bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost–utility analysis in evaluating prophylaxis in haemophilia
Authors: Carcao M. , Ungar W. J. , Feldman B. M.
Published: February 2004

Summary.  Prophylaxis is an expensive form of management in haemophilia but has demonstrated many advantages with respect to decreasing joint bleeds and potentially preventing joint damage. The valuation of prophylaxis and how the costs and benefits of this intervention compare with other interventions in the management of haemophiliacs can be evaluated through cost–utility analysis (CUA). CUA is an economic method of analysis where the benefits of a healthcare intervention are expressed as an overall utility or preference, usually in the form of quality‐adjusted life years (QALYs). This is a composite measure, which takes into consideration both an individual's lifespan and quality of life (QoL). The most difficult aspect of performing a CUA is the measurement of health‐related QoL (HRQoL). Much work is ongoing into evaluating HRQoL in haemophiliacs. This paper addresses some of the ways in which this can be achieved and some of the problems with evaluating HRQoL. Ultimately CUA may provide a tool to allow societies to decide if prophylaxis is worth the cost and how the costs and benefits of prophylaxis compare to other healthcare interventions for other disease entities.
Setting research priorities to improve cost‐effectiveness estimations of primary prophylaxis with clotting factor for people with severe haemophilia
Authors: Miners A. H. , Lee C. A.
Published: February 2004

Summary.  Primary prophylaxis with clotting factor is the clinical treatment of choice for people with severe haemophilia, as evidence suggests it can prevent the onset and progression of joint‐ and muscle‐related problems caused by bleeding episodes. However, the major limitation of this approach is that it requires considerably more clotting factor compared with treating on‐demand. Thus, there is a need to establish its cost‐effectiveness. The aim of this paper is to review the published evidence on the cost‐effectiveness of prophylaxis and to highlight areas for future research that would decrease the uncertainty around these findings.
Utilization of care in haemophilia: a resource‐based method for cost analysis from the Haemophilia Utilization Group Study (HUGS)
Authors: Globe D. R. , Curtis R. G. , Koerper M. A. ,   For the HUGS Steering Committee
Published: February 2004

Summary.  The Haemophilia Utilization Group Study (HUGS) was created 10 years ago to examine the annual utilization and cost of haemophilia‐related healthcare services. Retrospective chart reviews for 336 patients with haemophilia A receiving treatment in one of five comprehensive haemophilia treatment centres (HTCs) during 1995 were completed through interview of the provider. This method provided adequate collection of data from patient charts without the abstractor having direct access to patient health information. Utilization data were used to impute the costs of different components of care (e.g. physician visits, factor VIII concentrate, emergency room, hospitalization). The total annual cost of care was $139 102 (SD $304 033). Factor VIII concentrate costs comprised the largest proportion of these costs; mean factor VIII concentrate use was 128 517 units per patient per year. Unbilled physician utilization accounted for 7.8% of the mean total physician costs per annum, while mean allied healthcare costs accounted for 33.5% of the total annual allied healthcare costs per patient. In the ordinary least‐squares regression model, higher costs were associated with severe factor VIII deficiency, arthropathy, more comorbid conditions, an inhibitor to factor VIII concentrate, infusing through a port and prophylaxis. Although factor VIII concentrate is the most costly component, the treatment of haemophilia uses many healthcare resources. HUGS has demonstrated that patient clinical characteristics and physician practices predominantly drive the costs of haemophilia care. Specifically, patients with more severe arthropathy had greater healthcare costs. As future funding decisions are made, it is important to provide for all components of care.
An association study of asthma and total serum immunoglobin E levels for Toll‐like receptor polymorphisms in a Japanese population
Authors: Noguchi E. , Nishimura F. , Fukai H. , Kim J. , Ichikawa K. , Shibasaki M. , Arinami T.
Published: February 2004

Background
The prevalence of atopic diseases has been increasing in developed countries. This could be explained by the hygiene hypothesis, which states that exposure to specific infections or endotoxins during infancy drives the maturing immune system towards a Th1 phenotype and away from the Th2 phenotype, which is associated with allergic diseases. Toll‐like receptors (TLRs) play important roles in the signalling of many pathogen‐related molecules and endogenous proteins associated with immune activation.

Objective
The aim of the present study was to investigate whether polymorphisms in genes encoding TLRs are associated with asthma or total serum IgE levels.

Methods
We screened the 5′ flanking and coding regions of the TLR2,TLR3, TLR4, and TLR9 genes for polymorphisms by direct sequencing of DNA from 32 asthmatics, and analysed the effect of the polymorphisms on the development of atopic asthma and on total serum IgE levels.

Results
We identified 16 variants in TLRs. The transmission disequilibrium test of the families revealed that none of the alleles or haplotypes were associated with asthma or total IgE levels (P>0.05). However, we found an insertion/deletion polymorphism in the 5′ untranslated region of TLR2, and an expression construct containing the deletion allele showed lower luciferase activity than the wild‐type alleles, suggesting that the deletion allele has reduced transcriptional activity.

Conclusion
Our results indicate that polymorphisms in TLRs are not likely to be associated with the development of atopy‐related phenotypes in a Japanese population.
Maternally delivered nutritive allergens in cord blood and in placental tissue of term and preterm neonates
Authors: Edelbauer M. , Loibichler C. , Nentwich I. , Gerstmayr M. , Urbanek R. , Szépfalusi Z.
Published: February 2004

Background
The proliferation of cord blood mononulear cells in response to nutritive and inhalant allergens implies intrauterine exposure with resulting T cell priming. However, the mechanisms triggering these fetal allergen‐specific immune responses are incompletely understood.

