To determine whether a link exists between the recruitment of inflammatory cells in the airways on a bronchial and bronchoalveolar level and the development of allergen-induced increase in bronchial ...hyperresponsiveness after allergen challenge, we used bronchial lavage and bronchoalveolar lavage to assess the airway responses to allergen. Twelve symptomatic atopic asthmatics were studied. In all patients bronchial and bronchoalveolar lavage was performed before, 3 h, and 24 h after allergen challenge. Monoclonal antibodies were used directed against T cells (CD3, CD4, CD8) and the eosinophil cationic protein (EG2). Eight patients showed a dual asthmatic response; four patients showed only an early asthmatic reaction after allergen challenge. Clear differences were found between bronchial and bronchoalveolar lavage. Activated eosinophils (EG2) were significantly increased both at 3 h (p = 0.01) and 24 h (p = 0.005). The number of activated eosinophils was significantly higher in the dual responders. A correlation was observed between the severity of the late asthmatic reaction (LAR) and the number of epithelial cells in the bronchial recovery at 3 h, but not at 24 h, in patients who clinically developed a LAR. No significant changes in the number of CD3, CD4, and CD8 cells 3 and 24 h after the challenge both in the bronchial and bronchoalveolar recovery were observed. We conclude that the number of activated eosinophils in bronchial lavage is associated with the development of the LAR and allergen-induced increase in bronchial hyperresponsiveness.
Le développement des techniques de thérapie génique destinées à délivrer localement des gènes thérapeutiques chez les patients souffrant d’arthrite suscite un intérêt croissant. Le transfert génique ...intra-articulaire (IA) utilisant un adénovirus codant pour le récepteur soluble du TNF s’est traduit par une forte diminution de l’œdème des pattes dans un modèle d’arthrite animale mais le traitement IA utilisant un vecteur similaire n’a pas produit des améliorations cliniques satisfaisantes chez le patient. Il reste à déterminer si un tel phénomène est dû par exemple à une transduction inefficace ou bien si le TNF constitue une cible thérapeutique inadaptée à un traitement IA. L’objectif de cette étude était d’explorer les effets du blocage IA du TNF.
Trente et un patients souffrant de polyarthrite rhumatoïde ou d’arthrite psoriasique ont été répartis aléatoirement dans deux groupes de traitement, étanercept ou placebo, et ont reçu une injection unique de 25mg dans le cadre d’un essai clinique randomisé, contrôlé, en double insu. Le critère d’évaluation principal était l’amélioration de l’articulation cible, selon un indice composite de changement (CCI).
Vingt-deux patients ont reçu l’étanercept et 9 patients le placebo. Dans l’ensemble, le traitement a été bien toléré. Le traitement par étanercept a conduit à une amélioration statistiquement significative de l’indice (p<0,001) comparé au placebo. Comme attendu, compte tenu de la demi-vie de l’étanercept, l’effet bénéfique était temporaire et statistiquement significatif seulement aux semaines 1 et 2 après l’injection IA.
Ces résultats confirment l’intérêt de mettre en œuvre de nouvelles stratégies d’inhibition à long terme du TNF au site d’inflammation telles que la thérapie génique.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the preferred treatment of peritoneal carcinomatosis (PC) of colorectal carcinoma. Patients with positive lymph node ...status have worse survival after CRS-HIPEC, which is probably due to higher rates of systemic failure. In this study, we analysed the effect of administration and timing of systemic chemotherapy on the outcome of lymph node positive colorectal carcinoma patients treated with CRS-HIPEC.
A prospective database was reviewed to identify lymph node positive patients with PC treated with CRS-HIPEC within 1 year after primary tumour diagnosis between 2004 and 2012. Medical history of the patients was studied for the administration of perioperative systemic chemotherapy and follow-up. Outcome parameters were progression-free survival (PFS), overall survival (OS) and pattern of recurrence.
Seventy-three patients treated with CRS-HIPEC for PC from lymph node positive colorectal carcinoma were identified. Fourteen patients received pre-CRS-HIPEC chemotherapy only, 32 patients underwent post-CRS-HIPEC chemotherapy only, 9 patients received chemotherapy both pre- and post-CRS-HIPEC and 16 patients did not receive any systemic chemotherapy. Of the 47 patients who did not receive pre-CRS-HIPEC chemotherapy, 11 (23%) did not receive any chemotherapy due to major postoperative complications. PFS and OS were significantly higher in patients who received systemic chemotherapy (PFS: median 15 versus 4 months, P = 0.024; OS: median 30 versus 14 months, P = 0.015), although this difference was attenuated after adjustment for major complications. Different chemotherapy timings did not differ significantly in either survival or recurrence patterns.
In patients with PC from lymph node positive colorectal carcinoma, perioperative systemic chemotherapy is associated with increased OS and PFS, although this difference may be partly explained by the occurrence of major postoperative complication; with no evidence of difference in PFS, OS and systemic recurrence rate by timing of systemic chemotherapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: IgE‐dependent histamine‐releasing factor (HRF) can distinguish between IgE+ and IgE−. In contrast to IgE−, IgE+ sensitizes basophils to release histamine in response to HRF. But we do not ...know what particular feature distinguishes IgE+ from IgE−. The objective was to investigate the hypothesis that IgE+ is polymeric IgE.
