Augmenting solute clearance in peritoneal dialysis

BACKGROUND: The removal of low molecular weight solutes by peritoneal dialysis is less than by hemodialysis. The targets for Kt/Vurea and creatinine clearance formulated in the Dialysis Outcome Quality Initiative are unlikely to be achieved in a substantial portion of peritoneal dialysis patients. Possibilities to increase small solute clearances have therefore been subject to many investigations. METHODS: A review of the literature and of recent new data on determinants of solute removal, such as residual renal function, the role of drained dialysate volume and manipulation of the diffusive capacity of the peritoneum are presented. RESULTS: The contribution of residual GFR is more important for the clearance of creatinine than for Kt/Vurea. It is even more important for the removal of organic acids that are removed from the body by tubular secretion. High dosages of furosemide increase the urinary volume and the fractional Na+ excretion, but have no effect on the magnitude of residual GFR, renal creatinine clearance, renal urea clearance, and peritoneal transport characteristics. The drained dialysate volume per day is the main determinant of the peritoneal removal of urea. Its effect decreases the higher the molecular weight of a solute. It can be augmented by using large instillation volumes, by the application of more exchanges, and by increasing peritoneal ultrafiltration. A large exchange volume is especially effective in patients with an average transport state, but in those with high solute transport rates, Kt/Vurea is especially influenced by the number of exchanges. Possibilities to increase ultrafiltration are discussed. The diffusive capacity of the peritoneum can be augmented by using low dosages of intraperitoneally administered nitroprusside. This increases solute transport most markedly when it is applied in combination with icodextrin as osmotic agent. CONCLUSIONS: Small solutes clearances cannot be increased by furosemide. Increasing the instilled volume of dialysis fluid and the number of exchanges both affect solute clearance. Studies are necessary on long-term effects of manipulation of the peritoneal membrane with nitroprusside.     

Exposure to physical movement in low back pain patients: Restricted effects of generalization.

Whether the effects of exposure to 1 movement generalize to another dissimilar movement was investigated in 37 patients with low back pain (15 men, 22 women). Two movements were executed twice: bending forward while standing and lifting 1 leg while lying down. During each trial, baseline pain, expected pain, and experienced pain were recorded. Similar ratings for perceived harm were obtained. Analyses revealed an initial overprediction of pain, but after exposure the overprediction was readily corrected. This exposure effect did not generalize toward another dissimilar movement. These results were only characteristic for patients with catastrophic thinking about pain. Low pain catastrophizers did not overpredict pain. There were no effects of exposure on perceived harm. Exposure may profitably be conceived of as the learning of exceptions to a general rule. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Synergy of cell–cell repulsion and vacuolation in a computational model of lumen formation

A key step in blood vessel development (angiogenesis) is lumen formation: the hollowing of vessels for blood perfusion. Two alternative lumen formation mechanisms are suggested to function in different types of blood vessels. The vacuolation mechanism is suggested for lumen formation in small vessels by coalescence of intracellular vacuoles, a view that was extended to extracellular lumen formation by exocytosis of vacuoles. The cell–cell repulsion mechanism is suggested to initiate extracellular lumen formation in large vessels by active repulsion of adjacent cells, and active cell shape changes extend the lumen. We used an agent-based computer model, based on the cellular Potts model, to compare and study both mechanisms separately and combined. An extensive sensitivity analysis shows that each of the mechanisms on its own can produce lumens in a narrow region of parameter space. However, combining both mechanisms makes lumen formation much more robust to the values of the parameters, suggesting that the mechanisms may work synergistically and operate in parallel, rather than in different vessel types.     

The nitric oxide donor nitroprusside intraperitoneally affects peritoneal permeability in CAPD

