Does continuous renal replacement therapy favourably influence the outcome of the patients?

Continuous haemodialysis and continuous haemofiltration are efficient and safe techniques for the treatment of acute renal failure. Theoretical advantages are improved haemodynamic stability and easier fluid removal. All 15 available studies comparing intermittent (522 patients) with continuous (651 patients) renal replacement therapy have been reviewed. From these studies it cannot be established, whether the use of a continuous instead of an intermittent treatment modality improves the outcome in patients with acute renal failure. Reviewing all 67 published studies dealing with continuous renal replacement therapy revealed a trend to a decreasing mortality rate (P<0.08) over the last 11 years, whereas the mean age and the severity of illness of the patients, measured by the APACHE II score, did not change. In order to establish whether the quality of treatment has improved as a function of time, two quality factors (QF) were created, i.e. QF for age (mean age/mean mortality rate of the patients treated) and QF for severity of diseases (mean APACHE II/mean mortality rate). Both QF improved from 1984 until 1994, when analyzed for continuous (P<0.001) or intermittent (P<0.001) treatment modality. Thus the quality of treatment of patients with acute renal failure improved during the last decade. However, there is no evidence with respect to survival rate that a continuous renal replacement therapy is superior to an intermittent on

Identifying factors limiting legume biomass production in a heterogeneous on-farm environment

Multipurpose legumes provide a wide range of benefits to smallholder production systems in the tropics. The degree of system improvement after legume introduction depends largely on legume biomass production, which in turn depends on the legumes' adaptation to environmental conditions. For Canavalia brasiliensis (canavalia), an herbaceous legume that has been recently introduced in the Nicaraguan hillsides, different approaches were tested to define the biophysical factors limiting biomass production on-farm, by combining information from topsoil chemical and physical properties, topography and soil profiles. Canavalia was planted in rotation with maize during two successive years on 72 plots distributed over six farms and at contrasting landscape positions. Above-ground biomass production was similar for both years and varied from 448 to 5357 kg/ha, with an average of 2117 kg/ha. Topsoil properties, mainly mineral nitrogen (N; ranging 25-142 mg/kg), total N (Ntot; 415-2967 mg/kg), soil organic carbon (SOC; 3-38 g/kg) and pH (5·3-7·1), significantly affected canavalia biomass production but explained only 0·45 of the variation. Topography alone explained 0·32 of the variation in canavalia biomass production. According to soil profiles descriptions, the best production was obtained on profiles with a root aggregation index close to randomness, i.e. with no major obstacles for root growth. When information from topsoil properties, topography and soil profiles was combined through a stepwise multiple regression, the model explained 0·61 of the variation in canavalia biomass (P<0·001) and included soil depth (0·5-1·70 m), slope position, amount of clay (19-696 kg/m2) and stones (7-727 kg/m2) in the whole profile, and SOC and N content in the topsoil. The linkages between topsoil properties, topography and soil profiles were further evaluated through a principal component analysis (PCA) to define the best landscape position for canavalia cultivation. The three data sets generated and used in the present study were found to be complementary. The profile description demonstrated that studies documenting heterogeneity in soil fertility should also consider deeper soil layers, especially for deep-rooted plants such as canavalia. The combination of chemical and physical soil properties with soil profile and topographic properties resulted in a holistic understanding of soil fertility heterogeneity and shows that a landscape perspective must be considered when assessing the expected benefits from multipurpose legumes in hillside environment

