bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prior Bordetella pertussis infection modulates allergen priming and the severity of airway pathology in a murine model of allergic asthma
Authors: Ennis D. P. , Cassidy J. P. , Mahon B. P. 
Published: September 2004

SummaryBackground
It has been proposed that T helper (Th)2‐driven immune deviation in early life can be countered by Th1 inducing childhood infections and that such counter‐regulation can protect against allergic asthma.Objective
To test whether Th1‐inducing infection with Bordetella pertussis protects against allergic asthma using well‐characterized murine models.Methods
Groups of mice were sensitized to ovalbumin (OVA) in the presence or absence of B. pertussis, a well‐characterized Th1 inducing respiratory infection. Immunological, pathological and physiological parameters were measured to assess the impact of infection on immune deviation and airway function.Results
We demonstrate that OVA sensitization does not affect the development of B. pertussis‐specific immune responses dominated by IgG2a and IFN‐γ and does not impair Th1‐mediated clearance of airway infection. In contrast, B. pertussis infection at the time of sensitization modulated the response to OVA and significantly reduced total serum and OVA‐specific IgE. The pattern of cytokine responses, in particular OVA‐specific IL‐5 responses in the spleen was also modulated. However, B. pertussis did not cause global suppression as IL‐10 and IL‐13 levels were enhanced in OVA‐stimulated spleen cell cultures and in lavage fluid from infected co‐sensitized mice. Histopathological examination revealed that B. pertussis infection prior to OVA sensitization resulted in increased inflammation of bronchiolar walls with accompanying hyperplasia and mucous metaplasia of lining epithelia. These pathological changes were accompanied by increased bronchial hyper‐reactivity to methacholine exposure.Conclusion
Contrary to the above premise, a Th1 response induced by a common childhood infection does not protect against bronchial hyper‐reactivity, but rather exacerbates the allergic asthmatic response, despite modulation of immune mediators.
Differential effect of mattress covers on the level of Der p 1 and Der f 1 in dust
Authors: Tempels‐Pavlica Ž. , Oosting A. J. , Terreehorst I. , Van Wijk R. Gerth , Bruijnzeel‐Koomen C. A. F. M. , De Monchy J. G. R. , Aalberse R. C. 
Published: September 2004

SummaryBackground
Exposure to house dust mite (HDM) allergens can lead to the development of allergic complaints. Mattress covers seem to be an obvious option for lowering allergen exposure in sensitized individuals. Previous studies have shown that Dermatophagoides pteronissinus was the most prevalent HDM species in the Netherlands.Objective
In the present study, we investigated the effect of mattress covers on Der p 1 and Der f 1 concentrations in dust samples in three areas in the Netherlands; Groningen, Utrecht and Rotterdam.Methods
Dust was obtained from mattresses of 277 patients at the beginning of the study and after 12 months of the placebo‐controlled intervention. It was analysed for allergen content by immunoassay. The differential effect of the intervention on Der p 1 vs. Der f 1 was analysed in a subgroup with Der p 1+Der f 1>1 μg/g dust (N=161). It was tested whether the intervention caused a significant change in the Der f 1/Der p 1 ratio.Results
At t=0 we found very similar levels of the group 1 allergens of both species. The relatively high prevalence of D. farinae in our study was geographically restricted: the median Der f 1/Der p 1 ratio was 11.1 in the Rotterdam area compared with 1.32 in the Utrecht area and 0.33 in the Groningen area. Analysis of our data showed that the favourable intervention effect found for the combined allergen data (reduction factor=2.9, P<0.001) is essentially due to a favourable effect of the intervention on the Der f 1 levels only (reduction factor=3.6, P<0.001). The effect on the Der p 1 level was remarkably small (reduction factor: 1.2, P=0.48). In the intervention group, the Der f 1/Der p 1 ratio decreased after 12 months by a factor 2.0, whereas in the placebo group it increased (probability of the intervention effect: P<0.005).Conclusion
Mite‐impermeable covers are more effective in reducing the level of Der f 1 than that of Der p 1.
Mode of delivery is not associated with asthma or atopy in childhood
Authors: Maitra A. , Sherriff A. , Strachan D. ,   ALSPAC Study Team, Henderson J. 
Published: September 2004