Methods
We studied the placental release of endogenous β‐lactoglobulin (BLG) and ovalbumin (OVA) by the use of an open ex vivo placental perfusion model. Preterm and term placentas were obtained immediately after delivery to recover functionally active fetal and maternal circulations. Fetal and maternal perfusate samples were collected throughout the perfusion experiments with medium. Matched cord blood samples were collected separately. All samples were tested for the presence of OVA and BLG by allergen‐specific ELISAs.

Results
In 16 out of 19 placentas, the nutritive allergens could be detected both in fetal and maternal perfusate samples. Fetal wash out levels of the allergens BLG and OVA from the placental tissue of preterm and term deliveries were observed in traces and up to 44.4 and 2.6 ng/mL, respectively. In cord blood of preterm and term neonates, BLG and OVA could be detected at concentrations up to 16.7 and 5 ng/mL, respectively.

Conclusion
These findings provide direct evidence for the release of tiny amounts of nutritive allergens from placental tissue indicating diaplacental allergen transfer and fetal exposure to nutritive allergens in vivo.
Differential modulation of mediator release from human basophils and mast cells by mizolastine
Authors: Triggiani M. , Giannattasio G. , Balestrieri B. , Granata F. , Gelb M. H. , De Paulis A. , Marone G.
Published: February 2004

Background
Basophils and mast cells play a major role in the pathogenesis of allergic disorders by releasing several proinflammatory mediators. Some histamine H1 receptor antagonists exert anti‐inflammatory activities by modulating mediator release from basophils and mast cells.

Objective
To study the in vitro effects of mizolastine, an H1 receptor antagonist, on the release of eicosanoids, histamine and IL‐4 from human basophils and lung mast cells.

Methods and results
Mizolastine (10−7–10−5 m) concentration‐dependently inhibited the release of cysteinyl leukotriene C4 from anti‐IgE‐stimulated basophils (IC50: 3.85±0.28 μm) and mast cells (IC50: 3.92±0.41 μm). The same concentrations of mizolastine did not affect anti‐IgE‐induced prostaglandin D2 release from lung mast cells. In contrast, mizolastine enhanced up to 80% IgE‐mediated histamine release (EC50: 4.63±0.14 μm) from basophils, but not from mast cells and it significantly potentiated IL‐4 release from basophils induced by anti‐IgE. Mizolastine did not affect histamine release from basophils induced by formyl peptide, whereas it inhibited cysteinyl leukotriene C4 release (IC50: 1.86±0.24 μm). Blockade of cytosolic phospholipase A2 and arachidonic acid mobilization by pyrrolidine‐1 did not alter the effect of mizolastine on histamine release from basophils, thereby excluding accumulation of arachidonic acid metabolic intermediates as the cause of this effect. Mizolastine did not influence anti‐IgE‐induced activation of extracellular signal‐regulated kinase‐1 and ‐2 (ERK‐1 and ‐2) in human basophils.

Conclusions
Mizolastine efficiently inhibits LTC4 synthesis in human basophils and mast cells presumably by interfering with 5‐lipoxygenase. In contrast, it enhances histamine and IL‐4 release only from anti‐IgE‐stimulated basophils. Therefore, mizolastine differentially regulates the production of mediators from basophils and mast cells in a cell‐ and stimulus‐specific fashion.
Inflammatory cell profiles and T‐lymphocyte subsets in chronic obstructive pulmonary disease and severe persistent asthma
Authors: Tsoumakidou M. , Tzanakis N. , Kyriakou D. , Chrysofakis G. , Siafakas N. M.
Published: February 2004

Background
Severe persistent asthma (SPA) and chronic obstructive pulmonary disease (COPD) are both associated with non‐reversible airflow limitation and airway neutrophilia.

Objective
To compare inflammatory cell profiles and T lymphocyte subsets between SPA and COPD patients with similar severity of airflow limitation.

Methods
Sputum induction and lung function tests were performed in 15 COPD patients aged (mean±SD) 68±8 years, ex‐smokers, mean forced expiratory volume in 1 s (FEV1) 45% of predicted (%pred) and 13 SPA aged 55±10 years, non‐smokers, mean FEV1 49%pred. All patients were on inhaled steroid treatment. Eight asthmatics exhibited irreversible airflow limitation. Differential cell count, metachromatic cell count and double immunocytochemistry for the analysis of T lymphocyte subsets were performed on sputum slides.

Results
COPD patients had increased sputum neutrophils in comparison with SPA (P<0.03), but similar to SPA with fixed obstruction. In COPD sputum neutrophils negatively correlated with the lung transfer factor for carbon monoxide (KCO) (r=−0.462, P=0.04). SPA showed significantly increased eosinophils and metachromatic cells vs. COPD patients (P<0.04, P<0.007, respectively). Increased CD4/CD8 and decreased CD4‐IFN‐γ/CD4‐IL4+ cell ratio (P<0.001) were found in SPA vs. COPD. In SPA, CD4/CD8+ cell ratio correlated with sputum eosinophils (r=0.567, P=0.04).

Conclusion
In spite of treatment with inhaled steroids, SPA and COPD exhibit distinct sputum inflammatory cell patterns, although SPA with fixed airflow limitation and COPD patients have similar numbers of neutrophils.
Biological characterization of glutaraldehyde‐modified Parietaria judaica pollen extracts
Authors: Ibarrola I. , Sanz M. L. , Gamboa P. M. , Mir A. , Benahmed D. , Ferrer A. , Arilla M. C. , Martínez A. , Asturias J. A.
Published: February 2004

Background
Allergoids are widely used in specific immunotherapy (SIT) for the treatment of IgE‐mediated allergic diseases, but all techniques for standardization of conventional allergic extracts may not be appropriate for standardization of a glutaraldehyde (GA)‐modified extract because of the unique characteristics of these extracts.