Haemodialysis activates phospholipase A2 enzyme

Background Clinical and experimental evidence suggest that haemodialysis (HD) procedure is an inflammatory process. For the production of proinflammatory lipid mediators in many inflammatory reactions, the release of arachidonic acid by phospholipase A2 (PLA2 enzyme is a prerequisite. Therefore, the purpose of the present investigation was to establish whether the activity of PLA2 increases during HD and whether the increase depends on the type of dialyser used. Methods We performed dialysis in eight chronic HD patients. Blood samples entering and leaving the dialyser were obtained before and at 15, 60, 120 and 180 min after the dialysis was started, on one occasion using a cuprophane and on another occasion a cellulose triacetate dialyser. PLA2 activity was assessed in crude plasma and in plasma extract. Results PLA2 activity in plasma extract exhibited similar biochemical properties to that of inflammatory human synovial fluid PLA2 enzyme which is of group II PLA2. PLA2 activity in crude plasma represents a type of PLA2 other than the synovial type. In HD patients, baseline PLA2 activities in crude plasma and plasma extract were significantly increased when compared to normal subjects. An increase in PLA2 activity was observed in crude plasma with a peak appearing at 15 min when the patients were dialysed with cuprophane and cellulose triacetate membranes. This increase was observed in both arterial and venous blood samples and was more pronounced when the patients were dialysed with cuprophane than with cellulose triacetate membranes. When PLA2 was assessed in plasma extract, the activity increased only with cuprophane but not with cellulose triacetate membranes. Conclusions PLA2 activity in plasma is increased in HD patients and increases during the dialysis procedure to a greater extent with a less biocompatible membrane. Continuous activation of PLA2 might be relevant for long-term deleterious consequences of H

Creating, moving and merging Dirac points with a Fermi gas in a tunable honeycomb lattice

Dirac points lie at the heart of many fascinating phenomena in condensed matter physics, from massless electrons in graphene to the emergence of conducting edge states in topological insulators [1, 2]. At a Dirac point, two energy bands intersect linearly and the particles behave as relativistic Dirac fermions. In solids, the rigid structure of the material sets the mass and velocity of the particles, as well as their interactions. A different, highly flexible approach is to create model systems using fermionic atoms trapped in the periodic potential of interfering laser beams, a method which so far has only been applied to explore simple lattice structures [3, 4]. Here we report on the creation of Dirac points with adjustable properties in a tunable honeycomb optical lattice. Using momentum-resolved interband transitions, we observe a minimum band gap inside the Brillouin zone at the position of the Dirac points. We exploit the unique tunability of our lattice potential to adjust the effective mass of the Dirac fermions by breaking inversion symmetry. Moreover, changing the lattice anisotropy allows us to move the position of the Dirac points inside the Brillouin zone. When increasing the anisotropy beyond a critical limit, the two Dirac points merge and annihilate each other - a situation which has recently attracted considerable theoretical interest [5-9], but seems extremely challenging to observe in solids [10]. We map out this topological transition in lattice parameter space and find excellent agreement with ab initio calculations. Our results not only pave the way to model materials where the topology of the band structure plays a crucial role, but also provide an avenue to explore many-body phases resulting from the interplay of complex lattice geometries with interactions [11, 12]

Artificial graphene as a tunable Dirac material

Artificial honeycomb lattices offer a tunable platform to study massless Dirac quasiparticles and their topological and correlated phases. Here we review recent progress in the design and fabrication of such synthetic structures focusing on nanopatterning of two-dimensional electron gases in semiconductors, molecule-by-molecule assembly by scanning probe methods, and optical trapping of ultracold atoms in crystals of light. We also discuss photonic crystals with Dirac cone dispersion and topologically protected edge states. We emphasize how the interplay between single-particle band structure engineering and cooperative effects leads to spectacular manifestations in tunneling and optical spectroscopies.Comment: Review article, 14 pages, 5 figures, 112 Reference

ALA- and ALA-hexylester-induced protoporphyrin IX fluorescence and distribution in multicell tumour spheroids

