Objectives. The trial was designed to assess the safety, pharmacodynamics and effects on reperfusion of the platelet glycoprotein (GP) IIb/IIIa inhibitor lamifiban when given with thrombolysis to ...patients with ST segment elevation acute myocardial infarction.
Background. Studies of fibrinolytic agents in acute myocardial infarction have demonstrated a direct relationship between early complete reperfusion and survival. Blockade of the platelet GP IIb/IIIa receptor complex inhibits platelet aggregation and may speed reperfusion when given in conjunction with thrombolysis to patients with acute myocardial infarction.
Methods. Patients with ST segment elevation presenting within 12 h of symptom onset who were treated with either tissue-plasminogen activator or streptokinase were enrolled in this three-part Phase II dose exploration study. In Part A, all patients received the GP IIb/IIIa inhibitor lamifiban in an open-label, dose escalation scheme. Parts B and C were a randomized, double-blind comparison of a bolus plus 24-h infusion of lamifiban versus placebo with patients randomized in a 2:1 ratio. The goal was to identify a dose(s) of lamifiban that provided >85% adenosine diphosphate (ADP)-induced platelet aggregation inhibition. A composite of angiographic, continuous electrocardiographic and clinical markers of reperfusion was the primary efficacy end point, and bleeding was the primary safety end point.
Results. Platelet aggregation was inhibited by lamifiban in a dose-dependent manner with the highest doses exceeding 85% ADP-induced platelet aggregation inhibition. There was more bleeding associated with lamifiban (transfusions in 16.1% lamifiban-treated vs. 10.3% placebo-treated patients). Lamifiban induced more rapid reperfusion as measured by all continuous electrocardiographic (ECG) parameters.
Conclusions. Lamifiban given with thrombolytic therapy appears to be associated with more rapid and complete reperfusion than placebo. As expected in this small sample, there were no obvious clinical benefits to lamifiban over placebo. Reconciliation of ECG monitoring with clinical outcomes will require a larger, adequately powered clinical trial.
L’Omalizumab est proposé chez les enfants de plus de 6 ans présentant un asthme sévère allergique non contrôlé, résistant à un traitement inhalé à forte dose (niveau IV du GINA). Son impact à long ...terme n’a pas été évalué chez l’enfant ni l’évolution de l’asthme après son arrêt.
Objectif Évaluer l’évolution de l’asthme (objectif principal=contrôle, critères GINA) chez les enfants ayant eu au moins 2 ans de traitement par omalizumab, en distinguant ceux l’ayant poursuivi de ceux l’ayant arrêté.
Cent enfants (10 centres) étaient inclus. Nous relevions (1) les caractéristiques de l’asthme et la durée du traitement par omalizumab, (2) le niveau de contrôle, le nombre d’exacerbations sévères sur l’année la dose de corticoïdes inhalés (CSI, μg/jour équivalent fluticasone), le VEMS à 2 ans de traitement, à l’arrêt du traitement par omalizumable cas échéant, puis au moment de la dernière visite programmée, et (3) les effets secondaires.
L’âge médian à l’initiation de l’omalizumab était de 11,32 ans8,7–13,1, le terrain atopique marqué : IgE totales(moyenne, DS) : 1079 kU/L (1103),>2 sensibilisations : 40 %, dermatite atopique (DA) : 51 %, allergie alimentaire (AA) : 24 %. L’asthme n’était jamais contrôlé et les exacerbations fréquentes (moyenne : 3,7 2,6 sur l’année) malgré une dose moyenne de CSI de 812μg/j (312). Le VEMS moyen était à 86 % (21) de la valeur prédite. L’omalizumab était toujours en cours chez 65 enfants et avait été interrompu chez 35, définitivement chez 27 (durée moyenne=44,8 mois), repris chez 8 pour non contrôle (durée moyenne avant arrêt=37,3 mois ; p=0,07). Chez les patients toujours traités (durée moyenne de traitement=37,2 mois), on observait au dernier recueil une amélioration significative du contrôle (bon contrôle : 72 % ; non contrôle : 3 %), du nombre moyen d’exacerbations (n=0,34), de la dose moyenne de CSI (396μg/j), de la fonction (VEMS=+12,5 %). Chez les patients ayant arrêté le traitement sans reprise, on observait au recueil et par rapport au moment de l’arrêt un maintien de l’amélioration du contrôle (bon contrôle : 92 %), des exacerbations (n=0,41), de la dose de CSI (492μg/j), de la fonction (VEMS=+10 %). Chez les patients ayant arrêté puis repris, on observait par rapport aux patients sans reprise une tendance à une fréquence plus importante de l’AA (50 %, p=0,07) et de l’association DA et AA (25 %, p=0,06), et à un traitement plus court (p=0,07). Enfin, aucun effet indésirable sérieux n’était recensé.
