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91.
92.
Mohamed-Aziz Barkaoui Emma Queheille Nathalie Aladjidi Geneviève Plat Eric Jeziorski Despina Moshous Anne Lambilliotte Kamila Kebaili Hélène Pacquement Guy Leverger Ludovic Mansuy Natacha Entz-Werlé Damien Bodet Pascale Schneider Anne Pagnier Anne Lutun Marion Gillibert-Yvert Fréderic Millot Fabienne Toutain Yves Reguerre Caroline Thomas Abdelatif Tazi Jean-François Emile Jean Donadieu Sébastien Héritier 《British journal of haematology》2020,191(5):825-834
The nucleoside analogue, 2-chlorodeoxyadenosine (2CDA), was reported to be an active treatment for childhood Langerhans cell histiocytosis (LCH) without risk organ (RO−) involvement. However, we lack data on long-term effects of 2CDA treatment, including the disease reactivation rate, permanent sequelae and long-term tolerance. This study included 44 children from the French LCH registry, treated for a RO− LCH with 2CDA monotherapy (median number of six courses). The median age at the beginning of 2CDA was 3·6 years (range, 0·3–19·7 years) and the median follow-up after was 5·4 years (range, 0·6–15·1 years). Objective response to 2CDA was observed in 25 patients (56·8%), while six patients (13·6%) had stable disease and 13 patients (29·5%) exhibited progressive disease. Among patients without progression, only two experienced disease reactivation after 2CDA discontinuation. The five-year cumulative incidence of disease progression or reactivation after 2CDA therapy initiation was 34·3%. The lymphopenia reported in all cases [72% below absolute lymphocyte count (ALC) of 0·5 G/l], was addressed with appropriate prophylactic measures. Other toxicities above grade 2 were uncommon, and no second malignant neoplasm or neuropathy was reported. The five-year overall survival was 97·7%. In conclusion, we could confirm that 2CDA monotherapy was a beneficial long-term therapy for treating patients with RO− LCH. Appropriate management of induced immune deficiency is mandatory. 相似文献
93.
Marlene H. van Knobelsdorff Nikki G. van Bergen John van der Kamp Ludovic Seifert Dominic Orth 《Scandinavian journal of medicine & science in sports》2020,30(12):2485-2497
The capability to adapt to changing conditions is crucial for safe and successful performance in physical activities and sports. According to the affordance-based control perspective, individuals act in such a way as to take into account the limits of their capability to act. However, it is not clear how strength interacts with skill in shaping performer-environment interactions. We, therefore, determined whether fingertip strength influences patterns of gaze and climbing behavior on new routes of ever-increasing difficulty. We expected that comparatively weaker climbers would show less complex behavior because of an inability to perceive and act. Stronger climbers would show more complex visuo-motor behavior because more opportunities for action remain, even as route difficulty increases. For very strong climbers the route would not be challenging enough, and less complex patterns suffice. Twenty climbers, ranging from lower grade to elite level participated. Maximum fingertip strength was obtained. Participants previewed and then climbed two separate 3 m long traverses, gradually decreasing in edge depth. Gaze and hip positions were collected for subsequent computation of gaze transition entropy (during preview) and hip displacement entropy (during climbing). Data revealed statistically significant curvilinear relationships between both fingertip strength and gaze transition entropy, and fingertip strength, and hip displacement entropy. Visuo-motor complexity is scaled by how close the individual must act relative to boundaries of what the environment affords and does not afford for action given the individual constraints. Future research should examine in greater detail relationships between action capabilities and functional movement variability. 相似文献
94.
