bluuebunny/crossref_metadata_2025_split huggingface dataset:
The actions of GR32191B, a thromboxane receptor antagonist, on the effects of inhaled PAF on human airways
Authors: STENTON S. C. , WARD C. , DUDDRIDGE M. , HARRIS A. , PALMER J. B. D. , HENDRICK D. J. , WALTERS E.‐H. 
Published: April 2006

SummaryWe investigated acute bronchoconstriction and changes in airway responsiveness to methacholine following the inhalation of platelet activating factor (PAF) in an open study of 12 non‐asthmatic subjects. Ventilatory function was monitored using a flow rate at 30% of vital capacity (V̇30) and airway responsiveness was measured as PD40V̇30, i.e. the dose of metacholine causing a 40% fall in V̇30. PAF (3–422 μg) resulted in dose‐related acute bronchoconstriction in 10 of the 12 subjects. There was no association between the airway responsiveness to PAF and to methacholine. Ten subjects showed some increase in airway responsiveness to methacholine 1 or 3 days following PAF. Overall, these changes were statistically significant (P < 0·05) but were of small magnitude (geometric mean PD40V̇30 pre‐PAF=457 μg; 24 hr after PAF = 259 μg; 72 hr after PAF =258 μg) and variable: only seven subjects showing increased airway responsiveness on both day 1 and day 3 after PAF. Six subjects who appeared to show increases in airway responsiveness following PAF were re‐studied with the inhaled PAF pre‐medicated by either placebo or a specific thromboxane receptor antagonist (GR32191B) in a double‐blind fashion. GR32191B did not reduce the acute bronchoconstriction due to PAF. In this part of the study, these six subjects did not show significant increases in airway responsiveness following the placebo pre‐medicated PAF challenge and so no effect of the drug on airway responsiveness could be shown. We conclude that PAF‐induced bronchoconstriction in normal individuals is not mediated by thromboxane and that any increases in airway responsiveness following PAF are frequently poorly sustained, are poorly reproducible, and are not readily detectable.
Modulation of the immune response to ragweed allergens by peptic fragments
Authors: MICHAEL J. G. , LITWIN A. , HASSERT V. , PESCE A. 
Published: April 2006

SummaryFragments of short ragweed extract were prepared by peptic digestion and fractionated by molecular exclusion chromatography. We focused on fragmenting a ragweed fraction that was enriched for Amb a I. Digestion products in the molecular weight range of 5–15 kD (fSRW) were examined for their antigenic, immunogenic and immunosuppressive properties. fSRW was poorly immunogenic and unable to induce ragweed‐specific PCA reactions in rat skin or to bind to anti‐ragweed IgG antibodies. Intravenous administration of fSRW either prior to or after intraperitoneal immunization with a ragweed preparation resulted in a significant suppression of the immune response. T cells isolated from lymph nodes of mice immunized with ragweed were stimulated by fSRW in a lymphoproliferation assay. Moreover, T cells from mice injected with fSRW were immunosuppressive when transferred into mice immunized with intact ragweed antigens. Our data demonstrate that peptic fragments (fSRW) of ragweed lack B‐cell determinants while retaining their T‐cell immunoregulatory properties. Potentially these peptides are less likely to cause adverse reactions in allergen sensitive patients and thus offer a new approach to allergen immunotherapy.
Antigen‐dependent activation of alveolar macrophages from ovalbumin‐sensitized guinea‐pigs: relevance of the route of administration and the amount of antigen provided
Authors: BACHELET M. , LAGENTE V. , FOUQUE F. , DUMAREY C. , HAVET N. , MASLIAH J. , BEREZIAT G. , VARGAFTIG B. B. 
Published: April 2006

SummaryAlveolar macrophages from guinea‐pigs sensitized by different amounts of ovalbumin, administered either by subcutaneous injection or aerosol exposure, liberate increased amounts of arachidonic acid and thromboxanc B2 when challenged in vitro with ovalbumin. This antigen‐dependent activation of macrophages was immunospecific. The comparison between different sensitization procedures showed that the aerosol exposure was the most efficient with respect to the activation of macrophages, as cells from guinea‐pigs sensitized subcutaneously were poorly activated by the antigen unless high doses were used for sensitization. The antigen‐dependent activation of macrophages was affected by acid and neutral washings, suggesting the involvement of a loosely bound antibody that could not be identified. These observations suggest that, as mast cells and basophils, alveolar macrophages from actively sensitized guinea‐pigs contribute to the allergic reaction by an antibody‐mediated mechanism.
The effect of intranasal nedocromil sodium on viral upper respiratory tract infections in human volunteers
Authors: BARROW G. I. , HIGGINS P. G. , AL‐NAKIB W. , SMITH A. P. , WENHAM R. B. M. , TYRRELL D. A. J. 
Published: April 2006