Nitroprusside is a nitric oxide (NO) donor. To investigate effects of nitroprusside i.p. on peritoneal permeability and perfusion, standard peritoneal permeability analyses were performed. Ten stable CAPD patients were studied twice within one week with glucose based dialysate (1.36% Dianeal) with and without addition of nitroprusside 4.5 mg/liter. Mass transfer area coefficients (MTAC) of CO2 were calculated to estimate peritoneal blood flow. Nitrate, a stable metabolite of NO, and cGMP, a second messenger of NO synthesis, were measured in plasma and dialysate. The MTACs of low molecular weight solutes were greater with nitroprusside (NP) compared to the control dwell (C): creatinine median 14.1 (NP) versus 9.9 ml/min (C), urea 21.7 (NP) versus 18.5 ml/min (C) and urate 10.5 (NP) versus 8.6 ml/min (C) (P < 0.05 for all). This points to an increased effective peritoneal surface area with nitroprusside. Furthermore, the restriction coefficient for the low molecular weight solutes decreased from 1.28 (C) to 1.23 (NP) (P = 0.02), suggesting some effect also on the size selectivity to these solutes. The effect of nitroprusside on the clearances of serum proteins was more pronounced. The increase with nitroprusside was 34% for beta 2-microglobulin, 70% for albumin, 77% for IgG and 143% for alpha 2-macroglobulin. This reduction in size selectivity was reflected in a decrease in the restriction coefficient for macromolecules from 2.29 (C) to 1.86 (NP), P < 0.01. This implies an increase in the intrinsic permeability of the peritoneal membrane. Kinetic modeling, using computer simulations, was done to analyze these effects in terms of the pore theory, using a convection model and a diffusion model for the transport of macromolecules. Nitroprusside led to an increase of both the large pore radius and the small pore radius and of the unrestricted area over diffusion distance. These effects were more pronounced with the diffusion model. The MTAC CO2 was not different: NP 76.9 and C 84.1 ml/min. MTACs of nitrate were not greater than expected on the basis of the molecular weight during both dwells. The dialysate/plasma (D/P) ratio of cGMP was greater after addition of nitroprusside: 0.36, range 0.21 to 0.77 (C) and 0.74, 0.23 to 2.50 (NP), P = 0.02. With nitroprusside the D/P ratio of cGMP was greater than expected on the basis of its molecular weight (P < 0.001). This points to local generation of cGMP after the addition of nitroprusside, induced by NO. No differences were found in the dialysate concentrations of the prostaglandins (PG) PGE2 and 6-keto-PGF1 alpha and thromboxane B2 after addition of nitroprusside. The transcapillary ultrafiltration rate and the net ultrafiltration rate during four hours were not different with nitroprusside. In conclusion, nitroprusside i.p. increased the effective peritoneal surface area and the intrinsic permeability, but the peritoneal blood flow did not change. The greater than expected D/P ratios of cGMP point to local generation of cGMP with nitroprusside, induced by NO.     

Non-denaturing low-temperature bonding of patterned poly(methyl methacrylate) enzymatic microreactors

A low-temperature solvent bonding system using methanol and water has been developed to bond poly(methyl methacrylate) (PMMA) microchips at 35 °C. The substrate/cover plate adhesion strengths obtained with this bonding protocol peaked at 4,000 kN/m² for unmodified PMMA substrates. Nanoindentation measurements performed using atomic force microscopy revealed that only the first 30 nm of the PMMA surface showed a decreased hardness following surface modification and solvent treatment of the PMMA surface allowing the channel architecture to be maintained. The low temperature utilized for bonding enabled both a temperature-robust and temperature-labile enzyme to be facilely patterned prior to bonding with little-to-no loss in enzyme activity. Furthermore, the bonding methodology could be customized and used to fabricate an enzyme microreactor with pepsin (a pH, temperature and solvent sensitive enzyme). The enzyme microreactor performance was characterized by the longevity of the microreactor, as well as the efficiency of the protein digest performed. Enzyme immobilized with WSC decreased over a period of days, whereas the enzyme immobilized with both WSC (water soluble carbodiimide and NHS (N-hydroxysuccinimide) remained active even after a month of use. Short 10 mm column lengths with limited residence time provided high protein sequence coverage.     

Rationale Visualization for Safety and Security

In safety and security domains where objects of interest (OOI), such as people, vessels, or transactions, are continuously monitored, automated reasoning is required due to their sheer number and volume of information. We present a method to visually explain the rationale of a reasoning engine that raises an alarm if a certain situation is reached. Based both on evidence from heterogeneous and possibly unreliable sources, and on a domain specific reasoning structure, this engine concludes with a certain probability that, e.g., the OOI is suspected of smuggling. To support decision making, we visualize the rationale, an abstraction of the complicated reasoning structure. The evidence is displayed in a color‐coded matrix that easily reveals if and where observations contradict. In it, domain and operational experts can quickly understand and find complicated patterns and relate them to real‐world situations. Also, two groups of these experts evaluate our system through maritime use cases based on real data.     

Analysis of a microstrip antenna with fractal multilayer substrate using iterative method

A microstrip antenna with fractal multilayer substrates is studied by using an iterative method based on the concept of waves. A two‐dimensional fast Fourier transformation algorithm is introduced to simplify calculations and accelerate the convergence with reduced central processing unit time. Good agreements are obtained with already published results on fractal antenna. © 2001 John Wiley & Sons, Inc. Int J RF and Microwave CAE 11: 212–218, 2001.     

Electronic Transport Properties of Ensembles of Perylene‐Substituted Poly‐isocyanopeptide Arrays

The electronic transport properties of stacks of perylene‐bis(dicarboximide) (PDI) chromophores, covalently fixed to the side arms of rigid, helical polyisocyanopeptides, are studied using thin‐film transistors. In device architectures where the transistor channel lengths are somewhat greater than the average polymer chain length, carrier mobilities of order 10^?3 cm² V^?1 s^?1 at 350 K are found, which are limited by inter‐chain transport processes. The influence of π–π interactions on the material properties is studied by using PDIs with and without bulky substituents in the bay area. In order to attain a deeper understanding of both the electronic and the electronic‐transport properties of these systems, studies of self‐assembly on surfaces are combined with electronic characterization using Kelvin probe force microscopy, and also a theoretical study of electronic coupling. The use of a rigid polymer backbone as a scaffold to achieve a full control over the position and orientation of functional groups is of general applicability and interest in the design of building blocks for technologically important functional materials, as well as in more fundamental studies of chromophoric interactions.