Objective
To assess an accurate methodology for standardization of chemically modified extracts.

Methods
GA‐modified extracts from Parietaria judaica pollen were purified by diafiltration. Biochemical properties were investigated by determination of amino groups, chromatography, and SDS‐PAGE. The IgE‐binding activity was determined by skin prick test, enzyme allergosorbent test inhibition, basophil activation, and histamine release tests. Peripheral blood mononuclear cells (PBMCs) from P. judaica pollen‐allergic subjects were stimulated with either native or allergoid extracts, and proliferation was measured.

Results
Biochemical data indicated a high degree of allergen polymerization resulting in extract components higher than 100 kDa. IgE‐binding activity, both in vivo and in vitro, was reduced by more than 99.8%. Both allergen and allergoid induced PBMC proliferation and synthesis of blocking IgG antibodies at similar rates. Moreover, no evidence of introduction of new determinants by chemical modification was found.

Conclusions
The preparation of GA‐modified extracts by diafiltration is faster and more reliable than previous chromatographic methods. These modified extracts have drastically reduced their allergenicity while maintaining their immunogenicity, and therefore they can be used in safer and shortened schedules of SIT.
Effect of repeated intradermal injections of heat‐inactivated Mycobacterium bovis bacillus Calmette–Guérin in adult asthma
Authors: Shirtcliffe P. M. , Easthope S. E. , Weatherall M. , Beasley R.
Published: February 2004

Background
There are a number of reports in the Chinese medical literature from the last 30 years regarding the efficacy of repeated doses of heat‐inactivated bacillus Calmette–Guérin (BCG) in established asthma. There is also epidemiological and experimental evidence that exposure to mycobacteria has the potential to suppress the development of asthma/atopy.

Methods
Thirty‐one Mantoux‐negative adults with stable moderately severe asthma who were skin prick test positive to house dust mite were randomized to receive one injection (0.1 mL) a week for 4 weeks of heat‐inactivated BCG or normal saline. Markers of asthma severity (including peak flow, forced expiratory volume in 1 s, major and minor exacerbations, symptom scores and β‐agonist use), blood eosinophil and IgE levels were monitored for 3 months.

Results
There were no statistically significant differences between the treatment group and placebo for any of the outcome variables. The recruitment to the trial was halted early and the number of injections reduced in a number of patients due to excessive local reactions to BCG.

Conclusions
In addition to the lack of efficacy of repeated heat‐inactivated BCG injections, the occurrence of severe local reactions will limit the therapeutic application of this approach in asthma.
A review of the effects of impermeable bedding encasements on dust‐mite allergen exposure and bronchial hyper‐responsiveness in dust‐mite‐sensitized patients
Authors: Recer G. M.
Published: February 2004

Background
Sensitization and exposure to dust‐mite antigens are causative factors in the development and exacerbation of asthma. Impermeable bedding encasements are considered a first‐line treatment to reduce dust‐mite antigen exposure in clinical asthma‐management guidelines. Public‐health recommendations for environmental asthma treatments should be based on the weight of evidence supporting the reliability of environmental interventions so that uncertainties regarding their effectiveness can be accurately communicated to patients, and so that limited public‐health resources can be most effectively utilized.

Objective
To evaluate the strength of a clinical‐trial evidence supporting the efficacy of bedding encasements as an asthma treatment.

Methods
A narrative review was conducted of all clinical trials involving bedding encasement for the treatment of asthma. Collective statistical analyses were also performed to characterize the quantitative effect of bedding encasement on dust‐mite allergen exposure and bronchial hyper‐responsiveness (BHR) when used by asthma patients.

Results
Over 30 clinical trials were reviewed. Of those studies reporting adequate exposure and BHR results, four reported significant reduction in dust‐mite allergen exposure and concomitant BHR reduction in active‐treatment groups using bedding encasements. In 10 studies, mite‐allergen exposure was reportedly decreased during the study, but BHR was not changed in the active‐treatment group or was reduced to a similar degree in the active‐treatment and control groups. Five other studies reported a lack of significant effect of the intervention on exposure and BHR. Collective paired analyses found that the effect of bedding encasement on allergen exposure and BHR tended toward only a modest, non‐significant improvement. Collectively, effects of bedding encasement on BHR and dust‐mite allergen exposure were modestly correlated only when the baseline exposure was above 2 μg Type 1 antigen per gram settled dust.

Conclusion
Although bedding encasement might be an effective asthma treatment under some conditions, when implemented in clinical trials by asthma patients, its effectiveness is inconsistent and appears to be, at best, modest. Therefore, its significance as a reliable asthma management modality for any individual asthma patient is uncertain. Where resource constraints are significant, targeting the use of variably effective interventions such as bedding encasements toward those patient sub‐populations most likely to derive substantial benefit may gain the largest net public‐health benefit.
Inflammatory changes associated with circadian variation in pulmonary function in subjects with mild asthma
Authors: Kelly E. A. B. , Houtman J. J. , Jarjour N. N.
Published: February 2004

Background
Nocturnal enhancement of airway inflammation has been demonstrated in patients with asthma who have a significant drop in pulmonary function at night.

Objective
To investigate the circadian changes in airway inflammation and their relationship with variations in pulmonary function in subjects with mild atopic asthma.