SummaryTwo studies involving double‐blind group comparative trials in human volunteers compared the effects of intranasal nedocromil sodium (2·6 mg active drug per nostril, q.i.d.) with placebo on clinical symptoms and performance impairment associated with the common cold. In the first study volunteers were challenged with rhinoviruses (RV9 and RV14), and in the second study with respiratory coronavirus. In both studies, active and placebo groups of volunteers were demographically similar. Infection rates in both groups were also similar. There were no withdrawals resulting from unusual symptoms related to either treatment. In the rhinovirus study (19, placebo; 20, nedocromil sodium) daily symptom scores and daily mean nasal secretion weights were significantly lower in the nedocromil sodium‐treated group. In the coronavirus study (26, placebo; 27, nedocromil sodium) there was little difference in the severity of colds between the active and placebo‐treated groups, but trends favoured nedocromil sodium. In both studies the impairment of performance in volunteers who developed a cold was significantly less in those treated with nedocromil sodium than in those treated with placebo.
Serum levels of IgG subclasses in relation to IgE and atopic disease in early infancy
Authors: LILJA G. , MAGNUSSON C. G. M. , ÖMAN H. , JOHANSSON S. G. O. 
Published: April 2006

SummaryThe levels of IgG1, IgG2, IgG3 and IgG4 were analysed by FLISA in cord serum and in serum samples collected at 6 and 18 months of age from infants whose mothers were atopic. None of the four IgG subclasses was significantly influenced on any sampling occasion by infant atopy, gender, month of birth, maternal IgE or maternal diet during pregnancy and early lactation. However, at 18 months of age, significantly higher levels of IgG1 (P < 0·05) and of IgG4 (P < 0·01) were found in infants with an elevated IgE ( 8·0 kU/1) than in those with a lower level. A weak positive correlation (rs= 0·26; P= 0·05) between IgE and IgG4 was also observed. Despite the fact that the serum levels of IgG4 at 18 months were significantly higher (P < 0·01) among infants with positive IgE‐RAST ( 0·15 PRU/ml) to ovomucoid or β‐lactoglobulin, our data suggest that the the concentration of IgG4 relates more to the level of IgE than to the clinical symptoms of atopy. Determination of IgG subclasses seems to be of limited value for predicting atopy during early infancy.
Platelet activating factor does not cause a reproducible increase in bronchial responsiveness in normal man
Authors: SPENCER D. A. , GREEN SALLY E. , EVANS JANE M. , PIPER PRISCTLLA J. , COSTELLO J. F. 
Published: April 2006

SummaryThe reproducibility of acute effects of inhaled PAF on airway calibre, circulating neutrophil count and any subsequent increase in bronchial responsiveness has been studied in six normal subjects and compared to the effects of inhaled lyso‐PAF, the inactive precursor and metabolite of PAF. PAF caused acute bronchoconstriction and a transient fall in neutrophil count on two separate occasions in five out of six subjects (minimum percentage of baseline values (mean): first PAF challenge; sGaw 69%, V̇max30 72%; neutrophil count 70%; second PAF challenge; sGaw 61 %, V̇max30 74%, neutrophil count 63%). In one subject inhaled PAF caused bronchoconstriction and a transient fall in neutrophil count once, but a second challenge resulted in no detectable changes. There was no significant increase in bronchiai responsiveness to methacholine in any subject studied on five occasions over a 2‐week period following each PAF challenge. Challenge with lyso‐PAF did not cause acute effects or any subsequent changes in bronchial responsiveness. These findings demonstrate that any effects of inhaled PAF on bronchial responsiveness in normal man are small and probably not of clinical significance. It would also be inappropriate to use this human model to study the mechanisms of bronchial hyperresponsiveness or for the preliminary assessment of potential new anti‐asthma drugs.
Changes in non‐specific nasal reactivity and eosinophil influx and activation after allergen challenge
Authors: KLEMENTSSON H. , ANDERSSON M. , BAUMGARTEN C. R. , VENGE P. , PIPKORN U. 
Published: April 2006

