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Biomedical subjects

D Falkenhagen

Publications and source records attributed to D Falkenhagen.

At least 19 recordsLinked to original sources
PubMed1999

Fractionated plasma separation and adsorption system: a novel system for blood purification to remove albumin bound substances.

The removal of albumin bound substances has gained increasing interest in different diseases, especially in acute and chronic liver disease. Therefore, a new system, the fractionated plasma separation and adsorption (FPSA) system, was developed based on combined membrane and adsorbent blood purification techniques. The most important contribution to the FPSA system was the development of a new polysulfone hollow-fiber filter, which is characterized by a sieving coefficient of 0.89 for human serum albumin (HSA) but only of 0.17 for fibrinogen, and 0 (zero) for IgM immunoglobulins. Using a closed filtrate circuit connected to the new polysulfone filter which integrates 1 or 2 adsorption columns and also a high flux dialyzer adapted to a dialysis machine, the FPSA system opens excellent possibilities for the relatively specific removal of albumin bound substances from the blood such as albumin bound bilirubin or even tryptophan. In comparison to other systems (for example, the Molecular Adsorbent Recirculating System [MARS] and albumin dialysis systems), the FPSA system enables much higher elimination of strongly bound albumin substances. The first clinical investigations have recently started based on a modified dialysis machine designed with all necessary safety measures.

Acute Disease↗
PubMed1999

In vitro cell culture systems as the basis for an extracorporeal blood purification strategy in multiorgan failure treatment.

Multiorgan failure (MOF) based on septic processes is very common but prognostically an extremely severe disease that has to be treated exclusively under intensive care conditions. Extracorporeal blood purification (ECBP) using specific and efficient systems such as the microspheres based detoxification system (MDS) (Artif Organs 1996;20:420) could improve significantly the situation of MOF in terms of the efficient removal of endotoxins as well as key mediators such as tumor necrosis factor alpha (TNF alpha). The purpose of the study was to test the effectiveness of endotoxin and cytokine removal to blunt cellular response. In terms of the in vitro principle methodology, isolated peripheral blood mononuclear cells (PBMC) were incubated with endotoxins and a selective endotoxin adsorbent, which was added at various times (immediately or 30, 60, 120, 240, or 360 min) after the onset of incubation. TNF alpha release of monocytes was measured following a standard procedure after 20 h. Human TNF alpha was incubated with cultured human endothelial cells with and without a specific TNF alpha adsorbent (polyclonal antibodies coated on polystyrene particles). The results showed that after the initial addition of endotoxins, the activation of monocytes can be stopped within 120 min by addition of endotoxin adsorbents. In addition, specific TNF alpha adsorbents are able to prevent intercellular adhesion molecule 1 (ICAM-1) expression of endothelial cells, therefore avoiding activation of endothelial cells. In conclusion, cell culture models are suitable to simulate cell interaction in MOF. Specific adsorbents are able to reduce or block pathophysiologically relevant cell interactions, and the time frame for effective ECBP seems to be very short, and therefore, efficiency must be high.

Cells, Cultured↗
PubMed1999

Microspheres based detoxification system: in vitro study and mathematical estimation of filter performance.

Because of the closed plasma (secondary) circuit in the Microspheres based Detoxification System (MDS), a convective blood purification system, the same amount of filtrated plasma is backfiltrated into the blood circuit. Therefore, there is no direct way to determine the ultrafiltrate production rate, which is an important factor of efficiency. The only possible way to estimate the filtration properties of the filter is to consider pressure values. In this study the pressure distribution in the filter was investigated in vitro. To explain the results and to calculate inaccessible parameters, a mathematical model was established which also considered the asymmetric behaviour of the filter membrane. The result was a linear pressure gradient, agreement with the measurements was reasonably good (calculated primary pressure loss differs <13% from measured value when using mean measured filter resistance as model parameter). Linear pressure distribution offers the possibility of easily calculating the filtration length, a parameter which can be used to estimate the filter condition. The comparison between calculated filtration and backfiltration rates offers an instrument of control for these values.