Methods
Twelve asthma subjects were admitted to the hospital for two separate 24‐h visits. Bronchoalveolar lavage (BAL) was performed at 04:00 hours during one visit, and at 16:00 hours during another visit. BAL cells were analysed for lymphocyte phenotype and the capacity to secrete cytokines following ex vivo stimulation with phytohaemagglutinin (PHA).

Results
The numbers of BAL lymphocytes and the percentage of CD4+ T cells were higher at 04:00 hours compared with 16:00 hours. At 04:00 hours, the forced expiratory volume in 1 s (FEV1) was inversely correlated with BAL lymphocytes and CD4+ cells. PHA‐induced generation of IL‐5 by BAL cells correlated with BAL eosinophils and CD4+ cells. Moreover, there was a linear relationship between the relative change (16:00–04:00 hours) in IL‐5 and circadian variation in FEV1.

Conclusions
These data suggest that the circadian variation in lung function in asthma is associated with increased airway CD4+ lymphocyte numbers and their capacity to generate IL‐5. Furthermore, in mild asthma, these circadian changes appear to fall into a continuous range, suggesting that day/night variations in airway inflammation and lung function occur on a continuum, rather than as an all‐or‐none phenomenon.
Gene–gene synergistic effect on atopic asthma: tumour necrosis factor‐α‐308 and lymphotoxin‐α‐NcoI in Taiwan's children
Authors: Wang T.‐N. , Chen W.‐Y. , Wang T.‐H. , Chen C.‐J. , Huang L.‐Y. , Ko Y.‐C.
Published: February 2004

Background
Asthma is now known to be an inflammatory response caused by the release of inflammatory mediators and cytokines. Tumour necrosis factor (TNF) is a potent cytokine in the inflammation response of the airway, and the polymorphisms of TNF genes have been associated with asthma.

Objective
This study investigated two variants, TNF‐α‐308*2 and lymphotoxin (LT)‐α‐NcoI*1, which may predispose individuals to asthma and atopy pathogenesis.

Methods
PCR‐based assays were performed to determine LT‐α‐NcoI*1 and TNF‐α‐308*2 genotypes among our subjects, with 128 atopic asthmatics and 51 non‐atopic asthmatics, 55 atopic controls, and 78 non‐atopic controls in this genetic case–control study.

Results
The TNF‐α‐308*2 polymorphism increased in subjects with atopic asthma vs. non‐atopic controls after adjusting for age distribution (adjusted odds ratios, AOR=2.73, 95% confidence interval, CI=1.16–6.64), but was not associated with non‐atopic asthma (AOR=2.40, 95% CI=0.81–7.09). LT‐α‐NcoI*1 did not show an independent association with either atopic asthma or any one phenotype of specific IgE. The synergistic effect between these two genes was conducted, and the interaction between TNF‐α‐308*2 and LT‐α‐NcoI*1 polymorphisms was seen for atopic asthma (OR=2.59, 95% CI=1.10–6.10) when compared with all controls.

Conclusion
We have concluded that TNF‐α‐308 may be a risk factor for atopic asthma, whereas the LT‐α‐NcoI polymorphism may modify risk to atopic asthma with TNF‐α‐308.
Resolution of allergic airways inflammation but persistence of airway smooth muscle proliferation after repeated allergen exposures
Authors: Leung S.‐Y. , Eynott P. , Noble A. , Nath P. , F. Chung K.
Published: February 2004

Background
Chronic inflammation in asthmatic airways can lead to characteristic airway smooth muscle (ASM) thickening and pathological changes within the airway wall.

Objective
We investigated the long‐term effects of repeated allergen exposure.

Methods
Brown‐Norway (BN) rats sensitized to ovalbumin (OVA) were exposed to OVA or saline aerosol every third day on six occasions and studied 24 h, 7 days and 35 days after the final exposure. We measured airway inflammation, ASM cell proliferation (by incorporation of bromodeoxyuridine; BrdU) and bronchial responsiveness to acetylcholine.

Results
At 24 h, in OVA‐exposed rats, we detected elevated OVA‐specific serum IgE, increased numbers of macrophages, eosinophils, lymphocytes and neutrophils in the bronchoalveolar lavage (BAL) fluid and increased numbers of MBP+ (major basic protein) eosinophils and CD2+ T cells within the bronchial submucosa. This coincided with increased numbers of ASM cells expressing BrdU and with bronchial hyper‐responsiveness (BHR). At 7 days, BHR was detected in OVA‐exposed rats, coincident with increased numbers of macrophages and lymphocytes in BAL fluid together with increased numbers of CD2+ T cells within the bronchial submucosa. This coincided with increased numbers of ASM cells expressing BrdU. By day 35, the number of ASM cells expressing BrdU remained elevated in the absence of cellular infiltration and BHR.

Conclusion
Repeated OVA‐challenge results in persistent ASM cell proliferation in the absence of bronchial inflammation and BHR, which lasts for at least 1 week following cessation of exposure.
Respiratory allergy to peach leaves and lipid‐transfer proteins
Authors: García B. E. , Lombardero M. , Echechipía S. , Olaguibel J. M. , Díaz‐Perales A. , Sánchez‐Monge R. , Barber D. , Salcedo G. , Tabar A. I.
Published: February 2004

Background
Several lipid‐transfer proteins (LTPs) have been identified as important food allergens, especially in fruits of the Rosaceae family. The major peach (Prunus persica) allergen has been identified, sequenced and designated Pru p 3.

Objective
To present Pru p 3 as an aeroallergen able to induce occupational asthma.