SummaryIt has been suggested that the eosinophilic granulocyte plays a crucial role in the genesis of increased reactivity of the airways. In order to characterize changes in non‐specific reactivity in the upper airways following a nasal allergen challenge further 16 subjects with strictly seasonal allergic rhinitis were studied. They were challenged with allergen outside the relevant pollen season and monitored at intervals for a period of 24 hr for nasal symptoms, changes in nasal reactivity, eosinophil influx and activation, and markers of inflammation. The same challenge sequence without an initial allergen challenge was used as a control. A symptom score technique was used to record nasal symptoms and methacholine challenges were used to monitor changes in non‐specific reactivity. A nasal lavage was made prior to each methacholine challenge to monitor the influx of cells, specifically eosinophils, and to determine changes in the levels of eosinophil cationic protein (ECP) and TAME‐esterase activity. Cells from the mucosal surface were also collected with a Rhinobrush® prior to the allergen challenge as well as at the 24‐hr follow up. The allergen challenge induced a five‐fold increase in non‐specific nasal reactivity, as measured by the methacholine challenges, at the 2‐hr follow up from 0·051 ml ± 0·012 (mean ± s.e.m.) to 0·255 ± 0·062 (P < 0·01) and a significant increase was also noted at all observation points, whereas no increases could be observed in the control setting. With a similar timing the allergen challenge also induced an increase in the proportion of eosinophils on the mucosal surface from an initial 0·8 ± 0·4% to 6·2 ± 2·1% of the cells as early as 2 hrs later (P < 0·05). A significant correlation was foundbetween the levels ofECP and eosinophils in the lavage fluid (r= 0·64, P < 0·001) and between the levels of ECP and TAME esterase (r= 0·43, P < 0·01). No correlations were, however, disclosed between the increases in non‐specific nasal reactivity and the number of eosinophils (regardless of the cell‐harvesting technique) or ECP levels at any of the observed time points. It is therefore suggested that the allergen‐induced change in non‐specific nasal reactivity is a complex phenomenon rather than just the recruitment and activation of eosinophilic granulocytes in the nasal cavity.
Ragweed IgE and IgG4 antibody in nasal secretions during immunotherapy
Authors: PENG Z. , LEE H.‐B. , PROUD D. , NACLERIO R. , ADKINSON N. F. 
Published: April 2006

SummaryWe have developed sensitive amplified immunoassays for measurement of IgE and IgG4 ragweed (RW) antibodies in unconcentrated nasal washes. IgE to Amb a I (formerly antigen E) can be assayed to <0·1 ng/ml using IgE capture by anti‐IgE on microtitre plates and an alkaline phosphatase‐conjugated Amb a I with an amplification substrate technique. IgG4 to whole RW extract was assayed to <0·01 ng/ml by amplification ELISA using monoclonal anti‐IgG4. Nasal washes (NW) (10 ml) and serum were obtained in December from 22 RW‐sensitive patients before and after 1 and 2 yr of RW immunotherapy (IT), and assayed for Amb a I IgE or RW IgE and R W IgG4 antibodies. Amb a I IgE could be measured in the NW of 15/22 pre IT, 19/22 at 1 yr IT, but only 3/10 at 2yr IT (compared with pre‐IT, P 0·05). Mean Amb a I IgE in NW was 0·66, 0·36 and 0·21 ng/ml at pre, 1 yr and 2 yr IT (P‐values > 0·05). Mean serum RW IgE, was 76, 55 and 27 ng/ml at pre, 1 yr and 2 yr IT (P‐values > 0·05). Amb a I IgE in nasal washes was correlated with RW IgE in serum (r=0·56, P <0·001, n=44). RW IgG4 was detectable in NW of 15/22pre‐IT, 18/22 at 1 yr IT and 9/10 at 2 yr IT (P‐ values > 0·05). Mean serum RW IgG4 in NW did not change with IT (0·12, 0·16 and 0·20 ng/ml at pre, 1 yr and 2 yr IT, P‐values > 0·05). whereas serum RW IgG4 rose substantially from a mean 23 ng/ml pre IT to 197ng/ml at 1 yr IT and 1324 ng/ml at 2 yr IT (P‐values < 0·0001). Nevertheless, RW IgG4 in NW and serum was significantly correlated (r= 0·59, P 0·001, n= 44). We conclude that using sensitive immunoassays IgE and IgG4 RW antibodies can be measured in unconcentrated NW of about two‐thirds of ragweed‐sensitive patients. Both isotypes in NW have strong correlation with corresponding serum antibodies, but the significant rise of serum RW IgG4 after IT is not reflected in NW of asymptomatic subjects out of season. Whether allergic inflammation can increase IgG4 in NW remains to be determined.
Plasma exudation as a first line respiratory mucosal defence
Authors: PERSSON C. G. A. , ERJEFÄLT I. , ALKNER U. , BAUMGARTEN C. , GREIFF L. , GUSTAFSSON B. , LUTS A. , PIPKORN U. , SUNDLER F. , SVENSSON C. , WOLLMER P. 
Published: April 2006