Adsorption↗
PubMed1998

Monocyte activation and humoral immune response to endotoxins in patients receiving on-line hemodiafiltration therapy.

With the on-line preparation of substitution fluid, an easy-to-operate and cost-effective alternative to conventional hemodiafiltration (HDF) has been realized. The continuous filtration of dialysis fluid, furthermore, allows high volumes of exchange. Microbial contamination and subsequently endotoxins, however, may be present in dialysis fluid, and thus the microbiological safety has become a pivotal issue. In this clinical study we evaluated the safety of the Fresenius Medical Care on-line HDF system which is based on a two-stage filtration of dialysis fluid with upstream DIASAFE and downstream on-line HDF filter. During the three-month study period we failed to detect germs or endotoxins in the substitution fluid. Augmented plasma interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) concentrations were found neither during the intradialytic period nor when pre-session values at study begin and study end were compared. In addition, changes in the anti-endotoxin core antibody levels and soluble CD14 (sCD14) concentration, or pyrogenic episodes were not observed. On-line HDF with DIASAFE and on-line HDF filter thus represents a safe treatment modality by effectively depleting dialysis fluid of cytokine-inducing substances.

Adult↗
PubMed1997

Permeability and adsorption capacity of dialysis membranes to lipid A.

Hemodialysis membranes were tested in vitro for possible penetration by low molecular weight endotoxins containing lipid A. Using lipid A from Escherichia coli as a model substance for this kind of pyrogen, different dialyzers (F4, E3. Acepal 1300, Altraflux, F 40, Polyflux 110, Filtral 12, F 60) were challenged by tangential filtration in aqueous medium. All membranes exhibited impermability to lipid A (as well as to LPS from Pseudomonas aeruginosa), which was proved by additional experiments using culture filtrates of Pseudomonas aeruginosa in bicarbonate dialysis fluid, as well as by employing miniaturized dialyzers with synthetic lipid A as a contaminant. Furthermore, the highest adsorption capacities were found for polysulfone and polyamide membranes.

Adsorption↗
PubMed1997

A novel field generator for magnetic stimulation in cell culture experiments.

A novel field generator specially designed to examine the influence of low frequency magnetic fields on specific cell material was constructed and characterized. The exposure unit described in this paper consists of a controller unit and three sets of coils. The field generator permits a precious definition of the revelant signal parameters and allows the superposition of alternating current (AC) and direct current (DC) magnetic fields. Critical system parameters were monitored continuously. The three sets of coils, each arranged in the Helmholtz Configuration were characterized. After data processing and visualization the results showed a constant and homogeneous field within the experimental area. The special coil design also allows their use in an incubator.

Cell Physiological Phenomena↗
PubMed1996

Microspheres based detoxification system: a new method in convective blood purification.

A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.

Adsorption↗
PubMed1996

Protein A carrying monosize PMMA microbeads for the removal of HIgG from human plasma.

Protein A-incorporated polymethylmethacrylate (PMMA) microbeads were investigated for specific removal of HIgG from human plasma. The microbeads were prepared by a phase inversion polymerization, and activated by periodate oxidation. Protein A was then incorporated by covalent binding onto these microbeads through hydroxyl groups coming from the stabilizer. The amount of incorporated protein A was controlled by the initial concentrations of protein A in the immobilization medium and pH. The maximum protein A immobilization of 0.615 mg protein A/g PMMA, was observed at a pH of 9.5 corresponding to an initial protein A concentration of 0.1 mg/ml. There was no HIgG adsorption onto the plain PMMA microbeads, while high HIgG adsorptions of up to 32 mg HIgG/g PMMA were achieved with human plasma.

Adsorption↗
PubMed1994

The Microspheres based Detoxification System (MDS). A new extracorporeal blood purification technology based on recirculated microspherical adsorbent particles.

