Intérêt du fondaparinux (Arixtra®) en hémodialyse dans les thrombopénies induites par l’héparine de type II (TIH II). À propos d’une nouvelle observation

Several alternative anticoagulation drugs are now available for patients with heparin induced thrombocytopenia type II (HIT II). However, their indication is not yet reaching a consensus. Moreover, some of them have not yet their marketing approval. The importantly use in hemodialyzed patients should be taken with caution since most of them are excreted by the kidneys. The use of fondaparinux, which exerts high anti-Xa activity, is not well documented. We report here our experience on the use of fondaparinux in an hemodialyzed patient with HIT II, not only as anticoagulation during hemodialysis sessions but also as interdialytic anticoagulation locking solution of her central venous catheter. The use of fondaparinux seems to us simple enough (even if its ready-for-use syringe requires adjustments to deliver the required doses) and its efficacy, safety and economic cost lead us to think that it is an indication of choice for an alternative anticoagulation in hemodialyzed patients with HIT II. Control prospective trials should be performed in order to confirm the preliminary favourable data and to support the proposal of marketing approval in this indication.     

Outcome of common iliac arteries after aortoaortic graft placement during elective repair of infrarenal abdominal aortic aneurysms

HYPOTHESIS: Supplemental oxygen can reduce intimal hyperplasia (IH) after stent deployment in a rabbit model. BACKGROUND: Endovascular stent placement is technically feasible, but long-term durability in vessels outside the aortoiliac system is compromised with postinterventional IH, which causes restenosis and failure of the arterial conduit. METHODS: Groups (n = 4 to 6) of female New Zealand white rabbits underwent placement of a 3-mm intraaortic stent with laparotomy and were placed in either normoxic (21% inspired oxygen concentration) or supplemental-oxygen (40% inspired oxygen concentration) environments for 0, 7, 14, and 28 days. The transarterial wall oxygen gradient was measured at 0, 7, and 28 days with an oxygen microelectrode. 5-Bromo-2'deoxyuridine (BrdU) was injected into the peritoneum before death to assess cellular proliferation. Aortic specimens were harvested en bloc and sectioned for analysis of cellular proliferation and intimal thickness. RESULTS: Intraaortic stent placement significantly decreased the transarterial wall oxygen gradient in the outer 70% of the vessel wall and was easily reversed at 7, 14, and 28 days with application of supplemental oxygen. Cellular proliferation was significantly decreased at 14 days (0.5% +/- 0.001% versus 2.3% +/- 0.002%; P <.001) and 28 days (0.4% +/- 0.001% versus 1.0% +/- 0.001%; P <.025) as measured with count of nuclei staining for 5-Bromo-2'deoxyuridine in the intima and media. Intimal thickness was significantly decreased at 28 days in oxygen-supplemented rabbits (intimal area/medial area = 0.50 +/- 0.07) as compared with controls (intimal area/medial area = 0.89 +/- 0.11; P <.025). CONCLUSION: This study shows the ability of supplemental oxygen to reverse arterial wall hypoxia, decrease cellular proliferation, and control IH at the deployment site of an intraarterial stent in a rabbit model. Forty-percent supplemental oxygen suppresses IH by 44% at 28 days as compared with normoxic control values. Cellular proliferation is reduced four-fold at 14 days and two-fold at 28 days in oxygen-supplemented rabbits as compared with control media after deployment. The clinical implications of these findings are significant, especially as the role of endovascular interventions continues to expand.     

New and antifungal xanthones from Calophyllum caledonicum

Two new xanthones, namely caledonixanthones E (1) and F (2), were isolated from the stem bark of Calophyllum caledonicum (Guttiferae). The structural elucidation of these compounds was mainly established on the basis of 1D, 2D NMR and HRMS spectroscopic analysis. Among the isolated compounds, eight other known xanthones were also identified in the course of this phytochemical study. In addition to this report, a preliminary evaluation of the antifungal properties of these polyphenolic compounds against Aspergillus fumigatus and Candida albicans is presented.     

