Double filtration plasmapheresis maintains normal adhesion molecule levels.

Levels of plasma soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), and von Willebrand factor (vWF) increase in patients with peripheral vascular or ischemic heart disease. These factors are related to the progression of atherosclerosis. Furthermore, these substances and thrombomodulin (TM) are indicators for assessing the degree of damage to the endothelium. To evaluate the effect of double filtration plasmapheresis (DFPP) on these molecules, the plasma levels of vWF, sICAM-1, sVCAM-1, and TM were measured in 4 familial hypercholesterolemia (FH) patients who underwent treatment with DFPP at 2 week intervals for more than 3 years. The levels of sVCAM-1 and sICAM-1 in hypercholesterolemia patients with ischemic heart disease as a control was 773 +/- 109 and 334 +/- 82 ng/ml. These values were higher than the normal value. In the FH patients who underwent DFPP treatment, the average sICAM-1 levels were 221 +/- 47 and 197 +/- 36 ng/ml before and after, respectively. The average sVCAM-1 levels were 601 +/- 87 and 486 +/- 60 ng/ml. There were no significant differences between the pre- and post-DFPP values. The activities of plasma vWF before and after DFPP treatment were 158 +/- 23 and 45 +/- 9%. The levels of plasma TM before and after treatment were 3.0 +/- 0.3 and 3.4 +/- 0.5 FU/ml. From these results, it is suggested that DFPP treatment does not damage the endothelium and may prevent the progression of atherosclerosis by removing the substances that induce the production of sICAM-1 and sVCAM-1 due to long-term treatment.

Evaluation of double filtration plasmapheresis, thermofiltration, and low-density lipoprotein adsorptive methods by crossover test in the treatment of familial hypercholesterolemia patients.

A comparative assessment has been made regarding efficacy and safety of the double filtration plasmapheresis (DFPP), thermofiltration (TFPP), and low-density lipoprotein (LDL) adsorptive (PA) methods by making a crossover test on heterozygous familial hypercholesterolemia patients. Treatments by DFPP, TFPP (secondary membrane Evalux 5A), and PA (Liposorber LA-40) were carried out 5 times each, with a 2-week interval, in 5 patients with heterozygous familial hypercholesterolemia. The same plasma separator (Plasmacure PS-60, polysulfone) was used in all cases, and the volume of plasma processed was set at 4 L. High removal rates were obtained of total cholesterol, LDL cholesterol, triglycerides TG, and apolipoprotein B (apoB) by all three methods, and no differences were observed. Lipoprotein (a), apoA-2, apoC-3, fibrinogen, and immunoglobulin M (IgM) showed significantly high removal rates by the DFPP and TFPP methods compared with the PA method. The sieving coefficient of albumin and high-density lipoprotein (HDL) cholesterol at 2 and 4 L of plasma processed exhibited high permeabilities using all three methods. Supplementing albumin was not necessary. An increase of the transmembrane pressure was observed in 1 case treated by DFPP but was not observed when using the TFPP or PA method. No changes were observed in serum interleukin 1beta (IL-1beta) or tumor necrosis factor-alpha (TNF-alpha) before and after treatment by any of the three methods. No remarkable side effects were observed using either the DFPP or TFPP method. The DFPP and TFPP methods showed efficacy and safety that was not inferior to the PA method in conventional LDL apheresis, and the dead-end method of the filter operation without the discarding of plasma was shown to be possible.

Measurement of peritoneal dialysate volume by CT.

Three-dimensional (3-D) graphic reconstruction of serial image data of x-ray CT on three dialysis patients was studied to measure peritoneal dialysate (PD) volume. Volume estimation with a surface reconstructed model provided a 16% error; a 35% error was found with a voxel model, although the total time required by the voxel model was 15 times less.

Ex vivo preclinical evaluation of membrane plasma separators.

Four different types of hollow-fiber membrane plasma separators, constructed of cellulose acetate, polyvinyl alcohol, polyethylene, and polymethylmethacrylate membranes, were evaluated in ex vivo dog perfusions under conditions simulating their clinical use. An arteriovenous (A-V) fistula constructed in the dogs for blood access enabled repeated access to be achieved without surgical intervention. All modules produced transient leukopenia and a reduction of platelet counts. The polymethylmethacrylate module showed minimum reductions of white blood cell counts and CH50. The early leukocyte count reduction in membrane plasmapheresis is most likely related to the magnitude of complement activation by the membrane, as is seen with hemodialysis.

Cryoglobulin removal with cryofiltration in the treatment of cryoglobulinemia.

The technique of cryofiltration has been applied in the treatment of cryoglobulinemia. Good clinical improvement has been demonstrated accompanied by decreases of cryoglobulin levels. Three treatments in a week produced transient improvement of clinical symptoms and reduction of cryoglobulin levels. Follow-up treatments performed at adequate frequency and volume processed maintained relief of symptoms and serologic improvement. The cryofilter demonstrates good selectivity for cryoglobulin removal in cryogel, confirmed by electrophoretic analysis of both the cryogel filtrate from the cryofilter used clinically. Plasma cryofiltration appears to be a safe alternative to plasma exchange, requiring no replacement fluids.

Cryogel studies for the optimization of cryofiltration (CF) therapy.

This study has shown that cryofilter plugging correlates with pretreatment pathologic macromolecule concentrations (e.g. rheumatoid factor and immune complexes) in the treatment of patients with rheumatoid arthritis. Pathologic macromolecules are concentrated relative to albumin in the cryogel. Molecular aggregation in the cryogel depends upon heparin concentration, exhibiting maximum aggregation in a specific range of heparin concentrations. Molecular aggregation in cryogel increases with decreasing temperature. In the use of cryofiltration in over 50 rheumatoid arthritis patients, clinical improvement has accompanied the removal of cryogel and the pathologic macromolecules it contains. Filter plugging or cryogel formation may be indicators of disease activity. Formation of cryogel is variable depending upon type of disease, severity of disease, temperature, heparin concentration, and membrane structure. These factors are important parameters to consider to optimize conditions for removal of cryogel and for continuing improvement of plasma therapeutic techniques for the treatment of rheumatoid arthritis.