Tiziana Bacchetti Simona Masciangelo Tatiana Armeni Virginia Bicchiega Gianna Ferretti 《Metabolism: clinical and experimental》2014
Objective
Methylglyoxal (MG), a reactive carbonyl compound formed primarily from triose phosphates, appears to be involved in the molecular mechanisms of diabetes, end-stage renal disease and neurodegenerative diseases. Methylglyoxal exerts several biological activities. Among these it promotes advanced glycation end products (AGEs), which are crucial in pathogenesis of human disease. Previous studies have demonstrated that MG reacts with proteins and compositional modifications reflect loss of biological activity. The aim of the study was to investigate the effect of in vitro MG-induced glycation on human high density lipoprotein (HDL) and on the activity of the enzyme paraoxonase-1 (PON1).Methods
HDL was incubated in the absence or in the presence of MG (0.2 mmol/L and 1.0 mmol/L) (MG-HDL) for different times (3, 6, 24 h) at 37 ° C. We evaluated apoprotein compositional changes, in both control and MG treated HDL, using intrinsic fluorescence of tryptophan and monitoring the decrease of free amino groups. Furthermore we evaluated fluorescent advanced glycation end products (Ex = 370 nm, Em = 440 nm) and the activity of HDL-paraoxonase.Results
We demonstrated that human HDL is susceptible to glycation by MG (0.2 mmol/L and 1 mmol/L). The decrease of free amino groups and of intrinsic fluorescence of tryptophan demonstrates HDL apoprotein modifications in HDL incubated with MG. The compositional changes are associated with a significant increase in fluorescent advanced glycation end products and with a significant decrease of paraoxonase-1 enzyme activity associated with the HDL surface.Conclusions
HDL-associated paraoxonase is responsible for the anti-inflammatory and anti-oxidative properties of HDL and detoxification against homocysteine-thiolactone. Therefore, modifications of apoprotein composition and the decrease of paraoxonase-1 activity in MG-treated HDL could affect the protective effect exerted by HDL against oxidative damage and could contribute to complications in patients affected by diseases associated with aging and oxidative stress. 相似文献95.
Julien Rohmer Amélie Couteau-Chardon Julie Trichereau Kewin Panel Cyrielle Gesquiere Raouf Ben Abdelali Audrey Bidet Jean-Sébastien Bladé Jean-Michel Cayuela Pascale Cony-Makhoul Vincent Cottin Eric Delabesse Mikaël Ebbo Olivier Fain Pascale Flandrin Lionel Galicier Catherine Godon Nathalie Grardel Aurélien Guffroy Mohamed Hamidou Mathilde Hunault Etienne Lengline Faustine Lhomme Ludovic Lhermitte Irène Machelart Laurent Mauvieux Catherine Mohr Marie-Joelle Mozicconacci Dina Naguib Franck E. Nicolini Jerome Rey Philippe Rousselot Suzanne Tavitian Louis Terriou Guillaume Lefèvre Claude Preudhomme Jean-Emmanuel Kahn Matthieu Groh CEREO GBMHM collaborators 《American journal of hematology》2020,95(11):1314-1323
FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia (F/P+ MN-eo) is a rare disease: robust epidemiological data are lacking and reported issues are scarce, of low sample-size and limited follow-up. Imatinib mesylate (IM) is highly efficient but no predictive factor of relapse after discontinuation has yet been identified. One hundred and fifty-one patients with F/P+ MN-eo (143 males; mean age at diagnosis 49 years; mean annual incidence: 0.18 case per million population) were included in this retrospective nationwide study involving all French laboratories who perform the search of F/P fusion gene (study period: 2003-2019). The main organs involved included the spleen (44%), skin (32%), lungs (30%), heart (19%) and central nervous system (9%). Serum vitamin B12 and tryptase levels were elevated in 74/79 (94%) and 45/57 (79%) patients, respectively, and none of the 31 patients initially treated with corticosteroids achieved complete hematologic remission. All 148 (98%) IM-treated patients achieved complete hematologic and molecular (when tested, n = 84) responses. Forty-six patients eventually discontinued IM, among whom 20 (57%) relapsed. In multivariate analysis, time to IM initiation (continuous HR: 1,01 [0.99-1,03]; P = .05) and duration of IM treatment (continuous HR: 0,97 [0,95-0,99]; P = .004) were independent factors of relapse after discontinuation of IM. After a mean follow-up of 80 (56) months, the 1, 5- and 10-year overall survival rates in IM-treated patients were 99%, 95% and 84% respectively. In F/P+ MN-eo, prompt initiation of IM and longer treatment durations may prevent relapses after discontinuation of IM. 相似文献
96.
