De novo once-monthly darbepoetin alpha treatment for the anemia of chronic kidney disease using a computerized algorithmic approach.

BACKGROUND: Anemia of chronic kidney disease (CKD) has been traditionally treated by erythropoiesis-stimulating agents (ESAs) and/or iron following manual determination of dose. We hypothesized that once-monthly (QM) algorithmically dosed darbepoetin α (DA) and iron administration would successfully treat anemia of CKD in ESA-naïve CKD subjects. METHODS: QM DA and iron doses were determined via a computerized program targeting a hemoglobin (Hb) of 10.5 - 12.5 g/dl in anemic, ESA-naïve, CKD Stages 3 - 5 subjects. Six consecutive QM doses were administered. Hb, ferritin, and transferrin saturation were recorded. Data are presented as means ± standard deviation. RESULTS: Anemia was identified in 133 subjects, with a mean follow-up of 188 days. DA doses and Hb were significantly greater at Months 3 and 6 compared to baseline (p < 0.05); DA doses were 109 ± 68 µg and 118 ± 91, respectively, at Months 3 and 6. Hemoglobin levels were correspondingly 11.3 ± 1.1 g/dl and 11.3 ± 1.0. 78% of patients achieved the target Hb by 6 months of therapy. The elevation of Hb was greater in non-proteinuric than proteinuric subjects at 6 months of treatment (11.6 ± 0.8 g/dl vs. 11.0 ± 1.1; p < 0.05), despite lower DA dose (96 ± 76 µg vs. 139 ± 98; p < 0.05). CONCLUSION: Successful treatment of the anemia of CKD by QM DA based upon a computerized dosing program was achieved by 6 months in 78% of ESA-naïve, CKD subjects.

Measurement of thermal properties of thin films up to high temperatures--pulsed photothermal radiometry system and Si-B-C-N films.

A new arrangement of two-detector pulsed photothermal radiometry measurement system has been developed enabling temperature dependence measurement of thermal properties of thin films up to high temperatures. Only a few methods are available in this temperature range for thin films' thermal properties investigation, but there is a need for their knowledge in the fields of high-temperature electronics and high-speed machining. The present system enables simultaneous determination of the thin film effusivity, thermal conductivity, and volumetric specific heat in the temperature range from room temperature to 600 °C. The samples are placed in a vacuum chamber. The temperatures in the system were verified by an independent measurement and the system was tested on known bulk samples. Advantages and shortcomings of the method when used at higher temperatures and in the vacuum are described and discussed. Furthermore, Si-B-C-N thin films were studied. These amorphous ceramic materials possess an interesting set of mechanical and thermal properties. In particular, the films of the investigated chemical composition exhibit an excellent thermal stability at temperatures of up to 1700 °C. In the studied temperature range, from 20 to 600 °C, the thermal conductivity increased with increasing temperature from 1.72 to 1.89 W m(-1) K(-1) and volumetric specific heat increased from 2.65 to 3.76 × 10(6) J m(-3) K(-1).

A distributed model of carbohydrate transport and metabolism in the liver during rest and high-intensity exercise.

A model of reaction and transport in the liver was developed that describes the metabolite concentration and reaction flux dynamics separately within the tissue and blood domains. The blood domain contains equations for convection, axial dispersion, and transport to the surrounding tissue; and the tissue domain consists of reactions representing key carbohydrate metabolic pathways. The model includes the metabolic heterogeneity of the liver by incorporating spatial variation of key enzymatic maximal activities. Simulation results of the overnight fasted, resting state agree closely with experimental values of overall glucose uptake and lactate output by the liver. The incorporation of zonation of glycolytic and gluconeogenic enzyme activities causes the expected increase in glycolysis and decrease in gluconeogenesis along the sinusoid length from periportal to perivenous regions, while fluxes are nearly constant along the sinusoid length in the absence of enzyme zonation. These results confirm that transport limitations are not sufficient to account for the observed tissue heterogeneity of metabolic fluxes. Model results indicate that changes in arterial substrate concentrations and hepatic blood flow rate, which occur in the high-intensity exercise state, are not sufficient to shift the liver metabolism enough to account for the 5-fold increase in hepatic glucose production measured during exercise. Changes in maximal activities, whether caused by exercise-induced changes in insulin, glucagon, or other hormones are shown to be needed to achieve the expected glucose output. This model provides a framework for evaluating the relative importance to hepatic function of various phenomenological changes that occur during exercise. The model can also be used to assess the potential effect of metabolic heterogeneity on metabolism.