SummaryBackground
Caesarean‐section delivery has been associated with the subsequent development of atopy and wheezing in childhood.Objective
To examine the association between mode of delivery (vaginal vs. caesarean section) and development of atopy, asthma and wheezing disorders in a population‐based cohort of children.Methods
The Avon Longitudinal Study of Parents and Children is a longitudinal birth cohort of children born 1 April 1991 to 31 December 1992. Mode of delivery was categorized as vaginal (including forceps and ventouse extractions) or caesarean section (elective and emergency). Primary outcomes were parental report of asthma or wheezing between 69 and 81 months of age, physician‐diagnosed asthma (PDA) at 91 months of age and atopy at 7 years by skin prick testing. Possible confounding factors were considered in a multivariable logistic regression model.Results
Total livebirths were 14 062, from which were selected 12 367 born to mothers resident in a defined area and delivered in one of two major obstetric hospitals. Of these infants, 10 980 (88.8%) were delivered vaginally and 1387 (11.2%) by caesarean section. Outcome data were available for 7495 (61%) subjects (asthma 69–81 months); 7389 (60%) (wheeze 69–81 months); 7196 (58%) (PDA 91 months) and 5916 (48%) (atopy 7 years). Adjusted odds ratios [95%confidence interval] for caesarean section compared with vaginal delivery were not statistically significant for any outcome we considered: asthma 69–81 months 1.16 [0.9, 1.5]; wheeze 69–81 months 0.95 [0.7, 1.3]; PDA 1.14 [0.9, 1.4]; atopy 1.04 [0.8, 1.3].Conclusion
Delivery by caesarean section was not associated with the subsequent development of asthma, wheezing or atopy in later childhood in this population.
The flow‐cytometric determination of basophil activation induced by aspirin and other non‐steroidal anti‐inflammatory drugs (NSAIDs) is useful for in vitro diagnosis of the NSAID hypersensitivity syndrome
Authors: Gamboa P. , Sanz M. L. , Caballero M. R. , Urrutia I. , Antépara I. , Esparza R. , De Weck A. L. 
Published: September 2004

SummaryBackground
Hypersensitivity reactions to non‐steroidal anti‐inflammatory drugs (NSAIDs), manifested by cutaneous symptoms and/or airway manifestations represent 20–25% of all hypersensitivity reactions to drugs. Today, it is still claimed that no in vitro diagnostic tests exist for that condition and that the only way to confirm the diagnosis is a provocation challenge.Objective
The objective of this study was to assess whether NSAIDs may provoke blood basophil activation in vitro in such patients, as detected by a flowcytometric technique.Methods
Sixty NSAID hypersensitive patients (38 with cutaneous, 20 with airway and two with cutaneous and airway symptoms) and 30 control patients (15 asthmatics) were selected. Their hypersensitivity was confirmed by documented history indicating at least two clinical episodes to two or more different NSAIDs or by positive oral provocation challenge. Isolated buffy coat leukcocytes were stimulated in vitro with aspirin, paracetamol, metamizol, diclofenac, and naproxen. The percentage of activated basophils was evaluated by an anti‐CD63.Results
Aspirin showed a sensitivity of 43.3%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 99.4%. For the other NSAIDs, the sensitivity and specificity values were: for paracetamol 11.7% and 100%, for metamizol 15% and 100%, for diclofenac 43.3% and 93.3% and for naproxen 54.8% and 74.1%. When considering the first four NSAIDs, the global sensitivity raised to 63.3% and specificity to 93.3%. If the number of tests is to be limited for practical reasons, the combination of acetylsalicylic acid and diclofenac at two concentrations yields a sensitivity of 58.3% and a specificity of 93.3%.Conclusions
Flowcytometric determinations of basophil activation following stimulation with NSAIDs show a high sensitivity (60–70%) with specificity above 90%. So this test may help avoiding some cumbersome and dangerous provocation challenges.
A survey of the quality of information leaflets on hayfever available from general practices and community pharmacies
Authors: White P. , Smith H. , Webley F. , Frew A. 
Published: September 2004