SummaryA great variety of provocations of the airway mucosa produce extravasation of plasma from the abundant subepithelial microvessels. A plasma exudate has important actions through its volume, its specific and unspecific binding proteins, its enzyme systems, and its potent peptides (of kinin. complement, coagulation, fibrinolysis and other systems). If allowed to operate on the surface of an intact mucosa the plasma exudale would have important roles in normal airway defence. Recent observations in guinea‐pig tracheo‐bronchial airways and in human nasal airways suggest that the mucosal exudation of plasma into the airway lumen is a non‐injurious fully reversible process. Threshold exudative responses thus resulted in the appearance of an ‘unfiltered’ plasma exudate not only in the lamina propria but also on the surface of an undisrupted mucosa. Even after extensive luminal entry of exudate the epithelial lining was intact, as judged by light, fluorescence and electron microscopy. Hence, the epithelial barrier was reversibly permeable when approached from beneath by the plasma exudate. This was a distinct increase in outward permeability, because even during the exudation of plasma the mucosa remained a barrier to luminal solutes. It is possible that the exudate itself, by a slight compressive action on the basolateral aspect of epithelial cells, creates intercellular pathways for its entry into the lumen. Contrary to current beliefs, we propose that plasma exudation should be considered a first line respiratory defence mechanism operating together with other systems of the mucosal surface.
Unexplained CD4‐positive T‐cell deficiency in non‐HIV patients presenting as a Pneumocystis carinii pneumonia
Authors: GAUTIER V. , CHANEZ P. , VENDRELL J. P. , PUJOL J. L. , LACOSTE J. Y. , DE FAUCAL H. , GODARD P. , MICHEL F. B. 
Published: April 2006

SummaryThree cases of Pneumocystis carinii pneumonia occurring in adults with unexplained T‐cell defects are reported. No HIV markers were found during the follow up, and neither was any immunosuppressive disease. The authors emphasize the possibility that Pneumocystis pneumonia may occur and may be treated successfully in previously healthy subjects.
Liposomes as carriers for allergy immunotherapy
Authors: AUDERA C. , RAMÍREZ J. , SOLER E. , CARREIRA J. 
Published: April 2006

SummaryWith the aim of obtaining an efficient but safer vaccine for allergy immunotherapy, the possibility of using liposomes as adjuvants has been considered given their proven low toxicity, adjuvant properties and ability to maintain the encapsulated substance in their interior for sonic time in vivo. Different methods of encapsulating allergenic extracts into neutral, positively, and negatively charged DPPC: cholesterol liposomes have been investigated and the immune response provoked by these in mice was studied and compared to the immune response to free allergen or other adjuvants such as aluminium hydroxide. The results obtained show that allergen encapsulated in all three types of liposomes elicit an increase in specific IgG levels higher than that provoked by free allergen, however, both encapsulation efficiency and specific FgG litre were higher when positively charged (DPPC.‐cholesterol steurylamine) liposomes were used. Specific IgF. levels to allergen in positive and neutral liposomes was lower than to allergen in negative liposomes or adsorbed to A1(OH)3 No differences were found in the behaviour of liposomes prepared by different methods (the results were obtained from pooled sera from different groups of mice so there is no statistical data). These results confirm the immunoadjuvanl effect of liposomes for allergy immunotherapy. Further studies to determine their lack of toxicity, pharmacokinetic studies and human clinical studies are necessary to confirm their adequacy for human use and advantage over current immunotherapy methods.
Adrenocortical suppression following treatment with beclomethasone and budesonide
Authors: PRAHL P. 
Published: April 2006

SummaryThe study was carried out to compare the adrenocortical suppression caused by inhaled beclomethasone dipropionate (BDP) with the suppression caused by budesonide (Bu). The study was of an open cross‐over design. Sixteen children with asthma were treated with high‐dose inhaled BDP and Bu via a 750 ml spacer (Nebuhaler), Each drug was used for periods of 6 weeks. The 24‐hr urinary cortisol excretion was unchanged in 11 subjects. A reproducible suppression of the urinary cortisol excretion was shown in three subjects following BDP and in two subjects following treatment with Bu. The results of the study indicate the occurrence of interpersonal variations of the sensitivity to the adrenocortical suppressive effect of BDP and Bu.
Double‐blind cross‐over trial of oral sodium cromoglycate in patients with irritable bowel syndrome due to food intolerance
Authors: LUNARDI C. , BAMBARA L. M. , BIASI D. , CORTINA P. , PEROLI P. , NICOLIS F. , FAVARI F. , PACOR M. L. 
Published: April 2006