Methods
A thorough investigation was performed in a fruit grower with occupational asthma. Skin prick–prick tests with peach leaves and prick tests with perennial respiratory allergens and pollens, fruits and peach leaf extracts were done. Serum‐specific IgE was tested for peach leaf, peach fruit, peach skin and respiratory allergens that were positive in skin prick tests. Specific bronchial provocation tests (BPTs) with extracts of peach leaf were also done. Before and 24 h after the BPT, BPTs with methacholine and sputum induction were done. The IgE reactivity pattern to peach leaf and fruit extracts and to Pru p 3 was identified by using SDS‐PAGE and immunoblotting. Blotting inhibition of peach leaf extract by Pru p 3 was also performed. The putative allergen was quantified in leaf and fruit skin extracts with ELISA based on an anti‐Pru p 3 antibody.

Results
Skin tests were positive for peach leaf and fruit. The BPT was positive, with immediate and delayed response. This test induced a decrease in PD20 (dose of agonist that induces a 20% fall in FEV1) methacholine and an increase in eosinophils and eosinophil cationic protein in sputum. Peach leaf extract contained concentrations of Pru p 3 similar to those found in peach skin. Specific IgE immunodetection showed that patient's sera reacted with Pru p 3, and with a single major band from the peach leaf extract fully inhibited by Pru p 3.

Conclusion
Pru p 3 from peach leaves can act as a respiratory allergen and cause occupational rhinoconjunctivitis and asthma.
Phleum pratense pollen starch granules induce humoral and cell‐mediated immune responses in a rat model of allergy
Authors: Motta A. , Peltre G. , Dormans J. A. M. A. , Withagen C. E. T. , Lacroix G. , Bois F. , Steerenberg P. A.
Published: February 2004

Background
Timothy grass (Phleum pratense) pollen allergens are an important cause of allergic symptoms. However, pollen grains are too large to penetrate the deeper airways. Grass pollen is known to release allergen‐bearing starch granules (SG) upon contact with water. These granules can create an inhalable allergenic aerosol capable of triggering an early asthmatic response and are implicated in thunderstorm‐associated asthma.

Objective
We studied the humoral (IgE) and bronchial lymph node cells reactivities to SG from timothy grass pollen in pollen‐sensitized rats.

Methods
Brown–Norway rats were sensitized (day 0) and challenged (day 21) intratracheally with intact pollen and kept immunized by pollen intranasal instillation by 4 weeks intervals during 3 months. Blood and bronchial lymph nodes were collected 7 days after the last intranasal challenge. SG were purified from fresh timothy grass pollen using 5 μm mesh filters. To determine the humoral response (IgE) to SG, we developed an original ELISA inhibition test, based on competition between pollen allergens and purified SG. The cell‐mediated response to SG in the bronchial lymph node cells was determined by measuring the uptake of [3H]thymidine in a proliferation assay.

Results
An antibody response to SG was induced, and purified SG were able to inhibit the IgE ELISA absorbance by 45%. Pollen extract and intact pollen gave inhibitions of 55% and 52%, respectively. A cell‐mediated response was also found, as pollen extract, intact pollen and SG triggered proliferation of bronchial lymph node cells.

Conclusions
It was confirmed that timothy grass pollen contains allergen‐loaded SG, which are released upon contact with water. These granules were shown to be recognized by pollen‐sensitized rats sera and to trigger lymph node cell proliferation in these rats. These data provide new arguments supporting the implication of grass pollen SG in allergic asthma.
A dose‐ranging study of the effects of mequitazine on actual driving, memory and psychomotor performance as compared to dexchlorpheniramine, cetirizine and placebo
Authors: Theunissen E. L. , Vermeeren A. , Van Oers A. C. M. , Van Maris I. , Ramaekers J. G.
Published: February 2004

Background
Mequitazine is a so‐called ‘non‐sedative’ second‐generation antihistamine even though it has never been firmly established that this drug's sedative potential actually differs from that of the ‘sedative’ first‐generation antihistamines.

Objective
The present study compares the sedative effects of three doses of mequitazine on actual driving, psychomotor performance and memory with those of a first‐ and a second‐generation antihistamine.

Methods
Eighteen healthy volunteers received on separate days a single dose of 5, 10 and 15 mg mequitazine, 10 mg cetirizine, 6 mg dexchlorpheniramine and placebo. Drug effects were assessed using two actual driving tests (highway‐driving test and car‐following test), cognitive and psychometric tests (tracking, divided attention, memory, reasoning and critical flicker fusion), pupil size and questionnaires.

Results
Highway‐driving data revealed an overall effect of Treatment on the standard deviation of lateral position (SDLP). Dexchlorpheniramine impaired driving performance as indicated by a significant rise in SDLP. Mequitazine significantly increased SDLP in a dose‐related manner, but the separate dose effects failed to reach statistical significance. Divided attention performance was also affected by Treatment. Reaction time (RT) during mequitazine treatments increased in a dose‐related manner and significantly differed from placebo at the highest dose. Subjects reported to be less alert after treatment with dexchlorpheniramine. Cetirizine did not affect performance in any of the tasks.

Conclusion
It was concluded that mequitazine is mildly sedating. The effects of mequitazine are comparable to those of other second‐generation antihistamines, in that it causes mild driving impairment, particularly at higher doses.
Incidence of anaphylaxis with circulatory symptoms: a study over a 3‐year period comprising 940 000 inhabitants of the Swiss Canton Bern
Authors: Helbling A. , Hurni T. , Mueller U. R. , Pichler W. J.
Published: February 2004

Background
Diagnosis of anaphylaxis is clinically based and usually straightforward. However, data on the epidemiology of anaphylaxis, particularly the most profound and life‐threatening form such as anaphylactic shock are limited and thought to be under‐reported.

