

Rationale  Information retrieval technology tends to become nothing less than crucial in physician daily practice, notably in family medicine. Nevertheless, few studies examine impacts of this technology and their results appear controversial.

Aims and objectives  Our article aims to explore these impacts using the medical literature, an organizational case study and the literature on organizations.

Methods  The case study was embedded in an evaluation of the implementation of medical and pharmaceutical databases on handheld computers in a Canadian family medicine centre. Six physicians were interviewed on specific events relative to the use of these databases and on their general perception of impacts of this use on clinical decision making and the doctor–patient relationship. A thematic data analysis was performed concomitantly by both authors.

Results and conclusion  Findings indicate six types of impact: practice improvement, reassurance, learning, confirmation, recall and frustration. These findings are interpreted in accordance with both a medical and organizational perspective. The fit with the literature on inter‐organizational memory supports the transferability of the findings. In turn, this fit suggests how information retrieval technology may change physician routine. This study suggests a new basis for evaluating the impact of information retrieval technology in daily clinical practice. In conclusion, our paper encourages policy‐makers to develop, and physicians to use, this technology.