SummaryTwenty patients with irritable bowel syndrome due to food intolerance were randomized to either oral sodium cromoglycate or placebo in a double‐blind cross‐over trial. The study consisted of treatment with either sodium cromoglycate or placebo for 8 weeks, followed by the cross‐over treatment for 8 further weeks. Patients were allowed to eat the offending foods during the study. Eighteen patients completed the study. Analysis of patients' diary card scores showed a statistically significant difference in favour of sodium cromoglycate. There was a long carry‐over effect in the active‐placebo order group. Therefore oral sodium cromoglycate seems to be a useful treatment in patients with irritable bowel syndrome and proven food intolerance.
Allergy from cellulase and xylanase enzymes
Authors: TARVAINEN K. , KANERVA L. , TUPASELA O. , GRENQUIST‐NORDEN B. , JOLANKI R. , ESTLANDER T. , KESKINEN H. 
Published: April 2006

SummaryModern biotechnical methods have enabled production of many new types of potentially allergenic proteins. Enzymes have long been known to be respiratory allergens, but relatively few cases of skin allergy have been reported. Here we describe four patients who developed occupational allergic respiratory symptoms, three with bronchial asthma and one with allergic rhinitis, caused by cellulase and/or xylanase enzymes. Each patient also had urticarial symptoms after skin contact with these enzymes. In addition, one of the patients had allergic contact dermatitis from cellulase, and one from xylanase. Allergic contact dermatitis was verified by positive patch tests with the enzymes, and the immediate allergy was revealed by skin prick tests, specific IgE determinations (RAST) and RAST‐inhibition tests. All patients had positive RASTs to both cellulase and xylanase. In the RAST inhibition test 20 μ1 of cellulase brought about a 94% inhibition, indicating the specificity of the RAST. Xylanase (20 μl, 5% w/v) gave an 92% inhibition of cellulase RAST, indicating cross‐reactivity between cellulase and xylanase. Three patients have been able to continue at their previous places of work, but at different worksites. One of the patients requires continuous medication for asthma and had to change her job because of persistent symptoms.
Emergency treatment of allergic reactions to Hymenoptera stings
Authors: MÜLLER U. , MOSBECH H. , BLAAUW P. , DREBORG S. , MALLING H. J. , PRZYBILLA B. , URBANEK R. , PASTORELLO E. , BLANCA M. , BOUSQUET J. , JARISCH R. , YOULTEN L. 
Published: April 2006

SummaryAllergic reactions to Hymenoptera stings are frequently observed all over Europe. Rarely they may induce long‐standing morbidity or even be fatal. Several investigations have shown that the emergency treatment given to these patients is often inadequate. Cutaneous symptoms respond well to antihistamines and also to adrenaline. Adrenaline is the mainstay for outside hospital treatment of more severe reactions involving the respiratory tract (bronchial asthma, laryngeal oedema) and the cardiovascular system (anaphylactic shock). Inhaled adrenaline is especially useful in respiratory symptoms, while parenteral application of adrenaline is prefered for shock treatment. All patients with severe respiratory or cardiovascular reactions must be hospitalized, treated under intensive care conditions and observed for at least 24 hr. Emergency medications including adrenaline for inhalation or for self‐injection must be given to all patients with a history of systemic allergic reactions to hymenoptera stings. These patients must also get instructions for safety measures to avoid further stings. They should be referred to an allergist in order to evaluate the indication for venom immunotherapy.
Effect of azelastine and ketotifen on the bronchial and skin responses to platelet‐activating factor in humans
Authors: LAI C. K. W. , OLLIER S. , LAU C. K. , HOLGATE S. T. 
Published: April 2006

SummaryIn a randomized, double‐blind placebo‐controlled study we investigated the effect of single oral doses of 8 mg azelastine and 2 mg ketotifen on the immediate response to platelet‐activating factor (PAF) inhalation and to increasing doses of PAF injected intradermally. Bronchial provocation with 100 μg of PAF resulted in marked bronchoconstrictor responses, but neither azelastine nor ketotifen had any significant effect on these responses. Intradermal injection of PAF (100, 200 and 400 ng) resulted in a dose‐related weal and flare response. Azelastine and ketotifen both caused significant reductions in this response (P < 0.002‐ P < 0.01). There was no significant difference between the effect of the two drugs.