Objective
The primary aim of this study was to investigate the incidence and the causes of severe anaphylaxis with circulatory signs in the Canton Bern, which comprises about 940 000 inhabitants or approximately one‐seventh of the population of Switzerland.

Methods
During a 3‐year period, 1 January 1996 to 31 December 1998, all medical records (7739 documents) from the two allergy clinics of the Canton Bern have been reviewed. In addition, all seven board‐certified specialists of the Foederatio Medicorum Helveticorum (FMH) in Allergology and Clinical Immunology of this Canton as well as all 17 hospitals with emergency units of this area have been contacted for cases with an anaphylactic event not referred to the allergy clinics.

Results
Overall, 226 individuals, 106 females (47%) with a mean age of 41 years (range, 5–74 years) and 120 males (53%) with a mean age of 38 years (8 months–83 years) were diagnosed as having presented generalized, life‐threatening anaphylaxis with circulatory symptoms. Altogether, these patients experienced 246 episodes of severe systemic reactions. In addition, death due to anaphylaxis occurred in three subjects. The annual incidence of anaphylaxis per 100 000 inhabitants per year ranged between 7.9 and 9.6 cases. Hymenoptera stings (58.8%), drugs (18.1%), and foods (10.1%) were the most commonly identified culprits for anaphylaxis. In 5.3% of all anaphylactic events, the cause could not be identified.

Conclusion
The incidence rate of severe life‐threatening anaphylaxis with circulatory signs in the Canton Bern, Switzerland, with 7.9–9.6 per 100 000 inhabitants per year is comparable to the findings of other epidemiological investigations. In most events, a causal agent or allergen could be identified by a careful allergological examination.
Exhaled nitric oxide: relation to sensitization and respiratory symptoms
Authors: Olin A.‐C. , Alving K. , Torén K.
Published: February 2004

Background
Conflicting data have been presented as to whether nitric oxide (NO) in exhaled air is merely reflecting atopy rather than airway inflammation.

Objective
To investigate the relationship between exhaled NO (eNO) and nasal NO (nNO), respiratory symptoms, and atopy, in the context of a cross‐sectional study of the respiratory health of bleachery workers.

Methods
Two hundred and forty‐six non‐smoking bleachery and paper‐mill workers answered a questionnaire and were examined by measurements of eNO and nNO and spirometry, outside the pollen season. Blood samples were collected and analysed for specific IgE against common aeroallergens (birch, timothy, cat and house dust mite). Atopy was defined as a positive Phadiatop™ test.

Results
The atopic and the non‐atopic subjects without asthma or rhinitis had similar levels of eNO. Subjects reporting asthma or rhinitis who were also sensitized to perennial allergens had higher levels of eNO, whereas those sensitized to only seasonal allergens had similar eNO levels as non‐atopic subjects with asthma or rhinitis. In multiple linear regression models adjusted for nNO, eNO was associated with asthma and sensitization to perennial allergens.

Conclusion
The results indicate that only atopic subjects who have recently been exposed to the relevant allergen have elevated levels of eNO. Atopic subjects who are not being exposed to a relevant allergen or have never experienced symptoms of asthma or rhinitis show normal eNO. These data indicate that eNO relates to airway inflammation in atopic subjects.
Acanthamoeba castellani encephalitis following partially mismatched related donor peripheral stem cell transplantation
Authors: Castellano‐Sanchez A. , Popp A.C. , Nolte F.S. , Visvesvara G.S. , Thigpen M. , Redei I. , Somani J.
Published: February 2004

Abstract: We describe a case of Acanthamoeba encephalitis in a 45‐year‐old Caucasian male with acute myelogenous leukemia, who was 140 days status post partially mismatched related donor peripheral blood stem cell transplant. The patient had been transplanted with a highly T‐cell‐depleted graft, and was not taking any immunosuppressive drugs, and had no history of graft‐versus‐host disease. He complained of nausea, vomiting, and occasional episodes of confusion; he also had a chronic cough since transplantation. Physical examination was unremarkable except for orthostatic hypotension. Neurologic examination was within normal limits. Laboratory values including electrolytes, white blood cells and platelet counts were normal. Computed tomographic scan of the brain showed a pansinusitis and a hyperdense lesion along the corona radiata suggestive of a fungal abscess. Magnetic resonance imaging showed multifocal areas with mass effect in the posterior fossa and parietal and occipital lobes. The patient had worsening respiratory failure and died three days after admission. At autopsy, specific immunofluorescent staining identified Acanthamoeba castellani in the brain and lungs.
Aspergillus vertebral osteomyelitis after simultaneous kidney–pancreas transplantation
Authors: Salvalaggio P.R.O. , Bassetti M. , Lorber M.I. , Micheletto G.C. , Friedman A.L. , Andriole V.T. , Basadonna G.P.
Published: February 2004

Abstract: Aspergillus osteomyelitis is a rare complication of invasive aspergillosis after organ transplantation. This is the report of a 46‐year‐old man who underwent a simultaneous pancreas and kidney transplantation, complicated by an Aspergillus osteomyelitis and diskitis of the lumbar spine. Prompt diagnosis with needle biopsy, followed by antifungal therapy using caspofungin, a new antifungal agent recommended for the treatment of refractory aspergillosis, in combination with amphotericin B and an early surgical intervention led to clinical resolution of the infection. Reported cases of spinal aspergillosis after transplantation are reviewed in terms of clinical presentation, risk factors, therapeutic options, and outcome.
Rapid diagnosis of invasive aspergillosis by antigen detection
Authors: Wheat L.J.
Published: February 2004