Le bénéfice important du traitement par Omalizumab se maintient au long cours, sans effet secondaire significatif. L’arrêt peut être proposé après un traitement prolongé (>3 ans) en cas d’asthme durablement contrôlé. En cas d’arrêt, le risque de perte de contrôle justifie un suivi rapproché.
Based on the Corona process and a substitution of air with specific gaseous mixtures into the discharge area, the newly developed surface treatment ALDYNE™ offers both high level improvement and high ...flexibility to film converters. By grafting nitrogen-based chemical functions, it confers to the treated surface excellent properties such as high surface energy and high adhesion of coatings.
Testing a C40-ST-09 Actidyn Systemes centrifuge Gryazin, D. G.; Kudryavtsev, M. D.; Yavorovskaya, N. L. ...
Gyroscopy and navigation (Online),
2013/10, Letnik:
4, Številka:
4
Journal Article
Recenzirano
The paper describes the measurement procedures used to estimate the parameters of a C40-ST-09 Actidyn Systemes centrifuge by independent external devices. A specific feature of the proposed ...procedures is that angular errors in compensation for the rotation of the main axis by the satellite table are determined with the use of an autocollimator, which makes it possible to gain information about the angular position of the article under test with a frequency of up to 10 kHz. The test results are discussed.
Les pneumopathies sont des infections fréquentes chez l’enfant, le plus souvent à pneumocoque ou mycoplasme. Les pneumopathies à staphylocoque aureus (SA) sécréteur de leucocidine de Panton Valentine ...(LPV) sont rares mais souvent sévères et engageant le pronostic vital.
Nous rapportons deux cas de patients présentant une pneumopathie nécrotique à SA producteur de LPV d’évolution favorable.
Le premier est un adolescent de 14 ans hospitalisé pour choc septique sur arthrite septique de hanche avec pneumopathie bilatérale, se compliquant d’une pleurésie et de bulles parenchymateuses. Le second est un nourrisson de 4 mois avec une pleuro-pneumopathie bulleuse présentant à 24h d’évolution une détresse respiratoire avec syndrome infectieux important. Les prélèvements bactériologiques effectués ont confirmé le diagnostic.
Ces deux patients ont été hospitalisés en réanimation avec mise en route d’une tri-antibiothérapie intraveineuse comportant de la clindamycine dès les premières 48h d’admission.
L’évolution de ces deux patients a été favorable, grâce a une suspicion précoce du diagnostic de SA sécréteur de LPV devant des arguments radio-cliniques et la mise en route d’une antibiothérapie anti staphylocoque comportant la clindamycine, avant même la confirmation bactériologique du diagnostic
Ocular contents from a horse with a 4-week history of severe unilateral uveitis were submitted for histopathologic examination. A severe unilateral granulomatous chorioretinitis with intralesional ...Halicephalobus deletrix was diagnosed. The horse developed progressive neurologic signs several days following the surgery to remove ocular contents and implant a prosthesis and was subsequently euthanatized. A severe multifocal granulomatous encephalitis with intralesional H. deletrix, localized primarily to the optic chiasm, thalamus, and brain stem, was diagnosed from tissues acquired at necropsy. The other eye was not affected. This is the first report of ocular parasitism by H. deletrix and suggests possible systemic dissemination from a primary site in the eye.
With new drugs being introduced to treat asthma it is timely to review criteria that can be used to assess efficacy in clinical trials. Anti-asthma drugs are classified into symptoms-modifying, ...symptom preventers and disease modifying agents. Attention is drawn to the types of experimental evidence required in preclinical studies to support further clinical development of a new therapy. Clinical trials demand careful selection of patients to maximise the strength of the efficacy signal according to the type of trial being designed. While provocation tests are useful in suggesting efficacy, negative tests do not necessarily indicate lack of anti-asthma activity. Therapeutic trial designs need to take account of duration of treatment, dose–response relationships and confirmatory trials. Outcome measures include symptoms, lung function, reduction in concomitant medication, exacerbations, quality of life and measures of inflammation. Interpretation of results need to include the clinical relevance of any changes as well as statistical significance. Special consideration needs to be given to the evaluation of drugs for acute severe asthma, asthma in children and older people, co-morbidity such as rhinitis, and inhaler devices. As with all drugs introduced into practice, careful attention needs to be paid to both short- and long-term safety.
