Pharmacokinetics and pharmacodynamics of tiotropium solution and tiotropium powder in chronic obstructive pulmonary disease

The aim of the study was to characterize pharmacokinetics of tiotropium solution 5 µg compared to powder 18 µg and assess dose-dependency of tiotropium solution pharmacodynamics in comparison to placebo. In total 154 patients with chronic obstructive pulmonary disease (COPD) were included in this multicenter, randomized, double-blind within-solution (1.25, 2.5, 5 µg, and placebo), and open-label powder 18 µg, crossover study, including 4-week treatment periods. Primary end points were peak plasma concentration (Cmax,ss ), and area under the plasma concentration-time profile (AUC0-6h,ss ), both at steady state. The pharmacodynamic response was assessed by serial spirometry (forced expiratory volume in 1 second/forced vital capacity). Safety was evaluated as adverse events and by electrocardiogram/Holter. Tiotropium was rapidly absorbed with a median tmax,ss of 5-7 minutes postdosing for both devices. The gMean ratio of solution 5 µg over powder 18 µg was 81% (90% confidence interval, 73-89%) for Cmax,ss and 76% (70-82%) for AUC0-6h,ss , indicating that bioequivalence was not established. Dose ordering for bronchodilation was observed. Powder 18 µg and solution 5 µg were most effective, providing comparable bronchodilation. All treatments were well tolerated with no apparent relation to dose or device. Comparable bronchodilator efficacy to powder18 µg at lower systemic exposure supports tiotropium solution 5 µg for maintenance treatment of COPD

Practice variation in the conservative and surgical treatment of chronic subdural hematoma

Objective: Chronic subdural hematoma (CSDH) is a condition that is frequently seen in the neurological and neurosurgical practice. Surgical treatment is overall preferred; however, conservative treatment is also an option. Both surgical and conservative treatment of CSDH vary across neurosurgeons. The aim of the present study was to evaluate different treatment strategies for CSDH among neurosurgeons in different countries. Material and Methods: We designed a survey that was sent to neurosurgeons affiliated with the Congress of Neurological Surgeons.The questions were related to the conservative and surgical treatment methods of CSDH. Furthermore, we also included questions related to post-operative care. Results: 443 neurosurgeons completed the survey. 46.2 % of the respondents sometimes use dexamethasone as monotherapy. Overall, 26.2 % estimated dexamethasone to have a high efficacy on CSDH. A Glas

Когнітивні структури репрезентації хрематонімійних знань

В запропонованій статті розглядаються основні структури репрезентації хрематонімів в ментальному лексиконі індивіда. Питання побудови моделей та схем організації ментального лексикону привертає велику увагу лінгвістів сьогодні.В предложенной статье рассматриваются основные структуры репрезентации хрематонимов в ментальном лексиконе индивида. Вопрос построения моделей и схем организации ментального лексикона привлекает огромное внимание лингвистов.The article deals with the main representation structures of chrematonyms in the mental lexicon of an individual. The task of model construction and scheme organization of mental lexicon attracts much attention of linguists today