Abstract: Aspergillosis is a serious and often fatal infection in the bone marrow or organ transplant patient, for which improved methods of diagnosis are desperately needed. Currently, the diagnosis is most often made based on clinical findings and radiographic findings, which are nonspecific, and toxic therapies are initiated empirically, often without ever establishing the diagnosis. Without a definitive diagnosis, physicians often withhold or reduce the doses of the antifungal agent when toxicity develops or the patient improves, permitting progression of disease in those with invasive aspergillosis. The Platelia Aspergillus galactomannan antigenemia assay may assist physicians in making these decisions. With a sensitivity of 81% and a specificity of 89% in the studies leading to its FDA clearance, physicians still must be aware of the potential for false‐positive and false‐negative results; the test does not replace careful microbiological and clinical evaluation. This report will review the relevant literature and provide guidelines for use of the test in patient management.
Low incidence of cytomegalovirus disease in liver transplant recipients receiving sirolimus primary immunosuppression with 3‐day corticosteroid taper
Authors: Trotter J.F. , Wallack A. , Steinberg T.
Published: February 2004

Abstract: Background. Cytomegalovirus (CMV) disease is the most common infection following liver transplantation, occurring in approximately 20% of recipients. In liver transplant recipients, CMV is associated with a higher cost following transplantation, subsequent infections, and recurrent hepatitis C. Since we have initiated a prednisone‐free immunosuppressive regimen in January 2000, we have noted an extremely low incidence of CMV disease in our cohort of liver transplant recipients. We report our findings here.

Methods. All 150 patients transplanted between January 2000 and December 2002 with tacrolimus (or cyclosporin A) and sirolimus, and 3‐day corticosteroid taper were retrospectively analyzed. Recipients who were CMV IgG negative with a CMV IgG‐positive donor (“CMV mismatch”) received conventional prophylactic therapy with intravenous and oral ganciclovir. The incidence of CMV disease (defined as positive tissue culture or positive immunohistochemical stain of affected tissue or CMV‐DNA >3000 associated with clinical symptoms) was recorded for each patient.

Results. The proportion of “CMV mismatches” (donor CMV IgG positive, recipient CMV IgG negative) was 15%. The mean total number of days of ganciclovir prophylaxis (intravenous and/or oral) administered to “CMV mismatch” patients was 45.6 days. The incidence of CMV disease in patients receiving sirolimus primary immunosuppression was 2%. The mean time to diagnosis of CMV disease was 139 days.

Conclusions. (1) The incidence of CMV disease is very low using a prednisone‐free, sirolimus immunosuppressive regimen. (2) Two possible explanations for this finding include appropriate prophylaxis with ganciclovir and low levels of immunosuppression including the absence of prednisone.
Infectious complications in patients randomized to receive allogeneic bone marrow or peripheral blood transplantation
Authors: Nucci M. , Andrade F. , Vigorito A. , Trabasso P. , Aranha J.F. , Maiolino A. , De Souza C.A.
Published: February 2004

Abstract: Very few data are available on the comparison of infectious complications in peripheral blood stem cell transplantation (PBSCT) and bone marrow transplant (BMT). The objective of this study was to evaluate the severity and frequency of infectious complications in patients randomized to receive PBSCT or BMT. We retrospectively reviewed the charts of all patients included in a randomized clinical trial comparing PBSCT (27 patients) and BMT (29 patients). We analyzed two periods: pre‐engraftment and post‐engraftment. In the pre‐engraftment period, we compared the two groups with respect to the duration of neutropenia, antibiotic use and hospitalization, and documentation of infection. In the post‐engraftment period, we analyzed the occurrence and severity of graft‐versus‐host disease (GVHD), duration of cyclosporine, corticosteroids, antibiotic, antiviral and antifungal prophylaxis, number of episodes of infection, and death rates. Patients receiving PBSCT had shorter duration of neutropenia, but there were no differences in the incidence of infections or duration of antibiotic therapy. Patients receiving PBSCT had a higher incidence of extensive chronic GVHD (65% vs. 39%, P=0.08), longer duration of cyclosporine use (risk ratio [RR] 1.97), corticosteroids (RR 1.66), antibacterial (RR 2.60), antifungal (RR 2.50), anti‐Pneumocystis carinii (RR 2.06) and anti‐cytomegalovirus (RR 1.44) prophylaxis, and more infectious episodes (3.65 vs. 2.32 per 1000 days at risk, RR 1.57). There were no differences in death rates. Multivariate analysis identified the use of steroids as the most significant variable associated with infectious episodes. PBSCT was associated with more infections in the post‐engraftment period.
Oerskovia xanthineolytica endocarditis in a renal transplant patient: case report and review of the literature
Authors: Urbina B.Y. , Gohh R. , Fischer S.A.
Published: February 2004

Abstract: Oerskovia species were, until recently, only rarely associated with human disease. This gram‐positive bacillus can be easily misidentified as a diphtheroid, a common contaminant in blood cultures. There have been 17 reports of invasive Oerskovia infection in immunocompromised hosts. We report a case of Oerskovia xanthineolytica endocarditis in a renal transplant patient and review the microbiologic and clinical characteristics of this potential pathogen.
Immunoglobulin deficiency in kidney allograft recipients: comparative effects of mycophenolate mofetil and azathioprine
Authors: Keven K. , Sahin M. , Kutlay S. , Sengul S. , Erturk S. , Ersoz S. , Erbay B.
Published: February 2004

