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Biomedical subjects

D Falkenhagen

Publications and source records attributed to D Falkenhagen.

100 records · Page 6Linked to original sources

Serum complement and protein metabolism in chronic dialysis patients.

1. Patients receiving regular hemodialysis treatment who are permitted to select their own diets are in danger of a protein deficiency manifested by a significant reduction in serum transferrin and in complement C3c. 2. Correlation analysis within the dialysis group revealed no secure connexion between the complement C3c and total hemolytic activity respectively, and transferrin levels. 3. Analysis of diets showed that protein intake and the serum transferrin level correlate. No such correlation was found for the complement C3c or total hemolytic activity. 4. Low transferrin levels in the serum appear to result in more severe anemia among dialysis patients. 5. Knowledge of the serum transferrin level permits much more exact assessment of the protein metabolism in regular hemodialysis patients than knowledge of the total hemolytic activity or the level of the complement C3c.

Blood Proteins↗

Blood purification by haemoperfusion.

Blood purification by haemoperfusion is considered, principally in terms of the European effort. The development of the different approaches which have emerged and the assessment of adsorbents and devices are described. The application of haemoperfusion is examined in the areas of acute poisoning, liver failure and uraemia.

Adsorption↗

[Application of a mathematical model to the penetration of amino acids through a dialysis membrane in chronic hemodialysis].

With the help of a one-pool-model from the clearance values measured for 4 different dialysator models the elimination rates for amino acids are calculated with special regard to the essential amino acids. In these cases the body-weight of the patient also belongs to the calculation of the elimination of the amino acids. The loss of the amino acids under the dialysis procedes corresponding to an e-function and is particularly high during the first period of dialysis.

Amino Acids↗

Development of cationically modified cellulose adsorbents for the removal of endotoxins.

The removal of endotoxins by extracorporeal adsorption processes seems the most promising therapeutic approach to Gram-negative sepsis and endotoxin shock. However, thus far adsorbents have failed to bind endotoxins efficiently or have shown adverse biocompatibility characteristics. To overcome these disadvantages, small particles of regenerated cellulose in the range of 1-8 microns in diameter were produced. Before use, the microspheres were cationically modified by substitution with polyethyleneimine (PEI) or diethylaminoethyl (DEAE) groups. A third kind of adsorbent was manufactured by (physically) coating the cellulose matrix with PEI. All three types of adsorbents exhibited a high adsorption capacity for endotoxins in human plasma, whereas activated charcoal and various anion exchange resins removed only small amounts of endotoxins under the same conditions. In addition, because the outer surface area is very large, adsorption takes place rapidly and diffusion becomes almost irrelevant. The adsorption process is primarily based on electrostatic interactions, which could be demonstrated by a significantly higher adsorption rate and binding capacity for lipid A-diphosphoryl, compared with lipid A-monophosphoryl. Use of these adsorbents in a newly developed plasma sorption system could be of great clinical interest because of the low production costs, the high adsorption efficiency, and the excellent biocompatibility data.

Animals↗

Extracorporeal removal of proinflammatory cytokines by specific absorption onto microspheres.

Elevated plasma concentrations of interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) derived from cellular stimulation have been found to correlate well with the systemic inflammatory response syndrome and clinical outcome of sepsis. Consequently, biologic inactivation and extracorporeal removal of these potent mediators gain increasing attractiveness as adjunctive therapeutic options. In realization of the latter strategy the authors developed specific adsorbents by covalently linking polyclonal antibodies against IL-1 beta and TNF alpha onto microspheres. The attachment process was characterized by high retention of antigen neutralizing activity. Batch testing of the adsorbents revealed specificity, biocompatibility, and high binding capacity (20.2 and 36.9 ng/mg of particles for IL-1 beta and TNF alpha, respectively). Employment of the particles in the Microspheres Based Detoxification System (MDS) resulted in efficient purification: human plasma spiked with recombinant IL-1 beta and TNF alpha (500 pg/ml) could be cleared at 42 ml/min (IL-1 beta) and 55 ml/min (TNF alpha) at a flow rate of 200 ml/min. These clearance rates are considerably higher than the values obtained with ultrafiltration. In conclusion, the microsphere technology allows efficient extracorporeal removal of cytokines from plasma. In addition, by combined application of IL-1 beta and TNF alpha binding particles and endotoxin adsorbents, such as cationically modified cellulose, it should be feasible to interfere with the complex pathobiochemical sequelae of sepsis.

Antibodies↗

Removal of lipid A and Pseudomonas aeruginosa endotoxin from dialysis fluids by high-flux polysulfone ultrafilter (dialyzer).

Ultrafilters (dialysis membranes) are generally considered to be impermeable to bacterial endotoxins (lipopolysaccharides) contaminating dialysates used for hemodialysis therapy, due to the self-aggregating properties of its molecules in aqueous media. The aim of the present investigation was to monitor the efficiency of high-flux polysulfone ultrafilters in removing lipid A and lipopolysaccharide (LPS) from dialysis fluids. To evaluate the safety of high-flux polysulfone membranes, an in-vitro circulation system (measuring lipopolysaccharide and lipid A penetrate from the ultrafilter to the other side and vice-versa), was utilized. Peritoneal dialysis solution was spiked with various concentration of Pseudomonas aeruginosa lipopolysaccharide (LPS) as well as lipid A diphosphoryl (E. coli F-583). Endotoxin and lipid A concentrations were detected by a chromogenic limulus amoebocyte lysate (LAL) assay. This investigation indicates that polysulfone ultrafiltration represents an efficient system to obtain an endotoxin and lipid A free dialysate when contaminated peritoneal solution was circulated through the dialysis membrane.

Hemodialysis Solutions↗