SummaryBackground
Hayfever affects at least one in 10 people. The majority of hayfever is managed in the community setting where the management options are pharmaceutical and behavioural. Hayfever medications are available over the counter and on prescription from the general practitioner. Patient information leaflets are published to augment the advice given and to promote self‐management, but these leaflets have rarely been subjected to critical review.Objective
To assess the quality of patient information leaflets written for people with hayfever and available from general practices and from community pharmacists.Method
A structured review of patient information leaflets about hayfever. During the peak grass pollen season copies of all leaflets available were collected from a random sample of community pharmacists and general practices in Wessex. The characteristics of the leaflet were recorded and the contents and presentation of each one was reviewed using the British Medical Association patient information appraisal system. Readability was assessed using the Simple Measure of Gobbledegook (SMOG). Two allergy‐accredited specialists assessed each leaflet for accuracy.Results
During the peak pollen season no leaflets were available in 30% of the Community Pharmacists and 23% general practices. In total, 38 different leaflets were identified. All the leaflets reviewed were written for adults. Forty‐seven percent of the leaflets had no publication date and one‐third of those dated were at least 5 years old. In general the leaflets scored highly on issues of presentation, but less than half contained information on the full range of management and treatment options, many being biased towards a single or limited range of interventions. Seventy‐nine percent leaflets were produced or sponsored by pharmaceutical companies and gave prominence to their own products. All the leaflets had readability scores requiring at least secondary education (SMOG score equal or greater than 9). At least one factual inaccuracy was identified in four‐fifths of leaflets.Conclusion
A large number of leaflets are published for people with hayfever, but they are of variable quality and not accessible to all patients because of limited distribution or high readability scores. If all patients are to benefit from written information the authors and publishers of leaflets need to follow published recommendations, especially with respect to content and readability. In the absence of a national public health information strategy or a body that systematically vets patient information materials, clinicians must pay attention to the quality of information provided for or obtained elsewhere by their patients.
Efficacy and safety of subcutaneous immunotherapy with a biologically standardized extract of Ambrosia artemisiifolia pollen: a double‐blind, placebo‐controlled study
Authors: Mirone C. , Albert F. , Tosi A. , Mocchetti F. , Mosca S. , Giorgino M. , Pecora S. , Parmiani S. , Ortolani C. 
Published: September 2004

SummaryBackground
The allergological relevance of Ambrosia in Europe is growing but the efficacy of the injective immunotherapy for this allergen has been documented only in Northern America.Objective
We sought to study the safety and efficacy of injective immunotherapy in European patients sensitized to Ambrosia artemisiifolia.Methods
Thirty‐two patients (18 M/14 F, mean age 36.78, range 23–60 years) suffering from rhinoconjunctivitis and/or asthma and sensitized to Ambrosia were enrolled and randomized in a double‐blind, placebo‐controlled (DBPC) study lasting 1 year. A maintenance dose corresponding to 7.2 μg of Amb a 1 was administered at 4‐week intervals after the build‐up. During the second and the third year, all patients were under active therapy in an open fashion. Symptom and medication scores, skin reactivity to Ambrosia (parallel line biological assay), and pollen counts were assessed throughout the trial.Results
Twenty‐three patients completed the trial. No severe adverse event was observed. During the DBPC phase, actively treated patients showed an improvement in asthmatic symptoms (P=0.02) and drug (P=0.0068) scores days with asthmatic symptoms (P=0.003), days with rhinitis symptoms (P=0.05), and days with intake of drugs (P=0.0058), as compared to before therapy. No improvement for any of these parameters was detected in the placebo group. Moreover, the number of days with rhinitis and asthma was significantly higher in the placebo as compared to the active group (P=0.048 and P<0.0001, respectively). Patients who switched from placebo to active therapy improved in rhinoconjunctivitis, asthma, and drug intake. The skin reactivity decreased significantly (12.2‐fold, P=0.0001) in the active group whereas a slight increase (1.07‐fold, P=0.87) was observed in the placebo group after the DBPC phase. After switching to active therapy, patients previously under placebo showed a significant decrease of this parameter (4.78‐fold, P=0.002).Conclusion
Injective immunotherapy is safe and clinically effective in European patients sensitized to Ambrosia.
Mixed antibody and T cell responses to peanut and the peanut allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6 in an oral sensitization model
Authors: Van Wijk F. , Hartgring S. , Koppelman S. J. , Pieters R. , Knippels L. M. J. 
Published: September 2004