Abstract:Mycophenolate mofetil (MMF) has commonly been substituted for azathioprine (AZA) in kidney transplantation and has been shown to have a greater effect on T cell function and also B cell function than AZA. Although immunoglobulin deficiency has been investigated in patients treated with protocols that include AZA, it has not extensively been studied in MMF‐based immunosuppressive protocols. To evaluate this effect, we conducted a prospective study and recruited 49 patients. The patients received either AZA‐ (group 1) or MMF‐ (group 2) based therapy. A total of 17 patients in group 1 and 24 patients in group 2 completed the study. Immunoglobulin levels were evaluated before and in every month after transplantation for a 6‐month period. Total infectious episodes were recorded and evaluated after 6 months in both groups. While no significant differences have been found in group 1, there were significant decreases in IgG, M, and A levels in group 2 after 6 months (IgG: 11.6±1.5–6.8±2.0 g/L,P<0.0001; IgM: 2.20±1.40–1.40±1.16 g/L,P=0.02; IgA: 1.40±0.70–1.07±0.86 g/LP=0.03). Two patients (11.7%) in group 1 and 11 patients in group 2 (45.8%) were found to have at least one low level of immunoglobulin (P=0.03). When the infectious complications were evaluated, the mean number of infection episodes in each patient was 1.3±1.6 and 0.5±0.7 for the MMF and AZA groups, respectively (P=0.06). Recurrent urinary tract infection developed in eight patients and seven of those were in group 2. In group 2, 7 of 11 patients with low immunoglobulin levels had recurrent urinary tract infection (63%), while no patient who had normal immunoglobulin levels developed any recurrent urinary tract infections (P<0.001). After 6 months, MMF was changed to AZA in these seven patients, who had both recurrent urinary tract infections and low immunoglobulin levels. All but one patient was found to have normal immunoglobulin levels after 3 months of conversion and only two episodes of infection were recorded during this period. We suggest that serum immunoglobulin levels can be monitored in patients taking MMF, and conversion from MMF to AZA may be an alternative for patients with low immunoglobulin levels and recurrent urinary tract infections.
Clostridium innocuum bacteremia secondary to infected hematoma with gas formation in a kidney transplant recipient
Authors: Castiglioni B. , Gautam A. , Citron D.M. , Pasculle W. , Goldstein E.J.C. , Strollo D. , Jordan M. , Kusne S.
Published: February 2004

Abstract: Clostridium innocuum is a relatively antimicrobial resistant, frequently misidentified anaerobe that has only rarely been associated with bacteremia. A 38‐year‐old female with chronic hepatitis C underwent a second kidney transplant operation. Two weeks after surgery a computed tomography scan of the abdomen showed a heterogeneous hematoma with pockets of gas adjacent to the allograft, which extended into the pelvis and left abdominal wall, associated with low‐grade fever. An anaerobic blood culture grew a Clostridium initially identified as C. subterminale and later re‐identified as C. innocuum. At abdominal exploration liquefied blood was evacuated, and the patient completed a course of antibiotics and recovered. C. innocuum should be considered as a cause of gas‐producing anaerobic infection in transplant patients. Because C. innocuum is frequently misidentified by the use of commercial anaerobic identification kits, its true incidence in serious infections is likely underestimated.
Behind Every Well Paid Married Man: The Impact of the Partner's Earning Opportunity
Authors: Skåtun John Douglas
Published: February 2004

This paper presents a theoretical bargaining model, which provides a new explanation for the married male wage premium. A worker can extract higher earnings from the firm when married. Whereas the married worker's wage is higher the higher is the income the spouse earns, should the bargaining break down, the worker's wage is negatively correlated with the spouse's current income.
Inter‐Temporal Decompositions of Labour Market and Social Outcomes
Authors: Le Anh T. , Miller Paul W.
Published: February 2004

This paper compares the Wellington (1993) and Smith and Welch (1989) decompositions of changes in labour market outcomes over time. The two examples considered are differences by gender in educational attainment and the gender wage differential. The results suggest that even though the procedure developed by Wellington (1993) has been favoured in recent research, the Smith and Welch decomposition is a more informative approach.
The Effectiveness of Incomes Policies, in Australia Bargaining and Inflation Targetting Enterprise
Authors: Lye Jenny N. , McDonald Ian M.
Published: February 2004

This paper updates earlier estimates that show the existence of a range of equilibrium rates of unemployment in Australia. Within the range of equilibria framework, the paper goes on to test the effectiveness of incomes policies, enterprise bargaining and inflation‐target based monetary policy for influencing the rate of inflation in Australia in the period 1965 to 2001. Incomes policies, especially the Accord, and enterprise bargaining are shown to have caused permanent reductions in the rate of inflation. The inflation‐target based monetary policy is shown to be associated with, but is not shown to have caused, a reduced impact on inflation of changes in the level of activity.
Key Features of Australian Business Cycles
Authors: Cashin Paul , Ouliaris Sam
Published: February 2004

This paper identifies and describes the key features of Australian business cycles during the period 1959–2002. In particular, we identify the chronologies in Australia's classical cycle (expansions and contractions in the level of output) and growth cycle (periods of above‐trend and below‐trend rates of economic growth). We find that while there are large asymmetries in the duration and amplitude of phases in Australia's classical cycle, on both measures the Australian growth cycle is much more symmetric. Further, our results indicate that over the sample period Australian (filtered) output and prices have moved in a counter‐cyclical fashion, suggesting a dominance of shocks to aggregate supply affecting the Australian economy.