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Els Cornelissen en Alexandre Livingstone-Smith De archeologie van Congo in kaart gebracht. De geschiedenis van 130 jaar veldwerk. [Mapping the history of archaeology in Congo]De Democratische Republiek Congo heeft een oppervlak dat overeenkomt met dat van West-Europa. De pioniers van de Congolese archeologie stonden in 1885 dan ook voor een onmetelijke taak. Tot op vandaag vertonen de kaarten met archeologische vindplaatsen nog heel wat lacunes. Els Cornelissen en Alexandre Livingstone-Smith nemen ons mee op een reis doorheen de geschiedenis van 130 jaar archeologisch veldwerk in Congo. Onderzoek waarvan de methoden, perspectieven en interesses varieerden doorheen de tijd. Onderzoek dat onder een voortdurende - maar niet altijd even intensieve - aandacht vanuit België stond en uiteraard ook onlosmakelijk verbonden is met het Koninklijk Museum voor Midden-Afrika in Tervuren.Koen Smets Hakhout- en middelhoutbeheer in Vlaanderen. [Coppice and coppice-with-standards woodlands managment in Flanders.]Traditioneel werden bomen en struiken in de Vlaamse bossen periodiek in korte cycli tot bij de grond afgekapt. Bij goed uitgevoerde kappingen gaan de meeste houtsoorten immers spontaan weer uitlopen en kunnen ze na korte tijd opnieuw worden geoogst. Tot het begin van de 20ste eeuw beantwoordde deze vorm van bosbeheer aan een economische noodzaak: de levering van vooral brand- en geriefhout. Heeft een dergelijk beheersvorm nu nog enige toekomst? Koen Smets neemt het op voor deze duurzame vorm van omgaan met hout als levend erfgoed.Eric Van Schoonenberghe De Balegemse landbouwstokerij van Damme, hoeder van industrieel en culinair erfgoed. [The Van Damme farm distillery in Balegem, keeper of industrial and culinary heritage.]De landbouwstokerij Van Damme in Balegem (Oosterzele) werd in 1864 opgericht en is de enige overblijvende stokerij in Vlaanderen waar de boer met eigen graan stookt. De Balegemse jenever wordt nog steeds met een grotendeels 19de-eeuwse apparatuur en volgens een 19de-eeuws recept gestookt. Europa erkende de naam Balegemse jenever in 2008 als geografische aanduiding. Eric Van Schoonenberghe maakte als doctor in de wetenschappen (biochemie) van jenever zijn studieonderwerp. In deze bijdrage verhaalt hij de geschiedenis van de jenever en van de landbouwstokerij Van Damme, sinds 2012 een beschermd monument.Summar

Wnt3a protein reduces growth factor-driven expansion of human hematopoietic stem and progenitor cells in serum-free cultures

Abstract Ex vivo expansion of hematopoietic stem and progenitor cells (HSPC) is a promising approach to improve insufficient engraftment after umbilical cord blood stem cell transplantation (UCB-SCT). Although culturing HSPC with hematopoietic cytokines results in robust proliferation, it is accompanied with extensive differentiation and loss of self-renewal capacity. Wnt signaling has been implicated in regulating HSPC fate decisions in vivo and in promoting HSPC self-renewal by inhibition of differentiation, but the effects of Wnt on the ex vivo expansion of HSPC are controversial. Here, we demonstrate that exogenous Wnt3a protein suppresses rather than promotes the expansion of UCB-derived CD34+ cells in serum free expansion cultures. The reduced expansion was also observed in cultures initiated with LinCD34+ CD38lowCD45RACD90+ cells which are highly enriched in HSC and was also observed in response to activation of beta-catenin signaling by GSK3 inhibition. The presence of Wnt3a protein during the culture reduced the frequency of multilineage CFU-GEMM and the long-term repopulation ability of the expanded HSPC. These data suggest that Wnt signaling reduces expansion of human HSPC in growth factor-driven expansion cultures by promoting differentiation of HSPC

Long term impact of hyperleukocytosis in newly diagnosed acute myeloid leukemia patients undergoing allogeneic stem cell transplantation : An analysis from the acute leukemia working party of the EBMT

Up to 20% of acute myeloid leukemia (AML) patients present initially with hyperleukocytosis, placing them at increased risk for early mortality during induction. Yet, it is unknown whether hyperleukocytosis still retains prognostic value for AML patients undergoing hematopoietic stem cell transplantation (HSCT). Furthermore, it is unknown whether hyperleukocytosis holds prognostic significance when modern molecular markers such as FLT3-ITD and NPM1 are accounted for. To determine whether hyperleukocytosis is an independent prognostic factor influencing outcome in transplanted AML patients we performed a retrospective analysis using the registry of the acute leukemia working party of the European Society of Blood and Marrow Transplantation. A cohort of 357 patients with hyperleukocytosis (159 patients with white blood count [WBC] 50 K-100 K, 198 patients with WBC >= 100 K) was compared to 918 patients without hyperleukocytosis. Patients with hyperleukocytosis were younger, had an increased rate of favorable risk cytogenetics, and more likely to be FLT3 and NPM1 mutated. In multivariate analysis, hyperleukocytosis was independently associated with increased relapse incidence (hazard ratio [HR] of 1.55, 95% confidence interval [CI], 1.14-2.12; P = .004), decreased leukemia-free survival (HR of 1.38, 95% CI, 1.07-1.78; P = .013), and inferior overall survival (HR of 1.4, 95% CI, 1.07-1.84; P = .013). Hyperleukocytosis retains a significant prognostic role for AML patients undergoing HSCT.Peer reviewe