Methods: IgE+plasma was separated by size‐exclusion chromatography. The basophil‐sensitizing capacity of the fractions was analyzed in response to HRF produced by mononuclear cells.
Results: We showed that monomeric IgE sensitized basophils to release histamine in response to HRF and to house‐dust mite, whereas no enhanced reactivity was found in the fractions containing polymeric IgE.
Conclusions: HRF reacts with monomeric IgE, and not (exclusively) with polymeric IgE.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Constraining the distribution of small-scale structure in our universe allows us to probe alternatives to the cold dark matter paradigm. Strong gravitational lensing offers a unique window into small ...dark matter halos (\(<10^{10} M_\odot\)) because these halos impart a gravitational lensing signal even if they do not host luminous galaxies. We create large datasets of strong lensing images with realistic low-mass halos, Hubble Space Telescope (HST) observational effects, and galaxy light from HST's COSMOS field. Using a simulation-based inference pipeline, we train a neural posterior estimator of the subhalo mass function (SHMF) and place constraints on populations of lenses generated using a separate set of galaxy sources. We find that by combining our network with a hierarchical inference framework, we can both reliably infer the SHMF across a variety of configurations and scale efficiently to populations with hundreds of lenses. By conducting precise inference on large and complex simulated datasets, our method lays a foundation for extracting dark matter constraints from the next generation of wide-field optical imaging surveys.
An important driving force behind urban expansion is the growth of the urban population. But for Europe, this is not a sufficient explanation. The major trend is that European cities have become much ...less compact. Since the mid-1950s European cities have expanded on average by 78%, whereas the population has grown by only 33%. In the PLUREL project - an integrated project within the EU’s 6th Research Framework Programme - more than 100 researchers from 15 countries analysed the impacts of urban land consumption at a pan-European level and, through six European and one Chinese case studies, identified how land use conflicts and the pressure towards peri-urban areas can be strategically managed in different development and regulatory contexts. To summarise, the following strategies were identified as important steps towards more sustainable urban-rural futures: (i) better coordination of transport, land use and open space planning; (ii) urban containment and densification – development of a green compact city; (iii) preservation of blue and green infrastructure; and (iv) preservation of agricultural land and the promotion of local production. The need also remains to strengthen governance at the regional level while at the pan-European level there is clearly a need for more policy attention to be given to urban-rural linkages.
We investigated whether treatment with a long-acting β2-agonist (LAβ2 ) is associated with a decrease in patient compliance with regard to inhalation corticosteroids (ICS).
Date on prescriptions ...collected by 15 760 patients suffering from airways disease were provided by 69 Dutch pharmacies. All prescriptions of ICS and LA β2were analysed and divided in four groups by LAβ2 use during 1997 and 1998.
Date from 15760 patients were available. In the 10 929 patients not treated with LA β2, compliance decreased slightly but not significantly. In 3281 patients receiving LAβ2 compliance also decreased slightly but not significantly. In 404 patients, who used a LAβ2 in 1997 and discontinued treatment in 1998, the compliance fell significantly (P<0·05). In 1147 patients who started to use a LA β2in 1998, compliance with ICS significantly improved (P<0·05).
These results suggest that the regular use of LAβ2 improves compliance with ICS. Therefore, the concern that compliance with inhaled corticosteroid therapy will decrease under concomitant use of LA β2appear to be unfounded.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Virtually all asthma patients use bronchodilators. Formoterol and salbutamol have a rapid onset of bronchodilating effect, whereas salmeterol acts slower. We studied the onset of improvement of ...dyspnoea sensation after inhalation with these bronchodilators and placebo to reverse a methacholine-induced bronchoconstriction as a model for an acute asthma attack.
Seventeen patients with asthma completed this randomised, double-blind, crossover, double-dummy study. On 4 test days, forced expiratory volume in 1
s (FEV
1) and Borg score were recorded and patients were challenged with methacholine until FEV
1 fell with ⩾30% of baseline value. Thereafter, formoterol 12
μg via Turbuhaler
®, salbutamol 50
μg via Turbuhaler
®, salmeterol 50
μg via Diskhaler™, or placebo was inhaled. FEV
1 and Borg scores were assessed during the following 60
min.
The first sensed improvement of Borg score was significantly (
P<0.05) faster achieved with formoterol (geometric mean (Gmean) (range) 1.5 (1–40)
min) and salbutamol 1.8 (1–10)
min than with salmeterol 4.5 (1–30)
min and placebo 3.4 (1–40)
min.
The Borg score returned significantly faster to the baseline value with formoterol, salbutamol, and salmeterol (Gmean time 13.8 (1–75), 13.4 (1–60), and 18.0 (1–75)
min, respectively) than with placebo (33.6 (1–75
min).
Formoterol and salbutamol act significantly faster than salmeterol in relieving dyspnoea induced by methacholine-induced bronchoconstriction, in patients with asthma.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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