Synthesis of protoporphyrin IX (PpIX) in intact murine mammary cancer cell spheroids is reported from optical sections obtained using a laser scanning confocal fluorescence microscope. EMT6 spheroids 275–350 μ m in diameter were incubated in 0.1–15 mM aminolevulinic acid (ALA) or 0.001–2 mM ALA-hexylester (h-ALA) to test the ability of both pro-drugs to diffuse into the spheroids and induce PpIX production. Spheroids incubated with ALA show significant fluorescence nonuniformity for all concentrations, with the outermost cells exhibiting greater porphyrin fluorescence. Comparable levels of fluorescence throughout the optical section are achieved with approximately 100-fold lower h-ALA concentrations, indicating that the interior cells maintain esterase activity and porphyrin synthesis and that h-ALA diffuses efficiently to the spheroid interior. Fluorescence gradients are less pronounced with h-ALA incubation, in part because of apparent saturation of esterase activity in the spheroid perimeter. Proliferating (Ki67 positive) and quiescent cell populations exhibit remarkably different h-ALA concentration dependencies. The incubation concentration resulting in maximum fluorescence with ALA is 10 mM, while the optimal concentration for h-ALA is 200-fold lower at 0.05 mM. Exceeding these optimal concentrations for both pro-drugs leads to an overall loss of fluorescence. © 2001 Cancer Research Campaign http://www.bjcancer.co

Development of an erythropoietin prescription simulator to improve abilities for the prescription of erythropoietin stimulating agents: Is it feasible?

BACKGROUND: The increasing use of erythropoietins with long half-lives and the tendency to lengthen the administration interval to monthly injections call for raising awareness on the pharmacokinetics and risks of new erythropoietin stimulating agents (ESA). Their pharmacodynamic complexity and individual variability limit the possibility of attaining comprehensive clinical experience. In order to help physicians acquiring prescription abilities, we have built a prescription computer model to be used both as a simulator and education tool. METHODS: The pharmacokinetic computer model was developed using Visual Basic on Excel and tested with 3 different ESA half-lives (24, 48 and 138 hours) and 2 administration intervals (weekly vs. monthly). Two groups of 25 nephrologists were exposed to the six randomised combinations of half-life and administration interval. They were asked to achieve and maintain, as precisely as possible, the haemoglobin target of 11-12 g/dL in a simulated naïve patient. Each simulation was repeated twice, with or without randomly generated bleeding episodes. RESULTS: The simulation using an ESA with a half-life of 138 hours, administered monthly, compared to the other combinations of half-lives and administration intervals, showed an overshooting tendency (percentages of Hb values &gt; 13 g/dL 15.8 ± 18.3 vs. 6.9 ± 12.2; P &lt; 0.01), which was quickly corrected with experience. The prescription ability appeared to be optimal with a 24 hour half-life and weekly administration (ability score indexing values in the target 1.52 ± 0.70 vs. 1.24 ± 0.37; P &lt; 0.05). The monthly prescription interval, as suggested in the literature, was accompanied by less therapeutic adjustments (4.9 ± 2.2 vs. 8.2 ± 4.9; P &lt; 0.001); a direct correlation between haemoglobin variability and number of therapy modifications was found (P &lt; 0.01). CONCLUSIONS: Computer-based simulations can be a useful tool for improving ESA prescription abilities among nephrologists by raising awareness about the pharmacokinetic characteristics of the various ESAs and recognizing the factors that influence haemoglobin variability

ALA and ALA hexyl ester induction of porphyrins after their systemic administration to tumour bearing mice

The use of synthetic lipophilic molecules derived from 5-aminolevulinic acid (ALA) is currently under investigation to enhance cellular ALA penetration. In this work we studied the effect of systemic administration to mice of the hexyl ester of ALA (He-ALA) on porphyrin tissue synthesis as compared to ALA. In most normal tissues as well as in tumour, He-ALA induced less porphyrin synthesis than ALA after its systemic administration either intravenous or intraperitoneal, although explant organ cultures exposed to either ALA or He-ALA revealed equally active esterases. The only tissue that accumulated higher porphyrin levels from He-ALA (seven times more than ALA) was the brain, and this correlated well with a rapid increase in ALA/He-ALA content in brain after administration of He-ALA. This may be ascribed to a differential permeability to lipophilic substances controlled by the blood–brain barrier, a feature which could be further exploited to treat brain tumours