Ludovic Jondreville Daphné Krzisch Elise Chapiro Florence Nguyen-Khac 《American journal of hematology》2020,95(11):1361-1367
Chromosomal abnormalities are frequently observed in patients with chronic lymphocytic leukemia (CLL) and have prognostic value. Deletions of the short arm of chromosome 17 (and/or mutations TP53) predict resistance to chemoimmunotherapy and shorter progression-free survival after targeted therapies. Although the complex karyotype (CK) is strongly predictive of a poor prognosis in hematologic malignancies such acute myeloid leukemia or myelodysplastic syndrome, its value in CLL is subject to debate. Here, we review the literature on the CK in CLL and examine its prognostic value with different treatments. We also propose a standardized method for defining a CK in all types of hematopoietic neoplasm. 相似文献
97.
Valentina Ferretti Zhe Zhang Raquel Yustos Fei Lan Qianzi Yang Dorothy W. U. Overington Alexei L. Vyssotski Hein A. van Lith William Wisden Nicholas P. Franks 《The European journal of neuroscience》2014,40(1):2311-2319
How external stimuli prevent the onset of sleep has been little studied. This is usually considered to be a non‐specific type of phenomenon. However, the hypnotic drug dexmedetomidine, an agonist at α2 adrenergic receptors, has unusual properties that make it useful for investigating this question. Dexmedetomidine is considered to produce an ‘arousable’ sleep‐like state, so that patients or animals given dexmedetomidine become alert following modest stimulation. We hypothesized that it might be more difficult to make mice unconscious with dexmedetomidine if there was a sufficient external stimulus. Employing a motorized rotating cylinder, which provided a continuous and controlled arousal stimulus, we quantitatively measured the ability of such a stimulus to prevent dexmedetomidine loss of righting reflex in two inbred strains of mice (C57BL/6 and 129X1). We found that whereas the C57BL/6 strain required a strong stimulus to prevent dexmedetomidine‐induced hypnosis, the 129X1 strain stayed awake even with minimal stimuli. Remarkably, this could be calibrated as a simple threshold trait, i.e. a binary ‘yes–no’ response, which after crossing the two mouse strains behaved as a dominant‐like trait. We carried out a genome‐wide linkage analysis on the F2 progeny to determine if the ability of a stimulus to prevent dexmedetomidine hypnosis could be mapped to one or more chromosomal regions. We identified a locus on chromosome 4 with an associated Logarithm of Odds score exceeding the pre‐established threshold level. These results show that complex traits, such as the ability of a stimulus to reverse drug‐induced hypnosis, may have precise genetic determinants. 相似文献
98.
Gianfranco Donatelli Stefano Ferretti Bertrand M. Vergeau Parag Dhumane Jean-Loup Dumont Serge Derhy Thierry Tuszynski Stavros Dritsas Alessio Carloni Jean-Marc Catheline Guillaume Pourcher Ibrahim Dagher Bruno Meduri 《Obesity surgery》2014,24(8):1400-1407
Background
Endoscopic treatment of gastric leaks (GL) following sleeve gastrectomy (SG) involves different techniques; however, standard management is not yet established. We report our experience about endoscopic internal drainage of leaks using pigtail stents coupled with enteral nutrition (EDEN) for 4 to 6 weeks until healing is achieved.Methods
In 21 pts (18 F, 41 years), one or two plastic pigtail stents were delivered across the leak 25.6 days (4–98) post-surgery. In all patients, nasojejunal tube was inserted. Check endoscopy was done at 4 to 6 weeks with either restenting if persistent leak, or removal if no extravasation of contrast in peritoneal cavity, or closure with an Over-the-Scope Clip® (OTSC®) if contrast opacifying the crossing stent without concomitant peritoneal extravasation.Results
Twenty-one out of 21 (100 %) patients underwent check endoscopy at average of 30.15 days (26–45) from stenting. In 7/21 (33.3 %) patients leak sealed, 2/7 needed OTSC®. Second check endoscopy, 26.7 days (25–42) later, showed sealed leak in 10 out 14; 6/10 had OTSC®. Four required restenting. One patient, 28 days later, needed OTSC®. One healed at 135 days and another 180 days after four and seven changes, respectively. One patient is currently under treatment. In 20/21 (95.2 %), GL have healed with EID treatment of 55.5 days (26–?180); all are asymptomatic on a normal diet at average follow-up of 150.3 days (20–276).Conclusions
EDEN is a promising therapeutic approach for treating leaks following SG. Multiple endoscopic sessions may be required. 相似文献99.
100.