SummaryBackground
Peanut allergy is known for its severity and persistence through life. Several peanut proteins have been identified as allergenic and are indicated as Ara h 1–7. Very little is known about the mechanisms that underlie sensitization to peanut proteins.Objective
The purpose of the present study was to reveal the immune responses that are induced against peanut and the peanut allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6 during sensitization, including the very early responses.Methods
Humoral and T cell responses against peanut and the peanut allergens were examined in an early and later stage of sensitization in an established murine model of peanut anaphylaxis. Therefore C3H/HeJ mice were orally exposed to two different doses of peanut extract plus cholera toxin.Results
Oral sensitization to peanut was characterized by an antigen‐induced mixed cytokine response in the spleen (IL‐4, IL‐5, IL‐10 and IFN‐γ), which could already be observed 7 days after the onset of exposure. Additionally, polyisotypic humoral responses (IgE, IgG1 and IgG2a) against peanut were found in the serum. Moreover, we demonstrated that these T helper (Th)1/Th2 cytokine and antibody responses were also directed specifically against the major peanut allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6.Conclusions
This study implicates that both Th1 and Th2 phenomena are involved in the development of peanut allergy in the C3H/HeJ murine model. Furthermore, we show that the present oral model is suitable to examine immune responses to food allergens during different stages of sensitization upon treatment with a whole food extract.
Regulation of glucocorticoid receptor gamma (GRγ) by glucocorticoid receptor haplotype and glucocorticoid
Authors: Stevens Adam , Donn Rachelle , Ray David 
Published: September 2004

Summaryobjective  To measure glucocorticoid receptor gamma (GRγ) expression in transformed lymphocytes from individuals of known GR gene haplotype. Recently, a glucocorticoid receptor haplotype (GAT) has been described that associates with increased sensitivity to dexamethasone. As there is strong linkage disequilibrium across the gene, this haplotype is likely to extend through exon 3, altered splicing of which generates the GRγ isoform, a splice variant with impaired transactivation activity. Therefore we proposed that the GR haplotype affects glucocorticoid sensitivity either by influencing GRγ expression basally, or in response to Gc exposure.design  We have measured expression of GRγ, using a validated RT–PCR assay in human B lymphoblast cells of known haplotype under basal conditions, and after dexamethasone treatment.patients  The A549 human lung cell line and normal volunteers, five with the GAT GR haplotype and three with the CGA haplotype.measurements  Relative expression of GRγ compared to total GR mRNA.results  GRγ made up 5–6% of all the GR transcripts. There was no effect of carriage of the GR gene GAT haplotype on this expression. There was no effect of dexamethasone on relative expression of GRγ.conclusions  We propose that the GRγ isoform is a product of constitutive splicing, that it does not explain the GR haplotype association with altered glucocorticoid sensitivity, and is unlikely to play an important physiological role in affecting glucocorticoid sensitivity. As glucocorticoids do not affect GRγ expression, relative to total GR, this splice variant is unlikely to influence glucocorticoid treatment response.
Effect of dieting on plasma leptin, soluble leptin receptor, adiponectin and resistin levels in healthy volunteers
Authors: Wolfe Barbara E. , Jimerson David C. , Orlova Christine , Mantzoros Christos S. 
Published: September 2004

Summaryobjective  Recent findings demonstrating important effects of the adipokines on metabolism, energy homeostasis and body weight regulation have prompted research on the possible role of negative energy balance in altering adipocytokine regulation. The goal of this study was to evaluate the effects of a hypocaloric diet in healthy normal‐weight volunteers. An additional goal was to help clarify the contribution of restricted caloric intake to altered plasma adipokine levels in the eating disorders anorexia nervosa and bulimia nervosa.design  Participants were studied before and after a 4‐week reduced‐calorie diet (1000–12000 kcal/day).patients  Subjects included 15 healthy, normal‐weight women (age 22 ± 3 years).measurements  Plasma concentrations of leptin, soluble leptin receptor protein (sOB‐R), adiponectin, resistin, thyroid hormones and β‐hydroxybutyrate were determined following overnight fast before and after the 4‐week reduced‐calorie diet.results  Subjects lost a mean of 3·4 ± 2·1 kg in response to the reduced‐calorie diet. The weight loss phase was associated with a 60·3% decrease in plasma leptin levels (P < 0·001), a 43·5% increase in sOB‐R levels (P < 0·002) and a 16·2% decrease in plasma adiponectin levels (P < 0·04). There was no significant change in plasma resistin levels.conclusions  These results demonstrate that a modest decrease in energy intake sustained over several weeks may play an important role in altering levels of plasma leptin and sOB‐R. The findings also provide preliminary evidence that, in contrast to previous results in obese subjects, caloric restriction with accompanying weight loss in healthy, normal‐weight volunteers may lead to decreased circulating adiponectin levels. Additional studies will be needed to clarify the contribution of altered energy intake to abnormalities in cytokine levels in the eating disorders.
Gonadotrophin receptor blocking antibodies measured by the use of cell lines stably expressing human gonadotrophin receptors are not detectable in women with 46,XX premature ovarian failure
Authors: Tonacchera Massimo , Ferrarini Eleonora , Dimida Antonio , Agretti Patrizia , De Marco Giuseppina , De Servi Melissa , Gianetti Elena , Chiovato Luca , Pucci Enrico , Pra Chiara Dal , Betterle Corrado , Aghini‐Lombardi Fabrizio , Vitti Paolo , Pinchera Aldo 
Published: September 2004