Biological efficacy of low versus medium dose aspirin after coronary surgery: results from a randomized trial [NCT00262275]

BACKGROUND: The beneficial effect of aspirin after coronary surgery is established; however, a recent study reported the inability of low doses (100 mg) to inhibit postoperative platelet function. We conducted a double-blind randomised trial to establish the efficacy of low dose aspirin and to compare it against medium dose aspirin. METHODS: Patients undergoing coronary surgery were invited to participate and consenting patients were randomised to 100 mg or 325 mg of aspirin daily for 5 days. Our primary outcome was the difference in platelet aggregation (day 5 – baseline) using 1 μg/ml of collagen. Secondary outcomes were differences in EC50 of collagen, ADP and epinephrine (assessed using the technique of Born). RESULTS: From September 2002 to April 2004, 72 patients were randomised; 3 patients discontinued, leaving 35 and 34 in the low and medium dose aspirin arms respectively. The mean aggregation (using 1.1 μg/ml of collagen) was reduced in both the medium and low dose aspirin arms by 37% and 36% respectively. The baseline adjusted difference (low – medium) was 6% (95% CI -3 to 14; p = 0.19). The directions of the results for the differences in EC50 (low – medium) were consistent for collagen, ADP and epinephrine at -0.07 (-0.53 to 0.40), -0.08 (-0.28 to 0.11) and -4.41 (-10.56 to 1.72) respectively, but none were statistically significant. CONCLUSION: Contrary to recent findings, low dose aspirin is effective and medium dose aspirin did not prove superior for inhibiting platelet aggregation after coronary surgery

Post-transplant cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia in first complete remission undergoing allogeneic stem cell transplantation from 10/10 HLA-matched unrelated donors

Background Graft-versus-host disease (GVHD) remains a major contributor to mortality and morbidity after allogeneic stem-cell transplantation (allo-HSCT). The updated recommendations suggest that rabbit antithymocyte globulin or anti-T-lymphocyte globulin (ATG) should be used for GVHD prophylaxis in patients undergoing matched-unrelated donor (MUD) allo-HSCT. More recently, using post-transplant cyclophosphamide (PTCY) in the haploidentical setting has resulted in low incidences of both acute (aGVHD) and chronic GVHD (cGVHD). Therefore, the aim of our study was to compare GVHD prophylaxis using either PTCY or ATG in patients with acute myeloid leukemia (AML) who underwent allo-HSCT in first remission (CR1) from a 10/10 HLA-MUD. Methods Overall, 174 and 1452 patients from the EBMT registry receiving PTCY and ATG were included. Cumulative incidence of aGVHD and cGVHD, leukemia-free survival, overall survival, non-relapse mortality, cumulative incidence of relapse, and refined GVHD-free, relapse-free survival were compared between the 2 groups. Propensity score matching was also performed in order to confirm the results of the main analysis Results No statistical difference between the PTCY and ATG groups was observed for the incidence of grade II-IV aGVHD. The same held true for the incidence of cGVHD and for extensive cGVHD. In univariate and multivariate analyses, no statistical differences were observed for all other transplant outcomes. These results were also confirmed using matched-pair analysis. Conclusion These results highlight that, in the10/10 HLA-MUD setting, the use of PTCY for GVHD prophylaxis may provide similar outcomes to those obtained with ATG in patients with AML in CR1.Peer reviewe