Using biomarkers to characterise contaminant exposure among eaters of Great Lakes and St. Lawrence River fish

Analyses of xenobiotics in human tissues are used to screen individuals whose habits or environments put them at high risk of overexposure, for the surveillance of exposure patterns over time and between places, and as part of research to identify the sources and pathways of exposure in a population. Both study goals and technical considerations should guide the choice of which xenobiotics to sample and in which tissues. Understanding the absorption and distribution of the specific compound to be measured is essential to the choice of when to sample and how to interpret results. Laboratory quality is of major concern. A particular issue in the statistical treatment of results are those near to the laboratory's detection limit. Theoretical concepts are discussed in the context of studies of xenobiotic exposure among eaters of Great Lakes and St. Lawrence River sport fish.     

Homer-dependent cell surface expression of metabotropic glutamate receptor type 5 in neurons

The metabotropic glutamate (mGlu) receptors are a family of receptors involved in the tuning of fast excitatory synaptic transmission in the brain. Experiments performed in heterologous expression systems suggest that cell surface expression of group I mGlu receptors is controlled by their auxiliary protein, Homer. However, whether or not this also applies to neurons remains controversial. Here we show that in cultured cerebellar granule cells, the group I mGlu receptor subtype, mGlu5, transfected alone is functionally expressed at the surface of these neurons. Transfected Homer1b caused intracellular retention and clustering of this receptor at synaptic sites. Recombinant Homer1a alone did not affect cell surface expression of the receptor, but in neurons transfected with Homer1b, excitation-induced expression of native Homer1a reversed the intracellular retention of mGlu5 receptors, resulting in the receptor trafficking to synaptic membranes. Transfected Homer1a also increased the latency and amplitude of the mGlu5 receptor Ca2+ response. These results indicate that Homer1 proteins regulate synaptic cycling and Ca2+ signaling of mGlu5 receptors, in response to neuronal activity.     

Phase IV study of liposomal daunorubicin (DaunoXome) in AIDS-related Kaposi sarcoma

The purpose of this article was to study the efficacy and tolerance of liposomal daunorubicin (DaunoXome) in the treatment of AIDS-associated Kaposi sarcoma (KS) as prescribed in France between September 1996 and September 1997. All patients with a positive HIV serology, histologically proven KS, and having received at least one daunorubicin treatment cycle during the study period were eligible for entry. Ninety-four patient files from 13 university hospital departments were retrospectively studied. Of 94 patients, 80% received cytostatic treatment before the first daunorubicin treatment cycle. Initial mean CD4 lymphocyte count was 114/microl. Ninety percent of the patients received highly active antiretroviral treatment (HAART) during daunorubicin treatment. Daunorubicin was administered as single chemotherapy to 70% of the patients. The total number of treatment cycles was 1,422, with a mean number of 16.1 treatment cycles (1-68) per patient and a mean cumulative daunorubicin dose of 674 mg/m2 (40-2,749). According to the AIDS Clinical Trial Group criteria, partial and complete response rates were 26.5% and 11.5%, respectively. A hematopoietic growth factor was prescribed in 29% of the treatment cycles. At the final evaluation, 71% of the patients were alive. No severe cardiotoxic event was observed despite high cumulative drug doses and prolonged follow-up. Since the introduction of HAART, this study constitutes the only evaluation of daunorubicin in a wide population. Our study confirms that daunorubicin is effective in patients with advanced KS. Daunorubicin is well tolerated over the long term in association with HAART.     

Guiding the study of brain dynamics by using first-person data: Synchrony patterns correlate with ongoing conscious states during a simple visual task

Even during well-calibrated cognitive tasks, successive brain responses to repeated identical stimulations are highly variable. The source of this variability is believed to reside mainly in fluctuations of the subject's cognitive "context" defined by his/her attentive state, spontaneous thought process, strategy to carry out the task, and so on...As these factors are hard to manipulate precisely, they are usually not controlled, and the variability is discarded by averaging techniques. We combined first-person data and the analysis of neural processes to reduce such noise. We presented the subjects with a three-dimensional illusion and recorded their electrical brain activity and their own report about their cognitive context. Trials were clustered according to these first-person data, and separate dynamical analyses were conducted for each cluster. We found that (i) characteristic patterns of endogenous synchrony appeared in frontal electrodes before stimulation. These patterns depended on the degree of preparation and the immediacy of perception as verbally reported. (ii) These patterns were stable for several recordings. (iii) Preparatory states modulate both the behavioral performance and the evoked and induced synchronous patterns that follow. (iv) These results indicated that first-person data can be used to detect and interpret neural processes.