Summarybackground  Premature ovarian failure (POF) is defined by cessation of ovarian function after puberty and before the age of 40. The syndrome is characterized by amenorrhoea, oestrogen deficiency and elevated levels of gonadotrophins. Autoimmunity has been proposed as a mechanism for some cases of destruction or malfunction of ovarian follicles. POF is often associated with type I and type II polyglandular autoimmune syndromes. It has also been postulated that receptors such as the LH and FSH receptors might become targets for blocking antibodies and such antibodies could be a cause of ovarian failure.patients and methods  Sixty‐nine patients with POF isolated or associated with other endocrine autoimmune diseases (autoimmune thyroid diseases, Addison's disease, type 1 diabetes mellitus, multiple sclerosis, myasthenia gravis) were studied. All the patients had secondary amenorrhoea. The patient group had a median age of 33·1 years (range 15–57). Ovarian failure had been diagnosed at a median age of 29 years (range 15–39). The median time since diagnosis was almost 1 year but in six patients gonadal insufficiency had appeared 10–30 years earlier. All had a normal chromosomal karyotype (46, XX). Patients with POF were characterized by duration of amenorrhoea > 1 year, with elevated FSH and LH levels and undetectable or low oestrogen levels. Cell lines stably expressing recombinant human LH (CHO‐LHr) and FSH (CHO‐FSHr) receptors were prepared and used to search for antibodies able to inhibit LH‐ or FSH‐stimulated cAMP production. Immunoglobulins extracted from sera of patients with POF were incubated with CHO‐LHr and CHO‐FSHr in the presence of human recombinant CG and FSH, respectively.results and conclusions  None of the immunoglobulin G (IgG) preparations from patients with POF was able to inhibit the activity of the FSH‐ and CG‐stimulated cAMP production.
Recombinant GH replacement in hypopituitary adults improves endothelial cell function and reduces calculated absolute and relative coronary risk
Authors: Abdu T. A. M. , Elhadd T. A. , Buch H. , Barton D. , Neary R. , Clayton R. N. 
Published: September 2004

Summaryobjective  Adult GH deficiency (GHD) is linked to endothelial dysfunction and vascular disease. We examined the effect of 12 months of GH therapy on endothelial function, C‐reactive protein (CRP) and coronary risk.design  Open‐design intervention study.patients  Fourteen GH‐deficient patients (nonsmokers, without diabetes, hypertension or vascular disease) studied before, 6 months and 12 months after GH therapy.measurements  Flow‐mediated dilatation (FMD), carotid intima–media thickness (IMT) thrombomodulin (TM), E‐selectin, CRP, lipid profile, blood pressure and anthropometric data were recorded. We used the Framingham equation to calculate coronary risk.results  FMD improved (7·5 ± 1·62 vs. 11·93 ± 1·52, P = 0·038). Overall there was no change in IMT, TM, E‐selectin or CRP. The correlation between TM and FMD showed a trend for statistical significance (r = −0·54, P = 0.056). Changes in CRP correlated with change in IGF‐1 (r = −0·67, P = 0·012); E‐selectin correlated with high density lipoprotein (HDL)‐cholesterol (r = −0·60, P = 0·028), triglycerides (r = 0·68, P = 0·01) and waist‐to‐hip ratio (WHR) (r = 0·71, P = 0·006). Systolic (127·36 ± 4·47 vs. 120·36 ± 3·50, P = 0·017) and diastolic (84·71 ± 2·73 vs. 76·93 ± 2·03, P = 0·005) blood pressure decreased. HDL‐cholesterol increased (0·70 ± 0·05 vs. 0·93 ± 0·06, P = 0·001). WHR decreased (0·90 ± 0·02 to 0·88 ± 0·02, P = 0·043) without changes in weight or body mass index (BMI). Ten‐year absolute (P = 0.009) and relative (P = 0.002) cardiac risk decreased.conclusion  Biophysical test of endothelial function (FMD) improved after 12 months of GH therapy but there was no significant change in biochemical endothelial or inflammatory markers. Calculated coronary risk decreased mainly due to reduction in systolic and diastolic blood pressure and increase in HDL‐cholesterol.