CYP84 is a recently identified family of cytochrome P450-dependent mono-oxygenases defined by a putative ferulate-5-hydroxylase (F5H) from Arabidopsis. Until recently F5H has been thought to catalyze ...the hydroxylation of ferulate to 5-OH ferulate en route to sinapic acid. Sinapine, a sinapate-derived ester in the seeds, is antinutritional and a target for elimination in canola meal. We have isolated three F5H-like genes (BNF5H1-3) from a cultivated Brassica napus, whose amphidiploid progenitor is considered to have arisen from a fusion of the diploids Brassica rapa and Brassica oleracea. Two cultivated varieties of the diploids were also found to contain BNF5H3 and additionally either BNF5H1 or BNF5H2, respectively. Whereas all three are >90% identical in their coding sequence, BNF5H1 and BNF5H2 are closer to each other than to BNF5H3. This and additional data suggest that the two groups of genes have diverged in an ancestor of the diploids. B. napus showed maximal F5H expression in the stems, least in the seeds, and subtle differences among the expression profiles of the three genes elsewhere. Transgenic B. napus with cauliflower mosaic virus 35S-antisense BNF5H contained up to 40% less sinapine, from 9.0 ± 0.3 mg in the controls to 5.3 ± 0.3 mg g-1 seed. F5H from Arabidopsis and a similar enzyme from sweetgum (Liquidamber styraciflua) has recently been shown to have coniferaldehyde hydroxylase activity instead of F5H activity. Thus the supply of 5-OH coniferaldehyde or 5-OH ferulate has a bearing on sinapine accumulation in canola seeds.
OBJECTIVE: The aim of this study is to compare the effects of traditional nonsteroidal anti-inflammatory drugs with nonsteroidal anti-inflammatory drugs that are selective cyclooxygenase-2 (COX-2) ...inhibitors in the process of bone regeneration in a rat model. MATERIALS AND METHODS: Forty-four Wistar strain rats were subjected to osteotomy of the right femur and randomly divided into 3 groups according to the drug to be given (diclofenac, rofecoxib, or placebo). Each group was divided into 2 subgroups according to the time to euthanasia after the surgery. The animals of Subgroup 1 were submitted to euthanasia 2 weeks after surgery, and those of Subgroup 2, underwent euthanasia 4 weeks after surgery. Radiographic examinations and bone callus histomorphometry were analyzed. RESULTS: No intergroup statistical difference was found in the bone callus area or in bone formation area 2 and 4 weeks after surgery. Intra-group analysis concerning the bone neoformation area inside the callus showed a significant difference within the diclofenac group, which presented less tissue. CONCLUSIONS: Fracture consolidation in Wistar rats occurs within less than 2 weeks, and the use of nonsteroidal anti-inflammatory drugs does not significantly influence this process.OBJETIVO: Comparar os efeitos do uso de antiinflamatórios não-esteróides tradicionais (AINES) e AINES que são inibidores seletivos da ciclooxigenase-2 (COX-2), no processo de regeneração óssea em ratos. MATERIAL E MÉTODO: Quarenta e quatro ratos da linhagem Wistar submetidos a osteotomia do femur direito e divididos em três grupos, conforme o medicamento que receberam (diclofenaco, rofecoxib e placebo). Cada grupo foi dividido em dois subgrupos, conforme o tempo até o sacrifício, após a cirurgia. Os animais do subgrupo 1 foram sacrificados duas semanas após a cirurgia e os do subgrupo 2, quatro semanas após a cirurgia. Foram analisados exames radiográficos e a histomorfometria do calo ósseo. RESULTADOS: Não foram encontradas diferenças estatísticas na área do calo ósseo 2 e 4 semanas após a cirurgia. No que se refere à área de neoformação óssea dentro do calo, observou-se diferença estatisticamente significante apenas dentro do grupo do diclofenaco, que apresentou menos tecido. CONCLUSÕES: A consolidação da fratura em ratos Wistar ocorre dentro de 2 semanas e o uso de antiinflamatórios não-esteróides não influi de forma significante neste processo.
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