Plasma sorption processes have so far been performed with filters and appropriate adsorption columns. In this paper, we introduce a newly developed plasma sorption system, which is based on the high adsorption capacity of microspheres in a recirculation system. The technology has been applied successfully in vitro to eliminate endotoxins, low density lipoproteins (LDL) and barbiturates from human plasma.

Animals↗
PubMed1993

Behaviour of white blood cells and the complement system.

Seven different types of dialysers were investigated in five dialysis centres in four countries with respect to behaviour of white blood cells and the complement system. The results of this controlled crossover study demonstrated significant differences in the dialysers. Those containing cuprammonium cellulose (G10-3N and G120 M) showed the greatest changes in white blood cell count, including monocytes and neutrophils, as well as the greatest complement activation. With regard to lymphocytes the subpopulation of low-mobility cells, which were predominantly the B-cells, showed the greatest mobility with dialysers containing cuprammonium cellulose. The PAN copolymer- and PMMA-containing dialysers Filtral and T 150 clearly caused the least changes in white blood cells and complement factors. Dialysers containing cellulose acetate and polysulphone membranes (Duo-Flux Artificial Kidney, CD 4000, and F 60) produced only a moderate decrease of WBC, monocyte, neutrophil, and lymphocyte counts, and this result corresponded to a relatively small change in complement factors.

Acrylic Resins↗
PubMed1993

Biocompatibility of a new high-permeability modified cellulose membrane for haemodialysis.

The biocompatibility and solute permeability characteristics of a high-permeability modified cellulose membrane (Hemophan-HP) (He-HP) were compared with those of two synthetic membranes (poly(ethylene-co-vinyl alcohol) (EVAL) and poly(acrylonitrile-co-sodium methallyl sulphonate) (AN69)) and Cuprophan in a multicentre, four-way cross-over clinical trial. Cuprophan membranes caused significant complement activation, leukopenia, and granulocyte elastase release. He-HP membranes demonstrated a lesser effect, which was similar to that observed for the EVAL membrane, although less than that seen with the AN69 membrane. A similar order for the four membranes was seen for their effect on platelets. Cuprophan membranes provided superior small-molecule removal to the other three membranes. In contrast, Cuprophan was essentially impermeable to beta 2-microglobulin, whereas He-HP, EVAL, and AN69 allowed the removal of 60-90 mg of beta 2-microglobulin per treatment. However, a decrease in the plasma concentration of beta 2-microglobulin was observed only with the AN69 membrane, most probably as a result of the ability of that membrane to adsorb proteins. Our results demonstrate that high-permeability membranes of comparable biocompatibility to some synthetic membranes can be fabricated from cellulose derivatives.

Adult↗
PubMed1993

Extracorporeal endotoxin removal by immobilized polyethylenimine.

The neutralization of bacterial endotoxins (ET) is still an unsolved problem in therapeutic medicine. The efficacy of anti-endotoxin antibodies or receptor antagonists and other substances interfering with the endotoxin-induced pathomechanisms is dependent on an intact cellular degradation system of the host. However, the phagocytosis function of that system seems to be impaired regularly in patients with intense or long-lasting endotoxemia or septic shock and in patients undergoing hemodialysis. Extracorporeal adsorption of ET might well be an effective support in the anti-ET therapy by lowering the amount of circulating ET and thus relieving the defense system of the body. In this work a new ET-adsorbent based on macroporous cellulosic beads with immobilized polyethylenimine (PEI) was tested for its ET-removal capacity in vitro. A test solution with 100 ng/ml ET from Escherichia coli 055:B5 was recirculated in a system containing the adsorbent beads. Polymyxin B immobilized to the same carrier was used for comparison. PEI as well as polymyxin B showed complete removal of ET from plasma and water as was measured by the Limulus Amebocyte Lysate (LAL) test (Chromogenix). The biocompatibility of the PEI absorber was superior to that of polymyxin B. The results indicate that the PEI absorber is of high efficacy and possibly of interest for the treatment of endotoxemia.

Adsorption↗